circSnd1 promotes atherosclerosis progression through the miR-485-3p/Olr1 signaling pathway.

Background: Circular RNAs (circRNAs) participate in the development of atherosclerotic cardiovascular disease. Identifying and verifying the key competing endogenous RNA (ceRNA) network related to atherosclerosis (AS) is significant for understanding the development of AS. The aim of this study was to investigate the circRNA-miRNA‒mRNA network, identify a key circRNA and explore its role in the development of atherosclerosis. Methods: Differentially expressed mRNAs (DEMs) and circRNAs (DECs) in the AS model were obtained from datasets in the Gene Expression Omnibus (GEO) database. R software and Cytoscape software were used to construct and visualize the ceRNA network. The dual-luciferase reporter experiment and the RNA pull-down experiment were used to verify the selected ceRNA axis. siRNA targeting circRNA, miRNA mimic, miRNA inhibitor, or gene overexpression plasmid was used for in vitro functional studies. ELISA and western blotting were used to detect inflammation and lipid transport-related proteins. Furthermore, an AS mouse model was established and treated with recombinant adeno-associated viral vectors to further verify the influence of the selected ceRNA axis on the occurrence and/or development of AS. Results: A total of 497 DEMs were enriched in 25 pathways, based on which the circ_0082139 (circSnd1)/miR-485-3p/Olr1 axis was selected. In vitro, the interaction among the three molecules of this axis was validated and it was found to affect inflammation and lipid transport, which were characterized by the significant change of inflammatory factors (Il-6, Il-8, Tnf-α, Mcp-1, Vcam-1, and Icam-1), and lipid transport-related genes, including Abca1, Abcg1, Ldlr, Hdlbp, Lp-pla2, and Srebp-1c. Through animal experiments, we further verified that the circSnd1/miR-485-3p/Olr1 axis regulated these molecules and participated in the formation and/or development of AS in vivo. Conclusions: The circSnd1/miR-485-3p/Olr1 axis participates in the formation and development of atherosclerosis by regulating inflammation and lipid transport.

Quantitative proteomics reveals the therapeutic effects of RFAP against depression via pathway regulation of long-term depression and potentiation.

Ethnopharmacological relevance: RFAP is a compound extraction complex of four Traditional Chinese Medicine (TCM), including the dry bark of Paeonia lactiflora Pall. (Radix Paeoniae Alba), Gardenia jasminoides J. Ellis (Fructus Gardeniae), Albizia julibrissin Durazz. (Albizia julibrissin Durazz), and Paeonia × suffruticosa Andrews (Peony bark). Not only RFAP but also the individual ingredients have been commonly used for the treatment of depression in the clinic. However, the underlying mechanism of pharmacology is difficult to interpret since its holistic and multidrug nature. Aim of the study: This study aimed to elucidate the potential antidepressant mechanism of RFAP in the treatment of chronic unpredictable mild stress (CUMS) rats' model via the quantitative proteomics approach. Materials and methods: We established the CUMS rats' model and evaluated the efficacy of RFAP using multiple behavior assays, including the sugar preference test, open field test, and forced swimming test. Then label-free quantitative proteomics analyses were performed to evaluate the integrated changes of proteome profiling in control, CUMS, RFAP low dose, and RFAP high dose groups. Finally, we validated the critical changed proteins in the pathways of long-term depression and potentiation via RT-PCR and Western blotting assays. Results: We successfully established the CUMS rats' model. The behavior assays indicated that the rats demonstrated a tendency to behavioral despair after four weeks. Label-free quantitative proteomics showed that 107 proteins were significantly upregulated and 163 proteins were downregulated in the CUMS group compared to the control group. These differentially expressed proteins were involved in long-term potentiation, long-term depression, nervous system development, neuronal synaptic structural constituent of ribosome, ATP metabolic process, learning or memory, and cellular lipid metabolic process. RFAP treatment partially restored the differentially expressed protein profile. The protective effect of RFAP on behavioral assessment were consistent with the results of proteomics. Conclusions: The results indicated that RFAP exerted a synergistic effect on CUMS by regulating long-term inhibition and potentiation-related proteins.

Millihertz magnetic resonance spectroscopy combining the heterodyne readout based on solid-spin sensors.

