Central venous catheters do not increase the hemorrhagic risk in acute promyelocytic leukemia patients during induction therapy.

In acute promyelocytic leukemia (APL), hemorrhage, particularly intracranial hemorrhage, is the most common cause of early death. A central venous catheter (CVC) may provide a greater guarantee of safety and comfort to APL patients. However, CVCs have seldom been attempted in APL patients during induction therapy because of concerns about increasing the risk of hemorrhagic complications after this invasive procedure. To evaluate the hemorrhagic risk after CVC placement in APL patients during induction therapy, we retrospectively analyzed 95 newly diagnosed patients with APL from January 2010 to December 2022. Among these patients, 39 patients in the CVC group and 56 patients in the non-CVC group were included. Laboratory and clinical parameters of the two groups were collected and compared. There were no significant differences in median platelet, fibrinogen (Fbg), D-dimer, prothrombin time (PT), white blood count (WBC) and hemoglobin (Hb) between the CVC and non-CVC groups on the first day of the visit (day 0) and the following days (day 4, day 7, day 11, day 14, day 18 and day 21) (p = 0.382, p = 0.805, p = 0.456, p = 0.902, p = 0.901 and p = 0.097, respectively). The consumption of transfused platelets and Fbg was not significantly different between the CVC group and non-CVC group (5.0 vs. 4.5 units, p = 0.34, and 6.8 vs. 6.0, p = 0.36, respectively). The last day of platelet and Fbg transfusion was also not significantly different (21 vs. 19, p = 0.238 and 7.5 vs. 8.5, p = 0.684, respectively). The incidences of total hemorrhagic events and hemorrhagic death were lower in the CVC group than in the non-CVC group (17.9% vs. 37.5%, p = 0.04 and 0% vs. 16.1%, p = 0.01, respectively). The 30-day survival rate was not significantly different (92.3% vs. 82.1%, respectively, p = 0.145) for the CVC group compared with the non-CVC group. Our study suggested that CVCs did not increase the hemorrhagic risk in APL patients during induction therapy and that a CVC should be considered in this type of clinical situation.

Direct readout of mirror reflectivity for cavity-enhanced gas sensing using Pound-Drever-Hall signals.

The operation of cavity-enhanced techniques usually requires independent pre-calibration of the mirror reflectivity to precisely quantify the absorption. Here we show how to directly calibrate the effective mirror reflectivity without using any gas samples of known concentration or high-speed optical/electrical devices. Leveraging a phase modulator to generate sidebands, we are able to record Pound-Drever-Hall error signals shaped by cavity modes that can reveal the effective reflectivity after waveform analysis. As an example, we demonstrated the reflectivity calibration of a pair of near-infrared mirrors over 80 nm with a free spectral range-limited resolution, illustrating a reflectivity uncertainty of 2 × 10-5 in the center part of the refection wavelength range of the mirrors and larger at the edges. With an effective reflectivity of 0.9982 (finesse ∼1746) inferred at 1531.6 nm, a short ∼ 8-cm Fabry-Pérot cavity achieved a minimum detectable absorption coefficient of 9.1 × 10-9 cm-1 for trace C2H2 detection. This method, by providing convenient calibration in an almost real-time manner, would enable more practical cavity-enhanced gas measurement even with potential mirror reflectivity degradation.

Exosomes derived miR-362 exacerbates pneumonia by increasing Interleukin-6 via targeting VENTX.

