Nanoelectrochemistry reveals how soluble Aß42 oligomers alter vesicular storage and release of glutamate.

Glutamate (Glu) is the major excitatory transmitter in the nervous system. Impairment of its vesicular release by ß-amyloid (Aß) oligomers is thought to participate in pathological processes leading to Alzheimer's disease. However, it remains unclear whether soluble Aß42 oligomers affect intravesicular amounts of Glu or their release in the brain, or both. Measurements made in this work on single Glu varicosities with an amperometric nanowire Glu biosensor revealed that soluble Aß42 oligomers first caused a dramatic increase in vesicular Glu storage and stimulation-induced release, accompanied by a high level of parallel spontaneous exocytosis, ultimately resulting in the depletion of intravesicular Glu content and greatly reduced release. Molecular biology tools and mouse models of Aß amyloidosis have further established that the transient hyperexcitation observed during the primary pathological stage is mediated by an altered behavior of VGLUT1 responsible for transporting Glu into synaptic vesicles. Thereafter, an overexpression of Vps10p-tail-interactor-1a, a protein that maintains spontaneous release of neurotransmitters by selective interaction with t-SNAREs, resulted in a depletion of intravesicular Glu content, triggering advanced-stage neuronal malfunction. These findings are expected to open perspectives for remediating Aß42-induced neuronal hyperactivity and neuronal degeneration.

Real-time monitoring of intracellular biochemical response in locally stretched single cell by a nanosensor.

Mechanotransduction is the essential process that cells convert mechanical force into biochemical responses, and electrochemical sensor stands out from existing techniques by providing quantitative and real-time information about the biochemical signals during cellular mechanotransduction. However, the intracellular biochemical response evoked by mechanical force has been poorly monitored. In this paper, we report a method to apply local stretch on single cell and simultaneously monitor the ensuing intracellular biochemical signals. Specifically, a ferromagnetic micropipette was fabricated to locally stretch a single cell labeled with Fe3O4 nanoparticles under the external magnetic field, and the SiC@Pt nanowire electrode (SiC@Pt NWE) was inserted into the cell to monitor the intracellular hydrogen peroxide (H2O2) production induced by the local stretch. As a proof of concept, this work quantitatively investigated the elevated amount of H2O2 levels in single endothelial cell under different stretching amplitudes. This work puts forward a new research modality to manipulate and monitor the mechanotransduction at the single-cell level.

Association of gene polymorphisms and the decreased expression of long non-coding RNA LOC553103 with rheumatoid arthritis.

BACKGROUND: Long non-coding RNAs (lncRNAs) are involved in many key bioprocesses, including the occurrence and development of rheumatoid arthritis (RA). We aimed to analyze the association of genetic variants of long non-coding RNA LOC553103 and its peripheral blood mononuclear cells (PBMC) expression with RA. METHODS: We enrolled 457 RA patients and 551 healthy controls and conducted a case-control study to analyze the relationship between LOC553103 gene rs272879 and the susceptibility of RA by TaqMan single nucleotide polymorphism genotyping. Among them, we sampled 92 cases and 92 controls, respectively, to detect the PBMC level of LOC553103 using quantitative real-time polymerase chain reaction technology. We explored the association between LOC553103 rs272879 and its PBMC expression levels in 71 RA patients. Mann-Whitney, Chi-square, and Spearman correlation analysis were used for statistical analysis and P-value <.05 was considered statistically significant. RESULTS: The genotype frequency of LOC553103 rs272879 CC was increased, and CG was decreased in RA patients compared to the control group (χ2 = 6.772, P = .034). The LOC553103 expression level in PBMC of RA patients was downregulated compared to healthy control (Z = -4.497, P < .001). Moreover, negative correlations were observed between the PBMC level of LOC553103 and erythrocyte sedimentation rate (rs = -0.262, P = .018), white blood cell count (rs = -0.382, P = .004), platelet (rs = -0.293, P = .030), and disease activity score in 28 joints (rs = -0.271, P = .016) in RA patients. CONCLUSIONS: This study provides the first evidence supporting an association between LOC553103 gene polymorphisms and susceptibility of RA and a relationship of PBMC level of LOC553103 with clinical manifestations and laboratory indicators of RA patients.

Rapidly Constructing Sodium Fluoride-Rich Interface by Pressure and Diglyme-Induced Defluorination Reaction for Stable Sodium Metal Anode.

