Torsional Twist of the SARS-CoV and SARS-CoV-2 SUD-N and SUD-M domains.

Coronavirus non-structural protein 3 (nsp3) forms hexameric crowns of pores in the double membrane vacuole that houses the replication-transcription complex. Nsp3 in SARS-like viruses has three unique domains absent in other coronavirus nsp3 proteins. Two of these, SUD-N (Macrodomain 2) and SUD-M (Macrodomain 3), form two lobes connected by a peptide linker and an interdomain disulfide bridge. We resolve the first complete x-ray structure of SARS-CoV SUD-N/M as well as a mutant variant of SARS-CoV-2 SUD-N/M modified to restore cysteines for interdomain disulfide bond naturally lost by evolution. Comparative analysis of all structures revealed SUD-N and SUD-M are not rigidly associated, but rather, have significant rotational flexibility. Phylogenetic analysis supports that the disulfide bond cysteines are also absent in pangolin-SARS and closely related viruses, consistent with pangolins being the presumed intermediate host in the emergence of SARS-CoV-2. The absence of these cysteines does not impact viral replication or protein translation.

The Mac1 ADP-ribosylhydrolase is a Therapeutic Target for SARS-CoV-2.

SARS-CoV-2 continues to pose a threat to public health. Current therapeutics remain limited to direct acting antivirals that lack distinct mechanisms of action and are already showing signs of viral resistance. The virus encodes an ADP-ribosylhydrolase macrodomain (Mac1) that plays an important role in the coronaviral lifecycle by suppressing host innate immune responses. Genetic inactivation of Mac1 abrogates viral replication in vivo by potentiating host innate immune responses. However, it is unknown whether this can be achieved by pharmacologic inhibition and can therefore be exploited therapeutically. Here we report a potent and selective lead small molecule, AVI-4206, that is effective in an in vivo model of SARS-CoV-2 infection. Cellular models indicate that AVI-4206 has high target engagement and can weakly inhibit viral replication in a gamma interferon- and Mac1 catalytic activity-dependent manner; a stronger antiviral effect for AVI-4206 is observed in human airway organoids. In an animal model of severe SARS-CoV-2 infection, AVI-4206 reduces viral replication, potentiates innate immune responses, and leads to a survival benefit. Our results pharmacologically validate Mac1 as a therapeutic target via a novel immune-restoring mechanism that could potentially synergize with existing therapies targeting distinct, essential aspects of the coronaviral life cycle. This approach could be more widely used to target other viral macrodomains to develop antiviral therapeutics beyond COVID-19.

Three distinct conductance states in polycyclic aromatic hydrocarbon derivatives.

Tight-binding model (TBM) and density functional theory (DFT) calculations were employed. Both simulations have demonstrated that the electrical conductance for eight polycyclic aromatic hydrocarbons (PAHs) can be modulated by varying the number of aromatic rings (NAR) within the aromatic derivatives. TBM simulations reveal three distinct conductance states: low, medium and high for the studied PAH derivatives. The three distinct conductance states suggested by TBM are supported by DFT transmission curves, where the low conductance evidenced by T(E) = 0, for benzene, naphthalene, pyrene and anthracene. While azulene and anthanthrene exhibit a medium conductance as T(E) = 1, and tetracene and dibenzocoronene possess a high conductance with T(E) = 2. Low, medium and high values were elucidated according to the energy gap E g and E g gaps are strongly dependent on the NAR in the PAH derivatives. This study also suggests that any PAH molecules are a conductor if E g < 0.20 eV. A linear relationship between the conductance and NAR (G ∝ NAR) was found and conductance follows the order G (benzene, 1 NAR) < G (anthanthrene, 4 NAR) < G (dibenzocoronene, 9 NAR). The proposed study suggests a relevant step towards the practical application of molecular electronics and future device application.

Orientational Effects and Molecular-Scale Thermoelectricity Control.

