Inference of the HIV-1 VRC01 Antibody Lineage Unmutated Common Ancestor Reveals Alternative Pathways to Overcome a Key Glycan Barrier.

Elicitation of VRC01-class broadly neutralizing antibodies (bnAbs) is an appealing approach for a preventative HIV-1 vaccine. Despite extensive investigations, strategies to induce VRC01-class bnAbs and overcome the barrier posed by the envelope N276 glycan have not been successful. Here, we inferred a high-probability unmutated common ancestor (UCA) of the VRC01 lineage and reconstructed the stages of lineage maturation. Env immunogens designed on reverted VRC01-class bnAbs bound to VRC01 UCA with affinity sufficient to activate naive B cells. Early mutations defined maturation pathways toward limited or broad neutralization, suggesting that focusing the immune response is likely required to steer B cell maturation toward the development of neutralization breadth. Finally, VRC01 lineage bnAbs with long CDR H3s overcame the HIV-1 N276 glycan barrier without shortening their CDR L1, revealing a solution for broad neutralization in which the heavy chain, not CDR L1, is the determinant to accommodate the N276 glycan.

Antibody light-chain-restricted recognition of the site of immune pressure in the RV144 HIV-1 vaccine trial is phylogenetically conserved.

In HIV-1, the ability to mount antibody responses to conserved, neutralizing epitopes is critical for protection. Here we have studied the light chain usage of human and rhesus macaque antibodies targeted to a dominant region of the HIV-1 envelope second variable (V2) region involving lysine (K) 169, the site of immune pressure in the RV144 vaccine efficacy trial. We found that humans and rhesus macaques used orthologous lambda variable gene segments encoding a glutamic acid-aspartic acid (ED) motif for K169 recognition. Structure determination of an unmutated ancestor antibody demonstrated that the V2 binding site was preconfigured for ED motif-mediated recognition prior to maturation. Thus, light chain usage for recognition of the site of immune pressure in the RV144 trial is highly conserved across species. These data indicate that the HIV-1 K169-recognizing ED motif has persisted over the diversification between rhesus macaques and humans, suggesting an evolutionary advantage of this antibody recognition mode.

Efficacy and safety of intra-arterial thrombolysis in patients with central retinal artery occlusion: a systematic review and meta-analysis.

PURPOSE: To investigate the efficacy and safety of intra-arterial thrombolysis (IAT) in patients with central retinal artery occlusion (CRAO). METHODS: PubMed and EMBASE were searched for potentially eligible studies that reported IAT in CRAO patients from inception to Nov 8, 2021. Standard mean difference (SMD) was pooled to compare visual acuity (VA) at baseline with final in IAT patients. The rates and odds ratios (OR) were meta-analyzed to compare VA improvement in IAT with non-IAT patients, stratified to different times from onset to procedure, different definitions of VA improvement, and three CRAO stages. Adverse effects were recorded. RESULTS: Fifteen studies were included, enrolling 507 CRAO patients who received IAT and 296 CRAO patients who did not. VA was significantly improved from baseline to final VA in IAT patients (SMD [LogMAR] 0.70, 95% CI [0.51, 0.90]). VA improvement rate was higher in IAT patients than that in non-IAT (56% vs 32%, OR 3.55, 95%CI [1.74, 7.24]), with greater OR in IAT within 6 h from onset to procedure (OR 4.60, 95%CI [1.24, 16.99]) than that beyond 6 h (OR 3.36, 95%CI [1.43, 7.85]). The benefit remained consistent when VA improvement was defined as ≥ 3 lines on the Snellen chart (OR 4.68, 95%CI [2.10, 10.41]) and was even greater when CRAO was incomplete. Five patients had a symptomatic intracranial hemorrhage and 21 patients had ischemic stroke or transient ischemic attack after IAT. CONCLUSIONS: IAT treatment has certain potential in ameliorating VA in CRAO patients, which should be balanced against cerebral complications.

Therapeutic responses and predictors of low-dose interleukin-2 in systemic lupus erythematosus.

