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Abstract Based on the existing plant layout and process flow, a simulation analysis was conducted using the Plant Simulation platform with the utilization efficiency of each station and production capacity of the dismantling system as indicators. A problem with long-term suspension in the disassembly process was determined. Based on the two optimization directions of increasing material transportation equipment and expanding the buffer capacity, a cost-oriented optimization model is established. A genetic algorithm and model simulation were used to solve the model. An optimization scheme that satisfies the production needs and has the lowest cost is proposed. The results show that the optimized dismantling system solves the suspended work problem at the dismantling station and a significant improvement in productivity and station utilization efficiency compared with the previous system.

AIM: To compare the distribution characteristics of axial sagittal front power(ASF), true net power(TNP), total corneal refractive power(TCRP)and the difference in back-front corneal radius ratio(B/F ratio)after cataract surgery.METHODS: A prospective study. A total of 156 patients(156 eyes)with age-related cataract who attend Weifang Eye Hospital for cataract surgery from December 2020 to May 2021 were collected. Pentacam was performed before operation and 3mo after operation to collect ASF, TNP and TCRP on 2, 4 and 6mm diameters rings and areas on the corneal apex and pupil-centered, as well as B/F ratio.RESULTS: 3mo after operation, there was no statistical difference in ASF on the 2mm diameters ring and area centered on the corneal apex compared with preoperative values(all P>0.05), however, the ASF values on the 4 and 6mm diameters rings and areas were significantly different from those before surgery(all P0.05). The postoperative values of TNP and TCRP on the 2, 4 and 6mm diameters rings and areas centered on the corneal apex and centered on the pupil were statistically different before surgery(all P

Abstract Background Familial hypercholesterolemia (FH) is a metabolic disease in which patients are prone to develop premature atherosclerosis (AS). Sorbin and SH3 Domain Containing 2 (SORBS2) is known to play a role in coronary heart disease (CHD). However, the mechanism underlying SORBS2 involvement in the development of hypercholesterolemia remains unknown. Here, we investigated the effects of SORBS2 on inflammation and foam cell formation and its underlying mechanisms. Methods Using Bioinformatics analysis, we established that SORBS2 is upregulated in patients with FH. Circulating concentrations of SORBS2 were measured using ELISA kit (n = 30). The association between circulating SORBS2 levels and inflammatory factors or lipid indexes were conducted using Spearman correlation analysis. We further conducted in vitro experiments that the expression of SORBS2 were analyzed, and SORBS2 siRNA were transfected into oxidized LDL (OxLDL)-induced macrophages, followed by western blot and immunofluorescence. Results Circulating SORBS2 levels were positively associated with inflammatory factors and lipid indexes. We also observed that high in vitro expression of SORBS2 in OxLDL-induced macrophages. After SORBS2 silencing, Nod like receptor family pyrin domain-containing 3 protein(NLRP3)-Caspase1 activation and NF-κB activation were attenuated, and secretion of pro-inflammatory cytokines (IL-1β and IL-18) was decreased. Moreover, SORBS2 silencing blocked reactive oxygen species (ROS) production and lipid accumulation, and promoted cholesterol efflux through ABCG1-PPARγ pathway. Conclusions SORBS2 regulates lipid-induced inflammation and foam cell formation, and is a potential therapeutic target for hypercholesterolemia.

microRNAs (miRNAs) and small interfering RNAs (siRNAs) are small non-coding RNAs (ncRNAs) that trigger RNA interference (RNAi) in eukaryotic organisms. The biogenesis pathways for these ncRNAs are well established in Drosophila melanogaster, Aedes aegypti, Bombyx mori and other insects, but lacking in hymenopteran species, particularly in parasitoid wasps. Pteromalus puparum is a parasitoid of pupal butterflies. This study identified and analyzed two pathways by interrogating the P. puparum genome. All core genes of the two pathways are present in the genome as a single copy, except for two genes in the siRNA pathway, R2D2 (two copies) and Argonaute-2 (three). Conserved domain analyses showed the protein structures in P. puparum were similar to cognate proteins in other insect species. Phylogenetic analyses of hymenopteran Dicer and Argonaute genes suggested that the siRNA pathway-related genes evolved faster than those in the miRNA pathway. The study found a decelerated evolution rate of P. puparum Dicer-2 with respect to Dicer-1, which was contrary to other hymenopterans. Expression analyses revealed high mRNA levels for all miRNA pathway genes in P. puparum adults and the siRNA related genes were expressed in different patterns. The findings add valuable new knowledge of the miRNA and siRNA pathways and their regulatory actions in parasitoid wasps.

