An HLA-E-targeted TCR bispecific molecule redirects T cell immunity against Mycobacterium tuberculosis.

Peptides presented by HLA-E, a molecule with very limited polymorphism, represent attractive targets for T cell receptor (TCR)-based immunotherapies to circumvent the limitations imposed by the high polymorphism of classical HLA genes in the human population. Here, we describe a TCR-based bispecific molecule that potently and selectively binds HLA-E in complex with a peptide encoded by the inhA gene of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis in humans. We reveal the biophysical and structural bases underpinning the potency and specificity of this molecule and demonstrate its ability to redirect polyclonal T cells to target HLA-E-expressing cells transduced with mycobacterial inhA as well as primary cells infected with virulent Mtb. Additionally, we demonstrate elimination of Mtb-infected cells and reduction of intracellular Mtb growth. Our study suggests an approach to enhance host T cell immunity against Mtb and provides proof of principle for an innovative TCR-based therapeutic strategy overcoming HLA polymorphism and therefore applicable to a broader patient population.

HIV, asymptomatic STI, and the rectal mucosal immune environment among young men who have sex with men.

Young men who have sex with men (YMSM) are disproportionately affected by HIV and bacterial sexually transmitted infections (STI) including gonorrhea, chlamydia, and syphilis; yet research into the immunologic effects of these infections is typically pursued in siloes. Here, we employed a syndemic approach to understand potential interactions of these infections on the rectal mucosal immune environment among YMSM. We enrolled YMSM aged 18-29 years with and without HIV and/or asymptomatic bacterial STI and collected blood, rectal secretions, and rectal tissue biopsies. YMSM with HIV were on suppressive antiretroviral therapy (ART) with preserved blood CD4 cell counts. We defined 7 innate and 19 adaptive immune cell subsets by flow cytometry, the rectal mucosal transcriptome by RNAseq, and the rectal mucosal microbiome by 16S rRNA sequencing and examined the effects of HIV and STI and their interactions. We measured tissue HIV RNA viral loads among YMSM with HIV and HIV replication in rectal explant challenge experiments among YMSM without HIV. HIV, but not asymptomatic STI, was associated with profound alterations in the cellular composition of the rectal mucosa. We did not detect a difference in the microbiome composition associated with HIV, but asymptomatic bacterial STI was associated with a higher probability of presence of potentially pathogenic taxa. When examining the rectal mucosal transcriptome, there was evidence of statistical interaction; asymptomatic bacterial STI was associated with upregulation of numerous inflammatory genes and enrichment for immune response pathways among YMSM with HIV, but not YMSM without HIV. Asymptomatic bacterial STI was not associated with differences in tissue HIV RNA viral loads or in HIV replication in explant challenge experiments. Our results suggest that asymptomatic bacterial STI may contribute to inflammation particularly among YMSM with HIV, and that future research should examine potential harms and interventions to reduce the health impact of these syndemic infections.

Instability of the HLA-E peptidome of HIV presents a major barrier to therapeutic targeting.

Naturally occurring T cells that recognize microbial peptides via HLA-E, a nonpolymorphic HLA class Ib molecule, could provide the foundation for new universal immunotherapeutics. However, confidence in the biological relevance of putative ligands is crucial, given that the mechanisms by which pathogen-derived peptides can access the HLA-E presentation pathway are poorly understood. We systematically interrogated the HIV proteome using immunopeptidomic and bioinformatic approaches, coupled with biochemical and cellular assays. No HIV HLA-E peptides were identified by tandem mass spectrometry analysis of HIV-infected cells. In addition, all bioinformatically predicted HIV peptide ligands (>80) were characterized by poor complex stability. Furthermore, infected cell elimination assays using an affinity-enhanced T cell receptor bispecific targeted to a previously reported HIV Gag HLA-E epitope demonstrated inconsistent presentation of the peptide, despite normal HLA-E expression on HIV-infected cells. This work highlights the instability of the HIV HLA-E peptidome as a major challenge for drug development.

