[Evaluation of kurtosis on hearing loss caused by non-steady state noise in general equipment manufacturing industry].

Objective: To study the effect of occupational exposure to non-steady state noise on hearing loss in the general equipment manufacturing industry, and to explore the feasibility of applying kurtosis index to evaluate hearing loss caused by non-steady state noise. Methods: A total of 233 workers exposed to non-steady state noise in 6 general equipment manufacturing enterprises were selected as the observation group, and 237 workers exposed to steady noise in 4 textile enterprises were selected as the control group between 2012 and 2018. Personal normalized continuous A-weighted sound pressure level equivalent to an 8 h-working-day (L(Aeq, 8 h)) was determined by a noise dosimeter. Cumulation noise exposure (CNE) was calculated from L(Aeq, 8 h) and related working age, and the CNE was adjusted by using noise kurtosis (CNE' after adjustment) . Meanwhile, questionnaires and hearing loss tests were performed for all subjects. The changes in the threshold of high-frequency hearing and the incidence of high-frequency hearing loss caused by noise in the two groups were compared before and after the adjustment of the kurtosis of CNE. The correlation between CNE and the incidence of high-frequency hearing loss before and after kurtosis adjustment was analyzed. Results: There was an difference between the 3000-8000 Hz hearing threshold of workers in different CNE groups (P<0.05) . logistic regression analysis showed that CNE was a risk factor of high-frequency hearing loss for workers in the observation group (OR=1.189, P<0.05) , and trend Chi-square test showed that the incidence of high-frequency hearing loss increased with CNE levels (χ(2)(trend)=34.415, P<0.05) .Before the kurtosis adjustment, in the CNE 95~<110 dB (A) ·year level group, the incidence of high-frequency hearing loss and the high-frequency hearing threshold in the observation group were significantly higher than those in the control group (P<0.05) . After kurtosis adjustment, there was no significant difference in the incidence of high-frequency hearing loss between the observation group and the control group in each level group (P>0.05) . The correlation between CNE after kurtosis adjustment and the incidence of high-frequency hearing loss was better than that before adjustment (after R(2) adjustment >before R(2) adjustment) . Conclusion: The effect of non-steady state noise on high-frequency hearing loss of workers in general equipment industry increases with the increase of CNE, and the effect of non-steady state noise on high-frequency hearing loss of workers is greater than that of steady noise. CNE' can be used to evaluate the hearing loss caused by non-steady state noise.

[Dose-response relationship between noise kurtosis and noise-induced hearing loss].

Objective: To analyse the dose-response relationships between the kurtosis metric of noise and noise-induced hearing loss (NIHL) and study the role of kurtosis in the evaluation of NIHL associated with non-Gaussian noise. Methods: From January 2012 to December 2017, a total of 1869 workers in seven manufacturing industries were selected as the study subjects. The basic data of the workers were investigated by questionnaire, personal noise waveform was collected for a long time, and pure tone hearing threshold was tested. The 8-hour continuous equivalent A sound level (L(Aeq, 8 h)) , cumulative noise exposure (CNE) and kurtosis structure indexes were calculated. The dose-response relationships between kurtosis and NIHL were analyzed by stratification analysis method, which controlled the influence of CNE, L(Aeq, 8 h), exposure duration, age and sex on hearing loss using high-frequency noise-induced permanent threshold shift (NIPTS(346)) and high-frequency noise-induced hearing loss (HFNIHL) as outcome indicators. Results: When CNE was <90 dB (A) ·year and ≥100 dB (A) ·year, NIPTS(346) in the extremely high kurtosis group was significantly greater than that in the Gaussian kurtosis, low kurtosis and medium kurtosis group (P<0.05) . In the workers exposed to L(Aeq, 8 h)<85 dB (A) and ≥94 dB (A) , NIPTS(346) in the extremely high kurtosis group was significantly greater than that in the Gaussian kurtosis group (P<0.05) . Among workers under the age of 50 or male workers, NIPTS(346) in the extremely high kurtosis group was significantly greater than that in the Gaussian kurtosis, low kurtosis and medium kurtosis group (P<0.05) . Kurtosis was positively correlated with NIPTS(346) (r=0.121, P<0.05) . When CNE was <100 dB (A) ·year, the detection rate of HFNIHL increased with the increase of kurtosis level (P<0.01) . Logistic regression analysis showed that kurtosis was an important influencing factor for HFNIHL (OR=1.321) . Conclusion: Kurtosis has a dose-response relationship with the detection rate of HFNIHL in noise exposed workers, and noise kurtosis is an influencing factor of NIHL.

