Discovery of TCP-(MP)-caffeic acid analogs as a new class of agents for treatment of osteoclastic bone loss.

Inhibition of LSD1 was proposed as promising and attractive therapies for treating osteoporosis. Here, we synthesized a series of novel TCP-(MP)-Caffeic acid analogs as potential LSD1 inhibitors to assess their inhibitory effects on osteoclastogenesis by using TRAP-staining assay and try to explore the preliminary SAR. Among them, TCP-MP-CA (11a) demonstrated osteoclastic bone loss both in vitro and in vivo, showing a significant improvement in the in vivo effects compared to the LSD1 inhibitor GSK-LSD1. Additionally, we elucidated a mechanism that 11a and its precursor that 11e directly bind to LSD1/CoREST complex through FAD to inhibit LSD1 demethylation activity and influence its downstream IκB/NF-κB signaling pathway, and thus regulate osteoclastic bone loss. These findings suggested 11a or 11e as potential novel candidates for treating osteoclastic bone loss, and a concept for further development of TCP-(MP)-Caffeic acid analogs for therapeutic use in osteoporosis clinics.

Exploratory analysis of choriocapillaris vasculature as a biomarker of idiopathic epiretinal membrane.

PURPOSE: To investigate the preoperative choriocapillaris perfusion (CCP) as a biomarker in patients with idiopathic epiretinal membrane (iERM). MATERIALS AND METHODS: 28 patients (28 eyes) with unilateral iERM who received pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling were included for retrospective observational study. Optical coherence tomography (OCT) and angiography (OCTA) was performed before and after PPV. Area, perimeter, and circularity of superficial foveal avascular zone (FAZ) were analyzed preoperatively in both eyes using OCTA. Preoperative CCP was also analyzed with binarized en-face OCTA images. Measurements of best-corrected visual acuity (BCVA) and central foveal thickness (CFT) by OCT were conducted at the baseline and 6 months following the surgery. The correlations of preoperative OCT parameters with postoperative BCVA and CFT reduction were analyzed. RESULTS: CCP was significantly lower (p < 0.001) and FAZ had shrunk (p < 0.001) in eyes with iERM compared to unaffected fellow eyes before surgery. BCVA and CFT became significantly improved after surgery (p = 0.001, p < 0.001). Multiple regression analysis revealed that preoperative CCP was significantly related with BCVA improvement (ß = 0.185, p = 0.005), postoperative BCVA (ß = 0.108, p = 0.023) and ratio of post- to preoperative CFT (ß = 0.106, p = 0.044). CONCLUSIONS: Preoperative CCP is a biomarker for poor functional and anatomical prognosis after surgery in iERM.

Choroidal and retinal vascular changes in HLA-B27-associated anterior uveitis.

PURPOSE: To quantitatively analyze choroidal and retinal vascular changes in HLA-B27-associated anterior uveitis. STUDY DESIGN: A retrospective study. METHODS: Medical records of 51 eyes with unilateral HLA-B27-associated anterior uveitis, their fellow eyes and 47 sex and age-matched healthy eyes were retrospectively reviewed. Their choroidal and retinal vasculature were analyzed using swept-source (SS) optical coherence tomography (OCT) and OCT angiography (OCTA) scans. RESULTS: Deep capillary plexus (DCP) vessel density (VD) (p < 0.001), choroidal vascularity index (CVI) (p = 0.012), and choriocapillary flow deficit (CCFD) (p < 0.001) of uveitic and fellow eye group were significantly higher than those of control group. On the contrary, superficial capillary plexus (SCP) VD (p < 0.001) of uveitic and fellow eye group were significantly lower than of control group. The vascular parameters of uveitis and fellow eye group showed no significant difference between uveitic and resolution period. CONCLUSION: Certain choroidal and retinal vascular parameters were significantly changed in both HLA-B27-associated anterior uveitis without posterior segment involvement and the quiet fellow eyes, suggesting their possible effects as a systemic inflammatory disorder.

The effect of heart rate variability on the choroidal vascularity of the optical coherence tomography and angiography in central serous chorioretinopathy.

