Human IgG Fc-engineering for enhanced plasma half-life, mucosal distribution and killing of cancer cells and bacteria.

Monoclonal IgG antibodies constitute the fastest growing class of therapeutics. Thus, there is an intense interest to design more potent antibody formats, where long plasma half-life is a commercially competitive differentiator affecting dosing, frequency of administration and thereby potentially patient compliance. Here, we report on an Fc-engineered variant with three amino acid substitutions Q311R/M428E/N434W (REW), that enhances plasma half-life and mucosal distribution, as well as allows for needle-free delivery across respiratory epithelial barriers in human FcRn transgenic mice. In addition, the Fc-engineered variant improves on-target complement-mediated killing of cancer cells as well as both gram-positive and gram-negative bacteria. Hence, this versatile Fc technology should be broadly applicable in antibody design aiming for long-acting prophylactic or therapeutic interventions.

Is income inequality linked to infectious disease prevalence? A hypothesis-generating study using tuberculosis.

We study the association between infectious disease incidence and income inequality. We hypothesize that random social mixing in an income-unequal society brings into contact a) susceptible and infected poor and b) the infected-poor and the susceptible-rich, raising infectious disease incidence. We analyzed publicly available, country-level panel data for a large cross-section of countries between 1995 and 2013 to examine whether countries with elevated levels of income inequality have higher rates of pulmonary Tuberculosis (TB) incidence per capita. A "negative control" using anemia and diabetes (both non-communicable diseases and hence impervious to the hypothesized mechanism) is also applied. We find that high levels of income inequality are positively associated with tuberculosis incidence. All else equal, countries with income-Gini coefficients 10% apart show a statistically significant 4% difference in tuberculosis incidence. Income inequality had a null effect on the negative controls. Our cross-country regression results suggest that income inequality may create conditions where TB spreads more easily, and policy action to reduce income inequities could directly contribute to a reduced TB burden.

Revitalizing primary care is the key to people's health in the post-COVID era.

Growing evidence shows that primary care-oriented systems achieve better health outcomes, more health equity, and lower costs. Despite this strong evidence, such care has been chronically underfunded. If a council focused on primary care had existed during the height of the coronavirus disease 2019 (COVID-19) pandemic, it could have helped rapidly mobilize primary care to address vaccine equity and shore up public health, particularly in rural and historically marginalized urban communities. We believe an infrastructure investment plan should include oversight, tools, and resources for rebuilding primary care. Researchers have tried to compare the number of deaths due to "neglected tropical diseases" and that due to COVID - total deaths in the former cases are greater than COVID deaths. We should take into consideration a few issues: (a) distinction between health (as a human right) and health care (as commodity), (b) "clinical health" and "public health," (3) primary health care (as the backbone of public health) as well as community-based horizontal program NOT to be replaced by selective primary health care or GOBI or any disease-centered vertical program.

Trends of humoral immune responses to heterologous antigenic exposure due to vaccination & omicron SARS-CoV-2 infection: Implications for boosting.

Background & objectives: Vaccination and natural infection can both augment the immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but how omicron infection has affected the vaccine-induced and hybrid immunity is not well studied in Indian population. The present study was aimed to assess the durability and change in responses of humoral immunity with age, prior natural infection, vaccine type and duration with a minimum gap of six months post-two doses with either ChAdOx1 nCov-19 or BBV152 prior- and post-emergence of the omicron variant. Methods: A total of 1300 participants were included in this observational study between November 2021 and May 2022. Participants had completed at least six months after vaccination (2 doses) with either ChAdOx1 nCoV-19 or an inactivated whole virus vaccine BBV152. They were grouped according to their age (≤ or ≥60 yr) and prior exposure of SARS-CoV-2 infection. Five hundred and sixteen of these participants were followed up after emergence of the Omicron variant. The main outcome was durability and augmentation of the humoral immune response as determined by anti-receptor-binding domain (RBD) immunoglobulin G (IgG) concentrations, anti-nucleocapsid antibodies and anti-omicron RBD antibodies. Live virus neutralization assay was conducted for neutralizing antibodies against four variants - ancestral, delta and omicron and omicron sublineage BA.5. Results: Before the omicron surge, serum anti-RBD IgG antibodies were detected in 87 per cent participants after a median gap of eight months from the second vaccine dose, with a median titre of 114 [interquartile range (IQR) 32, 302] BAU/ml. The levels increased to 594 (252, 1230) BAU/ml post-omicron surge (P<0.001) with 97 per cent participants having detectable antibodies, although only 40 had symptomatic infection during the omicron surge irrespective of vaccine type and previous history of infection. Those with prior natural infection and vaccination had higher anti-RBD IgG titre at baseline, which increased further [352 (IQR 131, 869) to 816 (IQR 383, 2001) BAU/ml] (P<0.001). The antibody levels remained elevated after a mean time gap of 10 months, although there was a decline of 41 per cent. The geometric mean titre was 452.54, 172.80, 83.1 and 76.99 against the ancestral, delta, omicron and omicron BA.5 variants in the live virus neutralization assay. Interpretation & conclusions: Anti-RBD IgG antibodies were detected in 85 per cent of participants after a median gap of eight months following the second vaccine dose. Omicron infection probably resulted in a substantial proportion of asymptomatic infection in the first four months in our study population and boosted the vaccine-induced humoral immune response, which declined but still remained durable over 10 months.

