Human cytomegalovirus infection activates NLRP3 inflammasome by releasing mtDNA into the cytosol in human THP-1 cells.

Human cytomegalovirus (HCMV) infection of monocytes results in the production of inflammatory cytokine through inflammasome. However, the mechanism of NLR family pyrin domain containing 3 (NLRP3) inflammasome activation in HCMV infection remains unclear. In this study, HCMV infection promoted the increase of mitochondrial fusion and caused mitochondrial dysfunction in THP-1 cells, including excessive reactive oxygen species production and decreased mitochondrial membrane potential (Δψm). Meanwhile, the expression of mitochondrial DNA (mtDNA)-binding protein TFAM (transcription factor A, mitochondrial) was decreased and mtDNA content in the cytoplasm was increased. Knockdown of TFAM caused an increase in mtDNA copy number in the cytoplasm and resulted in elevated NLRP3 expression, active caspase-1, and mature IL-1ß. After a 3 h treatment with MCC950, an NLRP3 inhibitor, the increase of cleaved caspase-1 and mature IL-1ß were suppressed. Besides, overexpression of TFAM inhibited the expression of NLRP3, cleaved caspase-1, and mature IL-1ß. In addition, knockdown of NLRP3 inhibited the IL-1ß process after HCMV infection. mtDNA-deficient cells showed a limited ability to produce NLRP3 and process IL-1ß after HCMV infection. In conclusion, HCMV infection of THP-1 cells resulted in decreased mitochondrial TFAM protein expression and increased mtDNA release into the cytoplasm, which eventually led to the activation of NLRP3 inflammasome.

Ultrasensitive tapered optical fiber refractive index glucose sensor.

Refractive index (RI) sensors are of great interest for label-free optical biosensing. A tapered optical fiber (TOF) RI sensor with micron-sized waist diameters can dramatically enhance sensor sensitivity by reducing the mode volume over a long distance. Here, a simple and fast method is used to fabricate highly sensitive refractive index sensors based on localized surface plasmon resonance (LSPR). Two TOFs (l = 5 mm) with waist diameters of 5 µm and 12 µm demonstrated sensitivity enhancement at λ = 1559 nm for glucose sensing (5-45 wt%) at room temperature. The optical power transmission decreased with increasing glucose concentration due to the interaction of the propagating light in the evanescent field with glucose molecules. The coating of the TOF with gold nanoparticles (AuNPs) as an active layer for glucose sensing generated LSPR through the interaction of the evanescent wave with AuNPs deposited at the tapered waist. The results indicated that the TOF (Ø = 5 µm) exhibited improved sensing performance with a sensitivity of 1265%/RIU compared to the TOF (Ø = 12 µm) at 560%/RIU towards glucose. The AuNPs were characterized using scanning electron microscopy and ultraviolent-visible spectroscopy. The AuNPs-decorated TOF (Ø = 12 µm) demonstrated a high sensitivity of 2032%/RIU toward glucose. The AuNPs-decorated TOF sensor showed a sensitivity enhancement of nearly 4 times over TOF (Ø = 12 µm) with RI ranging from 1.328 to 1.393. The fabricated TOF enabled ultrasensitive glucose detection with good stability and fast response that may lead to next-generation ultrasensitive biosensors for real-world applications, such as disease diagnosis.

Mitofusin 1-Mediated Redistribution of Mitochondrial Antiviral Signaling Protein Promotes Type 1 Interferon Response in Human Cytomegalovirus Infection.

