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Neuropathic pain (NP) represents a considerable clinical challenge, profoundly impacting patients’ quality of life. Presently, pharmacotherapy serves as a primary approach for NP alleviation, yet its efficacy often remains suboptimal. Melatonin (MLT), a biologically active compound secreted by the pineal gland, has long been associated with promoting and maintaining sleep. Although recent studies suggest analgesic effects of MLT, the underlying mechanism remains largely unknown, particularly its impact on the cortex. In this study, we induced an NP model in mice through spared nerve injury (SNI) and observed a considerable, dose-dependent alleviation in NP symptoms following intraperitoneal or anterior cingulate cortex (ACC) administration of MLT. Our findings further indicated that the NP management of MLT is selectively mediated by MLT-related receptor 2 (MT2R), rather than MT1R, on neurons and microglia within the ACC. Transcriptome sequencing, complemented by bioinformatics analysis, implicated MLT in the modulation of Gα(i) and immune-inflammatory signals. Specifically, MLT inhibited the excitability level of pyramidal cells in the ACC by activating the Gα(i) signaling pathway. Simultaneously, MLT attenuated M1 polarization and promoted M2 polarization of microglia, thereby mitigating the inflammatory response and type II interferon response within the ACC. These findings unveil a hitherto unrecognized molecular mechanism: an MLT-mediated neuroimmune modulation pathway in the ACC mediated by MT2R. This elucidation sheds light on the regulatory character of MLT in chronic nociceptive pain conditions, offering a prospective therapeutic strategy for NP management.

Abstract Background The study aims to investigate the relationship between the volume-accumulated reflectivity (termed “integral”) on spectral domain optical coherence tomography (SD-OCT) and cone density on adaptive optics (AO) imaging. Methods In this cross-sectional study, both eyes of 32 healthy subjects and 5 patients with inherited retinal diseases (IRD) were studied. The parameter, integral, was defined as the volume-accumulated reflectivity values in a selected region on OCT images; integrals of the ellipsoid zone (EZ) and interdigitation zone (IZ) were measured at 2°, 3°, 4°, 5°and 6° eccentricity along the four meridians on fovea-centered OCT B-scans. Cone density in the same region was measured using a flood illumination adaptive optics camera RTX1. Results Integrals of EZ, IZ and cone density shared similar distribution patterns. Integral of the IZ was better correlated with cone density in both healthy people (r = 0.968, p

Abstract Background To identify retinal changes using spectral-domain optical coherence tomography (SD-OCT) and ultra-widefield images in eyes with primary vitreoretinal lymphoma (PVRL) during intravitreal methotrexate (MTX) treatment. Methods This study retrospectively reviewed 111 eyes of 58 patients with vitreous cytology-proven confirmed PVRL, who received intravitreal injections of MTX. Results At the initial visit, the OCT manifestations included vitreous cells (105 eyes, 94.6%), intraretinal infiltration (44 eyes,39.6%), subretinal infiltration (45 eyes, 40.5%,), retinal pigment epithelium (RPE) abnormalities (66 eyes, 59.5%), disruption of the ellipsoid zone (58 eyes, 52.3%), subretinal fluid (4 eyes, 3.6%), RPE detachment (PED) (28 eyes, 25.2%), epiretinal membrane (ERM) (8 eyes, 7.2%), macular edema (10 eyes, 9%). After therapy, tumor regression was achieved in all eyes. Between the initial presentation and regression, the vitreous cells (94.6% vs. 0%, P

