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1.
Growth Factors ; 42(2): 62-73, 2024 05.
Article in English | MEDLINE | ID: mdl-38954805

ABSTRACT

BACKGROUND AND OBJECTIVE: Dysregulated expression of Forkhead Box N2 (FOXN2) has been detected in various cancer types. However, the underlying mechanisms by which FOXN2 contributes to the onset and progression of gastric cancer (GC) remain largely unexplored. This study aimed to elucidate the potential role of FOXN2 within GC, its downstream molecular mechanisms, and its feasibility as a novel serum biomarker for GC. METHODS: Tissue samples from GC patients and corresponding non-cancerous tissues were collected. Peripheral blood samples were obtained from GC patients and healthy controls. The expression of FOXN2 was determined using quantitative real-time PCR, western blotting, and immunohistochemistry. The expression of FOXN2 in GC cells was modulated by transfection with small interfering RNA (siRNA) or the pcDNA 3.1 expression vector. Cell proliferation was assessed using the Cell Counting Kit-8 and 5-ethynyl-2'-deoxyuridine incorporation assays. The migratory and invasive capacities of cells were evaluated by Transwell assays, apoptosis rates were measured by flow cytometry, and the expression of proliferative, apoptotic, and epithelial-mesenchymal transition (EMT) markers were assessed by western blot analysis. RESULTS: FOXN2 was found to be overexpressed in the serum, tissues, and cells of GC, correlating with distant metastasis and TNM staging. FOXN2 demonstrated diagnostic value in differentiating GC patients from healthy individuals, with higher levels of FOXN2 being indicative of poorer survival rates. Silencing FOXN2 in vitro inhibited the proliferation, invasion, migration, and EMT of GC cells, while promoting apoptosis. FOXN2 was shown to regulate the transforming growth factor-beta (TGFß) receptor signaling pathway in GC cells via its interaction with Partitioning Defective 6 Homolog Alpha (PARD6A). CONCLUSION: In summary, our data suggest that FOXN2 acts as an oncogenic factor in GC, modulating the TGFß pathway by binding to PARD6A, thereby influencing gastric carcinogenesis. This study underscores the functional significance of FOXN2 as a potential serum biomarker and therapeutic target in GC.


Subject(s)
Biomarkers, Tumor , Epithelial-Mesenchymal Transition , Forkhead Transcription Factors , Signal Transduction , Stomach Neoplasms , Transforming Growth Factor beta , Aged , Female , Humans , Male , Middle Aged , Apoptosis , Biomarkers, Tumor/blood , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Cell Line, Tumor , Cell Movement , Cell Proliferation , Forkhead Transcription Factors/metabolism , Forkhead Transcription Factors/genetics , Gene Expression Regulation, Neoplastic , Stomach Neoplasms/blood , Stomach Neoplasms/pathology , Stomach Neoplasms/metabolism , Stomach Neoplasms/genetics , Transforming Growth Factor beta/metabolism , Transforming Growth Factor beta/blood
2.
BMC Cancer ; 24(1): 257, 2024 Feb 23.
Article in English | MEDLINE | ID: mdl-38395838

ABSTRACT

BACKGROUND: CCRT is presently the standard treatment for LA-NSCLC. RP is one of the main obstacles to the completion of thoracic radiation therapy, resulting in limited survival benefits in NSCLC patients. This research aims to explore the role of Endostar in the occurrence of grade≥2 RP and clinical curative effect in LA-NSCLC patients. METHODS: This study retrospectively analyzed 122 patients with stage III NSCLC who received CCRT from December 2008 to December 2017, or Endostar intravenous drip concurrently with chemoradiotherapy (Endostar + CCRT group). Standard toxicity of the pneumonitis endpoint was also collected by CTCAE V5.0. We further summarized other available studies on the role of Endostar in the prognosis of NSCLC patients and the incidence of RP. RESULTS: There were 76 cases in the CCRT group and 46 cases in the CCRT+ Endostar group. In the CCRT+ Endostar group, the occurrence of grade ≥2 RP in patients with V20Gy ≥25% was significantly higher than that in patients with V20Gy < 25% (p = 0.001). In the cohorts with V20Gy < 25%, 0 cases of 29 patients treated with Endostar developed grade ≥2 RP was lower than in the CCRT group (p = 0.026). The re-analysis of data from other available studies indicated that Endostar plus CCRT could be more efficient and safely in the occurrence of grade≥2 RP with LA-NSCLC. CONCLUSIONS: When receiving CCRT for LA-NSCLC patients, simultaneous combination of Endostar is recommended to enhance clinical benefit and reduce pulmonary toxicity.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Endostatins , Lung Neoplasms , Pneumonia , Radiation Pneumonitis , Recombinant Proteins , Humans , Carcinoma, Non-Small-Cell Lung/radiotherapy , Carcinoma, Non-Small-Cell Lung/drug therapy , Lung Neoplasms/radiotherapy , Lung Neoplasms/drug therapy , Retrospective Studies , Chemoradiotherapy/adverse effects , Chemoradiotherapy/methods , Pneumonia/chemically induced , Pneumonia/epidemiology , Radiation Pneumonitis/epidemiology , Radiation Pneumonitis/etiology
3.
BMC Infect Dis ; 24(1): 868, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39192216