Adult Cerebral Malaria: Acute and Subacute Imaging Findings, Long-term Clinical Consequences.

Cerebral malaria is an important cause of mortality and neurodisability in endemic regions. We show magnetic resonance imaging (MRI) features suggestive of cytotoxic and vasogenic cerebral edema followed by microhemorrhages in 2 adult UK cases, comparing them with an Indian cohort. Long-term follow-up images correlate ongoing changes with residual functional impairment.

Repurposing FDA-approved drugs to target malaria through inhibition of dihydrofolate reductase in the folate biosynthesis pathway: A prospective approach.

Dihydrofolate reductase (DHFR) is a ubiquitous enzyme that regulates the biosynthesis of tetrahydrofolate among various species of Plasmodium parasite. It is a validated target of the antifolate drug pyrimethamine (Pyr) in Plasmodium falciparum (Pf), but its clinical efficacy has been hampered due to the emergence of drug resistance. This has made the attempt to screen Food & Drug Administration-approved drugs against wild- and mutant PfDHFR by employing an in-silico pipeline to identify potent candidates. The current study has followed a virtual screening approach for identifying potential DHFR inhibitors from DrugBank database, based on a structure similarity search of candidates, followed by absorption, distribution, metabolism, and excretion estimation. The screened drugs were subjected to various parameters like docking, molecular mechanics with generalized born and surface area solvation calculations, and molecular simulations. We have thus identified two potential drug candidates, duloxetine and guanethidine, which can be repurposed to be tested for their efficacy against wild type and drug resistant falciparum malaria.

Investigating the therapeutic potential of Allium cepa extract in combating pesticide exposure induced ocular damage.

The ocular surface is subject to a range of potentially hazardous environmental factors and substances, owing to its anatomical location, sensitivity, and physiological makeup. Xenobiotic stress exerted by chronic pesticide exposure on the cornea is primarily responsible for ocular irritation, excessive tear production (hyper-lacrimation), corneal abrasions and decreased visual acuity. Traditional medicine hails the humble onion (Allium cepa) for its multi-faceted properties including but not limited to anti-microbial, antioxidant, anti-inflammatory and wound healing. However, there is a lacuna regarding its impact on the ocular surface. Thereby, the current study investigated whether topical application of crude extract of Allium cepa aided in mitigating pesticide-induced damage to the ocular surface. The deleterious effects of pesticide exposure and their mitigation through the topical application of herbal extract of Allium cepa were analysed initially through in vitro evaluation on cell lines and then on the ocular surface via various in-vivo and ex-vivo techniques. Pathophysiological alterations to the ocular surface that impacted vision were explored through detailed neurophysiological screening with special emphasis on visual acuity wherein it was observed that the murine group treated with topical application of Allium cepa extract had comparable visual capacity to the non-pesticide exposed group. Additionally, SOD2 was utilized as an oxidative stress marker along with the expression of cellular apoptotic markers such as Bcl-xL to analyse the impact of pesticide exposure and subsequent herbal intervention on oxidative stress-induced corneal damage. The impact on the corneal epithelial progenitor cell population (ABCG2 and TERT positive cells) was also flowcytometrically analysed. Therefore, from our observations, it can be postulated that the topical application of Allium cepa extract might serve as an effective strategy to alleviate pesticide exposure related ocular damage.

Designer probiotics: Opening the new horizon in diagnosis and prevention of human diseases.

