The quantification of root exudation by an in-situ method based on root morphology over three incubation periods.

Investigating the quantity and spatiotemporal dynamics of metabolite release from plant roots is essential if we are to understand the ecological significance of root exudates in the rhizosphere; however, this is difficult to quantify. In the present study, we quantified in situ root exudation rates during three incubation periods (0-24, 24-48, and 48-72 h) and fine roots within four diameter ranges (<0.8, 0.8-1.0, 1.0-1.2, and 1.2-2.0 mm), and also measured nine morphological traits in the fine roots of Pinus massoniana. Higher root carbon (C) exudation rates were detected during the 0-24 h period. During the 0-24 h and 24-48 h periods, nitrogen (N) uptake rates were higher than N exudation rates, while during the 48-72 h period, N exudation rates exceeded uptake rates. As C exudation increased during 0-48h incubation period, the uptake of N tended to level out. We concluded that the 24-48 h incubation period was the most suitable for capturing root exudates from P. massoniana. The exudation of C from the roots was positively associated with root mass, length, surface area, volume, the number of root tips, and the root tissue density, when incubated for 0-24 h and 24-48 h. Furthermore, length-specific C exudation rates, along with N exudation and uptake rates, all increased as the diameter of the fine roots increased. The release of root exudates could be efficiently predicted by the fine root morphological traits, although the accuracy of prediction depended on the incubation period. Higher values for fine root morphological traits were generally indicative of higher nutrient requirements and tissue investment, as well as higher C exudation rates.

Switch to fixed-dose ainuovirine, lamivudine, and tenofovir DF versus elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in virologically suppressed people living with HIV-1: the 48-week results of the SPRINT trial, a multi-centre, randomised, double-blind, active-controlled, phase 3, non-inferiority trial.

Background: We compared the efficacy and safety profiles of ainuovirine (ANV), a new-generation non-nucleoside reverse transcriptase inhibitor (NNRTI), with boosted elvitegravir (EVG), both coformulated with two nucleoside reverse transcriptase inhibitors (NRTIs), in people living with HIV-1 (PLWH) who had achieved virological suppression on previous NNRTI-based antiretroviral (ARV) regimen. Methods: This study was a multi-centre, randomised, double-blind, active-controlled, non-inferiority trial recruiting PLWH from 10 clinical centres across China. Main inclusion criteria included age of 18-65 years (inclusive), and stably staying on an ARV regimen combining an NNRTI with a two-drug NRTI backbone for at least 12 months. Eligible participants must have maintained plasma HIV-1 ribonucleic acid (RNA) titre below 50 copies per mL confirmed on two successive tests at an interval of at least one month prior to randomisation. Participants were randomly assigned to receive ANV 150 mg plus lamivudine (3TC) 300 mg, and tenofovir disoproxil fumarate (TDF) 300 mg (ANV/3TC/TDF), or cobicistat (Cobi) 150 mg boosted EVG plus emtricitabine (FTC) 200 mg, and tenofovir alafenamide (TAF) 10 mg. The primary efficacy endpoint was the proportion of participants with HIV-1 RNA titre at 50 copies per mL or above at week 48 using the US Food and Drug Administration snapshot algorithm, with a non-inferiority margin of 4 percentage points at a two-side 95% confidence level. This trial is active, but not recruiting, and is registered with Chinese Clinical Trial Registry (ChiCTR), number ChiCTR2100051605. Findings: Between October 2021 and February 2022, 923 patients were screened for eligibility, among whom 762 participants were randomized and had received at least one dose of ANV/3TC/TDF (n = 381) or EVG/Cobi/FTC/TAF (n = 381). At week 48, 7 (1.8%) participants on ANV/3TC/TDF and 6 (1.6%) participants on EVG/Cobi/FTC/TAF had plasma HIV-1 RNA titre at 50 copies per mL or above, including missing virological data within the time window (the Cochran-Mantel-Haenszel method, estimated treatment difference [ETD], 0.3%, 95% CI -1.6 to 2.1), establishing the non-inferiority of ANV/3TC/TDF to EVG/Cobi/FTC/TAF. The proportions of participants experiencing at least one treatment-emergent adverse events (AEs) were comparable between the two arms (97.6% versus 97.6%). A small proportion of participants discontinued study drug due to AEs (0.3% versus 0.3%). Serious AEs occurred in 11 (2.9%) participants on ANV/3TC/TDF and 9 (2.4%) participants on EVG/Cobi/FTC/TAF, respectively, none of which was considered related to study drug at the jurisdiction of the investigator. At week 48, participants on ANV/3TC/TDF showed a significantly less weight gain from baseline compared to those on EVG/Cobi/FTC/TAF (least square mean, 1.16 versus 2.05 kg, ETD -0.90 kg, 95% CI, -1.43 to -0.37). The changes in serum lipids from baseline also favoured ANV/3TC/TDF over EVG/Cobi/FTC/TAF. Interpretation: In virologically suppressed PLWH on previous NNRTI-based ARV regimen, switch to ANV/3TC/TDF resulted in less weight gain, and improved lipid metabolism while maintaining virological suppression non-inferior to that to EVG/Cobi/FTC/TAF. Funding: Jiangsu Aidea Pharmaceutical & the National "Thirteenth Five-year Period" Major Innovative Drugs Research and Development Key Project of the People's Republic of China Ministry of Science and Technology.

