Multicolumn Nanoflow Liquid Chromatography with Accelerated Offline Gradient Generation for Robust and Sensitive Single-Cell Proteome Profiling.

Peptide separations that combine high sensitivity, robustness, peak capacity, and throughput are essential for extending bottom-up proteomics to smaller samples including single cells. To this end, we have developed a multicolumn nanoLC system with offline gradient generation. One binary pump generates gradients in an accelerated fashion to support multiple analytical columns, and a single trap column interfaces with all analytical columns to reduce required maintenance and simplify troubleshooting. A high degree of parallelization is possible, as one sample undergoes separation while the next sample plus its corresponding mobile phase gradient are transferred into the storage loop and a third sample is loaded into a sample loop. Selective offline elution from the trap column into the sample loop prevents salts and hydrophobic species from entering the analytical column, thus greatly enhancing column lifetime and system robustness. With this design, samples can be analyzed as fast as every 20 min at a flow rate of just 40 nL/min with close to 100% MS utilization time and continuously for as long as several months without column replacement. We utilized the system to analyze the proteomes of single cells from a multiple myeloma cell line upon treatment with the immunomodulatory imide drug lenalidomide.

Unveiling Pre-Transmetalation Intermediates in Base-Free Suzuki-Miyaura Cross-Couplings: A Computational Study.

The pre-transmetalation intermediates are critically important in Suzuki-Miyaura cross-coupling (SMC) reactions and have become a hot spot of the current research. However, the pre-transmetalation intermediates under base-free conditions have not been clear. Herein, a comprehensive theoretical study is performed on the base-free Pd-catalyzed desulfonative SMC reaction. The fragile coordination feature and the acceleration role of the RuPhos chelate ligand are revealed. The hydrogen-bond complex between the Pd-F complex and aryl boronic acid is identified as an important pre-transmetalation intermediate, which increases the energy span to 32.5 kcal/mol. The controlling factor for the formation of the hydrogen-bond complexes is attributed to the electronegativities of halogen atoms in the metal halide complexes. What is more, other reported SMC reaction systems involving metal halide complexes and aryl boronic acids are reconsidered and suggest that the hydrogen-bond complexes widely exist as stable pre-transmetalation intermediates with influencing the catalytic activities. The earth-abundant Ni-catalyzed desulfonative SMC reaction is further designed and predicted to have a higher activity than the original Pd-catalyzed SMC reaction.

Co-doped NaYF4:Yb/Er/Tm upconversion luminescent coating to enhance the efficiency of photovoltaic cells.

The use of upconversion luminescent materials to broaden the utilization range of the solar spectrum to enhance the efficiency of photovoltaic cells offers a promising and sustainable approach. However, the low luminescence intensity and easy quenching of upconversion luminescent materials bring serious challenges to the practical application. Herein, a novel method using Co2+ ion doping to regulate the luminescence properties of NaYF4:Yb/Er/Tm is proposed. NaYF4:Yb/Er/Tm microcrystals doped with different proportions of Co2+ ions are prepared and used as coatings on the surface of photovoltaic cells. Co2+ ions regulate the crystallinity and size of the NaYF4:Yb/Er/Tm microcrystals and reduce the crystal field symmetry of the activator (Er3+ and Tm3+) ions. The results show that the emission intensity of green and red light is 18.19% and 83.24% times higher than that of undoped Co2+ ion materials, respectively. Besides, the efficiency of photovoltaic cells after coating Co2+ ion doped NaYF4:Yb/Er/Tm is 2.08% higher than that of the uncoated one. This work underscores the importance of Co2+ ion doping to improve and enhance the luminescence properties of NaYF4:Yb/Er/Tm, to further enhance the efficiency of photovoltaic cells.

Prevalence of postprandial hypotension in older adults: a systematic review and meta-analysis.

