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Non-infectious uveitis (NIU) is a disorder with various etiologies and is characterized by eye inflammation, mainly affecting people of working age. An accurate diagnosis of NIU is crucial for appropriate therapy. The aim of therapy is to improve vision, relieve ocular inflammation, prevent relapse, and avoid treatment side effects. At present, corticosteroids are the mainstay of topical or systemic therapy. However, repeated injections are required for the treatment of chronic NIU. Recently, new drug delivery systems that may ensure intraocular delivery of therapeutic drug levels have been highlighted. Furthermore, with the development of immunosuppressants and biologics, specific therapies can be selected based on the needs of each patient. Immunosuppressants used in the treatment of NIU include calcineurin inhibitors and antimetabolites. However, systemic immunosuppressive therapy itself is associated with adverse effects due to the inhibition of immune function. In patients with refractory NIU or those who cannot tolerate corticosteroids and immunosuppressors, biologics have emerged as alternative treatments. Thus, to improve the prognosis of patients with NIU, NIU should be managed with different drugs according to the response to treatment and possible side effects. [ABSTRACT FROM AUTHOR]

Histone methylation is an important epigenetic modification that affects various biological processes, including the inflammatory response. In this study, we found that infection with Japanese encephalitis virus (JEV) leads to an increase in H3K27me3 in BV2 microglial cell line, primary mouse microglia and mouse brain. Inhibition of H3K27me3 modification through EZH2 knockdown and treatment with EZH2 inhibitor significantly reduces the production of pro-inflammatory cytokines during JEV infection, which suggests that H3K27me3 modification plays a crucial role in the neuroinflammatory response caused by JEV infection. The chromatin immunoprecipitation-sequencing (ChIP-sequencing) assay revealed an increase in H3K27me3 modification of E3 ubiquitin ligases Rnf19a following JEV infection, which leads to downregulation of Rnf19a expression. Furthermore, the results showed that Rnf19a negatively regulates the neuroinflammatory response induced by JEV. This is achieved through the degradation of RIG-I by mediating its ubiquitination. In conclusion, our findings reveal a novel mechanism by which JEV triggers extensive neuroinflammation from an epigenetic perspective. [ABSTRACT FROM AUTHOR]

Objective. This meta-analysis was performed to evaluate the anatomical efficacy and functional improvement of the conventional inverted internal limiting membrane (ILM), flap covering technique, and ILM flap filling technique for patients with idiopathic macular hole (MH). Methods. Literature from Pubmed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science were comprehensively retrieved. The primary outcomes included the MH closure rate and postoperative best-corrected visual acuity (BCVA). The secondary outcomes were the proportion of external limiting membrane (ELM) and ellipsoid zone (EZ) defect recovery. Pooled odds ratios (ORs), weighted mean differences (WMDs), and 95% confidence intervals (CIs) were calculated using STATA 17.0 software. Results. 7 studies that contained 139 eyes in the inverted ILM flap covering group and 121 eyes in the ILM flap filling group were selected. Pooled data suggested that the surgical treatment resulted in an overall MH closure rate of up to 97.12% (135/139 eyes) in the inverted ILM flap covering group and 99.17% (120/121 eyes) in the filling group, with no significant difference between the 2 groups (OR = 1.98, 95% CI: 0.55 to 7.09, and P = 0.29). Similarly, the 2 techniques demonstrated equal effectiveness on the anatomical closure in MH with the average diameter smaller than 650 μm (OR = 2.17, 95% CI: 0.48 to 9.77, and P = 0.31) and larger than 650 μm (OR = 1.58, 95% CI: 0.14 to 17.37, and P = 0.71). However, compared with the filling technique, the inverted ILM flap covering technique was superior in postoperative BCVA (WMD = 0.11, 95% CI: 0.04 to 0.18, and P = 0.0017) and presented a significantly higher proportion of reconstitution of ELM (OR = 0.02, 95% CI: 0.00 to 0.08, and P < 0.0001) and EZ (OR = 0.11, 95% CI: 0.04 to 0.32, and P = 0.0001). Conclusion. The inverted ILM flap covering technique was associated with the superior reconstitution of outer layers of the retina, including ELM and EZ, and more improvement in postoperative BCVA than the ILM flap filling technique. [ABSTRACT FROM AUTHOR]

The left eye was vitrectomized for vitreous opacities, and pathological examination of the vitrectomy stained with alkaline Congo red showed amyloid deposits, which confirmed ATTRv amyloidosis. Nerve conduction studies showed the amplitude reduction of compound muscle action potentials (CMAPs) in the right common peroneal nerve. Hereditary transthyretin (ATTRv) amyloidosis is an autosomal dominant disease mainly characterised by abnormal deposition of amyloid fibrils that lead to multisystem disorders [[1]]. [Extracted from the article]

Highlights: [•] The solubility of pioglitazone hydrochloride in different binary solvents was investigated. [•] The results show that the two models agree well with the experimental data. [•] The thermodynamic functions of solution were obtained from these solubility data. [•] The dominant mechanisms of solvent action are enthalpy–entropy compensation. [Copyright &y& Elsevier]

