Optimising first-line subtyping-based therapy in triple-negative breast cancer (FUTURE-SUPER): a multi-cohort, randomised, phase 2 trial.

BACKGROUND: Triple-negative breast cancers display heterogeneity in molecular drivers and immune traits. We previously classified triple-negative breast cancers into four subtypes: luminal androgen receptor (LAR), immunomodulatory, basal-like immune-suppressed (BLIS), and mesenchymal-like (MES). Here, we aimed to evaluate the efficacy and safety of subtyping-based therapy in the first-line treatment of triple-negative breast cancer. METHODS: FUTURE-SUPER is an ongoing, open-label, randomised, controlled phase 2 trial being conducted at Fudan University Shanghai Cancer Center (FUSCC), Shanghai, China. Eligible participants were females aged 18-70 years, with an Eastern Cooperative Oncology Group performance status of 0-1, and histologically confirmed, untreated metastatic or recurrent triple-negative breast cancer. After categorising participants into five cohorts according to molecular subtype and genomic biomarkers, participants were randomly assigned (1:1) with a block size of 4, stratified by subtype, to receive, in 28-day cycles, nab-paclitaxel (100 mg/m2, intravenously on days 1, 8, and 15) alone (control group) or with a subtyping-based regimen (subtyping-based group): pyrotinib (400 mg orally daily) for the LAR-HER2mut subtype, everolimus (10 mg orally daily) for the LAR-PI3K/AKTmut and MES-PI3K/AKTmut subtypes, camrelizumab (200 mg intravenously on days 1 and 15) and famitinib (20 mg orally daily) for the immunomodulatory subtype, and bevacizumab (10 mg/kg intravenously on days 1 and 15) for the BLIS/MES-PI3K/AKTWT subtype. The primary endpoint was investigator-assessed progression-free survival for the pooled subtyping-based group versus the control group in the intention-to-treat population (all randomly assigned participants). Safety was analysed in all patients with safety records who received at least one dose of study drug. This study is registered with ClinicalTrials.gov (NCT04395989). FINDINGS: Between July 28, 2020, and Oct 16, 2022, 139 female participants were enrolled and randomly assigned to the subtyping-based group (n=69) or control group (n=70). At the data cutoff (May 31, 2023), the median follow-up was 22·5 months (IQR 15·2-29·0). Median progression-free survival was significantly longer in the pooled subtyping-based group (11·3 months [95% CI 8·6-15·2]) than in the control group (5·8 months [4·0-6·7]; hazard ratio 0·44 [95% CI 0·30-0·65]; p<0·0001). The most common grade 3-4 treatment-related adverse events were neutropenia (21 [30%] of 69 in the pooled subtyping-based group vs 16 [23%] of 70 in the control group), anaemia (five [7%] vs none), and increased alanine aminotransferase (four [6%] vs one [1%]). Treatment-related serious adverse events were reported for seven (10%) of 69 patients in the subtyping-based group and none in the control group. No treatment-related deaths were reported in either group. INTERPRETATION: These findings highlight the potential clinical benefits of using molecular subtype-based treatment optimisation in patients with triple-negative breast cancer, suggesting a path for further clinical investigation. Phase 3 randomised clinical trials assessing the efficacy of subtyping-based regimens are now underway. FUNDING: National Natural Science Foundation of China, Natural Science Foundation of Shanghai, Shanghai Hospital Development Center, and Jiangsu Hengrui Pharmaceuticals. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Transcriptomic analysis of large yellow croaker (Larimichthys crocea) reveals the suppression of the inflammatory response from Cryptocaryon irritans infection.

