Keratinocyte-to-macrophage communication exacerbate psoriasiform dermatitis via LRG1-enriched extracellular vesicles.

Rationale: Macrophage-associated inflammation and keratinocytes excessive proliferation and inflammatory cytokines secretion induced by stimulation play an important role in the progression of psoriasiform dermatitis. However, how these two types of cells communicate remains obscure. Methods: We induced a mouse model with experimental psoriasiform dermatitis by Imiquimod (IMQ). To investigate whether damaged keratinocytes promote macrophage polarization and accelerate skin lesions by releasing extracellular vesicle (EV), purified EV were isolated from the primary epidermis of 5-day IMQ-induced psoriasiform dermatitis model mice, and then fluorescence-labeled the EV with PKH67. The EV was injected into the skin of mice treated with IMQ or vehicle 2 days in situ. In addition, we established a co-culture system of the human monocytic cell line (THP-1) and HaCaT, and THP-1/HaCaT conditioned media culture model in vitro respectively. Subsequently, we evaluated the effect of Leucine-rich α-2-glycoprotein 1 (LRG1)-enriched EV on macrophage activation. Results: We demonstrated macrophages can significantly promote keratinocyte inflammation and macrophage polarization may be mediated by intercellular communication with keratinocytes. Interestingly, IMQ-induced 5-day, keratinocyte-derived EV recruited macrophage and enhanced the progression of skin lesions. Similar to results in vivo, EV released from M5-treated HaCaT significantly promotes Interleukin 1ß (IL-1ß) and Tumor necrosis factor α (TNF-α) expression of THP-1 cells. Importantly, we found that LRG1-enriched EV regulates macrophages via TGF beta Receptor 1 (TGFßR1) dependent process. Conclusion: Our findings indicated a novel mechanism for promoting psoriasiform dermatitis, which could be a potential therapeutic target.

Correction of axial length measurement error by IOLMaster 700 could improve refractive prediction accuracy in silicone oil-filled eyes.

PURPOSE: To determine whether correcting the axial length (AL) measurement error of the IOLMaster 700 could improve the refractive prediction accuracy in silicone oil-filled eyes. METHODS: This study included 265 cataract patients (265 eyes) with silicone oil tamponade who were scheduled for phacoemulsification with intraocular lens (IOL) implantation. The performances of various formulas, including Barrett Universal II, Emmetropia Verifying Optical, Hoffer-QST, Kane, Ladas Super Formula, Pearl-DGS, Radial Basis Function and traditional formulas (Haigis, Hoffer Q, Holladay 1 and SRK/T), were evaluated. The refractive prediction errors (PE) calculated with measured AL (ALmeas) and corrected AL with silicone oil adjustment (SOAL) were compared. Subgroup analysis was performed based on the ALmeas (<23 mm; 23-26 mm; ≥26 mm). RESULTS: Using SOAL significantly reduced the hyperopic PE of formulas when compared to ALmeas (-0.05 to 0.17 D vs 0.15 to 0.38 D, p < 0.001). After applying AL correction, all formulas showed a lower mean absolute PE (0.47-0.57 D vs 0.50-0.69 D). The percentage of eyes within ±1.0 D of PE increased from 84.91%-88.68% to 89.81%-91.32% for new formulas and from 78.11%-83.40% to 85.66%-88.68% for traditional formulas, with the use of SOAL. Subgroup analysis showed that the majority of formulas with SOAL in prediction accuracy for eyes with an AL ≥26 mm (p < 0.05). CONCLUSIONS: The refractive prediction accuracy in silicone oil-filled eyes was improved by correcting the AL measurement error of the IOLMaster 700, especially for long eyes.

Effect of Posterior Keratometry on the Accuracy of 10 Intraocular Lens Calculation Formulas: Standard Keratometry versus Total Keratometry.

