ABSTRACT
Soft-matter-based photonic crystals like blue-phase liquid crystals (BPLC) have potential applications in wide-ranging photonic and bio-chemical systems. To date, however, there are limitations in the fabrication of large monocrystalline BPLCs. Traditional crystal-growth process involves the transition from a high-temperature disordered phase to an ordered (blue) phase and is generally slow (takes hours) with limited achievable lattice structures, and efforts to improve molecular alignment through post-crystallization field application typically prove ineffective. Here we report a systematic study on the molecular self-assembly dynamics of BPLC starting from a highly ordered phase in which all molecules are unidirectionally aligned by a strong electric field. We have discovered that, near the high-temperature end of the blue phase, if the applied field strength is then switched to an intermediate level or simply turned off, large-area monocrystalline BPLCs of various symmetries (tetragonal, orthorhombic, cubic) can be formed in minutes. Subsequent temperature tuning of the single crystal at a fixed applied field allows access to different lattice parameters and the formation of never-before-seen monoclinic structures. The formed crystals remain stable upon field removal. The diversity of stable monocrystalline BPLCs with widely tunable crystalline symmetries, band structures, and optical dispersions will significantly improve and expand their application potentials.
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Sinojackia Hu represents the first woody genus described by Chinese botanists, with all species classified as endangered ornamental plants endemic to China. Their characteristic spindle-shaped fruits confer high ornamental value to the plants, making them favored in gardens and parks. Nevertheless, the fruits likely pose a germination obstacle, contributing to the endangered status of this lineage. Here we report the chromosome-scale genome of S. xylocarpa, and explore the mechanisms underlying its endangered status, as well as its population dynamics throughout evolution. Population genomic analysis has indicated that S. xylocarpa experienced a bottleneck effect following the recent glacial period, leading to a continuous population reduction. Examination of the pericarp composition across six stages of fruit development revealed a consistent increase in the accumulation of lignin and fiber content, responsible for the sturdiness of mature fruits' pericarps. At molecular level, enhanced gene expression in the biosynthesis of lignin, cellulose and hemicellulose was detected in pericarps. Therefore, we conclude that the highly lignified and fibrotic pericarps of S. xylocarpa, which inhibit its seed germination, should be its threatening mechanism, thus proposing corresponding strategies for improved conservation and restoration. This study serves as a seminal contribution to conservation biology, offering valuable insights for the study of other endangered ornamental plants.
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PURPOSE: This study aimed to measure and analyze the transverse indicators of normodivergent patients with different sagittal skeletal malocclusions, to explore the transverse characteristics of different sagittal skeletal malocclusions. METHODS: Lateral cephalograms and CBCT of 90 normodivergent patients with skeletal Class â , â ¡ and â ¢ in their permanent dentition were collected. Dolphin software was applied to measure the widths of the basal bone, alveolar bone, dental arch and buccolingual inclination angle of the corresponding teeth in the maxillary and mandibular canine, premolar and molar areas. SPSS 22.0 software package was applied for statistical analysis of the data. RESULTS: The widths of the mandibular basal bone in canine, premolar and molar areas of skeletal Class â ¢ were (27.15±2.74), (39.30±2.82) and (59.97±2.93) mm, respectively. The widths of the mandibular alveolar bone of skeletal Class â ¢ were (25.38±1.78), (34.51±2.28) and (47.72±2.73) mm, respectively. The dental arch widths of the maxillary premolar and mandibular canine areas of skeletal Class â ¢ were (48.70±2.35) and (30.69±2.31)mm, respectively. The above data of skeletal Class â ¢ were significantly larger than those of skeletal Class â and â ¡(Pï¼0.01). The dental arch widths of the maxillary canine, maxillary molar and mandibular molar areas of skeletal Class â ¢ were (38.88±1.90), (59.51±3.40) and (56.01±2.86)mm, respectively, which were significantly larger than those of skeletal Class â ¡(Pï¼0.05). The maxillomandibular width difference of basal bone in the canine, premolar and molar areas of skeletal Class â ¢ were (4.69±2.84), (2.31±2.39) and (3.27±2.05) mm, respectively, which were significantly less than that of skeletal Class â and â ¡(Pï¼0.01). Compared with skeletal Class â , the maxillary canines and first molars of skeletal Class â ¡ had larger lingual inclination level, while the maxillary first premolars and first molars of skeletal Class â ¢ had larger buccal inclination level, the mandibular canines and the mandibular first premolars of skeletal Class â ¢ had larger lingual inclination level(Pï¼0.01). CONCLUSIONS: For normodivergent patients, the width of the mandibular base bone, alveolar bone, and maxillary and mandibular dental arch in skeletal Class â ¢ is the widest, which is more likely to have width discrepancy in basal bone. In skeletal Class â ¢, the maxillary teeth are buccally inclined, and the mandibular teeth are ingually inclined. In skeletal Class â ¡, the maxillary teeth are lingually inclined, and the mandibular teeth are compensatory upright.
