Impacts of Tumor Stage at Diagnosis and Adjuvant Therapy on Long-Term Survival Outcomes in Patients With Triple-Negative Breast Cancer Achieving Pathologic Complete Response After Neoadjuvant Chemotherapy.

BACKGROUND: It remains unknown whether the tumor stage at initial diagnosis and adjuvant treatments had any impacts on the long-term survival outcomes of patients with triple-negative breast cancer (TNBC) achieving pathologic complete response (pCR) following neoadjuvant chemotherapy (NACT). METHODS: Clinical stage II-III patients with TNBC who achieved pCR after NACT were identified from the Surveillance, Epidemiology, and End Results (SEER) program (SEER cohort) and the National Clinical Research Center for Cancer (Tianjin) in China (TMUCIH cohort). Survival analyses were conducted based on tumor stages and the types of adjuvant treatment received by the patients. The outcomes of interest were overall survival (OS) and breast cancer-specific survival (BCSS). RESULTS: The TMUCIH cohort comprised 178 patients with a median follow-up of 55.5 months. Two and 3 patients experienced BCSS and OS events, respectively. The SEER cohort included 1218 patients with a median follow-up of 65.5 months, where 53 and 78 patients experienced BCSS and OS events, respectively. Patients diagnosed with stage III disease had significantly higher hazards of death compared to stage II disease (OS: hazard ratio [HR], 3.34; 95% confidence interval [CI], 1.84-6.07; P < .001; BCSS: HR, 2.86; 95% CI, 1.38-5.92; P < .001). Adjuvant systemic and radiation therapy did not confer additional benefits to OS and BCSS. CONCLUSION: Tumor stage at initial diagnosis remains an independent predictor of long-term survival outcomes in patients with TNBC achieving pCR after NACT. Postoperative adjuvant chemotherapy and radiation therapy do not appear to provide additional benefit to their long-term prognosis.

Preservation of the pectoralis major fascia has no impact on the long-term oncologic outcomes of patients with breast cancer treated with conservative mastectomy and immediate breast reconstruction: A propensity score matching analysis.

BACKGROUND: The oncologic safety of preserving the pectoralis major fascia (PMF) in patients with breast cancer remains controversial. In this study, we aimed to determine the impact of preserving the PMF on long-term oncologic outcomes in patients with breast cancer treated with immediate implant-based breast reconstruction (IBBR) following conservative mastectomy. METHODS: We selected women with early-stage breast cancer who underwent conservative mastectomy and submuscular IBBR in our center during 2014-2019. The propensity score matching method was used to create well-balanced fascia-preserved and fascia-removed groups. Locoregional recurrence-free survival (LRFS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates were calculated using the Kaplan-Meier method and compared using log-rank tests between the fascia-preserved and fascia-removed groups. RESULTS: After matching, there were 219 patients in each group. The mean follow-up time was 64.8 ± 18.1 months for the fascia-preserved group and 64.9 ± 18.4 months for the fascia-removed group. There were no significant differences between the groups in terms of LRFS (91.3% vs. 93.8%; p = 0.818), DMFS (94.0% vs. 92.3%; p = 0.056), DFS (89.9% vs. 88.4%; p = 0.261), and OS (95.8% vs. 95.4%; p = 0.783) rates. In the fascia-preserved group, 61.5% of the locoregional recurrence events occurred within 2 years after surgery. CONCLUSION: Preservation of the PMF did not significantly impact the long-term oncologic outcomes in patients with breast cancer who underwent conservative mastectomy and IBBR. The PMF might be safely preserved in patients without suspicious tumor invasion into this fascia.

Laparoscopic liver resection for hepatocellular carcinoma complicated with significant portal hypertension: A propensity score-matched survival analysis.

