Association of LDL-C/HDL-C ratio with coronary heart disease: A meta-analysis.

BACKGROUND: Coronary heart disease (CHD) is a common heart disease and a leading cause of death in developed countries and some developing countries such as China. It is recognized as a multifactorial disease, with dyslipidemia being closely associated with the progression of coronary atherosclerosis. Numerous studies have confirmed the relationship between a single indicator of low-density lipoprotein cholesterol (LDL-C) or high-density lipoprotein cholesterol (HDL-C) and CHD. However, the association between LDL-C to HDL-C ratio (LHR) and CHD remains unclear. This study aimed to comprehensively explore the association between LHR and CHD. METHODS: This meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses. PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases were comprehensively searched up to June 15, 2023, to find the studies that indicated the connection between LHR and CHD. A total of 12 published studies were selected. The random-effects model was used to pool the data and mean difference (MD), and the 95% confidence intervals (CI) were taken as the overall outcome. No language restrictions existed in the study selection. The Review Manager 5.4 and Stata 12 were used to analyze the data. RESULTS: Twelve high-quality clinical studies involving 5544 participants, including 3009 patients with CHD, were enrolled in the meta-analysis. The findings revealed that the LHR was higher by 0.65 in patients with CHD than in those without CHD (MD, 0.65; 95% CI, 0.50-0.80). CONCLUSION: The LHR was found to be positively correlated with CHD, suggesting that it may serve as a potential indicator of CHD.

Functional Characterization of CsSWEET5a, a Cucumber Hexose Transporter That Mediates the Hexose Supply for Pollen Development and Rescues Male Fertility in Arabidopsis.

Pollen cells require large amounts of sugars from the anther to support their development, which is critical for plant sexual reproduction and crop yield. Sugars Will Eventually be Exported Transporters (SWEETs) have been shown to play an important role in the apoplasmic unloading of sugars from anther tissues into symplasmically isolated developing pollen cells and thereby affect the sugar supply for pollen development. However, among the 17 CsSWEET genes identified in the cucumber (Cucumis sativus L.) genome, the CsSWEET gene involved in this process has not been identified. Here, a member of the SWEET gene family, CsSWEET5a, was identified and characterized. The quantitative real-time PCR and ß-glucuronidase expression analysis revealed that CsSWEET5a is highly expressed in the anthers and pollen cells of male cucumber flowers from the microsporocyte stage (stage 9) to the mature pollen stage (stage 12). Its subcellular localization indicated that the CsSWEET5a protein is localized to the plasma membrane. The heterologous expression assays in yeast demonstrated that CsSWEET5a encodes a hexose transporter that can complement both glucose and fructose transport deficiencies. CsSWEET5a can significantly rescue the pollen viability and fertility of atsweet8 mutant Arabidopsis plants. The possible role of CsSWEET5a in supplying hexose to developing pollen cells via the apoplast is also discussed.

High-Performance and Stable Colloidal Quantum Dots Imager via Energy Band Engineering.

Solution-processed colloidal quantum dot (CQD) photodiodes are compatible for monolithic integration with silicon-based readout circuitry, enabling ultrahigh resolution and ultralow cost infrared imagers. However, top-illuminated CQD photodiodes for longer infrared imaging suffer from mismatched energy band alignment between narrow-bandgap CQDs and the electron transport layer. In this work, we designed a new top-illuminated structure by replacing the sputtered ZnO layer with a SnO2 layer by atomic layer deposition. Benefiting from matched energy band alignment and improved heterogeneous interface, our top-illuminated CQD photodiodes achieve a broad-band response up to 1650 nm. At 220 K, these SnO2-based devices exhibit an ultralow dark current density of 3.5 nA cm-2 at -10 mV, reaching the noise limit for passive night vision. The detectivity is 4.1 × 1012 Jones at 1530 nm. These SnO2-based devices also demonstrate exceptional operation stability. By integrating with silicon-based readout circuitry, our CQD imager realizes water/oil discrimination and see-through smoke imaging.

Integrated analysis of single-cell and bulk transcriptome identifies a signature based on NK cell marker genes to predict prognosis and therapeutic response in clear cell renal cell carcinoma.

