Bacterial infection promotes tumorigenesis of colorectal cancer via regulating CDC42 acetylation.

Increasing evidence highlights the role of bacteria in promoting tumorigenesis. The underlying mechanisms may be diverse and remain poorly understood. Here, we report that Salmonella infection leads to extensive de/acetylation changes in host cell proteins. The acetylation of mammalian cell division cycle 42 (CDC42), a member of the Rho family of GTPases involved in many crucial signaling pathways in cancer cells, is drastically reduced after bacterial infection. CDC42 is deacetylated by SIRT2 and acetylated by p300/CBP. Non-acetylated CDC42 at lysine 153 shows an impaired binding of its downstream effector PAK4 and an attenuated phosphorylation of p38 and JNK, consequently reduces cell apoptosis. The reduction in K153 acetylation also enhances the migration and invasion ability of colon cancer cells. The low level of K153 acetylation in patients with colorectal cancer (CRC) predicts a poor prognosis. Taken together, our findings suggest a new mechanism of bacterial infection-induced promotion of colorectal tumorigenesis by modulation of the CDC42-PAK axis through manipulation of CDC42 acetylation.

Global profiling of ribosomal protein acetylation reveals essentiality of acetylation homeostasis in maintaining ribosome assembly and function.

Acetylation is a global post-translational modification that regulates various cellular processes. Bacterial acetylomic studies have revealed extensive acetylation of ribosomal proteins. However, the role of acetylation in regulating ribosome function remains poorly understood. In this study, we systematically profiled ribosomal protein acetylation and identified a total of 289 acetylated lysine residues in 52 ribosomal proteins (r-proteins) from Salmonella Typhimurium. The majority of acetylated lysine residues of r-proteins were found to be regulated by both acetyltransferase Pat and metabolic intermediate acetyl phosphate. Our results show that acetylation plays a critical role in the assembly of the mature 70S ribosome complex by modulating r-proteins binding to rRNA. Moreover, appropriate acetylation is important for the interactions between elongation factors and polysomes, as well as regulating ribosome translation efficiency and fidelity. Dysregulation of acetylation could alter bacterial sensitivity to ribosome-targeting antibiotics. Collectively, our data suggest that the acetylation homeostasis of ribosomes is crucial for their assembly and function. Furthermore, this mechanism may represent a universal response to environmental signals across different cell types.

The non-linear relationship between serum albumin and diabetic retinopathy in type 2 diabetes mellitus: a secondary analysis based on a cross-sectional study.

BACKGROUND: Most studies had shown a linear relationship between serum albumin (sALB) and the prevalence of diabetic retinopathy (DR). Thus, the purpose of this study is to investigate whether their relationship is non-linear. METHODS: We included 426 patients with type 2 diabetes who were hospitalized in Guangdong Provincial People's Hospital from December 2017 to November 2018. The outcome was the prevalence of DR. A two-piecewise logistics regression model was performed to identify the non-linear relationship between sALB and the prevalence of DR. The inflection point was calculated to determine the saturation effect through the maximum likelihood ratio and a recursive algorithm. RESULTS: DR was diagnosed in 167 of 426 type 2 diabetic patients. The relationship between sALB and DR was nonlinear. When sALB was less than 38.10 g/L, a significant negative association was observed (OR = 0.82; 95% CI, 0.72-0.94; P = 0.0037), while no significant association was observed when sALB was greater than 38.10 g/L (OR = 1.12; 95% CI, 0.92-1.35; P = 0.2637). CONCLUSIONS: The relationship between sALB and the prevalence of DR is non-linear. sALB is negatively associated with the prevalence of DR when sALB is less than 38.10 g/L. Our findings need to be confirmed by further prospective research.

Clinical efficacy of a new surgical technique of oral mucosal epithelial transplantation for severe ocular surface disorders.