Pneumonia is a condition characterized by lung damage resulting from a robust immune response by the host. While the defense and immunity against bacterial lung infections have been extensively studied, little is known about the specific immune factors involved in the progression of bacterial pneumonia. To address this knowledge gap, our study aimed to compare normal lung tissues with pneumonia tissues using various techniques, including HE staining, RNA sequencing, RT-PCR, and Elisa assay. Our analysis revealed a significant increase in the levels of interleukin-6 (IL-6) in pneumonia tissues compared to normal lung tissues. To further investigate the underlying mechanism, we extracted exosomes from both pneumonia and normal lung tissues using ultracentrifugation. The exosomes were then examined using electron microscopy, diameter analysis, and western blot assay. RNA sequencing of the exosomes revealed an upregulation of several microRNAs (miRNAs), with miR-362 exhibiting the most significant change. This finding was confirmed through RT-PCR analysis conducted on lung tissues and alveolar lavage fluid. To gain insights into the specific target genes of miR-362, we employed bioinformatics analysis, which identified VENTX as a potential target gene. This finding was further validated through RT-PCR, western blot, and luciferase assay. Our experimental evidence demonstrated that miR-362 regulates VENTX expression, as evidenced by the use of miR-362 mimics or inhibitors on lung cells. Furthermore, we discovered that exosomes derived from pneumonia tissues upregulate IL-6 production through the miR-362/VENTX axis. Importantly, the blocking of IL-6 generation, which is facilitated by miR-362 inhibitor and VENTX overexpression lentivirus, can be achieved by treating exosomes. Moreover, we conducted in vivo experiments using pneumonia models. Rats were treated with IL-6, miR-362 mimics, or VENTX knock-down lentivirus. The results demonstrated a worse prognosis for rats treated with these factors, indicating their potential as prognostic markers. Taken together, our study suggests that exosomes facilitate IL-6 generation by transferring miR-362, thereby suppressing VENTX transcription. Consequently, the IL-6/miR-362/VENTX axis emerges as a promising therapeutic target for pneumonia.

Anti-LGI1 encephalitis with initiating symptom of seizures in children.

Background: Anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis is infrequently reported but more and more recognizable in children. Here we give detailed description of the clinical features and long-term outcome of three cases of childhood onset anti-LGI1 encephalitis. Methods: Three anti-LGI1 encephalitis patients were hospitalized in the Department of Pediatrics at Qilu Hospital of Shandong University. Data about the clinical manifestations, treatments and long-term follow-up outcomes were described in detail. Results: Case 1 showed an adolescent girl with initiating symptom of acute-onset frequent focal seizures. Her serum LGI1-antibody test was positive, and she had a good response to antiseizure medication (ASM) and IVIG. Case 2 showed a preschool-age boy with long-period refractory focal seizures and recent behavioral change. Both serum and cerebrospinal fluid (CSF) tests of LGI1-antibody were positive, and the MRI showed progressive atrophy in the left hemisphere. The symptoms got improved after receiving second-line immunotherapy initially but there are still the sequelae of drug-resistant epilepsy and mild to moderate intellectual disability. Case 3 showed an adolescent boy with initiating symptom of acute-onset frequent focal seizures. Both serum and CSF tests of LGI1-antibody were positive, and he had a good response to immunotherapy. By analyzing all literature-reported 19 pediatric cases, we found pediatric anti-LGI1 encephalitis is more common in female and adolescent. Seizures and behavioral changes were the most common symptoms. CSF pleocytosis and LGI1-antibodies results were mostly negative. Most patients showed good response to immunotherapy. Conclusion: Childhood onset anti-LGI1 encephalitis is a heterogeneous clinical syndrome, ranging from typical limbic encephalitis to isolating focal seizures. It is important to test autoimmune antibodies when encountering similar cases and repeat antibody testing if necessary. Timely recognition leads to earlier diagnosis and more rapid initiation of effective immunotherapy and potentially better outcomes.

Phytoremediation of fluoroalkylethers (ether-PFASs): A review on bioaccumulation and ecotoxilogical effects.

Fluoroalkylethers (ether-PFASs), as alternatives to phased-out per- and perfluoroalkyl substances (PFASs), have attracted mounting attention due to their ubiquitous detection in aquatic environment and their similarity to legacy PFASs in terms of persistence and toxicity. In this review, the sources and distribution of ether-PFASs in soil ecosystem as well as their toxic impacts on soil microbial community are summarized. The plant uptake and bioaccumulation potential of ether-PFASs are presented, and a wide range of the influencing factors for their uptake and translocation is discussed. In response to ether-PFASs, the corresponding phytotoxic effects, such as seed germination, plant growth, photosynthesis, oxidative damage, antioxidant enzymes activities, and genotoxicity, are systematically elucidated. Finally, the current knowledge gaps and future research prospective are highlighted. The findings of this review will advance our understanding for the environmental behavior and implications ether-PFASs in soil-plant systems and help explore the strategies for ether-PFASs remediation to minimize their adverse toxicity.

