Predicting prognosis and immunotherapy response in colorectal cancer by pericytes insights from single-cell RNA sequencing.

Immunotherapy has revolutionized the treatment of tumors, but there are still a large number of patients who do not benefit from immunotherapy. Pericytes play an important role in remodeling the immune microenvironment. However, how pericytes affect the prognosis and treatment resistance of tumors is still unknown. This study jointly analyzed single-cell RNA sequencing (scRNA-seq) data and bulk RNA sequencing data of multiple cancers to reveal pericyte function in the colorectal cancer microenvironment. Analyzing over 800 000 cells, it was found that colorectal cancer had more pericyte enrichment in tumor tissues than other cancers. We then combined the TCGA database with multiple public datasets and enrolled more than 1000 samples, finding that pericyte may be closely related to poor prognosis due to the higher epithelial-mesenchymal transition (EMT) and hypoxic characteristics. At the same time, patients with more pericytes have higher immune checkpoint molecule expressions and lower immune cell infiltration. Finally, the contributions of pericyte in poor treatment response have been demonstrated in multiple immunotherapy datasets (n = 453). All of these observations suggest that pericyte can be used as a potential biomarker to predict patient disease progression and immunotherapy response.

Microstructure regulation and microwave absorption properties of ZnO/RGO composites.

Electromagnetic waves can cause different degrees of damage to the human body. People are developing unique nanomaterials with excellent reflection loss (RL), thin thickness, wide frequency band and light weight to improve the absorption efficiency of electromagnetic waves. Using a hydrothermal method, ZnO nanocrystals are combined with graphene oxide (GO). After heat treatment, evenly dispersed ZnO nanocrystals are attached to the GO surface or inserted into the lamellae, and the amount of Zn(CH3COO)2·2H2O and GO is selected to obtain ZnO/RGO nanocomposites with different mass ratios (1 : 1, 1 : 2, 1 : 3). The ZnO/RGO nanocomposites were mixed with paraffin wax with different mass ratios (15, 20, 25, 30 wt%) to explore their electromagnetic parameters and wave absorption properties. It is found that at 25 wt%, ZnO : GO = 3 : 1 and thickness of 3 mm, the sample exhibits excellent wave absorption performance (-36.6 dB) and wide effective absorption bandwidth (6.6 GHz). The microwave absorption performance is enhanced because ZnO nanocrystals inhibit RGO agglomeration and improve impedance matching between the heterostructure interface and RGO.

Ferrous sulfate combined with ultrasound emulsified cinnamaldehyde nanoemulsion to cause ferroptosis in Escherichia coli O157:H7.

The purpose of this study was to investigate ferroptosis in Escherichia coli O157:H7 caused by ferrous sulfate (FeSO4) and to examine the synergistic effectiveness of FeSO4 combined with ultrasound-emulsified cinnamaldehyde nanoemulsion (CALNO) on inactivation of E. coli O157:H7 in vitro and in vivo. The results showed that FeSO4 could cause ferroptosis in E. coli O157:H7 via generating reactive oxygen species (ROS) and exacerbating lipid peroxidation. In addition, the results indicated that FeSO4 combined with CALNO had synergistic bactericidal effect against E. coli O157:H7 and the combined treatment could lead considerable nucleic acids and protein to release by damaging the cell membrane of E. coli O157:H7. Besides, FeSO4 combined with CALNO had a strong antibiofilm ability to inhibit E. coli O157:H7 biofilm formation by reducing the expression of genes related on biofilm formation. Finally, FeSO4 combined with CALNO exhibited the significant antibacterial activity against E. coli O157:H7 in hami melon and cherry tomato.

Evaluation of Iron Chlorin e6 disappearance and hydrolysis in soil and garlic using salting-out assisted liquid-liquid extraction coupled with high-performance liquid chromatography and ultraviolet-visible detection.