Subject(s)
Cephalometry , Dental Arch , Mandible , Maxilla , Humans , Mandible/anatomy & histology , Mandible/diagnostic imaging , Cephalometry/methods , Maxilla/anatomy & histology , Maxilla/diagnostic imaging , Dental Arch/anatomy & histology , Malocclusion/pathology , Cone-Beam Computed Tomography/methods , Molar/anatomy & histology , Molar/diagnostic imaging , Cuspid/anatomy & histology , Cuspid/diagnostic imaging , Bicuspid/anatomy & histology , Bicuspid/diagnostic imaging , Malocclusion, Angle Class III , Alveolar Process/anatomy & histology , Alveolar Process/diagnostic imaging , Dentition, PermanentABSTRACT
The properties of nanopipettes largely rely on the materials introduced onto their inner walls, which allow for a vast extension of their sensing capabilities. The challenge of simultaneously enhancing the sensitivity and selectivity of nanopipettes for pH sensing remains, hindering their practical applications. Herein, we report insulin-modified nanopipettes with excellent pH response performances, which were prepared by introducing insulin onto their inner walls via a two-step reaction involving silanization and amidation. The pH response intensity based on ion current rectification was significantly enhanced by approximately 4.29 times when utilizing insulin-modified nanopipettes compared with bare ones, demonstrating a linear response within the pH range of 2.50 to 7.80. In addition, insulin-modified nanopipettes featured good reversibility and selectivity. The modification processes were monitored using the I-V curves, and the relevant mechanisms were discussed. The effects of solution pH and insulin concentration on the modification results were investigated to achieve optimal insulin introduction. This study showed that the pH response behavior of nanopipettes can be greatly improved by introducing versatile molecules onto the inner walls, thereby contributing to the development and utilization of pH-responsive nanopipettes.
Subject(s)
Insulin , Hydrogen-Ion Concentration , Insulin/chemistry , Biosensing Techniques/methods , Ions/chemistryABSTRACT
Neurosyphilis is a central nervous system infection caused by Treponema pallidum that imitates various neurological and mental disorders. Therefore, patients with this disease are prone to misdiagnoses. Here, we report a case of neurosyphilis with a psychotic disorder as the main manifestation. A young girl exhibited mental and behavioural abnormalities after a heartbreak, which manifested as alternating low mood, emotional irritability, and a lack of interest in social relations, followed by memory loss. The cerebrospinal fluid protein - Treponema pallidum particle agglutination test was positive, the toluidine red unheated serum test titre was 1:4, the white blood cell count was 5 × 10^6/L, the cerebrospinal fluid protein level was 0.97 g/L, and the brain CT was abnormal. After admission, the possibility of neurosyphilis was considered and the patient received intravenous penicillin G treatment. The patient's clinical symptom ms improved. This case emphasises that doctors should maintain clinical suspicion of Treponema pallidum infection in adolescent patients with mental abnormalities.
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Mitogen-activated protein kinase inhibitors (MAPKi) were the first line drugs for advanced melanoma patients with BRAF mutation. Targeted therapies have significant therapeutic effects; however, drug resistance hinders their long-term efficacy. Therefore, the development of new therapeutic strategies against MAPKi resistance is critical. Our previous results showed that MAPKi promote feedback activation of STAT3 signaling in BRAF-mutated cancer cells. Studies have shown that alantolactone inhibited the activation of STAT3 in a variety of tumor cells. Our results confirmed that alantolactone suppressed cell proliferation and promoted apoptosis by inhibiting STAT3 feedback activation induced by MAPKi and downregulating the expression of downstream Oct4 and Sox2. The inhibitory effect of alantolactone combined with a MAPKi on melanoma cells was significantly stronger than that on normal cells. In vivo and in vitro experiments showed that combination treatment was effective against drug-resistant melanomas. Our research indicates a potential novel combination therapy (alantolactone and MAPKi) for patients with BRAF-mutated melanoma.
