Clinical analysis of 314 patients with high-grade squamous intraepithelial lesion who underwent total hysterectomy directly: a multi-center, retrospective cohort study.

OBJECTIVE: To identify the risk factors of cervical high-grade squamous intraepithelial lesion(HSIL) complicated with occult cervical cancer and standardize the management of initial treatment for HSIL. METHOD: The clinical data of patients who underwent total hysterectomy directly due to HSIL in the obstetrics and gynecology department of two tertiary hospitals and three secondary hospitals from 2018 to 2023 were collected. Their general characteristics, pathological parameters and survival status were analyzed. Logistic regression model was used to analyze the correlation between clinical parameters and postoperative pathological upgrading. RESULT: 1. Among the 314 patients with HSIL who underwent total hysterectomy directly, 73.2% were from primary hospitals. 2. 25 patients (7.9%) were pathologically upgraded to cervical cancer, all of which were early invasive cancer. 3. Up to now, there was no recurrence or death in the 25 patients with early-stage invasive cancer, and the median follow-up period was 21 months(range 2-59 months). 4. Glandular involvement(OR 3.968; 95%CI 1.244-12.662) and lesion range ≥ 3 quadrants (OR 6.527; 95% CI 1.78-23.931), HPV 16/18 infection (OR 5.382; 95%CI 1.947-14.872), TCT ≥ ASC-H (OR 4.719; 95%CI 1.892-11.766) were independent risk factors that affected the upgrading of postoperative pathology. 5. The area under the curve (AUC) calculated by the Logistic regression model was 0.840, indicating that the predictive value was good. CONCLUSION: There is a risk of occult cervical cancer in patients with HSIL. Glandular involvement, Lesion range ≥ 3 quadrants, HPV 16/18 infection and TCT ≥ ASC-H are independent risk factors for HSIL combined with occult cervical cancer. The prognosis of biopsy-proved HSIL patients who underwent extrafascial hysterectomy and unexpected early invasive cancer was later identified on specimen may be good.

Quantification of eosinophilic area and its potential molecular feature in clear cell renal cell carcinoma.

OBJECTIVE: Previous studies have acknowledged the presence of eosinophilic cytoplasm in clear cell renal cell carcinoma, yet the precise quantification method and potential molecular attributes in clear cell renal cell carcinoma remain elusive. This study endeavours to precisely quantify the eosinophilic attribute and probe into the molecular mechanisms governing its presence in clear cell renal cell carcinoma. METHODS: Data from cohorts of clear cell renal cell carcinoma patients who underwent nephrectomy, comprising The Cancer Genome Atlas cohort (n = 475) and Sun Yat-sen University Cancer Center cohort (n = 480), were aggregated to assess the eosinophilic attribute. Additionally, Omics data from Clinical Proteomic Tumor Analysis Consortium (CPTAC) (n = 58) were leveraged to explore the potential molecular features associated with eosinophilic clear cell renal cell carcinoma. Employing receiver operating characteristic curve analysis, the proportion of tumour cells with eosinophilic cytoplasm was determined, leading to the classification of each cohort into distinct groups: a clear group (<5%) and an eosinophilic group (≥5%). RESULTS: In both cohorts, the eosinophilic feature consistently correlated with higher International Society of Urological Pathology (ISUP) grade, elevated tumor stage, and the presence of necrosis. Furthermore, the Kaplan-Meier method demonstrated that patients in the eosinophilic group exhibited shorter overall survival or disease-free survival compared with those in the clear group, a pattern reaffirmed in various stratified survival analyses. Intriguingly, within The Cancer Genome Atlas cohort, the pathological characterization of cell cytoplasm (eosinophilic vs. clear) emerged as an independent risk factor for overall survival (hazard ratio = 2.507 [95% confidence interval: 1.328-4.733], P = 0.005) or disease-free survival (hazard ratio = 1.730 [95% confidence interval: 1.062-2.818], P = 0.028) via Cox regression analysis. Moreover, multi-Omics data unveiled frequent BAP1 mutations and down-regulation of Erythroblast Transformation-Specific-Related Gene associated with the eosinophilic feature in clear cell renal cell carcinoma. Additionally, patients with low expression of Erythroblast Transformation-Specific-Related Gene showed worse overall survival (P < 0.001). CONCLUSIONS: The quantification of the eosinophilic feature serves as a robust predictor of clinical prognosis in clear cell renal cell carcinoma. Furthermore, the manifestation of this feature may be linked to BAP1 mutations and the down-regulation of Erythroblast Transformation-Specific-Related Gene in clear cell renal cell carcinoma. Significantly, the expression levels of Erythroblast Transformation-Specific-Related Gene manifest as an exemplary prognostic marker, providing exceptional predictive accuracy for the clinical prognosis in clear cell renal cell carcinoma.