PURPOSE: To investigate the effect of posterior keratometry (PK) on the accuracy of 10 intraocular lens (IOL) power calculation formulas using standard keratometry (K) and total keratometry (TK). METHODS: This is a retrospective consecutive case-series study. The IOL power was calculated using K and TK measured by IOLMaster 700 in 6 new-generation formulas (Barrett Universal II, Emmetropia Verifying Optical (EVO) 2.0, RBF Calculator 3.0, Hoffer QST, Kane, and Ladas Super Formula) and 4 traditional formulas (Haigis, Hoffer Q, Holladay 1, and SRK/T). The arithmetic prediction error (PE) and mean absolute PE (MAE) were evaluated. The locally-weighted scatterplot smoothing was performed to assess the relationship between PE and PK. RESULTS: A total of 576 patients (576 eyes) who underwent cataract surgery were included. Compared with using K, all formulas using TK showed a hyperopic shift in the whole group. Specifically, for eyes with PK exceeding -5.90 D, all formulas using TK exhibited a hyperopic shift (all P < 0.001), while eyes with PK less than -5.90 D showed a myopic shift (all P < 0.001). The MAE of new-generation formulas calculated with TK and K showed no statistical differences, while the MAE of traditional formulas with TK was larger (TK: 0.34 ~ 0.43 D; K: 0.33 ~ 0.42 D, all P < 0.05). CONCLUSIONS: The prediction bias of formulas with TK increased as PK deviated from -5.90 D. TK did not improve the prediction accuracy of new-generation formulas, and even performed worse in traditional formulas.

Let-7c-3p suppresses lens epithelial-mesenchymal transition by inhibiting cadherin-11 expression in fibrotic cataract.

Fibrotic cataract, including anterior subcapsular cataract (ASC) and posterior capsule opacification, always lead to visual impairment. Epithelial-mesenchymal transition (EMT) is a well-known event that causes phenotypic alterations in lens epithelial cells (LECs) during lens fibrosis. Accumulating studies have demonstrated that microRNAs are important regulators of EMT and fibrosis. However, the evidence explaining how microRNAs modulate the behavior and alter the cellular phenotypes of the lens epithelium in fibrotic cataract is insufficient. In this study, we found that hsa-let-7c-3p is downregulated in LECs in human ASC in vivo as well as in TGFß2-induced EMT in vitro, indicating that hsa-let-7c-3p may participate in modulating the profibrotic processes in the lens. We then demonstrated that overexpression of hsa-let-7c-3p markedly suppressed human LEC proliferation and migration and attenuated TGFß2-induced EMT and injury-induced ASC in a mouse model. In addition, hsa-let-7c-3p mediated lens fibrosis by directly targeting the CDH11 gene, which encodes cadherin-11 protein, an important mediator in the EMT signaling pathway. It decreased cadherin-11 protein expression at the posttranscriptional level but not at the transcriptional level by binding to a specific site in the 3-untranslated region (3'-UTR) of CDH11 mRNA. Moreover, blockade of cadherin-11 expression with a specific short hairpin RNA reversed TGFß2-induced EMT in LECs in vitro. Collectively, these data demonstrated that hsa-let-7c-3p plays a clear role in attenuating ASC development and may be a novel candidate therapeutic for halting fibrosis and maintaining vision.

Visible-Light-Induced and Iodoform-Promoted Functionalization of Ether with Secondary Sulfonyl Amides.

An iodoform-promoted functionalization of ether with secondary sulfonyl amides under visible-light irradiation was developed toward synthesis of hemiaminal skeleton with good to excellent isolated yields. The characterization of the isolated ether and iodoform complex revealed regioselective hydrogen atom transfer to initiate carbon radical formation and enabled the amination reaction with the sulfonamide.

Is Astigmatism Correction Necessary for Patients With Cataract Who Have Corneal Astigmatism of Less Than 0.75 D?