Iron Chlorin e6 (ICE6), a star plant growth regulator (PGR) with independent intellectual property rights in China, has demonstrated its efficacy through numerous field experiments. We innovatively employed salting-out assisted liquid-liquid extraction (SALLE) with HPLC-UV/Vis to detect ICE6 residues in water, soil, garlic seeds, and sprouts. Using methanol and a C18 column with acetonitrile: 0.1% phosphoric acid mobile phase (55:45, v:v), we achieved a low LOQ of 0.43 to 0.77 µg kg-1. Calibration curves showed strong linearity (R2 > 0.992) within 0.01 to 5.00 mg kg-1. Inter-day and intra-day recoveries (0.05 to 0.50 mg kg-1) demonstrated high sensitivity and accuracy (recoveries: 75.36% to 107.86%; RSD: 1.03% to 8.78%). Additionally, density functional theory (DFT) analysis aligned UV/Vis spectra and indicated ICE6's first-order degradation (2.03 to 4.94 days) under various environmental conditions, mainly driven by abiotic degradation. This study enhances understanding of ICE6's environmental behavior, aids in risk assessment, and guides responsible use in agroecosystems.

Establishment, optimization and validation of a fluorescence polarization-based high-throughput screening assay targeting cathepsin L inhibitors.

Cathepsin L (CTSL), a lysosomal cysteine proteinase, is primarily dedicated to the metabolic turnover of intracellular proteins. It is involved in various physiological processes and contributes to pathological conditions such as viral infection, tumor invasion and metastasis, inflammatory status, atherosclerosis, renal disease, diabetes, bone diseases, and other ailments. The coronavirus disease 2019 (COVID-19), with its rapid global spread and significant mortality, has been a worldwide epidemic since the late 2019s. Notably, CTSL plays a role in the processing of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, providing a potential avenue to block coronavirus host cell entry and thereby inhibit SARS-CoV-2 infection in humans. In this study, we have developed a novel method using fluorescence polarization (FP) for screening CTSL inhibitors in a high-throughput format. The optimized assay demonstrated its appropriateness for high-throughput screening (HTS) with a Z-factor of 0.9 in a 96-well format. Additionally, the IC50 of the known inhibitor, Z-Phe-Tyr-CHO, was determined to be 188.50 ± 46.88 nM. Upon screening over 2000 small molecules, we identified, for the first time, the anti-CTSL properties of a benzothiazoles derivative named IMB 8015. This work presents a novel high-throughput approach and its application in discovering and evaluating CTSL inhibitors.

Waterlogging in soil restricts the growth of Gleditsia sinensis seedlings and inhibits the accumulation of lignans and phenolic acids in thorns.

Gleditsia sinensis, commonly known as Chinese Zaojiao, has important economic value and medicinal compounds in its fruits and thorns, making it widely cultivated artificially in China. However, the available literature on the impact of waterlogging on the growth of G. sinensis seedlings and the accumulation of metabolite compounds in its thorns is limited. To address this knowledge gap, G. sinensis seedlings were planted in soil supplemented with pindstrup substrate, which enhances the water-holding capacity of the soil. The analyses of morphological traits and nutrient elements in one-year-old G. sinensis seedlings grown naturally under ambient conditions and metabolite accumulation in its thorns were conducted. The results showed that the waterlogged soil significantly diminished the height, fresh weight, and dry weight of seedling roots and stems (P < 0.05). Furthermore, waterlogging hindered the uptake of iron (Fe) and manganese (Mn), as well as the transport of potassium (K). The identified metabolites within the thorns were categorized into 16 distinct groups. Relative to the control soil, fatty acids and derivatives were the most down-regulated metabolites in the waterlogged soil, accounting for 40.58% of the total metabolites, followed by lignans (38.71%), phenolic acids (34.48%), saccharides and alcohols (34.15%), steroids (16.67%), alkaloids (12.24%), flavonoids (9.28%), and glycerophospholipids (7.41%). Conversely, nucleotides and derivatives experienced the greatest up-regulation in the waterlogged soil, accounting for 50.00% of the total metabolites. In conclusion, waterlogging negatively impacted the growth of G. sinensis seedlings and inhibited the accumulation of metabolites. Hence, when considering the accumulation of secondary metabolites such as lignans and phenolic acids, appropriate management of soil moisture levels should be taken into account.