Large yellow croaker (Larimichthys crocea) is the most productive marine fish in China. Cryptocaryon irritans is an extremely destructive parasite that causes great economic losses in large yellow croaker aquaculture industry. Therefore, it is very necessary to study the immune response of large yellow croaker in response to C. irritans infection. In this study, the transcriptomic profiles of large yellow croaker were sequenced and analyzed in the brain and head kidney at 72 h after C. irritans infection. Cytokines and chemokines related terms were significantly enriched based on the GO enrichment of down-regulated differentially expressed genes (DEGs) from the head kidney. Meanwhile, cytokine-cytokine receptor interaction was significantly enriched based on the KEGG enrichment of up-regulated DEGs from the brain and down-regulated DEGs from the head kidney, respectively. Moreover, the majority of inflammation-related DEGs were significantly up-regulated in the brain, but distinctly down-regulated in the head kidney. These results showed that the brain and head kidney might play different roles against C. irritans infection, and the inflammatory response of large yellow croaker may be restrained during C. irritans infection. Taken together, the transcriptomic analyses will be helpful to more comprehensively understand the immune mechanism of teleost against C. irritans infection, and provide a theoretical basis for the prevention and treatment of Cryptosporidiosis.

[Mechanism of total glucosides of White Paeony Capsules in ameliorating acute lung injury based on NLRP3 inflammasome].

This study deciphered the ameliorating effect and molecular mechanism of the total glucosides of White Paeony Capsules(TGP) in the treatment of mice model with acute lung injury(ALI) via NOD-like receptor thermal protein domain associated protein 3(NLRP3) signaling pathway of the inflammasome. The study established an inflammasome activation model of primed bone marrow-derived macrophages(BMDMs), and its molecular mechanism was investigated by Western blot(WB), immunofluorescence staining, enzyme-linked immunosorbent assay(ELISA), and flow cytometry. C57BL/6J mice were randomly divided into a blank control group, a TGP group, a model group(LPS group), LPS+low-and high-dose TGP groups, LPS+MCC950 group, and LPS+MCC950+TGP group, with eight mice per group. The ALI model was induced in mice. Finally, bronchoalveolar lavage fluid(BALF) and lung tissue were collected. Lung index and lung weight wet-to-dry ratio were determined for each group of mice. The pathological changes in lung tissue were observed through hematoxylin-eosin(HE) staining. The number of neutrophils in the BALF of each group was detected using flow cytometry. The levels of interleukin(IL)-1ß, IL-6, and tumor necrosis factor(TNF)-α in the BALF were determined by ELISA. The expressions of IL-1ß, IL-18, IL-6, and TNF-α in the lung tissue were determined by real-time quantitative PCR(RT-qPCR). This study demonstrated that TGP dramatically blocked the activation of the NLRP3 inflammasome by inhibiting the production of upstream mitochondrial reactive oxygen species(mtROS) and the subsequent oligomerization of apoptosis-associated specks(ASC). Additionally, in the ALI mice model, compared with the blank control group, the model group showed alveolar structure rupture, thic-kening of alveolar septa, and dramatically increased lung index, lung weight wet-to-dry ratio in lung tissue, neutrophil count, and inflammatory factor levels. Compared with the model group, the pathological morphology of lung tissue was significantly ameliorated in the TGP and MCC950 groups, and the lung index and lung weight wet-to-dry ratio were significantly reduced. Neutrophil counts were reduced, and levels of inflammatory factors were significantly downregulated. Notably, compared with the MCC950 group, there was no significant difference in effect in the MCC950+TGP group. Collectively, the study reveals that TGP may ameliorate ALI in mice by inhibiting the activation of NLRP3 inflammasome, providing a safe and effective drug candidate for the prevention or treatment of ALI/ARDS.

Protein-Scaffolded DNA Nanostructures for Imaging of Apurinic/Apyrimidinic Endonuclease 1 Activity in Live Cells.

Nucleic acids are valuable tools for intracellular biomarker detection and gene regulation. Here we propose a new type of protein (avidin)-scaffolded DNA nanostructure (ADN) for imaging the activity of apurinic/apyrimidinic endonuclease 1 (APE1) in live cells. ADN is designed by assembling an avidin-displayed abasic site containing DNA strands labeled with a fluorophore or a quencher via a complementary linker strand. ADN is nonemissive due to the close proximity of fluorophores and quenchers. APE1-mediated cleavage separates the fluorophores from the quenchers, delivering activated fluorescence. In vitro assays show that ADN is responsive to APE1 with high sensitivity and high specificity. ADN can efficiently enter the cells, and its capability to visualize and detect intracellular APE1 activities is demonstrated in drug-treated cells and different cell lines. The modular and easy preparation of our nanostructures would afford a valuable platform for imaging and detecting APE1 activities in live cells.

