Insulin-induced gene 2 protects against hepatic ischemia-reperfusion injury via metabolic remodeling.

BACKGROUND: Hepatic ischemia-reperfusion (IR) injury is the primary reason for complications following hepatectomy and liver transplantation (LT). Insulin-induced gene 2 (Insig2) is one of several proteins that anchor the reticulum in the cytoplasm and is essential for metabolism and inflammatory responses. However, its function in IR injury remains ambiguous. METHODS: Insig2 global knock-out (KO) mice and mice with adeno-associated-virus8 (AAV8)-delivered Insig2 hepatocyte-specific overexpression were subjected to a 70% hepatic IR model. Liver injury was assessed by monitoring hepatic histology, inflammatory responses, and apoptosis. Hypoxia/reoxygenation stimulation (H/R) of primary hepatocytes and hypoxia model induced by cobalt chloride (CoCl2) were used for in vitro experiments. Multi-omics analysis of transcriptomics, proteomics, and metabolomics was used to investigate the molecular mechanisms underlying Insig2. RESULTS: Hepatic Insig2 expression was significantly reduced in clinical samples undergoing LT and the mouse IR model. Our findings showed that Insig2 depletion significantly aggravated IR-induced hepatic inflammation, cell death and injury, whereas Insig2 overexpression caused the opposite phenotypes. The results of in vitro H/R experiments were consistent with those in vivo. Mechanistically, multi-omics analysis revealed that Insig2 is associated with increased antioxidant pentose phosphate pathway (PPP) activity. The inhibition of glucose-6-phosphate-dehydrogenase (G6PD), a rate-limiting enzyme of PPP, rescued the protective effect of Insig2 overexpression, exacerbating liver injury. Finally, our findings indicated that mouse IR injury could be attenuated by developing a nanoparticle delivery system that enables liver-targeted delivery of substrate of PPP (glucose 6-phosphate). CONCLUSIONS: Insig2 has a protective function in liver IR by upregulating the PPP activity and remodeling glucose metabolism. The supplementary glucose 6-phosphate (G6P) salt may serve as a viable therapeutic target for alleviating hepatic IR.

The global emergence of Chikungunya infection: An integrated view.

Chikungunya virus (CHIKV) is one of the emerging viruses around the globe. It belongs to the family Togaviridae and genus Alphavirus and is an arthropod borne virus that transmits by the bite of an infected mosquito, mainly through Aedes aegypti and Aedes albopcitus. It is a spherical, enveloped virus with positive single stranded RNA genome. It was first discovered during 1952-53 in Tanganyika, after which outbreaks were documented in many regions of the world. CHIKV has two transmission cycles; an enzootic sylvatic cycle and an urban cycle. CHIKV genome contains 11,900 nucleotides and two open reading frames and shows great sequence variability. Molecular mechanisms of virus host-cell interactions and the pathogenesis of disease are not fully understood. The disease involves three phases; acute, post-acute and chronic with symptoms including high-grade fever, arthralgia, macupapular rashes and headache. There is no licensed vaccine or specific treatment for CHIKV infection. This lack of specific interventions combined with difficulties in making a precise diagnosis together make the disease difficult to manage. In this review we aim to present the current knowledge of global epidemiology, transmission, structure, various aspects of diagnosis as well as highlight potential antiviral drugs and vaccines against CHIKV.

A Computational First Principle Examination of the Elastic, Optical, Structural and Electronic Properties of AlRF3 (R = N, P) Fluoroperovskites Compounds.

