Fiber-integrated catenary ring-array metasurfaces for beam shaping.

Catenary is referred to as "the real mathematical and mechanical form" in the architectural field. Because of the unique phase control characteristic of the catenary, it has excellent ability in optical manipulation. Here, we propose an optical waveform conversion device based on optical fiber-integrated catenary ring-array metasurfaces. The device consists of a cascade structure of a single-mode fiber (SMF) and a graded-index fiber (GIF). At the GIF end, two kinds of catenary ring-array metasurfaces are introduced to realize beam shaping from Gaussian beam (GB) to Bessel beam. The device can selectively generate a focused or non-diffracting Bessel beam by changing the circular polarization state of the incident light. It is worth noting that under some parameters of the device, the output Bessel beam can break through the diffraction limit, which has potential applications in the fields of optical imaging, optical communication, and optical trapping.

Optical fiber-integrated achromatic metalens based on catenary metasurfaces.

A challenge in all-fiber-integrated metasurface devices is to efficiently control dispersion in the limited fiber end area to build metasurfaces, therefore, the design of metasurfaces with a special structure becomes crucial to meet the demands of dispersion control. A unique phase response of circularly polarized light in catenary metasurfaces can offer new opportunities for polarization-sensitive arbitrary chromatic dispersion control. Herein, we proposed an optical achromatic metalens based on equal width catenary metasurfaces integrated on the large-mode optical fiber (LMF) end. To reduce phase distortions, the LMF is designed to generate quasi-plane waves (QPW), and then QPW converts from catenary metasurfaces to realize achromatic focusing. A notable feature of this device is its axial focal length shift as low as 0.09% across the working wavelength range from 1.33 µm to 1.55 µm, commonly used in optical fiber communication, demonstrating its excellent dispersion control capability. Furthermore, the device exhibits exceptional capabilities to break through the diffraction limit of the output field. This research has potential applications in the fields of achromatic devices, chromatic aberration correction, fiber lasers, and optical communication and modulation.

Palladin Is a Neuron-Specific Translational Target of mTOR Signaling That Regulates Axon Morphogenesis.

The mTOR signaling pathway regulates protein synthesis and diverse aspects of neuronal morphology that are important for brain development and function. To identify proteins controlled translationally by mTOR signaling, we performed ribosome profiling analyses in mouse cortical neurons and embryonic stem cells upon acute mTOR inhibition. Among proteins whose translation was significantly affected by mTOR inhibition selectively in neurons, we identified the cytoskeletal regulator protein palladin, which is localized within the cell body and axons in hippocampal neurons. Knockdown of palladin eliminated supernumerary axons induced by suppression of the tuberous sclerosis complex protein TSC1 in neurons, demonstrating that palladin regulates neuronal morphogenesis downstream of mTOR signaling. Our findings provide novel insights into an mTOR-dependent mechanism that controls neuronal morphogenesis through translational regulation.SIGNIFICANCE STATEMENT This study reports the discovery of neuron-specific protein translational responses to alterations of mTOR activity. By using ribosome profiling analysis, which can reveal the location and quantity of translating ribosomes on mRNAs, multiple aspects of protein translation were quantitatively analyzed in mouse embryonic stem cells and cortical neurons upon acute mTOR inhibition. Neurons displayed distinct patterns of ribosome occupancy for each codon and ribosome stalling during translation at specific positions of mRNAs. Importantly, the cytoskeletal regulator palladin was identified as a translational target protein of mTOR signaling in neurons. Palladin operates downstream of mTOR to modulate axon morphogenesis. This study identifies a novel mechanism of neuronal morphogenesis regulated by mTOR signaling through control of translation of the key protein palladin.

A mass spectrometric insight into the origins of benign gynecological disorders.

Applications of mass spectrometry (MS) are rapidly expanding and encompass molecular and cellular biology. MS aids in the analysis of in vivo global molecular alterations, identifying potential biomarkers which may improve diagnosis and treatment of various pathologies. MS has added new dimensionality to medical research. Pioneering gynecologists now study molecular mechanisms underlying female reproductive pathology with MS-based tools. Although benign gynecologic disorders including endometriosis, adenomyosis, leiomyoma, and polycystic ovarian syndrome (PCOS) carry low mortality rates, they cause significant physical, mental, and social detriments. Additionally, some benign disorders are unfortunately associated with malignancies. MS-based technology can detect malignant changes in formerly benign proteomes and metabolomes with distinct advantages of speed, sensitivity, and specificity. We present the use of MS in proteomics and metabolomics, and summarize the current understanding of the molecular pathways concerning female reproductive anatomy. Highlight discoveries of novel protein and metabolite biomarkers via MS-based technology, we underscore the clinical application of these techniques in the diagnosis and management of benign gynecological disorders. © 2015 Wiley Periodicals, Inc. Mass Spec Rev 36:450-470, 2017.