BACKGROUND: Significant portal hypertension (SPH) is a relative contraindication for patients with resectable hepatocellular carcinoma (HCC). However, increasing evidence indicates that liver resection is feasible for HCC patients with SPH. METHODS: HCC patients with cirrhosis who underwent laparoscopic liver resection (LLR) in two centers from January 2013 to April 2018 were included. Surgical and survival outcomes were analyzed to explore potential prognostic factors. Propensity score matching (PSM) analysis was performed to minimize bias. RESULTS: A total of 165 patients were divided into two groups based on the presence (SPH, n = 76) or absence (non-SPH, n = 89) of SPH. Patients in the SPH group had longer operative time, more blood loss, and more advanced TNM stage than patients in the non-SPH group (P < 0.05). However, there were no significant differences in the postoperative 90-day mortality rate (n = 0), overall postoperative complications (47.4% vs. 41.6%, P = 0.455), Clavien-Dindo classification (P = 0.347), conversion to open surgery (9.2% vs. 6.7%, P = 0.557), or length of hospitalization (16 vs. 15 days, P = 0.203) between the SPH and non-SPH groups before PSM. Similar results were obtained after PSM. The 1-, 3-, and 5-year overall survival (OS) and recurrence-free survival rates in the SPH group were not significantly different from those in the non-SPH group both before and after PSM (log-rank P > 0.05). After PSM, alpha-fetoprotein (AFP) ≥ 400 µg/L [hazard ratio (HR) = 4.71, 95% confidence interval (CI): 2.69-8.25], ascites (HR = 2.18, 95% CI: 1.30-3.66), American Society of Anesthesiologists (ASA) classification (III vs. II) (HR = 2.13, 95% CI: 1.11-4.07) and tumor diameter > 5 cm (HR = 3.91, 95% CI: 2.02-7.56) independently predicted worse OS. CONCLUSIONS: LLR for patients with HCC complicated with SPH appears feasible at the price of increasing operative time and blood loss. AFP, ascites, ASA classification and tumor diameter may predict the prognosis of HCC complicated with SPH after LLR.

CT radiomics nomogram for prediction of the Ki-67 index in head and neck squamous cell carcinoma.

OBJECTIVES: To construct and validate a contrast-enhanced computed tomography (CECT)-based radiomics nomogram to predict Ki-67 expression level in head and neck squamous cell carcinoma (HNSCC). METHODS: A total of 217 patients with HNSCC who underwent CECT scans and immunohistochemical examination of their Ki-67 index were enrolled in this study. The patients were divided into a training set (n = 140; Ki-67: ≥ 50% [n = 72] and < 50% [n = 68]) and an external test set (n = 77; Ki-67: ≥ 50% [n = 38] and < 50% [n = 39]). The least absolute shrinkage and selection operator method was used to select key features for a CECT-image-based radiomics signature and a radiomics score (Rad-score) was calculated. A clinical model was established using clinical data and CT findings. The independent clinical factors and Rad-score were then combined to construct a radiomics nomogram. The performance characteristics of the Rad-score, clinical model, and nomogram were assessed using ROCs and decision curve analysis. RESULTS: Twenty features were finally selected to construct the Rad-score. The radiomics nomogram incorporating the Rad-score, low histological grade, and lymphatic spread showed higher predictive value for the Ki-67 index (≥ 50% vs. < 50%) than the clinical model on both the training (AUC, 0.919 vs. 0.648, p < 0.001) and test (AUC, 0.832 vs. 0.685, p = 0.030) sets. Decision curve analysis demonstrated that the radiomics nomogram was more clinically useful than the clinical model. CONCLUSIONS: A CECT-based radiomics nomogram was constructed to predict the expression of Ki-67 in HNSCC. This model showed favorable predictive efficacy and might be useful for prognostic evaluation and clinical decision-making in patients with HNSCC. KEY POINTS: • Accurate pre-treatment prediction of Ki-67 index in HNSCC is crucial. • A CECT-based radiomics nomogram showed favorable predictive efficacy in estimation of Ki-67 expression status in HNSCC patients.

WRKY74 regulates cadmium tolerance through glutathione-dependent pathway in wheat.