[Clinical characteristics of myelin oligodendrocyte glycoprotein antibody associated myelitis].

Objective: To evaluate the clinical characteristics of myelin oligodendrocyte glycoprotein antibody (MOG-IgG) associated myelitis in a cohort of Chinese Han adults. Methods: From January 2016 to December 2017, 70 patients with MOG-IgG associated disorders (MOGAD) and 120 patients with aquaporin 4 antibody (AQP4-IgG) positive neuromyelitis optica spectrum disorders (NMOSD) visited the NMO/MS clinic or the neurology ward of Huashan Hospital, and the neurophthalmology clinic of Eye and ENT hospital, Shanghai Medical College, Fudan University were enrolled. The clinical and paraclinical data of the patients were retrospectively reviewed. The characteristics of MOG-IgG associated myelitis were further clarified. Results: Sixteen of the 70 patients with MOGAD had ever experienced myelitis. The frequency of myelitis was 18.6% at the first attack and 22.9% throughout the disease duration. The onset age of MOG-IgG associated myelitis was 9-57(30±11) years, and the female to male ratio was 0.6∶1. Compared with AQP4-IgG positive myelitis attacks, MOG-IgG associated myelitis attacks were more common to be accompanied by feverish prodromal symptom (30.8%) while less common to exhibit painful tonic (12.5%). Longitudinally extensive myelitis (>3 vertebral segments) was less frequent (56.3%), and short-segment myelitis and multiple short-segment myelitis could also be seen. MRI showed that MOGAD patients had more lower spinal cord lesions (20%), fewer cervical cord lesions (40%) and less transverse lesions (52%). Axial H sign was a distinct feature (36%). MOG-IgG associated myelitis attack also demonstrated a lower EDSS score after treatment. Conclusion: MOG-IgG associated myelitis should be recognized as an important clinical component of MOGAD.

[A single-center retrospective study on axillary evaluation in 1 557 breast ductal carcinoma in situ patients between 2006 and 2016].

Objectives: To examine the influence factors on axillary evaluation in ductal carcinoma in situ (DCIS) patients, and the prognosis of different choices of axillary evaluation in a single-center retrospective study. Methods: Totally 1 557 DCIS patients admitted in Department of Breast Surgery, Fudan University Shanghai Cancer Center from January 2006 to November 2016 were retrospectively enrolled. All patients were female. The median age was 49 years (range: 21 to 85 years). Surgical methods included modified radical mastectomy, simple mastectomy (with or without axillary evaluation) and breast conservation surgery (with or without axillary evaluation). Axillary evaluation included axillary lymph node dissection (ALND) and sentinel lymph node biopsy (SLNB). T tests, χ(2) test and Logistic regression analysis was used to analyze influence factors on axillary evaluation, respectively. Kaplan-Meier curve and Log-rank analysis were used to evaluate recurrence-free survival (RFS) and loco-regional recurrence-free survival (LRRFS) in patients with different surgical methods. Results: Among the 1 557 DCIS patients, there were 1 226 cases received axillary evaluation, while 331 cases not received axillary evaluation. Patients were separated into 3 groups by different axillary evaluation choices: SLNB group (957 cases, 61.46%), ALND group (197 cases, 12.65%) and no evaluation group (403 cases, 25.88%). The patients in SLNB group increased significantly (P=0.000), from 3.85% (60/1 557) in 2006 to 75.19% (1 170/1 557) in 2016. The independent influence factors of receiving axillary evaluation were high nuclear grade (OR=3.191, 95%CI: 1.722 to 5.912, P=0.001) and tumor size>15 mm (OR=1.698, 95%CI: 1.120 to 2.573, P=0.012). Also, patients received breast conservation surgery were more likely to refuse axillary evaluation (OR=0.155, 95%CI: 0.103 to 0.233, P=0.000). There were no significant differences in RFS and LRRFS in patients with different axillary evaluation choices. Conclusions: The investigation in trends and influence factors of different axillary evaluation choices provided basis on surgical precision medicine in DCIS patients. Patients received SLNB increased significantly. The independent influence factors of axillary evaluation were nuclear grade, tumor size and surgical methods. There was no significant differences in prognosis among the groups receiving different axillary evaluations.

