Development and Evaluation of Nano‑scale Systems for Targeted Delivery to Treat Liver Fibrosis

Excessive deposition of ECM is the common characteristic of liver fibrosis. During hepatic fibrosis, various inflammatory cytokines are released and trigger the activation of quiescent HSCs. The activated HSCs play the major role in producing extra amount collagen. It becomes very crucial to focus on HSCs to find out therapeutics, such as inhibiting collagen synthesis, inhibiting activation to myofibroblasts, or controlling inflammation. To control excessive collagen synthesis, one triplex forming oligonucleotides (TFO), was systemically administrated to prevent type I collagen mRNA transcription. To enhance circulation time and targeted delivery efficiency, TFO was conjugated to M6P‑HPMA and showed efficient targeted delivery to HSCs. Two week short term in vivo i.v. administration also showed the therapeutic effects on liver fibrosis by M6P‑HPMA‑TFO. Transforming growth factor β1 (TGF‑β1) acts as the initial factor for liver fibrosis. TGF‑β1 gene was demonstrated to be interfered by siRNA in a sequence and dose dependent mode in HSC‑T6 cell line. Later, GFAP promoter driven HSC‑specific pri‑miRNA mimic and pri‑miRNA cluster mimic showed HSC‑specific TGF‑β1 gene silencing to avoid nonspecific inhibition of TGF‑β1 expression in other cells and organs. The novel LPA antagonist, PTP, can interact with LPA receptor on the surface of cells to inhibit the proliferation, which is also one consequence of HSCs activation. However, the low aqueous solubility affects its in vivo application. Therefore, poly(ethylene glycol)‑b‑poly(carbonate‑co‑lactide) copolymers were used to make micellar formulation to enhance solubility. PEG‑PCcL micelles were applied to increase the aqueous solubility of PTP. In vivo administration of PTP loaded PEG‑PCcL showed therapeutic effects on fibrosis in common bile duct ligated mice

Numerical Simulation of Fracture Width Influencing Law on Reservoir Permeability after Fracturing

Based on the fluid-solid coupling theory in porous media, a finite element simulation model for dynamic fracture creation is established and the finite element simulation program is developed, and then relevant finite element simulation is conducted on the permeability distribution under the simultaneous influence of fracture creation and pressure-released production. Research results demonstrate that the permeability distribution law after fracturing is similar for fractures with different widths, and the permeability distribution shapes in ellipse. When the maximal fracture width is greater than or equal to 6mm, the influence region on the permeability increases apparently with the increment of fracture width, so does the influence in the vicinity of the wellbore. The fracture creation and pressure-released production alternately dominates the alteration of permeability in different regions. Dynamic fracture creation plays a more important role in permeability alteration within the region less than 5m away from the wellbore axis. The larger for the fracture width, the more sensitive for the permeability alteration gradient is observed in the region in the vicinity of the wellbore. In the region 20m away from the wellbore axis, the pressure-released production affect more apparently since dynamic fracture creation has a negligible effect in the region.Key words:Fluid-solid coupling; Permeability; Fracture; Wellbore; Simulatio

Texture features based microscopic image classification of liver cellular granuloma using artificial neural networks

Automated classification of Schistosoma mansoni granulomatous microscopic images of mice liver using Artificial Intelligence (AI) technologies is a key issue for accurate diagnosis and treatment. In this paper, three grey difference statistics-based features, namely three Gray-Level Co-occurrence Matrix (GLCM) based features and fifteen Gray Gradient Co-occurrence Matrix (GGCM) features were calculated by correlative analysis. Ten features were selected for three-level cellular granuloma classification using a Scaled Conjugate Gradient Back-Propagation Neural Network (SCG-BPNN) in the same performance. A cross-entropy is then calculated to evaluate the proposed Sigmoid input and the ten-hidden layer network. The results depicted that SCG-BPNN with texture features performs high recognition rate compared to using morphological features, such as shape, size, contour, thickness and other geometry-based features for the classification. The proposed method also has a high accuracy rate of 87.2% compared to the Back-Propagation Neural Network (BPNN), Back-Propagation Hopfield Neural Network (BPHNN) and Convolutional Neural Network (CNN)

Analysis of risk factors for recurrence in infertile endometrial cancer patients after in vitro fertilization treatment

