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Background: Craving-related brain responses have been associated with the emergence and maintenance of addictions. However, little is known about brain network organizations underlying cravings in internet gaming disorder (IGD)., Methods: Sixty-six IGD subjects and 61 matched individuals with recreational game use (RGU) were scanned while performing a cue-craving task. A recently developed whole-brain analysis approach, connectome-based predictive modelling (CPM) with leave-one-out cross-validation was conducted to identify networks that predicted craving responses in IGD. Then, the craving network was tested in different brain states (cue-craving under deprivation) to investigate replicability., Results: CPM identified an IGD craving network, as indicated by a significant correspondence between predicted and actual craving values (r = 0.49, p < 0.001), characterized by within-network default mode (DMN) connectivity and connectivity between canonical networks implicated in executive/cognitive control (frontoparietal, medial frontal, DMN) and reward responsiveness (subcortical, motor/sensory). Network strength in the cue-craving task during gaming deprivation also predicted IGD craving scores (r = 0.43, p = 0.017), indicating network replication across brain states., Conclusions: The CPM results demonstrate that individual differences in cognitive, attention, and control network function can predict craving intensities in IGD subjects. These networks may be targets for potential interventions using brain modulation., (© 2021 Society for the Study of Addiction.)

Cancer cells acquire genetic heterogeneity to escape from immune surveillance during tumor evolution, but a systematic approach to distinguish driver from passenger mutations is lacking. Here we investigate the impact of different immune pressure on tumor clonal dynamics and immune evasion mechanism, by combining massive parallel sequencing of immune edited tumors and CRISPR library screens in syngeneic mouse tumor model and co-culture system. We find that the core microRNA (miRNA) biogenesis and targeting machinery maintains the sensitivity of cancer cells to PD-1-independent T cell-mediated cytotoxicity. Genetic inactivation of the machinery or re-introduction of ANKRD52 frequent patient mutations dampens the JAK-STAT-interferon-γ signaling and antigen presentation in cancer cells, largely by abolishing miR-155-targeted silencing of suppressor of cytokine signaling 1 (SOCS1). Expression of each miRNA machinery component strongly correlates with intratumoral T cell infiltration in nearly all human cancer types. Our data indicate that the evolutionarily conserved miRNA pathway can be exploited by cancer cells to escape from T cell-mediated elimination and immunotherapy., (© 2021. The Author(s).)

Background: Internet gaming disorder (IGD) is a type of behavioral addiction characterized by poorly controlled and interfering patterns of game playing. Studies have suggested that the IGD is usually accompanied by increased desire or craving for gaming, suggesting that secondary rewards related to gaming may become more salient than those for primary rewards like food. However, this hypothesis has not been formally tested and potential neural mechanisms remain unclear., Methods: This is a functional magnetic resonance imaging (fMRI) study. Twenty-one IGD subjects and 23 matched individuals with recreational game use (RGU) were scanned when exposed to gaming (secondary rewards), food (primary rewards) and neutral cues. Group-by-cue-type interaction analyses and subsequent within-group analyses for fMRI data were performed and seed-based functional connectivity (FC) analyses explored further potential neural features., Results: IGD subjects' subjective craving responses to gaming cues were higher than to food cues, while the opposite was observed in RGU subjects. Group-by-cue interaction effects implicated the precuneus and precuneus-caudate FC. Simple effect analysis showed that for IGD subjects, gaming-related cues elicited higher FC in precuneus-caudate relationships than did food-related cues. In the RGU subjects, the opposite was observed. Significant correlations were found between brain features and craving scores., Conclusions: These results support the hypothesis regarding imbalances in sensitivities to different types of reward in IGD, and suggest neural mechanisms by which craving for gaming may make secondary rewards more salient than primary ones, thus promoting participation in addictive patterns of gaming.

