Changing Cinnamaldehyde Skeleton Achieves Antibacterial Nanoswitch.

Changeable substituent groups of organic molecules can provide an opportunity to clarify the antibacterial mechanism of organic molecules by tuning the electron cloud density of their skeleton. However, understanding the antibacterial mechanism of organic molecules is challenging. Herein, we reported a molecular view strategy for clarifying the antibacterial switch mechanism by tuning electron cloud density of cinnamaldehyde molecule skeleton. The cinnamaldehyde and its derivatives were self-assembled into nanosheets with excellent water solubility, respectively. The experimental results show that α-bromocinnamaldehyde (BCA) nanosheets exhibits unprecedented antibacterial activity, but there is no antibacterial activity for α-methylcinnamaldehyde nanosheets. Therefore, the BCA nanosheets and α-methylcinnamaldehyde nanosheets achieve an antibacterial switch. Theoretical calculations further confirmed that the electron-withdrawing substituent of the bromine atom leads to a lower electron cloud density of the aldehyde group than that of the electron-donor substituent of the methyl group at the α-position of the cinnamaldehyde skeleton, which is a key point in elucidating the antimicrobial switch mechanism. The excellent biocompatibility of BCA nanosheets was confirmed by CCK-8. The mouse wound infection model, H&E staining, and the crawling ability of drosophila larvae show that as-prepared BCA nanosheets are safe and promising for wound healing. This study provides a new strategy for the synthesis of low-cost organic nanomaterials with good biocompatibility. It is expected to expand the application of natural organic small molecule materials in antimicrobial agents.

The PHYB-FOF2-VOZ2 module functions to fine-tune flowering in response to changes in light quality by modulating FLC expression in Arabidopsis.

Proper timing for plants to flower under different environmental conditions is critical for their propagation. Light quality is a pivotal environmental cue that plays a critical role in regulating flowering. Plants tend to flower late under light with high red (R)/far-red (FR) light ratio, whereas flower early under light with a low R/FR light ratio. However, how plants fine-tune flowering in response to changes in light quality is not well understood. Here, we demonstrate that the F-box Protein F-box of Flowering 2 (FOF2), an autonomous pathway-related regulator, physically interacts with VASCULAR PLANT ONE-ZINC FINGER 1 and 2 (VOZ1 and VOZ2), which are the direct downstream factors of R/FR light receptor phytochrome B (PHYB). Furthermore, we show that PHYB physically interacts with FOF2 and mediates FR light and end-of-day far-red light (EOD-FR) stabilization of the FOF2 protein and enhances FOF2 binding to VOZ2, leading to VOZ2 protein degradation by SCFFOF2 E3 ligase. In contrast, PHYB mediates R light and end-of-day red light (EOD-R) degradation of FOF2 protein. Genetic interaction studies demonstrate that FOF2 functions downstream of PHYB to promote FLC expression and inhibit flowering under both high R/FR light and simulated shade conditions, which partially depend on VOZ proteins. Taken together, our findings suggest a novel mechanism whereby plants fine-tune flowering time through PHYB-FOF2-VOZ2 module that modulates FLC expression in response to changes in light quality.

Diversity and growth-promoting characteristics of rhizosphere bacteria of three naturally growing plants at the sand iron ore restoration area in Qinghe County.