Ipsilateral breast tumor recurrence after breast-conserving surgery: insights into biology and treatment.

Despite modern surgical and irradiation techniques, ipsilateral breast tumor recurrence (IBTR) accounts for 5-15% of all cancer recurrence in women treated with breast conservative treatment. Historically, this event has been treated definitively with salvage mastectomy and completion axillary clearance. However, many local recurrences are small and without nodal involvement at presentation. Thus, there has been an interest in performing a surgical de-escalation procedure in the breast and the axilla. The current guidelines do not provide detailed descriptions and treatment suggestions for these selected patients, resulting in inconsistent treatment strategies. Moreover, the methods to define true recurrence (TR) and new primary tumor (NP) for IBTR remain controversial. Most developed classification methods mainly rely on clinical and pathological criteria, limiting the accuracy of the discerption and causing misclassification. In this editorial, we will discuss the current trends in surgical de-escalation for patients with IBTR. Moreover, we will focus on recent IBTR innovations, highlighting molecular-integrated classification and multimodal staging methods for clinical practice and postoperative surveillance strategies.

Omission of axillary surgery for ipsilateral breast tumor recurrence with negative nodes after previous breast-conserving surgery: is it oncologically safe?

PURPOSE: Salvage mastectomy is traditionally recommended for patients who developed ipsilateral breast tumor recurrence (IBTR) in light of previous breast irradiation. However, it remains controversial whether surgical axillary staging (SAS) is necessary for IBTR patients with negative nodes. This study aimed to evaluate the oncologic safety of omitting SAS for IBTR. METHODS: We retrospectively identified patients who developed invasive IBTR with negative nodes after undergoing breast-conserving surgery (BCS) from 2010 to 2018. Patterns of care in nodal staging were analyzed based on prior axillary staging status. Clinicopathologic characteristics and adjuvant treatment of the initial tumor, as well as the IBTR, were compared between the SAS and no SAS groups. Kaplan-Meier method and Cox regression model were utilized to compare the locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), and overall survival (OS) rates after IBTR removal between the two groups. RESULTS: A total of 154 IBTR patients were eligible for final analysis. Compared to the no SAS group, SAS group was less likely to undergo ALND (15.1 vs 73.3%, p < 0.001) at initial BCS, had a longer recurrence interval (2.8 vs 2.1 years, p = 0.03), and were more likely to have discordant molecular subtype (35.8 vs 12.9%, p = 0.001) and different quadrant location (37.7 vs 19.8%, p = 0.02) with primary tumor. However, the extent of axillary staging did not affect systemic or radiation recommendations. In the subgroup of patients without previous ALND, the clinicopathologic characteristics were roughly comparable. No significant differences were observed in LRRFS, DMFS or OS between the two groups. CONCLUSION: For node-negative IBTR patients, we observed selection bias on the basis of prior ALND, shorter recurrence interval, and concordant molecular subtype favoring no SAS but comparable LRRFS, DMFS, and OS. These results support a wider consideration of sparing SAS in the management of IBTR, especially in patients without previous ALND.

Late-Stage Dehydroxyazidation of Alcohols Promoted by Trifunctional Hypervalent Azido-Iodine(III) Reagents.

The development of convenient new methods for the synthesis of organic azides is highly desirable. Herein, we report a practical method for dehydroxyazidation of alcohols via an SN 2 pathway involving PPh3 and trifunctional benziodazolone-based hypervalent azido-iodine(III) reagents, which function as an electrophilic center, an azido source, and a base. This mild, chemoselective method was used for late-stage azidation of structurally complex alcohols, as well as for a new synthetic route to the antiepileptic drug rufinamide. The reaction mechanism was also investigated both experimentally and computationally.

