Discontinuation of HIV oral pre-exposure prophylaxis: findings from programmatic surveillance within two general population HIV programs in Nigeria.

BACKGROUND: As oral PrEP scales up in Nigeria, information about uptake, use pattern and client preference in a real-world, implementation setting is invaluable to guide refining service provision and incorporation of oral PrEP and other prevention measures into routine health services. To add to this body of knowledge, our study examines factors associated with discontinuation of PrEP among HIV negative individuals across two large scale programs in Nigeria. METHODS: Using program implementation data from two large-scale HIV projects in Akwa Ibom and Cross River states in Nigeria between January 2020 and July 2021, we used logistic regression to explore factors associated with early discontinuation (i.e., stopping PrEP within one month of starting) among HIV-negative individuals who initiated PrEP in the programs. RESULTS: Of a total of 26,325 clients; 22,034 (84%) discontinued PrEP within the first month. The odds of PrEP discontinuation were higher among clients who enrolled in community-based distribution sites (aOR 2.72; 95% C.I: 2.50-2.96) compared to those who enrolled in program-supported facilities and never married (aOR 1.76; 95% C.I: 1.61-1.92) compared to married clients. Clients who initiated PrEP because of high-risk sexual behaviour (aOR 1.15, 95% C.I 1.03-1.30) or inconsistent use or non-use of condoms (aOR 1.96, 95% C.I 1.60-2.41) had greater odds of discontinuing PrEPthan those who initiated PrEP because they were in a serodifferent relationship. CONCLUSION: The behavioural and demographic factors associated with early discontinuation of PrEP suggest that risk stratification of pre-initiation and follow up counselling may be helpful in raising continuation rates. On the service delivery side, strategies to strengthen follow-up services provided by community-based distribution sites need to be introduced. Overall, the low continuation rate calls for a review of programmatic approaches in provision of PrEP services in Nigeria.

Predictors of treatment interruption among patients on antiretroviral therapy in Akwa Ibom, Nigeria: outcomes after 12 months.

Understanding the characteristics of people living with HIV who interrupt antiretroviral therapy (ART) is critical for designing client-centered services to ensure optimal outcomes. We assessed predictors of treatment interruption in 22 HIV clinics in Nigeria. We reviewed records of HIV-positive patients aged ≥15 years who started ART 1 January and 31 March 2019. We determined treatment status over 12 months as either active, or interrupted treatment (defined as interruption in treatment up to 28 days or longer). Potential predictors were assessed using Cox hazard regression models. Overall, 1185 patients were enrolled on ART, 829 (70%) were female, and median age was 32 years. Retention at 1, 3, 6, 9, and 12 months was 85%, 80%, 76%, 72%, and 68%, respectively. Predictors of treatment interruption were post-secondary education (p = 0.04), diagnosis through voluntary counseling and testing (p < 0.001), receiving care at low-volume facilities (p < 0.001), lack of access to a peer counselor (p < 0.001), and residing outside the clinic catchment area (p = 0.03). Treatment interruption was common but can be improved by focusing on lower volume health facilities, providing peer support especially to those with higher education, and client-centered HIV services for those who live further from clinics..

Improved access to HIV diagnosis and linkage to antiretroviral therapy among children in Southern Nigeria: a before-after study.

BACKGROUND: Globally, two out of five children living with HIV (CLHIV) are unaware of their HIV status, and a little more than 50% are receiving antiretroviral therapy (ART). This paper describes case-finding strategies and their contribution to identifying CLHIV and linking them to ART in Nigeria. METHODS: This before-after study used program data abstracted during the implementation of different paediatric-focused strategies (provider-initiated testing and counselling, orphans and vulnerable children testing, family-based index testing, early infant diagnosis (EID), community-driven EID, and community-based testing) delivered in health facilities and in communities to improve HIV case identification. Data were abstracted for children (0 to 14 years) who received HIV testing services and were initiated on ART in Akwa Ibom State, Nigeria during the pre-implementation period (April-June 2021) and during the implementation period (July-September 2021). Descriptive statistics were used to describe the testing coverage, positivity rate (proportion of tests that were positive for HIV), linkage to ART, and ART coverage, by age, sex, and testing modality. Interrupted time series analysis (ITSA) on STATA 14 was used to estimate the effect of the implementation of these strategies on HIV testing uptake and positivity rate at a 0.05 significance level. RESULTS: A total of 70,210 children were tested for HIV within the six-month period, and 1,012 CLHIV were identified. A total of 78% (n = 54,821) of the tests and 83.4% (n = 844) CLHIV were diagnosed during the implementation period. During implementation, the HIV positivity rate increased from 1.09% (168/15,389) to 1.54% (844/54,821), while linkage to ART increased from 99.4% (167/168) to 99.8% (842/844). The contribution from community-based modalities to CLHIV identified increased from 63% (106/168) to 84% (709/844) during the implementation, with the majority, 60.8% (431/709), from community-based index testing. Overall, ART coverage increased from 39.7 to 55.6% at the end of the intervention period. CONCLUSION: The findings show that expanding differentiated HIV testing approaches provided mostly in the community significantly increased pediatric case identification. However, ART coverage remains low, especially for younger age groups, and requires further efforts.

