APTES and CTAB Synergistic Induce a Heterozygous CsPbBr3/Cs4PbBr6 Perovskite Composite and its Application on the Sensitive Fluorescent Detection of Iodide ions.

Recently, all-inorganic halide perovskite quantum dots (IPQD) as a new fluorescent material with excellent fluorescence properties have attracted wide attention. However, their instability in polar solvents is the main factor hindering their application in analysis. Herein, a heterozygous perovskite (CsPbBr3/Cs4PbBr6) was simultaneously prepared and stabilized by a silylanization strategy using (3-aminopropyl)-triethoxysilane (APTES) and cetyltrimethyl ammonium bromide (CTAB) assisted precipitation encapsulation method. The synthesized CsPbBr3/Cs4PbBr6 emitted an independent fluorescence at 520 nm. The obtained CsPbBr3/Cs4PbBr6 exhibited good stability in ethanol/water mixtures. It was used as a fluorescent probe for sensitively detecting iodide ions (I-) by fluorescence quenching mechanism in the concentration range of 1 ~ 70.0 µM with the detection limit (LOD) of 0.83 µM (relative standard deviation (RSD) = 1.33%, n = 20). The simplicity and high selectivity of the proposed fluorescent analysis method were the prominent features. This work could be extended to the other target ion detection by a perovskite fluorescent quenching.

Comparison of the O-RADS and ADNEX models regarding malignancy rate and validity in evaluating adnexal lesions.

OBJECTIVE: This study aimed to compare the ability of the O-RADS and ADNEX models to classify benign or malignant adnexal lesions. METHODS: This retrospective single-center study included women who underwent surgery for adnexal lesions. Two gynecologists independently categorized the adnexal lesions according to the O-RADS and ADNEX models. Four additional readers were included to validate the new quick-access O-RADS flowchart. RESULTS: Among the 322 patients included in this study, 264 (82.0%) had a benign diagnosis, and 58 (18.0%) had a malignant diagnosis. The malignant rates of O-RADS 2, O-RADS 3, O-RADS 4, and O-RADS 5 were 0%, 3.0%, 37.7%, and 78.9%, respectively. The AUC of the O-RADS in the 322 patients was 0.93. On comparing the O-RADS and ADNEX models in the remaining 281 patients, the AUCs of the O-RADS, ADNEX model with CA125, and ADNEX model without CA125 were 0.92, 0.95, and 0.94, respectively. When setting a uniform cutoff of ≥ 10% (≥ O-RADS 4) to predict malignancy, the O-RADS had higher sensitivity than the ADNEX model (96.6% vs. 91.4%), and relatively similar specificity. In addition, the readers with the quick-access flowchart spent less time categorizing O-RADS than the readers with only the original O-RADS table (mean analysis time: 99 min 15 s vs. 111 min 55 s). CONCLUSIONS: The O-RADS classification of the adnexal lesions as benign or malignant was comparable to that of the ADNEX model and had higher sensitivity at the 10% cutoff value. A quick-access O-RADS flowchart was helpful in O-RADS categorization and might shorten the analysis time. KEY POINTS: • Both O-RADS and ADNEX models had good diagnostic performance in distinguishing adnexal malignancy, and O-RADS had higher sensitivity than ADNEX model in uniform 10% cutoff to predict malignancy. • Quick-access O-RADS flowchart was developed to help review O-RADS classification and might help reduce the analysis time.

Maintenance Therapy for Preventing Endometrioma Recurrence after Endometriosis Resection Surgery - A Systematic Review and Network Meta-analysis.