Background: Correction surgery for cleft palate is recommended between 9 and 18 months of age. Patients suffer from acute pain after palatoplasty. Clinicians are hesitant to use opioids for analgesia concerning the potential high risk of respiratory adverse events. Intravenous ibuprofen perhaps be a suitable adjuvant to pain relief. We try to assess whether preoperative administration of intravenous ibuprofen can decrease opioid requirements following cleft palate repair in infants., Methods: This single center prospective randomized clinical trial was performed from February to April 2021 at Department of Anesthesiology in Shanghai Children's Medical Center. Forty patients ASA I-II, aged 9-24 months with isolated cleft palate and undergoing palatoplasty were randomized in a 1:1 ratio to receive either a single dose of 10 mg/kg ibuprofen intravenously or normal saline at induction. Children and infants postoperative pain scale (CHIPPS) was used for pain assessment. Those patients CHIPPS pain score equal or higher than 4 received analgesic rescue with titrating intravenous fentanyl 0.5 μg/kg and repeated in 10 min if required. The primary outcome was the amount of postoperative fentanyl used for rescue analgesia in postanesthesia care unit (PACU)., Results: Patients (n = 20 in each group) in IV-Ibuprofen group required less postoperative fentanyl than those in placebo group (p<0.001). There was no significant difference between two groups in first rescue analgesia time (p = 0.079) and surgical blood loss (p = 0.194). No incidence of obvious adverse events had been found within the first 24 h after surgery in both groups., Conclusions: Preemptive intravenous administration ibuprofen 10 mg/kg at induction had a significant opioid sparing effect in early postoperative period without obvious adverse effects in infants undergoing palatoplasty., Trial Registration: CHICTR, CTR2100043718, 27/02/2021 http://www.chictr.org.cn/showproj.aspx?proj=122187., (© 2021. The Author(s).)

Background: Previous studies have shown that gaming-related cues could induce gaming cravings and bring about changes in brain activities in subjects with Internet gaming disorder (IGD). However, little is known about the brain network organizations in IGD subjects during a cue-craving task and the relationship between this network organization and IGD severity., Methods: Sixty-one IGD subjects and 61 matched recreational game users (RGUs) were scanned while performing a cue-craving task. We calculated and compared the participation coefficient (PC) among brain network modules between IGD subjects and RGUs. Based on the results, further group comparison analyses were performed to explain the PC changes and to explore the relationship between PCs and IGD severity., Results: While performing a cue-craving task, compared with RGUs, IGD subjects showed significantly decreased PCs in the default-mode network (DMN) and the frontal-parietal network (FPN). Specifically, the number of connections between nodes in the ventromedial prefrontal cortex, anterior cingulate cortex, posterior cingulate cortex and other nodes in the DMN of IGD subjects was much larger than that in RGUs. Correlation results showed that the number of DMN intra-modular connections was positively correlated with addiction severity and craving degree., Conclusions: These results provide neural evidence that can explain why cognitive control, emotion, attention and other functions are impaired in IGD subjects in the face of gaming cues, which leads to compulsive behavior toward games. These findings extend our understanding of the neural mechanism of IGD and have important implications for developing effective interventions to treat IGD subjects., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Mg-Li-based alloys were investigated for future cardiovascular stent application as they possess excellent ductility. However, Mg-Li binary alloys exhibited reduced mechanical strengths due to the presence of lithium. To improve the mechanical strengths of Mg-Li binary alloys, aluminum and rare earth (RE) elements were added to form Mg-Li-Al ternary and Mg-Li-Al-RE quarternary alloys. In the present study, six Mg-Li-(Al)-(RE) alloys were fabricated. Their microstructures, mechanical properties and biocorrosion behavior were evaluated by using optical microscopy, X-ray diffraction, scanning electronic microscopy, tensile tests, immersion tests and electrochemical measurements. Microstructure characterization indicated that grain sizes were moderately refined by the addition of rare earth elements. Tensile testing showed that enhanced mechanical strengths were obtained, while electrochemical and immersion tests showed reduced corrosion resistance caused by intermetallic compounds distributed throughout the magnesium matrix in the rare-earth-containing Mg-Li alloys. Cytotoxicity assays, hemolysis tests as well as platelet adhesion tests were performed to evaluate in vitro biocompatibilities of the Mg-Li-based alloys. The results of cytotoxicity assays clearly showed that the Mg-3.5Li-2Al-2RE, Mg-3.5Li-4Al-2RE and Mg-8.5Li-2Al-2RE alloys suppressed vascular smooth muscle cell proliferation after 5day incubation, while the Mg-3.5Li, Mg-8.5Li and Mg-8.5Li-1Al alloys were proven to be tolerated. In the case of human umbilical vein endothelial cells, the Mg-Li-based alloys showed no significantly reduced cell viabilities except for the Mg-8.5Li-2Al-2RE alloy, with no obvious differences in cell viability between different culture periods. With the exception of Mg-8.5Li-2Al-2RE, all of the other Mg-Li-(Al)-(RE) alloys exhibited acceptable hemolysis ratios, and no sign of thrombogenicity was found. These in vitro experimental results indicate the potential of Mg-Li-(Al)-(RE) alloys as biomaterials for future cardiovascular stent application and the worthiness of investigating their biodegradation behaviors in vivo., (Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