Cryptoanalysis on optical image encryption systems based on the vector decomposition technique in the Fourier domain.

In this paper, the security of optical cryptosystems based on the vector decomposition technique in the Fourier domain is analyzed. Compared to the conventional cryptosystem based on the equal modulus decomposition (EMD) technique, an additional EMD structure is introduced in the cascaded EMD-based cryptosystem; hence, the mask including the phase information of the Fourier spectrum is further encoded in the second EMD structure to enhance the security level. However, it is shown that the number of the private keys has not been increased in the cascaded EMD-based cryptosystem, which makes it possible to crack the cascaded EMD-based cryptosystem. Therefore, a chosen-plaintext attack (CPA) and a special attack with an arbitrarily given private key are proposed to retrieve information from encoded images obtained by the cascaded EMD-based cryptosystem. In addition, the security of the cryptosystem based on the random modulus decomposition (RMD) technique is also analyzed. Compared to the EMD-based cryptosystem in which the Fourier spectrum is decomposed into two vectors with equal moduli, the security level of the cryptosystem has been improved by using the RMD technique to decompose the spectrum into vectors with unequal moduli to decrease the number of the amplitude constraints. However, it is found that the arbitrarily given ciphertext provides the attackers enough information to retrieve the precise information of the plaintext without any knowledge of the private keys. A special attack is proposed to crack the RMD-based cryptosystem. This is the first time to report that these two cryptosystems based on the vector decomposition technique are attacked successfully. Numerical simulation is conducted to validate the feasibility and effectiveness of the proposed attacks.

Security analysis and enhancement of a cryptosystem based on phase truncation and a designed amplitude modulator.

In this paper, the security of a cryptosystem based on phase truncation and a designed amplitude modulator (AM) is evaluated. In the cryptosystem, an undercover AM used as an additional key is added to modulate the amplitude information of the spectrum in the Fourier plane. Compared to the conventional phase-truncated Fourier transform (PTFT)-based cryptosystem, the security of the cryptosystem is improved by increasing the number of unknown keys. However, it is found that the designed AM is irrelative to the plaintext, and one of the parameters in the designed AM contributes less to the security enhancement of the cryptosystem due to low key sensitivity. Based on the analysis, a special attack containing two iterative processes is proposed to crack the cryptosystem, in which the known-plaintext-attack-based iterative process I with a specific normalization operator is used to retrieve the designed AM and the amplitude-phase-retrieval-technique-based iterative process II is used to retrieve the corresponding plaintext from the arbitrarily given ciphertext with the help of the retrieved AM. In addition, an inherent drawback widely existing in PTFT-based cryptosystems is reported for the first time: most information of the original image could be retrieved using two correct phase keys (or only the first phase key) generated in the encryption process, even without the corresponding ciphertext in PTFT-based cryptosystems. To address this issue, a security-enhanced cryptosystem is proposed in this paper. Numerical simulation is carried out to demonstrate the effectiveness and feasibility of the proposed attack and cryptosystem.

Encephalitis is an important clinical component of myelin oligodendrocyte glycoprotein antibody associated demyelination: a single-center cohort study in Shanghai, China.

