Catharanthus roseus-mediated CuAl2O4 nanocomposites for evaluation of killing kinetics.

The present article portrayed on the killing kinetic of human pathogenic bacteria using bioinspired mesoporous CuAl2O4 nanocomposites (NCs). The NCs was fabricated using leaf extract of medicinal plant Catharanthus roseus (CR) as a green reducer and stabilizer. As bio-fabricated material was calcined at 800 °C and characterized by several analytical techniques like X-ray Diffraction (XRD), Fourier Transform Infrared Spectroscopy (FT-IR), Ultraviolet-Visible Diffuse Reflectance Spectroscopy (UV-DRS), Energy Dispersive X-Ray Spectroscopy (EDS), X-Ray Photoelectron Spectroscopy (XPS), Raman, Brunauer-Emmett-Teller (BET), Scanning Electron Microscopy (SEM), and Transmission Electron Microscopy (TEM) to authenticate its structure, phase, chemical bonding, chemical state, size and morphology behaviors. XRD and TEM revealed a reduced crystallite and nanoscale sizes of biosynthesized NCs. Moreover, XRD study exposed a cubic-structure of material, while transmission electron microscopy rendered an average particles size in range 10-15 nm. However, BET profile advocates a mesoporous nature of the particles. An effective biological molecular docking modulation assessed by substituting natural inhibitor by bioinspired NCs, while the protein PDB ID 4Z8D FabH as a receptor site for the present investigation. After assessment of molecular docking examination, the antibacterial activity of bioinspired NCs were performed against Staphylococcus aureus, Bacillus subtillis, Klebsiella pneumoniae and Escherichia coli using agar-well method. The broth culture method was employed on different pathogenic strains by kinetic growth assays and colony forming unit.

Dynamic SARS-CoV-2 surveillance model combining seroprevalence and wastewater concentrations for post-vaccine disease burden estimates.

BACKGROUND: Despite wide scale assessments, it remains unclear how large-scale severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination affected the wastewater concentration of the virus or the overall disease burden as measured by hospitalization rates. METHODS: We used weekly SARS-CoV-2 wastewater concentration with a stratified random sampling of seroprevalence, and linked vaccination and hospitalization data, from April 2021-August 2021 in Jefferson County, Kentucky (USA). Our susceptible ( S ), vaccinated ( V ), variant-specific infected ( I 1 and I 2 ), recovered ( R ), and seropositive ( T ) model ( S V I 2 R T ) tracked prevalence longitudinally. This was related to wastewater concentration. RESULTS: Here we show the 64% county vaccination rate translate into about a 61% decrease in SARS-CoV-2 incidence. The estimated effect of SARS-CoV-2 Delta variant emergence is a 24-fold increase of infection counts, which correspond to an over 9-fold increase in wastewater concentration. Hospitalization burden and wastewater concentration have the strongest correlation (r = 0.95) at 1 week lag. CONCLUSIONS: Our study underscores the importance of continuing environmental surveillance post-vaccine and provides a proof-of-concept for environmental epidemiology monitoring of infectious disease for future pandemic preparedness.

It is unclear how large-scale COVID-19 vaccination impacts wastewater concentration or overall disease burden. Here, we developed a mathematical surveillance model that allows estimation of overall vaccine impact based on the amount of SARS-CoV-2 in wastewater, seroprevalence and the number of cases admitted to hospitals between April 2021­August 2021 in Jefferson County, Kentucky USA. We found that a 64% vaccination coverage correlated to a 61% decrease in COVID-19 cases. The emergence of the SARS-CoV-2 Delta variant during the time of the surveillance directly correlated with a sharp increase in infection incidence as well as viral counts in wastewater. The hospitalization burden was closely reflected by the viral count found in the wastewater, indicating that post-vaccine environmental surveillance can be an effective method of estimating changing disease prevalence in future pandemics.

Comparative evaluation of different modalities for measuring in vivo carnosine levels.