BACKGROUND: Older adults with postprandial hypotension (PPH) increase susceptibility to falls, syncope, stroke, acute cardiovascular diseases and even death. However, the prevalence of this condition varies significantly across studies. We aimed to determine the prevalence of PPH in older adults. METHODS: Web of Science, PubMed, Cochrane Library, Embase and CINAHL were searched from their inception until February 2023. Search terms included 'postprandial period', 'hypotension' and 'postprandial hypotension'. Eligible studies were assessed using the Joanna Briggs Institute tool. Meta-analyses were performed among similar selected studies. RESULTS: Thirteen eligible studies were included, and data from 3,021 participants were pooled. The meta-analysis revealed a PPH prevalence of 40.5% [95% confidence interval (CI): 0.290-0.519] in older adults, and this was prevalent in the community (32.8%, 95% CI: 0.078-0.647, n = 1,594), long-term healthcare facility (39.4%, 95% CI: 0.254-0.610, n = 1,062) and geriatrics department of hospitals (49.3%, 95% CI: 0.357-0.630, n = 365). The pooled results showed significant heterogeneity (I2 > 90%), partially related to the different ages, sex, pre-prandial systolic blood pressure levels of participants, or the different criteria and methodology used to diagnose PPH. CONCLUSIONS: PPH is a prevalent condition in older adults. Further research is needed to confirm this result, and priority should be given to establishing international consensus on PPH diagnostic criteria and designing its diagnostic procedure.

Sample Preparation Methods for Targeted Single-Cell Proteomics.

We compared three cell isolation and two proteomic sample preparation methods for single-cell and near-single-cell analysis. Whole blood was used to quantify hemoglobin (Hb) and glycated-Hb (gly-Hb) in erythrocytes using targeted mass spectrometry and stable isotope-labeled standard peptides. Each method differed in cell isolation and sample preparation as follows: 1) FACS and automated preparation in one-pot for trace samples (autoPOTS); 2) limited dilution via microscopy and a novel rapid one-pot sample preparation method that circumvented the need for the solid-phase extraction, low-volume liquid handling instrumentation and humidified incubation chamber; and 3) CellenONE-based cell isolation and the same one-pot sample preparation method used for limited dilution. Only the CellenONE device routinely isolated single-cells from which Hb was measured to be 540-660 amol per red blood cell (RBC), which was comparable to the calculated SI reference range for mean corpuscular hemoglobin (390-540 amol/RBC). FACSAria sorter and limited dilution could routinely isolate single-digit cell numbers, to reliably quantify CMV-Hb heterogeneity. Finally, we observed that repeated measures, using 5-25 RBCs obtained from N = 10 blood donors, could be used as an alternative and more efficient strategy than single RBC analysis to measure protein heterogeneity, which revealed multimodal distribution, unique for each individual.

Development of the semi-dry dot-blot method for intraoperative detecting micropapillary component in lung adenocarcinoma based on proteomics analysis.

BACKGROUND: Micropapillary (MIP) component was a major concern in determining surgical strategy in lung adenocarcinoma (LUAD). We sought to develop a novel method for detecting MIP component during surgery. METHODS: Differentially expressed proteins between MIP-positive and MIP-negative LUAD were identified through proteomics analysis. The semi-dry dot-blot (SDB) method which visualises the targeted protein was developed to detect MIP component. RESULTS: Cellular retinoic acid-binding protein 2 (CRABP2) was significantly upregulated in MIP-positive LUAD (P < 0.001), and the high CRABP2 expression zone showed spatial consistency with MIP component. CRABP2 expression was also associated with decreased recurrence-free survival (P < 0.001). In the prospective cohort, the accuracy and sensitivity of detecting MIP component using SDB method by visualising CRABP2 were 82.2% and 72.7%, which were comparable to these of pathologist. Pathologist with the aid of SDB method would improve greatly in diagnostic accuracy (86.4%) and sensitivity (78.2%). In patients with minor MIP component (≤5%), the sensitivity of SDB method (63.6%) was significantly higher than pathologist (45.4%). CONCLUSIONS: Intraoperative examination of CRABP2 using SDB method to detect MIP component reached comparable performance to pathologist, and SDB method had notable superiority than pathologist in detecting minor MIP component.

