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Purpose: Disorders of sex development (DSD) have complex pathogenesis, and evidence suggests an association between MAMLD1defects and DSD. MAMLD1is expressed in gonadal tissues and affected males exhibit hypospadias, steroid hormone abnormalities, or gonadal underdevelopment. We performed genetic testing on a newborn patient with severe hypospadias and an elevation of 17-hydroxyprogesterone (17α-OH) for the diagnosis of DSD. Methods: Genetic testing of the proband and parents was conducted using whole-exome and Sanger sequencing. The identified variant was transfected into HEK293T cells to assess mutant protein expression using western blot (WB) and into steroidogenic NCI-H295R cells to assess MAMLD1and CYP17A1transcript levels using qPCR. Molecular dynamics simulations were performed to construct a structural model and analyze potential biological implications. Results: A novel heterozygous variant was identified in the proband’s MAMLD1, NM_005491.5: c.1619_1637del (p.Gln540Alafs*72), inherited from the mother. In transfected cells, the wild-type and mutant proteins were 86.2 and 68.3 kDa, respectively, indicating the formation of a truncated protein. While MAMLD1transcription was not affected, CYP17A1transcription levels decreased with the variant compared to wild-type, suggesting an impact on the transactivation of CYP17A1. The truncated protein exhibited enhanced hydrophobicity, owing to the absence of the C-terminal structural portion, resulting in a looser protein structure. Conclusion: Severe hypospadias in the proband may be attributed to a novel MAMLD1variant, whereas the 17α-OH elevation might be related to interference with CYP17A1transcriptional activation. This study expands the spectrum of MAMLD1variants and underscores the critical role of genetic testing in the diagnosis of DSD.

A hybrid optoelectronic bistability is realized with the assistance of an ultrahigh-order mode (UHM) excited in a symmetrical metal-cladding waveguide (SMCW). PMN-PT ceramics is selected as the guiding layer, which possesses the voltage modulated refractive index and thickness by means of an electro-optical effect and converse-piezoelectric effect. An amplified voltage signal translated from the intensity of reflected light is exerted on the guiding layer, whose parameter variations can alter the resonance condition of the UHM and finally lead to a dramatic change in the intensity of the reflected light. Since the full width at half-maximum of the UHM is extremely narrow, a hysteresis behavior with a milliwatt threshold between the incident light and the reflected light can be achieved when a positive feedback is established. Our bistability configuration is simple and not limited to TM polarization.

A band-rejection filter is proposed based on a prism-waveguide cascaded coupling system, which is composed of an equilateral trapezium prism and a deposited multilayer structure. By properly adjusting the thickness of the coupling layer and the light extinction coefficient of the guiding layer, the radiative and intrinsic dampings matching condition could be well satisfied, and then a series of reflectivity dips will appear in the reflectivity wavelength spectrum. Since the module of reflectivity is smaller than one, the extinction ratio of the rejected frequency via the cascaded coupling system is twice as high as that of the single-coupling technology. By narrowing the guiding layer to a micrometer scale, the free spectral range is broad enough to cover the Raman spectrum scattered from the frequently used sample. In addition, the numerically calculated results show that the light in the free spectral range is mostly reflected, with an insertion loss down to 0.45 dB. Compared to previously reported band-rejection filters, it is relatively simple to manufacture our device, which possesses potential applications to help distinguish the Raman signal from the elastic scattering background.

In order to improve the spatial resolution of time-domain (TD) fluorescence molecular lifetime tomography (FMLT), an accelerated nonlinear orthogonal matching pursuit (ANOMP) algorithm is proposed. As a kind of nonlinear greedy sparsity-constrained methods, ANOMP can find an approximate solution of L_0 minimization problem. ANOMP consists of two parts, i.e., the outer iterations and the inner iterations. Each outer iteration selects multiple elements to expand the support set of the inverse lifetime based on the gradients of a mismatch error. The inner iterations obtain an intermediate estimate based on the support set estimated in the outer iterations. The stopping criterion for the outer iterations is based on the stability of the maximum reconstructed values and is robust for problems with targets at different edge-to-edge distances (EEDs). Phantom experiments with two fluorophores at different EEDs and in vivo mouse experiments demonstrate that ANOMP can provide high quantification accuracy, even if the EED is relatively small, and high resolution.

Abstract: The character of Synovial sarcoma is the chromosomal translocation t(X; 18)(p11.2;q11.2), which results in the fusion of the SYT gene with a SSX gene. There is little study that could fully elucidate the mechanism of pathogenesis of this fusion transcript. This study is designed to gain more insight into the function of this fusion gene. We evaluated the whole genome expression in SYO-1 cells inhibited as a result of specific small interfering RNA for SYT-SSX. Cell proliferation and apoptosis were analyzed by flow cytometer and MTT. The proteins correlated with proliferation were also detected using western blot. TUNEL and Immunohistochemical stain assessment were also carried out on TMA of SS tissues. The mRNA level reduced over 90% caused by SYT-SSX specific siRNA. Five pathways were employed, that ERK1/2 pathway was differential significantly (p = 0.043218). Meanwhile, down-regulation of SYT-SSX fusion gene expression would inhibit the proliferation of SS cell and the survival rate decreased (34.1%), while apoptotic rate increased (10.92%). After transfected with SYT-SSX-specific siRNA it caused a block in G1/G0 phase (31.99%) of SYO-1 cells compared with control cells. The protein level of ERK1/2, p-ERK, and cyclin D1 altered in same trend with expression of SYT-SSX. In TMA stain assessment, SYT-SSX positive group with high ki-67 LI expressed more cyclin D1and CDK4 than the SYT-SSX negative group. High ki-67 LI was detected in cases with p-ERK expression. Meanwhile, cyclin D1 and CDK4 were shown to be more expressed in tumor cells with p-ERK expression. Our results suggest that the fusion gene SYT-SSX should be considered to play important role on SS cell growth via ERK pathway. This study may be valuable for understanding the pathogenic role and molecular mechanism of the fusion gene SYT-SSX in synovial sarcoma through the proposed genome-wide approach. Furthermore, the research would open up the possibility of using SYT-SSX and ERK as a therapeutic target.