Recent Progress of Low-Dimensional Metal-Organic Frameworks for Aqueous Zinc-Based Batteries.

Aqueous zinc-based batteries (AZBs) are promising energy storage solutions with remarkable safety, abundant Zn reserve, cost-effectiveness, and relatively high energy density. However, AZBs still face challenges such as anode dendrite formation that reduces cycling stability and limited cathode capacity. Recently, low-dimensional metal-organic frameworks (LD MOFs) and their derivatives have emerged as promising candidates for improving the electrochemical performance of AZBs owing to their unique morphologies, high structure tunability, high surface areas, and high porosity. However, clear guidelines for developing LD MOF-based materials for high-performance AZBs are scarce. In this review, the recent progress of LD MOF-based materials for AZBs is critically examined. The typical synthesis methods and structural design strategies for improving the electrochemical performance of LD MOF-based materials for AZBs are first introduced. The recent noteworthy research achievements are systematically discussed and categorized based on their applications in different AZB components, including cathodes, anodes, separators, and electrolytes. Finally, the limitations are addressed and the future perspectives are outlined for LD MOFs and their derivatives in AZB applications. This review provides clear guidance for designing high-performance LD MOF-based materials for advanced AZBs.

The profile of HIV-1 drug resistance in Shanghai, China: a retrospective study from 2017 to 2021.

BACKGROUND: HIV-1 drug resistance is a huge challenge in the era of ART. OBJECTIVES: To investigate the prevalence and characteristics of acquired HIV-1 drug resistance (ADR) in Shanghai, China. METHODS: An epidemiological study was performed among people living with human immunodeficiency virus (PLWH) receiving ART in Shanghai from January 2017 to December 2021. A total of 8669 PLWH were tested for drug resistance by genotypic resistance testing. Drug resistance mutations (DRMs) were identified using the Stanford University HIV Drug Resistance Database program. RESULTS: Ten HIV-1 subtypes/circulating recombinant forms (CRFs) were identified, mainly including CRF01_AE (46.8%), CRF07_BC (35.7%), B (6.4%), CRF55_01B (2.8%) and CRF08_BC (2.4%). The prevalence of ADR was 48% (389/811). Three NRTI-associated mutations (M184V/I/L, S68G/N/R and K65R/N) and four NNRTI-associated mutations (V179D/E/T/L, K103N/R/S/T, V106M/I/A and G190A/S/T/C/D/E/Q) were the most common DRMs. These DRMs caused high-level resistance to lamivudine, emtricitabine, efavirenz and nevirapine. The DRM profiles appeared to be significantly different among different subtypes. CONCLUSIONS: We revealed HIV-1 subtype characteristics and the DRM profile in Shanghai, which provide crucial guidance for clinical treatment and management of PLWH.

Rheumatoid arthritis patients harbour aberrant enteric bacteriophages with autoimmunity-provoking potential: a paired sibling study.

OBJECTIVES: Viruses have been considered as important participants in the development of rheumatoid arthritis (RA). However, the profile of enteric virome and its role in RA remains elusive. This study aimed to investigate the atlas and involvement of virome in RA pathogenesis. METHODS: Faecal samples from 30 pairs of RA and healthy siblings that minimise genetic interferences were collected for metagenomic sequencing. The α and ß diversity of the virome and the virome-bacteriome interaction were analysed. The differential bacteriophages were identified, and their correlations with clinical and immunological features of RA were analysed. The potential involvement of these differential bacteriophages in RA pathogenesis was further investigated by auxiliary metabolic gene annotation and molecular mimicry study. The responses of CD4+ T cells and B cells to the mimotopes derived from the differential bacteriophages were systemically studied. RESULTS: The composition of the enteric bacteriophageome was distorted in RA. The differentially presented bacteriophages correlated with the immunological features of RA, including anti-CCP autoantibody and HLA-DR shared epitope. Intriguingly, the glycerolipid and purine metabolic genes were highly active in the bacteriophages from RA. Moreover, peptides of RA-enriched phages, in particular Prevotella phage and Oscillibacter phage could provoke the autoimmune responses in CD4+ T cells and plasma cells via molecular mimicry of the disease-associated autoantigen epitopes, especially those of Bip. CONCLUSIONS: This study provides new insights into enteric bacteriophageome in RA development. In particular, the aberrant bacteriophages demonstrated autoimmunity-provoking potential that would promote the occurrence of the disease.