Sodium (Na) metal is able to directly use as a battery anode but have a highly reductive ability of unavoidably occurring side reactions with organic electrolytes, resulting in interfacial instability as a primary factor in performance decay. Therefore, building stable Na metal anode is of utmost significance for both identifying the electrochemical performance of laboratory half-cells employed for quantifying samples and securing the success of room-temperature Na metal batteries. In this work, we propose an NaF-rich interface rapidly prepared by pressure and diglyme-induced defluorination reaction for stable Na metal anode. Once the electrolyte is dropped into the coin-type cells followed by a slight squeeze, the Na metal surface immediately forms a protective layer consisting of amorphous carbon and NaF, effectively inhibiting the dendrite growth and dead Na. The resultant Na metal anode exhibits a long-term cycling lifespan over 1800 h even under the area capacity of 3.0 mAh cm-2 . Furthermore, such a universal and facile method is readily applied in daily battery assembly regarding Na metal anode.

Trophoblast retrieval from the cervical canal to predict abnormal pregnancy early in gestation: a pilot study.

BACKGROUND: The current detection of fetal chromosomal abnormalities by non-invasive prenatal testing (NIPT) mainly relies on the cell free DNA(cfDNA) in the maternal blood. However, a gestational age of less than 12 weeks or a high maternal BMI affects cfDNA fetal fraction and further the detection by NIPT negatively. In this study, we aim to retrieve the trophoblast cells from the maternal cervix to develop a new sampling method for NIPT enabling an earlier use of NIPT. METHODS: We enrolled three patients who wanted to undergo induced abortion at Beijing Hospital between January 2022 and March 2022. Peripheral blood, cervix specimen, and the abortion tissue were collected and processed for each patient. Allele frequencies of the mutated gene loci of the maternal blood and the cervix sample were compared and the Sex Determining Region Y (SRY) gene was tested. RESULTS: The allele frequencies of the mutated gene loci showed no significant difference between the maternal blood and the cervix sample. But we successfully detected signal of the SRY gene in the cervix sample of the only patient carrying a male fetus. CONCLUSIONS: The detection of the SRY gene in a cervix sample indicated a successful retrieval of trophoblast cells from the cervix canal. Further study needs to be conducted to verify our finding before its application to the clinical settings.

Long-term outcomes of cable-suspended suture technique versus conventional suture for anterior vaginal wall prolapse: a retrospective cohort study.

BACKGROUND: Anterior colporrhaphy (AC) is a conventional surgical repair technique for cystocele but with high recurrence rate. We present a novel technique: Cable-suspended structure (CSS) by non-absorbable suture combined with "bridge" formation in surgical treatment of cystocele. This study aimed to evaluate and compare the long-term outcome of CSS technique for anterior vaginal wall repair with AC. METHODS: A retrospective review was performed on patients who underwent anterior vaginal wall repair between January 2012 and March 2017 at our center. All the patients were under a follow-up survey. The primary outcomes were objective cure (anterior prolapse POP-Q ≤ stage 1) and subjective cure (no symptoms of bulge or retreatment for prolapse). Secondary outcomes included quality of life (QOL) and patients' satisfaction, outcomes of site-specific POP-Q points Aa, Ba and C, as well as postoperative complications. RESULTS: Of 91 included participants, 43 underwent AC and 48 underwent CSS. The proportion of sarcrospinous ligament fixation in the CSS group was higher than in the AC group (81.4% vs. 77.1%, P < 0.05). At a median follow-up of 69 months, the CSS group showed significantly higher objective cure rate compared with the AC group (72.9% vs. 51.2%, odds ratio 2.57, 95%CI 1.07-6.16). After adjusting for sarcrospinous ligament fixation, the CSS group still significantly showed higher objective cure rate (adjusted odds ratio 2.88, 95%CI 1.16-7.21). The proportion of the patients with POP-Q 0 stage in the CSS group was particularly higher than the AC group (25% vs. 7.0%, P = 0.025). There was no difference between the groups with respect to subjective cure, patients' satisfaction and postoperative complication. CONCLUSIONS: The CSS technique showed better objective outcome than AC, however, subjective cure rate did not significantly differ between the two. Future prospective trial with large-scale should confirm the effectiveness and safety of CSS in sexually active women.