ABSTRACT

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a special clinical presentation mostly associated with autoimmune disorders. Here we report a rare case of PAP secondary to infection of Bacillus megaterium. CASE PRESENTATION: A 58-year-old woman presented with intermittent cough and dyspnea for half a year. Chest CT scan showed "crazy paving" pattern. B. megaterium was identified by percutaneous CT-guided needle biopsy. She continuously received antimicrobial treatment since the diagnosis and follow-up examination suggested great improvement. CONCLUSIONS: To our knowledge, this is the first case of B. megaterium infection presented with PAP pattern in healthy individuals. Attention should be paid on the secondary causes including rare pathogen infection when patients presented with PAP syndrome.


Subject(s)
Bacillus megaterium , Pulmonary Alveolar Proteinosis , Tomography, X-Ray Computed , Humans , Female , Middle Aged , Pulmonary Alveolar Proteinosis/diagnosis , Pulmonary Alveolar Proteinosis/diagnostic imaging , Pulmonary Alveolar Proteinosis/pathology , Bacillus megaterium/isolation & purification , Gram-Positive Bacterial Infections/diagnosis , Gram-Positive Bacterial Infections/microbiology , Gram-Positive Bacterial Infections/drug therapy , Anti-Bacterial Agents/therapeutic use
4.
Phys Chem Chem Phys ; 26(2): 1396-1405, 2024 Jan 03.
Article in English | MEDLINE | ID: mdl-38112118

ABSTRACT

Intrinsic magnetic semiconductors hold great promise in the fields of fundamental magnetization and spintronics. One such semiconductor is Cr2Si2Ti6 (CST), a quasi two-dimensional (2D) magnetic semiconductor with potential applications in future magnetic devices. However, the origin of ferromagnetism in CST remains a mystery. To investigate this, ac/dc susceptibility and electronic spin resonance (ESR) measurements were conducted. Based on ac susceptibility scaling, the critical temperature (TC) for the ferromagnetic (FM) to paramagnetic (PM) phase transition was found to be ∼32.5 K, with a critical exponent of δ = 6.7 from the critical isotherm, ß + γ = 1.72 from the temperature dependence of the crossover line, and γ = 1.43 from the temperature dependence of susceptibility along the same line. All critical exponents were found to be consistent with the dc magnetization scaling method. However, above and below TC, the origin of magnetism cannot be explained by a single theory. To explore the origin of abnormal magnetic critical behavior, ESR measurements were performed. Below T* ∼ 130 K, the ESR measurements revealed that the resonance field width (ΔH) tends to increase and decrease for the applied magnetic field H parallel and perpendicular to the c axis, respectively, indicating the onset of magnetic interaction even in the PM state. Meanwhile, the deviation from Curie-Weiss behavior below T* also confirmed the occurrence of magnetic correlation above the TC in CST. These observations suggest that the competition and cooperation among the direct and indirect interactions, the structural distortion and the van der Waals interaction at high temperature should be considered to investigate the origin of anomalous magnetism in CST. The present results provide valuable insights into the nature of ferromagnetism in 2D magnetic semiconductors.

