Ecotoxicity of hexavalent chromium [Cr (VI)] in soil presents predominate threats to agricultural production with the increase of soil Cr contamination.

The relative severity between chromium (Cr)-mediated ecotoxicity and its bioaccumulation has rarely been compared and evaluated. This study employed pot incubation experiments to simulate the soil environment with increased Cr pollution and study their effects on the growth of crops, including pepper, lettuce, wheat, and rice. Results showed that increasing total Cr presented ascendant ecotoxicity in upland soils when pH > 7.5, and significantly reduced the yield of pepper, lettuce and wheat grain by 0.3-100 %, whereas, this effect was weakened even reversed as the pH decreased. Surprisingly, a series of soils with Cr concentration of 22.7-623.5 mg kg-1 did not cause Cr accumulation in four crops over the Chinese permissible limit. The toxicity of Cr was highly associated with extractable Cr, where Cr (VI) made the greater contributions than Cr (III). Conclusively, the ecotoxicity of Cr poses a greater environmental issue as compared to the bioaccumulation of Cr in crops in upland soils, while extractable Cr (VI) makes the predominant contributions to the ecotoxicity of Cr as the total Cr increased. Our study proposes a synchronous consideration involving total Cr and Cr (VI) as the theoretical basis to establish a more reliable soil quality standard for safe production in China.

Dataset of core and differentially abundant bacteria in various compartments of farm-cultivated and home-planted chilli plants (Capsicum frutescens).

Chillies are members of the genus Capsicum L. (family Solanaceae). They are native to Central and South America and consist of approximately 35 species [1,2]. Among these, five species (C. annuum L., C. baccatum L., C. chinense Jacq., C. frutescens L., and C. pubescens Ruiz & Pav.) have been domesticated and are mainly cultivated for consumption as vegetables and spices. Of the domesticated chillies, C. annuum is commercially cultivated worldwide, while C. frutescens and C. chinense are mainly cultivated in American, Asian, and African countries [3]. We compared the diversity of microbiota in various compartments of farm-cultivated (FC) and home-planted (HP) chilli plants (Capsicum frutescens). Targeted 16S rRNA gene (V5-V6 region) was sequenced using the Illumina NovaSeq 6000 platform. Proteobacteria, Actinobacteriota, Acidobacteriota, Gemmatimonadota, Bacteroidota, and Firmicutes were present in all compartments of both the FC and HP plants. Proteobacteria (or Pseudomonadota) was the predominant phylum in all the compartments of both HP and FC plants, while Actinobacteriota (or Actinomycetota) was the second most abundant phylum. Most plant compartments (leaves, fruits and roots) exhibited a higher relative abundance of Proteobacteria compared to the soil samples. With few exceptions, the soil compartments (bulk and rhizospheric soils) displayed a higher relative abundance of the phyla Myxococcota, Acidobacteriota, Gemmatimonadota, Bacteroidota, Nitrospirota, Verrucomicrobiota, and Firmicutes than the plant compartments. Diversity indices revealed that the bacterial community in chili plants clustered based on both compartment and cultivation area.

Facile fabrication of linezolid/strontium coated hydroxyapatite/graphene oxide nanocomposite for osteoporotic bone defect.