Cadmium (Cd) is a toxic heavy metal to plants and human health. Ascorbate (ASA)-glutathione (GSH) synthesis pathway plays key roles in Cd detoxification, while its molecular regulatory mechanism remains largely unknown, especially in wheat. Here, we found a WRKY transcription factor-TaWRKY74, and its function in wheat Cd stress is not clear in previous studies. The expression levels of TaWRKY74 were significantly induced by Cd stress. Compared to control, the activities of GST, GR, or APX were significantly increased by 1.55-, 1.43-, or 1.75-fold and 1.63-, 2.65-, or 2.30-fold in shoots and roots of transiently TaWRKY74-silenced wheat plants under Cd stress. Similarly, the contents of hydrogen peroxide (H2O2), malondialdehyde (MDA), GSH, or Cd were also significantly increased by 2.39- or 1.25-fold, 1.54- or 1.20-fold, and 1.34- or 5.94-fold in shoots or roots in transiently TaWRKY74-silenced wheat plants, while ASA content was decreased by 47.4 or 43.3% in shoots, 10.7 or 6.5% in roots in these silenced wheat plants, respectively. Moreover, the expression levels of GSH, GPX, GR, DHAR, MDHAR, and APX genes, which are involved in ASA-GSH synthesis, were separately induced by 2.42-, 2.16-, 3.28-, 2.08-, 1.92-, and 2.23-fold in shoots, or by 10.69-, 3.33-, 3.26-, 1.81-, 16.53-, and 3.57-fold in roots of the BSMV-VIGS-TaWRKY74-inoculated wheat plants, respectively. However, the expression levels of TaNramp1, TaNramp5, TaHMA2, TaHMA3, TaLCT1, and TaIRT1 metal transporters genes were decreased by 21.2-76.3% (56.6%, 59.2%, 76.3%, 53.6%, 35.8%, and 21.2%) in roots of the BSMV-VIGS-TaWRKY74-inoculated wheat plants. Taken together, our results suggested that TaWRKY74 alleviated Cd toxicity in wheat by affecting the expression of ASA-GSH synthesis genes and suppressing the expression of Cd transporter genes, and further affecting Cd uptake and translocation in wheat plants.

Exogenous melatonin mitigates cadmium toxicity through ascorbic acid and glutathione pathway in wheat.

Cadmium (Cd) is a dispensable element that can be absorbed by crops, posing a threat to human health through the food chains. Melatonin (MT), as a plant growth regulator, has been used to alleviate Cd toxicity in many plant species; however, the underlying molecular mechanisms responsible for Cd toxicity in wheat are still poorly understood. In this study, the suitable exogenous MT concentration (50 µM) was screened to mitigate Cd toxicity of wheat plants by increasing the plant height, root length, fresh or dry weight and chlorophyll content, or decreasing the malondialdehyde (MDA) content. In addition, MT application significantly increased ascorbic acid (ASA) and glutathione (GSH) content by reducing ROS production, especially in roots, further decreasing Cd content in fraction of organelles. Moreover, the expression levels of ASA-GSH synthesis genes, APX, GR, and GST were significantly increased by 171.5%, 465.2%, and 256.8% in roots, respectively, whereas GSH, DHAR, or MDHAR were significantly decreased by 48.5%, 54.3%, or 60.0% in roots under MT + Cd stress. However, the expression levels of Cd-induced metal transporter genes TaNramp1, TaNramp5, TaHMA2, TaHMA3, and TaLCT1 were significantly decreased by 53.7%, 50.1%, 86.5%, 87.2%, and 94.5% in roots under MT + Cd stress compared with alone Cd treatment, respectively. In conclusion, our results suggesting that MT alleviate Cd toxicity in wheat by enhancing ASA-GSH metabolism, suppressing Cd transporter gene expression, and regulating Cd uptake and translocation in wheat plants.

Regulation of Myogenesis by a Na/K-ATPase α1 Caveolin-Binding Motif.

