Fabry-Pérot optical frequency comb based mm-wave RoF system using pilot-assisted equalizer.

The emergence of the millimeter wave (mm-Wave; 30 GHz to 300 GHz) frequency band holds a lot of promise for addressing the congestion at low frequency in future mobile networks. Among many mm-Wave generation schemes, optical heterodyning is considered one of the most promising approaches due to its scalability and potential for integration on chip. Employing optical frequency combs (OFC) for optical heterodyning alleviates the significant phase distortions/noise introduced by the optical sources. However, any residual phase noise in these systems can deteriorate the transmission performance. Here we demonstrate a high-capacity mm-Wave radio-over-fiber (RoF) system using Fabry-Pérot (FP) laser comb overcoming the typical limitations of this source. The temporal phase perturbation induced by the frequency fluctuation of the FP laser is theoretically analyzed, and then estimated and compensated by a pilot-based phase equalizer. Performance evaluation of the proposed phase equalizer is conducted through experiment and simulation. Enabled by the proposed compensation scheme, ten 200 MHz filtered orthogonal frequency division multiplexing (f-OFDM) signal bands modulated by 16-quadrature amplitude modulation (QAM) are transmitted over 10 km fiber, with the ability to serve multiple users. The transmission of 16-QAM modulated single carrier signals with 2 GBd and 8 Gbps data rate is also performed for comparison, which offers better resilience to phase noise, demonstrating the first commercial Quantum Well FP laser-based optical heterodyning mm-Wave RoF system for both multi-carrier and single carrier signals.

Identification of Genes and Key Pathways Associated with the Pathophysiology of Lung Cancer and Atrial Fibrillation.

Background: Lung cancer is a malignant tumor originating from respiratory epithelial cells in the bronchi, bronchioles, and alveoli, often associated with atrial fibrillation; However, there is a lack of in-depth understanding of its genetic basis and molecular mechanisms. Our goal is to study the genes and signaling networks associated with cancer and atrial fibrillation. Materials and methods: We obtained microarray datasets for lung tumors from the Gene Expression Omnibus (GEO) database and AF for this investigation: GSE30219, GSE79768, and screened the candidate specimens in both microarrays for differential genes at P < .05 using GEO2R. The outcomes were also examined using the Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Gene and Gene Combinations (KEGG) pathway analysis methods. Using STRING and Cytoscape, protein interaction networks (PPI) were analyzed and visualized. The Molecular Complex Detection (MOCDE) plugin is responsible for filtering important compounds. Candidate genes are then screened by the cytoHubba plugin according to MCC criteria. After taking the intersection of the Hub genes by the Wayne diagram, the ROC curves were plotted separately by combining the data from one lung cancer dataset GSE19804, two AF datasets GSE41177/GSE14975 in the GEO database. Results: An aggregate of 49 co-expressed differentially expressed genes (co-DEGs) were discovered in lung cancer/AF and healthy controls. Most co-DEGs were found in neutrophil activation, where they were linked to immunological response and interactions between cytokines and cytokine receptors, according to GO and KEGG pathway analyses. Furthermore, due of their significant connectedness in both the lung carcinoma and AF datasets, we chose six key genes. They are MNDA, HP, LYZ, S100A9, S100A8, and S100A12, among others. Conclusions: The findings of this research indicate that the onset of lung cancer and AF depends on a small number of distinctive genes. We investigated the functional enrichment, differential gene expression, and PPI of DEGs in lung cancer and AF, and the results offer fresh perspectives on the discovery of prospective biomarkers and priceless therapeutic precursors in these two diseases.

Novel SNX13 Frameshift Variant in an Individual with Developmental Delay.

Recently, an increasing number of genes have been associated with global developmental delay (GDD) and intellectual disability (ID). The sorting nexin (SNX) protein family plays multiple roles in protein trafficking and intracellular signaling. SNXs have been reported to be associated with several disorders, including Alzheimer disease and Down syndrome. Despite the growing evidence of an association of SNXs with neurodegeneration, SNX13 deficiency has not been associated with GDD or ID. In this study, we present the case of a 4-year-old boy with brain dysplasia and GDD, including language delay, cognitive delay, and dyskinesia. Exome sequencing revealed a 1-bp homozygous deletion in SNX13 (NM_015132.5: exon8: c.742_743del; p.Tyr248Leufs*20), which caused a frameshift and predicted early termination. Sanger sequencing confirmed that the variant was inherited from his parents respectively. Our findings associate SNX13 variation with GDD for the first time and provide a new GDD candidate gene.