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TGA transcription factors belong to Group D of the bZIP transcription factors family and play vital roles in the stress response of plants. Brassica napus is an oil crop with rich economic value. However, a systematic analysis of TGA gene family members in B. napus has not yet been reported. In this study, we identified 39 full-length TGA genes in B. napus, renamed TGA1~TGA39. Thirty-nine BnTGA genes were distributed on 18 chromosomes, mainly located in the nucleus, and differences were observed in their 3D structures. Phylogenetic analysis showed that 39 BnTGA genes could be divided into five groups. The BnTGA genes in the same group had similar structure and motif compositions, and all the BnTGA genes had the same conserved bZIP and DOG1 domains. Phylogenetic and synteny analysis showed that the BnTGA genes had a close genetic relationship with the TGA genes of the Brassica juncea, and BnTGA11 and BnTGA29 may play an important role in evolution. In addition, qRT-PCR revealed that three genes (BnTGA14/17/23) showed significant changes in eight experimental materials after drought treatment. Meanwhile, it can be inferred from the results of drought treatment on different varieties of rapeseed that the stress tolerance of parental rapeseed can be transmitted to the offspring through hybridization. In short, these findings have promoted the understanding of the B. napus TGA gene family and will contribute to future research aimed at B. napus resistant breeding.
Subject(s)
Basic-Leucine Zipper Transcription Factors , Brassica napus , Droughts , Gene Expression Regulation, Plant , Multigene Family , Phylogeny , Plant Proteins , Stress, Physiological , Brassica napus/genetics , Plant Proteins/genetics , Plant Proteins/metabolism , Stress, Physiological/genetics , Basic-Leucine Zipper Transcription Factors/genetics , Basic-Leucine Zipper Transcription Factors/metabolism , Genome, Plant , Chromosomes, Plant/genetics , Gene Expression Profiling , Synteny/geneticsABSTRACT
BACKGROUND: Efficient monitoring of glucose concentration in the human body necessitates the utilization of electrochemically active sensing materials in nonenzymatic glucose sensors. However, prevailing limitations such as intricate fabrication processes, lower sensitivity, and instability impede their practical application. Herein, ternary Cu-Co-Ni-S sulfides nanoporous network structure was synthesized on carbon fiber paper (CP) by an ultrafast, facile, and controllable technique through on-step cyclic voltammetry, serving as a superior self-supporting catalytic electrode for the high-performance glucose sensor. RESULTS: The direct growth of free-standing Cu-Co-Ni-S on the interconnected three-dimensional (3D) network of CP boosted the active site of the composites, improved ion diffusion kinetics, and significantly promoted the electron transfer rate. The multiple oxidation states and synergistic effects among Co, Ni, Cu, and S further promoted glucose electrooxidation. The well-architected Cu-Co-Ni-S/CP presented exceptional electrocatalytic properties for glucose with satisfied linearity of a broad range from 0.3 to 16,000 µM and high sensitivity of 6829 µA mM- 1 cm- 2. Furthermore, the novel sensor demonstrated excellent selectivity and storage stability, which could successfully evaluate the glucose levels in human serum. Notably, the novel Cu-Co-Ni-S/CP showed favorable biocompatibility, proving its potential for in vivo glucose monitoring. CONCLUSION: The proposed 3D hierarchical morphology self-supported electrode sensor, which demonstrates appealing analysis behavior for glucose electrooxidation, holds great promise for the next generation of high-performance glucose sensors.
Subject(s)
Biosensing Techniques , Carbon Fiber , Cobalt , Copper , Electrochemical Techniques , Electrodes , Nickel , Sulfides , Copper/chemistry , Nickel/chemistry , Catalysis , Humans , Cobalt/chemistry , Electrochemical Techniques/methods , Biosensing Techniques/methods , Sulfides/chemistry , Carbon Fiber/chemistry , Glucose/analysis , Glucose/chemistry , Nanopores , Oxidation-Reduction , Blood Glucose/analysisABSTRACT
Fast, sensitive, and portable detection of genetic modification contributes to agricultural security and food safety. Here, we developed RPA-CRISPR/Cas12a-G-quadruplex colorimetric assays that can combine with intelligent recognition by deep learning algorithms to achieve sensitive, rapid, and portable detection of the CaMV35S promoter. When the crRNA-Cas12a complex recognizes the RPA amplification product, Cas12 cleaves the G-quadruplex, causing the G4-Hemin complex to lose its peroxide mimetic enzyme function and be unable to catalyze the conversion of ABTS2- to ABTS, allowing CaMV35S concentration to be determined based on ABTS absorbance. By utilizing the RPA-CRISPR/Cas12a-G4 assay, we achieved a CaMV35S limit of detection down to 10 aM and a 0.01 % genetic modification sample in 45 min. Deep learning algorithms are designed for highly accurate classification of color results. Yolov5 objective finding and Resnet classification algorithms have been trained to identify trace (0.01 %) CaMV35S more accurately than naked eye colorimetry. We also coupled deep learning algorithms with a smartphone app to achieve portable and rapid photo identification. Overall, our findings enable low cost ($0.43), high accuracy, and intelligent detection of the CaMV35S promoter.