Ancestral SARS-CoV-2-Driven Antibody Repertoire Diversity in an Unvaccinated Individual Correlates with Expanded Neutralization Breadth.

Understanding the quality of immune repertoire triggered during natural infection can provide vital clues that form the basis for development of a humoral immune response in some individuals capable of broadly neutralizing pan-SARS-CoV-2 variants. In the present study, we report variations in neutralization potential against Omicron variants of two novel neutralizing monoclonal antibodies (MAbs), THSC20.HVTR11 and THSC20.HVTR55, isolated from an unvaccinated convalescent individual that represent distinct B cell lineage origins and epitope specificity compared to five MAbs we previously reported that were isolated from the same individual. In addition, we observed neutralization of Omicron variants by plasma antibodies obtained from this particular individual postvaccination with increased magnitude. Interestingly, this observation was found to be comparable with six additional individuals who initially were also infected with ancestral SARS-CoV-2 and then received vaccines, indicating that hybrid immunity can provide robust humoral immunity likely by antibody affinity maturation. Development of a distinct antigen-specific B cell repertoire capable of producing polyclonal antibodies with distinct affinity and specificities offers the highest probability of protecting against evolving SARS-CoV-2 variants. IMPORTANCE Development of robust neutralizing antibodies in SARS-CoV-2 convalescent individuals is known; however, it varies at the population level. We isolated monoclonal antibodies from an individual infected with ancestral SARS-CoV-2 in early 2020 that not only varied in their B cell lineage origin but also varied in their capability and potency to neutralize all the known variants of concern (VOCs) and currently circulating Omicron variants. This indicated establishment of unique lineages that contributed in forming a B cell repertoire in this particular individual immediately following infection, giving rise to diverse antibody responses that could complement each other in providing a broadly neutralizing polyclonal antibody response. Individuals who were able to produce polyclonal antibody responses with higher magnitude have a higher chance of being protected from evolving SARS-CoV-2 variants.

Performance and cell toxicity studies for the use of graphene oxide-bimetallic oxide hybrids in the absorptive removal of Pb(II) from wastewater: fixed-bed column study with regeneration.

The current study involves the removal of Pb(II) ions from an aqueous solution using GO/Mn-Fe hybrids in a fixed bed column study. The capability of the hybrid in the Pb removal was examined using a continuous flow fixed bed column which revealed that the hybrid had the maximum adsorption capacity of 172.768 mg/g at a flow rate of 2 mL/min, bed height of 1 cm, and influent concentration of 200 mg/L. The breakthrough curves obtained from the experiments were examined using three different models, i.e., Bohart-Adams model, Thomas Model, and Yoon-Nelson model, wherein all the models showed high correlation coefficient values. Three consecutive adsorption-desorption cycles in the column yielded regeneration efficiencies of 91.71%, 88.31%, and 85.41%. The column life factor indicated that the fixed bed would have enough capacity to avoid a zero breakthrough time for up to 9 cycles, implying that GO/Mn-Fe could be used as a cheap and efficient adsorbent in the removal of Pb(II) from contaminated water. The adsorption mechanism was postulated based on the characterization of the spent adsorbent by FTIR and SEM. The phenomenon of the adsorption process can be described in accordance with the surface complex formation theory, which suggests that an increase in pH decreases the competition between metal ions and protons, favoring metal ion adsorption. The toxicity of the synthesized hybrid was evaluated on HeLa cells and compared to the toxicity of GO. Increasing the concentration of GO/Mn-Fe hybrid from 50 to 250 g/mL resulted in a decrease in cell viability from 91.90 to 56.52%, whereas increasing the concentration of GO resulted in a decrease in cell viability from 61.59 to 37.19%. The study clearly demonstrates the use of GO/Mn-Fe hybrid as an adsorbent for efficient sequestration of Pb(II) ions with lower environmental toxicity.