The orientational effect concept in a molecular-scale junction is established for asymmetric junctions, which requires the fulfillment of two conditions: (1) design of an asymmetric molecule with strong distinct terminal end groups and (2) construction of a doubly asymmetric junction by placing an asymmetric molecule in an asymmetric junction to form a multicomponent system such as Au/Zn-TPP+M/Au. Here, we demonstrate that molecular-scale junctions that satisfy the conditions of these effects can manifest Seebeck coefficients whose sign fluctuates depending on the orientation of the molecule within the asymmetric junction in a complete theoretical investigation. Three anthracene-based compounds are investigated in three different scenarios, one of which displays a bithermoelectric behavior due to the presence of strong anchor groups, including pyridyl and thioacetate. This bithermoelectricity demonstration implies that if molecules with alternating orientations can be placed between an asymmetric source and drain, they can be potentially utilized for increasing the thermovoltage in molecular-scale thermoelectric energy generators (TEGs).

SARS-CoV-2 seropositivity in African women living with HIV and their infants.

BACKGROUND: SARS-CoV-2 seropositivity data in women living with HIV (WLHIV), their infants and associated factors in this subpopulation remain limited. We retrospectively measured SARS-CoV-2 seropositivity from 07/2020-11/2021 among WLHIV and their children in the PROMOTE observational cohort in Uganda, Malawi, and Zimbabwe prior to widespread SARS-CoV-2 vaccination in those countries. METHODS: Plasma stored during 3 waves of the COVID-19 pandemic in East/Southern Africa were tested for SARS-CoV-2 specific IgG antibodies (Ab) using serological assays that detect adaptive immune responses to SARS-CoV-2 spike protein. (EUROIMMUN, Mountain Lakes, New Jersey and Roche Diagnostics, Indianapolis, IN). Modified-Poisson regression models were used to calculate prevalence rate ratios (PRR) and 95% confidence intervals (CI) to identify sociodemographic and clinical risk factors. RESULTS: PROMOTE samples from 918 mothers and 1237 children were analysed. Overall, maternal SARS-CoV-2 seropositivity was 60.1% (95% CI: 56.9 -63.3) and 41.5% (95%CI: 38.8 - 44.2) for children. Non-breastfeeding mothers had a 31% higher risk of SARS-CoV-2 seropositivity compared to breastfeeding mothers (aPRR=1.31, 95%CI: 1.08-1.59). WLHIV with undetectable viral load had a 10% increased risk of SARS-CoV-2 seropositivity (aPRR=1.10, 95%CI: 0.89-1.37). Moreover, those who were normotensive had 12% increased risk SARS-CoV-2 seropositivity (aPRR= 1.12, 95% CI: 0.68-1.85) compared to women with hypertension. Children between 2 and 5 years had a 19% reduced risk of SARS-CoV-2 seropositivity (aPRR=0.81, 95%CI: 0.64-1.02) when compared to younger children. Mother/infant SARS-CoV-2 serostatuses were discordant in 346/802 (43.1%) families tested: mothers+/children- in 72.3%; mothers-/children+ in 26.3%; child+/sibling+ concordance was 34.6%. CONCLUSIONS: These SARS-CoV-2 seropositivity data indicate that by late 2021, about 60% of mothers and about 40% of children in a cohort of HIV-affected families in eastern/southern Africa had been infected with SARS-CoV-2. More mothers than their infants tested SARS-CoV-2+, likely due to a greater external exposure for mothers linked to daily routines/employment, and school closures. Breastfeeding was protective for mothers, likely because of higher likelihood of staying home with young children, and thus less exposure. Discordant results between children within the same families underscores the need to further understand transmission dynamics within households.

NF-κB inhibitor alpha controls SARS-CoV-2 infection in ACE2-overexpressing human airway organoids.

As SARS-CoV-2 continues to spread worldwide, tractable primary airway cell models that recapitulate the cell-intrinsic response to arising viral variants are needed. Here we describe an adult stem cell-derived human airway organoid model overexpressing the ACE2 receptor (ACE2-OE) that supports robust viral replication while maintaining 3D architecture and cellular diversity of the airway epithelium. ACE2-OE organoids were infected with SARS-CoV-2 variants and subjected to single-cell RNA-sequencing. Interferon-lambda was upregulated in cells with low-level infection while the NF-kB inhibitor alpha gene (encoding IkBa) was consistently upregulated in infected cells, and its expression positively correlated with infection levels. Confocal microscopy showed more IkBa expression in infected than bystander cells, but found concurrent nuclear translocation of NF-kB that IkBa usually prevents. Overexpressing a nondegradable IkBa mutant reduced NF-kB translocation and increased viral infection. These data demonstrate the functionality of ACE2-OE organoids in SARS-CoV-2 research and underscore that the strength of the NF-kB feedback loop in infected cells controls viral replication.

