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1.
J Cell Sci ; 135(5)2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33912962

RESUMO

Membrane contact sites (MCSs) between the endoplasmic reticulum (ER) and late endosomes/lysosomes (LE/lys) are emerging as critical hubs for diverse cellular events, and changes in their extents are linked to severe neurological diseases. While recent studies show that the synaptotagmin-like mitochondrial-lipid-binding (SMP) domain-containing protein PDZD8 may mediate the formation of ER-LE/lys MCSs, the cellular functions of PDZD8 remain largely elusive. Here, we attempt to investigate the lipid transfer activities of PDZD8 and the extent to which its cellular functions depend on its lipid transfer activities. In accordance with recent studies, we demonstrate that PDZD8 is a protrudin (ZFYVE27)-interacting protein and that PDZD8 acts as a tether at ER-LE/lys MCSs. Furthermore, we discover that the SMP domain of PDZD8 binds glycerophospholipids and ceramides both in vivo and in vitro, and that the SMP domain can transport lipids between membranes in vitro. Functionally, PDZD8 is required for LE/lys positioning and neurite outgrowth, which is dependent on the lipid transfer activity of the SMP domain.


Assuntos
Retículo Endoplasmático , Endossomos , Lipídeos , Lisossomos , Crescimento Neuronal
2.
Cancer Lett ; 524: 82-90, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34626692

RESUMO

Long non-coding RNAs (lncRNAs) play important roles in cancer development and progression; however, their contributions to gastric cancer metastasis remain largely unknown. By lncRNA microarray screening, our study showed that 453 lncRNAs are dysregulated in gastric cancer tissues with or without lymph node metastasis, of which lnc-LEMGC ranks as one of the most significantly downregulated lncRNAs. Lnc-LEMGC inhibited cell migration and invasion both in vitro and in vivo, by combining with protein DNA-PKcs. Importantly, nucleotides 1300-1800 of lnc-LEMGC prevented DNA-PKcs phosphorylation of serine 2056 and partially abrogated the effects of downstream effectors, ErbB1, SRC and protein tyrosine kinase 2 (FAK), in the epidermal growth factor receptor (EGFR) pathway. The results of this study extend our knowledge of lncRNA's molecular mechanisms, in which lnc-LEMGC functions by directly suppressing the phosphorylation of its combined protein DNA-PKcs and inactivating the DNA-PKcs downstream EGFR signaling.

3.
Front Immunol ; 12: 769775, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34804060

RESUMO

The crosstalk between the immune system and microbiota drives an amazingly complex mutualistic symbiosis. In mammals, the upper respiratory tract acts as a gateway for pathogen invasion, and the dynamic interaction between microbiota and mucosal immunity on its surface can effectively prevent disease development. However, the relationship between virus-mediated mucosal immune responses and microbes in lower vertebrates remains uncharacterized. In this study, we successfully constructed an infection model by intraperitoneally injecting common carp (Cyprinus carpio) with spring viremia of carp virus (SVCV). In addition to the detection of the SVCV in the nose and pharynx of common carp, we also identified obvious histopathological changes following viral infection. Moreover, numerous immune-related genes were significantly upregulated in the nose and pharynx at the peak of SVCV infection, after which the expression levels decreased to levels similar to those of the control group. Transcriptome sequencing results revealed that pathways associated with bacterial infection in the Toll-like receptor pathway and the Nod-like receptor pathway were activated in addition to the virus-related Rig-I-like receptor pathway after SVCV infection, suggesting that viral infection may be followed by opportunistic bacterial infection in these mucosal tissues. Using 16S rRNA gene sequencing, we further identified an upward trend in pathogenic bacteria on the mucosal surface of the nose and pharynx 4 days after SVCV infection, after which these tissues eventually reached new homeostasis. Taken together, our results suggest that the dynamic interaction between mucosal immunity and microbiota promotes the host to a new ecological state.

