Polymer Fiber Rigid Network with High Glass Transition Temperature Reinforces Stability of Organic Photovoltaics.

Organic photovoltaics (OPVs) need to overcome limitations such as insufficient thermal stability to be commercialized. The reported approaches to improve stability either rely on the development of new materials or on tailoring the donor/acceptor morphology, however, exhibiting limited applicability. Therefore, it is timely to develop an easy method to enhance thermal stability without having to develop new donor/acceptor materials or donor-acceptor compatibilizers, or by introducing another third component. Herein, a unique approach is presented, based on constructing a polymer fiber rigid network with a high glass transition temperature (Tg) to impede the movement of acceptor and donor molecules, to immobilize the active layer morphology, and thereby to improve thermal stability. A high-Tg one-dimensional aramid nanofiber (ANF) is utilized for network construction. Inverted OPVs with ANF network yield superior thermal stability compared to the ANF-free counterpart. The ANF network-incorporated active layer demonstrates significantly more stable morphology than the ANF-free counterpart, thereby leaving fundamental processes such as charge separation, transport, and collection, determining the device efficiency, largely unaltered. This strategy is also successfully applied to other photovoltaic systems. The strategy of incorporating a polymer fiber rigid network with high Tg offers a distinct perspective addressing the challenge of thermal instability with simplicity and universality.

Causal Relationship Between Circulating Immune Cells and Recurrent Spontaneous Abortion: A Bidirectional Mendelian Randomization Study.

BACKGROUND: Recurrent spontaneous abortion (RSA) is a serious and common complication of pregnancy caused by multiple factors. The etiology remains incompletely understood, but immunologic factors play important roles. Here, we aimed to evaluate whether circulating immune cells causally impacted RSA. METHODS: In this study, we conducted a comprehensive two-sample Mendelian randomization (MR) study to determine the causal association between the 731 immunophenotypes of human peripheral blood lymphocytes and the number of spontaneous abortions as well as recurrent miscarriage. Sensitivity analyses were performed to assess and minimize heterogeneity and horizontal pleiotropy. Reverse MR analysis was used to assess reverse causality. RESULTS: After Bonferroni-correction, eight immunophenotypes were significantly associated with the number of spontaneous abortions: FSC-A on CD4+ T cell (beta = -0.051, 95% CI = [-0.085, -0.017], P-value = 0.004), CD8 on HLA DR+ CD8+ T cell (beta = -0.040, 95% CI = [-0.067, -0.014], P-value = 0.003), HLA DR on CD33dim HLA DR+ CD11b- (beta = -0.021, 95% CI = [-0.036, -0.005], P-value = 0.010), HLA DR+ T cell Absolute Count (beta = 0.022, 95% CI = [0.006, 0.037], P-value = 0.008), HLA DR+ T cell % lymphocyte (beta = 0.026, 95% CI = [0.010, 0.041], P-value = 0.001), HLA DR+ T cell % T cell (beta = 0.023, 95% CI = [0.007, 0.039], P-value = 0.004), HLA DR+ CD4+ T cell % lymphocyte (beta = 0.034, 95% CI = [0.007, 0.060], P-value = 0.012), and HLA DR on B cell (beta = 0.012, 95% CI = [0.003, 0.021], P-value = 0.010). In addition, we identified two immunophenotypes associated with recurrent miscarriage: HLA DR on B cell (OR = 0.854, 95% CI = [0.757, 0.964], P-value = 0.011), and CD19 on naive-mature B cell (OR = 4.595, 95% CI = [1.674, 12.617], P-value = 0.003). There was no evidence of heterogeneity, horizontal pleiotropy and reverse causality. CONCLUSIONS: Our study demonstrated a tight link between adaptive immune cells and RSA through genetic means, thus providing potential therapeutic targets or novel diagnostic biomarkers.

[Opening experiments: synthesis, purification, and characterization of polyethyleneimine-modified carbon dots].