The sensitivities of quantum sensing in metrology and spectroscopy are drastically influenced by the resolution of the frequency spectrum. However, the resolution is hindered by the decoherence effect between the sensor and the environment. Along these lines, the continue-wave optically detected magnetic resonance (CWODMR) method combined with the heterodyne readout was proposed to break the limitation of the sensor's coherence time. The frequency of the magnetic field was swept to match the unknown signal, and the signal can be transformed to a real-time frequency-domain curve via the heterodyne readout, with a frequency resolution of 4.7 millihertz. Using the nitrogen-vacancy (NV) center ensemble in a diamond as the solid-spin sensors, it was demonstrated that the frequency resolution and precision could be improved proportionally to the low-pass filter parameters of Tc -1 and Tc -1.5, respectively. Furthermore, the introduced method performed the sensing of arbitrary audio signals with a sensitivity of 7.32 nT·Hz-1/2@10 kHz. Our generic approach can be extended to several fields, such as molecular structure determination and biomagnetic field detection, where high-fidelity detection properties across multiple frequency bands are required within small sensing volumes (∼ mm3).

Development of a Machine Learning Algorithm for Drug Screening Analysis on High-Resolution UPLC-MSE/QTOF Mass Spectrometry.

BACKGROUND: Ultra-performance liquid chromatography (UPLC)-MSE/quadrupole time-of-flight (QTOF) high-resolution mass spectrometry employs untargeted, data-independent acquisition in a dual mode that simultaneously collects precursor ions and product ions at low and ramped collision energies, respectively. However, algorithmic analysis of large-scale multivariate data of comprehensive drug screening as well as the positivity criteria of drug identification have not been systematically investigated. It is also unclear whether ion ratio (IR), the intensity ratio of a defined product ion divided by the precursor ion, is a stable parameter that can be incorporated into the MSE/QTOF data analysis algorithm. METHODS: IR of 91 drugs were experimentally determined and variation of IR was investigated across 5 concentrations measured on 3 different days. A data-driven machine learning approach was employed to develop multivariate linear regression (MLR) models incorporating mass error, retention time, number of detected fragment ions and IR, accuracy of isotope abundance, and peak response using drug-supplemented urine samples. Performance of the models was evaluated in an independent data set of unknown clinical urine samples in comparison with the results of manual analysis. RESULTS: IR of most compounds acquired by MSE/QTOF were low and concentration-dependent (i.e., IR increased at higher concentrations). We developed an MLR model with composite score outputs incorporating 7 parameters to predict positive drug identification. The model achieved a mean accuracy of 89.38% in the validation set and 87.92% agreement in the test set. CONCLUSIONS: The MLR model incorporating all contributing parameters can serve as a decision-support tool to facilitate objective drug identification using UPLC-MSE/QTOF.

Machine learning reveals neutrophil-to-lymphocyte ratio as a crucial prognostic indicator in severe Japanese encephalitis patients.

Japanese encephalitis (JE) is a severe infectious disease affecting the central nervous system (CNS). However, limited risk factors have been identified for predicting poor prognosis (PP) in adults with severe JE. In this study, we analyzed clinical data from thirty-eight severe adult JE patients and compared them to thirty-three patients without organic CNS disease. Machine learning techniques employing branch-and-bound algorithms were used to identify clinical risk factors. Based on clinical outcomes, patients were categorized into two groups: the PP group (mRs ≥ 3) and the good prognosis (GP) group (mRs ≤ 2) at three months post-discharge. We found that the neutrophil-to-lymphocyte ratio (NLR) and the percentage of neutrophilic count (N%) were significantly higher in the PP group compared to the GP group. Conversely, the percentage of lymphocyte count (L%) was significantly lower in the PP group. Additionally, elevated levels of aspartate aminotransferase (AST) and blood glucose were observed in the PP group compared to the GP group. The clinical parameters most strongly correlated with prognosis, as indicated by Pearson correlation coefficient (PCC), were NLR (PCC 0.45) and blood glucose (PCC 0.45). In summary, our findings indicate that increased serum NLR, N%, decreased L%, abnormal glucose metabolism, and liver function impairment are risk factors associated with poor prognosis in severe adult JE patients.

Comparison of 5-year outcomes and quality of life between endovenous laser (980†nm) and microwave ablation combined with high ligation for varicose veins.