It is a great challenge to restore northern mines after mining and achieve optimal results due to the extremely harsh environment and climate, as in Qinghe County of Xinjiang Province, China. Qinghe County has a climate of drought, cold, strong winds, and high altitude. After sand and iron mining, the soil in this area contains a large amount of sand and gravel with extremely low organic matter, nitrogen deficiency, and a high pH of 9.26. Our preliminary studies disclosed that only three plants, including Caligonum junceum, Atraphaxis virgata, and Melilotus albus Medic, can grow naturally in this environment without any artificial management. For effective ecology restoration, this study explored the mechanism of plant-microbial interaction and stress resistance in this environment. It was found that although the soil condition in the sand iron ore landfill area is extreme, the bacterial diversity remained high, with Shannon and Simpson indices reaching 9.135 and 0.994, respectively. The planting of three types of remediation plants did not significantly improve, or even decreased, the soil bacterial diversity index, but greatly changed the composition of dominant bacterial genera. Significant differences in the composition of rhizosphere soil bacterial communities among these three remediation plants were observed. Potential new bacterial species accounted for 9.8 %, and the proportion of unique genera reached 30 % or 50 %, respectively. Among all the isolated strains, 74 % had nitrogen fixation and other growth-promoting properties. In summary, the soil microbial community structure in this extreme environment is unique and diverse. The types of remediation plants play a major role in the composition of the rhizosphere bacterial community structure, and the recruited growth-promoting bacteria are diverse and functional. This study may offer valuable information for further studies in vegetation restoration and aid in ecology restoration, especially under extreme conditions.

Dipole moment regulation for enhancing internal electric field in covalent organic frameworks photocatalysts.

Covalent organic frameworks (COFs) have recently emerged as a kind of promising photocatalytic platform in addressing the growing threat of trace pollutants in aquatic environments. Along this, we propose a strategy of constructing internal electric field (IEF) in COFs through the dipole moment regulation, which intrinsically facilitates the separation and transfer of photogenerated excitons. Two COFs of BTT-TZ-COF and BTT-TB-COF are developed by linking the electron-donor of benzotrithiophene (BTT) block and the electron-acceptor of triazine (TZ) or tribenzene (TB) block, respectively. DFT calculations demonstrate TZ block with larger dipole moment can achieve more efficient IEF due to the stronger electron-attractive force and hence narrower bandgap. Moreover, featuring the highly-order crystalline structure for accelerating photo-excitons transfer and rich porosity for facilitating the adsorption, BTT-TZ-COF exhibited an excellent universal performance of photocatalytic degradations of various dyes. Specifically, a superior photodegradation efficiency of 99% Rhodamine B (RhB) is achieved within 20 min under the simulated sunlight. Therefore, this convenient construction approach of enhanced IEF in COFs through rational regulation of the dipole moment can be a promising way to realize high photocatalytic activity.

Copper and conjugated carbonyls of metal-organic polymers as dual redox centers for Na storage.

Metal-organic polymers (MOPs) are fascinating electrode materials for high-performance sodium-ion batteries due to their multiple redox centers and low cost. Herein, a flower-like π-d conjugated MOP (Cu-TABQ) was synthesized using tetramino-benzoquinone (TABQ) as an organic ligand and Cu2+ as a transition metal node under the slow release of Cu2+ from [Cu(NH3)4]2+ and subsequent dehydrogenation. It possesses dual redox centers of Cu2+/Cu+ and C[double bond, length as m-dash]O/C-O to render a three-electron transfer reaction for each coordination unit with a high reversible capacity of 322.9 mA h g-1 at 50 mA g-1 in the voltage range of 1.0 to 3.0 V. The flower-like structure enhances fast Na+ diffusion and highly reversible organic/inorganic redox centers. This results in excellent cycling performance with almost no degradation within 700 cycles and great rate performance with 198.8 mA h g-1 at 4000 mA g-1. The investigation of the Na-storage mechanism and attractive performance will shed light on the insightful design of MOP cathode materials for further batteries.

Cardiac magnetic resonance-derived mitral annular plane systolic excursion: a robust indicator for risk stratification after myocardial infarction.

