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Introduction: Despite radiotherapy being one of the major treatments for triple-negative breast cancer (TNBC), new molecular targets for its treatment are still required due to radioresistance. CDK2 plays a critical role in TNBC. However, the mechanism by which CDK2 promotes TNBC radioresistance remains to be clearly elucidated. Objectives: We aimed to elucidate the relationship between CDK2 and TRIM32 and the regulation mechanism in TNBC. Methods: We performed immunohistochemical staining to detect nuclear TRIM32, CDK2 and STAT3 on TNBC tissues. Western blot assays and PCR were used to detect the protein and mRNA level changes. CRISPR/Cas9 used to knock out CDK2. shRNA-knockdown and transfection assays also used to knock out target genes. GST pull-down analysis, immunoprecipitation (IP) assay and in vitro isomerization analysis also used. Tumorigenesis studies also used to verify the results in vitro. Results: Herein, tripartite motif-containing protein 32 (TRIM32) is revealed as a substrate of CDK2. Radiotherapy promotes the binding of CDK2 and TRIM32, thus leading to increased CDK2-dependent phosphorylation of TRIM32 at serines 328 and 339. This causes the recruitment of PIN1, involved in cis–trans isomerization of TRIM32, resulting in importin α3 binding to TRIM32 and contributing to its nuclear translocation. Nuclear TRIM32 inhibits TC45-dephosphorylated STAT3, Leading to increased transcription of STAT3 and radioresistance in TNBC. These results were validated by clinical prognosis confirmed by the correlative expressions of the critical components of the CDK2/TRIM32/STAT3 signaling pathway. Conclusions: Our findings demonstrate that regulating the CDK2/TRIM32/STAT3 pathway is a promising strategy for reducing radioresistance in TNBC.

Abstract Annexin A2 (ANXA2) is a widely reported oncogene. However, the mechanism of ANXA2 in esophageal cancer is not fully understood. In this study, we provided evidence that ANXA2 promotes the progression of esophageal squamous cell carcinoma (ESCC) through the downstream target threonine tyrosine kinase (TTK). These results are consistent with the up-regulation of ANXA2 and TTK in ESCC. In vitro experiments by knockdown and overexpression of ANXA2 revealed that ANXA2 promotes the progression of ESCC by enhancing cancer cell proliferation, migration, and invasion. Subsequently, animal models also confirmed the role of ANXA2 in promoting the proliferation and metastasis of ESCC. Mechanistically, the ANXA2/TTK complex activates the Akt/mTOR signaling pathway and accelerates epithelial-mesenchymal transition (EMT), thereby promoting the invasion and metastasis of ESCC. Furthermore, we identified that TTK overexpression can reverse the inhibition of ESCC invasion after ANXA2 knockdown. Overall, these data indicate that the combination of ANXA2 and TTK regulates the activation of the Akt/mTOR pathway and accelerates the progression of ESCC. Therefore, the ANXA2/TTK/Akt/mTOR axis is a potential therapeutic target for ESCC.

Abstract Point‐to‐point (P2P) flexible transceivers are the key technical enabler to cost‐effectively offer fast, dynamic, and ‘just‐the‐right‐size’ ultra‐dense P2P connectivity for various applications including remote equipment control and distributed fibre networks. However, existing flexible transceivers originally designed for hub‐and‐spoke traffic patterns are sub‐optimal. To effectively address such technical issue, a P2P flexible transceiver incorporating a cascaded inverse fast fourier transform/fast fourier transform‐based multi‐channel aggregation/de‐aggregation technique and analogue in‐phase and quadrature (IQ) mixers is proposed and numerically evaluated in a 56Gbps@20 km intensity modulation and direct detection transmission system. The proposed P2P flexible transceivers not only support adaptive and flexible variations in both channel count and channel line rate but also offer additional physical layer network security.

Background: Cuproptosis is a copper-induced mitochondrial cell death, and regulating cuproptosis is becoming a rising cancer treatment modality. Here, we attempted to establish a cuproptosis-associated lncRNAs (CRLs) signature (CRlncSig) to predict the survival, immune landscape, and treatment response in ovarian cancer (OC) patients. Methods: A series of statistical analyses were used to identify the key CRLs that are closely related to the prognosis, and a prognostic CRlncSig was constructed. The predictive accuracy of the CRlncSig was further validated in an independent Gene Expression Omnibus (GEO) set. Then, we compared the immune cell infiltration, immune checkpoints, tumor microenvironment (TME), tumor mutational burden (TMB), drug sensitivity, and efficacy of immunotherapy between the two subgroups. We further built a nomogram integrating the CRlncSig and different clinical traits to enhance the clinical application of the CRlncSig. Results: Nine hub CRLs, namely RGMB-AS1, TYMSOS, DANCR, LINC00702, LINC00240, LINC00996, DNM1P35, LINC00892, and TMEM254-AS1, were correlated with the overall survival (OS) of OC and a prognostic CRlncSig was established. The CRlncSig classified OC patients into two risk groups with strikingly different survival probabilities. The time-dependent ROC (tdROC) curves demonstrated good predictive ability in both the training cohort and an independent validation cohort. Multivariate analysis confirmed the independent predictive performance of the CRlncSig. We constructed a nomogram based on the CRlncSig, which can predict the prognosis of OC patients. The high-risk score was characterized by decreased immune cell infiltration and activation of stroma, while activation of immunity was observed in the low-risk subgroup. Moreover, patients in low-risk subgroups had more Immunophenoscore (IPS) and fewer immune escapes compared to high-risk subgroups. Finally, an immunotherapeutic cohort confirmed the value of the CRlncSig in predicting immunotherapy outcomes. Conclusions: The developed CRlncSig may be promising for the clinical prediction of OC patient outcomes and immunotherapeutic responses.

Driven by a large number of emerging diversified services, in the 5G and beyond era, concurrent direct inter-ONU and upstream communications inside a PON-based mobile access network are highly desirable to provide dynamic, ultra-dense, and fast ONU-to-ONU (without involving an OLT) and ONU-to-OLT connections. To cost-effectively deliver highly dynamic and low latency direct inter-ONU communications, this paper proposes and experimentally demonstrates novel concurrent direct inter-ONU and upstream communications in an upstream 27 km, >62.47 Gbit/s IMDD PON. For supporting inter-ONU communications between a large number of ONUs, an advanced passive remote node is also proposed. Based on different passive optical components, this remote node can be implemented using two approaches, which can, respectively, reduce the inter-ONU signal power losses by >12.2 dB and >16.6 dB (for 128 ONUs) in comparison with existing inter-ONU communication techniques’ remote nodes. In each ONU and OLT, a single pair of cascaded IFFT/FFT-based point-to-multipoint (P2MP) flexible optical transceivers are employed to simultaneously and dynamically establish multiple ONU-to-ONU and ONU-to-OLT communications according to actual users’ requirements. Experimental results show that the proposed network has excellent robustness against various transmission system impairments, including chromatic dispersion, the Rayleigh and Brillouin backscattering effects, and the channel interference effects. For each ONU, dynamic channel allocation can be made without compromising its overall performance.