Probiotic microorganisms have been used for therapeutic purposes for over a century, and recent advances in biotechnology and genetic engineering have opened up new possibilities for developing therapeutic approaches using indigenous probiotic microorganisms. Diseases are often related to metabolic and immunological factors, which play a critical role in their onset. With the help of advanced genetic tools, probiotics can be modified to produce or secrete important therapeutic peptides directly into mucosal sites, increasing their effectiveness. One potential approach to enhancing human health is through the use of designer probiotics, which possess immunogenic characteristics. These genetically engineered probiotics hold promise in providing novel therapeutic options. In addition to their immunogenic properties, designer probiotics can also be equipped with sensors and genetic circuits, enabling them to detect a range of diseases with remarkable precision. Such capabilities may significantly advance disease diagnosis and management. Furthermore, designer probiotics have the potential to be used in diagnostic applications, offering a less invasive and more cost-effective alternative to conventional diagnostic techniques. This review offers an overview of the different functional aspects of the designer probiotics and their effectiveness on different diseases and also, we have emphasized their limitations and future implications. A comprehensive understanding of these functional attributes may pave the way for new avenues of prevention and the development of effective therapies for a range of diseases.

High-Performance Porous Organic Polymers for Environmental Remediation of Toxic Gases.

Sulfur dioxide (SO2) is a harmful acidic gas generated from power plants and fossil fuel combustion and represents a significant health risk and threat to the environment. Benzimidazole-linked polymers (BILPs) have emerged as a promising class of porous solid adsorbents for toxic gases because of their chemical and thermal stability as well as the chemical nature of the imidazole moiety. The performance of BILPs in SO2 capture was examined by synergistic experimental and theoretical studies. BILPs exhibit a significantly high SO2 uptake of up to 8.5 mmol g-1 at 298 K and 1.0 bar. The density functional theory (DFT) calculations predict that this high SO2 uptake is due to the dipole-dipole interactions between SO2 and the functionalized polymer frames through O2S(δ+)···N(δ-)-imine and O═S═O(δ-)···H(δ+)-aryl and intermolecular attraction between SO2 molecules (O═S═O(δ-)···S(δ+)O2). Moderate isosteric heats of adsorption (Qst ≈ 38 kJ mol-1) obtained from experimental SO2 uptake studies are well supported by the DFT calculations (≈40 kJ mol-1), which suggests physisorption processes enabling rapid adsorbent regeneration for reuse. Repeated adsorption experiments with almost identical SO2 uptake confirm the easy regeneration and robustness of BILPs. Moreover, BILPs possess very high SO2 adsorption selectivity at low concentration over carbon dioxide (CO2), methane (CH4), and nitrogen (N2): SO2/CO2, 19-24; SO2/CH4, 118-113; SO2/N2, 600-674. This study highlights the potential of BILPs in the desulfurization of flue gas or other gas mixtures through capturing trace levels of SO2.

Time series analysis of malaria cases to assess the impact of various interventions over the last three decades and forecasting malaria in India towards the 2030 elimination goals.

BACKGROUND: Despite the progress made in this decade towards malaria elimination, it remains a significant public health concern in India and many other countries in South Asia and Asia Pacific region. Understanding the historical trends of malaria incidence in relation to various commodity and policy interventions and identifying the factors associated with its occurrence can inform future intervention strategies for malaria elimination goals. METHODS: This study analysed historical malaria cases in India from 1990 to 2022 to assess the annual trends and the impact of key anti-malarial interventions on malaria incidence. Factors associated with malaria incidence were identified using univariate and multivariate linear regression analyses. Generalized linear, smoothing, autoregressive integrated moving averages (ARIMA) and Holt's models were used to forecast malaria cases from 2023 to 2030. RESULTS: The reported annual malaria cases in India during 1990-2000 were 2.38 million, which dropped to 0.73 million cases annually during 2011-2022. The overall reduction from 1990 (2,018,783) to 2022 (176,522) was 91%. The key interventions of the Enhanced Malaria Control Project (EMCP), Intensified Malaria Control Project (IMCP), use of bivalent rapid diagnostic tests (RDT-Pf/Pv), artemisinin-based combination therapy (ACT), and involvement of the Accredited Social Health Activists (ASHAs) as front-line workers were found to result in the decline of malaria significantly. The ARIMA and Holt's models projected a continued decline in cases with the potential for reaching zero indigenous cases by 2027-2028. Important factors influencing malaria incidence included tribal population density, literacy rate, health infrastructure, and forested and hard-to-reach areas. CONCLUSIONS: Studies aimed at assessing the impact of major commodity and policy interventions on the incidence of disease and studies of disease forecasting will inform programmes and policymakers of steps needed during the last mile phase to achieve malaria elimination. It is proposed that these time series and disease forecasting studies should be performed periodically using granular (monthly) and meteorological data to validate predictions of prior studies and suggest any changes needed for elimination efforts at national and sub-national levels.

