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The interface with spin defects in hexagonal boron nitride has recently become a promising platform and has shown great potential in a wide range of quantum technologies. Varieties of spin properties of V B - defects in hexagonal boron nitride (hBN) have been researched widely and deeply, like their structure and coherent control. However, little is known about the influence of off-axis magnetic fields on the coherence properties of V B - defects in hBN. Here, by using optically detected magnetic resonance (ODMR) spectroscopy, we systematically investigated the variations in ODMR resonance frequencies under different transverse and longitudinal external magnetic fields. In addition, we measured the ODMR spectra under off-axis magnetic fields of constant strength but various angles and observed that the splitting of the resonance frequencies decreases as the angle increases, aligning with our theoretical calculation based on the Hamiltonian, from which we came up with a solution of detecting the off-axis magnetic field angle. Through Rabi oscillation measurements, we found that the off-axis magnetic field suppresses the spin coherence time. These results are crucial for optimizing V B - defects in hBN, establishing their significance as robust quantum sensors for quantum information processing and magnetic sensing in varied environments.

Purpose: Idiopathic granulomatous mastitis (IGM) poses diagnostic challenges due to its diverse clinical and radiological presentations, often mimicking malignancies. This study aimed to assess the diagnostic efficacy of multimodal ultrasound for mass and non-mass enhancements in Dynamic Contrast-Enhanced MRI (DCE-MRI) of IGM and breast cancer., Methods: A retrospective analysis involved patients confirmed histopathologically with IGM and BC. All patients underwent conventional ultrasound (C-US), ultrasound elastography (UE), contrast-enhanced ultrasound (CEUS), and DCE-MRI examinations. Blinded experienced radiologists assessed imaging findings. Diagnostic accuracy, sensitivity, and specificity were calculated for mass and non-mass enhancements., Results: For mass enhancements (ME), multimodal ultrasound demonstrated strong efficacy (AUC = 0.8651, 95 % CI: 0.7431 to 0.9871), exhibiting high sensitivity (83.3 %) and specificity (92.4 %) in differentiating IGM from breast cancer. However, for non-mass enhancements (NME), multimodal ultrasound showed limited accuracy (AUC = 0.6306) with lower sensitivity (65.6 %) and specificity (81.2 %) in distinguishing between IGM and breast cancer., Conclusion: Multimodal ultrasound displayed good diagnostic efficacy for mass enhancements in DCE-MRI for IGM and breast cancer, while for non-mass enhancement patterns, DCE-MRI remains the most valuable radiological modality for comprehensively assessing this condition's complexities., Competing Interests: Declaration of competing interests The authors declare that they have no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: P53 is a suppressor gene closely related to carcinogenesis. However, the associations between genetic variants in the p53 signaling pathway and prognosis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remain unknown. The current study aims to analyze associations between the single nucleotide polymorphisms (SNPs) in p53 pathway-related genes and survival of patients with HBV-HCC., Methods: We evaluated the associations between 4698 SNPs in 70 genes of the p53 pathway and overall survival (OS) of 866 patients in additive genetic models by using Cox proportional hazards regression analysis. Stepwise multivariable Cox regression analysis was conducted to determine the independent effects of identified SNPs in single-locus analyses. The expression of quantitative trait loci (eQTL) was also analyzed using data from GTEx and 1000 Genomes Project, and functional prediction of SNPs was performed by using RegulomeDB v2.2, 3DSNP v2.0, HaploReg v4.2 and VannoPortal., Results: We found that two novel SNPs of CD82 rs7925603 A > G and PMAIP1 rs4396625 A > T, were significantly and independently associated with OS [adjusted hazards ratios (HRs) and 95% confidence intervals (CI) were 1.27 (1.10-1.48) and 0.77 (0.66-0.91), respectively; P = 0.001 and = 0.002, respectively] and that the combined risk genotypes of these SNPs showed a significant association with OS in patients with HBV-HCC ( P trend < 0.001). Further eQTL analysis in the GTEx dataset showed that the rs7925603 G allele was associated with lower CD82 mRNA expression levels, while the rs4396625 T allele was associated with higher PMAIP1 mRNA expression levels in whole blood cells., Conclusion: We identified two observed survival-associated SNPs in CD82 and PMAIP1 in the p53 pathway, which influenced HBV-HCC survival possibly through a mechanism of altering mRNA expression. Large studies are warranted to validate our findings., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Qin et al.)

Background: The nod-like receptor protein 3 (NLRP3) is one of the most characterized inflammasomes involved in the pathogenesis of several cancers, including hepatocellular carcinoma (HCC). However, the effects of genetic variants in the NLRP3 inflammasome-related genes on survival of hepatitis B virus (HBV)-related HCC patients are unclear., Methods: We performed multivariable Cox proportional hazards regression analysis to evaluate associations between 299 single-nucleotide polymorphisms (SNPs) in 16 NLRP3 inflammasome-related genes and overall survival (OS) of 866 patients with HBV-related HCC. We further performed expression quantitative trait loci (eQTL) analysis using the data from the GTEx project and 1000 Genomes projects, and performed differential expression analysis using the TCGA dataset to explore possible molecular mechanisms underlying the observed associations., Results: We found that two functional SNPs (PANX1 rs3020013 A > G and APP rs9976425 C > T) were significantly associated with HBV-related HCC OS with the adjusted hazard ratio (HR) of 0.83 [95% confidence interval (CI) = 0.73-0.95, P = 0.008], and 1.26 (95% CI = 1.02-1.55, P = 0.033), respectively. Moreover, the eQTL analysis revealed that the rs3020013 G allele was correlated with decreased mRNA expression levels of PANX1 in both normal liver tissues (P = 0.044) and whole blood (P < 0.001) in the GTEx dataset, and PANX1 mRNA expression levels were significantly higher in HCC samples and associated with a poorer survival of HCC patients. However, we did not observe such correlations for APP rs9976425., Conclusions: These results indicated that SNPs in the NLRP3 inflammasome-related genes may serve as potential biomarkers for HBV-related HCC survival, once replicated by additional larger studies., (© 2024. The Author(s).)