One of the most potent anti-human cytomegalovirus (HCMV) immune mechanisms possessed by host cells is type I interferon (IFN1), which induces the expression of IFN-stimulated genes (ISGs). During this process, mitochondria play an important role in the IFN1 response, and mitofusin 1 (MFN1) is a key regulator of mitochondrial fusion located on the outer mitochondrial membrane. However, the underlying mechanism of MFN1's promotion of IFN1 during HCMV infection still remains unknown. In this study, HCMV infection promoted IFN1 production and enhanced ISG expression. Meanwhile, it promoted the increase of mitochondrial fusion in THP-1 cells and peripheral blood mononuclear cells (PBMCs), especially the expression of MFN1. Phosphorylation of tank binding kinase 1 (p-TBK1), interferon regulatory factor 3 (p-IRF3), and ISGs was significantly decreased in MFN1 or mitochondrial antiviral signaling protein (MAVS)-knockdown THP-1 cells, and MFN1 was constitutively associated with MAVS, positively regulated mitochondrial fusion, and IFN1 production. Knockdown of MFN1 inhibited the MAVS redistribution without affecting the MAVS expression, whereas the HCMV-induced IFN1 production decreased. Conversely, leflunomide could induce the expression of MFN1, thereby producing IFN1 and stimulating the expression of ISG in leflunomide-treated THP-1 cells. These observations reveal that HCMV infection leads to MFN1-mediated redistribution of MAVS and then induces an antiviral response of IFN1 and that the MFN-agonist leflunomide promotes IFN1 responses and may serve as a potential anti-HCMV therapy. IMPORTANCE Human cytomegalovirus (HCMV) infection is ubiquitous and is often asymptomatic in healthy individuals, but it can cause great damage to newborns, AIDS patients, and other immune deficiency patients. In this study, we found that HCMV infection caused mitochondrial fusion, and expression of mitofusin 1 (MFN1), which is a protein associated with mitochondrial antiviral signaling protein (MAVS), positively regulates mitochondrial fusion and HCMV-induced IFN1 response. Knockdown of MFN1 or MAVS can inhibit the HCMV-induced IFN1 production. What is more, confocal laser-scanning microscope showed that knockdown of MFN1 inhibits the HCMV-induced redistribution of MAVS. Conversely, MFN1 agonist leflunomide could induce IFN1 production. In conclusion, we provide new insight into the relationship between MFN1 and IFN1 during HCMV infection and show that MFN1 may serve as a potential strategy against HCMV infection.

Chronic Pediatric Immune Thrombocytopenia Is Not Associated With Herpes Virus Infection Status.

Background: Immune thrombocytopenia (ITP) is characterized by non-chronic (transient, <12 months) and chronic (≥12 months) decline in the number of platelets. Herpes virus infections have been shown, in many studies, to be associated with the development of ITP. However, it remains unclear whether the herpes virus infection status is associated with the chronic ITP. Methods: We reviewed 480 primary pediatric patients with ITP in the period from January 2017 to December 2019. The prevalence of herpes virus antibodies including the Cytomegalovirus (CMV), Herpes simplex virus 1 (HSV-1), Herpes simplex virus 2 (HSV-2), and Epstein Barr virus were recorded. The levels of serum complement C3 and C4, T (CD3+, CD4+, CD8+), B (CD19+) lymphocytes, and natural killer (CD16+ 56+) cells were also analyzed. Multivariate analysis was used to evaluate the associations between chronic ITP and herpes virus infection status. Results: Compared with non-chronic, patients with chronic ITP had older age (≥3 years), lower levels of hemoglobin and complement C3, and lower probability of CMV and HSV-2 infections (IgM positive; p < 0.05). Patients with herpes virus infection had lower serum platelet counts (p < 0.001), lower complement C3 levels and lower CD4+/CD8+ cells ratio (p < 0.05). Furthermore, platelet counts were positively correlated with CD4+/CD8+ cells ratios (r = 0.519; p = 0.0078), and negatively correlated with T cells (CD3+: r = -0.458, p = 0.0213; CD8+: r = -0.489, p = 0.0131). Multivariate analysis showed that age (OR, 1.644; 95%CI, 1.007-2.684; p = 0.047) was an adverse risk factor for chronic ITP and CMV IgM positive (OR, 0.241; 95%CI, 0.072-0.814; p = 0.022) had lower risk of chronic ITP development, while other herpes virus infection statuses and clinical features were not. Conclusion: Although herpes virus infections were associated with the onset of ITP, our findings indicated that herpes virus infection status might not be a risk factor for chronic ITP.

The Value of High-Sensitivity C-reactive Protein in Evaluating Myocardial Damage and the Prognosis in Children with Mycoplasmal Pneumonia.