Subject(s)
CRISPR-Cas Systems , Colorimetry , Deep Learning , G-Quadruplexes , Colorimetry/methods , CRISPR-Cas Systems/genetics , Promoter Regions, Genetic , CRISPR-Associated Proteins/genetics , CRISPR-Associated Proteins/metabolism , Limit of Detection , Bacterial Proteins/genetics , EndodeoxyribonucleasesABSTRACT
OBJECTIVES: The purpose of this study was to investigate fatigue, mental workload, and burnout among health care workers (HCWs) and explore the possible underlying factors. MATERIALS AND METHODS: An online cross-sectional survey design was used to collect data from HCWs in Chongqing, China. The online survey included the Fatigue Severity Scale, NASA Task Load Index, and Chinese version of the Maslach Burnout Inventory-General Survey to assess fatigue, mental workload, and burnout, respectively, and was conducted from February 1 to March 1, 2023. RESULTS: In this study, the incidence of fatigue and burnout among HCWs was 76.40% and 89.14%, respectively, and the incidence of moderate to intolerable mental workloads was 90.26%. Work-family conflict, current symptoms, number of days of COVID-19 positivity, mental workload, burnout and reduced personal accomplishment were significantly associated with fatigue. Mental workload was affected by fatigue and reduced personal accomplishment. Furthermore, burnout was influenced by marital status and fatigue. Moreover, there was a correlation among mental workload, fatigue, and burnout. CONCLUSIONS: Fatigue, mental workload and burnout had a high incidence and were influenced by multiple factors during COVID-19 public emergencies in China.
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Background: The COVID-19 pandemic has required teachers and students to suddenly transition from face-to-face formats to distance education (DE). The uniqueness of nursing discipline is that it requires both theoretical and skills-based learning. Therefore, it is necessary to explore the influencing factors and effectiveness of DE in nursing education. This exploration can guide teaching practice and provide a basis for the future application of DE in nursing education. Aims: To describe the current distance education readiness and depth of learning among undergraduate nursing students and explore possible influencing factors. To determine the relationship between students' distance education readiness and the depth of learning. Design: This is a descriptive and cross-sectional online study. Settings: School of Nursing in a traditional Chinese medicine university, Beijing, China. Participants: A total of 222 undergraduate nursing students from a traditional Chinese medicine university were recruited. Methods: A questionnaire, which is composed of information form, the Online Learning Readiness Scale, and the Scale of Students Making Deep Learning, was used for data collection. Frequency, percentage, arithmetic mean, standard deviation, t-test, one-way ANOVA, and Pearson correlations were used in the analysis of the data. Result: Undergraduate nursing students have lower averages in distance education readiness and higher averages in the depth of learning. Significant differences in distance education readiness and depth of learning between different grade groups. A positive correlation was found between distance education readiness and depth of learning (r = 0.894, p < 0.001). Conclusion: Distance education is a feasible approach to learning today. Undergraduate nursing students have exhibited poor readiness for distance education but demonstrated deeper learning conditions. Upper grades may lead to better learning outcomes. Better distance education readiness can lead to deeper learning. These conclusions prompt teachers and students to be prepared before participating in distance education to obtain better academic performance.
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The challenge of drug resistance in intrahepatic cholangiocarcinoma (ICC) is intricately linked with lipid metabolism reprogramming. The hepatic lipase (HL) and the membrane receptor CD36 are overexpressed in BGJ398-resistant ICC cells, while they are essential for lipid uptake, further enhancing lipid utilization in ICC. Herein, a metal-organic framework-based drug delivery system (OB@D-pMOF/CaP-AC, DDS), has been developed. The specifically designed DDS exhibits a successive targeting property, enabling it to precisely target ICC cells and their mitochondria. By specifically targeting the mitochondria, DDS produces reactive oxygen species (ROS) through its sonodynamic therapy effect, achieving a more potent reduction in ATP levels compared to non-targeted approaches, through the impairment of mitochondrial function. Additionally, the DDS strategically minimizes lipid uptake through the incorporation of the anti-HL drug, Orlistat, and anti-CD36 monoclonal antibody, reducing lipid-derived energy production. This dual-action strategy on both mitochondria and lipids can hinder energy utilization to restore drug sensitivity to BGJ398 in ICC. Moreover, an orthotopic mice model of drug-resistant ICC was developed, which serves as an exacting platform for evaluating the multifunction of designed DDS. Upon in vivo experiments with this model, the DDS demonstrated exceptional capabilities in suppressing tumor growth, reprogramming lipid metabolism and improving immune response, thereby overcoming drug resistance. These findings underscore the mitochondria-targeted DDS as a promising and innovative solution in ICC drug resistance.