The aim of this work was to investigate the effect of various sterilization methods on surface characteristics and biocompatibility of MgCa alloy, with pure Mg as a comparison, including steam autoclave sterilization (SA), ethylene oxide steam sterilization (EO), glutaraldehyde sterilization (GD), dry heat sterilization (DH) and Co60 γ ray radiation sterilization (R) technologies. The surface characterizations were performed by environmental scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray photoelectron spectroscopy, grazing incidence X-ray diffraction, water contact angle and surface free energy measurement, whereas the cytotoxicity and hemocompatibility were evaluated by cellular adhesive experiment, platelet adhesion and hemolysis test. The results showed that the five sterilization processes caused more changes on the surface of MgCa alloy than that on the surface of pure Mg. The GD sterilization caused the most obvious changes on the surface of the pure Mg, and the SA sterilization made the largest alteration on the MgCa alloy surface. The GD and DH sterilization processes could cause increases on surface free energy for both pure Mg and MgCa alloys, while the other three sterilization processes reduced the surface free energy. The DH and GD sterilization processes caused the least alteration on the cell adhesion on pure Mg surface, whereas the EO sterilization performed the greatest impact on the cell adhesion on the Mg-Ca alloy surface. The hemolysis percentage of pure Mg and MgCa alloys were reduced by SA sterilization, meanwhile the other four sterilization processes increased their hemolysis percentages significantly, especially for the EO sterilization., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The Mg-Ca alloy system has been proposed as a potential new kind of degradable biomaterial with possible application within bone. Here microarc oxidation (MAO) coatings were fabricated on top of a Mg-Ca alloy using different applied voltages and the effect of applied voltage on the surface morphology and phase constitution, hydrogen evolution, pH variation in the immersion solution and in vitro biocompatibility of the MAO coating on the Mg-Ca alloy were extensively studied. It was found that the thickness and pore size of the MAO coating increased with the increasing applied voltage, whereas some micro-pores could be seen inside the 400 V treated MAO coating. The 360 V treated MAO coating gave the best long-term corrosion resistance during a 50 days immersion test. All the MAO coatings could promote MG63 cell adhesion, proliferation and differentiation in comparison with the uncoated Mg-Ca alloy sample, due to significantly reduced Mg ion release and pH value variations in the culture medium. After 5 days culture well-spread and elongated MG63 cells could be seen on the surface of the 360 V and 400 V MAO coatings, in contrast to no cells on the uncoated Mg-Ca alloy sample. In summary, MAO showed beneficial effects on the corrosion resistance of, and thus improved cell adhesion to, the Mg-Ca alloy, and should be a good surface modification method for other biomedical magnesium alloys., (Copyright © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Magnesium alloys have been recently developed as biodegradable implant materials, yet there has been no study concerning their corrosion fatigue properties under cyclic loading. In this study the die-cast AZ91D (A for aluminum 9%, Z for zinc 1% and D for a fourth phase) and extruded WE43 (W for yttrium 4%, E for rare earth mischmetal 3%) alloys were chosen to evaluate their fatigue and corrosion fatigue behaviors in simulated body fluid (SBF). The die-cast AZ91D alloy indicated a fatigue limit of 50MPa at 10⁷ cycles in air compared to 20MPa at 10⁶ cycles tested in SBF at 37°C. A fatigue limit of 110MPa at 10⁷ cycles in air was observed for extruded WE43 alloy compared to 40MPa at 10⁷ cycles tested in SBF at 37°C. The fatigue cracks initiated from the micropores when tested in air and from corrosion pits when tested in SBF, respectively. The overload zone of the extruded WE43 alloy exhibited a ductile fracture mode with deep dimples, in comparison to a brittle fracture mode for the die-cast AZ91D. The corrosion rate of the two experimental alloys increased under cyclic loading compared to that in the static immersion test., (Copyright © 2010 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Rapidly solidified (RS) Mg–3Ca alloy ribbons were prepared by the melt-spinning technique at different wheel rotating speeds (15 m s(-1), 30 m s(-1) and 45 m s(-1) with the as-cast Mg–3Ca alloy ingot as a raw material. The RS45 Mg–3Ca alloy ribbon showed a much more fine grain size feature (approximately 200–500 nm) in comparison to the coarse grain size (50–100 μm)of the original as-cast Mg–3Ca alloy ingot. The corrosion electrochemical tests in simulated body fluid indicated that the corrosion rate of the as-cast Mg–3Ca alloy was strongly reduced by the RS procedure and tended to be further decreased with increasing wheel rotating speeds(1.43 mm yr(-1) for RS15, 0.94 mm yr(-1) for RS30 and 0.36 mm yr(-1) for RS45). The RS Mg–3Ca alloy ribbons showed more uniform corrosion morphology compared with the as-cast Mg–3Ca alloy after polarization. The cytotoxicity evaluation revealed that the three experimental as-spun Mg–3Ca alloy ribbon extracts did not induce toxicity to the L-929 cells,whereas the as-cast Mg–3Ca alloy ingot extract did. The L-929 cells showed more improved adhesion on the surfaces of the three as-spun Mg–3Ca alloy ribbons than that of the as-cast Mg–3Ca alloy ingot.