PurposeTo investigate the oncologic outcomes of patients with early-stage endometrioid endometrial cancer (EEC) treated with in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) following fertility-sparing treatment (FST).MethodsA total of 62 patients who underwent IVF/ICSI treatment in a single fertility center between June 2010 and December 2021 after conservative treatment for early-stage EEC were assigned to a recurrence group and a non-recurrence group. Their clinical characteristics and disease outcomes were retrospectively evaluated.ResultsThe 62 women with complete remission (CR) after FST for EEC underwent 103 IVF cycles, resulting in 41 fresh embryo transfers (ETs) and 70 frozen–thawed transfers; 27 (43.55%) achieved clinical pregnancies, and 20 (32.26%) gave birth to a total of 23 live neonates. Additionally, nine patients had live births from natural pregnancies after IVF failure, bringing the cumulative live birth rate to 46.77% (29/62). After a median follow-up period of 53.88 months (range 20.2–127.5 months), 17 patients (27.42%) experienced recurrence within 2.8 to 57.9 months after the first controlled ovarian stimulation (COS). The probability of relapse at 1, 2, and 3 years after the initiation of COS was 14.52% (9/62), 21% (13/62), and 25.81% (16/62), respectively. Factors such as the time to CR, the time to IVF, the frequency of COS, maintenance treatment before IVF, and histology type were not found to significantly affect recurrence (p = 0.079, 0.182, 0.093, 0.267, and 0.41, respectively). Live births (hazard ratio (HR): 0.28, 95% CI: 0.082–0.962, p = 0.043) and the protocol of letrozole plus gonadotropin-releasing hormone (GnRH) antagonist/agonist used during IVF (HR: 0.1, 95% CI: 0.011–0.882, p = 0.038) were identified as independent favorable factors for recurrence.ConclusionsLive birth was associated with decreased recurrence of EEC. Reducing estrogen levels during COS may serve to mitigate the risk of endometrial cancer recurrence

Effect of Annealing Process on CH 3

The morphology of compact TiO2 film used as an electron-selective layer and perovskite film used as a light absorption layer in planar perovskite solar cells has a significant influence on the photovoltaic performance of the devices. In this paper, the spin coating speed of the compact TiO2 is investigated in order to get a high-quality film and the compact TiO2 film exhibits pinhole- and crack-free films treated by 2000 rpm for 60 s. Furthermore, the effect of annealing process, including annealing temperature and annealing program, on CH3NH3PbI3-XClX film morphology is studied. At the optimal annealing temperature of 100°C, the CH3NH3PbI3-XClX morphology fabricated by multistep slow annealing method has smaller grain boundaries and holes than that prepared by one-step direct annealing method, which results in the reduction of grain boundary recombination and the increase of Voc. With all optimal procedures, a planar fluorine-doped tin oxide (FTO) substrate/compact TiO2/CH3NH3PbI3-XClX/Spiro-MeOTAD/Au cell is prepared for an active area of 0.1 cm2. It has achieved a power conversion efficiency (PCE) of 14.64%, which is 80.3% higher than the reference cell (8.12% PCE) without optimal perovskite layer. We anticipate that the annealing process with optimal compact TiO2 layer would possibly become a promising method for future industrialization of planar perovskite solar cells

Pressure tuning of optical reflectivity in LuH2

Recently, the claim of room-temperature superconductivity in nitrogen-doped lutetium hydride at near-ambient conditions has attracted tremendous attention. Criticism of the work rises shortly, while further explorations are needed to settle the dispute. One of the intriguing observations is the pressured-induced color change, which has been reproduced in the lutetium dihydride LuH2 while its mechanism remains unclear. Through optical reflectivity measurements of LuH2 in the visible to near-infrared region, we observe strong light absorption next to the sharp plasmon resonance, which continuously shifts to higher energies with increasing pressure. It gives rise to the increased reflection of red light and suppressed reflection of blue light. Our work sheds light on resolving the puzzles regarding the pressure induced color change in LuH2.Comment: 8 pages, 6 figure

Loss of Parietal Memory Network Integrity in Alzheimer’s Disease

A functional brain network, termed the parietal memory network (PMN), has been shown to reflect the familiarity of stimuli in both memory encoding and retrieval. The function of this network has been separated from the commonly investigated default mode network (DMN) in both resting-state fMRI and task-activations. This study examined the deficit of the PMN in Alzheimer’s disease (AD) patients using resting-state fMRI and independent component analysis (ICA) and investigated its diagnostic value in identifying AD patients. The DMN was also examined as a reference network. In addition, the robustness of the findings was examined using different types of analysis methods and parameters. Our results showed that the integrity as an intrinsic connectivity network for the PMN was significantly decreased in AD and this feature showed at least equivalent predictive ability to that for the DMN. These findings were robust to varied methods and parameters. Our findings suggest that the intrinsic connectivity of the PMN is disrupted in AD and further call for considering the PMN and the DMN separately in clinical neuroimaging studies