Nanocarriers have emerged as a promising cancer drug delivery strategy. Multi-drug resistance caused by overexpression of multiple-drug excretion transporters in tumor cells is the major obstacle to successful chemotherapy. Vitamin E derivatives have many essential functions for drug delivery applications, such as biological components that are hydrophobic, stable, water-soluble enhancing compounds, and anticancer activity. In addition, vitamin E derivatives are also effective mitocan which can overcome multi-drug resistance by binding to P glycoproteins. Here, we developed a carboxymethyl chitosan/vitamin E succinate nano-micellar system (O-CMCTS-VES). The synthesized polymers were characterized by Fourier Transform IR, and 1H NMR spectra. The mean sizes of O-CMCTS-VES and DOX-loaded nanoparticles were around 177 nm and 208 nm. The drug loading contents were 6.1%, 13.0% and 10.6% with the weight ratio of DOX to O-CMCTS-VES corresponding 1:10, 2:10 and 3:10, and the corresponding EEs were 64.3%, 74.5% and 39.7%. Cytotoxicity test, hemolysis test and histocompatibility test showed that it had good biocompatibility in vitro and in vivo. Drug release experiments implied good pH sensitivity and sustained-release effect. The DOX/O-CMCTS-VES nanoparticles can be efficiently taken up by HepG2 cancer cells and the tumor inhibition rate is up to 62.57%. In the in vivo study by using H22 cells implanted Balb/C mice, DOX/O-CMCTS-VES reduced the tumor volume and weight efficiently with a TIR of 35.58%. The newly developed polymeric micelles could successfully be utilized as a nanocarrier system for hydrophobic chemotherapeutic agents for the treatment of solid tumors.

PurposeTo seek novel diagnostic approaches, we improved the workflow of cell-free DNA (cfDNA) sequencing and evaluated its feasibility in vitreoretinal lymphoma (VRL) specimens; the profile of mutations was preliminarily analyzed for potential diagnostic value.MethodsThe study was a diagnostic trial. 23 eyes of 23 patients with VRL and 25 eyes of 25 patients with inflammatory eye diseases were enrolled. Approximate 500μl undiluted vitreous humor and 10ml diluted vitreous fluid was obtained through diagnostic vitrectomy and sent for cytopathological examinations. 500μl of the diluted vitreous fluid was spared for cfDNA sequencing. For cfDNA sequencing, DNA fragmentation procedure was added to the workflow to improve the extraction efficiency; mutations detected were analyzed for potential diagnostic model. The sensitivity and specificity of the cytopathology and cfDNA sequencing were compared. The clinical manifestations were preliminarily analyzed for potential correlations with the genotypes.ResultsCfDNA sequencing was accomplished in 23 eyes with VRL and 20 eyes with inflammatory eye diseases. VRL-related mutated genes included MYD88 (18 eyes, 78%), ETV6 (11 eyes, 48%), PIM1 (11 eyes,48%), BTG2 (7 eyes, 30%), IRF4 (7 eyes, 30%), CD79B (6 eyes, 26%), LRP1B (6 eyes, 26%), etc. Logistic regression based on the mutations of MYD88 and ETV6 was of the potential for the diagnosis of VRL (P

Abstract Background To investigate the effect of intravitreal conbercept (IVC) injections on the incidence of postoperative vitreous hemorrhage (VH) in eyes undergoing surgery for severe proliferative diabetic retinopathy. Methods This was a pilot prospective, comparative, and randomized study. Thirty patients, who underwent vitrectomy for severe proliferative diabetic retinopathy, were assigned randomly to either group 1 (intravitreal conbercept [IVC] injection at the end of pars plana vitrectomy) or group 2 (no IVC injection). Postoperative follow-up was performed on the first day, first week, first month, third month, sixth month and first year after surgery. The primary outcome was the incidence of postoperative VH. Secondary outcomes were the initial time of vitreous clearing (ITVC), best-corrected visual acuity (BCVA) and central retinal thickness (CRT) after surgery. Results A total of 30 eyes, from 30 patients, were included. Fifteen eyes were enrolled in the IVC group and fifteen in the control group. The incidence of early and late postoperative VH was not significantly different between the control and IVC groups. ITVC was shorter in the IVC group than that in the control group, but this was not significant (7.38 ± 10.66 vs 13.23 ± 17.35, P = 0.31). Final BCVA, 1 year after surgery, showed significant improvement compared to baseline in both groups. However, analysis of the BCVA at any postoperative visit after surgery showed no significant differences between the two groups. There were two cases of recurrent VH identified at 3 and 6 months after surgery in each group, requiring a second round of surgery. Foveal thickness was significantly different between the two groups at the 3-month, 6-month and 1-year follow-up visits. Conclusions In this pilot study, the effect of IVC injection in reducing the incidence of postoperative VH after diabetic vitrectomy at the end of vitrectomy was not shown. Trial registration The study was registered with the Chinese Clinical Trial Registry. (Reference Number: ChiCTR1800015751).

