Ultra-processed foods intake and sex hormone levels among children and adolescents aged 6-19 years: a cross-sectional study.

Background: Sex hormones are crucial for the development of children and adolescents. The increasing consumption of ultra-processed foods (UPFs) among children and adolescents in the United States (US) has raised concerns about their potential impact on health, including hormonal balance. Methods: Data from 3,354 participants aged 6-19 years from the NHANES 2013-2016 were analyzed. UPF intake was categorized using the NOVA food classification system, and the percentage of total daily energy intake from UPFs was calculated. The serum levels of total testosterone (TT), sex hormone-binding globulin (SHBG), and estradiol (E2) were measured. The free androgen index (FAI) and TT/E2 ratio were calculated to estimate bioavailable testosterone levels and the balance between androgens and estrogens, respectively. Multiple linear regression models, adjusted for potential confounders, estimated the associations. Results: Our results showed that higher intake of UPFs was marginally associated with decreased serum SHBG levels (quartile (Q) 2 vs. Q1: ß = -5.3, 95% confidence interval (CI): -17.0, 8.1%; Q3 vs. Q1: ß = -14.6, 95%CI: -25.1, -2.5%; Q4 vs. Q1: ß = -9.0, 95%CI: -20.3, 3.8%; P trend = 0.081), and significantly associated with increased serum FAI in female adolescents (Q2 vs. Q1: ß = 3.2, 95%CI: -3.3, 9.7; Q3 vs. Q1: ß = 7.6, 95%CI: -0.7, 16.0; Q4 vs. Q1: ß = 9.5, 95%CI: 1.5, 17.6; P trend = 0.019). Additionally, UPF intake showed a marginally positive association with increased serum SHBG levels (P trend = 0.057) in male children and FAI (P trend = 0.150) in male adolescents, respectively. Similar results were observed when participants were stratified by puberty status, except for the association between UPF intake and SHBG in male children. However, there were no associations between UPF consumption and TT, E2, or the TT/E2 ratio, both in males and females. Conclusion: Higher UPF consumption is associated with increased FAI in adolescents, particularly in girls, indicating higher bioavailable testosterone levels. Future studies should validate these findings with direct free testosterone measurements and more precise dietary intake assessments.

Development and characterisation of [18F]TTDP, a novel T cell immunoglobulin and ITIM domain tracer, in humanised mice and non-human primates.

PURPOSE: The T cell immunoglobulin and ITIM domain (TIGIT) blockade immunotherapy response is directly associated with individual differences of TIGIT expression on tumour-infiltrating lymphocytes (TILs) in tumour immune microenvironment (TIME) of non-small cell lung cancer (NSCLC). Here, we developed a TIGIT-targeted PET tracer to evaluate its feasibility in predicting immunotherapy efficacy, aiming to manage NSCLC patients accurately. METHODS: We synthesised a 18F-labeled TIGIT-targeted D-peptide, [18F]TTDP, and investigated the specificity of [18F]TTDP both to murine TIGIT and human TIGIT by a series of in vitro and in vivo assays. [18F]TTDP PET imaging was performed in humanised immune system (HIS) mice models bearing NSCLC patient-derived xenografts (PDXs) to evaluate the predictive value of FDA-approved combination immunotherapy of atezolizumab plus tiragolumab. Lastly, rhesus macaque was applied for [18F] TTDP PET to explore the tracer's in vivo distribution and translational potential in non-human primates. RESULTS: [18F]TTDP showed high specificity for both murine TIGIT and human TIGIT in vitro and in vivo. The HIS NSCLC PDX platform was successfully established for [18F]TTDP PET imaging, and tumour uptake of [18F]TTDP was significantly correlated with the TIGIT expression of TILs in the TIME. [18F]TTDP PET imaging, in predicting treatment response to the combination immunotherapy in NSCLC HIS-PDX models, showed a sensitivity of 83.33% and a specificity of 100%. In addition, [18F]TTDP PET also showed cross-species consistency of the tracer biodistribution between non-human primate and murine animals, and no adverse events were observed. CONCLUSION: The combined implementation of the [18F]TTDP and HIS-PDX model creates a state-of-the-art preclinical platform that will impact the identification and validation of TIGIT-targeted PET image-guided diagnosis, treatment response prediction, beneficial patient screening, novel immunotherapies, and ultimately the outcome of NSCLC patients. We first provided in vivo biodistribution of [18F]TTDP PET imaging in rhesus macaque, indicating its excellent translational potential in the clinic.

