[Identification and functional analysis of combined oxidative phosphorylation deficiency 28 gene mutation].

Objective: To report a case of combined oxidative phosphorylation deficiency 28 (COXPD28) in China, identified the pathogenic mutation and explored the pathogenic mechanism preliminarily. Methods: The clinical characteristics of a patient with COXPD28 were retrospectively analyzed and the pathogenic mutations were identified by mitochondrial gene sequencing and whole exome sequencing. The wild-type and mutant plasmids of pathogenic genes were constructed, and effect of mutation on protein expression by quantitative real-time PCR (qPCR) and Western blot were evaluated. Statistical methods mainly used one-way ANOVA and LSD test. Results: A 21 year old female patient presented with lactic acid poisoning due to repeated chest distress and wheezing since childhood. The sequencing of the whole exon group gene found that solute carrier family 25 member 26 (SLC25A26) gene had a compound heterozygous mutation (c.34G>C, p.A12P; c.197C>A, p.A66E), which was the first report in China. In vitro function test showed that the expression levels of SLC25A26 mRNA and S-adenosylmethionine carrier (SAMC) protein in cells transfected with SLC25A26 mutant plasmid were significantly lower than those transfected with wild type plasmid. The p.A66E mutant plasmid reduced the expression level of SLC25A26 mRNA and SAMC protein to 6% and 26% of wild type plasmids respectively (both P<0.001), while p.A12P mutant plasmid decreased to 62% and 82% of wild type plasmids respectively (P<0.001, P=0.044). When the double mutant (p.A66E+p.A12P) plasmids were co-transfected, the expression levels of SLC25A26 mRNA and SAMC protein decreased to 47% and 57% of the wild type plasmids, respectively (P<0.001, P=0.001). Conclusion: The pathogenic mutation gene of this patient with COXPD28 is SLC25A26 gene mutation (p.A66E, p.A12P), which causes the decrease of SLC25A26 expression level, mitochondrial oxidative phosphorylation dysfunction, and induces COXPD28.

[Imaging and cerebrospinal fluid features of two cases with lymphomatosis cerebri].

This article reported the clinical experience of diagnosis and treatment for two patients with lymphomatosis cerebri. Case 1 was female and aged 53 years old, while case 2 was male and aged 69 years old. Progressive cognitive impairment was the main clinical manifestation in both patients. Brain magnetic resonance imaging (MRI) suggested leukoencephalopathy with patchy or mass enhancement. Cerebral blood flow was reduced on perfusion imaging in one patient. Brain biopsy confirmed diffuse large B-cell lymphoma in both cases. The concentration of interleukin-10 in cerebrospinal fluid (CSF) of two patients was significantly increased, however, the result of CSF flow cytology was negative. The current study suggests that interleukin-10 in CSF is an important biological indicator for the diagnosis of lymphomatosis cerebri, but CSF flow cytometry may not be helpful. Moreover, cerebral hypoperfusion can be present in patients with lymphomatosis cerebri.

[Analysis of China's influenza vaccine application policy based on the macro model of the health system].

This article uses the analysis framework of the macro model of the health system to analyze the influenza vaccine policy documents issued by the state and governments at all levels from three perspectives: structure, process and results, and provides a scientific basis for improving the application strategy of influenza vaccine. It is suggested that on the basis of continuing to strengthen publicity, mobilization and organizational guarantee, measures to promote the application of influenza vaccine in China by exploring multi-channel financing mechanisms, combining the experience of new crown vaccination to improve the convenience of influenza vaccination, and scientifically setting vaccination rate targets, improve preparedness for an influenza pandemic.

Space-efficient optical computing with an integrated chip diffractive neural network.

Large-scale, highly integrated and low-power-consuming hardware is becoming progressively more important for realizing optical neural networks (ONNs) capable of advanced optical computing. Traditional experimental implementations need N2 units such as Mach-Zehnder interferometers (MZIs) for an input dimension N to realize typical computing operations (convolutions and matrix multiplication), resulting in limited scalability and consuming excessive power. Here, we propose the integrated diffractive optical network for implementing parallel Fourier transforms, convolution operations and application-specific optical computing using two ultracompact diffractive cells (Fourier transform operation) and only N MZIs. The footprint and energy consumption scales linearly with the input data dimension, instead of the quadratic scaling in the traditional ONN framework. A ~10-fold reduction in both footprint and energy consumption, as well as equal high accuracy with previous MZI-based ONNs was experimentally achieved for computations performed on the MNIST and Fashion-MNIST datasets. The integrated diffractive optical network (IDNN) chip demonstrates a promising avenue towards scalable and low-power-consumption optical computational chips for optical-artificial-intelligence.

