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Krupa Kansara, Pal Patel, Ritesh K Shukla, Alok Pandya, Rishi Shanker, Ashutosh Kumar, Alok Dhawan Institute of Life Sciences, School of Science and Technology, Ahmedabad University, Ahmedabad, Gujarat, India Abstract: Over the last decade, there has been growing interest in developing novel nanoparticles (NPs) for biomedical applications. A safe-by-design approach was used in this study to synthesize biocompatible iron oxide NPs. The size of the particles obtained was ~100 nm. Although these NPs were significantly (P

Pal Patel, Krupa Kansara, Ragini Singh, Ritesh K Shukla, Sanjay Singh, Alok Dhawan, Ashutosh Kumar Division of Biological and Life Sciences (Formerly Institute of Life Sciences), School of Arts and Sciences, Ahmedabad University, Ahmedabad, Gujarat, India Abstract: Overproduction of free radicals contributes to oxidative stress and inflammation leading to various disease conditions. Cerium oxide nanoparticles (nanoceria) have been shown to scavenge free radicals and have the potential for being used as a therapeutic agent in disease conditions. Therefore, in the present study, human monocytic leukemia cells (THP-1) were used as a model to evaluate the uptake and free radical scavenging activity of nanoceria. Our data showed a significant (P

Eclipta prostrata belongs to the Asteraceae family. The plant contains bioactive compounds like wedelolactone (WDL) and demethylwedelolactone (DW). Its transcriptomic information engaged with secondary metabolite biosynthesis is not available. Based on differential accumulation of WDL and DW in root, shoot of the mature plant, we performed comparative de novo transcriptome of root and shoot tissue in three independent biological replicates and generated 49820 unique transcripts. Annotation resulted in significant matches for 43,015 unigenes. Based on differential gene expression data, we found WDL biosynthesis-related transcripts, which were mainly upregulated in shoot. Finally, 13 selected differentially expressed transcripts related to WDL biosynthesis that were validated by qRT-PCR. Detailed tissue-specific metabolite and transcript profiling revealed that DW highly accumulated in root and WDL accumulation was high in aerial part along with transcripts. For WDL pathway exploration, we did integrated profiling of 08 metabolites and 13 transcripts and witnessed that only naringenin, apigenin, DW, and WDL were detected in different developmental stages. Taking leads from the findings, we postulated that naringenin to apigenin pathway is one potential route for WDL biosynthesis. Moreover, wound stress led to accumulation of DW and WDL and related biosynthetic transcripts. Furthermore, the selected enzymes were subjected to molecular docking and binding studies for the predicted substrates involved in crucial and advance steps of WDL biosynthesis. A comprehensive analysis integrating de novo transcriptomics, metabolomics, and molecular docking of targeted proteins paves the way for the elucidation of the putative wedelolactone biosynthesis pathway from E. prostrata., Competing Interests: Declarations. Competing of interest: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Polymerase Chain Reaction (PCR) has transformed forensic DNA analysis but is still limited when dealing with compromised trace or inhibitor-containing samples. Nanotechnology has been integrated into nanoPCR (nanoparticle-assisted PCR) to overcome these obstacles. Nanomaterials improve PCR sensitivity, selectivity, and efficiency. Examples of these materials are semiconductor quantum dots and metal nanoparticles. They enhance DNA binding to primers, stabilize enzymes, and function as effective heat conductors, making accurate amplification possible even with tainted samples. The developments in nanoPCR have potential uses in forensics, as they allow for the more sensitive analysis of smaller, polluted, or deteriorated samples. Nevertheless, there are methodological and ethical issues. To provide credible and legitimate forensic evidence, rigorous validation and standardization of NanoPCR techniques are vital. The article addresses the relevant ethical and methodological aspects in forensic casework while examining the integration of nanotechnology into PCR., Competing Interests: Declarations. Conflicts of interest/Competing interests All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The present study aimed to evaluate the nutrition value, phytochemical content, and diverse pharmacological activities of different solvent extracts of Borassus flabellifer L. fruit. Among all, the hydro-alcoholic extract showed high DPPH and ABTS radical scavenging activities with IC 50 values of 82.98 ± 0.93, and 75.67 ± 0.48 μg/mL, respectively. The hydro-alcoholic extract offered a noticeableα-amylase (IC 50 = 82.90 ± 0.73 µg/mL) and α-glucosidase inhibitory effects (IC 50 = 62.5 ± 0.39 µg/mL), which were comparable to standard drug Acarbose. In anti-denaturation assay, the hydro-alcoholic extract showed a weaker inhibitory effect (IC 50 = 93.47 ± 0.93) than standard Diclofenac-Na (IC 50 =65.85 ± 0.42 µg/mL). Furthermore, the hydro-alcoholic extract showed the highest potential in preventing the harmful effects of UV radiation with a sun protection factor of 37.12 ± 0.28.

Ficus rumphii is a plant belonging to the Moraceae family. This study aimed to profile the functional groups using FTIR, as well as nutritional, elements using ICP-MS technique, and anti-nutritional analyses of Ficus rumphii leaves. The results of nutritional analysis of Ficus rumphii leaves revealed that the leaves had a diverse proximate composition with derived nutritional value to be 314.11 ± 0.31 kcal/100g. The leaves demonstrated good levels of ash, crude fibre, carbohydrate, crude fat, moisture, crude protein and nutritive value. The anti-nutrients were present at proportions that are not dangerous. Furthermore, the ICP-MS analysis revealed that Ficus rumphii leaves were also abundant in essential elements. FTIR analysis identified several functional groups such as O-H, N-H, C-H, O = C = O, C = O, C = N, C = C, etc. Hence, the findings of this study indicate that the leaves of wild plant Ficus rumphii possess significant nutritional potential, making it an excellent plant for meeting dietary requirements.