Mixed Infections and Rifampin Heteroresistance among Mycobacterium tuberculosis Clinical Isolates.

Mixed infections and heteroresistance of Mycobacterium tuberculosis contribute to the difficulty of diagnosis, treatment, and control of tuberculosis. However, there is still no proper solution for these issues. This study aimed to investigate the potential relationship between mixed infections and heteroresistance and to determine the high-risk groups related to these factors. A total of 499 resistant and susceptible isolates were subjected to spoligotyping and 24-locus variable-number tandem repeat methods to analyze their genotypic lineages and the occurrence of mixed infections. Two hundred ninety-two randomly selected isolates were sequenced on their rpoB gene to examine mutations and heteroresistance. The results showed that 12 patients had mixed infections, and the corresponding isolates belonged to Manu2 (n = 8), Beijing (n = 2), T (n = 1), and unknown (n = 1) lineages. Manu2 was found to be significantly associated with mixed infections (odds ratio, 47.72; confidence interval, 9.68 to 235.23; P < 0.01). Four isolates (1.37%) were confirmed to be heteroresistant, which was caused by mixed infections in three (75%) isolates; these belonged to Manu2. Additionally, 3.8% of the rifampin-resistant isolates showing no mutation in the rpoB gene were significantly associated with mixed infections (χ(2), 56.78; P < 0.01). This study revealed for the first time that Manu2 was the predominant group in the cases of mixed infections, and this might be the main reason for heteroresistance and a possible mechanism for isolates without any mutation in the rpoB gene to become rifampin resistant. Further studies should focus on this lineage to clarify its relevance to mixed infections.

Fiber-integrated optical tweezers for ballistic transport and trapping yeast cells.

Due to their unique operational flexibility and ability to facilitate functional integration, the fascinating application of optical fibers has recently attracted significant attention in the field of optical tweezers and optical manipulation. The traditional optical fiber tweezers (OFTs) can easily trap microparticles in the front or side of the trapping tool, instead of behind. Herein, we propose and demonstrate a novel capillary optical fiber tweezer (COFT) to break the limitation of the optical trapping direction and extend the spatial range of optical trapping. The device consists of a cascade structure of single-mode fiber and capillary optical fiber (COF), which was used to excite higher-order modes in the COF. A COF taper tip was introduced to converge the multimode field, which created a focused output beam, realizing the ballistic transport of multi-yeast cells at the surface of the COF taper tip and their trapping by multiple optical potential wells of the focused output beam. The experimental results showed that the maximum transport length and speed of the cells were greater than 150 µm and 10 µm s-1, respectively, and at least three cells could be trapped simultaneously. The simulation results showed that the trap stiffness of COFT in several potential wells was in the range of 10-40 pN µm-1 W-1, which indicates that COFT has a good trap performance. Therefore, COFT greatly expands the region of the optical potential well, thus guiding and trapping microparticles distributed on the entire surface of the COF taper tip. This device can also greatly improve the optical trapping ability of single or multiple microparticles, providing a new tool for researchers committed to research on micro-nano objects and cells, which is expected to be widely used in the fields of targeted drug delivery, cell dynamic analysis, microfluidic chip driving, etc.

A Human Induced Pluripotent Stem Cell-Derived Tissue Model of a Cerebral Tract Connecting Two Cortical Regions.

Cerebral tracts connect separated regions within a brain and serve as fundamental structures that support integrative brain functions. However, understanding the mechanisms of cerebral tract development, macro-circuit formation, and related disorders has been hampered by the lack of an in vitro model. Here, we developed a human stem cell-derived model of cerebral tracts, which is composed of two spheroids of cortical neurons and a robust fascicle of axons linking these spheroids reciprocally. In a microdevice, two spheroids of cerebral neurons extended axons into a microchannel between the spheroids and spontaneously formed an axon fascicle, mimicking a cerebral tract. We found that the formation of axon fascicle was significantly promoted when two spheroids extended axons toward each other compared with axons extended from only one spheroid. The two spheroids were able to communicate electrically through the axon fascicle. This model tissue could facilitate studies of cerebral tract development and diseases.