Enhanced immune reconstitution with albuvirtide in HIV-infected immunological non-responders.

Background: Incomplete immune recovery in people living with HIV/AIDS (PLWHA) remains an important clinical challenge with the lack of an effective strategy currently available to restore their T-cell immune response. This study aimed to evaluate the effect of Albuvirtide (ABT) on immune recovery in immunological non-responders (INRs) and attempted to explore potential mechanisms of ABT on the functionality of immune cells. Methods: In this prospective, open-label, controlled clinical study, participants with incomplete immune reconstitution (continuous ART over 5 years and CD4+T lymphocyte absolute count of <500 cells/µl or ART for 2-5 years and CD4+T cell count of <200 cells/µl with undetectable viral load) were received intensive treatment with ABT or maintained on the original ART regimen at a ratio of 1:1. Immune response and safety were examined within 24 weeks. In the cytological study, T subsets, cell apoptosis and cell autophagy were analyzed using immunofluorescence staining and flow cytometry from 25 blood specimens. Results: Both groups (n=25 each) were comparable in age, gender, and ART duration. At week 12, CD4+T cell count increased significantly in the intensive ABT group compared with control group (the change from baseline in CD4+T cell count: 45 vs. -5 cells/µL, p<0.001). After ABT discontinuation, CD4+T cell counts remained significantly higher in the intensive ABT group at week 24 (55 vs. -5 cells/µL, p=0.012). In laboratory analysis, naïve CD4+ T cell amounts were lowest among participants with unsatisfactory immune response (uIR) to ABT (p=0.001). The proportion of caspase 3+CD45RA+CD31+CD4+ T cells was significantly lower in participants with satisfactory immune response (sIR) to ABT (p<0.05). Conclusion: Significant CD4+T cell count increase suggests ABT enhances immune function in INRs which may be attributed to its antiviral properties as well as its ability to increase thymic cell output and decrease cell apoptosis.

Quenching and enhancement mechanisms of a novel Cd-based coordination polymer as a multiresponsive fluorescent sensor for nitrobenzene and aniline.

BACKGROUND: Nitroaromatic compounds are inherently hazardous and explosive, so convenient and rapid detection strategies are needed for the sake of human health and the environment. There is an urgent demand for chemical sensing materials that offer high sensitivity, operational simplicity, and recognizability to effectively monitor nitroaromatic residues in industrial wastewater. Despite its importance, the mechanisms underlying fluorescence quenching or enhancement in fluorescent sensing materials have not been extensively researched. The design and synthesis of multiresponsive fluorescent sensing materials have been a great challenge until now. RESULTS: In this study, a one-dimensional Cd-based fluorescent porous coordination polymer (Cd-CIP-1) was synthesized using 5-(4-cyanobenzyl)isophthalic acid (5-H2CIP) and 4,4'-bis(1-imidazolyl)biphenyl (4,4'-bimp) and used for the selective detection of nitrobenzene in aqueous solution by fluorescence quenching, with a limit of detection of 1.38 × 10-8 mol L-1. The presence of aniline in the Cd-CIP-1 solution leads to the enhancement of fluorescence property. Density functional theory and time-dependent density functional theory calculations were carried out to elucidate the mechanisms of the fluorescence changes. This study revealed that the specific pore size of Cd-CIP-1 facilitates analyte screening and enhances host-guest electron coupling. Furthermore, π-π interactions and hydrogen bond between Cd-CIP-1 and the analytes result in intermolecular orbital overlap and thereby boosting electron transfer efficiency. The different electron flow directions in NB@Cd-CIP-1 and ANI@Cd-CIP-1 lead to fluorescence quenching and enhancement. SIGNIFICANCE AND NOVELTY: The multiresponsive coordination polymer (Cd-CIP-1) can selectively detect nitrobenzene and recognize aniline in aqueous solutions. The mechanism of fluorescence quenching and enhancement has been thoroughly elucidated through a combination of density functional theory and experimental approaches. This study presents a promising strategy for the practical implementation of a multiresponsive fluorescent chemical sensor.