Development of Rice Straw-derived Biochar-Bentonite Composite and its Application for in situ Sequestration of Ammonium and Phosphate Ions in the Degraded Mine Soil.

Nutrient pollution has a diverse impact on the environment and human health. The presence of nutrients, such as ammonium and phosphate, is ubiquitous in the environment due to their extensive use in agricultural land and leaching through non-point sources. In this context, biochar-based composites could play an essential role in improving the soil's nutrient retention capacity. The present study aims to develop bentonite-biochar composites (BNT@BC 400 and 600) and utilize them as an ameliorating material in the coal mine degraded soil to reduce the leaching of ammonium and phosphate ions. The bentonite-biochar composite (BNT@BC 400 and 600) was synthesized using the pristine rice straw-derived biochar using the solvothermal method. The biochar was produced at two different pyrolytic temperatures, 400 °C and 600 °C, and denoted as BC 400 and 600, respectively. Hence, the bentonite-biochar composite was denoted as BNT@BC 400 and 600. The BNT@BC 400 and 600 were characterized using the elemental, proximate, SEM, XRD, and FTIR analysis. Subsequently, the BNT@BC composites were evaluated for the adsorptive removal of NH4+ and PO43- ions using batch adsorption and column leaching studies. In the soil columns, the BNT@BC 400 and 600 were mixed with the soil at two different application rates, viz. 1 and 2.5% (w/w). The leaching characteristics data were fitted using three different fixed-bed models to predict the maximum adsorption capacity of the amended soil columns and the dominant mechanism of adsorption. Results indicated that the BNT@BC 600 showed the maximum adsorption capacity of 33.77 and 64.23 mg g-1 for the adsorption of NH4+ and PO43- ions, respectively. The dominant adsorption mechanisms in the aqueous solution were the electrostatic attraction, complexation, ion exchange, and precipitation processes. In the soil columns, the sorption of NH4+ and PO43- ions was governed by diffusive mass transfer and electrostatic interaction. Findings of the study indicated that incorporating the BNT@BC composite in the soil can significantly reduce the leaching of the NH4+ and PO43- ions and increase the overall soil fertility.

Treatment of textile industry wastewater based on coagulation-flocculation aided sedimentation followed by adsorption: Process studies in an industrial ecology concept.

This study examines the feasibility of treatment of textile industry wastewater using a two-step process that includes coagulation-flocculation aided sedimentation and adsorption. It also aims at finding reuse potential of the generated sludge while making the treated water recyclable for the same industry in an industrial ecology concept. The wastewater was collected from a small-scale textile plant with a discharge of 400 L/week, where more than 70 similar textile plants are located in and around the area. FeCl3 was selected as the coagulant for the initial step in the treatment process, and a bimetallic oxide Graphene Oxide (GO) hybrid was selected as the adsorbent for the latter step of the treatment process. The experimental conditions for the coagulation process included the optimization of dose, stirring speed, stirring time, and settling time. For the adsorption process it included the optimization of stirring time, dose, and rate. The parameters like Chemical Oxygen Demand (COD) and color were checked during the treatment process and near complete removal of COD and color were achieved using the suggested materials and process. The treated water was found fit for recycling - towards making zero liquid discharge plant. Later, the sludge generated from both the steps in the processes was sundried and mixed with cement and tested for 7 days and 28 days of compressive strength. A total of 26 kg of cement was replaced, by using sludge generated from treating 100 L of textile wastewater, in the sludge-cement mix. In addition to solving the sludge problem, the process can help in reducing the requirement of cement in concrete. Finally, a detailed economic assessment for the entire study was also performed and is reported.

Photoinduced micropatterning on biodegradable aliphatic polyester surfaces for anchoring dual brushes and its application in bacteria and cell patterning.