Open experiments are an effective means of cultivating top-notch innovative talents. Based on student interests, research hotspots and our laboratory conditions, an experimental scheme was designed. In this experiment, polyethyleneimine modified carbon dots (PEI-CDs) were prepared via a one-step hydrothermal method using citric acid (CA) as the carbon source and PEI as the surface passivator. First, CA and PEI were completely dissolved in 0.1 mol/L HCl and transferred into an autoclave. The autoclave was heated to 130 ℃ for 2 h. PEI-CDs solution was obtained. After cooling to room temperature, the solution was concentrated to 2 mL by rotary evaporation. Finally, the PEI-CDs were precipitated, washed with ethanol, and dried under vacuum at 70 ℃ for 12 h. The obtained PEI-CDs were characterized by fluorescence spectrophotometry, absorption spectrophotometry, infrared spectrometry, and transmission electron microscopy. The results indicated that anhydrous-ethanol precipitation is a simple, rapid, economical, and green purification method. The as-prepared PEI-CDs had unique properties, such as good water solubility, high luminescence, uniform particle sizes, and good stability. Through this open experiment, students can not only master the operation of large-scale instruments but also enhance their interest in scientific research.

Establishing Meaningful Change Thresholds in Patient-Reported Outcomes Among Patients With Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer in ALTA-1L Trial.

OBJECTIVES: An earlier study from the ALTA-1L trial of patients with anaplastic lymphoma kinase-positive non-small cell lung cancer demonstrated that brigatinib produces superior health-related quality of life (QoL) outcomes over crizotinib. This study aimed to derive meaningful change thresholds (MCTs) for European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 and EORTC QLQ-LC13 to refine the earlier results. METHODS: Patients from the ALTA-1L trial were administered the EORTC QLQ-C30 and EORTC QLQ-LC13 questionnaires. Responses were analyzed using anchor-based analysis, graphical analysis, distribution-based analysis, longitudinal responder analysis, and time to deterioration. RESULTS: The patient-reported outcome population comprised 262 patients who completed the EORTC QLQ-C30 at baseline and at least 1 follow-up timepoint. Both anchors (QLQ-C30 items for overall health and QoL) had correlations >0.40 or < -0.40 with all functioning domains, fatigue, pain, appetite loss, and all dyspnea scores. Within-group analysis for most scales found the derived MCT was consistent with a cutoff of 10 points for classifying individual-patient change, except for 3-item dyspnea. The probability of improvement/remaining stable was significantly greater in the brigatinib group over crizotinib for the EORTC QLQ-C30 emotional functioning, appetite loss, and constipation domains. CONCLUSIONS: This study derived MCTs for EORTC QLQ-C30 and QLQ-LC13 domains that may be applied in future studies and again demonstrated the superiority of brigatinib over crizotinib in health-related QoL outcomes in patients with non-small cell lung cancer.

Wavelength sensitivity reconfigurable SPR photodetector with a blazed grating profile.

Surface plasmonic detectors based on one-dimensional half-wavelength gratings have attracted attention due to their wavelength- or polarization-specific photodetection. Although the effect of a grating period and a grating depth on the photoelectric conversion of 1D half-wavelength grating-based surface plasmon resonance (SPR) detectors has been discussed thoroughly in recent years, the effect of different grating profiles on device performance is still limited to the rectangular shape. In this article, we proposed a wavelength sensitivity reconfigurable photodetector enhanced by SPR with a blazed grating profile. The gold layer was fabricated on a silicon-based blazed grating to form a Schottky barrier and act as an SPR coupler. By measuring the photocurrent in the range of -58° to -48°of an incident angle, the peak shifts of a photocurrent signal waveform are found to depend on the wavelength over 800-1000 nm.

A multicenter noninferior randomized controlled study comparing the efficacy of laparoscopic versus abdominal radical hysterectomy for cervical cancer (stage IB3 and IIA2): study protocol of the LAUNCH 3 trial.