To explore the predictive value of mitral annular plane systolic excursion (MAPSE) derived by cardiac magnetic resonance (CMR) for major adverse cardiovascular events (MACE) in postmyocardial infarction (MI) patients. Patients with MI who underwent 3.0 T CMR (Chinese Clinical Trial Registry, ChiCTR2200055158) were recruited retrospectively. CMR parameters included MAPSE and LVEF. Patients were followed up for MACE for more than 6 months and were separated into a No-MACE group and a MACE group. A total of 165 post-MI patients were included, and 103 patients were finally analyzed (61 patients belonged to the No-MACE group, and 42 patients belonged to the MACE group). The LVEF and MAPSE of the patients belonging to the No-MACE group were considerably higher than those of the patients belonging to the MACE group. Both LVEF and MAPSE were effective indicators of the occurrence of MACE after MI. The risk of MACE decreased as LVEF and MAPSE increased. For the risk prediction of MACE after MI, compared with model I (chi-square value 4.0 vs. 31.4, P < 0.001) and model II (chi-square value 22.7 vs. 31.4, P = 0.003), model III had a significant incremental predictive value. Moreover, the cutoff value of MAPSE was 9.70 mm. CMR-derived MAPSE is an effective predictor of MACE occurrence in patients with MI, and MAPSE provided a significant incremental predictive value. Moreover, MAPSE could complement LVEF for superior risk stratification of MI patients.

Multivariate prognostic index and triplet regimen efficacy predictive index in locally advanced and metastatic gastric cancer: pooled analysis from three clinical trials using individual patient data.

Background: To construct an effective prognostic index to predict overall survival (OS) and triplet regimen efficacy for advanced gastric cancer (AGC) patients treated with platinum-based and fluorouracil-based chemotherapy. Objectives: Between 2011 and 2021, 679 patients from two randomized phase III trials and one phase II trial were enrolled. Designs: We collected 11 baseline clinicopathological and 14 hematological parameters to establish a prognostic index. Methods: Univariate and multivariate Cox analyses were used to screen prognostic factors, and a prognostic index nomogram was conducted. Results: Seven prognostic factors were identified: primary tumor site in the non-proximal gastric area, signet-ring cell carcinoma (SRCC)/mucinous carcinoma, peritoneal metastasis, neutrophil count higher than the upper limit of normal value (ULN), lymphocyte count lower than the lower limit of normal value, lactate dehydrogenase level higher than the ULN, and alkaline phosphatase level higher than the ULN as significant for prognosis. A prognostic nomogram named the Fudan advanced gastric cancer prognostic risk score (FARS) index was constructed, and patients in the high-risk group had significantly shorter OS than those in the low-risk group (median OS, 15.5 versus 8.0 months, p < 0.001). The areas under the curve of the FARS index for 1-, 2-, and 3-year OS were 0.70, 0.72, and 0.77, respectively. A validation and external cohort verified the prognostic value of the FARS index. Moreover, three triplet regimen efficacy parameters were identified: SRCC/mucinous adenocarcinoma, primary tumor location in the non-proximal gastric area, and peripheral neutrophil count higher than the ULN; a TRIS index was subsequently conducted. In patients with any two of the three parameters, the triplet regimen showed significantly longer OS than the doublet regimen (p = 0.018). Conclusion: The constructed FARS index to predict the OS of AGC patients and the TRIS index to screen out the dominant population for triplet regimens can be used to aid clinical decision-making and individual risk stratification.

A prognostic index in locally advanced and metastatic gastric cancer To date, no recognized systematic prognostic score has been established for advanced gastric cancer (AGC). Our research aims to construct an effective prognostic index to predict overall survival (OS) for AGC patients to aid clinical decision-making and individual risk stratification. In our research, seven prognostic factors were identified: primary tumor site in the non-proximal gastric area, signet-ring cell carcinoma (SRCC)/mucinous carcinoma, peritoneal metastasis, neutrophil count higher than the upper limit of normal value (ULN), lymphocyte count lower than the lower limit of normal value, lactate dehydrogenase level higher than the ULN, and alkaline phosphatase level higher than the ULN as significant for prognosis. A prognostic index named the Fudan advanced gastric cancer prognostic risk score (FARS) index was constructed, and patients in the high-risk group had significantly shorter OS than those in low-risk group (median OS, 15.5 months vs. 8.0 months, P < 0.001). Moreover, three triplet regimen efficacy parameters were identified: SRCC/mucinous adenocarcinoma, primary tumor location in the non-proximal gastric area, and peripheral neutrophil count higher than the ULN; a TRIS index was subsequently conducted. In patients with any two of the three parameters, the triplet regimen showed significantly longer OS than the doublet regimen (P = 0.018).