Hydroxyapatite (HAp) coatings currently have limited therapeutic applications because they lack anti-infection, osteoinductivity, and poor mechanical characteristics. On the titanium substrate, electrochemical deposition (ECD) was used to construct the strontium (Sr)-featuring hydroxyapatite (HAp)/graphene oxides (GO)/linezolid (LZ) nanomaterial coated with antibacterial and drug delivery properties. The newly fabricated nanomaterials were confirmed by X-ray diffraction analysis (XRD), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS) analysis and morphological features were examined by scanning electron microscope (SEM) analysis. The results reveal multiple nucleation sites for SrHAp/GO/LZ composite coatings due to oxygen-comprising moieties on the 2D surface of GO. It was shown to be favorable for osteoblast proliferation and differentiation. The elastic modulus and hardness of LZ nanocomposite with SrHAp/GO/LZ coatings were increased by 67 % and 121 %, respectively. An initial 5 h burst of LZ release from the SrHAp/GO/LZ coating was followed by 14 h of gradual release, owing to LZ's physical and chemical adsorption. The SrHAp/GO/LZ coating effectively inhibited both S. epidermidis and S. aureus, and the inhibition lasted for three days, as demonstrated by the inhibition zone and colony count assays. When MG-63 cells are coated with SrHAp/GO/LZ composite coating, their adhesion, proliferation, and differentiation greatly improve when coated with pure titanium. A novel surface engineering nanomaterial for treating and preventing osteoporotic bone defects, SrHAp/GO/LZ, was shown to have high mechanical characteristics, superior antibacterial abilities, and osteoinductivity.

"One-Stone-Three-Birds" H2S-Photothermal Therapy for Enhanced Thrombolysis and Vascular Healing.

Thrombus causes a serious condition characterized by the formation of blood clots in blood vessels or heart, potentially leading to life-threatening emergencies. Photothermal therapy (PTT) serves as a treatment for thrombosis that provides noninvasive thrombus dissolution and fewer bleeding side effects. However, the high temperatures generated by PTT can exacerbate vascular inflammation and promote thrombus recurrence. In this study, a photothermal hydrogen sulfide (H2S) nanogenerator (PSA@ADT-OH) is constructed using a perylene-cored photothermal agent (PSA) coassembled with a H2S donor ADT-OH. The system PSA@ADT-OH demonstrates outstanding targeting and accumulation efficiency against blood flow shear forces. It also provides sustained H2S release at thrombus sites, contributing to antiplatelet aggregation, reactive oxygen species clearance, and vascular healing. This approach opens up new possibilities for advanced thrombus treatment.

Viral Communities Suppress the Earthworm Gut Antibiotic Resistome by Lysing Bacteria on a National Scale.

Earthworms are critical in regulating soil processes and act as filters for antibiotic resistance genes (ARGs). Yet, the geographic patterns and main drivers of earthworm gut ARGs remain largely unknown. We collected 52 earthworm and soil samples from arable and forest ecosystems along a 3000 km transect across China, analyzing the diversity and abundance of ARGs using shotgun metagenomics. Earthworm guts harbored a lower diversity and abundance of ARGs compared to soil, resulting in a stronger distance-decay rate of ARGs in the gut. Greater deterministic assembly processes of ARGs were found in the gut than in soil. The earthworm gut had a lower frequency of co-occurrence patterns between ARGs and mobile genetic elements (MGEs) in forest than in arable systems. Viral diversity was higher in the gut compared to soil and was negatively correlated with bacterial diversity. Bacteria such as Streptomyces and Pseudomonas were potential hosts of both viruses and ARGs. Viruses had negative effects on the diversity and abundance of ARGs, likely due to the lysis on ARG-bearing bacteria. These findings provide new insights into the variations of ARGs in the earthworm gut and highlight the vital role of viruses in the regulation of ARGs in the soil ecosystem.

Silibinin Targeting Heat Shock Protein 90 Represents a Novel Approach to Alleviate Nonalcoholic Fatty Liver Disease by Simultaneously Lowering Hepatic Lipotoxicity and Enhancing Gut Barrier Function.

Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological condition characterized by intrahepatic ectopic steatosis. Due to the increase in high-calorie diets and sedentary lifestyles, NAFLD has surpassed viral hepatitis and become the most prevalent chronic liver disease globally. Silibinin, a natural compound, has shown promising therapeutic potential for the treatment of liver diseases. Nevertheless, the ameliorative effects of silibinin on NAFLD have not been completely understood, and the underlying mechanism is elusive. Therefore, in this study, we used high-fat diet (HFD)-induced mice and free fatty acid (FFA)-stimulated HepG2 cells to investigate the efficacy of silibinin for the treatment of NAFLD and elucidate the underlying mechanisms. In vivo, silibinin showed significant efficacy in inhibiting adiposity, improving lipid profile levels, ameliorating hepatic histological aberrations, healing the intestinal epithelium, and restoring gut microbiota compositions. Furthermore, in vitro, silibinin effectively inhibited FFA-induced lipid accumulation in HepG2 cells. Mechanistically, we reveal that silibinin possesses the ability to ameliorate hepatic lipotoxicity by suppressing the heat shock protein 90 (Hsp90)/peroxisome proliferator-activated receptor-γ (PPARγ) pathway and alleviating gut dysfunction by inhibiting the Hsp90/NOD-like receptor pyrin domain-containing 3 (NLRP3) pathway. Altogether, our findings provide evidence that silibinin is a promising candidate for alleviating the "multiple-hit" in the progression of NAFLD.

Sublingual Misoprostol-Induced Rhabdomyolysis and Convulsions in Postpartum Hemorrhage: A Case Report and Literature Review.

Postpartum hemorrhage (PPH) remains the leading cause of maternal mortality, primarily attributed to uterine atony. Both the World Health Organization (WHO) and the International Federation of Gynecology and Obstetrics (FIGO) endorse the use of misoprostol not only for the prevention but also for the treatment of PPH. However, the administration of misoprostol is commonly associated with transient pyrexia, attributed to a shift in the hypothalamic set point observed in certain animal studies. Misoprostol-induced hyperpyrexia can occasionally manifest with a prodrome of shivering, particularly when administered via the sublingual route, which achieves a higher and faster maximum plasma concentration compared to vaginal and rectal routes. General management strategies to reduce fever involve removing clothing and blankets, applying cool compresses, administering oral acetaminophen, and ensuring adequate hydration. While some cases have reported misoprostol-induced convulsions, hyperpyrexia leading to convulsions and subsequent rhabdomyolysis is a rare and potentially lethal side effect. In this case presentation, we emphasize a scenario where misoprostol was employed for the treatment of PPH but led to rhabdomyolysis. Our goal is to highlight the side effects of misoprostol and the significance of considering the initial combination of misoprostol with anti-pyretic management to minimize the risk of hyperthermia-related side effects and prevent additional severe complications.

Pharmacological Interventions for Menière's Disease: A Systematic Review and Network Meta-Analysis.

Objective: Evaluation of the effectiveness and posttreatment effects of intratympanic gentamicin and corticosteroids in treating patients with Ménière's disease (MD). Methods: Based on PubMed and Embase databases, randomized controlled trials using intratympanic injections of 4 drugs (gentamicin, methylprednisolone, dexamethasone, and placebo) for the treatment of MD were searched from 1995 to October 2023, and the literature was screened according to inclusion and exclusion criteria, and data were netted for meta-analysis using Stata 17. Results: A total of 13 studies were selected, involving 559 participants, with follow-up time ranging from 3 to 28 months. Meta-analysis showed that there was no statistically significant difference in pure-tone average between gentamicin and dexamethasone [standardized mean difference (SMD) = 0.09, 95% confidence interval (CI) (-0.42, 0.24), P < .05]. Compared to placebo, intratympanic injection of gentamicin [risk ratio (RR) = 1.18, 95% CI (0.43, 1.93)], methylprednisolone [RR = 0.88, 95% CI (0.07, 1.70)], and dexamethasone [RR = 0.70, 95% CI (-0.01, 1.41)] all showed better efficacy in treating vertigo. For the treatment of tinnitus, the SUCRA ranking results showed that dexamethasone was the most effective, followed by methylprednisolone and gentamicin. Conclusion: Pharmacological intervention is more effective than placebo in treating MD. Although gentamicin treatment shows significant effects in treating vertigo, corticosteroid combination therapy is markedly superior to gentamicin in controlling hearing loss and vertigo symptoms.