Surfactant-Aided Stabilization of Individual Carbon Nanotubes in Water around the Critical Micelle Concentration.

Surfactants are widely used to disperse single-walled carbon nanotubes (SWCNTs) and other nanomaterials for liquid-phase processing and characterization. Traditional techniques, however, demand high surfactant concentrations, often in the range of 1-2 wt/v% of the solution. Here, we show that optimal dispersion efficiency can be attained at substantially lower surfactant concentrations of approximately 0.08 wt/v%, near the critical micelle concentration. This unexpected observation is achieved by introducing "bare" nanotubes into water containing the anionic surfactant sodium deoxycholate (DOC) through a superacid-surfactant exchange process that eliminates the need for ultrasonication. Among the diverse ionic surfactants and charged biopolymers explored, DOC exhibits the highest dispersion efficiency, outperforming sodium cholate, a structurally similar bile salt surfactant containing just one additional oxygen atom compared to DOC. Employing all-atomistic molecular dynamics simulations, we unravel that the greater stabilization by DOC arises from its higher binding affinity to nanotubes and a substantially larger free energy barrier that resists nanotube rebundling. Further, we find that this barrier is nonelectrostatic in nature and does not obey the classical Derjaguin-Landau-Verwey-Overbeek (DLVO) theory of colloidal stability, underscoring the important role of nonelectrostatic dispersion and hydration interactions at the nanoscale, even in the case of ionic surfactants like DOC. These molecular insights advance our understanding of surfactant chemistry at the bare nanotube limit and suggest low-energy, surfactant-efficient solution processing of SWCNTs and potentially other nanomaterials.

Rapid detection of four major HFMD-associated enteroviruses by multiplex HiFi-LAMP assays.

Hand, foot, and mouth disease (HFMD) caused by various enteroviruses is a major public health concern globally. Human enterovirus 71(EVA71), coxsackievirus A16 (CVA16), coxsackievirus A6 (CVA6), and coxsackievirus A10 (CVA10) are four major enteroviruses responsible for HFMD. Rapid, accurate, and specific point-of-care (POC) detection of the four enteroviruses is crucial for the prevention and control of HFMD. Here, we developed two multiplex high-fidelity DNA polymerase loop-mediated isothermal amplification (mHiFi-LAMP) assays for simultaneous detection of EVA71, CVA16, CVA6, and CVA10. The assays have good specificity and exhibit high sensitivity, with limits of detection (LOD) of 11.2, 49.6, 11.4, and 20.5 copies per 25 µL reaction for EVA71, CVA16, CVA6, and CVA10, respectively. The mHiFi-LAMP assays showed an excellent clinical performance (sensitivity 100.0%, specificity 83.3%, n = 47) when compared with four singleplex RT-qPCR assays (sensitivity 93.1%, specificity 100%). In particular, the HiFi-LAMP assays exhibited better performance (sensitivity 100.0%, specificity 100%) for CVA16 and CVA6 than the RT-qPCR assays (sensitivity 75.0-92.3%, specificity 100%). Furthermore, the mHiFi-LAMP assays detected all clinical samples positive for the four enteroviruses within 30 min, obviously shorter than about 1-1.5 h by the RT-qPCR assays. The new mHiFi-LAMP assays can be used as a robust point-of-care testing (POCT) tool to facilitate surveillance of HFMD at rural and remote communities and resource-limited settings.

Novel Circovirus in Blood from Intravenous Drug Users, Yunnan, China.