In the present work, a comparative study on eco-friendly synthesis of zinc oxide (ZnO) sample 1 and sample 2 with 3.17 and 4.17 M NaOH, respectively, is reported. Sample 2 with 4.17 M NaOH is applied in the photocatalytic degradation of paracetamol (pure and raw both) using the ultraviolet (UV, 280-400 nm) and UV/H 2 O 2 reaction systems. Pure paracetamol (PCM1) and raw paracetamol (PCM2) from tablets are used for photocatalytic degradation by photocatalysis. Our experimental evidence show that ZnO sample 2 was more active in the UV/H 2 O 2 reaction system than under ultraviolet (UV, 280-400 nm) irradiation only in the photocatalytic degradation process. Field emission scanning electron microscopy (FE-SEM) confirms the homogeneous growth of a rod-like structure for sample 1 and brittle and randomly aggregated rod-like and wire-like nanostructures for sample 2. The peaks observed in the region around 440 to 900 cm -1 in the FTIR spectra for sample 1 and sample 2 annealed at 250 °C confirms the presence of ZnO bonds. UV absorption spectroscopy indicates a red shift in the absorption spectra due to the increase in the molar concentration of NaOH to 4.17 M for sample 2. In this study, the band gap values are found to be 3.33 and 3.01 eV for the synthesized ZnO sample 1 and sample 2, respectively, which are 40 and 360 meV less as compared to that of bulk ZnO (3.37 eV). The oxidation rate is increased in the UV/H 2 O 2 reaction system, producing the highest rate for PCM1 drug removal with rate constant 9.7 × 10 -3 min -1 and half-life 71.5 min. The kinetic study results for the removal of PCM1 and PCM2 show good results and follow the pseudo-first-order kinetic model with correlation coefficients 0.69556 and 0.90851, respectively, whereas PCM2 follows the pseudo-second-order kinetic model with correlation coefficient 0.9993. The experimental and calculated values of removal capacity ( q e ) at equilibrium is found close to those of the pseudo-second order kinetic model for the removal of both the paracetamol forms PCM1 and PCM2 with the catalyst ZnO nanostructure. The photostability of ZnO sample 2 is also tested with a reusability test in photocatalytic degradation of paracetamol at least four times. The absence of a maxima peak at 243 of PCM1 in the UV/H 2 O 2 reaction system indicates nearly 100% successful conversion of 20 ppm PCM1 by using synthesized catalyst ZnO sample 2. The comparative results of both reaction systems, i.e., UV and UV/H 2 O 2 , show that the hydroxyl radicals, as the active species, are responsible for major degradation of both paracetamol forms (PCM1 and PCM2)., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Sulfur-doped Eosin-B (SDE-B) photocatalysts were synthesized for the first time utilizing sublimed sulfur (S 8 ) as a dopant in an in situ thermal copolymerization technique. Sulfur doping not only increased Eosin-B (E-B) absorption range for solar radiation but also improved fixation and oxygenation capabilities. The doped sulfur bridges the S-S bond by substituting for the edge bromine of the E-B bond. The improved photocatalytic activity of SDE-B in the fixation and oxygenation of NAD + /NADP + and sulfides using solar light is attributed to the photo-induced hole of SDE-B's high fixation and oxygenation capacity, as well as an efficient suppression of electron and hole recombination. The powerful light-harvesting bridge system created using SDE-B as a photocatalyst works extremely well, resulting in high NADH/NADPH regeneration (79.58/76.36%) and good sulfoxide yields (98.9%) under solar light. This study focuses on the creation and implementation of a sulfur-doped photocatalyst for direct fine chemical regeneration and organic transformation., (© 2023 American Society for Photobiology.)

Chronic edema, which has multiple etiologies, is predicted to be a significant underlying cause of lymphedema, potentially leading to serious complications. Elephantiasis, characterized by massive swelling of any body part, is a rare but debilitating condition often associated with lymphatic obstruction or anomalies in the lymphatic system. Lymphedema can predispose a patient to cellulitis, an infectious condition with multiple risk factors. This case study presents a 45-year-old male with a history of chronic lymphatic obstruction due to elephantiasis and recurrent cellulitis in his lower limb. Despite receiving multiple courses of antibiotics, the patient continued to experience multiple episodes of cellulitis, along with worsening lymphedema and functional impairment of the limb. The mainstay of treatment for this condition includes compression stockings and surgery, but addressing the root cause of the disease is crucial. Typically, a multidisciplinary approach is required, involving antibiotics, lymph drainage, and compression therapy. This case highlights the challenges faced in managing elephantiasis and its related complications and emphasizes the need for preventive strategies., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Singh et al.)

This study aimed to evaluate the potential therapeutic effects of  Piper chaba ( PC ) growing in the northern region of India, having differences in the phytochemicals, nutritional content, antimicrobial and antioxidant properties by reducing power assay (RPA), 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, phosphomolybdate assay, and antidiabetic potential by α-amylase assay with change in the geographical location. Outcomes of the gas chromatography-mass spectrometry (GC-MS) analysis revealed that phytochemicals such as piperine (46.69%), kusunokinin (8.9%), and sitostenone (7.57%) are the prominent compounds found in PC . The plant has also shown a good nutritional value, i.e., iron (11.25 mg), calcium (147 mg), and vitamin C (9.30 mg) per 100 g. PC has a higher phenolic content than other species (⁓ 13.75 g/100 g plant powder). Among the four tested bacterial strains, the extract is best responsive toward Escherichia coli (35 ± 0.68 mm) which is more than the standard ciprofloxacin (24 ± 0.8 mm). Similarly, among two tested fungal strains, Saccharomyces cerevisiae shows the best zone of inhibition (ZOI) (27.5 ± 0.8 mm), which is greater than tat of standard amphotericin (20.25 ± 0.28 mm). The DDPH method demonstrated the highest antioxidant activity (⁓ 42.61 ± 1.82 µg/ml). IC 50 for the antidiabetic potential of PC was found to be 23.09 ± 0.3 µg/ml against α-amylase assay. A molecular docking study revealed that three compounds, piperine, sitostenone and kusunokinin, showed strong binding affinity toward bacterial tyrosyl-tRNA synthetases, fungal dihydrofolate reductase, and α-amylase, respectively. Therefore, the findings of the current study indicate that PC can be considered as a source of food and medicines, either in the form of traditional preparations or as pure active constituents., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-03996-7., Competing Interests: Conflict of interestThe authors declare no conflict of interests., (© King Abdulaziz City for Science and Technology 2024. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

