High spatiotemporal resolution scintillation imaging of pulsed pencil beam scanning proton beams produced by a gantry-mounted synchrocyclotron.

BACKGROUND: A dosimeter with high spatial and temporal resolution would be of significant interest for pencil beam scanning (PBS) proton beams' characterization, especially when facing small fields and beams with high temporal dynamics. Optical imaging of scintillators has potential in providing sub-millimeter spatial resolution with pulse-by-pulse basis temporal resolution when the imaging system is capable of operating in synchrony with the beam-producing accelerator. PURPOSE: We demonstrate the feasibility of imaging PBS proton beams as they pass through a plastic scintillator detector to simultaneously obtain multiple beam parameters, including proton range, pencil beam's widths at different depths, spot's size, and spot's position on a pulse-by-pulse basis with sub-millimeter resolution. MATERIALS AND METHODS: A PBS synchrocyclotron was used for proton irradiation. A BC-408 plastic scintillator block with 30 × 30 × 5 cm3 size, and another block with 30 × 30 × 0.5 cm3 size, positioned in an optically sealed housing, were used sequentially to measure the proton range, and spot size/location, respectively. A high-speed complementary metal-oxide-semiconductor (CMOS) camera system synchronized with the accelerator's pulses through a gating module was used for imaging. Scintillation images, captured with the camera directly facing the 5-cm-thick scintillator, were corrected for background (BG), and ionization quenching of the scintillator to obtain the proton range. Spots' position and size were obtained from scintillation images of the 0.5-cm-thick scintillator when a 45° mirror was used to reflect the scintillation light toward the camera. RESULTS: Scintillation images with 0.16 mm/pixel resolution corresponding to all proton pulses were captured. Pulse-by-pulse analysis showed that variations of the range, spots' position, and size were within ± 0.2% standard deviation of their average values. The absolute ranges were within ± 1 mm of their expected values. The average spot-positions were mostly within ± 0.8 mm and spots' sigma agreed within 0.2 mm of the expected values. CONCLUSION: Scintillation-imaging PBS beams with high-spatiotemporal resolution is feasible and may help in efficient and cost-effective acceptance testing and commissioning of existing and even emerging technologies such as FLASH, grid, mini-beams, and so forth.

Synaptotagmin-11 regulates immune functions of microglia in vivo.

Membrane trafficking pathways mediate key microglial activities such as cell migration, cytokine secretion, and phagocytosis. However, the underlying molecular mechanism remains poorly understood. Previously, we found that synaptotagmin-11 (Syt11), a non-Ca2+ -binding Syt associated with Parkinson's disease (PD) and schizophrenia, inhibits cytokine release and phagocytosis in primary microglia. Here we reported the in vivo function of Syt11 in microglial immune responses using an inducible microglia-specific Syt11-conditional-knockout (cKO) mouse strain. Syt11-cKO resulted in activation of microglia and elevated mRNA levels of IL-6, TNF-α, IL-1ß, and iNOS in various brain regions under both resting state and LPS-induced acute inflammation state in adult mice. In a PD mouse model generated by microinjection of preformed α-synuclein fibrils into the striatum, a reduced number of microglia migrated toward the injection sites and an enhanced phagocytosis of α-synuclein fibrils by microglia were found in Syt11-cKO mice. To understand the molecular mechanism of Syt11 function, we identified its direct binding proteins vps10p-tail-interactor-1a (vti1a) and vti1b. The linker domain of Syt11 interacted with both proteins and a peptide derived from it competitively inhibited the interaction of Syt11 with vti1a/vti1b in vitro and in cells. Importantly, application of this peptide induced more cytokine secretion in wild-type microglia upon LPS treatment, phenocopying defects in Syt11 knockdown cells. Altogether, we propose that Syt11 inhibits microglial activation in vivo and regulates cytokine secretion through interactions with vti1a and vti1b.

Phase retrieval from single interferogram without carrier using Lissajous ellipse fitting technology.

Phase extraction from single interferogram is of high significance and increasingly interest in optical metrology. In this contribute we propose an advanced Pixel-level Lissajous Ellipse Fitting (APLEF) method to extract the phase from single interferogram without carrier. At each pixel, a Lissajous figure is created by plotting N against D, where N and D are subtractions and additions of intensities of adjacent pixels in a small window. The so created Lissajous figure is already in phase quadrature because of the subtraction and addition process, and the Lissajous Figure is forced to be closed by taking the opposite values of N and D, i.e. -N and -D into account. The closed and in phase quadrature Lissajous Figure is the key point for APLEF to demodulate the single inteferogram without carrier in theoretically. The simulation shows its higher accuracy than existed SPT and Garbusi's method and the experiments finally corroborate its effectiveness.