In this paper, we experimentally illustrate the effectiveness of neural networks (NNs) as non-linear equalisers for multilevel pulse amplitude modulation (PAM-M) transmission over an optical wireless communication (OWC) link. In our study, we compare the bit-error-rate (BER) performances of two decision feedback equalisers (DFEs)—a multilayer-perceptron-based DFE (MLPDFE), which is the NN equaliser, and a transversal DFE (TRDFE)—under two degrees of non-linear distortion using an eye-safe 850 nm single-mode vertical-cavity surface-emitting laser (SM-VCSEL). Our results consistently show that the MLPDFE delivers superior performance in comparison to the TRDFE, particularly in scenarios involving high non-linear distortion and PAM constellations with eight or more levels. At a forward error correction (FEC) threshold BER of 0.0038, we achieve bit rates of ~28 Gbps, ~29 Gbps, ~22.5 Gbps, and ~5 Gbps using PAM schemes with 2, 4, 8, and 16 levels, respectively, with the MLPDFE. Comparably, the TRDFE yields bit rates of ~28 Gbps and ~29 Gbps with PAM-2 and PAM-4, respectively. Higher PAM levels with the TRDFE result in BERs greater than 0.0038 for bit rates above 2 Gbps. These results highlight the effectiveness of the MLPDFE in optimising the performance of SM-VCSEL-based OWC systems across different modulation schemes and non-linear distortion levels.

Abstract Purpose Oral adenoid cystic carcinoma (OACC) has high rates of both local–regional recurrence and distant metastasis. The objective of this study is to investigate the impact of Khib on OACC and its potential as a targeted therapeutic intervention. Experimental design We investigated the DEPs (differentially expressed proteins) and DHMPs between OACC-T and OACC-N using LC–MS/MS-based quantitative proteomics and using several bioinformatics methods, including GO enrichment analysis, KEGG pathway analysis, subcellular localization prediction, MEA (motif enrichment analysis), and PPI (protein–protein interaction networks) to illustrate how Khib modification interfere with OACC evolution. Results Compared OACC-tumor samples (OACC-T) with the adjacent normal samples (OACC-N), there were 3243 of the DEPs and 2011 Khib sites were identified on 764 proteins (DHMPs). DEPs and DHMPs were strongly associated to glycolysis pathway. GAPDH of K254, ENO of K228, and PGK1 of K323 were modified by Khib in OACC-T. Khib may increase the catalytic efficiency to promote glycolysis pathway and favor OACC progression. Conclusions and clinical relevance Khib may play a significant role in the mechanism of OACC progression by influencing the enzyme activity of the glycolysis pathway. These findings may provide new therapeutic options of OACC.

Abstract Urogenital congenital anomalies (UCAs) is defined as “any live-birth with a urinary or genital condition” and affects millions of men and women worldwide. However, sex differences and related environmental risk factors in UCAs burden on a global scale have not been assessed. Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we estimated prevalence, incidence, mortality and disability-adjusted life years (DALYs) of UCAs from 1990 to 2019 by sex, region, and socio-demographic Index (SDI) in 204 countries and territories. The disease burden of UCAs was also estimated attributable to each risk factor were estimated according to risk exposure. In 2019, UCAs caused 10,200 all-ages deaths (95% UI 7550–13,400). The combined global incidence rate was 8.38 per 1000 (95% UI 5.88–12.0) live births. The ASIR increased slightly, while the ASDR decreased from 1990 to 2019.The UCAs burden varies greatly depending on the development level and geographical location. The UCAs burden was significantly higher in men than in women, and the sex differences showed an enlarging trend. Health risks and issues, including pollution, child and maternal malnutrition, diet habits, unsafe sanitation and water source, were detected to be positively related to UCAs burden. Albeit the age-standardised prevalence, mortality, incidence, and DALYs of UCAs have decreased, they still cause a public health challenge worldwide. The high deaths and DALYs rates in low and low-middle SDI countries highlight the urgent need for improved preventive, diagnostic, and therapeutic measures. Global strategies for enhancing water safety, reducing pollution, and healthy diets are crucial steps in reducing the burden of UCAs.

The Upper Ordovician Wufeng Formation-Lower Silurian Longmaxi Formation in Lintanchang area of the southeastern Sichuan Basin has good exploration and development conditions, and clarifying the paleo-fluid pressure evolution is of great significance for revealing the process of shale gas accumulation and fugitive emission. Taking the shale tectonic fractures and fluid overpressure fracture veins of the Wufeng-Longmaxi formations in Lintanchang area as the research object, the paleo-fluid pressure evolution process in this area and its controlling impact were investigated using cathodoluminescence, inclusion temperature measurement, laser Raman analysis, and basin simulation. The study shows that: (1) Lintanchang area has experienced four stages: normal pressure, mild overpressure to normal pressure, overpressure, and pressure relief. Overpressure is mainly due to hydrocarbon generation. Pressure relief is mainly caused by shale gas fugitive emission. The gas reservoir pressure relief reaches 54% of the initial pressure during the pressure relief stage. (2) There are two stages of vein filling in the fractures at the bottom of the black shale in the Wufeng-Longmaxi formations. The first stage is formed in the sedimentation and burial stage at 131-118 Ma, the temperature is 178-205 ℃, and the trapping pressure of methane inclusions is 105.6-119.8 MPa. The second stage is formed in the tectonic uplift stage at 25-18 Ma, the temperature is 150-175 ℃, the methane inclusions have relatively low salinity and its trapping pressure is 80.8-92.1 MPa. The low pressure coefficient (1.37-1.49) indicates that mass fugitive emission has occurred. (3) The late tectonic movement, especially the rapid uplift in the late Himalayan period, is the root cause of the fugitive emission and pressure relief of the gas reservoirs. The decrease of the roundness and pore size of the organic pores indicates the deterioration of reservoir physical properties. However, due to the long formation and preservation time of the gas reservoirs, the shale in the Wufeng-Longmaxi formations in Lintanchang area still has good exploration potential. This study is helpful to deepen the understanding of the accumulation mechanism of the normal-pressure shale gas reservoirs in Lintanchang area and can provide theoretical guidance for optimal selection of favorable shale gas exploration areas.