Development of a machine learning-based model for predicting positive margins in high-grade squamous intraepithelial lesion (HSIL) treatment by Cold Knife Conization(CKC): a single-center retrospective study.

OBJECTIVES: This study aims to analyze factors associated with positive surgical margins following cold knife conization (CKC) in patients with cervical high-grade squamous intraepithelial lesion (HSIL) and to develop a machine-learning-based risk prediction model. METHOD: We conducted a retrospective analysis of 3,343 patients who underwent CKC for HSIL at our institution. Logistic regression was employed to examine the relationship between demographic and pathological characteristics and the occurrence of positive surgical margins. Various machine learning methods were then applied to construct and evaluate the performance of the risk prediction model. RESULTS: The overall rate of positive surgical margins was 12.9%. Independent risk factors identified included glandular involvement (OR = 1.716, 95% CI: 1.345-2.189), transformation zone III (OR = 2.838, 95% CI: 2.258-3.568), HPV16/18 infection (OR = 2.863, 95% CI: 2.247-3.648), multiple HR-HPV infections (OR = 1.930, 95% CI: 1.537-2.425), TCT ≥ ASC-H (OR = 3.251, 95% CI: 2.584-4.091), and lesions covering ≥ 3 quadrants (OR = 3.264, 95% CI: 2.593-4.110). Logistic regression demonstrated the best prediction performance, with an accuracy of 74.7%, sensitivity of 76.7%, specificity of 74.4%, and AUC of 0.826. CONCLUSION: Independent risk factors for positive margins after CKC include HPV16/18 infection, multiple HR-HPV infections, glandular involvement, extensive lesion coverage, high TCT grades, and involvement of transformation zone III. The logistic regression model provides a robust and clinically valuable tool for predicting the risk of positive margins, guiding clinical decisions and patient management post-CKC.

Sinusoidal alternating electromagnetic field accelerates fracture healing in rats. / æ­£å¼¦äº¤å˜ç”µç£åœºå¯åŠ é€Ÿå¤§é¼ éª¨æŠ˜æ„ˆåˆ.

OBJECTIVES: To investigate the effect of sinusoidal alternating electromagnetic field (SEMF) on fracture healing and its mechanism. METHODS: Femoral fracture model was established using specific pathogen free male Wistar rats. Thirty rats were randomly divided into the control and SEMF groups with 15 rats in each group. The SEMF group was given 50 Hz 1.8 mT for 90 min every day, while the control group was not treated. X-ray examinations were performed every two weeks to determine the formation of bone scabs. Three rats from both groups were sacrificed after 2 and 4 weeks of treatment. Protein was extracted from the fractured femurs, and the expression of type Ⅰ collagen (COL-1), osterix (OSX), Runt-related transcription factor 2 (RUNX2), and vascular endothelial growth factor (VEGF) was detected by Western blotting. After 8 weeks, the femur on the operated side was taken for micro-CT scanning to observe fracture healing, angiography to observe blood vessel growth, and organs such as hearts, livers, spleens, lungs, and kidneys were taken for safety evaluation by hematoxylin-eosin staining (HE staining). RESULTS: The bone scab scores of the SEMF group were significantly higher than those of the control group after 2, 4, 6, and 8 weeks of treatment (all P<0.01). The fracture healing of the SEMF group was better than that of the control group after 8 weeks, and the bone volume scores of the two groups were 0.243±0.012 and 0.186±0.008, respectively (P<0.01); the number of blood vessels in the SEMF group was also more than that of the control group after 8 weeks. Western blotting results showed that the expressions of COL-1, OSX, RUNX2, and VEGF were higher in the SEMF group than those in the control group after 2 and 4 weeks of treatment (all P<0.05). HE staining showed that histopathological results of the examined organs were normal in both groups. CONCLUSIONS: SEMF can accelerate fracture healing by promoting the expression of osteogenic factors and vascular proliferation without significant adverse effects.

