Enhancing antibody detection sensitivity in lateral flow immunoassays using endospores of Bacillus subtilis as signal amplifiers.

Antibody detection is the critical first step for tracking the spread of many diseases including COVID-19. Lateral flow immunoassay (LFIA) is the most commonly used method for rapid antibody detection because it is easy-to-use and inexpensive. However, LFIA has limited sensitivity when gold nanoparticles (AuNPs) are used as the signals. In this study, the endospores of Bacillus subtilis were used in combination with AuNP in a LFIA to detect antibodies. The endospores serve as a signal amplifier. The detection limit was about 10-8 M for anti-beta galactosidase antibody detection whereas the detection limit of conventional LFIA is about 10-6 M. Furthermore, the proposed methods have no additional user steps compared with the traditional LFIA. This method, therefore, improved the sensitivity 100-fold without compromising any advantages of LFIA. We believe that the proposed method will be useful for detection of antibodies against HIV, Zika virus, SARS-CoV-2, and so on.

Developing and validating a nomogram for early predicting the need for intestinal resection in pediatric intussusception.

Purpose: Develop and validate a nomogram for predicting intestinal resection in pediatric intussusception suspecting intestinal necrosis. Patients & methods: Children with intussusception were retrospectively enrolled after a failed air-enema reduction in the outpatient setting and divided into two groups: the intestinal resection group and the non-intestinal resection group. The enrolled cases were randomly selected for training and validation sets with a split ratio of 3:1. A nomogram for predicting the risk of intestinal resection was visualized using logistic regression analysis with calibration curve, C-index, and decision curve analysis to evaluate the model. Results: A total of 547 cases were included in the final analysis, of which 414 had non-intestinal necrosis and 133 had intestinal necrosis and underwent intestinal resection. The training set consisted of 411 patients and the validation cohort included 136 patients. Through forward stepwise regression, four variables (duration of symptoms, C-reaction protein, white blood cells, ascites) were selected for inclusion in the nomogram with a concordance index 0.871 (95% confidence interval: 0.834-0.908). Conclusion: We developed a nomogram for predicting intestinal resection in children with intussusception suspecting intestinal necrosis after a failed air-enema based on multivariate regression. This nomogram could be directly applied to facilitate predicting intestinal resection in pediatric intussusception suspecting necrosis.

DFT investigation of the DDQ-catalytic mechanism for constructing C-O bonds.

In this study, we investigated the photo-catalytic mechanisms for the construction of C-O bonds from arenes (benzene, 2',6'-dimethyl-[1,1'-biphenyl]-2-carboxylic acid, or 2,4-dichloro-1-fluorobenzene), catalyzed by 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ). All the structures for the Gibbs free surfaces were calculated at the M06-2X-D3/ma-def2-SVP level in the SMD solvent model. Also, TDDFT calculations of DDQ were performed at the PBE1PBE-D3/ma-def2-SVP level in the SMD solvent model. The computational results indicated that DDQ, serving as a photo-catalyst, would be excited under visible light of 450 nm, aligning well with experimental observations as reflected in the UV-vis spectrum. Gibbs free energy surface analyses of the three reactions suggested that the path involving 3DDQ* activating the reactant (-COOH, H2O, or CH3OH) is favorable. Additionally, the role of O2 was investigated, revealing that it could facilitate the recycling of DDQ by lowering the energy barrier for the conversion of the DDQH˙ radical (not DDQH2) into DDQ. The use of ρhole and ρele can reveal the photo-catalytic reaction and charge transfer processes, while localized orbital locator isosurfaces and electron spin density isosurface graphs were employed to analyze structures and elucidate the single electron distribution. These computational results offer valuable insights into the studied interactions and related processes, shedding light on the mechanisms governing C-O bond formation from arenes catalyzed by DDQ.

Association of the second birth mode of delivery and interval with maternal pelvic floor changes: a prospective cohort study.