BACKGROUND: Cervical cancer is and will remain to be an important health problem in China, especially with an increasing proportion of younger patients who has more specific needs. In China, surgery to remove tumor burden followed by postoperative treatment with radiotherapy and chemotherapy based on clinicopathologic factors may be the best choice for stages IB3 and IIA2 patients. Radical hysterectomy in cervical cancer has been a classic landmark surgery in gynecology. The current trial is designed to evaluate whether there is a difference between laparoscopic RH and abdominal RH in cervical cancer (stages IB3 and IIA2) patient survival under stringent operation standards and consistent surgical oncologic principles. This paper reports the rationale, design, and implementation of the trial. METHODS/DESIGN: This is an investigator-initiated, prospective, randomized, open, blinded endpoint (PROBE) controlled trial. A total of 1104 patients with stage IB3 and IIA2 cervical cancer will be enrolled over a period of 3 years. Patients are randomized (1:1) to either the laparoscopic RH or the abdominal RH group. Patients will then be followed up for at least 5 years. The primary end point will be 5-year overall survival, and secondary endpoints include 5-year progression-free survival, recurrence, and quality of life measurements. DISCUSSION: The study results will provide more convincing evidence-based information for stages IB3 and IIA2 cervical cancer patients and their gynecologic cancer surgeons in their choice of surgical method. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04939831 , retrospectively registered on 25 June 2021.

Analysis of coexisting pathogens in nasopharyngeal swabs from COVID-19.

Background: The impact of COVID-19 on the world is still ongoing, and it is currently under regular management. Although most infected people have flu-like symptoms and can cure themselves, coexisting pathogens in COVID-19 patients should not be taken lightly. The present study sought to investigate the coexisting pathogens in SARS-CoV-2 infected patients and identify the variety and abundance of dangerous microbes to guide treatment strategies with a better understanding of the untested factors. Methods: We extracted total DNA and RNA in COVID-19 patient specimens from nasopharyngeal swabs to construct a metagenomic library and utilize Next Generation Sequencing (NGS) to discover chief bacteria, fungi, and viruses in the body of patients. High-throughput sequencing data from Illumina Hiseq 4000 were analyzed using Krona taxonomic methodology for species diversity. Results: We studied 56 samples to detect SARS-CoV-2 and other pathogens and analyzed the species diversity and community composition of these samples after sequencing. Our results showed some threatening pathogens such as Mycoplasma pneumoniae, Klebsiella pneumoniae, Streptococcus pneumoniae, and some previously reported pathogens. SARS-CoV-2 combined with bacterial infection is more common. The results of heat map analysis showed that the abundance of bacteria was mostly more than 1000 and that of viruses was generally less than 500. The pathogens most likely to cause SARS-CoV-2 coinfection or superinfection include Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Klebsiella pneumoniae, and Human gammaherpesvirus 4. Conclusions: The current coinfection and superinfection status is not optimistic. Bacteria are the major threat group that increases the risk of complications and death in COVID-19 patients and attention should be paid to the use and control of antibiotics. Our study investigated the main types of respiratory pathogens prone to coexisting or superinfection in COVID-19 patients, which is valuable for identifying and treating SARS-CoV-2.

Semi-transparent organic photovoltaics.

As an economical solar energy conversion technology, organic photovoltaics (OPVs) are regarded as a promising solution to environmental problems and energy challenges. With the highest efficiency of OPVs exceeding 20%, the research focus will shift from efficiency-oriented aspects to commercialization-oriented aspects in the near future. Semi-transparent OPVs (STOPVs) are one of the most possible commercialized forms of OPVs, and have achieved power conversion efficiency over 14% with average visible light transmittance over 20% so far. In this tutorial review, we first systematically summarize the device structures, operating principles and evaluation parameters of STOPVs, and compare them with those of opaque OPVs. Then, strategies to construct high-performance STOPVs by cooperatively optimizing materials and devices are proposed. Methods to realize the scale-up of STOPVs in terms of minimization of electrode and interconnect resistance are summarized. The potential applications of STOPVs in multifunctional windows, agrivoltaics and floating photovoltaics are also discussed. Finally, this review highlights major challenges and research directions that need to be addressed prior to the future commercialization of STOPVs.

Giant tunneling magnetoresistance in in-plane double-barrier magnetic tunnel junctions based on MXene Cr2C.

