Vandetanib in locally advanced or metastatic differentiated thyroid cancer refractory to radioiodine therapy.

The VERIFY study aimed to determine the efficacy of vandetanib in patients with differentiated thyroid cancer (DTC) that is either locally advanced or metastatic and refractory to radioiodine (RAI) therapy. Specifically, VERIFY is a randomized, double-blind, multicenter phase III trial aimed to determine the efficacy and safety of vandetanib in tyrosine kinase inhibitor-naive patients with locally advanced or metastatic RAI-refractory DTC with documented progression (NCT01876784). Patients were randomized 1:1 to vandetanib or placebo. The primary endpoint was progression-free survival (PFS). Secondary endpoints included best objective response rate, overall survival (OS), safety, and tolerability. Patients continued to receive randomized treatment until disease progression or for as long as they were receiving clinical benefit unless criteria for treatment discontinuation were met. Following randomization, 117 patients received vandetanib, and 118 patients received a placebo. Median PFS was 10.0 months in the vandetanib group and 5.7 months in the placebo group (hazard ratio: 0.75; 95% CI: 0.55-1.03; P = 0.080). OS was not significantly different between treatment arms. Common Terminology Criteria for Adverse Events (CTCAE) of grade ≥3 were reported in 55.6% of patients in the vandetanib arm and 25.4% in the placebo arm. Thirty-three deaths (28.2%; one related to study treatment) occurred in the vandetanib arm compared with 16 deaths (13.6%; two related to treatment) in the placebo arm. No statistically significant improvement was observed in PFS in treatment versus placebo in patients with locally advanced or metastatic, RAI-refractory DTC. Moreover, active treatment was associated with more adverse events and more deaths than placebo, though the difference in OS was not statistically significant.

Proposal for an optimised definition of adverse pathology (unfavourable histology) that predicts metastatic risk in prostatic adenocarcinoma independent of grade group and pathological stage.

AIMS: Histological grading of prostate cancer is a powerful prognostic tool, but current criteria for grade assignment are not fully optimised. Our goal was to develop and test a simplified histological grading model, based heavily on large cribriform/intraductal carcinoma, with optimised sensitivity for predicting metastatic potential. METHODS AND RESULTS: Two separate non-overlapping cohorts were identified: a 419-patient post-radical prostatectomy cohort with long term clinical follow-up and a 209-patient post-radical prostatectomy cohort in which all patients had pathologically confirmed metastatic disease. All prostatectomies were re-reviewed for high-risk histological patterns of carcinoma termed 'unfavourable histology'. Unfavourable histology is defined by any classic Gleason pattern 5 component, any large cribriform morphology (> 0.25 mm) or intraductal carcinoma, complex intraluminal papillary architecture, grade 3 stromogenic carcinoma and complex anastomosing cord-like growth. For the outcome cohort, Kaplan-Meier analysis compared biochemical recurrence, metastasis and death between subjects with favourable and unfavourable histology, stratified by pathological stage and grade group. Multivariable Cox proportional hazards models evaluated adding unfavourable histology to the Memorial Sloan Kettering Cancer Center (MSKCC) post-prostatectomy nomogram and stratification by percentage of unfavourable histology. At 15 years unfavourable histology predicted biochemical recurrence, with sensitivity of 93% and specificity of 88%, metastatic disease at 100 and 48% and death at 100 and 46%. Grade group 2 prostate cancers with unfavourable histology were associated with metastasis independent of pathological stage, while those without had no risk. Histological models for prediction of metastasis based on only large cribriform/intraductal carcinoma or increasing diameter of cribriform size improved specificity, but with lower sensitivity. Multivariable Cox proportional hazards models demonstrated that unfavourable histology significantly improved discriminatory power of the MSKCC post-prostatectomy nomogram for biochemical failure (likelihood ratio test P < 0.001). In the retrospective review of a separate RP cohort in which all patients had confirmed metastatic disease, none had unequivocal favourable histology. CONCLUSIONS: Unfavourable histology at radical prostatectomy is associated with metastatic risk, predicted adverse outcomes better than current grading and staging systems and improved the MSKCC post-prostatectomy nomogram. Most importantly, unfavourable histology stratified grade group 2 prostate cancers into those with and without metastatic potential, independent of stage. While unfavourable histology is driven predominantly by large cribriform/intraductal carcinoma, the recognition and inclusion of other specific architectural patterns add to the sensitivity for predicting metastatic disease. Moreover, a simplified dichotomous model improves communication and could increase implementation.