This study was designed to analyze the causes of cervical adjacent segment degenerative disease (ASDis), evaluate the surgical outcomes of longitudinal spinous‐splitting laminoplasty with coral bone (SLAC) during cervical reoperation, and accumulate data on reoperation with SLAC in a primary hospital. Based on the inclusion and exclusion criteria, we conducted a retrospective study involving 52 patients who underwent cervical reoperation for ASDis using SLAC at the spinal surgery department of the Beijing Jishuitan Hospital from 1998 to 2014. Among them, 39 were treated with anterior cervical fusion and internal fixation during the first operation (anterior cervical corpectomy with fusion [ACCF], n = 24; anterior cervical discectomy and fusion [ACDF], n = 11; and cervical disc arthroplasty [CDA], n = 4). Outcomes were the Japanese Orthopaedic Association (JOA) score, neck disability index (NDI) score, upper limb/neck and shoulder evaluated using a visual analogue scale (VAS), and rates of ASDis. In patients who underwent an anterior cervical approach in the first instance, the incidence of ASDis was significantly higher in the C3/4 gap than in the other gaps. In the ACCF group, the lateral radiograph of the cervical spine revealed that the distance between the anterior cervical plate and the adjacent segment disc was 5 (average, 6.2) years. The pre‐reoperation and last follow‐up values were as follows: mean Japanese Orthopaedic Association score, 10.2 ± 1.5 vs 15.5 ± 0.7 (P = 0.03); neck disability index, 26.2 vs 13.6 points (P = 0.01); upper‐limb visual analog scale (VAS) score, 6.1 vs 2.6 points (P = 0.04); and neck and shoulder VAS score, 6.6 vs 2.1 points (P = 0.03). SLAC is a simple technique in which the local anatomy is clearly visible and satisfactory clinical outcomes are obtained.

Abstract Background The risk of liver fibrosis in non-alcoholic fatty liver disease (NAFLD) can be easily evaluated by noninvasive scoring systems, of which the NAFLD fibrosis score (NFS) is the most commonly used. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a new predictor of cardiovascular events, has been reported to be associated with cardiovascular outcomes and NAFLD. However, the relationship of NFS with PCSK9 and their prognostic abilities in cardiovascular risks are unknown. Methods A total of 2008 hospitalized subjects who had chest pain without lipid-lowering therapy were consecutively included. Baseline clinical data were collected, and the NFS was calculated. The circulating PCSK9 concentration was determined by enzyme immunoassay. The major adverse cardiovascular event (MACE) occurrences were recorded in the follow-up period. Associations of PCSK9 concentration with NFS were examined. All of the participants were categorized into three groups according to NFS levels and were further stratified by PCSK9 tertiles to evaluate the MACEs. Results 158 (7.87%) MACEs were observed during a mean of 3.2 years of follow-up. NFS levels were independently related to higher PCSK9 levels according to multivariable linear regression analysis. Furthermore, elevated PCSK9 and NFS concentrations were respectively associated with increased MACE incidence in multivariable Cox regression models. When combining NFS status with PCSK9 tertiles as a stratifying factor, patients with intermediate-high NFS and high PCSK9 levels had higher risks of events than those with low NFS and low PCSK9 levels. Conclusions This study revealed for the first time that NFS is positively related to PCSK9 and that the combination of NFS and PCSK9 greatly increased the risk of MACEs in patients with chest pain, providing a potential link between NFS and PCSK9 for predicting cardiovascular events.