This work describes an ab initio principle computational examination of the optical, structural, elastic, electronic and mechanical characteristics of aluminum-based compounds AlRF3 (R = N, P) halide-perovskites. For optimization purposes, we used the Birch-Murnaghan equation of state and discovered that the compounds AlNF3 and AlPF3 are both structurally stable. The IRelast software was used to compute elastic constants (ECs) of the elastic properties. The aforementioned compounds are stable mechanically. They exhibit strong resistance to plastic strain, possess ductile nature and anisotropic behavior and are scratch-resistant. The modified Becke-Johnson (Tb-mBJ) approximation was adopted to compute various physical properties, revealing that AlNF3 and AlPF3 are both metals in nature. From the density of states, the support of various electronic states in the band structures are explained. Other various optical characteristics have been calculated from the investigations of the band gap energy of the aforementioned compounds. These compounds absorb a significant amount of energy at high levels. At low energy levels, the compound AlNF3 is transparent to incoming photons, whereas the compound AlPF3 is somewhat opaque. The examination of the visual details led us to the deduction that the compounds AlNF3 and AlPF3 may be used in making ultraviolet devices based on high frequency. This computational effort is being made for the first time in order to investigate the aforementioned properties of these chemicals, which have yet to be confirmed experimentally.

Genomic Characterization of SARS-CoV2 from Peshawar Pakistan Using Next-Generation Sequencing.

This study aimed to characterize the whole genome of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV2) isolated from an oropharyngeal swab specimen of a Pashtun Pakistani patient using next-generation sequencing. Upon comparing the SARS-CoV2 genome to the reference genome, a total of 10 genetic variants were identified. Among the 10 genetic variants, 1 missense mutation (c.1139A > G, p.Lys292Glu) in the Open Reading Frame 1ab (ORF1ab) positioned at 112 in the non-structural protein 2 (NSP2) was found to be unique. Phylogenetic analysis (n = 84) revealed that the current SARS-CoV2 genome was closely clustered with 8 Pakistani strains belonging to Punjab, Federal Capital, Azad Jammu and Kashmir (AJK), and Khyber Pakhtunkhwa (KP). In addition, the current SARS-CoV2 genome was very similar to the genome of SARS-CoV2 reported from Guam, Taiwan, India, the USA, and France. Overall, this study reports a slight mismatch in the SARS-CoV2 genome, indicating the presence of a single unique missense mutation. However, phylogenetic analysis revealed that the current SARS-CoV2 genome was closely clustered with 8 other Pakistani strains.

1-Phenyl ethyl substituted tetrahydro-2H-1,3,5-thiadiazine-2-thione derivatives as promising antimicrobial agents.

Seven derivatives of 1-phenyl ethyl group containing 3,5-disubstituted tetrahydro-2H-1,3,5-thiadiazine-thiones (THTT) were prepared and examined for their antibacterial and antifungal properties by using Microplate Alamar Blue Assay (MABA) and agar tube dilution protocol respectively. In vitro antifungal potential was investigated against five human pathogens and compared with the standard drugs amphotericin B and miconazole. In vitro antibacterial activity was investigated against four pathogens and compared with the ofloxacin. All compounds exhibited very promising antifungal activities against all tested pathogens. Structure activity relationship showed the importance of the presence of 1-phenyl ethyl substituent at N-3 of THTT nucleus for antifungal effects. However, these compounds showed significant antibacterial activity only against S. aureus. The compound 6c of the series was found most active compound that displayed promising antifungal potential against all tested pathogens [Growth Inhibition (GI) = 100%], and also showed promising antibacterial potential against S. aureus (GI% = 83.49) which is very much closer to the standard ofloxacin (GI% = 88.05). The study may be useful in the development of improved antimicrobial agents.

Genome-Wide Profiling of Alternative Splicing Signatures Associated with Prognosis and Immune Microenvironment of Hepatocellular Carcinoma.