4.
Front Oncol ; 11: 734407, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722280

RESUMO

Background: Brain tumor ranks as the most devastating cancer type. The complex tumor immune microenvironment prevents brain tumor from receiving therapeutic benefits. The purpose of this study was to stratify brain tumors based on their distinct immune infiltration signatures to facilitate better clinical decision making and prognosis prediction. Methods: We developed a deep learning model to characterize immune infiltration from transcriptome. The developed model was applied to distill expression signatures of transcriptome of brain tumor samples. We performed molecular subtyping with the extracted expression signatures to unveil brain tumor subtypes. Computational methods, including gene set enrichment analysis, Kaplan-Meier survival and multivariate Cox regression analyses, were employed. Results: We identified two distinctive subtypes (i.e. C1/2) of brain tumor featured by distinct immune infiltration signatures. The C1 subtype is characterized by protective immune infiltration signatures, including high infiltration of CD8+ T cells and activation of CX3CL1. The C2 subtype has an extensive infiltration of tumor-associated macrophages and microglia, and was enriched with immune suppressive, wound-healing, and angiogenic signatures. The C1 subtype had significantly better prognosis as compared with C2 (Log-rank test, HR: 2.5, 95% CI: 2.2 - 2.7; P = 8.2e-78). This difference remained statistically significant (multivariate Cox model, HR: 2.2, 95% CI: 1.7 - 2.9; P = 3.7e-10) by taking into account age, gender, recurrent/secondary status at sampling time, tumor grade, histology, radio-chemotherapy, IDH mutation, MGMT methylation, and co-deletion of 1p and 19q. This finding was validated in six datasets. The C2 subtype of glioblastoma patients with IDH mutation has poor survival analogous to those without IDH mutation (Log-rank test, adjusted P = 0.8), while C1 has favorable prognosis as compared with glioblastoma of C2 subtype with IDH mutation (Log-rank test, adjusted P = 1.2e-3) or without IDH mutation (Log-rank test, adjusted P = 1.3e-6). Conclusions: We identified two distinctive subtypes of brain tumor with different immune infiltration signatures, which might be helpful as an independent prognosticator for brain tumor.

6.
Am J Transl Res ; 13(10): 11384-11398, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34786066

RESUMO

OBJECTIVE: Pneumonia is an infectious pulmonary disease with a high morbidity and mortality. It has been reported that multiple long noncoding RNAs (LncRNAs) are involved in the progression of pneumonia, such as LncRNA SNHG16. However, the role and underlying mechanism of LncRNA H19 in the pyroptosis of pneumonia has not been elucidated. The purpose of this research was to explore the mechanism by which LncRNA H19 regulates LPS-induced pneumonia in WI-38 cells. METHODS: An LPS induced pneumonia model in WI-38 cells was established. Total RNA extracted from WI-38 cells was analyzed using RT-qPCR, and the total proteins isolated from the WI-38 cells were analyzed using Western blotting. MTT assays, TUNEL staining, bioinformatics, and luciferase reporter assays were subsequently conducted. RESULTS: In the LPS induced pneumonia model, LncRNA H19 silences inhibited LPS-induced WL-38 cell pyroptosis, and LncRNA H19 overexpression promotes LPS-induced WL-38 cell pyroptosis. Also, LncRNA H19 acts as a sponge of miR-22-3p, which targets NLRP3, and NLRP3 attenuates the effect of LncRNA H19 silencing on LPS-induced WL-38 cell pyroptosis. CONCLUSION: Our data demonstrated the roles and potential mechanisms of LncRNA H19 in the regulation of pneumonia cell pyroptosis, indicating that LncRNA H19 is an efficient predictive and curative target for pneumonia.

7.
Sci Adv ; 7(47): eabi9535, 2021 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-34788098

RESUMO

[Figure: see text].

8.
Artigo em Inglês | MEDLINE | ID: mdl-34788868

RESUMO

PURPOSE: The purpose of the study was to investigate the safety and efficacy of endovascular embolization of ruptured intracranial aneurysms within 72 hours of subarachnoid hemorrhage (SAH). MATERIALS AND METHODS: Patients with intracranial aneurysms treated with embolization were divided into group A (n = 277), patients with ruptured aneurysms treated within 72 hours of SAH; group B (n = 138), patients with ruptured aneurysms treated beyond 72 hours; and group C (n = 93), patients with unruptured aneurysms. RESULTS: Embolization was successful in all but four patients (99.2%). The periprocedural complication rate was 36.2% in group B, significantly (p < 0.05) greater than that in group A (24.5%) or group C (11.8%). The rebleeding rate was 9.7% (6/62 patients) in groups A and B after embolization and only 0.3% (1/346 patients) in aneurysms with total or subtotal occlusion. Of these three groups of patients, 69.7% in group A, 58.7% in group B, and 76.3% in group C achieved Glasgow Outcome Scale (GOS) score of 5 or modified Rankin Scale (mRS) score of 0- to 1 at discharge. A significant difference (p < 0.05) existed in the clinical outcome between the three groups. The percentages of patients without deficits (GOS 5 or mRS 0-1) and slight disability (mRS 2) were 80.2% in group A, 81.2% in group B, and 96.7% in group C. The mortality rate was 4.3% (12/277 patients) in group A and 7.2% (10/138 patients) in group B with no significant (p = 0.21) difference. Follow-up was performed at 3 to 54 months (mean 23.2), and the recanalization rate was 28.6% (32/112 patients) in group A, 22.4% (11/49 patients) in group B, and 28.6% (16/56 patients) in group C, with no significant differences (p = 0.15). Hydrocephalus occurred in 30.5% (39/128 patients) in group B, which was significantly (p < 0.01) greater than that in group A (9.4%) or group C (2.2%). CONCLUSION: Early embolization of ruptured cerebral aneurysms within 72 hours of rupture is safe and effective and can significantly decrease periprocedural complications compared with management beyond 72 hours. Timely management of cisternal and ventricular blood can reduce hydrocephalus incidence and improve prognosis.

