Phosphorylation of WRKY16 by MPK3-1 is essential for its transcriptional activity during fiber initiation and elongation in cotton (Gossypium hirsutum).

Cotton, one of the most important crops in the world, produces natural fiber materials for the textile industry. WRKY transcription factors play important roles in plant development and stress responses. However, little is known about whether and how WRKY transcription factors regulate fiber development of cotton so far. In this study, we show that a fiber-preferential WRKY transcription factor, GhWRKY16, positively regulates fiber initiation and elongation. GhWRKY16-silenced transgenic cotton displayed a remarkably reduced number of fiber protrusions on the ovule and shorter fibers compared to the wild-type. During early fiber development, GhWRKY16 directly binds to the promoters of GhHOX3, GhMYB109, GhCesA6D-D11, and GhMYB25 to induce their expression, thereby promoting fiber initiation and elongation. Moreover, GhWRKY16 is phosphorylated by the mitogen-activated protein kinase GhMPK3-1 at residues T-130 and S-260. Phosphorylated GhWRKY16 directly activates the transcription of GhMYB25, GhHOX3, GhMYB109, and GhCesA6D-D11 for early fiber development. Thus, our data demonstrate that GhWRKY16 plays a crucial role in fiber initiation and elongation, and that GhWRKY16 phosphorylation by GhMPK3-1 is essential for the transcriptional activation on downstream genes during the fiber development of cotton.

The Application of Rho Kinase Inhibitors in the Management of Glaucoma.

Glaucoma is a chronic neurodegenerative disease that poses a significant threat of irreversible blindness worldwide. Current treatments for glaucoma focus on reducing intraocular pressure (IOP), which is the only modifiable risk factor. Traditional anti-glaucomatous agents, including carbonic anhydrase inhibitors, beta-blockers, alpha-2 agonists, and prostaglandin analogs, work by either improving uveoscleral outflow or reducing aqueous humor production. Rho kinase (ROCK) inhibitors represent a novel class of anti-glaucomatous drugs that have emerged from bench to bedside in the past decade, offering multifunctional characteristics. Unlike conventional medications, ROCK inhibitors directly target the trabecular meshwork outflow pathway. This review aims to discuss the mechanism of ROCK inhibitors in reducing IOP, providing neuroprotection, and preventing fibrosis. We also highlight recent studies and clinical trials evaluating the efficacy and safety of ROCK inhibitors, compare them with other clinical anti-glaucomatous medications, and outline future prospects for ROCK inhibitors in glaucoma treatment.

Erythropoietin in Glaucoma: From Mechanism to Therapy.

Glaucoma can cause irreversible vision loss and is the second leading cause of blindness worldwide. The disease mechanism is complex and various factors have been implicated in its pathogenesis, including ischemia, excessive oxidative stress, neurotropic factor deprivation, and neuron excitotoxicity. Erythropoietin (EPO) is a hormone that induces erythropoiesis in response to hypoxia. However, studies have shown that EPO also has neuroprotective effects and may be useful for rescuing apoptotic retinal ganglion cells in glaucoma. This article explores the relationship between EPO and glaucoma and summarizes preclinical experiments that have used EPO to treat glaucoma, with an aim to provide a different perspective from the current view that glaucoma is incurable.

Overview of Recent Advances in Nano-Based Ocular Drug Delivery.

Ocular diseases profoundly impact patients' vision and overall quality of life globally. However, effective ocular drug delivery presents formidable challenges within clinical pharmacology and biomaterial science, primarily due to the intricate anatomical and physiological barriers unique to the eye. In this comprehensive review, we aim to shed light on the anatomical and physiological features of the eye, emphasizing the natural barriers it presents to drug administration. Our goal is to provide a thorough overview of various characteristics inherent to each nano-based drug delivery system. These encompass nanomicelles, nanoparticles, nanosuspensions, nanoemulsions, microemulsions, nanofibers, dendrimers, liposomes, niosomes, nanowafers, contact lenses, hydrogels, microneedles, and innovative gene therapy approaches employing nano-based ocular delivery techniques. We delve into the biology and methodology of these systems, introducing their clinical applications over the past decade. Furthermore, we discuss the advantages and challenges illuminated by recent studies. While nano-based drug delivery systems for ophthalmic formulations are gaining increasing attention, further research is imperative to address potential safety and toxicity concerns.