The need for sunlight chemical renewal and contemporary organic transformation has fostered the advancement of environmentally friendly photocatalytic techniques. For the first time, we report on the novel crafting of a bright future with selenium-infused Eosin-B (Se in -E-B) nanocomposite photocatalysts in this work. The Se in -E-B nanocomposite materials were created using a hydrothermal process for solar chemical regeneration and organic transformation under visible light. The synthesized samples were subjected to UV-DRS-visible spectroscopy, FT-IR, SEM, EDX, EIS and XRD analysis. The energy band gap of the Se in -E-B nanocomposite photocatalyst was measured using UV-DRS, and the result was around 2.06 eV. to investigate the generated Se in -E-B catalytic activity as a nanocomposite for 1,4-NADH/NADPH re-formation and C-N bond activation. This novel photocatalyst offers a promising alternative for the regeneration of solar chemicals and C-N bond creation between pyrrole and aryl halides., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Key Message: Thchit42 constitutive expression for fungal resistance showed synchronisation with leaf augmentation and transcriptome analysis revealed the Longifolia and Zinc finger RICESLEEPER gene is responsible for plant growth and development. Pelargonium graveolens essential oil possesses significant attributes, known for perfumery and aromatherapy. However, optimal yield and propagation are predominantly hindered by biotic stress. All biotechnological approaches have yet to prove effective in addressing fungal resistance. The current study developed transgenic geranium bridging molecular mechanism of fungal resistance and plant growth by introducing cassette 35S::Thchit42. Furthermore, 120 independently putative transformed explants were regenerated on kanamycin fortified medium. Primarily transgenic lines were demonstrated peak pathogenicity and antifungal activity against formidable Colletotrichum gloeosporioides and Fusarium oxysporum. Additionally, phenotypic analysis revealed ~ 2fold increase in leaf size and ~ 2.1fold enhanced oil content. To elucidate the molecular mechanisms for genotypic cause, de novo transcriptional profiles were analyzed to indicate that the auxin-regulated longifolia gene is accountable for augmentation in leaf size, and zinc finger (ZF) RICESLEEPER attributes growth upregulation. Collectively, data provides valuable insights into unravelling the mechanism of Thchit42-mediated crosstalk between morphological and chemical alteration in transgenic plants. This knowledge might create novel opportunities to cultivate fungal-resistant geranium throughout all seasons to fulfil demand., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Wild fruits play a vital role in the diets and economic well-being of tribal communities of Uttarakhand, India. Despite their significance, there is limited information on some of the wild Ficus species such as Ficus drupacea, Ficus rumphii, Ficus semicordata, Ficus subincisa and Ficus hispida . This research aimed to analyse the nutritional potential, anti-nutritional compositions, mineral composition, antioxidant and finally the phytochemical properties of Ficus fruits to ascertain their medicinal and nutritional significance. The proximate analysis results of all the five wild Ficus species displayed varying percentages of protein, moisture, fat, ash, crude fibre, carbohydrates. Ficus species exhibited superior nutritional and mineral parameters along with a significant amount of vitamin C. Additionally, these fruits significantly showed lower levels of anti-nutritional and good amount of antioxidant parameters. Thus, adequate consumption of these wild Ficus fruits could potentially contribute to human nutritional needs and may serve as sources for dietary enhancements.

This study is focused to highlight the phytochemical, nutrient content and in vitro antioxidant capacity of the wildly growing plant Calyptocarpus vialis (CV) of the Asteraceae family collected from the Garhwal region of India. Phytochemical and nutritional analysis of CV is done by qualitative and quantitative methods. Fourier-transform infrared spectroscopy (FT-IR) analysis confirmed the presence of phenols, alkanes, aliphatic primary amines, carboxylic acids, nitrile, aromatics and alcohols. Gas chromatography and mass spectroscopy (GC-MS) revealed the presence of terpenoids, plant sterols and phenols such as phytol (14.9%), stigmasterol (10.02%), viridiflorol (4.19%), squalene (2.54%) and various other phytochemicals. The plant's study reveals the existence of numerous nutritious elements, including proteins, vitamins, carbohydrates and amino acids. It also revealed the presence of the huge amount of phenolic content ⁓13.49 g in a 100-g dried CV plant sample. The antioxidant potential of methanolic extract of CV was estimated using DPPH (2, 2-diphenyl-1-picrylhydrazyl) free radical scavenging assay, phosphomolybdate assay and reducing power assay. The highest percentage of antioxidant activity determined from three assays is 74 to 87% for 1 mg of dry extract. It is observed that the CV extract act as a good antioxidant when compared to other plants of the Asteraceae family even at very low concentration of the sample. Hence, CV found in the foothills of Himalayas can be further explored as a source of potent bioactive compounds and natural and economical antioxidant for biomedical and immunity-boosting applications., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Ficus drupacea is a medicinal tree found in temperate regions. Various parts of this plant had been used traditionally for the treatment of various ailments such as root powder applied externally for skin infections. Analysis was carried out on the bioactive lipids extracted from Ficus drupacea fruit using both petroleum-based solvent (Hexane) and an environmentally friendly solvent Dimethyl carbonate (DMC). The results showed that DMC extraction yielded a high oil content in Ficus drupacea fruit (6.51 %). When examining the fatty acid composition using GC-FID analysis, Ficus drupacea oil extracted with DMC contained significant proportions of essential fatty acids such as linoleic acid (32.317 %), oleic acid (20.946 %), palmitic acid (25.841 %), etc. Additionally, DMC extraction resulted in higher levels of total phenolics in Ficus drupacea fruit oil compared to hexane. Moreover, DMC extracted oil exhibited stronger antioxidant properties, such as radical scavenging, anti- arthritic, photoprotective activity while displayed similar anti-inflammatory and anti-microbial activity as hexane-extracted oil. In summary, these findings demonstrate that DMC is an efficient and safer alternative to conventional solvent hexane for extracting oils from Ficus drupacea fruit. It is rich in bioactive compounds essential for human nutrition, including polyunsaturated fatty acids, flavonoids, and phenolic compounds, with enhanced biological activities., (© 2024 Wiley‐VHCA AG, Zurich, Switzerland.)