Design and preparation of a multi-responsive Cd-based fluorescent coordination polymer for smart sensing of nitrobenzene and ornidazole.

The improper utilization of nitrobenzene (NB) and ornidazole (ORN) has resulted in irreversible effects on the environment. By combining experimental investigation, density functional theory (DFT) calculations, and machine learning, an effective green strategy for detecting NB and ORN in aqueous solutions can be developed. In this study, a one-dimensional Cd-based coordination polymer (Cd-HCIA-3) was designed and synthesized using 5-((4-carboxybenzyl)oxy)isophthalic acid and rigid 2,2'-bipyridine under solvothermal reaction conditions. Cd-HCIA-3 exhibits excellent fluorescence properties and stability in aqueous solutions. DFT calculations were performed to predict the fluorescence sensing performance of Cd-HCIA-3, revealing that photoinduced electron transfer is the key mechanism for inducing fluorescence quenching in the presence of NB and ORN, with weak molecular interactions promoting electron transfer. Fluorescence sensing experiments were conducted to verify the DFT results, showing that Cd-HCIA-3 can selectively detect NB and ORN in aqueous solutions with limits of detection of 7.22 × 10-8 and 1.31 × 10-7 mol/L, respectively. This study's findings provide valuable insights into the design and synthesis of fluorescent coordination polymers for target analytes.

The diagnostic value of metagenomics next-generation sequencing in HIV-infected patients with suspected pulmonary infections.

Background: Traditional microbiological detection methods used to detect pulmonary infections in people living with HIV (PLHIV) are usually time-consuming and have low sensitivity, leading to delayed treatment. We aimed to evaluate the diagnostic value of metagenomics next-generation sequencing (mNGS) for microbial diagnosis of suspected pulmonary infections in PLHIV. Methods: We retrospectively analyzed PLHIV who were hospitalized due to suspected pulmonary infections at the sixth people hospital of Zhengzhou from November 1, 2021 to June 30, 2022. Bronchoalveolar lavage fluid (BALF) samples of PLHIV were collected and subjected to routine microbiological examination and mNGS detection. The diagnostic performance of the two methods was compared to evaluate the diagnostic value of mNGS for unknown pathogens. Results: This study included a total of 36 PLHIV with suspected pulmonary infections, of which 31 were male. The reporting period of mNGS is significantly shorter than that of CMTs. The mNGS positive rate of BALF samples in PLHIV was 83.33%, which was significantly higher than that of smear and culture (44.4%, P<0.001). In addition, 11 patients showed consistent results between the two methods. Futhermore, mNGS showed excellent performance in identifying multi-infections in PLHIV, and 27 pathogens were detected in the BALF of 30 PLHIV by mNGS, among which 15 PLHIV were found to have multiple microbial infections (at least 3 pathogens). Pneumocystis jirovecii, human herpesvirus type 5, and human herpesvirus type 4 were the most common pathogen types. Conclusions: For PLHIV with suspected pulmonary infections, mNGS is capable of rapidly and accurately identifying the pathogen causing the pulmonary infection, which contributes to implement timely and accurate anti-infective treatment.

Characteristics of drug resistance mutations in ART-experienced HIV-1 patients with low-level viremia in Zhengzhou City, China.

Although most people living with HIV (PLWH) receiving antiretroviral therapy (ART) achieve continuous viral suppression, some show detectable HIV RNA as low-level viremia (LLV) (50-999 copies/mL). Drug resistance mutations (DRMs) in PLWH with LLV is of particular concern as which may lead to treatment failure. In this study, we investigated the prevalence of LLV and LLV-associated DRMs in PLWH in Zhengzhou City, China. Of 3616 ART-experienced PLWH in a long-term follow-up cohort from Jan 2022 to Aug 2023, 120 were identified as having LLV. Of these PLWH with LLV, we obtained partial pol and integrase sequences from 104 (70 from HIV-1 RNA and 34 from proviral DNA) individuals. DRMs were identified in 44 individuals. Subtyping analysis indicated that the top three subtypes were B (48.08%, 50/104), CRF07_BC (31.73%, 33/104), and CRF01_AE (15.38%, 16/104). The proportions of nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs) associated DRMs were 23.83% (24/104), 35.58% (37/104), 5.77% (6/104), and 3.85% (4/104), respectively, which contributed to an overall prevalence of 42.31% (44/104). When analyzed by individual DRMs, the most common mutation(s) were V184 (18.27%, 19/104), followed by V179 (11.54%, 12/104), K103 (9.62%, 10/104), Y181 (9.62%, 10/104), M41 (7.69%, 8/104), and K65R (7.69%, 8/104). The prevalence of DRMs in ART-experienced PLWH with LLV is high in Zhengzhou City and continuous surveillance can facilitate early intervention and provision of effective treatment.