Biodegradable Polymer-Based Drug-Delivery Systems for Ocular Diseases.

Ocular drug delivery is a challenging field due to the unique anatomical and physiological barriers of the eye. Biodegradable polymers have emerged as promising tools for efficient and controlled drug delivery in ocular diseases. This review provides an overview of biodegradable polymer-based drug-delivery systems for ocular diseases with emphasis on the potential for biodegradable polymers to overcome the limitations of conventional methods, allowing for sustained drug release, improved bioavailability, and targeted therapy. Natural and synthetic polymers are both discussed, highlighting their biodegradability and biocompatibility. Various formulation strategies, such as nanoparticles, hydrogels, and microemulsions, among others, are investigated, detailing preparation methods, drug encapsulation, and clinical applications. The focus is on anterior and posterior segment drug delivery, covering glaucoma, corneal disorders, ocular inflammation, retinal diseases, age-related macular degeneration, and diabetic retinopathy. Safety considerations, such as biocompatibility evaluations, in vivo toxicity studies, and clinical safety, are addressed. Future perspectives encompass advancements, regulatory considerations, and clinical translation challenges. In conclusion, biodegradable polymers offer potential for efficient and targeted ocular drug delivery, improving therapeutic outcomes while reducing side effects. Further research is needed to optimize formulation strategies and address regulatory requirements for successful clinical implementation.

A Rare Case of Orbital Castleman Disease with Overlapping IgG4-Related Disease.

Multicentric Castleman disease (MCD) is a systemic lymphoproliferative disorder that can lead to mass lesions in various body parts, including the lungs, kidneys, and extranodal sites. Meanwhile, orbital Castleman disease is extremely rare. Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized fibroinflammatory disorder and is characterized by the formation of tumor-like lesions with lymphoplasmacytic infiltrates, which are enriched in IgG4-positive plasma cells and may present with a characteristic storiform pattern of fibrosis to variable degrees. In this study, we report a case of a 67-year-old Taiwanese man with a 7-year history of bilateral eyelid swelling and proptosis. Orbital magnetic resonance imaging revealed soft tissue lesions in the bilateral intraconal region, demonstrating strong enhancement in the lacrimal glands, and extension into the bilateral infraorbital foramen, suggesting an orbital lymphoproliferative disease. The histopathological results of the intraorbital tumor excision were suggestive of a plasma-cell-predominant mixed-cell variant of MCD. However, the patient also showed definitive signs of IgG4-RD, including lacrimal gland enlargement and histopathological results of plasmacytosis, fibrosis, and germinal centers, with an increased ratio of IgG4 cells and elevated serum IgG4 levels. This case suggests a potential interacting pathway between these two disease entities that needs further studies.

Efficient soliton self-frequency shift in hydrogen-filled hollow-core fiber.

We report a study of soliton self-frequency shifting in a hydrogen-filled hollow-core fiber. The combination of hydrogen and short 40-fs input pulses underlies clean and efficient generation of Raman solitons between 1080 and 1600 nm. With 240-nJ input pulses, the Raman soliton energy ranges from 110 to 20 nJ over that wavelength range, and the pulse duration is approximately 45 fs. In particular, 70-nJ and 42-fs pulses are generated at 1300 nm. Numerical simulations agree reasonably well with experiments and predict that microjoule-energy tunable pulses should be possible with higher-energy input pulses.

Pyrroloquinoline quinone ameliorates diabetic cardiomyopathy by inhibiting the pyroptosis signaling pathway in C57BL/6 mice and AC16 cells.