BACKGROUND AND PURPOSE: Besides a distinct spectrum of demyelinating syndromes, encephalitis was observed in patients with myelin oligodendrocyte glycoprotein antibodies (MOG-abs). METHODS: The clinical records of 690 patients with idiopathic demyelinating diseases of the central nervous system seen in our center from June 2015 to December 2017 were retrospectively reviewed. All underwent serum aquaporin 4 antibody (AQP4-ab) and MOG-ab detection by cell-based assays as a routine diagnostic approach. Patients with MOG-abs or AQP4-abs who had ever experienced an encephalitis-like illness during the disease course were identified. Whether diagnoses of possible or definite autoimmune encephalitis could be reached with regard to these particular episodes of encephalitis was determined. The incidence and clinical features of encephalitis in anti-MOG disease are described in detail and compared with those in anti-AQP4 disease. RESULTS: Amongst the 690 patients, 87 were MOG-ab-positive whilst 140 were AQP4-ab-positive. 20.7% (18/87) of the MOG-ab-positive patients had typical presentations of encephalitis. Unique cortical lesions (72.2%, 13/18) were observed; fever (55.6%), intracranial hypertension (41.2%) and cerebrospinal fluid pleocytosis (64.7%) were common during MOG-ab-associated encephalitis. Sixteen of the 18 patients fulfilled the criteria of definite autoimmune encephalitis (specific disease with MOG-ab) during encephalitis, and five patients overlapped with anti-N-methyl-d-aspartate-receptor encephalitis (NMDARE). Only 3.6% (5/140) of the AQP4-ab-positive patients had encephalitis, and none overlapped with NMDARE. The Expanded Disability Status Scale scores and the Cerebral Functional System Scores at last follow-up were lower in patients with MOG-ab-associated encephalitis than in those with AQP4-ab-associated encephalitis. CONCLUSIONS: Encephalitis should be recognized as an important clinical component in anti-MOG diseases.

Recurrent fungal infections in a Chinese patient with CARD9 deficiency and a review of 48 cases.

Deficiency of CARD9 (caspase recruitment domain-containing protein 9) has been reported in individuals with recurrent and invasive fungal infections. We report on a patient who first had Trichosporon asahii affecting the skin then Candida albicans infections involving the digestive tract and knee joint, along with elevated serum IgE. After stimulation with C. albicans, peripheral blood mononuclear cells of this patient produced less tumour necrosis factor-α, interferon-γ and interleukin-17 than those of healthy controls. Furthermore, the serum IgE levels of this patient were positively correlated with the severity of fungal infection during the course of treatment. Sanger sequencing identified one homozygous frameshift mutation (p.D274fsX60) in CARD9. We further performed a review including 48 cases with CARD9 deficiency. According to the data published previously, CARD9-deficient patients demonstrated obviously elevated IgE in serum (median 1300 IU mL-1 ), which could distinguish them from otherwise healthy people with fungal infections (area under the curve 0·94, P < 0·001). Patients carrying the mutations Q289X and Q295X had a higher mortality rate (24% vs. 0%, P < 0·05). Patients with the mutations R18W, R35Q, R70W, G72S or Y91H in the CARD domain, and the nonsense mutation Q295X in the coiled-coil domain, seemed to be more prone to Candida infections (90% vs. 20%, P < 0·005) and central nervous system infections (60% vs. 12%, P < 0·005).

Hybrid attack on an optical cryptosystem based on phase-truncated Fourier transforms and a random amplitude mask.

In this paper, the security of a cryptosystem based on phase-truncated Fourier transforms (PTFTs) and a random amplitude mask (RAM) is evaluated. In the cryptosystem, fake keys used as encryption keys in the second PTFT-based structure are generated by the first PTFT-based structure in which the RAM is encoded by random phase masks (RPMs) used as public keys. Compared to the classical PTFT-based encryption scheme, the security level of the cryptosystem is improved by using cascaded PTFTs to encode the encryption keys and the plaintext simultaneously. However, it is found that a known plaintext-ciphertext pair can provide enough constraints in the iterative process to retrieve the fake keys, which then can be used to retrieve unknown arbitrary plaintext from the corresponding ciphertext. Based on the analysis, we propose a specific attack based on hybrid iterative processes to break the cryptosystem. Two iterative processes with different constraints are involved in the proposed attack. The first known-plaintext-attack (KPA)-based iterative process is used to retrieve two fake keys with the help of two public keys and a known plaintext-ciphertext pair, while the second amplitude-phase retrieval algorithm-based iterative process with a median filter is employed to retrieve the plaintext from the corresponding ciphertext using two retrieval fake keys. To the best of our knowledge, it is the first time that the cryptosystem is attacked by the KPA-based iterative algorithm successfully. Numerical simulation results validate the feasibility and effectiveness of the proposed attack.

Reference-plane-based fast pixel-by-pixel absolute phase retrieval for height measurement.