9.
Zhongguo Dang Dai Er Ke Za Zhi ; 23(11): 1154-1160, 2021 Nov 15.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-34753548

RESUMO

OBJECTIVES: To investigate the diversity of peripheral blood T cell receptor (TCR) ß chain complementarity-determining region 3 (CDR3) based on immune repertoire sequencing in neonates with sepsis and the possible pathogenesis of neonatal sepsis. METHODS: A total of 12 neonates with sepsis were enrolled as the case group, and 9 healthy full-term infants, matched for gestational age, birth weight, and age, were enrolled as the control group. Omega nucleic acid purification kit (SQ blood DNA Kit II) was used to extract DNA from peripheral blood samples, TCR ß chain CDR3 was amplified by multiplex PCR, and then high-throughput sequencing was performed for the products to analyze the diversity of TCR ß chain CDR3 and the difference in expression. RESULTS: The length and type of TCR ß chain CDR3 were similar between the case and control groups, and Gaussian distribution was observed in both groups. With D50 and Shannon-Wiener index as the evaluation indices for diversity, the case group had a significantly lower diversity of TCR ß chain CDR3 than the control group (P<0.05). The frequency of 48 genes in TCR ß chain V segment was compared, and the results showed that compared with the control group, the case group had significantly higher frequencies of TRBV10-3, TRBV2, and TRBV20-1 (P<0.05). The frequency of 13 genes in TCR ß chain J segment were compared, and the results showed that compared with the control group, the case group had significantly higher frequencies of TRBJ2-3, TRBJ2-5, and TRBJ2-7 (P<0.05). CONCLUSIONS: There is a significant change in the diversity of TCR ß chain CDR3 in the peripheral blood of neonates with sepsis, suggesting that it might be associated with the immune pathogenesis of neonatal sepsis.


Assuntos
Regiões Determinantes de Complementaridade , Sepse Neonatal , Regiões Determinantes de Complementaridade/genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Reação em Cadeia da Polimerase Multiplex , Receptores de Antígenos de Linfócitos T alfa-beta/genética
10.
Plant Biotechnol J ; 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34726307

RESUMO

MicroRNAs (miRNAs) play vital roles in plant development and defence responses against various stresses. Here, we show that blocking miR1871 improves rice resistance against Magnaporthe oryzae and enhances grain yield simultaneously. The transgenic lines overexpressing miR1871 (OX1871) exhibit compromised resistance, suppressed defence responses and reduced panicle number resulting in slightly decreased yield. In contrast, the transgenic lines blocking miR1871 (MIM1871) show improved resistance, enhanced defence responses and significantly increased panicle number leading to enhanced yield per plant. The RNA-seq assay and defence response assays reveal that blocking miR1871 resulted in the enhancement of PAMP-triggered immunity (PTI). Intriguingly, miR1871 suppresses the expression of LOC_Os06g22850, which encodes a microfibrillar-associated protein (MFAP1) locating nearby the cell wall and positively regulating PTI responses. The mutants of MFAP1 resemble the phenotype of OX1871. Conversely, the transgenic lines overexpressing MFAP1 (OXMFAP1) or overexpressing both MFAP1 and miR1871 (OXMFAP1/OX1871) resemble the resistance of MIM1871. The time-course experiment data reveal that the expression of miR1871 and MFAP1 in rice leaves, panicles and basal internode is dynamic during the whole growth period to manipulate the resistance and yield traits. Our results suggest that miR1871 regulates rice yield and immunity via MFAP1, and the miR8171-MFAP1 module could be used in rice breeding to improve both immunity and yield.