The discovery of two-dimensional (2D) magnetic materials makes it possible to realize in-plane magnetic tunnel junctions. In this study, the transport characteristics of an in-plane double barrier magnetic tunnel junction (IDB-MTJ) based on Cr2C have been studied by density functional theory combined with the nonequilibrium Green's function method. The results showed its maximum tunneling magnetoresistance ratio (TMR) value reached 6.58 × 1010. Its minimum TMR value (3.86 × 106) was also comparable to those of conventional field effect transistors (FETs). Due to its giant TMR and unique structural characteristics, the IDB-MTJ based on Cr2C has great potential applications in magnetic random access memory (MRAM) and logic computing.

Enhanced Thermoelectric Properties of Coated Vanadium Oxynitride Nanoparticles/PEDOT:PSS Hybrid Films.

Thermoelectric (TE) materials transform thermal energy into electricity, which can play an important role for global sustainability. Conducting polymers are suitable for the preparation of flexible TE materials because of their low-cost, lightweight, flexible, and easily synthesized properties. Here, we fabricate organic-inorganic hybrids by combining vanadium oxynitride nanoparticles coated with nitrogen-doped carbon (NC@VNO) and poly(3,4-ethylenedioxy thiophene):poly(styrene sulfonate) (PEDOT:PSS). We find that the electrical conductivity, Seebeck coefficient, and power factor of the NC@VNO/PEDOT:PSS film can be enhanced up to 4158 S/cm, 45.8 µV/K, and 873 µW/mK2 at 380 K, respectively. The large enhancement of the power factor may be due to the facilitation of the interfacial charge transport tunnel between the NC@VNO nanoparticles and PEDOT:PSS. The improvement of the Seebeck coefficient may be due to the energy filter effect as induced by interfacial contact and internal electric field between the NC@VNO nanoparticles and PEDOT:PSS. Our measurement suggests that the high binding energy of pyrrolic-N enhances the Seebeck coefficient, and the high binding energy of oxide-N increases electrical conductivity.

Prognostic significance and risk factors for pelvic and para-aortic lymph node metastasis in type I and type II ovarian cancer: a large population-based database analysis.

BACKGROUND: To compare the prognosis of lymphatic metastasis in type I and type II epithelial ovarian cancer (OC) and to identify the risk factors for pelvic lymph node metastases (PLNs) and para-aortic lymph node metastases (PALNs). METHODS: Patients diagnosed with epithelial OC were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and cancer-specific survival (CSS) were estimated. The Cox proportional hazards regression model was used to identify independent predictors of survival. RESULTS: A total of 11,275 patients with OC were enrolled, including 31.2% with type I and 68.8% with type II. Type II and high tumour stage were risk factors for lymph node involvement (p < 0.05). The overall rate of lymph node metastasis in type I was 11.8%, and that in type II was 36.7%. In the type I group, the lymph node metastasis rates in stages T1, T2, T3 and TXM1 were 3.2%, 14.5%, 40.4% and 50.0%, respectively. In the type II group, these rates were 6.4%, 20.4%, 54.1% and 61.1%, respectively. Age and tumour size had little effect on lymph node metastasis, and grade 3 was not always a risk factor. For the type I group, the 10-year CSS rates of LN(-), PLN( +), PALN( +), and PLN + PALN( +) were 80.6%, 46.6%, 36.3%, and 32.3%, respectively. The prognosis of PLN ( +) was better than that of PALN ( +) in the type I group (p > 0.05). For the type II group, the 10-year CSS rates of LN(-), PLN( +), PALN( +), and PLN + PALN( +) were 55.6%, 18.5%, 25.7%, and 18.2%, respectively. PALN ( +) had a significantly better prognosis than PLN ( +) in the type II group (p < 0.05). CONCLUSIONS: The clinical characteristics and prognoses of patients with type I and type II OC differed greatly. Patients with type II and higher tumour stages had poorer prognoses. Type I with PALN metastasis and type II with PLN metastasis indicated a worse prognosis. Patients with stage TI did not require lymph node dissection, especially in the type I group.

Preparation of polyaluminium silicate sulphate by gravity supercritical method and its coagulation in oily sewage.