Background: Accumulating evidence has highlighted the effects of natural killer (NK) cells on shaping anti-tumor immunity. This study aimed to construct an NK cell marker gene signature (NKMS) to predict prognosis and therapeutic response of clear cell renal cell carcinoma (ccRCC) patients. Methods: Publicly available single-cell and bulk RNA profiles with matched clinical information of ccRCC patients were collected from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), ArrayExpress, and International Cancer Genome Consortium (ICGC) databases. A novel NKMS was constructed, and its prognostic value, associated immunogenomic features and predictive capability to immune checkpoint inhibitors (ICIs) and anti-angiogenic therapies were evaluated in ccRCC patients. Results: We identified 52 NK cell marker genes by single-cell RNA-sequencing (scRNA-seq) analysis in GSE152938 and GSE159115. After least absolute shrinkage and selection operator (LASSO) and Cox regression, the most prognostic 7 genes (CLEC2B, PLAC8, CD7, SH3BGRL3, CALM1, KLRF1, and JAK1) composed NKMS using bulk transcriptome from TCGA. Survival and time-dependent receiver operating characteristic (ROC) analysis exhibited exceptional predictive capability of the signature in the training set and two independent validation cohorts (E-MTAB-1980 and RECA-EU cohorts). The seven-gene signature was able to identify patients within high Fuhrman grade (G3-G4) and American Joint Committee on Cancer (AJCC) stage (III-IV). Multivariate analysis confirmed the independent prognostic value of the signature, and a nomogram was built for clinical utility. The high-risk group was characterized by a higher tumor mutation burden (TMB) and greater infiltration of immunocytes, particularly CD8+ T cells, regulatory T (Treg) cells and follicular helper T (Tfh) cells, in parallel with higher expression of genes negatively regulating anti-tumor immunity. Moreover, high-risk tumors exhibited higher richness and diversity of T-cell receptor (TCR) repertoire. In two therapy cohorts of ccRCC patients (PMID32472114 and E-MTAB-3267), we demonstrated that high-risk group showed greater sensitivity to ICIs, whereas the low-risk group was more likely to benefit from anti-angiogenic therapy. Conclusions: We identified a novel signature that can be utilized as an independent predictive biomarker and a tool for selecting the individualized treatment for ccRCC patients.

Prediction of Anthocyanidins Content in Purple Chinese Cabbage Based on Visible/Near Infrared Spectroscopy.

Purple Chinese cabbage (PCC) has become a new breeding trend due to its attractive color and high nutritional quality since it contains abundant anthocyanidins. With the aim of rapid evaluation of PCC anthocyanidins contents and screening of breeding materials, a fast quantitative detection method for anthocyanidins in PCC was established using Near Infrared Spectroscopy (NIR). The PCC samples were scanned by NIR, and the spectral data combined with the chemometric results of anthocyanidins contents obtained by high-performance liquid chromatography were processed to establish the prediction models. The content of cyanidin varied from 93.5 mg/kg to 12,802.4 mg/kg in PCC, while the other anthocyanidins were much lower. The developed NIR prediction models on the basis of partial least square regression with the preprocessing of no-scattering mode and the first-order derivative showed the best prediction performance: for cyanidin, the external correlation coefficient (RSQ) and standard error of cross-validation (SECV) of the calibration set were 0.965 and 693.004, respectively; for total anthocyanidins, the RSQ and SECV of the calibration set were 0.966 and 685.994, respectively. The established models were effective, and this NIR method, with the advantages of timesaving and convenience, could be applied in purple vegetable breeding practice.

Rock-on-a-chip: "Seeing" the association/disassociation of an adaptive polymer in solutions flowing through porous media.

The flow and transport of polymer solutions through porous media are ubiquitous in myriad scientific and engineering applications. With escalating interest in adaptive polymers, understanding the flow dynamics of their solutions is indispensable (yet lacking). Here, the hydrophobic-effect-driven reversible associations in a self-adaptive polymer (SAP) solution and its flow characteristics in a microfluidic-based "rock-on-a-chip" device have been analyzed. The hydrophobic aggregates were fluorescent labeled; this enabled a direct visualization of the in situ association/disassociation of the polymer supramolecular assemblies in pore spaces and throats. Furthermore, the influence of this adaptation on the macroscopic flow behavior of the SAP solution was analyzed by comparing its flow with that of two partially-hydrolyzed polyacrylamide (the molecular weight (MW)-equivalent HPAM-1 and ultrahigh-MW HPAM-2) solutions in the semi-dilute regime with similar initial viscosities. At low flow rates (with shear predominance), the SAP solution showed a low shear viscosity compared to HPAM-1, indicating a higher shear susceptibility for association than chain entanglement. Although the SAP exhibited the same elastic instability as the non-adaptive polymers above a threshold flow rate, the adaptable structure of the former advanced the onset of its viscoelastic-governed flow, providing a stronger flow resistance, possibly through an extension resistance. Furthermore, 3D-media analysis indicated that the reversible association/disassociation of SAP increased the accessible pore space during nonaqueous-liquid displacement, facilitating oil production.

