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1.
World J Diabetes ; 15(6): 1299-1316, 2024 Jun 15.
Article in English | MEDLINE | ID: mdl-38983806

ABSTRACT

BACKGROUND: Diabetic foot ulcers (DFU), as severe complications of diabetes mellitus (DM), significantly compromise patient health and carry risks of amputation and mortality. AIM: To offer new insights into the occurrence and development of DFU, focusing on the therapeutic mechanisms of X-Paste (XP) of wound healing in diabetic mice. METHODS: Employing traditional Chinese medicine ointment preparation methods, XP combines various medicinal ingredients. High-performance liquid chromatography (HPLC) identified XP's main components. Using streptozotocin (STZ)-induced diabetic, we aimed to investigate whether XP participated in the process of diabetic wound healing. RNA-sequencing analyzed gene expression differences between XP-treated and control groups. Molecular docking clarified XP's treatment mechanisms for diabetic wound healing. Human umbilical vein endothelial cells (HUVECs) were used to investigate the effects of Andrographolide (Andro) on cell viability, reactive oxygen species generation, apoptosis, proliferation, and metastasis in vitro following exposure to high glucose (HG), while NF-E2-related factor-2 (Nrf2) knockdown elucidated Andro's molecular mechanisms. RESULTS: XP notably enhanced wound healing in mice, expediting the healing process. RNA-sequencing revealed Nrf2 upregulation in DM tissues following XP treatment. HPLC identified 21 primary XP components, with Andro exhibiting strong Nrf2 binding. Andro mitigated HG-induced HUVECs proliferation, metastasis, angiogenic injury, and inflammation inhibition. Andro alleviates HG-induced HUVECs damage through Nrf2/HO-1 pathway activation, with Nrf2 knockdown reducing Andro's proliferative and endothelial protective effects. CONCLUSION: XP significantly promotes wound healing in STZ-induced diabetic models. As XP's key component, Andro activates the Nrf2/HO-1 signaling pathway, enhancing cell proliferation, tubule formation, and inflammation reduction.

2.
Eur J Med Chem ; 275: 116645, 2024 Sep 05.
Article in English | MEDLINE | ID: mdl-38959730

ABSTRACT

Hypoxia-inducible factor 2α (HIF-2α) is a critical transcription factor that regulates cellular responses under hypoxic conditions. In situations of insufficient oxygen supply or patients with Von Hippel-Lindau (VHL) mutations, HIF-2α accumulates and forms a heterodimeric complex with aryl hydrocarbon receptor nuclear translocator (ARNT, or HIF-ß). This complex further binds to coactivator p300 and interacts with hypoxia response elements (HREs) on the DNA of downstream target genes, regulating the transcription of a variety of genes (e.g. VEGFA, CCND1, CXCR4, SLC2A1, etc) involved in various processes like angiogenesis, mitochondrial metabolism, cell proliferation, and metastasis. Targeting HIF-2α holds great promise for effectively addressing solid tumors associated with aberrant oxygen-sensing pathways and hypoxia mechanisms, offering broad application prospects. In this review, we provide an overview of recent advancements (2009-2024) in HIF-2α modulators such as inhibitors, agonists, and degraders for cancer therapy. Additionally, we discuss in detail the challenges and future directions regarding HIF-2α modulators.


Subject(s)
Antineoplastic Agents , Basic Helix-Loop-Helix Transcription Factors , Drug Development , Animals , Humans , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Basic Helix-Loop-Helix Transcription Factors/agonists , Basic Helix-Loop-Helix Transcription Factors/antagonists & inhibitors , Basic Helix-Loop-Helix Transcription Factors/metabolism , Molecular Structure , Neoplasms/drug therapy , Neoplasms/metabolism , Neoplasms/pathology
3.
Nano Lett ; 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39007505

ABSTRACT

Tumor-associated macrophages (TAMs), as the most prevalent immune cells in the tumor microenvironment, play a pivotal role in promoting tumor development through various signaling pathways. Herein, we have engineered a Se@ZIF-8 core-satellite nanoassembly to reprogram TAMs, thereby enhancing immunotherapy outcomes. When the nanoassembly reaches the tumor tissue, selenium nanoparticles and Zn2+ are released in response to the acidic tumor microenvironment, resulting in a collaborative effort to promote the production of reactive oxygen species (ROS). The generated ROS, in turn, activate the nuclear factor κB (NF-κB) signaling pathway, driving the repolarization of TAMs from M2-type to M1-type, effectively eliminating cancer cells. Moreover, the nanoassembly can induce the immunogenic death of cancer cells through excess ROS to expose calreticulin and boost macrophage phagocytosis. The Se@ZIF-8 core-satellite nanoassembly provides a potential paradigm for cancer immunotherapy by reversing the immunosuppressive microenvironment.

