Suppression of Strawberry Anthracnose by Paenibacillus polymyxa TP3 In Situ and from a Distance.

Strawberry is a popular fruit with valuable nutrition and an attractive fragrance, but its production and propagation are limited by various diseases, including anthracnose and gray mold. For disease management, biological control measures are environmentally friendly and good alternatives to fungicides to avoid crop losses, reduce carbon emissions, and improve food safety. In this study, Paenibacillus polymyxa TP3, which originated from the strawberry phyllosphere, was shown to antagonize the anthracnose fungal pathogen Colletotrichum siamense and reduce leaf symptoms on strawberry plants. Several mass spectra corresponding to fusaricidin were detected in the confrontation assay of P. polymyxa TP3 and C. siamense by image mass spectrometry. The transcription of fusA and fusG in the fusaricidin biosynthesis gene cluster increased while P. polymyxa TP3 was cultured in the medium containing the culture filtrate of C. siamense, as detected by reverse-transcription polymerase chain reaction, indicating the involvement of fusaricidins in P. polymyxa TP3 antagonism against the anthracnose pathogen. Further disease control assays demonstrated the time frame and spatial mode of P. polymyxa TP3-induced systemic resistance of strawberry against C. siamense. The transcript level of the marker gene FaPDF1.2 of the jasmonic acid pathway increased in strawberry leaves after drenching treatment with P. polymyxa TP3, and the callose deposition was enhanced by further flg22 treatment. In addition, P. polymyxa TP3 treatments of the strawberry mother plants reduced C. siamense infection in the daughter plants, which would be a potent feature for the application of P. polymyxa TP3 in strawberry nurseries and fields to reduce the impact of diseases, especially anthracnose.

Black Phosphorus Mid-Infrared Light-Emitting Diodes Integrated with Silicon Photonic Waveguides.

Light-emitting diodes (LEDs) based on III-V/II-VI materials have delivered a compelling performance in the mid-infrared (mid-IR) region, which enabled wide-ranging applications in sensing, including environmental monitoring, defense, and medical diagnostics. Continued efforts are underway to realize on-chip sensors via heterogeneous integration of mid-IR emitters on a silicon photonic chip, but the uptake of such an approach is limited by the high costs and interfacial strains, associated with the processes of heterogeneous integrations. Here, the black phosphorus (BP)-based van der Waals (vdW) heterostructures are exploited as room-temperature LEDs. The demonstrated devices emit linearly polarized light, and the spectra cover the technologically important mid-IR atmospheric window. Additionally, the BP LEDs exhibit fast modulation speed and exceptional operation stability. The measured peak extrinsic quantum efficiency is comparable to the III-V/II-VI mid-IR LEDs. By leveraging the integrability of vdW heterostructures, we further demonstrate a silicon photonic waveguide-integrated BP LED.

Study on the Effects of Quantum Well Location on Optical Characteristics of AlGaN/GaN Light-Emitting HEMT.

In this study, AlGaN/GaN light-emitting HEMTs (LE-HEMT) with a single quantum well inserted in different locations in the epitaxy layers are fabricated and analyzed. For both structures, light-emitting originated from electrons in the 2DEG and holes from the p-GaN for radiative recombination is located in the quantum well. To investigate the importance of the location of single quantum well, optical characteristics are compared by simulation and experimental results. The experimental results show that the main light-emitting wavelength is shifted from 365 nm in the UV range to 525 nm in the visible range when the radiative recombination is confined in the quantum well and dominates among other mechanisms. Epi B, which has a quantum well above the AlGaN barrier layer in contrast to Epi A which has a quantum well underneath the barrier, shows better intensity and uniformity in light-emitting. According to the simulation results showing the radiative distribution and electron concentrations for both structures, the lower quantum efficiency is due to the diverse current paths in Epi A. On the other hand, Epi B shows better quantum confinement and therefore better luminescence in the same bias condition, which is consistent with experimental observations. These findings are critical for advancing the performance of LE-HEMTs.