Evaluation of the target-specific therapeutic potential of herbal compounds for the treatment of cancer.

Cancer is among one of the most fatal diseases leading to millions of death around the globe. Chemotherapy is the most popular conventional approach for the treatment of cancer. However, this is usually associated with various side effects and puts the patients under extreme physical and mental stress. Besides, there are increasing concerns about drug resistance. Thus, to surmount these limitations, there is a need to explore some alternative treatments. Studies related to plant-derived compounds are crucial in the search for safer and more efficient treatments. Plants and their associated secondary metabolites have been a revolutionary approach in the field of cancer treatment, as they give answers to almost all the constraints faced by synthetic drugs. Various plants and associated secondary metabolites display a great prospective as cytotoxic anticancer agents due to their specific interference with validated drug targets, such as inhibitors of mitosis, topoisomerase I and II inhibitor, DNA interactive agent, protein kinase inhibitors, inhibitors of DNA synthesis. In this review, the therapeutic potential of various natural compounds and their derivatives are presented based on their molecular targets. These herbal compounds and their derivatives could provide a rich resource for novel anticancer drug development.

Identification of novel inhibitors of angiotensin-converting enzyme 2 (ACE-2) receptor from Urtica dioica to combat coronavirus disease 2019 (COVID-19).

The pandemic outbreak of coronavirus (SARS-CoV-2) is rapidly spreading across the globe, so the development of anti-SARS-CoV-2 agents is urgently needed. Angiotensin-converting enzyme 2 (ACE-2), a human receptor that facilitates entry of SARS-CoV-2, serves as a prominent target for drug discovery. In the present study, we have applied the bioinformatics approach for screening of a series of bioactive chemical compounds from Himalayan stinging nettle (Urtica dioica) as potent inhibitors of ACE-2 receptor (PDB ID: 1R4L). The molecular docking was applied to dock a set of representative compounds within the active site region of target receptor protein using 0.8 version of the PyRx virtual screen tool and analyzed by using discovery studio visualizer. Based on the highest binding affinity, 23 compounds were shortlisted as a lead molecule using molecular docking analysis. Among them, ß-sitosterol was found with the highest binding affinity - 12.2 kcal/mol and stable interactions with the amino acid residues present on the active site of the ACE-2 receptor. Similarly, luteoxanthin and violaxanthin followed by rutin also displayed stronger binding efficiency. We propose these compounds as potential lead candidates for the development of target-specific therapeutic drugs against COVID-19.

A spotlight on the diagnostic methods of a fatal disease Visceral Leishmaniasis.

Leishmania donovani (a causative agent of visceral leishmaniasis) poses a serious health threat to the human population which is fatal if left untreated. The life cycle of Leishmania alternates between vertebrate host and Phlebotomine fly as intermediate ones. Due to the difficulties linked to vector (sandfly) control and the lack of an effective vaccine, the control of leishmaniasis relies mostly on chemotherapy. Unfortunately, the prevalence of parasites becoming resistant to the first-line drug pentavalent antimonial (SbV )/sodium antimony gluconate (SAG) and some other anti-leishmanial drug is increasing in several parts of the world. With the alarming rise of drug resistance and other issues related to VL, there is an urgent need to focus on early detection and quick diagnosis of VL case. Therefore, we have reviewed most of the methods used in the diagnostic process of VL. Along with existing diagnostic methods, developing more effective and sensitive diagnostic methods and biomarkers is also vital for enhancing VL identification and control programs. This review gathers the comprehensive information on diagnostics methods of VL under a single umbrella that could be the prominent tools for the development of rapid, accurate and cost-effective diagnostic kits for VL which can be used in field conditions.