5.
Int J Med Sci ; 21(8): 1399-1407, 2024.
Article in English | MEDLINE | ID: mdl-38903924

ABSTRACT

Background: Hemoptysis is prevalent in acute pulmonary embolism (PE) and significantly influences clinical decision-making. Despite the increasing reports of PE in patients with autoimmune diseases, limited studies have investigated the association between acute PE with hemoptysis and autoimmune disease. Methods: The retrospective study aimed to investigate patients with autoimmune disease who presented with acute PE and hemoptysis at Peking Union Medical College Hospital (PUMCH) between January 2012 and October 2020. A comparative analysis was conducted between patients with and without hemoptysis, as well as between those with autoimmune diseases and those without. Clinical characteristics, PE severity stratification, the amount of hemoptysis, initial anticoagulation management, and prognosis were analyzed descriptively. Results: The study analyzed 896 patients diagnosed with acute PE, of whom 105 (11.7%) presented with hemoptysis. Hemoptysis in PE patients was frequently associated with autoimmune diseases (39%, 41/105), a younger patient population (42.0 vs. 52.7 years old, P =0.002), and a higher prevalence of low-risk PE (53.7 vs. 28.1, P=0.008) compared with non-autoimmune disease patients. Multivariate logistic analysis showed PE patients with primary or metastatic lung cancer, chest pain, age < 48 years old, chronic heart failure, autoimmune disease, pulmonary infection and male were more likely to develop hemoptysis. Patients were grouped based on maximum daily sputum blood volume and PE risk stratification. Most patients (73.2%) received therapeutic-dose anticoagulation. Poor prognosis is observed in patients with moderate to massive hemoptysis and intermediate-high-risk or high-risk PE. Conclusions: Hemoptysis is a relatively common manifestation in patients with PE, and its presence during the diagnostic workup of acute PE necessitates careful analysis of underlying comorbidities. In cases where hemoptysis occurs in individuals with autoimmune diseases in the context of PE, proactive management strategies targeting the primary disease are crucial. Therapeutic decisions should consider both PE severity stratification and the volume of hemoptysis.


Subject(s)
Autoimmune Diseases , Hemoptysis , Pulmonary Embolism , Humans , Hemoptysis/etiology , Hemoptysis/diagnosis , Male , Autoimmune Diseases/complications , Pulmonary Embolism/complications , Pulmonary Embolism/diagnosis , Middle Aged , Female , Retrospective Studies , Adult , Prognosis , Aged , Acute Disease , Risk Factors , Anticoagulants/therapeutic use , China/epidemiology
6.
Gerontology ; : 1-10, 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39137736

ABSTRACT

INTRODUCTION: Renal interstitial fibrosis is an important pathological basis for kidney ageing and the progression of ageing nephropathy. In the present research, we established an aged mouse model of faecal microbiota transplantation (FMT), identified the rejuvenation features of the kidney in aged male mice, and preliminarily analysed the possible mechanism by which the rejuvenation of the intestinal microbiota reduces renal interstitial fibrosis and delays senescence in aged male mice. METHODS: We established an aged male mice model that was treated with FMT (FMT-Old) and a normal aged male mice control group (Old). Differentially expressed cytokines were identified using a cytokine array, and changes in protein expression related to signal transduction pathways in renal tissues were detected using a signalling pathway array. Senescence-associated ß-galactosidase and Masson staining were performed to observe the degrees of renal senescence and tubule interstitial fibrosis. Immunohistochemistry was utilized to detect changes in the expression of the ageing markers p53 and p21 and the inflammation-related protein nuclear factor (NF-κB) subunit (RelA/p65). RESULTS: The pathological features of renal senescence in the FMT-Old group were significantly alleviated, and the levels of the ageing indicators p53 and p21 were decreased (p < 0.05). Ingenuity Pathway Analysis revealed that six differentially expressed cytokines, MIP-3ß (CCL-19), E-selectin (SELE), Fas ligand (Fas L/FASLG), CXCL-11 (I-TAC), CXCL-1 and CCL-3 (MIP-1α) were related to a common upstream regulatory protein, RelA/p65, and the expression of this protein was significantly different between groups according to the signalling pathway array. CONCLUSION: Our findings suggest that the intestinal microbiota regulates the renal microenvironment by reducing immune inflammatory responses through the inhibition of the NF-κB signalling pathway, thereby delaying renal senescence in aged male mice.