Pathological Extramural Venous Invasion in High-stage Urothelial Carcinoma of the Bladder has Shorter Locoregional Recurrence-free Survival.

Extramural venous invasion is an independent prognostic factor in colorectal cancers; the pathological identification of extramural venous invasion in bladder cancer remains unclear. By focusing on high-stage urothelial carcinoma of the bladder, we provide insights into the pathological identification of extramural venous invasion in this particular clinical context. Clinical and demographic details and pathological reports were extracted from electronic medical records. Histological sections were reviewed for the pathological identification of extramural venous invasion. Statistical analysis was done using SPSS version 23 software. Survival analysis was done using Kaplan-Meier method. In patients with available follow-up data, 62% (n = 21) exhibited pathologically evidenced extramural venous invasion, whereas 38% (n = 13) did not. The extramural venous invasion positive group showed trends toward more advanced and pathological staging and a higher occurrence of extra-nodal extension. Positive margins were more frequent in the extramural venous invasion positive group (33%) compared to the extramural venous invasion negative group (8%). However, these differences were not statistically significant. Notably, all instances of recurrence were in the extramural venous invasion positive group of patients. The extramural venous invasion positive group of patients showed a significantly shorter locoregional recurrence-free survival (P-value of 0.045). However, extramural venous invasion did not emerge as a significant factor in univariate analyses for recurrence-free survival. These findings highlight the potential role of extramural venous invasion as a prognostic factor in bladder cancer but underscore the need for further research with larger cohorts to confirm its significance.

Elucidating applied voltage on the fate of antibiotic resistance genes in microbial electrolysis cell: Focusing on its transmission between anolyte and biofilm microbes.

Microbial electrolysis cell (MEC) system to treat wastewater containing antibiotics has been researched actively in past years. However, the fate of antibiotic resistant genes (ARGs) in MEC is not fully revealed. The effect of applied voltage on the migration of ARGs between anolyte and biofilm microbes via examining the microbial physiology and abundances of macrolide resistance genes (MRGs) and mobile genetic elements (MGEs) was elucidated in this research. Results showed that the abundance of MRGs and MGEs was decreased in the anolyte, but their abundances were increased on the electrode biofilm, indicating their transmission from anolyte to biofilm microbes. Increased applied voltage enhanced adenosine triphosphate (ATP), reactive oxygen species (ROS), and cell membrane permeability of electrode microorganisms. The structure of the electrode microbial community was shifted through applied voltage, and the abundance of electroactive microorganisms (Geobacter, Azospirillum and Dechlorobacter) was significantly improved. Network analysis revealed that Geobacter and Geothrix were potential hosts for MRGs. Therefore, the horizontal and vertical gene transfer of ARGs could be increased by the applied voltage, leading to the enriched ARGs at the electrode biofilm. This study provides evidence and insights into the transmission of ARGs between anolyte and biofilm microbes in MEC system. SYNOPSIS: This study revealed the effect of applied voltage on ARGs in MEC and the potential migration mechanism of ARGs.

Extramural venous invasion: a novel magnetic resonance imaging biomarker for adverse pathology in bladder cancer.

