Gut bacterium Burkholderia cepacia (BsNLG8) and immune gene Defensin A contribute to the resistance against Nicotine-induced stress in Nilaparvata lugens (Stål).

Nicotine, a naturally occurring alkaloid found in tobacco, is a potent neurotoxin extensively used to control Nilaparvata lugens (Stål), a destructive insect pest of rice crops. The insect gut harbors a wide array of resident microorganisms that profoundly influence several biological processes, including host immunity. Maintaining an optimal gut microbiota and immune homeostasis requires a complex network of reciprocal regulatory interactions. However, the underlying molecular mechanisms driving these symbiotic exchanges, particularly between specific gut microbe and immunity, remain largely unknown in insects. Our previous investigations identified and isolated a nicotine-degrading Burkholderia cepacia strain (BsNLG8) with antifungal properties. Building on those findings, we found that nicotine intake significantly increased the abundance of a symbiotic bacteria BsNLG8, induced a stronger bacteriostatic effect in hemolymph, and enhanced the nicotine tolerance of N. lugens. Additionally, nicotine-induced antimicrobial peptides (AMPs) exhibited significant antibacterial effects against Staphylococcus aureus. We adopted RNA-seq to explore the underlying immunological mechanisms in nicotine-stressed N. lugens. Bioinformatic analyses identified numerous differentially expressed immune genes, including recognition/immune activation (GRPs and Toll) and AMPs (i.e., Defensin, Lugensin, lysozyme). Temporal expression profiling (12, 24, and 48 hours) of immune genes revealed pattern recognition proteins and immune effectors as primary responders to nicotine-induced stress. Defensin A, a broad-spectrum immunomodulatory cationic peptide, exhibited significantly high expression. RNA interference-mediated silencing of Defensin A reduced the survival, enhanced nicotine sensitivity of N. lugens to nicotine, and decreased the abundance of BsNLG8. The reintroduction of BsNLG8 improved the expression of immune genes, aiding nicotine resistance of N. lugens. Our findings indicate a potential reciprocal immunomodulatory interaction between Defensin A and BsNLG8 under nicotine stress. Moreover, this study offers novel and valuable insights for future research into enhancing nicotine-based pest management programs and developing alternative biocontrol methods involving the implication of insect symbionts.

PTCH/SMO gene mutations in odontogenic keratocysts and drug interventions.

BACKGROUND: Odontogenic keratocysts (OKCs) are odontogenic jaw lesions that cause destruction and dysfunction of the jawbone. OKCs can be sporadic or associated with nevoid basic cell carcinoma syndrome (NBCCS). However, the factors that initiate OKCs and the mechanism of cyst formation remain unclear. Here, we investigated the impact of PTCH1 and SMO mutations on disease progression, as well as the effects of sonic hedgehog (SHH) signaling pathway inhibitors GDC-0449 and GANT61 on OKC fibroblasts. METHODS: Eight sporadic OKC fibroblasts without gene mutations were used as the control, and six NBCCS-related fibroblasts were cultured in vitro. The effect of PTCH1 non-truncated mutation 3499G>A (p.G1167R) and SMO c.2081C>G (p.P694R) mutation on OKC fibroblast proliferation was examined by EdU assay. CCK8 and wound-healing assays detected the effects of OKC fibroblasts carrying PTCH1 c.3499G>A (p.G1167R) and SMO c.2081C>G (p.P694R) mutations on the proliferation and migration of HaCaT cells after co-culture. Quantitative real-time PCR detected the effects of GDC-0449 or GANT61 on the SHH signaling pathway in NBCCS-related OKCs with PTCH1 truncated mutations and PTCH1 c.3499G>A (p.G1167R) and/or SMO c.2081C>G (p.P694R) mutations. RESULTS: PTCH1 c.3499G>A (p.G1167R) and SMO c.2081C>G (p.P694R) promoted the proliferation of OKC fibroblasts. The proliferation and migration of HaCaT cells were affected by NBCCS-related OKC fibroblasts carrying PTCH1 c.3499G>A (p.G1167R) and SMO c.2081C>G (p.P694R) mutations. GDC-0449 significantly inhibited the SHH signaling pathway in NBCCS-related OKC fibroblasts with PTCH1 truncated mutations. An NBCCS-related OKC carrying PTCH1 c.3499G>A (p.G1167R) and SMO c.2081C>G (p.P694R) mutations were resistant to GDC-0449 but inhibited by GANT61. CONCLUSIONS: Genetic mutations in OKC fibroblasts may affect the biological behavior of epithelial and stromal cells and cause disease. GDC-0449 could be used to treat OKCs, especially NBCCS-related OKCs with PTCH1 truncated mutations. SMO c.2081C>G (p.P694R) may lead to resistance to GDC-0449; however, GANT61 may be used as an alternative inhibitor.