In this work, different synthetic methods of polymeric aluminum silicate sulfate (PASS) and their coagulability to oily sewage were comparatively studied. PASS was synthesized by two methods: gravity supercritical method and basic titration method, denoted as PASS-B and PASS-S, respectively. The results show that the PASS prepared by gravity supercritical method has better Alb and stability. By applying two coagulants to oily sewage, it was found that PASS-B exhibited better turbidity and oil removal. It was found that PASS-B still has good coagulation by testing its coagulation after placing the coagulant for 2 months. In acidic test water, PASS-B exhibited stronger deprotonation ability. Finally, the polymerization mechanism and coagulation mechanism of PASS-B were analyzed in combination with Al morphology distribution and coagulation experiments. Gravity supercritical method as a new polymerization method may replace the traditional preparation method of inorganic polymer coagulants in the future, especially in large-scale applications.

Modulation of intracellular kinase signaling to improve TIL stemness and function for adoptive cell therapy.

INTRODUCTION: Adoptive cellular therapy with tumor-infiltrating lymphocytes (TIL) has demonstrated promising clinical benefits in several solid tumors, but the efficacy of this therapy might be compromised by the "prone-to-exhaustion" phenotype of TIL and poor persistence in vivo. This calls for a robust expansion process to produce a large number of cells for clinical usage while at the same time maintaining favorable anti-tumor function and memory phenotype. Previous studies showed that the PI3K-AKT signaling pathway plays a key role in the regulation of T cell activation, differentiation and memory formation. METHOD: We modulated the PI3K-AKT pathway in TIL isolated from cervical and ovarian cancer by application of AKT or PI3K inhibitors or CRISPR knockout of AKT1 and/or AKT2, and characterized their effects on TIL phenotype and effector function. Mechanistic study was further performed with RNA-seq analysis of AKT1/2 KO TIL in comparison to control TIL. RESULT: The inhibition of either PI3K or AKT led to an increase in the population of effector CD8+ T cells with upregulation of activation markers, elevated CD39- CD69- memory T cells, and significantly enhanced cytotoxicity when cocultured with tumor cell lines and patient-derived tumor samples. Moreover, dual knockout of AKT1 and AKT2 largely phenocopies the functional impact of AKT or PI3K inhibition on TIL. This result was further validated by RNA-seq analysis indicating that AKT1/2 ablation primarily regulates T cell differentiation and function-related programs. CONCLUSION: Modulation of PI3K-AKT signaling represents a promising strategy to enhance TIL stemness and cytotoxicity and improve the clinical outcome of current TIL-based therapy to treat solid tumors.

Evaluation of the self-assembled functional PPFS-P-AM composite for treating oilfield sewage.

Oilfield sewage has a complex composition with large amounts of emulsified oils, polymers and surfactants. Efficient coagulants are required to purify such sewage to meet emissions standards. In this study, oxidized FeSO4·7H2O and NaHCO3were condensed by basic titration and polyferric sulfate phosphate (PPFS) was prepared by the addition of NaH2PO4·2H2O to improve its charge and stability. In addition, by adding modified palygorskite and cationic amylum, a functional polyferric sulfate phosphate, palygorskite and cationic amylum copolymer (PPFS-P-AM) composite coagulant was synthesized through self-assembly, and then used to treat oilfield sewage. The characteristic functional groups and crystal forms of the coagulant were characterized by FTIR and XRD. The zeta potential and radius of gyration (Rh) indicate that the introduction of palygorskite and cationic amylum enhance the charge neutralization and bridging adsorption abilities, respectively. The optimal dosage of cationic amylum is 5% in 80 mg·L-1 PPFS-P-AM, which provides turbidity and oil removal rates of 98% and 94%, respectively. Observation by SEM shows that the micro-morphology of PPFS-P-AM flocs has adendritic distribution with a reticular macromolecular structure that provides good sweeping performance during the sedimentation process. Finally, an analysis of its properties and performance reveals the mechanism by which PPFS-P-AM coagulates oilfield sewage. PPFS-P-AM provides better coagulation than the other studied coagulants via the synergistic effects of reinforced charge neutralization, bridging adsorption and sweeping.

A multicenter noninferior randomized controlled study comparing the efficacy of laparoscopic versus abdominal radical hysterectomy for cervical cancer (stage IA1 with LVSI, IA2): study protocol of the LAUNCH 1 trial.

