Potential Actions Research Articles

Targeted RNA sequencing in diagnostically challenging head and neck carcinomas identifies novel MON2::STAT6, NFATC2::NUTM2B, POC5::RAF1, and NSD3::NCOA2 gene fusions.

Although molecular tests developed for a growing list of oncogenic alterations have significantly aided in the classification of head and neck carcinomas, tumours in which prototypical histologic and immunophenotypic features are lacking or only partially developed continue to pose diagnostic challenges. Searching for known diagnostic and therapeutic targets by clinical next-generation sequencing (NGS) assays can often lead to new discoveries. We present our institutional experience in applying targeted RNA NGS in 36 head and neck carcinomas that were morphologically difficult to classify between 2016 and 2023. The patients ranged in age from 5 to 83 years (median, 64), with the majority of tumors occurring in the major salivary glands and the sinonasal tract. Overall, seven (19%) cases showed unusual gene rearrangements, including five novel alterations: MON2::STAT6 in a hard palate adenocarcinoma with mucinous features, POC5::RAF1 in apocrine intraductal carcinoma of the lacrimal gland, EWSR1::CDADC1 fusion in a basaloid carcinoma of the submandibular gland, NFATC2::NUTM2B in myoepithelial carcinoma, and NSD3::NCOA2 fusion in a peculiar high-grade carcinoma with a peritheliomatous growth pattern, and focal myogenic differentiation. Potential therapeutic actionability was identified in three cases (RAF1 and FGFR2 fusions). These findings broaden the current spectrum of gene rearrangements in head and neck carcinomas and support the utility of clinical NGS in identifying unusual, actionable alterations in diagnostically challenging cases.

BIOACTIVE COMPOUNDS POTENTIATION AND ANTIBACTERIAL ACTIVITIES OF A PETALONIA FASCIA EXTRACT ON METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS STRAINS

The bioactive algal components that contribute to their antimicrobial properties have garnered significant attention, particularly in light of the rising incidence of antibiotic resistance. The current study aimed to evaluate the antibacterial activity of a Petalonia fascia methanolic extract and to explore the potentiation action of extract–antibiotic combinations with the available antibiotics, as well as the effects of their mixture on multidrug-resistant (MDR) bacteria, namely, five methicillin-resistant Staphylococcus aureus (MRSA) strains. The algal crude extract displayed antibacterial activity against all assayed isolates, with an inhibition zone ranging from 16 to 21 mm and the best spectrum of bactericidal effect with a ratio of MBC/MIC < 4 obtained on the five tested bacterial strains. Amoxicillin–extract mixtures decreased the bacterial growth rate dramatically on all five S. aureus isolates in a time-dependent manner. These results indicate the ability of the extract to modulate antibiotic activity. However, the possibility of its use to solve the issue of antibiotic-resistant bacterial strains and their application as therapeutic agents against infectious diseases warrants further investigation.

Can one hear the shape of a crystal?

Isospectrality is a general fundamental concept often involving whether various operators can have identical spectra, i.e., the same set of eigenvalues. In the context of the Laplacian operator, the famous question “Can one hear the shape of a drum?” concerns whether different shaped drums can have the same vibrational modes. The isospectrality of a lattice in d-dimensional Euclidean space Rd is a tantamount to whether it is uniquely determined by its theta series, i.e., the radial distribution function g2(r). While much is known about the isospectrality of Bravais lattices across dimensions, little is known about this question of more general crystal (periodic) structures with an n-particle basis (n≥2). Here, we ask what is nmin(d), the minimum value of n for inequivalent (i.e., unrelated by isometric symmetries) crystals with the same theta function in space dimension d? To answer these questions, we use rigorous methods as well as a precise numerical algorithm that enables us to determine the minimum multiparticle basis of inequivalent isospectral crystals. Our algorithm identifies isospectral four-, three- and two-particle bases in one, two, and three spatial dimensions, respectively. For many of these isospectral crystals, we rigorously show that they indeed possess identically the same g2(r)'s for all values of r. Based on our analyses, we conjecture that nmin(d)=4, 3, 2 for d=1, 2, 3, respectively. The identification of isospectral crystals enables one to study the degeneracy of the ground-state under the action of isotropic pair potentials. Indeed, using inverse statistical-mechanical techniques, we find an isotropic pair potential whose low-temperature configurations in two dimensions obtained via simulated annealing can lead to both of two isospectral crystal structures with n=3, the proportion of which can be controlled by the cooling rate. Our findings provide general insights into the structural and ground-state degeneracies of crystal structures as determined by radial pair information. Published by the American Physical Society 2024