Nicotine perturbs the microbiota of brown planthopper (Nilaparvata lugens stål Hemiptera: Delphinidae).

Bacterial symbionts exhibiting co-evolutionary patterns with insect hosts play a vital role in the nutrient synthesis, metabolism, development, reproduction, and immunity of insects. The brown planthopper (BPH) has a strong ability to adapt to various environmental stresses and can develop resistance to broad-spectrum insecticides. We aimed to investigate whether gut symbionts of BPH play a major role in the detoxification of insecticides and host fitness in unfavorable environments. Nicotine-treated rice plants were exposed to BPH (early stage) and the gut microbiome of the emerging female adults were analyzed using high throughput sequencing (HTS). Nicotine administration altered the diversity and community structure of BPH symbionts with significant increases in bacterial members such as Microbacteriaceae, Comamondaceae, Enterobacteriaceae, and these changes may be associated with host survival strategies in adverse environments. Furthermore, the in-vitro study showed that four intestinal bacterial strains of BPH (Enterobacter NLB1, Bacillus cereus NL1, Ralstonia NLG26, and Delftia NLG11) could degrade nicotine when grown in a nicotine-containing medium, with the highest degradation (71%) observed in Delftia NLG11. RT-qPCR and ELISA analysis revealed an increased expression level of CYP6AY1 and P450 enzyme activities in Delftia NLG11, respectively. CYP6AY1 increased by 20% under the action of Delftia and nicotine, while P450 enzyme activity increased by 18.1%. After CYP6AY1 interference, nicotine tolerance decreased, and the mortality rate reached 76.65% on the first day and 100% on the third day. Moreover, Delftia NLG11 helped axenic BPHs to increase their survival rate when fed nicotine in the liquid-diet sac (LDS) feeding system. Compared with axenic BPHs, the survival rate improved by 25.11% on day 2% and 6.67% on day 3. These results revealed an altered gut microbiota and a cooperative relationship between Delftia NLG11 and CYP6AY1 in nicotine-treated BPH, suggesting that insects can adapt to a hostile environment by interacting with their symbionts and providing a new idea for integrated pest management strategies.

Exosomes from adipose-derived stem cells attenuate UVB-induced apoptosis, ROS, and the Ca2+ level in HLEC cells.

Cartilage acid protein 1 (CRTAC1) encodes a protein containing the Ca2+binding domain, which can promote apoptosis of human lens epithelial cells (HLECs) induced by ultraviolet B radiation. Exosomes secreted from adipose-derived stem cells (ASC-exo) have been used to treat many diseases, but the effect of ASC-exo on cataracts has not been established. We hypothesized that ASC-exo has a therapeutic effect on cataracts by regulating CRTAC1. We established the UVB-induced injured HLECs model to test the interactions between CRTAC1 and miR-10a-5p, and the effect on the Ca2+ level and reactive oxygen species (ROS) generation in apoptotic HLECs. We found that UVB significantly increased the level of CRTAC1 expression and induced HLEC apoptosis, while ASC-exo inhibited the induction of UVB and exosome inhibitor reduced the inhibition of ASC-exo. The qRT-PCR results showed that miR-10a-5p had a low level of expression in cataract lesions, whereas CRTAC1 was highly expressed. There was a negative correlation between the expression of CRTAC1 and miR-10a-5p. ASC-exo reversed UVB-inhibited miR-10a-5p expression and miR-10a-5p negatively regulated CRTAC1. In vitro data showed that miR-10a-5p reversed UVB-induced ROS, apoptosis, and the Ca2+ level in HLECs. Overexpression of CRTAC1 reversed the induction of ASC-exo in UVB-injured HLECs, and low expression of CRTAC1 reversed the induction of miR-10a-5p inhibitor. By upregulating the level of miR-10a-5p expression and downregulating the level of CRTAC1 expression, exosomes from ASCs attenuated UVB-induced apoptosis, ROS generation, and the Ca2+ level in HLECs. Our research provides novel insight into the treatment methods and associated mechanisms underlying cataracts.

