Zonular instability-associated morphologic features in eyes with primary angle closure disease using the swept-source anterior segment - optical coherence tomography system.

BACKGROUND: This study aims to investigate the morphologic features of the crystalline lens in Primary Angle Closure Disease (PACD) patients with zonular instability during cataract surgery using the swept-source CASIA 2 Anterior Segment-Optical Coherence Tomography (AS-OCT) system. METHODS: A total of 398 eyes (125 PACD eyes with zonular instability, 133 PACD eyes with zonular stability, and 140 cataract patient controls) of 398 patients who underwent cataract surgery combined or not glaucoma surgery between January 2021 and January 2023 were enrolled. The crystalline lens parameters were measured by CASIA2 AS-OCT. Then, logistic regression was performed to evaluate the risk factors associated with zonular instability. RESULTS: The results revealed that PACD eyes had a more anterior lens equator position, a steeper anterior curvature of lens, shorter Axial Length (AL), shallower Anterior Chamber Distance (ACD), higher Lens Vault (LV) and thicker Lens Thickness (LT), when compared to eyes in the cataract control group. Furthermore, PACD eyes in the zonular instability group had steeper front R, front Rs and Front Rf, flatter back Rf, thicker lens anterior part thickness, higher lens anterior-to-posterior part thickness ratios, shallower ACD, and greater LV, when compared to PACD eyes with zonular stability. The logistic regression analysis, which was adjusted for age and gender, revealed that zonular instability was positively correlated with anterior part thickness, lens anterior-to-posterior part thickness ratio, and LV, but was negatively correlated with lens anterior radius and ACD. CONCLUSION: Steeper anterior curvature, increased lens anterior part thickness, higher anterior-to-posterior part thickness ratio, shallower ACD, and greater LV are the anatomic features of PACD eyes associated with zonular instability.

Nanoengineered Red Blood Cells Loaded with TMPRSS2 and Cathepsin L Inhibitors Block SARS-CoV-2 Pseudovirus Entry into Lung ACE2+ Cells.

The enzymatic activities of Furin, Transmembrane serine proteinase 2 (TMPRSS2), Cathepsin L (CTSL), and Angiotensin-converting enzyme 2 (ACE2) receptor binding are necessary for the entry of coronaviruses into host cells. Precise inhibition of these key proteases in ACE2+ lung cells during a viral infection cycle shall prevent viral Spike (S) protein activation and its fusion with a host cell membrane, consequently averting virus entry to the cells. In this study, dual-drug-combined (TMPRSS2 inhibitor Camostat and CTSL inhibitor E-64d) nanocarriers (NCs) are constructed conjugated with an anti-human ACE2 (hACE2) antibody and employ Red Blood Cell (RBC)-hitchhiking, termed "Nanoengineered RBCs," for targeting lung cells. The significant therapeutic efficacy of the dual-drug-loaded nanoengineered RBCs in pseudovirus-infected K18-hACE2 transgenic mice is reported. Notably, the modular nanoengineered RBCs (anti-receptor antibody+NCs+RBCs) precisely target key proteases of host cells in the lungs to block the entry of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), regardless of virus variations. These findings are anticipated to benefit the development of a series of novel and safe host-cell-protecting antiviral therapies.

"All about the value?" Decisional needs of breast reconstruction for breast cancer patients in the Chinese context: A mixed-methods study.

OBJECTIVE: To explore breast cancer (BC) patients' participation in breast reconstruction (BR) decision-making and specific decisional needs, especially the manifestations and causes of decisional conflicts, in China. METHODS: A mixed-methods study was conducted using triangulation of data from interviews and a questionnaire survey with health care professionals (HCPs) and BC patients with BR decision-making experience at 5 Beijing centers. The Ottawa Decision Support Framework guided (ODSF) the qualitative and quantitative data analyses. RESULTS: A total of 82.53% of Chinese BC patients would consider BR. Seven themes captured patients' BR decisional needs per the ODSF: inadequate support/resources (100%, 58.82%) and knowledge (75%, 52.94%) were most frequently cited. Health beliefs (unclear values) reflected Chinese characteristics. Patients had inadequate knowledge (M=19.99/50, SD=8.67) but positive BR attitudes (M=59.48/95, SD=10.45). CONCLUSIONS: BR decisions for Chinese BC patients are complex and often accompanied by decisional conflicts. Inadequate knowledge and inadequate support and resources contribute to these conflicts, emphasizing the need for culturally tailored information and support to promote SDM. PRACTICE IMPLICATIONS: HCPs need specialized training in SDM to guide patients in decision-making. It is essential to provide relevant resources and support that are culturally and clinically appropriate for Chinese patients.