Protection of primary cilia is an effective countermeasure against the impairment of osteoblast function induced by simulated microgravity.

The molecular mechanism for the microgravity-induced decrease in bone formation remains unclear and there is a lack of effective specific preventative therapies. We recently reported that primary cilia of osteoblasts became shorter and even disappeared when the cells were exposed to random positioning machine (RPM)-simulated microgravity and that the microgravity-induced loss of osteogenic potential of osteoblasts could be attenuated when the resorption of primary cilia was prevented by treatment with 0.1 µM cytochalasin D. In the current study, it was further found that the loss of the osteogenic capacity of rat calvarial osteoblasts (ROBs) was associated with the inhibition of the BMP-2/Smad1/5/8 signalling pathway, of which most of the signalling proteins including BMP-2, BMPRII, Smad1/5/8 and p-Smad1/5/8 were found localized to primary cilia. Accompanying the resorption of primary cilia following the cells being exposed to simulated microgravity, the expression levels of these signalling proteins were reduced significantly. Furthermore, the expression of miRNA-129-3p, a microRNA previously reported to control cilium biogenesis, was found to be reduced quickly and changed in a similar tendency with the length of primary cilia. Moreover, overexpression of miRNA-129-3p in ROBs significantly attenuated microgravity-induced inhibition of BMP-2 signalling and loss of osteogenic differentiation and mineralization. These results indicated the important role of miRNA-129-3p in microgravity-induced resorption of primary cilia of osteoblasts and the potential of replenishing the miRNA-129-3p as an effective countermeasure against microgravity-induced loss of primary cilia and impairment of osteoblast function.

Simulated microgravity-induced oxidative stress and loss of osteogenic potential of osteoblasts can be prevented by protection of primary cilia.

Oxidative stress has been considered to be closely related to spaceflight-induced bone loss; however, mechanism is elusive and there are no effective countermeasures. Using cultured rat calvarial osteoblasts exposed to microgravity simulated by a random positioning machine, this study addressed the hypotheses that microgravity-induced shortening of primary cilia leads to oxidative stress and that primary cilium protection prevents oxidative stress and osteogenesis loss. Microgravity was found to induce oxidative stress (as represented by increased levels of reactive oxygen species (ROS) and malondialdehyde production, and decreased activities of antioxidant enzymes), which was perfectly replicated in osteoblasts growing in NG with abrogated primary cilia (created by transfection of an interfering RNA), suggesting the possibility that shortening of primary cilia leads to oxidative stress. Oxidative stress was accompanied by mitochondrial dysfunction (represented by increased mitochondrial ROS and decreased mitochondrial membrane potential) and intracellular Ca2+ overload, and the latter was found to be caused by increased activity of Ca2+ channel transient receptor potential vanilloid 4 (TRPV4), as also evidenced by TRPV4 agonist GSK1016790A-elicited Ca2+ influx. Supplementation of HC-067047, a specific antagonist of TRPV4, attenuated microgravity-induced mitochondrial dysfunction, oxidative stress, and osteogenesis loss. Although TRPV4 was found localized in primary cilia and expressed at low levels in NG, microgravity-induced shortening of primary cilia led to increased TRPV4 levels and Ca2+ influx. When primary cilia were protected by miR-129-3p overexpression or supplementation with a natural flavonoid moslosooflavone, microgravity-induced increased TRPV4 expression, mitochondrial dysfunction, oxidative stress, and osteogenesis loss were all prevented. Our data revealed a new mechanism that primary cilia function as a controller for TRPV4 expression. Microgravity-induced injury on primary cilia leads to increased expression and overactive channel of TRPV4, causing intracellular Ca2+ overload and oxidative stress, and primary cilium protection could be an effective countermeasure against microgravity-induced oxidative stress and loss of osteogenic potential of osteoblasts.