PURPOSE: To investigate the proportion of patients with predicted refractive astigmatism (PRA) of 0.75 diopters (D) or greater and associated risk factors among cataract surgery candidates with low corneal astigmatism. METHODS: A retrospective cross-sectional study was conducted in Zhongshan Ophthalmic Center, Guangzhou, China. Patients with cataract who had preoperative simulated keratometric astigmatism of less than 0.75 D were recruited. The PRA was calculated by Barrett toric calculator using posterior corneal astigmatism (PCA) measured by the IOLMaster 700 (Carl Zeiss Meditec AG) and corneal surgically induced astigmatism (SIA). Two corneal incision locations (temporal [0°/180°], 135° incision) and varying magnitudes (0.10 to 0.60 D) were considered for SIA. Multiple logistic regression analysis was used to explore risk factors associated with PRA of 0.75 D or greater and build predictive model. Sensitivity analysis was performed using PRA threshold of 0.50 D. RESULTS: A total of 1,750 eyes from 1,750 patients were included (mean age: 60.14 ± 13.24 years, 42.91% male, 1,010 right eyes and 740 left eyes). The 135° incision (odds ratio [OR]: 17.86) and against-the-rule (ATR) astigmatism (OR: 37.55) are the major risk factors for PRA of 0.75 D or greater. Higher simulated keratometric astigmatism (OR: 2.03), larger PCA (OR: 1.64), and surgically induced astigmatism (OR: 1.29) also significantly increased the risk of PRA of 0.75 D or greater. Nomogram model were constructed with an area under curve of 0.90. CONCLUSIONS: For patients with corneal astigmatism of less than 0.75 D, temporal incision and measured PCA is preferred. Those patients with ATR astigmatism should be considered for astigmatism correction when using a 135° incision. [J Refract Surg. 2023;39(12):850-855.].

Clinical analysis, diagnosis, and treatment strategies for otogenic brain abscesses.

Objective: To explore the clinical features, diagnosis, and treatment strategies for otogenic brain abscesses (OBA). Methods: Clinical data from 10 patients with OBA were analyzed retrospectively. Clinical characteristics, diagnosis, and treatment experiences were summarized. Results: Two were first diagnosed in the Department of Otorhinolaryngology, 5 in Neurosurgery, and 3 in other departments. There were 6 cases of temporal lobe abscess and 4 cases of cerebellar abscesses. Five cases were accompanied by 1 or more intracranial complications. Headache is a common presentation in all cases. The main pathogenic bacteria were anaerobic bacteria. All patients had no previous ear or brain surgery history, and no history of traumatic brain injury, 7 received surgical treatment in the neurosurgery and/or otolaryngology department. Two patients died, the other 8 fully recovered and so were discharged. Conclusions: Diagnosis and treatment of OBA must involve multiple departments. Multidisciplinary consultation (MDT) is crucial to the success of the first OBA diagnosis. The diagnosis and treatment team develops personalized treatment plans by integrating MDT treatment opinions and combining the actual condition of patients, thereby making the diagnosis and treatment of OBA accurate and timely.

Tunicates as Sources of High-Quality Nutrients and Bioactive Compounds for Food/Feed and Pharmaceutical Applications: A Review.

Tunicates are widely distributed worldwide and are recognized as abundant marine bioresources with many potential applications. In this review, state-of-the-art studies on chemical composition analyses of various tunicate species were summarized; these studies confirmed that tunicates contain nutrients similar to fish (such as abundant cellulose, protein, and ω-3 fatty acid (FA)-rich lipids), indicating their practical and feasible uses for food or animal feed exploration. However, the presence of certain toxic elements should be evaluated in terms of safety. Moreover, recent studies on bioactive substances extracted from tunicates (such as toxins, sphingomyelins, and tunichromes) were analyzed, and their biological properties were comprehensively reviewed, including antimicrobial, anticancer, antioxidant, antidiabetic, and anti-inflammatory activities. In addition, some insights and prospects for the future exploration of tunicates are provided which are expected to guide their further application in the food, animal feed, and pharmaceutical industries. This review is critical to providing a new pathway for converting the common pollution issues of hydroponic nutrients into valuable marine bioresources.