Our study aims to evaluateand compare the long-term results of endovenous laser (EVLA) and microwave ablation (EMA) combined with high ligation in treating varicose veins (VVs). A total of 122 patients (150 legs) underwent EMA combined with high ligation, and 127 patients (167 legs) underwent EVLA procedures (980 nm) combined with high ligation in this retrospective study. Outcomes included the Aberdeen Varicose Vein Questionnaire (AVVQ) score, the Venous Clinical Severity Score (VCSS), clinical recurrence of VVs and patient satisfaction duringthe 5-year follow-up.During the 5-year follow-up, patients who underwent the EVLA procedure showed a higher recurrence of VVs than those who underwent the EMA procedure (22.75% vs. 13.33%, P = 0.03, odds ratio (OR): 1.91, 95% confidence interval (CI): 1.06-3.45), especially at the primary site (6% vs. 14.37%, P = 0.01; OR: 2.63; 95% CI: 1.21-5.72). VV recurrence within 3 years was higher in patients who underwent EVLA than in those who underwent the EMA procedure (73.68% vs. 40%, P = 0.01; OR: 4.2; 95% CI: 1.37-12.86). Compared with those at baseline, the AVVQ score, VCSS and EQ-5D score improved significantly at 5 years for patients who underwent either procedure (P < 0.01); however, the VCSS and AVVQ score were higher for patients who underwent the EVLA procedure (P = 0.05). The patient reintervention rate was higher for EVLA than for EMA (14.79% vs. 7.33%, P = 0.033; OR: 2.19; 95% CI: 2.06-5.34). Our results confirmed that EMA and EVLA improve the QoL of patients and that EMA combined with high ligation demonstrates lower 5-year recurrence, especially at primary sites.

iTRAQ-based proteomic analysis of Deinococcus radiodurans in response to 12C6+ heavy ion irradiation.

BACKGROUND: Deinococcus radiodurans (D. radiodurans) is best known for its extreme resistance to diverse environmental stress factors, including ionizing radiation (IR), ultraviolet (UV) irradiation, oxidative stress, and high temperatures. Robust DNA repair system and antioxidant system have been demonstrated to contribute to extreme resistance in D. radiodurans. However, practically all studies on the mechanism underlying D. radiodurans's extraordinary resistance relied on the treated strain during the post-treatment recovery lag phase to identify the key elements involved. The direct gene or protein changes of D. radiodurans after stress have not yet been characterized. RESULTS: In this study, we performed a proteomics profiling on D. radiodurans right after the heavy ion irradiation treatment, to discover the altered proteins that were quickly responsive to IR in D. radiodurans. Our study found that D. radiodurans shown exceptional resistance to 12C6+ heavy ion irradiation, in contrast to Escherichia coli (E.coli) strains. By using iTRAQ (Isobaric Tags for Relative and Absolute Quantitation)-based quantitative mass spectrometry analysis, the kinetics of proteome changes induced by various dosages of 12C6+ heavy ion irradiation were mapped. The results revealed that 452 proteins were differentially expressed under heavy ion irradiation, with the majority of proteins being upregulated, indicating the upregulation of functional categories of translation, TCA cycle (Tricarboxylic Acid cycle), and antioxidation regulation under heavy ion irradiation. CONCLUSIONS: This study shows how D. radiodurans reacts to exposure to 12C6+ heavy ion irradiation in terms of its overall protein expression profile. Most importantly, comparing the proteome profiling of D. radiodurans directly after heavy ion irradiation with research on the post-irradiation recovery phase would potentially provide a better understanding of mechanisms underlying the extreme radioresistance in D. radiodurans.

Clinical outcomes of different endovenous procedures among patients with varicose veins and iliac vein compression: A retrospective cohort study.