BACKGROUND The potential roles of alternative splicing (AS) in HCC remain unknown. This study aimed to identify AS signatures associated with the prognosis that influence the immune microenvironment of HCC. MATERIAL AND METHODS The SpliceSeq tool was employed for genome-wide profiling of 7 AS events in 361 HCC patients from The Cancer Genome Atlas (TCGA). A prognostic signature was built by integrating Cox regression and the least absolute shrinkage and selection operator (LASSO). The support vector machine (SVM) and receiver operating characteristic curve (ROC) were employed to analyze the AS events in the signatures to discriminate the immune microenvironment. RESULTS There were 3546 AS events highly linked to the survival of patients with HCC. The AS signature could effectively stratify HCC patients. Clustering analysis revealed 3 different immune clusters characterized with significantly different prognoses and were significantly correlated with AS signatures. The AS events in the final prognostic signature classified the immune cluster with an average AUC of the ROC (0.88). Moreover, a potential regulatory network of splicing events in HCC is presented. CONCLUSIONS We established the prognostic signature based on AS, which can effectively stratify HCC patients and predict the immune subtypes. Moreover, novel RNA splicing patterns and splicing-regulatory networks involved in HCC were discovered.

Recent advances in immunotherapy for hepatocellular carcinoma.

BACKGROUND: Treatment of hepatocellular carcinoma (HCC) is challenging as most patients are diagnosed at advanced stage with underlying chronic liver conditions. Conventional systemic chemotherapy has failed in HCC, and the clinical efficacy of FDA-approved molecular targeted agents such as sorafenib and lenvatinib remains unsatisfactory. DATA SOURCES: Literature search was conducted in PubMed for relevant articles published before January 2021. The search aimed to identify recent developments in immune-based treatment approaches for HCC. Information of clinical trials was obtained from https://clinicaltrials.gov/. RESULTS: Two immune checkpoint inhibitors (ICIs), nivolumab and pembrolizumab were approved as monotherapies, which has revolutionized HCC treatment. Besides, combination ICIs have also got accelerated FDA approval recently. Immune-based therapies have challenged targeted drugs owing to their safety, tolerability, and survival benefits. In addition to the significant success in ICIs, other immunotherapeutic strategies such as cancer vaccine, chimeric antigen receptor T-cells, natural killer cells, cytokines, and combination therapy, have also shown promising outcomes in clinical trials. Various diagnostic and prognostic biomarkers have been identified which can help in clinical decision making when starting treatment with ICIs. CONCLUSIONS: Immunotherapy has emerged as one of the mainstream treatment modalities for advanced HCC in recent years. However, challenges such as low response rate and acquired resistance in previously respondent patients still exist. Further research is needed to understand the unique resistance mechanism to immunotherapy and to discover more predictive biomarkers to guide clinical decision making.

Pulling the Brakes on Fast and Furious Multiple Drug-Resistant (MDR) Bacteria.

Life-threatening bacterial infections have been managed by antibiotics for years and have significantly improved the wellbeing and lifetime of humans. However, bacteria have always been one step ahead by inactivating the antimicrobial agent chemically or by producing certain enzymes. The alarming universal occurrence of multidrug-resistant (MDR) bacteria has compelled researchers to find alternative treatments for MDR infections. This is a menace where conventional chemotherapies are no longer promising, but several novel approaches could help. Our current review article discusses the novel approaches that can combat MDR bacteria: starting off with potential nanoparticles (NPs) that efficiently interact with microorganisms causing fatal changes in the morphology and structure of these cells; nanophotothermal therapy using inorganic NPs like AuNPs to destroy pathogenic bacterial cells; bacteriophage therapy against which bacteria develop less resistance; combination drugs that act on dissimilar targets in distinctive pathways; probiotics therapy by the secretion of antibacterial chemicals; blockage of quorum sensing signals stopping bacterial colonization, and vaccination against resistant bacterial strains along with virulence factors. All these techniques show us a promising future in the fight against MDR bacteria, which remains the greatest challenge in public health care.

Nanoniosome-encapsulated levoflaxicin as an antibacterial agent against Brucella.

