Clinical features and risk factors for pyogenic liver abscess caused by multidrug-resistant organisms: A retrospective study.

The incidence rate of pyogenic liver abscess caused by multidrug-resistant bacteria has increased in recent years. This study aimed to identify the clinical characteristics and risk factors for pyogenic liver abscess caused by multidrug-resistant bacteria. We conducted a retrospective analysis of the clinical features, laboratory test results, and causes of pyogenic liver abscesses in 239 patients admitted to a tertiary hospital. Multivariable logistic regression was used to identify risk factors for multidrug resistance. Among patients with pyogenic liver abscesses, the rate of infection caused by multidrug-resistant organisms was observed to be 23.0% (55/239), with a polymicrobial infection rate of 14.6% (35/239). Additionally, 71 cases (29.7%) were associated with biliary tract disease. Patients with pyogenic liver abscesses caused by multidrug-resistant organisms had a significantly higher likelihood of polymicrobial infection and increased mortality (7/44 [15.9%] vs. 3/131 [2.3%]; p = .003). The Charlson Comorbidity Index (adjusted odds ratio [aOR]: 1.32, 95% confidence interval [CI]: 1.06-1.68), hospitalization (aOR: 10.34, 95% CI: 1.86-60.3) or an invasive procedure (aOR: 9.62; 95% CI: 1.66-71.7) within the past 6 months, and gas in the liver on imaging (aOR: 26.0; 95% CI: 3.29-261.3) were independent risk factors for pyogenic liver abscess caused by multidrug-resistant bacteria. A nomogram was constructed based on the risk factors identified. The nomogram showed high diagnostic accuracy (specificity, 0.878; sensitivity 0.940). Multidrug-resistant organisms causing pyogenic liver abscesses have specific characteristics. Early identification of patients at high risk of infection with multidrug-resistant organisms could help improve their management and enable personalized treatment.

Highly sensitive dual-function sensor for refractive index and temperature using D-shaped microchannel photonic crystal fiber.

An innovative ultra-sensitive, dual-functional sensor employing a D-shaped microchannel photonic crystal fiber (PCF) for refractive index (RI) and temperature measurements is proposed and comprehensively investigated. Its high-sensitivity is achieved through the incorporation of gold (Au) and magnesium fluoride (MgF2) as plasmonic materials in the micro-rectangular channel. This configuration significantly enhances the interaction between the surface plasmon polaritons (SPPs) field and y-polarized evanescent field on external surfaces. Additionally, the integration of a temperature-sensitive fluid within the sensor allows for precise detection of temperature changes. Our simulations demonstrate a broad detection spectrum, covering RI values from 1.27 to 1.43 and temperatures ranging from 45°C to 100°C. The sensor achieves peak sensitivities of 31800nm/RIU for RI and 49 nm/°C for temperature. Besides, the sensor only has a cladding consisting of three air holes to enhance coupling and reduce the difficulty of preparation. Importantly, the sensor's performance remains robust against minor structural alterations in the PCF, indicating high fault tolerance. Given its high sensitivity, extensive detection range, and strong fabrication stability, this PCF-SPR sensor offers significant potential for applications in biochemical sensing and environmental monitoring.

Small extracellular vesicle piR-hsa-30937 derived from pancreatic neuroendocrine neoplasms upregulates CD276 in macrophages to promote immune evasion.

The role of PIWI-interacting RNAs (piRNAs) in small extracellular vesicles (sEV) derived from pancreatic neuroendocrine neoplasms (PNEN) in the tumor microenvironment (TME) remains unexplored. We used multiplex immunohistochemistry (mIHC) to analyze the expression of CD68, CD276 (B7H3) and CD3 on PNEN. CD276+ tumor-associated macrophages (TAMs) were more abundant in tumor tissues than nontumor tissues and negatively correlated with T-cell infiltration. Serum sEV piRNA sequencing was performed to identify piRNAs enriched in PNEN patients. We then investigated the function and mechanism of sEV piR-hsa-30937 in the crosstalk between tumor cells and macrophages in the PNEN TME. PNEN-derived sEV piR-hsa-30937 targeted PTEN to activate the AKT pathway and drive CD276 expression. CD276+ macrophages inhibited T-cell proliferation and IFN- production. piR-hsa-30937 knockdown and anti-CD276 treatment suppressed progression and metastasis in a preclinical model of PNEN by enhancing T-cell immunity. Thus, our data show that PNEN-derived sEV piR-hsa-30937 promotes CD276 expression in macrophages through the PTEN/AKT pathway and that CD276+ TAMs suppress T-cell antitumor immunity. sEV piR-hsa-30937 and CD276 are potential therapeutic targets for immunotherapy of PNEN.