Acetylation regulates the oligomerization state and activity of RNase J, the Helicobacter pylori major ribonuclease.

In the gastric pathogen Helicobacter pylori, post-transcriptional regulation relies strongly on the activity of the essential ribonuclease RNase J. Here, we elucidated the crystal and cryo-EM structures of RNase J and determined that it assembles into dimers and tetramers in vitro. We found that RNase J extracted from H. pylori is acetylated on multiple lysine residues. Alanine substitution of several of these residues impacts on H. pylori morphology, and thus on RNase J function in vivo. Mutations of Lysine 649 modulates RNase J oligomerization in vitro, which in turn influences ribonuclease activity in vitro. Our structural analyses of RNase J reveal loops that gate access to the active site and rationalizes how acetylation state of K649 can influence activity. We propose acetylation as a regulatory level controlling the activity of RNase J and its potential cooperation with other enzymes of RNA metabolism in H. pylori.

Research Progress on the Mechanism and Management of Septic Cardiomyopathy: A Comprehensive Review.

Sepsis is defined as a kind of life-threatening organ dysfunction due to a dysregulated host immune response to infection and is a leading cause of mortality in the intensive care unit. Sepsis-induced myocardial dysfunction, also called septic cardiomyopathy, is a common and serious complication in patients with sepsis, which may indicate a bad prognosis. Although efforts have been made to uncover the pathophysiology of septic cardiomyopathy, a number of uncertainties remain. This article sought to review available literature to summarize the existing knowledge on current diagnostic tools and biomarkers, pathogenesis, and treatments for septic cardiomyopathy.

Overexpression of the First Peanut-Susceptible Gene, AhS5H1 or AhS5H2, Enhanced Susceptibility to Pst DC3000 in Arabidopsis.

Salicylic acid (SA) serves as a pivotal plant hormone involved in regulating plant defense mechanisms against biotic stresses, but the extent of its biological significance in relation to peanut resistance is currently lacking. This study elucidated the involvement of salicylic acid (SA) in conferring broad-spectrum disease resistance in peanuts through the experimental approach of inoculating SA-treated leaves. In several other plants, the salicylate hydroxylase genes are the typical susceptible genes (S genes). Here, we characterized two SA hydroxylase genes (AhS5H1 and AhS5H2) as the first S genes in peanut. Recombinant AhS5H proteins catalyzed SA in vitro, and showed SA 5-ydroxylase (S5H) activity. Overexpression of AhS5H1 or AhS5H2 decreased SA content and increased 2,5-DHBA levels in Arabidopsis, suggesting that both enzymes had a similar role in planta. Moreover, overexpression of each AhS5H gene increased susceptibility to Pst DC3000. Analysis of the transcript levels of defense-related genes indicated that the expression of AhS5H genes, AhNPR1 and AhPR10 was simultaneously induced by chitin. Overexpression of each AhS5H in Arabidopsis abolished the induction of AtPR1 or AtPR2 upon chitin treatment. Eventually, AhS5H2 expression levels were highly correlated with SA content in different tissues of peanut. Hence, the expression of AhS5H1 and AhS5H2 was tissue-specific.

S100A9 Regulated M1/M2 Macrophage Polarization in Interleukin-10-Induced Promotion of Malignant Pleural Effusion.

Interleukin-10 (IL-10) promotes the formation and development of malignant pleural effusion (MPE). Previous studies have elucidated the pathogenesis from the view of the immune-regulation function of CD4+ T-cells. However, the underlying mechanism is still not fully understood. In this study, our results showed that IL-10 deficiency reduced the percentage of macrophages in mouse MPE and regulated M1/M2 polarization in vivo and in vitro. The migration capacity of tumor cells was suppressed, and apoptosis was promoted when tumor cells were cocultured with MPE macrophages in the absence of IL-10. Messenger RNA sequencing of MPE macrophages showed that S100A9 was downregulated in IL-10-/- mice. Bone marrow-derived macrophages obtained from wild-type mice transfected with S100A9-specific small interfering RNAs (siRNAs) also showed less M2 and more M1 polarization than those from the siRNA control group. Furthermore, downregulation of S100A9 using S100A9-specific siRNA suppressed MPE development, decreased macrophages, and modulated macrophage polarization in MPE in vivo. In conclusion, S100A9 plays a vital role in the process of IL-10 deficiency-mediated MPE suppression by regulating M1/M2 polarization, thus influencing the tumor-migration capacity and apoptosis. This could result in clinically applicable strategies to inhibit the formation of MPE by regulating the polarization of MPE macrophages.