Extramural venous invasion (EMVI) recognized on magnetic resonance imaging (MRI) is an unequivocal biomarker for detecting adverse outcomes in rectal cancer: however it has not yet been explored in the area of bladder cancer. In this study, we assessed the feasibility of identifying EMVI findings on MRI in patients with bladder cancer and its avail in identifying adverse pathology. In this single-institution retrospective study, the MRI findings inclusive of EMVI was described in patients with bladder cancer that had available imaging between January 2018 and June 2020. Patient demographic and clinical information were retrieved from our electronic medical records system. Histopathologic features frequently associated with poor outcomes including lymphovascular invasion (LVI), variant histology, muscle invasive bladder cancer (MIBC), and extravesical disease (EV) were compared to MRI-EMVI. A total of 38 patients were enrolled in the study, with a median age of 73 years (range 50-101), 76% were male and 23% were females. EMVI was identified in 23 (62%) patients. There was a significant association between EMVI and MIBC (OR = 5.30, CI = 1.11-25.36; P = 0.036), and extravesical disease (OR = 17.77, CI = 2.37-133; P = 0.005). We found a higher probability of presence of LVI and histologic variant in patients with EMVI. EMVI had a sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) of 90%, 73%, 94% and 63% respectively in detecting extravesical disease. Our study suggests, EMVI may be a useful biomarker in bladder cancer imaging, is associated with adverse pathology, and could be potentially integrated in the standard of care with regards to MRI reporting systems. A larger study sample size is further warranted to assess feasibility and applicability.

Characterizing the penumbras of white matter hyperintensities in patients with cerebral small vessel disease.

PURPOSE: The white matter hyperintensity penumbra (WMH-P) is the subtly changed normal-appearing white matter (NAWM) that surrounds white matter hyperintensities (WMHs). The goal of this study was to define WMH-P in cerebral small vessel disease (CSVD) by arterial spin labeling (ASL) and diffusion tensor imaging (DTI)/diffusion kurtosis imaging (DKI). MATERIALS AND METHODS: We prospectively analyzed 42 patients with CSVD. To determine the range of cerebral blood flow (CBF) and DTI/DKI penumbras around white matter hyperintensities, we generated NAWM layer masks from periventricular WMHs (PVWMHs) and deep WMHs (DWMHs). Mean values of CBF, fractional anisotropy, mean diffusivity, axial diffusivity, radial diffusivity, mean kurtosis, axial kurtosis, and radial kurtosis within the WMHs and their corresponding NAWM layer masks were analyzed. Paired sample t tests were used for analysis, and differences were considered statistically significant if the associated p value was ≤ 0.05. RESULTS: For DWMHs, the CBF penumbras were 13 mm, and the DTI/DKI penumbras were 8 mm. For PVWMHs, the CBF penumbras were 14 mm, and the DTI/DKI penumbras were 14 mm. CONCLUSIONS: Our findings revealed that DTI/DKI and ASL can show structural and blood flow changes in brain tissue surrounding WMHs. In DWMHs, the blood flow penumbra was larger than the structural penumbra, while in PVWMHs, the blood flow penumbra was almost the same as the structural penumbra.

MicroRNA-196a-5p targeting LRP1B modulates phenotype of thyroid carcinoma cells.

INTRODUCTION: Thyroid cancer (TC) is a common endocrine malignancy, comprising nearly one-third of all head and neck malignancies worldwide. MicroRNAs (miRNAs) have been implicated in the malignant progression of multiple cancers; however, their contribution to thyroid diseases has not been fully explored. MATERIAL AND METHODS: This study aimed to illustrate the regulatory mechanism of microRNA-196a-5p in TC progression and to investigate whether microRNA-196a-5p affects progression of TC cells by targeting low-density lipoprotein receptor-associated protein 1B (LRP1B). MicroRNA-196a-5p and LRP1B expression status in TC cells and normal human thyroid cells was detected by quantative reverse transcription polymerase chain reaction (qRT-PCR) and western blot. Dual-luciferase reporter assay, cell counting kit-8 (CCK-8) assay, scratch healing assay, and Transwell assay were also performed. RESULTS: The results showed that microRNA-196a-5p expression was up-regulated and LRP1B expression was down regulated in TC cells. In addition, the upregulation of microRNA-196a-5p facilitated progression of TC cells. Silencing microRNA-196a-5p led to the opposite results. Dual-luciferase reporter assay offered evidence for microRNA-196a-5p targeting LRP1B in TC. MicroRNA-196a-5p could target LRP1B to facilitate proliferation, invasion, and migration of TC cells. CONCLUSION: Overall, this study revealed that microRNA-196a-5p may be a cancer-promoting microRNA that plays an important role in TC progression.

Heterogeneous activation of peroxymonosulfate by magnetic hybrid CuFe2O4@N-rGO for excellent sulfamethoxazole degradation: Interaction of CuFe2O4 with N-rGO and synergistic catalytic mechanism.