Water-Free Cyclosporine Ophthalmic Solution vs Vehicle for Dry Eye Disease: A Randomized Clinical Trial.

Importance: Dry eye disease (DED) is a prevalent eye disorder. Cyclosporine is an effective immunomodulator that is widely used in DED; however, due to its highly hydrophobic nature, delivery of cyclosporine to the ocular surface is challenging. Objective: To evaluate the efficacy and safety of SHR8028, a water-free cyclosporine ophthalmic solution, 0.1%, compared with vehicle in Chinese participants with DED. Design, Setting, and Participants: This was a multicenter, double-blind, vehicle-controlled, phase 3 randomized clinical trial conducted from March 4, 2021, to July 22, 2022. Adult participants with moderate to severe DED were recruited from 12 hospitals in China. Study data were analyzed April 2, 2022, for the primary analysis. Interventions: Following a 14-day run-in period with an artificial tear, participants were randomly assigned (1:1) to receive water-free cyclosporine or vehicle (1 eye drop in each eye twice daily). After a 29-day treatment, participants of both groups were given the option to receive water-free cyclosporine for an additional 12 weeks for longer-term safety assessment. Main Outcomes and Measures: The primary end points were changes from baseline in total corneal fluorescein staining (tCFS) using the National Eye Institute scale and in dryness score on a visual analog scale at day 29. Results: A total of 206 participants (mean [SD] age, 47.8 [14.2] years; 185 female [90%]) were enrolled, with 103 each in the cyclosporine group and the vehicle group. At day 29, the cyclosporine group experienced improved tCFS compared with vehicle (change [Δ] = -1.8; 95% CI, -2.7 to -1.0; P < .001), with a tCFS score decrease from baseline of -4.8 in the cyclosporine group and -3.0 in the vehicle group. Dryness score decreased from baseline in both groups (-19.2 vs -15.4; Δ = -3.8; 95% CI, -9.2 to 1.6; P = .17). During the 29-day treatment, treatment-related adverse events were reported in 15 participants (14.6%) in the cyclosporine group and 11 participants (10.7%) in the vehicle group. Conclusions And Relevance: Results demonstrated superiority of a water-free cyclosporine, 0.1%, eye solution over vehicle in improving tCFS score at day 29 in Chinese participants with DED. However, dryness score (VAS) was not improved at day 29. Trial Registration: ClinicalTrials.gov Identifier: NCT05841043.

[The role of jasmonic acid in stress resistance of plants: a review].

Jasmonic acid (JA), a plant endogenously synthesized lipid hormone, plays an important role in response to stress. This manuscript summarized the biosynthesis and metabolism of JA and its related regulatory mechanisms, as well as the signal transduction of JA. The mechanism and regulatory network of JA in plant response to biotic and abiotic stresses were systematically reviewed, with the latest advances highlighted. In addition, this review summarized the signal crosstalk between JA and other hormones in regulating plant resistance to various stresses. Finally, the problems to be solved in the study of plant stress resistance mediated by JA were discussed, and the application of new molecular biological technologies in regulating JA signaling to enhance crop resistance was prospected, with the aim to facilitate future research and application of plant stress resistance.

Atmospheric pollutant black carbon induces ocular surface damage in mice.