OBJECTIVE: To investigate the value of high-sensitivity C-reactive protein (hs-CRP) in evaluating the myocardial damage and prognosis in children with mycoplasmal pneumonia. MATERIALS: A total of 150 children with mycoplasmal pneumonia were selected. According to their serum creatine kinase isoenzyme (CK-MB) level, they were divided into 72 cases of the myocardial damage group and 78 cases of the non-myocardial damage group. Eighty healthy children undergoing physical examination were selected as the control group. The electrocardiography results and serum CK-MB and hs-CRP levels were compared among the subjects. The correlations among the above indexes were analyzed. RESULTS: The levels of hs-CRP and CK-MB in the myocardial damage group were significantly higher than those in the nonmyocardial damage group and control group, respectively (P<0.05). The rates of abnormal hs-CRP and abnormal electrocardiogram in the myocardial damage group were significantly higher than those in the non-myocardial damage group, respectively (P<0.05). In the 150 children with mycoplasmal pneumonia, the serum hs-CRP and CK-MB levels were positively correlated (P<0.001), and the abnormal hs-CRP rate was positively correlated with the abnormal electrocardiogram rate (P<0.001). In the myocardial damage group, the serum levels of hs-CRP and CK-MB after treatment were significantly lower than those before treatment, respectively (P<0.05). After treatment, each index in the myocardial damage group had no significant difference with those in the control group (P>0.05). CONCLUSION: hs-CRP may be an important index for evaluating the myocardial damage and prognosis in children with mycoplasmal pneumonia. The combination of hs-CRP and CK-MB detection has obvious guiding significance for the monitoring and treatment of mycoplasmal pneumonia complicated by myocardial damage.

Label-free tapered optical fiber plasmonic biosensor.

We designed and fabricated a novel label-free ultrasensitive tapered optical fiber (TOF) plasmonic biosensor that successfully detected a five panel of microRNAs with good selectivity. The biosensing platform integrates three different metallic nanoparticles: gold spherical nanoparticles (AuNPs), gold nanorods (AuNRs), and gold triangular nanoprisms (AuTNPs) laminated TOF to enhance the evanescent mode. The dip in the intensity profile of the transmission spectrum corresponded to the specific wavelength of the nanoparticle. The AuTNPs laminated TOF was found to exhibit the highest refractive index sensitivity and was therefore used to assay the panel of microRNAs. Single stranded DNA probes were self-assembled on the AuTNPs TOF plasmonic biosensors to achieve the highest sensitivity from the formation of hydrogen bonds between the ssDNAs and the target microRNAs. Experimentally, we observed that by measuring the spectral shifts, a limit of detection (LOD) between 103 aM and 261 aM for the panel of microRNAs can be achieved. Additionally, the ssDNA layer immobilized on the TOF plasmonic biosensor resulted in an extended dynamic range of 1 fM - 100 nM. In human serum solution, clinically relevant concentration of the panel of microRNAs were successfully detected with a LOD between 1.097 fM to 1.220 fM. This is the first report to demonstrate the applicability of our TOF plasmonic biosensor approach to detect a panel of microRNAs. This simple yet highly sensitive approach can provide a high-throughput and scalable sensor for detecting and quantifying large arrays of microRNAs, thereby expanding the applications of biosensors.

Analysis of mycoplasma pneumoniae infection among children with respiratory tract infections in hospital in Chengdu from 2014 to 2020.

BACKGROUND: Respiratory tract infection (RTIs) is one of common diseases among the children. In recent years, the incidence of mycoplasma pneumoniae (M. pneumoniae) infection rate has been increasing, which cause respiratory tract infection. This study sought to analyze the epidemiological characteristics of M. pneumoniae hospitalized children with RTIs to provide a theoretical basis for clinical diagnosis and treatments in Chengdu, China. METHODS: The data of 22,882 cases of children who had been hospitalized for RTIs were collected. M. pneumoniae immunoglobulin M (IgM) antibody was detected using the indirect immunofluorescence method and passive agglutination method. The demographic features of patients, clinical diagnoses and laboratory data were also analyzed. RESULTS: A total of 4,213 children tested positive for M. pneumoniae. The total positive rate was 18.41% (18.30% for males and 22.72% for females). Female children had statistically significant higher positive rates than male children (χ2=198.078, P<0.01). The positive rates of M. pneumoniae differed significantly among children of different ages (F=162.7532, P<0.01). The incidence rate of M. pneumoniae in 2017 and 2019 was significantly higher than the average (F=538.95, P<0.01). There were higher M. pneumoniae positive rates from April to May, and September to October (P<0.05) in 2016, 2017, 2018, and 2019. There was no correlation between M. pneumoniae infection and temperature and humidity (P>0.05). There was negative correlation with PM2.5 (particulate matter in the air <2.5 µm) (R=-0.293, P<0.01) and PM10 (particulate matter in the air <10 µm). (R=-0.285, P<0.01). There were significant differences in the constituent ratios of cases of M. pneumoniae infection between in 2020 and other years (F=159.35, P<0.01). Bronchopneumonia accounted for the highest proportion of cases, followed by acute bronchitis and the exacerbation of asthma in 2020. CONCLUSIONS: The epidemiological distribution of M. pneumoniae in children with RTIs in Chengdu was found to be related to gender, age, year and month; however, no relationship was found to temperature and humidity. There was a higher M. pneumoniae positive rate in children with bronchial pneumonia and asthma in cases. The prevention measures used to control Coronavirus Disease 2019 (COVID-19) also effectively controlled the M. pneumoniae infection rate.