OBJECTIVE: To evaluate the efficacy of different hormone therapies in preventing postoperative endometrioma recurrence. DATA SOURCES: The MEDLINE, COCHRANE, and Embase electronic databases were searched from inception to 30 April 2021. METHODS OF STUDY SELECTION: Randomized controlled trials (RCTs) or cohort studies including reproductive age women with endometriosis undergoing ovarian cystectomy or excision of endometriotic lesions compared the effects of postoperative adjuvant therapy (gonadotropin-releasing hormone agonist [GnRHa]) and postoperative maintenance hormone interventions for more than 1 year (i.e., oral contraceptive pills [OCPs], dienogest [DNG], levonorgestrel-releasing intrauterine system [LNGIUS]) on endometrioma recurrence. TABULATION, INTEGRATION, AND RESULTS: Data collection and analysis of the data were independently performed 2 two reviewers. A total of 11 studies were included, of which 2 were RCTs, and 9 were cohort studies. There were 2394 patients with 6 interventions (cases: 1665, 69.6%) and expectant management (cases: 729, 30.4%). Relative treatment effects were estimated using network meta-analysis and ranked in descending order. The clinical effectiveness of these drugs (vs expectant management) was as follows: GnRHa plus DNG (odds ratio [OR], 0.04; 95% confidence interval [CI], 0.01-0.27), surface under the cumulative ranking (SUCRA) = 94.0; DNG (OR, 0.11; 95% CI, 0.04-0.32), SUCRA = 69.7; GnRHa plus OCP (OR, 0.12; 95% CI, 0.02-0.64), SUCRA = 63.4; GnRHa plus LNGIUS (OR, 0.13; 95% CI, 0.03-0.66), SUCRA = 59.4; and OCP (OR, 0.21; 95% CI, 0.13-0.36), SUCRA = 43.6. The effectiveness of GnRHa (OR, 0.47; 95% CI, 0.12-1.89), SUCRA = 17.3 was not significantly different from that of controls. CONCLUSION: In network meta-analysis, combined postoperative adjuvant therapy and longer maintenance hormone treatment are better than a single agent in preventing postoperative endometrioma recurrence. GnRHa plus DNG maintenance treatment might be the most effective intervention. Large-scale RCTs of these agents are still required.

Expression of eosinophil in peripheral blood of patients with COVID-19 and its clinical significance.

AIMS: To investigate the eosinophil cell (EC) expression in peripheral blood of patients infected with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2) and its clinical significance of diagnosis and prognosis. METHODS: 95 patients, whose nucleic acid test of SARS-CoV-2 was positive to make a definite diagnosis of COVID-19, were selected as the study group. They were admitted at the Chengdu Public Health Clinical Medical Center from January 21 to March 2, 2020. Another 95 healthy subjects and 95 non-infectious fever patients during the same period were selected as the control group. The BC-6900 blood cell analyzer was used to continuously observe and detect ECs in 95 patients with COVID-19 and the control group. The differences in expression levels of ECs in peripheral blood were analyzed. RESULTS: ECs were significantly decreased in 95 (75.8%) COVID-19 patients (P < .01). The absolute EC count IQR was 0.01 × 109/L (0 × 109/L - 0.04 × 109/L), and the EC percentage IQR was 0.3% (0.1% - 0.8%). As the patients' condition improved, the ECs returned to normal, but for those without improvement, ECs continued to decline. CONCLUSIONS: ECs decreased remarkably in patients with COVID-19, and gradually returned to normal after the improvement of the patients' condition, while EC continued to decrease in patients without improvement. It is suggested that ECs have certain clinical significance in the diagnosis and prognosis of COVID-19, and may be a useful index in the early warning of acute infectious diseases.

Invasiveness of the Yersinia pestis ail protein contributes to host dissemination in pneumonic and oral plague.

Yersinia pestis, a Gram-negative bacterium, is the etiologic agent of plague. A hallmark of Y. pestis infection is the organism's ability to rapidly disseminate through an animal host. Y. pestis expresses the outer membrane protein, Ail (Attachment invasion locus), which is associated with host invasion and serum resistance. However, whether Ail plays a role in host dissemination remains unclear. In this study, C57BL/6J mice were challenged with a defined Y. pestis strain, KimD27, or an isogenic ail-deleted mutant derived from KimD27 via metacarpal paw pad inoculation, nasal drops, orogastric infection, or tail vein injection to mimic bubonic, pneumonic, oral, or septicemic plague, respectively. Our results showed that ail-deleted Y. pestis KimD27 lost the ability to invade host cells, leading to failed host dissemination in the pneumonic and oral plague models but not in the bubonic or septicemic plague models, which do not require invasiveness. Therefore, this study demonstrated that whether Ail plays a role in Y. pestis pathogenesis depends on the infection route.

Yersinia pseudotuberculosis Exploits CD209 Receptors for Promoting Host Dissemination and Infection.