Unlabelled: URPOSE: To isolate and culture dental pulp stem cells from human deciduous teeth, and induce them to osteoblasts., Methods: Dental pulp stem cells were separated from deciduous teeth with enzyme digestionìthen isolated and purified by limited dilution. The cells clone form rate was carried out, and cell growth curve was measured by counting the number of cells. HE stain and immunhistochemistry stain of VimentinìCD44 and STRO-1 were tested. Then the cells were induced to osteoblasts, and HE stain,AKP stain, Von Kossa stain,Van Gieson stain,and immunhistochemistry stain of osteocalcin were used for evaluation., Results: Dental pulp stem cells were obtained from deciduous teeth by limited dilution. The cells were induced to osteoblasts, which elicited a biological and morphologic characteristics similar to those of osteoblasts., Conclusions: The results show that dental pulp stem cells are obtained from deciduous teeth and induced to osteoblasts successfully.

A variant strain of rabbit hemorrhagic disease virus, designated "whn-1", was isolated and identified in China. The virus lacked haemagglutinating activity at 25, 37 and 4 degrees C, respectively, and gave negative results in the HAT after two passages in experimentally infected rabbits, but gave positive results in Agar Diffusion Reaction (ADR) and Counter Immunoelectrophoresis (CIE). Using electron microscopy, negatively stained particles of the RHDV isolate showed that the virions was approximately 35 nm in diameter. The capsid protein VP60 gene of whn-1 strain was cloned into pMD18-T vector by RT-PCR assays and sequenced. The obtained VP60 gene sequence has been submitted to GenBank with the accession number: DQ069280. The whole VP60 gene of whn-1 was 1740 nt in size and encodes 579 aa. Alignment with other 16 strains of RHDV in the world, including such "RHDVa" strains as France 99-05, France-Reu-00, Germany-Triptis and ChinaTP, in addition to RCV and EBHSV, showed that the homology of RHDV strains were 90.0-98.0% for nucleotide sequence, 94.3-99.0% for amino acid sequence, respectively. The results indicated that the sequences of VP60 gene of different RHDV isolates, including non-haemagglutinating whn-1 strain and low-haemagglutinating Rainham strain, were relatively highly homologous, and the major variant amino acid were located within region C (301-328 aa) and region E(344-434 aa), which were specific to "RHDVa" strains. Moreover, the molecular characterisation of VP60 protein of RHDV whn-1 strain, such as Hydrophilicity plot, Flexible regions, Antigenic index, etc., were compared with reference RHDV strains of Spanish-AST/89, France-99-5 and UK-Rainham in this article. From the experiment, it's concluded that, the "whn-1" strain is probably an antigenic variant of "RHDVa", and the 3 amino acids of Phe (304), Ala (305), Ser (309), and 5 amino acids of Gly (359), Asn (365), Ala (369), Ala (370), Asn (386), located in P2 region in the VP60 protein, probably played an important role in the haemagglutination activity.