The threats of air pollution to human health have been gradually discovered, including its effects on eyes. The purpose of the study is to investigate the potential correlation between ocular surface exposure to black carbon and ocular surface structural damage as well as tear film dysfunction. To achieve this goal, 60 6-8-week-aged male BALB/C mice were randomly divided into 4 groups (n = 15). 0.5 mg/ml (group A), 1 mg/ml (group B), 5 mg/ml (group C) black carbon suspension droplets and PBS solution (group D) were used in the right eyes, 4 µl per time of three times per day. Tear break-up time, corneal fluorescein staining scores, and tear volume were assessed before treatment (day 0) and on days 4, 7, 10, and 14 after treatment. On day 14, the mice were sacrificed, and corneal and conjunctival tissues were collected for histological analysis. As the exposure time increased, there were no significant changes in the measured parameters from PBS-treated group of mice (P > 0.05). However, in the black carbon-treated group, there were significant decreases in tear film break-up time, significant increases in corneal fluorescein staining scores, and significant reductions in tear secretion (all P < 0.05). After 14 days, H&E staining of the corneal epithelium showed that in the PBS-treated group of mice, the corneal epithelial cells were neatly arranged, with no inflammatory cell infiltration, while in the black carbon-treated group, the corneal epithelium was significantly thickened, the basal cell arrangement was disrupted, the number of cell layers increased, and there was evidence of inflammatory cell infiltration. In the ultrastructure of the corneal epithelium, it could be observed that the black carbon-treated group had an increased amount of corneal epithelial cell detachment compared to the PBS-treated group, at the same time, the intercellular connections were looser, and there was a decrease in the number of microvilli and desmosomes in the black carbon-treated group. The results indicate that the ocular surface exposure to black carbon can result in a decrease in tear film stability and tear secretion in mice. Moreover, it can induce alterations in the corneal structure.

Up-regulation of scleral C5b-9 and its regulation of the NLRP3 inflammasome in a form-deprivation myopia mouse model.

BACKGROUND: Myopia has become a major public health problem worldwide. Although the involvement of the complement system in myopia progression has been reported, the underlying mechanism has not been well established. In this study, we induced a form deprivation (FD) myopia mouse model to investigate the mechanisms. METHODS: Both C6-knockout (KO) and wild-type (WT) mice were divided into FD and normal control (NC) groups. The FD myopia was induced in the right eyes of 24-day-old mice using a translucent balloon for 4 weeks. The left eye remained untreated and served as self-control. NC group received no treatment. Refractive error and axial length were measured at baseline, 2 weeks, and 4 weeks later under normal visual, 4 weeks after FD. Scleral transcriptome sequencing analysis was performed in in FD mice. The scleral levels of C5b-9, NLRP3, Caspase-1, IL-1ß, MMP-2, and collagen I were evaluated using immunohistochemistry. RESULTS: RNA-seq analysis showed 1058 differentially expressed genes. The GO analysis showed these genes were mainly related to the extracellular matrix, and immune response. The KEGG enrichment analysis showed that complement cascades were upregulated. Under normal visual conditions, both genotypes of mice exhibited comparable refractive error and axial length. However, after four weeks of FD, C6-KO mice showed a significantly less myopic shift (-2.28 ± 0.28 D versus -5.40 ± 1.33 D, P = 0.003), and axial shift (0.043 ± 0.032 mm versus 0.083 ± 0.026 mm, P = 0.042) in comparison to WT mice. Furthermore, the levels of C5b-9, NLRP3, caspase-1, IL-1ß, and MMP-2 were found to be elevated in the deprived eyes of WT mice in comparison to their fellow eyes, whereas the extent of this increase was significantly lower in C6-KO mice. CONCLUSIONS: Complement cascades are activated in FD myopia model. Upregulation of C5b-9 might participate in scleral remodeling during myopia progression via regulation of NLRP3 inflammasome activation.

Intraperitoneal Injection of MCC950 Inhibits the Progression of Myopia in Form-Deprivation Myopic Mice.