An optical neural chip for implementing complex-valued neural network.

Complex-valued neural networks have many advantages over their real-valued counterparts. Conventional digital electronic computing platforms are incapable of executing truly complex-valued representations and operations. In contrast, optical computing platforms that encode information in both phase and magnitude can execute complex arithmetic by optical interference, offering significantly enhanced computational speed and energy efficiency. However, to date, most demonstrations of optical neural networks still only utilize conventional real-valued frameworks that are designed for digital computers, forfeiting many of the advantages of optical computing such as efficient complex-valued operations. In this article, we highlight an optical neural chip (ONC) that implements truly complex-valued neural networks. We benchmark the performance of our complex-valued ONC in four settings: simple Boolean tasks, species classification of an Iris dataset, classifying nonlinear datasets (Circle and Spiral), and handwriting recognition. Strong learning capabilities (i.e., high accuracy, fast convergence and the capability to construct nonlinear decision boundaries) are achieved by our complex-valued ONC compared to its real-valued counterpart.

Effects of varying dietary intoxication with lead on the performance and ovaries of laying hens.

In this study, we explored the effect of dietary lead nitrate on zootechnical performance, egg quality, accumulation of ovarian plumbum (Pb), follicular atresia rate, and ovarian oxidative stress in laying hens. Furthermore, the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling molecule was studied to reveal the molecular mechanism of the stress. A total of 512 Hy-Line Brown laying hens aged 40 wk were randomly allocated to 4 groups (with 8 pens per group and 16 hens per pen). The Pb concentrations used to treat the 4 groups were 3.20, 33.20, 63.20, and 93.20 mg/kg. The results revealed that dietary Pb exposure significantly linearly reduced the zootechnical performance (P < 0.01) but significantly linearly increased the feed conversion ratio (P < 0.01). The dietary Pb exposure significantly linearly reduced the Haugh units (P < 0.01), albumen height (P < 0.01), eggshell thickness (P < 0.01), and eggshell strength (P < 0.01). In addition, the dietary Pb exposure significantly enhanced the follicular atresia rate (P < 0.01). After dietary Pb exposure, superoxide dismutase (P < 0.01) and glutathione peroxidase (GSH-Px) (P < 0.01) activities and glutathione (P < 0.01) contents were significant decreased quadratically, and there were significant linear decreases in the activities of catalase (CAT) (P < 0.01) and glutathione reductase (GR) (P < 0.01), whereas malondialdehyde content was significantly linearly increased (P < 0.01). In addition, except for manganese superoxide dismutase, the gene expressions of copper-zinc superoxide dismutase (P < 0.01), CAT (P < 0.01), and GR (P < 0.01) were significant decreased linearly. In addition, there were significantly quadratic decreases in the mRNA expressions of GSH-Px (P < 0.01) and Nrf2 (P < 0.01). By way of contrast, the Kelch-like ECH-associated protein 1 (Keap1) gene expression was significantly linearly increased (P < 0.01). In conclusion, dietary Pb exposure could induce oxidative stress by impairing the Nrf2-Keap1 signal pathway in the ovaries of laying hens.

Author Correction: Sculpting nanoparticle dynamics for single-bacteria-level screening and direct binding-efficiency measurement.

The original version of this Article omitted the author Kuan Wang, who is from the 'College of Biomedical Engineering, Taipei Medical University, Taipei 11031, Taiwan' and 'Nanyang Environment & Water Research Institute, Nanyang Technological University, Singapore 637141, Singapore.'Also, the author S.H. Lim was incorrectly given as L.S. Hoi and A. Larsson was incorrectly given as A. Larson.The "Author contributions" was amended to reflect the authorship changes. It previously read 'Y.Z.S., C.-W.Q., and A.Q.L. jointly conceived the idea. Y.Z.S., S.X., Y.Z., J.B.Z., W.S., J.H.W., T.N.C., Z.C.Y., Y.L.H., B.L., P.H.Y., D.P.T., and C.-W.Q. performed the numerical simulations and theoretical analysis. Y.Z.S., S.X., and L.K.C. did the fabrication and experiments of particle hopping, biomolecule binding and flow cytometry. A.L. and L.S.H. did the SPR experiments. S.X., Y.Z.S., Y.Z., C.-W.Q., Y.-Y.C., L.K.C., T.H.Z., and A.Q.L. prepared the manuscript. S.X., Y.Z., C.-W.Q., and A.Q.L. supervised and coordinated all the work. All authors commented on the manuscript.' The correct version states 'B.L., K. W., P.H.Y.' instead of 'B.L., P.H.Y.' and 'S.H.L.' in place of 'L.S.H.'This has been corrected in both the PDF and HTML versions of the Article.