Pyrotinib combined with trastuzumab and chemotherapy for the treatment of human epidermal growth factor receptor 2-positive metastatic breast cancer: a single-arm exploratory phase II trial.

PURPOSE: A substantial need for effective and safe treatment options is still unmet for patients with heavily pre-treated human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC). Herein, we assessed the efficacy and safety of pyrotinib plus trastuzumab and chemotherapy in patients with heavily treated HER2-positive MBC. METHODS: In this single-arm exploratory phase II trial, patients with HER2-positive MBC previously treated with trastuzumab plus lapatinib or pertuzumab, received pyrotinib plus trastuzumab and chemotherapy. The primary end point was progression-free survival (PFS) in the total population (TP). Secondary end points included PFS in the subgroup with brain metastases (Sub-BrM), confirmed objective response rate (ORR), clinical benefit rate (CBR), disease control rate (DCR), exploration of predictive factors of PFS, and safety. RESULTS: Between November 1, 2018, and March 31, 2021, 40 patients were eligible for this study. The median PFS reached 7.5 months (95% confidence interval [CI] 4.7 to 9.9 months) and 9.4 months (95% CI 6.6 to 12.1 months) in the TP and Sub-BrM, respectively. ORR was 50.5% (20/40). CBR was 75.5% (30/40) and DCR reached 97.5% (39/40). Cox univariate and multivariate analyses demonstrated that liver or/and lung metastases was the significant adverse prognostic factor for PFS (p = 0.018; p = 0.026; respectively). The most frequent grade 3 or 4 treatment-related adverse events were diarrhea, neutropenia and leukopenia. No new safety signals were observed. CONCLUSION: Pyrotinib plus trastuzumab and chemotherapy offered a promising option with manageable safety profile for heavily pre-treated HER2-positive MBC, especially for those without liver or/and lung metastases.

Clinical characteristics of peripherally inserted central catheter-related complications in cancer patients undergoing chemotherapy: a prospective and observational study.

PURPOSE: The incidence of peripherally inserted central catheter (PICC)-related complications is higher in cancer patients than in noncancer patients. However, the pattern of specific complication occurrence over time remains unclear. The purpose of this study was to investigate the clinical characteristics of PICC-related complications in cancer patients undergoing chemotherapy. METHODS: This prospective, observational study was conducted at a university-affiliated hospital in Western China. Cancer patients undergoing PICC insertion for anticancer treatment were recruited and followed up until the first week after catheter removal. Any complications, including occurrence time and outcomes, were recorded. The trajectory of specific PICC-related complications over time were identify based on the Kaplan‒Meier curve analysis. RESULTS: Of the 233 patients analyzed, nearly half (n = 112/233, 48.1%) developed 150 PICC-related complication events. The most common were symptomatic catheter-related thrombosis (CRT) (n = 37/233, 15.9%), medical adhesive-related skin injury (MARSI) (n = 27/233, 11.6%), and catheter dislodgement (n = 17/233, 7.3%), accounting for 54.0% (n = 81/150, 54.0%) of total complications events. According to Kaplan‒Meier curve analysis, symptomatic CRT, pain, phlebitis, and insertion site bleeding were classified as the "early onset" group mainly occurring within the first month post-insertion. Catheter fracture and catheter-related bloodstream infection were classified as the "late onset" group occurring after the second month post-insertion. MARSI, catheter dislodgement, occlusion, and insertion site infection were classified as the "persistent onset" group persistently occurring during the whole catheter-dwelling period. Among the 112 patients with PICC-related complications, 50 (44.6%) patients had their catheters removed due to complications, and 62 (55.4%) patients successfully retained their catheters until treatment completion through conventional interventions. The major reasons for unplanned catheter removal were catheter dislodgement (n = 12/233, 5.2%), symptomatic CRT (n = 10/233, 4.3%), and MARSI (n = 7/233, 3.0%), accounting for 58.0% (n = 29/50, 58.0%) of the total unplanned catheter removal cases. Catheter dwelling times between patients with complications under successful interventions (130.5 ± 32.1 days) and patients with no complications (138.2 ± 46.4 days) were not significantly different (t = 1.306, p = 0.194; log-rank test = 2.610, p = 0.106). CONCLUSIONS: PICC-related complications were pretty common in cancer patients undergoing chemotherapy. The time distribution of PICC-related complications varied, and medical staff should develop time-specific protocols for prevention. Because more than half of the patients with PICC-related complications could be managed with conventional interventions, PICCs remain a priority for cancer patients undergoing short-term chemotherapy. The study was registered in 02/08/2019 at Chinese Clinical Trial Registry (registration number: ChiCTR1900024890).