Inflammatory pain is one of the most common symptoms of clinical pain that seriously affects patient quality of life, but it currently has limited therapeutic options. Proanthocyanidins, a group of polyphenols enriched in plants and foods, have been reported to exert anti-inflammatory pain-alleviating effects. However, the mechanism by which proanthocyanidins relieve inflammatory pain in the central nervous system is unclear. In the present study, we observed that intrathecal injection of proanthocyanidins inhibited mechanical and thermal pain sensitivity in mice with inflammatory pain induced by Complete Freund’s Adjuvant (CFA) injection. Electrophysiological results further showed that proanthocyanidins inhibited the frequency of spontaneous excitatory postsynaptic currents without affecting the spontaneous inhibitory postsynaptic currents or the intrinsic properties of parabrachial nucleus-projecting neurons in the spinal cord. The effect of proanthocyanidins may be mediated by their inhibition of phosphorylated activation of the PI3K/Akt/mTOR pathway molecules in dorsal root ganglia neurons. In summary, intrathecal injection of procyanidin induces an obvious anti-inflammatory pain effect in mice by inhibiting peripheral excitatory inputs to spinal neurons that send nociceptive information to supraspinal areas.

Background: Soil salinization is one of the key factors restricting the production of cropland. Once rice is subjected to alkali stress at the bud burst stage, the yield will suffer irreparable serious loss. Compared with salt tolerance, studies on QTL mapping and candidate gene analysis of rice alkali tolerance are limited. Results: In this study, we used the F2:3 population derived from the alkali-tolerant cultivar LD21 and the alkali-sensitive cultivar WL138 to construct an alkali-tolerant DNA mixing pool, and the BSA (Bulked Segregation Analysis) method was used for re-sequencing. The main QTL qRSLB9 controlling the relative shoot length of rice under alkali stress was mapped by QTL-seq. The candidate interval was narrowed to 346.5 kb by regional linkage mapping, which containing 6 DEGs screened through transcriptome sequencing. The qRT-PCR and candidate gene sequencing showed that LOC_Os09g24260 was most likely to control relative shoot length (RSL) in rice as a major gene who encodes the WD domain, G-beta repeat domain-containing protein. Conclusions: Based on these results, LOC_Os09g24260 was the candidate gene of qRSLB9 conferring alkalinity tolerance to rice at the bud burst stage. Our study provides valuable genetic information and materials for breeding new rice varieties with alkalinity tolerance.How to cite: Wang J, Bian J, Liu L, et al. Screening and analysis of candidate genes conferring alkalinity tolerance in rice (Oryza sativa L.) at the bud burst stage based on QTL-seq and RNA-seq. Electron J Biotechnol 2024;71. https://doi.org/10.1016/j.ejbt.2024.07.002.

The magnesium oxysulfate (MOS) cement has problems of short setting time, poor water resistance, and volume instability. This paper investigates the potential of steel slag (SS) to modify the properties and microstructure of the MOS cement prepared by magnesium desulfurization byproducts (MDBs). The results showed that SS delayed the setting time, restrained the volume shrinkage, and improved the water resistance of the MOS cement. The hydration products of the MOS cement were the fibrous 318 phase (3 Mg(OH)2•MgSO4•8H2O), lamellar Mg(OH)2, and MgCO3. The addition of SS increased the pH and decreased the overall hydration reaction rate and the amount of Mg(OH)2 in the MOS cement. SS reacted with Mg(OH)2 at the late stage to form an amorphous M–S–H gel, which increased the gel pore volume and the density of the cement. In conclusion, SS enhanced the application potential of MOS cement, through improving its macroscopic properties.