OBJECTIVES: Interleukin-2 (IL-2) is effective and well tolerated in patients with systemic lupus erythematosus (SLE). However, patient response to IL-2 therapy varies. Therefore, biomarkers are needed to efficiently identify patients who may respond well to IL-2 treatment. We investigated clinical and immunological biomarkers to predict low-dose IL-2 responses. METHODS: A pooled post-hoc analysis was performed in SLE patients who received low-dose IL-2 treatment in two clinical trials. Factors predicting responses in clinical and T-cell subset changes were evaluated by logistic regression. Good response (GR) and poor response (PR) were defined according to whether patients achieved or did not achieve an SLE Responder Index-4 (SRI-4), respectively. RESULTS: A good response at 68% was achieved in patients with lower Treg, compared to 0% in patients with higher Treg. In comparison to PR, GR was more strongly associated with low Treg proportions at baseline (12.85±6.07% vs. 9.43±2.82%, p<0.01). There were more patients with skin rash in the GR group than in the PR group (68.75% vs. 30.77%, p=0.042). Multivariate analysis showed that low Treg proportions and skin rash presence were both independently associated with GR to low-dose IL-2 treatment. A nomogram to identify GR probability exhibited a clear discrimination (concordance index, 0.812; 95% confidence interval, 0.64-0.97). Based on the area under the receiver operating characteristic (ROC) curve (AUC) of 0.813, the specificity of a low regulatory T cells (Tregs) proportion (≤13.35%) plus skin rash to predict GR to IL-2 therapy was 100%, with a sensitivity of 68.75%. CONCLUSIONS: A low Treg proportion and skin rash indicate GR to low-dose IL-2 treatment in SLE patients.

Prognostic value of a nomogram based on peripheral blood immune parameters in unresectable hepatocellular carcinoma after intensity-modulated radiotherapy.

BACKGROUND: For patients with unresectable hepatocellular carcinoma (uHCC), intensity-modulated radiotherapy (IMRT) has become one of the options for clinical local treatment. Immune parameters, including platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and systemic immune inflammatory (SII), predict survival in various cancers. This study aimed to determine whether peripheral immune parameters can predict survival in patients with uHCC undergoing IMRT and establish a clinically useful prognostic nomogram for survival prediction. METHODS: The clinical data of 309 HCC patients were retrospectively analyzed and randomly divided into training (n = 216) and validation (n = 93) cohorts. PLR, NLR and SII were collected before and after IMRT. Univariate and multivariate Cox analyses were performed to identify independent prognostic factors affecting survival, which were used to generate a nomogram. RESULTS: The median survival was 16.3 months, and significant increases in PLR, NLR, and SII were observed after IMRT (P < 0.001). High levels of immune parameters were associated with poor prognosis (P < 0.001); enlarged spleen, Barcelona clinic liver cancer stage (B and C), post-SII, and delta-NLR were independent risk factors for survival and were included in the nomogram, which accurately predicted 3- and 5-year survival. The nomogram was well verified in the validation cohort. CONCLUSIONS: High levels of immune parameters are associated with poor prognosis in uHCC patients receiving IMRT. Our nomogram accurately predicts the survival of patients with uHCC receiving IMRT.

Transcriptome Analysis Reveals the Genes Related to Pollen Abortion in a Cytoplasmic Male-Sterile Soybean (Glycine max (L.) Merr.).

Cytoplasmic male sterility (CMS) lays a foundation for the utilization of heterosis in soybean. The soybean CMS line SXCMS5A is an excellent CMS line exhibiting 100% male sterility. Cytological analysis revealed that in SXCMS5A compared to its maintainer SXCMS5B, its tapetum was vacuolated and abnormally developed. To identify the genes and metabolic pathways involving in pollen abortion of SXCMS5A, a comparative transcriptome analysis was conducted between SXCMS5A and SXCMS5B using flower buds. A total of 372,973,796 high quality clean reads were obtained from 6 samples (3 replicates for each material), and 840 differentially expressed genes (DEGs) were identified, including 658 downregulated and 182 upregulated ones in SXCMS5A compared to SXCMS5B. Among them, 13 DEGs, i.e., 12 open reading frames (ORFs) and 1 COX2, were mitochondrial genome genes in which ORF178 and ORF103c were upregulated in CMS lines and had transmembrane domain(s), therefore, identified as CMS candidate mitochondrial genes of SXCMS5A. Furthermore, numerous DEGs were associated with pollen wall development, carbohydrate metabolism, sugar transport, reactive oxygen species (ROS) metabolism and transcription factor. Some of them were further confirmed by quantitative real time PCR analysis between CMS lines with the same cytoplasmic source as SXCMS5A and their respective maintainer lines. The amount of soluble sugar and adenosine triphosphate and the activity of catalase and ascorbic acid oxidase showed that energy supply and ROS scavenging decreased in SXCMS5A compared to SXCMS5B. These findings provide valuable information for further understanding the molecular mechanism regulating the pollen abortion of soybean CMS.