Mg/S@g-C3N4 nanosheets: A promising fluorescence sensor for selective Cu2+ detection in water.

This work describes the development of a novel fluorescence sensor based on magnesium/S@g-C3N4 nanosheets for selective detection of copper (Cu2+) ions in water. Mg/S@g-C3N4 nanosheets were prepared by the polycondensation technique and investigated by X-ray diffraction (XRD), ATR-FTIR spectroscopy, scanning electron microscopy (SEM), surface area (BET), and UV-Vis optical absorption measurements. XRD and ATR-FTIR analysis showed the characteristic peaks for S@g-C3N4. The broad full width at half maximum (0.056 radians) implies a smaller crystallite size, representing smaller Mg/S@g-C3N4 sheets. SEM micrograph showed non-exfoliated nanosheets with flake-like structures. The EDS mapping confirmed the presence of magnesium, carbon, nitrogen, and sulfur throughout the nanosheets. The Mg/S@g-C3N4 nanosheets possess a high surface area of 40 m2/g and mesopores within the nanosheets, with a size of 1.57 nm. The band gap of the Mg/S@g-C3N4 nanosheet was estimated to be 3.0 eV. The sensor exhibits a strong quenching response towards Cu2+ ions, with a decrease in fluorescence intensity as the concentration of Cu2+ increased from 1 µM to 20 µM. The Stern-Volmer quenching constant (KSV) showed a relatively high value of 185053 M-1. The estimated value of LOD by the Mg/S@g-C3N4 sensor for Cu2+ was 16.2 nM. The sensor offered high sensitivity and selectivity for Cu2+ detection over other heavy metals.

Integrated management of groundwater quantity, physicochemical properties, and microbial quality in West Nile delta using a new MATLAB code and geographic information system mapping.

Groundwater is an excellent alternative to freshwater for drinking, irrigation, and developing arid regions. Agricultural, commercial, industrial, residential, and municipal activities may affect groundwater quantity and quality. Therefore, we aimed to use advanced methods/techniques to monitor the piezometric levels and collect groundwater samples to test their physicochemical and biological characteristics. Our results using software programs showed two main types of groundwater: the most prevalent was the Na-Cl type, which accounts for 94% of the groundwater samples, whereas the Mg-Cl type was found in 6% of samples only. In general, the hydraulic gradient values, ranging from medium to low, could be attributed to the slow movement of groundwater. Salinity distribution in groundwater maps varied between 238 and 1350 mg L-1. Although lower salinity values were observed in northwestern wells, higher values were recorded in southern ones. The collected seventeen water samples exhibited brackish characteristics and were subjected to microbial growth monitoring. Sample WD12 had the lowest total bacterial count (TBC) of 4.8 ± 0.9 colony forming unit (CFU mg L-1), while WD14 had the highest TBC (7.5 ± 0.5 CFU mg L-1). None of the tested water samples, however, contained pathogenic microorganisms. In conclusion, the current simulation models for groundwater drawdown of the Quaternary aquifer system predict a considerable drawdown of water levels over the next 10, 20, and 30 years with the continuous development of the region.

Effects of preterm birth, maternal ART and breastfeeding on 24-month infant HIV-free survival in a randomized trial.