Subject(s)
Bile Duct Neoplasms , Cholangiocarcinoma , Drug Delivery Systems , Drug Resistance, Neoplasm , Lipid Metabolism , Mitochondria , Cholangiocarcinoma/drug therapy , Cholangiocarcinoma/pathology , Cholangiocarcinoma/metabolism , Animals , Mitochondria/metabolism , Mitochondria/drug effects , Humans , Drug Resistance, Neoplasm/drug effects , Lipid Metabolism/drug effects , Cell Line, Tumor , Mice , Bile Duct Neoplasms/drug therapy , Bile Duct Neoplasms/pathology , Bile Duct Neoplasms/metabolism , CD36 Antigens/metabolism , Metal-Organic Frameworks/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Mice, Nude , Reactive Oxygen Species/metabolism , Mice, Inbred BALB C , Lipase/metabolismABSTRACT
In esophageal cancer (EC), clinical specimen testing has uncovered a significant increase in BTB and CNC homolog 1 (BACH1) expression and a shift towards an immunosuppressive environment, alongside a notable decrease in p53 protein expression. Therefore, therapeutic strategies focusing on BACH1 inhibition and p53 upregulation appear promising. Traditional oral treatments for EC lack precision and efficacy. Here, we propose a novel approach employing tumor-targeted nanoparticles (NPs) for drug delivery. However, the formation of a drug reservoir at the esophageal site, crucial for the sustained release of therapeutics, presents significant challenges in nano-delivery systems for EC treatment. To address this, we developed a thermosensitive hydrogel composed of F127 and tannic acid, serving as a vehicle for NP loading. These NPs, synthesized through the emulsion/volatization methods of mPEG-PLGA-PLL-cRGD, facilitate in situ drug delivery. Upon contacting esophageal tissue, the hydrogel transitions to a gel, adhering to the lining and enabling sustained release of encapsulated therapeutics. The formulation encompasses NPs laden with small interfering RNA targeting BACH1 (siBACH1) and the p53 activator PRIMA-1, creating a cohesive gel-nano system. Preliminary biological assessments demonstrate that this injectable, thermosensitive gel-nano system adheres effectively to esophageal tissue and targets EC cells. For better modeling clinical outcomes, a patient-derived organoid xenograft (PDOX) model was innovated, involving transplantation of EC-derived organoids into humanized mice, reconstructed with peripheral blood mononuclear cells (PBMCs). Post-treatment analysis showed substantial EC growth inhibition (89.51% tumor inhibition rate), significant BACH1 level reduction, restored anti-tumor immune responses, and pronounced tumor apoptosis. In summary, our study introduces a thermosensitive gel-nano system for EC treatment via restoring p53 activity and boosting T-cell immunity, with potential for clinical application.
Subject(s)
Esophageal Neoplasms , Nanoparticles , Tumor Suppressor Protein p53 , Esophageal Neoplasms/drug therapy , Esophageal Neoplasms/immunology , Animals , Humans , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Cell Line, Tumor , Hydrogels/administration & dosage , Hydrogels/chemistry , T-Lymphocytes/immunology , T-Lymphocytes/drug effects , Female , Mice , Temperature , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Drug Delivery SystemsABSTRACT
Purpose: To (1) investigate the changes in 5 domains (lack of family support, impact on finance, impact on daily schedule, impact on health, and self-esteem) of family caregiver (FC) burden and overall burden for first diagnosed colorectal cancer; (2) exploring changes in FC burden for colorectal cancer patients over time and analyze the trajectory and sub-trajectories of FC burden; and (3) identify the FC-related and patient-related factors most associated with the overall FC burden and each of its sub-trajectories. Patients and methods: This study is a descriptive longitudinal study. A convenience sampling method was used to recruit patients with colorectal cancer and their primary FCs from seven hospitals. Results: A total of 185 pairs of first diagnosed colorectal cancer patient and their FC were investigated for 4 times. The results reveal the overall burden and 5 domains of burden showed a trend of increasing first and then decreasing, and the burden was the heaviest at the time in the middle of chemotherapy. In the course of time, the aspect that caused the greatest amount of burden on average transitioned from the "effect on daily schedule" (range= 3.3 and 3.9) to the "effect on finances" (range= 3.1 to 3.4). Conclusion: Almost 88% of FCs have a either a moderate or a high level of burden. The quality of life of patients and the self-efficacy, social support and care ability of FCs have a great impact on the overall FC burden and each sub-trajectory.
