Quantitative assessment whole-rock iron content in magnetite protolith based on terahertz time-domain spectroscopy: publisher's note.

This publisher's note serves to correct errors in Appl. Opt.63, 2528 (2024)APOPAI0003-693510.1364/AO.517400.

Vitamin D is involved in the effects of the intestinal flora and its related metabolite TMAO on perirenal fat and kidneys in mice with DKD.

BACKGROUND: Vitamin D was shown to directly exert a protective effect on diabetic kidney disease (DKD) in our previous study. However, whether it has an effect on perirenal adipose tissue (PRAT) or the intestinal flora and its metabolites (trimethylamine N-oxide, TMAO) is unclear. METHODS: DKD mice were received different concentrations of 1,25-(OH)2D3 for 2 weeks. Serum TNF-α levels and TMAO levels were detected. 16S rRNA sequencing was used to analyze gut microbiota. qPCR was used to detect the expression of TLR4, NF-Κb, PGC1α, and UCP-1 in kidney and adipose tissue. Histological changes in kidney and perirenal adipose tissue were observed using HE, PAS, Masson and oil red staining. Immunofluorescence and immunohistochemistry were used to detect the expression of VDR, PGC1α, podocin, and UCP-1 in kidney and adipose tissue. Electron microscopy was used to observe the pathological changes in the kidney. VDR knockout mice were constructed to observe the changes in the gut and adipose tissue, and immunofluorescence and immunohistochemistry were used to detect the expression of UCP-1 and collagen IV in the kidney. RESULTS: 1,25-(OH)2D3 could improve the dysbiosis of the intestinal flora of mice with DKD, increase the abundance of beneficial bacteria, decrease the abundance of harmful bacteria, reduce the pathological changes in the kidney, reduce fat infiltration, and downregulate the expression of TLR4 and NF-κB in kidneys. The serum TMAO concentration in mice with DKD was significantly higher than that of the control group, and was significantly positively correlated with the urine ACR. In addition, vitamin D stimulated the expression of the surface markers PGC1α, UCP-1 and VDR in the PRAT in DKD mice, and TMAO downregulated the expression of PRAT and renal VDR. CONCLUSIONS: The protective effect of 1,25-(OH)2D3 in DKD mice may affect the intestinal flora and its related metabolite TMAO on perirenal fat and kidneys.

Quantitative assessment whole-rock iron content in magnetite protolith based on terahertz time-domain spectroscopy.

Terahertz time-domain spectroscopy was first used to establish a correlation with the whole-rock iron (TFe) content in different depths of the Bayan Obo protolith. Compared with element content obtained by the traditional method of X-ray fluorescence spectroscopy (XRF), a similar tendency of the absorption coefficient and refractive index is presented. Furthermore, three machine learning algorithms, namely, partial least squares regression (PLSR), random forest (RF), and multi-layer perceptron (MLP), were used to develop a quantitative analytical model for TFe content of the protolith minerals. Among the three algorithms, MLP has the highest detection accuracy, with a model coefficient of determination R 2 reaching up to 0.945. These findings demonstrate that terahertz time-domain spectroscopy can be used to rapidly quantify the TFe elemental content of protolith, providing a method of detecting the content of mineral components.

Endothelium-targeted Ddx24 conditional knockout exacerbates ConA-induced hepatitis in mice due to vascular hyper-permeability.