Ultrafast and Broad-Band Graphene Heterojunction Photodetectors with High Gain.

Graphene possesses an exotic band structure that spans a wide range of important technological wavelength regimes for photodetection, all within a single material. Conventional methods aimed at enhancing detection efficiency often suffer from an extended response time when the light is switched off. The task of achieving ultrafast broad-band photodetection with a high gain remains challenging. Here, we propose a devised architecture that combines graphene with a photosensitizer composed of an alternating strip superstructure of WS2-WSe2. Upon illumination, n+-WS2 and p+-WSe2 strips create alternating electron- and hole-conduction channels in graphene, effectively overcoming the tradeoff between the responsivity and switch time. This configuration allows for achieving a responsivity of 1.7 × 107 mA/W, with an extrinsic response time of 3-4 µs. The inclusion of the superstructure booster enables photodetection across a wide range from the near-ultraviolet to mid-infrared regime and offers a distinctive photogating route for high responsivity and fast temporal response in the pursuit of broad-band detection.

Van der Waals Heterostructure Mid-Infrared Emitters with Electrically Controllable Polarization States and Spectral Characteristics.

Modern infrared (IR) microscopy, communication, and sensing systems demand control of the spectral characteristics and polarization states of light. Typically, these systems require the cascading of multiple filters, polarization optics, and rotating components to manipulate light, inevitably increasing their sizes and complexities. Here, we report two-terminal mid-infrared (mid-IR) emitters, in which tuning the polarity of the applied bias can switch their emission peak wavelengths and linear polarization states along two orthogonal orientations. Our devices are composed of two back-to-back p-n junctions formed by stacking anisotropic light-emitting materials, black phosphorus and black arsenic-phosphorus with MoS2. By controlling the crystallographic orientations and engineering the band profile of heterostructures, the emissions of two junctions exhibit distinct spectral ranges and polarization directions; more importantly, these two electroluminescence (EL) units can be independently activated, depending on the polarity of the applied bias. Furthermore, we show that when operating our emitter under the polarity-switched pulse mode, the time-averaged EL exhibits the characteristics of broad spectral coverage, encompassing the entire first mid-IR atmospheric window (λ: 3-5 µm), and electrically tunable spectral shapes.

Bilateral popliteal arterial dissection.

A clinical feature of bilateral popliteal arterial dissection without involving the descending aorta, bilateral iliac, as well as femoral arteries has never been reported in the past literature. We report a 56-year-old man with hypertension and coronary artery disease who presented to our emergency department with complaints of bilateral knee pain after long-distance walking. Physical examination was notable for elevated blood pressure, but there was no palpable pulsation over dorsalis pedis arteries on his feet. Laboratory evaluation revealed a d-dimer level of 35.2 mg/L (FEU) on the day of the test and 1.2 mg/L one and a half months ago (normal level, <0.55). These findings were suggestive of a recent-onset peripheral arterial occlusive disorder. Computed tomography of the aorta showed bilateral popliteal arterial dissection with arterial intimal flap. Abdominal aorta, bilateral iliac, and femoral arteries remained intact with only arteriosclerotic change. Minimally invasive endovascular stent grafting was then performed. The patient had an uneventful recovery.

Characteristics of responders to atropine 0.01% as treatment in Asian myopic children.

Recently, low-concentration atropine (0.01%) has gained increased attention in controlling myopia progression with satisfying effects and minimal side effects. However, studies concerning responders to 0.01% atropine are limited. This retrospective observational cohort study aimed to determine the responder characteristics of 0.01% atropine in Asian children. One hundred forty children (aged between 3 and 15 years) receiving 0.01% atropine were analyzed for the factors influencing annual spherical equivalent changes (SE). The mean age was 9.13 (2.6) years, the mean baseline SE was - 1.56 (1.52) diopters (D), and the mean annual SE change was - 0.52 (0.49) D. A 58.63% responder rate (146/249) of myopic control was achieved with 0.01% atropine in our entire cohort under the criteria of less than 0.5 D of myopic progression annually. The subjects were stratified into 4 subgroups based on a cut-off point of baseline SE of - 1.5 D and baseline age of 9 years. The responder rate differed significantly with the highest being the youngest with the lowest myopia subgroups. Our results demonstrated that children with myopia better than - 1.5 D and younger than 9 years had the highest potential to achieve successful myopic control under 0.01% atropine therapy.