The interdependent relationship between the nitric oxide signaling pathway and primary cilia in pulse electromagnetic field-stimulated osteoblastic differentiation.

Pulsed electromagnetic fields (PEMFs) have long been recognized being safe and effective in treating bone fracture nonunion and osteoporosis. However, the mechanism of osteogenic action of PEMFs is still unclear. While primary cilia are reported to be a sensory organelle for PEMFs, and nitric oxide (NO) plays an indispensable role in osteogenic effect of PEMFs, the relationship between NO and primary cilia is unknown. In this study, effects of treatment with 50 Hz 0.6 mT PEMFs on osteogenic differentiation and mineralization, NO secretion, and ciliary location of specific proteins were examined in rat calvarial osteoblasts (ROBs) with normal or abrogated primary cilia. It was found that PEMFs stimulated the osteogenic differentiation by activating the NOS/NO/sGC/cGMP/PKG signaling pathway, which need the existence of primary cilia. All components of the signaling pathway including iNOS, eNOS, sGC, PKG-1, and PKG-2 were localized to primary cilia, and eNOS was phosphorylated inside the primary cilia. Besides, primary cilia were elongated significantly by PEMF treatment and changed dynamically with the activation NO/cGMP pathway. When the pathway was blocked by L-NAME, PEMFs could no longer elongate the primary cilia and stimulate the osteoblastic differentiation. Thus, this study for the first time observed activation of the NO/cGMP signaling pathway in ciliary compartment of osteoblasts, and PEMFs could not stimulate the osteoblastic differentiation if the NO signaling pathway was blocked or the ciliogenesis was inhibited. Our findings indicate the interdependent relationship between NO and primary cilia in the PEMF-promoted osteogenesis.

Chelativorans petroleitrophicus sp. nov., a paraffin oil-degrading bacterium isolated from a mixture of oil-based drill cuttings and paddy soil.

We isolated a paraffin oil-degrading bacterial strain from a mixture of oil-based drill cutting and paddy soil, and characterized the strain using a polyphasic approach. The Gram-positive, aerobic, rod-shaped and non-spore-forming strain (SCAU 2101T) grew optimally at 50 °C, pH 7.0 and 0.5 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequence indicated that the strain represented a distinct clade in the genus Chelativorans, neighbouring Chelativorans intermedius LMG 28482T (97.1 %). The genome size and DNA G+C content of the strain were 3 969 430 bp and 63.1 mol%, respectively. Whole genome based phylogenomic analyses showed that the average nucleotide identity and digital DNA-DNA hybridization values between strain SCAU 2101T and C. intermedius LMG 28482T were 77.5 and 21.2 %, respectively. The major respiratory quinone was Q-10. The dominant fatty acids were C19 : 0 cyclo ω8c (50.6 %), summed feature 8 (C18 : 1 ω7c and/or C18 : 1 ω6c; 22.5 %) and C18 : 0 (13.8 %). The polar lipids of the strain included phosphatidylethanolamine, phosphatidylmonomethylethanolamine, phosphatidylglycerol, phosphatidylcholine and diphosphatidylglycerol. Based on the results, strain SCAU 2101T was considered to represent a novel species in the genus Chelativorans, for which the name Chelativorans petroleitrophicus sp. nov. is proposed. The type strain is SCAU 2101T (= CCTCC AB 2021125T=KCTC 92067T).

Temperature-controlled microalgae biofilm adsorption/desorption in a thermo-responsive light-guided 3D porous photo-bioreactor for CO2 fixation.

Microalgae biofilm-based culture provides an efficient CO2 reduction and wastewater treatment method for its high photosynthetic efficiency and density. As supporting substrates for microalgae biofilm, porous materials have a big available adsorption area, but mutual shading makes it difficult to transmit external light to the internal surface for attached cells' photosynthesis. Thus, light-guided particles (SiO2) were introduced into photosensitive resin to fabricate a light-guided ordered porous photobioreactor (PBR) by 3D printing technology in this study. The space utilization of the PBR was significantly enhanced and the effective microalgae adsorption area was increased by 13.6 times. Further, a thermo-responsive hydrogel was grafted onto the surface of the substrate to form a smart temperature-controllable interface that could enhance microalgae adsorption and desorption in both directions. When the thermo-responsive layer received light, it would generate heat due to the hydrogel's photo-thermal effect. And the surface temperature would then raise to 33 °C, higher than the hydrogel phase transition point of 32 °C, making the surface shrinking and more hydrophobicity for microalgae cells attachment. The microalgae cells' adsorption capacity increased by 103%, resulting in a high microalgae growth rate of 3.572 g m-2 d-1. When turning off the light, the surface temperature would cool down to below 20 °C, the surface would shrink. And the biofilm shows a 564.7% increase in desorption ability, realizing temperature-controlled microalgae harvesting.