Pretreatment of rice straw with recycled ionic liquids by phase-separation process for low-cost biorefinery.

An efficient ionic liquids (ILs) recycle technology will increase the economic viability of lignocellulosic biorefinery. The availability of recycling 1-butyl-3-methylimidazolium chloride for rice straw (RS) pretreatment was conducted. The kosmotropic salt K3 PO4 (TKP) solution was used as antisolvent for cellulose precipitation and forming a three-phase system consisting of biomass, ILs-rich, and salt-rich phases. The upper ILs phase and the bottom TKP phase were recycled without additional purification, which significantly simplifies the process for recovering ILs. Subsequently, the RS pretreated with multiple reusing ILs (RPRS) were investigated by components analysis, structure evolution, enzymatic hydrolysis, and fermentation experiments. The results showed that unpurified reusing ILs led to further delignification and improvement of enzyme accessibility of the pretreated RS. The reducing sugar yield of RS pretreated with 8th reusing IL (8th RPRS) could still reach 98.9%, and the ethanol and succinic acid concentrations achieved 91.9 and 29.3 g/L by simultaneous saccharification and cofermentation. The present study demonstrated that the ILs recovered by phase-separation process could be used for RS pretreatment, and achieving high titer ethanol fermentation.

Porcine Deltacoronavirus Accessory Protein NS6 Antagonizes Interferon Beta Production by Interfering with the Binding of RIG-I/MDA5 to Double-Stranded RNA.

Porcine deltacoronavirus (PDCoV) has recently emerged as an enteric pathogen that can cause serious vomiting and diarrhea in suckling piglets. The first outbreak of PDCoV occurred in the United States in 2014 and was followed by reports of PDCoV in South Korea, China, Thailand, Lao People's Democratic Republic, and Vietnam, leading to economic losses for pig farms and posing a considerable threat to the swine industry worldwide. Our previous studies have shown that PDCoV encodes three accessory proteins, NS6, NS7, and NS7a, but the functions of these proteins in viral replication, pathogenesis, and immune regulation remain unclear. Here, we found that ectopic expression of accessory protein NS6 significantly inhibits Sendai virus-induced interferon beta (IFN-ß) production as well as the activation of transcription factors IRF3 and NF-κB. Interestingly, NS6 does not impede the IFN-ß promoter activation mediated via key molecules in the RIG-I-like receptor (RLR) signaling pathway, specifically RIG-I, MDA5, and their downstream molecules MAVS, TBK1, IKKε, and IRF3. Further analyses revealed that NS6 is not an RNA-binding protein; however, it interacts with RIG-I/MDA5. This interaction attenuates the binding of double-stranded RNA by RIG-I/MDA5, resulting in the reduction of RLR-mediated IFN-ß production. Taken together, our results demonstrate that ectopic expression of NS6 antagonizes IFN-ß production by interfering with the binding of RIG-I/MDA5 to double-stranded RNA, revealing a new strategy employed by PDCoV accessory proteins to counteract the host innate antiviral immune response.IMPORTANCE Coronavirus accessory proteins are species specific, and they perform multiple functions in viral pathogenicity and immunity, such as acting as IFN antagonists and cell death inducers. Our previous studies have shown that PDCoV encodes three accessory proteins. Here, we demonstrated for the first time that PDCoV accessory protein NS6 antagonizes IFN-ß production by interacting with RIG-I and MDA5 to impede their association with double-stranded RNA. This is an efficient strategy of antagonizing type I IFN production by disrupting the binding of host pattern recognition receptors (PRRs) and pathogen-associated molecular patterns (PAMPs). These findings deepen our understanding of the function of accessory protein NS6, and they may direct us toward novel therapeutic targets and lead to the development of more effective vaccines against PDCoV infection.

PTCH1 alterations are frequent but other genetic alterations are rare in sporadic odontogenic keratocysts.