Detection of influenza and non-influenza respiratory viruses in lower respiratory tract specimens among hospitalized adult patients and analysis of the clinical outcome.

BACKGROUND: Lower respiratory tract infection (LRTI) is one of the most fatal diseases for adults. Influenza is a well-recognized cause of severe pneumonia; however, the outcomes of LRTI caused by non-influenza respiratory viruses (NIRVs) have not been sufficiently investigated. This study aimed to describe the characteristics and outcomes of LRTI associated with respiratory viruses (RVs) in adults. MATERIALS/METHODS: A retrospective review was performed using medical records of adult patients whose lower respiratory tract (LRT) specimens (endotracheal aspirate and bronchoalveolar lavage fluid) tested positive for RVs using multiplex PCR. Underlying comorbidities, laboratory data, and clinical outcomes were analyzed. RESULTS: Among the 808 LRT specimens collected from 666 adult patients, RV was identified in 115 specimens (14%) from 106 patients (16%). The underlying comorbidities and laboratory data did not differ between patients with influenza- and NIRV-related LRTI. The 14-day and 30-day mortality rates were higher in the influenza group than in the NIRV group (24% versus 7%, p = 0.03 and 33% versus 13%, p = 0.02, respectively), whereas the 90-day mortality rate did not. In a multivariate Cox model to predict 90-day mortality, shock and acute kidney injury independently predicted a higher mortality rate (hazard ratio (HR): 4.28, 95% CI: 1.46-12.58, p = 0.01 and HR: 2.80, 95% CI: 1.28-6.15, p = 0.01, respectively), whereas the detection of influenza did not. CONCLUSIONS: Influenza and NIRVs were associated with increased mortality due to LRTI in adults. Therefore, NIRVs are among key pathogens causing LRTI and should not be neglected by clinicians.

A Novel Method Ensuring an Immediate Target Angle After Horizontal Strabismus Surgery in Children.

Purpose: Pediatric strabismus surgery has low success rates and high reoperation rates because of difficult alignment measurements and the nature of different strabismus types. Furthermore, adjustable sutures are not easily employed in children on an OPD basis. Methods: This was a retrospective comparative case study of children less than 12 years old who underwent strabismus surgery and were followed up at least 6 months postoperatively. We proposed a novel method that combines adjustable sutures and corneal light reflexes in regular strabismus surgery to improve surgical results. Efficacy and safety were evaluated and compared with those in a regular fixed-suture group. Results: In total, 128 children (88: exotropia and 41: esotropia) in the novel method group (Group 1) and 109 (71: exotropia and 38: esotropia) in the regular fixed-suture group (Group 2) were enrolled. The primary outcome was the immediate target angle (for esotropia within 4 PD of orthotropia and exotropia within 8 PD of esotropia within the first week postoperatively); the secondary outcome was success at the 6-month visit (angle of deviation < 10 PD). Consequently, there was a significantly higher proportion of achieving the immediate target range and success rate in both exotropic and esotropic patients in Group 1 than in Group 2. A significantly lower reoperation rate was also demonstrated in Group 1. No complications were noted in either group.Conclusions: The novel method enabled a higher proportion of subjects to achieve an immediate target range and success rate and a lower chance of reoperation among both esotropic and exotropic patients.

Electric control of valley polarization in monolayer WSe2 using a van der Waals magnet.