Enhanced photocatalytic performance of Bi-doped TiO2 under sunlight and UV light: mechanistic insights and comparative analysis.

Bismuth-doped metal oxides exhibit favourable photocatalytic features when exposed to both sunlight and UV light. In this approach, Bi0/TiO2 and Bi+3/TiO2 photocatalysts were prepared and their structural and optical properties are analysed using various characterization techniques. These developed photocatalysts were further tested for the photocatalytic elimination of Nitrobenzene in UV light and sunlight and compared with the performance of bare TiO2. The catalyst Bi+3/TiO2 performed better in UV light with 72.31% degradation, and 4.74 × 10-6 mol.litre-1.min-1 initial rate of reaction. However, when exposed to sunlight, Bi0/TiO2 outperformed with 73.85% degradation, and 4.63 × 10-6 mol.min-1 initial rate of reaction. This significant increase in photocatalytic activity of Bi0/TiO2 under sunlight could be accredited to increased light harvesting and enhanced efficiency in charge carrier separation, both of which were made possible by bismuth-induced surface plasmon resonance.

Metabolomics-driven investigation of plant defense response against pest and pathogen attack.

The advancement of metabolomics has assisted in the identification of various bewildering characteristics of the biological system. Metabolomics is a standard approach, facilitating crucial aspects of system biology with absolute quantification of metabolites using minimum samples, based on liquid/gas chromatography, mass spectrometry and nuclear magnetic resonance. The metabolome profiling has narrowed the wide gaps of missing information and has enhanced the understanding of a wide spectrum of plant-environment interactions by highlighting the complex pathways regulating biochemical reactions and cellular physiology under a particular set of conditions. This high throughput technique also plays a prominent role in combined analyses of plant metabolomics and other omics datasets. Plant metabolomics has opened a wide paradigm of opportunities for developing stress-tolerant plants, ensuring better food quality and quantity. However, despite advantageous methods and databases, the technique has a few limitations, such as ineffective 3D capturing of metabolites, low comprehensiveness, and lack of cell-based sampling. In the future, an expansion of plant-pathogen and plant-pest response towards the metabolite architecture is necessary to understand the intricacies of plant defence against invaders, elucidation of metabolic pathway operational during defence and developing a direct correlation between metabolites and biotic stresses. Our aim is to provide an overview of metabolomics and its utilities for the identification of biomarkers or key metabolites associated with biotic stress, devising improved diagnostic methods to efficiently assess pest and pathogen attack and generating improved crop varieties with the help of combined application of analytical and molecular tools.

Exploring Steroidal Saponin Composition and Morphometric Characteristics of Rhizomes from Trillium govanianum Wall. ex D. Don: Inference for Medicinal Properties and Genetic Stock Improvement.