BACKGROUND: IMPAACT 1077BF/FF (PROMISE) compared the safety/efficacy of two HIV antiretroviral therapy (ART) regimens to zidovudine (ZDV) alone during pregnancy for HIV prevention. PROMISE found an increased risk of preterm delivery (<37 weeks) with antepartum triple ART (TDF/FTC/LPV+r or ZDV/3TC/LPV+r) compared with ZDV alone. We assessed the impact of preterm birth, breastfeeding, and antepartum ART regimen on 24-month infant survival. METHODS: We compared HIV-free and overall survival at 24 months for liveborn infants by gestational age, time-varying breastfeeding status, and antepartum ART arm at 14 sites in Africa and India. Kaplan-Meier survival probabilities and Cox proportional hazards ratios were estimated. RESULTS: Three thousand four hundred and eighty-two live-born infants [568 (16.3%) preterm and 2914 (83.7%) term] were included. Preterm birth was significantly associated with lower HIV-free survival [0.85; 95% confidence interval (CI) 0.82-0.88] and lower overall survival (0.89; 95% CI 0.86-0.91) versus term birth (0.96; 95% CI 0.95-0.96). Very preterm birth (<34 weeks) was associated with low HIV-free survival (0.65; 95% CI 0.54-0.73) and low overall survival (0.66; 95% CI 0.56-0.74). Risk of HIV infection or death at 24 months was higher with TDF-ART than ZDV-ART (adjusted hazard ratio 2.37; 95% CI 1.21-4.64). Breastfeeding initiated near birth decreased risk of infection or death at 24 months (adjusted hazard ratio 0.05; 95% CI 0.03-0.08) compared with not breastfeeding. CONCLUSION: Preterm birth and antepartum TDF-ART were associated with lower 24-month HIV-free survival compared with term birth and ZDV-ART. Any breastfeeding strongly promoted HIV-free survival, especially if initiated close to birth. Reducing preterm birth and promoting infant feeding with breastmilk among HIV/antiretroviral drug-exposed infants remain global health priorities.

Unintended pregnancy and contraception use among African women living with HIV: Baseline analysis of the multi-country US PEPFAR PROMOTE cohort.

BACKGROUND: About 90% of unintended pregnancies are attributed to non-use of effective contraception-tubal ligation, or reversible effective contraception (REC) including injectables, oral pills, intra-uterine contraceptive device (IUCD), and implant. We assessed the prevalence of unintended pregnancy and factors associated with using RECs, and Long-Acting-Reversible-Contraceptives (LARCs)-implants and IUCDs, among women living with HIV (WLHIV) receiving antiretroviral therapy (ART). METHODS: We conducted cross-sectional analyses of the US-PEPFAR PROMOTE study WLHIV on ART at enrollment. Separate outcome (REC and LARC) modified-Poisson regression models were used to estimate prevalence risk ratio (PRR) and corresponding 95% confidence interval (CI). RESULTS: Of 1,987 enrolled WLHIV, 990 (49.8%) reported their last/current pregnancy was unintended; 1,027/1,254 (81.9%) non-pregnant women with a potential to become pregnant reported current use of effective contraception including 215/1,254 (17.1%) LARC users. Compared to Zimbabwe, REC rates were similar in South Africa, aPRR = 0.97 (95% CI: 0.90-1.04), p = 0.355, lower in Malawi, aPRR = 0.84 (95% CI: 0.78-0.91), p<0.001, and Uganda, 0.82 (95% CI: 0.73-0.91), p<0.001. Additionally, REC use was independently associated with education attained, primary versus higher education, aPRR = 1.10 (95% CI: 1.02-1.18), p = 0.013; marriage/stable union, aPRR = 1.10 (95% CI: 1.01-1.21), p = 0.039; no desire for another child, PRR = 1.10 (95% CI: 1.02-1.16), p = 0.016; infrequent sex (none in the last 3 months), aPRR = 1.24 (95% CI: 1.15-1.33), p<0001; and controlled HIV load (≤ 1000 copies/ml), PRR = 1.10 (95% CI: 1.02-1.19), p = 0.014. LARC use was independently associated with country (Zimbabwe ref: South Africa, PRR = 0.39 (95% CI: 0.26-0.57), p<0.001; Uganda, PRR = 0.65 (95% CI: 0.42-1.01), p = 0.054; and Malawi, aPRR = 0.87 (95% CI: 0.64-1.19), p = 0.386; HIV load (≤ 1000 copies/ml copies/ml), aPRR=1.73 (95% CI: 1.26-2.37), p<0.001; and formal/self-employment, aPRR = 1.37 (95% CI: 1.02-1.91), p = 0.027. CONCLUSIONS: Unintended pregnancy was common while use of effective contraception methods particularly LARCs was low among these African WLHIV. HIV viral load, education, sexual-activity, fertility desires, and economic independence are pertinent individual-level factors integral to the multi-level barriers to utilization of effective contraception among African WLHIV. National programs should prioritize strategies for effective integration of HIV and reproductive health care in the respective African countries.