Genetically modified live attenuated vaccine: A potential strategy to combat visceral leishmaniasis.

Visceral leishmaniasis (VL) is caused by a protozoan parasite Leishmania donovani mainly influencing the population of tropical and subtropical regions across the globe. The arsenal of drugs available is limited, and prolonged use of such drugs makes parasite to become resistant. Therefore, it is very imperative to develop a safe, cost-effective and inexpensive vaccine against VL. Although in recent years, many strategies have been pursued by researchers, so far only some of the vaccine candidates reached for clinical trial and more than half of them are still in pipeline. There is now a broad consent among Leishmania researchers that the perseverance of parasite is very essential for eliciting a protective immune response and may perhaps be attained by live attenuated parasite vaccination. For making a live attenuated parasite, it is very essential to ensure that the parasite is deficient of virulence and should further study genetically modified parasites to perceive the mechanism of pathogenesis. So it is believed that in the near future, a complete understanding of the Leishmania genome will explore clear strategies to discover a novel vaccine. This review describes the need for a genetically modified live attenuated vaccine against VL, and obstacles associated with its development.

HIV comprehensive knowledge and prevalence among young adolescents in Nigeria: evidence from Akwa Ibom AIDS indicator survey, 2017.

BACKGROUND: Despite the recent increase in HIV infections among adolescents, little is known about their HIV knowledge and perceptions. This study, therefore, sought to examine the factors associated with comprehensive HIV knowledge, stigma, and HIV risk perceptions among young adolescents aged 10-14 years in Akwa Ibom State, Nigeria. Additionally, consenting parents and assenting young adolescents were tested for HIV. METHODS: We used cross-sectional data from the 2017 Akwa Ibom AIDS Indicator Survey to analyze comprehensive HIV knowledge, stigma, and HIV risk perceptions among young adolescents. Demographic characteristics of young adolescents were summarized using descriptive statistics. Chi-square test (or Fisher's exact test in cases of small subgroup sample sizes) was used to elicit associations between demographics and study outcomes. Separate multivariable logistic regression models were then conducted to determine associations with the study outcomes. Sampling weights were calculated in order to adjust for the sample design. P-values less than 0.05 were considered to be significant. RESULTS: A total of 1818 young adolescents were interviewed. The survey highlighted significant low levels of comprehensive HIV knowledge (9.4%) among young adolescents. Adolescent-parent discussions [AOR = 2.19, 95% C.I (1.10-4.38), p = 0.03], schools as sources of HIV information [AOR = 8.06, 95% C.I (1.70-38.33), p < 0.001], and sexual activeness [AOR = 2.55, 95% C.I (1.16-5.60), p = 0.02] were associated with comprehensive HIV knowledge. Majority (93%) of young adolescents perceived themselves not to be at risk of HIV. Overall, 81.5% of young adolescents reported stigmatizing tendencies towards people living with HIV. HIV prevalence among young adolescents was 0.6%. CONCLUSIONS: Results indicate low comprehensive HIV knowledge among young adolescents. Our findings suggest that there is a need for increased attention towards young adolescents particularly in the provision of comprehensive, functional sexuality education, including HIV at the family- and school-levels. Consequently, age appropriate interventions are needed to address the epidemiological risks of young adolescents that are influenced by a myriad of social issues.

Facile synthesis of triphenylenes and triphenylene/phenanthrene fused heteroaromatics.

In the recent past, development of milder, safer and comparatively less toxic methods in organic synthesis has received great attention. We report a simple and facile method for the synthesis of substituted triphenylenes and their heteroaryl analogues using ceric ammonium nitrate (CAN) via oxidative biaryl coupling. We describe the structural and photophysical properties of these unique heteroaryl fused triphenylenes.

Innovations in Providing HIV Index Testing Services: A Retrospective Evaluation of Partner Elicitation Models in Southern Nigeria.