N 6 -methyladenosine (m 6 A) is a dynamic and reversible modification process involving in a series of important biological and pathophysiological processes, including the progression of cancers. Herein, we aimed to assess the relationships of genetic variants in m6A modification genes with the survival of hepatitis B virus -related hepatocellular carcinoma (HBV-HCC). We performed a two-stage survival analysis to investigate the associations of 4425 single nucleotide polymorphisms (SNPs) in 36 m 6 A modification genes with the overall survival (OS) of HBV-HCC patients. Then, the identified SNPs were further used to functionally annotate. We identified that METTL3 rs1263790 (A > G) and ADARB1 rs57884102 (C > T) were significantly associated with the HBV-HCC OS (hazard ratios [HR] = 0.68, 95% confidence interval [CI] = 0.52-0.89, p = 0.004; and HR = 1.70, 95% CI = 1.33-2.18, p < 0.001, respectively). Combined analysis revealed that patients carrying more risk genotypes of two variants had a progressively poorer OS. Moreover, the expression quantitative trait loci (eQTL) analysis indicated that rs1263790 G allele decreased mRNA expression levels of METTL3 in 483 cell-cultured fibroblasts samples. And we found the mRNA expression levels of METTL3 and ADARB1 in HCC tissues were higher than in normal tissues, and the higher METTL3 and the lower ADARB1 were associated with poorer HCC OS. Our results demonstrated that two novel genetic variants (METTL3 rs1263790 and ADARB1 rs57884102) may be potential prognostic markers for HBV-HCC, but these results need larger different ethnic cohorts and functional experiments to validate in the future., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Background: Potentially modifiable risk factors for hepatocellular carcinoma (HCC) have been investigated in observational epidemiology studies in East Asian and European populations, whereas the causal associations of most of these risk factors remain unclear., Methods: We collected genome-wide association summary statistics of 22 modifiable risk factors in East Asians and 33 risk factors in Europeans. Genetic summary statistics of HCC were sourced from the Biobank Japan study (1,866 cases and 195,745 controls) for East Asians, and the deCODE genetics study (406 cases and 49,302 controls) and the UK Biobank (168 cases and 372 016 controls) for Europeans. Two-sample Mendelian randomization (MR) analyses were performed independently for East Asian and European populations., Results: In East Asians, genetically predicted alcohol frequency, ever drinkers, aspartate aminotransferase (AST), hypothyroidism, chronic hepatitis B, and chronic hepatitis C, metabolic dysfunction-associated steatotic liver disease (MASLD), and autoimmune hepatitis were significantly associated with an increased HCC risk (P < 0.05/22). Among European population, alanine transaminase, AST, MASLD, percent liver fat, and liver iron content were significantly associated with a higher risk of HCC (P < 0.05/33). The replication dataset and meta-analysis further confirmed these results., Conclusions: Although East Asian and European populations have different factors for HCC, their common modifiable risk factors AST and MASLD for HCC, offer valuable insights for targeted intervention strategies to mitigate society burden of HCC., (© 2024. The Author(s).)

The progestin regimen is one of the main therapeutic strategies for women with endometrial cancer who undergo conservative management. Although many patients respond well to initial therapy, progestin-refractory disease inevitably emerges, and the molecular basis underlying progestin resistance has not been comprehensively elucidated. Herein, they demonstrated progestin results in p38-dependent IDH1 Thr 77 phosphorylation (pT77-IDH1). pT77-IDH1 translocates into the nucleus and is recruited to chromatin through its interaction with OCT6. IDH1-produced α-ketoglutarate (αKG) then facilitates the activity of OCT6 to promote focal adhesion related target gene transcription to confer progestin resistance. Pharmacological inhibition of p38 or focal adhesion signaling sensitizes endometrial cancer cells to progestin in vivo. The study reveals p38-dependent pT77-IDH1 as a key mediator of progestin resistance and a promising target for improving the efficacy of progestin therapy., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Disulfidptosis is a novel form of programmed cell death involved in migration and invasion of cancer cells, but few studies investigated the roles of genetic variants in disulfidptosis-related genes in survival of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). We used Cox proportional hazards regression analyses, Kaplan-Meier curves and receiver operating characteristic curves to assess effects of genetic variants in 14 disulfidptosis-related genes on overall survival of 866 HBV-HCC patients. The Bayesian false discovery probability was used for multiple testing corrections. We also investigated biological mechanisms of the significant variants through expression quantitative trait loci analyses using the data from publicly available databases, luciferase reporter assays and differential expression analyses. As a result, we identified two independently functional single nucleotide polymorphisms (SNPs) (INF2 rs4072285 G > A and INF2 rs4444271 A > T) that predicted overall survival of HBV-HCC patients, with adjusted hazard ratios of 1.60 (95% CI = 1.22-2.11, P = 0.001) and 1.50 (95% CI = 1.80-1.90, P < 0.001), respectively, after multiple testing correction. Luciferase reporter assays indicated that both INF2 rs4072285 A and INF2 rs4444271 T alleles increased INF2 mRNA expression levels (P < 0.001) that were also higher in HCC tumor tissues than in adjacent normal tissues (P < 0.001); such elevated INF2 expression levels were associated with a poorer survival of HBV-HCC patients (P < 0.001) in the TCGA database. In summary, this study supported that INF2 rs4072285 and INF2 rs4444271 may be novel biomarkers for survival of HBV-HCC patients., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Although the Notch pathway plays an important role in formation and progression of hepatocellular carcinoma (HCC), few studies have reported the associations between functional genetic variants and the survival of hepatitis B virus (HBV)-related HCC., Methods: In the present study, we performed multivariable Cox proportional hazard regression analysis to evaluate associations between 36,101 SNPs in 264 Notch pathway-related genes and overall survival (OS) of 866 patients with HBV-related HCC., Results: It was found that three independent SNPs (NEURL1B rs4868192, CNTN1 rs444927 and FCER2 rs1990975) were significantly associated with the HBV-related HCC OS. The number of protective genotypes (NPGs) were significantly associated with better survival in a dose-response manner (p trend  <0.001). Compared with the model with sole clinical factors, the addition of protective genotypes to the predict models significantly increased the AUC, i.e., from 72.72% to 75.13% (p = 0.002) and from 72.04% to 74.76 (p = 0.004) for 3-year and 5-year OS, respectively. The expression quantitative trait loci (eQTL) analysis further revealed that the rs4868192 C allele was associated with lower mRNA expression levels of NEURL1B in the whole blood (p = 1.71 × 10 -3 ), while the rs1990975 T allele was correlated with higher mRNA expression levels of FCER2 in the whole blood and normal liver tissues (p = 3.51 × 10 -5 and 0.033, respectively)., Conclusions: Three potentially functional SNPs of NEURL1B, CNTN1 and FCER2 may serve as potential prognostic biomarkers for HBV-related HCC., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors with a high mortality rate. The 5-methylcytosine (m5C), a type of RNA modification, plays crucial regulatory roles in HCC carcinogenesis, metastasis, and prognosis. However, a few studies have investigated the effect of genetic variants in m5C modification genes on survival of patients with hepatitis B virus (HBV)-related HCC. In the present study, we evaluated associations between 144 SNPs in 15 m5C modification genes and overall survival (OS) in 866 patients with the HBV-related HCC. Expression quantitative trait loci (eQTL) analysis and differential expression analysis were conducted to investigate biological mechanisms. As a result, we identified that two SNPs (NSUN7 rs2437325 A > G and TRDMT1 rs34434809 G > C) were significantly associated with HBV-related HCC OS with adjusted allelic hazards ratios of 1.25 (95% confidence interval = 1.05-1.48 and P = 0.011) and 1.19 (1.02-1.38 and P = 0.027), respectively, with a trend of combined risk genotypes (P trend  < 0.001). Moreover, the results of eQTL analyses showed that both NSUN7 rs2437325 G and TRDMT1 rs34434809 C alleles were associated with a reduced mRNA expression level in 208 normal liver tissues (P = 0.007 and P < 0.001, respectively). Taken together, genetic variants in the m5C modification genes may be potential prognostic biomarkers of HBV-related HCC after hepatectomy, likely through mediating the mRNA expression of corresponding genes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The first quantum revolution has brought us the classical Internet and information technology. Today, as technology advances rapidly, the second quantum revolution quietly arrives, with a crucial moment for quantum technology to establish large-scale quantum networks. However, solid-state quantum bits (such as superconducting and semiconductor qubits) typically operate in the microwave frequency range, making it challenging to transmit signals over long distances. Therefore, there is an urgent need to develop quantum transducer chips capable of converting microwaves into optical photons in the communication band, since the thermal noise of optical photons at room temperature is negligible, rendering them an ideal information carrier for large-scale spatial communication. Such devices are important for connecting different physical platforms and efficiently transmitting quantum information. This paper focuses on the fast-developing field of optomechanical quantum transducers, which has flourished over the past decade, yielding numerous advanced achievements. We categorize transducers based on various mechanical resonators and discuss their principles of operation and their achievements. Based on existing research on optomechanical transducers, we compare the parameters of several mechanical resonators and analyze their advantages and limitations, as well as provide prospects for the future development of quantum transducers.