Comparison of ocular biometric parameters between two swept-source optical coherence tomography devices and Scheimpflug tomography in patients with cataract.

AIM: To assess and compare the variations and agreements across different ocular biometric parameters using swept-source optical coherence tomography (SS-OCT) and Scheimpflug tomography in patients diagnosed with cataract. METHODS: This prospective case series was conducted at Tianjin Medical University Eye Hospital. In total, 212 eyes from 212 patients scheduled for phacoemulsification were included. Eyes were evaluated preoperatively using two SS-OCT devices (IOLMaster700 and CASIA2) and Scheimpflug tomography (Pentacam). Central corneal thickness (CCT), anterior chamber depth (ACD), aqueous depth (AQD), white-to-white distance (WTW), flat simulated keratometry (Kf), steep simulated keratometry (Ks), mean keratometry (Km), and total corneal keratometry (TKm) were measured. Intraclass correlation coefficient (ICC), 95% confidence intervals (CI) and limits of agreement (LoA) widths were conducted to assess differences and correlations between devices. RESULTS: All parameters, except for Ks, were significantly different. Pairwise comparison revealed no significant differences between keratometry obtained by IOLMaster 700 and Pentacam. LoA widths of all paired comparisons for Ks were >0.80 D. Except for WTW between IOLMaster 700 and CASIA2 and between CASIA2 and Pentacam, other Pearson's coefficients between devices showed a strong correlation (all r>0.95). The ICC of WTW (ICC=0.438, 95%CI 0.167-0.625) showed poor reliability. The reliability of CCT, ACD, and AQD was excellent (all ICC>0.95), whereas that of TKm was good (ICC=0.827, 95%CI 0.221-0.939). A significant linear correlation was also observed among devices. CONCLUSION: The ocular parameters derived from the use of IOLMaster700, CASIA2, and Pentacam exhibit significant discrepancies; as such, measurements from these devices should not be deemed as interchangeable.

The Influence of Corneal Thickness on Surgically Induced Corneal Astigmatism Derived from Total Keratometry Measured by Anterior Segment Swept-Source OCT.

INTRODUCTION: The purpose of the study was to explore the possible correlations between the anterior segment parameters derived from anterior segment swept-source optical coherence tomography (AS-SS-OCT) with the surgically induced corneal astigmatism (CSIA) calculated from total keratometry (TK) measured by AS-SS-OCT. METHODS: Seventy-one eyes of 67 patients with age-related cataract who underwent phacoemulsification combined with intraocular lens implantation with 2.2-mm incision were included. The CSIA values were calculated from anterior keratometry (CSIAKant) and TK (CSIATK) measured by AS-SS-OCT, respectively. Hotelling's T2 test was used to evaluate the difference. The correlation of CSIA with various parameters derived from AS-SS-OCT was tested with the Spearman correlation coefficient. RESULTS: The centroid of CSIAKant and of CSIATK were 0.31 ± 0.55 D @ 54° and 0.41 ± 0.59 D @ 51°, with no significant difference (F = 1.283, p = 0.281, Hotelling's T2). The mean absolute CSIAKant and CSIATK were 0.58 ± 0.24 D and 0.65 ± 0.28 D. Spearman test showed that the magnitude of CSIAKant was negatively correlated with preoperative peripheral corneal thickness (PCT, p = 0.045) and the magnitude of anterior keratometry (p = 0.044). The magnitude of CSIATK was negatively correlated with preoperative central corneal thickness (CCT, p = 0.003) and preoperative PCT (p = 0.015). CONCLUSIONS: The increased thickness of the peripheral cornea is correlated with the decrease in the magnitude of the CSIA. The correlation we identified between the corneal thickness and the CSIA indicated that certain preoperative parameters should be considered for the prediction of CSIA for a more precise refractive outcome.