7.
Proc Natl Acad Sci U S A ; 118(8)2021 02 23.
Article in English | MEDLINE | ID: mdl-33558418

ABSTRACT

The expansion of anatomically modern humans (AMHs) from Africa around 65,000 to 45,000 y ago (ca. 65 to 45 ka) led to the establishment of present-day non-African populations. Some paleoanthropologists have argued that fossil discoveries from Huanglong, Zhiren, Luna, and Fuyan caves in southern China indicate one or more prior dispersals, perhaps as early as ca. 120 ka. We investigated the age of the human remains from three of these localities and two additional early AMH sites (Yangjiapo and Sanyou caves, Hubei) by combining ancient DNA (aDNA) analysis with a multimethod geological dating strategy. Although U-Th dating of capping flowstones suggested they lie within the range ca. 168 to 70 ka, analyses of aDNA and direct AMS 14C dating on human teeth from Fuyan and Yangjiapo caves showed they derive from the Holocene. OSL dating of sediments and AMS 14C analysis of mammal teeth and charcoal also demonstrated major discrepancies from the flowstone ages; the difference between them being an order of magnitude or more at most of these localities. Our work highlights the surprisingly complex depositional history recorded at these subtropical caves which involved one or more episodes of erosion and redeposition or intrusion as recently as the late Holocene. In light of our findings, the first appearance datum for AMHs in southern China should probably lie within the timeframe set by molecular data of ca. 50 to 45 ka.


Subject(s)
Archaeology , Caves/chemistry , DNA, Ancient/analysis , Fossils , Geologic Sediments/analysis , Human Migration/history , Radiometric Dating/methods , China , History, Ancient , Humans
8.
Ren Fail ; 46(2): 2387933, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39177234

ABSTRACT

We aimed to test whether red blood cell distribution width (RDW) to monocyte percentage ratio (RMR) was associated with the acute-phase prognosis of coronavirus disease 2019 (COVID-19) in chronic kidney disease (CKD) patients. Prospective enrollment and 90-day follow-up of CKD patients with COVID-19 were conducted from December 1, 2022 to January 31, 2023. Demographics, clinical data, and laboratory and radiographic findings were collected, and multiple logistic regression, subgroup analysis, and receiver operating characteristic (ROC) curve analysis were performed. A total of 218 patients were enrolled, with a mean age of 59 years and 69.7% being male. The 90-day mortality rate was 24.8%. The lnRMR level was 5.18 (4.91-5.43) and emerged as an independent risk factor (OR: 3.01, 95% CI: 1.72-5.85). The lnRMR-mortality association was consistent across sex, age, CKD stage, COVID-19 vaccination, and comorbidity subgroups. The area under the ROC curve of lnRMR was 0.737 (95% CI: 0.655-0.819). Our findings indicate that lnRMR is a simple and practical predictor for identifying high-risk CKD patients during the acute phase of COVID-19.


Subject(s)
COVID-19 , Erythrocyte Indices , Monocytes , Renal Insufficiency, Chronic , Humans , COVID-19/mortality , COVID-19/blood , COVID-19/complications , Male , Female , Middle Aged , Prospective Studies , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/mortality , Renal Insufficiency, Chronic/complications , Aged , Prognosis , SARS-CoV-2 , ROC Curve , Risk Factors , Adult
9.
Angew Chem Int Ed Engl ; 63(1): e202315238, 2024 Jan 02.
Article in English | MEDLINE | ID: mdl-37953400

ABSTRACT

Ambient electrochemical ammonia (NH3 ) synthesis is one promising alternative to the energy-intensive Haber-Bosch route. However, the industrial requirement for the electrochemical NH3 production with amperes current densities or gram-level NH3 yield remains a grand challenge. Herein, we report the high-rate NH3 production via NO2 - reduction using the Cu activated Co electrode in a bipolar membrane (BPM) assemble electrolyser, wherein BPM maintains the ion balance and the liquid level of electrolyte. Benefited from the abundant Co sites and optimal structure, the target modified Co foam electrode delivers a current density of 2.64 A cm-2 with the Faradaic efficiency of 96.45 % and the high NH3 yield rate of 279.44 mg h-1 cm-2 in H-type cell using alkaline electrolyte. Combined with in situ experiments and theoretical calculations, we found that Cu optimizes the adsorption behavior of NO2 - and facilitates the hydrogenation steps on Co sites toward a rapid NO2 - reduction process. Importantly, this activated Co electrode affords a large NH3 production up to 4.11 g h-1 in a homemade reactor, highlighting its large-scale practical feasibility.