Structure-Property Relationships in PVDF/SrTiO3/CNT Nanocomposites for Optoelectronic and Solar Cell Applications.

The optical properties of polyvinylidene fluoride (PVDF) polymer nanocomposite films incorporating SrTiO3/carbon nanotubes (CNTs) as nanofillers are investigated. PVDF/SrTiO3/CNTs films were prepared by the solution casting technique. X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) analyses confirmed the incorporation of SrTiO3/CNTs into the PVDF matrix. The addition of nanofillers influenced the crystalline structure, morphology, and optical properties of the films. SEM images showed spherulite morphology, which is a spherical aggregate of crystalline polymer chains. The addition of a SrTiO3/CNTs nanofiller modified the polymer's electronic structure, causing a variation in the energy gap. The addition of SrTiO3/CNTs at 0.1 wt% increased the band gap, refractive index, and nonlinear optical properties of the PVDF films. These improvements indicate the potential of these nanocomposite films in optoelectronic applications such as solar cells, image sensors, and organic light-emitting diodes.

Systemic inflammation in pregnant women with HIV: relationship with HIV treatment regimen and preterm delivery.

OBJECTIVE: HIV treatment regimen during pregnancy was associated with preterm delivery (PTD) in the PROMISE 1077 BF trial. Systemic inflammation among pregnant women with HIV could help explain differences in PTD by treatment regimen. We assessed associations between inflammation, treatment regimen, and PTD. DESIGN/METHODS: A nested 1 : 1 case-control study ( N  = 362) was conducted within a multicountry randomized trial comparing three HIV regimens in pregnant women: zidovudine alone, or combination antiretroviral therapy (ART) with lopinavir/ritonavir and either zidovudine or tenofovir. Cases were women with PTD (<37 weeks of gestational age). The following inflammatory biomarkers were measured in plasma samples using immunoassays: soluble CD14 (sCD14) and sCD163, intestinal fatty acid-binding protein, interleukin (IL)-6, interferon γ, and tumor necrosis factor α. We fit regression models to assess associations between second trimester biomarkers (measured before ART initiation at 13-23 weeks of gestational age and 4 weeks later), treatment regimen, and PTD. We also assessed whether inflammation was a mediator in the relationship between ART regimen and PTD. RESULTS: Persistently high interleukin-6 was associated with increased PTD. Compared with zidovudine alone, the difference in biomarker concentration between week 0 and week 4 was significantly higher ( P  < 0.05) for both protease inhibitor-based regimens. However, the estimated proportion of the ART effect on increased PTD mediated by persistently high biomarker levels was 5% or less for all biomarkers. CONCLUSION: Persistently high IL-6 during pregnancy was associated with PTD. Although protease inhibitor-based ART was associated with increases in inflammation, factors other than inflammation likely explain the increased PTD in ART-based regimens compared with zidovudine alone.

A High-Performance Cr2O3/CaCO3 Nanocomposite Catalyst for Rapid Hydrogen Generation from NaBH4.