Mechanistic insights into antifungal potential of Alexidine dihydrochloride and hexachlorophene in Candida albicans: a drug repurposing approach.

Candida albicans has been listed in the critical priority group by the WHO in 2022 depending upon its contribution in invasive candidiasis and increased resistance to conventional drugs. Drug repurposing offers an efficient, rapid, and cost-effective solution to develop alternative therapeutics against pathogenic microbes. Alexidine dihydrochloride (AXD) and hexachlorophene (HCP) are FDA approved anti-cancer and anti-septic drugs, respectively. In this study, we have shown antifungal properties of AXD and HCP against the wild type (reference strain) and clinical isolates of C. albicans. The minimum inhibitory concentrations (MIC50) of AXD and HCP against C. albicans ranged between 0.34 and 0.69 µM and 19.66-24.58 µM, respectively. The biofilm inhibitory and eradication concentration of AXD was reported comparatively lower than that of HCP for the strains used in the study. Further investigations were performed to understand the antifungal mode of action of AXD and HCP by studying virulence features like cell surface hydrophobicity, adhesion, and yeast to hyphae transition, were also reduced upon exposure to both the drugs. Ergosterol content in cell membrane of the wild type strain was upregulated on exposure to AXD and HCP both. Biochemical analyses of the exposed biofilm indicated reduced contents of carbohydrate, protein, and e-DNA in the extracellular matrix of the biofilm when compared to the untreated control biofilm. AXD exposure downregulated activity of tissue invading enzyme, phospholipase in the reference strain. In wild type strain, ROS level, and activities of antioxidant enzymes were found elevated upon exposure to both drugs. FESEM analysis of the drug treated biofilms revealed degraded biofilm. This study has indicated mode of action of antifungal potential of alexidine dihydrochloride and hexachlorophene in C. albicans.

Construction of the Z-Scheme Heterogeneous HKUST-1/BiVO4 Nanorod Composite for Enhanced Piezo-Photocatalytic Reduction Performance of Cr(VI).

In recent years, piezo-photocatalysis has become a promising strategy for solving environmental pollution problems by adding additional mechanical energy to the photocatalysis process. This work reported the effective synthesis of a variety of HKUST-1/BiVO4 heterogeneous materials by combining monoclinic BiVO4 and porous HKUST-1 semiconductors. The piezo-photocatalytic properties of HKUST-1/BiVO4 were studied by the reduction of hexavalent chromium (Cr(VI)) under visible-light irradiation and ultrasonic waves. In the piezo-photocatalysis process, the best reduction rates among as-prepared HKUST-1/BiVO4 composites were up to 96.20% of 10 ppm Cr(VI) solution, which was approximately 1.80 times that under visible light and about 4.13 times that under ultrasound. Under the action of the piezoelectric potential, the availability of free radicals increased the reduction rate of Cr(VI) and reached a synergistic effect of 1.14-fold.

Diagnostic and clinical utility of comprehensive multigene panel testing for patients with neuropathy.

Prior to next-generation sequencing (NGS), the evaluation of a patient with neuropathy typically consisted of screening for acquired causes, followed by clinical genetic testing of PMP22, MFN2, GJB1, and MPZ in patients with a positive family history and symptom onset prior to age 50. In this study, we examined the clinical utility of NGS in a large cohort of patients analyzed in a commercial laboratory. A cohort of 6849 adult patients underwent clinician-ordered peripheral neuropathy multigene panel testing ranging from 66 to 111 genes that included NGS and intragenic deletion/duplication analysis. A molecular diagnosis was identified for 8.4% of the cohort (n = 573/6849). Variants in PMP22, MFN2, GJB1, MPZ, and TTR accounted for 73.8% of molecular diagnoses. Results had potential clinical actionability for 398 (69.5%) patients. Our results suggest that 225/573 (39.3%) of molecular diagnoses and 113/398 (28.4%) of clinical interventions would have been missed if the testing approach had been restricted to older guidelines. Our results highlight the need for expanded genetic testing guidelines that account for the increased number of genes associated with hereditary neuropathy, address the overlap of acquired and hereditary neuropathy, and provide broader access to genetic diagnosis for patients.