10.
J Transl Med ; 21(1): 323, 2023 05 13.
Article in English | MEDLINE | ID: mdl-37179292

ABSTRACT

BACKGROUND: Pericyte-myofibroblast transition (PMT) has been confirmed to contribute to renal fibrosis in several kidney diseases, and transforming growth factor-ß1 (TGF-ß1) is a well-known cytokine that drives PMT. However, the underlying mechanism has not been fully established, and little is known about the associated metabolic changes. METHODS: Bioinformatics analysis was used to identify transcriptomic changes during PMT. PDGFRß + pericytes were isolated using MACS, and an in vitro model of PMT was induced by 5 ng/ml TGF-ß1. Metabolites were analyzed by ultraperformance liquid chromatography (UPLC) and tandem mass spectrometry (MS). 2-Deoxyglucose (2-DG) was used to inhibit glycolysis via its actions on hexokinase (HK). The hexokinase II (HKII) plasmid was transfected into pericytes for HKII overexpression. LY294002 or rapamycin was used to inhibit the PI3K-Akt-mTOR pathway for mechanistic exploration. RESULTS: An increase in carbon metabolism during PMT was detected through bioinformatics and metabolomics analysis. We first detected increased levels of glycolysis and HKII expression in pericytes after stimulation with TGF-ß1 for 48 h, accompanied by increased expression of α-SMA, vimentin and desmin. Transdifferentiation was blunted when pericytes were pretreated with 2-DG, an inhibitor of glycolysis. The phosphorylation levels of PI3K, Akt and mTOR were elevated during PMT, and after inhibition of the PI3K-Akt-mTOR pathway with LY294002 or rapamycin, glycolysis in the TGF-ß1-treated pericytes was decreased. Moreover, PMT and HKII transcription and activity were blunted, but the plasmid-mediated overexpression of HKII rescued PMT inhibition. CONCLUSIONS: The expression and activity of HKII as well as the level of glycolysis were increased during PMT. Moreover, the PI3K-Akt-mTOR pathway regulates PMT by increasing glycolysis through HKII regulation.


Subject(s)
Signal Transduction , Transforming Growth Factor beta1 , Transforming Growth Factor beta1/pharmacology , Transforming Growth Factor beta1/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Hexokinase/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Pericytes/metabolism , Myofibroblasts/metabolism , TOR Serine-Threonine Kinases/metabolism , Sirolimus , Glycolysis
11.
Opt Express ; 31(12): 19048-19064, 2023 Jun 05.
Article in English | MEDLINE | ID: mdl-37381330

ABSTRACT

Confocal microscopy is one of the most widely used tools for high-resolution cellular, tissue imaging and industrial inspection. Micrograph reconstruction based on deep learning has become an effective tool for modern microscopy imaging techniques. While most deep learning methods neglect the imaging process mechanism, which requires a lot of work to solve the multi-scale image pairs aliasing problem. We show that these limitations can be mitigated via an image degradation model based on Richards-Wolf vectorial diffraction integral and confocal imaging theory. The low-resolution images required for network training are generated by model degradation from their high-resolution counterparts, thereby eliminating the need for accurate image alignment. The image degradation model ensures the generalization and fidelity of the confocal images. By combining the residual neural network with a lightweight feature attention module with degradation model of confocal microscopy ensures high fidelity and generalization. Experiments on different measured data report that compared with the two deconvolution algorithms, non-negative least squares algorithm and Richardson-Lucy algorithm, the structural similarity index between the network output image and the real image reaches a high level above 0.82, and the peak signal-to-noise ratio can be improved by more than 0.6 dB. It also shows good applicability in different deep learning networks.

12.
Opt Express ; 31(19): 30319-30331, 2023 Sep 11.
Article in English | MEDLINE | ID: mdl-37710576

ABSTRACT

In recent years, the manipulation of structured optical beam has become an attractive and promising area. The Gaussian beam is the most common beam as the output beam of the laser, and the Airy beam is recently proposed with fascinating properties and applications. In this paper, for the first time to our knowledge, the polarization is used as a tool to design a new kind of Airy-Gaussian vector beam by connecting the Gaussian and Airy functions, which opens a new avenue in designing new beams based on the existed beams. We realize the Airy-Gaussian vector beam with space-variant polarization distribution in theory and experiment, and find that the vector beam can autofocus twice during propagation. The optical chains with flexible intensity peaks are achieved with the Airy-Gaussian vector beam, which can be applied in trapping and delivering particles including biological cells and Rydberg atoms. Such optical chains can significantly improve the trapping efficiency, reduce the heat accumulation, and sweep away the impurity particles.