Development of Vitamin C-Loaded Electrospun Nanofibers of Mixture of Polysaccharides of Pullulan/Xanthan Gum for Fast Dissolving Oral Film Applications.

In this study, polysaccharide-based nanofibrous fast dissolving oral films (FDOFs) were developed using pullulan (PUL) and xanthan gum (XG) via electrospinning. The edible, continuous, and bead-free nanofibers with average diameters ranging from 181.17 nm to 260.84 nm were prepared. The morphological, thermal, mechanical, and water-soluble properties of the nanofibrous FDOFs were characterized. For prospective future applications of the developed PUL/XG FDOFs, a model nutrient of vitamin C (VC) was encapsulated into the FDOFs. The success of VC encapsulation was confirmed by Fourier transform infrared spectroscopy. The encapsulation efficiency of VC was above 85% by ultraviolet-visible spectrophotometer. The amorphous structure of PUL/XG in the nanofibers film was demonstrated by X-ray diffractometer. In addition, the edible FDOFs could dissolve in water within 3 s. The nanofibers film we prepared could be used as nutrient or drug carriers and edible packaging film.

Learning curve in relation to health-related quality of life in long-term, disease free survivors after McKeown minimally invasive esophagectomy.

BACKGROUND: The potential impact of learning curve on long-term health-related quality of life (QoL) after esophagectomy for cancer has not been investigated. The aim of this article is to investigate the relationship between learning curve for McKeown minimally invasive esophagectomy (MIE) and health-related quality of life (QoL) in long-term, disease free survivors up to 10 years after esophageal cancer resection. METHODS: Esophageal cancer patients who underwent McKeown MIE between 2009 and 2019 were identified in which 280 who were free of disease at the time of survey and completed health-related QoL and symptom questionnaires, including EORTC QLQ-C30, EORTC QLQ-OES18, and Digestive Symptom Questionnaire. Patients were assessed in 3 cohorts according to the learning phases of expertise reported by our previous study: initial phase; plateau phase, and; experienced phase. RESULTS: Median time from operation to survey was 5.8 years (interquartile range 4.6-8.2). The QLQ-C30 mean scores of functional scales, and symptom scales of respiratory and digestive systems including dyspnea (P = 0.006), shortness of breath (P = 0.003), and dysphagia (P = 0.031) were significantly better in experienced phase group. Furthermore, in the subgroup analyses for patients without postoperative major complications, patients in the initial learning phase remained suffering from more symptoms of dyspnea (P = 0.040) and shortness of breath (P = 0.001). CONCLUSION: Esophageal cancer patients undergoing McKeown MIE in initial learning phase tend to suffer from a deterioration in long-term health-related QoL and higher symptomatic burden as compared to experienced learning phase, which did not improved over time and warranted more attention.

Clinical evaluation of a new COVID-19 antigen rapid test kit for detection of SARS-CoV-2.

The antigen rapid diagnostic test (Ag-RDT) is an assay kit for detecting the SARS-COV-2 nucleocapsid proteins, based on the colloidal gold method.Accurate diagnosis has an important role in limiting the transmission of SARS-COV-2, and also helps patients to receive earlier treatment .The object of this study was to perform the clinical evaluation of a novel Ag-RDTs with samples collected from two different swabs.DEEPBLUE®COVID-19 antigen detection kit used for the examination of the subjects in the experiment.For antigen testing on samples collected with nasal swabs, sensitivity was 91.7 % (95 % CI 83.6-96.6 %) and specificity was 100 %(95 %CI 98.1-100 %).For nasopharyngeal swabs, the sensitivity was 96.8 % (95 % CI 93.6-98.7 %) and the specificity was 100 % (95 % CI 98.2-100 %).Fisher Precision test showed a significant correlation between nasopharyngeal swab Ag-RDTs and nasal swab Ag-RDTs and RT-qPCR test (p-value <0.001).The results showed that the patients use the kit for testing were comparable to the RT-qPCR.