Postbiotic as Novel Alternative Agent or Adjuvant for the Common Antibiotic Utilized in the Food Industry.

Antibiotic resistance is a serious public health problem as it causes previously manageable diseases to become deadly infections that can cause serious disability or even death. Scientists are creating novel approaches and procedures that are essential for the treatment of infections and limiting the improper use of antibiotics in an effort to counter this rising risk. With a focus on the numerous postbiotic metabolites formed from the beneficial gut microorganisms, their potential antimicrobial actions, and recent associated advancements in the food and medical areas, this review presents an overview of the emerging ways to prevent antibiotic resistance. Presently, scientific literature confirms that plant-derived antimicrobials, RNA therapy, fecal microbiota transplantation, vaccines, nanoantibiotics, haemofiltration, predatory bacteria, immunotherapeutics, quorum-sensing inhibitors, phage therapies, and probiotics can be considered natural and efficient antibiotic alternative candidates. The investigations on appropriate probiotic strains have led to the characterization of specific metabolic byproducts of probiotics named postbiotics. Based on preclinical and clinical studies, postbiotics with their unique characteristics in terms of clinical (safe origin, without the potential spread of antibiotic resistance genes, unique and multiple antimicrobial action mechanisms), technological (stability and feasibility of largescale production), and economic (low production costs) aspects can be used as a novel alternative agent or adjuvant for the common antibiotics utilized in the production of animal-based foods. Postbiotic constituents may be a new approach for utilization in the pharmaceutical and food sectors for developing therapeutic treatments. Further metabolomics investigations are required to describe novel postbiotics and clinical trials are also required to define the sufficient dose and optimum administration frequency of postbiotics.

Symplectic Quantization III: Non-relativistic Limit

First of all we shortly illustrate how the symplectic quantization scheme (Gradenigo and Livi, Found Phys 51(3):66, 2021) can be applied to a relativistic field theory with self-interaction. Taking inspiration from the stochastic quantization method by Parisi and Wu, this procedure is based on considering explicitly the role of an intrinsic time variable, associated with quantum fluctuations. The major part of this paper is devoted to showing how the symplectic quantization scheme can be extended to the non-relativistic limit for a Schrödinger-like field. Then we also discuss how one can obtain from this non-relativistic theory a linear Schrödinger equation for the single-particle wavefunction. This further passage is based on a suitable coarse-graining procedure, when self-interaction terms can be neglected, with respect to interactions with any external field. In the Appendix we complete our survey on symplectic quantization by discussing how this scheme applies to a non-relativistic particle under the action of a generic external potential.

In Ukrainian

Brownian motors belong to the class of nanoscale devices that use the thermal noise of the environment as one of the necessary components in the mechanism of their operation. Today, there are a lot of practical implementations of such nanomachines, both inorganic, fairly simple mechanisms produced artificially, and more complex ones created from separate biological components available at the cellular level. One of the options for implementing the mechanism of straightening the chaotic thermal noise of the environment into unidirectional motion is the presence of a motor particle in the field of action of an asymmetric periodic stationary potential, which undergoes certain small disturbances (fluctuations) periodically over time. To describe such asymmetric one-dimensional structures (for example, dipole chains or fibers of the cytoskeleton) in the theory of Brownian motors, two model potentials are most often used: piecewise linear sawtooth and double sinusoidal. In this work, within the framework of the approximation of small fluctuations, a model of a pulsating Brownian motor with a stationary double sinusoidal potential and a disturbing small harmonic signal is considered. A new method of parametrization of such a problem is proposed, which allows to separate the contributions from various factors affecting the operation of the ratchet, and the numerical procedure for calculating the average speed of the directional movement of nanoparticles for the selected type of model potentials is specified. A number of numerical dependences of the average speed on the main parameters of the system were obtained. Peculiarities of the behavior of the motor as dependent on the parameter responsible for asymmetry and the number of potential wells on the spatial period of the stationary potential have been investigated. It is shown that the direction of the generated flux of nanoparticles depends not only on the phase shift between the stationary and fluctuating components of the potential, but also on the temperature of the system and the frequency of fluctuations, i.e., a possibility of temperature-frequency control of the direction of movement in the considered model has been found. Diagrams have been constructed that allow you to choose the ratio between the parameters of the nanomotor to create a flux of particles in the desired direction.