In order to address the low catalytic performance of magnetic CuFe2O4 caused by the agglomeration, low conductivity and potential metal ion leaching risk, N-doped reduced graphene oxide (N-rGO) with high charge density and rich active sites was employed as support to synthesize CuFe2O4@N-rGO (CuFe@NG), which was used for peroxymonosulfate (PMS) activation to degrade sulfamethoxazole (SMX). Results showed that the CuFe@NG/PMS system exhibited excellent degradation rate and mineralization efficiency on SMX in 60 min, which exceeded 93.15% and 31.96%, respectively. Besides, its degradation rate constants was 1.68 times higher than that of the CuFe2O4/PMS system. The enhanced performance could be mainly ascribed to the efficient synergistic activation of PMS by two components: I. the successful dispersion of CuFe2O4 on N-rGO and the interaction between them exposed more Fe3+-O2- and Cu2+-O2- active sites via decreasing size and aggregation of CuFe2O4 particles; II. the supported N-rGO supplied extra CO, C-OH and C-NC active groups, resulting in a large number of π electrons; III. the pyrrole N formed by further doping of N could activate the π electrons and reduce the energy barrier of electron transfer. The abundant active groups and sites and excellent electron transfer ability co-accelerate the production of active species. Specifically, surface-bound radical (•OH, SO4•-) and singlet oxygen 1O2 played a dominant role according to ESR and quenching tests. Furthermore, M-O-C binding site between two components enhanced catalyst stability and reduced metal leaching, leading to its availability on reusability in the 5 cyclic experiments. Lastly, CuFe@NG/PMS system also possessed a strong application ability in actual aquatic environment for SMX treatment.

Tuning oxygen vacancy in Bi2WO6 by heteroatom doping for enhanced photooxidation-reduction properties.

Heteroatom doping was recently regarded as an effective method to tune the band gap and improve the separation and transfer of photogenerated electron-hole pairs in semiconductor photocatalysts. Herein, a novel S,F-codoped Bi2WO6 (S,F-Bi2WO6) with suitable oxygen vacancies was synthesized via the hydrothermal-calcination and post-sulfurization, for efficient Cr(VI) reduction and methyl orange (MO) degradation under visible light. The amount of surface oxygen vacancies could be controlled by adjusting the S/F ratio during the doping process, which modulated the band structure and photogenerated charge behavior of Bi2WO6. The optimal S0.10F-Bi2WO6 exhibited an excellent photooxidation-reduction performance, which Cr(VI) reduction and MO degradation efficiencies were 1.6 and 2.6 times than those of the pristine Bi2WO6 without oxygen vacancy under visible-light, respectively. The enhanced photooxidation-reduction performance was because the right amount of oxygen vacancies could effectively narrow the bandgap and improve the separation efficiency of electron-hole pairs. Thus, this work offered a mild and simply approach for preparing heteroatom doped Bi2WO6 and a potential to be extended to the synthesis of other doped materials for environmental remediation.

Generating Talking Face With Controllable Eye Movements by Disentangled Blinking Feature.

In virtual reality, talking face generation is committed to using voice and face images to generate real face speech videos to improve the communication experience in the case of limited user information exchange. In a real video, blinking is an action often accompanied by speech, and it is also one of the indispensable actions in real face speech videos. However, the current methods either do not pay attention to the generation of eye movements, or cannot control the blinking in the generated results. To this end, this article proposes a novel system which produces vivid talking face with controllable eye blinks driven by the joint features including identity feature, audio feature, and blink feature. In order to disentangle the blinking action, we designed three independent features to individually drive the main components in the generated frame, namely the facial appearance, mouth movements, and eye movements. Through the adversarial training of the identity encoder, we filter out the information of the eye state from the identity feature, thereby strengthening the independence of the blinking feature. We introduced the blink score as the leading information of the blink feature, and through training, the value can be consistent with human perception to form a complete and independent control of the eyes. Experimental results on multiple datasets show that our method can not only reproduce real talking faces, but also ensure that the blinking pattern and time are fully controllable.

A Case Report and Brief Literature Review on Dedifferentiated Chondrosarcoma in Proximal Phalanx: A Rare Location.

