Abstract Increased levels of circulating cell-free DNA (cfDNA) are associated with poor clinical outcomes in patients with acute kidney injury (AKI). Scavenging cfDNA by nanomaterials has been regarded as a promising remedy for cfDNA-associated diseases. Nevertheless, the nanomaterials-based cfDNA scavenging tactic has not yet been reported in AKI treatment. Herein, polyglycerol-amine (PGA) covered MoS 2 nanosheet with medium size (M-PGA-M) was erected to bind negatively charged cfDNA for AKI treatment. M-PGA-M exhibited excellent cfDNA scavenging efficacy and low cytotoxicity, which effectively reduced serum cfDNA levels, dominantly accumulated in kidney to inhibit neutrophil extracellular trap formation and inflammation, thereby alleviating LPS-induced AKI in mice. The renoprotective effects of M-PGA-M were superior to corresponding polymer PGA attributed to its unique two-dimensional nanostructure. Further, M-PGA-M showed to decrease serum cfDNA from AKI patients. Collectively, M-PGA-M could serve as a potent cfDNA scavenger, suggesting its potential application in treating AKI and other cfDNA-associated diseases. Teaser Scavenging cell-free DNA (cfDNA) with polyglycerol-amine (PGA)-covered MoS 2 nanosheets may represent a novel treatment for AKI.
Despite the promising achievements of immune checkpoint blockade (ICB) therapy for tumor treatment, its therapeutic effect against solid tumors is limited due to the suppressed tumor immune microenvironment (TIME). Herein, a series of polyethyleneimine (Mw = 0.8k, PEI0.8k )-covered MoS2 nanosheets with different sizes and charge densities are synthesized, and the CpG, a toll-like receptor-9 agonist, is enveloped to construct nanoplatforms for the treatment of head and neck squamous cell carcinoma (HNSCC). It is proved that functionalized nanosheets with medium size display similar CpG loading capacity regardless of low or high PEI0.8k coverage owing to the flexibility and crimpability of 2D backbone. CpG-loaded nanosheets with medium size and low charge density (CpG@MM -PL ) could promote the maturation, antigen-presenting capacity, and proinflammatory cytokines generation of bone marrow-derived dendritic cells (DCs). Further analysis reveals that CpG@MM -PL effectively boosts the TIME of HNSCC in vivo including DC maturation and cytotoxic T lymphocyte infiltration. Most importantly, the combination of CpG@MM -PL and ICB agents anti-programmed death 1 hugely improves the tumor therapeutic effect, inspiring more attempts for cancer immunotherapy. In addition, this work uncovers a pivotal feature of the 2D sheet-like materials in nanomedicine development, which should be considered for the design of future nanosheet-based therapeutic nanoplatforms.
The risk of zoonosis transmission when handling livestock or animal products is substantial, ‘One Health’ interventions should be an effective strategy for the control of many zoonotic bacteria. In this study, 26 fresh fecal samples from 2 clinically healthy goats were collected at different day ages to survey goat-borne zoonotic bacterial infection, and 19 fresh fecal samples from diarrhetic goats were tested to evaluate the possible role of zoonotic pathogens in goat diarrhea. Following all samples were analyzed by Metagenomic Sequencing, a total of 20 kinds of zoonotic bacteria were screened from healthy goats, and 11 (55%) of them were infection mainly during the preweaned period. Of the 19 fresh fecal samples from diarrhetic goats, all were confirmed to be zoonotic bacterial infection positive (range from 11 to 12 species). After comparison with healthy samples of the same or similar day-age goats, it was found that Lactococcus garvieae, Helicobacter pylori, Klebsiella pneumoniae, Shigella sonnei, Shigella boydii, Campylobacter coli, Salmonella enterica, Acinetobacter baumannii, Shigella flexneri, Shigella dysenteriae and Clostridium perfringens and Campylobacter fetus were highly increased incases in some diarrheic cases, while the remains had no significant change. The results suggest that goats may act as a reservoir for many zoonotic bacteria, and some of them may be associated with goat intestinal inflammation.
