Analysis of the causal relationship between gut microbiota and bone remodeling growth factor from the gene association.

BACKGROUND: A growing body of evidence indicates a close association between the gut microbiota (GM) and the bone remodeling (BR) process, raising suspicions that the GM may actively participate in BR by modulating the levels of growth factors. However, the precise causal relationship between them remains unclear. Due to many confounding factors, many microorganisms related to BR growth factors have not been identified. We aimed to elucidate the causal relationship between the GM and BR growth factors. METHODS: We evaluated the genome-wide association study (GWAS) summary statistics for GM and five common growth factors associated with BR: namely, bone morphogenetic proteins (BMP), transforming growth factors(TGF), insulin growth factors (IGFs), epidermal growth factors (EGFs), and fibroblast growth factors (FGF). The causal relationship between the GM and BR growth factors was studied by double-sample Mendelian randomized analysis. We used five Mendelian randomization (MR) methods, including inverse variance-weighted (IVW), MR-Egger, simple mode, weighted median, and weighted model methods. RESULTS: Through MR analysis, a total of 56 bacterial genera were co-identified as associated with BMP, TGF, IGF, EGF, and FGF. Among them, eight genera were found to have a causal relationship with multiple growth factors: Marvinbryantia was causally associated with BMP-6 (P = 0.018, OR = 1.355) and TGF-ß2 (P = 0.002, OR = 1.475); Lachnoclostridium, BMP-7 (P = 0.021, OR = 0.73) and IGF-1 (P = 0.046, OR = 0.804); Terrisporobacter, TGF-ß (P = 0.02, OR = 1.726) and FGF-23 levels (P = 0.016, OR = 1.76); Ruminiclostridium5, TGF-ß levels (P = 0.024, OR = 0.525) and FGFR-2 (P = 0.003, OR = 0.681); Erysipelatoclostridium, TGF-ß2 (P = 0.001, OR = 0.739) and EGF and its receptor (EGFR) (P = 0.012, OR = 0.795); Eubacterium_brachy_group, FGFR-2 (P = 0.045, OR = 1.153) and EGF (P = 0.013, OR = 0.7); Prevotella9 with EGFR (P = 0.022, OR = 0.818) and FGFR-2 (P = 0.011, OR = 1.233) and Faecalibacterium with FGF-23 (P = 0.02, OR = 2.053) and IGF-1 (P = 0.005, OR = 0.843). CONCLUSION: We confirmed the causal relationship between the GM and growth factors related to BR, which provides a new perspective for the study of BR, through targeted regulation of specific bacteria to prevent and treat diseases and growth factor-mediated BR disorders.

Association between dermatology follow-up and melanoma survival: A population-based cohort study.

BACKGROUND: Guidelines recommend that patients with melanoma undergo dermatologic examination at least annually. Adherence to follow-up and its impact on survival are unclear. OBJECTIVE: To determine the level of adherence to annual dermatologic follow-up in patients with primary cutaneous melanoma, identify predictors for better adherence, and evaluate whether adherence was associated with melanoma-related mortality. METHODS: Retrospective inception cohort analysis of adults with primary invasive melanoma in Ontario, Canada from 2010 to 2013 with follow-up until December 31, 2018. RESULTS: Adherence to dermatologic follow-up was variable with only 28.0% of patients seeing a dermatologist at least annually (median follow-up 5.0 years). Younger age, female sex, higher income, greater access to dermatology care, stage 2/3 melanoma, prior keratinocyte carcinoma, fewer comorbidities, and any outpatient visit in the 12 months prior to melanoma diagnosis were predictors for adherence. Greater adherence to annual dermatology visits was associated with reduced melanoma-specific mortality compared with lower levels of adherence (adjusted hazard ratio 0.64, 95% CI 0.52-0.78). LIMITATIONS: Observational study design and inability to identify skin examinations performed by non-dermatologists. CONCLUSION: Adherence to annual dermatology visits after melanoma diagnosis was low. Greater adherence may promote better patient survival but warrants confirmation in further research including randomized trials.