Dedifferentiated chondrosarcoma (DDCS) is a rare entity, constituting only 1-2% of all primary bone tumors, and has a dismal prognosis. Nearly two-thirds of the primary tumors of DDCSs are found in the appendicular skeleton, mostly involving the femur, humerus, and pelvis. DDCS of the small bones of the hand and foot are exceedingly rare with only four cases documented in the literature so far. In this report, we present a case of a 91-year-old woman with a rapidly growing bone tumor initially thought to be a trigger finger, which, on histologic examination of the amputation, turned out to be DDCS. On a follow-up CT scan, multiple pulmonary metastases were identified. Next-generation sequencing identified isocitrate dehydrogenase 2 (IDH2) (p.R172S, c.516G>T), TERT (c.-146C>T), and TP53 (c.559+1G>A) mutations. Microsatellite instability was equivocal and tumor mutation burden was low. Due to the advanced age of the patient, she was given palliative treatment and was alive at the six-month follow-up.

Critical Role of Osteopontin in Maintaining Urinary Phosphate Solubility in CKD.

Background: Nephron loss dramatically increases tubular phosphate to concentrations that exceed supersaturation. Osteopontin (OPN) is a matricellular protein that enhances mineral solubility in solution; however, the role of OPN in maintaining urinary phosphate solubility in CKD remains undefined. Methods: Here, we examined (1) the expression patterns and timing of kidney/urine OPN changes in CKD mice, (2) if tubular injury is necessary for kidney OPN expression in CKD, (3) how OPN deletion alters kidney mineral deposition in CKD mice, (4) how neutralization of the mineral-binding (ASARM) motif of OPN alters kidney mineral deposition in phosphaturic mice, and (5) the in vitro effect of phosphate-based nanocrystals on tubular epithelial cell OPN expression. Results: Tubular OPN expression was dramatically increased in all studied CKD murine models. Kidney OPN gene expression and urinary OPN/Cr ratios increased before changes in traditional biochemical markers of kidney function. Moreover, a reduction of nephron numbers alone (by unilateral nephrectomy) was sufficient to induce OPN expression in residual nephrons and induction of CKD in OPN-null mice fed excess phosphate resulted in severe nephrocalcinosis. Neutralization of the ASARM motif of OPN in phosphaturic mice resulted in severe nephrocalcinosis that mimicked OPN-null CKD mice. Lastly, in vitro experiments revealed calcium-phosphate nanocrystals to induce OPN expression by tubular epithelial cells directly. Conclusions: Kidney OPN expression increases in early CKD and serves a critical role in maintaining tubular mineral solubility when tubular phosphate concentrations are exceedingly high, as in late-stage CKD. Calcium-phosphate nanocrystals may be a proximal stimulus for tubular OPN production.

Deeper insight into the effect of salinity on the relationship of enzymatic activity, microbial community and key metabolic pathway during the anaerobic digestion of high strength organic wastewater.

The threshold salt concentration to inhibit the anaerobic digestion (AD) has been intensively investigated, but its insight mechanism is not fully revealed. Therefore, this study systematically investigated the effect of salinity on acidogenesis and methanogenesis and its mechanism. Results showed that low salinity level (i.e. 0.6%) had stimulatory effect on volatile fatty acids (VFA) and methane production, while significant inhibition was observed with further increased salinity. Moreover, high salinity limited the butyric acid degradation at acidogenesis process. The decreases of enzymes (AK and PTA) activity and functional genes (ackA, pta and ACOX) expression that related to ß-oxidation explained the butyric acid accumulation at high salinity levels. Microbial community analysis revealed high salinity levels significantly inhibited the proliferation of Syntrophomonas sp., which are known to be associated with butyric acid degradation. Similarly, the relative abundance of acetoclastic methanogen (Methanothrix sp.) and methylotrophic methanogen (Methanolinea sp.) significantly decreased at salinity condition.

A Giant Sporadic Intra-abdominal Desmoid Tumor in a Male Patient: A Case Report.

