Microplastics from polyvinyl chloride agricultural plastic films do not change nitrogenous gas emission but enhance denitrification potential.

The effects of microplastics (MPs) from agricultural plastic films on soil nitrogen transformation, especially denitrification, are still obscure. Here, using a robotized flow-through system, we incubated vegetable upland soil cores for 66 days with MPs from PE mulching film (F-PE) and PVC greenhouse film (F-PVC) and directly quantified the emissions of nitrogenous gases from denitrification under oxic conditions, as well as the denitrification potential under anoxic conditions. The impact of MPs on soil nitrogen transformation was largely determined by the concentration of the additive phthalate esters (PAEs) containing in the MPs. The F-PE MPs with low level of PAEs (about 0.006 %) had no significant effect on soil mineral nitrogen content and nitrogenous gas emissions under oxic conditions. In contrast, the F-PVC MPs with high levels of PAEs (about 11 %) reduced soil nitrate content under oxic conditions, probably owing to promoted microbial assimilation of nitrogen, as the emissions of denitrification products (N2, NO, and N2O) was not affected. However, the F-PVC MPs significantly enhanced the denitrification potential of the soil due to the increased abundance of denitrifiers under anoxic conditions. These findings highlight the disturbance of MPs from agricultural films, particularly the additive PAEs on nitrogen transformation in soil ecosystems.

Auranofin inhibits the occurrence of colorectal cancer by promoting mTOR-dependent autophagy and inhibiting epithelial-mesenchymal transformation.

Colorectal cancer (CRC) is one of the world's most common and deadly cancers. According to GLOBOCAN2020's global incidence rate and mortality estimates, CRC is the third main cause of cancer and the second leading cause of cancer-related deaths worldwide. The US Food and Drug Administration has approved auranofin for the treatment of rheumatoid arthritis. It is a gold-containing chemical that inhibits thioredoxin reductase. Auranofin has a number of biological activities, including anticancer activity, although it has not been researched extensively in CRC, and the mechanism of action on CRC cells is still unknown. The goal of this research was to see how Auranofin affected CRC cells in vivo and in vitro . The two chemical libraries were tested for drugs that make CRC cells more responsive. The CCK-8 technique was used to determine the cell survival rate. The invasion, migration, and proliferation of cells were assessed using a transwell test and a colony cloning experiment. An electron microscope was used to observe autophagosome formation. Western blotting was also used to determine the degree of expression of related proteins in cells. Auranofin's tumor-suppressing properties were further tested in a xenograft tumor model of human SW620 CRC cells. Auranofin dramatically reduced the occurrence of CRC by decreasing the proliferation, migration, and invasion of CRC cells, according to our findings. Through a mTOR-dependent mechanism, auranofin inhibits the epithelial-mesenchymal transition (EMT) and induces autophagy in CRC cells. Finally, in-vivo tests revealed that auranofin suppressed tumor growth in xenograft mice while causing no harm. In summary, auranofin suppresses CRC cell growth, invasion, and migration. Auranofin inhibits the occurrence and progression of CRC by decreasing EMT and inducing autophagy in CRC cells via a mTOR-dependent mechanism. These findings suggest that auranofin could be a potential chemotherapeutic medication for the treatment of human CRC.

Pemigatinib, a selective FGFR inhibitor overcomes ABCB1-mediated multidrug resistance in cancer cells.

P: -glycoprotein (P-gp/ABCB1) overexpression is one of the primary causes of multidrug resistance (MDR). Therefore, it is crucial to discover effective pharmaceuticals to combat multidrug resistance mediated by ABCB1. Pemigatinib is a selective the fibroblast growth factor receptor (FGFR) inhibitor that is used to treat a variety of solid tumors, Clinical Trials for Urothelial Carcinoma (NCT02872714) completed its research on Pemigatinib. This study aimed to determine whether Pemigatinib can reverse ABCB1-mediated multidrug resistance, as well as its mechanism of action. Pemigatinib substantially reversed ABCB1-mediated multidrug resistance, as determined by a CCK8 assay, and immunofluorescence experiments revealed that Pemigatinib had no effect on the intracellular localization of ABCB1. Pemigatinib was discovered to increase intracellular drug accumulation, thereby reversing multidrug resistance. In addition, Docking analysis revealed that Pemigatinib and ABCB1 have a high affinity for one another. This study concludes that Pemigatinib is capable of reversing the multidrug resistance mediated by ABCB1, offering ideas and references for the clinical application of Pemigatinib.