Myopia, one of the most prevalent ocular diseases worldwide, is projected to affect nearly half of the global population by 2050. The main cause of myopia in most patients is axial myopia, which primarily occurs due to the elongation of the eyeball, driven by changes in the extracellular matrix (ECM) of scleral cells. Previous studies have shown that NLRP3, an important inflammatory mediator, plays a critical role in regulating the expression of MMP-2 in the sclera. This, in turn, leads to a decrease in the expression of Collagen-1, a major component of the scleral ECM, triggering the remodeling of the scleral ECM. This study aimed to investigate the effect of MCC950, an inhibitor of NLRP3, on the progression of myopia using a mouse form-deprivation myopia (FDM) model. The FDM mouse model was constructed by subjecting three-week-old C57BL/6J mice to form-deprivation. The mice were divided into experimental (n = 10/group; FDM2M, FDM4M, FDM2W, and FDM4W) and control groups (n = 5/group). The experimental groups were further categorized based on the duration of form deprivation (2 and 4 weeks, labeled as 2 and 4, respectively) and the type of injection received (MCC950 or saline, labeled as M and W, respectively). MCC950 was injected at a concentration of 50 mg/mL, with a dose of 10 mg per kilogram of body weight. Meanwhile, the saline group received the same volume of saline. Refraction and axial length measurements were performed for each eye. The expression levels of NLRP3, caspase-1, IL-1ß, IL-18, MMP-2, and Collagen-1 in the sclera were assessed using immunohistochemistry and Western blotting. The intraperitoneal injection of MCC950 did not significantly affect refraction or axial length in normal mice (p > 0.05). However, in FDM mice, MCC950 attenuated the elongation of the axial length and resulted in a smaller shift towards myopia compared to the saline group (FDM4M vs. FDM4W, p = 0.03 and p < 0.05, respectively). MCC950 decreased MMP-2 expression (p < 0.05) but increased Collagen-1 expression (p < 0.05) in the experimental eyes when compared to the saline group. Within the MCC950 group, the expression of MMP-2 was increased in the experimental eyes at 4 weeks (p < 0.05), while that of Collagen-1 was decreased (p < 0.05), which is consistent with changes in refractive error. Immunohistochemical analysis yielded similar results (p < 0.05). MCC950 also reduced the expression levels of NLRP3 (p = 0.03), caspase-1 (p < 0.05), IL-1ß (p < 0.05), and IL-18 (p < 0.05) in the experimental eyes compared to the saline group. Within the MCC950 group, the expression levels of NLRP3 and caspase-1 were comparable between the experimental and control eyes (p > 0.05), whereas IL-18 expression was higher in experimental eyes (p < 0.05). IL-1ß expression was higher in the experimental eyes only at week 4 (p < 0.05). The intraperitoneal injection of MCC950 can inhibit the progression of myopia in FDM mice, possibly by regulating collagen remodeling in the sclera through the NLRP3-MMP-2 signaling pathway. Therefore, MCC950 holds promise as a potential therapeutic agent for controlling the progression of myopia.

An endolysin gene from Candidatus Liberibacter asiaticus confers dual resistance to huanglongbing and citrus canker.

The most damaging citrus diseases are Huanglongbing (HLB) and citrus canker, which are caused by Candidatus Liberibacter asiaticus (CaLas) and Xanthomonas citri pv. citri (Xcc), respectively. Endolysins from bacteriophages are a possible option for disease resistance in plant breeding. Here, we report improvement of citrus resistance to HLB and citrus canker using the LasLYS1 and LasLYS2 endolysins from CaLas. LasLYS2 demonstrated bactericidal efficacy against several Rhizobiaceae bacteria and Xcc, according to inhibition zone analyses. The two genes, driven by a strong promoter from Cauliflower mosaic virus, 35S, were integrated into Carrizo citrange via Agrobacterium-mediated transformation. More than 2 years of greenhouse testing indicated that LasLYS2 provided substantial and long-lasting resistance to HLB, allowing transgenic plants to retain low CaLas titers and no obvious symptoms while also clearing CaLas from infected plants in the long term. LasLYS2 transgenic plants with improved HLB resistance also showed resistance to Xcc, indicating that LasLYS2 had dual resistance to HLB and citrus canker. A microbiome study of transgenic plants revealed that the endolysins repressed Xanthomonadaceae and Rhizobiaceae populations in roots while increasing Burkholderiaceae and Rhodanobacteraceae populations, which might boost the citrus defense response, according to transcriptome analysis. We also found that Lyz domain 2 is the key bactericidal motif of LasLYS1 and LasLYS2. Four endolysins with potential resistance to HLB and citrus canker were found based on the structures of LasLYS1 and LasLYS2. Overall, the work shed light on the mechanisms of resistance of CaLas-derived endolysins, providing insights for designing endolysins to develop broad-spectrum disease resistance in citrus.