The N-terminal caveolin-binding motif (CBM) in Na/K-ATPase (NKA) α1 subunit is essential for cell signaling and somitogenesis in animals. To further investigate the molecular mechanism, we have generated CBM mutant human-induced pluripotent stem cells (iPSCs) through CRISPR/Cas9 genome editing and examined their ability to differentiate into skeletal muscle (Skm) cells. Compared with the parental wild-type human iPSCs, the CBM mutant cells lost their ability of Skm differentiation, which was evidenced by the absence of spontaneous cell contraction, marker gene expression, and subcellular myofiber banding structures in the final differentiated induced Skm cells. Another NKA functional mutant, A420P, which lacks NKA/Src signaling function, did not produce a similar defect. Indeed, A420P mutant iPSCs retained intact pluripotency and ability of Skm differentiation. Mechanistically, the myogenic transcription factor MYOD was greatly suppressed by the CBM mutation. Overexpression of a mouse Myod cDNA through lentiviral delivery restored the CBM mutant cells' ability to differentiate into Skm. Upstream of MYOD, Wnt signaling was demonstrated from the TOPFlash assay to have a similar inhibition. This effect on Wnt activity was further confirmed functionally by defective induction of the presomitic mesoderm marker genes BRACHYURY (T) and MESOGENIN1 (MSGN1) by Wnt3a ligand or the GSK3 inhibitor/Wnt pathway activator CHIR. Further investigation through immunofluorescence imaging and cell fractionation revealed a shifted membrane localization of ß-catenin in CBM mutant iPSCs, revealing a novel molecular component of NKA-Wnt regulation. This study sheds light on a genetic regulation of myogenesis through the CBM of NKA and control of Wnt/ß-catenin signaling.

Synergistic Experimental and Theoretical Studies of Luminescent-Magnetic Ln2Zn6 Clusters.

The present work is part of our ongoing quest for developing functional inorganic complexes using unorthodox pyridyl-pyrazolyl-based ligands. Accordingly, we report herein the synthesis, characterization, and luminescence and magnetic properties of four 3d-4f mixed-metal complexes with a general core of Ln2Zn6 (Ln = Dy, Gd, Tb, and Eu). In stark contrast to the popular wisdom of using a compartmental ligand with separate islands of hard and soft coordinating sites for selective coordination, we have vindicated our approach of using a ligand with overcrowded N-coordinating sites that show equal efficiency with both 4f and 3d metals toward multinuclear cage-cluster formation. The encouraging red and green photolumiscent features of noncytotoxic Eu2Zn6 and Tb2Zn6 complexes along with their existence in nanoscale dimension have been exploited with live-cell confocal microscopy imaging of human breast adenocarcinoma (MCF7) cells. The magnetic features of the Dy2Zn6 complex confirm the single-molecule-magnet behavior with befitting frequency- and temperature-dependent out-of-phase signals along with an Ueff value of ∼5 K and a relaxation time of 8.52 × 10-6 s. The Gd2Zn6 complex, on the other hand, shows cryogenic magnetic refrigeration with an entropy change of 11.25 J kg-1 K-1 at a magnetic field of 7 T and at 2 K. Another important aspect of this work reflects the excellent agreement between the experimental results and theoretical calculations. The theoretical studies carried out using the broken-symmetry density functional theory, ORCA suite of programs, and MOLCAS calculations using the complete-active-space self-consistent-field method show an excellent synergism with the experimentally measured magnetic and spectroscopic data.

TaWRKY74 participates copper tolerance through regulation of TaGST1 expression and GSH content in wheat.