Abstract Background Although the presence of physical signs [tendon xanthomas and/or corneal arcus (TX/CA)], are associated with the risk of coronary artery disease in patients with heterozygous familial hypercholesterolemia (HeFH), their relationship with genotypes and clinical characteristics has not been fully determined. This study aimed to examine the association of TX/CA with genetic mutation, lipid- and inflammation-related markers, the severity of coronary stenosis or calcification, and cardiovascular events (CVEs) in patients with HeFH. Methods LDLR, APOB, and PCSK9 genes were screened in 523 HeFH patients, and patients with TX/CA (n = 50) were 1:4 propensity score-matched to patients without TX/CA (n = 200) to adjust for age and sex. Laboratory markers (proprotein convertase subtilisin/kexin type 9 [PCSK9], lipoprotein(a) and high-sensitivity C-reactive protein [hsCRP]), computed tomography angiography, coronary angiography, and follow-up for CVEs were performed. Results Patients with physical signs had significantly higher low-density lipoprotein cholesterol levels; higher PCSK9 or hsCRP concentrations; more LDLR positive mutations; and higher prevalence of high tertiles of Gensini, SYNTAX and Jeopardy scores as well as coronary artery calcium scores than did those without. Over an average follow-up of 3.7 years, the incidence of CVEs was significantly higher in patients with TX/CA (log-rank p

Abstract Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) is considered to have multiple roles in the development of atherosclerosis, which is recently reported to participate in the thrombotic process. We aimed to examine the relationship between PCSK9 concentration, coagulation indexes and cardiovascular events. Methods A total of 2293 consecutive patients with angina-like chest pain and without lipid-lowering drugs treatment were enrolled and followed up for major adverse cardiovascular events (MACEs). Circulating PCSK9 concentration was determined by ELISA. The routine coagulation tests including activated partial thromboplastin time (APTT), prothrombin time (PT) and thrombin time were performed. The associations between PCSK9 concentration, routine coagulation indicators and MACEs were analyzed. Results Patients with high PCSK9 levels had lower PT and APTT levels (all p

Abstract Background Neospora caninum is one of the main causes of abortion in pregnant animals. However, N. caninum-induced reproductive injury in male mice is still unclear. Methods Male BALB/c mice were infected with a bovine isolate of N. caninum, and the organ coefficients of the testis and epididymis were measured. Lesions in the testis and epididymis were observed by light microscopy and transmission electron microscopy. Expression of the spermatogenic cell apoptosis-related proteins p53 and caspase-3 was detected by western blot. The expression of spermatogenesis-related genes in the testis was detected by reverse transcription-PCR. Sperm morphology and motility were observed. The levels of nitric oxide (NO) and antisperm antibody (AsAb) in the testicular homogenates and hormones in the serum were detected by enzyme-linked immunosorbent assay. The reproductive capacity of the male mice was detected using a reproduction test. Results The organ coefficients of the testis and epididymis of the experimental group were significantly downregulated. Light microscopy examination revealed that the spermatogenic cells of the testis were arranged in a disordered manner, and the number was reduced. The number of sperm in the epididymal lumen was significantly reduced, and the cytoplasm exhibited vacuolation and degeneration. Ultrastructural studies revealed that the cells of the testis and epididymis tissues showed varying degrees of disease. The level of p53 and caspase-3 expression in the testis was significantly upregulated. The expression of the testicular spermatogenesis-related genes Herc4, Ipo11 and Mrto4 were strongly downregulated. Observation of sperm by microscopic examination revealed significantly reduced sperm density and sperm motility, and the number of sperm deformities was significantly increased. The level of NO and AsAb was significantly increased. The levels of luteinizing hormone, follicle-stimulating hormone and gonadotropin-releasing hormone were significantly upregulated, whereas the levels of testosterone, thyrotropin-releasing hormone, thyroxine and thyroid-stimulating hormone were significantly downregulated. After challenge, the infected male mice and healthy female mice were caged together: the subsequent fetal death rate was increased, and the conception rate, litter size, number of live births and the birth weight were significantly reduced. Conclusions Infection of male BALB/c mice with the bovine isolate of N. caninum induced varying degrees of injury to the testis, epididymis and sperm of the mice, destroyed spermatogenesis and affected the reproductive capacity.