PURPOSE: Diabetic cardiomyopathy (DCM), a common complication of diabetes mellitus and is characterized by myocardial hypertrophy and myocardial fibrosis. Pyrroloquinoline quinone (PQQ), a natural nutrient, exerts strong protection against various myocardial diseases. Pyroptosis, a type of inflammation-related programmed cell death, is vital to the development of DCM. However, the protective effects of PQQ against DCM and the associated mechanisms are not clear. This study aimed to investigate whether PQQ protected against DCM and to determine the underlying molecular mechanism. METHODS: Diabetes was induced in mice by intraperitoneal injection of streptozotocin, after which the mice were administered PQQ orally (10, 20, or 40 mg/kg body weight/day) for 12 weeks. AC16 human myocardial cells were divided into the following groups and treated accordingly: control (5.5 mmol/L glucose), high glucose (35 mmol/L glucose), and HG + PQQ groups (1 and 10 nmol/L PQQ). Cells were treated for 24 h. RESULTS: PQQ reduced myocardial hypertrophy and the area of myocardial fibrosis, which was accompanied by an increase in antioxidant function and a decrease in inflammatory cytokine levels. Moreover, myocardial hypertrophy-(ANP and BNP), myocardial fibrosis-(collagen I and TGF-ß1), and pyroptosis-related protein levels decreased in the PQQ treatment groups. Furthermore, PQQ abolished mitochondrial dysfunction and the activation of NF-κB/IκB, and decreased NLRP3 inflammation-mediated pyroptosis in AC16 cells under high-glucose conditions. CONCLUSION: PQQ improved DCM in diabetic mice by inhibiting NF-κB/NLRP3 inflammasome-mediated cell pyroptosis. Long-term dietary supplementation with PQQ may be greatly beneficial for the treatment of DCM. Diagram of the underlying mechanism of the effects of PQQ on DCM. PQQ inhibits ROS generation and NF-κB activation, which stimulates activation of the NLRP3 inflammasome and regulates the expression of caspase-1, IL-1ß, and IL-18. The up-regulated inflammatory cytokines trigger myocardial hypertrophy and cardiac fibrosis and promote the pathological process of DCM.

The Latest Evidence of Erythropoietin in the Treatment of Glaucoma.

Erythropoietin (EPO) is a circulating hormone conventionally considered to be responsible for erythropoiesis. In addition to facilitating red blood cell production, EPO has pluripotent potential, such as for cognition improvement, neurogenesis, and anti-fibrotic, anti-apoptotic, anti-oxidative, and anti-inflammatory effects. In human retinal tissues, EPO receptors (EPORs) are expressed in the photoreceptor cells, retinal pigment epithelium, and retinal ganglion cell layer. Studies have suggested its potential therapeutic effects in many neurodegenerative diseases, including glaucoma. In this review, we discuss the correlation between glaucoma and EPO, physiology and potential neuroprotective function of the EPO/EPOR system, and latest evidence for the treatment of glaucoma with EPO.

Erythropoietin in Optic Neuropathies: Current Future Strategies for Optic Nerve Protection and Repair.

Erythropoietin (EPO) is known as a hormone for erythropoiesis in response to anemia and hypoxia. However, the effect of EPO is not only limited to hematopoietic tissue. Several studies have highlighted the neuroprotective function of EPO in extra-hematopoietic tissues, especially the retina. EPO could interact with its heterodimer receptor (EPOR/ßcR) to exert its anti-apoptosis, anti-inflammation and anti-oxidation effects in preventing retinal ganglion cells death through different intracellular signaling pathways. In this review, we summarized the available pre-clinical studies of EPO in treating glaucomatous optic neuropathy, optic neuritis, non-arteritic anterior ischemic optic neuropathy and traumatic optic neuropathy. In addition, we explore the future strategies of EPO for optic nerve protection and repair, including advances in EPO derivates, and EPO deliveries. These strategies will lead to a new chapter in the treatment of optic neuropathy.

Successful Resection of Retrobulbar Carcinosarcoma without Recurrence: A Case Report.

Carcinosarcomas are biphasic tumors comprising carcinoma and sarcoma components that occur in many tissues but are rarely found in the orbit. A 70-year-old male presented to the ophthalmic clinic with progressive proptosis, having decreased vision in the left eye for 8 months. On examination, severe exophthalmos and lagophthalmos with limited extraocular movement were noted. Orbital computed tomography scans revealed a large, well-defined, heterogeneously enhanced mass in the left retrobulbar orbital cavity. The tumor was completely resected, and the pathological examination revealed a carcinosarcoma. The prognosis was excellent without local recurrence at 48 months postoperatively. Thus, when considering treatment for effective management of such tumors, tumor resection followed by radiotherapy or chemotherapy is highly recommended.