Association between contrast sensitivity function and structural damage in primary open-angle glaucoma.

AIMS: To evaluate the association between contrast sensitivity function (CSF) and glaucomatous structural damage in primary open-angle glaucoma (POAG). METHODS: A cross-sectional study was performed with 103 patients (103 eyes) aged 25-50 years who had POAG without any other ocular disease. CSF measurements were obtained by the quick CSF method, a novel active learning algorithm that covers 19 spatial frequencies and 128 contrast levels. The peripapillary retinal nerve fibre layer (pRNFL), macular ganglion cell complex (mGCC), radial peripapillary capillary (RPC) and macular vasculature were measured by optical coherence tomography and angiography. Correlation and regression analyses were used to assess the association of area under log CSF (AULCSF), CSF acuity and contrast sensitivities at multiple spatial frequencies with structural parameters. RESULTS: AULCSF and CSF acuity were positively associated with pRNFL thickness, RPC density, mGCC thickness and superficial macular vessel density (p<0.05). Those parameters were also significantly associated with contrast sensitivity at 1, 1.5, 3, 6, 12, 18 cycles per degree spatial frequencies (p<0.05) and, the lower the spatial frequency, the higher the correlation coefficient. RPC density (p=0.035, p=0.023) and mGCC thickness (p=0.002, p=0.011) had significant predictive value for contrast sensitivity at 1 and 1.5 cycles per degree, with adjusted R 2 of 0.346 and 0.343, respectively. CONCLUSIONS: Full spatial frequency contrast sensitivity impairment, most notably at low spatial frequencies, is a characteristic change in POAG. Contrast sensitivity is a potential functional endpoint for the measurement of glaucoma severity.

MicroRNA-345-3p is a potential biomarker and ameliorates rheumatoid arthritis by reducing the release of proinflammatory cytokines.

OBJECTIVES: The study was to explore the influence of microRNA (miR)-345-3p on proinflammatory cytokines in patients with rheumatoid arthritis (RA). METHODS: A total of 32 RA patients and 32 healthy patients were enrolled. Proinflammatory factors in patients' serum were detected by ELISA, and miR-345-3p was detected by RT-qPCR. The correlation between miR-345-3p expression and proinflammatory factors in RA patients was analyzed. The diagnostic value of miR-345-3p and proinflammatory factors in RA patients was analyzed by receiver operating curve diagnosis. The predictive value of miR-345-3p levels and proinflammatory factors in RA patients was analyzed by multivariate Cox regression. HFLS-RA and HFLS cells were cultured, in which miR-345-3p and proinflammatory cytokines were detected by RT-qPCR. Cell proliferation and apoptosis were determined by CCK-8 and flow cytometry, respectively. RESULTS: MiR-345-3p was lowly expressed in the serum of RA patients. MiR-345-3p and proinflammatory factors were of diagnostic and predictive values in RA. Elevated miR-345-3p restrained the production of proinflammatory factors of HFLS-RA cells, improved cell proliferation, and reduced apoptosis. CONCLUSION: MiR-345-3p is a potential biomarker and ameliorates RA by reducing the release of proinflammatory cytokines.

A Nomogram Model for Prediction of Mortality Risk of Patients with Dangerous Upper Gastrointestinal Bleeding: A Two-center Retrospective Study.