Long-term effect of antiretroviral therapy on mortality among HIV-positive children and adolescents in China.

Introduction: Highly active antiretroviral therapy (HAART) was piloted in 2002 and was scaled up in 2003 in mainland China. The aim of this study was to evaluate the mortality and its possible predictors based on the long-term initial antiretroviral therapy (ART) cohort among HIV positive children and adolescents. Methods: This prospective open-labeled multicenter cohort study was conducted from January 2008 to July 2021. The participants were recruited from six representative sites in mainland China. A total of 609 participants with an HIV-positive serostatus and <18 years old were recruited and each participant was informed consent at the time of enrollment. Mortality and annual hazard were calculated, and predictors for death were analyzed using Cox regression models generating hazard ratios (HR). Results: The results showed that the mortality was 0.721 per hundred person-years, and the annual hazard was less than 0.10 over time. Both CD4+T cell count and CD4+T cell percentage declined in the death group during the follow-up. The Cox regression model showed that the baseline low CD4+T cell count level (Low vs. High: aHR = 8.309, 95% CI: (1.093, 63.135)) and age >5 years old at HIV diagnosis (6-12 vs. 0-5: aHR = 3.140, 95%CI: (1.331, 27.411)); 13-18 vs. 0-5: aHR = 5.451, 95%CI: (1.434, 20.724)) were possible risk factors for death. Conclusion: The longitudinal cohort study demonstrated the efficacy of China's ART program among HIV-positive children and adolescents which could be beneficial to other countries with limited resources.

Toxoplasma gondii seropositivity and cognitive functioning in older adults: an analysis of cross-sectional data of the National Health and Nutrition Examination Survey 2011-2014.

OBJECTIVES: This study sought to examine the relationship between Toxoplasma gondii seropositivity and cognitive function in older adults. DESIGN: An observational cross-sectional study. SETTING: The National Health and Nutrition Examination Survey (NHANES) study took place at participants' homes and mobile examination centres. PARTICIPANTS: A total of 2956 older adults aged 60 and above from the NHANES from 2011 to 2014 were included in the study. Exposure of interest: participants had serum Toxoplasma gondii antibody analysed in the laboratory. A value>33 IU/mL was categorised as seropositive for Toxoplasma gondii infection; <27 IU/mL was categorised as seronegative for Toxoplasma gondii infection. PRIMARY AND SECONDARY OUTCOME MEASURES: Cognitive tests included the Consortium to Establish a Registry for Alzheimer's Disease Word Learning subtest (CERAD-WL) for immediate and delayed memory, the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST). RESULTS: About half of the 2956 participants (mean age 70.0) were female (51.0%), non-Hispanic White (48.3%), and completed some college or above (48.3%). A total of 703 participants were positive for Toxoplasma gondii infection (23.8%). Adjusted linear regression showed that compared with participants with negative Toxoplasma gondii infection, those with positive Toxoplasma gondii infection had lower CERAD-WL immediate memory (beta (ß) -0.16, 95% CI -0.25 to -0.07), CERAD-WL delayed memory (ß -0.15, 95% CI -0.24 to -0.06), AFT (ß -0.15, 95% CI -0.24 to -0.06), DSST (ß -0.34, 95% CI -0.43 to -0.26), and global cognition (ß -0.24, 95% CI -0.32 to -0.16) z-scores after controlling for the covariates. CONCLUSIONS: Toxoplasma gondii seropositivity is associated with worse immediate and delayed verbal learning, language proficiency, executive functioning, processing speed, sustained attention, working memory, as well as global cognition in older adults. Public health measures aiming at preventing Toxoplasma gondii infection may help preserve cognitive functioning in older adults.

Elimination of methylmercury production potential in excessive sludge in wastewater treatment plants by sulfur addition.