Objective: Photodynamic therapy (PDT) is a minimally invasive treatment approach for precancerous and cancerous lesions, known for its ability to activate the host immune response. This study conducted a bibliometric analysis to identify the research trends and hotspots related to the immune response in PDT.Methods: We analyzed articles and reviews published from 1989 to 2023, retrieved from the Web of Science database. Using Citespace and VOSviewer, we visualized the distribution patterns of these studies in time and space.Results: The analysis revealed a substantial increase in the number of publications on PDT-related immune response since 1989. A total of 1,688 articles from 1,701 institutions were included in this analysis. Among thei nstitutions, the Chinese Academy of Sciences demonstrated exceptional productivity and a willingness to collaborate with others. Additionally, 8,567 authors contributed to the field, with Mladen Korbelik, Michael R. Hamblin, and Wei R. Chen being the most prolific contributors. The current research focus revolves around novel strategies to enhance antitumor immunity in PDT, including PDT-based dendritic cell vaccines, combination therapies with immune checkpoint inhibitors (ICIs), and the use of nanoparticles for photosensitizer delivery. Furthermore, genes such as CD8A, TNF, CD4, IFNG, CD274, IL6, IL10, CALR, HMGB1, and CTLA4 have been evaluated in the context of PDT-related immunity.Conclusion: PDT not only achieves tumor ablation but also stimulates the immune response, bolstering antitumor immunity. This study highlights the emerging hotspots in PDT-related immune response research and provides valuable insights for future investigations aimed at further enhancing antitumor immunity.

Surgery combined with systemic chemotherapy is currently the main modality of cancer treatment. However, the development of cancer multidrug resistance and inevitable surgical residual lesions lead to high rates of cancer recurrence and mortality. Meanwhile, systemic drug toxic side effects and surgical bleeding complications seriously reduce the quality of life of patients. To avoid cancer multidrug resistance and comprehensively optimize cancer treatment, this work provides a novel injectable cell penetrating peptide octa-arginine (R8)-modified RADA16 (RR) self-assembling peptide nanofiber hydrogel as an anticancer drug carrier for multidrug-resistant cancer therapy. In RR hydrogel, highly compatible RADA16 functions as the β-sheet-based self-assembling backbone which tightly adheres to cancer tissue, prevents postoperative bleeding, and sustainedly releases anticancer drugs for long-term effects. The introduced R8 motifs endow RR hydrogel with the capacity to selectively kill cancer cells and reverse cancer multidrug resistance, which minimally impact normal tissue cells. Specifically, R8 motifs on the hydrogel scaffold selectively interfere with cancer cell membranes, increase drug uptake and penetration into cancer cells and tissues by enhancing multiple internalization pathways, and reduce drug efflux by inhibiting P-gp and BCRP multidrug-resistant transporters. Therefore, this study provides a multifunctional hydrogel material with strong potential for multidrug-resistant cancer clinical translation.

Abstract Radiotherapy is the first‐line treatment for locally advanced cervical squamous cell cancer (CSCC). However, ≈50% of patients fail to respond to therapy and, in some cases, tumors progress after radical radiotherapy. Here, single‐nucleus RNA‐seq is performed to construct high‐resolution molecular landscapes of various cell types in CSCC before and during radiotherapy, to better understand radiotherapy related molecular responses within tumor microenvironment. The results show that expression levels of a neural‐like progenitor (NRP) program in tumor cells are significantly higher after radiotherapy and these are enriched in the tumors of nonresponding patients. The enrichment of the NRP program in malignant cells from the tumors of nonresponders in an independent cohort analyzed by bulk RNA‐seq is validated. In addition, an analysis of The Cancer Genome Atlas dataset shows that NRP expression is associated with poor prognosis in CSCC patients. In vitro experiments on the CSCC cell line demonstrate that downregulation of neuregulin 1 (NRG1), a key gene from NRP program, is associated with decreased cell growth and increased sensitivity to radiation. Immunohistochemistry staining in cohort 3 validated key genes, NRG1 and immediate early response 3 from immunomodulatory program, as radiosensitivity regulators. The findings reveal that the expression of NRP in CSCC can be used to predict the efficacy of radiotherapy.

A modulation format identification (MFI) scheme based on multi-dimensional amplitude features is proposed for elastic optical networks. According to the multi-dimensional amplitude features, incoming polarization division multiplexed (PDM) signals can be identified as QPSK, 8QAM, 16QAM, 32QAM, 64QAM and 128QAM signals using the k-nearest neighbors (KNNs) algorithm in the digital coherent receivers. The proposed scheme does not require any prior training or optical signal-to-noise ratio (OSNR) information. The performance of the proposed MFI scheme is verified based on numerical simulations with 28GBaud PDM-QPSK/-8QAM/-16QAM/-32QAM/-64QAM/-128QAM signals. The results show that the proposed scheme can achieve 100% of the correct MFI rate for all six modulation formats when the OSNR values are greater than their thresholds corresponding to the 20% forward error correction (FEC) related to a BER of 2.4 × 10−2. Meanwhile, the effects of residual chromatic dispersion, polarization mode dispersion and fiber nonlinearities on the proposed scheme are also explored. Finally, the computational complexity of the proposed scheme is analyzed, which is compared with relevant MFI schemes. The work indicates that the proposed technique could be regarded as a good candidate for identifying modulation formats up to 128QAM.

A set of methods for predicting the favorable reservoir of deep shale gas based on machine learning is proposed through research of parameter correlation feature analysis principle, intelligent prediction method based on convolution neural network (CNN), and integrated fusion characterization method based on kernel principal component analysis (KPCA) nonlinear dimension reduction principle. (1) High-dimensional correlation characteristics of core and logging data are analyzed based on the Pearson correlation coefficient. (2) The nonlinear dimension reduction method of KPCA is used to characterize complex high-dimensional data to efficiently and accurately understand the core and logging response laws to favorable reservoirs. (3) CNN and logging data are used to train and verify the model similar to the underground reservoir. (4) CNN and seismic data are used to intelligently predict favorable reservoir parameters such as organic carbon content, gas content, brittleness and in-situ stress to effectively solve the problem of nonlinear and complex feature extraction in reservoir prediction. (5) KPCA is used to eliminate complex redundant information, mine big data characteristics of favorable reservoirs, and integrate and characterize various parameters to comprehensively evaluate reservoirs. This method has been used to predict the spatial distribution of favorable shale reservoirs in the Ordovician Wufeng Formation to the Silurian Longmaxi Formation of the Weirong shale gas field in the Sichuan Basin, SW China. The predicted results are highly consistent with the actual core, logging and productivity data, proving that this method can provide effective support for the exploration and development of deep shale gas.