4.
Chem Commun (Camb) ; 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38993155

ABSTRACT

A nano-immunomodulator modified with N-acetylgalactosamine (GalNAc) on calcium carbonate (CaCO3) was prepared for targeted and responsive immunotherapy. And the immunologic adjuvant (CpG ODNs) and doxorubicin (DOX) were released to synergistically improve immune response for treating orthotopic liver cancer.

5.
Chem Commun (Camb) ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38946429

ABSTRACT

By employing an aptamer as the bridge and combining catalytic hairpin assembly with the Au aggregation amplification effect, a lateral flow assay (LFA) is designed for simultaneous detection of liver cancer-associated miRNA and exosomes. The LFA can differentiate between liver cancer patients and healthy individuals with simple operation and high accuracy.

6.
Chem Commun (Camb) ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38979965

ABSTRACT

Destruction of subcellular organelles can cause dysfunction and even death of cells to elicit immune responses. In this review, the characteristics and functions of important organelles are mainly summarized. Then, the intelligent immunotherapeutic strategies and suggestions based on influencing the organelles are further highlighted. This review will provide ideas for developing novel and effective immunotherapy strategies and advance the development of cancer immunotherapy.

7.
Transplantation ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38946036

ABSTRACT

BACKGROUND: Donation after circulatory death livers are more susceptible to ischemia/reperfusion injury (IRI) because of a longer period of warm ischemia. Growing evidence now suggests that ferroptosis plays a key regulatory role in the development of IRI, so targeting ferroptosis may be an effective strategy to alleviate IRI in liver transplantation (LT). METHODS: Using donation after circulatory death LT models in rats and oxygen-glucose deprivation/reoxygenation (OGD/R) models in BRL-3A cells, we tested the effect of the Chinese medicine monomer wogonin on liver IRI and explored the specific mechanism. RESULTS: Wogonin attenuated liver IRI and increased the survival rate of rats by inhibiting lipid peroxidation and ferroptosis. Mechanistically, arachidonic acid 15-lipoxygenase-1 (ALOX15) and inducible nitric oxide synthase (iNOS) were identified as potential targets of baicalein through bioinformatics analysis combined with in vivo and in vitro experiments. This result was further confirmed by molecular docking and cellular thermal shift assays. Finally, we silenced ALOX15 and iNOS in the OGD/R cell model and found that silencing ALOX15 and iNOS could reproduce the regulatory effect of wogonin and abrogate the regulatory effect of wogonin. CONCLUSIONS: In brief, this study emphasizes that wogonin exerts a protective effect in liver IRI through the regulation of ALOX15- and iNOS-mediated ferroptosis. ALOX15 and iNOS are potential targets for intervention in IRI induced by LT, and wogonin is a drug candidate for LT patients.