The 1074-bp phyCs gene (optimized phyC gene) encoding neutral phytase was designed and synthesized according to the methylotrophic yeast Pichia pastoris codon usage bias without altering the protein sequence. The expression vector, pP9K-phyCs, was linearized and transformed in P. pastoris. The yield of total extracellular phytase activity was 17.6 U/ml induced in Buffered Methanol-complex Medium (BMMY) and 18.5 U/ml in Wheat Bran Extract Induction (WBEI) medium at the flask scale, respectively, improving over 90 folds compared with the wild-type isolate. Purified enzyme showed temperature optimum of 70 degrees and pH optimum of 7.5. The enzyme activity retained 97% of the relative activity after incubation at 80 degrees for 5 min. Because of the heavy glycosylation the expressed phytase had a molecular size of approximately 51 kDa. After deglycosylation by endoglycosylase H (EndoH(f)), the enzyme had an apparent molecular size of 42 kDa. Its property and thermostability was affected by the glycosylation.

Osteoclastic resorption was studied by scanning electron microscopy on the trabeculae of femoral heads collected from 7 cases of aged women at an average age of 72.4 years, who underwent endoprosthetic replacement for intracapsular fracture of femoral neck. Femoral head trabeculae from 3 young adults killed in traffic accident served as control. The trabeculae of the femoral head formed round or roundish arch structure. The columnar trabeculae of the femoral head in the aged women showed overt osteoclastic resorption, manifesting thinning, tapering and perforation. The icicle-like trabeculae then became rounded, lost height and eventually turned into a small tubercle. As a result, the inter-trabecular space enlarged markedly. Under high magnification, on the trabeculae could be discerned oval, narrow oval or spindle-shaped Howship lacunae, which were various in size, depth and content, but all revealed punch-out edge. Around the lacunae the collagen fibril lamella normally covering the quiscient bone surface became resorbed sooner or later. During bone resorption, the inorganic component of the bone matrix were first dissolved and resorbed leaving behind rough and irregular collagen fibrils; nevertheless, the collagen might be degraded and resorbed first with residual inorganic crystals and irregular bone nodules. Then emerged in the Howship lacunae and surrounding area newly formed collagen fibrils and bone tissue, signifying reversal and new bone formation phases following the the bone resorption phase. In the aged women, however, this phenomenon was rather infrequently encountered, thereby leaving the bone turnover always in a negative balance state.

We studied ultrastructurally the cancellous bone tissues of the upper femoral ends, collected from 12 patients undergoing endoprosthesis replacement for fractures of the femoral neck and from 7 fresh cadavers. The bone tissues were composed of meshwork of trabeculae, that constituted tier upon tier of anisotropic arch structures of different diameters and sizes. The arch structures of the cancellous bone tissues in the femoral heads assumed round or roundish configurations, whereas those of the femoral head-neck junctions revealed oval outlines and those of the femoral necks showed narrow oval profiles. The fine structures of the trabeculae in the femoral head could be divided into superficial zone, central zone, and transitional zone. Under weight-bearing, the central zone suited to sustain the load, while the superficial zone could produce elastic deformation lest fracture of the trabecaulae should ensue. The long axes of the oval arch structures of the femoral head-neck junction and the narrow oval arch structures of the femoral neck coincided with those of the femoral neck, thereby facilitating weight-bearing under physiological conditions. However, external violence in the form of either adduction or abduction force would act in a horizontal direction on the long axes of the oval and narrow oval arches so as to produce subcapital or transverse fracture of the femur in the aged.