Electrical manipulation of the valley degree of freedom in transition metal dichalcogenides is central to developing valleytronics. Towards this end, ferromagnetic contacts, such as Ga(Mn)As and permalloy, have been exploited to inject spin-polarized carriers into transition metal dichalcogenides to realize valley-dependent polarization. However, these materials require either a high external magnetic field or complicated epitaxial growth steps, limiting their practical applications. Here we report van der Waals heterostructures based on a monolayer WSe2 and an Fe3GeTe2/hexagonal boron nitride ferromagnetic tunnelling contact that under a bias voltage can effectively inject spin-polarized holes into WSe2, leading to a population imbalance between ±K valleys, as confirmed by density functional theory calculations and helicity-dependent electroluminescence measurements. Under an external magnetic field, we observe that the helicity of electroluminescence flips its sign and exhibits a hysteresis loop in agreement with the magnetic hysteresis loop obtained from reflective magnetic circular dichroism characterizations on Fe3GeTe2. Our results could address key challenges of valleytronics and prove promising for van der Waals magnets for magneto-optoelectronics applications.

Waveguide-Integrated van der Waals Heterostructure Mid-Infrared Photodetector with High Performance.

Extending the operation wavelength of silicon photonics to the mid-infrared (mid-IR) band will significantly benefit critical application areas, including health care, astronomy, and chemical sensing. However, a major hurdle for mid-IR silicon photonics has been the lack of high-speed, high-responsivity, and low noise-equivalent power (NEP) photodetectors. Here, we demonstrate a van der Waals (vdW) heterostructure mid-IR photodetector integrated on a silicon-on-insulator (SOI) waveguide. The detector is composed of vertically stacked black phosphorus (BP)/molybdenum ditelluride (MoTe2). We measured high responsivity (up to 0.85 A/W) over a 3-4 µm spectral range, indicating that waveguide-confined light could strongly interact with vdW heterostructures on top. In addition, the waveguide-integrated detector could be modulated at high speed (>10 MHz) and its switching performance shows excellent stability. These results, together with the noise analysis, indicate that the NEP of the detector is as low as 8.2 pW/Hz1/2. This reported critical missing piece in the silicon photonic toolbox will enable the wide-spread adoption of mid-IR integrated photonic circuits.

Van der Waals Heterostructure Photodetectors with Bias-Selectable Infrared Photoresponses.

A bias-selectable photodetector, which can sense the wavelength of interest by tuning the polarity of applied bias, is useful for target discrimination and identification applications. So far, those detectors are generally based on the back-to-back photodiode configuration via exploiting epitaxial semiconductors as optoelectronic materials, which inevitably lead to high fabrication costs and complex device architectures. Here, we demonstrate that our band-engineered van der Waals heterostructures can be applied as bias-selectable photodetectors. Our first prototypical device is mainly composed of black phosphorus (BP) and MoTe2 light absorbers sandwiching a thin MoS2 hole blocking layer. By varying the bias polarity, its spectral photoresponse can be switched between near-infrared and short-wave infrared bands, and our optoelectronic characterizations indicate that the detector can exhibit high external quantum efficiency (EQE) and fast operation speed. With this framework, we further demonstrate the detector with bias-selectable photoresponses within the mid-wave infrared band using BP/MoS2/arsenic-doped BP heterostructures and show that our developed detectors can be integrated into a single-pixel imaging system to capture dual-band infrared imaging.

Dexmedetomidine controls agitation and facilitates reliable, serial neurological examinations in a non-intubated patient with traumatic brain injury.