BACKGROUND: This study aimed to explore the association of the second birth delivery mode and interval with maternal pelvic floor changes. METHODS: This prospective cohort study included women who had a first delivery and were in weeks 36-41 of a subsequent pregnancy at Panzhihua Central Hospital between July 2017 and June 2018. The primary outcomes of the study were the hiatus area at 6 months postpartum and bladder neck (mm) at rest and during a maximum Valsalva maneuver. RESULTS: There were 112 women with vaginal delivery and 182 with Cesarean section. The hiatus area and hiatus circumference decreased at all time points (all P < 0.001). The women with Cesarean section had a smaller hiatus area and circumference (P < 0.001 and P < 0.001). The hiatus diameters decreased with time in both groups (all P < 0.001) and were smaller after Cesarean section (both P < 0.001). The bladder neck at maximum Valsalva increased with time (all P < 0.001) without significant differences between the two groups. Finally, the proportion of patients with POP-Q stage 0/I increased with time in both groups (all P < 0.001), with the proportions being higher in the Cesarean group (P = 0.002). The birth interval was negatively correlated with the hiatus area (B=-0.17, 95%CI: -0.25, -0.08, P < 0.001) and positively correlated with the bladder neck at rest (B = 0.22, 95%CI: 0.08, 0.35, P = 0.001) and at maximum Valsalva (B = 0.85, 95%CI: 0.65, 1.05, P < 0.001). CONCLUSIONS: In conclusion, the mode of delivery at the second birth could influence the hiatus area and circumference and bladder neck size. The birth interval was negatively correlated with the hiatus area and positively correlated with the bladder neck at rest and at maximum Valsalva.

pH-responsive size-adjustable liposomes induce apoptosis of fibroblasts and macrophages for rheumatoid arthritis treatment.

In rheumatoid arthritis (RA), macrophages infiltrate joints, while fibroblast-like synovial cells proliferate abnormally, forming a barrier against drug delivery, which hinders effective drug delivery to joint focus. Here we firstly designed a pH-responsive size-adjustable nanoparticle, composed by methotrexate (MTX)-human serum albumin (HSA) complex coating with pH-responsive liposome (Lipo/MTX-HSA) for delivering drugs specifically to inflamed joints in acidic environments. We showed in vitro that the nanoparticles can induce mitochondrial dysfunction, promote apoptosis of fibroblast-like synoviocytes and macrophages, further reduce the secretion of inflammatory factors (TNF-α, IL-1ß, MMP-9), and regulate the inflammatory microenvironment. We also demonstrated similar effects in a rat model of arthritis, in which Lipo/MTX-HSA accumulated in arthritic joints, and at low pH, liposome phospholipid bilayer cleavage released small-sized MTX-HSA, which effectively reduced the number of fibroblast-synoviocytes and macrophages in joints, alleviated joint inflammation, and repaired bone erosion. These findings suggest that microenvironment-responsive size-adjustable nanoparticles show promise as a treatment against rheumatoid arthritis. STATEMENT OF SIGNIFICANCE: Abnormal proliferation of fibroblast synoviocytes poses a physical barrier to effective nanoparticle delivery. We designed size-adjustable nano-delivery systems by preparing liposomes with cholesterol hemisuccinate (CHEM), which were subsequently loaded with small-sized albumin nanoparticles encapsulating the cytotoxic drug MTX (MTX-HSA), termed Lipo/MTX-HSA. Upon tail vein injection, Lipo/MTX-HSA could be aggregated at the site of inflammation via the ELVIS effect in the inflamed joint microenvironment. Specifically, intracellular acidic pH-triggered dissociation of liposomes promoted the release of MTX-HSA, which was further targeted to fibroblasts or across fibroblasts to macrophages to exert anti-inflammatory effects. The results showed that liposomes with adjustable particle size achieved efficient drug delivery, penetration and retention in joint sites; the strategy exerted significant anti-inflammatory effects in the treatment of rheumatoid arthritis by inducing mitochondrial dysfunction to promote apoptosis in fibrosynoviocytes and macrophages.