Background: This analysis aimed to evaluate the effectiveness of eliciting sexual partners from HIV-positive clients using the elicitation box model (where an HIV-positive index can report sexual contacts on paper and insert in a box for a health care provider to contact at a later time) compared to the conventional model (in which a health care provider elicits sexual contacts directly from clients) in Akwa Ibom, Southern Nigeria.Methods: Between March 2021 and April 2022, data were collected from index testing registers at 4 health facilities with a high volume of HIV clients currently on treatment in 4 local government areas in Akwa Ibom State. Primary outcome analyzed was the elicitation ratio (number of partners elicited per HIV-index offered index testing services). Secondary outcomes were the index testing acceptance (index HIV-positive clients accepted index testing service), testing coverage (partners tested for HIV from a list of partners elicited from HIV-index accepted index testing services), testing yield (index partners identified HIV positive from index partners HIV-tested), and linkage rate (index partners identified HIV positive and linked to antiretroviral therapy).Results: Of the total 2,705 index clients offered index testing services, 91.9% accepted, with 2,043 and 439 indexes opting for conventional elicitation and elicitation box models, respectively. A total of 3,796 sexual contacts were elicited: 2,546 using the conventional model (elicitation ratio=1:1) and 1,250 using the elicitation box model (elicitation ratio=1:3). Testing coverage was significantly higher in the conventional compared to the elicitation box model (P<.001). However, there was no significant difference in the testing yield (P=.81) and linkage rate using the conventional compared to elicitation box models (P=.13).Conclusion: The implementation of the elicitation box model resulted in an increase in partner elicitation compared to the conventional model. Increasing the testing coverage by implementing the elicitation box model should be considered.

Targeting bacterial biofilms using vancomycin and multivalent cell-penetrating peptide labeled quantum dots.

Bacterial biofilms are highly resilient microbial musters that are difficult to eradicate, driving the development of novel therapeutic strategies. The current study aims to investigate the therapeutic efficacy of cell-penetrating peptide-based targeted delivery of vancomycin functionalized quantum dots in eradicating biofilm formation in gram-positive and gram-negative bacterial strains. The conjugate was characterized using fluorimetry, UV-visible spectroscopy, gel electrophoresis, and zeta potential. The conjugate was then tested for antimicrobial and antibiofilm activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli, and it demonstrated excellent antimicrobial as well as antibiofilm activity against all the tested strains. The findings indicated that the conjugate was capable of overcoming bacterial resistance of bacteria in addition to the eradication of biofilms at effective concentrations.

Willingness to pay for antiretroviral therapy, viral load, and premium services; A contingent valuation survey of people living with HIV in southern Nigeria.

BACKGROUND: With stagnating funding for HIV and AIDS control programs in Nigeria, alternative funding models for antiretroviral therapy (ART) including out of pocket payment are being considered to sustain momentum epidemic control targets. We assessed willingness to pay for ART related services, and factors associated with willingness to pay. METHODS: Between July and August 2019, we conducted a survey among people living with HIV (PLHIV) on ART in 3 states in southern Nigeria. Randomly sampled respondents on ART for at least 6 months, aged ≥ 18 years, able to communicate in English or pidgin English, and consenting to the survey were enrolled. Respondents were asked if they were willing to pay for clinical consultation, antiretroviral drugs (ARVs), viral load testing services and premium ART services (including fast track services). Respondents indicating willingness to pay for any of these services were asked the maximum amount they were willing to pay using contingent valuation methodology. We assessed the weighted proportions of PLHIV on ART willing to pay for ART and used survey-featured logistic regression measures to assess sociodemographic and ART related factors associated with willingness to pay for ART services. RESULTS: Overall, 1,598 PLHIV with a mean age of 39.03 years (standard deviation [SD]: 11.23 years), were included in this analysis. Of these, 65.8% (1,079), 73.9% (1,192), 61.0% (995) and 33.6% (472) were willing to pay for ART consultation, ARVs, viral load testing services and premium ART services respectively. The median maximum amount PLHIV were willing to pay for clinical consultation and for ARVs was NGN1,000 (USD equivalent of $2.78; interquartile range [IQR]: 500-2,000) respectively, and NGN2,500 (USD equivalent of $6.94; IQR: NGN1,000-5,000) and NGN2,000 (USD equivalent of $5.56; IQR: NGN1,000-3,000) for viral load testing and premium ART services respectively. Receiving ART in Lagos state, being employed and having a monthly income of NGN100,000 or more was associated with willingness to pay for the various ART services. CONCLUSION: We found generally high-level of willingness to pay for ART consultation, ARVs and viral load testing services but low willingness to pay for premium ART services among PLHIV on ART. The maximum amount PLHIV were willing to pay for various ART services fell short of benchmarks for alternative funding but can potentially supplement ART by funding differentiated service delivery models that require nominal amounts to facilitate person-centered differentiated service delivery models.