A study was conducted to examine the prevalence of brucellosis (in animal farms) in the vicinity of Islamabad and Rawalpindi. A total of 170 milk samples were collected randomly from several farmhouses. The collected milk samples were initially screened by a Brucella selective medium. The bacterial isolates grown on the selective medium were subjected to biochemical identification for further confirmation of Brucella species. Among the tested samples, 28 (16.4%) were found positive for selective medium and 14 (8.2%) were found positive after biochemical confirmation. The antimicrobial susceptibility of several antibiotics performed by the disc-diffusion method did not yield any significant findings. Encapsulating antimicrobial drugs in unilamellar niosomes is an effective approach to treat the endemic infection. In this study, the antimicrobial activity of niosome-encapsulated levofloxacin is compared with free drug. The drug-encapsulating and empty niosomes were synthesized by using two surfactants Tween 80 and Span 40. Niosomal characterization included electron microscopy, dynamic light scattering, and zeta potential. The encapsulation efficiency was found to be 78% and 74% for Span 40 and Tween 80 niosomes, respectively. The antibacterial activity of niosomal levofloxacin was evaluated against the identified Brucella species and the antimicrobial activity of the free drug was increased many folds after encapsulation. In this study, levofloxacin niosomes were successfully synthesized against Brucellosis.

Development of the Next Generation Sequencing-Based Diagnostic Test for ß-Thalassemia and its Validation in a Pashtun Family.

ß-Thalassemia (ß-thal) is a common monogenic disease with ethnic-specific mutations on the HBB gene throughout the world. The reported mutations either reduce the expression or completely inactivate the HBB gene. In Pakistan, the prevalence of ß-thal is high due to consanguineous marriages. Accurate identification of mutations in carriers is imperative for prevention of ß-thal in subsequent generations. To overcome the limitations of traditional testing methods for ß-thal, a next-generation sequencing (NGS)-based diagnostic test was designed and validated by sequencing the entire HBB gene. The primer set covering the entire HBB gene was designed and validated in a Pashtun ß-thalassemic family. The polymerase chain reaction (PCR) product was sequenced using an Illumina MiSeq platform. A homozygous pathogenic insertion of A>AC/AC (rs35699606) was detected in an affected member of the family, while unaffected members were heterozygous for it. In addition, all family members were homozygous for the synonymous variant, A>G/G (rs713040), except the father who was heterozygous for it. We sequenced the entire HBB gene using the NGS-based test, which is highly sensitive, robust and specific for the diagnosis and screening of ß-thal in Pakistan, especially for families practicing consanguineous marriages.

KLF17 attenuates estrogen receptor α-mediated signaling by impeding ERα function on chromatin and determines response to endocrine therapy.

Luminal-like breast cancer expressing estrogen receptor α (ERα) is among the aggressive breast tumor subtypes and shows poor prognosis. KLF17 plays a key role in breast cancer inhibition. However, the underlying mechanisms by which KLF17 control breast cancer progression remains unknown. Here, we show that KLF17 antagonizes ERα-dependent signaling to suppress breast cancer progression. KLF17 alters ERα-binding pattern throughout the genome and co-localizes with ERα on chromatin. Mechanistically, KLF17 forms a complex with ERα that interferes with ERα binding on chromatin and thereby attenuates ERα-dependent pathway. KLF17 increases the methylation status of ERE target promoters by recruiting transcriptional corepressor N-CoR/HDAC1 complex and prevents RNA polymerase II binding to suppress ERα-dependent transcriptional activation. Importantly, KLF17 preoccupies a subset of ERE target gene promoters and inhibits interaction of ERα with chromatin. Conversely, estrogen signaling suppresses KLF17 transcription via ERα/HDAC1-dependent mechanism. KLF17 expression negatively correlates with ERα target genes in multiple breast cancer samples. Enhanced KLF17 expression sensitizes ERα-positive breast cancer cells to endocrine therapy. KLF17 expression is downregulated in luminal breast cancer subtypes and is associated with poor survival rates in breast cancer patients. Taken together, these results indicate that KLF17-ERα interaction plays a potential role in inhibition of ERα-dependent breast cancer progression and suggests an improved strategy for treatment of ERα-positive breast cancer patients.

