Tea is the world＇s oldest and most popular caffeine-containing beverage with immense economic, medicinal, and cultural importance. Here, we present the first high-quality nucleotide sequence of the ...repeat-rich （80.9%）, 3.02-Gb genome of the cultivated tea tree Camellia sinensis. We show that an extraordinarily large genome size of tea tree is resulted from the slow, steady, and long-term amplification of a few LTR retrotransposon families. In addition to a recent whole-genome duplication event, lineage-specific expansions of genes associated with flavonoid metabolic biosynthesis were discovered, which enhance catechin production, terpene enzyme activation, and stress tolerance, important features for tea flavor and adaptation. We demonstrate an independent and rapid evolution of the tea caffeine synthesis pathway relative to cacao and coffee. A comparative study among 25 Camellia species revealed that higher expression levels of most flavonoid- and caffeinebut not theanine-related genes contribute to the increased production of catechins and caffeine and thus enhance tea-processing suitability and tea quality. These novel findings pave the way for further metabolomic and functional genomic refinement of characteristic biosynthesis pathways and will help develop a more diversified set of tea flavors that would eventually satisfy and attract more tea drinkers worldwide.
Background
MR imaging has been applied to determine therapeutic response to glucocorticoid (GC) before treatment in thyroid‐associated ophthalmopathy (TAO), while the performance was still poor.
...Purpose
To investigate the value of T2‐weighted imaging (T2WI)‐derived radiomics for pretreatment determination of therapeutic response to GC in TAO patients, and compare its diagnostic performance with that of semiquantitative parameters.
Study Type
Retrospective.
Population
A total of 110 patients (49 ± 12 years; male/female, n = 48/62; responsive/unresponsive, n = 62/48), divided into training (n = 78) and validation (n = 32) cohorts.
Field Strength/Sequence
3.0 T, T2‐weighted fast spin echo.
Assessment
W.C. and H.H. (6 and 10 years of experience, respectively) performed the measurements. Maximum, mean, and minimum signal intensity ratios (SIRs) of extraocular muscle (EOM) bellies were collected to construct a semiquantitative imaging model. Radiomics features from volumes of interest covering EOM bellies were extracted and three machine learning‐based (logistic regression LR; decision tree DT; support vector machine SVM) models were built.
Statistical Tests
The diagnostic performances of models were evaluated using receiver operating characteristic curve analyses, and compared using DeLong test. Two‐sided P < 0.05 was considered statistically significant.
Results
The responsive group showed higher minimum signal intensity ratio (SIRmin) of EOMs than the unresponsive group (training: 1.46 ± 0.34 vs. 1.18 ± 0.39; validation: 1.44 ± 0.33 vs. 1.19 ± 0.20). In both cohorts, LR‐based radiomics model demonstrated good diagnostic performance (area under the curve AUC = 0.968, 0.916), followed by DT‐based (AUC = 0.933, 0.857) and SVM‐based models (AUC = 0.919, 0.855). All three radiomics models outperformed semiquantitative imaging model (SIRmin: AUC = 0.805) in training cohort. In validation cohort, only LR‐based radiomics model outperformed that of SIRmin (AUC = 0.745). The nomogram integrating LR‐based radiomics signature and disease duration further elevated the diagnostic performance in validation cohort (AUC: 0.952 vs. 0.916, P = 0.063).
Data Conclusion
T2WI‐derived radiomics of EOMs, together with disease duration, provides a promising noninvasive approach for determining therapeutic response before GC administration in TAO patients.
Level of Evidence
3
Technical Efficacy
Stage 4
Gadolinium (Gd)-based contrast agents (GBCAs) have been widely used for acute ischemic stroke (AIS) patients. GBCAs or AIS alone may cause the adverse effects on kidney tissue, respectively. However, ...whether GBCAs and AIS would generate a synergistic negative effect remains undefined.
To evaluate synergistic negative effects of AIS and GBCAs on renal tissues in a mouse model of AIS, and to compare the differences of these negative effects between linear and macrocyclic GBCAs.
Animal study.
Seventy-two healthy mice underwent transient middle cerebral artery occlusion (tMCAO) and sham operation to establish AIS and sham model (N = 36/model). 5.0 mmol/kg GBCAs (gadopentetate or gadobutrol) or 250 μL saline were performed at 4.5 hours and 1 day after model establishing (N = 12/group).
Inductively coupled plasma mass spectrometry (ICP-MS) was performed to detect Gd concentrations. Serum biochemical analyzer was performed to measure the serum creatinine (Scr), uric acid (UA), and blood urea nitrogen (BUN). Pathological staining was performed to observe tubular injury, cell apoptosis, mesangial hyperplasia, and interstitial fibrosis.