Risk factors for development of anti-adalimumab antibodies in non-infectious uveitis.

Purpose: To evaluate risk factors associated with development of anti-adalimumab antibodies (AAA) in patients with non-infectious uveitis treated with adalimumab. Methods: A retrospective, cross-sectional, case-control study was done evaluating patients with non-infectious uveitis treated with adalimumab for at least 12 months and have undergone testing for AAA levels. Demographics, clinical characteristics, grading of ocular inflammation, and previous and concomitant immunomodulatory therapy were assessed. Univariate and multivariate analysis were done to estimate odds ratio (OR) with 95% confidence intervals for the various risk factors. Results: A total of 31 patients were included in the analysis, in which 12 patients who tested positive (Group 1) were matched with 19 patients who tested negative for AAA (Group 2). The groups differed significantly in terms of sex (female) (91.7% vs 52.6%, p = 0.046), presence of systemic disease (91.7% vs 42.1%, p = 0.008), and presence of anterior chamber inflammation at baseline (100% vs 63.2%, p = 0.026). A history of interruption in anti-TNF therapy prior to starting or restarting adalimumab was found to have an increased odds for development of AAA (OR 16.89 [2.92, 107.11], p = 0.008), as well as flare-ups (reactivation of disease) during adalimumab therapy (OR 6.77 [1.80, 61.80], p = 0.027). Weekly dosing of adalimumab was shown to decrease odds of AAA development (OR 0.34 [0.02, 0.70], p = 0.040), while concomitant anti-metabolite therapy was not shown to be a statistically significant protective factor (OR 2.22 [0.50, 9.96], p = 0.148). Conclusions: History of interruption in anti-TNF therapy and flare during adalimumab were associated with development of AAA, while weekly dosing of adalimumab was protective against AAA. Identification of those with higher risk of developing AAA may guide in clinical decision making to optimize management for these patients.

Importance of Baseline Fluorescein Angiography for Patients Presenting to Tertiary Uveitis Clinic.

PURPOSE: To ascertain whether the use of ultra-wide-field fluorescein angiography (UWFFA) at baseline visit alters the assessment of disease activity and localization, as well as the management of patients presenting to a tertiary uveitis clinic. DESIGN: Retrospective comparison of diagnostic approaches. METHODS: Baseline visits of 158 patients who presented to the Uveitis Clinic at the Byers Eye Institute at Stanford between 2017 and 2022 were evaluated by 3 uveitis-trained ophthalmologists (I.K., A.B., and H.G.). Each eye had undergone clinical examination along with ultra-wide-field fundus photography (UWFFP) (Optos Plc), spectral-domain optical coherence tomography (SD-OCT, Spectralis Heidelberg, Heidelberg Engineering) and UWFFA (Optos Plc) at the baseline visit. Investigators were asked to successively determine disease activity, localization of disease (anterior, posterior or both), and management decisions based on clinical examination and UWFFP and SD-OCT (Set 1) and Set 1 plus UWFFA (Set 2). The primary outcome was the percentage of eyes whose management changed based on the availability of UWFFA compared with Set 1. RESULTS: The mean age of the patients was 46.9 ± 22.4 years (range, 7-96), and 91 (57.6%) were female. With Set 1 alone, 138 eyes (55.2%) were found to have active disease; localization was anterior in 58 eyes (42.0%), posterior in 53 eyes (38.4%), and anterior + posterior in 27 eyes (19.6%). With Set 2, 169 eyes of 107 patients had active anterior, posterior, or panuveitis. In comparison with Set 1, assessment with Set 2 identified additional 31 eyes (18.3%) with active disease (P = .006) and an additional 31 eyes (18.3%) having disease in both anterior + posterior segments (P < .001). Regarding the primary outcome, management was changed in 68 eyes (27.4%) in Set 2 compared with Set 1. CONCLUSIONS: Baseline UWFFA may alter assessment of disease activity, localization, and management decisions compared with clinical examination with only UWFFP and SD-OCT for eyes with uveitis. Thus, UWFFA may be considered as an essential tool in the evaluation of patients with uveitis at the baseline visit.