Changes of Choroidal Thickness in Children after Short-erm Application of 1% Atropine Gel.

INTRODUCTION: To assess changes of choroidal thickness (ChT) after administration of 1% atropine for 1 week in myopia, emmetropia, and hyperopia children. METHODS: A total of 235 children aged 4-8 years, which included 46 myopia, 34 emmetropia, and 155 hyperopia patients were recruited and divided into three groups according to the spherical equivalent with the use of 1% atropine twice a day for 1 week. The ChT was measured at baseline and 1 week. RESULTS: In the myopia and emmetropia groups, following administration of 1% atropine gel, the ChT thickened significantly under the fovea (i.e., from 278.29 ± 53.01 µm to 308.24 ± 57.3 µm, P < 0.05; from 336.10 ± 78.60 µm to 353.46 ± 70.22 µm, P < 0.05, respectively) and at all intervals from the fovea, while in the hyperopia group, there was no significant difference in the ChT except the nasal side (P < 0.05) . CONCLUSION: Topical administration of 1% atropine gel for 1 week significantly increased the subfoveal and parafoveal ChT in children with myopia and emmetropia. Atropine did not increase the ChT in hyperopia children, except at the nasal side.

Systematic insight into the active constituents and mechanism of Guiqi Baizhu for the treatment of gastric cancer.

Traditional Chinese medicine treatment of diseases has been recognized, but the material basis and mechanisms are not clear. In this study, target prediction of the antigastric cancer (GC) effect of Guiqi Baizhu (GQBZP) and the analysis of potential key compounds, key targets, and key pathways for the therapeutic effects against GC were carried out based on the method of network analysis and Kyoto Encyclopedia of Genes and Genomes enrichment. There were 33 proteins shared between GQBZP and GC, and 131 compounds of GQBZP had a high correlation with these proteins, indicating that the PI3K-AKT signaling pathway might play a key role in GC. From these studies, we selected human epidermal growth factor receptor 2 (HER2) and programmed cell death 1-ligand 1 (PD-L1) for docking; the results showed that 385 and 189 compounds had high docking scores with HER2 and PD-L1, respectively. Six compounds were selected for microscale thermophoresis (MST). Daidzein/quercetin and isorhamnetin/formononetin had the highest binding affinity for HER2 and PD-L1, with Kd values of 3.7 µmol/L and 490, 667, and 355 nmol/L, respectively. Molecular dynamics simulation studies based on the docking complex structures as the initial conformation yielded the binding free energy between daidzein/quercetin with HER2 and isorhamnetin/formononetin with PD-L1, calculated by molecular mechanics Poisson-Boltzmann surface area, of -26.55, -14.18, -19.41, and -11.86 kcal/mol, respectively, and were consistent with the MST results. In vitro experiments showed that quercetin, daidzein, and isorhamnetin had potential antiproliferative effects in MKN-45 cells. Enzyme activity assays showed that quercetin could inhibit the activity of HER2 with an IC50 of 570.07 nmol/L. Our study provides a systematic investigation to explain the material basis and molecular mechanism of traditional Chinese medicine in treating diseases.

Clinical observation of the regeneration process of defects after breast cancer resection.