Background: The enriched proteins within in vitro fertilisation (IVF)-generated human embryonic microenvironment could reverse progestin resistance in endometrial cancer (EC)., Methods: The expression of thymic stromal lymphopoietin (TSLP) in EC was evaluated by immunoblot and IHC analysis. Transcriptome sequencing screened out the downstream pathway regulated by TSLP. The role of TSLP, androgen receptor (AR) and KANK1 in regulating the sensitivity of EC to progestin was verified through a series of in vitro and in vivo experiments., Results: TSLP facilitates the formation of a BMP4/BMP7 heterodimer, resulting in activation of Smad5, augmenting AR signalling. AR in turn sensitises EC cells to progestin via KANK1. Downregulation of TSLP, loss of AR and KANK1 in EC patients are associated with tumour malignant progress. Moreover, exogenous TSLP could rescue the anti-tumour effect of progestin on mouse in vivo xenograft tumour., Conclusions: Our findings suggest that TSLP enhances the sensitivity of EC to progestin through the BMP4/Smad5/AR/KANK1 axis, and provide a link between embryo development and cancer progress, paving the way for the establishment of novel strategy overcoming progestin resistance using embryo original factors., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Mastectomy (MT) and breast conservation surgery (BCS) are two common surgical options for the treatment of locally advanced breast cancer (LABC). Neoadjuvant chemotherapy (NACT) is frequently administered before surgery to shrink tumors and improve surgical outcomes. However, there is a lack of consensus on the optimal surgical approach after NACT and its impact on survival outcomes., Objective: This meta-analysis aims to compare the survival outcomes between MT and BCS in patients treated with NACT., Method: A PRISMA selection was used to identify studies across electronic database such as PubMed, and Cochrane Library from inception until 11 th July, 2023. A total of 10 comparative studies involving a total of 5018 patients were included. Among them, 2898 patients underwent MT while 2120 underwent BCS after receiving NACT. The outcomes assessed were the 5-year overall survival (OS) and 5-year disease-free survival (DFS). The data from the included studies were pooled, and odds ratios (OR) with 95% confidence intervals (CI) were calculated to evaluate the differences between MT and BCS in terms of survival outcomes. Prospero: CRD42024496831., Result: The meta-analysis revealed that patients who underwent MT after NACT had a higher 5-year OS compared to those who underwent BCS (OR 2.68, 95% CI [2.19-3.28; p < 0.00001]). Additionally, the 5-year DFS was significantly better for patients who underwent MT (OR 3.11, 95% CI [1.80-5.38; p < 0.0001])., Conclusion: MT after NACT may be associated with better 5-year OS and DFS compared to BCS., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Ferroptosis is a known crucial player in the development of cancers. However, the effect of single nucleotide polymorphisms (SNPs) in ferroptosis-related genes on survival in hepatitis B virus (HBV)-related hepatocellular carcinoma (HBV-HCC) patients remains unknown., Methods: We used two-stage multivariable Cox proportional hazards regression analyses to estimate the associations between 48,774 SNPs in 480 ferroptosis-related genes and overall survival (OS) of 866 HBV-HCC patients., Results: We identified that two potentially functional SNPs (CREB3 rs10814274 C > T and GALNT14 rs17010547 T > C) were significantly independently associated with the OS of HBV-HCC patients (CT + TT verse CC, hazards ratio (HR) = 0.77, 95% confidence interval (CI) = 0.67-0.89, p < 0.001 for rs10814274 and TC + CC verse TT, HR = 0.66, 95% CI = 0.53-0.82, p < 0.001 for rs17010547, respectively). Additional joint assessment of protective genotypes of these two SNPs showed that patients with 1-2 protective genotypes had a significantly better OS compared with those carrying 0 protective genotypes (HR = 0.56, 95% CI = 0.45-0.70, p < 0.001). Moreover, the expression quantitative trait loci (eQTL) analysis revealed that the survival-associated SNP rs10814274 T allele was significantly correlated with reduced CREB3 transcript levels in both normal liver tissues and whole blood cells, while the GALNT14 rs17010547 C allele had a significant correlation with increased GALNT14 transcript levels in whole blood cells., Conclusion: These results suggest that genetic variants of CREB3 and GALNT14 may affect the survival of HBV-HCC patients, likely via transcriptional regulation of respective genes. However, further studies are required to confirm these findings., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