PURPOSE: To investigate the correlation between the autonomic nervous system and choroidal vascularity in patients with central serous chorioretinopathy (CSC), using heart rate variability (HRV) analysis, optical coherence tomography (OCT) and OCT angiography (OCTA). METHODS: We retrospectively analyzed data of 25 patients with unilateral CSC (50 eyes, including the unaffected fellow eyes) and 25 healthy controls. The assessment involved a 5-minute HRV analysis encompassing both frequency and time domains, especially low frequency (LF), high frequency (HF), and LF/HF ratio. In OCT (12 × 9 mm) and en-face OCTA (3 × 3 mm) scans, we measured parameters including choroidal vascularity index (CVI), choroidal vessel density in the middle and deep layers, and choriocapillaris flow void. Regression analysis was conducted to elucidate the associations between HRV parameters and OCT/OCTA measurements. RESULTS: Normalized LF(LFnorm) and LF/HF ratios were higher in patients with CSC than in healthy controls. LFnorm and the log-transformed ratio of LF to HF [log(LF/HF)] demonstrated a significant and borderline correlation with CVI in the linear regression analysis (P = 0.040, R2 = 0.171, and P = 0.059, R2 = 0.147, respectively). Both CVI and deep choroid vessel density showed a more significant association with LFnorm and log (LF/HF) in the non-linear quadratic regression analysis than in the linear analysis (all, P < 0.04, R2 > 0.25). CONCLUSION: The frequency-domain parameters of HRV, including LFnorm and log (LF/HF), demonstrated a significant association with indicators reflective of large choroidal vessel luminal area on macular OCT/OCTA scans. This observation implies complicated modulation of choroidal blood flow by the autonomic nervous system in CSC.

Decrease of alpha crystallin A by miR-325-3p in retinal cells under blue light exposure.

Exposure to blue light can lead to retinal degeneration, causing adverse effects on eye health. Although the loss of retinal cells due to blue light exposure has been observed, the precise molecular mechanisms underlying this process remain poorly understood. In this study, we investigate the role of alpha crystallin A (CRYAA) in neuro-retinal degeneration and their regulation by blue light. We observed significant apoptotic cell death in both the retina of rats and the cultured neuro-retinal cells. The expressions of Cryaa mRNA and protein were significantly down-regulated in the retina exposed to blue light. We identified that miR-325-3p reduces Cryaa mRNA and protein by binding to its 3'-untranslated region (UTR). Up-regulation of miR-325-3p destabilized Cryaa mRNA and suppresses CRYAA, whereas down-regulation of miR-325-3p increased both expressions. Blue light-induced neuro-retinal cell death was alleviated by CRYAA overexpression. These results highlight the critical role of Cryaa mRNA and miR-325-3p molecular axis in blue light-induced retinal degeneration. Consequently, targeting CRYAA and miR-325-3p presents a potential strategy for protecting against blue light-induced retinal degeneration.

HIV-1 neutralizing antibodies in SHIV-infected macaques recapitulate structurally divergent modes of human V2 apex recognition with a single D gene.

Broadly neutralizing antibodies targeting the V2 apex of the HIV-1 envelope trimer are among the most common specificities elicited in HIV-1-infected humans and simian-human immunodeficiency virus (SHIV)-infected macaques. To gain insight into the prevalent induction of these antibodies, we isolated and characterized 11 V2 apex-directed neutralizing antibody lineages from SHIV-infected rhesus macaques. Remarkably, all SHIV-induced V2 apex lineages were derived from reading frame two of the rhesus DH3-15*01 gene. Cryo-EM structures of envelope trimers in complex with antibodies from nine rhesus lineages revealed modes of recognition that mimicked three canonical human V2 apex-recognition modes. Notably, amino acids encoded by DH3-15*01 played divergent structural roles, inserting into a hole at the trimer apex, H-bonding to an exposed strand, or forming part of a loop scaffold. Overall, we identify a DH3-15*01-signature for rhesus V2 apex broadly neutralizing antibodies and show that highly selected genetic elements can play multiple roles in antigen recognition. Highlights: Isolated 11 V2 apex-targeted HIV-neutralizing lineages from 10 SHIV-infected Indian-origin rhesus macaquesCryo-EM structures of Fab-Env complexes for nine rhesus lineages reveal modes of recognition that mimic three modes of human V2 apex antibody recognitionAll SHIV-elicited V2 apex lineages, including two others previously published, derive from the same DH3-15*01 gene utilizing reading frame twoThe DH3-15*01 gene in reading frame two provides a necessary, but not sufficient, signature for V2 apex-directed broadly neutralizing antibodiesStructural roles played by DH3-15*01-encoded amino acids differed substantially in different lineages, even for those with the same recognition modePropose that the anionic, aromatic, and extended character of DH3-15*01 in reading frame two provides a selective advantage for V2 apex recognition compared to B cells derived from other D genes in the naïve rhesus repertoireDemonstrate that highly selected genetic elements can play multiple roles in antigen recognition, providing a structural means to enhance recognition diversity.