The development of an efficient strategy for facile access to quinoline-based bis-heterocycles holds paramount importance in medicinal chemistry. Herein, we describe a unified approach for accessing 8-(indol-3-yl)methyl-quinolines by integrating Cp*Rh(iii)-catalyzed C(sp 3 )-H bond activation of 8-methylquinolines followed by nucleophilic cyclization with o -ethynylaniline derivatives. Remarkably, methoxybiaryl ynones under similar catalytic conditions delivered quinoline tethered spiro[5.5]enone scaffolds via a dearomative 6 -endo-dig C-cyclization. Moreover, leveraging this method for C8(sp 2 )-H bond activation of quinoline- N -oxide furnished biologically relevant oxindolyl-quinolines. This reaction proceeds via C(sp 2 )-H bond activation, regioselective alkyne insertion, oxygen-atom-transfer (OAT) and intramolecular nucleophilic cyclization in a cascade manner. One C-C, one C-N and one C[double bond, length as m-dash]O bond were created with concomitant formation of a quaternary center., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Key Message: The present study reports differentially expressed transcripts in the waterlogging-induced adventitious root (AR) of Mentha arvensis; the identified transcripts will help to understand AR development and improve waterlogging stress response. Waterlogging notably hampers plant growth in areas facing waterlogged soil conditions. In our previous findings, Mentha arvensis was shown to adapt better in waterlogging conditions by initiating the early onset of adventitious root development. In the present study, we compared the transcriptome analysis of adventitious root induced after the waterlogging treatment with the control taproot. The biochemical parameters of total carbohydrate, total protein content, nitric oxide (NO) scavenging activity and antioxidant enzymes, such as catalase activity (CAT) and superoxide dismutase (SOD) activity, were enhanced in the adventitious root compared with control taproot. Analysis of differentially expressed genes (DEGs) in adventitious root compared with the control taproot were grouped into four functional categories, i.e., carbohydrate metabolism, antioxidant activity, hormonal regulation, and transcription factors that could be majorly involved in the development of adventitious roots. Differential expression of the upregulated and uniquely expressing thirty-five transcripts in adventitious roots was validated using qRT-PCR. This study has generated the resource of differentially and uniquely expressing transcripts in the waterlogging-induced adventitious roots. Further functional characterization of these transcripts will be helpful to understand the development of adventitious roots, leading to the resistance towards waterlogging stress in Mentha arvensis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Bacosides are dammarane-type triterpenoidal saponins in Bacopa monnieri and have various pharmacological applications. All the bacosides are diversified from two isomers, i.e., jujubogenin and pseudojujubogenin. The biosynthetic pathway of bacoside is not well elucidated. In the present study, we characterized a UDP-glycosyltransferase, UGT79A18, involved in the glycosylation of pseudojujubogenin. UGT79A18 shows higher expression in response to 5 h of wounding, and 3 h of MeJA treatment. The recombinant UGT79A18 shows in vitro activity against a wide range of flavonoids and triterpenes and has a substrate preference for protopanaxadiol, a dammarane-type triterpene. Secondary metabolite analysis of overexpression and knockdown lines of UGT79A18 in B. monnieri identify bacopasaponin D, bacopaside II, bacopaside N2 and pseudojujubogenin glucosyl rhamnoside as the major bacosides that were differentially accumulated. In the overexpression lines of UGT79A18, we found 1.7-fold enhanced bacopaside II, 8-fold enhanced bacopasaponin D, 3-fold enhanced pseudojujubogenin glucosyl rhamnoside, and 1.6-fold enhanced bacopaside N2 content in comparison with vector control plant, whereas in the knockdown lines of UGT79A18, we found 1.4-fold reduction in bacopaside II content, 3-fold reduction in the bacopasaponin D content, 2-fold reduction in the pseudojujubogenin glucosyl rhamnoside content, and 1.5-fold reduction in bacopaside N2 content in comparison with vector control. These results suggest that UGT79A18 is a significant UDP glycosyltransferase involved in glycosylating pseudojujubogenin and enhancing the pseudojujubogenin-derived bacosides., (© 2024 Scandinavian Plant Physiology Society.)

Aloe vera-derived graphene (ADG) coupled system photocatalyst, mimicking natural photosynthesis, is one of the most promising ways for converting solar energy into ammonia (NH 3 ) and nicotinamide adenine dinucleotide (NADH) that have been widely used to make the numerous chemicals such as fertilizer and fuel. In this study, we report the synthesis of the aloe vera-derived graphene-coupled phenosafranin (ADGCP) acting as a highly efficient photocatalyst for the generation of NH 3 and regeneration of NADH from nitrogen (N 2 ) and oxidized form of nicotinamide adenine dinucleotide (NAD + ). The results show a benchmark instance for mimicking natural photosynthesis activity as well as the practical applications for the solar-driven selective formation of NH 3 and the regeneration of NADH by using the newly designed photocatalyst., (© 2023 The American Society for Photobiology.)

Importance: Simian immunodeficiency virus (SIV), which originated in African monkeys, crossed the species barrier into humans and ultimately gave rise to HIV and the global HIV/AIDS epidemic. While SIV infects over 40 primate species in sub-Saharan Africa, testing for RNA viruses in wild primate populations can be challenging. Optimizing field-friendly methods for assessing viral presence/abundance in non-invasively collected biological samples facilitates the study of viruses, including potentially zoonotic viruses, in wild primate populations. This study compares SIV RNA preservation and recovery from non-human primate feces stored in four different buffers. Our results will inform future fieldwork and facilitate improved approaches to characterizing prevalence, shedding, and transmission of RNA viruses like SIV in natural hosts including wild-living non-human primates., Competing Interests: The authors declare no conflict of interest.

Mesenteric cysts are rare entities that are challenging to diagnose and treat because of their variable presentation and histological characteristics. They have been majorly classified into six groups, out of which, the chylo-lymphatic type is the most common. Their etiology remains poorly understood but is usually linked to lymphatic pathologies. They are thin-walled cysts, present in the mesentery of the gastrointestinal tract. They can mimic multiple other cysts; hence, their timely diagnosis is of utmost importance. Imaging techniques aid in the preoperative diagnosis along with a thorough physical exam. The mainstay of treatment is surgical excision of the cyst, which is essential to prevent the recurrence of malignant transformation; the usual method of removal is laparoscopy. Alternative treatments are aspiration and marsupialization, which are only utilised for specific cases. The recurrence rate is usually low after total excision, but follow-ups are recommended for early detection of recurrence. This case study highlights the significance of prompt diagnosis and proper management of mesenteric cysts., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Singh et al.)

Ingrown nail or onychocryptosis is a common and prevalent condition associated with pain and discomfort resulting from recurrent inflammation. It is further categorized into 3 grades on the basis of severity as per classification by Heifetz and Mogensen, grade 1 can be easily managed with medical treatment; whereas grades 2 and 3 often requires surgical treatment; the most common surgical technique employed for ingrown nail is the simple nail avulsion by using a nail clipper. we have observed that due to the force of the nail clipper small amount of detachment in between nail plate and nail bed in addition to longer downtime post-procedure, so we proposed a new surgical modification of nail avulsion by using 11 no. surgical blade instead of nail clippers leading to very less trauma to nail bed and fine post-procedure outcomes., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Cutaneous and Aesthetic Surgery.)