Mercury ions (Hg(II)) in wastewater can accumulate and transform into the highly neurotoxic methylmercury (MeHg) in activated sludge. The release of MeHg can have severe environmental consequences, making the treatment of MeHg-contaminated sludge a pressing concern. In this study, we found that all the collected activated sludge samples, from different wastewater treatment plants in four cities, had the potential for Hg methylation. The Hg-methylating capacity reached a maximum level of 0.70-0.92 µg/g volatile suspended solids after 48 h of exposure to 5 µg/L Hg(II) and showed an average MeHg production rate of 4.8±0.5%. Accordingly, a sludge treatment method involving the addition of elemental sulfur (S0) for a short-term or long-term duration (3 or 180 days, respectively) was proposed. The results demonstrated that this treatment approach effectively mitigated and potentially eliminated MeHg formation by simultaneously reducing Hg bioavailability and Hg-methylating bioactivity. We found that bioavailable Hg(II) ions were converted to a secondary phase similar to insoluble HgS after S0 addition treatment, leading to a decrease in Hg bioavailability in sludge. The enhancement of Hg and extracellular polymeric substances (EPS) complexation via the increasing amount of thiol groups in EPS also reduced the Hg bioavailability after the long-term treatment. Furthermore, the long-term S0 addition significantly reduced the abundance of Hg-methylators with hgcA gene and promoted the growth of Hg-reducers with merA gene, which ensured the complete elimination of MeHg production potential of the excessive activated sludge. Our findings demonstrated that the proposed S0-addition sludge treatment is a promising and safe biotechnology for treating Hg-contaminated sludge. This approach has the potential to contribute significantly to the mitigation of MeHg pollution within environmental contexts.

Fluorescence-quenching mechanisms of novel isomorphic Zn/Cd coordination polymers for selective nitrobenzene detection.

Nitroaromatic compounds in aqueous undermine environmental sustainability and affect human health. The development of a fluorescent sensor capable of efficiently and selectively detecting trace amounts of nitroaromatic compounds presents a considerable challenge. This study introduced Zn/Cd isomeric coordination polymers (Zn-H2CIA-1/Cd-H2CIA-2), which are synthesized using 5-((4-carboxybenzyl)oxy)isophthalic acid (5-H3CIA) and 1,10-phenanthroline (Phen). The polymers have zero-dimensional discrete crystal structure with a six-coordinated scissor-like shape. The two coordination polymers can be used as fluorescent sensors for detecting nitrobenzene (NB) and demonstrated favorable sensitivity, with detection limits of 1.95 × 10-8 and 4.66 × 10-7 mol/L, respectively. Zn-H2CIA-1 exhibited stronger fluorescence and a more sensitive response to NB compared with Cd-H2CIA-2. To elucidate their fluorescence-quenching mechanisms, we analyzed Zn-H2CIA-1 by performing DFT and TD-DFT calculations. The pore structure, density of states, excitation energy, hole-electron distribution, and orbital composition were analyzed. The suitable size of pores in Zn-H2CIA-1 is the main reason for its high NB selectivity. Moreover, intermolecular π-π stacking interactions result in an orbital overlap between Zn-H2CIA-1 and NB, enabling the transfer of electrons from Zn-H2CIA-1 to NB. This electron transfer is identified as the fundamental cause of fluorescence quenching in Zn-H2CIA-1.

Increased prevalence of pretreatment drug resistance mutations in treatment-naïve people living with HIV-1 in Henan Province, China (2022/23).

Human deficiency virus type 1 (HIV-1) harboring drug resistance mutations (DRMs) before the initiation of antiretroviral therapy (ART) poses a serious threat to the efficacy of current ART regimens. Currently, the prevalence of pre-treatment drug resistance mutations (PDRMs) including transmitted DRMs (TDRMs) is not completely clear. Understanding this prevalence better should offer valuable data for clinical- and government-level decision-making. To closely monitor the PDRM trend in treatment-naïve people living with HIV/AIDS (PLWHA) in Henan Province, China, plasma samples from the patients seeking treatments at our hospital from January 2022 to February 2023 were collected for genotypic drug resistance testing. From the 645 patients whose samples were collected, partial pol and integrase gene sequences were obtained from 637 patients. Subtyping analysis indicated that the top-three most common subtypes, in descending order, were CRF07_BC (41.76%, 266/637), CRF01_AE (28.26%, 180/637), and B (20.41%, 130/637). PDRMs were observed in 5.18% (33/637), 6.28% (40/637), 0.31% (2/637), and 2.83% (18/637) cases for nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs), respectively; all these medications contributed to an overall PDRM prevalence of 11.93% (76/637). On analyzing individual PDRMs, we noted that the most commonly observed mutation(s) were K103S/N (3.77%, 24/637), M184I/V (3.14%, 20/637), followed by K65R (1.26%, 8/637), and V106A/M (1.10%, 7/637). PDRM prevalence in ART-naïve PLWHA of Henan Province is high and increased compared with that noted in previous years. However, evidence of cluster-linked outbreaks of PDRMs is lacking, suggesting that measures such as education about adherence and improved treatment strategies with a low incidence of failure can effectively reduce PDRM prevalence.