Concurrence of novel mutations causing Gilbert's and Dubin-Johnson syndrome with poor clinical outcomes in a Han Chinese family.

Dual-hereditary jaundice (Dubin-Johnson syndrome (DJS) and Gilbert's syndrome (GS)) is a rare clinical entity resulting from defects of the ATP binding cassette subfamily C member 2 (ABCC2) and UDP glucuronosyltransferase family 1 member A1 (UGT1A1) genes with autosomal recessive inheritance. In this study, we aimed to investigate the mutation profiles and characterize the phenotypes in a Han Chinese family with DJS and GS. Genetic screening for variants in the ABCC2 and UGT1A1, immunohistochemistry for expression of ABCC2, and histopathological examination were carried out. The proband and his brother had unconjugated and conjugated hyperbilirubinemia after birth. The proband's sister had only conjugated hyperbilirubinemia after birth. The proband developed into pleural effusions and ascites, pericardial thickening, intrahepatic and extrahepatic biliary duct dilatation, and enlarged gallbladder at age 50. Hepatocellular carcinoma occurred in the proband's brother at age 46. Seven compound defects of the ABCC2 gene [c.2414delG, p.(Ile1489Gly), p.(Thr1490Pro), and p.(Ile1491Gln)] and the UGT1A1 gene (c.-3279T>G, p.(Gly71Arg), and p.(Pro451Leu)) were identified in family members. Accumulation of pigment in hepatocytes characteristic of that in DJS was present in the proband and his brother. Expression of ABCC2 protein was markedly diminished in the patient's liver. Our results show a different genetic profile of DJS and GS in a Han Chinese family, indicating a more complex pattern of dual-hereditary jaundice among different populations. The present study illuminates the underpinnings of DJS and GS and extends the mutation profiles and phenotypes of these two syndromes in dual-hereditary jaundice.

Immunogenicity, durability, and safety of an mRNA and three platform-based COVID-19 vaccines as a third dose following two doses of CoronaVac in China: A randomised, double-blinded, placebo-controlled, phase 2 trial.