ABSTRACT
Pancreatic ductal adenocarcinoma (PDAC) features an immunosuppressive tumor microenvironment (TME) that resists immunotherapy. Tumor-associated macrophages, abundant in the TME, modulate T cell responses. Bone marrow stromal antigen 2-positive (BST2+) macrophages increase in KrasG12D/+; Trp53R172H/+; Pdx1-Cre mouse models during PDAC progression. However, their role in PDAC remains elusive. Our findings reveal a negative correlation between BST2+ macrophage levels and PDAC patient prognosis. Moreover, an increased ratio of exhausted CD8+ T cells is observed in tumors with up-regulated BST2+ macrophages. Mechanistically, BST2+ macrophages secrete CXCL7 through the ERK pathway and bind with CXCR2 to activate the AKT/mTOR pathway, promoting CD8+ T cell exhaustion. The combined blockade of CXCL7 and programmed death-ligand 1 successfully decelerates tumor growth. Additionally, cGAS-STING pathway activation in macrophages induces interferon (IFN)α synthesis leading to BST2 overexpression in the PDAC TME. This study provides insights into IFNα-induced BST2+ macrophages driving an immune-suppressive TME through ERK-CXCL7 signaling to regulate CD8+ T cell exhaustion in PDAC.
Subject(s)
Bone Marrow Stromal Antigen 2 , GPI-Linked Proteins , Interferon-alpha , Pancreatic Neoplasms , Tumor-Associated Macrophages , Animals , Female , Humans , Mice , Antigens, CD/metabolism , Carcinoma, Pancreatic Ductal/pathology , Carcinoma, Pancreatic Ductal/immunology , Carcinoma, Pancreatic Ductal/metabolism , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Cell Line, Tumor , GPI-Linked Proteins/metabolism , Immune Tolerance , Interferon-alpha/metabolism , Mice, Inbred C57BL , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/immunology , Pancreatic Neoplasms/metabolism , Signal Transduction , Tumor Microenvironment/immunology , Tumor-Associated Macrophages/metabolism , Tumor-Associated Macrophages/immunology , Tumor-Associated Macrophages/pathologyABSTRACT
BACKGROUND: Leptospirosis, an important zoonotic bacterial disease, commonly affects resource-poor populations and results in significant morbidity and mortality worldwide. The value of antibiotics in leptospirosis remains unclear, as evidenced by the conflicting opinions published. METHODS: We conducted a search in the PubMed, Web of Science, and Cochrane Library databases for studies. These studies included clinical trials and retrospective studies that evaluated the efficacy or safety of antibiotics for leptospirosis treatment. The primary outcomes assessed were defervescence time, mortality rate, and hospital stays. Subgroup analyses were performed based on whether there were cases involving children and whether there were cases of severe jaundice. Safety was defined as the prevalence of adverse events associated with the use of antibiotics. p scores were utilized to rank the efficacy of the antibiotics. RESULTS: There are included 9 randomized controlled trials (RCTs), 1 control trial (CT), and 3 retrospective studies (RS) involving 920 patients and 8 antibiotics. Six antibiotics resulted in significantly shorter defervescence times compared to the control, namely cefotaxime (MD, - 1.88; 95% CI = - 2.60 to - 1.15), azithromycin (MD, - 1.74; 95% CI = - 2.52 to - 0.95), doxycycline (MD, - 1.53; 95% CI = - 2.05 to - 1.00), ceftriaxone (MD, - 1.22; 95% CI = - 1.89 to - 0.55), penicillin (MD, - 1.22; 95% CI = - 1.80 to - 0.64), and penicillin or ampicillin (MD, - 0.08; 95% CI = - 1.01 to - 0.59). The antibiotics were not effective in reducing the mortality and hospital stays. Common adverse reactions to antibiotics included Jarisch-Herxheimer reaction, rash, headache, and digestive reactions (nausea, vomiting, diarrhea, abdominal pain, and others). CONCLUSIONS: Findings recommend that leptospirosis patients be treated with antibiotics, which significantly reduced the leptospirosis defervescence time. Cephalosporins, doxycycline, and penicillin are suggested, and azithromycin may be a suitable alternative for drug-resistant cases. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022354938.