Screening the Impact of Surfactants and Reaction Conditions on the De-Inkability of Different Printing Ink Systems for Plastic Packaging.

One of the major applications (40% in Europe) of plastic is packaging, which is often printed to display required information and to deliver an attractive aesthetic for marketing purposes. However, printing ink can cause contamination in the mechanical recycling process. To mitigate this issue, the use of surfactants in an alkaline washing process, known as de-inking, has been employed to remove printing ink and improve the quality of recyclates. Despite the existence of this technology, there are currently no data linking the de-inking efficiency with typical printing ink compositions. Additionally, it is necessary to investigate the de-inking process under the process parameters of existing recycling plants, including temperature, NaOH concentration, and retention time. This study aims to evaluate the performance of commonly used printing inks with different compositions under various washing scenarios for plastic recycling in conjunction with different de-inking detergents containing surfactants or mixtures of surfactants. The results indicate that the pigments applied to the ink have no significant effect on the de-inking process, except for carbon black (PBk 7). Nitrocellulose (NC) binder systems exhibit high de-inkability (over 95%) under the condition of 55 °C and 1 wt.% NaOH. However, crosslinked binder systems can impede the de-inking effect, whether used as a binder system or as an overprint varnish (OPV). The de-inking process requires heating to 55 °C with 1 wt.% NaOH to achieve a substantial effect. Based on the findings in this work, breaking the Van der Waals forces, hydrogen bonds, and covalent bonds between the printing ink and plastic film is an essential step to achieve the de-inking effect. Further research is needed to understand the interaction between surfactants and printing inks, enabling the development of de-inkable printing inks and high-performance surfactants that allow for de-inking with less energy consumption. The surfactant and NaOH have a synergistic effect in cleaning the printing ink. NaOH provides a negative surface charge for the adsorption of the cationic head of the surfactant and can hydrolyze the covalent bonds at higher concentrations (>2 wt.%).

A Quantitative Approach to Determine Hydrophobe Content of Associating Polyacrylamide Using a Fluorescent Probe.

Hydrophobically associating polymers have found widespread applications in many domains due to their unique rheological behavior, which is primarily dictated by the hydrophobe content. However, the low fraction of hydrophobic monomers in polymers makes this parameter's precise and straightforward measurement difficult. Herein, a variety of hydrophobically associating polyacrylamides (HAPAM) with different alkyl chain lengths (L) and hydrophobic contents ([H]) were prepared by post-modification and accurately characterized by 1H NMR spectroscopy. The maximal fluorescence emission intensity (I) of 8-anilino-1-naphthalenesulfonic acid, which is sensitive to hydrophobic environments, was then detected in those polymer solutions and shown as a ratio to that in the polymer-free solution (I0). It was found that I/I0 for 0.5 wt% HAPAM can be scaled versus CH, which is a variate related to both L and [H], as I/I0 = 1.15 + 1.09 × 108CH3.42, which was also verified to be applicable for hydrophobic associating hydrolyzed polyacrylamide (HHAPAM). This relationship provides a handy method for determining the hydrophobic content of hydrophobically associating polymers, particularly for field applications.

A Comparative Study on CO2-Switchable Foams Stabilized by C22- or C18-Tailed Tertiary Amines.

The CO2 aqueous foams stabilized by bioresource-derived ultra-long chain surfactants have demonstrated considerable promising application potential owing to their remarkable longevity. Nevertheless, existing research is still inadequate to establish the relationships among surfactant architecture, environmental factors, and foam properties. Herein, two cases of ultra-long chain tertiary amines with different tail lengths, N-erucamidopropyl-N,N-dimethylamine (UC22AMPM) and N-oleicamidopropyl-N,N-dimethylamine (UC18AMPM), were employed to fabricate CO2 foams. The effect of temperature, pressure and salinity on the properties of two foam systems (i.e., foamability and foam stability) was compared using a high-temperature, high-pressure visualization foam meter. The continuous phase viscosity and liquid content for both samples were characterized using rheometry and FoamScan. The results showed that the increased concentrations or pressure enhanced the properties of both foam samples, but the increased scope for UC22AMPM was more pronounced. By contrast, the foam stability for both cases was impaired with increasing salinity or temperature, but the UC18AMPM sample is more sensitive to temperature and salinity, indicating the salt and temperature resistance of UC18AMPM-CO2 foams is weaker than those of the UC22AMPM counterpart. These differences are associated with the longer hydrophobic chain of UC22AMPM, which imparts a higher viscosity and lower surface tension to foams, resisting the adverse effects of temperature and salinity.