Graphene quantum dots (GQDs) are prepared and characterized via X-ray diffraction (XRD), UV-Visible spectroscopy, atomic force microscopy (AFM), transmission electron microscopy (TEM) and photoluminescence (PL). GQDs are doped (5 mg and 10 mg) in the lyotropic liquid crystalline (LLC) lamellar and hexagonal phases to prepare GQD/LLC nanocolloids. Polarizing optical microscopy and X-ray diffraction measurement reveals that GQDs do not affect the lamellar and hexagonal LLC structures and may organize on their interface. Pure LLC phases and nanocolloids are studied for steady and dynamic rheological behavior. LLC phases and GQD/LLC nanocolloids possess shear thinning and frequency dependent liquid viscoelastic behavior. A complex moduli study of LLCs and GQD/LLC nanocolloids is carried out which indicates the gel to viscous transition in LLCs and GQD/LLC nanocolloids as a function of frequency. LLC phases and GQD/LLC nanocolloids are tested for antibacterial activity against Listeria ivanovii. The effect of surfactant concentration, LLC phase geometry and GQD concentration has been studied and discussed. A probable mechanism for the strong antimicrobial activity of LLCs and GQD/LLC nanocolloids is presented considering intermolecular interactions. The viscoelastic behavior and strong antibacterial activity (inhibition zone 49.2 mm) of LLCs and GQD/LLC nanocolloids make them valuable candidates for lubrication, cleaning, cosmetics and pharmaceutical applications.

Pseudomonas aeruginosa (P.a.) infection accounts for nearly 20% of all cases of hospital acquired pneumonia with mortality rates >30%. P.a. infection induces a robust inflammatory response, which ideally enhances bacterial clearance. Unfortunately, excessive inflammation can also have negative effects, and often leads to cardiac dysfunction with associated morbidity and mortality. However, it remains unclear how P.a. lung infection causes cardiac dysfunction. Using a murine pneumonia model, we found that P.a. infection of the lungs led to severe cardiac left ventricular dysfunction and electrical abnormalities. More specifically, we found that neutrophil recruitment and release of S100A8/A9 in the lungs activates the TLR4/RAGE signaling pathways, which in turn enhance systemic inflammation and subsequent cardiac dysfunction. Paradoxically, global deletion of S100A8/A9 did not improve but aggravated cardiac dysfunction and mortality likely due to uncontrolled bacterial burden in the lungs and heart. Our results indicate that P.a. infection induced release of S100A8/9 is double-edged, providing increased risk for cardiac dysfunction yet limiting P.a. growth., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kumar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

HIV-infected patients are at higher risk of developing oral mucosal infection and Epstein-Barr virus (EBV)-associated B cell malignancies. However, the potential role of oral immunity in the pathogenesis of oral lesions is unknown. Tonsils are oral-pharyngeal mucosal-associated lymphoid tissues that play an important role in oral mucosal immunity. In this study, we investigated the changes of innate and adaptive immune cells in macaque tonsils during chronic SIV infection. We found significantly higher frequencies of classical monocytes, CD3+CD56+ (NKT-like) cells, CD3 + CD4 + CD8 + (DP), and CD161 + CD4 T cells in tonsils from chronic infected compared to naïve animals. On the contrary, intermediate monocytes and CD3 + CD4 - CD8 - (DN) cells were lower in chronic SIV-infected macaques. We further confirmed a recently described small B-cell subset, NKB cells, were higher during chronic infection. Furthermore, both adaptive and innate cells showed significantly higher TNF-α and cytotoxic marker CD107a, while IL-22 production was significantly reduced in innate and adaptive immune cells in chronic SIV-infected animals. A dramatic reduction of IFN-γ production by innate immune cells might indicate enhanced susceptibility to EBV infection and potential transformation of B cells in the tonsils. In summary, our observation shows that the SIV-associated immune responses are distinct in the tonsils compared to other mucosal tissues. Our data extends our understanding of the oral innate immune system during SIV infection and could aid future studies in evaluating the role of tonsillar immune cells during HIV-associated oral mucosal infections., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Shukla, Gunasena, Reinhold-Larsson, Duncan, Hatharasinghe, Cray, Weragalaarachchi, Kasturiratna, Demberg and Liyanage.)

Since its inception, DNA typing technology has been practiced as a robust tool in criminal investigations. Experts usually utilize STR profiles to identify and individualize the suspect. However, mtDNA and Y STR analyses are also considered in some sample-limiting conditions. Based on DNA profiles thus generated, forensic scientists often opine the results as Inclusion, exclusion, and inconclusive. Inclusion and exclusion were defined as concordant results; the inconclusive opinions create problems in conferring justice in a trial- since nothing concrete can be interpreted from the profile generated. The presence of inhibitor molecules in the sample is the primary factor behind these indefinite results. Recently, researchers have been emphasizing studying the sources of PCR inhibitors and their mechanism of inhibition. Furthermore, several mitigation strategies- to facilitate the DNA amplification reaction -have now found their place in the routine DNA typing assays with compromised biological samples. The present review paper attempts to provide a comprehensive review of PCR inhibitors, their source, mechanism of inhibition, and ways to mitigate their effect using PCR facilitators., Competing Interests: Declaration of Competing Interest The authors reported no potential conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

This work reports the measurement of impedance variations under various humidity conditions at frequency ranges between 100 Hz and 5 MHz. An electrochemical polymerization process has been used in the synthesis including varying the mass ratios of graphene oxide (GO) in polyaniline. An electrochemical deposition method has been used to produce a sample film on an indium tin oxide glass slide. The percentage relative humidity (RH%) of the samples has been estimated to be 20-90%. Impedance and humidity had an inverse relationship, i.e. the impedance value decreased with an increase in humidity. In contrast with platinum capacitive humidity sensors (HS), the GO-based HS had a sensitivity of 75-99%, which was ~10-fold more than that of traditional sensors. With three different parameter weight % of GO, the frequency range have been 100 Hz to 5 MHz and RH% has been found to 20-90%. The HS showed a fast response and recovery time. Therefore, GO appears to be a useful material for building HS with high sensitivity for a comprehensive approach., (© 2022 John Wiley & Sons Ltd.)