Background: More effective vaccine candidates against variants of concern as a booster dose are needed in people primed with two-dose inactivated COVID-19 vaccines. Methods: This randomised, double-blinded, investigator-initiated phase 2 trial aims to evaluate immunogenicity, durability, and safety of an mRNA vaccine candidate (RQ3013) and three other platform vaccines (an adenovirus-vectored vaccine candidate [ChAdTS-S], a recombinant protein vaccine candidate [ZR202-CoV], and an inactivated vaccine [CoronaVac]) as a booster. 250 eligible volunteers, who had received a prime two-dose CoronaVac (3 to 5 weeks apart) vaccination 100-270 days before, were randomly assigned in a 1:1:1:1:1 ratio to receive a third dose of RQ3013 (30 µg mRNA per 0.15 mL), ChAdTS-S (5×1010 viral particles per 0.5 mL), ZR202-CoV (25 µg prefusion-stabilized Spike ectodomain trimer per 0.5 mL), CoronaVac (3 µg inactivated CN02 strain of SARS-CoV-2 per 0.5 mL) or placebo (0.5 mL of 0.9% sodium chloride solution) via intramuscular injection into the upper arm at a single clinical site in Kunming, China. Participants, investigators, and immunogenicity laboratory were masked to group assignment. The primary immunogenicity outcomes were geometric mean titres (GMTs) of neutralising antibodies against live SARS-CoV-2 (wild-type, delta and omicron) virus at day 0 (before vaccination), day 7, day 14 and day 28 after vaccination, as analysed in a modified intention-to-treat (mITT) population (all participants who completed their booster doses and had at least one post-dose immunogenicity data). Secondary outcomes include T cell responses against the wild-type and omicron SARS-CoV-2 Spike protein. The primary safety outcome was incidence of adverse events within 14 days after the booster vaccination. This trial is registered with ChiCTR.org.cn, ChiCTR2200057758. Findings: Between January 1, 2022, and February 28, 2022, 235 eligible participants were enrolled and vaccinated, and the primary analysis included 234 participants. At baseline, neutralising antibodies against wild-type virus, the delta, or omicron variants were low or undetectable in all groups. After the booster vaccination, GMTs of neutralising antibodies ranged from 75.4 (95% confidence interval [CI] 61.4-92.5) in CoronaVac to 950.1 (95% CI 785.4-1149.3) in RQ3013 against live wild-type SARS-CoV-2, and from 8.1 (95% CI: 6.1-10.7) in CoronaVac to 247.0 (95% CI 194.1-314.3) in RQ3013 against the omicron variant at day 14. Immunogenicities of all heterologous regimens were superior to that of homologous regimen in neutralisation against all tested SARS-CoV-2 strains, with RQ3013 showing the highest geometric mean ratios (GMRs) of 12.6, 14.7, and 31.3 against the wild-type, the delta variant and the omicron variant compared to CoronaVac at day 14 post-vaccination, respectively. Durability analysis at day 90 showed that >90% of participants in RQ3013 and ZR202-CoV were seropositive for the omicron variant while ZR202-CoV with adjuvants containing CpG showed a slightly better durability than RQ3013. T cell responses specific to the omicron variant were similar to that of the wild-type, with RQ3013 showing the highest boosting effect. Any solicited injection site or systemic adverse events reported within 14 days after vaccination were most commonly observed in RQ3013 (47/47, 100%), followed by ZR202-CoV (46/47, 97.9%) and ChAdTS-S (43/48, 89.6%), and then CoronaVac (37/46, 80.4%) and placebo (21/47, 44.7%). More than 90% of the adverse events were grade 1 (mild) or 2 (moderate) with a typical resolution time of 3 days. No grade 4 adverse events or serious adverse events were reported by study vaccines. Interpretation: Although all study vaccines boosted neutralising antibodies with no safety concerns, RQ3013 showed much stronger cross-neutralisation and cellular responses, adding more effective vaccine candidates against the omicron variant. Funding: Yunnan Provincial Science and Technology Department China (202102AA100051 and 202003AC100010), the Double First-class University funding to Yunnan University, National Natural Science Foundation of China (81960116, 82060368 and 82170711), Yunnan Natural Science Foundation (202001AT070085), High-level Health Technical Personnel Project of Yunnan Province (H-2018102) and Spring City Plan: The High-level Talent Promotion and Training Project of Kunming.

Diastolic blood pressure predicts enlarged vertebral venous plexus and intracranial pressure in patients with bilateral transverse sinus stenosis.

Background: Bilateral transverse sinus stenosis (BTSS) is associated with intracranial hypertension. Enlarged vertebral venous plexus (EVVP) refers to a compensation mechanism against elevated intracranial pressure (ICP) in patients with BTSS. This study aims to investigate the influencing factors of EVVP. Methods: Patients with BTSS were prospectively recruited from the neurology department and neurosurgery department of Xuanwu Hospital Capital Medical University from January 2020 to December 2021. Results: A total of 37 patients were enrolled with a mean age of 45.42 ± 15.64 years. Women tend to be more susceptible to BTSS. The most common co-morbid disease was hypertension. The most common clinical manifestations were visual disorders, headaches, and tinnitus. BMI and DBP were significantly higher in BTSS patients without EVVP than those with EVVP. Multivariate analysis revealed that diastolic blood pressure (DBP) was negatively correlated with EVVP. In addition, a positive correlation between DBP and the ICP was also observed. A DBP of 81.5 mmHg was calculated as the cutoff value for the presence of EVVP. BTSS patients with DBP ≤ 81.5 mmHg had a higher incidence of EVVP and a lower ICP compared to those with DBP > 81.5 mmHg. Conclusions: DBP was identified as an independent predictor of EVVP. DBP was lower (≤81.5 mmHg) in patients with EVVP and therefore was associated with a lower ICP in patients with BTSS.

Mitochondrial DNA haplogroup F confers genetic susceptibility to chronic HBV infection for the Yi nationality in Lijiang, China.