13.
J Hum Evol ; 178: 103344, 2023 05.
Article in English | MEDLINE | ID: mdl-36947893

ABSTRACT

Chuandong Cave is an important Late Paleolithic site because it documents the early appearance of bone tools in southern China. We used the single-aliquot regenerative-dose protocol for optically stimulated luminescence dating to improve the precision of the chronology for the Chuandong Cave sedimentary sequence. The age of each layer was determined using a Bayesian modeling approach which combined optically stimulated luminescence ages with published AMS 14C dates. The results showed that Layer 10 began accumulating since 56 ± 14 ka and provides the upper age limit for all artifacts from the sequence. Bone awl tools from Layer 8, the earliest grinding bone tools in this site, were recovered within sediments between 40 ± 7 ka and 30 ± 4 ka. Layer 8 also indicates the appearance of modern humans in the Chuandong Cave sequence. Layers 4-2, ranging from 15 ± 3 ka until 11 ± 1 ka and including the Younger Dryas period, contain a few bone awls and an eyed bone needle. The shift from bone awls to eyed bone needles in the Chuandong Cave sequence indicates that modern humans adapted to the changing climate of southern China. We conclude that modern human behavior in bone tools appeared in southern China as early as 40 ± 7 ka, became more sophisticated during the Last Glacial Maximum, and spread more widely across southern China during the Younger Dryas.


Subject(s)
Hominidae , Animals , Humans , Bayes Theorem , Caves , Bone and Bones , China , Radiometric Dating , Archaeology , Fossils
14.
Semin Dial ; 36(3): 214-220, 2023.
Article in English | MEDLINE | ID: mdl-36450343

ABSTRACT

INTRODUCTION: Along with the peritoneal dialysis (PD)-favored policy in China and the implementation of more comprehensive PD management, PD has evolved in Chinese mainland over the last decade. Despite the existence of national registries and several provincial epidemiological descriptive studies, there was almost no national research on the changing trajectory in PD population. A comparison study, based on two national surveys that were 10 years apart, was conducted to reveal the evolvement of PD care in Chinese mainland. METHODS: Two national surveys have been done respectively in 2010 and 2020 to capture the epidemiological status, application of different modalities, management of perioperative infection, and long-term complications among PD patients. RESULTS: In the study with 730 participating hospitals (n = 14,912 PD patients) in 2010 and 746 hospitals (n = 101,537) in 2020, prevalent PD patients have increased in the past 10 years with increased numbers of PD patients in both secondary (average 5 ± 16 vs. 43 ± 41, p < 0.01) and tertiary hospitals (32 ± 53 vs. 153 ± 215, p < 0.01). Automated PD has been accessible in 0.4% of all hospitals, only in tertiary centers in 2010 and its application increased to 51% in 2020. PD centers have become more engaged in PD catheter placement, treated properly for the PD-related infection, and carried out the follow-up in compliance with the national protocols. CONCLUSIONS: Our study indicates that over the past decade, the prevalent PD population has quickly expanded with increased APD availability in Chinese mainland. The management of PD patients has become better conforming to the guidelines and long-term follow-up of patients have remained stable. Further studies are warranted to evaluate whether the rapidly changing paradigm of PD could translate into the socio-economic benefits in the society.


Subject(s)
Peritoneal Dialysis , Peritonitis , Humans , East Asian People , Renal Dialysis , Peritoneal Dialysis/methods , Surveys and Questionnaires , Catheterization
15.
Acta Pharmacol Sin ; 44(9): 1815-1825, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37055531