A Practical Approach to Bicyclic Carbamoyl Pyridones with Application to the Synthesis of HIV-1 Integrase Strand Transfer Inhibitors.

An efficient one-pot synthetic method has been developed for the preparation of bicyclic carbamoyl pyridones from the known common intermediate methyl 5-((2,4-difluorobenzyl)carbamoyl)-1-(2,2-dimethoxyethyl)-3-methoxy-4-oxo-1,4-dihydropyridine-2-carboxylate (8). The scalable protocol is facile and employs readily available reagents, needing only a single purification as the final step. The utility of the approach was demonstrated by preparing a library of HIV-1 integrase strand transfer inhibitors (INSTIs) that differ by the presence or absence of a double bond in the B-ring of the bicyclic carbamoyl pyridines 6 and 7. Several of the analogs show good antiviral potencies in single-round HIV-1 replication antiviral assays and show no cytotoxicity in cell culture assays. In general, the compounds with a B-ring double bond have higher antiviral potencies than their saturated congeners. Our methodology should be applicable to the synthesis of a range of new metal-chelating analogs.

Thrombotic thrombocytopenic purpura developed after pegylated interferon treatment for hepatitis B infection.

BACKGROUND: Thrombotic thrombocytopenic purpura (TTP) is a rare and life-threatening thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, severe thrombocytopenia, and organ ischemia. It is related to severe deficiency in ADAMTS13, which is usually acquired via ADAMTS13 autoantibodies or inherited via mutations of the ADAMTS13 gene. The etiology of acquired TTP including HIV infection, pregnancy, autoimmune disease, organ transplantation, drugs, malignancy and so on. Here, we firstly reported a patient diagnosed as acquired TTP after pegylated interferon therapy for hepatitis B and COVID-19 vaccination. CASE PRESENTATION: A 36-year-old male attended to our unit with a five-day history of intermittent hematuria and progressive fatigue on January 5th, 2022. He had a 13 years history of hepatitis B infection and undergone pegylated interferon treatment (which was paused for two months because of COVID-19 vaccination) for nearly 3 years. Laboratory evaluation revealed a haemoglobin level of 61 g/L, platelet count of 11 × 109/L, lactate dehydrogenase 2133 U/L. The direct and indirect Coombs test were both negative. On a peripheral blood smear, there were about 18.8% schistocytes. Meanwhile, the results of ADAMTS 13 activity and antibody were < 5% and 181.34 ng/ml (131.25-646.5), respectively CONCLUSION: This case firstly reported the rare complication of TTP after pegylated interferon treatment for hepatitis B and COVID-19 vaccine injection. This unique sign warrants more attention as an early cue of diagnosis of TTP and be aware of the rarity adverse effect of interferon therapy and COVID-19 vaccination.

In situ micro-emulsification during surfactant enhanced oil recovery: A microfluidic study.

HYPOTHESIS: It is generally believed that the improved efficiency of surfactant enhanced oil recovery (EOR) comes from ultra-low interfacial tension (IFT) between oil and surfactant solution owing to the formation of middle-phase microemulsion. However, hindered visibility in underground porous media prevents direct observation of in situ generation of middle-phase microemulsion during surfactant flooding. Thus, direct visualization of the process is vital, and could clarify its contribution to EOR. EXPERIMENTS: Micro-emulsification of a displacing fluid containing sodium 4-dodecylbenzenesulfonate and alcohol propoxy sulfate with model oil was investigated. Phase diagrams were drawn using salinity scans, and the influence of polymer on emulsification was analyzed. Micro-emulsification was monitored through in situ fluorescent tagging via 2D-microfluidics and ex situ visualization via cryo-electron microscopy and small angle X-ray scattering. Its contribution to the oil recovery factor was quantified by measuring the volume of each phase in the eluates. FINDINGS: On-chip experiments indicated that in situ micro-emulsification occurred when the prescreened surfactant solution flowed in contact with trapped oil. The aqueous phase initially invaded the residual oil, forming a low mobility microemulsion. This microemulsion was then diluted by subsequent displacing fluid, forming a new driving fluid that caused ultra-low IFT in the trapped oil downstream. Under the synergistic effect of micellar solubilization and trapped-oil mobilization, the recovery factor could be increased by up to 40% over waterflooding and 43% on polymer inclusion in the formulation.