Safety and efficacy of extracorporeal shock wave lithotripsy vs. flexible ureteroscopy in the treatment of urinary calculi: A systematic review and meta-analysis.

Objective: This study aims to compare the safety and efficacy of extracorporeal shock wave lithotripsy (SWL) and flexible ureteroscopy lithotripsy (f-URS) in treating urinary tract stones. Methods: We systematically searched PubMed, Embase, and Cochrane for literature comparing SWL with f-URS. The primary outcomes we focused on were stone-free rate (SFR) and complications; the secondary outcomes were operation time, hospital stay, retreatment rate, number of sessions, and auxiliary procedures rate. We used ReviewManager version 5.4.1 and STATA version 14.2 for meta-analysis. Results: Seventeen studies with a total of 2,265 patients were included in the meta-analysis, including 1,038 patients in the SWL group and 1,227 patients in the f-URS group. The meta-analysis indicated that patients in the f-URS group had higher SFR than those in the SWL group [odds ratio (OR): 2.00, 95% confidence interval (CI): 1.29-3.12, p = 0.002]. In addition, we found no significant difference in complications (OR: 1.08, 95% CI: 0.85-1.37) between the two treatments. Also, we found that the retreatment rate and the auxiliary procedure rate in the f-URS group were significantly lower than those in the SWL group (OR: 0.08, 95% CI: 0.02-0.24, p < 0.00001; OR: 0.30, 95% CI: 0.11-0.83, p = 0.02). Moreover, the number of sessions in the f-URS group was significantly lower than that in the SWL group [mean difference (MD): -1.96, 95% CI: -1.55 to -0.33, p = 0.003]. However, the operation time and hospital stay in the f-URS group were significantly longer than those in the SWL group (MD: 11.24, 95% CI: 3.51-18.56, p = 0.004; MD: 1.14, 95% CI: 0.85-1.42, p < 0.00001). Conclusion: For 1-2-cm urinary stones, f-URS can achieve a higher SFR than SWL while having a lower retreatment rate, number of sessions, and auxiliary procedure rate. For urinary stones <1 cm, there was no significant difference in SFR between SWL and f-URS groups. The SWL group has a shorter operative time and hospital stay than the f-URS group.

Case report: Durable response to alectinib in ALK-rearranged lung adenocarcinoma with acquired, crizotinib-resistant ALK C1156F mutation.

Treatment of ALK-rearranged non-small cell lung cancer (NSCLC) with tyrosine kinase inhibitors (TKIs) is challenged by the almost inevitable emergence of therapeutic resistance. Different profiles of resistance mechanisms have been reported for the currently available ALK TKIs. The ALK C1156Y mutation is reported in 2% of patients with acquired resistance to crizotinib. A rare substitution at the same site, C1156F, remains largely unknown. Existing evidence includes identification of C1156F and G1202R in an alectinib-resistant patient and sensitivity to crizotinib and resistance to later-generation 3ALK inhibitors in preclinical models. In this report, we present two cases in which NSCLC patients acquired the ALK C1156F mutation on crizotinib monotherapy. Both patients were men, and one had been heavily treated with chemotherapeutic regimens before identification of ALK rearrangement, whereas the other received crizotinib as first-line treatment. Genomic profiling of blood biopsies after progression on crizotinib suggested emergence of the ALK C1156F variant. Both patients subsequently received and responded favorably to alectinib, achieving respective progression-free survival of 21 and 15 months as of the latest follow-ups. To the best of our knowledge, this work is the first to provide clinical evidence of resistance to crizotinib and sensitivity to alectinib in NSCLC patients harboring acquired ALK C1156F mutation.

Comparison of flexible ureteroscopy and mini-percutaneous nephrolithotomy in the treatment for multiple nephrolithiasis.