The solubility of pioglitazone hydrochloride (Form II)in N,N-dimethylacetamide, methanol, dimethyl sulfoxide,and acetic acid was determined at temperatures ranging from 283.15to323.15 K. The experimental data were correlated with the modifiedApelblat equation, λhequation, van’tHoff equation, ideal model, Wilson model, and nonrandom two-liquidmodel. Calculation results show that the λhequation, van’t Hoff equation, and the ideal model are moresuitable in determining the solubility of pioglitazone hydrochloride(Form II) compared with the other three models. By using the van’tHoff equation, the dissolution enthalpy, entropy, and molar Gibbsfree energy of pioglitazone hydrochloride (Form II) are predictedin different solvents. [ABSTRACT FROM AUTHOR]

The solubility of pioglitazone hydrochloride (form I) in methanol, ethanol, 1-propanol, acetic acid, and N,N-dimethylacetamide has been measured between 278.15 and 323.15 K at atmospheric pressure. The solubility of pioglitazone hydrochloride (form I) increases with increasing temperature and the order is N,N-dimethylacetamide > methanol > acetic acid > ethanol >1-propanol. The experimental data were correlated well by the Apelblat equation. [ABSTRACT FROM AUTHOR]

• Developing a centrifugal integrated purification-CRISPR array for meat adulteration (CIPAM). • The microneedles for DNA extraction integrated with on-chip RAA-CRISPR/Cas12a for detection. • The CIPAM system shows excellent practical performance in food adulteration. Rapid, accurate, and sensitive analytical methods for the detection of food fraud are now an urgent requirement in the global food industry to ensure food quality. In response to this demand, a centrifugal integrated purification-CRISPR array for meat adulteration (CIPAM) was established. In detail, CIPAM system combines microneedles for DNA extraction and RAA-CRISPR/Cas12a integrated into a centrifugal microfluidic chip for the detection of meat adulteration. The RAA-CRISPR/Cas12a reaction reagents were pre-embedded into the different reaction chambers on the microfluidic chip to achieve the streamline of operations, markedly simplifying the detection process. The whole reaction was completed within 30 min with a detection limit of 0.1 % (w/w) in pig, chicken, duck, and lamb products. Referring to the results of the standard method, CIPAM system achieved 100 % accuracy. The automatic multiplex detection process implemented in the developed CIPAM system met the needs of food regulatory authorities. [ABSTRACT FROM AUTHOR]

[Display omitted] • IO-TiO 2 /Chl/IL composite with chloroplast-inspired microenvironment was prepared. • Tunning and improve range of visible light adsorption of IO-TiO 2 /Chl/IL by Chl(Cu) addition. • Microenvironment for CO 2 adsorption was formed by anchoring IL on IO-TiO 2 /Chl/IL surface. • The slow light effect of IO-TiO 2 /Chl/IL enhanced the light utilization efficiency. • IO-TiO 2 /Chl/IL showed high CO 2 reduction (44.9 μmol·g−1·h−1) and CH 4 selectivity (93%). Low CO 2 capture and sunlight utilization, rapid recombination of photocarriers restrict application of TiO 2 photocatalyst in CO 2 photoreduction. Herein, inverse opal structured IO-TiO 2 /Chl/IL with chloroplast-inspired microenvironment was constructed to achieve the synergistic effect of CO 2 capture and light-reaction system for efficient photoreduction CO 2 to CH 4. Ionic liquid ([BMIM][BF 4 ]) coated on Chl(Cu)/TiO 2 surface through Ti-F bond resembled the CO 2 capture function of stroma in chloroplast, while TiO 2 combined with Chl(Cu) to mimic the light-reaction system of thylakoid in chloroplast, these two parts imitating chloroplast microenvironment. The photonic band tuning of IO-TiO 2 /Chl/IL to overlap Chl(Cu) visible absorption band, enhancing light utilization of IO-TiO 2 /Chl/IL by slow photon effect. [BMIM][BF 4 ] and Chl(Cu) coordinated with TiO 2 significantly promoted electron transfer ability, redox ability and photogenerated carriers separation of IO-TiO 2 /Chl/IL. IO-TiO 2 /Chl/IL exhibited excellent photocatalytic performance (44.9 μmol·g−1·h−1) with high CH 4 selectivity (93%), providing a biomimetic chloroplast microenvironment strategy with high efficiency photocatalytic CO 2 reduction. [ABSTRACT FROM AUTHOR]