CsBZIP40 confers resistance against citrus bacterial canker by repressing CsWRKY43-CsPrx53/CsSOD13 cascade mediated ROS scavenging.

As the bacterial etiologic agent causing citrus bacterial canker (CBC), Xanthomonas citri subsp. citri (Xcc) seriously impacts citrus plantation and fruit production globally. In an earlier study, we demonstrated that CsBZIP40 can positively impact CBC resistance in the sweet orange (Citrus sinensis). However, the mechanistic basis for the protective benefits conferred by CsBZIP40 is yet to be delineated. Here, we show that CsBZIP40 positively regulates CBC resistance and reactive oxygen species (ROS) homeostasis in transgenic sweet orange overexpressing CsBZIP40. CsBZIP40 directly binds to the TGA-box of the CsWRKY43 promoter to repress its transcriptional activity. CsWRKY43 overexpression induces CBC susceptibility in transgenic sweet oranges. In contrast, its inhibition produces strong resistance to CBC. CsWRKY43 directly binds to the W-boxes of the CsPrx53 and CsSOD13 promoters to positively regulate the activities of these antioxidant enzymes, resulting in the negative regulation of ROS homeostasis and CBC resistance in sweet orange plants. CsPrx53/CsSOD13 knockdown enhances ROS accumulation and CBC resistance. Overall, our results outline a regulatory pathway through which CsBZIP40 transcriptionally represses CsWRKY43-CsPrx53/CsSOD13 cascade-mediated ROS scavenging in a manner conducive to CBC resistance. These mechanisms underscore the potential importance of CsBZIP40, CsWRKY43, CsPrx53, and CsSOD13, providing promising strategies for the prevention of CBC.

Management of a nursing unit in a COVID-19 shelter hospital in China: A case study.

OBJECTIVE: Fangcang shelter hospital is a form of large temporary hospital developed in China to tackle public health events. Through the case study and analysis of managing a nursing unit in a huge Fangcang shelter hospital transformed from the National Exhibition and Convention Center during the Omicron wave in Shanghai, China between April 9, 2022 and May 24, 2022, this paper aimed to highlight critical implications of public health nurses in health emergencies. DESIGN: A case study was conducted using data collected from a nursing unit with 570 beds. The five characteristics of management were organized as follows: human resource management, establishment and optimization of the core workflow, safety management of high-risk patients, the grid cooperation mechanism with patient volunteers, as well as humanistic nursing. RESULTS: Analysis of the data of the nursing unit indicated close team cooperation, efficient and orderly process scheduling, good outcomes of patients, and the indispensable role of volunteers. CONCLUSION: Practice indicated that nursing unit management in a large Fangcang shelter hospital is important to ensure medical order and efficiency. This practical experience can provide valuable reference and data to support for the nursing management of large-scale public health events, such as infectious disease epidemics.

Complement-mediated inflammation and mitochondrial energy metabolism in the proteomic profile of myopic human corneas.

Myopia is one of the most common causes of visual impairment worldwide. To identify proteins related to myopiagenesis, data-independent acquisition proteomic analysis was performed using corneal lenticules of myopic patients who underwent small incision lenticule extraction surgery. A total of 19 lenticules from 19 age and sex-matched patients were analyzed, 10 in high refractive error (HR, spherical equivalent over -6.00 D) group and 9 in low refractive error (LR, spherical equivalent between -3.00 and - 1.00 D) group. Differentially expressed proteins (DEPs) were identified by comparing the corneal proteome between the two groups. Functional analyses were performed to explore the biological pathways and interactions of the DEPs. 107 DEPs (67 upregulated and 40 downregulated in HR group, compared to LR) were identified from 2138 quantified proteins. Functional analyses indicated that upregulated proteins were primarily involved in the complement pathways and extracellular matrix (ECM) remodeling, while downregulated proteins were involved in mitochondrial energy metabolism. Western blot analysis confirmed increased complement C3a and apolipoprotein E in HR samples, further supporting the proteomics data. In conclusion, this proteomic study reveals that proteins associated with the complement system, ECM remodeling, and mitochondrial energy metabolism might be key effectors in myopiagenesis. SIGNIFICANCE: Myopia has become one of the most prevalent causes of visual impairment, especially in Asia. The underlying mechanism of myopia development is still up for debate. This study compares the proteomic profiles of high and low myopic corneas, identifying differentially expressed proteins associated with the complement system, ECM remodeling, and mitochondrial energy metabolism. The findings of this study could provide novel insights into the pathogenesis of myopia. The complement system and mitochondrial energy metabolism may provide potential therapeutic targets in the treatment and prevention of myopia.