Low-power and high-speed 2 × 2 thermo-optic MMI-MZI switch with suspended phase arms and heater-on-slab structure.

We propose a ${2} \times {2}$ thermo-optic switch with high switching performance. The switch is based on multimode interferometer (MMI) couplers and a Mach-Zehnder interferometer (MZI) structure, where the phase arms are designed as laterally supported suspended ridge waveguides (LSSRWs) with a metallic heater placed on the slab. It is experimentally demonstrated that this switch has a power consumption of 1.07 mW, a thermal time constant ${\sim}{4.7}\;\unicode{x00B5} {\rm s}$, an extinction ratio ${\sim}{30}\;{\rm dB}$, and an insertion loss ${\sim}{0.5}\;{\rm dB}$. Particularly, the corresponding figure of merit (FOM) has been improved by 1 order magnitude compared with general thermo-optic switches. This ${2} \times {2}$ thermo-optic MMI-MZI switch may find potential application for network reconfiguration and on-chip optical information processing.

Overcoming the hypoxia-induced drug resistance in liver tumor by the concurrent use of apigenin and paclitaxel.

The chemotherapeutic efficacy of paclitaxel against hypoxic tumors is usually unsatisfactory, which is partially due to the so-called hypoxia-induced drug resistance. The mechanism of hypoxia-induced resistance is primarily associated with hypoxia-inducible factor 1α (HIF-1α), which is an oxygen-sensitive transcriptional activator coordinating the cellular response to hypoxia. Apigenin is a natural occurring HIF-1α inhibitor that can suppress the expression of HIF-1α through multiple pathways and reverse the hypoxia-induced resistance found in cancer cells. Here we report that the use of apigenin can suppress the HIF-1α expression in hypoxic tumors through the simultaneous inhibition of the AKT/p-AKT pathway and HSP90, which is beneficial for enhancing the anticancer activity of the co-administered paclitaxel. The potential synergistic effect of apigenin and paclitaxel was further validated on HepG2 cell line and tumor-bearing mouse models.

Novel variants in AP4B1 cause spastic tetraplegia, moderate psychomotor development delay and febrile seizures in a Chinese patient: a case report.

INTRODUCTION: The AP4B1 gene encodes a subunit of adaptor protein complex-4 (AP4), a component of intracellular transportation of proteins which plays important roles in neurons. Bi-allelic mutations in AP4B1 cause autosomal recessive spastic paraplegia-47(SPG47). CASE PRESENTATION: Here we present a Chinese patient with spastic tetraplegia, moderate psychomotor development delay and febrile seizures plus. Brain MRIs showed dilated supratentorial ventricle, thin posterior and splenium part of corpus callosum. The patient had little progress through medical treatments and rehabilitating regimens. Whole exome sequencing identified novel compound heterozygous truncating variants c.1207C > T (p.Gln403*) and c.52_53delAC (p.Cys18Glnfs*7) in AP4B1 gene. Causal mutations in AP4B1 have been reported in 29 individuals from 22 families so far, most of which are homozygous mutations. CONCLUSIONS: Our study enriched the genetic and phenotypic spectrum of SPG47. Early discovery, diagnosis and proper treatment on the conditions generally increase chances of improvement on the quality of life for patients.

Molecular Control of Innate Immune Response to Pseudomonas aeruginosa Infection by Intestinal let-7 in Caenorhabditis elegans.