Adsorption-desorption behavior of florpyrauxifen-benzyl on three microplastics in aqueous environment as well as its mechanism and various influencing factors.

Microplastics (MPs) and pesticides are two categories contaminants with proposed negative impacts to aqueous ecosystems, and adsorption of pesticides on MPs may result in their long-range transport and compound combination effects. Florpyrauxifen-benzyl, a novel pyridine-2-carboxylate auxin herbicide has been widely used to control weeds in paddy field, but the insights of which are extremely limited. Therefore, adsorption and desorption behaviors of florpyrauxifen-benzyl on polyvinyl chloride (PVC), polyethylene (PE) and disposable face masks (DFMs) in five water environment were investigated. The impacts of various environmental factors on adsorption capacity were evaluated, as well as adsorption mechanisms. The results revealed significant variations in adsorption capacity of florpyrauxifen-benzyl on three MPs, with approximately order of DFMs > PE > PVC. The discrepancy can be attributed to differences in structural and physicochemical properties, as evidenced by various characterization analysis. The kinetics and isotherm of florpyrauxifen-benzyl on three MPs were suitable for different models, wherein physical force predominantly governed adsorption process. Thermodynamic analysis revealed that both high and low temperatures weakened PE and DFMs adsorption, whereas temperature exhibited negligible impact on PVC adsorption. The adsorption capacity was significantly influenced by most environmental factors, particularly pH, cations and coexisting herbicide. This study provides valuable insights into the fate of florpyrauxifen-benzyl in presence of MPs, suggesting that PVC, PE and DFMs can serve as carriers of florpyrauxifen-benzyl in aquatic environment.

In Vitro Assessment of Ozone-Treated Deoxynivalenol by Measuring Cytotoxicity and Wheat Quality.

Deoxynivalenol (DON), a trichothecene mycotoxin, could lead to cytotoxicity in both animal bodies and plant seed cells. Ozone degradation technology has been applied to DON control. However, the safety and quality of the contaminated grain after DON degradation are largely obscured. In this work, we evaluated the cytotoxicity of ozone-treated DON through seed germination experiments and cytotoxicity tests. Cell experiments showed that the inhibition rate of HepG2 viability gradually increased within the concentrations of 1-10 mg/L of DON, alongside which an IC50 (half maximal inhibitory concentration) of 9.1 mg/L was determined. In contrast, degrading DON had no significant inhibitory effect on cell growth. Moreover, a 1-10 mg/L concentration of DON increased production of a large amount of reactive oxygen radicals in HepG2, with obvious fluorescence color development. However, fluorescence intensity decreased after DON degradation. Further, DON at a concentration of >1 mg/L significantly inhibited the germination of mung bean seeds, whereas no significant inhibition of their germination or growth were observed if DON degraded. Changes in total protein content, fatty acid value, and starch content were insignificant in wheat samples suffering ozone degradation, compared to the untreated group. Lastly, the ozone-treated wheat samples exhibited higher tenacity and whiteness. Together, our study indicated that the toxicity of DON-contaminated wheat was significantly reduced after ozone degradation.

Establishment and Corresponding Nursing Measures of Intelligent Health Education Platform for Parkinson's Patients Based on Behavior Change Theory.