Clinical features and prognosis of advanced intra- and extra-pulmonary neuroendocrine carcinomas.

Objective: We examined the clinical features and prognosis of advanced intra- and extra-pulmonary neuroendocrine carcinomas (NECs) to offer additional guidance for the clinical treatment of small-cell lung cancer (SCLC), which is a type of advanced intrapulmonary NEC (IPNECs). Materials and Methods: The clinical data and survival of 123 patients with advanced IPNECs and extrapulmonary NECs (EPNECs) were obtained. We retrospectively examined the corresponding clinical diagnosis and treatment and investigated the significant factors influencing the survival prognosis of patients with NECs. Results: There were 90 cases of IPNECs (including 81 cases of SCLC), and 33 cases of EPNECs. The median overall survival (OS) of IPNECs was significantly longer than that of the EPNECs in the gastrointestinal tract and in the other regions (P < 0.05). The median OS of patients with other IPNECs was longer than that of patients with SCLC (P > 0.05). Multivariate analysis demonstrated that age, liver metastasis, number of cycles of first-line chemotherapy, and chest radiotherapy were risk factors influencing OS in patients with NECs (P < 0.05). Conclusions: The survival of IPNECs was significantly longer than that of EPNECs in the gastrointestinal tract and other regions. Nevertheless, patients with advanced NECs who were older and had liver metastases had a poorer prognosis. Multidisciplinary treatments including multicycle chemotherapy and a combination of chemotherapy and radiotherapy should function significantly in extending the survival of NECs.

Choice of intraocular lens calculation formula for cataract patients with prior pars plana vitrectomy.

PURPOSE: To determine the optimal intraocular lens (IOL) calculation formula for vitrectomized eyes with diverse surgical and biometric characteristics. SETTING: Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. DESIGN: Retrospective consecutive case series study. METHODS: This study included 974 vitrectomized eyes (974 patients) scheduled for phacoemulsification with IOL implantation. 11 formulas were evaluated: Barrett Universal II (BUII), Emmetropia Verifying Optical, Hoffer-QST, Kane, Ladas Super Formula, Pearl-DGS, Radial Basis Function (RBF), Haigis, HofferQ, Holladay1, and SRK/T. Risk factors for prediction error (PE) exceeding 1 diopter (D) were determined using multiple logistic regression. Subgroup analyses were performed based on surgical history and biometric parameters. RESULTS: The risk of hyperopic PE (>1 D) was higher in patients with silicone oil tamponade (odds ratio [OR], 1.82) and longer axial length (AL) (OR, 1.55), while patients with previous scleral buckling (OR, 2.43) or ciliary sulcus IOL implantation (OR, 6.65) were more susceptible to myopic PE (<-1 D). The Kane formula had the highest overall prediction accuracy, and also the best in silicone oil-filled eyes and the flat cornea subgroup. The BUII and RBF displayed the optimal performance in eyes with previous scleral buckle and steep cornea, respectively. In eyes with an AL ≥ 26 mm, the Holladay1 with the nonlinear version of the Wang-Koch AL adjustment (Holladay1-WKn) showed the lowest absolute PE and highest percentage within ± 1.0 D of PE. CONCLUSIONS: The Kane achieved the highest overall prediction accuracy in vitrectomized eyes. The optimal formula for eyes with previous scleral buckle, steep cornea, or long AL was BUII, RBF, and Holladay1-WKn, respectively.

Combined impacts of microplastics and cadmium on the liver function, immune response, and intestinal microbiota of crucian carp (Carassius carassius).