Management and follow-up of uveal effusion syndrome: a case report.

BACKGROUND: We present the management and follow-up of a case of uveal effusion syndrome (UES). CASE PRESENTATION: We study the relevant recent literature reports and review the aetiology, clinical classification, pathogenesis, diagnostic characteristics, treatment methods, and prognosis of this disease. When we encounter UES patients clinically, we can classify them according to their clinical characteristics and adopt different treatment plans for different types. The retina of this patient reattached 5 months after receiving eight periocular injections of triamcinolone acetonide (TA). CONCLUSIONS: For type III UES patients, local hormone therapy can be applied, and follow-up should be done to optimize the clinical outcome.

Effects of rehabilitation therapy based on exercise prescription on motor function and complications after hip fracture surgery in elderly patients.

BACKGROUND: Exercise rehabilitation training is an important measure for improving the prognosis of patients with hip fractures. However, the particular program that works effectively and the efficiency of exercise therapy are still controversial. OBJECTIVE: To compare the effects of usual postoperative care combined with rehabilitation based on exercise prescription on motor function and complications in elderly patients who underwent surgery for hip fracture. METHODS: This was an observational study. A total of 71 elderly patients with hip fractures who were treated with hip arthroplasty and internal fixation of the proximal femur with an intramedullary nail at Suzhou Municipal Hospital from October 2020 to December 2021 were included; 11 cases were excluded (eight cases were excluded due to loss of follow-up, two due to deaths from other causes, and one due to other reasons). Finally, 60 patients (18 males and 42 females) were included. Patients were randomly assigned to the control (n = 30) and experimental (n = 30) groups using a random number generator. Patients in the control group received usual postoperative care, whereas those in the experimental group received usual postoperative care combined with rehabilitation training based on the principles of exercise prescription. We recorded the motor function (Harris hip score), daily living ability (Barthel Index), and complications at discharge and 1, 3, and 6 months postoperatively for statistical analysis. RESULTS: The Harris hip score and Barthel Index score were significantly higher at 1, 3, and 6 months postoperatively than at discharge in both groups (p < 0.05). The Harris hip score and Barthel Index score at discharge and 1, 3, and 6 months postoperatively were significantly higher in the experimental group than in the control group (p < 0.05). The incidence of complications at 6 months postoperatively was significantly lower in the experimental group than in the control group (13% vs. 37%). CONCLUSIONS: Rehabilitation therapy based on exercise prescription helps improve hip function and the ability to perform activities of daily living and related postoperative complications after hip fracture surgery in elderly patients. The findings of our study will guide decision-making in clinical practice and improve the clinical management of hip fractures in elderly patients postoperatively.

Mongolian HCC vs. Caucasian HCC: The Metabolic Reprogramming Process in Mongolian HCC is an Interesting Difference.