Due to a great increase in the plasticity of deep marine shale reservoirs in southern Sichuan under high-temperature and high-pressure conditions, the single brittleness evaluation method is difficult to effectively characterize its fracability, which significantly limits the selection of sweet spots and fracturing reconstruction in the area. In the case of the deep marine shale reservoir of the Wufeng-Longmaxi formations in the southern Sichuan Basin, through triaxial high-temperature and high-pressure experiments, fracture toughness and X-ray diffraction experiments, the mechanical properties and its influencing factors in the shale reservoir are studied, and the rock fracture morphology under various loading conditions is quantified. According to the morphological characteristics of shale, the analysis of influencing factors and comprehensive quantitative evaluation of the brittleness has been carried out. The deep marine shale resource in the southern Sichuan Basin is likely to be characterized by its high elastic modulus and low I fracture toughness. The mineral composition, temperature, pressure, and degree of bedding development are the primary factors for determining the brittleness; with high quartz mineral content (>50%), low confining pressure (

Abstract Histones are DNA‐binding basic proteins found in chromosomes. After the histone translation, its amino tail undergoes various modifications, such as methylation, acetylation, phosphorylation, ubiquitination, malonylation, propionylation, butyrylation, crotonylation, and lactylation, which together constitute the “histone code.” The relationship between their combination and biological function can be used as an important epigenetic marker. Methylation and demethylation of the same histone residue, acetylation and deacetylation, phosphorylation and dephosphorylation, and even methylation and acetylation between different histone residues cooperate or antagonize with each other, forming a complex network. Histone‐modifying enzymes, which cause numerous histone codes, have become a hot topic in the research on cancer therapeutic targets. Therefore, a thorough understanding of the role of histone post‐translational modifications (PTMs) in cell life activities is very important for preventing and treating human diseases. In this review, several most thoroughly studied and newly discovered histone PTMs are introduced. Furthermore, we focus on the histone‐modifying enzymes with carcinogenic potential, their abnormal modification sites in various tumors, and multiple essential molecular regulation mechanism. Finally, we summarize the missing areas of the current research and point out the direction of future research. We hope to provide a comprehensive understanding and promote further research in this field.

Cascaded inverse fast Fourier transform/fast Fourier transform (IFFT/FFT)-based multi-channel aggregation/de-aggregation offers a promising solution in constructing highly desirable flexible optical transceivers for considerably improving optical networks’ elasticity, flexibility, and adaptability. However, the multi-channel aggregation operation unavoidably results in generated signals having high peak-to-average power ratios (PAPRs). To solve this technical challenge, this paper first explores the PAPR characteristics of the corresponding flexible transceivers in optical back-to-back (B2B) and 20 km intensity modulation and direct detection (IMDD) transmission systems, and then numerically investigates the feasibility and effectiveness of utilizing the conventional clipping techniques in reducing their PAPR reductions. The results show that the last IFFT operation size is the primary factor determining the PAPRs rather than the channel count and modulation format. For a given last IFFT operation size, the optimal clipping ratio can be identified, which is independent of channel count. With the identified optimal clipping ratio, when the channel count is >4, every two-channel increase in the channel count can only lead to

SNIP1 methylation initiates its oncogenic functions. Here, the authors show that SNIP1 is methylated by KMT5A and this leads to downstream signalling that activates the YAP pathway, resulting in tumorigenesis and metastasis.

A novel digital signal processing (DSP)-based scheme for physical layer security in coherent optical communication systems is proposed and numerically investigated. The optical layer signal encryption is accomplished by two dispersive elements and one phase modulator (PM) driven by a DSP-generated encryption key, whilst signal decryption uses similar components but with inverted dispersion values and security keys. A critical aspect of the DSP-based physical layer security is that the security keys, driving the PMs to hide/recover the data signals, must be highly unpredictable and noise-like, thus orthogonal frequency division multiplexing (OFDM) signals are employed as they possess these characteristics, they can also be easily generated and cover a suitably wide range of unique keys. Numerical simulations are conducted to determine optimum system parameters for achieving a high level of security, the key parameters requiring optimization are the dispersion of the dispersive elements and the bandwidth of the security keys. Using these determined optimum parameters, in-depth investigations are undertaken of encryption/decryption induced transmission performance penalties, sensitives to various parameter offsets and operation over various transmission distances. To observe any data signal dependencies, various performance metrics are investigated for different combinations of modulation formats (DQPSK and 16QAM) and baud rates (40 Gbaud and 100 Gbaud) for the transmitted data signals. The proposed DSP-based physical layer security scheme is shown to have the potential to achieve, in a low-cost and highly effective manner, a high level of physical layer security with acceptable performance penalties for existing coherent optical communication systems.

Polycystic ovary syndrome (PCOS) and periodontal disease (PDD) share common risk factors. The bidirectional interaction between PCOS and PDD has been reported, but until now, the underlying molecular mechanisms remain unclear. Endocrine disorders including hyperandrogenism (HA) and insulin resistance (IR) in PCOS disturb the oral microbial composition and increase the abundance of periodontal pathogens. Additionally, PCOS has a detrimental effect on the periodontal supportive tissues, including gingiva, periodontal ligament, and alveolar bone. Systemic low-grade inflammation status, especially obesity, persistent immune imbalance, and oxidative stress induced by PCOS exacerbate the progression of PDD. Simultaneously, PDD might increase the risk of PCOS through disturbing the gut microbiota composition and inducing low-grade inflammation and oxidative stress. In addition, genetic or epigenetic predisposition and lower socioeconomic status are the common risk factors for both diseases. In this review, we will present the latest evidence of the bidirectional association between PCOS and PDD from epidemiological, mechanistic, and interventional studies. A deep understanding on their bidirectional association will be beneficial to provide novel strategies for the treatment of PCOS and PDD.

Abstract Although reports implicate radioresistance as an important obstacle for the management of breast cancer, its molecular mechanism is elusive. Herein, we found that high HDGF levels are expressed significantly in breast cancer and exhibit a positive association with poor survival prognosis. Heparin-binding growth factor (HDGF) was upregulated in radioresistant breast cancer cells, however, its knockdown could reduce breast cancer radioresistant both in vitro and in vivo. Additionally, the binding of RXRα to HDGF promoter blocked HDGF transcriptional activity, consequently inhibiting breast cancer radioresistance. The enhanced radioresistant activity of HDGF is induced by TKT and STAT3, impacting the STAT3-Tyr705 and STAT3-Ser727 phosphorylation and STAT3 transcriptional activity. Notably, HDGF depletion renders radioresistant hypersensitive to the drug that targets STAT3 phosphorylation. This article demonstrates the novel function of HDGF as a promising molecular target for predicting radioresistance in breast cancer.

Ribonuclease P/MRP Subunit P40 (RPP40), a component of ribonuclease P and multimeric ribonuclease P complex, was reported as one of the promoting factors for the chemoresistance of acute myeloid leukemia and a recurrence predictor of early-stage triple-negative breast cancer. However, the functional role of RPP40 in uterine corpus endometrial carcinoma (UCEC) is unclear. In this study, comprehensive bioinformatic analyses were conducted to explore the predictive role of RPP40 on UCEC diagnosis and prognosis, as well as the underlying mechanism. Differential analyses of multiple databases showed that both messenger RNA (mRNA) and the protein expression of RPP40 were significantly upregulated in UCEC tumor tissues. Furthermore, the RPP40 mRNA expression level was significantly correlated with the clinicopathological characteristics of UCEC patients, including the clinical stage, primary therapy outcome, histological type, histologic grade, overall survival event, disease-specific survival event, and progression-free interval event. Receiver operating characteristic (ROC) analysis showed that RPP40 was a reliable predictor for UCEC diagnosis with an area under the curve (AUC) of 0.775, a sensitivity of 0.829, and a specificity of 0.719. Kaplan–Meier, Cox regression, and nomogram analyses showed that high RPP40 expression was an independent prognostic factor for the 1-year, 3-year, and 5-year survival of UCEC patients. In addition, the enrichment analysis of RPP40-associated differentially expressed genes and correlation analyses showed that the expression of RPP40 was correlated with the regulation of extracellular matrix and immune cell infiltration. In conclusion, the upregulation of RPP40 is significantly correlated with the poor survival and tumor microenvironment of UCEC, suggesting that RPP40 is a promising biomarker of poor prognosis and a potential target of chemotherapy or immunotherapy in UCEC.