Evaluation of the cytotoxic potential of a new pentacyclic triterpene from Rhododendron arboreum stem bark.

CONTEXT: Traditionally, Rhododendron arboreum Sm. (Ericaceae) is a very important medicinal plant having oxytocic, estrogenic, anti-inflammatory, analgesic and hepatoprotective activities; it also inhibits the prostaglandin synthetase. OBJECTIVES: This study determines the cytotoxic potential of 15-oxoursolic acid isolated from R. arboreum against selected human cancer cell lines. MATERIALS AND METHODS: Extraction from stem bark (5 kg) of R. arboreum was performed with methanol, which was successively partitioned into hexane, dichloromethane and ethyl acetate fractions, respectively. The new antitumor agent [15-oxoursolic acid (1)] was isolated from ethyl acetate fraction through column chromatography. Structure elucidation of new compound was performed through extensive spectroscopy i.e., IR, MS and 1D and 2D NMR. Cytotoxicity of isolated compound was determined at doses 5-100 µM for a period of 72 h on specified human cancer cell lines [renal cell carcinoma (A498), non-small cell lung (NCI-H226), squamous cell carcinoma (H157) and human ovarian carcinoma (MDR-2780AD)]. RESULTS: Structure of isolated compound was characterized as 15-oxoursolic acid on the basis of various extensive spectroscopic techniques. 15-Oxoursolic acid revealed considerable anticancer activity with IC50 values of 2.3 ± 0.1 µM, 4.9 ± 0.2 µM, 9.2 ± 0.2 µM and 10.3 ± 0.1 µM against MDR 2780AD, Hep G2, H157 and NCI-H226, respectively, while in the case of A498, the activity was good (IC50 32.8 ± 1.2 µM). CONCLUSIONS: This study highlighted the potential of 15-oxoursolic acid to be further explored as a new lead compound for cancer chemotherapy.

Synthesis of secondary metabolites by Cladosporium resinae (NRL-6437) under different growth media and chemical inducers and their pharmaceutical activity.

The role of different growth media and chemical enhancer on synthesis of secondary metabolites Cladosporium resinae (NRL-6437) was investigated for their in vitro biological activities. Cladosporium resinae (NRL-6437) were grown in various nutrient media (Czapeak-dox Broth (CB), Czapeak Yeast-extract Broth (CYB), Yeast Extract Sucrose (YES), Potato Dextrose Broth (PDB) and Czapeak-dox (supplemented with glucose and starch) Broth (CGSB) for the production of metabolites. Two chemical epigenetic modifiers (suberoyl-anilide hydroxamic acid (SAHA) and 5-azacytidine (5-AZA) were also used for the expression of silent genes for secondary metabolite production. Our results indicated that among different media, Czapeak yeast extract broth produced more secondary metabolites. Application of 15mM of both modifiers was effective for the expressions of silent genes resulting in an increased metabolites production. Secondary metabolites extracted in ethyl acetate and fractionized in n-Hexane were also tested for their biological activity. The secondary metabolites revealed varying degrees of growth inhibitions of the tested organisms. Similarly, these metabolites were also active against brine shrimps and Lemna.

Role of growth media and chemical enhancers in secondary metabolites production from Aspergillus carbonarius (NRL-369) and their pharmaceutical potentials.

The present study investigates the effect of different growth media and chemical enhancer on silent genes in Aspergillus carbonarius (NRL-369) for secondary metabolites production and its in vitro biological activities. Results revealed that Aspergillus carbonarius (NRL-369) grown in Czapeak yeast extract broth medium produced more metabolites compared with other media. Chemical epigenetic modifiers (suberoyl-anilide hydroxamic acid (SAHA) and 5-azacytidine (5-AZA) at concentration of 15mM were effective for the expression of silent genes resulting in increased secondary metabolites production. Secondary metabolites extracted in ethyl acetate and fractionized in n-Hexane showed variable degree of growth inhibitions of the tested microorganisms. Similarly, these samples were also active against brine shrimps and Lemna.