INTRODUCTION: We report the effective use of dexmedetomidine in the treatment of a patient with a history of chronic alcohol abuse and an acute traumatic brain injury who developed agitation that was unresolved if from traumatic brain injury, or alcohol withdrawal or the combination of both. Treatment with benzodiazepines failed; lorazepam therapy obscured our ability to do reliable neurological testing to follow his brain injury and nearly resulted in intubation of the patient secondary to respiratory suppression. Upon admission to hospital, the patient was first treated with intermittent, prophylactic doses of lorazepam for potential alcohol withdrawal based upon our institution's standard of care. His neurological examinations including a motor score of 6 (obeying commands) on his Glasgow Coma Scale testing, laboratory studies, and repeat CT head imaging remained stable. For lack of published literature in diagnosing symptoms of patients with a history of both alcohol withdrawal and traumatic brain injury, a diagnosis of agitation secondary to presumed alcohol withdrawal was made when the patient developed acute onset of tachycardia, confusion, and extreme anxiety with tremor and attempts to climb out of bed requiring him to be restrained. Additional lorazepam doses were administered following a hospital-approved protocol for titration of benzodiazepine therapy for alcohol withdrawal. The patient's mental status and respiratory function deteriorated with the frequent lorazepam dosing needed to control his agitation. Dexmedetomidine IV infusion at a rate of 0.5 mcg/kg/h was then administered and was titrated ultimately to 1.5 mcg/kg/h. After 8 days of therapy with dexmedetomidine, the patient was transferred from the ICU to a step-down unit with an intact neurological examination and no evidence of alcohol withdrawal. Airway intubation was avoided during the patient's entire hospitalization. This case report highlights the intricate balance between the side effects of benzodiazepine sedation for treatment of agitation and the difficulties of monitoring the neurological status of non-intubated patients with traumatic brain injury. CONCLUSION: Given the large numbers of alcohol-dependent patients who suffer a traumatic brain injury and subsequently develop agitation and alcohol withdrawal in hospital, dexmedetomidine offers a novel strategy to facilitate sedation without neurological or respiratory depression. As this case report demonstrates, dexmedetomidine is an emerging treatment option for agitation in patients who require reliable, serial neurological testing to monitor the course of their traumatic brain injury.

The clinical manifestations and interval changes of reverse-transcriptase quantitative polymerase chain reactions among different specimens of coronavirus disease 2019 patients.

BACKGROUND: Since December 2019, a number of cases and deaths due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic have been reported worldwide. In spite of clinical manifestations similar to the SARS-CoV epidemic in 2003, affected organs and severity are yet to be defined. Moreover, viral load alterations and viral shielding among different specimens remained scarce. Therefore, clarifying clinical presentations and correlations among viral loads, disease severity, and viral shielding of SARS-CoV-2 infection is crucial in the disease prevention. METHODS: The clinical courses of SARS-CoV-2 cases were presented through Gantt charts. Laboratory examinations and reverse-transcriptase quantitative polymerase chain reactions (RT-qPCR) among different specimens were tested periodically. Cycle thresholds (CT) were recorded and presented as viral loads. RESULTS: From March 2020 to April 2020, 4 SARS-CoV-2 cases were presented, of which, cases 1 and 2 manifested the symptoms severer than cases 3 and 4, along with higher serum lactate dehydrogenase levels and graded for lymphocytopenia. Case 4 initially exhibited anosmia but recovered within a short period. Curves of the CT of all the cases, except case 2, concaved upward after prescribing hydroxychloroquine (HCQ) and azithromycin. Except for case 4, the CT in most stool specimens remained undetectable; however, none of the cases presented gastrointestinal symptoms. Surprisingly, the CT values of the saliva specimens were inconsistent with those of the nasopharyngeal swabs and sputum. CONCLUSION: SARS-CoV-2 manifests various symptoms. Sudden onset of central nervous system symptoms should be considered. The timing of HCQ and azithromycin administration might be a key factor in the viral load reduction. Positive prediction values of RT-qPCR of different specimens should be tested carefully to prevent false-negative results.

Ultra-Broadband, High Speed, and High-Quantum-Efficiency Photodetectors Based on Black Phosphorus.

Black phosphorus (BP), a narrow band gap semiconductor without out-of-plane dangling bonds, has shown promise for broadband and integrable photodetector applications. Simultaneously exhibiting high speed and high-efficiency operation, however, remains a critical challenge for current BP-based photodetectors. Here, we demonstrate a photodetector based on the BP-based van der Waals heterostructures. The developed photodetector enables broadband responses in the visible to mid-infrared range with external quantum efficiency ranging from 20 to 52% at room temperature. These results together with noise measurements indicate that the photodetector can detect light in the picowatt range. Furthermore, the demonstrated BP detector has ultrafast rise (1.8 ns) and fall (1.68 ns) times, and its photoresponse exhibits reproducible switching behavior even under consecutive and rapid light intensity modulations (2100 cycles, 200 MHz), as indicated by the eye-diagram measurement. By leveraging these features, we show our BP heterostructures can be configured as a point-like detector in a scanning confocal microscopy, useful for mid-infrared imaging applications.