800 Gb/s/200 m FSO link with a WDM-PAM4 scheme and SLM-based beam tracking technology.

An 800 Gb/s/200 m free-space optical (FSO) link with a wavelength-division multiplexing (WDM)-four-level pulse amplitude modulation (PAM4) scheme and spatial light modulator (SLM)-based beam tracking technology is constructed. To the best of our knowledge, this is the first one that adopts a WDM-PAM4 scheme and an SLM-based beam tracking technology to simultaneously afford a high transmission capacity of 800 Gb/s and resolve the laser beam misalignment problem due to target device movement. By adopting a 16-wavelength WDM-PAM4 scheme, the transmission capacity of the FSO link is considerably enhanced with an 800 Gb/s (50Gb/sPAM4/λ×16λ) total capacity. By deploying an SLM-based beam tracking technology, the laser beam misalignment problem is practically resolved for providing an FSO link with high link accessibility. This demonstrated WDM-PAM4 FSO link fully meets the requirements of high-speed, long-reach, and high-reliability transmissions.

Starting Dynamics of a Linear-Cavity Femtosecond Mamyshev Oscillator.

Mamyshev oscillators can generate high-power femtosecond pulses, but starting a mode-locked state has remained a major challenge due to the suppression of continuous-wave lasing. Here, we study the starting dynamics of a linear Mamyshev oscillator designed to generate high-power femtosecond pulses while avoiding component damage. Reliable starting to stable mode-locking is achieved with a combination of modulation of the pump power and shifting of a filter passband. The starting process is automated, with full electronic control. The laser delivers 21-nJ pulses that are dechirped to 65 fs in duration outside the cavity.

Axial length of cataract eyes: a comparison of two cohorts over a span of 10 years apart.

BACKGROUND: To assess the associations of axial length with age-related cataract within a span of 10 years in an Asian population in southern Taiwan. METHODS: A retrospective cohort study examined 960 adults who underwent cataract surgery at the Kaohsiung Chang Gung Memorial Hospital in year 2008 and year 2018. Axial length was assessed with the ultrasound biometry and/or the Zeiss IOLMaster. Eyes with prior blunt eye trauma or had underwent vitrectomy operations were excluded. The significance of the changes in axial length between the two cohorts was determined after performing age-matched analyses. Due to utilization of ultrasound biometry and/or Zeiss IOLMaster, axial length corrections with our mean difference in measurement results, which were similar to previous studies on comparison between the two measurement tools, were carried out. RESULTS: Axial length showed an age-related elongation in 10-year cross-sectional data, from a mean of 23.65 ± 1.80 mm in year 2008 to a mean of 24.30 ± 1.90 in year 2018 (p = 0.003). Patients with high myopia (axial length > 26 mm) increased significantly over the 10-year period from 8.1 to 16 % (p < 0.001). A birth cohort effect on axial length was evident as the axial lengths of year 2008 cohort were shorter than the 2018 cohort when they were in the same operation age group. In particular, persons born after the 1960s demonstrated a predominant increase in axial length in both cohorts. CONCLUSIONS: Our study confirms a trend in increase of axial myopia, especially high myopias, over the 10-year period. A novel finding of this study was discovering a birth cohort effect on axial length, especially in persons born after the 1960s in southern Taiwan.

Chorioretinal Folds in the Trabeculectomized Eye with Normal Intraocular Pressure after Phacoemulsification.