BACKGROUND: Severe ocular surface disorders are one of the major blinding diseases, and a paucity of original tissue obscures successful reconstruction. We developed a new surgical technique of direct oral mucosal epithelial transplantation (OMET) to reconstruct severely damaged ocular surfaces in 2011. This study elaborates on the clinical efficacy of OMET. METHODS: A retrospective review of patients with severe ocular surface disorders who underwent OMET from 2011 to 2021 at the Department of Ophthalmology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine was conducted. Patients who were followed up for at least 3 months postoperatively and had sufficient pre or postoperative records were included. Surgical efficacy was evaluated by comparing the best-corrected visual acuity (BCVA), corneal transparency, neovascularization grade, and symblepharon grade. Additionally, postoperative ocular surface impression cytology was used to study the morphology of the newborn epithelial cells. RESULTS: Forty-eight patients (49 eyes; mean age: 42.55 ± 12.40 years, range:12-66 years) were enrolled in the study. The etiology included chemical burns (30 eyes), thermal burns (16 eyes), explosive injuries (1 eye), Stevens-Johnson syndrome (1 eye), and multiple pterygiums (1 eye). The mean follow-up period was 25.97 ± 22.99 months. Postoperatively, 29 eyes (59.18%) showed improved corneal transparency, 26 eyes (53.06%) had improved BCVA, 47 eyes (95.92%) had a stable epithelium until the final follow-up, 44 eyes (89.80%) had a reduced neovascularization grade. Of the 20 eyes with preoperative symblepharon, 15 (75%) were completely resolved, and five (25%) were partially resolved. Impression cytological studies showed no postoperative conjunctival invasion onto the corneal surface. CONCLUSIONS: OMET is a safe and effective surgical technique for reconstruction in severe ocular surface disorder by maintaining a stable epithelium and reducing the neovascularization and symblepharon grade.

Corneal endothelial regeneration in human eyes using endothelium-free grafts.

BACKGROUND: To report on corneal endothelial regeneration, graft clarity, and vision recovery when using endothelium-free grafts. METHODS: We evaluated the donor's cell viability using trypan blue staining and dual staining with calcein acetoxy methyl ester and ethidium homodimer-1. To preserve eyeball integrity, we performed therapeutic penetrating keratoplasty using cryopreserved donor tissue without endothelium on 195 consecutive patients who suffered from corneal perforation due to progressive primary corneal disease such as herpes simplex keratitis, fungal keratitis, ocular thermal burns, keratoconus, and phlyctenular keratoconjunctivitis. Of these, 18 eyes recovered corneal graft clarity and underwent periodic slit-lamp microscopy, A-scan pachymetry, and in vivo confocal microscopy to observe the clinical manifestations, variations in corneal thickness, and repopulation of the corneal endothelial cells on the donor grafts. RESULTS: No viable cells were detected in the cryopreserved corneas. After the therapeutic penetrating keratoplasty, notable corneal graft edema was observed in all 18 eyes for 1-4 months, and no corneal endothelial cells were detected on the grafts during this period. Thereafter, we observed gradual and progressive regression and final resolution of the stromal edema, with complete recovery of corneal graft clarity. Through periodic confocal microscopy, we observed the corneal endothelium's regenerating process, along with single cells bearing multiple nuclei and cell division-like morphology. The regenerated endothelium on the grafts reached a mean cell density of 991 cells/mm2. Remarkable vision rehabilitation was achieved in all 18 patients. CONCLUSIONS: We obtained conclusive evidence that host-derived endothelial cells can regenerate a new endothelium over the endothelium-free graft, which possesses normal functions for corneal clarity and vision recovery.

Acetylation of PhoP K88 Is Involved in Regulating Salmonella Virulence.

The PhoP-PhoQ two-component regulation system of Salmonella enterica serovar Typhimurium is involved in the response to various environmental stresses and is essential for bacterial virulence. Our previous studies showed that acetylation plays an important role in regulating the activity of PhoP, which consequently mediates the change in virulence of S Typhimurium. Here, we demonstrate that a conserved lysine residue, K88, is crucial for the function of PhoP and its acetylation-downregulated PhoP activities. K88 could be specifically acetylated by acetyl phosphate (AcP), and the acetylation level of K88 decreased significantly after phagocytosis of S Typhimurium by macrophages. Acetylation of K88 inhibited PhoP dimerization and DNA-binding abilities. In addition, mutation of K88 to glutamine, mimicking the acetylated form, dramatically attenuated intestinal inflammation and systemic infection of S Typhimurium in the mouse model. These findings indicate that nonenzymatic acetylation of PhoP by AcP is a fine-tuned mechanism for the virulence of S Typhimurium and highlights that virulence and metabolism in the host are closely linked.

Anti-fibrosis potential of pirarubicin via inducing apoptotic and autophagic cell death in rabbit conjunctiva.