Analysis of the clinical diagnosis and treatment of fetal meconium peritonitis.

BACKGROUND: The purpose of this study was to improve diagnostic and therapeutic standards by examining the clinical features, treatment, and prognosis of fetal meconium peritonitis (FMP), as well as the diagnostic efficacy of ultrasound for FMP. METHODS: The clinical data of 41 infants and pregnant women diagnosed with meconium peritonitis (MP) and treated at the Fujian Maternal and Child Health Hospital from January 2013 to January 2020 were analyzed retrospectively. Clinical data, imaging data, complications, treatment strategies, pregnancy outcomes, neonatal prognoses, and follow-up outcomes were all analyzed. RESULTS: The MP prenatal diagnosis rate was 56.1% (23/41), the neonatal surgery rate was 53.7% (22/41), and the survival rate was 85.4% (35/41). Intraperitoneal calcification (23 pregnant women, 56.1%), intestinal dilatation (13 pregnant women, 31.7%), peritoneal effusion (22 pregnant women, 53.7%), intraperitoneal pseudocyst (7 pregnant women, 17.1%), and polyhydramnios were diagnosed via prenatal ultrasound (18 pregnant women, 43.9%). Twenty-two pregnant women were assigned to the surgical treatment (operation) group, while 18 were assigned to the conservative treatment group. In the operation group, there were 9 cases of ileal atresia (40.9%), 7 cases of jejunal atresia (31.8%), 2 cases of atresia at the jejunum-ileum junction (9.1%), 2 cases of ileal perforation (9.1%), 1 case of ileal necrosis (4.5%), and 1 case of adhesive obstruction (4.5%). There was no statistically significant difference (p > .05) in the occurrence of various prenatal ultrasound findings by etiology. CONCLUSION: Multiple prenatal ultrasound markers have been identified for MP. To improve the efficacy of newborn treatment for FMP and reduce neonatal mortality, dynamic monitoring of ultrasound image alterations and strengthened integrated perinatal management are necessary.

Neuroprotective mechanism of salvianolic acid B against cerebral ischemia-reperfusion injury in mice through downregulation of TLR4, p-p38MAPK, p-JNK, NF-κB, and IL-1ß.

OBJECTIVE: Tissue injury and inflammation are two potential outcomes of cerebral ischemia-reperfusion (I/R) injury. Salvianolic acid B (Sal B), isolated from the roots of Salvia miltiorrhiza, is one of the major water-soluble compounds with a wide range of pharmacological effects including antioxidant, anti-inflammatory, antiproliferative, and neuroprotective effects. In the present study, we explored the neuroprotective effects and potential mechanisms of Sal B after I/R injury. METHODS: We induced cerebral ischemia in male CD-1 mice through transient (60 min) middle cerebral artery occlusion (tMCAO), and then injected Sal B (30 mg/kg) intraperitoneally. Neurological deficits, infarct volumes, and brain edema were assessed at 24 and 72 h after tMCAO. We detected the expression of Toll-like receptor 4 (TLR4), phosphorylated-p38 mitogen-activated protein kinase (P-p38 MAPK), phosphorylated c-Jun amino (N)-terminal kinases (p-JNK), nuclear factor-κB (NF-κB), and interleukin-1ß (IL-1ß) in the brain tissue. RESULTS: Compared with the tMCAO group, Sal B significantly improved neurological deficits, reduced infarct size, attenuated cerebral edema, and downregulated the expression of pro-inflammatory mediators TLR4, p-p38MAPK, p-JNK, nuclear NF-κB, and IL-1ß in brain tissue after I/R injury. CONCLUSION: We found that Sal B protects brain tissues from I/R injury by activating its anti-inflammatory properties.

Chiral lanthanide-silver(I) cluster-based metal-organic frameworks exhibiting solvent stability, and tunable photoluminescence.