ABSTRACT

Damage to peritubular capillaries is a key process that contributes to acute kidney injury (AKI) progression. Vascular endothelial growth factor A (VEGFA) plays a critical role in maintaining the renal microvasculature. However, the physiological role of VEGFA in various AKI durations remains unclear. A severe unilateral ischemia‒reperfusion injury model was established to provide an overview of VEGFA expression and the peritubular microvascular density from acute to chronic injury in mouse kidneys. Therapeutic strategies involving early VEGFA supplementation protecting against acute injury and late anti-VEGFA treatment for fibrosis alleviation were analyzed. A proteomic analysis was conducted to determine the potential mechanism of renal fibrosis alleviation by anti-VEGFA. The results showed that two peaks of extraglomerular VEGFA expression were observed during AKI progression: one occurred at the early phase of AKI, and the other occurred during the transition to chronic kidney disease (CKD). Capillary rarefaction progressed despite the high expression of VEGFA at the CKD stage, and VEGFA was associated with interstitial fibrosis. Early VEGFA supplementation protected against renal injury by preserving microvessel structures and counteracting secondary tubular hypoxic insults, whereas late anti-VEGFA treatment attenuated renal fibrosis progression. The proteomic analysis highlighted an array of biological processes related to fibrosis alleviation by anti-VEGFA, which included regulation of supramolecular fiber organization, cell-matrix adhesion, fibroblast migration, and vasculogenesis. These findings establish the landscape of VEGFA expression and its dual roles during AKI progression, which provides the possibility for the orderly regulation of VEGFA to alleviate early acute injury and late fibrosis.


Subject(s)
Acute Kidney Injury , Renal Insufficiency, Chronic , Mice , Animals , Vascular Endothelial Growth Factor A , Proteomics , Acute Kidney Injury/drug therapy , Acute Kidney Injury/metabolism , Fibrosis
16.
Gerontology ; 69(5): 628-640, 2023.
Article in English | MEDLINE | ID: mdl-36720215

ABSTRACT

INTRODUCTION: Youthful blood environment was shown to decelerate the aging process of the kidney and to attenuate senile renal fibrosis in a young-old parabiotic animal model; in addition, we identified a stem cell factor (SCF) that is closely linked with the process. This research was to investigate the effect of youthful blood environment on senile renal interstitial fibrosis and the role of SCF. METHODS: We bred SCF receptor c-Kit gene loss-of-function Wps/Wps mice and established a combination mice model that was subjected to unilateral ureteral obstructive (UUO) and parabiotic surgeries. Parabiotic mice were divided into isochronic parabiotic (young-young [Y-IP] and old-old [O-IP]) and heterochronic parabiotic (young-old [HP]) groups. UUO surgery was performed in one of the parabiotic pairs in the IP group (Y-IPuuo and O-IPuuo) and in the elderly mice in the HP group (O-HPuuo). In order to study the role of SCF/c-kit on renal interstitial fibrosis, UUO surgery was performed in wildtype (WT) and Wps/Wps mice. RESULTS: Fourteen days after UUO surgery, the kidney interstitial fibrosis area, kidney function, and the expressions of SCF/c-Kit, pNF-κB, and fibrosis-related proteins in the O-HPuuo group were significantly lower than those in the Ouuo and O-IPuuo groups. Compared with WT UUO mice, the expressions of pNF-κB and fibrosis-related proteins and the kidney function were all significantly decreased in Wps/Wps UUO mice. CONCLUSION: Youthful blood environment downregulated the expressions of SCF/c-Kit in elderly UUO mice and ameliorated UUO-induced kidney fibrosis and function loss.


Subject(s)
Kidney Diseases , Ureteral Obstruction , Mice , Animals , Stem Cell Factor/genetics , Stem Cell Factor/metabolism , Stem Cell Factor/pharmacology , Ureteral Obstruction/complications , Ureteral Obstruction/metabolism , Ureteral Obstruction/pathology , Kidney Diseases/genetics , Kidney Diseases/metabolism , Kidney/pathology , Fibrosis , Disease Models, Animal
17.
Int J Mol Sci ; 24(14)2023 Jul 13.
Article in English | MEDLINE | ID: mdl-37511165

ABSTRACT

The affinity of peptides is a crucial factor in studying peptide-protein interactions. Despite the development of various techniques to evaluate peptide-receptor affinity, the results may not always reflect the actual affinity of the peptides accurately. The current study provides a free tool to assess the actual peptide affinity based on virtual docking data. This study employed a dataset that combined actual peptide affinity information (active and inactive) and virtual peptide-receptor docking data, and different machine learning algorithms were utilized. Compared with the other algorithms, the random forest (RF) algorithm showed the best performance and was used in building three RF models using different numbers of significant features (four, three, and two). Further analysis revealed that the four-feature RF model achieved the highest Accuracy of 0.714 in classifying an independent unknown peptide dataset designed with the PEDV spike protein, and it also revealed overfitting problems in the other models. This four-feature RF model was used to evaluate peptide affinity by constructing the relationship between the actual affinity and the virtual docking scores of peptides to their receptors.