Catalytic synthesis of nanodiamond based on CDC principle: influence of different catalysts on types and sizes.

Recently, we have successfully realized the catalytic synthesis of nanodiamond (ND) by embedding the Fe catalyst into carbide under high stress, followed by chlorine-etching at atmospheric pressure. In this work, we selected Fe, Co and Ni as the catalyst, and TiC as the precursor, aiming at investigating the influence of the catalyst type on the synthesis of NDs. The results have shown that all the three catalysts can catalyze the synthesis of ND structure, where various types of NDs have been observed. Furthermore, the crystal type and plasticity of the catalyst may have an important influence on the type and size of the resultant ND. In the case of Fe and Ni as the catalyst, both of which have a face centered cubic crystal structure, the types of NDs obtained are mainly C-type and R-type but only a few H-type. However, when the Co with a close-packed hexagonal crystal structure is used as the catalyst, more H-type NDs can be catalytically synthesized. Moreover, more small-sized NDs have been catalytically synthesized by Co, which may be ascribed to the worse plasticity of Co by comparison to Fe and Ni.

Safety of intravenous thrombolysis in stroke of unknown time of onset: A systematic review and meta-analysis.

The safety of intravenous tissue plasminogen activator (IV-tPA) in patients with stroke of unknown time of onset (SUTO) was unclear and mostly concerned. We sought to investigate the safety in terms of symptomatic intracranial hemorrhage (sICH) and death in SUTO patients treated with IV-tPA. We searched PubMed and EMBASE from inception to 2 December 2020 for eligible studies reporting IV-tPA in SUTO patients compared to conservative medical therapy, or to stroke of known onset time (SKOT) treated with IV-tPA within standard time window. We pooled relative risk (RR) with 95% confidence interval (95%CI) with random-effects model. Twenty-four studies were included, enrolling 77,398 patients. SUTO patients with IV-tPA had higher incidence of sICH than that in SUTO patients without IV-tPA (3.8% versus 0.96%; RR = 3.75, 95%CI: 2.69-5.22) but comparable to that in SKOT patients with IV-tPA (3.8% versus 4.1%; RR = 1.16, 95%CI: 0.94-1.44). There was no significant difference in death risk in SUTO patients with IV-tPA versus SUTO patients without IV-tPA (RR = 1.34, 95%CI: 0.60-3.01) and versus SKOT patients with IV-tPA (RR = 1.19, 95%CI: 0.95-1.50). Compared with SUTO patients without IV-tPA, SUTO patients with IV-tPA had higher likelihood of favorable functional outcome (adjusted RR = 1.28, 95%CI: 1.03-1.60) and functional independence (adjusted RR = 1.95, 95%CI: 1.24-3.06), comparable to that in SKOT patients with IV-tPA in favorable functional outcome (adjusted RR = 0.67, 95%CI: 0.38-1.20) and functional independence (adjusted RR = 0.84, 95%CI: 0.59-1.18). SUTO patients could be treated safely and effectively with IV-tPA under the guidance of imaging evaluation.

Efficacy and safety of low-dose IL-2 in the treatment of systemic lupus erythematosus: a randomised, double-blind, placebo-controlled trial.