OBJECTIVE: This study aimed to establish a nomogram model to predict the mortality risk of patients with dangerous upper gastrointestinal bleeding (DUGIB), and identify high-risk patients who require emergent therapy. METHODS: From January 2020 to April 2022, the clinical data of 256 DUGIB patients who received treatments in the intensive care unit (ICU) were retrospectively collected from Renmin Hospital of Wuhan University (n=179) and the Eastern Campus of Renmin Hospital of Wuhan University (n=77). The 179 patients were treated as the training cohort, and 77 patients as the validation cohort. Logistic regression analysis was used to calculate the independent risk factors, and R packages were used to construct the nomogram model. The prediction accuracy and identification ability were evaluated by the receiver operating characteristic (ROC) curve, C index and calibration curve. The nomogram model was also simultaneously externally validated. Decision curve analysis (DCA) was then used to demonstrate the clinical value of the model. RESULTS: Logistic regression analysis showed that hematemesis, urea nitrogen level, emergency endoscopy, AIMS65, Glasgow Blatchford score and Rockall score were all independent risk factors for DUGIB. The ROC curve analysis indicated the area under curve (AUC) of the training cohort was 0.980 (95%CI: 0.962-0.997), while the AUC of the validation cohort was 0.790 (95%CI:0.685-0.895). The calibration curves were tested for Hosmer-Lemeshow goodness of fit for both training and validation cohorts (P=0.778, P=0.516). CONCLUSION: The developed nomogram is an effective tool for risk stratification, early identification and intervention for DUGIB patients.

Macrophage-derived exosome promotes regulatory T cell differentiation in malignant pleural effusion.

Introduction: Tumor-associated macrophages are one of the key components of the tumor microenvironment. The immunomodulatory activity and function of macrophages in malignant pleural effusion (MPE), a special tumor metastasis microenvironment, have not been clearly defined. Methods: MPE-based single-cell RNA sequencing data was used to characterize macrophages. Subsequently, the regulatory effect of macrophages and their secreted exosomes on T cells was verified by experiments. Next, miRNA microarray was used to analyze differentially expressed miRNAs in MPE and benign pleural effusion, and data from The Cancer Genome Atlas (TCGA) was used to evaluate the correlation between miRNAs and patient survival. Results: Single-cell RNA sequencing data showed macrophages were mainly M2 polarized in MPE and had higher exosome secretion function compared with those in blood. We found that exosomes released from macrophages could promote the differentiation of naïve T cells into Treg cells in MPE. We detected differential expression miRNAs in macrophage-derived exosomes between MPE and benign pleural effusion by miRNA microarray and found that miR-4443 was significantly overexpressed in MPE exosomes. Gene functional enrichment analysis showed that the target genes of miR-4443 were involved in the regulation of protein kinase B signaling and lipid biosynthetic process. Conclusions: Taken together, these results reveal that exosomes mediate the intercellular communication between macrophages and T cells, yielding an immunosuppressive environment for MPE. miR-4443 expressed by macrophages, but not total miR-4443, might serve as a prognostic marker in patients with metastatic lung cancer.

Genome Resource of Streptomyces atratus PY-1, a Broad-Spectrum Antimicrobial Strain in Particular Antagonistic Against Plasmopara viticola.

Streptomyces atratus PY-1 exhibited promising antimicrobial properties; in particular, it is highly inhibitory to Plasmopara viticola, which causes downy mildew of grape. It is very necessary to carry out systematic and in-depth research on the PY-1 strain for the improvement, application, and promotion of biocontrol agents. The PY-1 genome was fully sequenced and assembled. We present the draft genome sequence of PY-1, with a size of 9, 254, and 781 bp. Preliminary analysis on the PY-1 genome sequence shows that at least 35 gene clusters are involved in the biosynthesis of polyketides, terpenes, and nonribosomally synthesized peptides.

Clinical value of a novel biological mesh in laparoscopic inguinal hernia repair: a multicenter prospective randomized controlled study / 中华消化外科杂志