Elevated plasma phage load as a marker for intestinal permeability in leukemic patients.

Microbial translocation (MT) and altered gut microbiota have been described in acute leukemic patients and contribute to immune activation and inflammation. However, phage translocation has not been investigated in leukemia patients yet. We recruited 44 leukemic patients and 52 healthy adults and quantified the levels of 3 phages in peripheral blood, which were the most positive phages screened from fecal samples. The content of 16S rRNA in plasma was detected by qPCR to assess the intestinal mucosa of these patients. Spearman's rank correlation was used to analyze the relationship between phage load and the relevant clinical data. We found the most prevalent phages in fecal samples were λ phage, Wphi phage, and P22 phage, and λ phage had the highest detection rate in plasma (68%). Phage content was affected by chemotherapy and course of disease and correlated with the levels of CRP (r = 0.43, p = 0.003), sCD14 (r = 0.37, p = 0.014), and sCD163 (r = 0.44, p = 0.003). Our data indicate that plasma phage load is a promising marker for gut barrier damage and that gut phage translocation correlates with monocyte/macrophage activation and systemic inflammatory response in leukemic patients.

Revision of serum ALT upper limits of normal facilitates assessment of mild liver injury in obese children with non-alcoholic fatty liver disease.

BACKGROUND: The serum alanine aminotransferase (ALT) level is a critical parameter for evaluating liver injury in non-alcoholic fatty liver disease (NAFLD). However, the currently accepted upper limits of normal (ULN) for serum ALT (ULN-ALT) are debated, as they may be excessively high. METHODS: A total of 1638 children aged 6-16 years, comprising 507 children with normal BMI (500 healthy children and 7 children with NAFLD), 199 overweight children, and 932 obese children, were included in the analysis. We re-evaluated the ULN-ALT in 500 healthy Chinese children using the 95th percentiles of serum ALT levels as revised ULN-ALT. Fatty liver was identified by ultrasound examination. RESULTS: Significant positive correlations between serum ALT levels and body mass index (BMI) were detected in overweight boys (r = .399, P < .001), obese boys (r = .398, P < .001), and obese girls (r = .392, P < .001). The prevalence percentages of NAFLD were 93.6%, 75.8%, and 37.9% in obese boys with serum ALT levels of >50, 25-50, and ≤25 U/L and were 81.6%, 67.9%, and 20.6% in obese girls with serum ALT levels of >40, 20-40, and ≤20 U/L, respectively. CONCLUSION: Serum ALT levels significantly correlated with abnormal BMI values in children, suggesting a rigorous BMI threshold is needed to establish the cutoffs for serum ULN-ALT in children. Besides, the revised serum ULN-ALT can uncover mild liver injury in obese children with NAFLD.

Label-Free MicroRNA Optical Biosensors.

MicroRNAs (miRNAs) play crucial roles in regulating gene expression. Many studies show that miRNAs have been linked to almost all kinds of disease. In addition, miRNAs are well preserved in a variety of specimens, thereby making them ideal biomarkers for biosensing applications when compared to traditional protein biomarkers. Conventional biosensors for miRNA require fluorescent labeling, which is complicated, time-consuming, laborious, costly, and exhibits low sensitivity. The detection of miRNA remains a big challenge due to their intrinsic properties such as small sizes, low abundance, and high sequence similarity. A label-free biosensor can simplify the assay and enable the direct detection of miRNA. The optical approach for a label-free miRNA sensor is very promising and many assays have demonstrated ultra-sensitivity (aM) with a fast response time. Here, we review the most relevant label-free microRNA optical biosensors and the nanomaterials used to enhance the performance of the optical biosensors.

Signatures of B-cell receptor diversity in B lymphocytes following Epstein-Barr virus transformation.