Trillium govanianum, a medicinal herb, exhibiting diverse morphometric traits and phytochemicals across developmental stages of plants. The changes in the chemical profile and steroidal saponin levels in the rhizome of T. govanianum across different developmental stages were previously unknown. This study categorizes rhizomes into three types based on scar presence: juvenile (5-10 scars, Type I), young (11-19 scars, Type II), and mature (21-29 scars, Type III). Rhizomes show varying sizes (length 1.2-4.7 cm, girth 0.3-1.6 cm), weight (0.18-5.0 g), and extractive yields (9.7-16.1 % w w-1), with notable differences in saponin content (5.95-21.9 mg g-1). Ultra-high performance liquid chromatography-MS/MS (UHPLC-QTOF-MS/MS)-based chemical profiling identifies 31 phytochemicals, mainly including diverse saponins. Ultra-high performance liquid chromatography coupled with evaporative light scattering detection (UHPLC-ELSD)-based quantitative analysis of seven key saponins reveals stage-specific accumulation patterns, with protodioscin (P) and dioscin (DS) predominant in mature rhizomes. Statistical analysis confirms significant variation (p=0.001) in saponin levels across developmental stages with chemical constituent protodioscin (P=4.03±0.03-15.76±0.14 mg g-1, PAve=9.79±3.03 mg g-1) and dioscin (DS=1.23±0.06-3.93±0.07 mg g-1, DSAve=2.59±0.70 mg g-1), with acceptable power (p=0.738; |δ|>0.5) statistics for effective sample size (n=27 samples used in the study) of T. govanianum. Principal Component Analysis (PCA) and Euclidean clustering further highlighted chemotype distinctions.

Sediment-water exchange and risk assessment of pesticidal persistent organic pollutants in Bharathappuzha and Periyar Riverine region along the Arabian Sea.

Considering the extensive agricultural practices along the perennial rivers, viz. Periyar and Bharathappuzha of Kerala in the southwest coast of India, the first comprehensive surveillance of new and legacy organochlorine pesticides (OCPs) in surface sediment was conducted. Further, the sediment-water exchange fluxes have been elucidated. Mean concentrations of total HCH, DDT and endosulfan were 0.84 ng/g, 0.42 ng/g and 0.30 ng/g for Bharathappuzha Riverine sediment (BRS) and 1.08 ng/g, 0.39 ng/g and 0.35 ng/g for Periyar Riverine sediment (PRS). The dominance α-HCH and ß-HCH isomers in PRS and BRS reflect the ongoing use of technical HCH in Kerala. The calculated KSW in both rivers was very low in comparison with other Indian rivers. The average log K'OC for all the detected OCPs in both the rivers was lower than the predicted log KOC in equilibrium indicating the higher adherence of OCPs to sediment. Furthermore, fugacity fraction (fs/fw) was < 1.0 for all OCPs confirming the net deposition of OCPs into the sediment. Sediment concentrations for each of the OCPs in PRS and BRS did not surpass the threshold effect level and probable effect level as stipulated by the Canadian Council of Ministry of the Environment Guidelines. In addition, all the sites of both rivers had sediment quality guideline quotient (SQGQ) values below 0.1 indicating the absence of significant biological and ecological risks.

Contradictory Recommendation in the Guideline for Antibiotic Prescription.

How to cite this article: Das PK, Nath SS, Parashar S. Contradictory Recommendation in the Guideline for Antibiotic Prescription. Indian J Crit Care Med 2024;28(7):713-714.

Optimal timing of PD-1 blockade in combination with oncolytic virus therapy.

Anti-PD-1 and oncolytic viruses (OVs) have non-overlapping anti-tumor mechanisms, since each agent works at different steps of the cancer-immunity cycle. Evidence suggests that OVs improve therapeutic responses to anti-PD-1 therapy by reversing immunosuppressive factors, increasing the number and diversity of infiltrating lymphocytes, and promoting PD-L1 expression in both injected and non-injected tumors. Many studies in preclinical models suggest that the timing of anti-PD-1 administration influences the therapeutic success of the combination therapy (anti-PD-1 + OV). Therefore, determining the appropriate sequencing of agents is of critical importance to designing a rationale OV-based combinational clinical trial. Currently, the combination of anti-PD-1 and OVs are being delivered using various schedules, and we have classified the timing of administration of anti-PD-1 and OVs into five categories: (i) anti-PD-1 lead-in → OV; (ii) concurrent administration; (iii) OV lead-in → anti-PD-1; (iv) concurrent therapy lead-in → anti-PD-1; and (v) OV lead-in → concurrent therapy. Based on the reported preclinical and clinical literature, the most promising treatment strategy to date is hypothesized to be OV lead-in → concurrent therapy. In the OV lead-in → concurrent therapy approach, initial OV treatment results in T cell priming and infiltration into tumors and an immunologically hot tumor microenvironment (TME), which can be counterbalanced by engagement of PD-L1 to PD-1 receptor on immune cells, leading to T cell exhaustion. Therefore, after initial OV therapy, concurrent use of both OV and anti-PD-1 is critical through which OV maintains T cell priming and an immunologically hot TME, whereas PD-1 blockade helps to overcome PD-L1/PD-1-mediated T cell exhaustion. It is important to note that the hypothetical conclusion drawn in this review is based on thorough literature review on current understanding of OV + anti-PD-1 combination therapies and rhythm of treatment-induced cancer-immunity cycle. A variety of confounding factors such as tumor types, OV types, presence or absence of cytokine transgenes carried by an OV, timing of treatment initiation, varying dosages and treatment frequencies/duration of OV and anti-PD-1, etc. may affect the validity of our conclusion that will need to be further examined by future research (such as side-by-side comparative studies using all five treatment schedules in a given tumor model).