In view of intrinsic challenges encountered in surface patterning on actual biomaterials such as the ones based on biodegradable polymers, we have demonstrated an innovative strategy to create micro-patterns on the surface of tartaric acid based aliphatic polyester P (poly(hexamethylene 2,3-O-isoprpylidentartarate)) without significant loss of its molecular weight. Around 10 wt% PAG (photoacid generator, 2-(4-methoxystyryl)-4,6-bis(trichloromethyl)-1,3,5-triazine) was purposefully encapsulated in a polyester matrix comprising of P and PLA (polylactide) at a ratio of 5 : 95. With the help of a photomask, selective areas of the matrix were exposed to UV radiation at 395 nm for 25 min to trigger the acid release from PAG entrapped unmasked areas for generating hydroxyl functionality that was later converted to an ATRP (atom transfer radical polymerization) initiating moiety on the irradiated domain of P. In subsequent steps, spatio-selective surface modification by surface initiated ATRP was carried out to generate an alternate pattern of polyPEGMA (poly(ethylene glycol)methyl ether methacrylate) and polyDMAPS (poly(3-dimethyl-(methacryloyloxyethyl)ammonium propane sulfonate)) brushes on the matrix. The patterned surface modified with dual brushes was found to be antifouling in nature (rejection of >97% of proteins). Strikingly, an alternate pattern of live bacterial cells (E. coli and S. aureus) was evident and a relatively high population of bacteria was found on the polyPEGMA brush modified domain. However, a complete reverse pattern was visible in the case of L929 mouse fibroblast cells, i.e., cells were found to predominantly adhere to and proliferate on the zwitterionic brush modified surface. An attempt was made to discuss a plausible mechanism of selective cell adhesion on the zwitterionic brush domain. This novel strategy employed on the biodegradable polymer surface provides an easy and straightforward way to micro-pattern various cells, bacteria, etc. on biodegradable substrates which hold great potential to function as biochips, diagnostics, bacteria/cell microarrays, etc.

Correction: Cytocompatible, soft and thick brush-modified scaffolds with prolonged antibacterial effect to mitigate wound infections.

Correction for 'Cytocompatible, soft and thick brush-modified scaffolds with prolonged antibacterial effect to mitigate wound infections' by Shaifali Dhingra et al., Biomater. Sci., 2022, 10, 3856-3877, https://doi.org/10.1039/d2bm00245k.

Cytocompatible, soft and thick brush-modified scaffolds with prolonged antibacterial effect to mitigate wound infections.

Biomedical device or implant-associated infections caused by pathogenic bacteria are a major clinical issue, and their prevention and/or treatment remains a challenging task. Infection-resistant antimicrobial coatings with impressive cytocompatibility offer a step towards addressing this problem. Herein, we report a new strategy for constructing highly antibacterial as well as cytocompatible mixed polymer brushes onto the surface of 3D printed scaffold made of biodegradable tartaric acid-based aliphatic polyester blends. The mixed brushes were nothing but a combination of poly(3-dimethyl-(methacryloyloxyethyl) ammonium propane sulfonate) (polyDMAPS) and poly((oligo ethylene glycol) methyl ether methacrylate) (polyPEGMA) with varying chain length (n) of the ethylene glycol unit (n = 1, 6, 11, and 21). Both homo and copolymeric brushes of polyDMAPS with polyPEGMA exhibited antibacterial efficacy against both Gram positive and Gram negative pathogens such as E. coli (Escherichia coli) and S. aureus (Staphylococcus aureus) because of the combined action of bacteriostatic effects originating from strongly hydrated layers present in zwitterionic (polyDMAPS) and hydrophilic (polyPEGMA) copolymer brushes. Interestingly, a mixed polymer brush comprising polyDMAPS and polyPEGMA (ethylene glycol chain unit of 21) at 50/50 ratio provided zero bacterial growth and almost 100% cytocompatibility (tested using L929 mouse fibroblast cells), making the brush-modified biodegradable substrate an excellent choice for an infection-resistant and cytocompatible surface. An attempt was made to understand their extraordinary performance with the help of contact angle, surface charge analysis and nanoindentation study, which revealed the formation of a hydrophilic, almost neutral, very soft surface (99.99% reduction in hardness and modulus) after modification with the mixed brushes. This may completely suppress bacterial adhesion. Animal studies demonstrated that these brush-modified scaffolds are biocompatible and can mitigate wound infections. Overall, this study shows that the fascinating combination of an infection-resistant and cytocompatible surface can be generated on biodegradable polymeric surfaces by modulating the surface hardness, flexibility and hydrophilicity by selecting appropriate functionality of the copolymeric brushes grafted onto them, making them ideal non-leaching, anti-infective, hemocompatible and cytocompatible coatings for biodegradable implants.