BACKGROUND: Acute hepatitis is a progressive inflammatory disorder that can lead to liver failure. Endothelial permeability is the vital pathophysiological change involved in infiltrating inflammatory factors. DDX24 has been implicated in immune signaling. However, the precise role of DDX24 in immune-mediated hepatitis remains unclear. Here, we investigate the phenotype of endothelium-targeted Ddx24 conditional knockout mice with Concanavalin A (ConA)-induced hepatitis. METHODS: Mice with homozygous endothelium-targeted Ddx24 conditional knockout (Ddx24flox/flox; Cdh5-Cre+) were established using the CRISPR/Cas9 mediated Cre-loxP system. We investigated the biological functions of endothelial cells derived from transgenic mice and explored the effects of Ddx24 in mice with ConA-induced hepatitis in vivo. The mass spectrometry was performed to identify the differentially expressed proteins in liver tissues of transgenic mice. RESULT: We successfully established mice with endothelium-targeted Ddx24 conditional knockout. The results showed migration and tube formation potentials of murine aortic endothelial cells with DDX24 silencing were significantly promoted. No differences were observed between Ddx24flox/flox; Cdh5-Cre+ and control regarding body weight and length, pathological tissue change and embryogenesis. We demonstrated Ddx24flox/flox; Cdh5-Cre+ exhibited exacerbation of ConA-induced hepatitis by up-regulating TNF-α and IFN-γ. Furthermore, endothelium-targeted Ddx24 conditional knockout caused vascular hyper-permeability in ConA-injected mice by down-regulating vascular integrity-associated proteins. Mechanistically, we identified Ddx24 might regulate immune-mediated hepatitis by inflammation-related permeable barrier pathways. CONCLUSION: These findings prove that endothelium-targeted Ddx24 conditional knockout exacerbates ConA-induced hepatitis in mice because of vascular hyper-permeability. The findings indicate a crucial role of DDX24 in regulating immune-mediated hepatitis, suggesting DDX24 as a potential therapeutic target in the disorder.

Clinical value of noninvasive lens advanced glycation end product detection in early screening and severity evaluation of patients with diabetic kidney disease.

BACKGROUND: Advanced glycation end products (AGEs) deposited in the lens are correlated with those in the kidneys, indicating a possible value in evaluating diabetic kidney disease (DKD). This study explored the value of noninvasively measuring lens AGEs to diagnose and evaluate the severity of diabetic nephropathy in patients with type 2 diabetes mellitus (T2DM). METHODOLOGY: A total of 134 T2DM patients admitted to the Fifth People's Hospital of Shanghai from March 2020 to May 2021 were selected randomly. Patients were divided into low-, medium-and high-risk groups according to the risk assessment criteria for DKD progression and into DKD and non-DKD (non-DKD) groups according to the Guidelines for the Prevention and Treatment of Diabetic Nephropathy in China. The concentrations of noninvasive AGEs in the lens in all the groups were retrospectively analyzed. RESULTS: The concentration of noninvasive lens AGEs in the high-risk patients, according to the 2012 guidelines of the Global Organization for Improving the Prognosis of Kidney Diseases, was significantly higher than that in the remaining groups. Regression analysis suggested the value of lens AGEs in diagnosing DKD and evaluating DKD severity. Cox regression analysis indicated that the noninvasive lens AGE concentration was positive correlated with the course of disease. CONCLUSION: The receiver operating characteristic (ROC) curve suggested that using noninvasive lens AGE measurements has clinical value in the diagnosis of DKD (area under the curve 62.4%,95% confidence interval (CI) 52.4%-73.9%, p = 0.014) and in assessing the severity of DKD (area under the curve 83.2%, 95% CI 74.1%-92.3%, P < 0.001). Noninvasive lens AGE testing helps screen T2DM patients for DKD and evaluate the severity of DKD.

Advances of antitumor drug discovery in traditional Chinese medicine and natural active products by using multi-active components combination.

The antitumor efficacy of Chinese herbal medicines has been widely recognized. Leading compounds such as sterols, glycosides, flavonoids, alkaloids, terpenoids, phenylpropanoids, and polyketides constitute their complex active components. The antitumor monomers derived from Chinese medicine possess an attractive anticancer activity. However, their use was limited by low bioavailability, significant toxicity, and side effects, hindering their clinical applications. Recently, new chemical entities have been designed and synthesized by combining natural drugs with other small drug molecules or active moieties to improve the antitumor activity and selectivity, and reduce side effects. Such a novel conjugated drug that can interact with several vital biological targets in cells may have a more significant or synergistic anticancer activity than a single-molecule drug. In addition, antitumor conjugates could be obtained by combining pharmacophores containing two or more known drugs or leading compounds. Based on these studies, the new drug research and development could be greatly shortened. This study reviews the research progress of conjugates with antitumor activity based on Chinese herbal medicine. It is expected to serve as a valuable reference to antitumor drug research and clinical application of traditional Chinese medicine.