Abstract Background To explore the correlation between the volume of putamen and brain cognitive impairment in patients with HIV and to predict the feasibility of early-stage HIV brain cognitive impairment through radiomics. Method Retrospective selection of 90 patients with HIV infection, including 36 asymptomatic neurocognitive impairment (ANI) patients and 54 pre-clinical ANI patients in Beijing YouAn Hospital. All patients received comprehensive neuropsychological assessment and MRI scanning. 3D Slicer software was used to acquire volume of interest (VOI) and radiomics features. Clinical variables and volume of putamen were compared between patients with ANI and pre-clinical ANI. The Kruskal Wallis test was used to analysis multiple comparisons between groups. The relationship between cognitive scores and VOI was compared using linear regression. For radiomics, principal component analysis (PCA) was used to reduce model overfitting and calculations and then a support vector machine (SVM) was used to build a binary classification model. For model performance evaluation, we used an accuracy, sensitivity, specificity and receiver operating characteristic curve (ROC). Result There were no significant differences in clinical variables between ANI group and pre-clinical-ANI group (P>0.05). The volume of bilateral putamen was significantly different between AHI group and pre-clinical group (P

Abstract Background Whether plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) levels is a predictor for cardiovascular outcomes has currently been controversial. No data is currently available regarding the relation of PCSK9 to cardiovascular metabolic markers (CVMMs) and major adverse cardiovascular events (MACEs) in stable coronary artery disease (CAD) patients with diabetes or without diabetes. Methods A total 1225 untreated patients with stable CAD were consecutively enrolled and their baseline plasma PCSK9 levels were determined by ELISA. Patients were divided into high and low PCSK9 groups according to PCSK9 median. All patients followed up for the occurrence of MACEs and received standard therapy after admission. The associations of PCSK9 with CVMMs and MACEs were evaluated. Results PCSK9 levels were positively correlated with multiple CVMMs including total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol and hemoglobin A1c at baseline (all p

The rice mutant ossac4 (starch accumulating 4) was raised from seeds of the rice (Oryza sativa L.) indica maintainer line Xinong 1B treated with ethyl methanesulfonate. The distal and medial portions of the second leaf displayed premature senescence in the ossac4 mutant at the four-leaf stage. Physiological and biochemical analysis, and cytological examination revealed that the ossac4 mutant exhibited the premature leaf senescence phenotype. At the four-leaf stage, the leaves of the ossac4 mutant exhibited significantly increased contents of starch compared with those of the wild type (WT). Quantitative real-time PCR analysis showed that the expression levels of photosynthesis-associated genes were down-regulated and the expression levels of glucose metabolism-associated genes were abnormal. Genetic analysis indicated that the ossac4 mutation was controlled by a single recessive nuclear gene. The OsSAC4 gene was localized to a 322.7-kb interval between the simple-sequence repeat marker XYH11-90 and the single-nucleotide polymorphism marker SNP5300 on chromosome 11. The target interval contained 20 annotated genes. The present results demonstrated that ossac4 represents a novel starch accumulation and premature leaf senescence mutant, and lays the foundation for cloning and functional analysis of OsSAC4.

Sepsis is a systemic inflammatory response syndrome caused by infection, following with acute injury to multiple organs. Sepsis-induced acute kidney injury (AKI) is currently recognized as one of the most severe complications related to sepsis. The pathophysiology of sepsis-AKI involves multiple cell types, including macrophages, vascular endothelial cells (ECs) and renal tubular epithelial cells (TECs), etc. More significantly, programmed cell death including apoptosis, necroptosis and pyroptosis could be triggered by sepsis in these types of cells, which enhances AKI progress. Moreover, the cross-talk and connections between these cells and cell death are critical for better understanding the pathophysiological basis of sepsis-AKI. Mitochondria dysfunction and oxidative stress are traditionally considered as the leading triggers of programmed cell death. Recent findings also highlight that autophagy, mitochondria quality control and epigenetic modification, which interact with programmed cell death, participate in the damage process in sepsis-AKI. The insightful understanding of the programmed cell death in sepsis-AKI could facilitate the development of effective treatment, as well as preventive methods.