OBJECTIVES: Open-labelled clinical trials suggested that low-dose IL-2 might be effective in treatment of systemic lupus erythematosus (SLE). A double-blind and placebo-controlled trial is required to formally evaluate the safety and efficacy of low-dose IL-2 therapy. METHODS: A randomised, double-blind and placebo-controlled clinical trial was designed to treat 60 patients with active SLE. These patients received either IL-2 (n=30) or placebo (n=30) with standard treatment for 12 weeks, and were followed up for additional 12 weeks. IL-2 at a dose of 1 million IU or placebo was administered subcutaneously every other day for 2 weeks and followed by a 2-week break as one treatment cycle. The primary endpoint was the SLE Responder Index-4 (SRI-4) at week 12. The secondary endpoints were other clinical responses, safety and dynamics of immune cell subsets. RESULTS: At week 12, the SRI-4 response rates were 55.17% and 30.00% for IL-2 and placebo, respectively (p=0.052). At week 24, the SRI-4 response rate of IL-2 group was 65.52%, compared with 36.67% of the placebo group (p=0.027). The primary endpoint was not met at week 12. Low-dose IL-2 treatment resulted in 53.85% (7/13) complete remission in patients with lupus nephritis, compared with 16.67% (2/12) in the placebo group (p=0.036). No serious infection was observed in the IL-2 group, but two in placebo group. Besides expansion of regulatory T cells, low-dose IL-2 may also sustain cellular immunity with enhanced natural killer cells. CONCLUSIONS: Low-dose IL-2 might be effective and tolerated in treatment of SLE. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registries (NCT02465580 and NCT02932137).

Fe-catalytic synthesis of nanodiamond during the chlorination of vanadium carbide at ambient pressure: influence of the Fe-introduction mode.

The development of technical strategies for synthesizing nanodiamond (ND) under moderate conditions is still an attractive and challenging issue. Herein, an attempt has been made to investigate the effect of the Fe-introduction mode on the catalytic synthesis of ND during the chlorination of vanadium carbide (VC) at ambient pressure. The results show that when Fe powder as a catalyst is adhered on the surface of the VC particle, the resultant carbide-derived carbon (CDC) by chlorinating VC at 800 °C behaves as a remarkably higher structural ordering. However, as the Fe powder is enclosed within the interior of VC particles, the structural ordering of the CDC obtained at the same chlorination temperature becomes greatly lower, and more interestingly, ND structures can be observed in the prepared CDC. This suggests that the catalytic synthesis of ND during VC chlorination at ambient pressure is heavily dependent upon the Fe-introduction mode.

Tea Consumption Is Associated with Decreased Disease Activity of Rheumatoid Arthritis in a Real-World, Large-Scale Study.

INTRODUCTION: The role of tea consumption on rheumatoid arthritis (RA) has been studied in recent years, but no clear conclusion has been drawn as a result of small sample size of the studies or the fact that only in vitro studies have been performed. OBJECTIVES: The aim of this study was to explore the possible association of tea consumption with RA through a large-scale, real-world study. METHODS: A total of 733 RA patients were investigated from June to December, 2016. The disease activity of RA was assessed according to disease activity score 28-erythrocyte sedimentation rate. The amount and types of tea consumption were recorded by on-site self-administered questionnaires. Logistic regression models were applied to analyze the correlation between tea consumption and disease activity, adjusting for demographics, clinical and laboratory factors. RESULTS: There was an inverse association between tea consumption and disease activity in RA patients (OR 0.66, 95% CI 0.46-0.94). Compared with non-tea drinkers, a higher-intake of tea (>750 mL/day) was associated with lower disease activity of RA (OR 0.39, 95% CI 0.19-0.79), but not low-intake (≤750 mL/day; OR 0.83, 95% CI 0.42-1.63). A significant dose-response association was found between the amount of tea consumption and disease activity (p for trend <0.01). Further hierarchical regression analysis showed that such inverse associations were mainly present in female patients (p = 0.004), non-smokers (p = 0.01) or elders (≥60 years; p = 0.01). CONCLUSION: Tea consumption is associated with decreased disease activity of RA, suggesting the potential beneficial effect of tea in the disease.

Intranasal Live Influenza Vaccine Priming Elicits Localized B Cell Responses in Mediastinal Lymph Nodes.