Due to the lack of effective synthetic strategies, the preparation of chemically stable chiral Ag(I) cluster-based materials for assembly remains challenging. Here, we have developed an approach to synthesize three pairs of chiral Ln-Ag(I) cluster-based metal-organic frameworks (MOFs) named l-LnAg5-3D (Ln = Gd for 1-L, Eu for 2-L, and Tb for 3-L) and d-LnAg5-3D (Ln = Gd for 1-D, Eu for 2-D, and Tb for 3-D) by employing a chiral Ag(I) cluster ({Ag5S6}) as the node and Ln3+ ion as the inorganic linker. Structural analysis revealed that the chiral ligands induced chirality through the entire structure, resulting in a chiral helix arrangement of the C3-symmetric chiral {Ag5S6} nodes and Ln3+ ions. These compounds showed high solvent stability in various polar organic solvents. The solid-state circular dichroism (CD) spectra of compounds l-LnAg5-3D and d-LnAg5-3D exhibited obvious mirror symmetrical peaks. The emission spectra in the solid state revealed that compound 1-L only exhibited the emission peak of {Ag5S6}, while compounds 2-L and 3-L exhibited overlapping peaks of Ln3+ and {Ag5S6} at different excitation wavelengths. This demonstrates the tunable photoluminescence from {Ag5S6} to Ln3+ by introducing different Ln3+ ions and manipulating the excitation wavelengths. The study underscores the enhanced stability of Ag(I) cluster-based MOFs achieved through the incorporation of Ln3+ ions and establishes chiral Ln-Ag(I) cluster-based MOFs as promising candidates for advanced materials with tunable photoluminescence.

Tumor-Associated Extracellular Microvesicles with Fluorine-Modified Carbohydrate Antigens Trigger a Stronger Antitumor Immune Response.

Abnormal glycosylation is a hallmark of tumor development, and tumor-associated carbohydrate antigens are potential immune targets for tumor therapy. Tumor-associated extracellular microvesicles are subcellular vesicles released from cell membranes that have immunogenicity similar to that of precursor cells. However, unmodified tumor-derived microvesicles have weaknesses, such as low immunogenicity, poor biostability, and short half-life in vivo. For the first time, we herein generated extracellular microvesicles containing modified tumor-associated carbohydrate antigens by constructing a cell line with highly expressed antigen-processing enzymes utilizing fluorine-modified monosaccharide substrates via a metabolic oligosaccharide engineering strategy. The microvesicles were applied to tumor immunity, achieving enhanced immunoprophylaxis and immunotherapy effects. Furthermore, the mechanisms of antitumor immunity were explored. Our findings may provide new insights into the adhibition of suitably modified extracellular microvesicles and the development of more effective carbohydrate-based anticancer vaccines.

Conductive Lanthanide Metal-Organic Frameworks with Exceptionally High Stability.

Electrically conductive metal-organic frameworks (MOFs) have been extensively studied for their potential uses in energy-related technologies and sensors. However, achieving that goal requires MOFs to be highly stable and maintain their conductivity under practical operating conditions with varying solution environments and temperatures. Herein, we have designed and synthesized a new series of {[Ln4(µ4-O)(µ3-OH)3(INA)3(GA)3](CF3SO3)(H2O)6}n (denoted as Ln4-MOFs, Ln = Gd, Tm, and Lu, INA = isonicotinic acid, GA = glycolic acid) single crystals, where electrons are found to transport along the π-π stacked aromatic carbon rings in the crystals. The Ln4-MOFs show remarkable stability, with minimal changes in conductivity under varying solution pH (1-12), temperature (373 K), and electric field as high as 800 000 V/m. This stability is achieved through the formation of strong coordination bonds between high-valent Ln(III) ions and rigid carboxylic linkers as well as hydrogen bonds that enhance the robustness of the electron transport path. The demonstrated lanthanide MOFs pave the way for the design of stable and conductive MOFs.

Clinical features of severe Mycoplasma pneumoniae pneumonia with pulmonary complications in childhood: A retrospective study.