OBJECTIVE: Odontogenic keratocysts (OKCs) are benign jaw lesions with high growth potential and propensity for recurrence. Our previous study revealed that PTCH1 mutations, which were frequently detected in sporadic OKCs, might be underestimated due to the masking effect of the stromal components within the tested tissues. We aimed to confirm these results in larger scale and further present the unbiased view of the genomic basis of sporadic OKCs except PTCH1. MATERIALS AND METHODS: We analyzed PTCH1 mutations in additional 19 samples. Using whole-exome sequencing (WES), we further characterized the mutational landscape of five sporadic OKC samples lacking PTCH1 mutation and loss of heterozygosity (LOH). RESULTS: Combined with our previously reported 19 cases, thirty of 38 (79%) cases harbored PTCH1 mutations. Through whole-exome sequencing and integrative analysis, 22 novel mutations were confirmed among five PTCH1-negative samples. No recurrent mutations were identified in the WES samples and validation cohort of 10 OKCs. CONCLUSIONS: Our data further confirmed the frequent PTCH1 mutation and other rare genetic alterations in sporadic OKCs, highlighting the central role of SHH signaling pathway. In PTCH1-negative cases, other rare mutations scattered in a subset of OKCs were independent of the SHH pathway. These results suggested that an SHH inhibitor may be effective to treat the majority of OKCs.

Adiponectin promotes human jaw bone marrow mesenchymal stem cell chemotaxis via CXCL1 and CXCL8.

Adiponectin (APN) is known to promote the osteogenic differentiation of human jaw bone marrow mesenchymal stem cells (h-JBMMSCs). However, the underlying mechanism has not been fully elucidated. Previously, we showed that APN could promote h-JBMMSC osteogenesis via APPL1-p38 by up-regulating osteogenesis-related genes. Here, we aimed to determine whether APN could promote h-JBMMSC chemotaxis through CXCL1/CXCL8. The CCK-8, wound healing and transwell assays were used to evaluate the proliferation, migration and chemotaxis of h-JBMMSCs with or without APN treatment. Chemotaxis-related genes were screened using RNA-seq, and the results were validated using real-time PCR and ELISA. We also performed Western blot using the AMPK inhibitor, WZ4003, and the p38 MAPK inhibitor, SB203580, to identify the signalling pathway involved. We found that APN could promote h-JBMMSC chemotaxis in the co-culture transwell system. CXCL1 and CXCL8 were screened and confirmed as the up-regulated target genes. The APN-induced CXCL1/8 up-regulation to promote chemotaxis could be blocked by CXCR2 inhibitor SB225002. Western blot revealed that the phosphorylation of AMPK and p38 MAPK increased in a time-dependent manner with APN treatment. Additionally, WZ4003 and SB203580 could suppress the APN-induced overexpression of CXCL1 and CXCL8. The results of the transwell chemotaxis assay also supported the above results. Our data suggest that APN can promote h-JBMMSC chemotaxis by up-regulating CXCL1 and CXCL8.

Discovery of a novel accessory protein NS7a encoded by porcine deltacoronavirus.

Porcine deltacoronavirus (PDCoV) is an emerging swine enteric coronavirus. Bioinformatics predicts that PDCoV encodes two accessory proteins (NS6 and NS7), the species-specific proteins for coronavirus. In this study, four mAbs against the predicted NS7 were prepared by using the purified recombinant NS7 protein. Indirect immunofluorescence assay demonstrated that all mAbs recognized cells transfected with an NS7 expression construct or infected with PDCoV. Western blot showed that NS7-specific mAbs recognized an additional protein band of about 12 kDa from PDCoV-infected cell lysates but not from cells with the ectopic expression of NS7. Detailed analysis suggested that this additional protein band represented a novel accessory protein, termed NS7a, a 100 amino acid polypeptide identical to the 3' end of NS7. Moreover, NS7a is encoded by a separate subgenomic mRNA with a non-canonical transcription regulatory sequence. In summary, our results identified a third accessory protein encoded by PDCoV, which will enhance our understanding of PDCoV.

Treatment of Salmonella-Contaminated Eggs and Pork with a Broad-Spectrum, Single Bacteriophage: Assessment of Efficacy and Resistance Development.