Pandemic live attenuated influenza vaccines (pLAIV) prime subjects for a robust neutralizing antibody response upon subsequent administration of a pandemic inactivated subunit vaccine (pISV). However, a difference was not detected in H5-specific memory B cells in the peripheral blood between pLAIV-primed and unprimed subjects prior to pISV boost. To investigate the mechanism underlying pLAIV priming, we vaccinated groups of 12 African green monkeys (AGMs) with H5N1 pISV or pLAIV alone or H5N1 pLAIV followed by pISV and examined immunity systemically and in local draining lymph nodes (LN). The AGM model recapitulated the serologic observations from clinical studies. Interestingly, H5N1 pLAIV induced robust germinal center B cell responses in the mediastinal LN (MLN). Subsequent boosting with H5N1 pISV drove increases in H5-specific B cells in the axillary LN, spleen, and circulation in H5N1 pLAIV-primed animals. Thus, H5N1 pLAIV primes localized B cell responses in the MLN that are recalled systemically following pISV boost. These data provide mechanistic insights for the generation of robust humoral responses via prime-boost vaccination.IMPORTANCE We have previously shown that pandemic live attenuated influenza vaccines (pLAIV) prime for a rapid and robust antibody response on subsequent administration of inactivated subunit vaccine (pISV). This is observed even in individuals who had undetectable antibody (Ab) responses following the initial vaccination. To define the mechanistic basis of pLAIV priming, we turned to a nonhuman primate model and performed a detailed analysis of B cell responses in systemic and local lymphoid tissues following prime-boost vaccination with pLAIV and pISV. We show that the nonhuman primate model recapitulates the serologic observations from clinical studies. Further, we found that pLAIVs induced robust germinal center B cell responses in the mediastinal lymph node. Subsequent boosting with pISV in pLAIV-primed animals resulted in detection of B cells in the axillary lymph nodes, spleen, and peripheral blood. We demonstrate that intranasally administered pLAIV elicits a highly localized germinal center B cell response in the mediastinal lymph node that is rapidly recalled following pISV boost into germinal center reactions at numerous distant immune sites.

Fu-SulfPred: Identification of Protein S-sulfenylation Sites by Fusing Forests via Chou's General PseAAC.

Protein S-sulfenylation is an essential post-translational modification (PTM) that provides critical information to understand molecular mechanisms of cell signaling transduction, stress response and regulation of cellular functions. Recent advancements in computational methods have contributed towards the detection of protein S-sulfenylation sites. However, the performance of identifying protein S-sulfenylation sites can be influenced by a class imbalance of training datasets while the application of various computational methods. In this study, we designed a Fu-SulfPred model using stratified structure of three kinds of decision trees in order to identify possible protein S-sulfenylation sites by means of reconstructing training datasets and sample rescaling technology. Experimental results showed that the correlation coefficient values of Fu-SulfPred model were found to be 0.5437, 0.3736 and 0.6809 on three independent test datasets, respectively, all of which outperformed the Matthews coefficient values of S-SulfPred model. Fu-SulfPred model provides a promising scheme for the identification of protein S-sulfenylation sites and other post-translational modifications.

Chemically exfoliated highly conductive layer-tunable graphene by simply controlling the exfoliating temperature.

The development of effective strategies for the massive production of layer-number tunable graphene is of great importance to satisfy the requirements in versatile applications such as energy storage, thermal management, photocatalysis. However, how to prepare the layer-tunable graphene by a simple and efficient way is still a great challenge. Herein, an attempt has been made to exfoliate graphite into layer-tunable graphene by simply soaking the graphite in a binary-component solution composed of H2SO4 and (NH4)2S2O8. In this one-step method, we demonstrate that the layer-number for the as-prepared graphene can be significantly reduced by increasing the exfoliating temperature. An average thickness of ∼20, ∼10, and ∼3 atomic layers can be obtained for the graphene samples exfoliated at the temperature of 30 °C, 60 °C, and 90 °C, respectively. Meanwhile, higher exfoliating temperature not only facilitates the higher efficiency in the exfoliation of graphite, but also achieves a superior conductivity for the prepared graphene. We have demonstrated for the first time that controlling in a sole factor of temperature can effectively tune the layer-number of graphene by a one-step chemical exfoliation method, which will find its great potential in the practical application where the designated property of graphene is required.

Ultrahigh-power supercapacitors based on highly conductive graphene nanosheet/nanometer-sized carbide-derived carbon frameworks.