The nuclear factor E2-related factor 2 (NRF2) signaling pathway is one of the most important cell defense pathways. However, it is unclear whether genetic variants in NRF2 signaling pathway genes are associated with the survival of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). In the present study, we utilized a new hypothesis-driven approach based on biological pathways to investigate the associations between 17919 single nucleotide polymorphisms (SNPs) in 137 NRF2 signaling pathway genes and the overall survival (OS) of 866 patients with HBV-related HCC. As a result, two independent SNPs with potential biological function were identified to be significantly associated with HBV-related HCC OS: [ SLC2A9 rs28643326 T>C: hazard ratio (HR) = 0.74, 95% confidence interval (95% CI) = 0.62-0.89, P < 0.001 and SLC5A10 rs2472711 G>T: HR = 0.81, 95% CI = 0.71-0.93, P = 0.003, respectively]. The expression quantitative trait loci (eQTL) analysis further revealed that the rs28643326 C allele was significantly associated with increased levels of SLC2A9 mRNA expression ( P < 0.001), and higher mRNA expression levels of SLC2A9 in adjacent normal liver tissues were associated with better survival. Although the association between the rs2472711 T allele and the mRNA expression of SLC5A10 was not statistically significant ( P = 0.200), the fact that rs2472711 is located at the DNase I hypersensitivity site and is a marker for promoter and enhancer histones also suggests that it may have the function of regulating its corresponding gene expression. In conclusion, genetic variants of NRF2 signaling pathway genes may serve as potential prognostic biomarkers for HBV-related HCC and also provide a solid basis for further mechanistic exploration., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Hepatocellular carcinoma (HCC) ranks the third leading cause of cancer deaths with a dismal 5-year survival rate. The mitogen-activated protein kinase (MAPK) signaling pathway is abnormally activated in HCC to promote growth and aggressive metastatic potential of cancer cells. Therefore, genetic variants in the MAPK signaling pathway may serve as potential predictors of Hepatitis B virus (HBV)-related HCC survival. In the present study, we performed a two-stage survival analysis to evaluate the associations between 10,912 single nucleotide polymorphisms (SNPs) in 79 MAPK signaling pathway genes and the overall survival (OS) of 866 HBV-related HCC patients, followed by functional annotation. In combined datasets, we identified two novel and potential functional SNPs (RPS6KA4 rs600377 T>G and MAP2K5 rs17300363 A>C) as prognostic factors for HBV-related HCC, with adjusted allelic hazards ratios of 1.24 (95% confidence interval [CI] = 1.05-1.46, p = 0.010) and 1.48 (1.15-1.91, p = 0.001), respectively. Furthermore, their combined risk genotypes also predicted a poor survival in a dose-response manner in the combined data set (P trend  < 0.001). Additional functional analysis showed that RPS6KA4 rs600377 G and MAP2K5 rs17300363 C alleles were associated with elevated mRNA expression levels of the corresponding genes in normal tissues. These results provide new insights into the role of genetic variants in the MAPK signaling pathway genes in HBV-related HCC survival., (© 2023 Wiley Periodicals LLC.)

Observational studies have reported associations between circulating biomarkers related to cardiovascular disease and the survival of patients with hepatocellular carcinoma. However, the relationship between these biomarkers and survival remains controversial. We conducted a two-sample Mendelian randomization analysis to investigate possible causal associations between cardiovascular disease biomarkers and hepatocellular carcinoma survival. Genetic risk scores, calculated using individual-level data from 866 cases of hepatitis B virus-related hepatocellular carcinoma in Guangxi, were utilized as proxies for four cardiovascular disease biomarkers: C-reactive protein, Apolipoprotein A-1, Cystatin C, and Lipoprotein(a). Associations between the genetic scores and survival were analyzed using Cox regression. The inverse-variance weighted method was used to estimate the summary statistics for the biomarkers and survival. Considering the multiple comparisons, the statistical significance was set at P < 0.0125. We observed a significant risk signal between genetically increased Cystatin C levels and poorer survival in hepatocellular carcinoma (HR for genetic scores = 1.29, 95% CI = 1.02-1.64; HR for inverse-variance weighted = 2.60, 95% CI = 1.45-4.65). Furthermore, we found a causal relationship of genetically determined Cystatin C and Lipoprotein(a) level with the survival of hepatocellular carcinoma patients with embolus. Our findings indicated the causal effects of increased levels of Cystatin C and Lipoprotein(a) on poorer survival in hepatocellular carcinoma., Competing Interests: None., (AJCR Copyright © 2023.)