Absolute phase retrieval is essential for height measurement in digital fringe projection. However, projections of additional structured patterns that are normally required for phase unwrapping increase the measurement complexity. In this paper, we propose two reference-plane-based pixel-by-pixel absolute phase retrieval techniques with as few projections as possible, suitable for different object depth ranges. The wrapped phase on the object is absolutely unwrapped by referring just to the absolute phase map on the reference plane. Single-frequency absolute phase retrieval with one-reference-plane-based calibration is first proposed for objects within a height limit that equals a calibrated system constant. To extend the measurement depth range, dual-frequency absolute phase retrieval with two parallel reference planes is further proposed. The additional low frequency is used to choose the unwrapping reference from the two reference plane phases for unwrapping the high-frequency phase. Moreover, the proposed techniques are capable of high-frequency absolute phase unwrapping for objects with step-height surface discontinuities. Experiments have been conducted to demonstrate the efficiency of the proposed two techniques.

Measurement of cytokines and chemokines and association with clinical severity of dermatomyositis and clinically amyopathic dermatomyositis.

BACKGROUND: Dermatomyositis (DM) is an autoimmune disease affecting primarily the skin, muscle and lung. Dysregulations of cytokines and chemokines are commonly found in inflammatory disorders. OBJECTIVES: To investigate the association between serum cytokines and chemokines and clinical severity, especially cutaneous lesions and interstitial lung disease (ILD) in patients with DM and clinically amyopathic DM (CADM). METHODS: Clinical features, laboratory findings and serum of 40 patients with DM or CADM were collected and analysed. Serum cytokines and chemokines were measured by enzyme-linked immunosorbent assay or cytometric bead array. A multiple unpaired t-test was performed to compare cytokines and chemokines in patients with DM and healthy controls. Correlations of serum cytokines and chemokines with disease severity were evaluated by Spearman's rank correlation test. RESULTS: Serum interferon (IFN)-ß [rs  = 0·37, 95% confidence interval (CI) 0·078-0·62; P = 0·019] and CXCL10 (rs  = 0·32, 95% CI to -0·004 to 0·57; P = 0·045) were significantly correlated with the Cutaneous Dermatomyositis Disease Area and Severity Index activity score in the subset of patients with DM or CADM. Serum levels of interleukin (IL)-6, IL-10, IL-18 and IFN-ß were significantly higher in the patients with acute/subacute interstitial pneumonia (A/SIP) than in the subset without A/SIP (P < 0·05). IL-6 (rs  = 0·54, 95% CI 0·27-0·72; P < 0·001) and IL-18 (rs  = 0·46, 95% CI 0·21-0·65; P = 0·003) were significantly correlated with the serum level of anti-melanoma differentiation-associated protein 5 antibody. CONCLUSIONS: Serum levels of IFN-ß and CXCL10 may be useful biomarkers for assessing cutaneous disease activity in patients with DM and CADM. In addition, serum IL-6, IL-10, IL-18 and IFN-ß were highly correlated with the occurrence of A/SIP. These cytokines may play a role in the pathogenesis of DM and CADM.

Security analysis of a double-image encryption technique based on an asymmetric algorithm.

In this paper, we evaluate the security of a double-image encryption technique based on an asymmetric algorithm. Compared with traditional cryptosystems based on a phase-truncated Fourier transform, the technique is able to improve the security of the encryption by combining a joint transform correlator; consequently, the encryption scheme is immune to some common attacks. We propose a special attack based on a phase retrieval algorithm with median filtering and normalization operation to break the cryptosystem. Low key sensitivity of a position parameter set has been found and an additional constraint is utilized to improve the attack to simplify the process and further decrease the computational time. Numerical simulation results show that the cryptosystem is vulnerable to the proposed special attack.

Simplified paraboloid phase model-based phase tracker for demodulation of a single complex fringe.