Abstract Background The basic helix-loop-helix (bHLH) gene family is one of the largest transcription factor families in plants and is functionally characterized in diverse species. However, less is known about its functions in the economically important allopolyploid oil crop, Brassica napus. Results We identified 602 potential bHLHs in the B. napus genome (BnabHLHs) and categorized them into 35 subfamilies, including seven newly separated subfamilies, based on phylogeny, protein structure, and exon-intron organization analysis. The intron insertion patterns of this gene family were analyzed and a total of eight types were identified in the bHLH regions of BnabHLHs. Chromosome distribution and synteny analyses revealed that hybridization between Brassica rapa and Brassica oleracea was the main expansion mechanism for BnabHLHs. Expression analyses showed that BnabHLHs were widely in different plant tissues and formed seven main patterns, suggesting they may participate in various aspects of B. napus development. Furthermore, when roots were treated with five different hormones (IAA, auxin; GA3, gibberellin; 6-BA, cytokinin; ABA, abscisic acid and ACC, ethylene), the expression profiles of BnabHLHs changed significantly, with many showing increased expression. The induction of five candidate BnabHLHs was confirmed following the five hormone treatments via qRT-PCR. Up to 246 BnabHLHs from nine subfamilies were predicted to have potential roles relating to root development through the joint analysis of their expression profiles and homolog function. Conclusion The 602 BnabHLHs identified from B. napus were classified into 35 subfamilies, and those members from the same subfamily generally had similar sequence motifs. Overall, we found that BnabHLHs may be widely involved in root development in B. napus. Moreover, this study provides important insights into the potential functions of the BnabHLHs super gene family and thus will be useful in future gene function research.

Gentamicin (GEN) is a kind of aminoglycoside antibiotic with the adverse effect of nephrotoxicity. Currently, no effective measures against the nephrotoxicity have been approved. In the present study, epigallocatechin gallate (EG), a useful ingredient in green tea, was used to attenuate its nephrotoxicity. EG was shown to largely attenuate the renal damage and the increase of malondialdehyde (MDA) and the decrease of glutathione (GSH) in GEN-injected rats. In NRK-52E cells, GEN increased the cellular ROS in the early treatment phase and ROS remained continuously high from 1.5 H to 24 H. Moreover, EG alleviated the increase of ROS and MDA and the decrease of GSH caused by GEN. Furthermore, EG activated the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). After the treatment of GEN, the protein level of cleaved-caspase-3, the flow cytometry analysis and the JC-1 staining, the protein levels of glutathione peroxidase 4 (GPX4) and SLC7A11, were greatly changed, indicating the occurrence of both apoptosis and ferroptosis, whereas EG can reduce these changes. However, when Nrf2 was knocked down by siRNA, the above protective effects of EG were weakened. In summary, EG attenuated GEN-induced nephrotoxicity by suppressing apoptosis and ferroptosis.

Abstract International oil and gas projects feature high capital-intensity, high risks and contract diversity. Therefore, in order to help decision makers make more reasonable decisions under uncertainty, it is necessary to measure the risks of international oil and gas projects. For this purpose, this paper constructs a probabilistic model that is based on the traditional economic evaluation model, and introduces value at risk (VaR) which is a valuable risk measure tool in finance, and applies VaR to measure the risks of royalty contracts, production share contracts and service contracts of an international oil and gas project. Besides, this paper compares the influences of different risk factors on the net present value ($$NPV$$ NPV ) of the project by using the simulation results. The results indicate: (1) risks have great impacts on the project’s $$NPV$$ NPV , therefore, if risks are overlooked, the decision may be wrong. (2) A simulation method is applied to simulate the stochastic distribution of risk factors in the probabilistic model. Therefore, the probability is related to the project’s $$NPV$$ NPV , overcoming the inherent limitation of the traditional economic evaluation method. (3) VaR is a straightforward risk measure tool, and can be applied to evaluate the risks of international oil and gas projects. It is helpful for decision making.