11.
J Phys Chem Lett ; 12(44): 10808-10814, 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34726059

RESUMO

On-surface fabrication of two-dimensional (2D) metal organic frameworks (MOFs) has been continuously attracting attentions for years. However, the synthesis of 2D MOFs with large-amplitude flexibility was rarely carried out since the bonding configurations in the coordination nodes are typically highly directional. Here we demonstrate that single alkali ions, which are fully isotropic in ionic bonding, can act as pivot joints for constructing tunable 2D MOFs by bonding to dihalogen groups in organic molecules. We take 2,3,6,7,10,11-hexabromotriphenylene, a 3-fold polycyclic molecule with three ortho-dibromo groups, and sodium (Na) atoms as a model system and successfully construct Na-based MOFs on Au(111) surface. The deflection angle of the Na coordination nodes is variable in an unprecedentedly large range between ±36° that allows the construction of multiple 2D MOF architectures. Such a flexible alkali-halogen bonding may provide a unique toolbox for designing and constructing more tunable MOFs by choosing various alkali atoms and halogen moieties.

12.
J Otolaryngol Head Neck Surg ; 50(1): 63, 2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34742355

RESUMO

BACKGROUND: While some studies suggest that the BRAF V600E mutation correlates with a high-risk phenotype in papillary thyroid microcarcinoma (PTMC), more evidence is necessary before this mutation can be used to help guide decision making in the management of small thyroid nodules. This study investigated whether BRAF V600E mutation is associated with aggressive features in PTMC (≤ 1 cm) and small PTC (1-1.5 cm). METHODS: Retrospective chart review was performed on 121 patient cases. Patients who underwent thyroid surgery for PTMC (≤ 1 cm) or small PTC (1-1.5 cm) were included if molecular testing was done for BRAF V600E mutation. Two study groups were created based on tumour size: PTMC (n = 55) and small PTC (n = 66). The groups were analysed for the presence of a BRAF V600E mutation and aggressive features, including macroscopic extrathyroidal extension (ETE), lymph node metastasis (LNM), and high-risk histological features (tall cell, columnar cell, hobnail, solid/trabecular, and diffuse sclerosing). The Fischer exact test was used to calculate statistical significance. RESULTS: BRAF V600E mutations were detected in 43.6% of PTMC and 42.4% of small PTC. Of the mutated PTMC nodules, 54.1% demonstrated aggressive characteristics as compared to 19.4% of the non-mutated PTMCs (p = 0.010). Of the mutated small PTC tumours, 82.1% had aggressive features. In contrast, 28.9% of the non-mutated small PTCs showed aggressive features (p < 0.001). CONCLUSIONS: Our findings demonstrate an association between a BRAF V600E mutation and aggressive features in PTMC (≤ 1 cm) and small PTC (1-1.5 cm). Therefore, determining the molecular status of these thyroid nodules for the presence of BRAF V600E can help guide patient management.

13.
Front Cell Dev Biol ; 9: 744969, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34778255

RESUMO

Management of laryngeal and hypopharyngeal squamous cell carcinoma (LHSCC) remains highly challenging due to highly variable therapeutic responses. By establishing an in vitro model for LHSCC based on conditional reprogramming (CR), a cell-culture technique, we aim to investigate its potential value on personalized cancer therapies. Herein, a panel of 28 human LHSCC CR cells were established from 50 tumor tissues using the CR method. They retained tumorigenic potential upon xenotransplantation and recapitulated molecular characteristics of LHSCC. Differential responses to anticancer drugs and radiotherapy were detected in vitro. CR cells could be transformed to xenograft and organoid, and they shared comparable drug responses. The clinical drug responses were consistent with in vitro drug responses. Collectively, the patient-derived CR cell model could promisingly be utilized in clinical decision-making and assisted in the selection of personalized therapies for LHSCC.

14.
Nat Commun ; 12(1): 6874, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34824280

RESUMO

Two-dimensional magnetic semiconductors provide a platform for studying physical phenomena at atomically thin limit, and promise magneto-optoelectronic devices application. Here, we report light helicity detectors based on graphene-CrI3-graphene vdW heterostructures. We investigate the circularly polarized light excited current and reflective magnetic circular dichroism (RMCD) under various magnetic fields in both monolayer and multilayer CrI3 devices. The devices exhibit clear helicity-selective photoresponse behavior determined by the magnetic state of CrI3. We also find abnormal negative photocurrents at higher bias in both monolayer and multilayer CrI3. A possible explanation is proposed for this phenomenon. Our work reveals the interplay between magnetic and optoelectronic properties in CrI3 and paves the way to developing spin-optoelectronic devices.