Novel variants near the central domain of RYR1 in two malignant hyperthermia-susceptible families from Taiwan.

BACKGROUND: Our primary objective was to detect malignant hyperthermia (MH)-susceptible persons and thereby prevent MH episodes. We identified variants in the ryanodine receptor isoform 1 using molecular pedigree analysis. METHODS: Nineteen exons covering major hotspots were chosen for the primary screening by polymerase chain reaction, denaturing high performance liquid chromatography, and confirmed by direct sequencing. RESULTS: Three novel variants involving amino acid changes were identified in two unrelated families as Met2698Arg, Glu2724Lys in exon 51 and Leu2785Val in exon 53. CONCLUSIONS: Three novel ryanodine receptor isoform 1 variants located either near or within the central domain might predispose carriers to MH.

Anisometropic amblyopia treated with spectacle correction alone: possible factors predicting success and time to start patching.

PURPOSE: To evaluate factors predicting resolution of amblyopia and the time course of improvement in VA in children 3 to 7 years old with anisometropic amblyopia treated with spectacles alone. DESIGN: Prospective, noncomparative intervention. METHODS: Measurement of corrected amblyopic logMAR visual acuity (VA) in newly diagnosed children at four-weekly intervals until VA stabilized or amblyopia resolved. The time course of improvement in VA and the factors related to amblyopia resolution were assessed. RESULTS: Sixty children with a mean age of 5.3 years and mean anisometropia of 2.95 diopters (D) were included. Amblyopia improved by 2 or more logMAR lines in 56 patients (93%) and resolved in 27 patients (45%), with a mean improvement in VA of 0.38 logMAR. The improvement in VA in the amblyopic eye was considerable at four to 12 weeks then reached a plateau, after which it improved only slowly. Resolution of amblyopia was related to better initial VA (0.2 to 0.6 logMAR) and lesser amounts of anisometropia (<4 D). The time to resolution ranged from four to 40 weeks, but no patient with residual amblyopia showed an improvement in VA of more than 0.1 logMAR over four consecutive visits. CONCLUSIONS: With spectacle correction alone, 3- to 7-year-old children with previously untreated anisometropic amblyopia achieved approximately four-line improvement and resolved nearly in half. The nearly two-month plateau periods during improvement of VA should be noticed. After four months with no improvement in VA, occlusion therapy or atropine penalization may be considered.

Efficacy of apraclonidine 0.5% in the diagnosis of Horner syndrome in pediatric patients under low or high illumination.

PURPOSE: To evaluate the efficacy and safety of apraclonidine 0.5% in the diagnosis of Horner syndrome in pediatric patients. DESIGN: Prospective, interventional case series. METHODS: Ten pediatric patients with a diagnosis of Horner syndrome and 10 age-matched controls with physiologic anisocoria underwent pharmacological testing with apraclonidine. The difference between the pupil diameters of both eyes under low (room light off) and high (room light on) ambient illumination before and one hour after apraclonidine was instilled was recorded. Any adverse effects during the examination or reported by the patient's parents were recorded. RESULTS: The mean differences in pupil diameters before and after apraclonidine testing in the Horner syndrome group were -2.05 mm and 0.97 mm, respectively, under low illumination (P = .0049) and -1.48 mm and 1.1 mm, respectively, under high illumination (P = .0051). Three patients with Horner syndrome showed positive values (reversal of anisocoria) only under high ambient illumination, but not under low illumination. There was no statistical difference in the mean differences in pupil diameter before and after apraclonidine testing in the control group. Conjunctival hyperemia was noted in two patients with Horner syndrome and in three patients in the control group. No systemic adverse effects were noted during the examination or were reported by patients' parents. CONCLUSIONS: The application of apraclonidine in pediatric patients is safe and effective in the diagnosis of Horner syndrome. The reversal of anisocoria was more obvious under high (room light on) ambient illumination.