Efficacy and safety of ainuovirine versus efavirenz combination therapies with lamivudine/tenofovir disoproxil fumarate for medication of treatment-naïve HIV-1-positive adults: week 48 results of a randomized controlled phase 3 clinical trial followed by an open-label setting until week 96.

Background: Ainuovirine (ANV) is a new non-nucleoside reverse transcriptase inhibitor (NNRTI), which was initially synthesized in Korea and later further developed in both Korea and China. Methods: A randomized, double-blind, double-dummy, positive parallel group, non-inferiority, phase 3 trial was conducted in 7 sites across China. Eligible HIV-1-positive antiretroviral therapy (ART)-naïve adults aged 18-65 years were randomly assigned in a 1:1 ratio to receive tenofovir disoproxil fumarate and lamivudine (TDF+3TC) in combination with either ANV (ANV group) or efavirenz (EFV group) for up to 48 weeks. Subsequently, participants in both groups received one of the two drug combinations according to their choice until week 96 in an observational study under an open-label setting. The primary endpoint was the proportion of participants achieving HIV RNA <50 copies/mL at week 48, with non-inferiority pre-specified at a margin of 10%. The secondary efficacy endpoints were logarithmic changes in HIV RNA, percentage of participants with HIV RNA levels ≤400 copies/mL and changes in the CD4 T-cell count after 48 and 96 weeks of treatment, as well as the percentage of participants with HIV RNA levels <50 copies/mL at 96 weeks of treatment. Safety endpoints were the incidence of adverse events and laboratory abnormalities evaluated according to the Division of AIDS criteria. This study was registered with the Chinese Clinical Trial Registry (Registration number: ChiCTR1800019041). Findings: Between November 27, 2018 and March 11, 2021, a total of 826 participants were screened, and 630 were finally enrolled and randomly assigned (1:1) to either ANV (n = 315) or EFV (n = 315) groups. The mean age was 30.6 ± 9.4 years and most participants were male (94.6%). At week 48, 274 (87.0%) of 315 participants in the ANV group and 288 (91.7%) of 314 in the EFV group achieved HIV-1 RNA <50 copies/mL and non-inferiority was established (difference: -4.7%, 95% CI: -9.6 to 0.1%). In the period, 293 participants continued to take the ANV regimen and 287 switched from the EFV to the ANV regimen. During the open-label period, 92.5% (271/293) of participants in the continued ANV group and 95.1% (273/287) in the ANV to EFV transfer group remained virologically suppressed (HIV-1 RNA <50 copies/mL) at week 96 (p = 0.189). The incidence of NNRTI treatment-related adverse events (TEAEs) at week 48 was 67.6% in 315 participants in the ANV group, which was significantly lower than in 91.4% of 314 participants in the EFV group (p < 0.001). The most common TEAEs (weeks 0-48) were dizziness (10.5%) and dyslipidemia (22.2%) in the ANV group vs. 51.0% and 34.4% in the EFV group, respectively, followed by transaminase elevation (9.2% vs. 29.0%), γ-glutamyl transferase elevation (8.3% vs. 19.1%), and rash (7.9% vs. 18.8%) (all p < 0.001). After switching from EFV to ANV, TEAEs in the former EFV participants were significantly reduced in the following observational period of 48-96 weeks. Interpretation: The week 48 results indicated that the efficacy of ANV was non-inferior to EFV when combined with two NRTIs. The per-protocol risk difference at week 48 for the primary endpoint also supported non-inferiority. TEAEs in ANV treated participants were less frequent with regard to liver toxicity, dyslipidemia, neuropsychiatric symptoms and rash compared to the EFV group during the first 48 weeks of therapy. The effects were maintained during the 48-96 weeks of therapy. Funding: Jiangsu Aidea Pharmaceutical Co., Ltd.

Pattern of infection and genotypes of human papillomavirus in Zhengzhou City based on a four-year (2015-2018) epidemiological study.