Numerous studies have assessed the efficacy of phage-based methods to inhibit Salmonella contamination in food products. As with most antibacterials, bacteria can develop resistance to phage in vitro. Here, we applied a single broad-spectrum Salmonella phage, vB_SalS_SJ_2 (SJ2; 108 PFU; MOI = 10), to Salmonella-contaminated meat and eggs to quantify the development of resistance in actual food matrices. Treatment with a single phage significantly reduced Salmonella Typhimurium contamination in both ground pork and liquid egg at various time points. Similarly, the same phage significantly reduced Salmonella Enteritidis in both food matrices. Efficacy was temperature dependent as larger reductions were seen at higher temperatures (21°C) versus lower temperatures (4°C) at 24 h. Following phage treatment, over 10,000 Salmonella isolates were examined for resistance to the treatment phage. The percentages of phage-resistant Salmonella (either serovar) recovered from phage-treated versus untreated pork did not differ. Conversely, significantly (p < 0.05) higher percentages of phage-resistant Salmonella Typhimurium (92.50% vs. 0.56% of control) and Salmonella Enteritidis (50.83% vs. 0.56% of control) isolates were observed in phage-treated versus untreated egg samples after incubation at room temperature for 48 h. Taken together, these data indicate that the food matrix may influence the emergence of phage resistance with resistance developing more rapidly in foods with less complex microbial communities. Future studies will focus on the impact the development of resistance in production and processing settings may have on the efficacy of phage treatments for longer term biocontrol of pathogens.

CMTM3 inhibits cell growth and migration and predicts favorable survival in oral squamous cell carcinoma.

Downregulation of CKLF-like MARVEL transmembrane domain-containing member 3 (CMTM3) has been reported in a number of human tumors. However, the role of CMTM3 in oral squamous cell carcinoma (OSCC) remains largely unknown. In this study, we showed that the expression of CMTM3 was significantly reduced in OSCC cell lines and primary tumor specimens (P < 0.001). Methylation-specific PCR showed hypermethylation in CMTM3 promoter in a significant proportion of tumor tissues (61 %). The expression of CMTM3 was associated with T stage, lymph node metastasis, tumor node metastasis (TNM) stage, and recurrence of OSCC patients (P < 0.05, n = 201). More importantly, CMTM3 expression was associated with the prognosis of OSCC patients (P < 0.001) and was an independent prognostic factor (hazard ratio = 0.593, 95 % confidence interval, 0.272-1.292; P = 0.039). Overexpression of CMTM3 inhibited the growth and migration of OSCC cells. In vivo experiments also showed that the growth of OSCC xenografts in nude mice was significantly inhibited by CMTM3 overexpression. These findings indicate that downregulation of CMTM3 due to promoter hypermethylation contributed to the proliferation and migration of OSCC cells and suggest that CMTM3 is an independent prognostic factor for the evaluation of the survival of OSCC patients.

Effect of Decentration, Rotation, and Tilt on Objective Optical Quality of Plate Haptic Toric Intraocular Lenses in the Early Postoperative Period.

Purpose: This study aimed to determine the influence of decentration, rotation, and tilt on objective optical quality of plate haptic toric intraocular lenses (tIOLs). Methods: The area ratio of modulation transfer function (MTF), strehl ratio of point spread function (PSF), and higher order aberrations (HOAs) for 3 mm and 5 mm pupil diameter (PD) were evaluated at postoperative 1 month. The retroillumination images pictured by OPD-scan III were used to quantify the degree of decentration and rotation, whereas the tIOL tilt was directly obtained by the tilt aberration. Patients were separated into two subgroups based on tIOL misalignment cutoff values. Results: There were 29 eyes (24 patients) in the study. The decentration of more than 0.25 mm did not substantially differ from those less than or equal to 0.25 mm. PSF of 3 mm PD and MTF, intraocular HOAs, and trefoil aberration for 3 mm and 5 mm PD significantly deteriorated with a rotation of more than 3 degrees, whereas only intraocular HOAs for 5 mm PD and coma for 3 mm and 5 mm PD were significantly severe with a tilt of more than 0.1 µm and 0.25 µm in corresponding PD. Furthermore, tIOL rotation and tilt were highly correlated with intraocular trefoil aberration and coma, respectively. Conclusions: The decentration of the monofocal bitoric IOLs is more tolerant to optical quality degradation after 1 month of surgery but more sensitive to intraocular trefoil aberration caused by rotation and coma aberration induced by tilt. Translational Relevance: As far as we know, this is the first study to investigate the relationship between the plate haptic bitoric IOL misalignment and objective optical quality measured by OPD-scan III in the real world, which may provide reference information for IOL selection to improve surgical outcomes.