Objective: To compare the outcomes of flexible ureteroscopy and mini-percutaneous nephrolithotomy in the treatment for multiple nephrolithiasis in 1-2 cm size. Methods: The clinical data of patients with multiple renal calculi in the range of 1-2 CM who underwent flexible ureteroscopy lithotripsy and percutaneous nephrolithotomy in Qilu Hospital of Shandong University from January 2016 to March 2021 were retrospectively collected and matched using propensity score matching. Then a subgrouping of the number of stones was performed. Patients were divided into Group A and Group B according to their stone numbers. Patients with no statistically significant differences in baseline data were matched to compare the safety and efficacy of the two procedures. Results: A total of 210 patients with clinical data were collected, and the patients' baseline data were not comparable, and 142 patients were finally included in the study after propensity score matching. There was no statistical difference in baseline data between the two groups of patients. The postoperative hospital days (3.00, 2.00 vs. 7.00, 3.00, P < 0.001), operation time (90.00, 50.00 vs. 110.00, 53.00, P = 0.018), complications (6, 6.8% vs. 14, 25.9%, P = 0.001) of patients in flexible ureteroscopy group %, P = 0.001) was significantly lower than that in the percutaneous nephrolithotomy group. There was no significant difference in stone clearance rate between the two groups (76, 86.4% vs. 42, 77.8%, P = 0.185). When the number of stones was no more than 3, the operation time (85.00, 49.00 vs. 110.00, 53.00, P = 0.005) and complications (2, 4.2% vs. 11, 29.7%, P = 0.001) of f-URS were significantly less than those of mPCNL, but when the number of stones was more than 3, there was no significant difference between the two operations. Conclusion: For multiple nephrolithiasis within 1-2 CM, when the number of stones does not exceed 3, flexible ureteroscopy can achieve the same stone clearance rate as percutaneous nephrolithotomy, while having shorter post-operation days, operative time and fewer complications. When the number of stones is more than 3, there are no significant difference between two operations.

Fate and mechanistic insights into nanoscale zerovalent iron (nZVI) activation of sludge derived biochar reacted with Cr(VI).

While nanoscale zero-valent iron modified biochar (nZVI-BC) have been widely investigated for the removal of heavy metals, the corrosion products of nZVI and their interaction with heavy metals have not been revealed yet. In this paper, nZVI-BC was synthesized and applied for the removal of Cr(VI). Batch experiments indicated that the adsorption of Cr(VI) fit Langmuir isotherm, with the maximum removal capacity at 172.4 mg/g at pH 2.0. SEM-EDS, BET, XRD, FT-IR, Raman and XPS investigation suggested that reduction of Cr(VI) to Cr(III) was the major removal mechanism. pH played an important role on the corrosion of nZVI-BC, at pH 4.5 and 2.0, FeOOH and Fe3O4 were detected as the major iron oxide, respectively. Therefore, FeOOH-BC and Fe3O4-BC were further prepared and their interaction with Cr were studied. Combining with DFT calculations, it revealed that Fe3O4 has higher adsorption capacity and was responsible for the effective removal of Cr(VI) through electrostatic attraction and reduction under acidic conditions. However, Fe3O4 will continue to convert to the more stable FeOOH, which is the key to for the subsequent stabilization of the reduced Cr(III). The results showed that the oxide corrosion products of nZVI-BC were subjected to the environment, which will eventually affect the fate and transport of the adsorbed heavy metal.

Characterizing the role of SLC3A2 in the molecular landscape and immune microenvironment across human tumors.

Background: Inducing ferroptosis in human tumors has become a potential strategy to improve the prognosis of patients, even in those with chemotherapeutic resistance. The xCT complex is a major target for ferroptosis induction, constituted by SLC7A11 and SLC3A2. The role of SLC7A11 in cancer has been widely studied in recent years. However, related research studies for its partner SLC3A2 are still rare. Methods: Bulk transcriptome, single-cell sequencing, and immunohistochemical staining were analyzed to explore the expression distribution of SLC3A2. Clinical outcomes were referred to uncover the relationship between SLC3A2 expression and patients' prognosis. Immune cell infiltration was estimated by multiple deconvolution algorithms. The effect of SLC3A2 on the proliferation and drug resistance of cancer cell lines was evaluated by DEPMAP. Results: Upregulated SLC3A2 may have an adverse effect on the survival of multiple cancers such as lower-grade glioma and acute myeloid leukemia. SLC3A2 expression is indispensable for multiple cell lines' proliferation, especially for ESO51 (a cell line for esophageal cancer). In addition, SLC3A2 expression level was related to the remodeling of the immune microenvironment in cancers and some immune checkpoints such as PD-1 and PD-L1, which were potential therapeutic targets in many distinct cancers. Conclusion: Our study systematically elucidated the role of SLC3A2 in the survival of cancer patients and the potential immunotherapeutic response. Few molecular mechanisms by which SLC3A2 regulates anti-tumor immunity have been clarified in the present study, which is the main limitation. Future research into the biological mechanism could further help with targeted treatment for cancer patients.