A Light-Triggered J-Aggregation-Regulated Therapy Conversion: from Photodynamic/Photothermal Therapy to Long-Lasting Chemodynamic Therapy for Effective Tumor Ablation.

Reactive oxygen species (ROS) have become an effective tool for tumor treatment. The combination of photodynamic therapy (PDT) and chemodynamic therapy (CDT) takes advantage of various ROS and enhances therapeutic effects. However, the activation of CDT usually occurs before PDT, which hinders the sustained maintenance of hydroxyl radicals (⋅OH) and reduces the treatment efficiency. Herein, we present a light-triggered nano-system based on molecular aggregation regulation for converting cancer therapy from PDT/photothermal therapy (PTT) to a long-lasting CDT. The ordered J-aggregation enhances the photodynamic properties of the cyanine moiety while simultaneously suppressing the chemodynamic capabilities of the copper-porphyrin moiety. Upon light irradiation, Cu-PCy JNPs demonstrate strong photodynamic and photothermal effects. Meanwhile, light triggers a rapid degradation of the cyanine backbone, leading to the destruction of the J-aggregation. As a result, a long-lasting CDT is sequentially activated, and the sustained generation of ⋅OH is observed for up to 48 hours, causing potent cellular oxidative stress and apoptosis. Due to their excellent tumor accumulation, Cu-PCy JNPs exhibit effective in vivo tumor ablation through the converting therapy. This work provides a new approach for effectively prolonging the chemodynamic activity in ROS-based cancer therapy.

A current reference-enhanced strategy endows the GFC in DC microgrids better dynamic response.

The constant voltage strategy (CVS) is more suitable for the small-capacity dc microgrid applications to form the dc bus voltage because it can eliminate the steady voltage deviation. However, its dynamic performance is slowed down by the integrator in the voltage loop and negatively influenced by the load steps. Some advanced methods have been conducted in the literature. However, their principle is to increase the system bandwidth, which is limited because the bandwidth is generally designed about one-tenth of the switching frequency and cannot be increased infinitely. This work pays efforts to increase the gain within the system bandwidth to accelerate the transient response and simultaneously eliminate the influence of the integrator. Therefore, the non-integrator disturbance observer-based (NIDOB) strategy is proposed in this work, and it can feed the load current into the current reference to replace the output of the integrator. Compared to the traditional and non-integrator directly-feedforward (NIDF) strategy, it has a better dynamic performance. Compared to the bandwidth-increased strategy, it does not introduce more noise. The theoretical analysis and experimental results prove its advantages.

Oxalisxishuiensis (Oxalidaceae), a new species from Danxia landforms in Guizhou, China.

Oxalisxishuiensis, a new species of Oxalidaceae from Danxia landforms of Xishui County, Guizhou, China, is described and illustrated. It is morphologically similar to O.wulingensis by the two lateral leaflets arranged at about 180° angle and oblong pink petals with lilac veins, but clearly differs from the latter by leaflets almost as long as wide, obliquely obcordate lateral leaflets, shorter peduncles, longer capsule (1.2-1.5 cm vs. 0.5-0.7 cm) and alveolate seeds.

An efficient ß-nucleating agent with high lattice matching rate for plate-like crystallization of polypropylene random copolymer.