Cardiac Dose Predicts the Response to Concurrent Chemoradiotherapy in Esophageal Squamous Cell Carcinoma.

Definitive concurrent chemoradiation (CCRT) is the standard treatment for cervical esophageal cancer and non-surgical candidates. Initial treatment response affects survival; however, few validated markers are available for prediction. This study evaluated the clinical variables and chemoradiation parameters associated with treatment response. Between May 2010 and April 2016, 86 completed CCRT patients' clinical, dosimetric, and laboratory data at baseline and during treatment were collected. Cox regression analysis assessed the risk factors for overall survival (OS). A receiver operating characteristic curve with Youden's index was chosen to obtain the optimal cut-off value of each parameter. Treatment response was defined per Response Evaluation Criteria in Solid Tumors v.1.1 at the first post-CCRT computed tomography scan. Responders had complete and partial responses; non-responders had stable and progressive diseases. Logistic regression (LR) was used to evaluate the variables associated with responders. The Cox regression model confirmed the presence of responders (n = 50) vs. non-responders (n = 36) with a significant difference in OS. In multivariate LR, cardiac dose-volume received ≥10 Gy; the baseline hemoglobin level, highest neutrophil to lymphocyte ratio during CCRT, and cumulative cisplatin dose were significantly associated with the responders. The initial clinical treatment response significantly determines disease outcome. Cardiac irradiation may affect the treatment response.

Real-World Use of Electronic Patient-Reported Outcome (ePRO) Tools Integrated in the Electronic Medical Record During Radiation Therapy for Head and Neck Cancer: Feasibility Study.

Purpose Use of electronic patient-reported outcome (ePRO) tools in routine oncology practice can be challenging despite evidence showing they can improve survival, improve patient and practitioner satisfaction, and reduce medical resource utilization. Head and neck cancer (HNC) patients receiving radiation therapy (RT) may be a group that would particularly benefit from interventions focused on early symptom management. Methods Patients undergoing definitive RT for HNC were enrolled in a feasibility study and received ePRO surveys integrated within the electronic medical record (EMR) on a weekly basis during RT. After completion of each ePRO survey, a radiation oncology registered nurse documented the findings and subsequent interventions within the EMR. Results Thirty-four patients with HNC who received curative RT at a single center were enrolled. The total number of surveys completed was 194 with a median of 7 surveys per patient (range 1-8). There was a total of 887 individual abnormal findings reported on the ePROs, and the authors found that all 887 had a corresponding documented intervention. Post-treatment practitioner questionnaires highlighted that ePROs were felt to be helpful for the care team in providing care to HNC patients. Conclusion For patients with HNC receiving RT, ePROs can be effectively utilized to address patient symptoms within an integrated health care system. Creating an infrastructure for the use of ePROs integrated within the EMR in routine care requires an approach that accounts for local workflows and buy-in from patients and the entire care team.

Clinical features of retinal amyloid angiopathy with transthyretin Gly83Arg variant.