A phase 1b single-arm trial of intratumoral oncolytic virus V937 in combination with pembrolizumab in patients with advanced melanoma: results from the CAPRA study.

BACKGROUND: CAPRA (NCT02565992) evaluated Coxsackievirus A21 (V937) + pembrolizumab for metastatic/unresectable stage IIIB-IV melanoma. METHODS: Patients received intratumoral V937 on days 1, 3, 5, and 8 (then every 3 weeks [Q3W]) and intravenous pembrolizumab 2 mg/kg Q3W from day 8. Primary endpoint was safety. RESULTS: Median time from first dose to data cutoff was 32.0 months. No dose-limiting toxicities occurred; 14% (5/36) of patients experienced grade 3‒5 treatment-related adverse events. Objective response rate was 47% (complete response, 22%). Among 17 responders, 14 (82%) had responses ≥ 6 months. Among 8 patients previously treated with immunotherapy, 3 responded (1 complete, 2 partial). Responses were associated with increased serum CXCL10 and CCL22, suggesting viral replication contributes to antitumor immunity. For responders versus nonresponders, there was no difference in baseline tumor PD-L1 expression, ICAM1 expression, or CD3+ infiltrates. Surprisingly, the baseline cell density of CD3+CD8- T cells in the tumor microenvironment was significantly lower in responders compared with nonresponders (P = 0.0179). CONCLUSIONS: These findings suggest responses to this combination may be seen even in patients without a typical "immune-active" microenvironment. TRIAL REGISTRATION NUMBER: NCT02565992.

Post-compression of multi-millijoule picosecond pulses to few-cycles approaching the terawatt regime.

Advancing ultrafast high-repetition-rate lasers to shortest pulse durations comprising only a few optical cycles while pushing their energy into the multi-millijoule regime opens a route toward terawatt-class peak powers at unprecedented average power. We explore this route via efficient post-compression of high-energy 1.2 ps pulses from an ytterbium InnoSlab laser to 9.6 fs duration using gas-filled multi-pass cells (MPCs) at a repetition rate of 1 kHz. Employing dual-stage compression with a second MPC stage supporting a close-to-octave-spanning bandwidth enabled by dispersion-matched dielectric mirrors, a record compression factor of 125 is reached at 70% overall efficiency, delivering 6.7 mJ pulses with a peak power of ∼0.3 TW. Moreover, we show that post-compression can improve the temporal contrast at multi-picosecond delay by at least one order of magnitude. Our results demonstrate efficient conversion of multi-millijoule picosecond lasers to high-peak-power few-cycle sources, prospectively opening up new parameter regimes for laser plasma physics, high energy physics, biomedicine, and attosecond science.

Characterization of C-X-C chemokine receptor type 5 in the cornea and role in the inflammatory response after corneal injury.