Sculpting nanoparticle dynamics for single-bacteria-level screening and direct binding-efficiency measurement.

Particle trapping and binding in optical potential wells provide a versatile platform for various biomedical applications. However, implementation systems to study multi-particle contact interactions in an optical lattice remain rare. By configuring an optofluidic lattice, we demonstrate the precise control of particle interactions and functions such as controlling aggregation and multi-hopping. The mean residence time of a single particle is found considerably reduced from 7 s, as predicted by Kramer's theory, to 0.6 s, owing to the mechanical interactions among aggregated particles. The optofluidic lattice also enables single-bacteria-level screening of biological binding agents such as antibodies through particle-enabled bacteria hopping. The binding efficiency of antibodies could be determined directly, selectively, quantitatively and efficiently. This work enriches the fundamental mechanisms of particle kinetics and offers new possibilities for probing and utilising unprecedented biomolecule interactions at single-bacteria level.

High-resolution and multi-range particle separation by microscopic vibration in an optofluidic chip.

An optofluidic chip is demonstrated in experiments for high-resolution and multi-range particle separation through the optically-induced microscopic vibration effect, where nanoparticles are trapped in loosely overdamped optical potential wells created with combined optical and fluidic constraints. It is the first demonstration of separating single nanoparticles with diameters ranging from 60 to 100 nm with a resolution of 10 nm. Nanoparticles vibrate with an amplitude of 3-7 µm in the loosely overdamped potential wells in the microchannel. The proposed optofluidic device is capable of high-resolution particle separation at both nanoscale and microscale without reconfiguring the device. The separation of bacteria from other larger cells is accomplished using the same chip and operation conditions. The unique trapping mechanism and the superb performance in high-resolution and multi-range particle separation of the proposed optofluidic chip promise great potential for a diverse range of biomedical applications.

First Report of Paulownia Witches'-Broom Phytoplasma in China.

Paulownia witches'-broom (PaWB) is one of the most important diseases affecting Paulownia tomentosa trees in China. According to 2006 statistics, the disease has affected 880,000 ha of trees for timber production causing billions of dollars in economic losses. During the spring and summer of 2006, a survey was done in Shaanxi Province to confirm phytoplasma infection of paulownia trees exhibiting symptoms of witches'-broom, stunting, yellowing, and proliferating secondary shoots. Foliage samples were collected from 24 symptomatic and 8 symptomless paulownia plants in eight different production fields. Total DNA was extracted from 0.5 g of leaf midrib and stem phloem tissue with a modified cetyltrimethylammoniumbromide (CTAB) method (3). Resulting DNA extracts were analyzed by a nested PCR assay using phytoplasma 16S rRNA gene primer pairs R16mF2/R16mR1 followed by R16F2n/ R16R2 (1), which amplified a 1.4-kb and a 1.2-kb product, respectively, from symptomatic plants. Restriction fragment length polymorphism (RFLP) analysis of the nested 1.2-kb 16S rDNA products with AluI, MseI, HhaI, HpaI, RsaI, BfaI, HinfI, and TaqI endonuclease (2) indicated that all symptomatic plants were infected by a phytoplasma belonging to aster yellows group (16SrI) subgroup D (16SrI-D) phytoplasma strains. A 1.2-kb 16S rDNA sequence (GenBank Accession No. DQ851169) derived from representative strain PaWB-Shaanxi was identical (100%) to that of PaWB phytoplasma (L27033), a known subgroup 16SrI-D strain from Taiwan (2). The agreement between the RFLP analysis and sequence data confirms that PaWB from Shaanxi is a member of subgroup 16SrI-D. To our knowledge, this is the first report of PaWB disease being present in China and of its association with the 16SrI-D subgroup. References: (1) D. E. Gundersen and I.-M. Lee. Phytopathol. Mediterr. 35:144, 1996. (2) I.-M. Lee et al. Inst. J. Syst. Bacteriol. 48:1153, 1998. (3) Y. Qi et al. Biotechnol. Bull. 4:44, 2004.