Comparing the ocular surface temperature and dry eye condition of keratoconus with normal eyes using infrared thermal imaging.

PURPOSE: This study was conducted to compare the ocular surface temperature in keratoconus eyes with that in normal eyes. METHODS: A total of 27 participants were enrolled, with 10 and 17 participants in the keratoconus and control groups, respectively. Participants in the control group underwent an ophthalmic slit lamp examination and ocular thermography, while an additional corneal tomography was performed for those in the keratoconus group. RESULTS: For patients with keratoconus, the mean upper eyelid temperature (UET) was 32.36 ± 1.02 °C, inner canthus temperature (ICT) was 34.25 ± 0.83 °C, outer canthus temperature (OCT) was 33.62 ± 0.96 °C, initial central corneal temperature (initial CCT) was 33.04 ± 1.03 °C, sixth-second CCT (6 s-CCT) was 32.67 ± 1.19 °C, and the mean change in CCT measured within 6 s (change in CCT within 6 s) was 0.36 ± 0.26 °C. For controls, the values for UET, ICT, OCT, initial CCT, 6 s-CCT, and change in CCT within 6 s were 32.35 ± 1.13 °C, 34.14 ± 0.91 °C, 33.51 ± 1.02 °C, 33.22 ± 1.01 °C, 32.99 ± 1.01 °C, and 0.22 ± 0.17 °C, respectively. Except for the change in CCT within 6 s (p = 0.022), no significant differences were observed in UET (p = 0.973), ICT (p = 0.659), OCT (p = 0.697), initial CCT (p = 0.556) or 6 s-CCT (p = 0.310) between the two groups. CONCLUSION: The keratoconus eyes showed faster changes in CCT and evaporation of tear film after opening the eyes. Therefore, the keratoconus eyes had a higher incidence of dry eye conditions.

Low-stray-light concave holographic gratings processed by combining the methods of photoresist hot-melting and oxygen-ion ashing.

The principal motivation for this paper is to reduce stray light and line roughness in concave holographic gratings (CHG). Compared with other previously reported line-smoothing grating techniques such as dynamic-exposure near-field holography, we successfully improve the line smoothing of CHG to approximately 10 nm from 2 nm. Our method uses optimization technologies and a combination of photoresist hot-melting (PHM) and oxygen-ion ashing (OIA), thereby improving the degree of stray light before and after optimization by one order of magnitude; the level processed by OIA, PHM, and OIA successively is ${7.85} \times {{10}^{ - 5}}$7.85×10-5. Combining the two technologies, we achieve lower stray light and straighter groove lines for the concave gratings, which is more effective, easy to implement, and incurs a low cost.

Two-dimensional stretchable blazed wavelength-tunable grating based on PDMS.

This paper reports a two-dimensional stretchable blazed wavelength-tunable grating based on polydimethylsiloxane (PDMS). In the elastic range, stretch the grating along (Y-axis) and perpendicular to (X-axis) the grating line, fix the position of the +1st-order spot to maintain the grating period, and only change the groove angle to tune the blazed wavelength. By stretching the grating up to 20% of the Y-axis, and 5.2% of the X-axis, the groove angle is reduced by 1.33°, and the blazed wavelength of the first-order diffraction shifts toward the short-wave direction by 42.3 nm. The sensitivity of a spectrometer can be enhanced by tuning the blazed wavelength of the PDMS grating to the wavelength of the spectrum peak under observation in the bands from 460.8 nm to 503.1 nm.

Analytical design of a high-performing +1st order diffraction convex grating imaging spectrometer.

A novel concentric spectrometer having one convex grating and one concave mirror, working at ${+}{1}$+1st order diffraction, and with a small size, high resolution, and high diffraction efficiency, is proposed. It can simultaneously achieve high resolution and compactness by increasing the grating groove density. A compact spectrometer operating at a wavelength of 740-790 nm with an excellent imaging quality is designed. Its spectral resolution reaches 0.049 nm, and its diffraction efficiency improves by 27% compared to the conventional Offner spectrometer with convex grating working at ${-}{1}$-1st order diffraction. This is suitable for small, light, and low-cost atmospheric gas monitoring satellites.