For direction of arrival (DOA) estimation with known waveform information, with a larger number of snapshots and a longer duration of the known waveforms, the required storage space for hardware implementation will increase. To save storage resources and also reduce the response time of the array system, the DOA estimation problem with short known waveforms in snapshot size is studied in this paper. We first establish the connection between DOA estimation for known waveform sources and the structured least squares (SLS) technique utilizing a potential rotation invariant property. Next, a constraint is formulated and then transformed into its real and imaginary parts to satisfy the requirements of SLS, and the resultant SLS optimization problem is solved iteratively. Simulation results show that the proposed method has a better performance than the existing DEML method for small numbers of snapshots.

Parasitoid wasps inject venom containing complex bioactive compounds to regulate the immune response and development of host arthropods and sometime paralyze host arthropods. Although extensive studies have been conducted on the identification of venom proteins in larval parasitoids, relatively few studies have examined the pupal parasitoids. In our current study, a combination of transcriptomic and proteomic methods was used to identify 64 putative venom proteins from Pachycrepoideus vindemmiae, an ectoparasitoid of Drosophila. Expression analysis revealed that 20 tested venom proteins have 419-fold higher mean expression in the venom apparatus than in other wasp tissues, indicating their specialization to venom. Comparisons of venom proteins from P. vindemmiae and other five species spanning three parasitoid families detected a core set of “ancient” orthologs in Pteromalidae. Thirty-five venom proteins of P. vindemmiae were assigned to the orthologous groups by reciprocal best matches with venoms of other pteromalids, while the remaining 29 were not. Of the 35 categories, twenty-seven have orthologous relationships with Nasonia vitripennis venom proteins and 25 with venoms of Pteromalus puparum. More distant relationships detected that five and two venom proteins of P. vindemmiae are orthologous with venoms of two Figitidae parasitoids and a Braconidae representative, respectively. Moreover, twenty-two venoms unique to P. vindemmiae were also detected, indicating considerable interspecific variation of venom proteins in parasitoids. Phylogenetic reconstruction based on a set of single-copy genes clustered P. vindemmiae with P. puparum, N. vitripennis, and other members of the family Pteromalidae. These findings provide strong evidence that P. vindemmiae venom proteins are well positioned for future functional and evolutionary studies.

The immunological interaction between Drosophila melanogaster and its larval parasitoids has been thoroughly investigated, however, little is known about the interaction between the host and its pupal parasitoids. Pachycrepoideus vindemmiae, a pupal ectoparasitoid of D. melanogaster, injects venom into its host while laying eggs on the puparium, which regulates host immunity and interrupts host development. To resist the invasion of parasitic wasps, various immune defense strategies have been developed in their hosts as a consequence of co-evolution. In this study, we mainly focused on the host immunomodulation by P. vindemmiae and thoroughly investigated cellular and humoral immune response, including cell adherence, cell viability, hemolymph melanization and the Toll, Imd, and JAK/STAT immune pathways. Our results indicated that venom had a significant inhibitory effect on lamellocyte adherence and induced plasmatocyte cell death. Venom injection and in vitro incubation strongly inhibited hemolymph melanization. More in-depth investigation revealed that the Toll and Imd immune pathways were immediately activated upon parasitization, followed by the JAK/STAT pathway, which was activated within the first 24 h post-parasitism. These regulatory effects were further validated by qPCR. Our present study manifested that P. vindemmiae regulated the cellular and humoral immune system of host D. melanogaster in many aspects. These findings lay the groundwork for studying the immunological interaction between D. melanogaster and its pupal parasitoid.

A two-dimensional numerical model is developed to investigate the phenomenon of resonance in narrow gaps. Instead of using commonly used Volume of Fluid method to capture the free surface which is sometimes difficult to capture the geometric properties of the geometrically complicated interface, the free surface is traced by using Arbitrary Lagrangian–Eulerian method. The numerical model is based on the two-dimensional Reynolds-Averaged Navier–Stokes equations. The numerical model is validated against wave propagation in wave flume. Comparisons between the numerical results and available theoretical data show satisfactory agreements. Fluid resonance in narrow gaps of fixed rectangular structures are simulated. Numerical results show that resonance wave height and wave frequency for rectangle boxes with sphenoid corners is larger than for rectangle boxes.