BACKGROUND: The present study aims to use two different kinds of filling materials, oxidized regenerated cellulose and gelatin sponge, to repair defects of breast-conserving surgery due to breast cancer, and compare the clinical efficacy, cosmetic effect and complication rate among groups. METHODS: A total of 125 patients, who had breast -conserving surgery due to breast cancer, were enrolled into the present study. Postoperative efficacy was assessed by a doctor and patient, according to the Harvard/NSABP/RTOG Breast Cosmetic Grading Scale. RESULTS: Among these patients, 41 patients received conventional breast-conserving surgery, and 84 patients received breast-conserving surgery plus filling implantation (41 patients in the oxidized regenerated cellulose group and 43 patients in the gelatin sponge group). All patients had small to medium sized breasts (cup size A and B). The average weight of tumor tissues was 56.61 ± 11.57 g in the conventional breast-conserving surgery group, 58.41 ± 8.53 g in the oxidized regenerated cellulose group, and 58.77 ± 9.90 g in the gelatin sponge group. The difference in pathological factors, average operation time, length of stay and local infection rate was not statistically significant among the three groups. 18 patients in the oxidized regenerated cellulose group and 15 patients in the gelatin sponge group were evaluated to have a good cosmetic effect by the surgeon and patient, while 12 patients in the conventional breast-conserving surgery group were evaluated to be have good cosmetic effect by the surgeon and patient. The cosmetic effects in the oxidized regenerated cellulose group and gelatin sponge group were comparable, and these were superior to those in the conventional breast-conserving surgery group. CONCLUSION: The use of oxidized regenerated cellulose and gelatin sponge is a feasible approach for defect repair after breast-conserving surgery.

Metabolomics Tools Assisting Classic Screening Methods in Discovering New Antibiotics from Mangrove Actinomycetia in Leizhou Peninsula.

Mangrove actinomycetia are considered one of the promising sources for discovering novel biologically active compounds. Traditional bioactivity- and/or taxonomy-based methods are inefficient and usually result in the re-discovery of known metabolites. Thus, improving selection efficiency among strain candidates is of interest especially in the early stage of the antibiotic discovery program. In this study, an integrated strategy of combining phylogenetic data and bioactivity tests with a metabolomics-based dereplication approach was applied to fast track the selection process. A total of 521 actinomycetial strains affiliated to 40 genera in 23 families were isolated from 13 different mangrove soil samples by the culture-dependent method. A total of 179 strains affiliated to 40 different genera with a unique colony morphology were selected to evaluate antibacterial activity against 12 indicator bacteria. Of the 179 tested isolates, 47 showed activities against at least one of the tested pathogens. Analysis of 23 out of 47 active isolates using UPLC-HRMS-PCA revealed six outliers. Further analysis using the OPLS-DA model identified five compounds from two outliers contributing to the bioactivity against drug-sensitive A. baumannii. Molecular networking was used to determine the relationship of significant metabolites in six outliers and to find their potentially new congeners. Finally, two Streptomyces strains (M22, H37) producing potentially new compounds were rapidly prioritized on the basis of their distinct chemistry profiles, dereplication results, and antibacterial activities, as well as taxonomical information. Two new trioxacarcins with keto-reduced trioxacarcinose B, gutingimycin B (16) and trioxacarcin G (20), together with known gutingimycin (12), were isolated from the scale-up fermentation broth of Streptomyces sp. M22. Our study demonstrated that metabolomics tools could greatly assist classic antibiotic discovery methods in strain prioritization to improve efficiency in discovering novel antibiotics from those highly productive and rich diversity ecosystems.

Phage-Guided Targeting, Discriminative Imaging, and Synergistic Killing of Bacteria by AIE Bioconjugates.

New agents with particular specificity toward targeted bacteria and superefficacy in antibacterial activity are urgently needed in facing the crisis of worldwide antibiotic resistance. Herein, a novel strategy by equipping bacteriophage (PAP) with photodynamic inactivation (PDI)-active AIEgens (luminogens with aggregation-induced emission property) was presented to generate a type of AIE-PAP bioconjugate with superior capability for both targeted imaging and synergistic killing of certain species of bacteria. The targeting ability inherited from the bacteriophage enabled the bioconjugates to specifically recognize the host bacteria with preserved infection activity of phage itself. Meanwhile, the AIE characteristic empowered them a monitoring functionality, and the real-time tracking of their interactions with targets was therefore realized via convenient fluorescence imaging. More importantly, the PDI-active AIEgens could serve as powerful in situ photosensitizers producing high-efficiency reactive oxygen species (ROS) under white light irradiation. As a result, selective targeting and synergistic killing of both antibiotic-sensitive and multi-drug-resistant (MDR) bacteria were successfully achieved in in vitro and in vivo antibacterial tests with excellent biocompatibility. This novel AIE-phage integrated strategy would diversify the existing pool of antibacterial agents and inspire the development of promising drug candidates in the future.