This study investigated the potential efficacy of pirarubicin (THP) in modulating rabbit conjunctival fibrosis both in vitro and in vivo and characterized the underlying mechanisms. Primary rabbit conjunctival fibroblasts (RCF) were cultured and treated with THP or mitomycin C (MMC) for 5 min, followed by assaying for cell viability, cell cycle distribution, apoptotic and autophagic pathways. The production of reactive oxygen species (ROS) and chemotaxis of macrophages by RCF were evaluated using 2',7'-dichlorofluorescein diacetate (DCFH-DA) labeling and transwell migration assay, respectively. Limbal stem cell excision in combination with alkali burn was performed on the rabbits to establish a model of limbal deficiency and conjunctival fibro-vascular invasion. After three months, the modeled fibro-vascular tissue was excised combined with topical subconjunctival 5-min exposure to THP compared with MMC intraoperatively. The recurrence of postoperative fibrosis and the expression of apoptosis, autophagy, and inflammation markers were evaluated by immunohistochemistry. All modeled rabbits developed conjunctival fibro-vascular lesions, which were similar to human recurrent pterygium (HRP). Both THP and MMC inhibited RCF proliferation and arrested cell cycle at the G0/G1 phase. In particular, 7.5 µmol/L THP remarkably promoted RCF autophagy by upregulating the levels of Beclin 1, Atg 5/12 conjugate, and LC3B, whereas, 15 µmol/L THP significantly triggered a cascade of mitochondrial-associated RCF apoptosis. THP induced the production of ROS and enhanced the chemoattraction of macrophages by RCF. Similar to 600 µmol/L MMC, both 7.5 µmol/L and 15 µmol/L THP attenuated postoperative conjunctival fibrosis in the models; 7.5 µmol/L THP preferentially enhanced autophagy while causing fewer side effects. THP exerted its antifibrotic action by modulating autophagy in RCF, inducing cell cycle arrest, and mitochondrial-mediated apoptosis. THP at the dose of 7.5 µmol/L prevented postoperative conjunctival fibrosis in an animal model.

Type VI secretion system contributes to Enterohemorrhagic Escherichia coli virulence by secreting catalase against host reactive oxygen species (ROS).

Enterohemorrhagic Escherichia coli (EHEC) is one major type of contagious and foodborne pathogens. The type VI secretion system (T6SS) has been shown to be involved in the bacterial pathogenicity and bacteria-bacteria competition. Here, we show that EHEC could secrete a novel effector KatN, a Mn-containing catalase, in a T6SS-dependent manner. Expression of katN is promoted by RpoS and OxyR and repressed by H-NS, and katN contributes to bacterial growth under oxidative stress in vitro. KatN could be secreted into host cell cytosol after EHEC is phagocytized by macrophage, which leads to decreased level of intracellular reactive oxygen species (ROS) and facilitates the intramacrophage survival of EHEC. Finally, animal model results show that the deletion mutant of T6SS was attenuated in virulence compared with the wild type strain, while the deletion mutant of katN had comparable virulence to the wild type strain. Taken together, our findings suggest that EHEC could sense oxidative stress in phagosome and decrease the host cell ROS by secreting catalase KatN to facilitate its survival in the host cells.

Acetylation of Lysine 201 Inhibits the DNA-Binding Ability of PhoP to Regulate Salmonella Virulence.

The two-component system PhoP-PhoQ is highly conserved in bacteria and regulates virulence in response to various signals for bacteria within the mammalian host. Here, we demonstrate that PhoP could be acetylated by Pat and deacetylated by deacetylase CobB enzymatically in vitro and in vivo in Salmonella Typhimurium. Specifically, the conserved lysine residue 201(K201) in winged helix-turn-helix motif at C-terminal DNA-binding domain of PhoP could be acetylated, and its acetylation level decreases dramatically when bacteria encounter low magnesium, acid stress or phagocytosis of macrophages. PhoP has a decreased acetylation and increased DNA-binding ability in the deletion mutant of pat. However, acetylation of K201 does not counteract PhoP phosphorylation, which is essential for PhoP activity. In addition, acetylation of K201 (mimicked by glutamine substitute) in S. Typhimurium causes significantly attenuated intestinal inflammation as well as systemic infection in mouse model, suggesting that deacetylation of PhoP K201 is essential for Salmonella pathogenesis. Therefore, we propose that the reversible acetylation of PhoP K201 may ensure Salmonella promptly respond to different stresses in host cells. These findings suggest that reversible lysine acetylation in the DNA-binding domain, as a novel regulatory mechanism of gene expression, is involved in bacterial virulence across microorganisms.

Different surface plasmon coupling behaviors of a surface Al nanoparticle between TE and TM polarizations in a deep-UV light-emitting diode.