COVID-19 and inflammatory bowel disease crosstalk: From emerging association to clinical proposal.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause coronavirus disease 2019 (COVID-19), an acute respiratory inflammation that has emerged worldwide since December 2019, and it quickly became a global epidemic. Inflammatory bowel disease (IBD) is a group of chronic nonspecific intestinal inflammatory diseases whose etiology has not been elucidated. The two have many overlapping symptoms in clinical presentation, such as abdominal pain, diarrhea, pneumonia, etc. Imbalance of the autoimmune system in IBD patients and long-term use of immunosuppressive drugs may increase the risk of infection; and systemic symptoms caused by COVID-19 may also induce or exacerbate intestinal inflammation. It has been found that the SARS-CoV-2 receptor angiotensin converting enzyme 2, which is highly expressed in the lung and intestine, is an inflammatory protective factor, and is downregulated and upregulated in COVID-19 and IBD, respectively, suggesting that there may be a coregulatory pathway. In addition, the immune activation pattern of COVID-19 and the cytokine storm in the inflammatory response have similar roles in IBD, indicating that the two diseases may influence each other. Therefore, this review aimed to address the following research questions: whether SARS-CoV-2 infection leads to the progression of IBD; whether IBD increases the risk of COVID-19 infection and poor prognosis; possible common mechanisms and genetic cross-linking between the two diseases; new treatment and care strategies for IBD patients, and the feasibility and risk of vaccination in the context of the COVID-19 epidemic.

Dysregulation of non-coding RNAs mediates cisplatin resistance in hepatocellular carcinoma and therapeutic strategies.

Hepatocellular carcinoma (HCC) is the fourth major contributor to cancer-related deaths worldwide, and patients mostly have poor prognosis. Although several drugs have been approved for the treatment of HCC, cisplatin (CDDP) is still applied in treatment of HCC as a classical chemotherapeutic drug. Unfortunately, the emergence of CDDP resistance has caused HCC patients to exhibit poor drug response. How to mitigate or even reverse CDDP resistance is an urgent clinical issue to be solved. Because of critical roles in biological functional processes and disease developments, non-coding RNAs (ncRNAs) have been extensively studied in HCC in recent years. Importantly, ncRNAs have also been demonstrated to be involved in the development of HCC to CDDP resistance process. Therefore, this review highlighted the regulatory roles of ncRNAs in CDDP resistance of HCC, elucidated the multiple potential mechanisms by which HCC develops CDDP resistance, and attempted to propose multiple drug delivery systems to alleviate CDDP resistance. Recently, ncRNA-based therapy may be a feasible strategy to alleviate CDDP resistance in HCC. Meanwhile, nanoparticles can overcome the deficiencies in ncRNA-based therapy and make it possible to reverse tumor drug resistance. The combined use of these strategies provides clues for reversing CDDP resistance and overcoming the poor prognosis of HCC.

Environmental factors and risk of gout.

Gout is a chronic disease with inflammatory arthritis caused by monosodium urate (MSU) crystals deposition, an elevated serum urate level (hyperuricaemia) is the critical factor leading to MSU crystals deposition and promoting the progression of gout. The onset and development of gout is generally the result of multiple factors, such as diet, heredity and environmental factors. Although genetics and diet are thought to play as major factors, a growing body of research evidence has highlighted that environmental factors also play a significant role in the onset and exacerbation of gout. Recent studies have shown that air pollutants such as particulate matter, sulfur dioxide (SO2) and carbon monoxide (CO) may increase the risk of hospitalizations for gout, and that the changes in temperature and humidity may affect uric acid (UA) levels. There is also seasonal trend in gout. It has been demonstrated that environmental factors may induce or accelerate the production and release of pro-inflammatory mediators, causing an unbalance oxidative stress and systemic inflammation, and then participating in the overall process or a certain link of gout. Moreover, several environmental factors have shown the ability to induce the production urate and regulate the innate immune pathways, involving in the pathogenesis of gout. Nevertheless, the role of environmental factors in the etiology of gout remains unclear. In this review, we summarized the recent literatures and aimed to discuss the relationship between environmental factors (such as microclimate, season, ambient/indoor air pollution and extreme weather) and gout. We further discussed the inflammatory mechanisms of environmental factors and gout and the comprehensive effects of environmental factors on gout. We also made a prospect of the management and treatment of gout, with special consideration to environmental factors associated with gout.

Chemical Tagging Assisted Mass Spectrometry Analysis Enables Sensitive Determination of Phosphorylated Compounds in a Single Cell.