Molecular Markers for Marker-Assisted Breeding for Biotic and Abiotic Stress in Melon (Cucumis melo L.): A Review.

Melon (Cucumis melo L.) is a globally grown crop renowned for its juice and flavor. Despite growth in production, the melon industry faces several challenges owing to a wide range of biotic and abiotic stresses throughout the growth and development of melon. The aim of the review article is to consolidate current knowledge on the genetic mechanism of both biotic and abiotic stress in melon, facilitating the development of robust, disease-resistant melon varieties. A comprehensive literature review was performed, focusing on recent genetic and molecular advancements related to biotic and abiotic stress responses in melons. The review emphasizes the identification and analysis of quantitative trait loci (QTLs), functional genes, and molecular markers in two sections. The initial section provides a comprehensive summary of the QTLs and major and minor functional genes, and the establishment of molecular markers associated with biotic (viral, bacterial, and fungal pathogens, and nematodes) and abiotic stress (cold/chilling, drought, salt, and toxic compounds). The latter section briefly outlines the molecular markers employed to facilitate marker-assisted backcrossing (MABC) and identify cultivars resistant to biotic and abiotic stressors, emphasizing their relevance in strategic marker-assisted melon breeding. These insights could guide the incorporation of specific traits, culminating in developing novel varieties, equipped to withstand diseases and environmental stresses by targeted breeding, that meet both consumer preferences and the needs of melon breeders.

Genetically engineered long-acting Esculentin-2CHa(1-30) fusion protein with potential applicability for the treatment of NAFLD.

Esculentin-2CHa(1-30) (?ESC") has been reported as a potent anti-diabetic peptide with little toxicity. However, its very short plasma residence time severely limits the therapeutic efficacy. To address this issue, we genetically engineered a fusion protein of tandem trimeric ESC with an albumin binding domain (ABD) and a fusion partner, SUMO (named ?SUMO-3×ESC-ABD"). The SUMO-3×ESC-ABD, successfully produced from E. coli, showed low cellular and hemolytic toxicity while displaying potent activities for the amelioration of hyperglycemia as well as non-alcoholic fatty liver disease (NAFLD) in vitro. In animal studies, the estimated plasma half-life of SUMO-3×ESC-ABD was markedly longer (427-fold) than that of the ESC peptide. In virtue of the extended plasma residence, the SUMO-3×ESC-ABD could produce significant anti-hyperglycemic effects that lasted for >2 days, while both the ESC or ESC-ABD peptides elicited little effects. Further, twice-weekly treatment for 10 weeks, the SUMO-3×ESC-ABD displayed significant improvement in blood glucose control with a reduction in body weight. Most importantly, a significant improvement in the conditions of NAFLD was observed in the SUMO-3×ESC-ABD-treated mice. Along the systemic effects (by improved glucose tolerance and body weight reduction), direct inhibition of the hepatocyte lipid uptake was suggested as the major mechanism of the anti-NAFLD effects. Overall, this study demonstrated the utility of the long-acting SUMO-3×ESC-ABD as a potent drug candidate for the treatment of NAFLD.

Analysis of retinal and choroidal microvascular changes using optical coherence tomography and optical coherence tomography angiography in patients with acute leukemia.

PURPOSE: Although leukemic retinopathy accounts for 80% of ocular complications in acute leukemia, its pathogenesis remains unclear. To evaluate changes in retinal and choroicapillaris and structural parameters in patients with acute leukemia, we analyzed the correlation between vascular perfusion metrics and laboratory parameters and assessed the changes after hematopoietic stem cell transplantation (HSCT). METHODS: Herein, 104 eyes of 52 patients aged 18 and above with acute leukemia were enrolled. 80 eyes of 40 healthy patients were recruited as control participants. All participants underwent optical coherence tomography (OCT) and OCT angiography (OCTA) at baseline. RESULTS: Patients with acute leukemia had a significantly thicker ganglion cell-inner plexiform layer (GCIPL) and lower circularity index than the control participants. Post-HSCT perfusion metrics did not differ significantly, but parafoveal thickness decreased significantly. During the active phase of acute leukemia, lower platelet levels were associated with significant GCIPL thickening and increased foveal avascular zone and perimeter. D-dimer levels positively correlated with GCIPL thickness. CONCLUSION: Patients with acute leukemia had subclinical retinal microvascular deficits on OCTA and GCIPL thickening on OCT, possibly associated with bone marrow function. GCIPL thickness may indicate acute ischemia in such patients. Further studies must elucidate their clinical and prognostic significance.