Desmoid tumors (DTs) are rare locally aggressive benign soft tissue tumors with an estimated annual incidence of two to four new cases per million people. The giant intra-abdominal mass presents a diagnostic challenge that includes a broad differential diagnosis of gastrointestinal stromal tumor (GIST), fibrosarcoma, retroperitoneal fibrosis, and other malignancies from adjacent organs. We report a case of a 38-year-old male patient with a giant intra­abdominal mass. Magnetic resonance imaging (MRI) of the abdomen and pelvis indicated mucinous cystic neoplasm or gastrointestinal stromal tumor (GIST), but histopathology confirmed it to be a desmoid tumor. The patient was discharged, and on follow-up five months until now, there is no recurrence. This case highlighted the importance of including DT in the differential diagnosis of very large intra­abdominal masses.

Concomitant Gastric Malignancy and Hepatocellular Carcinoma.

Multiple primary malignant tumors (MPMTs) are two or more separate malignancies found at different sites concurrently. Prior studies have shown that the most common tumor associations in MPMTs are typically between two tumors in the digestive system. We present a case of a male patient in his 60s who initially presented with melena and was found to have a clean-based gastric ulcer on initial endoscopic evaluation. Repeat endoscopy on later admission revealed persistent ulceration. Biopsy showed Epstein-Barr virus (EBV) positive lymphoepithelioma-like gastric carcinoma (LELGC), a rare gastric malignancy. The patient underwent endoscopic ultrasound (EUS) for assessment of tumor depth and involvement of perigastric lymph nodes, but was incidentally found to have a liver lesion. Biopsy of the liver lesion was positive for hepatocellular carcinoma (HCC) with no morphologic similarity to the gastric malignancy. This case highlights a rare finding of MPMTs. In addition to the diagnosis of a rare gastric malignancy, the patient developed a well-known but uncommon phenomenon of non-cirrhotic HCC associated with hepatitis C virus (HCV). Due to an increasing number of advances in cancer therapy that are leading to increased survival times, clinicians can expect for a patient to develop MPMTs in their lifetime. A high index of suspicion must exist for the possibility of MPMTs because treatment options and outcomes can be vastly affected by their findings.

MicroRNA-873-5p suppresses cell malignant behaviors of thyroid cancer via targeting CXCL5 and regulating P53 pathway.

We aimed to examine the roles of microRNA-873-5p and CXCL5 in thyroid cancer (TC) cells. qRT-PCR was adopted to measure the expression levels of CXCL5 mRNA and microRNA-873-5p in TC cells, and western blot was adopted to evaluate the CXCL5 protein expression level. Bioinformatics analysis was done to predict the upstream gene of CXCL5. Dual-luciferase assay was applied to validate the binding relationship of CXCL5 and the upstream regulatory gene. Cell experiments were done to detect the effects of microRNA-873-5p targeting CXCL5 on malignant progression of cancer cells. Western blot was adopted to demonstrate the phosphorylation level of P53 pathway related-proteins. CXCL5 was upregulated in TC cells and tissues. The results of in vitro assays displayed that CXCL5 downregulation dramatically suppressed the malignant behaviors of TC cells. MicroRNA-873-5p suppressed CXCL5 expression, but the suppressive effect of microRNA-873-5p on TC cells was abolished through CXCL5 overexpression. Additionally, microRNA-873-5p could mediate p53 pathway and thereby inhibit the malignant behaviors of TC cells through targeting CXCL5. In summary, we proved that microRNA-873-5p repressed the malignant behaviors of TC cells through targeting CXCL5 and P53 pathway, indicating that microRNA-873-5p can be a biomarker for TC.

Anti-microRNA-21 Therapy on Top of ACE Inhibition Delays Renal Failure in Alport Syndrome Mouse Models.