The formulations and numerical algorithms of a three-level model for studying the Purcell effect produced by the scattering of an air/AlGaN interface and the surface plasmon (SP) coupling effect induced by a surface Al nanoparticle in a two-polarization emission system to simulate the transverse-electric- (TE-) and transverse-magnetic- (TM-) polarized emissions in an AlxGa1-xN/AlyGa1-yN (y > x) quantum well (QW) are built. In reasonably selected ranges of Al content for an AlGaN QW to emit deep-ultraviolet (UV) light, the enhancement (suppression) of TE- (TM-) polarized emission is mainly caused by the SP-coupling (interface-scattering) effect. Different from a two two-level model, in the three-level model the TE- and TM-polarized emissions compete for electron in the shared upper state, which is used for simulating the conduction band, such that either interface-scattering or SP-coupling effect becomes weaker. In a quite large range of emission wavelength, in which the intrinsic emission is dominated by TM polarization, with the interface-scattering and SP-coupling effects, the TE-polarized emission becomes dominant for enhancing the light extraction efficiency of a deep-UV light-emitting diode.

Coupling of a light-emitting diode with surface plasmon polariton or localized surface plasmon induced on surface silver gratings of different geometries.

A metal grating on top of a light-emitting diode (LED) with a designed grating period for compensating the momentum mismatch can enhance the surface plasmon polariton (SPP) coupling effect with the quantum wells (QWs) to improve LED performance. Here, we demonstrate the experimental results showing that the induced localized surface plasmon (LSP) resonance on such a metal grating can dominate the QW coupling effect for improving LED performance, particularly when grating ridge height is large. The finding is illustrated by fabricating Ag gratings on single-QW, green-emitting LEDs of different p-type thicknesses with varied grating ridge height and width such that the distance between the grating ridge tip and the QW can be controlled. Reflection spectra of the Ag grating structures are measured and simulated to identify the SPP or LSP resonance behaviors at the QW emission wavelength. The measured results of LED performances show that in the LED samples under study, both SPP and LSP couplings can lead to significant enhancements of internal quantum efficiency and electroluminescence intensity. At the designated QW emission wavelength, with a grating period theoretically designed for momentum matching, the LSP coupling effect is stronger, when compared with SPP coupling.

Efficiency enhancement of light color conversion through surface plasmon coupling.

The efficiency enhancement of light color conversion from blue quantum well (QW) emission into red quantum dot (QD) emission through surface plasmon (SP) coupling by coating CdSe/ZnS QDs on the top of an InGaN/GaN QW light-emitting diode (LED) is demonstrated. Ag nanoparticles (NPs) are fabricated within a transparent conductive Ga-doped ZnO interlayer to induce localized surface plasmon (LSP) resonance for simultaneously coupling with the QWs and QDs. Such a coupling process generates three enhancement effects, including QW emission, QD absorption at the QW emission wavelength, and QD emission, leading to an overall enhancement effect of QD emission intensity. An Ag NP geometry for inducing an LSP resonance peak around the middle between the QW and QD emission wavelengths results in the optimized condition for maximizing QD emission enhancement. Internal quantum efficiency and photoluminescence (PL) decay time measurements are performed to show consistent results with LED performance characterizations, even though the QD absorption of PL excitation laser may mix with the SP-induced QD absorption enhancement effect in PL measurement.

Further emission efficiency improvement of a commercial-quality light-emitting diode through surface plasmon coupling.

It is usually believed that surface plasmon (SP) coupling is practically useful only for improving the performance of a light-emitting diode (LED) with a low intrinsic internal quantum efficiency (IQE). In this Letter, we demonstrate that the performance of a commercial-quality blue LED with a high IQE (>80%) can still be significantly improved through SP coupling based on a surface Ag nanoparticle (NP) structure. The performance improvement of such an LED is achieved by increasing the Mg doping concentration in its p-AlGaN electron blocking layer to enhance the hole injection efficiency such that the p-GaN layer thickness can be significantly reduced without sacrificing its electrical property. In this situation, the distance between surface Ag NPs and quantum wells is decreased and hence SP coupling strength is increased. By reducing the distance between the surface Ag NPs and the top quantum well to 66 nm, the IQE can be increased to almost 90% (an ∼11% enhancement) and the electroluminescence intensity can be enhanced by ∼24%.

Case Report: Acute Hydrops with Descemet Membrane Schisis in Corneal Ectasia after Radial Keratotomy.