In order to develop energy storage devices with high power performance, electrodes should hold well-defined pathways for efficient ionic and electronic transport. Herein, we demonstrate a highly conductive graphene nanosheet/nanometer-sized carbide-derived carbon framework (hcGNS/nCDC). In this architecture, nCDC possesses short transport paths for electrolyte ions, thus ensuring the rapid ions transportation. The excellent electrical conductivity of hcGNS can reduce the electrode internal resistance for the supercapacitor and thus endows the hcGNS/nCDC composite electrodes with excellent electronic transportation performance. Electrochemical measurements show that the cyclic voltammogram of hcGNS/nCDC can maintain a rectangular-like shape with the increase of the scan rate from 5 mV s-1 to 20 V s-1, and the specific capacitance retention is up to 51% even at a high scan rate of 20 V s-1, suggesting ultrahigh power performance, which, to the best of our knowledge, is among the best power performances reported so far for the carbon materials. Furthermore, the hcGNS/nCDC composite also shows an excellent cycling stability (no drop in its capacitance occurs even after 10000 cycles). This work demonstrates the advantage in the ultrahigh power performance for the framework having both short transport pathways for electrolyte ions and high electrical conductivity.

A novel and facile synthesis approach for a porous carbon/graphene composite for high-performance supercapacitors.

We propose a novel and facile synthesis approach to a porous carbon/graphene composite. Graphene is obtained from room-temperature expanded graphite (RTEG), not involving the use of graphite oxide (GO). Porous carbon is acquired by carbonization and KOH-activation of polyvinylpyrrolidone (PVP), which is used to exfoliate RTEG into graphene and inhibit the restacking of the resultant graphene in the present work. The prepared porous carbon/graphene composite has a high specific surface area (SSA) (3008 m2 g-1) and a hierarchical micro- and meso- pore structure (dominant pores in the range of 1-5 nm). Electrochemical measurement demonstrates that the as-prepared porous carbon/graphene composite can deliver an outstanding specific capacitance of up to 340 F g-1 at 5 mV s-1 in 6 M KOH electrolyte. This specific capacitance is among the highest reported so far for porous carbon/graphene materials. Moreover, the prepared composite as an electrode material also exhibits excellent cycling stability (94.4% capacitance retention over 10 000 cycles). The as-fabricated symmetrical supercapacitor exhibits a high energy density of 10.9 W h kg-1 (based on total mass of electrode materials) and an outstanding energy density retention, even at high power density. Compared with conventional preparation routes for porous carbon/graphene composites, the present approach is significantly simple, convenient and cost-effective, which will make it more competent in the development of electrode materials for high-performance supercapacitors.

HIV-1 Envelope Mimicry of Host Enzyme Kynureninase Does Not Disrupt Tryptophan Metabolism.

The HIV-1 envelope protein (Env) has evolved to subvert the host immune system, hindering viral control by the host. The tryptophan metabolic enzyme kynureninase (KYNU) is mimicked by a portion of the HIV Env gp41 membrane proximal region (MPER) and is cross-reactive with the HIV broadly neutralizing Ab (bnAb) 2F5. Molecular mimicry of host proteins by pathogens can lead to autoimmune disease. In this article, we demonstrate that neither the 2F5 bnAb nor HIV MPER-KYNU cross-reactive Abs elicited by immunization with an MPER peptide-liposome vaccine in 2F5 bnAb VHDJH and VLJL knock-in mice and rhesus macaques modified KYNU activity or disrupted tissue tryptophan metabolism. Thus, molecular mimicry by HIV-1 Env that promotes the evasion of host anti-HIV-1 Ab responses can be directed toward nonfunctional host protein epitopes that do not impair host protein function. Therefore, the 2F5 HIV Env gp41 region is a key and safe target for HIV-1 vaccine development.

The attachment potential and N-acyl-homoserine lactone-based quorum sensing in aerobic granular sludge and algal-bacterial granular sludge.