Reduced p21(WAF1/CIP1) expression is an early event in gallbladder carcinogenesis and is of prognostic significance for patients with carcinomas of the gallbladder.

The molecular basis underlying the development and progression of gallbladder carcinoma (GBC) remains poorly understood. To evaluate the roles of p21(WAF1/CIP1) and p53 in gallbladder carcinogenesis and to assess their prognostic significance for patients with GBC, we used immunohistochemistry to examine the expression of p21(WAF1/CIP1) and p53 protein in a series of surgically resected specimens, including normal epithelia, precancerous lesions adenoma, and dysplasia, and carcinomas of the gallbladder. Reduced p21(WAF1/CIP1) expression was frequently observed in carcinomas (18 of 37 lesions; 49%), and even in precancerous lesions adenomas (3 of 7; 43%) and dysplasias (5 of 5; 100%). p53 overexpression was detected in 43% of the adenomas, 60% of the dysplasias and 57% of the carcinomas. There was an inverse relationship between p21(WAF1/CIP1) and p53 expression in GBCs (P =.01). Survival analysis indicated that reduced p21(WAF1/CIP1) expression was significantly associated with shortened disease-free and overall survival (P =.04 and.03, respectively) for patients with stages II to IV GBCs. These observations suggest that reduced p21(WAF1/CIP1) expression and p53 overexpression contribute to GBC from an early stage and that determination of p21(WAF1/CIP1) expression in surgically resected specimens would add prognostic information to conventional pathologic examinations for patients with advanced-stage GBC.

[Treatment effects of electroacupuncture on gentamycin ototoxicity and its mechanism in guinea pigs].

AIM: To investigate the effects of electroacupuncture on gentamycin (GE) ototoxicity in guinea pigs. METHODS: Brainstem auditory evoked potential (BAEP) and histochemistry were used in our study. RESULTS: Electroacupuncture reduced the elevated BAEP thresholds and shortened the prolongated BAEP wave latencies and interpeak latencies. It protected the activity of mitochondrial enzyme in the cochlear hair cells and cochlear stria vascularis. CONCLUSION: Electroacupuncture therapy can reduce GE ototoxicity. The mechanism of electroacupuncture therapy may be associated with its protected activity of mitochondrial enzyme and maintenance of energy metabolism of the cochlear hair cells and cochlear stria vascularis.

Alterations of retinoblastoma protein and p16INK4 protein expression in extrahepatic bile duct carcinomas.

BACKGROUND/AIMS: Human cancer development results from dysfunction of G1-phase regulators of the cell cycle. Retinoblastoma protein and p16INK4 are the most essential links between cell cycle control and cancer. We examined the expression of p16INK4 and pRb and their possible prognostic relevance in 34 extrahepatic bile duct carcinomas. METHODOLOGY: Expression of pRb and p16INK4 was determined using immunohistochemical techniques. Associations between expression of pRb and p16INK4 and the clinicopathological features were analyzed by using the chi 2 test and survival analysis was performed by Log-rank test. RESULTS: Two (6%) extrahepatic bile duct carcinomas were pRb negative, 26 (76%) showed pRb overexpression, and 6 (18%) demonstrated moderate expression. Twenty-two (65%) tumors were p16INK4 negative and 12 (35%) were p16INK4-positive. Cases with pRb-negative or pRb overexpression were significantly correlated with tumor progression (P = 0.004) and TNM stage (P = 0.009). Alterations in pRb and p16INK4 expression did not correlate with patient outcome. CONCLUSIONS: Alterations of pRb and p16INK4 expression are frequently involved in extrahepatic bile duct carcinomas, and that aberrant pRb expression significantly associates with tumor progression.

Cyclin D1 overexpression is a critical event in gallbladder carcinogenesis and independently predicts decreased survival for patients with gallbladder carcinoma.