Cytological and functional effect of complement 3a on Human Scleral Fibroblasts.

PURPOSE: The complement system is considered to play an important role in the progression of myopia, whereas the influence of complement activation on the human scleral fibroblasts (HSFs) remains unknown. Hence, the effect of complement 3a (C3a) on HSFs was investigated in this study. METHODS: HSFs were cultured with exogenous C3a at 0.1 µM for various periods following different measurement protocols, and cells without C3a treatment served as negative control (NC). Cell viability was investigated using the MTS assay after 3 days of C3a treatment. Cell proliferation was evaluated by the 5-Ethynyl-20-Deoxyuridine (EdU) assay following C3a stimulation for 24 hours. Apoptosis was assessed by Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double staining following C3a stimulation for 48 hours and the stained cells were analysed using flow cytometry. The levels of type I collagen and matrix metalloproteinase-2 (MMP-2) were analysed using ELISA following C3a stimulation for 36 and 60 hours. The level of CD59 were analysed using western blot following C3a stimulation for 60 hours. RESULTS: The MTS assay revealed that cell viability was attenuated by 13% and 8% after C3a for 2 and 3 days, respectively (P < 0.05). The EdU assay demonstrated a 9% decrease in proliferation rate for the C3a-treated cells after 24 hours (P < 0.05). The apoptosis analysis revealed an increased percentage of cells in early apoptosis (P = 0.02) and total apoptosis (P = 0.02) in the C3a-treated group. Compared with NC group, the level of MMP-2 was increased by 17.6% (P = 0.002), whereas the levels of type I collagen and CD59 were respectively decreased by 12.5% (P = 0.024) and 21.6% (P = 0.044) with C3a treatment for 60 hours. CONCLUSIONS: These results indicated that C3a-induced complement activation is potentially involved in inducing myopic-associated scleral extracellular matrix remodelling via mediating the proliferation and function of HSFs.

Conjunctival microbiome changes in soft contact lens users and contact lens discomfort patients.

INTRODUCTION: Contact lens discomfort (CLD) acts as a challenging problem, and the associated conjunctival microbiome changes were unclear. MATERIAL AND METHODS: Conjunctival sac swab samples were collected from 12 eyes of nonwearers (NW), 12 eyes of asymptomatic contact lens (ACL) wearers, and 11 eyes of CLD. The V3-V4 region of the 16S rRNA gene sequencing was used to investigate differences among three groups. RESULTS: No differences in alpha diversity were observed among the three groups. The beta diversity showed a distinct microbiome composition between ACL and CLD group (P = 0.018) with principal coordinate analysis. The relative abundance of Firmicutes was significantly higher in CLD (48.18%) than in ACL (13.21%) group (P = 0.018). The abundance of Bacillus in patients with ACL (0.05%) or with CLD (0.02%) were significantly lower than that in the NW (1.27%) group (P = 0.024, 0.028, respectively). Moreover, the abundance of Firmicutes was positively correlated with the OSDI scores in CLD patients (r = 0.817, P < 0. 01, Spearman). DISCUSSIONS: Patients with CLD have various degrees of bacterial microbiota imbalance in the conjunctival sac, compared with NW and ACL groups. CONCLUSION: Firmicutes may serve as a potential biomarker for the CLD patients.