Background: Super-enhancer (SE) refers to a regulatory element with super transcriptional activity, which can enrich transcription factors and drive gene expression. SE-related genes play an important role in the pathogenesis of malignant tumors, including hepatocellular carcinoma (HCC)., Methods: The SE-related genes were obtained from the human super-enhancer database (SEdb). Data from the transcriptome analysis and related clinical information with HCC were obtained from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) database. The upregulated SE-related genes from TCGA-LIHC were identified by the DESeq2R package. Multivariate Cox regression analysis was used to construct a four-gene prognostic signature. According to the median risk score, HCC patients were divided into high-risk and low-risk group patients., Results: The Kaplan-Meier (KM) curve showed that a significantly worse prognosis was found for the high-risk group ( P <0.001). In the TCGA-LIHC dataset, the area under the curve (AUC) values were 0.737, 0.662, and 0.667 for the model predicting overall survival (OS) over 1-, 3-, and 5- years, respectively, indicating the good prediction ability of our prediction model. This model's prognostic value was further validated in the LIRI-JP dataset and HCC samples (n=65). Furthermore, we found that higher infiltration level of M0 macrophages and upregulated of CTLA4 and PD1 in the high-risk group, implying that immunotherapy could be effective for those patients., Conclusion: These results provide further evidence that the unique SE-related gene model could accurately predict the prognosis of HCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wei, Zhou, Long, Lin, Qiu, Chen, Huang, Qiu, Jiang, Wen, Liu, Li, Nong, Guo, Yu and Zhou.)

With a younger tendency in morbidity age, endometrial cancer (EC) incidence has grown year after year. Worse, even more commonly occurring is endometrial hyperplasia (EH), which is a precancerous endometrial proliferation. For young women with early EC and EH who want to preserve fertility, progestin therapy has been utilized as a routine fertility-preserving treatment approach. Nevertheless, progestin medication failure in some patients is mostly due to progestin resistance and side effects. In order to further analyze the potential mechanisms of progestin resistance in EH and EC, to provide theoretical support for effective therapeutic strategies, and to lay the groundwork for searching novel treatment approaches, this article reviews the current therapeutic effects of progestin in EH and EC, as well as the mechanisms and molecular biomarkers of progestin resistance, and systematically expounds on the potential therapeutic methods to overcome progestin resistance.

Research Question: What is the effect of letrozole use in patients undergoing frozen embryo transfer (FET) with normal ovulation? Although the number of FETs is increasing, an optimal protocol for FET (particularly vitrified-warmed embryo transfer) is yet to be determined. The aim of this study was to evaluate letrozole use on patients with normal menstrual cycles compared with hormone replacement therapy (HRT) cycles and natural cycles., Design: The study involved 2849 patients. Patients were divided into three groups: HRT cycle (n = 2115), letrozole cycle (n = 532) and natural cycle (n = 202). Inverse probability of treatment weighting aimed to equate each group according to measured baseline covariates to achieve a comparison with reduced selection bias and live birth rate as main pregnancy outcome was analysed., Results: In the crude analysis, the letrozole group had a higher live birth rate compared with the HRT cycle (OR 1.18, 95% CI 1.06 to 1.33) and natural cycle (OR 1.24, 95% CI 1.11 to 1.41); after adjusting for confounding factors, live birth rate was consistently higher in the letrozole group. Moreover, the biochemical pregnancy, clinical pregnancy, ongoing pregnancy and full-term delivery rates were higher in the letrozole group., Conclusion: For infertile women with normal menstrual cycle undergoing FET, mildly stimulated cycles with letrozole present a relatively large advantage compared with HRT cycle and natural cycle, with higher live birth pregnancy, indicating that letrozole administration could improve pregnancy outcomes in this population., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Immunological-related genes (IRGs) play a critical role in the immune microenvironment of tumors. Our study aimed to develop an IRG-based survival prediction model for hepatocellular carcinoma (HCC) patients and to investigate the impact of IRGs on the immune microenvironment., Methods: Differentially expressed IRGs were obtained from The Genomic Data Commons Data Portal (TCGA) and the immunology database and analysis portal (ImmPort). The univariate Cox regression was used to identify the IRGs linked to overall survival (OS), and a Lasso-regularized Cox proportional hazard model was constructed. The International Cancer Genome Consortium (ICGC) database was used to verify the prediction model. ESTIMATE and CIBERSORT were used to estimate immune cell infiltration in the tumor immune microenvironment (TIME). RNA sequencing was performed on HCC tissue specimens to confirm mRNA expression., Results: A total of 401 differentially expressed IRGs were identified, and 63 IRGs were found related to OS on the 237 up-regulated IRGs by univariate Cox regression analyses. Finally, five IRGs were selected by the LASSO Cox model, including SPP1 , BIRC5 , STC2 , GLP1R , and RAET1E . This prognostic model demonstrated satisfactory predictive value in the ICGC dataset. The risk score was an independent predictive predictor for OS in HCC patients. Immune-related analysis showed that the immune infiltration level in the high-risk group was higher, suggesting that the 5-IRG signature may play an important role in mediating immune escape and immune resistance in the TIME of HCC. Finally, we confirmed the 5-IRG signature is highly expressed in 65 HCC patients with good predictive power., Conclusion: We established and verified a new prognosis model for HCC patients based on survival-related IRGs, and the signature could provide new insights into the prognosis of HCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Long, Zhou, Wei, Lin, Qiu, Zhou, Chen, Jiang, Wen, Liu, Li, Zhou and Yu.)