Optimized multielement accommodative intraocular lens with a four-freeform-surface Alvarez lens and a separate aspheric lens.

This paper proposes an accommodative intraocular lens (IOL), which consists of a two-element Alvarez lens and an aspheric lens for changing focal power and refractive power, respectively. The four-freeform-surface Alvarez lens is optimized for a multiple field of view; further, the aspheric lens also corrects the aberrations induced by the corneal asphericity of the human eye over the whole range of accommodation. A simulation using optical design software demonstrates its excellent performance in that the values of the modulation transfer function at 100 cycles/mm all reach ∼0.4 with a ±5° field of view for 3 and 5 mm pupils.

Multifacet echelle grating for intensity broadening on spectral plane fabricated by rotating ion-beam etching.

This paper describes a new type of multifacet echelle grating (MFEG) for use in an echelle spectrometer. This new type of echelle grating broadens the spectral distribution on the spectral plane. We built a geometric model of MFEG to analyze the influence of the blaze angle and number of facet shapes on the spectral evolution. A dual-facet echelle grating and a four-facet echelle grating with different parameters were fabricated by rotating ion-beam etching with a self-shadowing rotating mask, based on the existing single-facet echelle grating (SFEG) with a line density of 52.7 g/mm and a blaze angle of 63.5°. The distributions of diffraction efficiency for different orders were measured with a He-Ne laser (632.8 nm); furthermore, these echelle gratings were applied in an echelle spectrometer (ICP-OES, Plasma2000), and testing spectra were obtained. The experimental results demonstrate that the MFEG can broaden the intensity distribution on the spectral plane, overcoming the weak spectral margin signal of SFEG spectrometers.

Computer-Aided Discovery of Small Molecule Inhibitors of Thymocyte Selection-Associated High Mobility Group Box Protein (TOX) as Potential Therapeutics for Cutaneous T-Cell Lymphomas.

Cutaneous T-cell lymphomas (CTCL) are the most common primary lymphomas of the skin. We have previously identified thymocyte selection-associated high mobility group (HMG) box protein (TOX) as a promising drug target in CTCL; however, there are currently no small molecules able to directly inhibit TOX. We aimed to address this unmet opportunity by developing anti-TOX therapeutics with the use of computer-aided drug discovery methods. The available NMR-resolved structure of the TOX protein was used to model its DNA-binding HMG-box domain. To investigate the druggability of the corresponding protein-DNA interface on TOX, we performed a pilot virtual screening of 200,000 small molecules using in silico docking and identified 'hot spots' for drug-binding on the HMG-box domain. We then performed a large-scale virtual screening of 7.6 million drug-like compounds that were available from the ZINC15 database. As a result, a total of 140 top candidate compounds were selected for subsequent in vitro validation. Of those, 18 small molecules have been characterized as selective TOX inhibitors.

Measurement of grating groove density using multiple diffraction orders and one standard wavelength.

A new method for measuring grating groove density is proposed using multiple diffraction orders and one standard wavelength to eliminate the eccentricity effect originated from the rotation of a diffraction grating. Based on the Littman configuration for autocollimation, the groove density can be obtained by measuring the internal angles between the zeroth-order and two nonzeroth-order diffracted beams for one laser wavelength at a certain incident angle. The method was applied to measure the groove density of a plane grating with a nominal groove density of 651 lines/mm, where the mean value of this grating was measured to be 650.76 lines/mm with a relative measurement error ΔN/N of 3.8×10-5.

Evidence of an oncogenic role of aberrant TOX activation in cutaneous T-cell lymphoma.