Bacteria and algae often coexist in the aerobic granular sludge (AGS) system in a photo-bioreactor, forming algal-bacterial granular sludge. In this study, the physicochemical characteristics and microbial attachment potential of the AGS and algal-bacterial granular sludge were comparatively analyzed. Results clearly showed that the larger and denser algal-bacterial granular sludge had stronger attachment potential compared to the AGS (as the control). A bioassay with Agrobacterium tumefaciens KYC55 indicated that N-acyl-homoserine lactones (AHLs) existed in both sludge types, but further investigations revealed that the relative AHL content of the algal-bacterial granular sludge obviously increased and slightly decreased during phases II and III, respectively, but was consistently higher than the AGS. Based on the EPS measurements and 3D-excitation-emission matrix (3D-EEM) fluorescence spectra analysis, the enhancement of AHL-based QS favored the hydrophobic protein production of algal-bacterial granular sludge, contributing to a good development of the granular sludge. In addition, it was also found that inhibition of AHLs resulted in the reduction of the protein content and attachment potential in algal-bacterial granular sludge, which was unfavorable to the structural stability of the granules. High-throughput sequencing analysis showed that the microbial community of AGS was different from the algal-bacterial granular sludge; specifically, algal-bacterial granulation facilitated the abundance of AHLs and EPS producers, such as the genera Acinetobacter, Chryseobacterium, and Flavobacterium.

Human Non-neutralizing HIV-1 Envelope Monoclonal Antibodies Limit the Number of Founder Viruses during SHIV Mucosal Infection in Rhesus Macaques.

HIV-1 mucosal transmission begins with virus or virus-infected cells moving through mucus across mucosal epithelium to infect CD4+ T cells. Although broadly neutralizing antibodies (bnAbs) are the type of HIV-1 antibodies that are most likely protective, they are not induced with current vaccine candidates. In contrast, antibodies that do not neutralize primary HIV-1 strains in the TZM-bl infection assay are readily induced by current vaccine candidates and have also been implicated as secondary correlates of decreased HIV-1 risk in the RV144 vaccine efficacy trial. Here, we have studied the capacity of anti-Env monoclonal antibodies (mAbs) against either the immunodominant region of gp41 (7B2 IgG1), the first constant region of gp120 (A32 IgG1), or the third variable loop (V3) of gp120 (CH22 IgG1) to modulate in vivo rectal mucosal transmission of a high-dose simian-human immunodeficiency virus (SHIV-BaL) in rhesus macaques. 7B2 IgG1 or A32 IgG1, each containing mutations to enhance Fc function, was administered passively to rhesus macaques but afforded no protection against productive clinical infection while the positive control antibody CH22 IgG1 prevented infection in 4 of 6 animals. Enumeration of transmitted/founder (T/F) viruses revealed that passive infusion of each of the three antibodies significantly reduced the number of T/F genomes. Thus, some antibodies that bind HIV-1 Env but fail to neutralize virus in traditional neutralization assays may limit the number of T/F viruses involved in transmission without leading to enhancement of viral infection. For one of these mAbs, gp41 mAb 7B2, we provide the first co-crystal structure in complex with a common cyclical loop motif demonstrated to be critical for infection by other retroviruses.

The impact of anionic polyacrylamide (APAM) on ultrafiltration efficiency in flocculation-ultrafiltration process.

With the purpose of improving the ultrafiltration (UF) efficiency, anionic polyacrylamide (APAM) has been used as a coagulant aid in the flocculation-UF process. In this study, the impact of APAM on UF efficiency has been investigated with regard to membrane fouling, membrane cleaning and effluent quality. The results indicated that the optimal dosage of APAM had positive impacts on membrane fouling control, membrane cleaning and effluent quality. According to the flux decline curve, scanning electron microscopy and contact angle characterization, the optimal dosage of APAM was determined to be 0.1 mg/L coupled with 2 mg/L (as Al3+) poly-aluminium chloride. Under this optimal condition, membrane fouling can be mitigated because of the formation of a porous and hydrophilic fouling layer. APAM in the fouling layer can improve the chemical cleaning efficiency of 0.5% NaOH due to the disintegration of the fouling layer when APAM is dissolved under strong alkaline conditions. Furthermore, with the addition of APAM in the flocculation-UF process, more active adsorption sites can be formed in the flocs as well as the membrane fouling layer, thus more antipyrine molecules in the raw water can be adsorbed and removed in the flocculation-UF process.