LncRNAs: the bridge linking RNA and colorectal cancer.

Long noncoding RNAs (lncRNAs) are transcribed by genomic regions (exceeding 200 nucleotides in length) that do not encode proteins. While the exquisite regulation of lncRNA transcription can provide signals of malignant transformation, lncRNAs control pleiotropic cancer phenotypes through interactions with other cellular molecules including DNA, protein, and RNA. Recent studies have demonstrated that dysregulation of lncRNAs is influential in proliferation, angiogenesis, metastasis, invasion, apoptosis, stemness, and genome instability in colorectal cancer (CRC), with consequent clinical implications. In this review, we explicate the roles of different lncRNAs in CRC, and the potential implications for their clinical application.

Epigenetic repression of PDZ-LIM domain-containing protein 2 promotes ovarian cancer via NOS2-derived nitric oxide signaling.

Ovarian cancer constitutes one of the most lethal gynaecological malignancies worldwide and currently no satisfactory therapeutic approaches have been established. Therefore, elucidation of molecular mechanisms to develop targeted therapy of ovarian cancer is crucial. PDLIM2 is critical to promote ubiquitination of nuclear p65 and thus its role in inflammation has been highlighted recently. We demonstrate that PDLIM2 is decreased in both ovarian high-grade serous carcinoma and in various human ovarian cancer cell lines compared with normal ovary tissues and human ovarian surface epithelial cells (HOSE). Further functional analysis revealed that PDLIM2 is epigenetically repressed in ovarian cancer development and inhibition of PDLIM2 promoted ovarian cancer growth both in vivo and in vitro via NOS2-derived nitric oxide signaling, leading to recruitment of M2 type macrophages. These results suggest that PDLIM2 might be involved in ovarian cancer pathogenesis, which could serve as a promising therapeutic target for ovarian cancer patients.

Tumor microenvironment: The culprit for ovarian cancer metastasis?

Despite chemotherapy and surgical debulking options, ovarian cancer recurs and disseminates frequently, with poor prognosis. However, the molecular mechanisms underlying ovarian cancer metastasis still remain unelucidated. The tumor microenvironment, consisting of stromal cells (including fibroblasts, macrophages, regulatory T cells, myeloid-derived suppressor cells, endothelial cells, pericytes and platelets), the extracellular matrix component (EMC) (including inflammatory cytokines, chemokines, matrix metalloproteinases, integrins, and other secreted molecules) and exosomes (small extracellular vesicles loaded with molecules), establishes an autocrine-paracrine communication circuit that reinforces invasion and cancer cell metastasis via reciprocal signaling. Recent evidences have unraveled the significant contribution of tumor microenvironment to ovarian cancer metastasis. In this review, we provide a comprehensive landscape of the reciprocity between tumor stroma and ovarian cancer cells upon metastasis, aiming to offer novel clues on the development of novel diagnostic biomarkers and therapeutic targets for ovarian cancer in future clinical practice.

Increased expression of fibroblast growth factor receptor 1 in endometriosis and its correlation with endometriosis-related dysmenorrhea and recurrence.

OBJECTIVE(S): This study aims to identify a critical molecule that potentially participates in endometriosis pathogenesis and characterize its correlation with dysmenorrhea and recurrence. STUDY DESIGN: We utilized a bioinformatics-based strategy to screen for candidate genes and fibroblast growth factor receptor 1(FGFR1) was chosen for further validation. FGFR1 expression was examined in specimens of ectopic and eutopic endometrium obtained from 48 patients with endometriosis and specimens of eutopic endometrium from 26 healthy control subjects using immunohistochemistry and Western blotting. In addition, FGFR shRNA treatment was applied in a nude mice endometriosis model to examine the functional role of FGFR1 in endometriosis formation in vivo. RESULTS: FGFR1 was found commonly overexpressed in ectopic endometrium of endometriosis compared with either its eutopic counterpart or endometrium from normal patients (P < 0.05). FGFR shRNA treatment impaired endometriosis formation and alleviated endometriosis-related symptoms in vivo. FGFR1 expression in ectopic endometrium was correlated with dysmenorrhea severity (P < 0.05) and recurrence in endometriosis patients (P < 0.05). CONCLUSION(S): FGFR1 might be involved in endometriosis development, which could possibly serve as a novel therapeutic target and prognostic marker for this disease.