Racial/ethnic and region disparities in incidence and mortality are obviously in liver cancer. Mongolia has the highest reported incidence and mortality of hepatocellular carcinoma (HCC) in the world, while the incidence of HCC is relatively low in the United States, but differences in their molecular characteristics remain largely elusive. Here we report differentially expressed genes (DEGs) in Mongolian hepatocellular carcinoma and in Caucasian HCC and their intersection DEGs, as well as their corresponding signaling pathways in Mongolian and Caucasian hepatocellular carcinoma patients based on the transcriptome sequences from Gene Expression Omnibus (GEO) database. We got 908 up-regulated genes and 1946 down-regulated genes in Mongolian HCC, 1244 up-regulated genes and 1912 down-regulated genes in Caucasian HCC, 254 Co-upregulated genes and 1035 co-downregulated genes in Mongolian and Caucasian. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that most of the genes with altered expression levels in Mongolian HCC participate in biological processes that involve metabolic reprogramming of various substances, accounting for about one-third of all biological processes. In particular, multiple amino acid biosynthesis and metabolic processes appear to be specific in Mongolian HCC compared with Caucasian HCC. The biological processes they share include those in which most immune cells are involved and cell cycle-related biological processes. In addition, we also found the genes UPP2, PCK1, GLYAT, GNMT, ADH1B and HPD, encode for key metabolic enzymes, whose expression level up-regulated or down-regulated more than 5 times in Mongolian HCC and was dramatically correlated with survival in Mongolian HCC (p value < 0.01), More importantly, these molecules are potential targets for some metabolic antitumor drugs. This study not only makes up for the shortcomings of previous studies on liver cancer, which paid more attention to its commonality, but ignored the specificity of liver cancer in different races and regions. More importantly, the purpose of this study is to identify robust molecular subclasses and information with underlying unique tumor biology. And this study may have important implications for the study of the pathogenic factors and molecular mechanisms of hepatocellular carcinoma and the precise therapy of Mongolian HCC.

Non-pharmacological interventions for older adults with postprandial hypotension: A scoping review.

BACKGROUND: Older adults frequently suffer from postprandial hypotension, associated with an increased risk of falls, syncope, acute cardiovascular and cerebrovascular diseases, and even death. Researchers use non-pharmacological interventions, but related literature is dispersed and lacks a latest summary. OBJECTIVE: The aim of this study was to map and examine non-pharmacological interventions currently employed to assist older adults with postprandial hypotension and lay a solid foundation for future studies. METHODS: This study adhered to the JBI methodology for scoping reviews and preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews. PubMed, Web of Science, Embase, Cochrane Library, CINAHL, SCOPUS, Chinese Biomedical Journal, China National Knowledge Infrastructure, VIP and WAN FANG Data were retrieved from their inception to 1 August 2022. RESULTS: Two randomized controlled trials and seven quasi-experimental studies were included. Small meals, exercise interventions, fibre with meals, green tea and water therapy have been reported to prevent postprandial hypotension effectively; however, position changes have been reported to have no impact on postprandial blood pressure decrease. Additionally, the blood pressure determination methods and test meals may affect observed trial effects. CONCLUSION: Large samples and long-term follow-up studies are needed to prove the efficacy and safety of existing non-pharmacological interventions. Future studies should develop a BP determination method based on the postprandial BP decline trajectory induced by a given test meal to improve the reliability of study results. RELEVANCE TO CLINICAL PRACTICE: This review broadly summarizes existing studies on developing and validating non-pharmacological interventions for older adults with postprandial hypotension. It also analyses special factors that may influence the trial effects. This may provide a useful reference for future research.

[Construction and Exploration of Model for Training Excellent Nursing Professionals].