Decreased cpg15 augments oxidative stress in sleep deprived mouse brain.

Sleep deprivation (SD) has detrimental effects on the physiological function of the brain. However, the underlying mechanism remains elusive. In the present study, we investigated the expression of candidate plasticity-related gene 15 (cpg15), a neurotrophic gene, and its potential role in SD using a REM-SD mouse model. Immunofluorescent and Western blot analysis revealed that the expression of cpg15 protein decreased in the hippocampus, ventral group of the dorsal thalamus (VENT), and somatosensory area of cerebral cortex (SSP) after 24-72 h of REM-SD, and the oxidative stress in these brain regions was increased in parallel, as indicated by the ratio of glutathione (GSH) to its oxidative product (GSSG). Over-expression of cpg15 in thalamus, hippocampus, and cerebral cortex mediated by AAV reduced the oxidative stress in these regions, indicating that the decrease of cpg15 might be a cause that augments oxidative stress in the sleep deprived mouse brain. Collectively, the results imply that cpg15 may play a protective function in the SD-subjected mouse brain via an anti-oxidative function. To our knowledge, this is the first time to provide evidences in the role of cpg15 against SD-induced oxidative stress in the brain.

Structural Basis for a Quadratic Relationship between Electronic Absorption and Electronic Paramagnetic Resonance Parameters of Type 1 Copper Proteins.

Type 1 copper (T1Cu) proteins play important roles in electron transfer in biology, largely due to the unique structure of the T1Cu center, which is reflected by its spectroscopic properties. Previous reports have suggested a correlation between a high ratio of electronic absorbance at ∼450 nm to that at ∼600 nm (R = A450/A600) and a large copper(II) hyperfine coupling in the z direction (Az) in electron paramagnetic resonance (EPR). However, this correlation does not have a clear physical meaning, nor does it hold for many proteins with a perturbed T1Cu center. To address this issue, a new parameter of R' [A450/(A450 + A600)] with a better physical meaning of a fractional SCys pseudo-σ to Cu(II) charge transfer transition intensity is defined and a quadratic relationship between R' and Az is found on the basis of a comprehensive analysis of ultraviolet-visible absorption, EPR, and structural parameters of T1Cu proteins. We are able to find good correlations between R' and the displacement of copper from the trigonal plane defined by the His2Cys ligands and the angle between the NHis1-Cu-NHis2 plane and the SCys-Cu-axial ligand plane, providing a structural basis for the observed correlation. These findings and analyses provide a new framework for a deeper understanding of the spectroscopic and electronic properties of T1Cu proteins, which may allow better design and applications of this important class of proteins for redox and electron transfer functions.

In Silico Typing and Comparative Genomic Analysis of IncFIIK Plasmids and Insights into the Evolution of Replicons, Plasmid Backbones, and Resistance Determinant Profiles.

IncFIIK plasmids are associated with the acquisition and dissemination of multiple-antimicrobial resistance in Klebsiella pneumoniae and often encountered in clinical isolates of this species. Since the phylogeny and evolution of IncFIIK plasmids remain unclear, here we performed large-scale in silico typing and comparative analysis of these plasmids in publicly available bacterial/plasmid genomes. IncFIIK plasmids are prevalent in K. pneumoniae, being found in 69% of sequenced genomes, covering 66% of sequenced STs (sequence types), but sparse in other Enterobacteriaceae IncFIIK replicons have three lineages. One IncFIIK allele could be found in distinct K. pneumoniae STs, highlighting the lateral genetic flow of IncFIIK plasmids. A set of 77 IncFIIK plasmids with full sequences were further analyzed. A pool of 327 antibiotic resistance genes or remnants were annotated in 75.3% of these plasmids. Plasmid genome comparison reiterated that they often contain other replicons belonging to IncFIA, IncFIB, IncFIIYp, IncFIIpCRY, IncR, IncL, and IncN groups and that they share a conserved backbone featuring an F-like conjugation module that has divergent components responsible for regulation and mating pair stabilization. Further epidemiological studies of IncFIIK plasmids are required due to the sample bias of K. pneumoniae genomes in public databases. This study provides insights into the evolution and structures of IncFIIK plasmids.