Yersinia pseudotuberculosis is a Gram-negative enteropathogen and causes gastrointestinal infections. It disseminates from gut to mesenteric lymph nodes (MLNs), spleen, and liver of infected humans and animals. Although the molecular mechanisms for dissemination and infection are unclear, many Gram-negative enteropathogens presumably invade the small intestine via Peyer's patches to initiate dissemination. In this study, we demonstrate that Y. pseudotuberculosis utilizes its lipopolysaccharide (LPS) core to interact with CD209 receptors, leading to invasion of human dendritic cells (DCs) and murine macrophages. These Y. pseudotuberculosis-CD209 interactions result in bacterial dissemination to MLNs, spleens, and livers of both wild-type and Peyer's patch-deficient mice. The blocking of the Y. pseudotuberculosis-CD209 interactions by expression of O-antigen and with oligosaccharides reduces infectivity. Based on the well-documented studies in which HIV-CD209 interaction leads to viral dissemination, we therefore propose an infection route for Y. pseudotuberculosis where this pathogen, after penetrating the intestinal mucosal membrane, hijacks the Y. pseudotuberculosis-CD209 interaction antigen-presenting cells to reach their target destinations, MLNs, spleens, and livers.

Salmonella enterica Serovar Typhimurium Interacts with CD209 Receptors To Promote Host Dissemination and Infection.

Salmonella enterica serovar Typhimurium, a Gram-negative bacterium, can cause infectious diseases ranging from gastroenteritis to systemic dissemination and infection. However, the molecular mechanisms underlying this bacterial dissemination have yet to be elucidated. A study indicated that using the lipopolysaccharide (LPS) core as a ligand, S Typhimurium was able to bind human dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin (hCD209a), an HIV receptor that promotes viral dissemination by hijacking antigen-presenting cells (APCs). In this study, we showed that S Typhimurium interacted with CD209s, leading to the invasion of APCs and potentially the dissemination to regional lymph nodes, spleen, and liver in mice. Shielding of the exposed LPS core through the expression of O-antigen reduces dissemination and infection. Thus, we propose that similar to HIV, S Typhimurium may also utilize APCs via interactions with CD209s as a way to disseminate to the lymph nodes, spleen, and liver to initiate host infection.

Genome-wide identification, classification and expression analysis of the JmjC domain-containing histone demethylase gene family in maize.

BACKGROUND: Histone methylation mainly occurs on the lysine residues and plays a crucial role during flowering and stress responses of plants, through changing the methylation status or ratio of lysine residues. Histone lysine residues of plants can arise in three forms of methylation (single, double and triple) and the corresponding demethylation can also ensue on certain occasions, by which the plants can accommodate the homeostasis of histone methylation by means of lysine methyltransferase and demethylase. The JmjC domain-containing proteins, an important family of histone lysine demethylases, play a vital role in maintaining homeostasis of histone methylation in vivo. RESULTS: In this study, we have identified 19 JmjC domain-containing histone demethylase (JHDM) proteins in maize. Based on structural characteristics and a comparison of phylogenetic relationships of JHDM gene families from Arabidopsis, rice and maize, all 19 JHDM proteins in maize were categorized into three different subfamilies. Furthermore, chromosome location and schematic structure revealed an unevenly distribution on chromosomes and structure features of ZmJMJ genes in maize, respectively. Eventually, the 19 ZmJMJ genes displayed different expression patterns at diverse developmental stages of maize based on transcriptome analysis. Further, quantitative real-time PCR analysis showed that all 19 ZmJMJ genes were responsive to heat stress treatment, suggesting their potential roles in heat stress response. CONCLUSIONS: Overall, our study will serve to present an important theoretical basis for future functional verification of JHDM genes to further unravel the mechanisms of epigenetic regulation in plants.

Overexpression of KIF18A promotes cell proliferation, inhibits apoptosis, and independently predicts unfavorable prognosis in lung adenocarcinoma.