Col4a3-/- Alport mice serve as an animal model for renal fibrosis. MicroRNA-21 (miR-21) expression has been shown to be increased in the kidneys of Alport syndrome patients. Here, we investigated the nephroprotective effects of Lademirsen anti-miR-21 therapy. We used a fast-progressing Col4a3-/- mouse model with a 129/SvJ background and an intermediate-progressing F1 hybrid mouse model with a mixed genetic background, with angiotensin-converting enzyme inhibitor (ACEi) monotherapy in combination with anti-miR-21 therapy. In the fast-progressing model, the anti miR-21 and ACEi therapies showed an additive effect in the reduction in fibrosis, the decline of proteinuria, the preservation of kidney function and increased survival. In the intermediate-progressing F1 model, the anti-miR-21 and ACEi therapies individually improved kidney pathology. Both also improved kidney function and survival; however, the combination showed a significant additive effect, particularly for survival. RNA sequencing (RNA-seq) gene expression profiling revealed that the anti-miR-21 and ACEi therapies modulate several common pathways. However, anti-miR-21 was particularly effective at normalizing the expression profiles of the genes involved in renal tubulointerstitial injury pathways. In conclusion, significant additive effects were detected for the combination of anti-miR-21 and ACEi therapies on kidney function, pathology and survival in Alport mouse models, as well as a strong differential effect of anti-miR-21 on the renal expression of fibrotic factors. These results support the addition of anti-miR-21 to the current standard of care (ACEi) in ongoing clinical trials in patients with Alport syndrome.

Efficient degradation of trimethoprim by catalytic ozonation coupled with Mn/FeOx-functionalized ceramic membrane: Synergic catalytic effect and enhanced anti-fouling performance.

In this study, the flat microfiltration ceramic membrane (CM) was modified by wet impregnation method (Mn-Fe-CM) to catalyze ozone (O3) for the oxidative degradation of trimethoprim (TMP). The conventional characterization test showed that the Mn-Fe binary oxides (Mn/FeOx) with the crystal structure of FeMnO3 were successfully loaded on the membrane and the catalytic performance of Mn-Fe-CM for O3 was apparently enhanced as compared to CM. Consequently, compared with O3 oxidation alone, the degradation and mineralization efficiencies of TMP in the O3/Mn-Fe-CM system were both improved and 98.6% of TMP could be removed within 10 min. The degradation efficiency of TMP decreased with the increasing pH and the addition of Cl-、HCO3-、PO43-, while humic acid (HA) exhibited negative effect on the TMP removal. Radical scavenger experiment and electron paramagnetic resonance (EPR) analysis confirmed that direct oxidation by O3 played an important role in the degradation of TMP, while hydroxyl radical (·OH) and 1O2 also participated. Fe(II) could act as an intermediate to transfer electrons and accelerate the transformation of Mn(III) to Mn(II) and Mn(IV) to Mn(III) during the ozonation process, which definitely strengthened the synergic catalytic effect of Mn-Fe-CM. The proposed degradation mechanism of TMP mainly contained hydroxylation, carbonylation, demethoxylation and deamination. Due to the strong catalytic ozonation performance for organic pollutants degradation, the O3/Mn-Fe-CM system revealed better anti-membrane fouling ability, strong cyclic usage performance and high applicability for the actual surface water treatment.

Identification of a novel missense mutation in the TPM1 gene via exome sequencing in a Chinese family with dilated cardiomyopathy: A case report and literature review.

RATIONALE: Dilated cardiomyopathy (DCM) is a cardiovascular disorder characterized by consecutive ventricular dilation and contractile dysfunction, often leading to congestive heart failure. DCM type 1Y (DCM1Y) is caused by a mutation in the TPM1 (tropomyosin 1) gene. To date, about thirty TPM1 gene mutations have been reported to be related to DCM1Y. However, mutational screening of the TPM1 gene is still far from being complete. Identification of TPM1 mutation is particularly important in the diagnosis of DCM1Y and will give more insights into the molecular pathogenesis of DCM1Y. PATIENT CONCERNS: A Chinese Han family with DCM phenotypes was examined. DIAGNOSIS: A novel missense mutation, c.340G > C in exon 3 of the TPM1 gene, was identified. INTERVENTIONS: Next-generation sequencing (NGS) of DNA samples was performed to detect the gene mutation in the proband, which was confirmed by Sanger sequencing. OUTCOMES: This novel heterozygous mutation results in the substitution of glutamic acid with glutamine (p.E114Q). Based on this finding and clinical manifestations, a final diagnosis of DCM1Y was made. LESSONS: We present evidence that p.E114Q mutation represents a novel TPM1 mutation in a Chinese Han family with DCM. Our data expand the mutation spectrum of the TPM1 gene and may facilitate the clinical diagnosis of DCM1Y.