A novel "double chemical bonding" electrochemical peptide biosensor 2FcP-GA-GDY(Fe)@NMIL-B was developed for highly selective, ultrasensitive, and ultrastable identification of prostate-specific antigen (PSA). The C–Fe–O chemical bond linking Fe-Graphdiyne (Fe-GDY) with NH 2 -MIL88B(Fe) (NMIL88B) as the first chemical bonding of electrode carrier Fe-GDY@NH 2 -MIL88B(Fe) (GDY(Fe)@NMIL) significantly accelerates electron transport. With glutaraldehyde (GA) as a crosslinking agent, the Schiff-base –N C- formed by GDY(Fe)@NMIL nanocomposites links the two Fc molecules labeled peptides (2FcP) as the second chemical bonding, facilitating high-density attachment of peptides to the electrode carrier in a firm manner. When the PSA analyte is introduced to identify and cleave the specific peptide, the release of ferrocene from its head leads to a decrease in the electrical signal, enabling sensitive detection. The prepared sensing platform exhibits exceptional analytical performance for PSA with an extended linear response range from 10 fg mL−1 to 50 ng mL−1. Additionally, the detection limit has been significantly reduced to an ultra-low level of only 0.94 fg mL−1, surpassing those reported in most literature by several orders of magnitude. Moreover, the 2FcP-GA-GDY(Fe)@NMIL-B sensor has excellent selectivity and stability while also showcasing great potential for practical application of PSA detection in human serum using the standard addition method. [Display omitted] • Electrochemical peptide sensor with dual chemical bonding for PSA detection. • The first chemical bonding C–Fe–O accelerate electron transport of sensor. • The second chemical bonding –N C- enhance detection stability and sensitivity. • Detection limits about 3 orders of magnitude lower than other biosensors. • The sensor shows a wide linear range of 10 fg mL−1 to 50.0 ng mL−1 [ABSTRACT FROM AUTHOR]

Purpose: This meta-analysis was conducted to evaluate the efficacy and safety of single-dose dexamethasone implantation for treating persistent DME (diabetic macular edema) refractory to anti-VEGF (anti-vascular endothelial growth factor) drugs over a period of 6 months. Methods: All related clinical trials were reviewed by searching electronic databases of PubMed, Medline, Web of Science, Cochrane Library, and EMBASE. The primary outcome parameters were best-corrected visual acuity (BCVA) and central macular thickness (CMT). We performed this meta-analysis by using Stata15.0. Results: Ten clinical trials involving 362 eyes from 328 patients were eligible in the final analysis. After single-dose dexamethasone implantation, there was a significant improvement in BCVA from baseline to 1, 3, and 6 months with an average increase of − 0.15 logMAR (p < 0.001), − 0.14 logMAR (p < 0.001), and − 0.07 logMAR (p = 0.004), respectively. Further, mean CMT decreased significantly with an average reduction of 249.18 μm (p < 0.001), 217.66 μm (p < 0.001), and 91.56 μm (p < 0.001) at months 1, 3, and 6, respectively. Conclusions: Our results indicate that switching to a dexamethasone implant could achieve significant anatomical and functional improvement among patients with refractory DME. Clinicians should be aware of this treatment option in refractory DME. [ABSTRACT FROM AUTHOR]

A novel X-shaped four-armed gemini-like peglyated distearylglycerol (Gemini-PEG 2K -GCDS), with two hydrophilic PEG heads and two hydrophobic stearic acid tails, was successfully synthesized and used as a nanomicellar carrier for delivery of doxorubicin. The critical micelle concentration of the amphiphilic copolymer was higher than 10 −6 . Mean particle size and zeta potential of DOX-encapsulated Gemini-PEG 2K -GCDS nanomicelles (DOX-GNMs) was 20.4 nm and +3.91 mv, respectively. Encapsulation efficiency of DOX-GNMs was as high as 94.6 and DOX release was pH-dependent from DOX-GNMs, ensuring the stability of nanomicelles in blood circulation and rapid release of DOX in tumor cells. Pharmacokinetic studies in rats following i.v. administration, DOX-GNMs demonstrated longer retention in blood and larger AUC (19.1-fold of t 1/2 and 12.9-fold of AUC) compared with DOX solutions (DOX-Sol). Tissue distribution studies indicate that DOX-GNMs had higher tumor accumulation (4.6-fold) and lower heart toxicity in H22 tumor-bearing mice (17.4-fold) at 48 h after administration in comparison with DOX-Sol. Moreover, IC 50 of DOX-GNMs increased by 3.3-fold, 2.0-fold and 2.3-fold compared with DOX-Sol in P-gp over-expressing MCF-7/Adr cells after 24 h, 48 h and 72 h, internalized via macropinocytosis-mediated and clathrin-mediated endocytosis. This study suggests that Gemini-PEG 2K -GCDS nanomicelle is a promising long circulating delivery system for anti-tumor drugs via extended blood circulation and improved tumor distribution. [ABSTRACT FROM AUTHOR]

Real-time control using process analyticaltechnology (PAT) toolsis required for the implementation of continuous crystallization withinintegrated continuous manufacturing (ICM) of pharmaceuticals. However,appropriate selection of PAT tools is challenging, and the designand operation of automated control loops for continuous crystallizationwithin a continuous pharmaceutical process brings forward importantquestions. This paper discusses the process design and operation ofa continuous reactive crystallization of aliskiren hemifumarate aspart of an ICM pilot plant. Several PAT tools were used within automatedcontrol loops to satisfy specifications on the critical materialsattributes of the crystallization process. The operational performanceof the process was maintained for periods of time over 100 h. Thepurity of the targeted product exceeded 99%, and the process yieldreached 91.4%. [ABSTRACT FROM AUTHOR]