TOX is a nuclear factor essential for the development of CD4(+) T cells in the thymus. It is normally expressed in low amounts in mature CD4(+) T cells of the skin and the peripheral blood. We have recently discovered that the transcript levels of TOX were significantly increased in mycosis fungoides, the most common type of cutaneous T-cell lymphoma (CTCL), as compared to normal skin or benign inflammatory dermatoses. However, its involvement in advanced CTCL and its biological effects on CTCL pathogenesis have not been explored. In this study, we demonstrate that TOX expression is also enhanced significantly in primary CD4(+)CD7(-) cells from patients with Sézary syndrome, a leukemic variant of CTCL, and that high TOX transcript levels correlate with increased disease-specific mortality. Stable knockdown of TOX in CTCL cells promoted apoptosis and reduced cell cycle progression, leading to less cell viability and colony-forming ability in vitro and to reduced tumor growth in vivo. Furthermore, TOX knockdown significantly increased 2 cyclin-dependent kinase (CDK) inhibitors, CDKN1B and CDKN1C. Lastly, blocking CDKN1B and CDKN1C reversed growth inhibition of TOX knockdown. Collectively, these findings provide strong evidence that aberrant TOX activation is a critical oncogenic event for CTCL.

Research on Straightness Error Compensation of Grating Ruling Machine.

Echelle grating is a kind of special diffraction grating. Working with high diffraction orders and big diffraction angle, which has the advantages of high resolution and full wave shining. It has been widely used in high-end spectrum instrument, which greatly promoted the development of aerospace, astronomy, medical, military, environment and other cutting-edge technology. However, professional scoring system needs to be customized, and the price is very expensive. The use of sophisticated ultra precision machining equipment to process in the ladder grating can greatly reduce the preparation cost of the mother plate of the ladder grating. Due to the bad straightness and high accumulative error of ultra precision single point diamond lathe, it can't satisfy the demand of preparation when preparing the echelle grating, casuing the bad diffraction wave front. In order to reduce the straightness error, this paper comes up with the error compensation for the single point diamond lathe. Firstly, we make the first compensation based on the accumulative error curve. When the compensation ratio is 0.75 to 0.85, the peak valley value (pv) of the diffraction wave front is about 400 nm, reaching its greatest effect of the first straightness compensation. Secondly, we make the straightness compensation according to the diffraction wave front curve of the blazed order. The pv of the diffraction wave front is about 83nm. The results show that the diffraction wave front is greatly improved which is beneficial to improve the quality of the grating, and has a guiding role in the actual grating characterization.

The prevalence of anxiety and depression in patients with or without hyperhidrosis (HH).

BACKGROUND: There are conflicting data about the correlation between hyperhidrosis (HH) and anxiety and depression. OBJECTIVE: We sought to determine the prevalence of anxiety and depression in patients with or without HH. METHODS: We examined 2017 consecutive dermatology outpatients from Vancouver, British Columbia, Canada, and Shanghai, China, using Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 scales for anxiety and depression assessments. Multivariable logistic regression analysis was performed to evaluate if the impact of HH on anxiety and depression is dependent on demographic factors and diagnoses of the patients' presenting skin conditions. RESULTS: The prevalence of anxiety and depression was 21.3% and 27.2% in patients with HH, respectively, and 7.5% and 9.7% in patients without HH, respectively (P value <.001 for both). There were positive correlations between HH severity and the prevalence of anxiety and depression. Multivariable analysis showed that HH-associated increase in anxiety and depression prevalence is independent of demographic factors and presenting skin conditions. LIMITATION: The data from the questionnaires relied on the accuracy of patients' self-reports. CONCLUSION: Both single variant and multivariable analyses showed a significant association between HH and the prevalence of anxiety and depression in a HH severity-dependent manner.

Optical notch filter with tunable bandwidth based on guided-mode resonant polarization-sensitive spectral feature.

A novel bandwidth-tunable notch filter is proposed based on the guided-mode resonance effect. The notch is created due to the superposition spectra response of two guided-mode resonant filters. The compact, bandwidth tuning capability is realized by taking advantage the effect of spectra-to-polarization sensitivity in one-dimensional classical guided-mode resonance filter, and using a liquid crystal polarization rotator for precise and simple polarization control. The operation principle and the design of the device are presented, and we demonstrate it experimentally. The central wavelength is fixed at 766.4 nm with a relatively symmetric profile. The full width at half maximum bandwidth could be tuned from 8.6 nm to 18.2 nm by controlling the applied voltage in electrically-driving polarization rotator.