Microplastics (MPs) and the heavy metal cadmium (Cd) have attracted global attention for their toxicological interactions in aquatic organisms. The purpose of this investigation was evaluating the effect of MPs (1 mg L-1) and Cd (5 mg L-1) on the liver function, immune response of crucian carp (Carassius carassius) after 96 h exposure, and intestinal microbiota after 21 days, respectively. Co-exposure to MPs and Cd significantly enhanced MP accumulation in the liver of the crucian carp compared to the accumulation with exposure to MPs alone. Co-exposure to MPs and Cd triggered notable histopathological alterations accompanied by increased hepatic cell necrosis and inflammation, and was associated with higher aspartate aminotransferase and alanine aminotransferase levels, lower superoxide dismutase and catalase activity levels, but higher malondialdehyde content and total antioxidant capacity in the liver. Moreover, the combined treatment of MPs and Cd led to the up-regulated transcription of genes related to immune response, such as interleukin 8 (il-8), il-10, il-1ß, tumor necrosis factor-α, and heat shock protein 70, both in the liver and spleen. Co-exposure to MPs and Cd reduced the variety and abundance of the intestinal microbiota in the crucian carp. Our research indicates that the combined exposure to MPs and Cd may exert synergistic toxic effects on crucian carp, which could impede the sustainable growth of the aquaculture industry and pose potential risks to food safety.

Clostridium perfringens epsilon prototoxin mutant rpETXY30A/Y71A/H106P/Y196A as a vaccine candidate against enterotoxemia.

Epsilon toxin (ETX) is secreted by Clostridium perfringens (C. perfringens)as a relatively inactive prototoxin (pETX), which is enzymatically activated to ETX by removing carboxy-terminal and amino-terminal peptides. Genetically engineered ETX mutants have been shown to function as potential vaccine candidates in the prevention of the enterotoxemia caused by C. perfringens. In the present study, two recombinant site-directed mutants of pETX, rpETXY30A/Y71A/H106P/Y196A (rpETXm41) and rpETXY30A/H106P/Y196A/F199E (rpETXm42), were synthesized by mutating four essential amino acid residues (Tyr30, Tyr71, His106, Tyr196 or Phe199). Compared to recombinant pETX (rpETX), both rpETXm41 and rpETXm42 lacked the detectable toxicity in MDCK cells and mice, which suggested that both rpETXm41 and rpETXm42 are sufficiently safe to be vaccine candidates. Despite the fact that rpETXm41 and rpETXm42 were reactogenic with polyclonal antibodies against crude ETX, both single- and double-dose vaccination (Vs and Vd, respectively) of rpETXm41 induced a higher level of IgG titer and protection in mice than that of rpETXm42. Therefore, we selected rpETXm41 for the further study. Sheep received Vs of 150 µg rpETXm41 developed significant levels of toxin-neutralizing antibodies persisting for at least 6 months, which conferred protection against crude ETX challenge without microscopic lesions. These data suggest that genetically detoxified rpETXY30A/Y71A/H106P/Y196A could form the basis of a next-generation enterotoxemia vaccine.

Iridoid from Eucommia ulmoides Oliv. Exerts Antiarthritis Effects by Inhibiting the JAK2/STAT3 Signaling Pathway In Vivo and In Vitro.

The purpose of this study was to investigate the anti-inflammatory effects of EU-Idd both in vivo and in vitro. In vivo, we used the collagen-induced arthritis (CIA) rat model to investigate the efficacy of EU-Idd on rheumatoid arthritis. Hematoxylin-eosin staining and Safranin O-fast green staining were used to evaluate the pathological status of the ankle joints in CIA rats. Micro-CT scanning was used to investigate bone erosion of the ankle joints. In vitro, the effect of EU-Idd on Th17 cell differentiation was identified by flow cytometry. TRAP staining was used to detect osteoclast cells. HFLS-RA model cells, induced by tumor necrosis factor-α(TNF-α), were used to evaluate the anti-inflammatory effects of EU-Idd while the levels of related inflammatory cytokines and JAK2/STAT3 proteins were detected by RT-qPCR and western blotting. EU-Idd alleviated joint inflammation in CIA rats and exerted protective effects on the ankle joints. EU-Idd also prevented the differentiation of CD4+ T cells into Th17 cells, reduced the number of osteoclasts, and improved the expression levels of bone metabolism-related proteins including OPG and RANKL. Moreover, EU-Idd inhibited the invasion and migration of HFLS-RA cells and downregulated the expression of related inflammatory cytokine genes and the protein expression levels of p-JAK2 and p-STAT3, both in vivo and in vitro. EU-Idd exerts anti-inflammatory and osteoprotective effects by regulating the JAK2/STAT3 pathway in rheumatoid arthritis. These results are beneficial to excavate new pharmaceutical ingredients for rheumatoid arthritis from iridoid.