Glutathione S-transferase (GST) is the key enzyme in glutathione (GSH) synthesis, and plays a crucial role in copper (Cu) detoxification. Nonetheless, its regulatory mechanisms remain largely unclear. In this study, we identified a Cu-induced glutathione S-transferase 1 (TaGST1) gene in wheat. Yeast one-hybrid (Y1H) screened out TaWRKY74, which was one member from the WRKY transcription factor family. The bindings between TaGST1 promoter and TaWRKY74 were further verified by using another Y1H and luciferase assays. Expression of TaWRKY74 was induced more than 30-folds by Cu stress. Functions of TaWRKY74 were tested by using transiently silence methods. In transiently TaWRKY74-silenced wheat plants, TaWRKY74 and TaGST1 expression, GST activity, and GSH content was significantly inhibited by 25.68%, 19.88%, 27.66%, and 12.68% in shoots, and 53.81%, 52.11%, 23.47%, and 17.11% in roots, respectively. However, contents of hydrogen peroxide, malondialdehyde, or Cu were significantly increased by 2.58%, 12.45%, or 37.74% in shoots, and 25.24%, 53.84%, and 103.99% in roots, respectively. Notably, exogenous application of GSH reversed the adverse effects of transiently TaWRKY74-silenced wheat plants during Cu stress. Taken together, our results suggesting that TaWRKY74 regulated TaGST1 expression and affected GSH accumulation under Cu stress, and could be useful to ameliorate Cu toxicity for crop food safety.

Exogenous Glutathione Alleviates Cadmium Toxicity in Wheat by Influencing the Absorption and Translocation of Cadmium.

Cadmium (Cd), a toxic heavy metal, is harmful to plants and human health. Glutathione (GSH) could alleviate Cd toxicity of plant species, whereas its mechanism responsible for wheat remains poorly understood. Here, we found that exogenous GSH application significantly increased the fresh and dry weight, root elongation, chlorophyll contents, while decreased the contents of malondialdehyde (MDA) and GSH, and translocation factor of Cd compared with Cd treatment. Moreover, GSH application significantly increased activities of antioxidant enzymes and expression of related genes, which involved in GSH synthesis, especially in roots. In addition, we found that GSH application suppressed Cd-induced expression of metal transporter genes TaNramp1, TaNramp5, TaHMA2, TaHMA3, TaLCT1 and TaIRT2 in roots. Taken together, our results suggested that GSH could alleviate Cd toxicity in wheat by increasing GSH synthesis gene expression or suppressing Cd transporter genes expression, and further affecting Cd uptake and translocation in wheat plants.

Effect of supplemental dexmedetomidine in interventional embolism on cerebral oxygen metabolism in patients with intracranial aneurysms.

OBJECTIVE: To investigate the effect of supplemental dexmedetomidine in interventional embolism on cerebral oxygen metabolism in patients with intracranial aneurysms. METHODS: Ninety patients who underwent interventional embolism of intracranial aneurysms were equally divided into Group A and Group B. In Group A, dexmedetomidine was injected intravenously 10 minutes before inducing anesthesia, with a loading dose of 0.6 µg/kg followed by 0.4 µg/kg/hour. Group B received the same amount of normal saline by the same injection method. Heart rate (HR), mean arterial pressure (MAP), arterial-jugular venous oxygen difference [D(a-jv) (O2)], cerebral oxygen extraction [CE (O2)], and intraoperative propofol use were recorded before inducing anesthesia (T0) and at five time points thereafter. RESULTS: The amount of propofol in Group A was lower vs Group B. At all five time points after T0, HR, MAP, D(a-jv) (O2), and CE (O2) in Group A were significantly lower vs Group B, with significant differences for jugular venous oxygen saturation (SjvO2) and the oxygen content of the internal jugular vein (CjvO2) between the groups. CONCLUSION: Dexmedetomidine resulted in less intraoperative propofol, lower D(a-jv) (O2) and CE (O2), and improved cerebral oxygen metabolism.

Lanthanide clusters of phenanthroline containing a pyridine-pyrazole based ligand: magnetism and cell imaging.

In this contribution, we report the synthesis, characterization and luminescence-magnetic properties of Ln-clusters (Ln = Gd3+, Eu3+ and Tb3+) using a new pyridine-pyrazole functionalized ligand fitted with a chromophoric phenanthroline backbone. The unorthodox N-rich ligand forms isostructural trinuclear lanthanide complexes with a topology that closely resembles two interdigitating hairpins. The clusters crystallize in chiral space groups and also exhibit chirality for bulk samples, which were further confirmed using solid state CD spectra. Magnetic studies on the complexes reveal their interesting features while the Gd cluster shows a significant cryogenic magnetic cooling behaviour with a moderately high magnetic entropy change of -23.42 J kg-1 K-1 at 7 T and 2 K. On the other hand, Eu and Tb complexes exhibit interesting fluorescence properties. The compounds were subsequently used as fluorescent probes for the imaging of human breast adenocarcinoma (MCF7) cells. Live cell confocal microscopy images show that the complexes penetrate beyond the usual cytoplasm region and can be useful in imaging the nucleus region of MCF7 cells.