It is challenging to naturally produce large amounts of ß-crystals by directly adding a commercial ß-nucleating agent (ß-NA) into polypropylene random copolymer (PPR) at present. In this work, a novel rare earth ß-NA WBN-28 was directly introduced into PPR to prepare ß-PPR with high ß-crystal conversion. The results of differential scanning calorimetry (DSC) and wide-angle X-ray diffraction (WAXD) indicated that it is an efficient ß-NA for PPR. The ß-conversion rate (ß-CR) could surpass 85% when the nucleating agent content was mere 0.05%. With the further increment of nucleating agent, the ß-CR increased gradually, which could reach 89.5% and 86.9% respectively calculated by DSC and WAXD when the addition amount was 0.4%. The incredible high ß-CR delayed the ßα-recrystallization in isothermal crystallization. The fusion peak of α-crystal was unobserved below the isothermal crystallization temperature of 122 °C when the addition amount was more than 0.2%. Furthermore, there was a highly ordered structure in WBN-28 with the periodicity of 12.89 Å, which was approximately twice of the unit cell parameter in the c direction of ß-PP, indicating a high lattice matching rate between them. Intuitively observed by polarizing optical microscope (POM), the crystal grains of the blends with ß-NA were more refined and finally crystallized in a plate-like shape. The forming process of the plate-like ß crystalline regions were proposed by scanning electron microscope (SEM) and POM.

The Crystallization Morphology and Conformational Changes of Polypropylene Random Copolymer Induced by a Novel ß-Nucleating Agent.

The crystal morphology and conformational changes during crystallization of a polypropylene random copolymer (PPR) are the basis for understanding its crystallization process. In this work, novel rare-earth ß-nucleating agent WBN-28 was directly added into PPR to induce ß-crystallization. The results of differential scanning calorimetry (DSC) showed that it has an excellent ß-crystal-induced effect. The ß-crystal content could surpass 85%, calculated from wide-angle X-ray diffraction (WAXD) data. The morphology of the ß-crystal and α-crystal was intuitively observed via a polarizing optical microscope (POM). The ß-crystallites were interconnected to naturally develop plate-like crystalline regions possessing a certain size, and the α-crystallites with sufficient thicknesses possessed a cross-hatched phenomenon. The bundle-like supramolecular structure of the ß-crystal induced by WBN-28 was further observed via a scanning electron microscope (SEM). The conformational changes in the crystallization process of PPR were resolved via high-resolution infrared spectroscopy to understand its ß-crystallization in depth. The conformational changes during the crystallization of PPR were found to be different from those of the isotactic polypropylene homopolymer (PPH); they had their own characteristics. This will provide guidance for understanding the ß-crystallization of PPR in depth.

The Role of Corticosteroids and Immunomodulatory Therapy in the Management of Infectious Uveitis.

PURPOSE: The index review aims to provide an update on the role of corticosteroids and steroid-sparing immunomodulatory therapy (IMT) in managing patients with infectious uveitis. METHOD: Narrative literature review. RESULTS: Corticosteroids and immunomodulatory therapy (IMT) focus on the host defense system instead of the pathogen, adjusting exaggerated inflammatory reactions to reduce potential harm to ocular tissues. Systemic or local corticosteroids are primarily selected as adjunctive medication for infectious uveitis. Concomitant corticosteroids have also been used in cases of paradoxical worsening in ocular tuberculosis and immune recovery uveitis in cytomegalovirus (CMV) retinitis. While there is no well-established evidence to support the use of IMT in infectious uveitis, it is occasionally used in clinical settings to treat persistent inflammation following resolution of infection such as cases of ocular tuberculosis and ocular syphilis where an insufficient response is observed with corticosteroids. CONCLUSION: There is no consensus on the position of immunomodulatory therapy in the management of infectious uveitis with different etiologies. The index review provides an overview of available adjunctive corticosteroids and IMT options to assist clinicians in managing such disease entities more efficiently.

Cytomegalovirus Corneal Endotheliitis: A Comprehensive Review.