SIGNIFICANCE: As patients with previous radial keratotomy (RK) are still occasionally encountered, recognition of the anatomy of post-RK corneas and management of their complications remain relevant. High-definition anterior segment optical coherence tomography (AS-OCT) is a very useful tool to assess these postsurgical corneas. PURPOSE: To describe a case of acute corneal hydrops with Descemet membrane schisis after RK with observation by AS-OCT. CASE REPORT: A 43-year-old woman presented with a 9-day history of sudden vision loss, foreign body sensation, and photophobia in her left eye. She had undergone bilateral RK 25 years ago at her local hospital. Slit-lamp examination revealed marked corneal edema and stromal clefts in the central cornea along with radial surgical scars in her left eye. Pentacam imaging showed the typical pattern of a post-RK cornea with ectasia in her right eye. Multiple dilacerations of collagen lamellae and fluid-filled intrastromal cysts together with epithelial edema were observed in her left eye using AS-OCT. A Descemet membrane detachment with schisis was also shown by AS-OCT. After 5 months of medication with topical 0.1% fluorometholone eye drops four times daily together with 3% ofloxacin eye ointment once daily, the corneal edema, Descemet membrane detachment, and Descemet membrane schisis had completely resolved resulting in pan-stromal scarring. CONCLUSIONS: This report describes acute corneal hydrops with Descemet membrane schisis after RK imaged using high-definition AS-OCT. The acute hydrops was possibly caused by corneal ectasia or underlying keratoconus, which was aggravated by RK. High-definition AS-OCT is a useful tool to demonstrate the details of different corneal layers and to observe the resolving process of acute hydrops. Topical medications consisting of antibiotic, lubrication, and corticosteroid can be used to treat the acute event effectively.

Assessment of Tear Film and Bulbar Redness by Keratograph 5M in Pediatric Patients After Orthokeratology.

OBJECTIVES: To assess the tear meniscus height (TMH), noninvasive tear breakup time (NITBUT), and bulbar redness in pediatric patients after orthokeratology (OK). METHODS: Pediatric patients who underwent overnight OK between December 2014 and November 2017 were retrospectively investigated. According to the time of wearing, subjects were divided into three groups: 1-week, 1-month, and over 1-year. Age-matched subjects were recruited as a control group. Keratograph 5M was used to assess TMH, NITBUT-first, NITBUT-average, and bulbar redness score. RESULTS: A total of 106 subjects aged from 7 to 15 years were included. Compared with control group, NITBUT-first was significantly lower in 1-week group (P=0.036) and NITBUT-average was significantly lower in 1-month group (P=0.019). Compared with over 1-year group, NITBUT-first was significantly lower in 1-week and 1-month groups (P=0.014, P=0.035, respectively), and NITBUT-average was significantly lower in 1-month group (P=0.022). Bulbar redness score was significantly lower in 1-month group than 1-week group (P=0.004). No significant difference in TMH was found between all groups. Significant correlation was found between NITBUT-first and NITBUT-average in all subjects (R=0.812, P<0.001). No other significant correlations were found between variables included TMH, NITBUT, bulbar redness score, or target correction. CONCLUSIONS: As a noninvasive method, Keratograph 5M was easily to be applied on pediatric patients. The OK lens did not induce significant tear deficiency or bulbar redness, but might affect tear film stability in a short term after wearing.

Qualitative and Quantitative Analysis of the Major Constituents in WLJ Herbal Tea Using Multiple Chromatographic Techniques.

Quality control of Chinese herbal tea remains a challenge due to our poor knowledge of their complex chemical profile. This study aims to investigate the chemical composition of one of the best-selling and famous brand of beverage in China, Wanglaoji Herbal Tea (WLJHT), via a full component quantitative analysis. In this paper, a total of thirty-two representative constituents were identified or tentatively characterized using ultra-high performance liquid chromatography coupled with quadrupole tandem time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Moreover, the quantitative analyses of fourteen constituents were performed by high performance liquid chromatography with a triple quadruple tandem mass spectrometry (HPLC-MS/MS) method and saccharide compositions of WLJHT were also quantitatively determined by high performance liquid chromatography (HPLC) with evaporative light scattering detector (ELSD) on a Hilic column, separately. Using multiple chromatographic techniques presented a good precision, sensitivity, repeatability and stability, and was successfully applied to analyze 16 batches of WLJHT samples. Therefore, it would be a reliable and useful approach for the quality control of WLJHT.

Identification and Pharmacokinetic Studies on Complanatuside and Its Major Metabolites in Rats by UHPLC-Q-TOF-MS/MS and LC-MS/MS.