The fragmentation dynamics of dicationic dimers of acetylene molecules initiated upon strong-field laser ionization is studied. Time-resolved pump-probe experiments with femtosecond laser pulses, accompanied by ab initio dynamical calculations, allow us to evaluate the detailed behavior of molecular ions during the dissociation process. The dynamical properties of the intermediate C_{2}H_{2}^{+}⋯C_{2}H_{2}^{+} state created by the pump pulse are probed by a second pulse which causes further ionization. The time-dependent yield of a coincident C_{2}H_{2}^{+} + C_{2}H_{2}^{2+} ion pair exhibits an oscillation feature with a periodicity of 240 ± 30 fs. Our studies demonstrate that this is caused by an ultrafast rotation of C_{2}H_{2}^{+} cations driven by intermolecular Coulomb force together with the orientation-dependent ionization rate. We suggest that the present observation of ultrafast molecular rotation can be a general phenomenon occurring in a wide variety of systems.

AIM: To explore whether ectopic expression of human melanopsin can effectively and safely restore visual function in rd1 mice. METHODS: Hematoxylin-eosin staining of retinal sections from rd1 mice was used to detect the thickness of the outer nuclear layer to determine the timing of surgery. We constructed a human melanopsin-AAV2/8 viral vector and injected it into the subretinal space of rd1 mice. The Phoenix Micron IV system was used to exclude the aborted injections, and immunohistochemistry was used to validate the ectopic expression of human melanopsin. Furthermore, visual electrophysiology and behavioral tests were used to detect visual function 30 and 45d after the injection. The structure of the retina was compared between the human melanopsin-injected group and phosphate buffer saline (PBS)-injected group. RESULTS: Retinas of rd1 mice lost almost all of their photoreceptors on postnatal day 28 (P28). We therefore injected the human melanopsin-adeno-associated virus (AAV) 2/8 viral vector into P30 rd1 mice. After excluding aborted injections, we used immunohistochemistry of the whole mount retina to confirm the ectopic expression of human melanopsin by co-expression of human melanopsin and YFP that was carried by a viral vector. At 30d post-injection, visual electrophysiology and the behavioral test significantly improved. However, restoration of vision disappeared 45d after human melanopsin injection. Notably, human melanopsin-injected mice did not show any structural differences in their retinas compared with PBS-injected mice. CONCLUSION: Ectopic expression of human melanopsin effectively and safely restores visual function in rd1 mice.

AIM: To investigate inhibitory γ-aminobutyric acid (GABA) ergic postsynaptic currents (IPSCs) and postsynaptic currents (PSCs) in layer IV of the rat visual cortex during the critical period and when plasticity was extended through dissolution of the perineuronal nets (PNNs).METHODS:We employed 24 normal Long-Evans rats to study GABAA-PSC characteristics of neurons within layer IV of the visual cortex during development. The animals were divided into six groups of four rats according to ages at recording:PW3 (P21-23d), PW4 (P28-30d), PW5 (P35-37d), PW6 (P42-44d), PW7 (P49-51d), and PW8 (56-58d). An additional 24 chondroitin sulfate proteoglycan (CSPG) degradation rats (also Long-Evans) were generated by making a pattern of injections of chondroitinase ABC (chABC) into the visual cortex 1 week prior to recording at PW3, PW4, PW5, PW6, PW7, and PW8. Immunohistochemistry was used to identify the effect of chABC injection on CSPGs. PSCswere detected with whole-cell patch recordings, and GABAA receptor-mediated IPSCs were pharmacologically isolated.RESULTS:IPSC peak current showed a strong rise in the age-matched control group, peaked at PW5 and were maintained at a roughly constant value thereafter. Although there was a small increase in peak current for the chABC group with age, the peak currents continued to decrease with the delayed highest value at PW6, resulting in significantly different week-by-week comparison with normal development. IPSC decay time continued to increase until PW7 in the control group, while those in the chABC group were maintained at a stable level after an initial increase at PW4. Compared with normal rats, the decay times recorded in the chABC rats were always shorter, which differed significantly at each age. We did not observe any differences in IPSC properties between the age-matched control and penicillinase (P-ase) group.However, the change in IPSCs after chABC treatment was not reflected in the total PSCs or in basic membrane properties in layer IV of the rat visual cortex.CONCLUSION:Our results demonstrate that rather than rapidly increasing during the critical period for neuronal plasticity, IPSCs in layer IV of rat visual cortex are maintained at an immature level when PNNs are removed by chABC. This suggests that GABA receptor maturation involves the conformation of the CSPGs in PNNs.