15.
Adv Sci (Weinh) ; : e2102466, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34825525

RESUMO

Diabetes mellitus (DM) refers to a group of metabolic disorders that are characterized by hyperglycemia. Oral subcutaneously administered antidiabetic drugs such as insulin, glipalamide, and metformin can temporarily balance blood sugar levels, however, long-term administration of these therapies is associated with undesirable side effects on the kidney and liver. In addition, due to overproduction of reactive oxygen species and hyperglycemia-induced macrovascular system damage, diabetics have an increased risk of complications. Fortunately, recent advances in nanomaterials have provided new opportunities for diabetes therapy and diagnosis. This review provides a panoramic overview of the current nanomaterials for the detection of diabetic biomarkers and diabetes treatment. Apart from diabetic sensing mechanisms and antidiabetic activities, the applications of these bioengineered nanoparticles for preventing several diabetic complications are elucidated. This review provides an overall perspective in this field, including current challenges and future trends, which may be helpful in informing the development of novel nanomaterials with new functions and properties for diabetes diagnosis and therapy.

16.
Front Neurol ; 12: 700516, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34744960

RESUMO

Purpose: To investigate the safety and efficacy of endovascular embolization of cerebral aneurysms at the P1-P3 segments of the posterior cerebral artery (PCA). Materials and Methods: Seventy-seven patients with 77 PCA aneurysms who were treated with endovascular embolization were enrolled, including 35 (45.5%) patients with ruptured aneurysms and 42 (54.5%) with unruptured ones. The pretreatment clinical data and aneurysm occlusion status after treatment and at follow-up were analyzed. Results: All patients were successfully treated endovascularly, including coiling alone in 10 (13.0%) patients, stent-assisted coiling in 18 (23.4%), parent artery occlusion in 25 (32.5%), and pipeline embolization device (PED) in 24 (31.2%). Complete occlusion was achieved in 48 (62.3%) aneurysms, residual neck in 4 (5.2%), and residual aneurysm in the other 25 (32.5%) at the end of embolization. Periprocedural complications occurred in eight patients, including acute thrombosis in seven (9.1%) and intraprocedural subarachnoid hemorrhage in one (1.3%), with the total complication rate of 10.4%. Follow-up was performed in 60 patients (77.9%) for 42 ± 11 months; the mRS score was 0-2 in 55 (91.7%) patients, three in four patients (6.7%), and six in one patient (1.7%). Fifty-three (88.3%) patients (53 aneurysms) had stable or complete occlusion, and seven (11.7%) patients had aneurysm recurrence or residual aneurysm. Among 19 patients treated with PED at follow-up, 15 aneurysms (78.9%) proceeded to complete occlusion while four (21.1%) aneurysms showed residual aneurysm. Conclusion: Endovascular embolization remains a good choice of treatment with high safety and efficacy for posterior cerebral artery aneurysms.

17.
Oncoimmunology ; 10(1): 1995166, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34745768

RESUMO

Plasma extracellular vesicles (EVs) have been reported to be a promising source of diagnostic and prognostic biomarkers in various cancers. However, further research in this area is needed due to the limitations of circulating extracellular vesicles detection methods. Using the Single Molecule array (SiMoa) technology, we developed two extracellular vesicle detection assays, CD9-CD63 and PD-L1-CD63, to determine circulating universal EVs and PD-L1 positive EVs, respectively. A total of 164 diffuse large B-cell lymphoma (DLBCL) patients were retrospectively included in this study. Compared with healthy volunteers (n = 25), elevated CD9-CD63 and PD-L1-CD63 signals were detected in the plasma of DLBCL patients (n = 164). High CD9-CD63 signals was associated with molecular subtype, extranodal site and treatment response in DLBCL. A high PD-L1-CD63 signal was also associated with certain clinical features, including extranodal site and treatment response. CD9-CD63 and PD-L1-CD63 signals were found to be important prognostic factors for both progression-free and overall survival. Furthermore, PD-L1-positive EVs were found in all patients, though PD-L1 protein expression was positive in only 35.4% (17/48) of tumor biopsies. No correlation was found between circulating PD-L1+ EVs and soluble PD-L1 (sPD-L1) levels. Our results show that plasma universal EV and PD-L1-positive EV levels are significantly elevated in DLBCL and might serve as biomarkers for predicting survival outcomes in DLBCL patients.