Cytomegalovirus (CMV) anterior uveitis and corneal endotheliitis are the most common ocular diseases caused by CMV infections in immunocompetent patients. The incidence of CMV corneal endotheliitis is relatively high in middle-aged men. CMV corneal endotheliitis presents with mild anterior chamber inflammation, corneal edema, keratic precipitates, and elevated intraocular pressure. It resembles Posner-Schlossman syndrome and Fuchs uveitis because of the elevated intraocular pressure. Without proper diagnosis and treatment, it may progress to bullous keratopathy or glaucoma, necessitating keratoplasty or glaucoma surgery. Therefore, early diagnosis and treatment are important for a good prognosis. Aqueous humor analysis can facilitate the diagnosis of CMV corneal endotheliitis, and early antiviral treatment can decrease the risk of corneal compensation or glaucomatous optic atrophy. In this article, we review the epidemiology, pathogenesis, clinical manifestations, diagnosis, treatment, and prognosis of CMV corneal endotheliitis along with the evidence for early clinical diagnosis and active antiviral treatment.

Molecular and functional characterization of a type-1 cystatin in amphioxus (Branchiostoma japonicum).

Cystatins comprise a vast superfamily of evolutionary conserved proteins, predominantly recognized for their roles as endogenous inhibitors by regulating the activity of cysteine proteases. Emerging lines of research evidence also provides insight into their alternative roles in a spectrum of biological and pathological processes, including neurodegenerative disorders, tumor progression, inflammatory diseases, and immune response. Nowadays, various type-1 cystatins (stefins) have been demonstrated among a variety of discovered vertebrate groups, while little is known about the related homologue in cephalochordate amphioxus, which are repositioned at the base of the chordate phylum. In the present study, a single type-1 cystatin homologue in Branchiostoma japonicum was first successfully cloned and designated as Bjcystatin-1. The deduced Bjcystatin-1 protein is structurally characterized by the presence of typical wedge-shaped cystatin features, including the 'QxVxG' and 'Px' motif, as well as the conserved N-terminal glycine residue. Phylogenomic analyses utilizing different cystatin counterparts affirmed the close evolutionary relationship of Bjcystatin-1 and type-1 cystatin homologue. Bjcystatin-1 was predominantly expressed in the gills and hind-gut in a tissue-specific pattern, and its expression was remarkably up-regulated in response to challenge with bacteria or their signature molecules LPS and LTA, suggesting the involvement in immune response. Additionally, the recombinant Bjcystatin-1 (rBjcystatin-1) protein showed significant inhibitory activity towards papain and binding ability to LPS and LTA, indicating its hypothesized role as a pattern recognition receptor in immune response. Subcellular localization results also showed that Bjcystatin-1 was located in the cytoplasm and nucleus, and its overexpression could attenuate the activation of LPS-induced nuclear transcription factors NF-κB. Taken together, our study suggests that amphioxus Bjcystatin-1 acts as a dual role in protease inhibitor and an immunocompetent factor, providing new insights into the immune defense effect of type-1 cystatin in amphioxus.

Challenges for further successful development of tumor necrosis factor targeting therapies for uveitis.

INTRODUCTION: Uveitis is a heterogeneous group of ocular conditions characterized by inflammation of the uveal tract and is one of the leading causes of vision impairment. In developed countries, noninfectious uveitis (NIU) represents most cases and is challenging to treat due to its severity, chronicity, and high recurrence rates. The advent of anti-tumor necrosis factor-α (anti-TNF-α) agents have dramatically improved outcomes and changed treatment paradigms in NIU. AREAS COVERED: The index article summarizes the present experience of anti-TNF-α agents in NIU pharmacotherapy and highlights the barriers to further research and development of anti-TNF-α agents for uveitis. Common challenges faced in NIU clinical drugs trials, specific difficulties in anti-TNF-α drug development, and promising competitor drug candidates are discussed and evaluated. EXPERT OPINION: Anti-TNF-α agents have revolutionized NIU pharmacotherapy and greatly improved outcomes with good safety profiles. The great success of systemic infliximab and adalimumab in NIU treatment has resulted in little impetus for further development of this class of medication. Attempts have been made to deliver anti-TNF-α agents intravitreally but that has not been successful thus far. With expiring patents, competition from biosimilars and newer, novel molecules, it may not be viable to continue pursuing anti-TNF-α drug development.