Objective: Parkinson's disease is a brain disorder that can cause mobility problems as well as mental health, sleep, pain and other health problems. To analyze the establishment of a platform for Parkinson's patients to cooperate with intelligent health education based on behavior change theory and the corresponding nursing measures. Methods: 80 patients with Parkinson's disease in the Affiliated Brain Hospital of Nanjing Medical University from October 2021 to September 2022 were selected and included in the conventional and wisdom education groups according to different health education methods, with 40 patients in each group. The conventional education group carried out routine health education and nursing. Based on routine health education and nursing, the wisdom education group established a smart health education platform based on behavior change theory. It implemented corresponding health education and nursing measures. The knowledge, belief and practice (KAP score), psychological status, self-efficacy [General self-efficacy scale (GSES) score], motor function [Parkinson's disease Uniform Scoring Scale (UPDRS) - III score], daily living ability (Barthel index), sleep quality (PSQI score), quality of life (QOL score), complication rate (pressure sores, constipation, bruises), and education satisfaction of the two groups were compared. Results: The KAP score of the wisdom education group after health education was higher than that of the conventional education group (P < .05); The SAS and SDS scores of the wisdom education group after health education were lower than those of the conventional education group (P < .05); The GSES score of the wisdom education group after health education was higher than that of the conventional education group (P < .05); The UPDRS - III score of the wisdom education group after health education was lower than that of the conventional education group, and the Barthel index was higher than that of the conventional education group, P < .05; The PSQI score of the wisdom education group after health education was lower than that of the conventional education group, and the QOL score was higher than that of the conventional education group, P < .05; The incidence of complications in the wisdom education group was lower than that in the conventional education group (P < .05); The satisfaction of the wisdom education group was higher than that of the conventional education group (P < .05). Conclusion: The establishment of an intelligent health education platform based on behavior change theory for Parkinson's patients and the implementation of corresponding health education and nursing measures can significantly improve the knowledge, belief, practice, and psychological status of patients. This will be helpful for those patients and clinicians. There are also limitations, such as little numbers of patients and no mechanisms.

Diagnostic and Prognostic Ability of Contrast-Enhanced Unltrasound and Biomarkers in Hepatocellular Carcinoma Subtypes.

OBJECTIVE: To investigate the diagnostic and prognostic value of contrast-enhanced ultrasound (CEUS) and clinical indicators of the vessels encapsulating tumor clusters (VETC) pattern and macrotrabecular-massive subtype in hepatocellular carcinoma (MTM-HCC). METHODS: This retrospective study included patients who underwent preoperative CEUS and hepatectomy for HCC between August 2018 and August 2021. Multivariable logistic regression was performed to select independent correlated factors of VETC-HCC and MTM-HCC to develop nomogram models. The association between model outcomes and early postoperative HCC recurrence was assessed using Kaplan-Meier curve and Cox regression analysis. RESULTS: The training cohort included 182 patients (54.3 ± 11.3 years, 168 males) and the validation cohort included 91 patients (54.8 ± 10.6 years, 81 males). Multivariate logistic regression analysis revealed that α-fetoprotein (AFP) levels (odds ratio [OR]: 2.26, 95% confidence interval [CI]: 1.49-3.42, p < 0.001), intratumoral nonenhancement (OR: 2.40, 95% CI: 1.02-5.64, p = 0.044), and the perfusion pattern in the CEUS arterial phase (OR: 2.27, 95% CI: 1.05-4.91, p = 0.038) were independent predictors of VETC-HCC. Besides, the former two were also independently associated with MTM-HCC (AFP level: OR: 2.36, 95% CI: 1.36-4.09, p = 0.002; intratumoral nonenhancement: OR: 3.72, 95% CI: 1.02-13.56, p = 0.046). Nomogram models were constructed based on the aforementioned indicators. Kaplan-Meier curve analysis indicated that predicted VETC-HCC or MTM-HCC exhibited higher rates of early recurrence (log-rank p < 0.001 and p = 0.002, respectively). Cox regression analysis showed that a high risk of VETC-HCC was independently correlated with early recurrence (p = 0.011). CONCLUSION: CEUS combined with AFP levels can predict VETC-HCC/MTM-HCC and prognosis preoperatively.

Expression, purification, and biological activity evaluation of cathepsin L in mammalian cells.