Reviving a ghost in the history of technology: the social construction of the recumbent bicycle.

Recumbent bicycles have never truly been associated with international cycling. Conventional safety (upright) bicycles have long been at the center of the cycling world, for both sport and transportation. This is despite the fact that recumbent bicycles are faster, more comfortable, and more efficient than the upright bicycles. The aim of this article is to explain the historical and social perspectives that led to the rejection of the recumbent bicycle by utilizing the theory of Social Construction of Technology (SCOT) and Bijker's two power theory, providing a contrast with the adoption of the safety bicycle.

Comparative study of heavy metals in dried and fluid milk in Peshawar by atomic absorption spectrophotometry.

Various essential and toxic heavy metals (Ca, Mg, Cu, Zn, Fe, Mn, Pb, Cd, Cr, and Ni) contents in various types of dried (infant formula and powdered) and fluid (fresh and processed) cow milk were assessed by atomic absorption spectrophotometry. The milk samples were collected from local markets of different parts of Peshawar city, Pakistan. Heavy metal concentrations varied significantly depending upon the type of milk. The heavy metal concentrations in most of the samples were within normal and permissible ranges. It was observed that the samples contained considerable amounts of calcium, while magnesium levels were well above the required levels. The results also revealed that copper levels were slightly lower than the permissible limits. The concentration of zinc in dried milk samples was greater than the values for the liquid milk types. Infant milk formulae had higher iron levels as compared to other milk samples because of the added constituents. Significant differences were observed in the mean values of manganese and cadmium in different types of milk. The toxic metals were within the acceptable limits and did not show significant levels leading to toxicity.

An early force prediction control scheme using multimodal sensing of electromyography and digit force signals.

Different grasping gestures result in the change of muscular activity of the forearm muscles. Similarly, the muscular activity changes with a change in grip force while grasping the object. This change in muscular activity, measured by a technique called Electromyography (EMG) is used in the upper limb bionic devices to select the grasping gesture. Previous research studies have shown gesture classification using pattern recognition control schemes. However, the use of EMG signals for force manipulation is less focused, especially during precision grasping. In this study, an early predictive control scheme is designed for the efficient determination of grip force using EMG signals from forearm muscles and digit force signals. The optimal pattern recognition (PR) control schemes are investigated using three different inputs of two signals: EMG signals, digit force signals and a combination of EMG and digit force signals. The features extracted from EMG signals included Slope Sign Change, Willison Amplitude, Auto Regressive Coefficient and Waveform Length. The classifiers used to predict force levels are Random Forest, Gradient Boosting, Linear Discriminant Analysis, Support Vector Machines, k-nearest Neighbors and Decision Tree. The two-fold objectives of early prediction and high classification accuracy of grip force level were obtained using EMG signals and digit force signals as inputs and Random Forest as a classifier. The earliest prediction was possible at 1000 ms from the onset of the gripping of the object with a mean classification accuracy of 90 % for different grasping gestures. Using this approach to study, an early prediction will result in the determination of force level before the object is lifted from the surface. This approach will also result in better biomimetic regulation of the grip force during precision grasp, especially for a population facing vision deficiency.

Assessment of occupational musculoskeletal disorders (MSDs) among heavy vehicle drivers.