INTRODUCTION: Incidence of severe M. pneumoniae pneumonia (SMPP) reported in China has been increasing over the last decade. We aimed to evaluate the clinical features of pediatric SMPP with pulmonary complications, according to laboratory tests and chest radiographic resolution patterns. MATERIAL AND METHODS: We retrospectively reviewed 93 SMPP patients between January 2016 and February 2019, and grouped them by pneumonia pattern: pulmonary complications (63 patients) and extensive lung lesions without pulmonary complications (30 patients). RESULTS: SMPP patients with pleural effusion (medium or large) and necrotizing pneumonia showed longer duration of fever, high serum value of lactate dehydrogenase (LDH), d-dimer, and LDH to albumin ratio (LAR). LAR and  d-dimer were associated with moderate or massive pleural effusion, and  d-dimer was associated with lung necrosis. The average time of radiographic resolution in the pulmonary complication group was 12 weeks, while those with elevated d-dimer were significantly more likely to have longer time for radiographic clearance. CONCLUSION: We conclude that M. pneumoniae pneumonia in patients with pleural effusion (medium or large) or lung necrosis was more severe than those without pulmonary complications. LAR and  d-dimer might be used as parameters to identify children susceptible to pleural effusion (medium or large) or lung necrosis, and longer time for radiographic clearance among pediatric patients of SMPP.

Lysine Deprivation Suppresses Adipogenesis in 3T3-L1 Cells: A Transcriptome Analysis.

Growing evidence proves that amino acid restriction can reverse obesity by reducing adipose tissue mass. Amino acids are not only the building blocks of proteins but also serve as signaling molecules in multiple biological pathways. The study of adipocytes' response to amino acid level changes is crucial. It has been reported that a low concentration of lysine suppresses lipid accumulation and transcription of several adipogenic genes in 3T3-L1 preadipocytes. However, the detailed lysine-deprivation-induced cellular transcriptomic changes and the altered pathways have yet to be fully studied. Here, using 3T3-L1 cells, we performed RNA sequencing on undifferentiated and differentiated cells, and differentiated cells under a lysine-free environment, and the data were subjected to KEGG enrichment. We found that the differentiation process of 3T3-L1 cells to adipocytes required the large-scale upregulation of metabolic pathways, mainly on the mitochondrial TCA cycle, oxidative phosphorylation, and downregulation of the lysosomal pathway. Single amino acid lysine depletion suppressed differentiation dose dependently. It disrupted the metabolism of cellular amino acids, which could be partially reflected in the changes in amino acid levels in the culture medium. It inhibited the mitochondria respiratory chain and upregulated the lysosomal pathway, which are essential for adipocyte differentiation. We also noticed that cellular interleukin 6 (IL6) expression and medium IL6 level were dramatically increased, which was one of the targets for suppressing adipogenesis induced by lysine depletion. Moreover, we showed that the depletion of some essential amino acids such as methionine and cystine could induce similar phenomena. This suggests that individual amino acid deprivation may share some common pathways. This descriptive study dissects the pathways for adipogenesis and how the cellular transcriptome was altered under lysine depletion.

[Clinical characteristics of plastic bronchitis and risk factors for recurrence in children]. / å„¿ç«¥å¡‘åž‹æ€§æ”¯æ°”ç®¡ç‚Žä¸´åºŠç‰¹å¾åŠå¤å‘å±é™©å› ç´ åˆ†æž.