The cultivation of excellent nursing professionals is an important guarantee of competent human resources essential to the implementation of the national strategy of Healthy China initiative. In the face of the health needs of the whole life cycle and the nursing development driven by emerging technologies, the training of excellence nursing professionals is confronted with new requirements and challenges. In order to cope with the new demands at home and abroad for the training of high-quality nursing staffs, meet the needs for health services that are based on precision, the whole population, the whole life cycle, and individualized care in the new era, and cultivate outstanding nursing staffs with clinical critical thinking skills, nursing decision-making skills, innovative research and practice ability, whole life cycle nursing knowledge and skills, and the ability to keep pace with the times, we wrote this paper to help clarify the needs and challenges of training excellent nursing staffs in China. Herein, taking "precision nursing of health and disease in the whole life cycle" as the core and utilizing the personnel training principle of emphasizing foundation, strengthening ability, improving quality, and promoting personality, we elaborated on the construction of the training model of excellent nursing staffs and suggested that efforts should be made in the following areas, setting up training objectives with a scientific orientation, setting up in a targeted way the knowledge system and the curriculum system, organizing the teaching mode reform into different types and implement them accordingly, making innovations in instructional methodology, and building up high-level teaching faculties. We explored for a path for training excellent nursing talents, a path that has Chinese characteristics and that can be further developed in a sustainable way, which will lay the foundation for attaining the strategic goal of Healthy China initiative.

Data-Dependent Acquisition with Precursor Coisolation Improves Proteome Coverage and Measurement Throughput for Label-Free Single-Cell Proteomics.

We combined efficient sample preparation and ultra-low-flow liquid chromatography with a newly developed data acquisition and analysis scheme termed wide window acquisition (WWA) to quantify >3,000 proteins from single cells in rapid label-free analyses. WWA employs large isolation windows to intentionally co-isolate and co-fragment adjacent precursors along with the selected precursor. Optimized WWA increased the number of MS2-identified proteins by ≈40 % relative to standard data-dependent acquisition. For a 40-min LC gradient operated at ≈15 nL/min, we identified an average of 3,524 proteins per single-cell-sized aliquot of protein digest. Reducing the active gradient to 20 min resulted in a modest 10 % decrease in proteome coverage. Using this platform, we compared protein expression between single HeLa cells having an essential autophagy gene, atg9a, knocked out, with their isogenic WT parental line. Similar proteome coverage was observed, and 268 proteins were significantly up- or downregulated. Protein upregulation primarily related to innate immunity, vesicle trafficking and protein degradation.

Deep convolutional neural network-based classification of cancer cells on cytological pleural effusion images.

Lung cancer is one of the leading causes of cancer-related death worldwide. Cytology plays an important role in the initial evaluation and diagnosis of patients with lung cancer. However, due to the subjectivity of cytopathologists and the region-dependent diagnostic levels, the low consistency of liquid-based cytological diagnosis results in certain proportions of misdiagnoses and missed diagnoses. In this study, we performed a weakly supervised deep learning method for the classification of benign and malignant cells in lung cytological images through a deep convolutional neural network (DCNN). A total of 404 cases of lung cancer cells in effusion cytology specimens from Shanghai Pulmonary Hospital were investigated, in which 266, 78, and 60 cases were used as the training, validation and test sets, respectively. The proposed method was evaluated on 60 whole-slide images (WSIs) of lung cancer pleural effusion specimens. This study showed that the method had an accuracy, sensitivity, and specificity respectively of 91.67%, 87.50% and 94.44% in classifying malignant and benign lesions (or normal). The area under the receiver operating characteristic (ROC) curve (AUC) was 0.9526 (95% confidence interval (CI): 0.9019-9.9909). In contrast, the average accuracies of senior and junior cytopathologists were 98.34% and 83.34%, respectively. The proposed deep learning method will be useful and may assist pathologists with different levels of experience in the diagnosis of cancer cells on cytological pleural effusion images in the future.

Identification of filigree pattern increases the diagnostic accuracy of micropapillary pattern on frozen section for lung adenocarcinoma.