8.
Autophagy ; : 1-21, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38873925

ABSTRACT

Thoracic aortic dissection (TAD) is a severe disease, characterized by numerous apoptotic vascular smooth muscle cells (VSMCs). EDIL3/Del-1 is a secreted protein involved in macrophage efferocytosis in acute inflammation. Here, we aimed to investigate whether EDIL3 promoted the internalization and degradation of apoptotic VSMCs during TAD. The levels of EDIL3 were decreased in the serum and aortic tissue from TAD mice. Global edil3 knockout (edil3-/-) mice and edil3-/- bone marrow chimeric mice exhibited a considerable exacerbation in ß-aminopropionitrile monofumarate (BAPN)-induced TAD, accompanied with increased apoptotic VSMCs accumulating in the damaged aortic tissue. Two types of phagocytes, RAW264.7 cells and bone marrow-derived macrophages (BMDMs) were used for in vitro efferocytosis assay. edil3-deficient phagocytes exhibited inefficient internalization and degradation of apoptotic VSMCs. Instead, EDIL3 promoted the internalization phase through interacting with phosphatidylserine (PtdSer) on apoptotic VSMCs and binding to the macrophage ITGAV/αv-ITGB3/ß3 integrin. In addition, EDIL3 accelerated the degradation phase through activating LC3-associated phagocytosis (LAP). Mechanically, following the engulfment, EDIL3 enhanced the activity of SMPD1/acid sphingomyelinase in the phagosome through blocking ITGAV-ITGB3 integrin, which facilitates phagosomal reactive oxygen species (ROS) production by NAPDH oxidase CYBB/NOX2. Furthermore, exogenous EDIL3 supplementation alleviated BAPN-induced TAD and promoted apoptotic cell clearance. EDIL3 may be a novel factor for the prevention and treatment of TAD.Abbreviations: BAPN: ß-aminopropionitrile monofumarate; BMDM: bone marrow-derived macrophage; C12FDG: 5-dodecanoylaminofluorescein-di-ß-D-galactopyranoside; CTRL: control; CYBB/NOX2: cytochrome b-245, beta polypeptide; DCFH-DA: 2',7'-dichlorofluorescin diacetate; EDIL3/Del-1: EGF-like repeats and discoidin I-like domains 3; EdU: 5-ethynyl-2'-deoxyuridine; EVG: elastic van Gieson; H&E: hematoxylin and eosin; IL: interleukin; LAP: LC3-associated phagocytosis; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; NAC: N-acetylcysteine; PtdSer: phosphatidylserine; rEDIL3: recombinant EDIL3; ROS: reactive oxygen species; SMPD1: sphingomyelin phosphodiesterase 1; TAD: thoracic aortic dissection; TEM: transmission electron microscopy; VSMC: vascular smooth muscle cell; WT: wild-type.

9.
Beijing Da Xue Xue Bao Yi Xue Ban ; 56(3): 431-440, 2024 Jun 18.
Article in Chinese | MEDLINE | ID: mdl-38864128

ABSTRACT

OBJECTIVE: To identify the factors associated with the care needs of the older adults aged 65-105 by age groups, and to compare these factors across different age groups. METHODS: A total of 12 244 older adults from the Chinese longitudinal healthy longevity survey (CLHLS) conducted in 2018 were included in the analyses. The participants were categorized into three age groups: young-old (aged 65-79), middle-old (aged 80-89), and oldest-old (aged 90-105). The level of disability was measured by the disability index (DI) in four dimensions, reflecting their care needs. Potential factors associated with care needs were selected based on the health ecological model (HEM), including perspectives of personal characteristics, behavioral characteristics, interpersonal network, living and working conditions, and policy environment. Multifactor analysis was performed using multinomial Logistic regression. RESULTS: Among China ' s 12 244 older adults, 43.4% had medium or high care needs. Factors for higher care needs of older adults included higher age, higher number of chronic diseases, no exercise habit, excessive sleep duration (≥9 h/d), depressive tendency, living with children or spouse, and uneducated (all P < 0.05). In addition, the young-old group who were past smokers (OR=2.009, 95% CI: 1.019-3.959), were past drinkers (OR=2.213, 95% CI: 1.141-4.291), and reported self-perceived poverty (OR=2.051, 95% CI: 1.189-3.540), had higher level of care needs. The middle-old group who were female (OR=1.373, 95% CI: 1.038-1.817), never drank alcohol (OR=1.551, 95% CI: 1.059-2.269), and were lack of medical insurance (OR=1.598, 95% CI: 1.053-2.426), and had higher level of care needs. The oldest-old group who were female (medium care needs vs. low care needs: OR=1.412, 95% CI: 1.062-1.878; high care needs vs. low care needs: OR=1.506, 95% CI: 1.137-1.993), reported self-perceived poverty (OR=2.064, 95% CI: 1.282-3.323), and were lack of medical insurance (OR=1.621, 95% CI: 1.148-2.291), and had higher level of care needs. CONCLUSION: The identical factors associated with care needs across different age groups include age, chronic disease, exercise, sleep, depression, living arrangement, and education. Smoking, alcohol consumption, and economic status are specific factors among the young-old group of the older adults, while gender and medical insurance are specific factors among the middle-old and the oldest-old group of the older adults. We recommend conducting prospective cohort studies and intervention studies among specific age groups on the above factors to provide reliable evidence for policy formulation.