This study aims to prepare new nanocomposites consisting of Cr2O3/CaCO3 as a catalyst for improved hydrogen production from NaBH4 methanolysis. The new nanocomposite possesses nanoparticles with the compositional formula Cr2-xCaxO3 (x = 0, 0.3, and 0.6). These samples were prepared using the sol-gel method, which comprises gelatin fuel. The structure of the new composites was studied using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, environmental scanning electron microscopy (ESEM), and X-ray spectroscopy (XPS). The XRD data showed the rhombohedral crystallinity of the studied samples, and the average crystal size was 25 nm. The FTIR measurements represented the absorption bands of Cr2O3 and CaO. The ESEM micrographs of the Cr2O3 showed the spherical shape of the Cr2O3 nanoparticles. The XPS measurements proved the desired oxidation states of the Cr2-xCaxO3 nanoparticles. The optical band gap of Cr2O3 is 3.0 eV, and calcium doping causes a reduction to 2.5 and 1.3 eV at 15.0 and 30.0% doping ratios. The methanolysis of NaBH4 involved accelerated H2 production when using Cr2-xCaxO3 as a catalyst. Furthermore, the Cr1.7Ca0.3O3 catalyst had the highest hydrogen generation rate, with a value of 12,750 mL/g/min.

Intimate partner violence and excess fertility among women of reproductive age in Malawi.

PURPOSE: Gender inequity and adverse health outcomes continue to be of concern among women in sub-Saharan Africa. We determined prevalence of intimate partner violence and excess fertility (having more children than desired) in reproductive age women in Malawi. We also explored factors associated with these outcomes and with spousal fertility intentions. PATIENTS AND METHODS: In a cross-sectional study, a total of 360 women and 410 men were recruited using multi-stage sampling from communities in a peri-urban setting in Blantyre District, Southern Malawi in 2021. Women and men were separately interviewed by trained study workers using a structured questionnaire. In addition to descriptive analyses, we used univariate and multivariate logistic regression models to assess associations of risk factors with the outcomes of intimate partner violence and excess fertility. RESULTS: Among women, lifetime prevalence of intimate partner violence was 23.1%, and excess fertility was experienced by 25.6%. Intimate partner violence was associated with male partners alcohol consumption (adjusted odds ratio 2.13; P = 0.019). Women were more likely to report excess fertility if they were older (adjusted odds ratio 2.0, P<0.001, for a 5-year increase). Alcohol consumption by the male partner (adjusted odds ratio 2.14; P = 0.025) and women being able to refuse sex with their male partner (adjusted odds ratio 0.50; P = 0.036) were associated with discordant fertility preferences. CONCLUSIONS: Intimate partner violence, excess fertility, and social and health inequities continue to be prevalent in Malawi. These data suggest the underlying proximal and distal factors associated with these adverse outcomes such as alcohol consumption may be addressed through education, couple interactive communication, and community dialogue. To ensure sustainability and effectiveness, strong leadership involvement, both governmental and non-governmental, is needed.

The long-term consequences of the hypospadias salvage repair issue.

PURPOSE: To present the long-term results of redo-hypospadias at our tertiary referral center following a failed prior repair. METHODS: One hundred sixty-four individuals with a history of unsuccessful repairs qualified for our retrospective cohort study. Our inclusion criteria were as follows: pre-operative data that was accessible, redo-hypospadias that was successfully repaired, and at least three years of follow-up at the last hospital visit. RESULTS: The mean patient age was 91.3 ± 21.1 months. The mean follow-up after successful repair was 41.3 ± 3.1 months. Ninety-two (group A) had one prior repair, and 72 (group B) had 2 or 3 repairs. Group A underwent six primary techniques: 32 underwent Onlay Island Flap (OIF), 10 underwent Mathieu, 12 underwent Tubularized Incised Plate Urethroplasty (TIPU), 8 underwent Urethral Mobilization (UM), and 34 underwent Buccal Mucosal Graft (BMG) { dorsal inlay Graft Urethroplasty (DIGU) in 4 and staged BMG in 30 patients}. In group B, four procedures were used: TIPU in 4, UM in 6, and BMG in 62 (staged BMG in 50 cases and DIGU in 12). CONCLUSIONS: The selected type of repair will depend on many factors, like residual healthy local skin and expertise. Safe techniques for repair of redo hypospadias after its 1st failure include TIPU, Mathieu, UM, OIF, and DIGU for distal varieties. After 2nd or 3rd repair DIGU, UM, and TIPU can be performed in distal types, while staged BMG can be applied for proximal ones.