Two-way analysis of variances with post hoc Sidak's tests and independent-samples t-tests were performed. A P-value <0.05 was considered statistically significant.
AIS groups showed higher Gd concentration than sham group on day 1 p.i. regardless of gadopentetate or gadobutrol used. Increased total Gd concentration was also found in AIS + gadopentetate group compared with the sham group on day 28 p.i. Significantly higher rates for renal dysfunction, higher tubular injury scores, and higher numbers of apoptotic cells on days 1 or 28 p.i. were found for AIS mice injected with GBCA. AIS + gadopentetate group displayed more severe renal damage than the AIS + gadobutrol group.
AIS and GBCAs may cause increased total Gd accumulation and nephrotoxicity in a mouse, especially linear GBCAs were used.
1 TECHNICAL EFFICACY: Stage 4.
Oligodendrocytes (OLs) death after spinal cord injury (SCI) contributes to demyelination, even leading to a permanent neurological deficit. Besides apoptosis, our previous study demonstrated that OLs ...underwent receptor-interacting serine-threonine kinase 3(RIP3)/mixed lineage kinase domain-like protein (MLKL)-mediated necroptosis. Considering that necroptosis is always accompanied with pro-inflammatory response and quercetin has long been used as anti-inflammatory agent, in the present study we investigated whether quercetin could inhibit necroptosis of OLs and suppress the M1 macrophages/microglia-mediated immune response after SCI as well as the possible mechanism.
In this study, we applied quercetin, an important flavonoid component of various herbs, to treat rats with SCI and rats injected with saline were employed as the control group. Locomotor functional recovery was evaluated using Basso-Beattie-Bresnahan (BBB) scoring and rump-height Index (RHI) assay. In vivo, the necroptosis, apoptosis, and regeneration of OLs were detected by immunohistochemistry, 5'-bromo-2'-deoxyuridine (BrdU) incorporation. The loss of myelin and axons after SCI were evaluated by Luxol fast blue (LFB) staining, immunohistochemistry, and electron microscopic study. The polarization of macrophages/microglia after SCI and the underlying mechanisms were detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry. In vitro, the ATP and reactive oxygen species (ROS) level examination, propidium iodide (PI) labeling, and Western blotting were used to analyze the necroptosis of cultured OLs, while the signaling pathways-mediated polarization of cultured macrophages/microglia was detected by qRT-PCR and Western blotting.
We demonstrated that quercetin treatment improved functional recovery in rats after SCI. We then found that quercetin significantly reduced necroptosis of OLs after SCI without influencing apoptosis and regeneration of OLs. Meanwhile, myelin loss and axon loss were also significantly reduced in quercetin-treated rats, as compared to SCI + saline control. Further, we revealed that quercetin could suppress macrophages/microglia polarized to M1 phenotype through inhibition of STAT1 and NF-κB pathway in vivo and in vitro, which contributes to the decreased necroptosis of OLs.
Quercetin treatment alleviated necroptosis of OLs partially by inhibiting M1 macrophages/microglia polarization after SCI. Our findings suggest that necroptosis of OLs may be a potential therapeutic target for clinical SCI.
Accurate evaluation of tumor response to preoperative chemotherapy is crucial for assigning appropriate patients with colorectal liver metastases (CRLM) to surgery or conservative therapy. However, ...there is no well‐recognized method for predicting pathological response before surgery. Our study constructed and validated a deep learning algorithm using prechemotherapy and postchemotherapy magnetic resonance imaging (MRI) to predict pathological response in CRLM. CRLM patients from center one who had ≤5 lesions and were scheduled to receive preoperative chemotherapy followed by liver resection between January 2013 and November 2016, were included prospectively and chronologically divided into a training cohort (80% of patients) and a testing cohort (20% of patients). Patients from center two were included January 2017 and December 2018 as an external validation cohort. MRI‐based models were constructed to discriminate according to pathology tumor regression grade (TRG) between the response (TRG1/2) and nonresponse (TRG3/4/5) groups at the lesion level. From center one, 155 patients (328 lesions) were included; chronologically, 101 (264 lesions) in the training cohort and 54 (64 lesions) in the testing cohort. The model achieved better accuracy (0.875 vs 0.578) and AUC (0.849 vs 0.615) than RECIST for discriminating response; it also distinguished the survival outcomes after hepatectomy better than the RECIST criteria. Evaluations of the external validation cohort (25 patients, 61 lesions) also showed good ability with an AUC of 0.833. In conclusion, the MRI‐based deep learning model provided accurate prediction of pathological tumor response to preoperative chemotherapy in patients with CRLM and may inform individualized treatment.