Subject(s)
Disabled Persons , Humans , Aged , Female , Male , Aged, 80 and over , Disabled Persons/statistics & numerical data , China , Age Factors , Chronic Disease , Longitudinal Studies , Health Services Needs and Demand , Depression/epidemiology
10.
Pharmacol Res ; : 107250, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38878917

ABSTRACT

Dynamin-related protein 1 (DRP1) is an essential controller of mitochondrial fission whose activity is tightly controlled to ensure balanced mitochondrial dynamics and maintain internal cellular homeostasis. Growing evidence suggests that DRP1-dependent mitochondrial fission plays a role in drug-induced toxicity (DIT). Therefore, understanding the molecular mechanisms underlying DIT and the precise regulation of DRP1 function will inform the development of potential therapeutic treatments for DIT. This review comprehensively summarizes the diverse DITs and their potential mechanism associated with DRP1-dependent mitochondrial fission and discusses in vivo and in vitro model studies of toxicity protection targeting DRP1.

11.
Article in English | MEDLINE | ID: mdl-38881171

ABSTRACT

PURPOSE: This study was conducted to determine whether orthokeratology (OK) lenses with a smaller back optic zone diameter (BOZD) could exhibit stronger myopia control effects. METHOD: A meta-analysis was registered in PROSPERO (CRD42023408184). A comprehensive systematic database search was conducted, encompassing PubMed, Cochrane Library, EMBASE, MEDLINE, Web of Science, Ovid, CNKI and CBM, to identify relevant studies up to 25 March 2023. The primary inclusion criteria for this meta-analysis were studies that investigated the myopia control effect of OK lenses with a small optical treatment area (≤5 mm). To assess the quality of the retrieved articles, two researchers evaluated them using the Cochrane bias risk assessment criteria. The primary outcome measures were the changes in axial length (AL) and refractive error, using the weighted mean differences (WMD) and 95% confidence intervals (CI) to assess differences between small and traditional back optical treatment zone groups in terms of these outcomes. RESULTS: The analysis encompassed five eligible studies, with a 1 year duration. The average difference in AL between the groups was 0.12 mm (WMD = -0.12, 95% CI [-0.16, -0.09], p < 0.00001). Likewise, the average difference in refractive error between the two groups was 0.44 D (WMD = 0.44, 95% CI [0.30, 0.57], p < 0.00001). None of the studies reported severe adverse events. CONCLUSIONS: Current evidence suggests that OK lenses with smaller back optical treatment zone are more effective in preventing myopia progression than traditional lenses. However, a longer-term evaluation is warranted.

12.
Cell Death Dis ; 15(6): 422, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38886389

ABSTRACT

TGF-ß1 plays a pivotal role in the metastatic cascade of malignant neoplasms. N6-methyladenosine (m6A) stands as one of the most abundant modifications on the mRNA transcriptome. However, in the metastasis of gallbladder carcinoma (GBC), the effect of TGF-ß1 with mRNA m6A modification, especially the effect of mRNA translation efficiency associated with m6A modification, remains poorly elucidated. Here we demonstrated a negative correlation between FOXA1 and TGF-ß1 expression in GBC. Overexpression of FOXA1 inhibited TGF-ß1-induced migration and epithelial-mesenchymal transition (EMT) in GBC cells. Mechanistically, we confirmed that TGF-ß1 suppressed the translation efficiency of FOXA1 mRNA through polysome profiling analysis. Importantly, both in vivo and in vitro experiments showed that TGF-ß1 promoted m6A modification on the coding sequence (CDS) region of FOXA1 mRNA, which was responsible for the inhibition of FOXA1 mRNA translation by TGF-ß1. We demonstrated through MeRIP and RIP assays, dual-luciferase reporter assays and site-directed mutagenesis that ALKBH5 promoted FOXA1 protein expression by inhibiting m6A modification on the CDS region of FOXA1 mRNA. Moreover, TGF-ß1 inhibited the binding capacity of ALKBH5 to the FOXA1 CDS region. Lastly, our study confirmed that overexpression of FOXA1 suppressed lung metastasis and EMT in a nude mice lung metastasis model. In summary, our research findings underscore the role of TGF-ß1 in regulating TGF-ß1/FOXA1-induced GBC EMT and metastasis by inhibiting FOXA1 translation efficiency through m6A modification.