Kinesin family member 18A (KIF18A), as a member of the kinesin superfamily, is significantly overexpressed and abnormally functions in various human cancers. But, its expression profiling in the lung adenocarcinoma (LUAD) remains unclear. In the present work, using the data derived from the Cancer Genome Atlas (TCGA), we assessed the expression pattern and prognostic value of KIF18A in LUAD. In addition, we analyzed the underlying mechanism of its gene dysregulation. Experimental and bioinformatic analysis results showed that KIF18A expression was dramatically increased in LUAD tissues compared with the normal counterparts. Moreover, the patients with high KIF18A expression had significantly poorer overall survival (OS) and recurrence-free survival (RFS). Univariate and multivariate analyses indicated that increased KIF18A expression was independently associated with unfavorable OS and RFS. In addition, by analyzing deep sequencing data from TCGA-LUAD, we found that KIF18A mutation was detected in 2.6% of LUAD cases, and increased KIF18A expression was associated with genetic amplification rather than DNA methylation. Moreover, gene co-expression network analysis revealed that a total of 339 KIF18A co-expressed genes were detected and enriched in several tumor-related pathways, especially cell cycle. Knockdown of KIF18A significantly inhibited cell proliferation in vitro and in vivo. Furthermore, silencing KIF18A induced LUAD cells apoptosis and arrested the cell cycle in the G2/M phase. KIF18A promotes cell proliferation, inhibits apoptosis, and is a valuable prognostic predictor and potential therapeutic target for the patients with LUAD. © 2019 IUBMB Life, 2019.

Long non-coding RNA and mRNA analysis of Ang II-induced neuronal dysfunction.

The sustained activation of Angiotensin II (Ang II) induces the remodelling of neurovascular units, inflammation and oxidative stress reactions in the brain. Long non-coding RNAs (lncRNAs) play a crucial regulatory role in the pathogenesis of hypertensive neuronal damage. The present study aimed to substantially extend the list of potential candidate genes involved in Ang II-related neuronal damage. This study assessed apoptosis and energy metabolism with Annexin V/PI staining and a Seahorse assay after Ang II exposure in SH-SY5Y cells. The expression of mRNA and lncRNA was investigated by transcriptome sequencing. The integrated analysis of mRNA and lncRNAs and the molecular mechanism of Ang II on neuronal injury was analysed by bioinformatics. Ang II increased the apoptosis rate and reduced the energy metabolism of SH-SY5Y cells. The data showed that 702 mRNAs and 821 lncRNAs were differentially expressed in response to Ang II exposure (244 mRNAs and 432 lncRNAs were upregulated, 458 mRNAs and 389 lncRNAs were downregulated) (fold change ≥ 1.5, P < 0.05). GO and KEGG analyses showed that both DE mRNA and DE lncRNA were enriched in the metabolism, differentiation, apoptosis and repair of nerve cells. This is the first report of the lncRNA-mRNA integrated profile of SH-SY5Y cells induced by Ang II. The novel targets revealed that the metabolism of the vitamin B group, the synthesis of unsaturated fatty acids and glycosphingolipids are involved in the Ang II-related cognitive impairment. Sphingolipid metabolism, the Hedgehog signalling pathway and vasopressin-regulated water reabsorption play important roles in nerve damage.

Transvaginal Natural Orifice Transluminal Endoscopic Surgery for Female-to-Male Transgender Men.

STUDY OBJECTIVE: Previous studies suggest female-to-male transgender men tend to choose less invasive procedures, but the superior route of hysterectomy for them remains undetermined. DESIGN: A retrospective study (Canadian Task Force Classification II-3). SETTING: An academic tertiary hospital. PATIENTS: Fifty-six female-to-male transsexuals received total vaginal hysterectomy (VH) with bilateral salpingo-oophorectomy (BSO) between April 2008 and August 2016 at Taipei Veterans General Hospital, Taipei, Taiwan. INTERVENTIONS: The patients underwent natural orifice transluminal endoscopic surgery (NOTES) (n = 14) or the conventional approach (n = 42). MEASUREMENTS AND MAIN RESULTS: Medical charts and surgical records were reviewed retrospectively. The general characteristics of the patients were similar in both groups. There were no statistically significant differences in operative time, estimated blood loss, intraoperative and immediate postoperative complications, or length of hospital stay between the 2 groups. However, postoperative pain was significantly reduced in the NOTES group compared with the conventional group as evidenced by lower mean scores on the visual analog scale (4.9 ± 3.0 vs 7.1 ± 1.4 at 2 hours, p = .008; 1.5 ± 1.2 vs 3.0 ± 1.7 at 48 hours, p = .001; and 1.7 ± 1.0 vs 2.7 ± 1.1 at 72 hours, p < .001) and a lower mean accumulated dose of postoperative analgesics (38.9 ± 49.2 mg vs 88.8 ± 82.3 mg meperidine hydrochloride, p = .037). Analysis of variance with repeated measures with a Greenhouse-Geisser correction also showed that the mean scores for wound pain were statistically lower in the NOTES group (p < .001). There was no significant difference in the complication rate between the NOTES and conventional groups (7% vs 12%, p = .618). There were no severe complications, including infection episodes or internal bleeding events, within the NOTES group. CONCLUSION: NOTES VH with BSO in female-to-male transgender men significantly decreases postoperative pain and analgesic use. NOTES in female-to-male sex reassignment surgery provides a novel choice for transgender men, with equivalent safety compared with VH.