AIMS: The presence of micropapillary (MIP) in early-stage lung adenocarcinoma is associated with a poorer prognosis, especially in patients undergoing sublobectomy. However, data on the sensitivity of frozen section (FS) evaluation of MIP is still limited. We included the concept of a filigree pattern on FS to assess its effect on the diagnostic sensitivity and specificity of MIP, and to verify its prognostic value in stage T1 lung adenocarcinoma. METHODS: A panel of five pathologists evaluated 125 patients with T1 lung adenocarcinoma from January to February 2014 as a study cohort, and 151 patients from January to February 2020 as a validation cohort. The diagnostic accuracy of the filigree and classical micropapillary (cMIP) pattern on FS was investigated. RESULTS: The diagnostic sensitivity of the MIP pattern on FS increased from 43.2% to 65.3% and 56.8% to 81.1% in the study cohort and validation cohort, respectively, and both with good specificity. Filigree not only increased the sensitivity of identifying MIP when there was an absence of cMIP, but also increased the sensitivity when the presence of a minor amount of cMIP. The almost perfect agreement among five pathologists was reached on cMIP and substantial agreement was reached on the filigree in the two cohorts. Moreover, the cMIP and filigree were both correlated with poorer recurrence-free survival (pcMIP = 0.003; pfiligree = 0.032) and overall survival (pcMIP = 0.004; pfiligree = 0.005). CONCLUSIONS: The identification of a filigree may improve the diagnostic sensitivity of the MIP pattern on FS. FS was feasible for the detection of filigree and cMIP patterns in stage T1 lung adenocarcinomas.

Ameliorative effect of allicin on vascular calcification via inhibiting endoplasmic reticulum stress.

OBJECTIVES: Vascular calcification (VC) is an independent predictor for cardiovascular events and mortality. However, there are currently no effective methods to reverse or prevent it. The present study aimed to determine the ameliorative effect of allicin on VC. METHODS: VC model of rats was induced by high-dose vitamin D3, which was valued by Alizarin Red staining, calcium contents, and alkaline phosphatase in the aorta. Systolic blood pressure, pulse pressure, and pulse wave velocity were measured to determine aortic stiffness. Protein levels were detected by Western blot. RESULTS: Allicin treatment rescued aortic VC and stiffness. The increased protein levels of RUNX2 and BMP2, two markers of osteoblastic phenotype of vascular smooth muscle cells, in the calcified aorta were attenuated by allicin, whereas the decreased levels of calponin and SM22α induced by calcification were improved. Allicin treatment significantly attenuated the increased protein levels of GRP78, GRP94, and CHOP, which are key markers of endoplasmic reticulum stress, in the calcified aorta. The activation of PERK/eIF2α/ATF4 cascades was also prevented by allicin. CONCLUSIONS: Allicin could ameliorate aortic VC and stiffness. The ameliorative effect of allicin on VC might be mediated by inhibiting PERK/eIF2α/ATF4 cascades. Our results might provide a new proof for VC treatment.

Choroidal changes in lens-induced myopia in guinea pigs.

INTRODUCTION: This study aimed to determine the role of the choroid in lens-induced myopia (LIM) in guinea pigs. METHODS: Guinea pigs were randomly divided into two groups: a normal control (NC) group and a LIM group. Refraction and axial length (AL) were measured by streak retinoscopy and A-scan ultrasonography. The choroidal thickness (ChT), vessel density of the choriocapillaris (VDCC) and vessel density of the choroidal layer (VDCL) were assessed by Spectral-domain Optical Coherence Tomography Angiography (SD-OCT). In addition, the choroidal expression of nitric oxide synthase (NOS) enzymes at the mRNA and protein levels was analyzed by real-time fluorescence quantitative PCR, enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. RESULTS: In the LIM group, refraction and AL were increased significantly compared with those in the NC group at 2 weeks (refraction: LIM vs. NC, -4.23 ± 0.43 D vs. 2.20 ± 0.48 D; AL: LIM vs. NC, 8.36 ± 0.05 mm vs. 8.22 ± 0.03 mm) and 4 weeks (refraction: LIM vs. NC, -5.88 ± 0.49 D vs. 1.63 ± 0.41 D; AL: 8.57 ± 0.06 mm vs. 8.40 ± 0.04 mm). The ChT and VDCC were decreased significantly compared with those in the NC group at 2 weeks (ChT: LIM vs. NC, 60.92 ± 8.15 µm vs. 79.11 ± 7.47 µm; VDCC: LIM vs. NC, 23.43 ± 3.85% vs. 28.74 ± 4.11%) and 4 weeks (ChT: LIM vs. NC, 48.43 ± 6.85 µm vs. 76.38 ± 7.84 µm; VDCC: LIM vs. NC, 21.29 ± 2.17% vs. 27.64 ± 2.91%). The VDCL was also decreased compared with that in the NC group at 2 weeks and 4 weeks (NC vs. LIM, 24.87 ± 5.16% vs. 22.45 ± 3.26%; 23.37 ± 5.85% vs. 21.39 ± 2.62%; all P > 0.05). Moreover, the ChT was positively correlated with the VDCC and VDCL. The mRNA and protein expression of NOS enzymes (eNOS and nNOS) was increased. CONCLUSIONS: During the development of myopia, the ChT, VDCC and VDCL were decreased, while NOS expression in the choroid was increased. The expression of NOS was negatively correlated with the ChT, VDCC and VDCL. NO may play an important role in regulating the choroid during myopia development.