Fisetin suppresses ferroptosis through Nrf2 and attenuates intervertebral disc degeneration in rats.

Low back pain, primarily caused by intervertebral disc degeneration (IVDD), lacks effective pharmacological treatments. Oxidative stress has been identified as a significant contributor to IVDD. This study aims to establish an in vitro model of IVDD induced by oxidative stress and identify potential therapeutic agents and their underlying mechanisms. By screening the natural product library, fisetin emerged as the most promising compound in suppressing cell death induced by oxidative stress in nucleus pulposus cells (NPCs). Furthermore, our investigation revealed that the cell death induced by oxidative stress was predominantly associated with ferroptosis, and fisetin demonstrated the ability to inhibit ferroptosis in NPCs. Mechanistic exploration suggested that the impact of fisetin on ferroptosis may be mediated through the Nrf2/HO-1 (Nuclear factor erythroid 2-related factor 2/heme oxygenase-1) axis. Notably, the in vivo study demonstrated that fisetin could alleviate IVDD in rats. These findings highlight fisetin as a potential therapeutic option for IVDD and implicate the involvement of the Nrf2/HO-1 pathway in its mechanism of action.

A novel adhesive dual-sensitive hydrogel for sustained release of exosomes derived from M2 macrophages promotes repair of bone defects.

The repair of bone defects remains a huge clinical challenge. M2 macrophage-derived exosomes (M2-Exos) can act as immunomodulators to promote fracture healing; however, how to retain the sustained release of exosomes to the target area remains a challenge. Here, we report a composite hydrogel loaded with M2-Exos aiming to accelerate bone defect healing. It was verified that the F127/HA-NB hydrogel had a dense network structure, tissue adhesiveness, and dual sensitivity to temperature and light. F127/HA-NB loaded with M2-Exos (M2-Exos@F127/HA-NB) exhibited good biocompatibility and achieved sustained release of exosomes for up to two weeks. The study showed that both M0-Exos and M2-Exos@F127/HA-NB significantly promoted osteogenic differentiation of rat bone marrow mesenchymal stem cells. The mechanism study implied that M2-Exos activates the Wnt/ß-catenin signaling pathway to promote osteogenic differentiation of BMSCs. Finally, we evaluated the osteogenetic effects of M2-Exos@F127/HA-NB in a rat cranial defect model, and the results showed that M2-Exos@F127/HA-NB had superior bone regeneration-promoting effects. This study provides a new strategy for cell-free treatment of bone defects.

A liquid biopsy signature of circulating extracellular vesicles-derived RNAs predicts response to first line chemotherapy in patients with metastatic colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most threatening tumors in the world, and chemotherapy remains dominant in the treatment of metastatic CRC (mCRC) patients. The purpose of this study was to develop a biomarker panel to predict the response of the first line chemotherapy in mCRC patients. METHODS: Totally 190 mCRC patients treated with FOLFOX or XEOLX chemotherapy in 3 different institutions were included. We extracted the plasma extracellular vesicle (EV) RNA, performed RNA sequencing, constructed a model and generated a signature through shrinking the number of variables by the random forest algorithm and the least absolute shrinkage and selection operator (LASSO) algorithm in the training cohort (n = 80). We validated it in an internal validation cohort (n = 62) and a prospective external validation cohort (n = 48). RESULTS: We established a signature consisted of 22 EV RNAs which could identify responders, and the area under the receiver operating characteristic curve (AUC) values was 0.986, 0.821, and 0.816 in the training, internal validation, and external validation cohort respectively. The signature could also identify the progression-free survival (PFS) and overall survival (OS). Besides, we constructed a 7-gene signature which could predict tumor response to first-line oxaliplatin-containing chemotherapy and simultaneously resistance to second-line irinotecan-containing chemotherapy. CONCLUSIONS: The study was first to develop a signature of EV-derived RNAs to predict the response of the first line chemotherapy in mCRC with high accuracy using a non-invasive approach, indicating that the signature could help to select the optimal regimen for mCRC patients.

Photosynthetic characteristics and genetic mapping of a new yellow leaf mutant crm1 in Brassica napus.