Prognostic factors associated with pulp status in patients with cracked teeth treated with occlusal veneer: A 6- through 24-month prospective clinical study.

BACKGROUND: The authors evaluated the prognostic factors associated with pulp status in patients with cracked teeth (CT) treated with occlusal veneer. METHODS: An analysis of 80 CT (71 patients) with 1 or more crack lines (CLs) and normal pulp vitality or reversible pulpitis was performed. All patients received occlusal veneer and their demographic and clinical data were recorded. Pulp status and clinical features were recorded at 1 week and posttreatment at 1, 2, 3, 6, 12, 18, and 24 months. RESULTS: Maxillary first molars were commonly involved (30 [38%]). The number of CLs on the finish line ranged from 1 through 7 and most had 3 CLs (24 [30%]). The number of CLs through preparation on the finish line ranged from 0 through 4, and 2 CLs (42 [53%]) were the most prevalent. During follow-up, 5 of 80 CT progressed to pulp disease, resulting in a success rate of 93.8%. Results of the Cox model and Kaplan-Meier analysis showed that probing depth greater than 6 mm, widening periodontal ligament of apical area, more than 4 CLs on finish line, and more than 2 CLs through preparation on the finish line were risk factors associated with pulp status (P < .05). CONCLUSIONS: Occlusal veneer can protect CT without preventive root canal therapy. PRACTICAL IMPLICATIONS: The success rate and risk factors of pulp disease in CT restored with occlusal veneer are reported.

Management and prognosis of a vital cracked tooth by occlusal veneer for 14 months: A case report.

Key Clinical Message: An occlusal veneer is an ultrathin restoration method and a minimally invasive approach that can preserve more dental tissue and provide better aesthetic outcomes, thus increasing patient satisfaction. Abstract: An occlusal veneer is an ultrathin restoration method and a minimally invasive approach that can preserve more dental tissue and provide better aesthetic outcomes, thus increasing patient satisfaction; however, no previous studies reported on treating cracked teeth using occlusal veneer. Accordingly, we described the diagnosis and treatment process of a cracked tooth using occlusal veneer in a single case. A 29-year-old male presented at our dental clinic complaining of biting pain in the mandibular molar on the right-hand side. A routine oral examination with radiography was performed to evaluate the oral condition and treatment planning. The #16 tooth had a crack line surrounding the whole distal-lingual cusp from the occlusal surface. After discussing various therapeutic options with the patient, an occlusal veneer was performed. One week after treatment with occlusal veneer, the patient had no complaints. A 14-month follow-up showed promising clinical and radiographic outcomes. Occlusal veneer is an alternative treatment option for a cracked tooth, as it can preserve more dental tissue and potentially save pulp vitality.

Biting and thermal sensitivity relief of cracked tooth restored by occlusal veneer: A 12-to 24 months prospective clinical study.

OBJECTIVES: To analyze the relief time and risk factors of biting/thermal sensitivity in cracked tooth (CT) restored using occlusal veneer. METHODS: 63 CT were analyzed, and their demographic and clinical data and medical history were collected. Patients were followed-up to examine the relief of thermal/biting sensitivity. RESULTS: The maxillary first molar was the most prevalent (N = 25, 40%). The number of crack lines on the finish line ranged from 1 to 6 while the number of crack lines through preparation on the finish line from 0 to 4. Pain relief achieved steadily to 52% for thermal and 62% for biting at 1 week to over 90% for each by 3 months and was completely resolved (no pain) for each by 12 months. Painful of lateral percussion was related to a long period of thermal sensitivity (≥1 month) after restoration with occlusal veneer. The number of crack lines through preparation on the finish line >2 was correlated with biting sensitivity (≥1 month) post-treatment. CONCLUSIONS: Most patients (>90%) became asymptomatic of biting and thermal sensitivity within 3 months of CT restored by occlusal veneer. Lateral percussion and the number of crack lines through preparation on the finish line could be significant factors affecting postoperative symptoms. CLINICAL SIGNIFICANCE: Occlusal veneer is an ultrathin restoration and had no need for restricting clinical crown height, which could protect and relief the biting/thermal sensitivity of CT without preventive root canal therapy.