A regularized phase tracker (RPT) is an effective method for demodulation of single closed-fringe patterns. However, lengthy calculation time, specially designed scanning strategy, and sign-ambiguity problems caused by noise and saddle points reduce its effectiveness, especially for demodulating large and complex fringe patterns. In this paper, a simplified paraboloid phase model-based regularized phase tracker (SPRPT) is proposed. In SPRPT, first and second phase derivatives are pre-determined by the density-direction-combined method and discrete higher-order demodulation algorithm, respectively. Hence, cost function is effectively simplified to reduce the computation time significantly. Moreover, pre-determined phase derivatives improve the robustness of the demodulation of closed, complex fringe patterns. Thus, no specifically designed scanning strategy is needed; nevertheless, it is robust against the sign-ambiguity problem. The paraboloid phase model also assures better accuracy and robustness against noise. Both the simulated and experimental fringe patterns (obtained using electronic speckle pattern interferometry) are used to validate the proposed method, and a comparison of the proposed method with existing RPT methods is carried out. The simulation results show that the proposed method has achieved the highest accuracy with less computational time. The experimental result proves the robustness and the accuracy of the proposed method for demodulation of noisy fringe patterns and its feasibility for static and dynamic applications.

The structural basis for the functional comparability of factor VIII and the long-acting variant recombinant factor VIII Fc fusion protein.

Essentials Recombinant factor VIII (rFVIII) Fc fusion protein has a 1.5-fold longer half-life than rFVIII. Five orthogonal methods were used to characterize the structure of rFVIIIFc compared to rFVIII. The C-terminal Fc fusion does not perturb the structure of FVIII in rFVIIIFc. The FVIII and Fc components of rFVIIIFc are flexibly tethered and functionally independent. SUMMARY: Background Fusion of the human IgG1 Fc domain to the C-terminal C2 domain of B-domain-deleted (BDD) factor VIII (FVIII) results in the recombinant FVIII Fc (rFVIIIFc) fusion protein, which has a 1.5-fold longer half-life in humans. Objective To assess the structural properties of rFVIIIFc by comparing its constituent FVIII and Fc elements with their respective isolated components, and evaluating their structural independence within rFVIIIFc. Methods rFVIIIFc and its isolated FVIII and Fc components were compared by the use of hydrogen-deuterium exchange mass spectrometry (HDX-MS). The structure of rFVIIIFc was also evaluated by the use of X-ray crystallography, small-angle X-ray scattering (SAXS), and electron microscopy (EM). The degree of steric interference by the appended Fc domain was assessed by EM and surface plasmon resonance (SPR). Results HDX-MS analysis of rFVIIIFc revealed that fusion caused no structural perturbations in FVIII or Fc. The rFVIIIFc crystal structure showed that the FVIII component is indistinguishable from published BDD FVIII structures. The Fc domain was not observed, indicating high mobility. SAXS analysis was consistent with an ensemble of rigid-body models in which the Fc domain exists in a largely extended orientation relative to FVIII. Binding of Fab fragments of anti-C2 domain antibodies to BDD FVIII was visualized by EM, and the affinities of the corresponding intact antibodies for BDD FVIII and rFVIIIFc were comparable by SPR analysis. Conclusions The FVIII and Fc components of rFVIIIFc are structurally indistinguishable from their isolated constituents, and show a high degree of structural independence, consistent with the functional comparability of rFVIIIFc and unmodified FVIII.

[Effects of bisphenol A on the expression of N-cadherin, Vimentin and FSHR in rat Sertoli cells].

Objective: To explore the effects of BPA on the expression of N-cadherin, Vimentin and FSHR in rat Sertoli cells. Methods: Primary Sertoli cells collected from prepuberty rats (18-21 d) were cultured for 48 h, and then they were treated with 0, 30, 50, 70 µmol/L BPA respectively for 24 h. The methods of MTT, real-time quantitative PCR and Western blotting were utilized to measure the cell ability of Sertoli cells, the mRNA and protein expression levels of N-cadherin, Vimentin and FSHR respectively. Results: Compared with control, the cell abilities of Sertoli cells in 50 µmol/L BPA group and 70 µmol/L BPA group increased significantly (P<0.05) . The cell abilities of Sertoli cells decreased with the increases of exposure doses of BPA. Compared with control, the expression of N-cadherin mRNA only increased in 30 µmol/L BPA group (P<0.05) , the expression of Vimentin mRNA decreased significantly in all doses group of BPA (P<0.05) , the expression of FSHR mRNA increased in all doses group of BPA (P<0.05) . Compared with the control, the protein levels of N-cadherin increased significantly in 50 µmol/L BPA group (P<0.05) , the protein levels of Vimentin decreased significantly in all doses group of BPA (P<0.05) , the protein levels of FSHR decreased significantly in 50 µmol/L BPA group and 70 µmol/L BPA group (P<0.05) . Conclusion: The mechanism of testicular toxicity from BPA might be the alterations of N-cadherin, Vimentin and FSHR by disturbing normal spermatogenesis.