Polar phosphorylated metabolites are involved in a variety of biological processes and play vital roles in energetic metabolism, cofactor regeneration, and nucleic acid synthesis. However, it is often challenging to interrogate polar phosphorylated metabolites and compounds from biological samples. Liquid chromatography-mass spectrometry (LC/MS) now plays a central role in metabolomic studies. However, LC/MS-based approaches have been hampered by the issues of the low ionization efficiencies, low in vivo concentrations, and less chemical stability of polar phosphorylated metabolites. In this work, we synthesized paired reagents of light and heavy isotopomers, 2-(diazomethyl)phenyl)(9-methyl-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indol-2-yl)methanone (DMPI) and d3-(2-(diazomethyl)phenyl)(9-methyl-1,3,4,9-tetrahydro-2H-pyrido[3,4-b]indol-2-yl)methanone (d3-DMPI). The paired reagents of DMPI and d3-DMPI carry diazo groups that can efficiently and selectively react with the phosphate group on polar phosphorylated metabolites under mild conditions. As a proof of concept, we found that the transfer of the indole heterocycle group from DMPI/d3-DMPI to ribonucleotides led to the significant increase of ionization efficiencies of ribonucleotides during LC/MS analysis. The detection sensitivities of these ribonucleotides increased by 25-1137-fold upon DMPI tagging with the limits of detection (LODs) being between 7 and 150 amol. With the developed method, we achieved the determination of all the 12 ribonucleotides from a single mammalian cell and from a single stamen of Arabidopsis thaliana. The method provides a valuable tool to investigate the dynamic changes of polar phosphorylated metabolites in a single cell under particular conditions.

Structural mechanism for guanylate-binding proteins (GBPs) targeting by the Shigella E3 ligase IpaH9.8.

The guanylate-binding proteins (GBPs) belong to the dynamin superfamily of GTPases and function in cell-autonomous defense against intracellular pathogens. IpaH9.8, an E3 ligase from the pathogenic bacterium Shigella flexneri, ubiquitinates a subset of GBPs and leads to their proteasomal degradation. Here we report the structure of a C-terminally truncated GBP1 in complex with the IpaH9.8 Leucine-rich repeat (LRR) domain. IpaH9.8LRR engages the GTPase domain of GBP1, and differences in the Switch II and α3 helix regions render some GBPs such as GBP3 and GBP7 resistant to IpaH9.8. Comparisons with other IpaH structures uncover interaction hot spots in their LRR domains. The C-terminal region of GBP1 undergoes a large rotation compared to previously determined structures. We further show that the C-terminal farnesylation modification also plays a role in regulating GBP1 conformation. Our results suggest a general mechanism by which the IpaH proteins target their cellular substrates and shed light on the structural dynamics of the GBPs.

Association of PER2 gene single nucleotide polymorphisms with genetic susceptibility to systemic lupus erythematosus.

The circadian clock plays a crucial role in the progress of systemic lupus erythematosus (SLE). In this study, we performed a case-control study to explore the association between Period 2 (PER2) gene single nucleotide polymorphisms (SNPs) and the susceptibility of systemic lupus erythematosus (SLE). A total of 492 SLE patients and 493 healthy controls were included. The improved multiple ligase detection reaction (iMLDR) was used for genotyping. The correlations between four SNPs of PER2 (rs10929273, rs11894491, rs36124720, rs934945) and the genetic susceptibility and clinical manifestations of SLE were analyzed. Significant differences were observed in the distributions of allele frequencies and genotype under dominant model in rs11894491 between SLE patients and controls (p = 0.030, p = 022, respectively). We hypothesized that PER2 gene SNPs was related to the genetic susceptibility and clinical manifestations, implying the potential role of PER2 in the pathogenesis of SLE.

Association of MALAT-1 gene single nucleotide polymorphisms with genetic susceptibility to systemic lupus erythematosus.

Background: Abnormal expression and function of long non-coding RNAs (lncRNAs) are closely related to the pathogenesis of systemic lupus erythematosus (SLE). In this study, we aimed to investigate the association of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT-1) gene single-nucleotide polymorphisms (SNPs) with susceptibility and clinical characteristics of SLE patients. Methods: A case-control study including 489 SLE patients and 492 healthy controls was conducted. Four MALAT-1 SNPs (rs4102217, rs591291, rs11227209, and rs619586) were genotyped in all subjects, their correlation with SLE susceptibility and clinical characteristics were also analyzed. Results: Results showed that the rs4102217 locus was associated with the risk of SLE. In recessive models, the GG+CG genotype of rs4102217 was associated with the decreased risk of SLE compared to CC (p = 0.036, OR = 0.348, 95% CI: 0.124-0.975). In additive models, the GG genotype of rs4102217 was associated with the decreased risk of SLE compared to CC (p = 0.040, OR = 0.355, 95% CI: 0.127-0.996). However, no association was found between MALAT-1 gene polymorphism and clinical manifestations of SLE (all p > 0.05). Conclusion: In summary, MALAT-1 rs4102217 is associated with susceptibility to SLE, suggesting that MALAT-1 may play a role in SLE.