OBJECTIVE: This study aimed to investigate the short-term outcomes of three endovenous procedures in patients with varicose veins (VVs) and severe iliac vein compression syndrome (IVCS). METHODS: A total of 158 consecutive patients were included in this multicenter retrospective study from May 2017 to December 2019; 54 patients underwent endovenous laser ablation (EVLA) alone, 47 patients underwent EVLA and balloon angioplasty (BA), and 57 patients underwent EVLA and stenting angioplasty (SA). Clinical outcomes and complications were assessed at one and twelve months post-surgery. The Quality of life (QoL) was assessed by the venous clinical severity score (VCSS) and Aberdeen Varicose Vein Questionnaire (AVVQ). RESULTS: Patients who underwent the SA procedure were older (P < 0.05). Incidence of laser ablation complications was similar among the three procedures; closure rates of the great saphenous vein were 96.8%, 98.0%, and 98.4%, respectively, at 12 months. Reflux times in the SA procedure were lower than those in the EVLA and BA procedures at 12 months, while ulcer healing time was faster with the SA procedure (P < 0.05) than with the other procedures. The VCSS and AVVQ values were significantly improved post-procedure (P < 0.05), with lower AVVQ scores in the SA procedure than in the EVLA and BA procedures at 12 months post-surgery. The EVLA and BA procedures (stenosis >70%) caused a significantly higher symptom recurrence than the SA procedure, with an odds ratios of 14.04 (95% confidence interval (CI), 1.99-99.18) and 10.50 (95% CI, 1.26-87.15), respectively. CONCLUSIONS: Our results demonstrate that EVLA and SA procedures relieve symptoms, improve the QoL, and decrease symptom recurrence in patients with VVs and severe IVCS (stenosis >70%).

A hybrid deep learning approach for driver anomalous lane changing identification.

Reliable knowledge of driving states is of great importance to ensure road safety. Anomaly detection in driving behavior means recognizing anomalous driving states as a direct result of either environmental or psychological factors. This paper provides an efficient anomaly recognition approach to identify anomalous lane-changing events in a personalized manner. The proposed framework includes three unsupervised algorithms. First, a Recurrent-Convolutional Autoencoder extracts the spatio-temporal characteristics from a high-dimensional naturalistic driving dataset. Second, in order to recognize anomalous lane-changing events of individual drivers, the extracted latent feature space is analyzed using Pauta criterion-based reconstruction loss analysis, as well as one-class Support Vector Machine. Last, t-Distributed Stochastic Neighbor Embedding is employed to visualize the latent space for better understanding and interpretability. Temporal anomalies of lane-changing events were analyzed by a personalized grey relational coefficient analysis, to represent robust similarities for individual drivers. Validation and calibration were performed with a natural driving study dataset collected from 50 drivers with 59,372 lane change events. The results showed heterogeneity in the pattern of abnormal lane changing behavior across the sample. At the same time, each driver exhibited heterogeneous anomalous behaviors in both temporal and spatial sequences. Without prior labels, the proposed model effectively captures personalized driving patterns and abnormal lane-changing events from high-dimensional time-series data. This unsupervised hybrid approach is a novel attempt to complete personalized anomalous lane-changing behaviors identification based on naturalistic driving data involving various traffic environments. Our approach enables the extraction of natural individual lane-changing behavior patterns and provides insights for the improvement of personalized driving behavior monitoring systems.

Proteomic landscape subtype and clinical prognosis of patients with the cognitive impairment by Japanese encephalitis infection.

BACKGROUND: Cognitive impairment is one of the primary sequelae affecting the quality of life of patients with Japanese encephalitis (JE). The clinical treatment is mainly focused on life support, lacking of targeted treatment strategy. METHODS: A cerebrospinal fluid (CSF) proteomic profiling study was performed including 26 patients with JE in Gansu province of China from June 2017 to October 2018 and 33 other concurrent hospitalized patients who were excluded central nervous system (CNS) organic or CNS infection diseases. The clinical and proteomics data of patients with JE were undergoing combined analysis for the first time. RESULTS: Two subtypes of JE associated with significantly different prognoses were identified. Compared to JE1, the JE2 subtype is associated with lower overall survival rate and a higher risk of cognitive impairment. The percentages of neutrophils (N%), lymphocyte (L%), and monocytes (M%) decreased in JE2 significantly. CONCLUSIONS: The differences in proteomic landscape between JE subgroups have specificity for the prognosis of cognitive impairment. The data also provided some potential target proteins for treatment of cognitive impairments caused by JE. Trial registration ChiCTR, ChiCTR2000030499. Registered 1st June 2017, http://www.medresman.org.cn/pub/cn/proj/projectshow.aspx?proj=6333.

The Usefulness of C-Reactive Protein to Albumin Ratio in the Prediction of Adverse Cardiovascular Events in Coronary Chronic Total Occlusion Undergoing Percutaneous Coronary Intervention.