Carnosine is an endogenous di-peptide (ß-alanine -L- histidine) involved in maintaining tissue homeostasis. It is most abundant in skeletal muscle where its concentration has been determined in biopsy samples using tandem mass spectrometry (MS-MS). Carnosine levels can also be assessed in intact leg muscles by proton magnetic resonance spectroscopy (1H-MRS) or in blood and urine samples using mass spectrometry. Nevertheless, it remains uncertain how carnosine levels from these distinct compartments are correlated with each other when measured in the same individual. Furthermore, it is unclear which measurement modality might be most suitable for large-scale clinical studies. Hence, in 31 healthy volunteers, we assessed carnosine levels in skeletal muscle, via 1H-MRS, and in erythrocytes and urine by MS-MS. While muscle carnosine levels were higher in males (C2 peak, p = 0.010; C4 peak, p = 0.018), there was no sex-associated difference in urinary (p = 0.433) or erythrocyte (p = 0.858) levels. In a linear regression model adjusted for age, sex, race, and diet, there was a positive association between erythrocyte and urinary carnosine. However, no association was observed between 1H-MRS and erythrocytes or urinary measures. In the relationship between muscle versus urinary and erythrocyte measures, females had a positive association, while males did not show any association. We also found that 1H-MRS measures were highly sensitive to location of measurement. Thus, it is uncertain whether 1H-MRS can accurately and reliably predict endogenous carnosine levels. In contrast, urinary and erythrocyte carnosine measures may be stable and in greater synchrony, and given financial and logistical concerns, may be a feasible alternative for large-scale clinical studies.

Stratified Simple Random Sampling Versus Volunteer Community-Wide Sampling for Estimates of COVID-19 Prevalence.

Objectives. To evaluate community-wide prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using stratified simple random sampling. Methods. We obtained data for the prevalence of SARS-CoV-2 in Jefferson County, Kentucky, from adult random (n = 7296) and volunteer (n = 7919) sampling over 8 waves from June 2020 through August 2021. We compared results with administratively reported rates of COVID-19. Results. Randomized and volunteer samples produced equivalent prevalence estimates (P < .001), which exceeded the administratively reported rates of prevalence. Differences between them decreased as time passed, likely because of seroprevalence temporal detection limitations. Conclusions. Structured targeted sampling for seropositivity against SARS-CoV-2, randomized or voluntary, provided better estimates of prevalence than administrative estimates based on incident disease. A low response rate to stratified simple random sampling may produce quantified disease prevalence estimates similar to a volunteer sample. Public Health Implications. Randomized targeted and invited sampling approaches provided better estimates of disease prevalence than administratively reported data. Cost and time permitting, targeted sampling is a superior modality for estimating community-wide prevalence of infectious disease, especially among Black individuals and those living in disadvantaged neighborhoods. (Am J Public Health. 2023;113(7):768-777. https://doi.org/10.2105/AJPH.2023.307303).

Biomedical,clinical and environmental applications of platinum-based nanohybrids: An updated review.

Platinum nanoparticles (Pt NPs) have numerous applications in various sectors, including pharmacology, nanomedicine, cancer therapy, radiotherapy, biotechnology and environment mitigation like removal of toxic metals from wastewater, photocatalytic degradation of toxic compounds, adsorption, and water splitting. The multifaceted applications of Pt NPs because of their ultra-fine structures, large surface area, tuned porosity, coordination-binding, and excellent physiochemical properties. The various types of nanohybrids (NHs) of Pt NPs can be fabricated by doping with different metal/metal oxide/polymer-based materials. There are several methods to synthesize platinum-based NHs, but biological processes are admirable because of green, economical, sustainable, and non-toxic. Due to the robust physicochemical and biological characteristics of platinum NPs, they are widely employed as nanocatalyst, antioxidant, antipathogenic, and anticancer agents. Indeed, Pt-based NHs are the subject of keen interest and substantial research area for biomedical and clinical applications. Hence, this review systematically studies antimicrobial, biological, and environmental applications of platinum and platinum-based NHs, predominantly for treating cancer and photo-thermal therapy. Applications of Pt NPs in nanomedicine and nano-diagnosis are also highlighted. Pt NPs-related nanotoxicity and the potential and opportunity for future nano-therapeutics based on Pt NPs are also discussed.

Clinical evaluation of feasibility and effectiveness using a virtual reality device during local anesthesia and extractions in pediatric patients.