Novel GO/Fe-Mn hybrid for the adsorptive removal of Pb(II) ions from aqueous solution and the spent adsorbent disposability in cement mix: compressive properties and leachability study for circular economy benefits.

GO/Fe-Mn hybrids were prepared by a single-pot chemical precipitation method and were characterized using FTIR, XRD, Raman, zeta potential, and FESEM, which confirmed the impregnation of Fe/Mn onto GO sheets. The synthesized hybrids were successively applied in removing the Pb(II) ions from aqueous solution and later utilizing the spent adsorbent to increase the properties of cement. The adsorption capability of the synthesized hybrid was seen in a set of batch studies to find out that about 15 min of contact time was required to remove 99% of the contaminant at a pH of 5 ± 0.2 and a dose of 0.83 g/L. The mechanism of the adsorption process for the synthesized hybrid was well described by Elovich kinetic model with an R2 of 0.99 and Langmuir isotherm model, also with an R2 of 0.99. The desorption studies conducted using 0.1 M HCl solution showed significant stability of the hybrid with a drop of 12% in the removal efficiency of Pb after up to five adsorption-desorption cycles. This points to an efficient adsorbent having potential for economical use. Later, the spent adsorbent was mixed with cement at ratios of 0.05%, 0.1%, and 0.5%, and compressive strength tests were performed, which showed an increase in the strength by 7.62%, 16.11%, and 26.82% at 28 days of curing time. The TCLP and SPLP tests performed on the hybrid and cement-spent adsorbent mix showed all the leaching parameters were well within the permissible limits. This development shows the potential for the use of spent adsorbent in a circular economy model.

A combination of potently neutralizing monoclonal antibodies isolated from an Indian convalescent donor protects against the SARS-CoV-2 Delta variant.

Although efficacious vaccines have significantly reduced the morbidity and mortality of COVID-19, there remains an unmet medical need for treatment options, which monoclonal antibodies (mAbs) can potentially fill. This unmet need is exacerbated by the emergence and spread of SARS-CoV-2 variants of concern (VOCs) that have shown some resistance to vaccine responses. Here we report the isolation of five neutralizing mAbs from an Indian convalescent donor, out of which two (THSC20.HVTR04 and THSC20.HVTR26) showed potent neutralization of SARS-CoV-2 VOCs at picomolar concentrations, including the Delta variant (B.1.617.2). One of these (THSC20.HVTR26) also retained activity against the Omicron variant. These two mAbs target non-overlapping epitopes on the receptor-binding domain (RBD) of the spike protein and prevent virus attachment to its host receptor, human angiotensin converting enzyme-2 (hACE2). Furthermore, the mAb cocktail demonstrated protection against the Delta variant at low antibody doses when passively administered in the K18 hACE2 transgenic mice model, highlighting their potential as a cocktail for prophylactic and therapeutic applications. Developing the capacity to rapidly discover and develop mAbs effective against highly transmissible pathogens like coronaviruses at a local level, especially in a low- and middle-income country (LMIC) such as India, will enable prompt responses to future pandemics as an important component of global pandemic preparedness.

Bimetallic Fe/Al-MOF for the adsorptive removal of multiple dyes: optimization and modeling of batch and hybrid adsorbent-river sand column study and its application in textile industry wastewater.