Chlorophyll is one of the key factors for photosynthesis and plays an important role in plant growth and development. We previously isolated an EMS mutagenized rapeseed chlorophyll-reduced mutant (crm1), which had yellow leaf, reduced chlorophyll content and fewer thylakoid stacks. Here, we found that crm1 showed attenuated utilization efficiency of both light energy and CO2 but enhanced heat dissipation efficiency and greater tolerance to high-light intensity. BSA-Seq analysis identified a single nucleotide change (C to T) and (G to A) in the third exon of the BnaA01G0094500ZS and BnaC01G0116100ZS, respectively. These two genes encode the magnesium chelatase subunit I 1 (CHLI1) that catalyzes the insertion of magnesium into protoporphyrin IX, a pivotal step in chlorophyll synthesis. The mutation sites resulted in an amino acid substitution P144S and G128E within the AAA+ domain of the CHLI1 protein. Two KASP markers were developed and co-segregated with the yellow leaf phenotype in segregating F2 population. Loss of BnaA01.CHLI1 and BnaC01.CHLI1 by CRISPR/Cas9 gene editing recapitulated the mutant phenotype. BnaA01.CHLI1 and BnaC01.CHLI1 were located in chloroplast and highly expressed in the leaves. Furthermore, RNA-seq analyses revealed the expression of chlorophyll synthesis-related genes were upregulated in the crm1 mutant. These findings provide a new insight into the regulatory mechanism of chlorophyll synthesis in rapeseed and suggest a novel target for improving the photosynthetic efficiency and tolerance to high-light intensity in crops. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01429-6.

Development of PLA/Lignin Bio-Composites Compatibilized by Ethylene Glycol Diglycidyl Ether and Poly (ethylene glycol) Diglycidyl Ether.

Poly (lactic acid) (PLA) is a promising green substitute for conventional petroleum-based plastics in a variety of applications. However, the wide application of PLA is still limited by its disadvantages, such as slow crystallization rate, inadequate gas barrier, thermal degradation, etc. In this study, lignin (1, 3, 5 PHR) was incorporated into PLA to improve the thermal, mechanical, and barrier properties of PLA. Two low-viscosity epoxy resins, ethylene glycol diglycidyl ether (EGDE) and poly (ethylene glycol) diglycidyl ether (PEGDE), were used as compatibilizers to enhance the performance of the composites. The addition of lignin improved the onset degradation temperature of PLA by up to 15 °C, increased PLA crystallinity, improved PLA tensile strength by approximately 15%, and improved PLA oxygen barrier by up to 58.3%. The addition of EGDE and PEGDE both decreased the glass transition, crystallization, and melting temperatures of the PLA/lignin composites, suggesting their compatabilizing and plasticizing effects, which contributed to improved oxygen barrier properties of the PLA/lignin composites. The developed PLA/lignin composites with improved thermal, mechanical, and gas barrier properties can potentially be used for green packaging applications.

20-Deoxyingenol alleviates intervertebral disc degeneration by activating TFEB in nucleus pulposus cells.

Intervertebral disc degeneration (IVDD) is a prevalent degenerative disease with significant adverse implications for patients' quality of life and socioeconomic status. Although the precise etiology of IVDD remains elusive, the senescence of nucleus pulposus cells is recognized as the primary pathogenic factor of IVDD; however, drugs that may targetedly inhibit senescence are still lacking. In the current study, we evaluated the small-molecule active drug 20-Deoxyingenol(20-DOI) for its effects on combating senescence and delaying the progression of IVDD. In vitro experiments revealed that the administration of 20-DOI displayed inhibitory effects on senescence and the senescence-related cGAS-STING pathway of nucleus pulposus cells. Additionally, it exhibited the ability to enhance lysosome activity and promote autophagy flux within nucleus pulposus cells. Subsequent investigations elucidated that the inhibitory impact of 20-DOI on nucleus pulposus cell senescence was mediated through the autophagy-lysosome pathway. This effect was diminished in the presence of transcription factor EB (TFEB) small hairpin RNA (shRNA), thereby confirming the regulatory role of 20-DOI on the autophagy-lysosome pathway and senescence through TFEB. In vivo experiments demonstrated that 20-DOI effectively impeded the progression ofIVDD in rats. These findings collectively illustrate that 20-DOI may facilitate the autophagy-lysosomal pathway by activating TFEB, thereby suppressing the senescence in nucleus pulposus cells, thus suggesting 20-DOI as a promising therapeutic approach for IVDD.