Inflammation and nutrition as main factors can affect the prognosis of patients with chronic total coronary occlusion (CTO) undergoing percutaneous coronary intervention (PCI). The C-reactive protein to albumin ratio (CAR) can clarify the inflammation and nutrition status, which are highly related to clinical outcomes. This study aims to investigate the association between CAR and adverse cardiovascular events in patients with CTO undergoing PCI. For this study, 664 patients were divided into three groups based on the tertiles of CAR. The primary endpoint was all-cause mortality and the secondary endpoint was major adverse cardiovascular events (MACE). Over a median follow-up of 33.7 months, the primary endpoint occurred in 64 patients (9.6%) and the secondary endpoint occurred in 170 patients (25.6%). The patients with higher CAR represented a worse prognosis with all-cause death and cardiovascular death after the adjustment for the baseline risk factors. Adding the CAR values raised the predictive value for the incidence of the all-cause death and cardiovascular death but not MACE. The capacity of prognosis prediction was improved after the addition of the CAR value to the traditional prediction model.

Prognostic value of malnutrition using geriatric nutritional risk index in patients with coronary chronic total occlusion after percutaneous coronary intervention.

BACKGROUND: Malnutrition is associated with poor prognosis in a wide range of chronic illnesses, however, the impact of malnutrition on long-term outcomes of patients at advanced stages of atherosclerosis, coronary chronic artery occlusion (CTO), is not known. AIMS: This study aims to investigate the relationship between malnutrition and adverse cardiovascular events in patients with CTO after percutaneous coronary intervention (PCI). METHODS: Baseline malnutrition risk was determined in 669 patients with CTO after PCI in this study. All patients were divided into 3 groups according to 3 categories of the geriatric nutritional risk index (GNRI): moderate to severe, GNRI of <92 (n = 70); low, GNRI of 92-98 (n = 197); and absence of risk, GNRI of ≥98 (n = 402). The primary endpoint was all-cause mortality and the secondary endpoint was major adverse cardiovascular events (MACE). RESULTS: Average age in this study was 65.32 ± 9.97 years old. More than one-third of patients were at risk of malnutrition (moderate to severe: 10.5%; low: 29.4%; and absence of risk: 60.1%). Over a median follow-up of 33 months, compared to those with absent risk for malnutrition, moderate to severe risk was associated with significantly increased risk for the all-cause death, cardiovascular death and MACE (hazard ratio [HR]: 2.90, 95% confidence interval [CI]: 1.43 to 5.87, P for trend = 0.002; HR: 3.72, 95% CI: 1.42 to 9.77, P for trend = 0.010; HR: 1.76, 95% CI: 1.02 to 3.03, P for trend = 0.040; respectively) after adjustment for baseline variables. Moreover, addition of the GNRI score significantly raised the predictive value for the all-cause death (0.383, p = 0.004 and 0.022, p = 0.011, NRI and IDI respectively), cardiovascular death (0.488, p < 0.001 and 0.013, p = 0.014, NRI and IDI respectively) and MACE (0.368, p = 0.004 and 0.014, p = 0.008, NRI and IDI respectively) as compared to traditional factors. CONCLUSIONS: Malnutrition assessed by the GNRI score on admission was an independent predictor for adverse cardiovascular events in CTO patients after PCI. Addition of the GNRI score to the existing risk prediction model significantly increased the predictive ability for cardiovascular events in CTO patients after PCI.

Quantitative proteomics reveal the protective effects of EDS against osteoarthritis via attenuating inflammation and modulating immune response.