We identified a novel circovirus (human-associated circovirus 2 [HuCV2]) from the blood of 2 intravenous drug users in China who were infected with HIV-1, hepatitis C virus, or both. HuCV2 is most closely related to porcine circovirus 3. Our findings underscore the risk for HuCV2 and other emerging viruses among this population.

Metal Selenide-Based Superstructure Nanoarrays with Ultrahigh Capacity for Alkaline Zn Batteries.

Transition metal selenides (TMSs) have great potential as cathode materials for alkaline Zn batteries (AZBs) owing to their high theoretical capacity and metallic conductivity. However, achieving a high specific capacity remains a formidable challenge due to the low structural stability and sluggish reaction kinetics of single-phase TMS. Herein, a facile method for fabricating a robust CoSe2 @Ni3 Se4 @Ni(OH)2 superstructure nanoarray (CNSNA) as an AZB cathode is presented. The sophisticated design enables structural stability and abundant active surface sites for efficient charge storage. Furthermore, the redox mediator K3 [Fe(CN)6 ] is employed to expedite the reaction kinetics and introduce supplementary redox reactions, further enhancing the charge storage capability. Consequently, the CNSNA electrode delivers an exceptional specific capacitance (609.08 mAh g-1 at 1 A g-1 ), surpassing all previously reported selenide-based materials. High-rate capability (239.37 mAh g-1 at 20 A g-1 ) and long cycling stability have also been achieved. The comprehensive charge storage mechanism studies confirmed the structural integrity, kinetic improvement, and high reactivity of the CNSNA superstructure. Moreover, the corresponding AZB based on CNSNA demonstrates an extraordinarily high energy density of 516.58 Wh kg-1 . The work offers guidance in the construction of superstructure-based TMS electrode materials, paving the way for the development of high-performance AZBs.

Brentuximab vedotin in combination with nivolumab in relapsed or refractory Hodgkin lymphoma: 3-year study results.

This phase 1-2 study evaluated brentuximab vedotin (BV) combined with nivolumab (Nivo) as first salvage therapy in patients with relapsed/refractory (r/r) classical Hodgkin lymphoma (cHL). In parts 1 and 2, patients received staggered dosing of BV and Nivo in cycle 1, followed by same-day dosing in cycles 2 to 4. In part 3, both study drugs were dosed, same day, for all 4 cycles. At end of study treatment, patients could undergo autologous stem cell transplantation (ASCT) per investigator discretion. The objective response rate (ORR; N = 91) was 85%, with 67% achieving a complete response (CR). At a median follow-up of 34.3 months, the estimated progression-free survival (PFS) rate at 3 years was 77% (95% confidence interval [CI], 65% to 86%) and 91% (95% CI, 79% to 96%) for patients undergoing ASCT directly after study treatment. Overall survival at 3 years was 93% (95% CI, 85% to 97%). The most common adverse events (AEs) prior to ASCT were nausea (52%) and infusion-related reactions (43%), all grade 1 or 2. A total of 16 patients (18%) had immune-related AEs that required systemic corticosteroid treatment. Peripheral blood immune signatures were consistent with an activated T-cell response. Median gene expression of CD30 in tumors was higher in patients who responded compared with those who did not. Longer-term follow-up of BV and Nivo as a first salvage regimen shows durable efficacy and impressive PFS, especially in patients who proceeded directly to transplant, without additional toxicity concerns. This trial was registered at www.clinicaltrials.gov as #NCT02572167.