LKB1 inhibits HPV-associated cancer progression by targeting cellular metabolism.

Liver kinase B1 (LKB1) is mutationally inactivated in Peutz-Jeghers syndrome and in a variety of cancers including human papillomavirus (HPV)-caused cervical cancer. However, the significance of LKB1 mutations in cervical cancer initiation and progress has not been examined. Herein, we demonstrated that, in mouse embryonic fibroblasts, loss of LKB1 and transduction of HPV16 E6/E7 had an additive effect on constraining cell senescence while promoting cell proliferation and increasing glucose consumption, lactate production and ATP generation. Knockdown of LKB1 increased and ectopic expression of LKB1 decreased glycolysis, anchorage-independent cell growth, and cell migration and invasion in HPV-transformed cells. In the tumorigenesis and lung metastasis model in syngeneic mice, depletion of LKB1 markedly increased tumor metastatic colonies in lungs without affecting subcutaneous tumor growth. We showed that HPV16 E6/E7 enhanced the expression of hexokinase-ll (HK-II) in the glycolytic pathway through elevated c-MYC. Ectopic LKB1 reduced HK-II along with glycolysis. The inverse relationship between HK-II and LKB1 was also observed in normal and HPV-associated cervical lesions. We propose that LKB1 acts as a safeguard against HPV-stimulated aerobic glycolysis and tumor progression. These findings may eventually aid in the development of therapeutic strategy for HPV-associated malignancies by targeting cell metabolism.

Exploration of candidate biomarkers for human psoriasis based on gas chromatography-mass spectrometry serum metabolomics.

BACKGROUND: Recent studies have shown that dysregulated metabolic pathways are linked to psoriasis pathogenesis. However, an extensive, unbiased metabolic analysis in patients with psoriasis has not been completely explored. The metabolome represents the end products of proteomics or cellular processes that may be closely associated with the pathogenesis of psoriasis. OBJECTIVES: To determine the differences in serum metabolomic profiles among patients with psoriasis and healthy controls with the goal of identifying potential biomarkers in patients with psoriasis. MATERIALS AND METHODS: Serum metabolomic profiles from 29 subjects (14 patients with psoriasis and 15 sex- and age-matched healthy controls). The serum metabolites were analysed by gas chromatography-mass spectrometry based on a combined full scan and selected-ion monitoring mode. RESULTS: Multivariate statistical analysis of metabolomics data revealed altered serum metabolites between the patients with psoriasis and healthy individuals. Compared with healthy individuals, patients with psoriasis had higher levels of amino acids including asparagine, aspartic acid, isoleucine, phenylalanine, ornithine and proline; higher levels of lactic acid and urea; and lower levels of crotonic acid, azelaic acid, ethanolamine and cholesterol. CONCLUSIONS: It appears that the glycolysis pathway and amino acid metabolic activity are increased in patients with psoriasis. These metabolic perturbations may stem from increased demand for protein biosynthesis and keratinocyte hyperproliferation. Our findings may help to elucidate the pathogenesis of psoriasis and provide insights into early diagnosis and therapeutic intervention.

Multi-subzone algorithm for absolute phase retrieval in digital fringe projection profilometry.

Codewords are important in encoded absolute phase retrieval techniques such as two-frequency, gray-code, and phase-coding. Each sinusoidal fringe is marked by a unique codeword so that an absolute fringe order can be determined by decoding the codeword. However, due to the limited number of unique codewords, sinusoidal fringe patterns do not contain high-frequency fringes without the use of additional patterns. A multi-subzone coding and decoding algorithm is thus proposed to overcome this limitation. Three multi-subzone coding methods based on two-frequency, gray-code, and phase-coding techniques are presented. The coding creates multiple subzones of unique codewords and the decoding enables it to use non-unique codewords to identify absolute fringe order. Specifically, the range of fringe order is estimated by the use of a wrapped phase map and the absolute fringe order is identified by a codeword. Experimental studies demonstrate the advantages of the proposed algorithm over existing coding methods. The proposed algorithm is suitable to measure objects with large step-height surface discontinuities.