Background and Objectives: This case report discusses possible causes of chorioretinal fold (CRF) formation. Materials and Methods: A case report. Results: A 48-year-old man presented with a history of high myopia and primary open-angle glaucoma in both eyes. He underwent a trabeculectomy followed by phacoemulsification in both eyes. Two months later, he complained of blurred vision in the right eye. The intraocular pressure (IOP) was 17 mmHg in the left eye and 9 mmHg in the right eye. Refraction showed a hyperopic shift in both eyes. Slit-lamp examination showed a deep anterior chamber without cells and a well-functional bleb without leakage. Fundus examination revealed CRFs in the macula of the right eye. No papilledema, choroidal lesions, or other retinal lesions were found. Wrinkling of CRFs at the macula, an increase in central foveal thickness, and a fluid cleft were demonstrated by spectral-domain optical coherence tomography. After using steroid eye drops, the IOP in the right eye and refraction in both eyes recovered to the baseline level. Visual acuity improved in both eyes. Conclusions: CRFs in trabeculectomized eyes with normal IOP after phacoemulsification have not been reported. This case demonstrated that the trabeculectomized eye remains at risk of CRF formation, even if the IOP is normal without hypotony. The importance of a detailed fundus examination in patients with unexplained blurred vision may be necessary after having undergone these procedures. The early recognition of the cause of visual loss may facilitate immediate treatment and may avoid irreversible changes with permanent visual loss.

A Pulmonary Pleomorphic Carcinoma Patient with Exudative Retinal Detachment Secondary to Choroid Metastasis as Initial Presentation-A Case Report.

Choroid metastasis is the initial presentation of pleomorphic carcinoma (PC) of the lung. PC is classified as poorly differentiated non-small cell lung carcinoma. It has a tendency to metastasize early and has a poor response to chemotherapy, which often results in poor prognosis. We report the case of a 63-year-old woman with a one-month history of deteriorating vision in the left eye. Fundus examination, fluorescein angiography, indocyanine green angiography, and B-scan sonography demonstrated choroidal metastasis of the left eye. Positron emission tomography/computed tomography (PET/CT) revealed a tumor with increased uptake in the left upper lung. Subsequent bronchoscopic biopsy confirmed a pleomorphic carcinoma of the lungs. Choroid metastasis as an initial presentation of PC in the lung is rare. Usually, it represents the late course of disseminated disease with hematogenous spread. Prompt diagnosis is imperative for patients to immediately initiate treatment.

A Novel Procedure for the Management of Severe Hyphema after Glaucoma Filtering Surgery: Air-Blood Exchange under a Slit-Lamp Biomicroscopy.

Background and Objectives: This study introduces a novel office-based procedure involving air-blood exchange under a slit-lamp microscope for treatment of severe hyphema after filtering surgery. Materials and Methods: This retrospective study enrolled 17 patients (17 eyes) with a diagnosis of primary open-angle glaucoma with severe hyphema (≥4-mm height) after filtering surgery. All patients were treated with air-blood exchange under a slit-lamp using room air (12 patients) or 12% perfluoropropane (C3F8; five patients). Results: The procedures were successful in all 17 patients; they exhibited clear visual axes without complications during follow-up. In the room air group, the mean visual acuity (VA) and hyphema height significantly improved from 1.70 ± 1.07 LogMAR and 5.75 ± 1.14 mm before the procedure to 0.67 ± 0.18 LogMAR and 2.83 ± 0.54 mm after the procedure (p = 0.004; p < 0.001). In the C3F8 group, the mean VA showed a trend, though not significant, for improvement from 1.70 ± 1.10 LogMAR to 0.70 ± 0.19 LogMAR (p = 0.08); the mean hyphema height showed a trend for improvement from 5.40 ± 0.96 mm to 3.30 ± 0.45 mm. Compared with the C3F8 group, the room air group showed the same efficacy with a shorter VA recovery time. Conclusions: "Air-blood exchange under a slit-lamp using room air" is a convenient, rapid, inexpensive, and effective treatment option for severe hyphema after filtering surgery, and may reduce the risk of failure of filtering surgery.

Genome-wide identification of the mitogen-activated protein kinase (MAPK) family in cotton (Gossypium hirsutum) reveals GhMPK6 involved in fiber elongation.