Identification of the C-Reactive Protein Interaction Network Using a Bioinformatics Approach Provides Insights into the Molecular Pathogenesis of Hepatocellular Carcinoma.

BACKGROUND/AIMS: C reactive protein (CRP) levels are elevated in many diseases, including malignant tumors and cardiovascular disorders. In this study, the protein interaction network for CRP was evaluated to determine the importance of CRP and its interacting proteins in the molecular pathogenesis of hepatocellular carcinoma (HCC). METHODS: Isobaric tags for relative and absolute quantitation (iTRAQ) and mass spectrometry were used to identify CRP interacting proteins in SMMC7721 cells. Moreover, Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to evaluate enriched genes and pathways for differentially expressed genes using DAVID and WebGestalt. Co-immunoprecipitation and western blot analyses were employed to assess interactions between CRP and KRT8, ANXA2, ENO2, and HSP90B1. RESULTS: In total, 52 proteins that interact with CRP were identified. A GO analysis suggested that most of the interacting proteins were involved in CRP complexes and regulated metabolic processes. A KEGG pathway analysis suggested that most CRP-interacting proteins contribute to the TRAIL signaling pathway, Class I PI3K/Akt signaling pathway, plasma membrane estrogen receptor signaling, Nectin adhesion pathway, and S1P1 pathway. Immunoprecipitation and western blot analyses revealed interactions between CRP and KRT8, ANXA2, ENO2, and HSP90B1. CONCLUSIONS: iTRAQ based proteomic profiling revealed the network of CRP interacting proteins. This network may activate the PI3K/Akt signaling pathway, thereby contributing to the pathogenesis of HCC.

Proteomic Analysis Reveals the Renoprotective Effect of Tribulus terrestris against Obesity-Related Glomerulopathy in Rats.

Tribulus terrestris L. (Zygophyllaceae) (TT) is usually used as a cardiotonic, diuretic, and aphrodisiac, as well as for herbal post-stroke rehabilitation in traditional Chinese medicine. However, little is known about the renoprotective effects of TT on obesity-related glomerulopathy (ORG). In this study, 340 monomeric compounds were identified from TT extracts obtained with ethyl acetate combined with 50% methanol. In vitro, IC50 of TT was 912.01 mg/L, and the appropriate concentration of TT against oxidized-low density lipoprotein (ox-LDL) induced human renal glomerular endothelial cells (HRGECs) was 4 mg/L. TT significantly increased the viability (63.2%) and migration (2.33-fold increase) of HRGECs. ORG model rats were induced by a chronic high-fat diet (45%) for 20 weeks and were then treated with TT extract (2.8 g/kg/d) for 8 weeks. Subsequently, the kidneys were removed and their differentially expressed protein profile was identified using two-dimensional electrophoresis coupled with matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF)-TOF MS. Molecular categorization and functional analysis of bioinformatic annotation suggested that excessive energy metabolism, decreased response to stress and low immunity were the potential etiologies of ORG. After TT administration for 8 weeks, body weight, blood pressure, serum cystatin C and cholesterol were decreased. Additionally, TT significantly enhanced the resistance of rats to ORG, decreased energy consumption and the hemorrhagic tendency, and improved the response to acute phase reactants and immunity. In conclusion, TT may play a protective role against ORG in rats.