Subject(s)
Adenosine , Epithelial-Mesenchymal Transition , Gallbladder Neoplasms , Hepatocyte Nuclear Factor 3-alpha , Mice, Nude , Protein Biosynthesis , Transforming Growth Factor beta1 , Hepatocyte Nuclear Factor 3-alpha/metabolism , Hepatocyte Nuclear Factor 3-alpha/genetics , Humans , Transforming Growth Factor beta1/metabolism , Gallbladder Neoplasms/pathology , Gallbladder Neoplasms/genetics , Gallbladder Neoplasms/metabolism , Animals , Epithelial-Mesenchymal Transition/genetics , Cell Line, Tumor , Adenosine/analogs & derivatives , Adenosine/metabolism , Mice , Neoplasm Metastasis , Gene Expression Regulation, Neoplastic , Cell Movement , RNA, Messenger/metabolism , RNA, Messenger/genetics , Mice, Inbred BALB C , Male
13.
Biochim Biophys Acta Mol Basis Dis ; 1870(7): 167273, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38844111

ABSTRACT

Age-related osteoporosis is characterized by a marked decrease in the number of osteoblasts, which has been partly attributed to the senescence of cells of the osteoblastic lineage. Epigenetic studies have provided new insights into the mechanisms of current osteoporosis treatments and bone repair pathophysiology. N6-methyladenosine (m6A) is a novel transcript modification that plays a major role in cellular senescence and is essential for skeletal development and internal environmental stability. Bioinformatics analysis revealed that the expression of the m6A reading protein Igf2bp2 was significantly higher in osteoporosis patients. However, the role of Igf2bp2 in osteoblast senescence has not been elucidated. In this study, we found that Igf2bp2 levels are increased in ageing osteoblasts induced by multiple repetition and H2O2. Increasing Igf2bp2 expression promotes osteoblast senescence by increasing the stability of Slc1a5 mRNA and inhibiting cell cycle progression. Additionally, Mettl3 was identified as Slc1a5 m6A-methylated protein with increased m6A modification. The knockdown of Mettl3 in osteoblasts inhibits the reduction of senescence, whereas the overexpression of Mettl3 promotes the senescence of osteoblasts. We found that administering Cpd-564, a specific inhibitor of Mettl3, induced increased bone mass and decreased bone marrow fat accumulation in aged rats. Notably, in an OVX rat model, Igf2bp2 small interfering RNA delivery also induced an increase in bone mass and decreased fat accumulation in the bone marrow. In conclusion, our study demonstrated that the Mettl3/Igf2bp2-Slc1a5 axis plays a key role in the promotion of osteoblast senescence and age-related bone loss.

14.
Int Immunopharmacol ; 136: 112288, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-38823181

ABSTRACT

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease known for its high mortality rate and its correlation with Cytokine Storms (CS). Timely detection of CS is crucial for improving the prognosis of the disease. The objective of this investigation was to develop a model for identifying cytokine storms in the acute phase of SFTS. METHODS: A total of 245 patients diagnosed with SFTS were included in this study between January 2020 and July 2022. Among them, 184 patients were part of the training set, while 61 patients were part of the validation set. Variables identified by LASSO were subsequently included in a multivariate logistic regression analysis to determine independent predictors. Subsequently, a nomogram was then developed to predict the likelihood of CS in SFTS patients. The predictive efficacy and clinical applicability of the nomogram model were further assessed through ROC analysis and the DCA curve. RESULTS: Following LASSO analysis, a total of 11 indicators were included in multivariate logistic regression analysis. The findings indicated that PLT (OR 0.865, P < 0.001), LDH (OR 1.002, P < 0.001), Na+ (OR 1.155, P = 0.005), and ALT (OR 1.019, P < 0.001) serve as independently predictors of CS in the acute phase of SFTS. Furthermore, a nomogram named the PLNA was constructed by integrating these four factors. The PLNA model exhibited favorable predictive accuracy with an AUC of 0.958. Moreover, the PLNA model exhibited excellent clinical applicability in both the training and validation sets, as evidenced by the DCA curve. CONCLUSIONS: The PLNA model, constructed using clinical indicators, can predict the probability of cytokine storm in the acute phase of SFTS patients.