KIBRA anchoring the action of PKMζ maintains the persistence of memory.

How can short-lived molecules selectively maintain the potentiation of activated synapses to sustain long-term memory? Here, we find kidney and brain expressed adaptor protein (KIBRA), a postsynaptic scaffolding protein genetically linked to human memory performance, complexes with protein kinase Mzeta (PKMζ), anchoring the kinase's potentiating action to maintain late-phase long-term potentiation (late-LTP) at activated synapses. Two structurally distinct antagonists of KIBRA-PKMζ dimerization disrupt established late-LTP and long-term spatial memory, yet neither measurably affects basal synaptic transmission. Neither antagonist affects PKMζ-independent LTP or memory that are maintained by compensating PKCs in ζ-knockout mice; thus, both agents require PKMζ for their effect. KIBRA-PKMζ complexes maintain 1-month-old memory despite PKMζ turnover. Therefore, it is not PKMζ alone, nor KIBRA alone, but the continual interaction between the two that maintains late-LTP and long-term memory.

Pharmacogenomic insights in psychiatric care: uncovering novel actionability, allele-specific CYP2D6 copy number variation, and phenoconversion in 15,000 patients

Pharmacogenomic testing has emerged as an aid in clinical decision making for psychiatric providers, but more data is needed regarding its utility in clinical practice and potential impact on patient care. In this cross-sectional study, we determined the real-world prevalence of pharmacogenomic actionability in patients receiving psychiatric care. Potential actionability was based on the prevalence of CYP2C19 and CYP2D6 phenotypes, including CYP2D6 allele-specific copy number variations (CNVs). Combined actionability additionally incorporated CYP2D6 phenoconversion and the novel CYP2C-TG haplotype in patients with available medication data. Across 15,000 patients receiving clinical pharmacogenomic testing, 65% had potentially actionable CYP2D6 and CYP2C19 phenotypes, and phenotype assignment was impacted by CYP2D6 allele-specific CNVs in 2% of all patients. Of 4114 patients with medication data, 42% had CYP2D6 phenoconversion from drug interactions and 20% carried a novel CYP2C haplotype potentially altering actionability. A total of 87% had some form of potential actionability from genetic findings and/or phenoconversion. Genetic variation detected via next-generation sequencing led to phenotype reassignment in 22% of individuals overall (2% in CYP2D6 and 20% in CYP2C19). Ultimately, pharmacogenomic testing using next-generation sequencing identified potential actionability in most patients receiving psychiatric care. Early pharmacogenomic testing may provide actionable insights to aid clinicians in drug prescribing to optimize psychiatric care.

Abstract PO5-13-09: Clinical usage of a CLIA accredited protein/phosphoprotein assay for breast cancer: Primary usage cases and significant findings in the HER2- setting