IntroductionDeep insights into adhering soil of root zones (rhizosphere and rhizoplane) microbial community could provide a better understanding of the plant-microbe relationship. To better understand the dynamics of these microbial assemblies over the plant life cycle in rhizodeposition along rice roots.MethodsHere, we investigated bacterial distribution in bulk, rhizosphere, and rhizoplane soils at tillering, heading, and mature stage, from rice (Oryza sativa) fields of the Northeast China.Results and DiscussionOur results revealed that soil bacterial α-diversity and community composition were significantly affected by root compartment niches but not by temporal change. Compared to rhizoplane soils in the same period, bulk in the heading and rhizosphere in the mature had the largest increase in Shannon’s index, with 11.02 and 14.49% increases, respectively. Proteobacteria, Chloroflexi, Bacteroidetes, and Acidobacteria are predominant across all soil samples, bulk soil had more phyla increased across the growing season than that of root related-compartments. Deterministic mechanisms had a stronger impact on the bacterial community in the compartments connected to the roots, with the relative importance of the bulk soil, rhizoplane and rhizosphere at 83, 100, and 56%, respectively. Because of ecological niche drivers, the bacterial networks in bulk soils exhibit more complex networks than rhizosphere and rhizoplane soils, reflected by more nodes, edges, and connections. More module hub and connector were observed in bulk (6) and rhizoplane (5) networks than in rhizosphere (2). We also detected shifts from bulk to rhizoplane soils in some functional guilds of bacteria, which changed from sulfur and nitrogen utilization to more carbon and iron cycling processes. Taken together, our results suggest distinct bacterial network structure and distribution patterns among rhizosphere, rhizoplane, and bulk soils, which could possibly result in potential functional differentiation. And the potential functional differentiation may be influenced by plant root secretions, which still needs to be further explored.

Purpose To investigate ultrasound biomicroscopy (UBM) characteristics of patients with ocular toxocariasis (OT) and to explore the role of UBM in the diagnosis and differential diagnosis of OT. Design Cross-sectional study. Methods 78 eyes of 77 patients clinically consistent with OT and confirmed by serum and/or intraocular antibodies in a single tertiary centre (Fudan University Eye and ENT Hospital, Shanghai) between July 2009 and July 2016 were included in the study. UBM was performed, and the outcomes were analysed. Results Mean age of the patients included was 12.8±10.3 years. Positive UBM findings were observed in 72 of 78 eyes (92.3%). The primary imaging feature was peripheral granulomas (66 eyes; 84.6%), of which 78.5% were adjacent to the nasal or temporal side of horizontal meridian and 79.7% located on the surface of the ciliary body, presenting as olivary foci on radical section and botuliform foci on coronal section. Moreover, 12 of the peripherally involved eyes were accompanied with posterior pole granulomas, which could be termed 'combined type'. Other UBM findings included vitreous strands (53 eyes; 67.9%), peripheral tractional retinal detachment (41 eyes; 52.6%) and tractional cyclodialysis (32 eyes; 41.0%). Conclusions The utilisation of UBM verifies the existence of the combined subtype (with both peripheral and posterior pole granulomas) and improves the detection rate of peripheral granulomas, which is of great importance to the diagnosis and differential diagnosis of OT. [ABSTRACT FROM AUTHOR]

Background: Plasmin is a serine protease that plays a critical role in fibrinolysis, which is a process that prevents blood clots from growing and becoming problematic. Recombinant human microplasminogen (rhμPlg) is a derivative of plasmin that solely consists of the catalytic domain of human plasmin and lacks the five kringle domains found in the native protein. Developing an industrial production method that provides high yields of this protein with high purity, quality, and potency is critical for preclinical research. Results: The human microplasminogen gene was cloned into the pPIC9K vector, and the recombinant plasmid was transformed into Pichia pastoris strain GS115. The concentration of plasmin reached 510.1 mg/L of culture medium. Under fermentation conditions, the yield of rhμPlg was 1.0 g/L. We purified rhμPlg to 96 % purity by gel-filtration and cation-exchange chromatography. The specific activity of rhμPlg reached 23.6 U/mg. The Km of substrate hydrolysis by recombinant human microplasmin was comparable to that of human plasmin, while rhμPlm had higher kcat/Km values than plasmin. The high purity and activity of the rhμPlg obtained here will likely prove to be a valuable tool for studies of its application in thrombotic diseases and vitreoretinopathies. Conclusions: Reliable rhμPlg production (for use in therapeutic applications) is feasible using genetically modified P. pastoris as a host strain. The successful expression of rhμPlg in lays a solid foundation for its downstream application. [ABSTRACT FROM AUTHOR]