In the current study, we investigated the conjunctival microbiome changes among nonwearers (NW), asymptomatic contact lens (ACL) wearers, and contact lens discomfort (CLD) patients using high-throughput 16S rRNA gene sequencing, and correlated relative abundances of the microbiota with clinical parameters.The relative abundance of Firmicutes was higher in CLD than that in ACL group. The abundance of Bacillus was lower in ACL or CLD group than that in NW group. The abundance of Firmicutes was positively correlated with the OSDI scores in CLD patients.Firmicutes may serve as a potential biomarker for the CLD patients.

Comparison of Conjunctival Sac Microbiome between Low and High Myopic Eyes.

Microbial communities played a vital role in maintaining homeostasis of ocular surface. However, no studies explored the myopia-associated conjunctiva microbiota changes until now. In this study, conjunctival sac swab specimens were collected from 12 eyes of low myopia (LM), and 14 eyes of high myopia (HM) patients. The V3-V4 region of the 16S rRNA gene was amplified and then sequenced. Statistical analysis was performed to investigate differences in the taxonomy and diversity between two groups. Compared to LM, higher Ocular Surface Disease Index (OSDI) scores were observed in HM group. The Shannon index of the HM was lower than that of the LM group (P = 0.017). Principle coordinate analysis and Partial Least Squares Discrimination Analysis showed distinct microbiome composition between two groups. At the phylum level, there were higher relative abundances of Proteobacteria (68.27% vs 38.51%) and lower abundances of Actinobacteria (3.71% vs 9.19%) in HM, compared to LM group (P = 0.031, 0.010, respectively). At the genus level, the abundances of Acinetobacter in HM (18.16%) were significantly higher than the LM (6.52%) group (P = 0.011). Actinobacteria levels were negatively correlated with the myopic spherical equivalent and OSDI scores. Moreover, positive correlations were found between Proteobacteria levels and OSDI scores, Acinetobacter levels were positively correlated with myopic spherical equivalent and OSDI scores. In conclusion, HM Patients have bacterial microbiota imbalance in the conjunctival sac, compared with LM patients. Proteobacteria, Actinobacteria, Acinetobacter may play roles in the HM associated ocular surface irritation.

Delivery of Apoplastic Extracellular Vesicles Encapsulating Green-Synthesized Silver Nanoparticles to Treat Citrus Canker.

The citrus canker pathogen Xanthomonas axonopodis has caused severe damage to citrus crops worldwide, resulting in significant economic losses for the citrus industry. To address this, a green synthesis method was used to develop silver nanoparticles with the leaf extract of Phyllanthus niruri (GS-AgNP-LEPN). This method replaces the need for toxic reagents, as the LEPN acts as a reducing and capping agent. To further enhance their effectiveness, the GS-AgNP-LEPN were encapsulated in extracellular vesicles (EVs), nanovesicles with a diameter of approximately 30-1000 nm naturally released from different sources, including plant and mammalian cells, and found in the apoplastic fluid (APF) of leaves. When compared to a regular antibiotic (ampicillin), the delivery of APF-EV-GS-AgNP-LEPN and GS-AgNP-LEPN to X. axonopodis pv. was shown to have more significant antimicrobial activity. Our analysis showed the presence of phyllanthin and nirurinetin in the LEPN and found evidence that both could be responsible for antimicrobial activity against X. axonopodis pv. Ferredoxin-NADP+ reductase (FAD-FNR) and the effector protein XopAI play a crucial role in the survival and virulence of X. axonopodis pv. Our molecular docking studies showed that nirurinetin could bind to FAD-FNR and XopAI with high binding energies (-10.32 kcal/mol and -6.13 kcal/mol, respectively) as compared to phyllanthin (-6.42 kcal/mol and -2.93 kcal/mol, respectively), which was also supported by the western blot experiment. We conclude that (a) the hybrid of APF-EV and GS-NP could be an effective treatment for citrus canker, and (b) it works via the nirurinetin-dependent inhibition of FAD-FNR and XopAI in X. axonopodis pv.

Up-Regulation of NLRP3 in the Sclera Correlates with Myopia Progression in a Form-Deprivation Myopia Mouse Model.