The development of an expedient strategy for the synthesis of biologically relevant multisubstituted furans is a much-desired yet challenging task. Herein, we report an efficient and versatile strategy involving two different pathways for the construction of diverse polysubstituted C3- and C2-substituted γ-furanyl carboxylic acid derivatives. The synthetic approach for C3-substituted furans involves intramolecular cascade oxy-palladation of alkyne-diols followed by the regioselective coordinative insertion of unactivated alkenes. In contrast, C2-substituted furans were obtained exclusively by performing the protocol in a tandem manner.

Recent years have seen the emergence of transition metal catalyzed C-H activation as a powerful synthetic tool in organic chemistry. Allenes have fascinated synthetic chemists due to their unique reactivity. While directing group assisted functionalization of C(sp 2 )-H bonds with allenes is well documented in the literature, their coupling with more challenging aliphatic C(sp 3 )-H bonds remains elusive. In this regard, we hereby report a Pd(ii) catalyzed 8-aminoquinoline directed aliphatic C(sp 3 )-H dienylation protocol using allenyl acetates. A variety of carboxylic acids including fatty acids and amino acids were efficiently functionalized at β and γ-positions to afford diversely functionalized 1,3-dienes. Preliminary mechanistic studies revealed the crucial role of the base in the success of the transformation. The reaction proceeds via regioselective 2,3-migratory insertion of the allene with the alkylpalladium(ii) species followed by β-acetoxy elimination., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Herein, we disclose an unprecedented and robust Ru(II)-catalyzed non-oxidative [5+1] annulation of 2-hydroxystyrenes with allenyl acetates to access biologically relevant chromene skeletons. The heteroatom on allene plays a pivotal role in controlling the regioselectivity of migratory insertion, and the reaction proceeds through a Ru-σ-allyl pathway, which has been elusive so far in C-H activation reactions with allenes. The protocol is sustainable in nature as it proceeds at room temperature and avoids the use of any toxic metal oxidants. In addition, the synthetic utility of the protocol was also demonstrated by late stage functionalization and modular synthesis of various natural product conjugates.

CD3-epsilon(CD3e) immunotoxins (IT), a promising precision reagent for various clinical conditions requiring effective depletion of T cells, often shows limited treatment efficacy for largely unknown reasons. Tissue-resident T cells that persist in peripheral tissues have been shown to play pivotal roles in local and systemic immunity, as well as transplant rejection, autoimmunity and cancers. The impact of CD3e-IT treatment on these local cells, however, remains poorly understood. Here, using a new murine testing model, we demonstrate a substantial enrichment of tissue-resident Foxp3+ Tregs following CD3e-IT treatment. Differential surface expression of CD3e among T-cell subsets appears to be a main driver of Treg enrichment in CD3e-IT treatment. The surviving Tregs in CD3e-IT-treated mice were mostly the CD3e dim CD62L lo  effector phenotype, but the levels of this phenotype markedly varied among different lymphoid and nonlymphoid organs. We also found notable variations in surface CD3e levels among tissue-resident T cells of different organs, and these variations drive CD3e-IT to uniquely reshape T-cell compositions in local organs. The functions of organs and anatomic locations (lymph nodes) also affected the efficacy of CD3e-IT. The multi-organ pharmacodynamics of CD3e-IT and potential treatment resistance mechanisms identified in this study may generate new opportunities to further improve this promising treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kim, Shukla, Yu, Baek, Cressman, Golconda, Lee, Choi, Reneau, Wang, Huang, Liyanage and Kim.)

5-methylcytosine (m 5 C) is one of the most prevalent modifications of RNA, playing important roles in RNA metabolism, nuclear export, and translation. However, the potential role of RNA m 5 C methylation in innate immunity remains elusive. Here, we show that depletion of NSUN2, an m 5 C methyltransferase, significantly inhibits the replication and gene expression of a wide range of RNA and DNA viruses. Notably, we found that this antiviral effect is largely driven by an enhanced type I interferon (IFN) response. The antiviral signaling pathway is dependent on the cytosolic RNA sensor RIG-I but not MDA5. Transcriptome-wide mapping of m 5 C following NSUN2 depletion in human A549 cells revealed a marked reduction in the m 5 C methylation of several abundant noncoding RNAs (ncRNAs). However, m 5 C methylation of viral RNA was not noticeably altered by NSUN2 depletion. In NSUN2-depleted cells, the host RNA polymerase (Pol) III transcribed ncRNAs, in particular RPPH1 and 7SL RNAs, were substantially up-regulated, leading to an increase of unshielded 7SL RNA in cytoplasm, which served as a direct ligand for the RIG-I-mediated IFN response. In NSUN2-depleted cells, inhibition of Pol III transcription or silencing of RPPH1 and 7SL RNA dampened IFN signaling, partially rescuing viral replication and gene expression. Finally, depletion of NSUN2 in an ex vivo human lung model and a mouse model inhibits viral replication and reduces pathogenesis, which is accompanied by enhanced type I IFN responses. Collectively, our data demonstrate that RNA m 5 C methylation controls antiviral innate immunity through modulating the m 5 C methylome of ncRNAs and their expression.