Activated γδ T Cells Promote Dendritic Cell Maturation and Exacerbate the Development of Experimental Autoimmune Uveitis (EAU) in Mice.

Our previous study reveals that gamma delta (γδ) T cells were activated and dendritic cells (DCs) underwent maturation during the inflammation phase in experimental autoimmune uveitis (EAU) mice, and the interaction between DCs and γδ T cells may significantly exacerbate the development of EAU. However, the interactions between DCs and γδ T cells that can affect DCs maturation to influence EAU development must be further addressed. In this study we showed that mature DC numbers in TCR-δ-/- (KO) EAU mice were lower than those in wild-type (WT) C57BL/6 (B6) mice. The γδ T cells harvested from WT EAU mice secreted more interferon-γ (IFN-γ), however, after blocking IFN-γ, the maturation of DCs was significantly downregulated. By contrast, the percentage of IFN-γ- and IL-17-producing CD4+ T cells in KO EAU mice decreased to a greater extent than that in WT EAU mice during the inflammatory phase. Additionally, the levels of IFN-γ/IL-17 in serum were in agreement with those of CD4+ T cells. Furthermore, after activated γδ T cells injection, the inflammatory symptoms of EAU mice were more aggravated. In vitro co-cultures of both cell types showed that activated γδ T cells may induce DCs to generate higher levels of intracellular cell adhesion molecule-1 (ICAM-1/CD54), CD80, CD83, and CD86. Moreover, co-culture of the two cells may induce the activation of CD4+ T cells. Taken together, our results demonstrated that activated γδ T cells may promote DCs maturation and further enhance the generation of Th1/Th17 cells in EAU mice, resulting in exacerbated EAU.

Photocatalytic Oxidation of SO2 by TiO2: Aerosol Formation and the Key Role of Gaseous Reactive Oxygen Species.

Photocatalytic materials are proved to effectively eliminate gaseous pollutants and are widely used in the environment. However, as one of the rare experiments focusing on their influence on secondary aerosol formation generated in the gas phase (SAg), our study demonstrated the high-yield SAg formation in the photocatalysis process. In this study, the photodegradation of SO2 by TiO2 under various relative humidity (RH) conditions was deeply explored with multiple methods. Unexpectedly, H2SO4 aerosols (SAg-H2SO4) in yields of 10.10-32.64% were observed under the studied RH conditions for the first time. Gaseous •OH and H2O2 generated from the oxidation of H2O and reduction of O2 by TiO2 were directly detected in the photocatalysis process, and they were identified as the determining factor for SAg-H2SO4 formation. The formation of SAg-H2SO4 was also influenced by RH, the heterogeneous reaction of SO2, and the uptake of H2SO4. The role of the released gaseous •OH and H2O2 on atmospheric chemistry was proved to be unignorable by adopting the obtained parameters into the real environment. These findings provided direct experimental evidence of secondary pollution in the photocatalysis process and are of great significance to the field of atmospheric environment and photocatalytic materials.