Modified Transsubxiphoid Thoracoscopic Extended Thymectomy in Patients with Myasthenia Gravis.

We developed a new minimally invasive thoracoscopic technique of extended thymectomy for myasthenia gravis by combining a subxiphoid incision with dual costal margin incisions. In our experience of 31 consecutive cases, this procedure provides a good operative view in the neck region and makes verification of the bilateral phrenic nerves easy. All the patients recovered smoothly with less trauma, less bleeding, less complication, and good cosmetic results. This modified transsubxiphoid approach is a satisfactory procedure for performing extended thymectomy in patients with myasthenia gravis.

Monoclonal antibody-conjugated superparamagnetic iron oxide nanoparticles for imaging of epidermal growth factor receptor-targeted cells and gliomas.

The objective of this study was to successfully synthesize epidermal growth factor receptor monoclonal antibody-conjugated superparamagnetic iron oxide nanoparticles (EGFRmAb-SPIONs) and explore their biocompatibility and potential applications as a targeted magnetic resonance imaging (MRI) contrast agent for the EGFR-specific detection of brain glioma in vivo. After conjugation of EGFRmAb with SPIONs, the magnetic characteristics of EGFRmAb-SPIONs were investigated. Thereafter, the targeting abilities of EGFRmAb-SPIONs with MRI were qualitatively and quantitatively assessed in EGFR-positive C6 glioma cells in vitro and in a Wistar rat model bearing C6 glioma in vivo. Furthermore, the preliminary biocompatibility and toxicity of EGFRmAb-SPIONs were evaluated in normal rats through hematology assays and histopathologic analyses. Statistical analysis was performed using one-way analysis of variance and Student t-test, with a significance level of p < .05. From the results of EGFRmAb-SPION characterizations, the average particle size was 10.21 nm and the hydrodynamic diameter was 161.5 ± 2.12 nm. The saturation magnetization was 55 emu/g·Fe, and T2 relaxivity was 92.73 s-1mM-1 in distilled water. The preferential accumulation of the EGFRmAb-SPIONs within glioma and subsequent MRI contrast enhancement were demonstrated both in vitro in C6 cells and in vivo in rats bearing C6 glioma. After intravenous administration of EGFRmAb-SPIONs, T2-weighted MRI of the rat model with brain glioma exhibited an apparent hypointense region within glioma from 2 to 48 hours. The maximal image contrast was reached at 24 hours, where the signal intensity decreased and the R2 value increased by 30% compared to baseline. However, T2-weighted imaging of the rat model administered with SPIONs showed no visible signal changes within the tumor over the same time period. Moreover, no evident toxicities in vitro and in vivo with EGFRmAb-SPIONs were clearly identified based on the laboratory examinations. EGFRmAb-SPIONs could potentially be employed as a targeted contrast agent in the molecule-specific diagnosis of brain glioma in MRI.

Host Langerin (CD207) is a receptor for Yersinia pestis phagocytosis and promotes dissemination.

Yersinia pestis is a Gram-negative bacterium that causes plague. After Y. pestis overcomes the skin barrier, it encounters antigen-presenting cells (APCs), such as Langerhans and dendritic cells. They transport the bacteria from the skin to the lymph nodes. However, the molecular mechanisms involved in bacterial transmission are unclear. Langerhans cells (LCs) express Langerin (CD207), a calcium-dependent (C-type) lectin. Furthermore, Y. pestis possesses exposed core oligosaccharides. In this study, we show that Y. pestis invades LCs and Langerin-expressing transfectants. However, when the bacterial core oligosaccharides are shielded or truncated, Y. pestis propensity to invade Langerhans and Langerin-expressing cells decreases. Moreover, the interaction of Y. pestis with Langerin-expressing transfectants is inhibited by purified Langerin, a DC-SIGN (DC-specific intercellular adhesion molecule 3 grabbing nonintegrin)-like molecule, an anti-CD207 antibody, purified core oligosaccharides and several oligosaccharides. Furthermore, covering core oligosaccharides reduces the mortality associated with murine infection by adversely affecting the transmission of Y. pestis to lymph nodes. These results demonstrate that direct interaction of core oligosaccharides with Langerin facilitates the invasion of LCs by Y. pestis. Therefore, Langerin-mediated binding of Y. pestis to APCs may promote its dissemination and infection.