Hybrid orthogonal frequency division multiplexing-digital filter multiple access passive optical networks (OFDM-DFMA PONs) offer a cost-effective solution to the challenging requirements of next-generation optical access networks and 5G and beyond radio access networks. It is crucial to consider the impact of timing jitter in any ADC/DAC-based system, therefore this paper presents an in-depth investigation into the impacts of DAC/ADC timing jitter on the hybrid OFDM-DFMA PON's performance. We introduce improved accuracy white and coloured, DAC and ADC timing jitter models, applicable to any DSP-based transmission system. We prove that DAC and ADC timing jitter effects are virtually identical and investigate the effects of white/coloured timing jitter on upstream performance in hybrid OFDM-DFMA PONs and determine the associated jitter-induced optical power penalties. To mitigate against the timing jitter-induced performance degradations, a simple, but highly effective DSP-based technique is implemented which increases robustness against the timing jitter effects and significantly reduces timing jitter-induced optical power penalties. This consequently relaxes DAC/ADC sampling clock jitter requirements and so reduces implementation costs. White (coloured) timing jitter effects are shown to be independent of (dependent on) ONU operating frequency band and a trade-off between DAC and ADC jitter levels can be exploited to reduce ONU costs.

Matching filter (MF)-free digital filter multiplexed (DFM) single sideband (SSB) OFDM intensity modulation and direct detection (IMDD) dual-channel transmissions of 51.25Gbit/s over 25km SSMFs are experimentally demonstrated. It is shown that both transmission system impairments and digital filter characteristic variations can only lead to

Loss of T‐type calcium channel (TCC) function has been reported to result in decreased cell viability and impaired muscle regeneration, but the underlying mechanisms remain largely unknown. We previously found that expression of TCC is reduced in aged pelvic floor muscle of multiple vaginal delivery mice, and this is related to endoplasmic reticulum stress (ERS) activation and autophagy flux blockade. In the present work, we further investigated the effects of TCC function loss on C2C12 myotubes and skeletal muscle, which is mediated by promotion of ERS and ultimately contributes to mitochondrial‐related apoptotic cell death. We found that application of a TCC inhibitor induced mitochondria‐related apoptosis in a dose‐dependent manner and also reduced mitochondrial transmembrane potential (MMP), induced mito‐ROS generation, and enhanced expression of mitochondrial apoptosis proteins. Functional inhibition of TCC induced ERS, resulting in disorder of Ca2+ homeostasis in endoplasmic reticulum, and ultimately leading to cell apoptosis in C2C12 myotubes. Tibialis anterior muscles of T‐type α1H channel knockout mice displayed a smaller skeletal muscle fiber size and elevated ERS‐mediated apoptosis signaling. Our data point to a novel mechanism whereby TCC blockade leads to ERS activation and terminal mitochondrial‐related apoptotic events in C2C12 myotubes and skeletal muscles.

Abstract The protein, tripartite motif containing 24 (TRIM24) is a member of the TRIM protein family, and acts as a critical co‐regulator of multiple nuclear receptors. TRIM24 is dysregulated in many cancers, including colorectal carcinoma. However, its biological functions and molecular mechanisms with respect to colorectal carcinoma are still largely unknown. In the current study, we found that TRIM24 promotes YAP signaling for driving cell proliferation in colorectal cancer. TRIM24 was significantly upregulated in colorectal carcinoma, and its expression was negatively correlated with the survival of patients. Depletion of TRIM24 impaired the ability of the cancer cells to proliferate and form colonies. Furthermore, this study also revealed the mechanism underlying the recruitment of TRIM24 by the DANCR/KAT6A complex, which is bound to acetylated lysine 23 of histone H3 (H3K23), resulting in binding to the YAP promoter and activation of YAP transcription that ultimately enhances the proliferation of colorectal cancer cells. Our results revealed a novel mechanism involving TRIM24‐YAP signaling for the regulation of colorectal cancer. We also identified TRIM24 as a potential therapeutic molecule for targeting colorectal cancer.

Primary cilia are ubiquitous mechanosensory organelles that specifically coordinate a series of cellular signal transduction pathways to control cellular physiological processes during development and in tissue homeostasis. Defects in the function or structure of primary cilia have been shown to be associated with a large range of diseases called ciliopathies. Inositol polyphosphate-5-phosphatase E (INPP5E) is an inositol polyphosphate 5-phosphatase that is localized on the ciliary membrane by anchorage via its C-terminal prenyl moiety and hydrolyzes both phosphatidylinositol-4, 5-bisphosphate (PtdIns(4,5)P2) and PtdIns(3,4,5)P3, leading to changes in the phosphoinositide metabolism, thereby resulting in a specific phosphoinositide distribution and ensuring proper localization and trafficking of proteins in primary cilia. In addition, INPP5E also works synergistically with cilia membrane-related proteins by playing key roles in the development and maintenance homeostasis of cilia. The mutation of INPP5E will cause deficiency of primary cilia signaling transduction, ciliary instability and ciliopathies. Here, we present an overview of the role of INPP5E and its coordination of signaling networks in primary cilia.

In this work, a prior-training-free and low-complexity modulation format identification (MFI) scheme, based on amplitude histogram distributions, was proposed and demonstrated, both numerically and experimentally, for autonomous digital coherent receivers. In the proposed scheme, after having performed power normalization, incoming polarization division multiplexed (PDM) signals were classified into QPSK, 8QAM, 16QAM, 32QAM and 64QAM signals, according to their ratios. Ratios were defined according to specific features of their amplitude histograms. The proposed MFI scheme used only amplitude information. As such, it was insensitive to carrier phase noise. Furthermore, the proposed scheme did not require any prior information, such as optical signal-to-noise ratio (OSNR). The performance of the proposed MFI scheme was numerically verified using 28GBaud PDM-QPSK/-8QAM/-16QAM/-32QAM/-64QAM signals. The numerical simulation results showed that the proposed scheme was able achieve a 100% correct identification rate for all five modulation formats when their OSNR values were higher than the thresholds corresponding to the 20% FEC correcting bit error rate (BER) of 2.4 × 10−2. To further explore the effectiveness of the proposed MFI scheme, proof-of-concept experiments in 28GBaud PDM-QPSK/-8QAM/-16QAM, and 21.5GBaud PDM-32QAM transmission systems were also undertaken, which showed that the proposed scheme as robust against fiber nonlinearities. To explore the scheme’s feasibility for use in practical transmission systems, the computational complexity analysis of the proposed scheme was conducted. It showed that, compared with relevant MFI schemes, the proposed MFI scheme was able to significantly reduce the computational complexity.