Human Equilibrative Nucleoside Transporter 1: Novel Biomarker and Prognostic Indicator for Patients with Gemcitabine-Treated Pancreatic Cancer.

Aim: This article aimed to find appropriate pancreatic cancer (PC) patients to treat with Gemcitabine with better survival outcomes by detecting hENT1 levels. Methods: We collected surgical pathological tissues from PC patients who received radical surgery in our hospital from September 2004 to December 2014. A total of 375 PC tissues and paired adjacent nontumor tissues were employed for the construction of 4 tissue microarrays (TMAs). The quality of the 4 TMAs was examined by HE staining. We performed immunohistochemistry analysis to evaluate hENT1 expression in the TMAs. Moreover, we detected hENT1 expression level and proved the role of hENT1 in cell proliferation, drug resistance, migration and invasion in vivo and vitro. Results: The results indicated that low hENT1 expression indicated a significantly poor outcome in PC patients, including shortened DFS (21.6±2.8 months versus 36.9±4.0 months, p<0.001) and OS (33.6±3.9 versus 39.6±3.9, p=0.004). Meanwhile, patients in stage I/II of TNM stage had a longer OS (40.2±3.4 versus 15.4±1.7, p=0.002) and DFS (31.0±3.1 versus 12.4±1.9, p=0.016) than patients in stage III/IV. Patients in M0 stage had a longer OS (39.7±3.4 versus 16.2±1.9, p=0.026) and DFS(30.7±3.0 versus 11.8±2.2, p=0.031) than patients in M1 stage, and patients with tumors not invading the capsule had a better DFS than those with tumor invasion into the capsule (30.8±3.0 versus 12.6±2.3, p=0.053). Patients with preoperative CA19-9 values ≤467 U/mL have longer DFS than that of patients who had preoperative CA19-9 values >467 U/mL (37.9±4.1 versus 22.9±4.0, p=0.04). In the subgroup analysis, a high hENT1 expression level was related to a longer OS(39.4±4.0 versus 31.5±3.9, p=0.001) and DFS(35.7±4.0 versus 20.6±2.7; p<0.0001) in the Gemcitabine subgroup. Conclusion: PC patients with high hENT1 expression have a better survival outcomes when receiving Gemcitabine. hENT1 expression can be a great prognostic indicator for PC patients to receive Gemcitabine treatment.

The predictive accuracy of Barrett toric calculator using measured posterior corneal astigmatism derived from swept source-OCT and Scheimpflug camera.

PURPOSE: To compare the performance of Barrett toric calculator incorporated with measured posterior corneal astigmatism (PCA) derived from IOL Master 700 and Pentacam HR versus predicted PCA. METHODS: The predicted residual astigmatism using Barrett toric IOL calculator with predicted PCA, measured PCA from IOL Master 700 and measured PCA from Pentacam were calculated with the preoperative keratometry and intended IOL axis with modification. The vector analysis was performed to calculate the mean absolute prediction error (MAE), the centroid of the prediction error and the percentage of eyes with a prediction error within ±0.50 D, ±0.75 D, and ±1.00 D. RESULTS: In 57 eyes of 57 patients with mean age of 70.42 ± 10.75 years, the MAE among the three calculation methods were 0.59 ± 0.38 D (Predicted PCA), 0.60 ± 0.38 D (Measured PCA from IOL Master 700) and 0.60 ± 0.36 D (Measured PCA from Pentacam) with no significant difference, either in the whole sample, the WTR eyes and the ATR eyes (F = 0.078, 0.306 and 0.083, p = 0.925, 0.739 and 0.920, respectively). Measured PCA obtained from IOL Master 700 resulted in one level reduction (from Tn to Tn-1) in 49.12% eyes in cylindrical model selection, while measured PCA obtained from Pentacam resulted in one level reduction of toric model selection in 18.18% eyes. CONCLUSION: The present study suggested that the incorporation of measured PCA values derived from IOL Master 700 and Pentacam produce comparable clinical outcome with the predicted PCA mode in Barrett toric calculator.