Land-use conversion controls on the mobility of Zn in paddy soils revealed by stable Zn isotopes.

Understanding Zn biogeochemical cycling is necessary for monitoring Zn supply for plants and life during land use conversion, which is critical for environmentally sustainable development. But little is known about how the conversion of paddy soil to abandoned land affects the Zn isotope signature. A comparative field observation was conducted in northeast Thailand to investigate the Zn isotope footprint of paddy soils and abandoned paddy soils (PL and NPL). Our results show that Zn (τZnint : 0.04) slightly retains on PL, but is lost from NPL (τZnint from - 0.81 to - 0.24) to the river during weathering. Compared to PL (Δ66Znparent-soil: -0.29 ‰), more 66Zn isotopes might enter the river when rice cultivation ceases in NPL (Δ66Znparent-soil from -0.26 ‰ to -0.47 ‰). Rice harvest and then root decay might result in heavy 66Zn isotopes accumulating at the topmost soil in PL (δ66Zn: 0.14 ‰) and short-term abandonment (1-2 years) in paddy soils (NPL1 δ66Zn: 0.18 ‰). The release of assimilated Zn, and then the high adsorption of Zn in the Fe-SOM-metal(loid)s ternary system positively contribute to the high [Zn] in PL, while this was not observed in NPL. Our findings provide a comprehensive insight into the Zn isotope signature in response to the conversion of land-use types, which is beneficial for understanding the terrestrial Zn geochemical cycle.

Inflammation-Regulated Nanodrug Sensitizes Hepatocellular Carcinoma to Checkpoint Blockade Therapy by Reprogramming the Tumor Microenvironment.

Immune checkpoint blockade (ICB) utilizing programmed death ligand-1 (PD-L1) antibody is a promising treatment strategy in solid tumors. However, in fact, more than half of hepatocellular carcinoma (HCC) patients are unresponsive to PD-L1-based ICB treatment due to multiple immune evasion mechanisms such as the hyperactivation of inflammation pathway, excessive tumor-associated macrophages (TAMs) infiltration, and insufficient infiltration of T cells. Herein, an inflammation-regulated nanodrug was designed to codeliver NF-κB inhibitor curcumin and PD-L1 antibody to reprogram the tumor microenvironment (TME) and activate antitumor immunity. The nanodrug accumulated in TME by an enhanced permeability and retention effect, where it left antibody to block PD-L1 on the membrane of tumor cells and TAMs due to pH-responsiveness. Simultaneously, a new curcumin-encapsulated nanodrug was generated, which was easily absorbed by either tumor cells or TAMs to inhibit the nuclear factor kappa-B (NF-κB) signal and related immunosuppressive genes. The inflammation-regulated nanodrug possessed good biocompatibility. Simultaneously, it reprogrammed TME effectively and exhibited an effective anticancer effect in immunocompetent mice. Overall, this study provided a potent strategy to improve the efficiency of ICB-based treatment for HCC.

Exploration of Noninvasive Detection of Advanced Glycation End Products in the Lens to Screen for Diabetic Kidney Disease.

Diabetic kidney disease (DKD) is a complication of diabetes, which is the most common cause of end-stage renal disease (dialysis). DKD has a high mortality rate, and only early detection can nip this disease in the bud. Advanced glycation end products (AGEs)are generally believed to be involved in the occurrence of DKD. Studies have shown that the lens AGEs fluorescence for noninvasive detection has high consistency with the gold standard OGTT, has high sensitivity and specificity, and could be used as a practical tool for the early screening of type 2 diabetes mellitus (T2DM).Therefore, we speculated that the noninvasive lens AGEs fluorescence detection method can be used to predict the occurrence of DKD. This study detected levels of AGEs in multiple cellular and tissues and analyzed the relationships between AGEs and lens, eyeballs, peripheral blood mononuclear cell (PBMC), serum, and kidney. Additionally, we examined the possible role of lens AGEs fluorescence in DKD screening. Our preexperimental study found that lens AGE levels in patients with T2DM were positively correlated with PBM and serum AGE levels. Lens AGE levels in patients with T2DM were negatively correlated with eGFR and positively correlated with urinary ACR. The animal and cell experiments showed that the AGE levels in the eyeballs of DM mice were also positively correlated with those in the serum and kidney. To increase the reliability of the experiment, we increased the sample size. In our results, lens AGEs levels were positively correlated with the occurrence of DKD, and the incidence of DKD in the high lens AGEs group was 2.739 times that in the low lens AGEs group. The receiver operating characteristic (ROC) curves showed that patients with T2DM with a lens AGEs value ≥ 0.306 were likely to have DKD. The area under the ROC curve of the noninvasive technique for identifying DKD was 0.757 (95% Cl: 0.677-0.838, p<0.001), and the sensitivity and specificity were 70.0% and 78.7%, respectively. These results suggest that noninvasive lens AGEs detection technology has certain clinical value in diagnosing whether patients with T2DM have DKD.