An effective HIV vaccine will need to stimulate immune responses against the sequence diversity presented in circulating virus strains. In this study, we evaluate breadth and depth estimates of potential T-cell epitopes (PTEs) in transmitted founder virus sequence-derived cohort-specific peptide reagents against reagents representative of consensus and global sequences. CD8 T-cells from twenty-six HIV-1+ PBMC donor samples, obtained at 1-year post estimated date of infection, were evaluated. ELISpot assays compared responses to 15mer consensus (n = 121), multivalent-global (n = 320), and 10mer multivalent cohort-specific (n = 300) PTE peptides, all mapping to the Gag antigen. Responses to 38 consensus, 71 global, and 62 cohort-specific PTEs were confirmed, with sixty percent of common global and cohort-specific PTEs corresponding to consensus sequences. Both global and cohort-specific peptides exhibited broader epitope coverage compared to commonly used consensus reagents, with mean breadth estimates of 3.2 (global), 3.4 (cohort) and 2.2 (consensus) epitopes. Global or cohort peptides each identified unique epitope responses that would not be detected if these peptide pools were used alone. A peptide set designed around specific virologic and immunogenetic characteristics of a target cohort can expand the detection of CD8 T-cell responses to epitopes in circulating viruses, providing a novel way to better define the host response to HIV-1 with implications for vaccine development.

Stereotactic body radiotherapy (SBRT) is now widely used in cancer therapy. However, the biological effects of SBRT compared with conventional radiotherapy (CRT) are not clear. The cytoskeleton plays an important role in many biological processes and cellular life activities. The effects of SBRT or CRT on the morphology and cytoskeletal structure of non-small cell lung cancer (NSCLC) cells remain unknown. Based on the biologically equivalent dose (BED) formula, we designed SBRT and CRT fractionation regimens with the same BED. The morphology was captured during radiation, and rhodamine-phalloidin immunofluorescence was used to study the cytoskeleton. A lactate dehydrogenase assay kit was used to determine the cell membrane permeability, and western blot was used to detect the cytoskeleton protein expression levels. The morphology and cytoskeleton expanded after SBRT or CRT, with an increase in cell membrane permeability and stable cytoskeleton protein levels. Besides, different dose of SBRT (10,20,30 Gy) induce similar morphology and cytoskeleton enlargement. Our findings indicate that SBRT and CRT can induce cytoskeleton reorganization and the enlargement of cell morphology (at different rates) in NSCLC. The morphology and cytoskeleton enlargement after SBRT are dose independence.

Alternaria alternata is a pathogen in a wide range of agriculture crops and causes significant economic losses. A strain of A. alternata (Y784-BC03) was isolated and identified from “Hongyang” kiwifruit and demonstrated to cause black spot infections on fruits. The genome sequence of Y784-BC03 was obtained using Nanopore MinION technology. The assembled genome is composed of 33,869,130bp (32.30Mb) comprising 10 chromosomes and 11,954 genes. A total of 2,180 virulence factors were predicted to be present in the obtained genome sequence. The virulence factors comprised genes encoding secondary metabolites, including non-host-specific toxins, cell wall-degrading enzymes, and major transcriptional regulators. The predicted gene clusters encoding genes for the biosynthesis and export of secondary metabolites in the genome of Y784-BC03 were associated with non-host-specific toxins, including cercosporin, dothistromin, and versicolorin B. Major transcriptional regulators of different mycotoxin biosynthesis pathways were identified, including the transcriptional regulators, polyketide synthase, P450 monooxygenase, and major facilitator superfamily transporters.

Background: DNA methylation affects the development, progression, and prognosis of various cancers. This study aimed to identify DNA methylated-differentially expressed genes (DEGs) and develop a methylation-driven gene model to evaluate the prognosis of ovarian cancer (OC).Methods: DNA methylation and mRNA expression profiles of OC patients were downloaded from The Cancer Genome Atlas, Genotype-Tissue Expression, and Gene Expression Omnibus databases. We used the R package MethylMix to identify DNA methylation-regulated DEGs and built a prognostic signature using LASSO Cox regression. A quantitative nomogram was then drawn based on the risk score and clinicopathological features.Results: We identified 56 methylation-related DEGs and constructed a prognostic risk signature with four genes according to the LASSO Cox regression algorithm. A higher risk score not only predicted poor prognosis, but also was an independent poor prognostic indicator, which was validated by receiver operating characteristic (ROC) curves and the validation cohort. A nomogram consisting of the risk score, age, FIGO stage, and tumor status was generated to predict 3- and 5-year overall survival (OS) in the training cohort. The joint survival analysis of DNA methylation and mRNA expression demonstrated that the two genes may serve as independent prognostic biomarkers for OS in OC.Conclusion: The established qualitative risk score model was found to be robust for evaluating individualized prognosis of OC and in guiding therapy.

Known hybrid orthogonal frequency division multiplexing-digital filter multiple access (OFDM-DFMA) PONs show promise of seamless and cost-effective convergence of optical and mobile networks for 5G and beyond. This paper reports, for the first time, a new hybrid OFDM-DFMA PON based on intensity modulation and direct detection (IMDD), obtained by modifying digital signal processing (DSP) algorithms embedded in both the OLT and ONUs. The proposed PON allows two spectrally overlapped sub-bands to occupy each individual sub-wavelength spectral region to independently transmit upstream ONU information. A model of the proposed PON is developed and its upstream transmission performances are numerically explored for different application scenarios. Compared with the previously published PON, the proposed PON doubles the number of supported ONUs and provides >1.7-fold aggregate upstream signal transmission capacity increases with 2.2-fold aggregate upstream signal transmission capacity increases and >0.7 dB upstream power budget improvements are achievable. The performance improvements vary by

Abstract Background Colorectal cancer is the fourth most common cancer globally and neoadjuvant concurrent chemoradiotherapy (nCRT) and surgery are the standard treatments for locally advanced colorectal carcinoma. This study investigated the association between dynamic changes in absolute lymphocyte counts (ALCs) and disease-free survival (DFS) in rectal cancer patients receiving nCRT and identified factors associated with these changes. Methods We retrospectively examined 34 patients with locally advanced rectal cancer who received nCRT followed by surgery and adjuvant chemotherapy. The association between ALCs and DFS and that between ALCs and downstaging were analyzed and potential clinical- and treatment-related factors related to dynamic changes in ALCs were subsequently evaluated. The patient eligibility criteria were as follows: pathologically confirmed rectal adenocarcinoma, clinical stages II–III, ≥ 18 years of age, and so on. Pre-RTL was defined as ALCs obtained before the initiation of nCRT and pre-SL was defined as ALCs obtained before surgery. We measured pre-SL to pre-RTL ratio (pre-SLR), DFS, and ALCs. Results The median ALC declined significantly during nCRT. A lower pre-SLR was associated with poorer DFS with statistical significance in Kaplan–Meier (p = 0.007), univariate regression (hazard ratio [HR] = 6.287, 95% confidence interval [CI] 1.374–28.781, p = 0.018), and multivariable regression (HR = 7.347, 95% CI 1.595–33.850, p = 0.011) analyses. Neither patient characteristics nor treatment-related factors were related to downstaging. The pelvic bone marrow (PBM) volume receiving at least 30 Gy (V30) was significantly associated with pre-SLR in the univariate (HR = 5.760, 95% CI 1.317–25.187, p = 0.020) and multivariable (HR = 5.760, 95% CI 1.317–25.187, p = 0.020) regression analyses. Limitations Our study had several limitations. The sample size was small and the study was performed in a selected population, which may limit the generalization of the findings. Conclusions Radiotherapy had a profound impact on the change in ALCs. A lower pre-SLR was significantly associated with poorer DFS in rectal cancer patients receiving nCRT. The V30 of PBM was a predictor of pre-SLR.