Comparison of two swept-source optical coherence tomography devices, a Scheimpflug camera system and a ray-tracing aberrometer in the measurement of corneal power in patients with cataract.

PURPOSE: To assess the differences and similarities in the corneal curvature obtained by two swept-source optical coherence tomography (SS-OCT) devices, Scheimpflug imaging system and one ray tracing aberrometer in patients with cataracts. Moreover, this study aimed to compare the differences in posterior corneal (PK), total corneal (TK) and true net power (TNP) measurements among the IOLMaster 700, CASIA2, and Pentacam. METHODS: A total of 200 eyes of 200 patients (116 female, 58%) were enrolled in this study, with a mean age of 65.9 ± 9.5 years. The flattest (Kf), steepest (Ks), and mean cornal powers (Km), J0, and J45 were obtained using two SS-OCT-based biometric devices, one rotating camera system and one ray-tracing aberrometer. The PK, TK and TNP values were also measured using these devices. To evaluate the differences and similarities between the devicves, the Friedman test, Pearson correlation coefficient (r), intraclass coefficient correlation (ICC) and Bland‒Altman plots with 95% limits of agreement (LoA) were used, and boxplots and stacked histograms were generated to describe the distributions of the data. RESULTS: There were no significant differences between the IOLMaster 700 and Pentacam for any of the keratometry values. Additionally, there were no significant differences between the IOLMaster 700 and iTrace in evaluating J0 and J45. Bland‒Altman plots revealed relatively wide LoA widths, almost larger than 1 diopter for the keratometry values and almost larger than 0.5 diopter for J0 and J45 values among the four devices. In terms of PK and TK values, significant differences and low ICCs were found among the three devices. CONCLUSIONS: Although strong correlations and good agreement were found among the IOLMaster700, CASIA2, Pentacam and iTrace for Kf, Ks, Km and J0, J45, it seems that the measurements should not be used interchangeably because of the wide LoA widths and the presence of significant differences among the devices. Similarly, due to significant differences and low ICCs, the PK, TK and TNP values obtained by IOLMaster 700, CASIA2, and Pentacam should not be used interchangeably.

RIT1 regulates mitosis and promotes proliferation by interacting with SMC3 and PDS5 in hepatocellular carcinoma.

BACKGROUND: As a small G protein of Ras family, Ras-like-without-CAAX-1 (RIT1) plays a critical role in various tumors. Our previous study has demonstrated the involvement of RIT1 in promoting malignant progression of hepatocellular carcinoma (HCC). However, its underlying mechanism remains unclear. METHODS: Gene set enrichment analysis (GSEA) was conducted in the TCGA LIHC cohort to investigate the underlying biological mechanism of RIT1. Live cell imaging, immunofluorescence (IF) and flow cytometry assays were used to verify biological function of RIT1 in HCC mitosis. Subcutaneous xenografting of human HCC cells in BALB/c nude mice was utilized to assess tumor proliferation in vivo. RNA-seq, co-immunoprecipitation (Co-IP), mass spectrometry analyses, western blot and IF assays were employed to elucidate the mechanisms by which RIT1 regulates mitosis and promotes proliferation in HCC. RESULTS: Our findings demonstrate that RIT1 plays a crucial role in regulating mitosis in HCC. Knockdown of RIT1 disrupts cell division, leading to G2/M phase arrest, mitotic catastrophe, and apoptosis in HCC cells. SMC3 is found to interact with RIT1 and knockdown of SMC3 attenuates the proliferative effects mediated by RIT1 both in vitro and in vivo. Mechanistically, RIT1 protects and maintains SMC3 acetylation by binding to SMC3 and PDS5 during mitosis, thereby promoting rapid cell division and proliferation in HCC. Notably, we have observed an upregulation of SMC3 expression in HCC tissues, which is associated with poor patient survival and promotion of HCC cell proliferation. Furthermore, there is a significant positive correlation between the expression levels of RIT1, SMC3, and PDS5. Importantly, HCC patients with high expression of both RIT1 and SMC3 exhibit worse prognosis compared to those with high RIT1 but low SMC3 expression. CONCLUSIONS: Our findings underscore the crucial role of RIT1 in regulating mitosis in HCC and further demonstrate its potential as a promising therapeutic target for HCC treatment.