Subject(s)
Anti-Bacterial Agents , Leptospirosis , Humans , Anti-Bacterial Agents/adverse effects , Azithromycin/adverse effects , Doxycycline/therapeutic use , Leptospirosis/drug therapy , Leptospirosis/chemically induced , Network Meta-Analysis , Penicillins/therapeutic useABSTRACT
CD47 blockade has emerged as a promising immunotherapy against liver cancer. However, the optimization of its antitumor effectiveness using efficient drug delivery systems or combinations of therapeutic agents remains largely incomplete. Here, patients with liver cancer co-expressing CD47 and CDC7 (cell division cycle 7, a negative senescence-related gene) are found to have the worst prognosis. Moreover, CD47 is highly expressed, and senescence is inhibited after the development of chemoresistance, suggesting that combination therapy targeting CD47 and CDC7 to inhibit CD47 and induce senescence may be a promising strategy for liver cancer. The efficacy of intravenously administered CDC7 and CD47 inhibitors is limited by low uptake and short circulation times. Here, inhibitors are coloaded into a dual-targeted nanosystem. The sequential release of the inhibitors from the nanosystem under acidic conditions first induces cellular senescence and then promotes immune responses. In an in situ liver cancer mouse model and a chemotherapy-resistant mouse model, the nanosystem effectively inhibited tumor growth by 90.33% and 85.15%, respectively. Overall, the nanosystem in this work achieved the sequential release of CDC7 and CD47 inhibitors in situ to trigger senescence and induce immunotherapy, effectively combating liver cancer and overcoming chemoresistance.
Subject(s)
CD47 Antigen , Liver Neoplasms , Animals , Mice , Liver Neoplasms/drug therapy , Liver Neoplasms/metabolism , CD47 Antigen/metabolism , Humans , Disease Models, Animal , Cellular Senescence/drug effects , Cell Cycle Proteins/metabolism , Immunotherapy/methods , Drug Delivery Systems/methods , Nanoparticles , Immunologic Factors/pharmacology , Cell Line, Tumor , Immunomodulating Agents/pharmacologyABSTRACT
INTRODUCTION: Liver disease causes 2 million deaths annually, accounting for 4% of all deaths worldwide. Liver surgery is one of the effective therapeutic options. Bleeding is a major complication during liver surgery. Perioperative bleeding and allogeneic blood transfusion may deteriorate the prognosis. Terlipressin (TP), a synthetic analogue of the antidiuretic hormone, may reduceblood loss during abdominal surgery. Several clinical centres have attempted to use TP during liver surgery, but the evidence for its effectiveness in reducing blood loss and the need for allogeneic blood transfusion, as well as its safety during the perioperative period, remains unclear. The aim of this systematic review and meta-analysis is to evaluate the efficacy and safety of TP in reducing blood loss and allogeneic blood transfusion needs during liver surgery. METHODS AND ANALYSIS: We will search PubMed, EMBASE, the Cochrane Library and Web of Science for studies on perioperative use of TP during liver surgery from inception to July 2023. We will limit the language to English, and two reviewers will independently screen and select articles. The primary study outcomes are estimated blood loss and the need for allogeneic blood transfusion. Secondary outcomes include operating time, intensive care unit stay, length of stay, intraoperative urine output, acute kidney injury rate, postoperative complications, hepatic and renal function during follow-up, and TP-related adverse effects. We will include studies that met the following criteria: (1) randomised controlled trials (RCTs), cohort studies or case-control studies; (2) the publication time was till July 2023; (3) adult patients (≥18 years old) undergoing elective liver surgery; (4) comparison of TP with other treatments and (5) the study includes at least one outcome. We will exclude animal studies, case reports, case series, non-original articles, reviews, paediatric articles, non-controlled trials, unpublished articles, non-English articles and other studies that are duplicates. We will use Review Manager V.5.3 software for meta-analysis and perform stratification analysis for the study quality of RCTs based on the Jadad score. For cohort or case-control studies, the study quality will be analysed based on Newcastle-Ottawa Scale scores. Grading of Recommendations, Assessment, Development and Evaluation will be used to assess confidence in the cumulative evidence. For primary outcomes, we will conduct subgroup analyses based on meta-regression. We will also perform leave-one-out sensitivity analyses to evaluate the effect of each individual study on the combined results by removing the individual studies one by one for outcomes with significant heterogeneity. The protocol follows the Cochrane Handbook for Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols guidelines. ETHICS AND DISSEMINATION: This study is a secondary analysis of existing data; therefore, it does not require ethical approval. We will disseminate the results through peer-reviewed publications. PROSPERO REGISTRATION NUMBER: CRD42023450333.