The long noncoding RNA (lncRNA) LINC00152, also known as CYTOR, displays aberrant expression in various cancers. However, its clinical value and functional mechanisms in breast cancer remain insufficiently understood. Our study found that LINC00152 is significantly upregulated in breast cancer, and that it acts as an indicator of poor survival prognosis. Further studies revealed that LINC00152 knockdown suppresses cell proliferation and tumorigenicity in vitro and in vivo. Mechanistic analyses demonstrated that LINC00152 directly binds to KLF5 protein and increases KLF5 stability. Moreover, LINC00152 is also a KLF5-responsive lncRNA, and KLF5 activates LINC00152 transcription by directly binding to its promoter. Our study suggests that LINC00152 promotes tumor progression by interacting with KLF5. LINC00152 may be a valuable prognostic predictor for breast cancer, and the positive feedback loop of LINC00152-KLF5 could be a therapeutic target in pharmacological strategies.

The prevalence of various comorbidities continue to rise in aging persons living with HIV-1 infection (PLWH), and our study here aimed to assess the rates and correlates of incident type 2 diabetes mellitus (T2DM) in PLWH from a retrospective, southeastern U.S. cohort. Based on electronic health records, we examined patient demographics, body mass index (BMI), HIV-1-related outcomes, hepatitis C virus co-infection, common comorbidities (e.g. shingles and asthma), usage of protease inhibitors, and usage of statins as potential correlates for T2DM occurrence. Among 3,975 PLWH with ≥12 months of follow-up between January 1999 and March 2018, the overall rate of incident T2DM was 135 per 10,000 person-years, almost 2-fold higher than the rate reported for the general U.S. population. In multivariable models (354 T2DM patients and 3,617 control subjects), sex, BMI, nadir CD4+ T-cell count, HIV-1 viral load (VL) and duration of statin use were independent correlates of incident T2DM (adjusted P 2.0 and P

Ferroptosis is a form of cell death characterized by non-apoptosis induced by small molecules in tumors. Studies have demonstrated that ferroptosis regulates the biological behaviors of tumors. Therefore, genes that control ferroptosis can be a promising candidate bioindicator in tumor therapy. Herein, functions of ferroptosis-related genes in glioma were investigated. We systematically assessed the relationship between ferroptosis-related genes expression profiles and prognosis in glioma patients based on The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) RNA sequencing datasets. Using the non-negative matrix factorization (NMF) clustering method, 84 ferroptosis-related genes in the RNA sequencing data were distinctly classified into two subgroups (named cluster 1 and cluster 2) in glioma. The least absolute shrinkage and selection operator (LASSO) was used to develop a 25 gene risk signature. The relationship between the gene risk signature and clinical features in glioma was characterized. Results show that the gene risk signature associated with clinical features can be as an independent prognostic indicator in glioma patients. Collectively, the ferroptosis-related risk signature presented in this study can potentially predict the outcome of glioma patients.

BackgroundThe long noncoding RNA actin filament associated protein 1 antisense RNA1 (AFAP1-AS1) is a critical player in various cancers. However, the clinical value and functional mechanisms of AFAP1-AS1 during the tumorigenicity of nasopharyngeal carcinoma (NPC) remain unclear. Here, we investigated the clinical application and potential molecular mechanisms of AFAP1-AS1 in NPC tumorigenesis and progression.MethodsThe expression level of AFAP1-AS1 was determined by qRT-PCR in 10 paired fresh human NPC tissues and adjacent normal tissues. RNAscope was performed on 100 paired paraffin-embedded NPC and adjacent nontumor specimens. The biological functions of AFAP1-AS1 were assessed by in vitro and in vivo functional experiments. RNA-protein pull-down assays were performed to detect and identify the AFAP1-AS1-interacting protein KAT2B. Protein-RNA immunoprecipitation (RIP) assays were conducted to examine the interaction of AFAP1-AS1 and KAT2B. Chromatin immunoprecipitation (ChIP) and luciferase analyses were utilized to identify the binding site of transcription intermediary factor 1 alpha (TIF1α) and H3K14ac on the RBM3 promoter.ResultsAFAP1-AS1 is upregulated in NPC and is a poor prognostic indicator for survival in NPC patients. AFAP1-AS1 was required for NPC proliferation in vitro and tumorigenicity in vivo. Mechanistic investigations suggested that AFAP1-AS1 binds to KAT2B and promotes acetyltransferase activation at two residues (E570/D610). KAT2B further promotes H3K14 acetylation and protein binding to the bromo domain of TIF1α. Consequently, TIF1α acts as a nuclear transcriptional coactivator of RBM3 transcription, leading to YAP mRNA stabilization and enhanced NPC tumorigenicity.ConclusionsOur findings suggest that AFAP1-AS1 functions as an oncogenic biomarker and promotes NPC tumorigenicity through enhanced KAT2B acetyltransferase activation and YAP mRNA stabilization.

In this paper, microwave photonic signal generation based on the period-one dynamic of optically injected discrete mode (DM) semiconductor lasers has been experimentally demonstrated and numerically simulated. The results show that the frequency of the generated microwave increases linearly with the frequency detuning or optical injection ratio. In addition, a single optical feedback loop is sufficient to reduce the microwave linewidth without significantly deteriorating side mode suppression. The simulation results using a model considering the nonlinear dependencies of the carrier recombination agree well with the experimental results, which indicates that the nonlinear carrier recombination effect is important in determining the nonlinear dynamics of optically injected DM lasers.