Total saponins from Trillium tschonoskii Maxim promote neurological recovery in model rats with post-stroke cognitive impairment.

Total saponins from Trillium tschonoskii Maxim (TSTT), a bioactive component of local natural herbs in the Enshi area, China, have been demonstrated to have functions of restoring cognitive capacity and promoting axonal regeneration post-stroke, but the mechanism of this process remains unclear. The hippocampus is a critical tissue for controlling learning and memory capacity, and the sonic hedgehog (Shh) signaling pathway plays a major role in the patterning and synaptic plasticity of hippocampal neural circuits. Therefore, we aimed to investigate whether TSTT could restore learning and cognitive functions by modulating the Shh pathway in rats with post-stroke cognitive impairment (PSCI). The ischemia model was established by permanent middle cerebral artery occlusion (MCAO) in 100 Sprague-Dawley (SD) rats, and the model rats were administered using TSTT (100 mg/kg) or donepezil hydrochloride as the positive control (daily 0.45 mg/kg, DON) for 4 weeks after the operation. As assessed by the Morris water maze test, the cognitive function of PSCI rats was significantly improved upon TSTT treatment. Meanwhile, the cerebral infarct volume reduced with TSTT, as shown by HE and TTC staining, and the number of Nissl bodies and dendritic spine density were significantly increased, as shown by Nissl and Golgi staining. In addition, TSTT upregulated PSD-95, SYN, and GAP-43, and inhibited neuronal apoptosis, as evidenced by increased Bcl-2 levels along with decreased Bax and caspase-3 expression. TSTT could also significantly upregulate Shh, Ptch1, Smo, and Gli1 proteins, indicating the activation of the Shh signaling pathway. Therefore, TSTT can protect PSCI rats by inhibiting apoptosis and promoting neuronal synaptic remodeling. The Shh pathway is also involved.

Syntaxin-6 promotes the progression of hepatocellular carcinoma and alters its sensitivity to chemotherapies by activating the USF2/LC3B axis.

Syntaxin-6 (STX6), a protein of the syntaxin family, is located in the trans-Golgi network and is involved in a variety of intracellular membrane transport events. STX6 is overexpressed in different human malignant tumors. However, little is known about its exact function and molecular mechanism in hepatocellular carcinoma (HCC). In this study, we found that the expression of STX6 was significantly increased in HCC tissues and was associated with poor survival. Gain- and loss-of-function experiments showed that STX6 promotes cell proliferation and metastasis of HCC cells both in vitro and in vivo. Mechanistically, STX6 was negatively regulated by the upstream stimulatory factor 2 (USF2). In addition, STX6 facilitates the association of autophagosomes with lysosomes. Importantly, we demonstrated that STX6 overexpression, despite enhanced resistance to lenvatinib, sensitizes HCC cells to the autophagy activator rapamycin. This study revealed that, under the control of USF2, STX6 accelerates the degradation of microtubule-associated protein 1 light chain 3 beta (LC3) by promoting autophagic flux, ultimately promoting HCC progression. Collectively, we suggest that the USF2-STX6-LC3B axis is a potential therapeutic target in liver cancer.

Comparison of two objective methods for measuring postoperative toric intraocular lens orientation under the natural pupil.