The growth and shape of the eyeball and crystalline lens in utero documented by fetal MR imaging.

Purpose: To study the growth model, shape, and developmental relationship of lens and eyeball, we used two-dimensional Magnetic Resonance (MR) imaging to investigate gestationally age-related changes in the selected ocular parameters in vivo. Materials and methods: We retrospectively reviewed the MR images from 126 fetuses ranging from 21 to 39 weeks' gestation. Ocular parameters on MR imaging of transverse plane were measured including lens diameter (LD), anteroposterior lens diameter (APLD), lens surface area (LS), globe diameter (GD), anteroposterior globe diameter (APGD), globe surface area (GS). The growth model of each biometric against gestational age (GA), aspect ratio of lens and globe (LD/APLD and GD/APGD), and growing relationship between the ratio of lens and globe surface area (LS/GS) were studied by statistical analysis. Results: The growth model of most biometry for gestational age is logarithmic, except for the diameter of the ocular globe (GD and APGD) showing a quadratic growth pattern. Our study showed that the lens was consistently larger in the transverse than the anteroposterior diameters during 21-39 weeks(P < 0.001). Besides, the ratio of surface area (LS/GS) was not significantly changing with GA(P = 0.4908), while the increase of LS was significantly accorded with that of GS(P < 0.001). Conclusion: The lens shape throughout fetal life may take part in the process, shape changing from vertical ellipsoid, spherical to transversal ellipsoid, based on the logarithmically increased ratio of lens transverse and anteroposterior diameters. In the meanwhile, the aspect ratio of eyeball in late fetal life may imply a gradually spherical shape during gestation. Nomogram data from this study may provide appropriate information about morphological changes in the fetal lens and the synchronous relationship between lens and eyeball.

ceRNA network construction and identification of hub genes as novel therapeutic targets for age-related cataracts using bioinformatics.

Background: The aim of this study is to investigate the genetic and epigenetic mechanisms involved in the pathogenesis of age-related cataract (ARC). Methods: We obtained the transcriptome datafile of th ree ARC samples and three healthy, age-matched samples and used differential expression analyses to identify the differentially expressed genes (DEGs). The differential lncRNA-associated competing endogenous (ceRNA) network, and the protein-protein network (PPI) were constructed using Cytoscape and STRING. Cluster analyses were performed to identify the underlying molecular mechanisms of the hub genes affecting ARC progression. To verify the immune status of the ARC patients, immune-associated analyses were also conducted. Results: The PPI network identified the FOXO1 gene as the hub gene with the highest score, as calculated by the Maximal Clique Centrality (MCC) algorithm. The ceRNA network identified lncRNAs H19, XIST, TTTY14, and MEG3 and hub genes FOXO1, NOTCH3, CDK6, SPRY2, and CA2 as playing key roles in regulating the pathogenesis of ARC. Additionally, the identified hub genes showed no significant correlation with an immune response but were highly correlated with cell metabolism, including cysteine, methionine, and galactose. Discussion: The findings of this study may provide clues toward ARC pathogenic mechanisms and may be of significance for future therapeutic research.

A Bayesian network meta-analysis on comparisons of intraocular lens power calculation methods for paediatric cataract eyes.