Longitudinal immune profiling reveals dominant epitopes mediating long-term humoral immunity in COVID-19-convalescent individuals.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly pathogenic and contagious coronavirus that caused a global pandemic with 5.2 million fatalities to date. Questions concerning serologic features of long-term immunity, especially dominant epitopes mediating durable antibody responses after SARS-CoV-2 infection, remain to be elucidated. OBJECTIVE: We aimed to dissect the kinetics and longevity of immune responses in coronavirus disease 2019 (COVID-19) patients, as well as the epitopes responsible for sustained long-term humoral immunity against SARS-CoV-2. METHODS: We assessed SARS-CoV-2 immune dynamics up to 180 to 220 days after disease onset in 31 individuals who predominantly experienced moderate symptoms of COVID-19, then performed a proteome-wide profiling of dominant epitopes responsible for persistent humoral immune responses. RESULTS: Longitudinal analysis revealed sustained SARS-CoV-2 spike protein-specific antibodies and neutralizing antibodies in COVID-19 patients, along with activation of cytokine production at early stages after SARS-CoV-2 infection. Highly reactive epitopes that were capable of mediating long-term antibody responses were shown to be located at the spike and ORF1ab proteins. Key epitopes of the SARS-CoV-2 spike protein were mapped to the N-terminal domain of the S1 subunit and the S2 subunit, with varying degrees of sequence homology among endemic human coronaviruses and high sequence identity between the early SARS-CoV-2 (Wuhan-Hu-1) and current circulating variants. CONCLUSION: SARS-CoV-2 infection induces persistent humoral immunity in COVID-19-convalescent individuals by targeting dominant epitopes located at the spike and ORF1ab proteins that mediate long-term immune responses. Our findings provide a path to aid rational vaccine design and diagnostic development.

An HFman probe-based reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for HIV-1 detection.

Loop-mediated isothermal amplification (LAMP) is suitable for the development of a rapid and cost-effective nucleic acid technique for point of care (POC) applications. However, LAMP methods often generate non-specific amplification, therefore inevitably resulting in false positive results especially when sequence-independent dyes are used to indirectly reflect the results. In this study, we established and optimized a reverse transcription LAMP (RT-LAMP) assay with a high-fidelity DNA polymerase-mediated fluorescent probe (HFman probe) for human immunodeficiency virus-1 (HIV-1) detection. The assay showed high sensitivity and specificity. Using 101 plasma samples with different HIV-1 viral load, we demonstrated that our assay can detect the major HIV-1 subtypes circulating in China, including CRF01_AE, CRF07_BC, CRF08_BC, CRF55_01B, and unique recombinant forms (URFs). We also compared our assay with an approved commercial real-time quantitative polymerase chain reaction (RT-qPCR) kit and found the sensitivity, specificity and consistency was 88.8%, 100% and 89.1%, respectively. The HFman probe-based RT-LAMP assay is a high specific detection method that is rapid, variant-tolerant and simple to operate, and thus is of great significance for timely disclosure of HIV status and rapid POC diagnosis.

High Quality Coal Foreign Object Image Generation Method Based on StyleGAN-DSAD.

Research on coal foreign object detection based on deep learning is of great significance to safe, efficient, and green production of coal mines. However, the foreign object image dataset is scarce due to collection conditions, which brings an enormous challenge to coal foreign object detection. To achieve augmentation of foreign object datasets, a high-quality coal foreign object image generation method based on improved StyleGAN is proposed. Firstly, the dual self-attention module is introduced into the generator to strengthen the long-distance dependence of features between spatial and channel, refine the details of the generated images, accurately distinguish the front background information, and improve the quality of the generated images. Secondly, the depthwise separable convolution is introduced into the discriminator to solve the problem of low efficiency caused by the large number of parameters of multi-stage convolutional networks, to realize the lightweight model, and to accelerate the training speed. Experimental results show that the improved model has significant advantages over several classical GANS and original StyleGAN in terms of quality and diversity of the generated images, with an average improvement of 2.52 in IS and a decrease of 5.80 in FID for each category. As for the model complexity, the parameters and training time of the improved model are reduced to 44.6% and 58.8% of the original model without affecting the generated images quality. Finally, the results of applying different data augmentation methods to the foreign object detection task show that our image generation method is more effective than the traditional methods, and that, under the optimal conditions, it improves APbox by 5.8% and APmask by 4.5%.

Genomic phylogenetic analyses of four major hand, foot and mouth disease-related enteroviruses.