Epstein-Barr virus (EBV) is a widespread human virus that establishes latent infection, potentially leading to tumors, hematological disorders, and other severe diseases. EBV infections are associated with diverse symptoms and affect various organs; therefore, early diagnosis and treatment are crucial. B cell receptor (BCR) repertoires of B cell surface immunoglobulins have been widely studied for their association with various infectious diseases. However, the specific genetic changes that modulate the BCR repertoires after an EBV infection are still poorly understood. In this study, we employed high-throughput sequencing (HTS) to investigate the diversity of BCR repertoires in an EBV-transformed lymphoblastic cell line (LCL). Compared with the noninfected control B cell line, the LCL exhibited a decrease in overall BCR diversity but displayed an increase in the expansion of some dominant rearrangements such as IGHV4-31/IGHJ4, IGHV4-59/IGHJ4, IGHV5-51/IGHJ3, and IGHV3-74/IGHJ3. A higher frequency of occurrence of these rearrangement types was confirmed in patients with EBV infection. Interestingly, the IGHV3-74 rearrangement was only detected in EBV-infected children, suggesting that our experimental observations were not coincidental. In addition, we identified a highly dominant consensus motif, CAR(xRx)YGSG(xYx)FD, in complementarity-determining region 3 (CDR3) sequences of the heavy chain in the LCL. Our findings demonstrated the utility of HTS technology for studying the variations in signature motifs of the BCR repertoires after EBV infection. We propose that the analysis of BCR repertoire sequences represents a promising method for diagnosing early EBV infections and developing novel antibody- and vaccine-based therapies against such infections.

Differential circRNA expression profiles in latent human cytomegalovirus infection and validation using clinical samples.

Human cytomegalovirus (HCMV) is an opportunistic prototypic beta-herpesvirus that can cause severe and even fatal diseases in immune-naive newborns and immunocompromised adults. Host-virus interactions occurring at the transcriptional and posttranscriptional levels are critical for establishing an HCMV latent or lytic infection, but the mechanisms remain poorly understood. Herein, we investigated the expression of circRNAs in human leukemia monocytes (THP-1 cells) latently infected with HCMV and explored the diagnostic value of circRNAs in children with HCMV infection. A total of 2,110 and 1,912 circRNAs were identified in mock-infected and HCMV latent-infected THP-1 cells, respectively. Of these, we identified 1,421 differently expressed circRNAs, of which 650 were upregulated and 771 were downregulated. The host genes corresponding to the differentially expressed circRNAs were mainly involved in the regulation of host cell secretion pathways, cell cycle, and cell apoptosis. The differentially expressed circRNAs had binding sites for microRNAs, suggesting an important role in the mechanism of HCMV latent infection. Furthermore, a clinical analysis showed that the expression levels of hsa_circ_0001445 and hsa_circ_0001206 were statistically significantly different in HCMV-infected patients vs. normal controls, suggesting that these circRNAs could potentially serve as biomarkers of HCMV-infection.

Elevation of plasma-soluble HLA-G in childhood nephrotic syndrome is associated with IgE.

Background Nephrotic syndrome is related to immune system dysfunction. Soluble human leukocyte antigen-G has been suggested to have an immunomodulatory role. Additionally, human leukocyte antigen-G expression may be influenced by the 14-base pair insertion/deletion polymorphism. However, this molecule has not been investigated in nephrotic syndrome. Methods Fifty-five children with nephrotic syndrome were enrolled: 24 primary nephrotic syndrome patients and 31 recurrent nephrotic syndrome patients. A group of 120 healthy subjects were included as reference controls. Additionally, 22 patients in nephrotic syndrome remission after treatments were also included. Both nephrotic syndrome patients and healthy subjects were genotyped for the 14-base pair insertion/deletion polymorphism. Plasma soluble human leukocyte antigen-G concentrations and serum immunoglobulin concentrations were determined. Results Nephrotic syndrome patients showed significantly higher levels of both soluble human leukocyte antigen-G and immunoglobulin E compared to normal controls. Nephrotic syndrome patients presented a higher frequency of the -14-base pair allele than did normal controls. Soluble human leukocyte antigen-G concentrations in remission patients were dramatically lower compared to in nephrotic syndrome patients. Moreover, soluble human leukocyte antigen-G and immunoglobulin E were moderately correlated in nephrotic syndrome patients. Conclusions The present study demonstrated that plasma soluble human leukocyte antigen-G concentrations were significantly elevated and that a relationship between serum total immunoglobulin E in nephrotic syndrome patients and the human leukocyte antigen-G -14-base pair allele may be a risk factor for nephrotic syndrome. These findings suggest that soluble human leukocyte antigen-G may be used as a monitoring marker for nephrotic syndrome patients' condition.