Cathepsin L (CTSL) could cleave and activate SARS-CoV-2 Spike protein to promote viral entry, making it a hopeful therapeutic target for COVID-19 prevention and treatment. So CTSL inhibitors are considered to be a promising strategy to SARS-CoV-2 infection. CTSL has previously been expressed in inclusion body in Escherichia coli. In order to prepare CTSL with high purity and activity in soluble active form, we transformed HEK-293T cells with a recombinant mammalian expression plasmid. CTSL was purified to a purity about 95%, found to migrate at approximately 43 kDa and exhibited substrate specificity against Z-Phe-Arg-AMC with specific activity of no less than 85 081 U/mg, characteristic of active CTSL. Although eukaryotic purified CTSL is commercially available, our study for the first time reported the details of the expression, purification, and characterization of active, recombinant CTSL in eukaryocyte system, which laid an experimental foundation for the establishment of high-throughput screening model for anti-coronavirus drugs targeting CTSL.

Heat inactivation does not alter host plasma cell-free DNA characteristics in infectious disease research.

BACKGROUND: Cell-free DNA (cfDNA) is a promising analyte for non-invasive liquid biopsy, carrying abundant signatures for disease diagnosis and monitoring. In infectious disease researches, blood plasma samples are routinely heat-inactivated before proceeding with downstream analyses. However, the effects of heat inactivation on cfDNA fragmentomic analysis remain largely unclear, potentially introducing biases or altering the characteristics of cfDNA. METHODS: We performed a comprehensive investigation of cfDNA concentrations and fragmentomics in 21 plasma samples from 7 healthy individuals, by comparing the sample group without the heat inactivation to those exposed to once or twice heat-inactivation at 56 °C for 30 min and following freeze-thaw. RESULTS: Plasma samples with once and twice heat inactivation displayed no significant deviations in primary characteristics, including cfDNA concentrations, size profiles, end motif features, and genome-wide distributions, compared to samples without heat treatment. CONCLUSIONS: Heat-inactivated cfDNA can be utilized for liquid biopsy in infectious disease researches, without substantial impact on cfDNA concentrations and fragmentomic properties. This study provides essential insights into the effects of heat inactivation on cfDNA properties and will contribute to the development of reliable non-invasive biomarkers for infectious disease.

Characterizing immune variation and diagnostic indicators of preeclampsia by single-cell RNA sequencing and machine learning.

Preeclampsia is a multifactorial and heterogeneous complication of pregnancy. Here, we utilize single-cell RNA sequencing to dissect the involvement of circulating immune cells in preeclampsia. Our findings reveal downregulation of immune response in lymphocyte subsets in preeclampsia, such as reduction in natural killer cells and cytotoxic genes expression, and expansion of regulatory T cells. But the activation of naïve T cell and monocyte subsets, as well as increased MHC-II-mediated pathway in antigen-presenting cells were still observed in preeclampsia. Notably, we identified key monocyte subsets in preeclampsia, with significantly increased expression of angiogenesis pathways and pro-inflammatory S100 family genes in VCAN+ monocytes and IFN+ non-classical monocytes. Furthermore, four cell-type-specific machine-learning models have been developed to identify potential diagnostic indicators of preeclampsia. Collectively, our study demonstrates transcriptomic alternations of circulating immune cells and identifies immune components that could be involved in pathophysiology of preeclampsia.

Potentiation effect of the AI-2 signaling molecule on postharvest disease control of pear and loquat by Bacillus amyloliquefaciens and its mechanism.

An autoinducer-2 (AI-2) signaling molecule from Bacillus was synthesized, and its mechanism on the biofilm formation and biocontrol ability of B. amyloliquefaciens was verified in vitro and in vivo. The 16S/ITS amplicon sequencing was used to analyze the effect of B. amyloliquefaciens B4 with or without AI-2 on the microflora of pears during storage. The results showed that B. amyloliquefaciens B4 secreted AI-2, which promoted biofilm formation. Additionally, AI-2 at a concentration of 40 µmol/L enhanced the biocontrol ability of B. amyloliquefaciens B4 on postharvest pear and loquat fruits. Finally, amplicon sequencing demonstrated that the addition of AI-2 increased the abundance of B. amyloliquefaciens B4 in fruit by stimulating the growth and biofilm formation of this bacterium.