Mitochondria are essential for hepatitis B virus (HBV) infection. Moreover, the findings of our previous study indicate that host mitochondrial genetic factors are associated with chronic hepatitis B (CHB) for the Han Chinese. However, in terms of genetic heterogeneity, the impact of mitochondria on host susceptibility to HBV infection in ethnic minorities in China remains unclear. Here, a total of 7070 subjects who had visited the hospital between June 1, 2019, and April 31, 2020, were enrolled for seroprevalence of HBV infection investigation. A total of 220 individuals with CHB (CHBs) and 223 individuals with a trace of HBV infection (spontaneously recovered subjects, SRs) were analyzed for mitochondrial DNA (mtDNA) sequence variations and classified into respective haplogroups. Haplogroup frequencies were compared between CHBs and SRs. Among eight nationalities, Yi nationality patients had the highest HBsAg prevalence rate (27.9% [95% CI: 25.3%-30.5%]) and the lowest vaccination rate (4.9% [95% CI: 3.7%-6.2%]). After adjustment for age and gender, haplogroup F was a risk factor for CHB infection (P = 0.049, OR = 2.079, 95% CI = 1.002-4.31), while D4 had a significant negative correlation with the HBeAg-positive rate (P = 0.024, OR = 0.215, 95% CI = 0.057-0.816). Together with our previous study, the findings indicate that different nationalities have different genetic susceptibility to HBV infection.

SNARE Proteins Mediate α-Synuclein Secretion via Multiple Vesicular Pathways.

The cell-to-cell transmission of pathological α-synuclein (α-syn) has been proposed to be a critical event in the development of synucleinopathies. Recent studies have begun to reveal the underlying molecular mechanism of α-syn propagation. As one of the central steps, α-syn secretion is reported to be Ca2+-dependent and mediated by unconventional exocytosis. However, the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) requirement and vesicle identity of α-syn secretion remain elusive. Here we found that α-syn secretion is SNARE-dependent by systematically knocking down Q-SNAREs and R-SNAREs in exocytosis pathways. α-Syn secretion was mainly mediated by syntaxin 4 (STX4) and synaptosomal-associated protein 23 (SNAP23), but did not require STX1 and SNAP25, in differentiated SH-SY5Y cells. On the other hand, vesicle-associated membrane protein 3 (VAMP3), VAMP7, and VAMP8 were all involved in α-syn secretion, most likely in overlapping pathways. Application of super-resolution microscopy revealed localization of both endogenous and overexpressed α-syn in endosomes, lysosomes, and autophagosomes in rat primary cortical neurons. α-Syn co-localized with microtubule-associated protein 1 light chain 3 (LC3) most extensively, suggesting its tight association with the autophagy pathway. Consistently, α-syn secretion was regulated by the autophagy-lysosome pathway. Collectively, our data suggest that α-syn secretion is SNARE-dependent and is mediated by multiple vesicular pathways including exocytosis of recycling endosomes, multivesicular bodies, autophagosomes, and lysosomes.

Combination of liquid crystal and deep learning reveals distinct signatures of Parkinson's disease-related wild-type α-synuclein and six pathogenic mutants.

α-Synuclein is a central player in Parkinson's disease (PD) pathology. Various point mutations in α-synuclein have been identified to alter the protein-phospholipid binding behavior and cause PD. Therefore, exploration of α-synuclein-phospholipid interaction is important for understanding the PD pathogenesis and helping the early diagnosis of PD. Herein, a phospholipid-decorated liquid crystal (LC)-aqueous interface is constructed to investigate the binding between α-synucleins (wild-type and six familial mutant A30P, E46K, H50Q, G51D, A53E and A53T) and phospholipid. The application of deep learning analyzes and reveals distinct LC signatures generated by the binding of α-synuclein and phospholipid. This system allows for the identification of single point mutant α-synucleins with an average accuracy of 98.3±1.3% in a fast and efficient manner. We propose that this analytical methodology provides a new platform to understand α-synuclein-lipid interactions, and can be potentially developed for easy identification of α-synuclein mutations in common clinic.

Simple, rapid and sensitive detection of Parkinson's disease related alpha-synuclein using a DNA aptamer assisted liquid crystal biosensor.