Comparison of flexible ureteroscopy and mini-percutaneous nephrolithotomy in the treatment for renal calculi larger than 2 cm: a matched-pair analysis.

To compare the effectiveness and safety of flexible ureteroscopy and mini-percutaneous nephrolithotomy for renal calculi > 2 cm and perform subgroup analysis of stone length and age. Patients received mini-percutaneous nephrolithotomy or flexible ureteroscopy in Qilu Hospital of Shandong University from 2016.01 to 2021.03 with renal calculi > 2 cm were retrospectively analyzed. Propensity score matching was performed to get comparable patients. The postoperative hospital days, operation time, complication rate, and stone free rate were compared. The age and stone length were analyzed by subgroup. 162 in 313 patients were finally included. Each group had 81 cases. Outcomes such as intraoperative transfusion, stone free rate show no difference either. Flexible ureteroscopy had shorter postoperative hospital days (3.2 days vs 7.2 days, P < 0.001) and fewer complications (9, 11.1% vs 25, 30.9%, P = 0.002) compared to mini-percutaneous nephrolithotomy. The postoperative hospital days, and complication of the flexible ureteroscopy were significantly lower than those in the mini-percutaneous nephrolithotomy for renal stones ≤ 2.5 cm; when the stone length > 2.5 cm, the stone free rate of flexible ureteroscopy was lower than that of the mini-percutaneous nephrolithotomy group, but not statistically significant. The complications of flexible ureteroscopy in the young group (18-39 years old) were significantly lower than those in the mini-percutaneous nephrolithotomy group. For 2-2.5 cm renal stones, flexible ureteroscopy can achieve a similar stone free rate with shorter hospital stay, and lower complications. For larger stones, flexible ureteroscopy performed poorly. Flexible ureteroscopy may be a better option for younger patients with fewer complications.

Identification of IL20RB as a Novel Prognostic and Therapeutic Biomarker in Clear Cell Renal Cell Carcinoma.

Background: Clear cell renal cell carcinoma (ccRCC) is a type of life-threatening malignant tumor of the urinary system. IL20RB, interleukin 20 receptor subunit beta, is a cytokine receptor subunit coding gene and was initially found to play a vital role in human cancers, while its role in ccRCC still remains unclear. Methods: In this work, we explored the prognostic value and therapeutic potential of IL20RB in ccRCC mainly by online tools. Firstly, we used UALCAN and GEPIA to explore the expression profile and prognostic value of IL20RB in various cancers; the expression profile in tumor cell lines was also analysed with CCLE and Expression Atlas. Then, we decided to focus on ccRCC for further analysis; we further demonstrated the significant correlation between expression and clinical features by GEPIA and UALCAN. In order to reveal the potential intrinsic mechanism responsible for the upregulation of IL20RB in ccRCC, we made genetic alternation analysis and methylation analysis. cBioPortal was used for genetic alternation analysis. UALCAN, MethSurv, and Xena were used for methylation analysis. To learn details of how IL20RB might function in ccRCC, we further conducted functional analysis and immune infiltration analysis. STRING and GSEA were used to do functional analysis. TIMER was used for immune infiltration analysis; KM plotter was used for survival analysis. Results: Results show that IL20RB is upregulated in ccRCC, and low methylation may be responsible for its upregulation. Both high expression and low methylation of IL20RB predict worse survival, and both have a strong positive correlation with clinical characteristics. In addition, results indicate that there exists a crosstalk between IL20RB and neutrophils. Furthermore, the immune microenvironment could influence the prognosis predicting ability of IL20RB. Conclusions: In conclusion, IL20RB plays an important role in ccRCC and is identified as a novel prognostic and potential therapeutic biomarker in ccRCC.