What's new?
Liver metastasis is a major cause of death in patients with colorectal cancer. Tumor regression grade (TRG) is a good way to assess tumor response and predict patient survival, and is typically measured by pathological evaluation. Here, the authors tested a deep learning algorithm that uses MRI data to obtain TRG in patients with colorectal liver metastasis who were undergoing preoperative chemotherapy. The deep learning model achieved diagnostic accuracy of 87.5%, a big improvement over the previous method, the RECIST criteria (57.8%). This system could help clinicians provide appropriate personalized information to patients about treatment response and prognosis.
Aim
Tyrosine kinase inhibitors target transarterial chemoembolization (TACE)‐mediated vascular endothelial growth factor to inhibit tumor revascularization and to slow tumor progression. The present ...study aimed to compare the clinical outcomes of TACE combined with lenvatinib (TACE‐lenvatinib) and TACE combined with sorafenib (TACE‐sorafenib) in patients with unresectable hepatocellular carcinoma (HCC).
Methods
The clinical data of patients diagnosed with unresectable HCC who received TACE‐lenvatinib or TACE‐sorafenib between January 2018 and April 2021 were retrospectively reviewed. The tumor response, progression‐free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated and compared between the two groups.
Results
A total of 112 patients were enrolled and classified into the TACE‐lenvatinib group (n = 53) and the TACE‐sorafenib group (n = 59). The objective response rates of patients in the TACE‐lenvatinib and TACE‐sorafenib groups were 54.7% and 44.1%, respectively (p = 0.260), and the disease control rates (DCRs) were 81.1% and 61.0% (p = 0.020). The median PFS time was significantly longer in the TACE‐lenvatinib group than in the TACE‐sorafenib group (10.7 vs. 6.0 months; p = 0.002). The median OS time between the TACE‐lenvatinib and TACE‐sorafenib groups also showed a significant difference (30.5 vs. 20.5 months, p = 0.018). All treatment‐related AEs and grade 3/4 AEs were comparable between the two groups (p > 0.05).
Conclusion
Compared to TACE‐sorafenib, TACE‐lenvatinib was associated with better DCR, PFS and OS outcomes in patients with unresectable HCC. In subgroups of Barcelona Clinic Liver Cancer B stage or TACE‐refractory patients, TACE‐lenvatinib also showed a trend of superiority.
High entropy alloy coatings show great potential for improving the wear resistance of the stainless-steel substrate. However, there are few comparative studies on the tribological properties of high ...entropy alloy coatings with different elements. In the present study, the FeCoCrNiCux and FeCoCrNiSix high entropy alloy coatings were designed and prepared by laser cladding. The microstructures of the high entropy coating were analyzed. The tribological properties of the high entropy alloy coatings sliding against Si3N4 balls at room temperature and 600 °C were investigated. The results show that after adding Cu/Si, the tribological properties of the coating change little at room temperature, but increased significantly at high temperature of 600 °C. The FeCoCrNiSi coating has the best tribological performance at 600 °C with an average friction coefficient and wear rate of 0.19 and 0.677 (×10−4 mm3/N·m), respectively. In general, the addition of Cu increases the thermal conduction ability of the coating, improves the toughness and the bonding strength of the coating; the addition of Si refines the grain size, increases the degree of work hardening and improves the wear resistance of the coating.
•The effect of Cu/Si on laser cladding FeCoCrNi coatings was investigated.•The addition of Cu/Si in equal molar ratio at room temperature improved wear resistance of FeCoCrNi coating.•At 600 °C, the addition of Cu/Si both improved the tribological properties of FeCoCrNi coating.•The FeCoCrNiSi coating showed the best tribological performance at high temperature (600 °C).
Purpose
To investigate the effects of gadolinium (Gd) retention of macrocyclic (gadobutrol) or linear (gadopentetate) Gd‐based contrast agents (GBCAs) on neuron loss, neurological deficits, and ...sensory behavior in mice with or without stroke.
Methods
Ninety C57BL/6 mice underwent sham (n = 36) or transient middle cerebral artery occlusion (tMCAO) (n = 54) surgery and then received intraperitoneal injections of 5.0 mmol/kg gadobutrol, 5.0 mmol/kg gadopentetate or saline (10 ml/kg/administration) per day for 3 consecutive days. The Gd concentration in the ischemic cerebrum was quantified by inductively coupled plasma mass spectrometry on Day 1 and Day 28 after the last injection (post‐injection, p. i.). Neuron loss, glia activation and neurological deficits were assessed on Day 1 and 28 p. i. Sensory behavior was also assessed on Day 28 p. i.