Key Message: OscWRKY1 from Ocimum sanctum positively regulates phenylpropanoid pathway genes and rosmarinic acid content. OscWRKY1 overexpression promotes resistance against bacterial pathogen in Arabidopsis. WRKY transcription factor (TF) family regulates various developmental and physiological functions in plants. PAL genes encode enzymes which are involved in plant defense responses, but the direct regulation of PAL genes and phenylpropanoid pathway through WRKY TF's is not well characterized. In the present study, we have characterized an OscWRKY1 gene from Ocimum sanctum which shows induced expression by methyl jasmonate (MeJA), salicylic acid (SA), and wounding. The recombinant OscWRKY1 protein binds to the DIG-labeled (Digoxigenin) W-box cis-element TTGAC[C/T] and activates the LacZ reporter gene in yeast. Overexpression of OscWRKY1 enhances Arabidopsis resistance towards Pseudomonas syringae pv. tomato Pst DC3000. Upstream activator sequences of PAL and C4H have been identified to contain the conserved W-box cis-element (TTGACC) in both O. sanctum and Arabidopsis. OscWRKY1 was found to interact with W-box cis-element present in the PAL and C4H promoters. Silencing of OscWRKY1 using VIGS resulted in reduced expression of PAL, C4H, COMT, F5H and 4CL transcripts. OscWRKY1 silenced plants exhibit reduced PAL activity, whereas, the overexpression lines of OscWRKY1 in Arabidopsis exhibit increased PAL activity. Furthermore, the metabolite analysis of OscWRKY1 silenced plants showed reduced rosmarinic acid content. These results revealed that OscWRKY1 positively regulates the phenylpropanoid pathway genes leading to the alteration of rosmarinic acid content and enhances the resistance against bacterial pathogen in Arabidopsis., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Key Message: The present review highlights the regulatory roles of microRNAs in plant secondary metabolism and focuses on different bioengineering strategies to modulate secondary metabolite content in plants. MicroRNAs (miRNAs) are the class of small endogenous, essential, non-coding RNAs that riboregulate the gene expression involved in various biological processes in most eukaryotes. MiRNAs has emerged as important regulators in plants that function by silencing target genes through cleavage or translational inhibition. These miRNAs plays an important role in a wide range of plant biological and metabolic processes, including plant development and various environmental response controls. Several important plant secondary metabolites like alkaloids, terpenoids, and phenolics are well studied for their function in plant defense against different types of pests and herbivores. Due to the presence of a wide range of biological and pharmaceutical properties of plant secondary metabolites, it is important to study the regulation of their biosynthetic pathways. The contribution of miRNAs in regulating plant secondary metabolism is not well explored. Recent advancements in molecular techniques have improved our knowledge in understanding the molecular function of genes, proteins, enzymes, and small RNAs involved in different steps of secondary metabolic pathways. In the present review, we have discussed the recent progress made on miRNA biogenesis, its regulation, and highlighted the current research developed in the field of identification, analysis, and characterizations of various miRNAs that regulate plant secondary metabolism. We have also discussed how different bioengineering strategies such as artificial miRNA (amiRNA), endogenous target mimicry, and CRISPR/Cas9 could be utilized to enhance the secondary metabolite production in plants., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The vaccine Mycobacterium bovis Bacillus Calmette-Guérin (BCG) elicits an immune response that is protective against certain forms of tuberculosis (TB); however, because BCG efficacy is limited it is important to identify alternative TB vaccine candidates. Recently, the BCG deletion mutant and vaccine candidate BCGΔBCG1419c was demonstrated to survive longer in intravenously infected BALB/c mice due to enhanced biofilm formation, and better protected both BALB/c and C57BL/6 mice against TB-induced lung pathology during chronic stages of infection, relative to BCG controls. BCGΔBCG1419c-elicited protection also associated with lower levels of proinflammatory cytokines (i.e. IL6, TNFα) at the site of infection in C57BL/6 mice. Given the distinct immune profiles of BCG- and BCGΔBCG1419c-immunized mice during chronic TB, we set out to determine if there are early immunological events which distinguish these two groups, using multi-dimensional flow cytometric analysis of the lungs and other tissues soon after immunization. Our results demonstrate a number of innate and adaptive response differences between BCG- and BCGΔBCG1419c-immunized mice which are consistent with the latter being longer lasting and potentially less inflammatory, including lower frequencies of exhausted CD4 + T helper (T H ) cells and higher frequencies of IL10-producing T cells, respectively. These studies suggest the use of BCGΔBCG1419c may be advantageous as an alternative TB vaccine candidate., (© 2022. The Author(s).)

Nontuberculous mycobacteria (NTM) are an increasingly common cause of respiratory infection in people with cystic fibrosis (PwCF). Relative to those with no history of NTM infection (CF-NTMNEG), PwCF and a history of NTM infection (CF-NTMPOS) are more likely to develop severe lung disease and experience complications over the course of treatment. In other mycobacterial infections (e.g., tuberculosis), an overexuberant immune response causes pathology and compromises organ function; however, since the immune profiles of CF-NTMPOS and CF-NTMNEG airways are largely unexplored, it is unknown which, if any, immune responses distinguish these cohorts or concentrate in damaged tissues. Here, we evaluated lung lobe-specific immune profiles of 3 cohorts (CF-NTMPOS, CF-NTMNEG, and non-CF adults) and found that CF-NTMPOS airways are distinguished by a hyperinflammatory cytokine profile. Importantly, the CF-NTMPOS airway immune profile was dominated by B cells, classical macrophages, and the cytokines that support their accumulation. These and other immunological differences between cohorts, including the near absence of NK cells and complement pathway members, were enriched in the most damaged lung lobes. The implications of these findings for our understanding of lung disease in PwCF are discussed, as are how they may inform the development of host-directed therapies to improve NTM disease treatment.

Anti-CD3-epsilon (CD3e) monoclonal antibodies (mAbs) and CD3e immunotoxins (ITs) are promising targeted therapy options for various T-cell disorders. Despite significant advances in mAb and IT engineering, vascular leakage syndrome (VLS) remains a major dose-limiting toxicity for ITs and has been poorly characterized for recent "engineered" mAbs. This study undertakes a direct comparison of non-mitogenic CD3e-mAb (145-2C11 with Fc-silent TM murine IgG1: S-CD3e-mAb) and a new murine-version CD3e-IT (saporin-streptavidin (sZAP) conjugated with S-CD3e-mAb: S-CD3e-IT) and identifies their distinct toxicity profiles in mice. As expected, the two agents showed different modes of action on T cells, with S-CD3e-mAb inducing nearly complete modulation of CD3e on the cell surface, while S-CD3e-IT depleted the cells. S-CD3e-IT significantly increased the infiltration of polymorphonuclear leukocytes (PMNs) into the tissue parenchyma of the spleen and lungs, a sign of increased vascular permeability. By contrast, S-CD3e-mAbs-treated mice showed no notable signs of vascular leakage. Treatment with control ITs (sZAP conjugated with Fc-silent isotype antibodies) induced significant vascular leakage without causing T-cell deaths. These results demonstrate that the toxin portion of S-CD3e-IT, not the CD3e-binding portion (S-CD3e-mAb), is the main driver of vascular leakage, thus clarifying the molecular target for improving safety profiles in CD3e-IT therapy.