"Two-zone and Three-segment" Laparoscopic Radical Cystectomy vs Conventional Laparoscopic Radical Cystectomy for Male Patients With Bladder Urothelial Carcinoma: A Retrospective Analysis.

PURPOSE: The aim of this study was to introduce an advanced surgical technique for laparoscopic radical cystectomy (LRC), evaluate the perioperative outcome and compare it to that of conventional LRC (CLRC). MATERIALS AND METHODS: Between March 2018 and March 2020, sixty patients were divided into the "two-zone and three-segment" laparoscopic radical cystectomy (TTLRC) group or the CLRC group. Patient baseline characteristics, preoperative characteristics and postoperative complications were collected. RESULTS: The TTLRC technique was developed based on the pelvic anatomy of six formalin fixed male cadavers. None of the patient baseline characteristics, including ECOG-PS score, comorbidity, ASA score and Hb, were significantly different between the two groups (p>0.05). There were significant differences in the operating time and estimated blood loss (total time: 3±0.2 vs 3.8±0.4, p<0.001; time to cystectomy and lymph node dissection: 1.7±0.2 vs 2.2±0.3, p<0.001; estimated blood loss 182.1±18.8 vs 264.3±27.4, p<0.001). Although there were no differences in late complications, early complications were significantly different between the two groups (p = 0.033). No statistically significant differences were found between the two groups in other outcomes (p>0.05). CONCLUSION: The TTLRC technique achieves a clearer surgical field, has a shorter operating time and produces less blood loss than CLRC. It is safe and feasible for urologists to perform this improved LRC procedure.

Mefatinib as first-line treatment of patients with advanced EGFR-mutant non-small-cell lung cancer: a phase Ib/II efficacy and biomarker study.

EGFR inhibitors have revolutionized the treatment of advanced non-small-cell lung cancer (NSCLC). Mefatinib is a novel, bioavailable, second-generation, irreversible pan-EGFR inhibitor. This phase Ib/II open-label, single-arm, multi-center study investigated the efficacy, safety, biomarker, and resistance mechanisms of mefatinib in the first-line treatment of patients with advanced EGFR-mutant NSCLC. This study included 106 patients with EGFR-mutant stage IIIB-IV NSCLC who received first-line mefatinib at a daily dose of either 60 mg (n = 51) or 80 mg (n = 55). The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. The cohort achieved an ORR of 84.9% and DCR of 97.2%. The median PFS was 15.4 months and the median OS was 31.6 months. Brain metastasis was detected in 29% of patients (n = 31) at diagnosis and demonstrated an ORR of 87.1%, PFS of 12.8 months, and OS of 25.2 months. Adverse events primarily involved skin and gastrointestinal toxicities, which were well-tolerated and manageable. Analyses of mutation profiles were performed using targeted sequencing of plasma samples at baseline, first follow-up 6 weeks from starting mefatinib therapy (F1), and at progression. Patients with concurrent TP53 mutations had comparable PFS as wild-type TP53 (14.0 vs 15.4 months; p = 0.315). Furthermore, circulating tumor DNA clearance was associated with longer PFS (p = 0.040) and OS (p = 0.002). EGFR T790M was the predominant molecular mechanism of mefatinib resistance (42.1%, 16/38). First-line mefatinib provides durable PFS and an acceptable toxicity profile in patients with advanced EGFR-mutant NSCLC.

Successful targeting of the NRG1 fusion reveals durable response to afatinib in lung adenocarcinoma: a case report.