Objective: To examine the efficacy of gonadotropin releasing hormone (GnRH) antagonist (GnRH-ant) protocol and the long GnRH agonist (GnRH-a) protocol during in vitro fertilization (IVF) therapy in patients with severe male infertile factors., Methods: A total of 983 women with severe male factor infertility undergoing IVF therapy from 2017 to 2020 at one center were retrospectively analyzed. Patients were divided into the GnRH-ant group (n=527) and the GnRH-a group (n=456) according to their ovarian stimulation protocols. Patient baseline characteristics, ovarian stimulation characteristics, and clinical pregnancy outcomes were compared between the groups. The live birth rate was considered the main pregnancy outcome., Results: GnRH-a group had a higher live birth rate compared with the GnRH-ant group (41.0% versus 31.3%, p=0.002). Moreover, the implantation (32.8% vs. 28.1%, p=0.033), biochemical pregnancy (52.4% versus 44.8%, p=0.017), clinical pregnancy (49.3% versus 39.7%, p=0.002) and ongoing pregnancy rates (43.2% vs. 34.9%, p=0.008) were higher in GnRH-a group. For patients with one embryo transferred, the GnRH-a group demonstrated higher live birth (37.0% vs. 19.4%, p=0.010) and ongoing pregnancy rate (38.9% vs. 24.5%, p=0.046) than the GnRH-ant group. Among patients with two embryos transferred, the live birth rate was also higher in the GnRH-a group than in the GnRH-ant group, with no statistical difference. No significant differences were observed in the biochemical abortion rate, clinical miscarriage rate, early miscarriage rate, late miscarriage rate, heterotopic pregnancy rate, twin pregnancy rate, and birth sex ratio between the two groups., Conclusion: For individuals with severe male infertility undergoing IVF, the GnRH-a protocol is considered a more efficient and feasible strategy with a higher live birth rate compared to the GnRH-ant protocol, especially in single embryo transfer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lv, Yu, Chen, Xiao, Lou, Luo, Yuan, Xu, Feng, Bai, Zhang and Li.)

Objective: This study aimed to examine the efficacy of HRT with gonadotropin-releasing hormone agonist (GnRH-a) pre-treatment in women with male-factor infertility who underwent a frozen embryo transfer (FET) programme., Design: Between January 2016 and October 2020, 2733 women with male-factor infertility who underwent the HRT protocol as the endometrial preparation method were enrolled at two Reproductive Medicine Centres. Patients were divided into two groups based on whether they had GnRH-a pre-treatment before HRTs: the GnRHa-HRT group and the HRT group. The inverse probability of treatment weighting (IPTW) method was conducted to balance patient baseline characteristics between treatment cohorts to reduce selection bias. The live birth rate was considered regarded as the primary pregnancy outcome., Results: Multivariate logistic regression adjusted for confounding factors, the GnRHa-HRT group showed a notably higher rate of live birth (OR 2.154, 95% CI 1.636~2.835, P<0.001) when compared to the HRT group. Additionally, the rate of miscarriage was significantly lower in the GnRHa-HRT group. The GnRHa-HRT group had significantly higher rates of biochemical pregnancy, clinical pregnancy, multiple pregnancy, and term birth., Conclusion: The endometrial preparation protocol of HRT with GnRH-a pre-treatment could obviously increase the live birth rate for women with male-factor infertility undergoing the FET programme., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yu, Chen, Luo, Lv, Lou, Xiao, Wang, Chen, Bai and Zhang.)

Current biopharmaceutical drugs are mainly a class of peptides or proteins that play an essential role in the treatment of many diseases. Such peptides/proteins are usually thermally unstable and may lose their bioactivity when exposed to ambient conditions. Therefore, they are not suitable for long-term storage. Lyophilisation is the most common method to prolong shelf life of solid peptide/protein drugs; however, the freeze-drying process can lead to irreversible damage. In the present study, human interferon-alpha 2a (IFN-α2a) was selected as a model protein drug; four disaccharides (β-lactose, β-maltose, sucrose, and trehalose) were selected as bioactive protectants. We investigated the effects of different protectants on IFN-α2a under various ambient conditions (vacuum, dry state, and aqueous solution) using replica exchange molecular dynamics simulation. The protective effect of β-maltose on IFN-α2a was the highest in aqueous solution and dry state, β-lactose showed a poor protective effect in all three conditions, the performance of sucrose was good in all conditions, and trehalose showed a better protective effect under vacuum conditions and in aqueous solution. Disaccharides form H-bonds with water, thereby preventing water from the tertiary structure of proteins. Trehalose forms strong H-bonds with water which explains its extraordinary stability., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The novel coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread worldwide for almost 2 years. It starts from viral adherence to host cells through an interaction between spike glycoprotein 1 (S1) containing a receptor-binding domain (RBD) and human angiotensin-converting enzyme-2 (ACE2). One of the useful strategies to prevent SARS-CoV-2 infection is to inhibit the attachment of RBD to ACE2. Therefore, the current work proposed potent peptides against SARS-CoV-2 infection by carrying out MM-PBSA calculation based on the binding of 52 antiviral peptides (AVPs) to RBD. Considering the binding free energies of AVPs to RBD, cyanovirin-N (CV-N) showed the strongest RBD binding affinity among 52 AVPs. Upon structural analysis of RBD complex with CV-N, it was observed that 12 of the 13 key residues of RBD binding to ACE2 were hijacked by CV-N. CV-N bound to RBD at a smaller affinity of 14.9 nM than that of ACE2 and inhibited the recruitment of S1 to human alveolar epithelial cells. Further analysis revealed that CV-N suppressed SARS-CoV-2 S pseudovirion infection with a half-maximal inhibitory concentration (IC 50 ) of 18.52 μg/mL. This study demonstrated a drug screening for AVPs against SARS-CoV-2 and discovered a peptide with inspiring antiviral properties, which provided a promising strategy for the COVID-19 therapeutic approach., (© 2021. International Association of Scientists in the Interdisciplinary Areas.)

The coronavirus (COVID-19) pandemic is still spreading all over the world. As reported, angiotensin-converting enzyme-2 (ACE2) is a receptor of SARS-CoV-2 spike protein that initializes viral entry into host cells. Previously, the human defensin 5 (HD5) has been experimentally confirmed to be functional against the SARS-CoV-2. The present study proposes a human cathelicidin known as LL37 that strongly binds to the carboxypeptidase domain of human ACE2 compared to HD5. Therefore, LL37 bears a great potential to be tested as an anti-SARS-CoVD-2 peptide. We investigated the molecular interactions formed between the LL37 and ACE2 as well as HD5 and ACE2 tailed by their thermodynamic stability. The MM-PBSA and free energy landscape analysis outcomes confirmed its possible inhibitory effect against the SARS-CoV-2. The results obtained here could help propose a promising therapeutic strategy against the havoc caused by SARS-CoV-2 infections., (© 2021. International Association of Scientists in the Interdisciplinary Areas.)