A V2O5 cathode for aqueous rechargeable Pb-ion batteries.

Aqueous rechargeable metal batteries (AMBs) have attracted great attention and have been regarded as a next-generation promising energy storage system. However, the high-activity metal anodes usually face side reactions, passivation, and hydrogen evolution reactions, which impede the development of high-performance AMBs. Here, we designed and assembled a Pb metal battery based on a highly reversible Pb metal anode and layered V2O5 cathode, which showed good electrochemical performance. This new-type battery will encourage more investigations for high-performance AMBs and open up an innovation pathway for traditional lead-acid batteries.

Multiphase CT radiomics nomogram for preoperatively predicting the WHO/ISUP nuclear grade of small (< 4 cm) clear cell renal cell carcinoma.

BACKGROUND: Small (< 4 cm) clear cell renal cell carcinoma (ccRCC) is the most common type of small renal cancer and its prognosis is poor. However, conventional radiological characteristics obtained by computed tomography (CT) are not sufficient to predict the nuclear grade of small ccRCC before surgery. METHODS: A total of 113 patients with histologically confirmed ccRCC were randomly assigned to the training set (n = 67) and the testing set (n = 46). The baseline and CT imaging data of the patients were evaluated statistically to develop a clinical model. A radiomics model was created, and the radiomics score (Rad-score) was calculated by extracting radiomics features from the CT images. Then, a clinical radiomics nomogram was developed using multivariate logistic regression analysis by combining the Rad-score and critical clinical characteristics. The receiver operating characteristic (ROC) curve was used to evaluate the discrimination of small ccRCC in both the training and testing sets. RESULTS: The radiomics model was constructed using six features obtained from the CT images. The shape and relative enhancement value of the nephrographic phase (REV of the NP) were found to be independent risk factors in the clinical model. The area under the curve (AUC) values for the training and testing sets for the clinical radiomics nomogram were 0.940 and 0.902, respectively. Decision curve analysis (DCA) revealed that the radiomics nomogram model was a better predictor, with the highest degree of coincidence. CONCLUSION: The CT-based radiomics nomogram has the potential to be a noninvasive and preoperative method for predicting the WHO/ISUP grade of small ccRCC.

Preliminary observational study of metabonomics in patients with early and late-onset type 2 diabetes mellitus based on UPLC-Q-TOF/MS.

Non-targeted metabonomic techniques were used to explore changes in metabolic profiles of patients with early onset and late onset T2DM. Newly diagnosed early onset T2DM (EarT2DM) and late onset T2DM (LatT2DM) patients were recruited, and the matched age, sex, and low-risk population of diabetes mellitus were selected as the control group. 117 adults were recruited in the study, including 21 in EarT2DM group with 25 in corresponding control group (heaCG1), and 48 in LatT2DM group with 23 in corresponding control group (heaCG2). There were 15 relatively distinctive metabolic variants in EarT2DM group and 10 distinctive metabolic variants in LatT2DM group. The same changing pathways mainly involved protein, aminoacyl-tRNA biosynthesis, fatty acid biosynthesis, taurine metabolism, arginine biosynthesis, lysosome and mTOR signaling pathway. The independent disturbed pathways in EarT2DM included branched chain amino acids, alanine, aspartate and glutamate metabolism. The independent disturbed pathways in LatT2DM involved linoleic acid metabolism, biosynthesis of unsaturated fatty acids, arginine, proline metabolism and FoxO signaling pathway. T2DM patients at different diagnosed ages may have different metabolite profiles. These metabolic differences need to be further verified.