The treatments for advanced non-small cell lung cancer (NSCLC) patients have been improved by developing tyrosine kinase inhibitors (TKIs) as targeted therapies. Oncogenic gene fusions resulting from structural DNA rearrangements have been proposed as a unique class of oncogenic drivers and therapeutic targets. Currently approved TKIs mainly focused on a few well-known fusion genes such as anaplastic lymphoma kinase (ALK) and ROS proto-oncogene 1 (ROS1). Fusions involving neuregulin 1 gene (NRG1) have been recently described in a small portion of solid tumors as actionable oncogenic drivers, leading to the activation of the erythroblastic leukemia viral oncogene homolog (ErbB)-mediated pathway. Therefore, gene fusions containing NRG1 could serve as a therapeutic candidate for ErbB-targeted treatment. In the present study, we report a lung adenocarcinoma patient harboring the CD74-NRG1 fusion, which was identified by next-generation sequencing (NGS). The patient received the irreversible pan-ErbB inhibitor, afatinib, as first-line treatment and showed a significant treatment response with a progression-free survival of 8 months. After progressive disease (PD), the second NGS did not identify novel genetic alterations that emerged after afatinib resistance. Our case supports the use of ErbB-targeted treatment for NRG1 fusion-positive NSCLC. Further studies are warranted to understand treatment effects and acquired resistance of afatinib in NGR1 fusion-positive patients.

Long Non-Coding RNA Myosin Light Chain Kinase Antisense 1 Plays an Oncogenic Role in Gallbladder Carcinoma by Promoting Chemoresistance and Proliferation.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been reported to play critical roles in human tumours, including gallbladder carcinoma (GBC). However, their biological functions and molecular mechanisms in tumorigenesis and progression remain largely unknown. METHODS: Quantitative polymerase chain reaction (qPCR) was used to verify the expression of lncRNA myosin light chain kinase antisense RNA 1 (MYLK-AS1) in 120 pairs of GBC tissues and paired adjacent non-tumour tissues, as well as in six different GBC cell lines (NOZ, EH-GB1, OCUG-1, GBC-SD, SGC-996 and QBC-939). Cell counting kit 8 was applied to explore cell proliferation and drug sensitivity assays. The target miRNAs (miR) of MYLK-AS1 and downstream target genes were predicted using Starbase 3.0 software and confirmed by double luciferase reporting test. The expression of proteins was assessed using Western blot assay. RESULTS: Here, we demonstrated that MYLK-AS1 was significantly upregulated and correlated with a poor prognosis and poor clinical characteristics in GBC. Furthermore, the forced expression of MYLK-AS1 significantly promoted GBC cell proliferation and resistance to gemcitabine in vitro. Mechanistically, MYLK-AS1 functioned as an efficient miR-217 sponge, thereby releasing the inhibition of enhancer of zeste 2 polycomb repressive complex 2 (EZH2) subunit expression. MYLK-AS1 promoted GBC cell proliferation and resistance to gemcitabine by upregulating EZH2 expression, and EZH2 was confirmed as a direct target of miR-217. DISCUSSION: Our results confirmed that the chemoresistant driver MYLK-AS1 might be a promising candidate as a therapeutic target for the treatment of advanced GBC.

Circular RNA circFAT1(e2) Promotes Colorectal Cancer Tumorigenesis via the miR-30e-5p/ITGA6 Axis.

circRNAs (circular RNAs) are a family of noncoding RNAs and have diverse physiological and pathological functions. However, the functions and mechanisms of circRNAs in the development and progression of colorectal cancer (CRC) remain largely unknown. Here, we aimed to explore the functions and roles of circFAT1(e2) in CRC. qRT-PCR revealed that circFAT1(e2) in CRC tumor tissues was upregulated compared with that in adjacent normal tissues and was also upregulated in CRC cell lines. Small interfering RNAs (siRNAs) against circFAT1(e2) were used to decrease the expression of circFAT1(e2) in HCT116 and RKO cells in vitro. The roles of circFAT1(e2) in CRC cell metastasis and proliferation were then determined by transwell and CCK-8 assays. The results showed that circFAT1(e2) silencing markedly suppressed CRC growth. Moreover, we identified circFAT1(e2) as a promoter of CRC metastasis. Knockdown of circFAT1(e2) evidently reduced HCT116 and RKO cell migration and invasion. Furthermore, the regulatory relationship between circFAT1(e2) and its target miRNAs was verified by a luciferase reporter assay. We demonstrated that circFAT1(e2) could sponge miR-30e-5p, which regulated the expression level of integrin α6 (ITGA6), the downstream target gene of miR-30e-5p. Rescue assays demonstrated that knockdown of miR-30e-5p enhanced CRC proliferation and migration via ITGA6. Taken together, our results reveal the novel oncogenic roles of circFAT1(e2) in CRC through the miR-30e-5p/ITGA6 axis.