Amine-functionalized cotton for the treatment of oily wastewater.

Common commercial demulsifiers are typically made from ethylene oxide and propylene oxide. The production process is dangerous and complex, with poor adaptability and high cost. In this work, cotton modified with polyethylene polyamine was utilized as a demulsifier for the treatment of oily wastewater. The chemical structure and morphology of the as-prepared sample (CPN) were characterized by IR spectrum and SEM. The effect of CPN dosage, pH value, and salinity on the demulsification performance of oily wastewater was explored through the bottle tests. The results showed that the light transmittance of separated water was 81.7% and the corresponding deoiling rate was 98.5% when a CPN dosage of 25 mg/L was used at room temperature for 30 min. The interfacial properties were also systematically investigated, and the results indicated that CPN had better interfacial activity and a stronger reduction capability of interfacial tension compared to asphaltenes. The finding initiated and accelerated the demulsification process of oily wastewater. Based on the outstanding performance of this biomass-derived demulsifier, it shows promising potential for application in the treatment of oily wastewater.

Matrix Gla protein (MGP), GATA3, and TRPS1: a novel diagnostic panel to determine breast origin.

BACKGROUND: Metastatic breast carcinoma is commonly considered during differential diagnosis when metastatic disease is detected in females. In addition to the tumor morphology and documented clinical history, sensitive and specific immunohistochemical (IHC) markers such as GCDFP-15, mammaglobin, and GATA3 are helpful for determining breast origin. However, these markers are reported to show lower sensitivity in certain subtypes, such as triple-negative breast cancer (TNBC). MATERIALS AND METHODS: Using bioinformatics analyses, we identified a potential diagnostic panel to determine breast origin: matrix Gla protein (MGP), transcriptional repressor GATA binding 1 (TRPS1), and GATA-binding protein 3 (GATA3). We compared MGP, TRPS1, and GATA3 expression in different subtypes of breast carcinoma of (n = 1201) using IHC. As a newly identified marker, MGP expression was also evaluated in solid tumors (n = 2384) and normal tissues (n = 1351) from different organs. RESULTS: MGP and TRPS1 had comparable positive expression in HER2-positive (91.2% vs. 92.0%, p = 0.79) and TNBC subtypes (87.3% vs. 91.2%, p = 0.18). GATA3 expression was lower than MGP (p < 0.001) or TRPS1 (p < 0.001), especially in HER2-positive (77.0%, p < 0.001) and TNBC (43.3%, p < 0.001) subtypes. TRPS1 had the highest positivity rate (97.9%) in metaplastic TNBCs, followed by MGP (88.6%), while only 47.1% of metaplastic TNBCs were positive for GATA3. When using MGP, GATA3, and TRPS1 as a novel IHC panel, 93.0% of breast carcinomas were positive for at least two markers, and only 9 cases were negative for all three markers. MGP was detected in 36 cases (3.0%) that were negative for both GATA3 and TRPS1. MGP showed mild-to-moderate positive expression in normal hepatocytes, renal tubules, as well as 31.1% (99/318) of hepatocellular carcinomas. Rare cases (0.6-5%) had focal MGP expression in renal, ovarian, lung, urothelial, and cholangiocarcinomas. CONCLUSIONS: Our findings suggest that MGP is a newly identified sensitive IHC marker to support breast origin. MGP, TRPS1, and GATA3 could be applied as a reliable diagnostic panel to determine breast origin in clinical practice.

Progress in gene therapy treatments for prostate cancer.