Effect of graft size matching on pediatric living-donor liver transplantation at a single center.

We retrospectively analyzed 252 patients with end-stage liver disease who had undergone LDLT from January 2009 to September 2015. Of these, 25 had a GRWR of <2.0% (Group A), 204 had a GRWR of ≥2.0% or <4.0% (Group B), and 23 had a GRWR ≥4.0% (Group C). The three GRWR groups demonstrated similar characteristics, except for recipient age and recipient BMI. The overall 1-, 2-, and 3-year graft survival rates were 95.1%, 93.5%, and 93.5%, respectively. However, among the three groups, graft survival rates at 1 year, 2 years, and 3 years were significantly different (P = .0009). Hepatic artery stenosis/thrombosis was more frequently observed in Group C than in Groups A and B (P = .001). Wound infection was also more frequently observed in Group C than in Group A and B (P = .002). However, intestinal fistula/bile leakage/biliary-enteric anastomotic fistula was more frequently observed in Group A than in Groups B and C (P = .001). In addition, reoperation more frequently occurred in Group A and C than in Group B (P = .001). Recipients with a GRWR between 2.0% and 4.0% had significantly better graft survival rates.

The expression change of RORγt, BATF, and IL-17 in Chinese vitiligo patients with 308 nanometers excimer laser treatment.

This study aims to explore the expression of RORγt, BATF, and IL-17 in Chinese vitiligo patients with 308 nm excimer laser treatment. One hundred and sixty-four vitiligo patients treated with 308 nm excimer laser were enrolled as Case group and 137 health examiners as Control group. Quantitative real-time polymerase chain reaction and immunohistochemistry were conducted to detect the expressions of RORγt, BATF, and IL-17. Expression of RORγt, BATF, IL-17A, and IL-17F were higher in Case group than Control group, with the diagnostic accuracy of 88.04, 87.38, 97.34, and 89.04%, respectively. Pearson correlation analysis showed a positive correlation in RORγt, BATF, IL-17A, and IL-17F mRNAs in vitiligo patients. Moreover, their expressions were higher in active vitiligo patients than stable ones. Besides, the expressions of RORγt, BATF, IL-17A, and IL-17F in vitiligo skin were significantly higher than those in non lesional skin and normal controls. After treatment, their expressions were significantly decreased. Active vitiligo and the high expressions of RORγt, BATF, and IL-17F were the independent risk factors for the ineffectiveness of 308 nm excimer laser treatment. The expressions of RORγt, BATF, IL-17 were significantly enhanced in vitiligo patients, which were correlated with the activity of vitiligo and 308 nm excimer laser therapeutic effects.

Smart Collaborative Caching for Information-Centric IoT in Fog Computing.

The significant changes enabled by the fog computing had demonstrated that Internet of Things (IoT) urgently needs more evolutional reforms. Limited by the inflexible design philosophy; the traditional structure of a network is hard to meet the latest demands. However, Information-Centric Networking (ICN) is a promising option to bridge and cover these enormous gaps. In this paper, a Smart Collaborative Caching (SCC) scheme is established by leveraging high-level ICN principles for IoT within fog computing paradigm. The proposed solution is supposed to be utilized in resource pooling, content storing, node locating and other related situations. By investigating the available characteristics of ICN, some challenges of such combination are reviewed in depth. The details of building SCC, including basic model and advanced algorithms, are presented based on theoretical analysis and simplified examples. The validation focuses on two typical scenarios: simple status inquiry and complex content sharing. The number of clusters, packet loss probability and other parameters are also considered. The analytical results demonstrate that the performance of our scheme, regarding total packet number and average transmission latency, can outperform that of the original ones. We expect that the SCC will contribute an efficient solution to the related studies.