Enteroviruses had diverged into many types, some of which cause hand, foot and mouth disease (HFMD) in children. The predominant enterovirus types associated with HFMD are EVA71, CVA16, CVA6 and CVA10. Four enterovirus types were classified into subtypes based on VP1 sequences. However, the phylogenetics of these enteroviruses is rarely concerned at the genomic level. In this study, we performed the phylogenetic analyses of the EVA71, CVA16, CVA6 and CVA10 using available full-length genomic sequences. We found that the topologies of phylogenetic trees of full-length genomic sequences and VP1 sequences were almost consistent, except few subtypes of EVA71 and CVA10. The mean genetic divergence was 15.8-27% between subtypes and less than 12% within subtypes/sub-subtypes at genomic level. Comparison of phylogenetic topologies between genomic and VP1 sequences helped us to identify two new EVA71 inter-subtype recombinants RF01_CC4 and RF02_CC4. Furthermore, EVA71 subtypes C1 and C2 and CVA10 subtype D were found to originate through inter-subtype recombination. The genomic reference sequences of these enteroviruses are provided here for subtyping. The results provide important insights into the understanding of the evolution and epidemiology of the four enteroviruses. Keywords: enterovirus; hand; foot and mouth disease; classification; genetic distance; recombination.

A rapid variant-tolerant reverse transcription loop-mediated isothermal amplification assay for the point of care detection of HIV-1.

Human immunodeficiency virus (HIV) continues to be a major burden on public health globally with on-going increases in the number of new infections each year. Rapid and sensitive point-of-care tests allow timely interventions and are essential to control the spread of the disease. However the highly variable nature of the virus, resulting in the evolution of many subtypes and inter-subtype recombinants, poses important challenges for its diagnosis. Here we describe a variant-tolerant reverse-transcription RT-LAMP amplification of the virus's INT gene, providing a simple to use, rapid (<30 min) in vitro point-of-care diagnostic test with a limit of detection <18 copies/reaction. The assay was first validated in clinical studies of patient samples, using both established RT-LAMP and RT-qPCR assays for reference, with results showing that this new variant-tolerant HIV-1 RT-LAMP diagnostic test is highly sensitive without compromising its high specificity for HIV-1 subtypes. The diagnostic test was subsequently configured within an easy-to-read paper microfluidic lateral flow test and was validated clinically using patient samples, demonstrating its future potential for use in timely, effective, low cost HIV diagnostics in global regions where healthcare resources may be limited.

Evolutionary dynamics of group A and B respiratory syncytial virus in China, 2009-2018.

Respiratory syncytial virus (RSV) is a major cause of acute respiratory tract infections in children and is a public health threat globally. To investigate the spatiotemporal dynamics of RSV evolution, we performed systematic phylogenetic analysis using all available sequences from the GenBank database, together with sequences from Shanghai, China. Both RSV-A and RSV-B appear to have originated in North America, with an inferred origin time of 1954.0 (1938.7-1967.6) and 1969.7 (1962.6-1975.5), respectively. BA-like strains of RSV-B, with a 60-nt insertion, and the ON1 strain of RSV-A, with a 72-nt insertion, emerged in 1997.6 (1996.2-1998.6) and 2010.1 (2009.1-2010.3), respectively. Since their origin, both genotypes have gradually replaced the former circulating genotypes to become the dominant strain. The population dynamic of RSV-A showed a seasonal epidemic pattern with obvious expansion in the periods of 2006-2007, 2010-2011, 2011-2012, and 2013-2014. Thirty fixed amino acid substitutions were identified during the divergence of NA4 from GA1 genotypes of RSV-A, and 13 were found during the divergence of SAB4 from GB1 of RSV-B. Importantly, ongoing evolution has occurred since the emergence of ON1, including four amino acid substitutions (I208L, E232G, T253K, and P314L). RSV-A genotypes GA5, NA4, NA1, and ON1 and RSV-B genotypes CB1, SAB4, BA-C, BA10, BA7, and BA9 were co-circulating in China from 2005 to 2015. In particular, RSV-A genotype ON1 was first detected in China in 2011, and it completely replaced GA2 to become the predominant strain after 2016. These data provide important insights into the evolution and epidemiology of RSV.