Deployment of the Ophthalmic and Facial Angiosomes in the Upper Nose Overlaying the Nasal Bones.

BACKGROUND: Nasal filler placement is associated with a high risk of blindness. The arterial supply to the upper nose overlaying the nasal bones is poorly understood. OBJECTIVES: The aim of this study was to visualize and analyze the deployment of the ophthalmic and facial angiosomes in the upper nose to help prevent blindness following nasal filler injections. METHODS: The arterial systems of 62 cadaveric heads were filled with lead oxide contrast agent, and computed tomography (CT) images were acquired and reconstructed in 3 dimensions. RESULTS: Twenty-six of the cadaveric noses examined demonstrated clear CT images of the facial and ophthalmic angiosomes in the upper nose. The Type 1 upper nose (15.4%) is supplied by 2 independent ophthalmic angiosomes that communicate indirectly through a choke anastomosis. The Type 2 upper nose (38.5%) is supplied by 2 ophthalmic angiosomes with a true anastomosis between them. The Type 3 upper nose (46.1%) is supplied by both ophthalmic and facial angiosomes with true anastomoses across the dorsal midline. These true anastomoses are mediated by the radix arcade in 46% of the noses and involve the dorsal nasal artery in 65% of the cases. The anastomoses all cross the upper dorsal midline and are directly linked to the ophthalmic angiosome. CONCLUSIONS: The deployment and anastomosis of the facial and ophthalmic angiosomes in the upper nose fall into 3 major patterns. About 85% of the noses have true anastomotic arteries that cross the upper dorsal midline and are directly linked to the ophthalmic circulation. Dorsum filler injection poses a significant risk of blindness.

A CT-based radiomics nomogram for differentiation of lympho-associated benign and malignant lesions of the parotid gland.

OBJECTIVES: Preoperative differentiation between benign lymphoepithelial lesion (BLEL) and mucosa-associated lymphoid tissue lymphoma (MALToma) in the parotid gland is important for treatment decisions. The purpose of this study was to develop and validate a CT-based radiomics nomogram combining radiomics signature and clinical factors for the preoperative differentiation of BLEL from MALToma in the parotid gland. METHODS: A total of 101 patients with BLEL (n = 46) or MALToma (n = 55) were divided into a training set (n = 70) and validation set (n = 31). Radiomics features were extracted from non-contrast CT images, a radiomics signature was constructed, and a radiomics score (Rad-score) was calculated. Demographics and CT findings were assessed to build a clinical factor model. A radiomics nomogram combining the Rad-score and independent clinical factors was constructed using multivariate logistic regression analysis. The performance levels of the nomogram, radiomics signature, and clinical model were evaluated and validated on the training and validation datasets, and then compared among the three models. RESULTS: Seven features were used to build the radiomics signature. The radiomics nomogram incorporating the clinical factors and radiomics signature showed favorable predictive value for differentiating parotid BLEL from MALToma, with AUCs of 0.983 and 0.950 for the training set and validation set, respectively. Decision curve analysis showed that the nomogram outperformed the clinical factor model in terms of clinical usefulness. CONCLUSIONS: The CT-based radiomics nomogram incorporating the Rad-score and clinical factors showed favorable predictive efficacy for differentiating BLEL from MALToma in the parotid gland, and may help in the clinical decision-making process. KEY POINTS: • Differential diagnosis between BLEL and MALToma in parotid gland is rather difficult by conventional imaging modalities. • A radiomics nomogram integrated with the radiomics signature, demographics, and CT findings facilitates differentiation of BLEL from MALToma with improved diagnostic efficacy.