Abstract Background: A CLIA-accredited assay that measures the expression and/or activation levels of 32 clinically actionable protein and phosphoprotein analytes in clinical tissue biopsy samples was launched in January 2021. The current intended use population for the assay is for patients with late/advanced stage breast cancer wherein molecular profiling is being utilized for clinical decision making. Assessment of physician ordering practices, clinical use dynamics as well as protein/phosphoprotein actionability frequencies were determined for clinically actionable biomarkers. Methods: A total of 219 cases have been processed to date, with mean turn-around time of 16.4 days. The assay utilizes laser capture microdissection to enrich tumor epithelium from FFPE core needle biopsy and resection material coupled to reverse phase protein array. Results for each of the 32 analytes are generated by comparing each patient to a reference population and reported both as a relative quartile and as a continuous percentile compared to the reference population (0-100%). For the purposes of this analysis, significant expression/activation cutpoints were set at the 40th percentile threshold. Results: To date, clinicians have requested the test most frequently to identify potential therapeutic targets in patients with HER2-negative disease (84% of all tested patients, 36% were triple-negative). Despite the majority of cases being HER2-negative, we found that phosphorylated (p) HER2 (Y1248) was found to be activated in 17% of all HER2-negative cases and 19% of triple negative breast cancer cases (TNBC). pHER2 was concurrently activated with pHER3 (Y1289) in 15% (12/80) of TNBC cases and 13% (24/187) of all HER2-negative cases. pHER2 presented concurrently with pEGFR (Y1068 or T654) in 14% (11/80) of TNBC cases and 14% (26/187) of all HER2- cases. Expression of TROP2 was observed in 16% of HER2-negative patients including 11% of ER+/HER2- and 23% of TNBC cancers. MHCII expression, a recently described candidate predictive biomarker of anti-PDL1/PD1 response in TNBC, was found to be expressed in 29% of TNBC patients. Activation frequencies of other clinically relevant drug targets in HER2-negative disease such AKT and mTOR pathway activation was also assessed. We found that pAKT (S473 and/or T308) was activated in 7% of ER+/HER2- cases and 14% of TNBC. Concurrent with AKT activation, at least one additional member of the AKT-mTOR pathway (mTORC1 (S2448), 4E-BP1 (S65), p70S6K (T389), or S6RP (S235/S236) was co-activated in 50% and 45% of ER+/HER2- and TNBC cancers respectively. Conclusion: This initial assessment of a CLIA LDT protein/phosphoprotein assay utilized to date found that physicians most often order the test for advanced stage HER2-negative breast cancer. Activation/expression of clinically important protein drug targets with potential actionability in HER2-negative disease was observed in a significant number of cases and demonstrates the power of the assay to elucidate actionable targets for potential therapeutic intervention. Citation Format: Claudius Mueller, Brian Corgiat, Emanuel Petricoin, Kayla Sparks, Joyce O'Shaughnessy, Chelsea Gawryletz, Matthew Schwartz, Justin Davis. Clinical usage of a CLIA accredited protein/phosphoprotein assay for breast cancer: Primary usage cases and significant findings in the HER2- setting [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-13-09.

Germline Genetic Mutations in Adult Patients with Sarcoma: Insight into the Middle East Genetic Landscape.

Data on germline mutations in soft tissue and bone sarcomas are scarce. We sought to identify the prevalence of germline mutations in adult sarcoma patients treated at a tertiary cancer center. Newly diagnosed patients were offered germline genetic testing via an 84-gene panel. The prevalence of pathogenic germline variants (PGVs) and their association with disease-, and patient- related factors are reported. A total of 87 patients were enrolled, the median age was 48 (19-78) years, and 47 (54%) were females. Gastrointestinal stromal tumors (n = 12, 13.8%), liposarcoma (n = 10, 11.5%), and Ewing sarcoma (n = 10, 11.5%) were the main subtypes. A total of 20 PGVs were detected in 18 (20.7%) patients. Variants of uncertain significance, in the absence of PGVs, were detected in 40 (45.9%) patients. Young age (p = 0.031), presence of a second primary cancer (p = 0.019), and female gender (p = 0.042) were correlated with the presence of PGVs. All identified PGVs have potential clinical actionability and cascade testing, and eight (44.44%) suggested eligibility for a targeted therapy. Almost one in five adult patients with soft tissue and bone sarcomas harbor pathogenic or likely pathogenic variants. Many of these variants are potentially actionable, and almost all have implications on cancer screening and family counselling. In this cohort from the Middle East, younger age, presence of a second primary tumor, and female gender were significantly associated with higher PGVs rates. Larger studies able to correlate treatment outcomes with genetic variants are highly needed.