Persistent human papillomavirus (HPV) infection has been associated with the development of cervical cancer. To reduce the incidence of cervical cancer and promote awareness of HPV, a government-sponsored epidemiological study was conducted from 2015 to 2018 in Zhengzhou City. A total of 184,092 women aged 25-64 years were included, of which 19,579 were infected with HPV, reflecting a prevalence of 10.64 percent (19,579/184,092). The HPV genotypes found were classified as high-risk (13 genotypes) and low-risk (8 genotypes). Single and multiple infections were detected in 13,787 (70.42 percent) and 5,792 (29.58 percent) women, respectively. The five most common high-risk genotypes detected, listed in descending order, were HPV52 (2.14 percent; 3,931/184,092), HPV16 (2.04 percent; 3,756/184,092), HPV58 (1.42 percent; 2,607/184,092), HPV56 (1.01 percent; 1,858/184,092), and HPV39 (0.81 percent; 1,491/184,092). Meanwhile, the most common low-risk genotype was HPV53 (0.88 percent; 1,625/184,092). The prevalence of HPV gradually increased with age, with the highest occurring in women aged 55-64 years. The prevalence of single-type HPV infection decreased with age, whereas that of multiple-type HPV infection increased with age. This study indicates a high burden of HPV infection in women in Zhengzhou City.

Microbial cell wall sorption and Fe-Mn binding in rhizosphere contribute to the obstruction of cadmium from soil to rice.

Screening high-tolerant microorganisms to cadmium (Cd) and revealing their bio-obstruction mechanism could be significant for Cd regulation from farmland to the food chain. We examined the tolerance and bio-removal efficiency of Cd ions of two bacterial strains, Pseudomonas putida 23483 and Bacillus sp. GY16, and measured the accumulation of Cd ions in rice tissues and its different chemical forms in soil. The results showed that the two strains had high tolerance to Cd, but the removal efficiency was decreased successively with increasing Cd concentrations (0.05 to 5 mg kg-1). Cell-sorption accounted for the major proportion of Cd removal compared with excreta binding in both strains, which was conformed to the pseudo-second-order kinetics. At the subcellular level, Cd was mostly taken up by the cell mantle and cell wall, and only a small amount entered into the cytomembrane and cytoplasmic with time progressed (0 to 24 h) in each concentration. The cell mantle and cell wall sorption decreased with increasing Cd concentration, especially in the cytomembrane and cytoplasmic. The scanning electron microscope (SEM) and energy dispersive X-ray (EDS) analysis verified that Cd ions were attached to the cell surface, and the functional groups of C-H, C-N, C=O, N-H, and O-H in the cell surface may participate in cell-sorption process tested by the FTIR analysis. Furthermore, inoculation of the two strains significantly decreased Cd accumulation in rice straw and grain but increased in the root, increased Cd enrichment ratio in root from soil, decreased Cd translocation ratio from root to straw and grain, and increased the Cd concentrations of Fe-Mn binding form and residual form in rhizosphere soil. This study highlights that the two strains mainly removed Cd ions in solution through biosorption and passivated soil Cd as Fe-Mn combined form ascribe to its characteristics of manganese-oxidizing, eventually achieving bio-obstruction of Cd from soil to rice grain.

The high fluorescence sensitivity property and quenching mechanism of one-dimensional Cd-HCIA-1 sensor for nitrobenzene.

The sensing of nitroaromatic compounds in aqueous solution is closely related to environmental sustainability and human health. In this study, a novel Cd(II) coordination polymer (Cd-HCIA-1) was designed and prepared, and its crystal structure, luminescence performance, detection of nitro pollutants in water, and fluorescence quenching mechanisms were studied. Cd-HCIA-1 exhibited a one-dimensional ladder-like chain based on a T-shape ligand of 5-((4-carboxybenzyl) oxy) isophthalic acid (5-H3CIA). The H-bonds and π-π stacking interactions were then used to construct the supramolecular skeleton in common. Luminescence studies revealed that Cd-HCIA-1 can detect nitrobenzene (NB) in aqueous solution with high sensitivity and selectivity, and the limit of detection was 3.03 × 10-9 mol L-1. The fluorescence quenching mechanism of the photo-induced electron transfer for NB by Cd-HCIA-1 was obtained through an investigation of the pore structure, density of states, excitation energy, orbital interactions, hole-electron analysis, charge transfer, and electron transfer spectra by using density functional theory (DFT) and time-dependent DFT methods. NB was absorbed in the pore, π-π stacking increased the orbital overlap, and the LUMO was mainly composed of NB fragments. The charge transfer between ligands was blocked, resulting in fluorescence quenching. This study on fluorescence quenching mechanisms can be used to develop efficient explosive sensors.

Pyruvate dehydrogenase kinase supports macrophage NLRP3 inflammasome activation during acute inflammation.