Decoy receptor 2 mediation of the senescent phenotype of tubular cells by interacting with peroxiredoxin 1 presents a novel mechanism of renal fibrosis in diabetic nephropathy.

Premature senescence of renal tubular epithelial cell (RTEC), which is involved in kidney fibrosis, is a key event in the progression of diabetic nephropathy. However, the underlying mechanism remains unclear. Here we investigated the role and mechanism of decoy receptor 2 (DcR2) in kidney fibrosis and the senescent phenotype of RTEC. DcR2 was specifically expressed in senescent RTEC and associated with kidney fibrosis in patients with diabetic nephropathy and mice with streptozotocin-induced with diabetic nephropathy. Knockdown of DcR2 decreased the expression of α-smooth muscle actin, collagen I, fibronectin and serum creatinine levels in streptozotocin-induced mice. DcR2 knockdown also inhibited the expression of senescent markers p16, p21, senescence-associated beta-galactosidase and senescence-associated heterochromatic foci and promoted the secretion of a senescence-associated secretory phenotype including IL-6, TGF-ß1, and matrix metalloproteinase 2 in vitro and in vivo. However, DcR2 overexpression showed the opposite effects. Quantitative proteomics and validation studies revealed that DcR2 interacted with peroxiredoxin 1 (PRDX1), which regulated the cell cycle and senescence. Knockdown of PRDX1 upregulated p16 and cyclin D1 while downregulating cyclin-dependent kinase 6 expression in vitro, resulting in RTEC senescence. Furthermore, PRDX1 knockdown promoted DcR2-induced p16, cyclin D1, IL-6, and TGF-ß1 expression, whereas PRDX1 overexpression led to the opposite results. Subsequently, DcR2 regulated PRDX1 phosphorylation, which could be inhibited by the specific tyrosine kinase inhibitor genistein. Thus, DcR2 mediated the senescent phenotype of RTEC and kidney fibrosis by interacting with PRDX1. Hence, DcR2 may act as a potential therapeutic target for the amelioration of diabetic nephropathy progression.

A caveolin binding motif in Na/K-ATPase is required for stem cell differentiation and organogenesis in mammals and C. elegans.

Several signaling events have been recognized as essential for regulating cell lineage specification and organogenesis in animals. We find that the gain of an amino-terminal caveolin binding motif (CBM) in the α subunit of the Na/K-adenosine triphosphatase (ATPase) (NKA) is required for the early stages of organogenesis in both mice and Caenorhabditis elegans. The evolutionary gain of the CBM occurred at the same time as the acquisition of the binding sites for Na+/K+. Loss of this CBM does not affect cell lineage specification or the initiation of organogenesis, but arrests further organ development. Mechanistically, this CBM is essential for the dynamic operation of Wnt and the timely up-regulation of transcriptional factors during organogenesis. These results indicate that the NKA was evolved as a dual functional protein that works in concert with Wnt as a hitherto unrecognized common mechanism to enable stem cell differentiation and organogenesis in multicellular organisms within the animal kingdom.

High-Throughput Screening of Full-Face Clinically Relevant Arterial Variations Using Three-Dimensional Postmortem Computed Tomography.

BACKGROUND: Vascular complications resulting from intravascular filler injection and embolism are major safety concerns for facial filler injection. It is essential to systematically screen full-face arterial variations and help design evidence-based safe filler injection protocols. METHODS: The carotid arteries of 22 cadaveric heads were infused with adequate lead oxide contrast. The facial and superficial temporal arteries of another 12 cadaveric heads were injected with the contrast in a sequential order. A computed tomographic scan was acquired after each contrast injection, and each three-dimensional computed tomographic scan was reconstructed using validated algorithms. RESULTS: Three-dimensional computed tomography clearly demonstrated the course, relative depth, and anastomosis of all major arteries in 63 qualified hemifaces. The ophthalmic angiosome consistently deploys two distinctive layers of branch arteries to the forehead. The superficial temporal and superior palpebral arteries run along the preauricular and superior palpebral creases, respectively. The study found that 74.6 percent of the hemifaces had nasolabial trunks coursing along the nasolabial crease, and that 50.8 percent of the hemifaces had infraorbital trunks that ran through the infraorbital region. Fifty percent of the angular arteries were the direct anastomotic channels between the facial and ophthalmic angiosomes, and 29.2 percent of the angular arteries were members of the ophthalmic angiosomes. CONCLUSIONS: Full-face arterial variations were mapped using postmortem three-dimensional computed tomography. Facial creases were in general correlated with underlying deep arteries. Facial and angular artery variations were identified at high resolution, and reclassified into clinically relevant types to guide medical practice.