SET7 methylates the deubiquitinase OTUB1 at Lys 122 to impair its binding to E2 enzyme UBC13 and relieve its suppressive role on ferroptosis.

The deubiquitinating enzyme OTUB1 possesses canonical deubiquitinase (DUB) activity and noncanonical, catalytic-independent activity, which has been identified as an essential regulator of diverse physiological processes. Posttranslational modifications of OTUB1 affect both its DUB activity and its noncanonical activity of binding to the E2 ubiquitin-conjugation enzyme UBC13, but further investigation is needed to characterize the full inventory of modifications to OTUB1. Here, we demonstrate that SET7, a lysine monomethylase, directly interacts with OTUB1 to catalyze OTUB1 methylation at lysine 122. This modification does not affect DUB activity of OTUB1 but impairs its noncanonical activity, binding to UBC13. Moreover, we found using cell viability analysis and intracellular reactive oxygen species assay that SET7-mediated methylation of OTUB1 relieves its suppressive role on ferroptosis. Notably, the methylation-mimic mutant of OTUB1 not only loses the ability to bind to UBC13 but also relieves its suppressive role on Tert-Butyl hydroperoxide-induced cell death and Cystine starvation/Erastin-induced cellular reactive oxygen species. Collectively, our data identify a novel modification of OTUB1 that is critical for inhibiting its noncanonical activity.

The impact of metabolic diseases and their comorbidities for stroke in a middle-income area of China: a case-control study.

BACKGROUND: There are few studies on the comorbidity of hypertension (HTN), diabetes mellitus (DM) and dyslipidemia (DLP) associated with stroke. We aimed to explore the relationship between the number of metabolic diseases and stroke and its different subtypes, and to reveal whether metabolic diseases alone or coexist can significantly increase the risk of stroke. METHODS: We completed a multi-center case-control study in Jiangxi Province, China. Neuroimaging examination was done in all cases. Controls were stroke-free adults recruited from the community in the case concentration area and matched with the cases in 1:1 ratio by age and sex. Odds ratios (OR) were calculated by conditional logistic regression. RESULTS: We enrolled 11,729 case-control pairs. The estimated ORs among patients with 1, 2 and 3 metabolic diseases were 3.16 (2.78-3.60), 7.11 (6.16-8.20), 12.22 (9.73-15.36), respectively after adjusting age, body mass index, urban-rural areas, cardiac disease, smoking, alcohol intake, physically active, high intake of salt, meat-biased diet, high homocysteine. The coexistence of HTN and DM (OR: 7.67), the coexistence of HTN and DLP (OR:7.58), and the coexistence of DM and DLP (OR:3.64) can all significantly increase the risk of stroke. HTN alone or combined other metabolic diseases were significantly more strongly associated with intracerebral haemorrhage than ischemic stroke. CONCLUSIONS: The risk of stroke increased with the number of chronic metabolic diseases. It is necessary to regularly monitor blood pressure, blood sugar and blood lipids and strengthen lifestyle management and take appropriate drug interventions to prevent exposure to multiple metabolic diseases based on existing conditions.

A prognostic risk model for ovarian cancer based on gene expression profiles from gene expression omnibus database.