Increasing multimonth dispensing of antiretrovirals and assessing the effect on viral load suppression among children and adolescents receiving HIV services in Nigeria.

INTRODUCTION: Multimonth dispensing (MMD) enables less frequent clinic visits and improved outcomes for people living with HIV, but few children and adolescents living with HIV (CALHIV) are on MMD. At the end of the October-December 2019 quarter, only 23% of CALHIV receiving antiretroviral therapy (ART) through SIDHAS project sites in Akwa Ibom and Cross River states, Nigeria, were receiving MMD. In March 2020, during COVID-19, the government expanded MMD eligibility to include children and recommended rapid implementation to minimize clinic visits. SIDHAS provided technical assistance to 36 "high-volume" facilities-≥5 CALHIV on treatment-in Akwa Ibom and Cross River to increase MMD and viral load suppression (VLS) among CALHIV, toward PEPFAR's 80% benchmark for people currently on ART. We present change in MMD, viral load (VL) testing coverage, VLS, optimized regimen coverage, and community-based ART group enrollment among CALHIV from the October-December 2019 quarter (baseline) to January-March 2021 (endline) based on retrospective analysis of routinely collected program data. MATERIALS AND METHODS: We compared MMD coverage (primary objective), and optimized regimen coverage, community-based ART group enrollment, VL testing coverage, and VLS (secondary objectives), among CALHIV 18 years and younger pre-/post-intervention (baseline/endline) at the 36 facilities. We excluded children younger than two years, who are not recommended for or routinely offered MMD. The extracted data included age, sex, ART regimen, months of ART dispensed at last refill, most recent VL test results, and community ART group enrollment. Data on MMD-three or more months of ARVs dispensed at one time-were disaggregated into three to five months (3-5-MMD) vs. six or more months (6-MMD). VLS was defined as ≤1,000 copies. We documented MMD coverage by site, optimized regimen, and VL testing and suppression. Using descriptive statistics, we summarized the characteristics of CALHIV on MMD and non-MMD, number of CALHIV on optimized regimens, and proportion enrolled in differentiated service delivery models and community-based ART refill groups. For the intervention, SIDHAS technical assistance was data driven: weekly data analysis/review, site-prioritization scoring, provider mentoring, line listing eligible CALHIV, pediatric regimen calculator, child-optimized regimen transitioning, and community ART models. RESULTS: The proportion of CALHIV ages 2-18 receiving MMD increased from 23% (620/2,647; baseline) to 88% (3,992/4,541; endline), while the proportion of sites reporting suboptimal MMD coverage among CALHIV (<80%) decreased (100% to 28%). In March 2021, 49% of CALHIV were receiving 3-5-MMD and 39% 6-MMD. In October-December 2019, 17%-28% of CALHIV were receiving MMD; by January-March 2021, 99% of those 15-18 years, 94% 10-14 years, 79% 5-9 years, and 71% 2-4 years were on MMD. VL testing coverage remained high (90%), while VLS increased (64% to 92%). The proportion on pediatric-optimized regimens increased (58% to 79%). CONCLUSIONS: MMD was feasible among CALHIV without compromising VLS. Expanded eligibility criteria, line listing eligible children, monitoring pediatric antiretroviral stock, and data use contributed to positive results. Future efforts should address low 6-MMD uptake related to stock limitations and synchronize antiretroviral refill pickup with VL sample collection.

Anticancer therapeutic potential of 5-fluorouracil and nisin co-loaded chitosan coated silver nanoparticles against murine skin cancer.

Cancer is a major health concern worldwide as conventional treatment modalities face several limitations such as drug resistance, toxicity etc. To overcome such deficits, combination therapy involving anticancer peptides and chemodrugs is being considered as an attractive strategy. Therefore, present study developed, characterized and evaluated the anticancer potential of a single nanoconstruct comprising of oligomeric chitosan coated silver nanoparticles co-loaded with nisin and 5-florouracil (5-FU/nisin-CHI-AgNPs) against DMBA/TPA-induced murine skin cancer. It was fabricated using wet reduction method of silver salt to form silver nanoparticles followed sequentially by oligomeric chitosan coating, nisin conjugation to deacetylated units of chitosan oligomers (EDC/NHS chemistry) and physical loading of 5-FU. Biophysical characterisation studies revealed that the developed nanoconstruct had UV-visible absorption maxima at 420 nm, zeta potential of + 32.90 mV and 72.39 nm particle size (TEM analysis). In vivo anticancer therapeutic potential was assessed in terms of tumor statistics, histopathological, scanning electron microscopic analyses and testing oxidant/antioxidant status which exhibited marked reduction both in mean tumor volume (68.34 %) and mean tumor burden (82.39 %); restored skin histoarchitecture and improved oxidant/antioxidant status. Interestingly, anticancer therapeutic potential of nisin and 5-florouracil was found to be enhanced in vivo when bound on single composite nanoconstruct. The study forms a basis for developing synergetic single platforms against variety of cancers.