Diagnosis of tuberculosis (TB) is still difficult. The development of rapid and sensitive laboratory tools for the diagnosis of tuberculosis is a priority. This study aimed to develop an indirect enzyme-linked immunoassay (ELISA) assay for detection of TB antibody and explore its diagnostic value in patients with pulmonary tuberculosis (PTB) via a multi-center clinical evaluation.The specific antigen, fusion antigen, and specific antibody peptide were obtained using molecular cloning and phage peptide library screening. An indirect ELISA assay was developed using multiple target materials. Further, the assay was validated in six institutions with clinically confirmed TB patients, non-TB patients with pulmonary disease, and healthy controls as research subjects.An indirect ELISA assay was developed with 16 kD antigen, 11,488 (CFP10-MPT48-TB8.4) fusion antigen, and TB18 and pl2 as target antigens against TB antibody. The results of this multicenter study showed that the sensitivity, specificity, and the area under the receiver operating characteristic curve (AUC) of the assay were 48.25% [95% confidence interval (CI): 45.5-51.1%], 92.20% (95% CI: 90.7-93.5%) and 0.724 (95% CI: 0.707-0.741), respectively, and the cut-off value was 0.119. According to the meta-analysis, the combined ROC was 0.736 (95% CI: 0.692-0.779), I2=83.73%. The sensitivity of the sputum-positive PTB group (culture or smear positive) was 58.75% (95% CI: 52.96-65.00%); the sensitivity in sputum-negative group (culture or smear negative) was 37.38% (95% CI: 32.71-42.52%), respectively; the sensitivity of the sputum-positive group was significantly higher than that of sputum-negative group (OR =1.57, 95% CI: 1.29-1.92, P<0.001).Multitarget indirect ELISA assay based on specific-TB antigen, fusion antigen, and antibody peptide is of value for the diagnosis of PTB and can be used as an auxiliary rapid diagnostic tool to improve the sensitivity of sputum-negative TB.
While serum bone turnover markers (BTMs) and bone mineral density (BMD) have been confirmed as useable risk assessment tools for postmenopausal osteoporosis, the associations between BTMs and BMD changes are still ambiguous. The aim of this study was to explore the underlying associations between BTMs and BMD changes in postmenopausal women.Between January 2015 and October 2020, 135 postmenopausal women were retrospectively enrolled. They were divided into two groups according to lumbar spine (LS) 1-4 BMD change (1 y T-score minus baseline T-score, Group 1 [n = 36] < 0 and Group 2 [n = 99] ≥ 0). The changes of BTMs (N-terminal middle segment osteocalcin [N-MID], propeptide of type I procollagen [P1NP], and β-C-terminal telopeptide of type I collagen [β-CTX]) and their associations with LS 1-4 BMD change were analyzed. The biochemical indices and clinical parameters related with LS 1-4 BMD change were also evaluated.The 1 year N-MID, P1NP, β-CTX and Phosphorus in Group 2 were lower than those in Group 1 (P < 0.05), their changes within 1 year were significantly negatively correlated with LS 1-4 BMD change (R2 = -0.200, P < 0.001; R2 = -0.230, P < 0.001; R2 = -0.186, P < 0.001; R2 = -0.044, P = 0.015; respectively). Except for the Phosphorus change (area under the curve [AUC] = 0.623), the changes of N-MID, P1NP, and β-CTX and their 1 year levels had similar AUC to diagnose the short-term LS 1-4 BMD change (AUC > 0.7 for all, with the AUC of 1 y P1NP being the largest at 0.803). Binary logistic regression analysis showed that the physical activity and drug intervention were the determinant factors for the LS 1-4 BMD change (odds ratio = 6.856, 95% confidence interval: 2.058-22.839, P = 0.002; odds ratio = 5.114, 95% confidence interval: 1.551-16.864, P = 0.007; respectively).Declining N-MID, P1NP, β-CTX, and Phosphorus are associated with the short-term increase of LS 1-4 BMD within 1 year. Physical activity and drug intervention are factors significantly influencing the change of LS 1-4 BMD in postmenopausal women.
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