In 2014 and 2021, two nucleic-acid vaccine candidates named MAV E2 and VGX-3100 completed phase III clinical trials in Mexico and U.S., respectively, for patients with human papillomavirus (HPV)-related, high-grade squamous intraepithelial lesions (HSIL). These well-tolerated but still unlicensed vaccines encode distinct HPV antigens (E2 versus E6+E7) to elicit cell-mediated immune responses; their clinical efficacy, as measured by HSIL regression or cure, was modest when compared with placebo or surgery (conization), but both proved highly effective in clearing HPV infection, which should help further optimize strategies for enhancing vaccine immunogenicity, toward an ultimate goal of preventing malignancies in millions of patients who are living with persistent, oncogenic HPV infection but are not expected to benefit from current, prophylactic vaccines. The major roadblocks to a highly efficacious and practical product remain challenging and can be classified into five categories: (i) getting the vaccines into the right cells for efficient expression and presentation of HPV antigens (fusion proteins or epitopes); (ii) having adequate coverage of oncogenic HPV types, beyond the current focus on HPV-16 and -18; (iii) directing immune protection to various epithelial niches, especially anogenital mucosa and upper aerodigestive tract where HPV-transformed cells wreak havoc; (iv) establishing the time window and vaccination regimen, including dosage, interval and even combination therapy, for achieving maximum efficacy; and (v) validating therapeutic efficacy in patients with poor prognosis because of advanced, recurrent or non-resectable malignancies. Overall, the room for improvements is still large enough that continuing efforts for research and development will very likely extend into the next decade.

A low-signal-modulation format-enabled highly spectrally efficient new transmission technique termed subcarrier index-power modulated optical OFDM with dual superposition multiplexing (SIPM-OOFDM-DSPM) is proposed and investigated, for the first time, in intensity modulation and direct detection (IMDD) passive optical network (PON) systems incorporating directly modulated DFB lasers (DMLs). The DSPM operation passively adds two low-signal-modulation format-encoded complex numbers and assigns the sum to subcarrier index-power modulation (SIPM)-generated low- and high-power subcarriers. Detailed numerical explorations of SIPM-OOFDM-DSPM performances over additive white Gaussian noise channels are undertaken, based on which optimum key transceiver parameters are identified. In comparison with previously published techniques, over simple DML-based IMDD PON systems, SIPM-OOFDM-DSPM considerably improves the signal transmission capacity, system power budget, and performance tolerance to both chromatic dispersion and fiber nonlinearity. The work suggests that SIPM-OOFDM-DSPM is a promising signal transmission technique capable of providing cost-sensitive PON systems with improved transmission capacity, performance flexibility, and adaptability.

A novel transmission technique—namely, a DFT-spread spectrally overlapped hybrid OFDM–digital filter multiple access (DFMA) PON based on intensity modulation and direct detection (IMDD)—is here proposed by employing the discrete Fourier transform (DFT)-spread technique in each optical network unit (ONU) and the optical line terminal (OLT). Detailed numerical simulations are carried out to identify optimal ONU transceiver parameters and explore their maximum achievable upstream transmission performances on the IMDD PON systems. The results show that the DFT-spread technique in the proposed PON is effective in enhancing the upstream transmission performance to its maximum potential, whilst still maintaining all of the salient features associated with previously reported PONs. Compared with previously reported PONs excluding DFT-spread, a significant peak-to-average power ratio (PAPR) reduction of over 2 dB is achieved, leading to a 1 dB reduction in the optimal signal clipping ratio (CR). As a direct consequence of the PAPR reduction, the proposed PON has excellent tolerance to reduced digital-to-analogue converter/analogue-to-digital converter (DAC/ADC) bit resolution, and can therefore ensure the utilization of a minimum DAC/ADC resolution of only 6 bits at the forward error correction (FEC) limit (1 × 10−3). In addition, the proposed PON can improve the upstream power budget by >1.4 dB and increase the aggregate upstream signal transmission rate by up to 10% without degrading nonlinearity tolerances.

EGF receptor (EGFR) amplification and mutation are major drivers in glioma tumorigenesis but this mechanism is not well understood. Here, the authors show EGFR-upregulated H3K23ac binds TRIM24 which recruits STAT3, leading to activation of STAT3 signaling, enhancing EGFR-driven tumorigenesis.

Despite extensive research on the mechanisms of HLA-mediated immune control of HIV-1 pathogenesis, it is clear that much remains to be discovered, as exemplified by protective HLA alleles like HLA-B*81 which are associated with profound protection from CD4+ T cell decline without robust control of early plasma viremia. Here, we report on additional HLA class I (B*1401, B*57, B*5801, as well as B*81), and HLA class II (DQB1*02 and DRB1*15) alleles that display discordant virological and immunological phenotypes in a Zambian early infection cohort. HLA class I alleles of this nature were also associated with enhanced immune responses to conserved epitopes in Gag. Furthermore, these HLA class I alleles were associated with reduced levels of lipopolysaccharide (LPS) in the plasma during acute infection. Elevated LPS levels measured early in infection predicted accelerated CD4+ T cell decline, as well as immune activation and exhaustion. Taken together, these data suggest novel mechanisms for HLA-mediated immune control of HIV-1 pathogenesis that do not necessarily involve significant control of early viremia and point to microbial translocation as a direct driver of HIV-1 pathogenesis rather than simply a consequence.

In a cohort of 4,225 persons living with human immunodeficiency virus type 1 (HIV-1) infection (PLWH) enrolled at a southeastern US clinic, the overall rate of incident herpes zoster (HZ) was 101 per 10,000 person-years (PY) between January 1999 and 2017, which nearly quadruples the rate reported for the general US population. In the same cohort, the median age of HZ diagnosis was 39.5 years [interquartile range (IQR) 31.5–49.2] in African American (AA) and 39.1 years (IQR 34.9–45.2) in European American (EA) PLWH, with the highest incidence seen in PLWH who were over 50 years old (144 and 93 per 10,000 PY in AA and EA, respectively, P = 0.18), showing no bias between men (100 per 10,000 PY) and women (101 per 10,000 PY). In multivariable models that were applicable to 245 HZ cases and 3,713 controls, age, nadir CD4+ T-cell (CD4) count, plasma viral load (VL), and duration of combination antiretroviral therapy were independent correlates of incident HZ (adjusted P ≤ 0.006 for all). Regardless of other factors, viremic PLWH (VL > 50 copies/mL) was at the highest risk of HZ [adjusted odds ratio (OR) > 3.0, P

In order to develop equipment adapted to the aircraft pulse final assembly line, a vision-based aircraft transport platform system is developed. This article explores a guiding method between assembly stations which is low-cost and easy to change routes by using two-dimensional code and two complementary metal oxide semiconductor (CMOS) cameras. The two cameras installed on the front and back of the platform read the two-dimensional code containing station information to guide the platform. In the process of guiding, the theoretical position and posture of the platform at each assembly station are known, but there is a difference between the actual and theoretical values due to motion errors. To reduce the influence of the deviation on the navigation route, a localization method is proposed based on the two-dimensional images captured by the cameras. Canny edge detection is applied to the processed image to obtain the position of the two-dimensional code in the image, which can measure the angle/distance deviation of the platform. Then, the computer can locate the platform precisely by the information in the two-dimensional code and the deviation measured by the image. To verify the feasibility of the proposed method, experiments have been performed on the developed platform system. The results show that the distance and angle errors of the platform are within ±10 mm and ±0.15° respectively.