SARS-CoV-2 infection begins with the association of its spike 1 (S1) protein with host angiotensin-converting enzyme-2 (ACE2). Targeting the interaction between S1 and ACE2 is a practical strategy against SARS-CoV-2 infection. Herein, we show encouraging results indicating that human cathelicidin LL37 can simultaneously block viral S1 and cloak ACE2. LL37 binds to the receptor-binding domain (RBD) of S1 with high affinity (11.2 nM) and decreases subsequent recruitment of ACE2. Owing to the RBD blockade, LL37 inhibits SARS-CoV-2 S pseudovirion infection, with a half-maximal inhibitory concentration of 4.74 μg/mL. Interestingly, LL37 also binds to ACE2 with an affinity of 25.5 nM and cloaks the ligand-binding domain (LBD), thereby decreasing S1 adherence and protecting cells against pseudovirion infection in vitro . Intranasal administration of LL37 to C57 mice infected with adenovirus expressing human ACE2 either before or after pseudovirion invasion decreased lung infection. The study identified a versatile antimicrobial peptide in humans as an inhibitor of SARS-CoV-2 attachment using dual mechanisms, thus providing a potential candidate for coronavirus disease 2019 (COVID-19) prevention and treatment.

Background: As a key component in artificial intelligence computing, a transistor design is updated here as a potential alternative candidate for artificial synaptic behavior implementation. However, further updates are needed to better control artificial synaptic behavior. Here, an updated channel-electrode transistor design is proposed as an artificial synapse device; this structure is different from previously published designs by other groups., Methods: A semiconductor characterization system was used in order to simulate the artificial synaptic behavior and a scanning electron microscope was used to characterize the device structure., Results: It was found that the electrode added to the transistor channel had a strong impact on the representative transmission behavior of such artificial synaptic devices, such as excitatory postsynaptic current (EPSC) and the paired-pulse facilitation (PPF) index., Conclusion: These behaviors were tuned effectively and the impact of the channel electrode is explained by the combined effects of the joint channel electrode and conventional gate. The voltage dependence of such oxide devices suggests more capability to emulate various synaptic behaviors for numerous medical and non-medical applications. This is extremely helpful for future neuromorphic computational system implementation., Competing Interests: The authors report no conflicts of interest in this manuscript., (© 2020 Qi et al.)

Hepatocellular carcinoma (HCC) is worldwide accepted most common malignancies, as well as the second major cause of death among Chinese with cancer. There is an increasing evidence that could prove the potential effect of long non-coding RNAs (lncRNAs) to the biological performance of HCC. In present study, with high expression level in The Cancer Genome Atlas (TCGA) HCC samples, lncRNA MFI2 Antisense RNA 1 (MFI2-AS1) was closely related to poor prognosis and advanced stage among patients with HCC. In addition, up-regulation of MFI2-AS1 was further comfirmed in HCC tissues and HCC cell line. Ectopic expression of MFI2-AS1 stimulated the proliferation and metastasis of HCC cells, but knockdown MFI2-AS1 suppressed HCC cell proliferation and metastasis, indicating that MFI2-AS1 exerted oncogenic functions in the tumorigenesis of HCC. Simultaneously, compared with the negative control group, xenograft tumors in MFI2-AS1 group were characterized with poor growth, smaller volumes and less liver metastases. The post-transcriptional regulation of FOXM1 by MFI2-AS1 occured mechanistically, playing a role of competing with endogenous RNA (ceRNA) in HCC to sponge miR-134. Over-expression of MFI2-AS1 increased FOXM1 expression both at mRNA and protein level, whereas it was reducd by miR-134. Meanwhile, knockdown of miR-134 abolished the repression of shMFI2-AS1 on FOXM1 expression. Furthermore, we demonstrated that miR-134 reverses the impact of MFI2-AS1 on HCC proliferation and metastasis through regulation on FOXM1. Collectively, we determined that MFI2-AS1 crucially acted in HCC progression via functioning as miR-134 sponge to upregulating FOXM1 expression, and was conducive to the promotion of better understanding the direct diagnostics and iatreusiology of lncRNA in HCC., Competing Interests: Declaration of Competing Interest The authors confirm that there are no conflicts of interest., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Logic functions are the key backbone in electronic circuits for computing applications. Complementary metal-oxide-semiconductor (CMOS) logic gates, with both n-type and p-type channel transistors, have been to date the dominant building blocks of logic circuitry as they carry obvious advantages over other technologies. Important physical limits are however starting to arise, as the transistor-processing technology has begun to meet scaling-down difficulties. To address this issue, there is the crucial need for a next-generation electronics era based on new concepts and designs. In this respect, a single-type channel multigate MOS transistor (SMG-MOS) is introduced holding the two important aspects of processing adaptability and low static dissipation of CMOS. Furthermore, the SMG-MOS approach strongly reduces the footprint down to 40% or even less area needed for current CMOS logic function in the same processing technology node. Logic NAND, NOT, AND, NOR, and OR gates, which typically require a large number of CMOS transistors, can be realized by a single SMG-MOS transistor. Two functional examples of SMG-MOS are reported here with their analysis based both on simulations and experiments. The results strongly suggest that SMG-MOS can represent a facile approach to scale down complex integrated circuits, enabling design flexibility and production rates ramp-up., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. Published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.)

Amorphous nano oxides (AO) are intriguing advanced materials for a wide variety of nanosystem medical applications including serving as biosensors devices with p-n junctions, nanomaterial-enabled wearable sensors, artificial synaptic devices for AI neurocomputers and medical mimicking research. However, p-type AO with reliable electrical properties are very difficult to obtain according to the literature. Based on the oxide thin film transistor, a phenomenon that could change an n-type material into a p-type semiconductor is proposed and explained here. The typical In-Ga-Zn-O material has been reported to be an n-type semiconductor, which can be changed by physical conditions, such as in processing or bias. In this way, here, we have identified a manner to change nano material electrical properties among n-type and p-type semiconductors very easily for medical application like biosensors in artificial skin., Competing Interests: The authors report no conflicts of interest in this work., (© 2019 Chen et al.)