OBJECTIVES: To study the clinical characteristics of plastic bronchitis (PB) in children and investigate the the risk factors for recurrence of PB. METHODS: This was a retrospective analysis of medical data of children with PB who were hospitalized in Children's Hospital of Chongqing Medical University from January 2012 to July 2022. The children were divided into a single occurrence of PB group and a recurrent PB group and the risk factors for recurrence of PB were analyzed. RESULTS: A total of 107 children with PB were included, including 61 males (57.0%) and 46 females (43.0%), with a median age of 5.0 years, and 78 cases (72.9%) were over 3 years old. All the children had cough, 96 children (89.7%) had fever, with high fever in 90 children. Seventy-three children (68.2%) had shortness of breath, and 64 children (59.8%) had respiratory failure. Sixty-six children (61.7%) had atelectasis and 52 children (48.6%) had pleural effusion. Forty-seven children (43.9%) had Mycoplasma pneumoniae infection, 28 children (26.2%) had adenovirus infection, and 17 children (15.9%) had influenza virus infection. Seventy-one children (66.4%) had a single occurrence of PB, and 36 cases (33.6%) had recurrent occurrence of PB (≥2 times). Multivariate logistic regression analysis showed that involvement of ≥2 lung lobes (OR=3.376) under bronchoscopy, continued need for invasive ventilation after initial removal of plastic casts (OR=3.275), and concomitant multi-organ dysfunction outside the lungs (OR=2.906) were independent risk factors for recurrent occurrence of PB (P<0.05). CONCLUSIONS: Children with pneumonia accompanied by persistent high fever, shortness of breath, respiratory failure, atelectasis or pleural effusion should be highly suspected with PB. Involvement of ≥2 lung lobes under bronchoscopy, continued need for invasive ventilation after initial removal of plastic casts, and concomitant multi-organ dysfunction outside the lungs may be risk factors for recurrent occurrence of PB.

Knowledge, attitudes, and practice of pelvic floor dysfunction and pelvic floor ultrasound among women of childbearing age in Sichuan, China.

Objective: Pelvic floor dysfunction (PFD) is highly prevalent among women. Pelvic floor ultrasound (PFU) is a critical method for assessing PFD. This study examined the knowledge, attitudes, and practice (KAP) of women of childbearing age regarding PFD and PFU. Methods: This cross-sectional study was conducted between August 18, 2022, and September 20, 2022, in Sichuan, China. A total of 504 women of childbearing age participated in this study. A self-administered questionnaire was developed to assess KAP regarding PFD and PFU. Univariable and multivariable logistic regression analyses were conducted to assess the association between demographic characteristics and KAP. Results: The average scores for knowledge, attitudes, and practice were 12.53, 39.98, and 16.51 out of 17, 45, and 20, respectively. Despite adequate knowledge of PFD symptoms, aging-related risks, and PFD harms (correct rates > 80%), participants showed poor knowledge about the benefits of PFU, PFU types, and Kegel exercise (correct rates < 70%). High scores in knowledge and attitude (odds ratio = 1.23 and 1.11, P < 0.001 and P = 0.005, respectively) were independent predictors of good practice, while never having been pregnant (odds ratio = 0.10, P < 0.001), alcohol consumption (odds ratio = 0.09, P = 0.027), and not being diagnosed with PFD or an unclear diagnosis independently predicted poor practice (both odds ratio = 0.03, both P < 0.001). Conclusion: Women of childbearing age in Sichuan, China, showed moderate knowledge, positive attitude, and good practice regarding PFD and PFU. Knowledge, attitude, pregnancy history, alcohol consumption, and PFD diagnosis are associated with practice.

[Clinical and bronchoscopy features of tracheobronchial tuberculosis in children]. / å„¿ç«¥æ°”ç®¡æ”¯æ°”ç®¡ç»“æ ¸çš„ä¸´åºŠåŠæ”¯æ°”ç®¡é•œä¸‹ç‰¹å¾åˆ†æž.