Focused Ultrasound as a Novel Non-Invasive Method for the Delivery of Gold Nanoparticles to Retinal Ganglion Cells.

Purpose: The blood-retinal barrier (BRB) restricts the delivery of intravenous therapeutics to the retina, necessitating innovative approaches for treating retinal disorders. This study sought to explore the potential of focused ultrasound (FUS) to non-invasively deliver intravenously administered gold nanoparticles (AuNPs) across the BRB. FUS-BRB modulation can offer a novel method for targeted retinal therapy. Methods: AuNPs of different sizes and shapes were characterized, and FUS parameters were optimized to permeate the BRB without causing retinal damage in a rodent model. The delivery of 70-kDa dextran and AuNPs to the retinal ganglion cell (RGC) layer was visualized using confocal and two-photon microscopy, respectively. Histological and statistical analyses were conducted to assess the effectiveness and safety of the procedure. Results: FUS-BRB modulation resulted in the delivery of dextran and AuNPs to the RGC and inner nuclear layer. Smaller AuNPs reached the retinal layers to a greater extent than larger ones. The delivery of dextran and AuNPs across the BRB with FUS was achieved without significant retinal damage. Conclusions: This investigation provides the first evidence, to our knowledge, of FUS-mediated AuNP delivery across the BRB, establishing a foundation for a targeted and non-invasive approach to retinal treatment. The results contribute to developing promising non-invasive therapeutic strategies in ophthalmology to treat retinal diseases. Translational Relevance: Modifying the BRB with ultrasound offers a targeted and non-invasive delivery strategy of intravenous therapeutics to the retina.

Factors related to central nervous system involvement of primary vitreoretinal lymphoma.

PURPOSE: This single center retrospective study aimed to investigate the factors associated with central nervous system (CNS) involvement of primary vitreoretinal lymphoma (PVRL). METHODS: Clinical features of patients with PVRL (Group 1), those diagnosed with vitreoretinal lymphoma (VRL) after primary CNS lymphoma diagnosis (Group 2), and those concurrently diagnosed with CNS lymphoma and VRL (Group 3), were compared. The main outcomes included sex, age, types of treatment, survival, visual acuity, diagnostic methods, VRL recurrence, ocular manifestations, and interleukin levels in the aqueous humor. RESULTS: Groups 1, 2, and 3 included 66 eyes in 38 patients, 29 eyes in 18 patients, and 14 eyes in 8 patients, respectively. Group 3 had shorter overall survival (OS) than Groups 1 and 2 (P = 0.042 and P = 0.009, respectively). The three groups did not differ in progression-free survival (P = 0.060). The 5-year survival rates of Groups 1, 2, and 3 were 56.5%, 44.0%, and 25.0%, respectively (P = 0.001). Patients with CNS involvement in Group 1 exhibited VRL recurrence (P < 0.001), high interleukin-10 (P = 0.024), and sub-retinal pigment epithelium (RPE) infiltration (P = 0.009). Patients experiencing VRL recurrence in Group 1 tended to show CNS involvement (P < 0.001). CONCLUSION: Patients concurrently diagnosed with CNS lymphoma and VRL had a shorter OS and a lower 5-year survival rate. In patients with PVRL, the recurrence of VRL, high interleukin-10, and sub-RPE infiltration were associated with CNS involvement.

Analysis of the progression rate of idiopathic macular holes and the optimal cut-off for baseline minimum linear diameter and base diameter.