Preliminary Observation of the Changes in the Intestinal Flora of Patients With Graves' Disease Before and After Methimazole Treatment.

Immune dysfunction caused by environmental factors plays an important role in the development of Graves' disease (GD), and environmental factors are closely related to the intestinal flora. Our previous study showed significant changes in the intestinal flora in GD patients compared with healthy volunteers. This study analyzed the relationships between changes in the intestinal flora, thyroid function and relevant thyroid antibodies in GD patients before and after methimazole treatment. The subjects were divided into the UGD group (18 newly diagnosed GD patients), the TGD group (10 GD patients with normal or approximately normal thyroid function after methimazole treatment) and the NC group (11 healthy volunteers). Their fresh stool samples were sent for 16S rRNA gene amplification and Illumina platform sequencing. The correlations of the relative abundance of Bifidobacterium with the levels of TRAb, TgAb and TPOAb in the NC group and the UGD group were analyzed. A total of 1,562,445 high-quality sequences were obtained. In the UGD group, the abundances of Bifidobacterium and Collinsella were higher than that in the NC group; Bacteroides abundance in the TGD group was higher than that in the NC group, while Prevotella and Dialister abundances were lower than that in the NC group; Prevotella and Collinsella abundances in the UGD group were higher than that in the TGD group. The predominant abundance distribution of Bifidobacteriaceae in the UGD group at the family level was superior to that in the NC group. The abundance of Bifidobacterium was positively correlated with the levels of TRAb, TgAb, and TPOAb. The biological diversity of the intestinal flora was reduced in GD patients. After methimazole treatment, the composition of the intestinal flora was significantly altered. The change in Bifidobacterium abundance was positively correlated with TRAb, TgAb and TPOAb, suggesting that it might be related to the immune mechanism of GD. The results of this study may deepen our understanding of the pathogenesis of GD and provide a new idea for the treatment of GD.

An electrochemical biosensor for the detection of epithelial-mesenchymal transition.

Epithelial-mesenchymal transition (EMT) is critically involved in a variety of biological processes. Electrochemical sensing offers potential to develop more effective technology for EMT detection. In this study, by using the unique performance of quantum dot (QD)-nanocomposite materials, we establish an electrochemical biosensor that can specifically detect the change of E-cadherin and analyze different stages of EMT. The signal for EMT is largely magnified due to the transmission of molecular information to the electronic device. In addition, differential pulse voltammetry reveals that the response of the electrochemical signals is rapid and sensitive, due to the synergistic effect of QDs and carbon nanotube-gold nanoparticles. Our study thus suggests that electrochemical sensing is an effective technology for detecting EMT and may have broad applications in analyzing various cell type transitions.

Development and validation of T-ARMS-PCR to detect CYP2C19*17 allele.

BACKGROUND: CYP2C19*17 (rs12248560) is a functional single nucleotide polymorphism (SNP) in the CYP2C19 gene. It has been shown that CYP2C19*17 is associated with the clinical outcome of some drugs metabolized by CYP2C19 and a decreased risk of some diseases. The aim of this study was to develop a reliable and simple method to detect this polymorphism. METHODS: Tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) was used to detect the CYP2C19*17 polymorphism. A total of 93 samples were screened by this method, and the results of T-ARMS-PCR were validated by DNA sequencing. RESULTS: There were 91 samples with the CC genotype (97.8%) and two samples with the CT genotype (2.2%). The frequency of the C allele was 98.9%, and the frequency of the T allele was 1.1%. The DNA sequencing results were completely concordant with the T-ARMS-PCR results. CONCLUSION: T-ARMS-PCR can detect the CYP2C19*17 polymorphism with high accuracy, low costs, and a simple process.