Consistency of spatial dynamics of HIV-1 and HCV among HIV-1/HCV coinfected drug users in China.

BACKGROUND: As the transmission routes of human immunodeficiency virus type 1 (HIV-1) and hepatitis C virus (HCV) are similar, previous studies based on separate research on HIV-1 and HCV assumed a similar transmission pattern. However, few studies have focused on the possible correlation of the spatial dynamics of HIV-1 and HCV among HIV-1/HCV coinfected patients. METHODS: A total of 310 HIV-1/HCV coinfected drug users were recruited in Yingjiang and Kaiyuan prefectures, Yunnan Province, China. HIV-1 env, p17, pol and HCV C/E2, NS5B fragments were amplified and sequenced from serum samples. The genetic characteristics and spatial dynamics of HIV-1 and HCV were explored by phylogenetic, bootscanning, and phylogeographic analyses. RESULTS: Among HIV-1/HCV coinfected drug users, eight HCV subtypes (1a, 1b, 3a, 3b, 6a, 6n, 6v, and 6u) and two HIV-1 subtypes (subtype B and subtype C), three HIV-1 circulating recombinant forms (CRF01_AE, CRF07_BC and CRF08_BC), and four unique recombinant forms (URF_BC, URF_01B, URF_01C and URF_01BC) were identified. HCV subtype 3b was the most predominant subtype in both Yingjiang and Kaiyuan prefectures. The dominant circulating HIV-1 subtypes for drug users among the two areas were CRF08_BC and URF_BC. Maximum clade credibility trees revealed that both HIV-1 and HCV were transmitted from Yingjiang to Kaiyuan. CONCLUSIONS: The spatial dynamics of HIV-1 and HCV among HIV-1/HCV coinfected drug users seem to have high consistency, providing theoretical evidence for the prevention of HIV-1 and HCV simultaneously.

Single-tube detection of nine bacterial antibiotic-resistance genes by a 2-dimensional multiplex qPCR assay based on fluorescence and melting temperature.

Simple, multiplex qPCR methods are advantages for rapid molecular diagnosis of multiple antibiotics-resistant genes simultaneously. However, the number of genes can be detected in a single reaction tube is often limited by the fluorescence channels of a real-time PCR instrument. In this study, we developed a simple 2-D multiplex qPCR method by combining the probe colors and amplicon Tm values to overcome the mechanical limit of the machine. The principle of the novel assay was validated by detection of nine bacterial antibiotic-resistance genes (KPC, NDM, VIM, OXA-48, GES, CIT, EBC, ACC and DHA) in a single reaction tube. This assay is highly sensitive within a range of 30-3000 copies per reaction. The simplicity, rapidity, high sensitivity and specificity, and low cost of the novel method make it a promising tool for developing clinical diagnostic kits for monitoring resistance and other genetic determinants of infectious diseases.

A Novel Reverse Transcription Loop-Mediated Isothermal Amplification Method for Rapid Detection of SARS-CoV-2.

COVID-19 has become a major global public health burden, currently causing a rapidly growing number of infections and significant morbidity and mortality around the world. Early detection with fast and sensitive assays and timely intervention are crucial for interrupting the spread of the COVID-19 virus (SARS-CoV-2). Using a mismatch-tolerant amplification technique, we developed a simple, rapid, sensitive and visual reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay for SARS-CoV-2 detection based on its N gene. The assay has a high specificity and sensitivity, and robust reproducibility, and its results can be monitored using a real-time PCR machine or visualized via colorimetric change from red to yellow. The limit of detection (LOD) of the assay is 118.6 copies of SARS-CoV-2 RNA per 25 µL reaction. The reaction can be completed within 30 min for real-time fluorescence monitoring, or 40 min for visual detection when the template input is more than 200 copies per 25 µL reaction. To evaluate the viability of the assay, a comparison between the RT-LAMP and a commercial RT-qPCR assay was made using 56 clinical samples. The SARS-CoV-2 RT-LAMP assay showed perfect agreement in detection with the RT-qPCR assay. The newly-developed SARS-CoV-2 RT-LAMP assay is a simple and rapid method for COVID-19 surveillance.