Subject(s)
Cytokine Release Syndrome , Nomograms , Severe Fever with Thrombocytopenia Syndrome , Humans , Male , Female , Middle Aged , Cytokine Release Syndrome/diagnosis , Cytokine Release Syndrome/immunology , Severe Fever with Thrombocytopenia Syndrome/diagnosis , Severe Fever with Thrombocytopenia Syndrome/immunology , Aged , Cohort Studies , Prognosis , Adult , Retrospective Studies
15.
Phytochemistry ; 225: 114192, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38901624

ABSTRACT

Meliasanines A-L, twelve previously unreported tirucallane-type triterpenoids, together with fifteen known ones, have been isolated from the stem bark of Melia toosendan. Their structures and absolute configurations were determined based on HRESIMS, and NMR, combined with calculated ECD and single-crystal X-ray diffraction analyses. Subsequently, all compounds except 10 were evaluated for their inhibitory effect on the production of nitric oxide induced by lipopolysaccharide in RAW264.7 macrophage cells. The results indicated that seven compounds (1, 13, 14, 16, 20, 22, and 23) exhibited significant NO inhibitory effects, with IC50 values ranging from 1.35 to 5.93 µM, which were more effective than the positive control indomethacin (IC50 = 13.18 µM). Moreover, the corresponding results of Western blot analysis revealed that meliasanine A (1) can significantly suppress the protein expression of inducible nitric oxide synthase and cyclooxygenase 2 in a concentration-dependent manner. The mechanism study suggested that meliasanine A exerts an anti-inflammatory effect via the nuclear factor-κB signaling pathway by suppressing phosphorylation of P65 and IκBα.


Subject(s)
Anti-Inflammatory Agents , Lipopolysaccharides , Melia , NF-kappa B , Nitric Oxide , Signal Transduction , Triterpenes , Mice , Animals , Triterpenes/pharmacology , Triterpenes/chemistry , Triterpenes/isolation & purification , NF-kappa B/metabolism , NF-kappa B/antagonists & inhibitors , RAW 264.7 Cells , Signal Transduction/drug effects , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Nitric Oxide/biosynthesis , Nitric Oxide/antagonists & inhibitors , Nitric Oxide/metabolism , Molecular Structure , Lipopolysaccharides/pharmacology , Lipopolysaccharides/antagonists & inhibitors , Melia/chemistry , Nitric Oxide Synthase Type II/metabolism , Nitric Oxide Synthase Type II/antagonists & inhibitors , Plant Bark/chemistry , Cyclooxygenase 2/metabolism , Dose-Response Relationship, Drug , Structure-Activity Relationship
16.
Pediatr Res ; 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38849481

ABSTRACT

BACKGROUND: Congenital unilateral renal agenesis (URA) is a kind of rare birth defect during fetal development with varies clinical phenotypes. The pathogenesis and the relationship between gene and phenotype are still unclear. METHODS: Ten URA fetuses were followed up after birth using postnatal renal ultrasound examination to confirm the diagnosis with nine children were URA and one was Renal Ectopy (RE). Trio- WES, CNV- seq were performed with the 10 children and their close relatives. RESULTS: There were 3 heterozygous variants of CHD7, PROKR2 and NRIP1 genes were identified in 3 children, respectively. CHD7 (c.2663T>C, p.M888T) is classified as likely pathogenic (LP), PROKR2 (c.685G>C, p.G229R) and NRIP1 (c.2705T>G, p.F902C) are classified as variants of uncertain significance (VUS). CHD7 (c.2663T>C, p.M888T) and PROKR2 (c.685G>C, p.G229R) as URA-related genes may be associated with idiopathic hypogonadotropic hypogonadism (IHH) or CHARGE syndrome (CS), and 3D-protein structure prediction revealed that the two variants may affect the stability in the CHD7 protein or PROKR2 protein, separately. The RE-related gene NRIP1 (c.2705T>G, p.F902C) may be causative of congenital anomalies of the kidneys and urinary tract (CAKUT). CONCLUSIONS: Identification of these variants can in exploring the etiology of URA or RE and improve the level of genetic counseling. IMPACTS: We performed trio-whole-exome sequencing (trio- WES) and copy number variation sequencing (CNV- seq) in 10 children, including 9 children with Unilateral Renal Agenesis and 1 with Renal Ectopy after birth. The possible pathogenic genes of URA can be screened using prenatal and postnatal diagnosis of URA fetuses and gene detection after birth. Future studies evaluating this association may lead to a better understanding of URA and elucidate exploring the etiology of URA or RE and improve the level of genetic counseling.