AIM: To report on the clinical features of patients with retinal amyloid angiopathy (RAA) who were identified to be caused by the transthyretin (TTR) Gly83Arg variant. METHODS: Case series of five patients diagnosed with RAA was collected at Affiliated Hospital of Zunyi Medical University from January 2010 to December 2021. The clinical features, therapeutic strategies, and prognoses of all patients were reviewed. RESULTS: Five patients with a mean age of 52.00±7.23y were diagnosed as RAA. These patients were previously diagnosed with hereditary transthyretin amyloidosis caused by the TTR Gly83Arg variant. Vitreous opacity was found in all 10 eyes, and 7 eyes developed RAA 2 to 20y after the onset of hereditary transthyretin amyloidosis. The clinical manifestations were recurrent vitreous hemorrhage in 2 eyes (29%), neovascular glaucoma in 2 eyes (29%), and iris neovascularization in 1 eye (14%). Microangioma lesions were found in all affected eyes that underwent fundus fluorescein angiography (FFA) in this group of cases, and the incidence of the retinal non-perfusion area was 67%. Although no cases of retinal neovascularization were found, the prognosis of visual acuity was not ideal. CONCLUSION: This is the first report of RAA in patients with the TTR Gly83Arg variant. Complications such as RAA and glaucoma will seriously affect the visual prognosis of patients. Thereafter, regular ophthalmic follow-up of patients with hereditary transthyretin amyloidosis is essential. And FFA after vitrectomy is very important, which can help ophthalmologists detect RAA earlier and treat it in time.

Blocking postsynaptic density-93 binding to C-X3-C motif chemokine ligand 1 promotes microglial phenotypic transformation during acute ischemic stroke.

We previously reported that postsynaptic density-93 mediates neuron-microglia crosstalk by interacting with amino acids 357-395 of C X3 C motif chemokine ligand 1 (CX3CL1) to induce microglia polarization. More importantly, the peptide Tat-CX3CL1 (comprising amino acids 357-395 of CX3CL1) disrupts the interaction between postsynaptic density-93 and CX3CL1, reducing neurological impairment and exerting a protective effect in the context of acute ischemic stroke. However, the mechanism underlying these effects remains unclear. In the current study, we found that the pro-inflammatory M1 phenotype increased and the anti-inflammatory M2 phenotype decreased at different time points. The M1 phenotype increased at 6 hours after stroke and peaked at 24 hours after perfusion, whereas the M2 phenotype decreased at 6 and 24 hours following reperfusion. We found that the peptide Tat-CX3CL1 (357-395aa) facilitates microglial polarization from M1 to M2 by reducing the production of soluble CX3CL1. Furthermore, the a disintegrin and metalloprotease domain 17 (ADAM17) inhibitor GW280264x, which inhibits metalloprotease activity and prevents CX3CL1 from being sheared into its soluble form, facilitated microglial polarization from M1 to M2 by inhibiting soluble CX3CL1 formation. Additionally, Tat-CX3CL1 (357-395aa) attenuated long-term cognitive deficits and improved white matter integrity as determined by the Morris water maze test at 31-34 days following surgery and immunofluorescence staining at 35 days after stroke, respectively. In conclusion, Tat-CX3CL1 (357-395aa) facilitates functional recovery after ischemic stroke by promoting microglial polarization from M1 to M2. Therefore, the Tat-CX3CL1 (357-395aa) is a potential therapeutic agent for ischemic stroke.

Single-string, closed-loop fixation modification to reposit a dislocated triple-looped haptic intraocular lens.

A technique using the single-string, closed-loop fixation method to reposit dislocated triple-looped haptic intraocular lens (IOL)-capsular bag complex is described. The long needle or curved needle with a 10-0/8-0 polypropylene suture and a 27/30-gauge needle were used as the guide needle to pass through the fenestrated haptics twice. The scleral interlaminar course was used as the fixed point. Last, a fixation knot was created in the sclerotomy by the 2 ends of the thread to close the suture loop for IOL fixation. Another knot was created about 2 to 3 mm from the exit point and was intrasclerally anchored by the aid of the attached needle. 4 eyes from 4 consecutive patients were studied retrospectively; during all follow-up visits, the IOLs were well centered and stable, and no suture erosion, hypotony, scleral atrophy, chronic inflammation, retinal tears, and/or detachments were observed.

Elevated CO2 does not necessarily enhance greenhouse gas emissions from rice paddies.