This study explored prognostic genes of ovarian cancer and built a prognostic model based on these genes to predict patient's survival, which is of great significance for improving treatment of ovarian cancer. GSE26712 dataset was downloaded from Gene Expression Omnibus database as training set, while OV-AU dataset was downloaded from ICGC website as validation set. All genes in GSE26712 were analyzed by univariate Cox regression, Lasso regression, and multivariate Cox regression analyses. Then prognosis-related feature genes were screened to construct a multivariate risk model. Meanwhile, Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was performed on samples in the high/low-risk groups using Gene Set Enrichment Analysis (GSEA) software. Finally, survival curve and receiver operating characteristic curve were drawn to verify the validity of the model. Ten feature genes related to prognosis of ovarian cancer were obtained: CMTM6, COLGALT1, F2R, GPR39, IGFBP3, RNF121, MTMR9, ORAI2, SNAI2, ZBTB16. GSEA enrichment analysis showed that there were notable differences in biological pathways such as gap junctions and homologous recombination between the high/low-risk groups. Through further verification of training set and validation set, the 10-gene prognostic model was found to be effective for the prognosis of ovarian cancer patients. In this study, we constructed a 10-gene prognostic model which predicted the prognosis of ovarian cancer patients well by integrating clinical prognostic parameters. It may have certain reference value for subsequent clinical treatment research of ovarian cancer patients and help in clinical treatment decision-making.

Building prediction models of clinically significant intraocular lens tilt and decentration for age-related cataract.

PURPOSE: To explore the risk factors and construct nomogram models to predict the risks of clinically significant intraocular lens (IOL) tilt and decentration after cataract surgery in patients with age-related cataract. SETTING: Zhongshan Ophthalmic Center, Guangzhou, China. DESIGN: Prospective cohort study. METHODS: 207 patients (207 eyes) who underwent phacoemulsification combined with IOL implantation were enrolled in the study. Casia2 was used to measure the tilt and decentration of crystalline lenses and IOLs before and 3 months after surgery. Univariate and multivariate logistic regression analyses were used to determine the risk factors of clinically significant IOL tilt and decentration, and nomogram prediction models were constructed according to the results of the multivariate logistic regression analysis. RESULTS: Two hundred and seven patients were included in analysis. 24 eyes (11.59%) and 16 eyes (7.73%) had clinically significant IOL tilt and decentration at 3 months after cataract surgery. Multivariate logistic regression analysis revealed that preoperative crystalline lens tilt and decentration were the risk factors for clinically significant IOL tilt (odds ratio [OR], 3.519, P < .001) and decentration (OR, 410.22, P = .001), respectively. Axial length was another association factor for clinically significant IOL decentration (OR, 2.155, P = .019). The risk models demonstrated good calibrations and discriminations for the predictions of clinically significant IOL tilt (receiver operating characteristic [ROC] area = 0.833, cutoff value = 6.5) and decentration (ROC area = 0.757, cutoff value = 0.08). CONCLUSIONS: The good performances of our models suggested that they may be useful risk prediction tools for postoperative IOL tilt and decentration. The measurement of preoperative crystalline lens tilt and decentration should be one of the routine examinations before cataract surgery, especially for toric and multifocal IOLs.

Risk factors and prognostic factors for pulmonary large cell neuroendocrine carcinoma with brain metastasis.