The study aimed to compare and rank the accuracy of formulas for calculating intraocular lens (IOL) power in paediatric eyes in a systematic way. A literature search was conducted in Pubmed, Web of Science, Cochrane Library, and EMBASE by December 2021. Combined with traditional and network meta-analysis, we analysed the percentages of paediatric eyes with prediction error (PE) within ±0.50 dioptres (D) and ±1.00 D as the outcome measurements among different formulas. Subgroup analyses stratified by age were also undertaken. Thirteen studies with 1781 eyes comparing 8 calculation formulas were included. For the traditional meta-analysis results, Sanders-Retzlaff-Kraff theoretical (SRK/T) (risk ratios (RR), 1.15; 95% confidence intervals (CI), 1.03-1.30) performed significantly better than the SRKII formula for the percentage of eyes with PE within ±0.50 D. In addition, SRK/T (RR, 1.10; 95% CI, 1.02-1.18) and Holladay 1(RR, 1.15; 95% CI, 1.01-1.30) both performed significantly better than the SRKII formula for the percentage of eyes with PE within ±1.00 D. Considering the ranking based on the surface under the cumulative ranking curve (SUCRA) by Bayesian method, the top four formulas were Barrett Universal II (UII), Haigis, Holladay 1, and SRK/T on the percentage of PE within ±0.50 D, whereas the top four formulas were Barrett UII, Holladay 1, SRK/T, and Hoffer Q formulas on the percentage of PE within ±1.00D. Concerning both outcome measurements of rank probabilities, the top three Barrett UII, SRK/T, and Holladay 1 formulas were considered to provide more accuracy for IOL power calculation in paediatric cataract eyes, and Barrett UII tends to perform better in older children.

Presbyopia-Correcting Intraocular Lenses Implantation in Eyes After Corneal Refractive Laser Surgery: A Meta-Analysis and Systematic Review.

Purpose: To assess the efficacy, safety, and predictability of presbyopia-correcting intraocular lenses (IOLs) in cataract patients with previous corneal refractive surgery. Methods: A systematic literature search was performed to identify studies evaluating the clinical outcomes of presbyopia-correcting IOLs implantation in cataract surgery after laser refractive surgery. Outcomes were efficacy, safety and predictability parameters. Results: The authors identified 13 studies, involving a total of 128 patients and 445 eyes. Presbyopia-correcting IOLs were effective at improving distance, intermediate and near visual acuity aftercataract surgery. The proportion of post-laser surgery eyes with uncorrected distance visual acuity (UDVA) ≥ 20/25 was 0.82 [95% confidence interval (CI), 0.74-0.90] and the pooled rates of spectacle independence at near, intermediate, and far distances were 0.98 (95% CI, 0.94-1.00), 0.99 (95% CI, 0.95-1.00) and 0.78 (95% CI, 0.65-0.94) respectively. The percentage of participants who suffered from halos and glare was 0.40 (95% CI, 0.25-0.64) and 0.31 (95% CI, 0.16-0.60), respectively. The predictability had a percentage of 0.66 (95% CI, 0.57-0.75) and 0.90 (95% CI, 0.85-0.96) of eyes within ±0.5 diopters (D) and ±1.0 D from the targeted spherical equivalent. Conclusions: Presbyopia-correcting IOLs provide satisfactory results in terms of efficacy, safety and predictability in patients with previous corneal refractive surgery, but have a higher risk of photopic side effects such as halos and glare.

Prognostic factors for hearing outcomes in patients that undergo adjuvant hyperbaric oxygen therapy for sudden sensorineural hearing loss.

Introduction: The aim of this study is to explore the potential factors in hearing outcomes and verify the role of oxidant-antioxidant equilibrium on the prognosis of sudden sensorineural hearing loss (SSNHL) treated with hyperbaric oxygen therapy (HBOT). Methods: Ninety-two patients who were diagnosed with SSNHL between January 2018 and December 2019 in our hearing clinic center were included in this study. All patients were treated with intravenous dexamethasone, and 72 cases were treated with additional HBOT for 10 consecutive days. Peripheral blood was collected prior to any treatment to determine the blood cell count and hemoglobin (HGB), hematocrit (HCT), and superoxide dismutase (SOD) levels. Pure tone audiometry was measured before and after treatment. Complete and overall recovery rate was evaluated. Multivariate logistic analysis was used to identify prognostic factors. Results: The rate of overall recovery was significantly higher in the patient with combined therapy compared to patients treated with steroids only (51.4% vs 25.0%, p = .036). The levels of HGB, HCT, and SOD were much higher in the patients with better hearing outcomes (p = .027, .033, and .011, respectively). Multivariate logistic analysis demonstrated that patients with higher initial hearing thresholds, or hearing loss at overall frequency, were more prone to have poor hearing gains after HBOT. Conclusion: HBOT is effective as an early adjuvant therapy for SSNHL. Hearing loss at low frequency, low initial hearing thresholds, as well as high HBG, HCT, and SOD levels are positive prognostic factors for SSNHL patients treated with HBOT.