17.
Opt Express ; 32(9): 15493-15506, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38859198

ABSTRACT

Orthogonal frequency-division multiplexing (OFDM) waveform is highly preferred as a dual-function candidate for integrated sensing and communication (ISAC) systems. However, the sensitivity to both carrier frequency offset (CFO) and phase noise greatly impedes its applications in millimeter-wave ISAC systems. Here, we propose and experimentally demonstrate a photonic millimeter-wave ISAC system employing the virtual-carrier-aided self-coherent OFDM technique, wherein a digitally-generated local oscillator is transmitted along with the OFDM signal. Then, a compact CFO-immune and phase noise-immune envelope detection method is implemented for down-converting millimeter-wave communication and radar echo signals. In experiments, a V-band ISAC system is successfully implemented with a simplified remote radio unit, using the remote photonic millimeter-wave heterodyning up-conversion for downlink and the envelope detection-assisted down-conversion for uplink (or radar echoes). In the converged transmission link with a 5-km fiber link and 2-m space link, the Kramers-Kronig (KK) receiver supports a communication data rate up to 16-Gbit/s by mitigating signal-signal beat interference (SSBI). More significantly, the SSBI leads to negligible effects on the sensing performance when classic matched filtering is adopted for target identification. Consequently, a 4.8-cm range resolution and a 4-mm range accuracy are obtained for the radar sensing function.

18.
Opt Express ; 32(8): 13342-13356, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38859307

ABSTRACT

Phase shifting profilometry is an important technique for reconstructing the three-dimensional (3D) geometry of objects with purely diffuse surfaces. However, it is challenging to measure the transparent objects due to the pattern aliasing caused by light refraction and multiple reflections inside the object. In this work, we analyze the aliasing fringe pattern formation for transparent objects and then, propose to learn the front surface light intensity distribution based on the formation principle by using the diffusion models for generating the non-aliased fringe patterns reflected from the front surface only. With the generated fringe patterns, the 3D shape of the transparent objects can be reconstructed via the conventional structured light. We show the feasibility and performance of the proposed method on the data of purely transparent objects that are not seen in the training stage. Moreover, we found it could be generalized to other cases with local-transparent and translucent objects, showing the potential capability of the diffusion based learnable framework in tackling the problems of transparent object reconstruction.

19.
Opt Express ; 32(8): 13500-13507, 2024 Apr 08.
Article in English | MEDLINE | ID: mdl-38859318

ABSTRACT

We experimentally demonstrate a total net-rate of 27.88 Tb/s for C-band wavelength-division multiplexing (WDM) transmission over an ultralong span-length of 150 km. It is the largest net capacity × span-length product of 4182 Tb/s·km for C-band, single-core, standard single-mode optical fiber transmission over a length of more than 3,000 km. A total of 99 channels, spaced at 50 GHz intervals, are employed for transmitting 32 GBaud probabilistically constellation-shaped (PCS) 64QAM signals with an information entropy of 5.5. High gain amplifiers can achieve wavelength-division multiplexing (WDM) transmission with a bandwidth of 6.25 THz, at a noise figure below 4.3 dB, without the assistance of distributed Raman amplification.

20.
Opt Express ; 32(12): 20471-20482, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38859428

ABSTRACT

In this paper, we propose a novel and simple multi-channel broadband optical chaos generation scheme based on phase modulation and chirped fiber Bragg grating (CFBG). Firstly, phase modulation is introduced to generate more new frequency components to broaden the spectrum of the phase chaos. Meanwhile, the accumulated dispersion from CFBG distorts the intensity chaos, converts phase chaos to intensity chaos, and weakens the laser relaxation oscillation. This process would lead to energy redistribution in the power spectrum, effectively increasing the chaotic bandwidth. Then, the wavelength detuning between CFBG and the semiconductor laser is introduced to enhance the chaotic bandwidth further. The experiment results show that the 10 dB bandwidths of the five channels are up to 31.0 GHz, 34.3 GHz, 36.3 GHz, 40 GHz, and 40 GHz, respectively. Note that the maximum bandwidth of the PD in our experiment is limited to 40 GHz. In addition, the multi-channel chaotic signals obtained from the experiment system are used to generate multi-channel physical random numbers. After the post-processing operations, the total rate of five parallel high-speed physical random number generation channels is 4.64 Tbit/s (160 GSa/s × 5bit × 1 channel + 160 GSa/s × 6bit × 4 channels). As far as we know, this is the highest record of using external cavity feedback semiconductor lasers to generate random numbers, which has great potential to meet the security requirements of next-generation Tbit/s optical communication systems.

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