Prostate cancer is one of the predominant cancers affecting men and has been widely reported. In the past, various therapies and drugs have been proposed to treat prostate cancer. Among these treatments, gene therapy has been considered to be an optimal and widely applicable treatment. Furthermore, due to the increased specificity of gene sequence complementation, the targeted delivery of complementary gene sequences may represent a useful treatment in certain instances. Various gene therapies, including tumor-suppressor gene therapy, suicide gene therapy, immunomodulation gene therapy and anti-oncogene therapies, have been established to treat a wide range of diseases, such as cardiac disease, cystic fibrosis, HIV/AIDS, diabetes, hemophilia, and cancers. To this end, several gene therapy clinical trials at various phases are underway. This overview describes the developments and progress in gene therapy, with a special focus being placed on prostate cancer.

Risk factors predicting residual lesion in subsequent hysterectomy following cold knife conization (CKC) for high-grade squamous intraepithelial lesion (HSIL).

OBJECTIVE: To determine risk factors predicting residual lesion in a subsequent hysterectomy follow a cold knife conization (CKC) for high-grade squamous intraepithelial lesion (HSIL). METHOD: Between January 2010 and December 2021, a total of 740 patients who underwent a hysterectomy within 3 months after CKC for HSIL were included in this study. We analyzed their demographic features and pathological parameters. A logistic regression model was used to analyze the relationship between parameters and residual lesion in subsequent hysterectomy specimens. RESULTS: 104 (14.1%) had residual lesion in the hysterectomy specimen, 3 patients with microinvasive carcinoma. The rate of residual lesion in patients with positive endocervical margin was 31.3%, with positive ectocervical margin was 15.3%, with positive combine margin was 38.6%. In multivariate analysis, positive margin (OR 4.015; 95% CI 2.526-6.381; P < 0.001), glandular involvement (OR 3.484; 95% CI 1.457-8.330; P = 0.005), HPV16/18 infection (OR 2.804; 95% CI 1.705-4.611; P < 0.001) and multiple HR-HPV infection (OR 1.813; 95% CI 1.130-2.909; P < 0.014) were independent risk factors for residual lesion. The AUC calculated by logistic regression model was 0.78. CONCLUSION: Positive margin, positive glandular involvement, HPV16/18 and multiple HR-HPV infection were independent high risk factors of residual lesion in a subsequent hysterectomy following CKC for HSIL.

A Linear-Power-Regulated Wireless Power Transfer Method for Decreasing the Heat Dissipation of Fully Implantable Microsystems.

Magnetic coupling resonance wireless power transfer can efficiently provide energy to intracranial implants under safety constraints, and is the main way to power fully implantable brain-computer interface systems. However, the existing maximum efficiency tracking wireless power transfer system is aimed at optimizing the overall system efficiency, but the efficiency of the secondary side is not optimized. Moreover, the parameters of the transmitter and the receiver change nonlinearly in the power control process, and the efficiency tracking mainly depends on wireless communication. The heat dissipation caused by the unoptimized receiver efficiency and the wireless communication delay in power control will inevitably affect neural activity and even cause damage, thus affecting the results of neuroscience research. Here, a linear-power-regulated wireless power transfer method is proposed to realize the linear change of the received power regulation and optimize the receiver efficiency, and a miniaturized linear-power-regulated wireless power transfer system is developed. With the received power control, the efficiency of the receiver is increased to more than 80%, which can significantly reduce the heating of fully implantable microsystems. The linear change of the received power regulation makes the reflected impedance in the transmitter change linearly, which will help to reduce the dependence on wireless communication and improve biological safety in received power control applications.

Opportunistic osteoporosis screening in multi-detector CT images using deep convolutional neural networks.