C-X-C chemokine receptor type 5 (CXCR5) regulates inflammatory responses in ocular and non-ocular tissues. However, its expression and role in the cornea are still unknown. Here, we report the expression of CXCR5 in human cornea in vitro and mouse corneas in vivo, and its functional role in corneal inflammation using C57BL/6J wild-type (CXCR5+/+) and CXCR5-deficient (CXCR5-/-) mice, topical alkali injury, clinical eye imaging, histology, immunofluorescence, PCR, qRT-PCR, and western blotting. Human corneal epithelial cells, stromal fibroblasts, and endothelial cells demonstrated CXCR5 mRNA and protein expression in PCR, and Western blot analyses, respectively. To study the functional role of CXCR5 in vivo, mice were divided into four groups: Group-1 (CXCR5+/+ alkali injured cornea; n = 30), Group-2 (CXCR5-/- alkali injured cornea; n = 30), Group-3 (CXCR5+/+ naïve cornea; n = 30), and Group-4 (CXCR5-/- naïve cornea; n = 30). Only one eye was wounded with alkali. Clinical corneal evaluation and imaging were performed before and after injury. Mice were euthanized 4 h, 3 days, or 7 days after injury, eyes were excised and used for histology, immunofluorescence, and qRT-PCR. In clinical eye examinations, CXCR5-/- mouse corneas showed ocular health akin to the naïve corneas. Alkali injured CXCR5+/+ mouse corneas showed significantly increased mRNA (p < 0.001) and protein (p < 0.01 or p < 0.0001) levels of the CXCR5 compared to the naïve corneas. Likewise, alkali injured CXCR5-/- mouse corneas showed remarkably amplified inflammation in clinical eye exams in live animals. The histological and molecular analyses of these corneas post euthanasia exhibited markedly augmented inflammatory cells in H&E staining and significant CD11b + cells in immunofluorescence (p < 0.01 or < 0.05); and tumor necrosis factor-alpha (TNFα; p < 0.05), cyclooxygenase 2 (COX-2; p < 0.0001), interleukin (IL)-1ß (p < 0.0001), and IL-6 (p < 0.0001 or < 0.01) mRNA expression compared to the CXCR5+/+ mouse corneas. Interestingly, CXCR5-/- alkali injured corneas also showed altered mRNA expression of fibrotic alpha smooth muscle actin (α-SMA; p > 0.05) and angiogenic vascular endothelial growth factor (VEGF; p < 0.01) compared to the CXCR5+/+ alkali injured corneas. In summary, the CXCR5 gene is expressed in all three major layers of the cornea and appears to influence corneal inflammatory and repair events post-injury in vivo. More studies are warranted to tease the mechanistic role of CXCR5 in corneal inflammation and wound healing.

Sulfonated Zinc Phthalocyanine Coating as an Efficient and Ecofriendly Corrosion Inhibitor for Copper Surfaces: An In Silico Led Design and Its Experimental Validation.

The current study highlights the successful integration of an in silico design with experimental validation to create a highly effective corrosion inhibitor for copper (Cu) surfaces. The synthesized sulfonated zinc phthalocyanine (Zn-Pc) is electrochemically characterized and demonstrates an impressive 97% inhibition efficiency, comparable to the widely used industrial corrosion inhibitor, BTA, for Cu surfaces. The corrosion inhibition is comprehensively analyzed through potentiodynamic polarization and impedance spectroscopy techniques, supported by their respective equivalent circuits. Furthermore, the sample undergoes thorough characterization using scanning electron microscopy, energy-dispersive X-ray analysis, X-ray photoelectron spectroscopy, contact angle measurements, and atomic force microscopy. Density functional theory calculations reveal that sulfonated Zn-Pc exhibits the highest interaction energy, underscoring its exceptional inhibition properties. These results open possibilities for utilizing computational methods to design and optimize corrosion inhibitors for protection of Cu surfaces.

Novel Mechanisms of Exosome-Mediated Phagocytosis of Dead Cells in Injured Heart.

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