18.
ESC Heart Fail ; 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34729942

RESUMO

AIMS: The management of heart failure (HF) in young children is challenging. The present study aimed to clarify the effect of left univentricular epicardial pacing on dilated cardiomyopathy with left bundle branch block (LBBB) in children. METHODS AND RESULTS: A total of five cases (30.86 ± 16.39 months, three female) of children weighing 5.8-15 kg with dilated cardiomyopathy and LBBB were included in this study. LBBB in one child occurred after device closure of peri-membranous ventricular septal defects, and the remaining four were idiopathically discovered early after birth. Before implantation, all children suffered from refractory HF and cardiac dilatation; the left ventricular ejection fraction was 33.48 ± 5.84% with Ross Heart Failure Classification III-IV. Electrical and mechanical dyssynchrony were observed in all children with QRS duration >140 ms and prolonged septal-to-left posterior wall motion delay. Left univentricular epicardial pacing was successfully implanted via left axillary minithoracotomy in the five children. Sensed atrioventricular delays (83 ± 15 ms) were optimized by velocity time integral of aortic blood flow before discharge. During the follow-up period (10.8 ± 2.68 months), the dilated failing heart was reversed significantly in terms of decreased left ventricular dimension (55.62 ± 3.46 vs. 38.94 ± 3.69 mm, P = 0.005), while the left ventricular ejection fraction improved to 60.18 ± 8.78% (P = 0.006). CONCLUSIONS: In young children with low body weight, if HF is caused by or related to LBBB, left ventricular epicardial pacing still has an excellent effect.

19.
J Inflamm Res ; 14: 5769-5785, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34764670

RESUMO

Background: Inflammation is considered essential in cancer progression, as it affects the nutritional status and prognosis of patients. In this study, we aim to analyze the efficacy of various inflammatory markers in predicting prognosis in cancer patients. Methods: Patients with malignant tumor were included as primary and validation cohort. Basic clinical information, anthropometric indicators, body composition analysis, and serological indicators were recorded. After proposing the optimal thresholds by time-dependent receiver operating characteristic (ROC), univariate and multivariate Cox regression analyses were performed to analyze the association between inflammatory markers and overall survival (OS). A nomogram was established to develop a scored-inflammatory marker system. Eight inflammatory models based on combinations of inflammatory markers were assessed. Cox regression analysis was used to analyze the relationship of each inflammatory model and mortality of participants. Then, subanalysis of specific tumor types was conducted by Cox regression. Logistic regression models were used to analyze the relationship between different inflammatory models and malnutrition. Results: Univariate and multivariate Cox regression analyses indicated that pack-years of cigarette smoking, C-reactive protein (CRP), and systemic immune-inflammation index (SII) were related to the OS of cancer patients. A nomogram was constructed to develop a scored-inflammatory marker system. Among the eight inflammatory models, patients in model A had worst prognosis compared with patients in other models. Subanalysis next showed lung cancer, breast cancer and digestive system neoplasms patients in model A suffered the worst prognosis. Logistic regression indicated that model A was also with predictive value for malnutrition. Conclusion: A scored-inflammatory marker system was established to predict the OS of cancer patients. The inflammatory models established in this study can be used to predict prognosis, as well as cancer-related malnutrition. Inflammatory model A suffered the worst OS and was with the predictive efficacy for malnutrition.

20.
Nat Biotechnol ; 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34782739

RESUMO

A main determinant of the spatial resolution of live-cell super-resolution (SR) microscopes is the maximum photon flux that can be collected. To further increase the effective resolution for a given photon flux, we take advantage of a priori knowledge about the sparsity and continuity of biological structures to develop a deconvolution algorithm that increases the resolution of SR microscopes nearly twofold. Our method, sparse structured illumination microscopy (Sparse-SIM), achieves ~60-nm resolution at a frame rate of up to 564 Hz, allowing it to resolve intricate structures, including small vesicular fusion pores, ring-shaped nuclear pores formed by nucleoporins and relative movements of inner and outer mitochondrial membranes in live cells. Sparse deconvolution can also be used to increase the three-dimensional resolution of spinning-disc confocal-based SIM, even at low signal-to-noise ratios, which allows four-color, three-dimensional live-cell SR imaging at ~90-nm resolution. Overall, sparse deconvolution will be useful to increase the spatiotemporal resolution of live-cell fluorescence microscopy.

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