This study aimed to determine the physicochemical quality of groundwater and its potential health risk for drinking in Oromia, Ethiopia. The groundwater samples were collected from 17 sampling stations in the dry and wet season in the Sebeta zone, Oromia, from March to August 2020. Metals and physicochemical parameters, and selected heavy metals, such as iron (Fe), copper (Cu), manganese (Mn), chromium (Cr), zinc (Zn), and lead (Pb) were monitored. The data were analyzed using multivariate statistical methods (Pearson's Correlation and T-test). The means seasonal variations were higher in the dry season than in the wet season except for pH and Turbidity. The variation was significant for most parameters except Pb, Zn, chlorine, Total Alkaline, Magnesium Hardness, Calcium Hardness ), and Turbidity. There was a strong and positive correlation between Total dissolved solids (TDS) and Conductivity), (pH and Cr), (T.H. and Magnesium (Mg)), (bicarbonate and Calcium (Ca), (Zn and Turbidity) in the dry season; and (T.H. with Potassium (K), (Pb and Fe); (bicarbonate and T.H.); (Ca and Mg); (Na and T.A.,) in the wet season. The hazard index (H.I.) values in the dry season (HI = 1.331) were higher than in the wet season (HI adults  = 0.075). Likewise, the H.I. (dry season) was higher (HI children  = 1.861) than in the wet season (HI children  = 0.105). Chronic groundwater exposure at drinking sources in the dry season is a potential health risk to humans in general and is relatively high for children. Urgent management and close monitoring are required for drinking groundwater sources and other nearby residents' safety areas., Competing Interests: Declaration of conflicting interests: The author declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Infection of rhesus macaques with simian-human immunodeficiency viruses (SHIVs) is the preferred model system for vaccine development because SHIVs encode human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (Envs)-a key target of HIV-1 neutralizing antibodies. Since the goal of vaccines is to prevent new infections, SHIVs encoding circulating HIV-1 Env are desired as challenge viruses. Development of such biologically relevant SHIVs has been challenging, as they fail to infect rhesus macaques, mainly because most circulating HIV-1 Envs do not use rhesus CD4 (rhCD4) receptor for viral entry. Most primary HIV-1 Envs exist in a closed conformation and occasionally transit to a downstream, open conformation through an obligate intermediate conformation. Here, we provide genetic evidence that open Env conformations can overcome the rhCD4 entry barrier and increase replication of SHIVs in rhesus lymphocytes. Consistent with prior studies, we found that circulating HIV-1 Envs do not use rhCD4 efficiently for viral entry. However, by using HIV-1 Envs with single amino acid substitutions that alter their conformational state, we found that transitions to intermediate and open Env conformations allow usage of physiological levels of rhCD4 for viral entry. We engineered these single amino acid substitutions in the transmitted/founder HIV-1 BG505 Envs encoded by SHIV-BG505 and found that open Env conformation enhances SHIV replication in rhesus lymphocytes. Lastly, CD4-mediated SHIV pulldown, sensitivity to soluble CD4, and fusogenicity assays indicated that open Env conformation promotes efficient rhCD4 binding and viral-host membrane fusion. These findings identify the conformational state of HIV-1 Env as a major determinant for rhCD4 usage, viral fusion, and SHIV replication. IMPORTANCE Rhesus macaques are a critical animal model for preclinical testing of HIV-1 vaccine and prevention approaches. However, HIV-1 does not replicate in rhesus macaques, and thus, chimeric simian-human immunodeficiency viruses (SHIVs), which encode HIV-1 envelope glycoproteins (Envs), are used as surrogate challenge viruses to infect rhesus macaques for modeling HIV-1 infection. Development of SHIVs encoding Envs from clinically relevant, circulating HIV-1 variants has been extremely challenging, as such SHIVs replicate poorly, if at all, in rhesus lymphocytes. This is most probably because many circulating HIV-1 Envs do not use rhesus CD4 efficiently for viral entry. In this study, we identified conformational state of HIV-1 envelope as a key determinant for rhesus CD4 usage, viral-host membrane fusion, and SHIV replication in rhesus lymphocytes.

Background: Molecular mechanisms underlying inflammation-associated breast tumor growth are poorly studied. S100A7, a pro-inflammatory molecule has been shown to enhance breast cancer growth and metastasis. However, the S100A7-mediated molecular mechanisms in enhancing tumor growth and metastasis are unclear., Methods: Human breast cancer tissue and plasma samples were used to analyze the expression of S100A7, cPLA2, and PGE2. S100A7-overexpressing or downregulated human metastatic breast cancer cells were used to evaluate the S100A7-mediated downstream signaling mechanisms. Bi-transgenic mS100a7a15 overexpression, TNBC C3 (1)/Tag transgenic, and humanized patient-derived xenograft mouse models and cPLA2 inhibitor (AACOCF3) were used to investigate the role of S100A7/cPLA2/PGE2 signaling in tumor growth and metastasis. Additionally, CODEX, a highly advanced multiplexed imaging was employed to delineate the effects of S100A7/cPLA2 inhibition on the recruitment of various immune cells., Results: In this study, we found that S100A7 and cPLA2 are highly expressed and correlate with decreased overall survival in breast cancer patients. Further mechanistic studies revealed that S100A7/RAGE signaling promotes the expression of cPLA2 to mediate its oncogenic effects. Pharmacological inhibition of cPLA2 suppressed S100A7-mediated tumor growth and metastasis in multiple pre-clinical models including transgenic and humanized patient-derived xenograft (PDX) mouse models. The attenuation of cPLA2 signaling reduced S100A7-mediated recruitment of immune-suppressive myeloid cells in the tumor microenvironment (TME). Interestingly, we discovered that the S100A7/cPLA2 axis enhances the immunosuppressive microenvironment by increasing prostaglandin E2 (PGE2). Furthermore, CO-Detection by indEXing (CODEX) imaging-based analyses revealed that cPLA2 inhibition increased the infiltration of activated and proliferating CD4 + and CD8 + T cells in the TME. In addition, CD163 + tumor associated-macrophages were positively associated with S100A7 and cPLA2 expression in malignant breast cancer patients., Conclusions: Our study provides new mechanistic insights on the cross-talk between S100A7/cPLA2 in enhancing breast tumor growth and metastasis by generating an immunosuppressive TME that inhibits the infiltration of cytotoxic T cells. Furthermore, our studies indicate that S100A7/cPLA2 could be used as novel prognostic marker and cPLA2 inhibitors as promising drugs against S100A7-overexpressing aggressive breast cancer., (© 2022. The Author(s).)