PURPOSE: Pediatric dentistry requires more than routine dental knowledge and skills in executing quality dental care. The quality of dental treatment is indirectly proportional to a child's anxiety and fear. The recent distraction technique, the use of virtual reality (VR) devices has intrigued many researcher's minds. Therefore, this study was conducted to assess the clinical feasibility and effectiveness of the VR device in reducing pain and anxiety in pediatric patients during mandibular primary molar extraction. METHODS: This research trial had 30 healthy children between the ages of 6 and 12 who required mandibular primary molar extraction. The subjects were divided into two groups using a simple randomization method. In the study group (n = 15), extraction was carried out using a VR device, whereas, in the control group (n = 15), extraction was carried out without the use of a VR device. Pre- and post-extraction anxiety levels were measured by Venham's picture test (VPT) and the heart rate. After the procedure, pain and behavior were evaluated by the Wong-Bakers Faces pain rating scale (WBS) and FLACC Scale respectively. RESULTS: The pre-extraction values of the VPT and heart rate showed no statistically significant difference. This indicates that participants of both groups had a similar level of anxiety at baseline. There was a statistically significant increase (p = 0.028) between pre- and post-heart rates in the control group, with no significant change in the study group. CONCLUSION: The use of a virtual reality device in children can reduce anxiety during primary molar extractions as evaluated by heart rate. Virtual reality devices might be an adjunct to high-quality dental care and to other behavior management methods. Definitive outcomes can be attained by encouraging studies overcoming the present limitations, and considering salivary biochemical indicators for the assessment of these devices.

Everolimus downregulates STAT3/HIF-1α/VEGF pathway to inhibit angiogenesis and lymphangiogenesis in TP53 mutant head and neck squamous cell carcinoma (HNSCC).

TP53 mutant head and neck squamous cell carcinoma (HNSCC) patients exhibit poor clinical outcomes with 50-60% recurrence rates in advanced stage patients. In a recent phase II clinical trial, adjuvant therapy with everolimus (mTOR inhibitor) significantly increased 2-year progression-free survival in p53 mutated patients. TP53-driven mTOR activation in solid malignancies causes upregulation of HIF-1α and its target, downstream effector VEGF, by activating STAT3 cell signaling pathway. Here, we investigated the effects of everolimus on the STAT3/HIF-1α/VEGF pathway in TP53 mutant cell lines and xenograft models. Treatment with everolimus significantly inhibited cell growth in vitro and effectively reduced the growth of TP53 mutant xenografts in a minimal residual disease (MRD) model in nude mice. Everolimus treatment was associated with significant downregulation of STAT3/HIF-1α/VEGF pathway in both models. Further, treatment with everolimus was associated with attenuation in tumor angiogenesis and lymphangiogenesis as indicated by decreased microvessel density of vascular and lymphatic vessels in HN31 and FaDu xenografts. Everolimus downregulated the STAT3/HIF-1α/VEGF pathway to inhibit growth and in vitro tube formation of HMEC-1 (endothelial) and HMEC-1A (lymphatic endothelial) cell lines. Our studies demonstrated that everolimus inhibits the growth of TP53 mutant tumors by inhibiting angiogenesis and lymphangiogenesis through the downregulation of STAT3/HIF-1α/VEGF signaling.

Wastewater and seroprevalence for pandemic preparedness: variant analysis, vaccination effect, and hospitalization forecasting for SARS-CoV-2, in Jefferson County, Kentucky.

Despite wide scale assessments, it remains unclear how large-scale SARS-CoV-2 vaccination affected the wastewater concentration of the virus or the overall disease burden as measured by hospitalization rates. We used weekly SARS-CoV-2 wastewater concentration with a stratified random sampling of seroprevalence, and linked vaccination and hospitalization data, from April 2021-August 2021 in Jefferson County, Kentucky (USA). Our susceptible (S), vaccinated (V), variant-specific infected I1 and I2, recovered (R), and seropositive (T) model SVI2RT tracked prevalence longitudinally. This was related to wastewater concentration. The 64% county vaccination rate translated into about 61% decrease in SARS-CoV-2 incidence. The estimated effect of SARS-CoV-2 Delta variant emergence was a 24-fold increase of infection counts, which corresponded to an over 9-fold increase in wastewater concentration. Hospitalization burden and wastewater concentration had the strongest correlation (r = 0.95) at 1 week lag. Our study underscores the importance of continued environmental surveillance post-vaccine and provides a proof-of-concept for environmental epidemiology monitoring of infectious disease for future pandemic preparedness.

Nucleic Acid Nanotechnology: Trends, Opportunities and Challenges.