Long Noncoding RNA WDFY3-AS2 Represses the Progression of Esophageal Cancer through miR-18a/PTEN Axis.

BACKGROUND: Understanding the role of lncRNAs in the development of human malignancies is necessary for the targeted therapy of malignant tumors, including esophageal cancer (EC). Nevertheless, the specific role and regulatory mechanism of lncRNA WDFY3-AS2 in EC are still unclear. Here, we examined the functional role and regulatory mechanism of WDFY3-AS2 in EC. MATERIALS AND METHODS: RT-qPCR assay was applied to measure the expression of WDFY3-AS2 and miR-18a in EC samples and cells. The luciferase reporter and RIP assays were used to check the relationship between WDFY3-AS2, miR-18a, and PTEN. Counting Clock Kit-8 (CCK-8) assay was carried out to detect cell viability, and transwell assays were used for measuring cell migration and invasion. RESULTS: Underexpression of WDFY3-AS2 was found in EC specimens and cells, which predicted a poor prognosis of EC patients. Reexpression of WDFY3-AS2 repressed the progression of EC via inhibiting cell proliferation, migration, and invasion. Additionally, WDFY3-AS2 was negatively correlated with miR-18a and positively with PTEN. Furthermore, we discovered that the expression of PTEN decreased by miR-18a mimic was rescued by WDFY3-AS2 overexpression. CONCLUSIONS: WDFY3-AS2 modulates the expressional level of PTEN as a competitive endogenous RNA via sponging miR-18a in EC, which suggests that the WDFY3-AS2/miR-18a/PTEN pathway might be involved in the progression of EC.

The efficient biomineralization and adsorption of cadmium (Cd2+) using secretory organo-biominerals (SOBs) produced by screened Alcaligenes faecalis K2.

Cadmium-contaminated wastewater has attracted increasing concerns due to its non-biodegradable properties and high toxicity. To explore eco-friendly and economically feasible strategies, the screened Alcaligenes faecalis K2 were employed for the biomineralization and recovery of Cd2+ from wastewater while producing considerable secretory organo-biominerals (SOBs) as bioadsorbents. At 75 mg/L Cd2+ exposure, 85.5% of Cd2+ was removed by K2, 43.0% of which was fixed in the granular SOBs. SOBs were convenient for separating from the solution. The adsorption capacity of granular sorbent made from SOBs was verified to be greater than 77.1 mg/g. Practically, 89.5% of 75 mg/L of Cd2+ could be stably removed while ereK2 continuously generated SOBs in a moving-bed biofilm reactor (MBBR). To sum up, the production of bioadsorbents can be achieved by K2, while removing Cd with live microorganisms, which was conducive to making full use of materials and improving Cd removal efficiency.

Cryo-EM structures reveal the molecular basis of receptor-initiated coxsackievirus uncoating.

Enterovirus uncoating receptors bind at the surface depression ("canyon") that encircles each capsid vertex causing the release of a host-derived lipid called "pocket factor" that is buried in a hydrophobic pocket formed by the major viral capsid protein, VP1. Coxsackievirus and adenovirus receptor (CAR) is a universal uncoating receptor of group B coxsackieviruses (CVB). Here, we present five high-resolution cryoEM structures of CVB representing different stages of virus infection. Structural comparisons show that the CAR penetrates deeper into the canyon than other uncoating receptors, leading to a cascade of events: collapse of the VP1 hydrophobic pocket, high-efficiency release of the pocket factor and viral uncoating and genome release under neutral pH, as compared with low pH. Furthermore, we identified a potent therapeutic antibody that can neutralize viral infection by interfering with virion-CAR interactions, destabilizing the capsid and inducing virion disruption. Together, these results define the structural basis of CVB cell entry and antibody neutralization.