Transcriptome altered by latent human cytomegalovirus infection on THP-1 cells using RNA-seq.

Human cytomegalovirus (HCMV) has been recognized as a cause of severe, sometimes life-threatening disease in congenitally infected newborns as well as in immunocompromised individuals. However, the molecular mechanisms of the host-virus interaction remain poorly understood. Here, we profiled the expression of mRNAs and long noncoding RNAs (lncRNAs) in THP-1 cells using the emerging RNA-seq to investigate the transcriptional changes during HCMV latent infection. At 4 days post HCMV infection, a total of 169,008,624 sequence reads and 180,616 transcripts were obtained, respectively. Of these transcripts, 1,354 noncoding genes and 12,952 protein-coding genes were observed in Refseq database. Differential gene expression analysis identified 2,153 differentially expressed genes (DEGs) between HCMV-infected and mock-infected THP-1 cells, including 1,098 up-regulated genes and 1,055 down-regulated genes. These regulated genes were involved in pathways of apoptosis, inflammatory response and cell cycle progression, all of which may be implicated in viral pathogenesis. In addition, 646 lncRNAs (208 known lncRNAs and 438 novel lncRNAs) were upregulated and 424 (140 known and 284 novel) were downregulated in infected THP-1 cells. These findings have provided a dynamic scenario of DE candidate genes and lncRNAs at the virus-host interface and clearly warrant further experimental investigation associated with HCMV infection.

Efficient induction of cross-presentating human B cell by transduction with human adenovirus type 7 vector.

Although human autologous B cells represent a promising alternative to dendritic cells (DCs) for easy large-scale preparation, the naive human B cells are always poor at antigen presentation. The safe and effective usage record of human adenovirus type 7 (HAdV7) live vaccines makes it attractive as a promising vaccine vector candidate. To investigate whether HAdV7 vector could be used to induce the human B cells cross-presentation, in the present study, we constructed the E3-defective recombinant HAdV7 vector encoding green fluorescent protein (GFP) and carcinoembryonic antigen (CEA). We demonstrated that naive human B cells can efficiently be transduced, and that the MAPKs/NF-κB pathway can be activated by recombinant HAdV7. We proved that cytokine TNF-α, IL-6 and IL-10, surface molecule MHC class I and the CD86, antigen-processing machinery (APM) compounds ERp57, TAP-1, and TAP-2. were upregulated in HAdV7 transduced human B cells. We also found that CEA-specific IFNγ expression, degranulation, and in vitro and ex vivo cytotoxicities are induced in autologous CD8(+) T cells presensitized by HAd7CEA modified human B cells. Meanwhile, our evidences clearly show that Toll-like receptors 9 (TLR9) antagonist IRS 869 significantly eliminated most of the HAdV7 initiated B cell activation and CD8(+) T cells response, supporting the role and contribution of TLR9 signaling in HAdV7 induced human B cell cross-presentation. Besides a better understanding of the interactions between recombinant HAdV7 and human naive B cells, to our knowledge, the present study provides the first evidence to support the use of HAdV7-modified B cells as a vehicle for vaccines and immunotherapy.

A novel mutation of SETBP1 in atypical chronic myeloid leukemia transformed from acute myelomonocytic leukemia.

To investigate an oncogenic mutation of SETBP1 in the evolution from acute myelomonocytic leukemia (M4) to secondary aCML. Clinical data and molecular studies were analyzed of paired aCML and 'normal'DNA from a case with M4. We identified a mutation in SETBP1 (encoding a p.Asp868Ala alteration). The analysis of paired sample indicated that SETBP1 mutation was acquired during leukemic evolution.

Transmission degradation and preservation for tapered optical fibers in rubidium vapor.

The use of subwavelength diameter tapered optical fibers (TOFs) in warm rubidium vapor has recently been identified as a promising system for realizing ultralow-power nonlinear optical effects. However, at the relatively high atomic densities needed for many of these experiments, rubidium atoms accumulating on the TOF surface can cause a significant loss of overall transmission through the fiber. Here we report direct measurements of the time scale associated with this transmission degradation for various rubidium density conditions. Transmission is affected almost immediately after the introduction of rubidium vapor into the system, and declines rapidly as the density is increased. More significantly, we show how a heating element designed to raise the TOF temperature can be used to reduce this transmission loss and dramatically extend the effective TOF transmission lifetime.