Although intracranial ependymoma is relatively rare, it is often associated with great clinical aggressiveness and poor overall survival. There are controversies over factors affecting the prognosis of the disease. The aim of this retrospective study was to evaluate factors that may affect the therapeutic outcome and prognosis of intracranial ependymoma by reviewing the medical records of 49 patients who were surgically treated in our hospital between 2001 and 2014. Univariate and multivariate analyses were performed to identify prognostic variables relative to patient and tumor characteristics, and treatment modalities. All 49 patients (24 men and 25 women; mean age 27.6 years) underwent surgical resection, of whom 14 patients also underwent postoperative radiotherapy. Local recurrence was found in 15 (48.8 %) patients, and 22 (51.2 %) patients died during the follow-up periods. The 5-year recurrence rate was 65 % and the survival rate was 51 %. The results of statistical analysis suggested that preoperative extraventricular drainage and surgical resection extent were prognostic factors related to progression-free survival, and that age, surgical resection extent and histological grade were closely associated with survival. Interestingly, there was a significant correlation between the symptom of hydrocephalus and age (P = 0.010), and patients with a better clinical status (KPS ≥ 80) were significantly associated with a lower WHO grade (P = 0.007). In conclusion, we confirmed that surgical resection extent was the major independent factor affecting both recurrence and survival of patients with intracranial ependymoma, while age and WHO grade were prognostic factors affecting survival but not recurrence.

The aim of this study was to elucidate the role of treatment modalities in primary spinal anaplastic ependymomas (PSAE) and identify promising prognostic factors. PSAE are rare tumors of the central nervous system with poorly understood clinical characteristics and treatment outcomes. We reviewed the literature in PubMed, Web of Science and Scopus databases to identify patients with PSAE. Multivariate Cox proportional hazards analysis and univariate Kaplan-Meier analysis were performed on the PSAE patients and overall survival (OS) and progression-free survival (PFS) were assessed to evaluate the clinical outcomes. Of the 40 patients with PSAE, the tumors were mostly intramedullary (n=19; 47.5%) and frequently involved the thoracic cord (n=25; 62.5%). Eighteen patients suffered recurrence during the follow-up with a median PFS of 24 months. The 1, 2, and 5year OS rates of the PSAE patients were 91.5%, 82.1%, and 63.1%, respectively. Gross total resection (GTR) was independently associated with prolonged PFS (hazard ratio [HR] 0.11; p=0.004) and OS (HR 0.11; p=0.003) in the multivariate analysis. Adjuvant radiotherapy also conferred improved PFS (HR 0.15; p=0.008) and OS (HR 0.16; p=0.022). Age, sex, tumor location and chemotherapy did not influence the outcomes in this group. The results of our study suggest that GTR and adjuvant radiotherapy are strong prognostic indicators in patients with PSAE and the role of chemotherapy is yet to be defined., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Polymorphisms in interleukin (IL)-4/IL-13 pathway genes have previously been reported to be associated with glioma susceptibility, although results are inconsistent. We therefore performed an updated meta-analysis to determine a more precise estimation of this relationship. Twelve eligible studies were identified by searching PubMed, EMBASE, Web of Science, and the Cochrane Library electronic databases. Nine polymorphisms in genes within the IL-4/IL-13 pathway (IL-4 rs2243250, rs2070874, rs2243248, IL-4R rs1805011, rs1805012, rs1805015, rs1801275, and IL-13 rs20541 and rs1800925) were assessed for their relationship with glioma risk by computing odds ratios (ORs) and corresponding 95 % confidence intervals (CIs). Akaike's information criterion (AIC) was used to identify the best genetic model for each polymorphism. No association between IL-4/IL-13 pathway genetic polymorphisms and glioma risk was observed in the overall population, although a significant association was found between rs2234248 and glioblastoma when stratified by histological subtype (log-additive model, OR 1.57, 95 % CI 1.11-2.24). This meta-analysis therefore suggested that IL-4/IL-13 pathway genetic polymorphisms are not associated with glioma risk.

Short interspersed elements, such as Alu elements, have propagated to more than one million copies in the human genome. They affect the genome in several ways, caused by retrotransposition, recombination between elements, gene conversion, and alterations in gene expression. These events, including novel insertions into active genes, have been associated with a number of human disorders. Hemophilia A is an X-linked severe bleeding disorder and is caused by mutations in the Factor VIII gene. The spectrum of mutations includes point mutations, rearrangements, insertions, and deletions. Recently, an Alu retrotransposition event in a coding exon has been reported in a family with a severe form of hemophilia A. This was the first report of an Alu insertion in the Factor VIII gene. Here, we report a second Alu insertion event that lies in an intron of the same gene that causes exon skipping and the complete disruption of gene expression.

Chemokines have received increasing attention due to their inhibitory activities on human immunodeficiency virus type-1 (HIV-1) and simian immunodeficiency virus (SIV) replication and the potential for chemokine receptors to assist in HIV-1/SIV entry into permissive cells. Besides CD4, which is the major receptor for HIV-1 and SIV, a number of chemokine receptors including but not limited to APJ, CCR3, CXCR4, and CCR5 may be coreceptors for HIV-1/SIV, not only in peripheral blood and lymphoid tissues but also in the central nervous system (CNS). The present studies reveal the lack of CD4, but the significant expression of various chemokine receptors, APJ, CCR3, CXCR4, and CCR5, plus C-type lectins DC-SIGN and L-SIGN on isolated primary human brain microvascular endothelial cells (MVECs). As these MVECs do not express CD4, this suggests a CD4-independent HIV/SIV entry/infection of these cells, which are the major cells constituting the human blood-brain barrier. We also found that chemokines for cognate chemokine receptors individually were unable to block binding of HIV-1 to brain MVECs. These results reveal that in primary isolated brain MVECs viral attachment is mediated by a possible previously unknown receptor(s) or by cooperative activity of various receptors. Moreover, mRNA transcripts for DC-SIGN/L-SIGN, as well as DC-SIGN protein expression, suggest the capability of MVECs to attach viral particles on cell surfaces, even though polyclonal antisera for DC-SIGN did not affect viral binding to these cells. These data will assist in further understanding lentiviral entry into the CNS., ((c) 2002 Elsevier Science (USA).)