Elevated atmospheric carbon dioxide (eCO2) greatly impacts greenhouse gas (GHG) emissions of CH4 and N2O from rice fields. Although eCO2 generally stimulates GHG emissions in the short term (<5 years) experiments, the responses to long-term (≥10 years) eCO2 remain poorly known. Here we show, through a series of experiments and meta-analysis, that the eCO2 does not necessarily increase CH4 and N2O emissions from rice paddies. In an experiment of free-air CO2 enrichment for 13-15 years, CH4 and N2O emissions were decreased by 11-54% and 33-54%, respectively. The decline of CH4 emissions was related to the reduction of CH4 production and enhancement of CH4 oxidation via raising soil Eh and soil-water interface [O2] under eCO2. Moreover, the eCO2 significantly decreased NH4+-N content, suggesting a reduction of soil nitrification and thereby N2O emissions. A meta-analysis showed that CH4 and N2O emissions were stimulated under short-term eCO2 while reduced under long-term eCO2. The eCO2-induced increase in yield and biomass and the ratio of mcrA genes/pmoA genes declined with eCO2 duration, indicating an eCO2-stimulation of methanogenesis lower than that of methanotrophy over time by fewer increased substrates. Upscaling the results of meta-analysis, the eCO2-induced global paddy CH4 and N2O emissions shifted from an increase (+0.17 Pg CO2-eq year-1) in the short term into a decrease (-0.11 Pg CO2-eq year-1) in the long term. Our findings suggest that the effect of eCO2 on GHG emissions changes over time, and this should be considered in future climate change research.

Clinical value of contrast-enhanced ultrasound enhancement patterns for differentiating solid pancreatic lesions.

OBJECTIVES: To explore the diagnostic value of contrast-enhanced ultrasound (CEUS) enhancement patterns for differentiating solid pancreatic lesions and compare them with conventional ultrasound (US) and enhanced computed tomography (CT). METHODS: A total of 210 patients with solid pancreatic lesions who had definite pathological or clinical diagnoses were enrolled. Six CEUS enhancement patterns were proposed for solid pancreatic lesions. Two US doctors blindly observed the CEUS patterns of solid pancreatic lesions and the interrater agreement was analyzed. The diagnostic value of CEUS enhancement patterns for differentiating solid pancreatic lesions was evaluated, and the diagnostic accuracy was compared with that of US and enhanced CT. RESULTS: There was good concordance for six CEUS enhancement patterns of solid pancreatic lesions between the two doctors, with a kappa value of 0.767. Hypo-enhancement (Hypo-E) or centripetal enhancement (Centri-E) as the diagnostic criteria for pancreatic carcinoma had an accuracy of 87.62%; hyper-enhancement (Hyper-E) for neuroendocrine tumors had an accuracy of 92.89%; capsular enhancement with low or uneven enhancement inside the tumor (Capsular-E) for solid pseudopapillary tumors had an accuracy of 97.63%; and iso-enhancement (Iso-E) or iso-enhancement with focal hypo-enhancement (Iso-fhypo-E) for focal pancreatitis had an accuracy of 89.10%. The diagnostic accuracy of CEUS was significantly different from that of US for 210 cases of solid pancreatic lesions (p < 0.05) and was not significantly different from that of enhanced CT for 146 cases of solid pancreatic lesions (p > 0.05). CONCLUSIONS: The different enhancement patterns of solid pancreatic lesions on CEUS were clinically valuable for differentiation. KEY POINTS: • Six CEUS enhancement (E) patterns, including Hyper-E, Iso-E, Iso-fhypo-E, Hypo-E, Centri-E, and Capsular-E, are proposed for the characterization of solid pancreatic lesions. • Using Hypo-E or Centri-E as the diagnostic criteria for pancreatic carcinoma, Hyper-E for neuroendocrine tumors, Capsular-E for solid pseudopapillary tumors, and Iso-E or Iso-fhypo-E for focal pancreatitis on CEUS had relatively high diagnostic accuracy. • The diagnostic accuracy of CEUS was greatly increased over that of US and was not different from that of enhanced CT.

Machine Learning Assisted Doppler Features for Enhancing Thyroid Cancer Diagnosis: A Multi-Cohort Study.