Bimetallic metal organic framework (MOF) has garnered interest over the years with its applications in industrial wastewater treatment. In this work, Fe-Al-1,4-benzene-dicarboxylic acid (FeAl(BDC)) MOF was synthesized, and adsorptive removal of Rhodamine B dye in batch and unique hybrid FeAl (BDC)-river sand fixed-bed column was studied. The experimental data from the batch studies corroborated well with the pseudo-second-order (PSO) (R2: 0.97) and Freundlich adsorption isotherm models (R2: 0.98) and achieved a maximum adsorption capacity of 48.59 mg/g in 90 min. Furthermore, a fixed-bed column study was conducted to assess the effect of varying flow rate (2, 5, 8 mL/min), bed height (5, 9, 13 cm), and feed concentration (10, 20, 30 mg/L) on the adsorption performance of FeAl(BDC) in continuous mode of operation. A uniform mixture of river sand and FeAl(BDC) by weight ratio (9:1) was packed into the column. The sand-FeAl(BDC) fixed-bed column could achieve the maximum adsorption capacity (qexp) of 113.05 mg/g at a 5 mL/min flow rate, feed concentration of 20 mg/L, and a bed height of 13 cm. The experimental data of the column study were successfully fitted well with BDST, Thomas (qcal: 114.94 mg/g), Yoon-Nelson, and dose-response models (qcal: 113.41 mg/g) and R2: 0.97-0.99. The fitting parameter values from the BDST model raise the scope of viable upscaling of the fixed-bed column. In all, it is proposed that these river sand-FeAl(BDC)-based filters can be widely used in areas facing critical contamination and in poor communities with a high demand for water.

Effectiveness of ChAdOx1 nCoV-19 vaccine against SARS-CoV-2 infection during the delta (B.1.617.2) variant surge in India: a test-negative, case-control study and a mechanistic study of post-vaccination immune responses.

BACKGROUND: SARS-CoV-2 variants of concern (VOCs) have threatened COVID-19 vaccine effectiveness. We aimed to assess the effectiveness of the ChAdOx1 nCoV-19 vaccine, predominantly against the delta (B.1.617.2) variant, in addition to the cellular immune response to vaccination. METHODS: We did a test-negative, case-control study at two medical research centres in Faridabad, India. All individuals who had a positive RT-PCR test for SARS-CoV-2 infection between April 1, 2021, and May 31, 2021, were included as cases and individuals who had a negative RT-PCR test were included as controls after matching with cases on calendar week of RT-PCR test. The primary outcome was effectiveness of complete vaccination with the ChAdOx1 nCoV-19 vaccine against laboratory-confirmed SARS-CoV-2 infection. The secondary outcomes were effectiveness of a single dose against SARS-CoV-2 infection and effectiveness of a single dose and complete vaccination against moderate-to-severe disease among infected individuals. Additionally, we tested in-vitro live-virus neutralisation and T-cell immune responses to the spike protein of the wild-type SARS-CoV-2 and VOCs among healthy (anti-nucleocapsid antibody negative) recipients of the ChAdOx1 nCoV-19 vaccine. FINDINGS: Of 2379 cases of confirmed SARS-CoV-2 infection, 85 (3·6%) were fully vaccinated compared with 168 (8·5%) of 1981 controls (adjusted OR [aOR] 0·37 [95% CI 0·28-0·48]), giving a vaccine effectiveness against SARS-CoV-2 infection of 63·1% (95% CI 51·5-72·1). 157 (6·4%) of 2451 of cases and 181 (9·1%) of 1994) controls had received a single dose of the ChAdOx1 nCoV-19 vaccine (aOR 0·54 [95% CI 0·42-0·68]), thus vaccine effectiveness of a single dose against SARS-CoV-2 infection was 46·2% (95% CI 31·6-57·7). One of 84 cases with moderate-to-severe COVID-19 was fully vaccinated compared with 84 of 2295 cases with mild COVID-19 (aOR 0·19 [95% CI 0·01-0·90]), giving a vaccine effectiveness of complete vaccination against moderate-to-severe disease of 81·5% (95% CI 9·9-99·0). The effectiveness of a single dose against moderate-to-severe disease was 79·2% (95% CI 46·1-94·0); four of 87 individuals with moderate-to-severe COVID-19 had received a single dose compared with 153 of 2364 participants with mild disease (aOR 0·20 [95% CI 0·06-0·54]). Among 49 healthy, fully vaccinated individuals, neutralising antibody responses were lower against the alpha (B.1.1.7; geometric mean titre 244·7 [95% CI 151·8-394·4]), beta (B.1.351; 97·6 [61·2-155·8]), kappa (B.1.617.1; 112·8 [72·7-175·0]), and delta (88·4 [61·2-127·8]) variants than against wild-type SARS-CoV-2 (599·4 [376·9-953·2]). However, the antigen-specific CD4 and CD8 T-cell responses were conserved against both the delta variant and wild-type SARS-CoV-2. INTERPRETATION: The ChAdOx1 nCoV-19 vaccine remained effective against moderate-to-severe COVID-19, even during a surge that was dominated by the highly transmissible delta variant of SARS-CoV-2. Spike-specific T-cell responses were maintained against the delta variant. Such cellular immune protection might compensate for waning humoral immunity. FUNDING: Department of Biotechnology India, Council of Scientific and Industrial Research India, and Fondation Botnar.