Dietary Paenibacillus polymyxa AM20 as a new probiotic: Improving effects on IR broiler growth performance, hepatosomatic index, thyroid hormones, lipid profile, immune response, antioxidant parameters, and caecal microorganisms.

The search for a natural antimicrobial agent is ongoing and critical because of the rise and rapid proliferation of antibiotic-resistant pathogenic bacteria. The current study aims to examine the effect of Paenibacillus polymyxa AM20 as an alternative antibiotic and feed additive on Indian river broiler performance, digestive enzymes, thyroid hormones, lipid profile, hepatosomatic index, immunological response, gut bacteria, and antioxidant parameters. The bacterial isolate AM20 was identified at the gene level by isolating DNA and using PCR to detect genes. Based on 16S rRNA gene sequence analysis, the bacterial isolate was identified as Paenibacillus polymyxa. One hundred twenty Indian river broilers (1-day old) were randomly divided into 4 groups of 10 chicks each, with 3 replicates. The control group was fed a basal diet only, while the other 3 were administered control diets supplemented with P. polymyxa at 3 concentrations: 0.5, 1, and 1.5 mg/kg. The findings revealed that all groups that received graded amounts of P. polymyxa increased all growth parameters throughout the study. P. polymyxa treatment at 1.5 mg/kg increased body gain by 9% compared to the control due to increased feed intake (P = 0.0001), growth rate (P = 0.0001), and decreased feed conversion ratio. Compared to the control group, P. polymyxa (1.5 mg/kg) enhanced kidney functions in chickens by reducing uric acid and creatinine levels (P = 0.0451). Compared to the control group, alanine aminotransferase and aspartate transaminase levels in the liver were significantly reduced at all P. polymyxa doses. Liver function values were highest for P. polymyxa at 1.5 mg/kg. Compared to the control group, those whose diets included P. polymyxa had significantly better blood cholesterol levels, high-density lipoprotein, low-density lipoprotein, immunological response, thyroid function, and gut microbiota. In general, broiler chickens' economic efficiency was improved by including P. polymyxa in their diet, which also improved their growth performance, carcass dressing, specific blood biochemical levels and enzymes, and the composition of the gut microbiota.

Breastfeeding Among Women Living With HIV in the Era of Lifelong ART: An Observational Multicountry Study in Eastern and Southern Africa.

BACKGROUND: Lifelong antiretroviral treatment (ART) use is recommended for pregnant and breastfeeding (BF) women living with HIV (WLWH) to prevent perinatal HIV transmission and improve maternal health. We address 2 objectives in this analysis: (1) determine timing and factors associated with BF cessation and (2) assess the impact of BF on health of WLWH on ART. SETTING: This multicountry study included 8 sites in Uganda, Malawi, Zimbabwe, and South Africa. METHODS: This was a prospective study of WLWH on lifelong ART. These women initially participated from 2011 to 2016 in a randomized clinical trial (PROMISE) to prevent perinatal HIV transmission and subsequently reenrolled in an observational study (PROMOTE, 2016-2021) to assess ART adherence, safety, and impact. RESULTS: The PROMOTE cohort included 1987 women on ART. Of them, 752 breastfed and were included in analyses of objective 1; all women were included in analyses of objective 2. The median time to BF cessation varied by country (11.2-19.7 months). Country of residence, age, and health status of women were significantly associated with time to BF cessation (compared with Zimbabwe: Malawi, adjusted hazard ratio [aHR] 0.50, 95% confidence interval [95% CI]: 0.40 to 0.62, P < 0.001; South Africa, aHR 1.49, 95% CI: 1.11 to 2.00, P = 0.008; and Uganda, aHR 1.77, 95% CI: 1.37 to 2.29, P < 0.001). Women who breastfed had lower risk of being "unwell" compared with women who never breastfed (adjusted rate ratio 0.87, 95% CI: 0.81 to 0.95 P = 0.030). CONCLUSION: Women on lifelong ART should be encouraged to continue BF with no concern for their health. Time to BF cessation should be monitored for proper counseling in each country.

Hepatitis C virus infects and perturbs liver stem cells.