Alpha-synuclein (αS) has been proposed as a potential biomarker for the diagnosis of Parkinson's disease (PD). However, the detection of αS using a simple, rapid and sensitive approach is still challenging. Herein, we construct a new type of biosensor for the detection of αS, combining the stimuli-responsiveness of liquid crystals (LCs) and the specific interaction of a DNA aptamer with proteins. In principle, the positively charged surfactant hexadecyltrimethylammonium bromide (CTAB) binds with the negatively charged DNA aptamer via electrostatic interactions; in the presence of αS, the DNA aptamer specifically binds with αS and releases CTAB, which is an amphiphilic molecule and subsequently assembles at the LC-aqueous interface, resulting in a homeotropic alignment of LCs with a dark optical signal. In the absence of αS, CTAB binds with the DNA aptamer without affecting the alignment of LCs, which shows planar anchoring with a bright optical signal. The response time of LCs towards αS is rapid and can be down to minutes. The LC biosensor established here has a good specificity for αS and can recognize αS even from a mixture of proteins. The LC biosensor also exhibits high sensitivity with a limit of detection of αS as low as 10 pM, which is comparable to that of the enzyme-linked immunosorbent assay. This work provides a new strategy for the detection of αS in a simple, rapid and sensitive manner, possessing promising potentials towards early diagnosis and clinical applications.

The association of the heterogeneity of HBV reverse transcriptase quasispecies with antiviral efficacy after treatment with nucleos(t)ide analogues for 10 years.

To assess the heterogeneity of HBV reverse transcriptase (RT) quasispecies during 10 years of antiviral therapy and their association with antiviral efficacy. Nineteen patients with chronic hepatitis B (CHB) infection receiving nucleos(t)ide analogues (NAs) were enrolled. Based on the antiviral efficacy after 1 year of treatment, 5 patients were grouped into an early virologic response (EVR) group, while 8 patients were grouped into a late virologic response (LVR) group. Furthermore, 6 CHB patients that had undergone antiviral treatment for 10 years were grouped into a virologic breakthrough (VBT) group. The HBV RT from each patient were amplified, cloned, and sequenced. The complexity of the RT gene in the EVR group was significantly higher than that in the LVR (P = 0.0393) and VBT groups (P = 0.0141). Phylogenetic tree analysis showed that the average branch length of the EVR and LVR groups were significantly greater than that of VBT group (P < 0.001). The complexity (at the nucleotide level) of the RT quasispecies was negatively correlated with the corresponding HBV DNA load (P = 0.0163) at one year post-antiviral treatment. Moreover, both the LVR and VBT groups accumulated more deleterious mutations than the EVR group. After 1 year of NAs treatment, the increased HBV quasispecies complexity and evolutionary topologies, coupled with less deleterious mutations, are likely associated with a favorable efficacy during long-term antiviral treatment.

Pathogenic Mutations Differentially Regulate Cell-to-Cell Transmission of α-Synuclein.

Recent studies suggest that the cell-to-cell spread of pathological α-synuclein (α-syn) plays important roles in the development of Parkinson's disease (PD). PD patients who carry α-syn gene mutations often have an earlier onset and more severe clinical symptoms and pathology than sporadic PD cases who carry the wild-type (WT) α-syn gene. However, the molecular mechanism by which α-syn gene mutations promote PD remains unclear. Here, we hypothesized that pathogenic mutations facilitate the intercellular transfer and cytotoxicity of α-syn, favoring an early disease onset and faster progression. We investigated the effects of eight known pathogenic mutations in human α-syn (A18T, A29S, A30P, E46K, H50Q, G51D, A53E, and A53T) on its pathological transmission in terms of secretion, aggregation, intracellular level, cytotoxicity, seeding, and induction of neuroinflammation in SH-SY5Y neuroblastoma cells, cultured rat neurons, and microglia, and the rat substantia nigra pars compacta. We found that 2 of the 8 mutations (H50Q and A53T) significantly increased α-syn secretion while 6 mutations (A18T, A29S, A30P, G51D, A53E, and E46K) tended to enhance it. In vitroα-syn aggregation experiments showed that H50Q promoted while G51D delayed aggregation most strongly. Interestingly, 3 mutations (E46K, H50Q, and G51D) greatly increased the intracellular α-syn level when cultured cells were treated with preformed α-syn fibrils (PFFs) compared with the WT, while the other 5 had no effect. We also demonstrated that H50Q, G51D, and A53T PFFs, but not E46K PFFs, efficiently seeded in vivo and acutely induced neuroinflammation in rat substantia nigra pars compacta. Our data indicate that pathogenic mutations augment the prion-like spread of α-syn at different steps and blockade of this pathogenic propagation may serve as a promising therapeutic intervention for PD.