PURPOSE: To evaluate and compare the accuracy of iTrace and CASIA2 in measuring the postoperative orientation of toric intraocular lens (IOL) without mydriasis. SETTING: Tianjin Medical University Eye Hospital, Tianjin, China. DESIGN: Prospective cohort study. METHODS: Patients with SN6AT toric IOLs implanted after cataract surgery were enrolled. 1 month after surgery, the toric IOL orientation were measured by iTrace and CASIA2 in non-mydriatic, semi-dark conditions. Then, the toric axis was directly reviewed using the slit-lamp under full mydriasis. Axis measurement differences between each of the 2 devices and the slit-lamp, described as their relative differences (RDs), were calculated and compared. The percentage of RDs within 5 degrees, within 10 degrees and greater than 30 degrees were analyzed. RESULTS: 77 eyes of 70 patients were included. Generally, the mean toric axis measurement RDs of CASIA2 and iTrace were 9.24 ± 10.53 degrees and 13.89 ± 15.47 degrees respectively ( P = .04). For CASIA2 (72 eyes), 54.17% (39), 72.22% (52), and 4.17% (3) of eyes had RDs within 5 degrees, within 10 degrees and greater than 30 degrees, compared with 40.00% (28), 61.43% (43) and 12.86% (9) for iTrace (70 eyes). The 95% limits of agreements of CASIA2 with slit-lamp was narrower than that of iTrace with slit-lamp. The median RD of CASIA2 was significantly smaller in eyes with pupil ≥4 mm under dark condition compared with eyes with pupil <4 mm ( P = .03). CONCLUSIONS: CASIA2 demonstrates greater precision in measuring toric IOL orientation under non-mydriatic conditions compared with iTrace. Moreover, the accuracy of CASIA2 is enhanced in cases of pupil >4 mm.

Genomic analysis and filtration of novel prognostic biomarkers based on metabolic and immune subtypes in pancreatic cancer.

PURPOSE: Patients with pancreatic cancer (PC) can be classified into various molecular subtypes and benefit from some precise therapy. Nevertheless, the interaction between metabolic and immune subtypes in the tumor microenvironment (TME) remains unknown. We hope to identify molecular subtypes related to metabolism and immunity in pancreatic cancer METHODS: Unsupervised consensus clustering and ssGSEA analysis were utilized to construct molecular subtypes related to metabolism and immunity. Diverse metabolic and immune subtypes were characterized by distinct prognoses and TME. Afterward, we filtrated the overlapped genes based on the differentially expressed genes (DEGs) between the metabolic and immune subtypes by lasso regression and Cox regression, and used them to build risk score signature which led to PC patients was categorized into high- and low-risk groups. Nomogram were built to predict the survival rates of each PC patient. RT-PCR, in vitro cell proliferation assay, PC organoid, immunohistochemistry staining were used to identify key oncogenes related to PC RESULTS: High-risk patients have a better response for various chemotherapeutic drugs in the Genomics of Drug Sensitivity in Cancer (GDSC) database. We built a nomogram with the risk group, age, and the number of positive lymph nodes to predict the survival rates of each PC patient with average 1-year, 2-year, and 3-year areas under the curve (AUCs) equal to 0.792, 0.752, and 0.751. FAM83A, KLF5, LIPH, MYEOV were up-regulated in the PC cell line and PC tissues. Knockdown of FAM83A, KLF5, LIPH, MYEOV could reduce the proliferation in the PC cell line and PC organoids CONCLUSION: The risk score signature based on the metabolism and immune molecular subtypes can accurately predict the prognosis and guide treatments of PC, meanwhile, the metabolism-immune biomarkers may provide novel target therapy for PC.

PRKRA promotes pancreatic cancer progression by upregulating MMP1 transcription via the NF-κB pathway.