BACKGROUND: This pilot study aims at exploiting machine learning techniques to extract color Doppler ultrasound (CDUS) features and to build an artificial neural network (ANN) model based on these CDUS features for improving the diagnostic performance of thyroid cancer classification. METHODS: A total of 674 patients with 712 thyroid nodules (TNs) (512 from internal dataset and 200 from external dataset) were randomly selected in this retrospective study. We used ANN to build a model (TDUS-Net) for classifying malignant and benign TNs using both the automatically extracted quantitative CDUS features (whole ratio, intranodular ratio, peripheral ratio, and number of vessels) and gray-scale ultrasound (US) features defined by the American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS). Then, we compared the diagnostic performance of the model, the performance of another ANN model based on the gray-scale US features alone (TUS-Net), and that of radiologists. RESULTS: The TDUS-Net (0.898, 95% CI: 0.868-0.922) achieved a higher area under the curve (AUC) than that of TUS-Net (0.881, 95% CI: 0.850-0.908) in the internal tests. Compared with radiologists, TDUS-Net (AUC: 0.925, 95% CI: 0.880-0.958) performed better than radiologists (AUC: 0.810, 95% CI: 0.749-0.862) in the external tests. CONCLUSIONS: Applying a machine learning model by combining both gray-scale US features and CDUS features can achieve comparable or even higher performance than radiologists in classifying TNs.

Chemical characters and protective effect of Baqi Lingmao formula on experimental liver injury.

OBJECTIVE: To investigate the chemical characters of water-extract of Baqi Lingmao formula (BQLM formula) and its effects on anti-liver injury in model mice and live cells. METHODS: BQLM formula was composed of ten herbal medicines. We determined the contents of alkaloids, saponins, phenolic acids and flavonoid in BQLM formula by UV spectrophotometry. The active components of alkaloids and phenolic acids in BQLM formula were identified by HPLC chromatography. The anti-hepatic injury effects of BQLM formula were investigated with concanavalin A (ConA)-induced hepatitis model of mice, human liver LO2 and HepG2.2.15 cells. RESULTS: BQLM formula (2 and 10 g/kg, orally) significantly improved the damages of liver tissues and functions caused by ConA in mice, reduced the infiltration of inflammatory cells into liver and inhibited the inflammatory cytokine secretion of interferon-γ, tumor necrosis factor-α and interleukin-6. BQLM formula simultaneously decreased the levels of alanine aminotransferase and aspartate aminotransferase of liver and serum, and recovered the superoxide dismutase and catalase activities of liver to normal levels in ConA-induced hepatic-injury mice. The serum of BQLM formula group stimulated the human liver LO2 cell proliferation in vitro. Further, BQLM formula obviously promoted the proliferation of normal hepatocytes (LO2 cells) and inhibited the hepatocytes death induced by ConA. It also significantly inhibited the proliferation of HepG2.2.15 cells and decreased the secretion of HBsAg and HBeAg in vitro. CONCLUSIONS: BQLM formula has anti-inflammation and anti-hepatitis virus Beffects, and is capable of improving liver injury in vivo and in vitro.

Added Value of Superb Microvascular Imaging and Virtual Touch Imaging Quantification in Assisting Thyroid Cancer Classification.

This prospective study determined the value added by superb microvascular imaging (SMI) and Virtual Touch imaging quantification (VTIQ) to conventional ultrasonography in classifying malignant and benign thyroid nodules. One hundred eighty-three thyroid nodules (TNs) in 120 patients (112 benign and 71 malignant TNs) were evaluated. SMI revealed noticeable variance between benign and malignant TNs (p < 0.001). Malignant nodules tended to have rich vascularity (grade 3: 38/71, 53.5%) compared with benign nodules (grade 3: 33/112, 29.5%). There is a statistically significant difference between malignant and benign TNs with respect to shear-wave speed (SWS) values (all p values <0.001). The SWS mean, maximum and ratio of malignant nodules were 3.97 ± 1.34, 4.79 ± 1.70 and 1.25 ± 0.39, respectively. The SWS mean, maximum and ratio of benign nodules were 2.65 ± 0.42, 2.97 ± 0.46 and 1.15 ± 0.35, respectively. With respect to area under the curve values, the combined use of SMI or VTIQ improved the diagnostic performance of classifying malignant and benign TNs compared with that of ultrasonography alone. The combination of three modalities achieved the greatest area under the curve values (0.9811, 95% confidence interval: 0.95529-1.000), followed by US + VTIQ (0.9747, 0.94543-1.000), US + SMI (0.9032, 0.85345-0.95391) and ultrasonography (0.8291, 0.76417-0.89403).