CsSWEET2, a Hexose Transporter from Cucumber (Cucumis sativus L.), Affects Sugar Metabolism and Improves Cold Tolerance in Arabidopsis.

Sugars, which are critical osmotic compounds and signalling molecules in plants, and Sugars Will Eventually be Exported Transporters (SWEETs), which constitute a novel family of sugar transporters, play central roles in plant responses to multiple abiotic stresses. In the present study, a member of the SWEET gene family from cucumber (Cucumis sativus L.), CsSWEET2, was identified and characterized. Histochemical analysis of ß-glucuronidase expression in transgenic Arabidopsis plants showed that CsSWEET2 is highly expressed in the leaves; subcellular localization indicated that CsSWEET2 proteins are localized in the plasma membrane and endoplasmic reticulum. Heterologous expression assays in yeast demonstrated that CsSWEET2 encodes an energy-independent hexose/H+ uniporter that can complement both glucose and fructose transport deficiencies. Compared with wild-type Arabidopsis plants, transgenic Arabidopsis plants overexpressing CsSWEET2 had much lower relative electrolyte leakage levels and were much more resistant to cold stress. Sugar content analysis showed that glucose and fructose levels in the transgenic Arabidopsis plants were significantly higher than those in the wild-type plants. Taken together, our results suggest that, by mediating sugar metabolism and compartmentation, CsSWEET2 plays a vital role in improving plant cold tolerance.

Broadband second-harmonic-generation in GdCOB crystals.

Broadband second-harmonic-generation (SHG) in GdCOB crystals was demonstrated for the first time. Theoretical calculation and experiments for the type-I frequency doubling of GdCOB crystal was performed. The result revealed that the spectral retracing point of phase-matching angle was at around 1.65 µm. For broadband fundamental laser source tuning in the range of 1.55-1.7 µm, efficient SHG was realized, the highest conversion efficiency was 56%, and the output bandwidth reached 16 nm.

Glucosinolate Profiles in Different Organs of 111 Radish Accessions and Candidate Genes Involved in Converting Glucobrassicin to 4-Hydroxyglucobrassicin.

Glucosinolate (GSL) not only has highly physiological function for plants but also has considerable human interest. We analyzed the GSL compositions and levels in four organs of 111 radish accessions. Seven major GSLs were detected (approximately 5-245 µmol g-1 DW), among which 4-(methylsulfinyl)but-3-enyl GSL and 4-methylsulfanyl-3-butenyl GSL were the dominant GSLs. GSL levels varied substantially among species and groups, and some genotypes/groups with special GSL profiles were identified. The total GSL level was higher in seeds than in sprouts, taproots, and leaves. Additionally, a correlation analysis revealed that seed 4-(methylsulfinyl)but-3-enyl GSL levels were highly correlated with sprout GSL levels. Moreover, a candidate gene (RsCYP81F2.3) encoding an enzyme that catalyzes the conversion of indol-3-ylmethyl GSL to 4-hydroxyindol-3-ylmethyl GSL was identified based on the detection and analysis of three radish accessions with relatively high indol-3-ylmethyl GSL, low 4-hydroxyindol-3-ylmethyl GSL, and 4-methoxyindol-3-ylmethyl GSL levels in their seeds. Our results provide some insights for finding materials and genes relevant for breeding new varieties with ideal GSL compositions and levels.

Comparison of Outcomes between Percutaneous and Surgical Placement of Peritoneal Dialysis Catheters in Uremic Patients: A Meta-Analysis.