Results
Gd concentrations were higher in the brains of tMCAO mice than in those of sham mice on Days 1 p. i. of both GBCAs (gadobutrol, p < 0.05; gadopentetate, p < 0.001) and 28 p. i of gadopentetate. (p < 0.001). Sham or tMCAO mice injected with GBCAs showed no significant difference in neuron loss, glia activation, neurological deficits, brain atrophy, or hippocampus‐dependent memory (all p > 0.05). Both gadobutrol and gadopentetate induced mechanical and heat hyperalgesia in sham mice (all p < 0.05). However, mechanical hyperalgesia but rather heat hyperalgesia was found in tMCAO mice with the highest force tested (1.0 g) and statistically significant in both paws (right and left) with gadopentetate only (p < 0.05).
Conclusions
Neither gadobutrol nor gadopentetate worsened neuron loss, glia activation, brain atrophy, neurological deficits, or hippocampus‐dependent memory after tMCAO. However, GBCA administration induced mechanical hyperalgesia in sham and tMCAO mice although in the same level, which may be an important consideration for patients with central post‐stroke pain and those who are sensitive to pain and about to receive multiple GBCA administrations.
We present a detection of 89 candidates of ultra-diffuse galaxies (UDGs) in a 4.9 degree2 field centered on the Hickson Compact Group 95 (HCG 95) using deep g- and r-band images taken with the ...Chinese Near Object Survey Telescope. This field contains one rich galaxy cluster (Abell 2588 at z = 0.199) and two poor clusters (Pegasus I at z = 0.013 and Pegasus II at z = 0.040). The 89 candidates are likely associated with the two poor clusters, giving about 50-60 true UDGs with a half-light radius and a central surface brightness mag arcsec−2. Deep -band images are available for 84 of the 89 galaxies from the Dark Energy Camera Legacy Survey (DECaLS), confirming that these galaxies have an extremely low central surface brightness. Moreover, our UDG candidates are spread over a wide range in g − r color, and ∼26% are as blue as normal star-forming galaxies, which is suggestive of young UDGs that are still in formation. Interestingly, we find that one UDG linked with HCG 95 is a gas-rich galaxy with H i mass M detected by the Very Large Array, and has a stellar mass of M . This indicates that UDGs at least partially overlap with the population of nearly dark galaxies found in deep H i surveys. Our results show that the high abundance of blue UDGs in the HCG 95 field is favored by the environment of poor galaxy clusters residing in H i-rich large-scale structures.
Purpose
To determine the optimal combination of parameters derived from 3T multiparametric (conventional magnetic resonance imaging MRI, diffusion‐weighted DW and dynamic contrast‐enhanced DCE) MRI ...for differentiating malignant from benign orbital lymphoproliferative disorders (OLPDs).
Materials and Methods
Forty patients with OLPDs (18 benign and 22 malignant) underwent conventional 3.0T MR, DW, and DCE‐MRI examination for presurgery evaluation. Conventional MRI features (including tumor laterality, shape, number of involved quadrants, signal intensity on T1‐weighted imaging (WI) and T2WI, flow void sign on T2WI, and findings suggestive of sinusitis) were reviewed, and multivariate logistic regression analysis was used to identify the most significant conventional MRI features. Apparent diffusion coefficient (ADC) and DCE‐MRI derived parameters (area under curve AUC, time to peak TTP, maximum rise slope Slopemax) were measured and compared between two groups. Receiver operating characteristic (ROC) curve analyses were used to determine the diagnostic ability of each combination that was established based on identified qualitative and quantitative parameters.
Results
Multivariate logistic regression analysis showed that the presence of flow void sign on T2WI significantly associated with benign OLPDs (P = 0.034). Malignant OLPDs demonstrated significantly lower ADC (P = 0.001) and AUC (P = 0.002) than benign mimics. ROC analyses indicted that, ADC alone showed the optimal sensitivity (threshold value, 0.886 × 10−3 mm2/s; sensitivity, 90.9%), while a combination of no presence of flow void sign on T2WI + ADC ≤ 0.886 × 10−3 mm2/s + AUC ≤ 7.366 showed optimal specificity (88.9%) in differentiating benign from malignant OLPDs.
Conclusion
Multiparametric MRI can help to differentiate malignant from benign OLPDs. DWI offers optimal sensitivity, while the combination of conventional MRI, DWI, and DCE‐MRI offers optimal specificity.
Level of Evidence: 3
J. Magn. Reson. Imaging 2017;45:167–176.
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