Nucleic acids (DNA and RNA) hold great potential for the advancement of future medicine but suffer from unsatisfactory clinical success due to the challenges accompanied with their delivery. Nucleic acid-mediated nanomaterials have riveted the researchers from the past two decades and exhilarating tasks have prevailed. Nucleic acid nanotechnology offers unique control over the shape, size, time, mechanics and anisotropy. It can transfect numerous types of tissues and cells without any toxic effect, minimize the induced immune response, and penetrate most of the biological barriers and hence it reveals itself as a versatile tool for multidisciplinary research field and for various therapeutic purposes. Nucleic acid combines with other nanoscale objects also by altering the chemical functional groups and reproducing the varied array of nanomaterials. Interestingly, nucleic acidderived nanomaterials are characterized easily at atomic level accuracy. However, this advent of nanoscience has vital issues which must be addressed, such as the high cost of nucleic acids, their self-assembly nature, etc. Hence, the aim of this review is to highlight the systematic advances and methodology of nucleic acid-mediated synthesis of nanomaterials and their therapeutic applications.

Association of electronic cigarette use with circulating angiogenic cell levels in healthy young adults: Evidence for chronic systemic injury.

BACKGROUND: Circulating angiogenic cells (CACs) are indicative of vascular health and repair capacity; however, their relationship with chronic e-cigarette use is unclear. This study aims to assess the association between e-cigarette use and CAC levels. METHODS: We analyzed CAC levels in 324 healthy participants aged 21-45 years from the cross-sectional Cardiovascular Injury due to Tobacco Use study in four groups: never tobacco users (n = 65), sole e-cigarette users (n = 19), sole combustible cigarette users (n = 212), and dual users (n = 28). A total of 15 CAC subpopulations with four cell surface markers were measured using flow cytometry: CD146 (endothelial), CD34 (stem), CD45 (leukocyte), and AC133 (early progenitor/stem). Generalized linear models with gamma distribution and log-link were generated to assess association between CACs and smoking status. Benjamini-Hochberg were used to adjust p-values for multiple comparisons. RESULTS: The cohort was 47% female, 51% Black/African American, with a mean (± SD) age of 31 ± 7 years. Sole cigarette use was significantly associated with higher levels of two endothelial marker CACs (Q ⩽ 0.05). Dual users had higher levels of four endothelial marker CACs and one early progenitor/stem marker CAC (Q ⩽ 0.05). Sole e-cigarette users had higher levels of one endothelial and one leukocyte marker CAC (Q ⩽ 0.05). CONCLUSION: Dual use of e-cigarettes and combustible cigarettes was associated with higher levels of endothelial origin CACs, indicative of vascular injury. Sole use of e-cigarettes was associated with higher endothelial and inflammatory CACs, suggesting ongoing systemic injury. Distinct patterns of changes in CAC subpopulations suggest that CACs may be informative biomarkers of changes in vascular health due to tobacco product use.

Quantifying the relationship between sub-population wastewater samples and community-wide SARS-CoV-2 seroprevalence.

Robust epidemiological models relating wastewater to community disease prevalence are lacking. Assessments of SARS-CoV-2 infection rates have relied primarily on convenience sampling, which does not provide reliable estimates of community disease prevalence due to inherent biases. This study conducted serial stratified randomized samplings to estimate the prevalence of SARS-CoV-2 antibodies in 3717 participants, and obtained weekly samples of community wastewater for SARS-CoV-2 concentrations in Jefferson County, KY (USA) from August 2020 to February 2021. Using an expanded Susceptible-Infected-Recovered model, the longitudinal estimates of the disease prevalence were obtained and compared with the wastewater concentrations using regression analysis. The model analysis revealed significant temporal differences in epidemic peaks. The results showed that in some areas, the average incidence rate, based on serological sampling, was 50 % higher than the health department rate, which was based on convenience sampling. The model-estimated average prevalence rates correlated well with the wastewater (correlation = 0.63, CI (0.31,0.83)). In the regression analysis, a one copy per ml-unit increase in weekly average wastewater concentration of SARS-CoV-2 corresponded to an average increase of 1-1.3 cases of SARS-CoV-2 infection per 100,000 residents. The analysis indicates that wastewater may provide robust estimates of community spread of infection, in line with the modeled prevalence estimates obtained from stratified randomized sampling, and is therefore superior to publicly available health data.