BACKGROUND: A retrospective study and a randomized controlled trial published in a high quality journal in late 2018 have shown that laparoscopic radical hysterectomy (RH) was associated with worse survival than abdominal RH among patients with early stage cervical cancer. Radical hysterectomy in cervical cancer has been a classic landmark surgery in gynecology, therefore this conclusion is pivotal. The current trial is designed to reconfirm whether there is a difference between laparoscopic RH and abdominal RH in cervical cancer (stage IA1 with LVSI, IA2) patient survival under stringent operation standards and consistent tumor-free technique. This paper reports the rationale, design, and implementation of the trial. METHODS: This is an investigator-initiated, prospective, randomized, open, blinded endpoint (PROBE) controlled trial. A total of 690 patients with stage IA1 (with intravascular), and IA2 cervical cancer will be enrolled over a period of three years. Patients are randomized (1:1) to either the laparoscopic RH or the abdominal RH group. Patients will then be followed-up for at least five years. The primary endpoint will be 5-year progression-free survival. Secondary endpoints will include 5-year overall survival rates, recurrence rates, operation time, intraoperative blood loss, surgery-related complications, and quality of life. DISCUSSION: The results of the trial will provide valuable evidence for guiding clinical decision of choosing appropriate treatment strategies for stage IA1 (LVSI) and stage IA2 cervical cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT04934982 , Registered on 22 June 2021).

Characterization of the Genomic Landscape in Cervical Cancer by Next Generation Sequencing.

Cervical cancer is the fourth leading cause of cancer-related deaths in women worldwide. Although many sequencing studies have been carried out, the genetic characteristics of cervical cancer remain to be fully elucidated, especially in the Asian population. Herein, we investigated the genetic landscape of Chinese cervical cancer patients using a validated multigene next generation sequencing (NGS) panel. We analyzed 64 samples, consisting of 32 tumors and 32 blood samples from 32 Chinese cervical cancer patients by performing multigene NGS with a panel targeting 571 cancer-related genes. A total of 810 somatic variants, 2730 germline mutations and 701 copy number variations (CNVs) were identified. FAT1, HLA-B, PIK3CA, MTOR, KMT2D and ZFHX3 were the most mutated genes. Further, PIK3CA, BRCA1, BRCA2, ATM and TP53 gene loci had a higher frequency of CNVs. Moreover, the role of PIK3CA in cervical cancer was further highlighted by comparing with the ONCOKB database, especially for E545K and E542K, which were reported to confer radioresistance to cervical cancer. Notably, analysis of potential therapeutic targets suggested that cervical cancer patients could benefit from PARP inhibitors. This multigene NGS analysis revealed several novel genetic alterations in Chinese patients with cervical cancer and highlighted the role of PIK3CA in cervical cancer. Overall, this study showed that genetic variations not only affect the genetic susceptibility of cervical cancer, but also influence the resistance of cervical cancer to radiotherapy, but further studies involving a larger patient population should be undertaken to validate these findings.

KHDRBS3 promotes paclitaxel resistance and induces glycolysis through modulated MIR17HG/CLDN6 signaling in epithelial ovarian cancer.

Paclitaxel (PTX) resistance contributes to mortality in epithelial ovarian cancer (EOC). Aerobic glycolysis is elevated in the tumor environment and may influence resistance to PTX in EOC. KH domain-containing, RNA-binding signal transduction-associated protein 3 (KHDRBS3) is an RNA binding protein that is up-regulated in EOC, but its underlying mechanism in EOC is unclear. Here, we investigate the role of KHDRBS3 in glycolysis and increased resistance to PTX. Expression of KHDRBS3 and Claudin (CLDN6) were measured in EOC tissue and cells by quantitative real-time PCR, western blotting and immunohistochemistry. The biological functions of KHDRBS3, MIR17HG and CLDN6 were examined using MTT, colony formation, apoptosis and seahorse assays in vitro. For in vivo experiments, a xenograft model was used to investigate the effects of KHDRBS3 and MIR17HG in EOC. Here, we investigate the role of KHDRBS3 in glycolysis and increased resistance to PTX. The expression of KHDRBS3 was up-regulated in PTX-resistant cells. KHDRBS3 knockdown restrained the IC50 of PTX, cell proliferation, colony formation and glycolysis in SKOV3-R and A2780-R cells in vitro and enhanced PTX sensitivity in a xenograft mouse model in vivo. KHDRBS3 interacts with lncRNA MIR17HG, which is down-regulated in EOC tissue and cells. The effect of KHDRBS3 overexpression on PTX resistance and glycolysis was rescued by MIR17HG overexpression. Additionally, MIR17HG interacts with the 3'UTR of CLDN6 and negatively regulates CLDN6 expression. MIR17HG overexpression suppressed the IC50 of PTX and glycolysis by targeting CLDN6. Our results reveal a KHDRBS3-MIR17HG-CLDN6 regulatory axis that contributes to enhanced glycolysis in EOC and represents a potential target for therapy.