Comparing efficacies of 0.5% apraclonidine with 4% cocaine in the diagnosis of horner syndrome in pediatric patients.

PURPOSE: The aim of this study was to compare the efficacy of 0.5% apraclonidine with that of 4% cocaine and to evaluate its safety in the diagnosis of Horner syndrome in pediatric patients. METHODS: This was a randomized, crossover study, wherein 10 patients with a probable diagnosis of Horner syndrome were assigned to undergo pharmacological testing with 4% cocaine and 0.5% apaconidine. The difference in the pupil diameters of each eye was recorded under dim light before and 1 h after 0.5% apraclonidine or 4% cocaine was instilled. Any adverse effects were noted during examination or reported by the patients' parents were recorded. RESULTS: The mean differences in pupil diameter before and after 4% cocaine testing were -2.08 and -2.97 mm, respectively (P = 0.0047). All patients had an anisocoria greater than 1 mm after 4% cocaine testing. The mean difference in pupil diameter before and after 0.5% apraclonidine was instilled were -2.04 and +1.08 mm, respectively (P = 0.005). All patients showed a reversal of anisocoria after 0.5% apraclonidine testing. Conjunctival hyperemia was noted in 2 patients, but systemic adverse effects were not noted during examination nor reported by the patients' parents. CONCLUSIONS: The application of 0.5% apraclonidine in pediatric patients is safe and effective in the diagnosis of Horner syndrome.

Glucosamine sulfate inhibits proinflammatory cytokine-induced icam-1 production in human conjunctival cells in vitro.

PURPOSE: We investigated whether glucosamine sulfate modulates the production of ICAM-1 induced by proinflammatory cytokines and whether glucosamine sulfate inhibits leukocyte adhesion to a monolayer of human conjunctival epithelial cells stimulated with proinflammatory cytokines. METHODS: We used flow cytometry and either primary cultured human conjunctival cells or the Chang conjunctival cell model to determine the effects of glucosamine sulfate on the production of ICAM-1 in response to tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma, interleukin (IL)-1beta, IL-6, TNF-alpha plus IFN-gamma, or TNF-alpha plus IL-1beta. The effects of glucosamine sulfate on the expression of the ICAM-1 gene, upregulated by various cytokines, were determined by semiquantitative reverse transcription-polymerase chain reaction. The activation and nuclear translocation of the nuclear factors NF-kappaB and STAT1 were evaluated by the transient transfection of reporter gene systems and immunocytochemistry. The influence of glucosamine-sulfate-modulated ICAM-1 on neutrophil adhesion was demonstrated in a model that measures the adherence of conjunctival cells and neutrophils. RESULTS: TNF-alpha, IFN-gamma, and IL-1beta significantly increased the production of ICAM-1 by both primary cultured human conjunctival cells and Chang conjunctival cells. Glucosamine sulfate effectively downregulated the production of ICAM-1 induced by TNF-alpha, IFN-gamma, IL-1beta, TNF-alpha plus IFN-gamma, or TNF-alpha plus IL-1beta. This downregulation occurred through the interferon-stimulated response element, IFN-gamma activation sequence, and binding sequence of NF-kappaB at the mRNA and protein levels. Glucosamine sulfate further inhibited the nuclear translocation of p65 protein in TNF-alpha- and IL-1beta-stimulated Chang conjunctival cells and phosphorylated STAT1 in IFN-gamma-stimulated Chang conjunctival cells. Glucosamine sulfate also significantly reduced the number of neutrophils adhering to a conjunctival monolayer in response to TNF-alpha, IFN-gamma, or IL-1beta. CONCLUSIONS: Our results suggest that glucosamine sulfate inhibits ICAM-1 production in conjunctival epithelial cells in vitro. Therefore, glucosamine sulfate might be valuable in the treatment of inflammatory ocular-surface conditions.