Pre-Existing Comorbidities Diminish the Likelihood of Seropositivity after SARS-CoV-2 Vaccination.

BACKGROUND: The impact of chronic health conditions (CHCs) on serostatus post-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is unknown. METHODS: We assessed serostatus post-SARS-CoV-2 vaccination among fully vaccinated adult residents of Jefferson County, Kentucky, USA, from April 2021 to August 2021. Serostatus was determined by qualitative analysis of SARS-CoV-2-specific Spike IgG antibodies via enzyme-linked immunoassay (ELISA) in peripheral blood samples. RESULTS: Of the 5178 fully vaccinated participants, 51 were seronegative and 5127 were seropositive. Chronic kidney disease (CKD) and autoimmune disease showed the highest association with negative serostatus in fully vaccinated individuals. The absence of any CHC was strongly associated with positive serostatus. The risk of negative serostatus increased as the total number of pre-existing CHCs increased. Similarly, the use of two or more CHC-related medications was associated with seronegative status. CONCLUSIONS: The presence of any CHC, especially CKD or autoimmune disease, increased the likelihood of seronegative status among individuals who were fully vaccinated to SAR-CoV-2. This risk increased with a concurrent increase in number of comorbidities, especially with multiple medications. The absence of any CHC was protective and increased the likelihood of a positive serological response. These results will help develop appropriate guidelines for booster doses and targeted vaccination programs.

A Novel Affinity Engineered Anti-CD47 Antibody With Improved Therapeutic Index That Preserves Erythrocytes and Normal Immune Cells.

Therapeutic blockade of the CD47/SIRPα axis by small molecules or monoclonal antibodies (mAbs) is a proven strategy to enhance macrophages-mediated anti-tumor activity. However, this strategy has been hampered by elevated on-target toxicities and rapid clearance due to the extensive CD47 expression on normal cells ("antigen sink") such as red blood cells (RBCs). To address these hurdles, we report on the development of STI-6643, an affinity-engineered fully human anti-CD47 IgG4 antibody with negligible binding to normal cells. STI-6643 exhibited no hemagglutination activity on human RBCs at concentrations up to 300 µg/mL yet specifically blocked the CD47/SIPRα interaction. Of particular interest, STI-6643 preserved T cell functionality in vitro and showed significantly lower immune cell depletion in vivo in contrast to three previously published competitor reference anti-CD47 clones Hu5F9, AO-176 and 13H3. In cynomolgus monkeys, STI-6643 was well-tolerated at the highest dose tested (300 mg/kg/week) and provided favorable clinical safety margins. Finally, STI-6643 displayed comparable anti-tumor activity to the high-affinity reference clone Hu5F9 in a RAJI-Fluc xenograft tumor model as monotherapy or in combination with anti-CD20 (rituximab) or anti-CD38 (daratumumab) mAbs. These data suggest that STI-6643 possesses the characteristics of an effective therapeutic candidate given its potent anti-tumor activity and low toxicity profile.

Inhibition of Fibroblast Growth Factor Receptor Attenuates UVB-Induced Skin Carcinogenesis.

Altered fibroblast GF receptor (FGFR) signaling has been shown to play a role in a number of cancers. However, the role of FGFR signaling in the development and progression of UVB-induced cutaneous squamous cell carcinoma remains unclear. In this study, the effect of UVB radiation on FGFR activation and its downstream signaling in mouse skin epidermis was examined. In addition, the impact of FGFR inhibition on UVB-induced signaling and skin carcinogenesis was also investigated. Exposure of mouse dorsal skin to UVB significantly increased the phosphorylation of FGFRs in the epidermis as well as the activation of downstream signaling pathways, including protein kinase B/mTOR, signal transducers and activators of transcription, and MAPK. Topical application of the pan-FGFR inhibitor AZD4547 to mouse skin before exposure to UVB significantly inhibited FGFR phosphorylation as well as mTORC1, signal transducer and activator of transcription 3, and MAPK activation (i.e., phosphorylation). Moreover, AZD4547 pretreatment significantly inhibited UVB-induced epidermal hyperplasia and hyperproliferation and reduced the infiltration of mast cells and macrophages into the dermis. AZD4547 treatment also significantly inhibited mRNA expression of inflammatory genes in the epidermis. Finally, mice treated topically with AZD4547 before UVB exposure showed decreased cutaneous squamous cell carcinoma incidence and increased survival rate. Collectively, the current data support the hypothesis that inhibition of FGFR in the epidermis may provide a new strategy to prevent and/or treat UVB-induced cutaneous squamous cell carcinoma.