PURPOSE: To determine the cut-off points of minimum linear diameter (MLD) and base diameter (BD) at which the progression rate of idiopathic full-thickness macular holes (MHs) decreases before vitrectomy. STUDY DESIGN: A retrospective study. METHODS: We investigated the differences in MLD and BD between baseline and operation days in patients with stages 2, 3, and 4 MHs using optical coherence tomography (OCT). Each difference in OCT parameters was divided by the time interval to calculate the MH progression rates and the cut-off points of MLD and BD. RESULTS: Overall, 269 patients (282 eyes) were included. It took an average of 36.02 ± 24.69 (7-197) days from baseline to operation. MLD and BD progressed faster in stages 2 and 3 without posterior vitreous detachment (PVD) than in stage 4 with PVD (MLD: p < 0.001 and p = 0.007; BD: p < 0.001 and p = 0.019, respectively). Simple linear regression showed the relationship between baseline MLD and BD, and the progression rate; the progression rate decreased as baseline MLD (p = 0.004) and BD increased ( p < 0.001). For baseline MLD and BD, the cut-off points where the progression rate decreased were 306.0 and 470.0 µm, respectively. CONCLUSION: The group without PVD progressed faster than the group with PVD. Moreover, the progression rates were faster in MHs with MLD < 306.0 µm and BD < 470.0 µm. In these patients, vitrectomy without delay is expected to improve the visual prognosis.

Uncovering the colorectal cancer immunotherapeutic potential: Evening primrose (Oenothera biennis) root extract and its active compound oenothein B targeting the PD-1/PD-L1 blockade.

BACKGROUND: The emergence of immune checkpoint inhibitors, a novel class of immunotherapy drugs, represents a major breakthrough in cancer immunotherapy, substantially improving patient survival post-treatment. Blocking programmed death-ligand 1 (PD-L1) and programmed death protein-1 (PD-1) has demonstrated promising clinical results in various human cancer types. The US FDA has recently permitted only monoclonal antibody (mAb)-based PD-L1 or PD-1 blockers. Although these antibodies exhibit high antitumor efficacy, their size- and affinity-induced side effects limit their applicability. PURPOSE: As small-molecule-based PD-1/PD-L1 blockers capable of reducing the side effects of antibody therapies are needed, this study focuses on exploring natural ingredient-based small molecules that can target hPD-L1/PD-1 using herbal medicines and their components. METHODS: The antitumor potential of evening primrose (Oenothera biennis) root extract (EPRE), a globally utilized traditional herbal medicine, folk remedy, and functional food, was explored. A coculture system was established using human PD-L1-expressed murine MC38 cells (hPD-L1-MC38s) and CD8+ tumor-infiltrating T lymphocytes (CD8+ TILs) expressing humanized PD-1. The in vivo experiments utilized a colorectal cancer (CRC) C57BL/6 J mouse model bearing MC38 cells expressing humanized PD-L1 and PD-1 proteins. RESULTS: EPRE and its active compound oenothein B effectively hindered the molecular interaction between hPD-L1 and hPD-1. EPRE stimulated tumor-specific T lymphocytes of a hPD-L1/PD-1 CRC mice. This action resulted in the elevated infiltration of cytotoxic CD8+T lymphocytes and subsequent tumor growth reduction. Moreover, the combined therapy of oenothein B, a PD-1/PD-L1 blocker, and FOLFOX (5-fluorouracil plus oxaliplatin) cooperatively suppressed hPD-L1-MC38s growth in the ex vivo model through activated CD8+ TIL antitumor immune response. Oenothein B exhibited a high binding affinity for hPD-L1 and hPD-1. We believe that this study is the first to uncover the inhibitory effects of EPRE and its component, oenothein B, on PD-1/PD-L1 interactions. CONCLUSION: This study identified a promising small-molecule candidate from natural products that blocks the hPD-L1/PD-1 signaling pathway. These findings emphasize the potential of EPRE and oenothein B as effective anticancer drugs.

Visualization with Prediction Scheme for Early DDoS Detection in Ethereum.

Blockchain technologies have gained widespread use in security-sensitive applications due to their robust data protection. However, as blockchains are increasingly integrated into critical data management systems, they have become attractive targets for attackers. Among the various attacks on blockchain systems, distributed denial of service (DDoS) attacks are one of the most significant and potentially devastating. These attacks render the systems incapable of processing transactions, causing the blockchain to come to a halt. To address the challenge of detecting DDoS attacks on blockchains, existing visualization schemes have been developed. However, these schemes often fail to provide early DDoS detection since they typically display only past and current system status. In this paper, we present a novel visualization scheme that not only portrays past and current values but also forecasts future expected system statuses. We achieve these future predictions by utilizing polynomial regression with blockchain data. Additionally, we offer an alternative DDoS detection method employing statistical analysis, specifically the coefficient of determination, to enhance accuracy. Through our experiments, we demonstrate that our proposed scheme excels at predicting future blockchain statuses and anticipating DDoS attacks with minimal error. Our work empowers system managers of blockchain-based applications to identify and mitigate DDoS attacks at an earlier stage.