ETHNOPHARMACOLOGICAL RELEVANCE: Epimedium brevicornu Maxim, Dioscorea nipponica Makino, and Salvia miltiorrhiza Bunge formula (EDS) are three traditional Chinese medicines commonly combined and used to treat osteoarthritis (OA). However, the mechanism of its therapeutic effect on OA is still unclear. AIM OF THE STUDY: The aim of this study was to investigate the potential anti osteoarthritis mechanism of EDS in the treatment of OA rats' model by quantitative proteomics. MATERIALS AND METHODS: A papain-induced rat OA model was established, and then EDS was intragastrically administered for 28 days. A label-free quantification proteomics was performed to evaluate the holistic efficacy of EDS against OA and identify the possible protein profiles mechanisms. The expression levels of critical changed proteins were validated by RT-qPCR and Western blotting. The effects of EDS were then assessed by evaluating pathologic changes in the affected knee joint and measuring pressure pain threshold, acoustic reflex threshold, angle of joint curvature. RESULTS: Proteomics analysis showed that 62 proteins were significantly upregulated and 208 proteins were downregulated in OA group compared to control group. The changed proteins were involved in activation of humoral immunity response, complement cascade activation, leukocyte mediated immunity, acute inflammatory response, endocytosis regulation, and proteolysis regulation. The EDS treatment partially restored the protein profile changes. The protective effects of EDS on pathologic changes in OA rats' knee joint and pain threshold assessment were consisted with the proteomics results. CONCLUSIONS: The results suggest that EDS exerted synergistic therapeutic efficacies to against OA through suppressing inflammation, modulating the immune system, relieving joint pain, and attenuating cartilage degradation.

Anemarrhena asphodeloides modulates gut microbiota and restores pancreatic function in diabetic rats.

Anemarrhena asphodeloides is an herb widely used to treat symptoms associated with diabetes in traditional Chinese medicine. However, its key components and metabolites have low bioavailability and poor host absorption. To clarify the anti-diabetic mechanism of A. asphodeloides extract (AAE), we examined the anti-diabetic effects of AAE in rats with diabetes induced by a high-fat diet and streptozotocin. Faeces levels of the main components and metabolites of AAE were significantly higher than levels in plasma, which indicated that gut microbiota might play important roles in its anti-diabetic effect. Microbiological studies showed that unabsorbed components increased the diversity of the gut microbiota, enriched potentially beneficial bacteria, and suppressed potentially harmful bacteria. In vitro studies showed that AAE promoted the proliferation of Blautia coccoides, a bacterium with positive implication for diabetes, in a dose-dependent manner. AAE also promoted pancreatic cell regeneration and restored the function of pancreatic islet cells via peroxiredoxin 4 overexpression. Overall, these results suggest that AAE alleviates diabetes via modulating gut microbiota and protein expression.

[Progress in cerebrospinal fluid proteome technology and its clinical application].

Cerebrospinal fluid surrounds and supports the central nervous system, including the ventricles and subarachnoid spaces. Cerebrospinal fluid should be an important source of biomarkers for central nervous system diseases because it is in direct contact with the central nervous system. Many studies are reported on cerebrospinal fluid proteomics, highlighting many recent progresses. Here, we review recent advances in proteomics technology and clinical application of cerebrospinal fluid.

Caloric Restriction Induces MicroRNAs to Improve Mitochondrial Proteostasis.

Both caloric restriction (CR) and mitochondrial proteostasis are linked to longevity, but how CR maintains mitochondrial proteostasis in mammals remains elusive. MicroRNAs (miRNAs) are well known for gene silencing in cytoplasm and have recently been identified in mitochondria, but knowledge regarding their influence on mitochondrial function is limited. Here, we report that CR increases miRNAs, which are required for the CR-induced activation of mitochondrial translation, in mouse liver. The ablation of miR-122, the most abundant miRNA induced by CR, or the retardation of miRNA biogenesis via Drosha knockdown significantly reduces the CR-induced activation of mitochondrial translation. Importantly, CR-induced miRNAs cause the overproduction of mtDNA-encoded proteins, which induces the mitochondrial unfolded protein response (UPRmt), and consequently improves mitochondrial proteostasis and function. These findings establish a physiological role of miRNA-enhanced mitochondrial function during CR and reveal miRNAs as critical mediators of CR in inducing UPRmt to improve mitochondrial proteostasis.

High-efficiency fluorescence collection for NV- center ensembles in diamond.

The negatively charged nitrogen vacancy (NV-) center ensembles in diamond have been demonstrated to be a promising platform for quantum metrology, but the poor fluorescence collection efficiency of a microscope objective limits the sensitivity of the NV- based sensors. Here we present a method for increasing the collected fluorescence intensity with a total internal reflection (TIR) lens. The detected fluorescence intensity is increased by approximately a factor of 56 compared with detection using a microscope objective with NA = 0.55, leading to a collection efficiency of 47.7% ± 3.1%. The signal-to-noise ratio is improved by a factor of 7.6 using the TIR lens. The proposed method is of great significance for collecting fluorescence from NV- centers in a large volume and can be used in weak fluorescence detection systems.