Mitogen-activated protein kinases (MAPKs) are important in regulating plant development as well as stress response. In this study, we genome-widely identified 56 MAPK genes in upland cotton. These MAPK genes unequally distribute on 22 chromosomes of cotton genome, but no MAPK gene is located on At_Chr6, Dt_Chr6, At_Chr13 and Dt_Chr13. The exons and introns in GhMAPK gene family vary widely at the position, number and length. Furthermore, GhMAPK family can be divided into 4 groups (A, B, C and D), and the TEY type of T-loop exists in three groups (A, B and C), but the TDY type of T-loop is only in group D. Further study revealed that some GhMAPK genes (including GhMPK6) are preferentially expressed in elongating fibers. GhMPK6 maintains a high phosphorylation level in elongating fibers, and its phosphorylation was enhanced in fibers by phytohormones brassinosteroid (BR), ethylene and indole-3-acetic acid (IAA). Additionally, GhMPK6 could interact with GhMKK2-2 and GhMKK4, suggesting that GhMKK2-2/4-GhMPK6 module may be involved in phosphorylation of its downstream proteins for regulating fiber elongation of cotton.

Genome-wide identification and functional characterization of cotton (Gossypium hirsutum) MAPKKK gene family in response to drought stress.

BACKGROUND: Mitogen-activated protein kinase kinase kinases (MAPKKKs) are significant components in the MAPK signal pathway and play essential roles in regulating plants against drought stress. To explore MAPKKK gene family functioning in cotton response and resistance to drought stress, we conducted a systematic analysis of GhMAPKKKs. RESULTS: In this study, 157 nonredundant GhMAPKKKs (including 87 RAFs, 46 MEKKs and 24 ZIKs) were identified in cotton (Gossypium hirsutum). These GhMAPKKK genes are unevenly distributed on 26 chromosomes, and segmental duplication is the major way for the enlargement of MAPKKK family. Furthermore, members within the same subfamily share a similar gene structure and motif composition. A lot of cis-elements relevant to plant growth and response to stresses are distributed in promoter regions of GhMAPKKKs. Additionally, these GhMAPKKKs show differential expression patterns in cotton tissues. The transcription levels of most genes were markedly altered in cotton under heat, cold and PEG treatments, while the expressions of some GhMAPKKKs were induced in cotton under drought stress. Among these drought-induced genes, we selected GhRAF4 and GhMEKK12 for further functional characterization by virus-induced gene silencing (VIGS) method. The experimental results indicated that the gene-silenced cotton displayed decreased tolerance to drought stress. Malondialdehyde (MDA) content was higher, but proline accumulation, relative leaf water content and activities of superoxide dismutase (SOD) and peroxidase (POD) were lower in the gene-silenced cotton, compared with those in the controls, under drought stress. CONCLUSION: Collectively, a systematic survey of gene structure, chromosomal location, motif composition and evolutionary relationship of MAPKKKs were performed in upland cotton (Gossypium hirsutum). The following expression and functional study showed that some of them take important parts in cotton drought tolerance. Thus, the data presented here may provide a foundation for further investigating the roles of GhMAPKKKs in cotton response and resistance to drought stress.

A basic helix-loop-helix protein (GhFP1) promotes fibre elongation of cotton (Gossypium hirsutum) by modulating brassinosteroid biosynthesis and signalling.

Basic helix-loop-helix (bHLH) proteins are involved in transcriptional networks controlling a number of biological processes in plants. However, little information is known on the roles of bHLH proteins in cotton fibre development so far. Here, we show that a cotton bHLH protein (GhFP1) positively regulates fibre elongation. GhFP1 transgenic cotton and Arabidopsis plants were generated to study how GhFP1 regulates fibre cell elongation. Fibre length of the transgenic cotton overexpressing GhFP1 was significantly longer than that of wild-type, whereas suppression of GhFP1 expression hindered fibre elongation. Furthermore, overexpression of GhFP1 in Arabidopsis promoted trichome development. Expression of the brassinosteroid (BR)-related genes was markedly upregulated in fibres of GhFP1 overexpression cotton, but downregulated in GhFP1-silenced fibres. BR content in the transgenic fibres was significantly altered, relative to that in wild-type. Moreover, GhFP1 protein could directly bind to the promoters of GhDWF4 and GhCPD to activate expression of these BR-related genes. Therefore, our data suggest that GhFP1 as a positive regulator participates in controlling fibre elongation by activating BR biosynthesis and signalling. Additionally, homodimerisation of GhFP1 may be essential for its function, and interaction between GhFP1 and other cotton bHLH proteins may interfere with its DNA-binding activity.