Low cardiac dose and neutrophil-to-lymphocyte ratio predict overall survival in inoperable esophageal squamous cell cancer patients after chemoradiotherapy.

We aimed to determine the prognostic significance of cardiac dose and hematological immunity parameters in esophageal cancer patients after concurrent chemoradiotherapy (CCRT). During 2010-2015, we identified 101 newly diagnosed esophageal squamous cell cancer patients who had completed definitive CCRT. Patients' clinical, dosimetric, and hematological data, including absolute neutrophil count, absolute lymphocyte count, and neutrophil-to-lymphocyte ratio (NLR), at baseline, during, and post-CCRT were analyzed. Cox proportional hazards were calculated to identify potential risk factors for overall survival (OS). Median OS was 13 months (95% confidence interval [CI]: 10.38-15.63). Univariate analysis revealed that male sex, poor performance status, advanced nodal stage, higher percentage of heart receiving 10 Gy (heart V10), and higher NLR (baseline and follow-up) were significantly associated with worse OS. In multivariate analysis, performance status (ECOG 0 & 1 vs. 2; hazard ratio [HR] 3.12, 95% CI 1.30-7.48), heart V10 (> 84% vs. ≤ 84%; HR 2.24, 95% CI 1.26-3.95), baseline NLR (> 3.56 vs. ≤ 3.56; HR 2.36, 95% CI 1.39-4.00), and follow-up NLR (> 7.4 vs. ≤ 7.4; HR 1.95, 95% CI 1.12-3.41) correlated with worse OS. Volume of low cardiac dose and NLR (baseline and follow-up) were associated with worse patient survival.

Longibramides A-E, Peptaibols Isolated from a Mushroom Derived Fungus Trichoderma longibrachiatum Rifai DMG-3-1-1.

Five new peptaibols, longibramides A-E (1-5) with 11 amino acid residues, were isolated from a fungus Trichoderma longibrachiatum Rifai DMG-3-1-1, which was isolated from a mushroom Clitocybe nebularis (Batsch) P. Kumm collected from coniferous forest in the subboreal area of northeast China. The structures of longibramides A-E were determined by their spectroscopic data (NMR and MS-MS spectra), their absolute configurations were determined by X-ray diffractions and Marfey's analyses. The X-ray diffractions of longibramides A, B, and the similar CD spectra of A-E showed that they all had α-helix conformations. Longibramides B and E showed moderate cytotoxicities against BV2 and MCF-7 cells and also showed some inhibitory effects against methicillin-resistant Staphylococcus aureus MRSA T144. L-trans-Hyp was not commonly found in natural peptaibols, which was the 6th or 10th amino acid residue in longibramides C-E. The X-ray diffractions of longibramides A and B afforded the accuracy conformations of their secondary structures, which maybe help to interpret the structure-activity relationships of the family of peptaibols in the future.

A Large-Scale Association Study Detects Novel Rare Variants, Risk Genes, Functional Elements, and Polygenic Architecture of Prostate Cancer Susceptibility.