In-vivo platelet activation and aggregation during and after acute atherothrombotic myocardial infarction in patients with and without Type-2 diabetes mellitus treated with ticagrelor.

INTRODUCTION: Patients with type-2 diabetes are twice as likely to suffer from acute myocardial infarction (AMI) and have a higher incidence of recurrent events than their non-diabetic counterparts. Ticagrelor is a platelet inhibitor known to reduce major adverse cardiovascular events (MACE) in AMI patients. This study measures the level and change in platelet activation and aggregation at the time of and following an AMI in patients with and without diabetes treated with ticagrelor. MATERIALS/METHODS: P2Y12 receptor inhibitor naïve patients presenting with AMI were prospectively enrolled. Blood collection occurred before coronary angiography (baseline: T0), 2, 4, 24, 48 h after baseline, and at a three-month follow-up. Ticagrelor was administered within five minutes of T0. We assessed platelet activation via measurements of surface P-selectin and platelet activated glycoprotein IIb/IIIa-1 (PAC-1) and assessed platelet aggregation via monocyte, lymphocyte, and granulocyte aggregates. We hypothesize that platelet activation and aggregation will be proportionally impacted to the same degree by ticagrelor, regardless of diabetes status. RESULTS: Ninety-seven patients were prospectively enrolled (diabetes, N = 33; no diabetes, N = 64). No difference was observed in the expression of P-selectin and PAC-1 at any given point between diabetes and non-diabetes groups (p > 0.05). No difference was observed in the percentage of platelet bound to leukocytes at any measured timepoint between patients with and without diabetes (p > 0.05). Platelet leukocyte aggregation was suppressed during the acute phase compared to quiescence equally among both groups. DISCUSSION: Ticagrelor demonstrated similar in-vivo effects on platelet activation and aggregation regardless of diabetes status in patients presenting with AMI.

Bioinspired NiO Nanospheres: Exploring In Vitro Toxicity Using Bm-17 and L. rohita Liver Cells, DNA Degradation, Docking, and Proposed Vacuolization Mechanism.

The present work demonstrated a novel Cleome simplicifolia-mediated green fabrication of nickel oxide nanoparticles (NiO NPs) to explore in vitro toxicity in Bm-17 and Labeo rohita liver cells. As-fabricated bioinspired NiO NPs were characterized by several analytical techniques. X-ray diffraction (XRD) revealed a crystalline face-centered-cubic structure. Fourier transform infrared spectroscopy (FTIR), ultraviolet-visible diffuse reflectance spectroscopy (UV-DRS), Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS) confirmed NiO formation. The chemical composition was confirmed by energy-dispersive X-ray spectroscopy (EDS) and X-ray photoelectron spectroscopy. Brunauer-Emmett-Teller (BET) revealed the mesoporous nature. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) revealed the formation of 97 nm diameter nanospheres formed due to the congregation of 10 nm size particles. Atomic force microscopy (AFM) revealed the nearly isotropic behavior of NiO NPs. Further, a molecular docking study was performed to explore their toxicity by binding with genetic molecules, and it was found that the docking energy was about -9.65284 kcal/mol. On evaluating the in vitro toxicity of NiO NPs for Bm-17 cells, the study showed that when cells were treated with a high concentration of NPs, cells were affected severely by toxicity, while at a lower concentration, cells were affected slightly. Further, on using 50 µg/mL, quick deaths of cells were observed due to the formation of more vacuoles in the cells. The DNA degradation study revealed that NiO NPs are significantly responsible for DNA degradation. For further confirmation, trypan blue assay was observed for cell viability, and morphological assessment was performed using inverted tissue culture microscopy. Further, the cytotoxicity of NiO NPs in L. rohita liver cells was studied. No toxicity was observed at 1 mg/L of NiO NPs; however, when the concentration was 30 and 90 mg/L, dark and shrank hepatic parenchyma was observed. Hence, the main cause of cell lysis is the increased vacuolization in the cells. Thus, the present study suggests that the cytotoxicity induced by NiO NPs could be used in anticancer drugs.

TP53 mutations in head and neck cancer.