Objectives:To investigate the clinical value of a novel non-crosslinked biological mesh in laparoscopic inguinal hernia repair.Methods:The prospective randomized controlled study was conducted. The clinical data of 50 adult patients with unilateral inguinal hernia who were admitted to 3 medical centers, including Ruijin Hospital of Shanghai Jiaotong University School of Medicine et al, from September 2019 to March 2020 were selected. Based on random number table, patients were divided into two groups. Patients using the novel non-crosslinked biological mesh in repair surgery were divided into the experiment group and patients using the lightweight, micro-porous, partially absorbable synthetic mesh in repair surgery were divided into the control group. Observation indicators: (1) grouping situations of the enrolled patients; (2) endpoint of the study. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range), and comparison between groups was conducted using the non-parameter rank sum test. Count data were described as absolute numbers and (or) persentages, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the non-parameter rank sum test. Repeated measurement data were analyzed using the repeated ANOVA. Taking the recurrence rate of hernia as the basis of efficacy evaluation, according to the intention-to-treat analysis, the confidence interval method (Newcombe Wilson method) was used to conduct non-inferiority statistical analysis of the recurrence rate of hernia between the experiment group and the control group. If the upper limit of 95% confidence interval of the difference of recurrence rate of hernia between the experiment group and the control group is less than 10%, the experiment group is considered to be non-inferior to the control group. Results:(1) Grouping situations of the enrolled patients. A total of 50 adult patients with inguinal hernia were selected for eligibility. There were 44 males and 6 females, aged (60±15)years. All 50 patients were randomly divided into to the experiment group and the control group with 25 cases each. One patient in the control group was not followed up at postoperative month 2, and the rest of 49 patients completed all expected follow-up. No patient in the two groups fell off or were removed. (2) Endpoint of the study. ① The primary endpoint of study. The recurrence rate of hernia was 0 in the experiment group, versus 4%(1/25) in the control group, respectively, showing no significant difference between the two groups ( P>0.05). Results of non-inferiority statistical analysis showed that the 95% confidence interval of the difference of recurrence rate of hernia between the two groups was -19.54% to 9.72%, with the upper limit as 9.72%, which was less than 10%. ② The secondary endpoint of study. There were 2 patients in the control group occurred seroma at postoperative day 14, and none of the rest of patient in the two groups occurred seroma during the follow-up, showing no significant difference in the occurrence of seroma between the two groups ( P>0.05). There was 1 patient in the control group feeling discomfort or foreign body sensation in groin area at postoperative month 2, and none of the rest of patient in the two groups feeling discomfort or foreign body sensation in groin area during the follow-up, showing no significant difference in the feeling discomfort or foreign body sensation in groin area between the two groups ( P>0.05). There was no patient occurred surgical site infection in the experiment group, and there was 1 patient in the control group occurred postoperative skin infection, which had no relationship with mesh. There was no patient in both two groups occurred fever, anaphylaxis and patch related serious adverse reaction during the follow-up. The resting visual analogue scale score, active visual analogue scale score of patients at postoperative 2 days and postoperative 18 months were 0.44±1.00, 1.28±1.46 and 0, 0 in the experiment group, versus 0.40±0.76, 1.28±1.14 and 0.24±1.20, 0.44±1.29 in the control group, respectively. There was a significant difference in the time effect of postoperative active visual analogue scale score of patients between the two groups ( Ftime=10.19, P<0.05). The thickness of the novel non-crosslinked biological mesh before implantation was 0.5?0.7 mm. Two months after operation, results of B-ultrasonic examination in groin area of 10 patients from the experiment group showed a strong echo area at the patch implant area with a thickness as 2 mm. Conclusion:Application of novel non-crosslinked biological mesh in laparoscopic inguinal hernia repair is safe and effective.

Screening, and Optimization of Fermentation Medium to Produce Secondary Metabolites from Bacillus amyloliquefaciens, for the Biocontrol of Early Leaf Spot Disease, and Growth Promoting Effects on Peanut (Arachis hypogaea L.).

A novel Bacillus amyloliquefaciens BAM strain, with novel fermentation nutrient mediums and compositions, could produce potent antifungal secondary metabolites, as the existing strains face resistance from fungus pathogens. In the current study, we introduced two novel nutrient mediums for the fermentation process, semolina and peanut root extract, as carbon and nitrogen sources in order to maximize the antifungal effects of B. amyloliquefaciens against Cercaspora arachidichola to control early leaf spot disease in peanuts. Based on a single-factor test and the central composite design of response surface methodology, the optimum fermentation medium for Bacillus amyloliquefaciens antagonistic substance was determined, containing 15 gm/L of semolina flour, 12.5 gm/L of beef extract, and 0.5 gm/L of magnesium sulfate, which inhibited the fungal growth by 91%. In vitro, antagonistic activity showed that the fermentation broth of B. amyloliquefaciens BAM with the optimized medium formulation had an inhibition rate of (92.62 ± 2.07)% on the growth of C. arachidichola. Disease control effects in pot experiments show that the pre-infection spray of B. amyloliquefaciens BAM broth had significant efficiency of (92.00 ± 3.79)% in comparison to post-infection spray. B. amyloliquefaciens BAM broth significantly promoted peanut plant growth and physiological parameters and reduced the biotic stress of C. archidechola. Studies revealed that B. amyloliquefaciens BAM with a novel fermentation formulation could be an ideal biocontrol and biofertilizer agent and help in early disease management of early leaf spots in peanuts.