A Label-Free Electrochemical Immunosensor for Detection of the Tumor Marker CA242 Based on Reduced Graphene Oxide-Gold-Palladium Nanocomposite.

As a tumor marker, carbohydrate antigen 24-2 (CA242) is a highly accurate and specific diagnostic indicator for monitoring pancreatic and colorectal cancers. The goal of this study was to create a novel label-free electrochemical immunosensor using a nanocomposite glassy carbon electrode for the detection of CA242. Graphene oxide (GO) and polyvinyl pyrrolidone were chosen as the dopants for the preparation of a high-performance reduced-GO-gold-palladium (rGO-Au-Pd) nanocomposite. RGO-Au-Pd was characterized using X-ray diffraction and transmission electron microscopy, revealing that the material exhibited superior electrochemical redox activity and electron transfer ability. The effects of the synthesis method, material concentration, reduction cycle, and pH were investigated to optimize the performance of the immunosensor. As a result of the catalytic activity and biocompatibility of rGO-Au-Pd, the prepared CA242 immunosensor displayed a wide linear range of detection from 0.001 U/mL to 10,000 U/mL with a detection limit of 1.54 × 10-3 U/mL and a sensitivity of 4.24 µA (log10CCA242)-1. More importantly, the immunosensor exhibited satisfactory reproducibility and selectivity when detected CA242 in PBS or human serum. The results of our study provide a platform for the development of novel bioassays for use in early cancer diagnosis and promote the application of biosensing technology in the medical field.

Phytoremediation: Climate change resilience and sustainability assessment at a coastal brownfield redevelopment.

Phytoremediation offers a nature based solution (NBS) for contaminated soil remediation; however, its application under a brownfield redevelopment context has not been well studied. Moreover, climate change could impact large numbers of contaminated sites, yet there remains little research on the potential impacts for remediation. This study examined phytoremediation at a brownfield redevelopment in the San Francisco Bay area, where thousands of cleanup sites are vulnerable to rising sea levels. Life cycle assessment (LCA) was used to determine both primary and secondary impacts and the system's resilience to various sea level scenarios and hydroclimatic conditions was investigated. It was found that the phytoremediation project rendered only a small environmental footprint, and was associated with low cost and substantial socioeconomic benefits. For instance, it fitted well with the site redevelopment setting by offering attractive landscape features. Moreover, under a modeled moderate sea level rise scenario, the groundwater hydraulic gradient at the site decreased, which was coupled with greater natural biodegradation and reduced plume migration, and, therefore, lower life cycle impact. There was also minimal increase in the vapor intrusion risk with increased sea level. Overall, phytoremediation at the site was found to be resilient to a moderate sea level rise and other hydroclimatic effects induced by climate change. However, the system performance responded to increasing sea level rise in a non-linear manner. Under a high sea level rise scenario, the system is predicted to perform abruptly worse.

Nature based solutions for contaminated land remediation and brownfield redevelopment in cities: A review.

Urban industrialization has caused severe land contamination at hundreds of thousands of sites in cities all around the world, posing a serious health risk to millions of people. Many contaminated brownfield sites are being left abandoned due to the high cost of remediation. Traditional physical and chemical remediation technologies also require high energy and resource input, and can result in loss of land functionality and cause secondary pollution. Nature-based solutions (NBS) including phytoremediation and conversion of brownfield sites to public greenspaces, holds much promise in maximizing a sustainable urban renaissance. NBS is an umbrella concept that can be used to capture nature based, cost effective and eco-friendly treatment technologies, as well as redevelopment strategies that are socially inclusive, economically viable, and with good public acceptance. The NBS concept is novel and in urgent need of new research to better understand the pros and cons, and to enhance its practicality. This review article summarizes NBS's main features, key technology choices, case studies, limitations, and future trends for urban contaminated land remediation and brownfield redevelopment.