Diagnostic Tools for Rapid Screening and Detection of SARS-CoV-2 Infection.

The novel coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has severely impacted human health and the health management system globally. The ongoing pandemic has required the development of more effective diagnostic strategies for restricting deadly disease. For appropriate disease management, accurate and rapid screening and isolation of the affected population is an efficient means of containment and the decimation of the disease. Therefore, considerable efforts are being directed toward the development of rapid and robust diagnostic techniques for respiratory infections, including SARS-CoV-2. In this article, we have summarized the origin, transmission, and various diagnostic techniques utilized for the detection of the SARS-CoV-2 virus. These higher-end techniques can also detect the virus copy number in asymptomatic samples. Furthermore, emerging rapid, cost-effective, and point-of-care diagnostic devices capable of large-scale population screening for COVID-19 are discussed. Finally, some breakthrough developments based on spectroscopic diagnosis that could revolutionize the field of rapid diagnosis are discussed.

Microbial Interventions in Bioremediation of Heavy Metal Contaminants in Agroecosystem.

Soil naturally comprises heavy metals but due to the rapid industrialization and anthropogenic events such as uncontrolled use of agrochemicals their concentration is heightened up to a large extent across the world. Heavy metals are non-biodegradable and persistent in nature thereby disrupting the environment and causing huge health threats to humans. Exploiting microorganisms for the removal of heavy metal is a promising approach to combat these adverse consequences. The microbial remediation is very crucial to prevent the leaching of heavy metal or mobilization into the ecosystem, as well as to make heavy metal extraction simpler. In this scenario, technological breakthroughs in microbes-based heavy metals have pushed bioremediation as a promising alternative to standard approaches. So, to counteract the deleterious effects of these toxic metals, some microorganisms have evolved different mechanisms of detoxification. This review aims to scrutinize the routes that are responsible for the heavy metal(loid)s contamination of agricultural land, provides a vital assessment of microorganism bioremediation capability. We have summarized various processes of heavy metal bioremediation, such as biosorption, bioleaching, biomineralization, biotransformation, and intracellular accumulation, as well as the use of genetically modified microbes and immobilized microbial cells for heavy metal removal.

Microwave-Induced CuO Nanorods: A Comparative Approach between Curcumin, Quercetin, and Rutin to Study Their Antioxidant, Antimicrobial, and Anticancer Effects against Normal Skin Cells and Human Breast Cancer Cell Lines MCF-7 and T-47D.

Herein, we explore the biological properties of curcumin, quercetin, and rutin by loading them onto porous CuO nanorods (NRs). The CuO NRs were synthesized using the microwave irradiation method through a chemical reaction between CuSO4·5H2O and NaOH in the presence of the anionic stabilizer sodium dodecyl sulfate. The shape and surface morphology of CuO NRs were examined with two microscopic techniques: high-resolution transmission electron microscopy (HR-TEM) and field emission scanning electron microscopy (FESEM). Their average diameter was measured by TEM to be 15 ± 2 nm. The porosity and interfacial area of the fabricated material were determined by Brunauer-Emmett-Teller analysis. After successful synthesis, CuO NRs were loaded with polyphenolic curcumin, quercetin, and rutin, with the loading efficiency of 57.8, 62.2, and 81.2%, respectively, which was confirmed by UV-visible and infra-red spectroscopy and finally with a thermal gravimetric technique. Their radical scavenging activity was measured with the 2,2-diphenyl-1-picrylhydrazyl radical and compared with the control (ascorbic acid). Further, good bactericidal effects were observed against both Gram-positive bacterial strains, including Staphylococcus aureus and Bacillus subtilis, and Gram-negative bacterial strains, including Salmonella typhi, Pseudomonas aeruginosa, Escherichia coli, and Klebsiella pneumoniae. Excellent anticancer activity was observed against normal skin cells and breast cancer cells T-47D and MCF-7.