Tuning the Nonradiative Electron-Hole Recombination with Defects in Monolayer Black Phosphorus.

We use nonadiabatic (NA) molecular dynamics to demonstrate that the nonradiative electron-hole recombination is delayed and accelerated by the Stone-Wales (SWs) and phosphorus divacancy (DV-(5|7)) defects in monolayer black phosphorus (BP). Both types of defects increase the bandgap by 0.1 eV without creating midgap states. Driven by P-P stretching vibrations, the recombination proceeds within 1 ns in the SW and within 100 ps in the DV-(5|7), respectively, which occurs within 332 ps in BP. The SW defect slows down recombination because the notably reduced NA coupling combined with a large bandgap competes to the long-lived coherence. In contrast, the DV defect accelerates recombination since long-lived coherence is superior to the slightly decreased NA coupling correlated with a tiny increased bandgap. The diverse time scales rationalize the broad range of charge carrier lifetimes reported experimentally. The study provides a strategy to engineer excited-state dynamics for improving the BP-based optoelectronics.

Effects of different antioxidants and their combinations on the oxidative stability of DHA algae oil and walnut oil.

Through monitoring Rancimat induction time (RIT), peroxide value (POV), and thiobarbituric acid-reactive substances (TBARS) of docosahexaenoic acid (DHA) algae oil and walnut oil during accelerated storage, the effects of the single and the combinations of seven kinds of antioxidants involving ascorbyl palmitate (AP), phytic acid (PA), vitamin E (VE), antioxidant of bamboo leaves (AOB), rosemary extract, tea polyphenols (TP), and tea polyphenol palmitate (TPP) against lipid oxidation were evaluated. RIT, POV, and TBARS results showed that the DHA algae oil sample containing 600 mg/kg TPP revealed the strongest stability and the walnut oil sample containing 450 mg/kg TPP and 100 mg/kg TP revealed the strongest stability. Then, the shelf lives of two oils were predicted from the extrapolation of the linear regression model between Log RIT and temperature. Our results indicated that the optimal antioxidant could prolong the shelf lives of DHA algae oil and walnut oil by 2.31- and 7.74-fold, respectively.

A Functional Screening Identifies a New Organic Selenium Compound Targeting Cancer Stem Cells: Role of c-Myc Transcription Activity Inhibition in Liver Cancer.

Cancer stem cells (CSCs) are reported to play essential roles in chemoresistance and metastasis. Pathways regulating CSC self-renewal and proliferation, such as Hedgehog, Notch, Wnt/ß-catenin, TGF-ß, and Myc, may be potential therapeutic targets. Here, a functional screening from the focused library with 365 compounds is performed by a step-by-step strategy. Among these candidate molecules, phenyl-2-pyrimidinyl ketone 4-allyl-3-amino selenourea (CU27) is chosen for further identification because it proves to be the most effective compound over others on CSC inhibition. Through ingenuity pathway analysis, it is shown CU27 may inhibit CSC through a well-known stemness-related transcription factor c-Myc. Gene set enrichment analysis, dual-luciferase reporter assays, expression levels of typical c-Myc targets, molecular docking, surface plasmon resonance, immunoprecipitation, and chromatin immunoprecipitation are conducted. These results together suggest CU27 binds c-Myc bHLH/LZ domains, inhibits c-Myc-Max complex formation, and prevents its occupancy on target gene promoters. In mouse models, CU27 significantly sensitizes sorafenib-resistant tumor to sorafenib, reduces the primary tumor size, and inhibits CSC generation, showing a dramatic anti-metastasis potential. Taken together, CU27 exerts inhibitory effects on CSC and CSC-associated traits in hepatocellular carcinoma (HCC) via c-Myc transcription activity inhibition. CU27 may be a promising therapeutic to treat sorafenib-resistant HCC.

Metabolic Landscape of Bronchoalveolar Lavage Fluid in Coronavirus Disease 2019 at Single Cell Resolution.