Impact of age-related macular degeneration on diabetic retinopathy: An electronic health record based big data analysis from a tertiary eye centre in South India.

PURPOSE: To determine whether the presence of age-related macular degeneration (AMD) decreases the risk of diabetic retinopathy. METHODS: This was a retrospective, case-cohort study performed in patients with a systemic diagnosis of diabetes at a tertiary health care center from May 2011 to April 2020. A total of 43,153 patients (1,024 AMD patients and 42,129 non-AMD patients) were included in the analysis. A total of 1,024 age and diabetes mellitus (DM) duration-matched controls were chosen from the non-AMD group for risk factor analysis. The severity of diabetic retinopathy was compared between the patients with AMD and the patients without AMD. RESULTS: Out of the enrolled 43,153 diabetic patients, 26,906 were males and 16,247 were females. A total of 1,024 patients had AMD and 42,129 had no AMD. The mean age of the cohort was 58.60 ± 0.09 years. The overall prevalence of DR was noted to be 22.8% (9,825 out of 43,153 eyes). A significantly lower prevalence of diabetic retinopathy (DR) (23% in non-AMD, 11.4% in AMD, OR = -0.43, P < 0.001), non-proliferative diabetic retinopathy (NPDR) (12% in non-AMD, 8.2% in AMD, OR = -0.66, P < 0.001), and proliferative diabetic retinopathy (PDR) (11% in non-AMD, 3.2% in AMD, OR = -0.27, P < 0.001) was seen in the AMD patients. No significant difference was seen between the dry and wet AMD. On multivariate logistic regression analysis, the lower age, absence of AMD, and male gender were associated with a higher risk of PDR. CONCLUSION: The presence of AMD was noted to statistically reduce the risk of DR. Our results may be useful in the field of resource allocation and awareness of DR.

Circular economy approach in solid waste management system to achieve UN-SDGs: Solutions for post-COVID recovery.

The COVID-19 pandemic and the ensuing socioeconomic crisis has impeded progress towards the UN Sustainable Development Goals (UN-SDGs). This paper investigates the impact of COVID 19 on the progress of the SDGs and provides insight into how green recovery stimulus, driven by circular economy (CE)-based solid waste management (SWM) could assist in attaining the intended targets of UN-SDG. It was understood in this review that the guiding principles of the UN-SDGs such as, public health, environmental concerns, resource value and economic development are similar to those that have driven the growth of waste management activities; thus, in order to achieve the goals of UN-SDG, a circular economy approach in solid waste management system should be prioritized in the post-COVID economic agenda. However, policy, technology and public involvement issues may hinder the shift to the CE model; therefore, niche growth might come from developing distinctive waste management-driven green jobs, formalizing informal waste pickers and by focusing in education and training of informal worker. The review also emphasized in creating green jobs by investing in recycling infrastructure which would enable us to address the climate change related concerns which is one of the key target of UN- SDG. The CE-based product designs and business models would emphasize multifunctional goods, extending the lifespan of products and their parts, and intelligent manufacturing to help the public and private sectors maximise product utility (thus reducing waste generation) while providing long-term economic and environmental benefits. The study also recommended strong policies that prioritized investments in decentralization of solid waste systems, localization of supply chains, recycling and green recovery, information sharing, and international collaboration in order to achieve the UN-SDGs.

Char from the co-pyrolysis of Eucalyptus wood and low-density polyethylene for use as high-quality fuel: Influence of process parameters.