To identify rare variants associated with prostate cancer susceptibility and better characterize the mechanisms and cumulative disease risk associated with common risk variants, we conducted an integrated study of prostate cancer genetic etiology in two cohorts using custom genotyping microarrays, large imputation reference panels, and functional annotation approaches. Specifically, 11,984 men (6,196 prostate cancer cases and 5,788 controls) of European ancestry from Northern California Kaiser Permanente were genotyped and meta-analyzed with 196,269 men of European ancestry (7,917 prostate cancer cases and 188,352 controls) from the UK Biobank. Three novel loci, including two rare variants (European ancestry minor allele frequency < 0.01, at 3p21.31 and 8p12), were significant genome wide in a meta-analysis. Gene-based rare variant tests implicated a known prostate cancer gene (HOXB13), as well as a novel candidate gene (ILDR1), which encodes a receptor highly expressed in prostate tissue and is related to the B7/CD28 family of T-cell immune checkpoint markers. Haplotypic patterns of long-range linkage disequilibrium were observed for rare genetic variants at HOXB13 and other loci, reflecting their evolutionary history. In addition, a polygenic risk score (PRS) of 188 prostate cancer variants was strongly associated with risk (90th vs. 40th-60th percentile OR = 2.62, P = 2.55 × 10-191). Many of the 188 variants exhibited functional signatures of gene expression regulation or transcription factor binding, including a 6-fold difference in log-probability of androgen receptor binding at the variant rs2680708 (17q22). Rare variant and PRS associations, with concomitant functional interpretation of risk mechanisms, can help clarify the full genetic architecture of prostate cancer and other complex traits. SIGNIFICANCE: This study maps the biological relationships between diverse risk factors for prostate cancer, integrating different functional datasets to interpret and model genome-wide data from over 200,000 men with and without prostate cancer.See related commentary by Lachance, p. 1637.

The 17-Gene Genomic Prostate Score Test as a Predictor of Outcomes in Men with Unfavorable Intermediate Risk Prostate Cancer.

OBJECTIVES: To evaluate the association of the Genomic Prostate Score (GPS) assay result with biochemical recurrence (BCR), distant metastases (DM), and prostate-specific death (PCD) in unfavorable intermediate (UFI) risk prostate cancer patients. The GPS assay is used to help guide management decisions for newly diagnosed low and favorable intermediate (FI) risk disease. METHODS: GPS results from 2 studies (Center for Prostate Disease Research [CPDR]; Kaiser Permanente Northern California [KPNC]) in men treated with radical prostatectomy were analyzed to determine associations of the GPS result with BCR, DM, and PCD in UFI risk disease. Analyses included 299 intermediate risk prostate patients, 175 of whom had UFI risk disease (KPNC = 103; CPDR = 72). RESULTS: The GPS result as a dichotomous value (≤40 vs >40) was a significant predictor of BCR in UFI patients in multivariate analyses (hazard ratio [HR] 6.0; 95% confidence interval [CI] 2.0-22.4; P = .0035; CPDR). The GPS result was a strong predictor of all 3 endpoints in multivariate analyses (BCR HR 7.1; 95% CI 5.7-8.8; P < .0001; DM HR 5.4; 95% CI 3.8-7.8; P < .0001; PCD HR 3.4; 95% CI 1.5-8.9; P = .006; KPNC). UFI patients with GPS >40 had outcomes consistent with high-risk disease, whereas UFI patients with GPS ≤40 had outcomes similar to FI risk patients (CPDR/KPNC). CONCLUSIONS: The GPS result was a strong independent predictor of BCR, DM, and PCD in intermediate risk prostate cancer. UFI patients with GPS >40 have a poor prognosis and may benefit from additional therapeutic options.

Magnetic resonance imaging and photothermal conversion properties of Gd-C nanocomposites for interstitial lymphography.

Dual-functional agents for magnetic resonance imaging (MRI) guided photothermal therapy (PTT) of lymph cancer are highly desired. Signal enhancement, selectivity between lymphatic nodes/vessels and blood vessels, and photothermal conversion property are the criteria for such dual-functional agent. In the current work, we demonstrated the potential of Gd-C nanocomposites as dual-functional agents for the MRI and PTT of lymph node cancer. Gd-C nanocomposites were synthesized via a hydrothermal carbonization approach with gadolinium chloride as Gd source and citric acid (CA) as C source. The particle size of the nanocomposites ranges from 40 to 100 nm which is smaller than the intercellular space of lymphatic vessels but much larger than that of the blood vessels. The nanocomposites were successfully applied to the MRI of cervical lymph nodes of rabbits. The signal enhancement of the lymph nodes reached the maximum value of 434% at 10 min after injection, without displaying any blood vessel. The Gd-C nanocomposites also exhibited strong photothermal conversion effect. Under the illumination of an 808 nm laser, the aqueous suspension containing 1.0 wt % Gd-C nanocomposites gave a maximum temperature rise of 28.2 °C and a light utilization efficiency of 30.4%. The results indicate that Gd-C nanocomposites have significant potential in MRI guided PTT of lymph cancer.