The metabolic and pharmacokinetic studies on complanatuside, a quality marker of a Chinese materia medicatonic, Semen Astragali Complanati, were carried out. The UHPLC-Q-TOF/MS (ultra-high performance liquid chromatography coupled with electrospray ionization tandem quadrupole-time-of-flight mass spectrometry) method was applied to identify the metabolites of complanatuside in rat plasma, bile, stool, and urine after oral administration at the dosage of 72 mg/kg. Up to 34 metabolites (parent, 2 metabolites of the parent drug, and 31 metabolites of the degradation products) were observed, including processes of demethylation, hydroxylation, glucuronidation, sulfonation, and dehydration. The results indicated glucuronidation and sulfonation as major metabolic pathways of complanatuside in vivo. Meanwhile, a HPLC-MS method to quantify complanatuside and its two major metabolites-rhamnocitrin 3-O-ß-glc and rhamnocitrin-in rat plasma for the pharmacokinetic analysis was developed and validated. The Tmax (time to reach the maximum drug concentration) of the above three compounds were 1 h, 3 h, and 5.3 h, respectively, while the Cmax (maximum plasma concentrations)were 119.15 ng/mL, 111.64 ng/mL, and 1122.18 ng/mL, and AUC(0-t) (area under the plasma concentration-time curve) was 143.52 µg/L·h, 381.73 µg/L·h, and 6540.14 µg/L·h, accordingly. The pharmacokinetic characteristics of complanatuside and its two metabolites suggested that complanatuside rapidly metabolized in vivo, while its metabolites-rhamnocitrin-was the main existent form in rat plasma after oral administration. The results of intracorporal processes, existing forms, and pharmacokinetic characteristics of complanatuside in rats supported its low bioavailability.

Acetylation Regulating Protein Stability and DNA-Binding Ability of HilD, thus Modulating Salmonella Typhimurium Virulence.

HilD, a dominant regulator of Salmonella pathogenicity island 1, can be acetylated by protein acetyltransferase (Pat) in Salmonella Typhimurium, and the acetylation is beneficial to its stability. However, the underlying mechanism of HilD stability regulated by acetylation is not clear. We show here that lysine 297 (K297) located in the helix-turn-helix motif, can be acetylated by Pat. Acetylation of K297 increases HilD stability, but reduces its DNA-binding affinity. In turn, the deacetylated K297 enhances the DNA-binding ability but decreases HilD stability. Under the Salmonella pathogenicity island 1-inducing condition, the acetylation level of K297 is down-regulated. The acetylated K297 (mimicked by glutamine substitution) causes attenuated invasion in HeLa cells, as well as impaired virulence in mouse model, compared with the deacetylated K297 (mimicked by arginine substitution), suggesting that deacetylation of K297 is essential for Salmonella virulence. These findings demonstrate that the acetylation of K297 can regulate both protein stability and DNA-binding ability. This regulation mediated by acetylation not only degrades redundant HilD to keep a moderate protein level to facilitate S. Typhimurium growth but also maintains an appropriate DNA-binding activity of HilD to ensure bacterial pathogenicity.

Dependencies of surface plasmon coupling effects on the p-GaN thickness of a thin-p-type light-emitting diode.

The high performance of a light-emitting diode (LED) with the total p-type thickness as small as 38 nm is demonstrated. By increasing the Mg doping concentration in the p-AlGaN electron blocking layer through an Mg pre-flow process, the hole injection efficiency can be significantly enhanced. Based on this technique, the high LED performance can be maintained when the p-type layer thickness is significantly reduced. Then, the surface plasmon coupling effects, including the enhancement of internal quantum efficiency, increase in output intensity, reduction of efficiency droop, and increase of modulation bandwidth, among the thin p-type LED samples of different p-type thicknesses that are compared. These advantageous effects are stronger as the p-type layer becomes thinner. However, the dependencies of these effects on p-type layer thickness are different. With a circular mesa size of 10 µm in radius, through surface plasmon coupling, we achieve the record-high modulation bandwidth of 625.6 MHz among c-plane GaN-based LEDs.

Extracellular vesicles: An overview of biogenesis, function, and role in breast cancer.

Extracellular vesicles have emerged as important mediators of intercellular communication and play an active role in cancer, including breast cancer. Despite limited studies, initial observations suggest that these vesicles are important in breast physiology and pathophysiology. We here, in brief, describe their potential use as future biomarkers and therapeutic agents in breast cancer. Extracellular vesicles in blood and breast fluid may have a great potential to detect and predict the presence of breast cancer, and extracellular vesicles modulation may emerge as a therapeutic approach in cancer therapy.