Development and Comparison of Prediction Models Based on Sonovue- and Sonazoid-Enhanced Ultrasound for Pathologic Grade and Microvascular Invasion in Hepatocellular Carcinoma.

OBJECTIVE: This study was aimed at developing and comparing prediction models based on Sonovue and Sonazoid contrast-enhanced ultrasound (CEUS) in predicting pathologic grade and microvascular invasion (MVI) of hepatocellular carcinoma (HCC). Also investigated was whether Kupffer phase images have additional predictive value for the above pathologic features. METHODS: Ninety patients diagnosed with primary HCC who had undergone curative hepatectomy were prospectively enrolled. All patients underwent conventional ultrasound (CUS), Sonovue-CEUS and Sonazoid-CEUS examinations pre-operatively. Clinical, radiologic and pathologic features including pathologic grade, MVI and CD68 expression were collected. We developed prediction models comprising clinical, CUS and CEUS (Sonovue and Sonazoid, respectively) features for pathologic grade and MVI with both the logistic regression and machine learning (ML) methods. RESULTS: Forty-one patients (45.6%) had poorly differentiated HCC (p-HCC) and 37 (41.1%) were MVI positive. For pathologic grade, the logistic model based on Sonazoid-CEUS had significantly better performance than that based on Sonovue-CEUS (area under the curve [AUC], 0.929 vs. 0.848, p = 0.035), whereas for MVI, these two models had similar accuracy (AUC, 0.810 vs. 0.786, p = 0.068). Meanwhile, we found that well-differentiated HCC tended to have a higher enhancement ratio in 6-12 min during the Kupffer phase of Sonazoid-CEUS, as well as higher CD68 expression compared with p-HCC. In addition, all of these models can effectively predict the risk of recurrence (p < 0.05). CONCLUSION: Sonovue-CEUS and Sonazoid-CEUS were comparably excellent in predicting MVI, while Sonazoid-CEUS was superior to Sonovue-CEUS in predicting pathologic grade because of the Kupffer phase. The enhancement ratio in the Kupffer phase has additional predictive value for pathologic grade prediction.

Simulating ozone degradation of deoxynivalenol and its bio-safety assessment by mouse model.

Deoxynivalenol (DON), a trichothecene mycotoxin, is one of the most prevalent mycotoxins globally, primarily produced by Fusarium species. DON exposure could cause a range of symptoms, including nausea, vomiting, gastroenteritis, growth retardation, immunosuppression, and intestinal flora disorders in both humans and animals. Recently, ozone degradation technology has been applied for DON control. However, the safety of the contaminated grain after degradation was often ignored. Therefore, the implementation technology for assessing the safety of DON-contaminated grain degradation is of great significance for food safety. In this study, based on previous degradation result of DON, we further studied and assessed the toxicity of corn contaminated with ozone-degrading DON by animal experiments in mice. We simulated feed made from corn contaminated with DON produced by inoculated Fusarium graminearum, which was treated with an ozone aqueous solution. DON treated by ozone could effectively increase the expression of total protein in mice and improve the immune system efficacy. Meanwhile, compared with DON directly-exposed mice, the corn with degrading DON could effectively maintain the level of liver and kidney immune function, and improved growth performance, enterohepatic circulation, and energy metabolism. Our study indicated that the toxicity of fed corn contaminated with degrading-DON decreased significantly after ozone degradation, resulting in a much lower toxicity compared to the DON group, or nontoxicity to some extent. Therefore, we hope that this mouse model could be used as a promising approach for assessing the risk of fungal toxins on metabolism, immunity, and intestinal health.

The robustness and disturbance within China's industrial complex network under carbon border tariffs.