Identification of a novel locus C2 controlling canary yellow flesh color in watermelons.

The flesh color of watermelon is an important trait that is determined by carotenoid composition and affects consumers' fruit desirability. Although a complete dominant control by C locus (Cllcyb) for canary yellow flesh (CY) over red flesh has been reported, red and CY colors frequently appear as a mixed pattern in the same flesh (incomplete canary yellow, ICY) in F1 and inbred lines carrying dominant C alleles. Therefore, we examined the genetic control of the mixed color pattern in ICY using whole-genome resequencing of three ICY (ICY group) and three CY inbred lines (CY group), as well as genetic linkage mapping of an F2 population. The segregation pattern in 135 F2 plants indicated that CY is controlled by a single locus (named C 2) dominant over ICY. The whole-genome resequencing of ICY and CY inbred lines revealed an ICY/CY-specific region of approximately 27.60-27.88 Mb on Chr. 2 that was polymorphic between the ICY and CY groups. Our genetic map, using nine cleaved amplified polymorphic sequence markers developed based on the single-nucleotide polymorphisms from the ICY/CY-specific region, confirmed that C 2 is located on Chr. 2 and cosegregated with the marker (M7) derived from a non-synonymous single-nucleotide polymorphism of the pentatricopeptide repeat (PPR) gene (ClPPR, Cla97C02G039880). Additionally, 27 watermelon inbred lines of ICY, CY, and red flesh were evaluated using previously reported Cllcyb (C locus)-based markers and our C 2 locus-linked ClPPR-based marker (M7). As a result, dominant alleles at the C 2 locus were required to produce CY, in addition to dominant alleles at the C locus, while a recessive homozygous genotype at the C locus gave the red flesh irrespective of the genotype at the C 2 locus. Using a ClPPR-based cleaved amplified polymorphic sequence developed in this study and Cllcyb-based markers, watermelon cultivars with CY, ICY, and red flesh could be successfully discerned, implying that the combined use of these markers will be efficient for marker-assisted selection of flesh color in watermelon breeding.

Molecular Marker-Assisted Mapping, Candidate Gene Identification, and Breeding in Melon (Cucumis melo L.): A Review.

Melon (Cucumis melo L.) is an important crop that is cultivated worldwide for its fleshy fruit. Understanding the genetic basis of a plant's qualitative and quantitative traits is essential for developing consumer-favored varieties. This review presents genetic and molecular advances related to qualitative and quantitative phenotypic traits and biochemical compounds in melons. This information guides trait incorporation and the production of novel varieties with desirable horticultural and economic characteristics and yield performance. This review summarizes the quantitative trait loci, candidate genes, and development of molecular markers related to plant architecture, branching patterns, floral attributes (sex expression and male sterility), fruit attributes (shape, rind and flesh color, yield, biochemical compounds, sugar content, and netting), and seed attributes (seed coat color and size). The findings discussed in this review will enhance demand-driven breeding to produce cultivars that benefit consumers and melon breeders.

Mutagenesis-based plant breeding approaches and genome engineering: A review focused on tomato.

Breeding is the most important and efficient method for crop improvement involving repeated modification of the genetic makeup of a plant population over many generations. In this review, various accessible breeding approaches, such as conventional breeding and mutation breeding (physical and chemical mutagenesis and insertional mutagenesis), are discussed with respect to the actual impact of research on the economic improvement of tomato agriculture. Tomatoes are among the most economically important fruit crops consumed worldwide because of their high nutritional content and health-related benefits. Additionally, we summarize mutation-based mapping approaches, including Mutmap and MutChromeSeq, for the efficient mapping of several genes identified by random indel mutations that are beneficial for crop improvement. Difficulties and challenges in the adaptation of new genome editing techniques that provide opportunities to demonstrate precise mutations are also addressed. Lastly, this review focuses on various effective and convenient genome editing tools, such as RNA interference (RNAi), zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and clustered regularly interspaced short palindromic repeats (CRISPR/Cas9), and their potential for the improvement of numerous desirable traits to allow the development of better varieties of tomato and other horticultural crops.