BACKGROUND: The optimal technique for inserting peritoneal dialysis catheters in uremic patients remains debated. This meta-analysis aimed to summarize the current evidence evaluating the efficacy and safety of percutaneous insertion methods compared to surgical methods. METHOD: A literature search was performed in the PubMed, EMBASE, Cochrane, and Web of Science databases. The primary outcome was defined as catheter survival. The secondary outcomes were mechanical and infectious complications related to catheter insertion. RESULTS: Twenty studies were finally identified, including 2 randomized controlled trials. The pooled results of catheter survival, overall mechanical complications, and infectious complications were not significant (odds ratio [OR] = 1.10, 95% confidence interval (CI) = 0.76-1.57, p = 0.62; OR = 0.73, 95% CI = 0.48-1.11, p = 0.14; and OR = 0.64, 95% CI = 0.37-1.09, p = 0.14, respectively). Comparison stratified by the blind percutaneous method versus open surgery indicated a lower overall number of mechanical complications (OR = 0.54, 95% CI = 0.31-0.93, I2 = 72%) and malposition rate (OR = 0.56, 95% CI = 0.34-0.90, I2 = 0%). The leakage rate was higher in the blind percutaneous group than in the open surgery group (OR = 2.55, 95% CI = 1.72-3.79, I2 = 0%); the guided percutaneous method achieved a similar leakage risk to the surgical methods. CONCLUSIONS: The blind percutaneous method performed better with fewer overall mechanical complications and less malposition than open surgery. The leakage risk was higher in the blind percutaneous group, while the guided percutaneous placement group showed similar outcomes to the surgical method groups. Percutaneous methods also had a lower infection risk, which needs further evidence to be confirmed.

miR-27b-3p is Highly Expressed in Serum of Patients with Preeclampsia and has Clinical Significance.

BACKGROUND: Preeclampsia (PE) is defined as a salient complication of late pregnancy. microRNAs (miRNAs) have emerged as critical biological regulators in PE. This study determined miR-27b-3p expression in serum of PE patients and investigated its clinical significance in PE. METHODS: This study enrolled a total of 130 pregnant women, including 90 PE patients (51 mild PE and 39 severe PE) and 40 healthy controls. miR-27b-3p expression in the serum of PE patients and healthy controls was detected using RT-qPCR. The correlation among miR-27b-3p expression and 24-h urine protein, systolic blood pressure (SBP), diastolic blood pressure (DBP), serum creatinine, and fetal birth weight was analyzed using Pearson's correlation coefficient. The targeting relationship between miR-27b-3p and PPARG was verified. PPARG protein level in PE patients was detected using ELISA kits. The predictive efficiency of miR-27b-3p and PPARG in PE was analyzed using the receiver operating characteristic (ROC) curve. RESULTS: Compared to normal pregnant women, PE pregnant women, especially severe PE patients, had higher miR-27b-3p expression. miR-27b-3p was positively correlated with 24-h urine protein, SBP, DBP, and serum creatinine but negatively correlated with fetal birth weight. PPARG was poorly expressed in PE patients and negatively correlated with miR-27b-3p. ROC curve showed that both miR-27b-3p and PPARG had good predictive efficacy on PE. CONCLUSION: miR-27b-3p expression in serum of pregnant women with PE was positively correlated with the severity of PE symptoms, suggesting the involvement of miR-27b-3p in PE occurrence.

Recalibration of the nonlinear optical coefficients of BaGa4Se7 crystal using second-harmonic-generation method.

Nonlinear optical coefficients are important parameters for nonlinear optical crystals. Based on the previously disclosed BaGa4Se7 crystal coefficients, the optimum phase-matching direction with the largest effective nonlinear optical coefficient appears in the second octant (90∘<θ<180∘, 0∘<ϕ<90∘). In this study, a recalibration was performed using the second-harmonic-generation method, and it was confirmed that the optimum phase-matching direction of the BaGa4Se7 crystal is located in its XZ principal plane (ϕ=0∘). Therefore, this study will serve as a good reference for future applications of this excellent crystal.

INSTIs and NNRTIs Potently Inhibit HIV-1 Polypurine Tract Mutants in a Single Round Infection Assay.

Integrase strand transfer inhibitors (INSTIs) are a class of antiretroviral compounds that prevent the insertion of a DNA copy of the viral genome into the host genome by targeting the viral enzyme integrase (IN). Dolutegravir (DTG) is a leading INSTI that is given, usually in combination with nucleoside reverse transcriptase inhibitors (NRTIs), to treat HIV-1 infections. The emergence of resistance to DTG and other leading INSTIs is rare. However, there are recent reports suggesting that drug resistance mutations can occur at positions outside the integrase gene either in the HIV-1 polypurine tract (PPT) or in the envelope gene (env). Here, we used single round infectivity assays to measure the antiviral potencies of several FDA-approved INSTIs and non-nucleoside reverse transcriptase inhibitors (NNRTIs) against a panel of HIV-1 PPT mutants. We also tested several of our promising INSTIs and NNRTIs in these assays. No measurable loss in potency was observed for either INSTIs or NNRTIs against the HIV-1 PPT mutants. This suggests that HIV-1 PPT mutants are not able, by themselves, to confer resistance to INSTIs or NNRTIs.