The microRNA (miRNA) let-7 is an important miRNA identified in Caenorhabditis elegans and has been shown to be involved in the control of innate immunity. The underlying molecular mechanisms for let-7 regulation of innate immunity remain largely unclear. In this study, we investigated the molecular basis for intestinal let-7 in the regulation of innate immunity. Infection with Pseudomonas aeruginosa PA14 decreased let-7::GFP expression. Intestine- or neuron-specific activity of let-7 was required for its function in the regulation of innate immunity. During the control of innate immune response to P. aeruginosa PA14 infection, SDZ-24 was identified as a direct target for intestinal let-7. SDZ-24 was found to be predominantly expressed in the intestine, and P. aeruginosa PA14 infection increased SDZ-24::GFP expression. Intestinal let-7 regulated innate immune response to P. aeruginosa PA14 infection by suppressing both the expression and the function of SDZ-24. Knockout or RNA interference knockdown of sdz-24 dampened the resistance of let-7 mutant to P. aeruginosa PA14 infection. Intestinal overexpression of sdz-24 lacking 3'-UTR inhibited the susceptibility of nematodes overexpressing intestinal let-7 to P. aeruginosa PA14 infection. In contrast, we could observed the effects of intestinal let-7 on innate immunity in P. aeruginosa PA14 infected transgenic strain overexpressing sdz-24 containing 3'-UTR. In the intestine, certain SDZ-24-mediated signaling cascades were formed for nematodes against the P. aeruginosa PA14 infection. Our results highlight the crucial role of intestinal miRNAs in the regulation of the innate immune response to pathogenic infection.

Performance-enhanced silicon thermo-optic Mach-Zehnder switch using laterally supported suspended phase arms and efficient electrodes.

We report a silicon thermo-optic Mach-Zehnder switch with a broadband, low switching power, and fast response. A broadband 3 dB directional coupler is used to act as a power splitter. Laterally supported suspended phase arms are employed to substantially reduce the switching power without sacrificing too much on the temporal response. Furthermore, two metallization steps are utilized to further decrease the power consumption. We experimentally obtain a switching power as low as 1.1 mW, as well as a fast response of 76 and 48 µs for rise time and fall time, respectively. The demonstrated device also has a relatively high mechanical strength and compact size, making it promising to be applied in silicon photonic integrated circuits.

[A genotyping study of 13 cases of early-onset Charcot-Marie-Tooth disease].

OBJECTIVE: To study the clinical characteristics and genetic variation of early-onset Charcot-Marie-Tooth disease (CMT). METHODS: Children with a clinical diagnosis of early-onset CMT were selected for the study. Relevant clinical data were collected, and electromyogram and CMT-related gene detection were performed and analyzed. RESULTS: A total of 13 cases of early-onset CMT were enrolled, including 9 males (69%) and 4 females (31%). The mean age at consultation was 4.0±2.1 years. Among them, 12 children (92%) had an age of onset less than 2 years, 9 children (69%) were diagnosed with CMT type 1 (including 6 cases of Dejerine-Sottas syndrome), 1 child (8%) with intermediate form of CMT, and 3 children (23%) with CMT type 2. The genetic test results of these 13 children showed 6 cases (46%) of PMP22 duplication mutation, 3 cases (23%) of MPZ gene insertion mutation and point mutation, 3 cases (23%) of MFN2 gene point mutation, and 1 case (8%) of NEFL gene point mutation. Eleven cases (85%) carried known pathogenic mutations and 2 cases (15%) had novel mutations. The new variant c.394C>G (p.P132A) of the MPZ gene was rated as "possibly pathogenic" and the new variant c.326A>G (p.K109R) of the MFN2 gene was rated as "pathogenic". CONCLUSIONS: Early-onset CMT is mainly caused by PMP22 gene duplication mutation and MPZ gene mutations. The clinical phenotype is mainly CMT type 1, among which Dejerine-Sottas syndrome accounts for a considerable proportion.

High-performance thermo-optic tunable grating filters based on laterally supported suspended silicon ridge waveguide.

We demonstrate a novel thermally tunable grating optical filter based on suspended silicon ridge waveguide with low power consumption, fast response and relatively high mechanical stability. An enhanced power efficiency of ~300 pm/mW is achieved by employing isolation trench. Periodic lateral tethers and anchors are utilized to support the overall waveguide for maintaining mechanical robustness. 10%-90% rising time and falling time are measured to be 78 µs and 52 µs, respectively. Simulations and experiments both indicate that the demonstrated device has a relatively homogeneous temperature distribution, which is essential for practical integrated photonic devices.

Doubly differential star-16-QAM for fast wavelength switching coherent optical packet transceiver.