High-level expression of the HIV entry inhibitor griffithsin from the plastid genome and retention of biological activity in dried tobacco leaves.

KEY MESSAGE: The potent anti-HIV microbicide griffithsin was expressed to high levels in tobacco chloroplasts, enabling efficient purification from both fresh and dried biomass, thus providing storable material for inexpensive production and scale-up on demand. The global HIV epidemic continues to grow, with 1.8 million new infections occurring per year. In the absence of a cure and an AIDS vaccine, there is a pressing need to prevent new infections in order to curb the disease. Topical microbicides that block viral entry into human cells can potentially prevent HIV infection. The antiviral lectin griffithsin has been identified as a highly potent inhibitor of HIV entry into human cells. Here we have explored the possibility to use transplastomic plants as an inexpensive production platform for griffithsin. We show that griffithsin accumulates in stably transformed tobacco chloroplasts to up to 5% of the total soluble protein of the plant. Griffithsin can be easily purified from leaf material and shows similarly high virus neutralization activity as griffithsin protein recombinantly expressed in bacteria. We also show that dried tobacco provides a storable source material for griffithsin purification, thus enabling quick scale-up of production on demand.

Insufficient Sleep Duration and Overweight/Obesity among Adolescents in a Chinese Population.

OBJECTIVES: The objective of this study was to investigate the relationship between sleep duration and overweight/obesity among Chinese adolescents. METHODS: A school-based cross-sectional study was conducted among Chinese adolescents in 2016. In total, 2795 school-aged Chinese children aged 12 to 13 years participated in this study. Participants were asked to complete self-administered surveys during a 45-min class period in their classroom. Details of the questionnaire about health-related behaviors included sleep habits, physical activity, screen time, cigarette use, and alcohol use. Height, weight, waist circumference and hip circumference were directly measured. RESULTS: The mean sleep duration was 8.7 h/day. In total, 43.0% of the participants had a sleep duration of less than 9 h/day. Sleep duration was significantly inversely related to BMI, waist circumference, hip circumference and WHtR in multiple linear regression analyses in both genders. Logistic regression models showed that insufficient sleep (<9 h/day) was associated with high odds of overweight/obesity among both young boys and girls. CONCLUSIONS: Insufficient sleep duration was associated with overweight/obesity in Chinese adolescents, and short sleep duration was probably associated with central adiposity, especially among boys.

Associations between sleep duration and physical activity and dietary behaviors in Chinese adolescents: results from the Youth Behavioral Risk Factor Surveys of 2015.

OBJECTIVE: To assess the association between sleep duration and physical activity and dietary behaviors among adolescents in a representative sample. METHODS: The analysis was performed using data from the 2015 Ningbo Youth Risk Behavior Survey. Associations between physical activity and dietary behaviors and sleep duration were examined on weighted data using logistic regression. RESULTS: Of the 10726 students, roughly 40% reported sleep duration <8 h. Longer sleep duration was associated with higher likelihood of milk intake, fruit consumption, vegetable consumption, water consumption, moderate physical activity, and muscle-strengthening physical activity, and with a lower likelihood of cigarette use, alcohol use, sweets intake, Western fast food intake, and breakfast skipping. CONCLUSION: Insufficient sleep may be common among Chinese adolescents. Sleep duration was associated with dietary behaviors, physical activity, and other health-related behaviors. These findings suggest that sleep duration could be a potential target for many health-risk behaviors in young adolescents.