Head and neck squamous cell carcinomas (HNSCCs) arising in the mucosal linings of the upper aerodigestive tract are highly heterogeneous, aggressive, and multifactorial tumors affecting more than half a million patients worldwide each year. Classical etiological factors for HNSCC include alcohol, tobacco, and human papillomavirus (HPV) infection. Current treatment options for HNSCCs encompass surgery, radiotherapy, chemotherapy, or combinatorial remedies. Comprehensive integrative genomic analysis of HNSCC has identified mutations in TP53 gene as the most frequent of all somatic genomic alterations. TP53 mutations are associated with either loss of wild-type p53 function or gain of functions that promote invasion, metastasis, genomic instability, and cancer cell proliferation. Interestingly, disruptive TP53 mutations in tumor DNA are associated with aggressiveness and reduced survival after surgical treatment of HNSCC. This review summarizes the current evidence and impact of TP53 mutations in HNSCC.

Public Awareness of and Support for the Use of Wastewater for SARS-CoV-2 Monitoring: A Community Survey in Louisville, Kentucky.

The majority of sewer systems in the United States and other countries are operated by public utilities. In the absence of any regulation, the public perception of wastewater monitoring for population health biomarkers is an important consideration for a public utility commission when allocating resources for this purpose. We conducted a survey in August 2021 as part of an ongoing COVID-19 community prevalence study in Louisville/Jefferson County, KY, US. The survey comprised seven questions about wastewater awareness and privacy concerns and was sent to approximately 35 000 households randomly distributed within the county. A total of 1220 adults were involved in the probability sample, and data from 981 respondents were used in the analysis. A total of 2444 adults additionally responded to the convenience sample, and data from 1751 respondents were used in the analysis. The samples were weighted to obtain estimates representative of all adults in the county. Public awareness of tracking the virus that causes COVID-19 in sewers was low. Opinions strongly support the public disclosure of monitoring results. Responses showed that people more strongly supported measurements in the largest areas (>50 000 households), typically representing population levels found in a large community wastewater treatment plant. Those with a history of COVID-19 infection were more likely to support highly localized monitoring. Understanding wastewater surveillance strategies and privacy concern thresholds requires an in-depth and comprehensive analysis of public opinion for continued success and effective public health monitoring.

Rapalogs induce non-apoptotic, autophagy-dependent cell death in HPV-negative TP53 mutant head and neck squamous cell carcinoma.

TP53 is the most frequently mutated gene in head and neck squamous cell carcinoma (HNSCC). Patients with HPV-negative TP53 mutant HNSCC have the worst prognosis, necessitating additional agents for treatment. Since mutant p53 causes sustained activation of the PI3K/AKT/mTOR signaling pathway, we investigated the effect of rapalogs RAD001 and CCI-779 on HPV-negative mutTP53 HNSCC cell lines and xenografts. Rapalogs significantly reduced cell viability and colony formation. Interestingly, rapalogs-induced autophagy with no effect on apoptosis. Pretreatment with autophagy inhibitors, 3-methyladenine (3-MA) and ULK-101 rescued the cell viability by inhibiting rapalog-induced autophagy, suggesting that both RAD001 and CCI-779 induce non-apoptotic autophagy-dependent cell death (ADCD). Moreover, rapalogs upregulated the levels of ULK1 and pULK1 S555 with concomitant downregulation of the mTORC1 pathway. However, pretreatment of cells with rapalogs prevented the ULK-101-mediated inhibition of ULK1 to sustained autophagy, suggesting that rapalogs induce ADCD through the activation of ULK1. To further translate our in vitro studies, we investigated the effect of RAD001 in HPV-negative mutTP53 (HN31 and FaDu) tumor cell xenograft model in nude mice. Mice treated with RAD001 exhibited a significant tumor volume reduction without induction of apoptosis, and with a concomitant increase in autophagy. Further, treatment with RAD001 was associated with a considerable increase in pULK1 S555 and ULK1 levels through the inhibition of mTORC1. 3-MA reversed the effect of RAD001 on FaDu tumor growth suggesting that RAD001 promotes ACDC in HPV-negative mutTP53 xenograft. This is the first report demonstrating that rapalogs promote non-apoptotic ADCD in HPV-negative mutTP53 HNSCC via the ULK1 pathway. Further studies are required to establish the promising role of rapalogs in preventing the regrowth of HPV-negative mutTP53 HNSCC.