A coherent optical packet transceiver based on doubly differential star 16-ary quadrature amplitude modulation (DD-star-16-QAM) is presented for spectrally and energy efficient reconfigurable networks. The coding and decoding processes for this new modulation format are presented, simulations and experiments are then performed to investigate the performance of the DD-star-16-QAM in static and dynamic scenarios. The static results show that the influence of frequency offset (FO) can be cancelled out by doubly differential (DD) coding and the correction range is only limited by the electronic bandwidth of the receivers. In the dynamic scenario with a time-varying FO and linewidth, the DD-star-16-QAM can overcome the time-varying FO, and the switching time of around 70 ns is determined by the time it takes the dynamic linewidth to reach the requisite level. This format can thus achieve a shorter waiting time after switching tunable lasers than the commonly used square-16-QAM, in which the transmission performance is limited by the frequency transients after the wavelength switch.

Wavelength bistability based on optical injection in a novel tunable dual mode laser.

A novel tunable dual mode laser is proposed based on a double-layer Bragg grating structure, named double-layer grating distributed Bragg reflector (DLG-DBR) laser. With controlling the gain saturation condition, different oscillating states can be observed. The nonlinear dynamics characteristics including bifurcation of the laser under optical injection with two different start-up sequences are analyzed with numerical simulations. Furthermore, we investigate the lasing wavelength bistability of the laser combined with its tuning characteristics theoretically. Optical memory operation based on the external optical injection locking bistability of the dual mode device is proposed. The memory operation can be achieved in the whole wavelength window with a 10 nm tuning range. A mode suppression ratio (MSR) of more than 45 dB is achieved between the two bistable states.

Clinically mild encephalitis/encephalopathy with a reversible splenial lesion associated with Mycoplasma pneumoniae infection.

BACKGROUND: Clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) is a clinico-radiological syndrome characterized by transient mild symptoms of encephalopathy and a reversible lesion in the splenium of the corpus callosum on magnetic resonance imaging (MRI). It is often triggered by infection. The common pathogens of MERS are viruses, especially influenza virus. However, Mycoplasma pneumoniae (M.pneumoniae) are relatively rare pathogens for MERS. CASE PRESENTATION: Here we report two paediatric cases of M.pneumoniae infection-induced MERS. The diagnosis of M.pneumoniae infection was established based on polymerase chain reaction (PCR) and specific serum antibodies (IgM). Both of the two patients presented with mild encephalopathy manifestations and recovered completely within a few days. The initial MRI showed a lesion in the central portion of the splenium of the corpus callosum, which completely resolved on the seventh and eighth day after admission for case 1 and case 2. Lumbar puncture was performed in both patients, which revealed no pleocytosis. In case 1, the patient had hyponatremia, peripheral facial nerve paralysis, and rash. To the best of our knowledge, it is the first MERS case associated with peripheral nerve damage. In case 2, interleukin-6(IL-6) was moderately increased in the cerebrospinal fluid (CSF). It suggested that IL-6 may play a role in the pathogenesis of M.pneumoniae-induced MERS. CONCLUSION: Our study enriches the available information on the pathogens of MERS and provides valuable data for better understanding of this syndrome.

Inhibitory effects of platelet-rich plasma on intervertebral disc degeneration: a preclinical study in a rabbit model.

BACKGROUND: Platelet-rich plasma (PRP) contains multiple growth hormones that may stimulate tissue repair. This study aimed to assess the effects of PRP in a rabbit model of IDD (annulus fibrosus puncture). MATERIAL/METHODS: Thirty-six adult New Zealand white rabbits were randomly divided into 3 groups: 0.1 mL PRP (group A), 0.1 mL phosphate-buffered saline (group B), and control (group C) (n=12/group). Annulus fibrosus puncture was performed to establish L4/5 and L5/6 IDD models. Two and 4 weeks later, 6 rabbits from each group were given an IVD injection at L4/5 and L5/6. Two or 4 weeks after injection, rabbits were scanned with X-ray and MRI before being sacrificed. IVDs were collected for hematoxylin and eosin, Masson's trichrome, and Safranin O staining, and type II collagen immunohistochemistry. RESULTS: Over time, IVD height and disc imaging signal intensity decreased gradually in groups B and C, but only slightly in group A (baseline: 100% for all groups; A: 95.9±4.2% at 4 weeks, 90.1±8.4 at 6 weeks; B: 75.3±5.7% at 4 weeks, 70.8±6.4% at 6 weeks; C: 74.7±5.5% at 4 weeks, 69.9±6.2% at 6 weeks; all P<0.001, P<0.01 between A vs. B and C). Degenerative histological changes in IVDs in groups B and C were more severe compared with group A. CONCLUSIONS: Platelet-rich plasma interventions can effectively attenuate the IDD process in rabbits.