Quantitative proteomics reveals mitochondrial respiratory chain as a dominant target for carbon ion radiation: Delayed reactive oxygen species generation caused DNA damage.

Heavy ion radiotherapy has shown great promise for cancer therapy. Understanding the cellular response mechanism to heavy ion radiation is required to explore measures of overcoming devastating side effects. Here, we performed a quantitative proteomic analysis to investigate the mechanism of carbon ion irradiation on human AHH-1 lymphoblastoid cells. We identified 4602 proteins and quantified 4569 proteins showing high coverage in the mitochondria. Data are available via ProteomeXchange with identifier PXD008351. After stringent filtering, 290 proteins were found to be significantly up-regulated and 16 proteins were down-regulated. Functional analysis revealed that these up-regulated proteins were enriched in the process of DNA damage repair, mitochondrial ribosome, and particularly mitochondrial respiratory chain, accounting for approximately 50% of the accumulated proteins. Bioinformatics and functional analysis demonstrated that these up-regulated mitochondrial respiratory chain proteins enhanced ATP production and simultaneously reactive oxygen species release. More importantly, increased reactive oxygen species led to secondary organelle injury and lagged DNA double-strand breaks. Consistently, the expression of antioxidant enzymes was up-regulated for free radical scavenging. The mechanism of lagged secondary injury originated from disturbances in the mitochondrial respiratory chain. Our results provided a novel target for cell self-repair against heavy ion radiation-induced cellular damage.

Construction of anti-BCMA chimeric antigen receptor (CAR-BCMA) modified T cells and its cytotoxicity against tumor cells / 中国肿瘤生物治疗杂志

@# Objective： ：To explore a novel chimeric antigen receptor (CAR)-T cell treatment to treat Multiple Myeloma (MM) via target B cell maturation antigen (BCMA). Methods： ：A CAR-BCMA molecular was constructed based on mouse originated BCMA scFv, and was packaged into lentiviral vector and transfected into T cells from healthy donors to construct CAR-BCMA-T cells. The BCMApositive cell lines A549-BCMA, A549-BCMAOFP and K562-BCMA were constructed as target cells. Then, the CAR-BCMA-T cells were co-incubated with the constructed target cells and human myeloma U266 cells, and the cytotoxic effects of CAR-BCMA-T cells were evaluated via CCK-8 and FACS. Finally, the CAR-BCMA-T cells originated from MM patients were constructed, and its cytotoxicity against A549-BCMA were examined; in addition, the IFN-γ release level in CAR-BCMA-T cells was evaluated by ELISA and FACS. Results: After 11 days’incubation, the CAR-BCMA-T cells originated from healthy donors amplified 300 times with a positive rate of 43%. The BCMApositive target cell lines were constructed successfully. Under an effector : target ratio of 5:1, the killing rates of CARBCMA-T cells against A549-BCMA, K562-BCMA and U266 were about 80%, 60%, and 80%, respectively, which were significantly higher than those against BCMA negative cells; and the cytotoxicity was related to the BCMA expression level in target cells. What’ s more, at the effector : target ratio of 20:1, the CAR-BCMA-T cells originated from MM patients were demonstrated to exhibit a killing rate of more than 95% againstA549-BCMApositive cells, and produced large amount of IFN-γ. Conclusion: CAR-BCMA-T cells originated from both healthy and MM donors were successfully constructed, and they can effectively and specifically kill BCMA positive tumor cells.

Few-period helically twisted all-solid photonic bandgap fibers.

We present a type of few-period helically twisted all-solid photonic bandgap fiber (AS-PBGFs). The helical structure leads to orbital resonance of a cladding rod light, which couples with the core mode. A two-period twist structure exhibits an extremely strong resonant dip of up to 30 dB. A series of samples with twist periods of 3.31-7.92 mm (yielding twist rates of 1.90-0.79 rad⋅mm-1) in association with different resonance orders are fabricated and demonstrated. The inherent physical mechanism underlying the resonance is analyzed. Moreover, the responses of the resonance to mechanical torsion, strain, and temperature are investigated. The twisted AS-PBGFs feature high reproducibility, stability, and robustness, and have great potential in tunable in-fiber filters and sensors.