Gemcitabine-based chemotherapy remains one of the standards in management of metastatic breast cancer. However, intrinsic and acquired resistance to gemcitabine inevitably occurs. The aims of this study were to assess the efficacy of the combination of src inhibition and gemcitabine in gemcitabine-resistant breast cancer cells.By using colony formation, sphere forming, flow cytometry, cell counting kit-8 and transwell assays, 231/GEM-res (gemcitabine-resistant) cell line, which was 10 times more resistant, was shown to have elevated drug tolerance, enhanced proliferative and self-renewal abilities, compared with its parental cells. Inhibition of src by both saracatinib (AZD0530) and siRNA could partially reverse gemcitabine resistance and attenuate resistance-associated anti-apoptosis, migration and stem cell capacities. In addition, the combination of src inhibition and gemcitabine had synergistic antitumor effects. Western blot analysis revealed up-regulation of pro-apoptotic protein BAX, along with the down-regulation of anti-apoptotic proteins (BCL-XL, Survivin), migration associated proteins (p-FAK, MMP-3) and cancer stem cell (CSC) markers (CD44, Oct-4), which was probably mediated by AKT/c-Jun pathway.In highly gemcitabine-resistant 231 cells, src inhibition can synergize with gemcitabine, reverse drug resistance, inhibit tumor growth/metastasis/stemness of cancer stem cells, possibly via the AKT/c-Jun pathway.

Background: The aim of the study was to provide a point of reference to study the Neospora caninum infections in China. Methods: Genome DNA was extracted from the brains of aborted fetuses and specific PCR was performed with N. caninum Nc5-targeted specific primers. Fetal bovine brain tissues were homogenized and continuously cultured in Vero cells with double antibodies. The medium was replaced at 2-d intervals and the state of cells was observed. Results: A 608 bp Nc5 gene band was detected by PCR amplification. After sequencing,the sequence of the sample shared 99.5% homology with GenBank(AF061249). Brain homogenates were continuously cultured in Vero cells for 34 d and N. caninum was found. The results of IFAT and Nc5 gene-based PCR detection were N. caninum-positive, and the parasite was tentatively named N. caninum China Yanbian strain. BABL/c mice were inoculated with the separated parasites and showed clinical symptoms of ataxia and limb paralysis after 12 d. Only 3 mice survived.The blood of dying mice and the hearts, livers, spleens, lungs, kidneys, andbrains of dead mice were collected aseptically. The Nc5 gene-based PCR showed that N. caninum may exist in brains, livers, and spleen. Based on immunohistochemical observations, we showed that N. caninum tachyzoites existed in the brains and livers. Conclusion: We have successfully isolated bovine-specific N. caninum strain from brain tissues of aborted cattle in the China Yanbian region. This isolated strain has a strong infectious ability towards BABL/c mice.

In the title molecule, C28H28O9, the phenol and the benzene rings adjacent to the α,β-unsaturated ketone unit are inclined at 9.15 (13)° to each other. The terminal phenyl ring is oriented with respect to the phenol ring at a dihedral angle of 85.88 (13)°. In the crystal, the methylene C atoms of the dihydrodioxine ring are disordered over two sites with an occupancy ratio of 0.463 (18):0.537 (18), and both disordered components of the dihydrodioxine ring adopt twisted-chair conformations. An intramolecular O—H...O hydrogen bond and weak intermolecular C—H...O hydrogen bonds are present in the crystal structure.