Alteration of perivascular reflectivity on optical coherence tomography of branched retinal vein obstruction.

This study aimed to evaluate perivascular reflectivity in patients with branched retinal vascular obstruction (BRVO) using en-face optical coherence tomography (OCT). The study retrospectively analyzed 45 patients with recurrent BRVO, 30 with indolent BRVO, and 45 age- and sex-matched controls. Using a 3.0 × 3.0-mm deep capillary plexus slab on macular scans, OCT angiography (OCTA) and structural en-face OCT scans were divided into four quadrants. Obstructive quadrants of OCTA scans were binarized using a threshold value of mean + 2 standard deviation. The selected area of high signal strength (HSS) was applied to the structural en-face OCT scans, and the corrected mean perivascular reflectivity was calculated as the mean reflectivity on the HSS area/overall en-face OCT mean reflectivity. The same procedure was performed in the quadrants of the matched controls. Regression analysis was conducted on several factors possibly associated with corrected perivascular reflectivity. The perivascular reflectivity in the obstructive BRVO quadrant was significantly higher than in the indolent BRVO and control quadrants (P = 0.009, P = 0.003). Both univariate and multivariate regression analyses showed a significant correlation between the average number of intravitreal injections (anti-vascular endothelial growth factor or dexamethasone implant) per year and refractive errors and image binarization threshold and perivascular reflectivity (P = 0.011, 0.013, < 0.001/univariate; 0.007, 0.041, 0.005/multivariate, respectively). En-face OCT scans of the deep capillary plexus slab revealed higher perivascular reflectivity in recurrent BRVO eyes than in indolent BRVO and control eyes. The results also indicate a remarkable correlation between perivascular reflectivity and the average number of intravitreal injections, suggesting a link to recurrence rates.

Elevated interleukin-10 levels in patients with ocular toxoplasmosis.

In elderly patients, ocular toxoplasmosis is one of the most common etiologies of uveitis, which should be differentially diagnosed from ocular lymphoma, another common pathology of uveitis in older adults. The high level of interleukin (IL)-10 and an IL-10/IL-6 ratio higher than 1 (>1.0) are helpful parameters to diagnose ocular lymphoma. In this study, we used aqueous humor samples to detect 4 cases of ocular toxoplasmosis in patients with high levels of IL-10 and an IL-10/IL-6 ratio higher than 1. Our results show that ocular toxoplasmosis may be associated with increased cytokine levels in aqueous humor.

Relative mutagenic effectiveness and efficiency of chemical mutagens (Caffeine and EMS) and heavy metals [(Pb(NO3)2 and Cd(NO3)2)] in developing chlorophyll and morphological mutants in lentil.

Mutagenic effectiveness and efficiency are the utmost vital indices to determine the effective and efficient mutagenic concentrations for the generation of high frequency of desirable mutation in mutation breeding. Nevertheless, there are meager study are available for employing effective and efficient concentration of caffeine, EMS, Pb(NO3)2 and Cd(NO3)2 for the crop improvement. Thus, the current study was performed to assess the mutagenic effectiveness and efficiency of caffeine, EMS and heavy metals [Pb(NO3)2 Cd(NO3)2] and to determine the genetic variability of M2 and M3 lentil mutant lines. The frequency of different chlorophyll and chromophyll mutation was found highest at moderate and higher concentrations of chemical mutagens and heavy metals in M1 and M2 generation. The highest effectiveness was in 20 ppm Cd(NO3)2, followed by 20 ppm Pb(NO3)2, 0.10% EMS, and 0.10% caffeine. The present investigation also showed lower doses of caffeine, EMS, Pb(NO3)2, and Cd(NO3)2 were more efficient than higher concentrations, and caffeine was found more efficient followed by EMS, Pb(NO3)2, and Cd(NO3)2. Furthermore, a broad spectrum of viable mutations affecting different morphological characters of the plants viz., leaves, plant height, growth habits, flowers, pods, and seeds in M2 and M3 generation were recorded. Ten morphological mutants showing acceptable agronomic and horticultural features were identified, as genetic resources for further breeding.