OBJECTIVES: To study the clinical and bronchoscopic characteristics of tracheobronchial tuberculosis (TBTB) in children and to identify factors influencing residual airway obstruction or stenosis. METHODS: The clinical data of children with TBTB were retrospectively collected. The children were divided into two groups based on the last bronchoscopic result within one year of follow-up: a group with residual airway obstruction or stenosis (n=34) and a group without residual airway obstruction or stenosis (n=58). A multivariate logistic regression analysis was used to identify the factors influencing residual airway obstruction or stenosis in children with TBTB. Receiver operating characteristic (ROC) curves were used to analyze the predictive value of the factors influencing residual airway obstruction or stenosis in children with TBTB. RESULTS: A total of 92 children with TBTB were included, and the main symptoms were cough (90%) and fever (68%). In children under 1 year old, the incidence rates of dyspnea and wheezing were significantly higher than in other age groups (P<0.008). Chest CT findings included mediastinal or hilar lymph node enlargement (90%) and tracheobronchial stenosis or obstruction (61%). The lymphatic fistula type was the main type of TBTB observed bronchoscopically (77%). All children received interventional treatment, and the effective rate was 84%. During one year of follow-up, 34 children had residual airway obstruction or stenosis. The TBTB diagnostic time and the initiation of interventional treatment were significantly delayed in the group with residual airway obstruction or stenosis compared with the group without residual airway obstruction or stenosis (P<0.05). The multivariate logistic regression analysis showed that the TBTB diagnostic time was closely related to residual airway obstruction or stenosis in children (P<0.05). ROC curve analysis showed that at the cut-off value of 92 days of TBTB diagnostic time, the area under the curve for predicting residual airway obstruction or stenosis in children with TBTB was 0.707, with a sensitivity of 58.8% and a specificity of 75.9%. CONCLUSIONS: The clinical manifestations of TBTB are nonspecific, and symptoms are more severe in children under 1 year old. TBTB should be suspected in children with tuberculosis and chest imaging indicating airway involvement. Delayed diagnosis of TBTB is associated with the development of residual airway obstruction or stenosis.

Self-Assembled Core-Shell Nanoscale Coordination Polymer Nanoparticles Carrying a Sialyltransferase Inhibitor for Cancer Metastasis Inhibition.

Despite hypersialylation of cancer cells together with a significant upregulation of sialyltransferase (ST) activity contributes to the metastatic cascade at multiple levels, there are few dedicated tools to interfere with their expression. Although transition state-based ST inhibitors are well-established, they are not membrane permeable. To tackle this problem, herein, we design and construct long-circulating, self-assembled core-shell nanoscale coordination polymer (NCP) nanoparticles carrying a transition state-based ST inhibitor, which make the inhibitor transmembrane and potently strip diverse sialoglycans from various cancer cells. In the experimental lung metastasis and metastasis prevention models, the nanoparticle device (NCP/STI) significantly inhibits metastases formation without systemic toxicity. This strategy enables ST inhibitors to be applied to cells and animals by providing them with a well-designed nanodelivery system. Our work opens a new avenue to the development of transition state-based ST inhibitors and demonstrates that NCP/STI holds great promise in achieving metastases inhibition for multiple cancers.

Messenger Nanozyme for Reprogramming the Microenvironment of Rheumatoid Arthritis.

Dysregulation of superoxide anion (O2-) and hydrogen peroxide (H2O2) metabolism in the microenvironment of rheumatoid arthritis (RA) drives the feedback loops of TNF-α and IL-1ß thereby inducing an inflammatory storm between immune cells and joint tissue cells. Here, we combine nanoscale manganese dioxide (MnO2) with microvesicles derived from macrophage (MMV). The former possesses superoxide dismutase (SOD) and catalase (CAT)-like activities that can modulate this imbalance, and we amplify the enzyme-like activities by using the amorphous hollow mesoporous structure and surface modification. The latter is a natural endogenous component with the parent cell-like inflammatory homing ability and a unique function of transmitting information to surrounding and distant cells (″messenger function″), which helps amorphous hollow MnO2 (H-MnO2) nanozymes to cloak in the blood and reach the site of inflammation, where they can not only accumulate in activated macrophages but also pretend to be ″messengers″ that are utilized by fibroblast-like synoviocytes (FLS) and chondrocytes. In addition, we also load dexamethasone sodium phosphate (DSP) for helping the nanozymes work. Messenger nanozyme (MMV-MnO2@DSP) inherits the natural properties of MMV and mimics the enzymatic activity of SOD and CAT. It accumulates in activated macrophages to restore the metabolism of O2- and H2O2 while promoting repolarization and inhibits the feedback loops of TNF-α and IL-1ß among macrophages, fibroblast-like synoviocytes, and chondrocytes, leading to anti-rheumatoid arthritis effects in vitro and in vivo.