Subject(s)
Blood Loss, Surgical , Meta-Analysis as Topic , Systematic Reviews as Topic , Terlipressin , Vasoconstrictor Agents , Humans , Terlipressin/therapeutic use , Terlipressin/administration & dosage , Blood Loss, Surgical/prevention & control , Vasoconstrictor Agents/administration & dosage , Vasoconstrictor Agents/therapeutic use , Research Design , Liver Diseases/surgery , Blood Transfusion/statistics & numerical data , Liver/surgeryABSTRACT
The reduction of soluble U(VI) to insoluble and less toxic U(IV) by photocatalysis is an effective method to control uranium contamination. The graphitic carbon nitride nanosheet (CNN)/UiO-66 composites (CNNU) were prepared by thermal polymerization and solvothermal methods for the removal of U(VI). The morphology, crystal structure and optical properties of composites were analyzed by SEM, XRD, BET, UV-DRS, PL and EIS. The results showed the introduction of UiO-66 increased the specific surface of CNN from 9.07 m2/g to 46.24 m2/g, and effectively suppressed the recombination of photogenerated electrons and holes and improved the photocatalytic activity. The U(VI) removal capacity by adsorption and photocatalysis of CNNU was reached 779.47 mg/g, which significantly higher than that of adsorption (478.38 mg/g). The adsorption process was found to conform to the pseudo-second-order kinetic model and the Langmuir isothermal model. Meanwhile, U(VI) adsorbed on the CNNU was reduced to U(IV) via e- and ·O2- generated in the photocatalytic process. Therefore, this outstanding performance of CNNU in U(VI) removal is attributed to the synergistic effect of adsorption and photocatalytic reduction.
Subject(s)
Metal-Organic Frameworks , Phthalic Acids , Uranium , Adsorption , Uranium/chemistry , SunlightABSTRACT
AIMS: To describe the changes in moderate-to-late preterm infants' (MLPIs) growth during 12 months of corrected age (CA) and to examine the predictive role of NICU-related stress, postpartum depression trajectory and family coping ability on the physical developmental trajectory of MLPIs. DESIGN: A prospective longitudinal study. METHODS: There were 237 mother-infant dyads with at least two follow-up data records included. General characteristics and NICU-related stress were recorded from medical records at baseline. Infants' physical growth was measured at 40 weeks, 1, 3, 6, 9 and 12 months CA during outpatient follow-up. Maternal postpartum depressive symptoms and family coping ability were assessed by questionnaires at 1, 3, 6, 9 and 12 months CA and 1 month CA respectively. We investigated the modifiable factors inside and outside of NICU on the trajectories of physical growth in the first year in MLPIs, mainly by using latent growth curve models with time-varying covariates. RESULTS: The curved trajectories of weight, length and head circumference in the first year in MLPIs demonstrated gradually slowed growth rates and these infants were above the WHO growth standards for the same age and sex. The latent growth curve models indicated that more NICU-related stress was negatively associated with the weight and length at 40 weeks CA, and family coping ability (parent-child relationship) at 1 month CA was associated with the growth rate of weight. Besides, more NICU-related stress predicted faster length growth rate. The infants of mothers who were in the group of high-level postpartum depression trajectory had a slower growth rate of head circumference. CONCLUSIONS: Our study identified the modifiable factors along the care continuum influencing the trajectory of MLPIs' physical growth. Nurses should receive more training about infant stress measurement and family-centred care to work in partnership with parents so that MLPIs can reach their full developmental potential. Also, multidisciplinary interventions including stress reduction strategies, close psychological monitoring and education improving parent-infant relationships should be further developed to achieve optimizing growth in the first year of MLPIs. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: It is recommended that nurses pay attention to the long-term physical growth status of MLPIs, and closely support their families. Quantifying NICU-related stress and developing reduction strategies should be the priority for clinical staff during hospitalization. After discharge, persistent screening of depressive symptoms, psychological intervention and education about the parent-child relationship need to be included in the follow-up visits. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution. The study only included patients who were research participants.