HDAC5 promotes osteosarcoma progression by upregulation of Twist 1 expression.

Histone deacetylases (HDACs) form a family of enzymes, which have fundamental roles in the epigenetic regulation of gene expression and contribute to the growth, differentiation, and apoptosis of cancer cells. In this study, we firstly investigated the biological function of HDAC5 in osteosarcoma cells. We found that mRNA and protein levels of HDAC5 were upregulated in osteosarcoma tissues and cell lines. Furthermore, overexpression of HDAC5 could promote cell proliferation in osteosarcoma cell lines. In contrast, HDAC5 knockdown using small interfering RNA inhibited cell proliferation. At the molecular level, we demonstrated that HDAC5 promoted mRNA expression of twist 1, which has been reported as an oncogene. Together, these results highlighted for the first time an unrecognized link between HDAC5 and osteosarcoma progression and demonstrated that its specific inhibition might contribute to the treatment of tumorigenesis.

Identification of novel variants in BRF1 gene from patient with developmental delay, hearing abnormality, and nervous system anomalies.

Cerebellofaciodental syndrome characterized with dysmorphic features, intellectual disability, and brain anomalies. Now its clinical spectrum expanded more manifestations including bilateral sensorineural hearing impairment and inner ear malformation. Here, we report a 14-month-old boy with global developmental delay and hearing disorder. Whole exome sequencing (WES) revealed the compound heterozygous variants [NM_001519.4: c.652 T > G (p.W218G); c.915 + 1G > T] in the BRF1 gene which inherited from his parents, respectively. The MRI results showed hypoplastic cerebellar vermis, enlarged cisterna magna, and prominent fourth ventricle, the rehabilitation therapy failed to improve the symptoms for our patient. Our finding expands the genetic spectrum of BRF1 variants, which indicates patients with the developmental delay caused by BRF1 variants require other treatments instead of rehabilitation.

Developing and validating machine learning-based prediction models for frailty occurrence in those with chronic obstructive pulmonary disease.

Background: Frailty is a medical syndrome caused by multiple factors, characterized by decreased strength, endurance, and diminished physiological function, resulting in increased susceptibility to dependence and/or death. Patients with chronic obstructive pulmonary disease (COPD) tend to be more vulnerable to frailty due to their physical and psychological burdens. Therefore, the aim of this study was to develop a reliable and accurate vulnerability risk prediction model for frailty in patients with COPD in order to improve the identification and prediction of patient frailty. The specific objectives of this study were to determine the prevalence of frailty in patients with COPD and develop a prediction model and evaluate its predictive power. Methods: Clinical information was analyzed using data from the 2018 China Health and Retirement Longitudinal Study (CHARLS) database, and 34 indicators, including behavioral factors, health status, mental health parameters, and various sociodemographic variables, were examined in the study. The adaptive synthetic sampling technique was used for unbalanced data. Three methods, ridge regressor, extreme gradient boosting (XGBoost) classifier, and random forest (RF) regressor, were used to filter predictors. Seven machine learning (ML) techniques including logistic regression (LR), support vector machines (SVM), multilayer perceptron, light gradient-boosting machine, XGBoost, RF, and K-nearest neighbors were used to analyze and determine the optimal model. For customized risk assessment, an online predictive risk modeling website was created, along with Shapley additive explanation (SHAP) interpretations. Results: Depression, smoking, gender, social activities, dyslipidemia, asthma, and residence type (urban vs. rural) were predictors for the development of frailty in patients with COPD. In the test set, the XGBoost model had an area under the curve of 0.942 (95% confidence interval: 0.925-0.959), an accuracy of 0.915, a sensitivity of 0.873, and a specificity of 0.911, indicating that it was the best model. Conclusions: The ML predictive model developed in this study is a useful and easy-to-use instrument for assessing the vulnerability risk of patients with COPD and may aid clinical physicians in screening high-risk patients.