Since the European Commission proposed in July 2021 to implement a Carbon Border Adjustment Mechanism (CBAM), the impact mechanism has received increasing attention worldwide. This study aims to analyze the impact of carbon border tariffs on China's carbon-intensive industries and simulate the risk transmission within China's industrial complex network based on the complex network modeling and cascading failure analysis. The results showed that the industries subject to carbon border tariffs played an essential role in China's entire industrial structure, which is closely related to industries including construction, metal, and manufacturing. If the carbon border tariffs are imposed on the steel industry, China's relevant industries will be reduced by 1.29%, followed by the fertilizer industry and non-ferrous metal industry with proportions of 1.11% and 0.95%, respectively. When the industrial transmission threshold reaches 0.8, the export shocks will affect the entire industrial network, leading to a rapid growth in the number of infected industries. By depicting the industrial linkage and impact mechanism of carbon border tariffs, this study is expected to provide practical suggestions and implications for carbon-intensive industries towards sustainable low-carbon transition under carbon border tariffs.

The fragmentomic property of plasma cell-free DNA enables the non-invasive detection of diabetic nephropathy in patients with diabetes mellitus.

Background: Diabetic nephropathy (DN) is one of the most prevalent complications of diabetes mellitus (DM). However, there is still a lack of effective methods for non-invasive diagnosis of DN in clinical practice. We aimed to explore biomarkers from plasma cell-free DNA as a surrogate of renal biopsy for the differentiation of DN patients from patients with DM. Materials and methods: The plasma cell-free DNA (cfDNA) was sequenced from 53 healthy individuals, 53 patients with DM but without DN, and 71 patients with both DM and DN. Multidimensional features of plasma DNA were analyzed to dissect the cfDNA profile in the DM and DN patients and identify DN-specific cfDNA features. Finally, a classification model was constructed by integrating all informative cfDNA features to demonstrate the clinical utility in DN detection. Results: In comparison with the DM patients, the DN individuals exhibited significantly increased cfDNA concentration in plasma. The cfDNA from the DN patients showed a distinct fragmentation pattern with an altered size profile and preferred motifs that start with "CC" in the cfDNA ending sites, which were associated with deoxyribonuclease 1 like 3 (DNASE1L3) expression in the kidney. Moreover, patients with DM or DN were found to carry more alterations in whole-genome cfDNA coverage when compared with healthy individuals. We integrated DN-specific cfDNA features (cfDNA concentration, size, and motif) into a classification model, which achieved an area under the receiver operating characteristic curve (AUC) of 0.928 for the differentiation of DN patients from DM patients. Conclusion: Our findings showed plasma cfDNA as a reliable non-invasive biomarker for differentiating DN patients from DM patients. The utility of cfDNA in clinical practice in large prospective cohorts is warranted.

Substrate-Controlled Diversity-Oriented Synthesis of Novel Polycyclic Frameworks via [4 + 2] and [3 + 2] Annulations of Ninhydrin-Derived MBH Adducts with 3,4-Dihydroisoquinolines.

Substrate-controlled diversity-oriented synthesis of polycyclic frameworks via [4 + 2] and [3 + 2] annulations between ninhydrin-derived Morita-Baylis-Hillman (MBH) adducts and 3,4-dihydroisoquinolines under similar reaction conditions have been developed. The reaction provides diversity-oriented synthesis of a series of novel and structurally complex spiro multi heterocyclic skeletons in good yields (up to 87% and 90%, respectively) with excellent diastereoselectivities (up to >25:1 dr). In particular, the switchable [4 + 2] and [3 + 2] annulation reactions are controlled by tuning the hydroxyl protecting group on the ninhydrin-derived MBH adduct to deliver structural diverse spiro[indene-2,2'-[1,3]oxazino[2,3-a]isoquinoline] and spiro[indene-2,1'-pyrrolo[2,1-a]isoquinoline], respectively. Furthermore, the relative configuration and chemical structure of two kinds of cycloadducts were confirmed through X-ray diffraction analysis.