Subject(s)
Algorithms , Random Forest , Peptides , Machine Learning
18.
J Transl Med ; 20(1): 143, 2022 03 26.
Article in English | MEDLINE | ID: mdl-35346252

ABSTRACT

BACKGROUND: Established prediction models of Diabetic kidney disease (DKD) are limited to the analysis of clinical research data or general population data and do not consider hospital visits. Construct a 3-year diabetic kidney disease risk prediction model in patients with type 2 diabetes mellitus (T2DM) using machine learning, based on electronic medical records (EMR). METHODS: Data from 816 patients (585 males) with T2DM and 3 years of follow-up at the PLA General Hospital. 46 medical characteristics that are readily available from EMR were used to develop prediction models based on seven machine learning algorithms (light gradient boosting machine [LightGBM], eXtreme gradient boosting, adaptive boosting, artificial neural network, decision tree, support vector machine, logistic regression). Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). Shapley additive explanation (SHAP) was used to interpret the results of the best performing model. RESULTS: The LightGBM model had the highest AUC (0.815, 95% CI 0.747-0.882). Recursive feature elimination with random forest and SHAP plot based on LightGBM showed that older patients with T2DM with high homocysteine (Hcy), poor glycemic control, low serum albumin (ALB), low estimated glomerular filtration rate (eGFR), and high bicarbonate had an increased risk of developing DKD over the next 3 years. CONCLUSIONS: This study constructed a 3-year DKD risk prediction model in patients with T2DM and normo-albuminuria using machine learning and EMR. The LightGBM model is a tool with potential to facilitate population management strategies for T2DM care in the EMR era.


Subject(s)
Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Diabetic Nephropathies/epidemiology , Electronic Health Records , Humans , Logistic Models , Machine Learning , Male
19.
Opt Express ; 30(7): 11848-11860, 2022 Mar 28.
Article in English | MEDLINE | ID: mdl-35473120

ABSTRACT

Image reconstruction based on deep learning has become an effective tool in fluorescence microscopy. Most deep learning reconstruction methods ignore the mechanism of the imaging process where a large number of datasets are required. In addition, a lot of time is spent solving the aliasing problem from multi-scaled image pairs for data pre-processing. Here we demonstrate an improved generative adversarial network for image scanning microscopy (ISM) that can be trained by simulation data and has good generalization. Based on physical imaging models, this method can generate matching image pairs from simulation images and uses them as datasets for network training, without capturing a large number of real ISM images and avoiding image alignment preprocessing. Simulation and experimental results show that this simulation data-driven method improves the imaging quality of conventional microscopic images and reduces the cost of experiments. This method provides inspiration for optimizing network generalizability of the deep learning network.

20.
Opt Express ; 30(15): 26275-26285, 2022 Jul 18.
Article in English | MEDLINE | ID: mdl-36236822

ABSTRACT

Optical needle has become a hot research topic in recent years, due to the excellent properties and potential applications. To achieve a sub-diffraction optical needle, there are three common methods including planar diffractive lenses, reflective mirrors or axicons, and high-NA objective lenses with the designed phase or amplitude elements. Here, we propose a new kind of designed phase and amplitude element called the sinusoidal-amplitude binary phase mask (SA-BPM), which modulates the amplitude and phase distributions of the incident vector optical fields (VOFs) simultaneously. Based on Richards-Wolf vector diffraction integral, the corresponding parameters of SA-BPM and the optimal optical needle length are calculated by exhaustive method and genetic algorithm. We further upgrade the SA-BPM by adding a Gaussian function in the amplitude modulation, and design the Gaussian SA-BPM (GSA-BPM). We find that the ultra-long optical needles are achieved with the SA-BPM and GSA-BPM, and the depth of focus of the optical needles are improved by 30%-70% compared with the case of binary phase mask. Such SA-BPM and GSA-BPM we proposed have great potential for manipulation and utilization of the ultra-long optical needles.

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