Gemykibivirus Genome in Lower Respiratory Tract of Elderly Woman With Unexplained Acute Respiratory Distress Syndrome.

Using metagenomics analysis, we are the first to identify the presence of a small, circular, single-stranded Gemykibivirus (GkV) genome from the respiratory tract of an elderly woman with severe acute respiratory distress syndrome. Our results suggest that further studies on whether GkVs infect humans and cause respiratory disease are needed.

Amino acids at positions 3, 168, and 169 are associated with the ability of Nef proteins from HIV-1 CRF01_AE to downmodulate CD4.

Several HIV-1 subtypes are co-circulating among various high-risk groups in China, and an increasing prevalence of CRF01_AE was observed among MSM (men who have sex with men) within recent years. Patients infected with CRF01_AE may experience a more rapid disease progression than patients infected with non-CRF01_AE; however, the underlying mechanisms remains elusive. HIV-1 Nef is a multifunctional protein and plays critical roles in viral pathogenesis. Nef downregulates CD4 and human leukocyte antigen (HLA) to promote viral transmission and escape from the host immune response. In this study, we investigated the CD4 downmodulation activity of Nef proteins isolated from HIV-1 CRF01_AE and analyzed a potential relationship of Nef's capacity to downregulate CD4 with disease progression. We found that the majority of these Nefs from HIV-1 CRF01_AE efficiently downregulated CD4; Nefs with weaker CD4 downmodulation activity tended to be associated with higher CD4 levels and lower viral loads. Further elucidation revealed that amino acid residues at positions 3, 168, and 169 of CRF01_AE Nefs were associated with the capacity to downregulate CD4. Our data suggest that the capacity of Nef-mediated CD4 downregulation is not the only determinant for controlling disease progression, and other host and viral factors should be considered to explain the rapid disease progression of patients infected with HIV-1 CRF01_AE.

Curcumin inhibits metastasis in human papillary thyroid carcinoma BCPAP cells via down-regulation of the TGF-ß/Smad2/3 signaling pathway.

Thyroid cancers usually possess a good prognosis while the risks of recurrence and metastasis turn out to be a disturbing issue. Curcumin [bis(4-hydroxy-3-methoxy-phenyl)-1,6-heptadiene-3,5-dione] is a natural polyphenolic compound mainly found in turmeric (Curcuma longa). Our previous studies have demonstrated that curcumin showed proliferation-inhibitory and apoptosis-inducing effects on K1 papillary thyroid cancer cells. However, the mechanism underlying the inhibition effects of curcumin on thyroid cancer cells remains unclear. Herein, we demonstrated that curcumin remarkably increased the expression of the epithelial marker E-cadherin and repressed the expression of the mesenchymal marker vimentin in human papillary thyroid carcinoma BCPAP cells. Curcumin also suppressed multiple metastatic steps of BCPAP cells, including cell attachment, spreading as well as migration. In addition, the transcription, secretion and activation of matrix metalloproteinases (MMPs) induced by transforming growth factor-ß1 (TGF-ß1) in BCPAP cells were mitigated upon curcumin treatment. Further evidence showed that curcumin decreased TGF-ß1-mediated phosphorylation of Smad2 and Smad3. These results revealed that curcumin inhibited the TGF-ß1-induced epithelial-mesenchymal transition (EMT) via down-regulation of Smad2/3 signaling pathways. Our findings provide new evidence that the anti-metastatic and anti-EMT activities of curcumin may contribute to the development of chemo-preventive agents for thyroid cancer treatment.