Tunable tunneling magnetoresistance in in-plane double barrier magnetic tunnel junctions based on B vacancy h-NB nanoribbons.

Magnetic tunnel junctions (MTJs) have attained new opportunities due to the emergence of two-dimensional (2D) magnetic materials after they were proposed more than forty years ago. Here, an in-plane double barrier magnetic tunnel junction (IDB-MTJ) based on B vacancy h-NB nanoribbons has been proposed firstly, and the transport properties have been studied using density functional theory combined with the nonequilibrium Green's function method. Due to its unique structural characteristics, the tunneling magnetoresistance (TMR) ratio can be tuned and the maximum TMR can reach 1.86 × 105. The potential applications of the IDB-MTJ in magnetic random-access memories and logical computation have also been discussed. We find that the IDB-MTJs have great potential in magnetic random-access memories and logical computation applications.

Patients with low nicotinamide N-methyltransferase expression benefit significantly from bevacizumab treatment in ovarian cancer.

BACKGROUND: The role of nicotinamide N-methyltransferase (NNMT) in ovarian cancer is still elusive. Our aim is to explore the expression of NNMT in ovarian cancer and to assess its association with patient prognosis and treatment response. METHODS: We first analyzed the differential expression of NNMT among fallopian tube epithelium, primary ovarian cancers, metastatic ovarian cancers, and recurrent ovarian cancers using Gene Expression Ominus (GEO) database (GSE10971, GSE30587, GSE44104 and TCGA datasets). Then, we assessed the association of NNMT expression with clinical and molecular parameters using CSIOVDB database and GSE28739 dataset. Next, we evaluate the association of NNMT expression with the prognosis of ovarian cancer patients in both GSE9891 dataset and TCGA dataset. Finally, GSE140082 dataset was used to explore the association of NNMT expression with bevacizumab response. RESULTS: NNMT expression was significantly elevated in lymphovascular space invasion (LVSI)-positive ovarian cancers compared with that in LVSI-negative ovarian cancers (TCGA dataset, P < 0.05), Moreover, increased expression of NNMT was associated with increased tumor stage, grade, and mesenchymal molecular subtype (CSIOVDB database). Survival analysis indicated that increased expression of NNMT was associated with a reduced OS in both GSE9891 dataset (HR: 2.28, 95%CI: 1.51-3.43, Log-rank P < 0.001) and TCGA dataset (HR: 1.55, 95%CI: 1.02-2.36, Log-rank P = 0.039). Multivariate analysis further confirmed the negative impact of NNMT expression on OS in ovarian cancer patients in those two datasets. Furthermore, the NNMT-related nomogram showed that NNMT shared a larger contribution to OS, compared with debulking status. More interestingly, bevacizumab conferred significant improvements in OS for patients with low NNMT expression (HR: 0.56, 95%CI: 0.31-0.99, Log-rank P = 0.049). In contrast, patients with high NNMT expression didn't benefit from bevacizumab treatment significantly (HR: 0.85, 95%CI: 0.48-1.49, Log-rank P = 0.561). NNMT expression was positively correlated with the expression of genes, LDHA and PGAM1, involved in Warburg effect. CONCLUSIONS: In conclusion, NNMT expression is associated with the aggressive behavior of ovarian cancer, correlates with a poor prognosis, and is predictive of sensitivity to bevacizumab treatment.