Objective: Pancreatic cancer (PC) is highly malignant, but the underlying mechanisms of cancer progression remain unclear. PRKRA is involved in cellular stress response, but its role in PC was unknown. Methods: The expression of PRKRA between normal and tumor tissues were compared, and the prognostic value of PRKRA was evaluated. SiRNA and plasmids were applied to investigate the effects of PRKRA on PC cells. Organoids and cell lines with knockout and overexpression of PRKRA were established by CRISPR/Cas9 and lentivirus. The effects of PRKRA on PC were evaluated in vivo by cell-derived xenografts. The downstream genes of PRKRA were screened by transcriptome sequencing. The regulation of the target gene was validated by RT-qPCR, western blot, ChIP and dual luciferase reporter assay. Besides, the correlation between PRKRA and gemcitabine sensitivity was investigated by PC organoids. Results: PRKRA was significantly overexpressed in PC tissues and independently associated with poor prognosis. PRKRA promoted the proliferation, migration, and chemoresistance of PC cells. The proliferation of PC organoids was decreased by PRKRA knockout. The growth and chemoresistance of xenografts were increased by PRKRA overexpression. Mechanistically, PRKRA upregulated the transcription of MMP1 via NF-κB pathway. ChIP and dual luciferase reporter assay showed that NF-κB subunit P65 could bind to the promoter of MMP1. The sensitivity of PC organoids to gemcitabine was negatively correlated with the expression of PRKRA and MMP1. Conclusions: Our study indicated that the PRKRA/NF-κB/MMP1 axis promoted the progression of PC and may serve as a potential therapeutic target and prognosis marker.

Pholcid spiders of the Pholcusphungiformes species-group (Araneae, Pholcidae) from Liaoning Province, China: an overview, with description of a new species.

Species of the Pholcusphungiformes group exhibit high diversity in Liaoning Province of northeastern China. This paper summarizes the current knowledge on this species-group from this area. A checklist of 22 species recorded from this province is given, accompanied with a distribution map of the species. Pholcusxiuyan Zhao, Zheng & Yao, sp. nov. (♂♀) is described as new to science, and P.yuhuangshan Yao & Li, 2021 is reported from Liaoning for the first time.

Drug Repurposing Flubendazole to Suppress Tumorigenicity via PCSK9-dependent Inhibition and Potentiate Lenvatinib Therapy for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most lethal malignant cancers across the world. It has a poor prognosis and lacks effective therapies, especially for patients with advanced-stage cancer, indicating an urgent need for new therapies and novel therapeutic targets. Here, by screening the U.S. Food and Drug Administration drug library against HCC cell lines, we identified that flubendazole, a traditional anthelmintic drug, could prominently suppress HCC cells in vivo and in vitro. RNA sequence analysis and cellular thermal shift assays showed that flubendazole reduced the expression of PCSK9 protein by direct targeting. The increased expression of PCSK9 in HCC tissues was demonstrated to be correlated with poor prognosis, and the inhibitory ability of flubendazole was selectively dependent on PCSK9 expression. PCSK9 knockdown abolished the antitumor effects of flubendazole in HCC. Mechanistically, flubendazole inhibited the Hedgehog signaling pathway induced by PCSK9, resulting in the downregulation of smoothened (SMO) and GLI Family Zinc Finger 1 (Gli1). Moreover, combining flubendazole with lenvatinib was found more effective than administering lenvatinib only for HCC treatment in vivo and in vitro. These findings reveal the therapeutic potential of flubendazole against HCC and provide clues on new repurposed drugs and targets for cancer treatment.

Diversity of Pholcus Spiders (Araneae: Pholcidae) in China's Lüliang Mountains: An Integrated Morphological and Molecular Approach.

Spiders of the genus Pholcus were collected for the first time during an expedition to the Lüliang Mountains in Shanxi Province, North China. Phylogenetic analyses of DNA sequence data from COI, H3, wnt, and 28S genes allowed us to group them into nine well-supported clades. We used morphology and four methods of molecular species delimitation, namely Automatic Barcode Gap Discovery (ABGD), the Generalized Mixed Yule Coalescent (GMYC), Bayesian Poisson Tree Processes (bPTP), and Bayesian Phylogenetics and Phylogeography (BPP), to investigate species boundaries. These integrative taxonomic analyses identified the nine clades as nine distinct species, comprising Pholcus luya Peng & Zhang, 2013 and eight other species new to science: Pholcus jiaocheng sp. nov., Pholcus linfen sp. nov., Pholcus lishi sp. nov., Pholcus luliang sp. nov., Pholcus wenshui sp. nov., Pholcus xiangfen sp. nov., Pholcus xuanzhong sp. nov., and Pholcus zhongyang sp. nov. The species occur in geographic proximity and show many morphological similarities. All of them belong to the P. phungiformes species group. The records from the Lüliang Mountains represent the westernmost distribution limit of this species group.