OBJECTIVE: To explore the application of deep learning in patients with primary osteoporosis, and to develop a fully automatic method based on deep convolutional neural network (DCNN) for vertebral body segmentation and bone mineral density (BMD) calculation in CT images. MATERIALS AND METHODS: A total of 1449 patients were used for experiments and analysis in this retrospective study, who underwent spinal or abdominal CT scans for other indications between March 2018 and May 2020. All data was gathered from three different CT vendors. Among them, 586 cases were used for training, and other 863 cases were used for testing. A fully convolutional neural network, called U-Net, was employed for automated vertebral body segmentation. The manually sketched region of vertebral body was used as the ground truth for comparison. A convolutional neural network, called DenseNet-121, was applied for BMD calculation. The values post-processed by quantitative computed tomography (QCT) were identified as the standards for analysis. RESULTS: Based on the diversity of CT vendors, all testing cases were split into three testing cohorts: Test set 1 (n = 463), test set 2 (n = 200), and test set 3 (n = 200). Automated segmentation correlated well with manual segmentation regarding four lumbar vertebral bodies (L1-L4): the minimum average dice coefficients for three testing sets were 0.823, 0.786, and 0.782, respectively. For testing sets from different vendors, the average BMDs calculated by automated regression showed high correlation (r > 0.98) and agreement with those derived from QCT. CONCLUSIONS: A deep learning-based method could achieve fully automatic identification of osteoporosis, osteopenia, and normal bone mineral density in CT images. KEY POINTS: • Deep learning can perform accurate fully automated segmentation of lumbar vertebral body in CT images. • The average BMDs obtained by deep learning highly correlates with ones derived from QCT. • The deep learning-based method could be helpful for clinicians in opportunistic osteoporosis screening in spinal or abdominal CT scans.

Thermoresponsive Surfaces Grafted by Shrinkable Hydrogel Poly(N-isopropylacrylamide) for Controlling Microalgae Cells Adhesion during Biofilm Cultivation.

Microalgae is a promising candidate for reducing greenhouse gas and producing renewable biofuels. For microalgae biofilm cultivation, a strong adhesion ability of microalgae cells onto the surface is a prerequisite to resist the fluid shear stress, while strong adhesion is not of benefit to the biofilm harvesting process. To solve this dilemma, a thermoresponsive surface (TMRS) with lower critical solution temperature of 33 °C was made by grafting N-isopropylacrylamide onto a silicate glass slide. The wettability of the TMRS changed from hydrophilic (contact angle of 59.4°) to hydrophobic (contact angle of 91.6°) when the temperature rose from 15 to 35 °C, resulting in the increase of adhesion energy of the TMRS to Chlorella vulgaris cells by 135.6%. The experiments showed that the cells were more likely to attach onto the TMRS at the higher temperature of 35 °C owing to the surface microstructures generated by the hydrogel layer shrinkage, which is similar in size to the microalgae cells. And the cell coverage rate on TMRS increased by 32% compared to the original glass surface. Conversely, the cells separate easily from the TMRS at a lower temperature of 15 °C, and the cell adhesion density was reduced by 19% due to hydrogel layer swelling to a relatively flat surface.

Retracted: Icariin attenuates methotrexate chemotherapy-induced bone marrow microvascular damage and bone loss in rats.

Methotrexate (MTX), a widely used antimetabolite in paediatric cancer to treatment, has been widely reported to cause bone loss and bone marrow (BM) microvascular (particularly sinusoids) damage. Investigations must now investigate how MTX-induced bone loss and microvasculature damage can be attenuated/prevented. In the present study, we examined the potency of icariin, an herbal flavonoid, in reducing bone loss and the dilation/damage of BM sinusoids in rats caused by MTX treatment. Groups of young rats were treated with five daily MTX injections (0.75 mg/kg) with and without icariin oral supplementation until Day 9 after the first MTX injection. Histological analyses showed a significant reduction in the bone volume/tissue volume (BV/TV) fraction (%) and trabecular number in the metaphysis trabecular bone of MTX-treated rats, but no significant changes in trabecular thickness and trabecular spacing. However, the BV/TV (%) and trabecular number were found to be significantly higher in MTX + icariin-treated rats than those of MTX alone-treated rats. Gene expression analyses showed that icariin treatment maintained expression of osteogenesis-related genes but suppressed the induction of adipogenesis-related genes in bones of MTX-treated rats. In addition, icariin treatment attenuated MTX-induced dilation of BM sinusoids and upregulated expression of endothelial cell marker CD31 in the metaphysis bone of icariin + MTX-treated rats. Furthermore, in vitro studies suggest that icariin treatment can potentially enhance the survival of cultured rat sinusoidal endothelial cells against cytotoxic effect of MTX and promote their migration and tube formation abilities, which is associated with enhanced production of nitric oxide.