Synaptotagmin-11 regulates the functions of caveolae and responds to mechanical stimuli in astrocytes.

Caveolae play crucial roles in intracellular membrane trafficking and mechanosensation. In this study, we report that synaptotagmin-11 (Syt11), a synaptotagmin isoform associated with Parkinson's disease and schizophrenia, regulates both caveolae-mediated endocytosis and the caveolar response to mechanical stimuli in astrocytes. Syt11-knockout (KO) accelerated caveolae-mediated endocytosis. Interestingly, the caveolar structures on the cell surface were markedly fewer in the absence of Syt11. Caveolar disassembly in response to hypoosmotic stimuli and astrocyte swelling were both impaired in Syt11-KO astrocytes. Live imaging revealed that Syt11 left caveolar structures before cavin1 during hypoosmotic stress and returned earlier than cavin1 after isoosmotic recovery. Chronic hypoosmotic stress led to proteasome-mediated Syt11 degradation. In addition, Syt11-KO increased the turnover of cavin1 and EH domain-containing protein 2 (EHD2), accompanied by compromised membrane integrity, suggesting a mechanoprotective role of Syt11. Direct interactions between Syt11 and cavin1 and EHD2, but not caveolin-1, are found. Altogether, we propose that Syt11 stabilizes caveolar structures on the cell surface of astrocytes and regulates caveolar functions under physiological and pathological conditions through cavin1 and EHD2.

[Acupoint puncture combined with Ilizarov technique for the treatment of elderly paitents with knee osteoarthritis].

OBJECTIVE: To explore the clinical effect of acupoint puncture combined with Ilizarov technique in the treatment of knee osteoarthritis in the elderly. METHODS: From March 2015 to February 2016, 76 patients with primary knee osteoarthritis were treated with tibial osteotomy acupoint puncture grouop and Ilizarov technique anatomical puncture group, including 24 males and 52 females, aged 56 to 75 years old with an average of 61.4 years old, and a course of 3 to 17 years with an average of 5.2 years. Among them, 38 cases were treated with external fixation of acupoint puncture needle and 38 cases were treated with external fixation of anatomical puncture needle. Preoperative full-length X-ray of both lower limbs showed tibial varus deformity, narrowing of medial knee joint space and enlargement of lateral knee joint space. The force line of the affected knee and lower limb was moved inward by body surface measurement, and the KSS knee function score was decreased. Symptoms included medial knee pain, flexion and extension, and conservative treatment for more than 2 years. RESULTS: The lower limb force lines of both groups were corrected and the osteotomy ends healed well. No nonunion of osteotomy, inadequate correction of lower limbs or recurrence of deformity were found. Seventy-five patients were followed up for 3, 6, 12 and 24 months after operation. There was no significant difference in knee joint mobility between the two groups before operation and on 6, 12, 24 months after operation(F=1.346, P>0.05). There were significant difference in KSS pain and total score between the two groups at 3 months after operation, acupoint puncture group was better than anatomical puncture group(P<0.05); there was no significant difference in KSS score at 12 months after operation(P>0.05). CONCLUSIONS: The acupoint puncture group formed a potential acupuncture effect in the acupoint area by continuously tightening the steel needle on Ilizarov ring external fixator during the post-operative adjustment. Within three months after wearing external fixator, the knee pain symptoms of knee osteoarthritis were relieved rapidly, continuously and effectively, which was significantly better than that of the anatomical puncture group.

Precise phase demodulation of single carrier-frequency interferogram by pixel-level Lissajous figure and ellipse fitting.

Phase demodulation from a single carrier-frequency fringe pattern is becoming increasingly important particularly in areas of optical metrology such as dynamic interferometry, deflectometry and profilometry. The Fourier transform (FT) method and the spatial-carrier phase-shifting technique (SCPS) are two popular and well-established approaches to demodulation. However FT has the drawback of significant edge errors because of the Gibbs effect, whilst detuning errors for the local phase shift occur when SCPS is applied. A novel demodulation method based on pixel-level Lissajous figure and ellipse fitting (PLEF) is presented in this paper. Local demodulation in the spatial domain makes PLEF more flexible than the FT method, without spectral leakage. Based on a more adaptable approach, account is taken of variations in illumination and phase distribution over a few neighboring pixels. The mathematic demodulation model is of interest and has been demonstrated via simulation. Theoretical phase extraction error is as low as 10-4 rad. Experiments further corroborate the effectiveness of the proposed method. In conclusion, various influencing factors, e.g. variations of background/modulation, phase amplitude, carrier frequency, additive noise that may affect the precision of PLEF are discussed in detail.