Providing a valuable application to the under-utilized solid residue of co-pyrolysis of biomass and plastics could substantially improve economic and environmental sustainability of the process, thereby fostering circular economy. This study focuses on the variation of thermal and physiochemical characteristics of solid char, produced from the co-pyrolysis of waste low-density polyethylene (WLDPE) and Eucalyptus wood with varying pyrolysis temperatures from 300 to 550 °C, residence times of 90-150 min, and relative percentage of 33% and 25% (w/w) WLDPE in the feedstock. The highest values of yield (37%), energy density (1.25) and high heat value (31 MJ/Kg) were observed with the char produced at 300 °C. The physical inhibition caused by the overlaying plastic coating on the surface of the char below 450 °C resulted in the same. However, with the increase in temperature, increase in fuel ratio by 78-79% and fixed carbon content by 68-69% were observed. The highest concentrations of fixed carbon (39%), fuel ratio (0.81) along with the lowest O/C and H/C ratios (0.07 and 0.13) were observed with the chars produced above 450 °C depicting their high degree of carbonization. The fuel value indices of all the chars were > 500 GJ/m3 indicating their suitability as high-quality fuels. Significant influences of residence time and feedstock ratio were also observed on properties of the char. The analysis of variance and principal component analysis also depicted significant variations in the properties of the char produced below and above the temperatures of 450 °C due to the inhibitory and synergetic effects. While the chars produced at 300-350 °C could be used for combustion/co-combustion in coal-fired boilers, chars produced above 450 °C can be opted as household fuel due to their low losses of energy, water vapour, and smoke during combustion.

Evaluation of heavy metal leaching under simulated disposal conditions and formulation of strategies for handling solar panel waste.

With the steady growth in the worldwide solar installed capacity, there is an immediate concern about the fate of the solar panels at the end of their life. Solar panel waste is often disposed of indiscriminately, exposing the environment to chemical hazards. The major objective of the current study was to evaluate the leaching potential of the polycrystalline solar panel waste under different simulated disposal conditions through toxicity characteristic leaching procedure (TCLP), synthetic precipitation leaching procedure (SPLP) and pH static leaching procedure tests. Moreover, the study evaluates the effects of ageing and the breakage of the Glass Laminate Encapsulation (GLE) of solar panels on their leaching potential. Among the metals studied (silver (Ag), aluminium (Al), cadmium (Cd), chromium (Cr), copper (Cu), manganese (Mn), lead (Pb), and zinc (Zn)), the concentrations of Pb were as high as 9.3 mg/L, 1.4 mg/L, 6.7 mg/L in the TCLP, SPLP, and pH static test respectively. This indicated the hazardous nature of the waste with leaching potential of Pb above the permissible limits stipulated by various regulatory bodies. The presence of GLE reduced the mobility of Pb by a factor of 4.1-8.8 in the TCLP test, thereby rendering the waste as non-hazardous for its disposal in a landfill. However, the indiscriminate disposal of solar panel waste in the natural environment as simulated by the SPLP test indicated its harmful nature irrespective of the physical condition. Ageing of the solar panels before disposal and acidic pH conditions also positively influenced the leaching potential of the selected metals subjected to their reactivity and the accessibility of internal layers of waste to the leaching solution. Strategies such as extended producer responsibilty, advance-recycling fee, and incentivizing the recycling industry will lead to both economic benefit creation and effective waste management of this waste stream.

Geospatial HIV-1 subtype C gp120 sequence diversity and its predicted impact on broadly neutralizing antibody sensitivity.

Evolving diversity in globally circulating HIV-1 subtypes presents a formidable challenge in defining and developing neutralizing antibodies for prevention and treatment. HIV-1 subtype C is responsible for majority of global HIV-1 infections. In the present study, we examined the diversity in genetic signatures and attributes that differentiate region-specific HIV-1 subtype C gp120 sequences associated with virus neutralization outcomes to key bnAbs having distinct epitope specificities. A total of 1814 full length HIV-1 subtype C gp120 sequence from 37 countries were retrieved from Los Alamos National Laboratory HIV database (www.hiv.lanl.gov). The amino acid sequences were assessed for their phylogenetic association, variable loop lengths and prevalence of potential N-linked glycosylation sites (pNLGS). Responses of these sequences to bnAbs were predicted with a machine learning algorithm 'bNAb-ReP' and compared with those reported in the CATNAP database. Subtype C sequences from Asian countries including India differed phylogenetically when compared with that from African countries. Variable loop lengths and charges within Indian and African clusters were also found to be distinct from each other, specifically for V1, V2 and V4 loops. Pairwise analyses at each of the 25 pNLG sites indicated distinct country specific profiles. Highly significant differences (p<0.001***) were observed in prevalence of four pNLGS (N130, N295, N392 and N448) between South Africa and India, having most disease burden associated with subtype C. Our findings highlight that distinctly evolving clusters within global intra-subtype C gp120 sequences are likely to influence the disparate region-specific sensitivity of circulating HIV-1 subtype C to bnAbs.