Quantitative Nano-amperometric Measurement of Intravesicular Glutamate Content and its Sub-Quantal Release by Living Neurons.

Quantitative measurements of intravesicular glutamate (Glu) and of transient exocytotic release contents directly from individual living neurons are highly desired for understanding the mechanisms (full or sub-quantal release?) of synaptic transmission and plasticity. However, this could not be achieved so far due to the lack of adequate experimental strategies relying on selective and sensitive Glu nanosensors. Herein, we introduce a novel electrochemical Glu nanobiosensor based on a single SiC nanowire that can selectively measure in real-time Glu fluxes released via exocytosis by large Glu vesicles (ca. 125 nm diameter) present in single hippocampal axonal varicosities as well as their intravesicular content before exocytosis. These measurements revealed a sub-quantal release mode in living hippocampal neurons, viz., only ca. one third to one half of intravesicular Glu molecules are released by individual vesicles during exocytotic events. Importantly, this fraction remained practically the same when hippocampal neurons were pretreated with L-Glu-precursor L-glutamine, while it significantly increased after zinc treatment, although in both cases the intravesicular contents were drastically affected.

Aß1-42 Oligomers Induced a Short-Term Increase of Glutamate Release Prior to Its Depletion As Measured by Amperometry on Single Varicosities.

Glutamate (Glu) is a critical neurotransmitter for neuronal communication in the nervous system. In vivo studies have shown that the concentration of Glu is reduced within the brains of those afflicted with Alzheimer's disease (AD), which is also associated with the accumulation of pathogenic amyloid-beta (Aß). However, the effects of Aß peptides on the level of Glu release, as well as how Aß-mediated Glu fluctuation is initiated, remain largely unknown. Here, we fabricated a Glu electrochemical biosensor and in situ quantitatively monitored the release of Glu from a single varicosity of Aß1-42-insulted hippocampal neurons. We found that before the depletion of Glu after 300 min of treatment with Aß1-42, a short-duration (30 min) incubation with Aß1-42 caused a dramatic increase in vesicular Glu release compared to that of a control. Further investigation demonstrated that the density of vesicular glutamate transporter 1 (VGLUT1), which is responsible for transport of Glu into synaptic vesicles, also displayed a significant elevation and then dramatic depletion with the extension of the time of treatment with Aß1-42. These results indicate that at the early stage of AD, Aß1-42 induces excessive Glu release, which may overstimulate the N-methyl-d-aspartic acid (NMDA) receptor, resulting in excitotoxicity and damage to neurons. In this work, the amount of Glu released together with its fluctuations under Aß1-42 oligomers toxicity conditions was monitored for the first time, and such monitoring could provide direct and new insights for current research on Aß1-42-induced abnormalities in neurotransmitter release and neuron functions.

Stimuli-Responsive Dipeptide-Protein Hydrogels through Schiff Base Coassembly.

Different from the conventional irreversible covalent conjugations, a simple and efficient dynamic Schiff base covalent assembly is developed to construct the stable and smart dipeptide-protein hydrogels under mild conditions. Diphenylalanine-hemoglobin hydrogel is chosen to investigate the gelation formation process and mechanism. It is found that such assembled dipeptide-protein hydrogels are sensitive to pH variation, and simultaneously the proteins can be released without changing the native secondary structures from the gels. Furthermore, these adaptive hydrogels can encapsulate a series of small molecules, multicomponent proteins, and functional nanoparticles. These versatile hydrogels may find a great potential in bioapplications.

Covalent-reaction-induced interfacial assembly to transform doxorubicin into nanophotomedicine with highly enhanced anticancer efficiency.