This study was designed to test the hypothesis that cyclin D1 overexpression is involved in the multistep process of gallbladder carcinogenesis and can be used to predict poor prognosis for patients with gallbladder carcinoma (GBC). Cyclin D1 expression was examined immunohistochemically in a series of specimens, including 8 normal epithelia, 8 benign adenomyoma lesions, 6 precancerous adenomas, and 37 carcinomas of the gallbladder. Four of the 6 (67%) adenomas and 15 of the 37 (41%) adenocarcinomas demonstrated cyclin D1 overexpression (>5% nuclear staining), whereas all normal epithelia and adenomyoma lesions were negative for cyclin D1. Kaplan-Meier curves showed that cyclin D1 overexpression was significantly related to decreased overall survival (P < 0.05) in patients with GBCs. The Cox proportional hazards model identified cyclin D1 overexpression as an independent prognostic marker for death (P = 0.024; risk ratio, 4.2; 95% confidence interval, 1.2-14.7). To test whether cyclin D1 overexpression is a critical event in gallbladder neoplasms, cyclin-dependent kinase inhibitor p27Kip1 was introduced to ascertain how cyclin D1 affects clinical outcomes. Subsequently, neoplasms were divided into three groups on the basis of the combination of cyclin D1 expression and p27Kip1 status, which had been determined previously. Group 1 showed no abnormality in either cyclin D1 or p27Kip1 expression. Group 2 showed aberrant expression of one of the two proteins, whereas group 3 showed concurrent abnormalities in both proteins. Results indicated that overall survival was greatest in group 1, followed by a significant decrease in group 2 and a more precipitous decrease in group 3. In conclusion, cyclin D1 overexpression is an early event in gallbladder carcinogenesis and independently predicts decreased survival for patients with GBC.

Overexpression of retinoblastoma protein predicts decreased survival and correlates with loss of p16INK4 protein in gallbladder carcinomas.

This study was designed to determine whether the level of retinoblastoma protein (pRb) expression predicts tumor progression and prognosis in gallbladder carcinomas (GBCs) and the relationship between pRb and pl6INK4 protein expression. The expression of these two proteins was evaluated immunohistochemically in 37 tumors from 36 patients with GBC. pRb loss and overexpression were observed in 5 (13.5%) and 18 (48.6%) of the 37 tumors, respectively. Both pRb loss and overexpression were significantly correlated with advanced TNM stage, lymph node metastasis, and tumor perineural invasion. Moreover, pRb overexpression was significantly associated with decreased overall survival (P = 0.001; log-rank test). Further analysis indicated that the influence of pRb overexpression on survival was independent of TNM stage and lymph node metastasis. Loss of p16INK4 protein was observed in 28 of the 37 GBCs (75.7%), but was not significantly associated with any clinicopathological factors or survival. pRb overexpression was significantly associated with the loss of p161NK4 protein (P < 0.0001). These results suggest that pRb overexpression significantly predicts decreased survival in GBCs.

Reduced p21(WAF1/CIP1) protein expression is predominantly related to altered p53 in hepatocellular carcinomas.

To investigate the relationship between the expression of p21(WAF1/CIP1) protein and p53 status and the possible role of the two proteins in hepatocellular carcinomas (HCCs), we examined the expression of p21(WAF1/CIP1) and p53 immunohistochemically in 81 tumours from 65 patients with hepatocellular carcinoma. p21(WAF1/CIP1) protein was absent from 59 of 81 tumours (72.8%), and altered p53 expression was found in 43 (53.1%). p21(WAF1/CIP1) expression was significantly associated with p53 status (P = 0.0008); 38 of 59 tumours lacking p21(WAF1/CIP1) protein were accompanied by altered p53 expression. Further analyses showed that p21(WAF1/CIP1) expression was inversely correlated with p53 expression in hepatitis C virus (HCV)-related HCCs, but not in HBV-related hepatocellular carcinomas and hepatocellular carcinomas without viral infection. All 11 tumours with intrahepatic metastasis showed altered p21(WAF1/CIP1) or p53 expression. In contrast, no intrahepatic metastasis was found in any of the 17 tumours without abnormal expression of either of the two proteins. These results suggest that: (1) different modes of p21(WAF1/CIP1) regulation are involved in HCCs differing in their hepatitis viral infection status, and p21(WAF1/CIP1) expression appears to be predominantly related to altered p53 in HCV-related HCCs; (2) disruption of the p53-p21(WAF1/CIP1) cell-cycle-regulating pathway may contribute to malignant progression of HCC.