Abnormal function of immune cells is one of the key mechanisms leading to severe clinical symptoms in coronavirus disease 2019 patients, and metabolic pathways can destroy the function of the immune system by affecting innate and adaptive immune responses. However, the metabolic characteristics of the immune cells of the SARS-CoV-2 infected organs in situ remaining elusive. We reanalyzed the metabolic-related gene profiles in single-cell RNA sequencing data, drew the metabolic landscape in bronchoalveolar lavage fluid immune cells, and elucidated the metabolic remodeling mechanism that might lead to the progression of COVID-19 and the cytokine storm. Enhanced glycolysis is the most important common metabolic feature of all immune cells in COVID-19 patients. CCL2+ T cells, Group 2 macrophages with high SPP1 expression and myeloid dendritic cells are among the main contributors to the cytokine storm produced by infected lung tissue. Two metabolic analysis methods, including Compass, showed that glycolysis, fatty acid metabolism, bile acid synthesis and purine and pyrimidine metabolism levels of CCL2+ T cells, Group 2 macrophages and myeloid dendritic cells were upregulated and correlated with cytokine storms of COVID-19 patients. This might be the key metabolic regulatory factor for immune cells to produce large quantities of cytokines.

Predictors of angle widening after laser iridotomy in Chinese patients with primary angle-closure suspect using ultrasound biomicroscopy.

AIM: To assess the predictive value of baseline parameters of ultrasound biomicroscopy (UBM) for angle widening after prophylactic laser peripheral iridotomy (LPI) in patients with primary angle-closure suspect (PACS). METHODS: Angle-opening distance (AOD), trabecular iris angle (TIA), iris thickness, trabecular-ciliary process angle, and trabecular-ciliary process distance were measured using UBM performed before and two weeks after LPI. Iris convexity (IC), iris insertion, angulation, and ciliary body (CB) size and position were graded. Uni- and multivariate regression analyses were used to determine factors predicting the change in AOD (ΔAOD500, calculated as an angle width change before and after LPI) in all quadrants and in subgroup quadrants based on IC. RESULTS: In 94 eyes of 94 patients with PACS, LPI led to angle widening with increases in AOD500 and TIA (P<0.01). Multivariable regression analysis showed that IC (P<0.001), CB position (P=0.007) and iris insertion (P=0.049) were significantly predictive for ΔAOD500. All quadrants were categorized into extreme IC (27.8%), moderate IC (62.3%), and absent IC (9.9%) subgroups. The AOD500 increased by 220% and no other predictive factor was found in the extreme IC quadrants. The AOD500 increased by 55%, and baseline iris angulation was predictive for smaller changes in ΔAOD500 in the moderate IC quadrants. CONCLUSION: In PACS patients, quadrants with greater iris bowing predict substantial angle widening after LPI. Quadrants with a flatter iris, anteriorly positioned CB, and basal iris insertion are associated with less angle widening after LPI. Quadrants with iris angulation as well as a flatter iris configuration predict a smaller angle change after LPI.

Diagnostic accuracy of interleukin-33 for tuberculous pleural effusion: A systematic review and meta-analysis.

BACKGROUND: The detection of interleukin 33 (IL-33) in pleural effusion may be more sensitive in diagnosing tuberculous pleural effusion (TPE). The present study aimed to assess the accuracy of pleural IL-33 for the diagnosis of TPE by means of meta-analysis and systematic review of relevant studies. METHOD: After retrieving the published studies, the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and a summary receiver operating characteristic curve were assessed to estimate the usefulness of pleural IL-33 in diagnosing TPE using meta-analysis with a random-effects model. We also performed meta-regression and subgroup analysis. RESULTS: A total of 639 patients from 6 studies were analyzed. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 0.87 (95% confidence interval [CI], 0.82-0.91), 0.76 (95% CI, 0.72-0.80), 6.54 (95% CI, 2.65-16.15), 0.17 (95% CI, 0.10-1.27), and 45.40 (95% CI, 12.83-160.70) respectively. The area under the curve was 0.94. The composition of the included population was the main cause of heterogeneity and subgroup analysis showed that pleural IL-33 had a higher specificity (0.93, 95% CI 0.87-0.96) when used for differential diagnosis between TPE and malignant pleural effusion. CONCLUSION: The detection of IL-33 alone in pleural effusion seems to not be an efficient diagnostic marker for TPE but may serve as a novel biomarker to differentiate between TPE and malignant pleural effusion.