BACKGROUND: NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) is a common inflammatory factor that induces inflammation by increasing the expression of related cytokines. Although the NLRP3 inflammasome has been implicated in many ophthalmic diseases, its role in myopia is largely unknown. The aim of this study was to explore the relationship between myopia progression and the NLRP3 pathway. METHODS: A form-deprivation myopia (FDM) mouse model was used. Different degrees of myopic shift were achieved via monocular form deprivation with 0-, 2-, and 4-week covering, and by 4-week covering followed by 1-week uncovering (the blank, FDM2, FDM4, and FDM5 groups, respectively) in both wild-type and NLRP3 (-/-) C57BL/6J mice. Axial length and refractive power were measured to assess the specific degree of myopic shift. The protein levels of NLRP3 and of related cytokines in the sclera were evaluated by Western blotting and immunohistochemistry. Collagen I and matrix metalloproteinase-2 (MMP-2), which affect extracellular matrix (ECM) remodeling of the sclera, were also examined to clarify the possible underlying mechanism. RESULTS: In wild-type mice, the FDM4 group had the most significant myopic shift. Both the increase in refractive power and the elongation in axial length were significantly different between the experimental and control eyes in the FDM2 group. The protein levels of NLRP3, caspase-1, IL-1ß, and IL-18 were significantly up-regulated in the FDM4 group compared to the other groups. The myopic shift was reversed and there was less up-regulation of cytokines in the FDM5 group compared to the FDM4 group. MMP-2 expression showed similar trends to NLRP3, while collagen I expression was inversely correlated. Similar results were found in NLRP3 -/- mice, although there was less myopic shift and less obvious changes in cytokine expression in the treatment groups as compared to the wild-type mice. In the blank group, no significant differences were found in refraction and axial length between wild-type mice and NLRP3 -/- mice of the same age. CONCLUSIONS: NLRP3 activation in the sclera could be involved in myopia progression in the FDM mouse model. Activation of the NLRP3 pathway up-regulated MMP-2 expression, which in turn affected collagen I and caused scleral ECM remodeling, eventually affecting myopic shift.

Two new antimicrobial monoterpenoid indole alkaloids from the roots of Rauvolfia yunnanensis.

Two new monoterpenoid indole alkaloids 3-hydroxylochnerine (1) and 10-hydroxyvinorine (2) were isolated from the roots of Rauvolfia yunnanensis. Their structures were elucidated based on the analysis of spectroscopic data and ECD calculation. Both compounds exhibited potent antimicrobial activity against Bacillus subtilis and Escherichia coli, and their activities were comparable to the well-known antibacterial drug berberine.

Possible risk factors of opaque bubble layer and its effect on high-order aberrations after small incision Lenticule extraction.

Purpose: To evaluate the possible risk factors of opaque bubble layer (OBL) formation in small incision lenticule extraction (SMILE) surgery and its effects on visual quality. Methods: Fifty-six eyes from 28 patients were included in this study. The preoperative parameters and intraoperative designs were recorded. Corneal high-order aberrations (HOAs), point spread function (PSF), and modulation transfer function (MTF) were measured using iTrace at pre-operation, 1 week, 1 month, and 3 months after SMILE. Generalized Estimating Equation and Linear Mixed Effects Model were employed for statistical analysis. Results: The mean OBL area in SMILE surgery was 2.75% ± 1.25%. The patients were divided into groups based on whether the OBL was greater than the mean group or less than the mean group. Compared to the group with a smaller OBL area, the group with the larger OBL area had steeper corneal curvature and thinner cap thickness, the OBL area was positively correlated with the preoperative keratometry (r = 0.21, p = 0.04) and preoperative spherical value (r = 0.47, p = 0.01). The group with the larger OBL area induced more corneal SA and trefoil at 1 week postoperatively, but the difference was not significant at 1 month and 3 months postoperatively. Conclusion: A steep corneal curvature, thin cap thickness, and high preoperative spherical value are possible risk factors for OBL formation in SMILE surgery. The OBL increased the ocular and corneal HOAs postoperatively for a short period (1 week), while it did not affect the long-term outcomes.