Surgical Treatment of Dextroversion, Isolated Persistent Left Superior Vena Cava Draining Into the Left Atrium.

We report a rare case of dextroversion accompanied with atrial septal defect (ASD), persistent left superior vena cava with absent right superior vena cava in a four-year-old male. A polytetrafluoroethylene (PTFE) graft as an extracardiac conduit was used to connect the persistent left superior vena cava (PLSVC) with the right atrial appendage.

Targeted activation of ferroptosis in colorectal cancer via LGR4 targeting overcomes acquired drug resistance.

Acquired drug resistance is a major challenge for cancer therapy and is the leading cause of cancer mortality; however, the mechanisms of drug resistance are diverse and the strategy to specifically target drug-resistant cancer cells remains an unmet clinical issue. Here, we established a colorectal cancer-derived organoid biobank and induced acquired drug resistance by repeated low-level exposures of chemo-agents. Chemosensitivity profiling and transcriptomic analysis studies revealed that chemoresistant cancer-derived organoids exhibited elevated expression of LGR4 and activation of the Wnt signaling pathway. Further, we generated a monoclonal antibody (LGR4-mAb) that potently inhibited LGR4-Wnt signaling and found that treatment with LGR4-mAb notably sensitized drug-induced ferroptosis. Mechanistically, LGR4-dependent Wnt signaling transcriptionally upregulated SLC7A11, a key inhibitor of ferroptosis, to confer acquired drug resistance. Our findings reveal that targeting of Wnt signaling by LGR4-mAb augments ferroptosis when co-administrated with chemotherapeutic agents, demonstrating a potential opportunity to fight refractory and recurrent cancers.

O-GlcNAcylation regulates phagocytosis by promoting Ezrin localization at the cell cortex.

O-GlcNAcylation is a post-translational modification that serves as a cellular nutrient sensor and participates in multiple physiological and pathological processes. However, it remains uncertain whether O-GlcNAcylation is involved in the regulation of phagocytosis. Here, we demonstrate a rapid increase in protein O-GlcNAcylation in response to phagocytotic stimuli. Knockout of the O-GlcNAc transferase or pharmacological inhibition of O-GlcNAcylation dramatically blocks phagocytosis, resulting in the disruption of retinal structure and function. Mechanistic studies reveal that the O-GlcNAc transferase interacts with Ezrin, a membrane-cytoskeleton linker protein, to catalyze its O-GlcNAcylation. Our data further show that Ezrin O-GlcNAcylation promotes its localization to the cell cortex, thereby stimulating the membrane-cytoskeleton interaction needed for efficient phagocytosis. These findings identify a previously unrecognized role for protein O-GlcNAcylation in phagocytosis with important implications in both health and diseases.

Do the stent blind insertion into the main portal vein (MPV) and stent diameter influence the surgical outcome of the transjugular intrahepatic portosystemic shunt (TIPS)?

Transjugular intrahepatic portosystemic shunt (TIPS) surgery is a clinical intervention to treat portal hypertension (PH) by deploying a covered stent to establish a shunt path for the portal vein (PV) system, and proper surgical strategy is of great importance to balance the shunt effect and the risk of complications. To understand the clinical strategies of the stent blind insertion and stent selection in clinic, this study investigated the effects of varying stent insertion positions and diameters on the PV hemodynamics and the shunt effect by computational fluid dynamics (CFD) analysis of five post-TIPS subjects. The results showed that the successful TIPS surgeries of the five PH subjects were confirmed by quantifying their pressure drops. The stent insertion positions at the main portal vein (MPV) slightly affected the clinically concerned hemodynamic indexes (i.e., MPV pressure, stent-outlet velocity) and the shunt index (SI). This indicated that the position of the stent going into the MPV may not need to be deliberately selected. Moreover, the covered stents with 6 mm and 8 mm diameters slightly influenced the hemodynamics as well, but the large-diameter stent better improved the shunt effect compared to the small-diameter one. Despite this, the 6 mm stent was suggested thanks to the higher risk of the hepatic encephalopathy (HE) observed in clinic, which indicated the excessive shunt of the 8 mm stent. The current work revealed the effects of different TIPS strategies on the surgical outcome, and could be useful for potential clinical practices.