Hepatitis C virus (HCV) is the leading cause of death from liver disease. How HCV infection causes lasting liver damage and increases cancer risk remains unclear. Here, we identify bipotent liver stem cells as novel targets for HCV infection, and their erroneous differentiation as the potential cause of impaired liver regeneration and cancer development. We show 3D organoids generated from liver stem cells from actively HCV-infected individuals carry replicating virus and maintain low-grade infection over months. Organoids can be infected with a primary HCV isolate. Virus-inclusive single-cell RNA sequencing uncovered transcriptional reprogramming in HCV+ cells supporting hepatocytic differentiation, cancer stem cell development, and viral replication while stem cell proliferation and interferon signaling are disrupted. Our data add a new pathogenesis mechanism-infection of liver stem cells-to the biology of HCV infection that may explain progressive liver damage and enhanced cancer risk through an altered stem cell state.ImportanceThe hepatitis C virus (HCV) causes liver disease, affecting millions. Even though we have effective antivirals that cure HCV, they cannot stop terminal liver disease. We used an adult stem cell-derived liver organoid system to understand how HCV infection leads to the progression of terminal liver disease. Here, we show that HCV maintains low-grade infections in liver organoids for the first time. HCV infection in liver organoids leads to transcriptional reprogramming causing cancer cell development and altered immune response. Our finding shows how HCV infection in liver organoids mimics HCV infection and patient pathogenesis. These results reveal that HCV infection in liver organoids contributes to liver disease progression.

Preparation and Characterization of Mono- and Biphasic Ca1-xAgxHPO4·nH2O Compounds for Biomedical Applications.

This study aimed to explore the effects of the full-scale replacement (up to 100%) of Ca2+ ions with Ag1+ ions in the structure of brushite (CaHPO4·2H2O). This substitution has potential benefits for producing monophasic and biphasic Ca1-xAgxHPO4·nH2O compounds. To prepare the starting solutions, (NH4)2HPO4, Ca(NO3)2·4H2O, and AgNO3 at different concentrations were used. The results showed that when the Ag/Ca molar ratio was below 0.25, partial substitution of Ca with Ag reduced the size of the unit cell of brushite. As the Ag/Ca molar ratio increased to 4, a compound with both monoclinic CaHPO4·2H2O and cubic nanostructured Ag3PO4 phases formed. There was a nearly linear relationship between the Ag ion ratio in the starting solutions and the wt% precipitation of the Ag3PO4 phase in the resulting compound. Moreover, when the Ag/Ca molar ratio exceeded 4, a single-phase Ag3PO4 compound formed. Hence, adjusting the Ag/Ca ratio in the starting solution allows the production of biomaterials with customized properties. In summary, this study introduces a novel synthesis method for the mono- and biphasic Ca1-xAgxHPO4·nH2O compounds brushite and silver phosphate. The preparation of these phases in a one-pot synthesis with controlled phase composition resulted in the enhancement of existing bone cement formulations by allowing better mixing of the starting ingredients.

Previous exposure to Spike-providing parental strains confers neutralizing immunity to XBB lineage and other SARS-CoV-2 recombinants in the context of vaccination.

The emergence of SARS-CoV-2 recombinants is of particular concern as they can result in a sudden increase in immune evasion due to antigenic shift. Recent recombinants XBB and XBB.1.5 have higher transmissibility than previous recombinants such as "Deltacron." We hypothesized that immunity to a SARS-CoV-2 recombinant depends on prior exposure to its parental strains. To test this hypothesis, we examined whether Delta or Omicron (BA.1 or BA.2) immunity conferred through infection, vaccination, or breakthrough infection could neutralize Deltacron and XBB/XBB.1.5 recombinants. We found that Delta, BA.1, or BA.2 breakthrough infections provided better immune protection against Deltacron and its parental strains than did the vaccine booster. None of the sera were effective at neutralizing the XBB lineage or its parent BA.2.75.2, except for the sera from the BA.2 breakthrough group. These results support our hypothesis. In turn, our findings underscore the importance of multivalent vaccines that correspond to the antigenic profile of circulating variants of concern and of variant-specific diagnostics that may guide public health and individual decisions in response to emerging SARS-CoV-2 recombinants.