Pulsed electromagnetic fields promote bone formation by activating the sAC-cAMP-PKA-CREB signaling pathway.

The application of pulsed electromagnetic fields (PEMFs) in the prevention and treatment of osteoporosis has long been an area of interest. However, the clinical application of PEMFs remains limited because of the poor understanding of the PEMF action mechanism. Here, we report that PEMFs promote bone formation by activating soluble adenylyl cyclase (sAC), cyclic adenosine monophosphate (cAMP), protein kinase A (PKA), and cAMP response element-binding protein (CREB) signaling pathways. First, it was found that 50 Hz 0.6 millitesla (mT) PEMFs promoted osteogenic differentiation of rat calvarial osteoblasts (ROBs), and that PEMFs activated cAMP-PKA-CREB signaling by increasing intracellular cAMP levels, facilitating phosphorylation of PKA and CREB, and inducing nuclear translocation of phosphorylated (p)-CREB. Blocking the signaling by adenylate cyclase (AC) and PKA inhibitors both abolished the osteogenic effect of PEMFs. Second, expression of sAC isoform was found to be increased significantly by PEMF treatment. Blocking sAC using sAC-specific inhibitor KH7 dramatically inhibited the osteogenic differentiation of ROBs. Finally, the peak bone mass of growing rats was significantly increased after 2 months of PEMF treatment with 90 min/day. The serum cAMP content, p-PKA, and p-CREB as well as the sAC protein expression levels were all increased significantly in femurs of treated rats. The current study indicated that PEMFs promote bone formation in vitro and in vivo by activating sAC-cAMP-PKA-CREB signaling pathway of osteoblasts directly or indirectly.

Flavonoid genistein protects bone marrow sinusoidal blood vessels from damage by methotrexate therapy in rats.

Cancer chemotherapy can cause significant damage to the bone marrow (BM) microvascular (sinusoidal) system. Investigations must now address whether and how BM sinusoidal endothelial cells (SECs) can be protected during chemotherapy. Herein we examined the potential protective effects of genistein, a soy-derived flavonoid, against BM sinusoidal damage caused by treatment with methotrexate (MTX). The groups of young adult rats were gavaged daily with genistein (20 mg/kg) or placebo. After 1 week, rats also received daily injections of MTX (0.75 mg/kg) or saline for 5 days and were killed after a further 4 days. Histological analyses showed that BM sinusoids were markedly dilated ( p < 0.001) in the MTX-alone group but were unaffected or less dilated in the genistein+MTX group. In control rats, genistein significantly enhanced expression of vascular endothelial growth factor (VEGF; p < 0.01), particularly in osteoblasts, and angiogenesis marker CD31 ( p < 0.001) in bone. In MTX-treated rats, genistein suppressed MTX-induced apoptosis of BM SECs ( p < 0.001 vs MTX alone group) and tended to increase expression of CD31 and VEGF ( p < 0.05). Our in vitro studies showed that genistein in certain concentrations protected cultured SECs from MTX cytotoxic effects. Genistein enhanced tube formation of cultured SECs, which is associated with its ability to induce expression of endothelial nitric oxide synthase and production of nitric oxide. These data suggest that genistein can protect BM sinusoids during MTX therapy, which is associated, at least partially, with its indirect effect of promoting VEGF expression in osteoblasts and its direct effect of enhancing nitric oxide production in SECs.

Evaluation of amplified spontaneous emission in thin disk lasers using the spectral linewidth.

Amplified spontaneous emission (ASE) is important to power scaling of the large-scale, high-gain thin disk laser. In this paper, spectral properties of ASE in Yb:YAG thin disk lasers are deeply studied in both theory and experiment. The experimental results show that the ASE strength is much stronger when emitted from the edge surface than the pumping area. And the spectrum of ASE emitted from the coarsened edge surface is angle independent. Meanwhile, the reabsorption effect in the Yb:YAG crystal on spectral linewidth is analyzed and corrected. Finally, ASE spectral linewidths have been measured. We demonstrate that the spectral linewidths can evaluate ASE strength effectively.