Herein, we show that a molecular assembly offers tremendous opportunities of affording existing building units with new physicochemical properties, holding promise in wide applications. Herein, we develop a facile covalent assembly using a natural occurring linker, genipin, to efficiently transform a traditional chemo drug, doxorubicin, into a nanophotomedicine. A possible mechanism is proposed, in which doxorubicin reacts with genipin through covalent bonding to produce poorly soluble units, which further form nuclei and mediate the interfacial assembly to generate uniform nanoparticles. Such assembled nanophotomedicine shows remarkably enhanced singlet oxygen generation ability (about 1000 folds), leading to a much higher photodynamic activity. Moreover, this self-carried nanodrug exhibits adjustable size, excellent colloidal stability, high capacity and preferable endocytosis. These favorable features lead to greatly improved anticancer efficiency under light at the same dosage, compared to that of pure doxorubin. We believe this study brings a new dimension to develop advanced drug delivery systems by molecular assembly.

Paper-Based Bipolar Electrode Electrochemiluminescence Switch for Label-Free and Sensitive Genetic Detection of Pathogenic Bacteria.

Genetic analysis is of great importance for the detection of pathogenic bacteria. Bacterial identification must become simpler, less expensive, and more rapid than the traditional methods. In this study, a low-cost, label-free, and wireless paper-based bipolar electrode electrochemiluminescence (pBPE-ECL) analysis system was constructed for the rapid and sensitive genetic detection of pathogenic bacteria. Wax-screen printing was used to form hydrophilic channels on filter paper, and a carbon ink-based bipolar electrode and driving electrodes were screen-printed into the channels. The "light-switch" molecule [Ru(phen)2dppz]2+ (phen = 1,10-phenanthroline; dppz = dipyridophenazine) was used to intercalate into the base pairs of the double-stranded DNA PCR amplification products, and the complexs were then applied to the paper-based bipolar electrode to perform the ECL assays; the ECL of [Ru(phen)2dppz]2+ is quenched in aqueous solution, but this molecule displays intense ECL when intercalated into double-stranded DNA. Under optimized experimental conditions, as little as 10 copies/µL of the genomic DNA of Listeria monocytogenes could be detected. Additionally, the system could also specifically distinguish Listeria monocytogenes from Salmonella, Escherichia coli O157:H7, and Staphylococcus aureus. This label-free, simple, and rapid method has potential in point-of-care applications for pathogen detection.

Evidence of epistatic interaction between DPP4 and CCR6 in patients with rheumatoid arthritis.

OBJECTIVE: A recent genome-wide association study identified that genetic variants in DPP4 and CCR6 are connected with a risk of RA in the Han Chinese population. The aim of this study was to estimate the epistatic interaction between DPP4 and CCR6 in RA. METHODS: Two single-nucleotide polymorphisms identified in a Han Chinese genome-wide association study (rs12617656 in DPP4, rs1854853 in CCR6) were genotyped. Logistic regression was used to estimate the multiplicative interaction and the additive interaction was analysed by 2 × 2 factorial design. RESULTS: A total of 1224 subjects (377 RA patients, 847 healthy controls) were included in the initial analysis. Additionally, 600 patients with lupus arthritis were included for comparison. Significant multiplicative interaction between DPP4 and CCR6 was observed in RA [codominant model: odds ratio (OR) = 1.49, P = 0.003]. The epistatic effect seems to be stronger in ACPA-positive RA (codominant model: OR = 1.66, P = 0.001). However, no significant multiplicative interactions were observed in ACPA-negative RA or lupus arthritis. Additive interaction analysis showed a significant epistatic effect, but only in ACPA-positive RA [attributable proportion due to interaction = 0.48 (95% CI 0.10, 0.85)]. A further replication study of an independent cohort (476 subjects) found similar results. Pooled results confirmed that there was significant interaction between DPP4 and CCR6 on both the multiplicative and additive scales. CONCLUSION: The study suggests that a genetic interaction between DPP4 and CCR6 is involved in RA susceptibility. Furthermore, these findings highlight Th17 cell response as an important contributor in the pathogenesis of RA.

Covalently Assembled Dipeptide Nanospheres as Intrinsic Photosensitizers for Efficient Photodynamic Therapy in Vitro.

Monodispersed diphenylalanine-based nanospheres with excellent biocompatibility are fabricated through a facile covalent reaction-induced assembly. Interestingly, the nanospheres exhibit red autofluorescence. Most importantly, such assembled dipeptide nanospheres can serve as intrinsic photosensitizer to convert O2 to singlet oxygen ((1) O2 ). Thus, photodynamic therapy in vitro can be achieved effectively. The versatile strategy could be extended to other biomolecules containing a primary amine group for the fabrication of potential intrinsic photosensitizers.