Activating the macrophage NLRP3 inflammasome can promote excessive inflammation with severe cell and tissue damage and organ dysfunction. Here, we show that pharmacological or genetic inhibition of pyruvate dehydrogenase kinase (PDHK) significantly attenuates NLRP3 inflammasome activation in murine and human macrophages and septic mice by lowering caspase-1 cleavage and interleukin-1ß (IL-1ß) secretion. Inhibiting PDHK reverses NLRP3 inflammasome-induced metabolic reprogramming, enhances autophagy, promotes mitochondrial fusion over fission, preserves crista ultrastructure, and attenuates mitochondrial reactive oxygen species (ROS) production. The suppressive effect of PDHK inhibition on the NLRP3 inflammasome is independent of its canonical role as a pyruvate dehydrogenase regulator. Our study suggests a non-canonical role of mitochondrial PDHK in promoting mitochondrial stress and supporting NLRP3 inflammasome activation during acute inflammation.

Treatment and remediation of metal-contaminated water and groundwater in mining areas by biological sulfidogenic processes: A review.

Heavy metal pollution in the mining areas leads to serious environmental problems. The biological sulfidogenic process (BSP) mediated by sulfidogenic bacteria has been considered an attractive technology for the treatment and remediation of metal-contaminated water and groundwater. Notwithstanding, BSP driven by different sulfidogenic bacteria could affect the efficiency and cost-effectiveness of the treatment performance in practical applications, such as the microbial intolerance of pH and metal ions, the formation of toxic byproducts, and the consumption of organic electron donors. Sulfur-reducing bacteria (S0RB)-driven BSP has been demonstrated to be a promising alternative to the commonly used sulfate-reducing bacteria (SRB)-driven BSP for treating metal-contaminated wastewater and groundwater, due to the cost-saving in chemical addition, the high efficiency in sulfide production and metal removal efficiency. Although the S0RB-driven BSP has been developed and applied for decades, the present review works mainly focus on the developments in SRB-driven BSP for the treatment and remediation of metal-contaminated wastewater and groundwater. Accordingly, a comprehensive review for metal-contaminated wastewater treatment and groundwater remediation should be provided with the incorporation of the SRB- and S0RB-driven BSP. To identify the bottlenecks and to improve BSP performance, this paper reviews sulfidogenic bacteria presenting in metal-contaminated water and groundwater; highlight the critical factors for the metabolism of sulfidogenic bacteria during BSP; the ecological roles of sulfidogenic bacteria and the mechanisms of metal removal by sulfidogenic bacteria; and the application of the present sulfidogenic systems and their drawbacks. Accordingly, the research knowledge gaps, current process limitations, and future prospects were provided for improving the performance of BSP in the treatment and remediation of metal-contaminated wastewater and groundwater in mining areas.

Consistency of drug-resistant mutations in plasma and peripheral blood mononuclear cells of patients with treatment-naïve and treatment-experienced HIV-1 infection.

Introduction: Genotypic drug resistance testing is cursrently recommended by the World Health Organization for all patients infected with human immunodeficiency virus type 1 (HIV-1) undergoing care or switching regimes due to failure with previous antiretroviral therapy (ART). Patients with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) who meet the criteria for free testing for genotypic drug resistance due to poor adherence in Henan Province may resume their previous regimens before resampling. Therefore, resistance testing based on plasma RNA can fail in a proportion of patients. Resistance testing based on peripheral blood mononuclear cells (PBMCs) is an alternative option. In this study, we investigated the differences in drug-resistant mutations (DRMs) between plasma HIV RNA and proviral DNA in treatment-experienced and treatment-naïve patients. Methods: Matched plasma RNA and proviral DNA samples of 66 HIV-1 infected treatment-naïve and 78 treatment-experienced patients were selected for DRM analysis and comparison. Results: DRMs were detected in 27.3% (18/66) of treatment-naïve and 80.8% (63/78) of treatment-experienced samples. Resistance to at least one drug was detected based on analysis of plasma RNA and proviral DNA in 7.6% (5/66) and 9.1% (6/66) of treatment-naïve patients and in 79.5% (62/78) and 78.2% (61/78) of treatment-experienced patients, respectively. Furthermore, 61/66 (92.4%) of treatment-naïve patients showed concordant RNA and DNA drug resistance. When drug resistance was defined as intermediate and high, the concordance of drug resistance profiles of paired RNA and proviral DNA samples derived from treatment-naïve patients were up to 97.0% compared with only 80.8% (63/78) in treatment-experienced patients. Discussion: Our data indicate that drug resistance testing based on plasma RNA or proviral DNA might be interchangeable in treatment-naïve patients, whereas plasma RNA-based testing remains the best choice for drug resistance analysis in patients with ART failure in clinical practice.