Removable partial prosthesis combined with swallowing training is an efficient clinical solution for oral cancer post-operation patients with palatal defect and dysphagia: a prospective study.

OBJECTIVE: Dysphagia is one of the major complications of oral cancer patients, and is disturbing thousands of patients worldwide. Our study aim to evaluate the clinical efficacy of prosthesis combined with swallowing training on palatal defect and dysphagia in post-operative oral cancer patients. MATERIALS AND METHODS: Sixteen oral cancer patients with palatal defect and dysphagia post-operation were treated with removable prosthesis and individualized swallowing function training. Swallowing function of patients before and after treatment was analyzed and compared by videofluoroscopic swallowing examination. The severity of depression and life quality were evaluated by Depression Scale (SDS) and Functional Assessment of Cancer Therapy-Head and Neck (FACT-H&N) scores, respectively. RESULTS: Oral transit time (OTT) significantly shortened after treatment (P < 0.01), and Penetration-Aspiration Scale (PAS) scores was significantly higher after treatment (P < 0.001). Different consistency bolus showed different risk of aspiration. Thickened liquids were related to lower PAS scores (P < 0.001). SDS standard score was significantly lower after treatment (P < 0.05). The total score of FACT-H&N after treatment was significantly higher (P < 0.05). No patients came back for regressed swallowing function during the follow-up period (17.06 ± 2.376 months). CONCLUSION: Removable prosthesis and swallowing training can significantly improve swallowing function, reduce depression degree, and improve quality of life (QOL). CLINICAL RELEVANCE: Removable prosthesis combined with swallowing training is a cheap and effective method to improve QOL in patients with palate defect and dysphagia after oral cancer.

Pentacyclic triterpenoids from spikes of Prunella vulgaris L. with thyroid tumour cell cytostatic bioactivities.

Five new triterpenoids, including four ursane types (1-4) and one oleanane type (5), together with 15 known ursane types pentacyclic triterpenoids (6-20) were isolated from the fruit spikes of Prunella vulgaris L., a traditional Chinese herbal medicine. Their structures were elucidated based on IR, HR-ESI-MS, and NMR spectroscopic data. The SW579 cell line was used to evaluate anti-thyroid cancer activities of (1-20). The results indicated that (7-9), (16), and (19) exhibited apparent inhibitory activity with IC50 values of 25.73-71.41 µM (cisplatin as positive control, IC50 14.49 ± 0.97 µM). Network pharmacology and molecular docking were also used for the prediction of the synergistic actions and the underlying mechanisms. Accordingly, four potential targets have been characterized.

Functionalization of Keggin Fe13-Oxo Clusters.

Two Keggin Fe13-oxo clusters, [Pr12Fe33(NO3)6(L-van)4(D-van)5(TEOA)12(µ3-OH)12(µ4-OH)12(µ4-O)28(H2O)4]·(ClO4)3·(NO3)·10H2O (1) and [Dy12Fe33(NO3)2(L-van)3(D-van)3(TEOA)12(µ3-OH)18(µ4-OH)6(µ4-O)28(H2O)9]·(ClO4)5·(NO3)6·15H2O (2), where L-van = l-valine, D-van = d-valine, and TEOA = triethanolamine, were prepared by using Ln3+ as a stabilizer. Cluster 1 crystallizes in a chiral space group of C2, while cluster 2 crystallizes in a centrosymmetric space group of Pnma. Dynamic magnetic measurements of 2 under a zero direct-current field reveal that 2 exhibits single-molecule-magnet characteristics with an energy barrier of 18.79 K. Significantly, the formation of the chiral cluster 1 is closely related to the larger radius of the Pr3+ ion.