Plasmin-Induced Lens Epithelial Cells Detachment for the Reduction of Posterior Capsular Opacification.

Purpose: We sought to evaluate the efficacy and safety of plasmin injection in the capsular bag during the cataract operation for the prevention of posterior capsule opacification. Methods: Thirty-seven anterior capsular flaps taken from phacoemulsification surgery were immersed in either 1 µg/mL plasmin (plasmin group, n = 27) or phosphate-buffered saline (control group, n = 10) for 2 minutes and photographed after fixation and nuclear staining to compare the numbers of residual lens epithelial cells. In the animal experiments, the plasmin solution was injected into the capsular bag and remained for 5 minutes during hydrodissection or after lens extraction. The degree of posterior capsular opacity of the rabbits at 2 months were photographed by slit lamp biomicroscopy. In HLE-B3 cell culture, the cell detachment rate, proliferation, and apoptosis after the plasmin digestion were analyzed. Results: The residual lens epithelial cell numbers on the capsule after plasmin treatment were 168 ± 190.7/mm2 in the 1 µg/mL plasmin group, which was significantly lower than that of the control (1012 ± 798.8/mm2; P < 0.0001). In a rabbit model, the treatment of plasmin resulted in a significantly clearer posterior capsule compared with that of the control group at 2 months postoperatively. Conclusions: This study suggested that plasmin injection can induce effective lens epithelial cell detachment, which could be a promising adjunctive treatment to further improve the success rate in posterior capsule opacification prevention. Translational Relevance: Plasmin injection for lens epithelial cell detachment could significantly decrease the number of residual lens epithelial cells. This approach could be a promising treatment incorporating the current treatment approach to further improve the success rate in posterior capsule opacification prevention.

Bilateral Diffuse Uveal Melanocytic Proliferation Initially Presented as Glaucoma.

PURPOSE: To report a bilateral diffuse uveal melanocytic proliferation (BDUMP) patient whose initial presentation was glaucoma. METHODS: Clinical review of a BDUMP case. RESULTS: A 65-year-old woman presented with ocular pain of the left eye for 1 day and vision loss of the right eye for 1 week. An ophthalmological examination revealed increased intraocularr pressure in the left eye and shallow anterior chamber in both eyes. BDUMP was diagnosed following a series of auxiliary examinations. After 1.5 years of follow-up, progressive cataracts appeared, and the patient accepted cataract surgery in both eyes. Visual acuity improved from light perception to 20/100 in both eyes 1.5 years after cataract surgery, but declined to light perception again at the last follow-up. CONCLUSION: BDUMP can be initially presented as glaucoma, and cataract surgery can be considered in BDUMP patients in order to improve the patients' quality of life, even if exudative retinal detachment exists.

A survey of pholcid spiders (Araneae, Pholcidae) from Guiyang, Guizhou Province, China.

The family Pholcidae C.L. Koch, 1850 is highly diverse in Guizhou Province, southwestern China, and currently contains four genera and 22 species. Nevertheless, the distribution of pholcid spiders is conspicuously patchy in Guizhou. Species from Guiyang are poorly studied, and only Pholcusspilis Zhu & Gong, 1991 has been recorded. A survey was undertaken for the first time to study the pholcids in Guiyang. A total of four species are reported, comprising Belisanayuhaoi Yang & Yao, sp. nov. and three other species: Leptopholcustanikawai Irie, 1999 (new record for Guiyang), Pholcusspilis Zhu & Gong, 1991 and Spermophorasenoculata (Dugès, 1836) (new record for Guizhou).