Electrically driving bandwidth tunable guided-mode resonance filter based on a twisted nematic liquid crystal polarization rotator.

A novel bandwidth-tunable filter is proposed based on nonpolarizing guided-mode resonance effect. The compact, electrically driving bandwidth-tunable optical filter is realized by taking advantage of the effect of bandwidth-to-polarization sensitivity and using a twisted nematic liquid crystal polarization rotator for simple and precise polarization control. The operation principle and the design of the device are presented. The center wavelength is fixed at 623.1 nm with a relatively symmetric line shape. The full-width at half-maximum bandwidth is tuned from 12 to 44.8 nm by controlling the voltage in the polarization rotator.

High-transmittance subwavelength metal grating with relief structure composed of multiple steps.

A new kind of subwavelength metal grating with relief structure is designed and analyzed, in which the shape of the grating lines is no longer a single rectangle, but a relief structure with multiple steps. GsolverV52 was used to determine the optimal values of the grating period, groove depth, and the number of steps. The optical performance of the novel structure is evaluated and compared in terms of the transmission efficiency and extinction ratio over the visible and near-infrared wavelength spectrum. It is shown that, in the near-infrared band, the maximum transmittance can be increased about 15% compared to the traditional metal grating under the same parameters. With the unique characteristics, the metal grating is expected to find applications in liquid crystal display fields, polarization imaging, optical communication, and so on.

[Retrospective analysis for clinical and histopathological characteristics of basal cell carcinoma in 418 patients].

OBJECTIVE: To investigate the clinical and histopathological characteristics of basal cell carcinoma (BCC) in Chinese patients. METHODS: Clinical and pathological data of BCC confirmed by histology from 2010 to 2012 in Peking University First Hospital were retrospectively analyzed. RESULTS: Among 418 patients enrolled, the male/female ratio was 0.77:1. The average age was (65.39±13.51) years. Among the patients younger than 60 years who occupied 29% of all the cases, the male/female ratio was 1.16:1. In terms of the histology subtypes of the BCCs, 81.8% were nodular, followed by superficial (9.8%), and the others were in very small proportion. The head and face were the most common sites of BCC (86.6%). All morpheaform subtypes, and the majority of the nodular subtypes were located on the head and face, whereas the trunk and extremities were the most common locations for the others. Clinically, 86.6% of the BCC were pigmented and 80.4% were not ulcerated. The diagnostic accordance rates of BCC on the head and face (84.7%) and on the trunk (79.1%) were higher than those on the extremities (46.2%, P<0.05). CONCLUSION: The most clinical and histopathological characteristics of our cases were similar to those of Caucasian. This study displays some unique characteristics. The young and middle aged patients occupied relative higher proportion, and their gender ration was different from that of the aged group. Tumor with hyperpigmentation was popular and few cases were ulcerated. In this study, multiple BCC cases were seldom, and the BCC patients with nevus sebaceous were older than those in other reports. The research of the diagnostic accordance rates of BCC revealed that both doctors and patients should pay more attention to BCC.

[Performance comparison of coronene film for UV-CCD prepared by spin-coating and physical vapor deposition].

In the present paper, the methods of spin-coating and physical vapor deposition (PVD) were researched to prepare the coronene film for UV-CCD, and their properties were characterized and compared with each other. The results of the experiment show that the process of spin-coating is relatively simple, which takes advantage of materials and retains the inherent crystal structure of coronene. However, the roughness of the film is a little more than that of PVD method; the film prepared by PVD method can absorb ultraviolet more effectively and then emits fluorescence with more intensity. Compared with the method of spin-coating, the surface of PVD film is more smoothly, and the process of thermal evaporation changes the crystal structure of coronene and forms another new crystalline state according to the XRD graph. While the whole process of PVD is morecomplex and it needs larger cost of production than spin-coating method. Besides, the comparison research work provided theoretical direction for preparing the photoluminescence down-conversion film under different requirements, such as fluorescence intensity, surface roughness and cost of production.