Expanding the genetic and phenotypic relevance of CLCN4 variants in neurodevelopmental condition: 13 new patients.

OBJECTIVES: CLCN4 variations have recently been identified as a genetic cause of X-linked neurodevelopmental disorders. This study aims to broaden the phenotypic spectrum of CLCN4-related condition and correlate it with functional consequences of CLCN4 variants. METHODS: We described 13 individuals with CLCN4-related neurodevelopmental disorder. We analyzed the functional consequence of the unreported variants using heterologous expression, biochemistry, confocal fluorescent microscopy, patch-clamp electrophysiology, and minigene splicing assay. RESULTS: We identified five novel (p.R41W, p.L348V, p.G480R, p.R603W, c.1576 + 5G > A) and three known (p.T203I, p.V275M, p.A555V) pathogenic CLCN4 variants in 13 Chinese patients. The p.V275M variant is found at high frequency and seen in four unrelated individuals. All had global developmental delay (GDD)/intellectual disability (ID). Seizures were present in eight individuals, and 62.5% of them developed refractory epilepsy. Five individuals without seizures showed moderate to severe GDD/ID. Developmental delay precedes seizure onset in most patients. The variants p.R41W, p.L348V, and p.R603W compromise the anion/exchange function of ClC-4. p.R41W partially impairs ClC-3/ClC-4 association. p.G480R reduces ClC-4 expression levels and impairs the heterodimerization with ClC-3. The c.1576 + 5G > A variant causes 22 bp deletion of exon 10. CONCLUSIONS: We further define and broaden the clinical and mutational spectrum of CLCN4-related neurodevelopmental conditions. The p.V275M variant may be a potential hotspot CLCN4 variant in Chinese patients. The five novel variants cause loss of function of ClC-4. Transport dysfunction, protein instability, intracellular trafficking defect, or failure of ClC-4 to oligomerize may contribute to the pathophysiological events leading to CLCN4-related neurodevelopmental disorder.

Compromised word-level neural tracking in the high-gamma band for children with attention deficit hyperactivity disorder.

Children with attention deficit hyperactivity disorder (ADHD) exhibit pervasive difficulties in speech perception. Given that speech processing involves both acoustic and linguistic stages, it remains unclear which stage of speech processing is impaired in children with ADHD. To investigate this issue, we measured neural tracking of speech at syllable and word levels using electroencephalography (EEG), and evaluated the relationship between neural responses and ADHD symptoms in 6-8 years old children. Twenty-three children participated in the current study, and their ADHD symptoms were assessed with SNAP-IV questionnaires. In the experiment, the children listened to hierarchical speech sequences in which syllables and words were, respectively, repeated at 2.5 and 1.25 Hz. Using frequency domain analyses, reliable neural tracking of syllables and words was observed in both the low-frequency band (<4 Hz) and the high-gamma band (70-160 Hz). However, the neural tracking of words in the high-gamma band showed an anti-correlation with the ADHD symptom scores of the children. These results indicate that ADHD prominently impairs cortical encoding of linguistic information (e.g., words) in speech perception.

A novel variant in BCL11B in an individual with neurodevelopmental delay: A case report.

BACKGROUND: B-Cell CLL/Lymphoma 11B (BCL11B) is a C2 H2 zinc finger transcription factor that has broad biological functions and is essential for the development of the immune system, neural system, cardiovascular system, dermis, and dentition. Variants of BCL11B have been found in patients with neurodevelopmental disorders and immunodeficiency. MATERIALS AND METHODS: Whole-exome sequencing (WES) and clinical examinations were performed to identify the etiology of our patient. A variant in the BCL11B gene, NM_138576.4: c.1206delG (p.Phe403Serfs*2) was found and led to frameshift truncation. RESULTS: We reported a male patient with developmental delay and cerebral palsy who carried the BCL11B variant. The detailed clinical features, such as brain structure and immune detection, were described and reviewed in comparison to previous patients. CONCLUSIONS: The BCL11B-related neurodevelopmental disorders are rare, and only 17 variants in 25 patients have been found to date. Our report expands the variants spectrum of BCL11B and increases the case of neurodevelopmental abnormalities.