Diabetic Osteoporosis: A Review of Its Traditional Chinese Medicinal Use and Clinical and Preclinical Research.

Aim. The incidence of diabetic osteoporosis (DOP) is increasing due to lack of effective management over the past few decades. This review aims to summarize traditional Chinese medicine (TCM) suitability in the pathogenesis and clinical and preclinical management of DOP. Methods. Literature sources used were from Medline (Pubmed), CNKI (China Knowledge Resource Integrated Database), and CSTJ (China Science and Technology Journal Database) online databases. For the consultation, keywords such as diabetic osteoporosis (DOP), TCM, clinical study, animal experiment, toxicity, and research progress were used in various combinations. Around 100 research papers and reviews were visited. Results. Liver-spleen-kidney insufficiency may result in development of DOP. 18 clinical trials are identified to use TCM compound prescriptions for management of patients with DOP. TCM herbs and their active ingredients are effective in preventing the development of DOP in streptozotocin (STZ) and alloxan as well as STZ combined with ovariectomy insulted rats. Among them, most frequently used TCM herbs in clinical trials are Radix Astragali, Radix et Rhizoma Salviae Miltiorrhizae, Radix Rehmanniae Preparata, and Herba Epimedii. Some of TCM herbs also exhibit toxicities in clinical and preclinical research. Conclusions. TCM herbs may act as the novel sources of anti-DOP drugs by improving bone and glucolipid metabolisms. However, the pathogenesis of DOP and the material base of TCM herbs still merit further study.

Phase shifting interferometry from two normalized interferograms with random tilt phase-shift.

We propose a novel phase shifting interferometry from two normalized interferograms with random tilt phase-shift. The determination of tilt phase-shift is performed by extracting the tilted phase-shift plane from the phase difference of two normalized interferograms, and with the calculated tilt phase-shift value the phase distribution can be retrieved from the two normalized frames. By analyzing the distribution of phase difference and utilizing special points fitting method, the tilted phase-shift plane is extracted in three different cases, which relate to different magnitudes of tilts. Proposed method has been applied to simulations and experiments successfully and the satisfactory results manifest that proposed method is of high accuracy and high speed compared with the three step iterative method. Additionally, both open and closed fringe can be analyzed with proposed method. What's more, it cannot only eliminate the small tilt-shift error caused by slight vibration in phase-shifting interferometry, but also detect the large tilt phase-shift in phase-tilting interferometry. Thus, it will relaxes the requirements on the accuracy of phase shifter, and the costly phase shifter may even be useless by applying proposed method in high amplitude vibrated circumstance to achieve high-precision analysis.

Effect of hydroxyapatite whisker surface graft polymerization on water sorption, solubility and bioactivity of the dental resin composite.

The aim of this study was to investigate the effect of poly bisphenol A glycidyl methacrylate (poly(Bis-GMA)) grafted hydroxyapatite whisker (PGHW) on water sorption, solubility and bioactivity of the dental resin composite. PGHW with different graft ratios was synthesized, by controlling grafting time, and filled into a dental resin matrix respectively. Fracture surface of the resin composites showed that PGHW-matrix interfacial compatibility and bonding were enhanced, and lower amounts of poly(Bis-GMA) on PGHW-1h (graft ratio: 8.5 wt.%) could facilitate the dispersion of PGHW-1 h in the composite. The PGHW-1h filled resin composite absorbed the lowest amount of water (27.16 µg/mm(3), 7 d), whereas the untreated hydroxyapatite whisker (HW) filled resin composite absorbed the highest. PGHW with higher graft ratios induced the decrease of the monomer conversion in the resulting composite, therefore, the PGHW-18 h (graft ratio: 32.8 wt.%) filled resin composite had the highest solubility. In vitro bioactivity of the studied resin composites in simulated body fluid (SBF) showed that a dense and continuous apatite layer was formed on the surface of the resin composite, and the surface graft polymerization on the whisker did not significantly affect the apatite forming ability of the resin composite. It was revealed that graft polymerization of an appropriate amount of Bis-GMA onto HW could be an effective method to improve the interfacial properties and stability in water of the dental resin composite without compromising the bioactivity.