A SAC Phosphoinositide Phosphatase Controls Rice Development via Hydrolyzing PI4P and PI(4,5)P2.

Phosphoinositides (PIs) as regulatory membrane lipids play essential roles in multiple cellular processes. Although the exact molecular targets of PI-dependent modulation remain largely elusive, the effects of disturbed PI metabolism could be employed to identify regulatory modules associated with particular downstream targets of PIs. Here, we identified the role of GRAIN NUMBER AND PLANT HEIGHT1 (GH1), which encodes a suppressor of actin (SAC) domain-containing phosphatase with unknown function in rice (Oryza sativa). Endoplasmic reticulum-localized GH1 specifically dephosphorylated and hydrolyzed phosphatidylinositol 4-phosphate (PI4P) and phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2]. Inactivation of GH1 resulted in massive accumulation of both PI4P and PI(4,5)P2, while excessive GH1 caused their depletion. Notably, superabundant PI4P and PI(4,5)P2 could both disrupt actin cytoskeleton organization and suppress cell elongation. Interestingly, both PI4P and PI(4,5)P2 inhibited actin-related protein2 and -3 (Arp2/3) complex-nucleated actin-branching networks in vitro, whereas PI(4,5)P2 showed more dramatic effects in a dose-dependent manner. Overall, the overaccumulation of PI(4,5)P2 resulting from dysfunction of SAC phosphatase possibly perturbs Arp2/3 complex-mediated actin polymerization, thereby disordering cell development. These findings imply that the Arp2/3 complex might be the potential molecular target of PI(4,5)P2-dependent modulation in eukaryotes, thereby providing insights into the relationship between PI homeostasis and plant growth and development.

The Value of Contrast-Enhanced Ultrasound Classification in Diagnosis of Pancreatic Cystic Lesions.

OBJECTIVE: To compare the consistency of contrast-enhanced ultrasound (CEUS) classification results with magnetic resonance imaging (MRI) and to investigate the diagnostic value of CEUS classification in pancreatic cystic lesions. METHODS: 84 cases of pancreatic cystic lesions were enrolled in this study. According to the CEUS classification methods of previous study in our center, all the lesions were classified into four types: type I, unilocular cysts; type II, microcystic lesions; type III, macrocystic lesions; and type IV, cystic lesions with enhanced solid components. The consistency of CEUS and MRI typing results was analysed. Among the 84 cases, 45 cases had pathological results. The CEUS results were compared with the pathological results, and the diagnostic value of CEUS classification in diagnosing pancreatic cystic lesions was explored. RESULTS: Among the 84 cases, CEUS diagnosed 8 cases of type I, 24 of type II, 8 of type III, and 45 of type IV. MRI diagnosed 10 cases of type I, 25 of type II, 7 of type III, and 43 of type IV. The classification typing results of CEUS were highly consistent with that of enhanced MRI (kappa value: 0.852). Among the 45 cases with pathological results, the diagnostic accuracy of each type was 91.1%, 95.6%, 93.3%, and 88.9%. The accuracy of CEUS and MRI in diagnosing pancreatic cystic lesions was 75.56% (34/45) and 80% (36/45), respectively. The diagnostic accuracy of CEUS had no significant difference from that of MRI (P=0.687). CONCLUSION: The classification results by CEUS and MRI are in excellent agreement. The classification of pancreatic cystic lesions by CEUS is significantly helpful for clinical diagnosis.