BACKGROUND: Professional driving requires long hours of work, uncomfortable seats, negotiating rough terrain and highways, and possibly minor repairs and other auxiliary transportation duties. Heavy vehicle drivers driving vehicles such as trucks, bulldozers, etc. due to such working structures are more prone to various musculoskeletal disorders (MSDs) and pain, which is of great concern. OBJECTIVES: In the present study, it is planned to investigate possible ergonomic risk factors such as age, weight, driving exposure, seat suspension systems, lifting heavy weights causing MSDs in drivers of various heavy vehicles. The results of the study are expected to help drivers reduce the risk of MSDs. METHODS: For the present study, the Nordic questionnaire on musculoskeletal disorders was modified and standardized and was administered to the 48 heavy vehicle drivers randomly selected to collect the data. RESULTS: The analysis divulged that over the past 12 months, lower back pain (LBP) emerged as the most dominant pain experienced by 56% of drivers, followed by knee pain (KP) (43%) and neck pain (NP) (39%) respectively. The prevalence of shoulder pain (SP) was observed to be much lower than in previous literature. The logistic regression model further revealed that increasing age, poor suspension system and poor body posture were significantly associated with lower back pain. Additionally, a poor suspension system and lifting heavy weights had significant effect on the drivers' knee pain. CONCLUSION: The results demonstrated the evident necessity for ergonomic consideration in vehicle designing and ergonomic training for heavy vehicle drivers.

Seasonal variation in abundance and characteristics of microplastic in sewage sludge from major cities across the upper stretch of River Ganga, India.

Microplastic (MP) load in urban sewage sludge could vary annually in wastewater treatment plants (WWTPs) depending on seasonal precipitation and human activities. We investigated the seasonal dynamics in abundance and characterization of MP loading in WWTPs located in two cities across River Ganga, India's ecologically sensitive upper stretch. During a 12-month seasonal sampling (pre-monsoon, monsoon, and post-monsoon), sludge samples (n = 36) (primary sludge, PS; drying bed sludge, DBS) were collected and analyzed for load, polymer types, shape, colour, and size (20-1000 µm). Across the three seasons, MP concentrations (particles/kg) were found to be in the ranges of 93.4 ± 5.0 × 103-189.4 ± 11 × 103 in the PS and 39.6 ± 4.0 × 103-152.0 ± 7 × 103 in the DBS. The trend of MP loading was in the following order: monsoon > post-monsoon > pre-monsoon. The dominant MP size was 50-200 µm (36.22%) followed by 20-50 µm (27.65%), 200-500 µm (24.55%) and 500-1000 µm (11.58%). ATR-FTIR results revealed polypropylene, polyethylene terephthalate, polyvinyl chloride, and nylon dominating MP in sludge. This study highlights the importance of long-term monitoring of MP loading in sewage sludge to offer a more accurate estimate of MP contamination in sludge from WWTPs and develop a possible mechanism for its elimination to safeguard the environment.

Synthesis of ZnO and PEG-ZnO nanoparticles (NPs) with controlled size for biological evaluation.

The objective of this research was to produce the smallest possible ZnO nanoparticles through an adapted wet chemical process and subsequently, to fabricate a core-shell structure utilizing polyethylene glycol (PEG) as the shell component. The synthesis, size, and shape of the NPs were confirmed using advanced techniques. The resulting clustered NPs were round and had a size of 9.8 nm. Both plain and core-shell NPs were tested for their antibacterial properties against multi-drug resistant bacteria strains (E. cloacae, E. amnigenus, S. flexneri, S. odorifacae, Citrobacter, and E. coli), with concentrations of 500, 1000, and 1500 µg ml-1 used for testing. Both types of NPs demonstrated antibacterial activity against the tested pathogens, with the core-shell NPs being more effective. The synthesized NPs were biocompatible with human red blood cells, with a low level of hemolysis observed. The biocompatibility of the core-shell NPs was significantly enhanced by the presence of the PEG added as the shell. In addition, their effectiveness as photosensitizers for cancer treatment via photodynamic therapy (PDT) was evaluated. MTT assay was used to evaluate the cytotoxicity of ZnO and PEG-ZnO, and the results showed that these NPs were able to generate ROS inside tumor cells upon irradiation, leading to apoptosis and cell death, making them a promising candidate for PDT.