Identification of Putative Elicitors From Plant Root Exudates Responsible for PsoR Activation in Plant-Beneficial Pseudomonas spp. by Docking and Molecular Dynamics Simulation Approaches to Decipher Plant-Microbe Interaction.

Plants and rhizobacteria are coexisting since the beginning, but the exact mechanism of communication between them remains enigmatic. The PsoR protein of plant-beneficial Pseudomonas spp., a group of root-associated bacteria, is known to produce a range of antifungal and insecticidal secondary metabolites like 2,4-diacetyl phloroglucinol (DAPG), pyrrolnitrin, and chitinase making them great biocontrol agents and thus helping in plant growth promotion. To better understand the inter-kingdom signaling between plants and plant growth-promoting rhizobacteria (PGPR), the interaction of PsoR with various root exudates was investigated computationally. For this, we first modeled the PsoR protein and confirmed it using the Ramachandran plot. A total of 59 different low molecular weight phytochemicals, secreted as root exudates by plants, were identified by extensive text mining. They were virtually screened with the PsoR protein by molecular docking. Based on the lowest binding energy, ranging from -7.1 to -6.3 kcal mol-1, the top five exudates were chosen. To analyze the stability of the docked protein-ligand complex, a molecular dynamics (MD) simulation of 100 nanoseconds was done. Two root exudates, saponarin and 2-benzoxazolinone (BOA), showed suitable binding with PsoR by forming hydrogen, hydrophobic, and Van der Waals interactions. To confirm the MD simulation results, RMSF, RG, SASA, and interaction energy were calculated. This computational study first time reports that saponarin and 2-BOA, predominantly present in the root exudates of barley and wheat, respectively, demonstrate effective binding with the modeled PsoR protein and are likely of showing cross-kingdom interactions.

Nanobioremediation: A sustainable approach for the removal of toxic pollutants from the environment.

In recent years, the proportion of organic and inorganic contaminants has increased rapidly due to growing human interference and represents a threat to ecosystems. The removal of these toxic pollutants from the environment is a difficult task. Physical, chemical and biological methods are implemented for the degradation of toxic pollutants from the environment. Among existing technologies, bioremediation in combination with nanotechnology is the most promising and cost-effective method for the removal of pollutants. Numerous studies have shown that exceptional characteristics of nanomaterials such as improved catalysis and adsorption properties as well as high reactivity have been subjects of great interest. There is an emerging trend of employing bacterial, fungal and algal cultures and their components, extracts or biomolecules as catalysts for the sustainable production of nanomaterials. They can serve as facilitators in the bioremediation of toxic compounds by immobilizing or inducing the synthesis of remediating microbial enzymes. Understanding the association between microorganisms, contaminants and nanoparticles (NPs) is of crucial importance. In this review, we focus on the removal of toxic pollutants using the cumulative effects of nanoparticles with microbial technology and their applications in different domains. Besides, we discuss how this novel nanobioremediation technique is significant and contributes towards sustainability.

Molecular docking and molecular dynamics simulation approaches for evaluation of laccase-mediated biodegradation of various industrial dyes.

Dyes are being increasingly utilized across the globe, but there is no appropriate method of bioremediation for their full mineralization from the environment. Laccases are key enzymes that help microbes to degrade dyes as well as their intermediate metabolites. Various dyes have been reported to be degraded by bacteria, but it is still unclear how these enzymes function during dye degradation. To effectively eradicate toxic dyes from the system, it is essential to understand the molecular function of enzymes. As a result, the interaction of laccase with different toxic dyes was investigated using molecular docking. Based on the highest binding energy we have screened ten dyes with positive interaction with laccase. Evaluating the MD simulation results, three out of ten dyes were more stable as potential targets for degradation by laccase of Bacillus subtilis. As a result, subsequent research focused solely on the results of three substrates: pigment red, fuchsin base, and Sudan IV. Analysis of MD simulation revealed that pigments red 23, fuchsin base, and Sudan IV form hydrogen and hydrophobic bond as well as Vander Waals interactions with the active site of laccase to keep it stable in aqueous solution. The conformation of laccase is greatly altered by the inclusion of all three substrates in the active site. The MD simulation findings show that laccase complexes remain stable throughout the catalytic reaction. Therefore, this research provides a molecular understanding of laccase expression and its role in the bioremediation of the pigments red 23, fuchsin base, and Sudan IV.Communicated by Ramaswamy H. Sarma.