BACKGROUND: As the studies regarding the brain metastasis (BM) of pulmonary large cell neuroendocrine carcinoma (LCNEC) are insufficient, the present research aims to describe the risk factors and prognostic factors that are related to cancer-specific survival (CSS) for LCNEC patients with BM. METHODS: The data of LCNEC patients between January 2010 and October 2018 were obtained from the SEER database. Binary logistic regression analyses were utilized to screen the possible risk factors related to BM. Prognostic factors for LCNEC patients with BM were indentified by Cox regression analyses. Moreover, a nomogram was established to predict the 6-, 12-, and 18-month CSS rates. The concordance index (C-index), receiver operating characteristic (ROC) curves and calibration curves were utilized to assess the discrimination and reliability of the model. Clinical decision curves (DCAs) were used to evaluate the clinical benefits and utility of our model. RESULTS: Totally, 1875 patients were enrolled, with 294 (15.7%) of them having BM at diagnosis. Multivariate logistic regression analyses revealed that patients with age < 65 (odds ratio, OR = 1.564) and N2 staging (OR = 1.775) had a greater chance of developing BM. Age (≥ 65 vs. < 65: hazard ratio, HR = 1.409), T staging (T1 vs. T0: HR = 4.580; T2 vs. T0: HR = 6.008; T3 vs. T0: HR = 7.065; T4 vs. T0: HR = 6.821), N staging (N2 vs. N0: HR = 1.592; N3 vs. N0: HR = 1.654), liver metastasis (HR = 1.410), primary site surgery (HR = 0.581) and chemotherapy (HR = 0.452) were independent prognostic factors for LCNEC patients with BM. A nomogram prediction model was constructed by incorporating these factors. Using the C-index, calibration curves, ROC curves, and DCAs, we found that the clinical prediction model performed well. CONCLUSION: We described the risk factors and prognostic factors that were associated with CSS for LCNEC patients with BM. The related nomogram was established and validated to help clinicians formulate more rational and effective treatment strategies.

Promotion of diet-induced obesity and metabolic syndromes by BID is associated with gut microbiota.

A growing body of evidence has indicated an expanding functional network of B-cell lymphoma 2 (BCL-2) family proteins beyond regulation of cell death and survival. Here, we examined the role and mechanisms of BH3 interacting-domain death agonist (BID), a pro-death BCL-2 family member, in the development of diet-induced metabolic dysfunction. Mice deficient in bid (bid-/- ) were resistant to high-fat diet (HFD)-induced obesity, hepatic steatosis, and dyslipidemia with an increased insulin sensitivity. Indirect calorimetry analysis indicated that bid deficiency increased metabolic rate and decreased respiratory exchange ratio, suggesting a larger contribution of lipids to overall energy expenditure. While expression of several genes related to lipid accumulation was only increased in wild-type livers, metabolomics analysis revealed a consistent reduction in fatty acids but an increase in certain sugars and Krebs cycle intermediates in bid-/- livers. Gut microbiota (GM) analysis indicated that HFD induced gut dysbiosis with differential patterns in wild-type and in bid-/- mice. Notably, abrogation of GM by antibiotics during HFD feeding eliminated the beneficial effects against obesity and hepatic steatosis conferred by the bid deficiency. Conclusion: These results indicate that the protective role of bid-deficiency against diet-induced metabolic dysfunction interacts with the function of GM.

Methyltransferase SMYD3 impairs hypoxia tolerance by augmenting hypoxia signaling independent of its enzymatic activity.

Hypoxia-inducible factor (HIF)1α, a main transcriptional regulator of the cellular response to hypoxia, also plays important roles in oxygen homeostasis of aerobic organisms, which is regulated by multiple mechanisms. However, the full cellular response to hypoxia has not been elucidated. In this study, we found that expression of SMYD3, a methyltransferase, augments hypoxia signaling independent of its enzymatic activity. We demonstrated SMYD3 binds to and stabilizes HIF1α via co-immunoprecipitation and Western blot assays, leading to the enhancement of HIF1α transcriptional activity under hypoxia conditions. In addition, the stabilization of HIF1α by SMYD3 is independent of HIF1α hydroxylation by prolyl hydroxylases and the intactness of the von Hippel-Lindau ubiquitin ligase complex. Furthermore, we showed SMYD3 induces reactive oxygen species accumulation and promotes hypoxia-induced cell apoptosis. Consistent with these results, we found smyd3-null zebrafish exhibit higher hypoxia tolerance compared to their wildtype siblings. Together, these findings define a novel role of SMYD3 in affecting hypoxia signaling and demonstrate that SMYD3-mediated HIF1α stabilization augments hypoxia signaling, leading to the impairment of hypoxia tolerance.