Cluster bearing of resident PAH/BTEXs contaminants under double-diffusion of invaded supercritical carbon dioxide in sedimentary geostorage media

This work reveals a key goestorage mechanism of supercritical carbon dioxide in a sedimentary soil sample, with a clustering response of resident contaminants such as benzene, naphthalene, and pyrene. These contaminants are deposited on the surface of the solid bundles with a mass film thickness of 5 μm. The injection boundaries of sCO2 are ranged between 300−330 K, and 8−10 MPa, with a mass flow rate of 0.05–0.15 kg/min. A variant of Color Fluid Lattice-Boltzmann model is developed to mimic the breakthrough of sCO2 front in the pore bodies under the effect of generated clusters such as BN-embedded tetraphene. During the spatiotemporal invasion, the interfacial mass diffusion is jumped in Gaussian magnitudes with dominant effects of mass flow rate and injection pressure. The growth of BN-tetraphene revealed the authority of a critical operating time to promote the action of the residual chemical potential on the solvation power of sCO2. However, this cluster is affected by a secondary degradation following the increased concentration of sCO2 in the pore throats of the microporous. Remarkable diffusion is achieved in the case of sCO2/naphthalene, with a large amount of collected naphthalene and relatively low clogged pores, due to the supercritical solvation power of CO2 inside the microporous. These results support the theory of carbon capture and storage in reactive porous reservoirs.

A Consequence-Informed Licensing Path Selection for the Design of Physical Protection Systems at Commercial Nuclear Power Facilities

The survivability of the domestic nuclear power industry depends on the cost-competitiveness of safe and secure nuclear power generation. Advanced reactor design concepts aim to have increased safety margins over traditional large light water reactors (LWRs). With increased safety margins comes the potential for a corresponding decrease in off-site risk to the general public from a hypothetical release of radioactivity due to sabotage or theft. Without sacrificing safety or security, advanced reactor designers may be able to achieve operational cost improvements over current LWRs in part by designing less burdensome physical protection systems (PPSs) and by replacing on-site response forces with off-site response forces. To accommodate these developments, the U.S. Nuclear Regulatory Commission is drafting new rulemakings for physical security when licensing through the current frameworks in 10 CFR 50 or 10 CFR 52 along with drafting an entirely new licensing framework: 10 CFR 53. A novel technology-inclusive consequence-informed methodology for the selection of the optimal licensing path for the design of PPSs at advanced fixed-site commercial nuclear power facilities is presented herein. This methodology proposes integrating security considerations at the beginning of a reactor facility design effort to streamline the licensing process. Off-site total effective dose equivalents at the exclusion area and low population zone boundaries were identified as the key metrics when determining a design’s most appropriate licensing path that in turn affects the design requirements placed upon the PPS. Given these metrics, source-term generation of potential adversary-induced physics-based sabotage actions utilizing severe accident modeling software and off-site plume dispersal modeling were identified as appropriate for determining siting constraints, potential target sets for hypothetical sabotage events, and their subsequent off-site dose consequences. The methodology proposes using the consequence results from the sabotage modeling, in combination with desired cost-saving PPS characteristics, to help inform the licensing path selection. Once a licensing path is chosen, the methodology utilizes the Design and Evaluation Process Outline to evaluate an effective PPS following the licensing requirements placed on the facility. This paper also presents examples of hypothetical commercial nuclear power facilities with varying consequence levels and demonstrations of how to select the optimal licensing pathways for each.

Phyto-cosmeceutical gel containing curcumin and quercetin loaded mixed micelles for improved anti-oxidant and photoprotective activity

Ultra Violet radiations induced skin damage and associated skin disorders are a widespread concern. The consequences of sun exposure include a plethora of dermal conditions like aging, solar urticaria, albinism and cancer. Sunscreens provide effective protection to skin from these damages. Besides FDA approved physical and chemical UV filters, phytoconstituents with their multi functionalities are emerging as frontrunners in Therapy of skin disorders. Objective of this study was to develop novel phyto-dermal gel (PDG) with dual action of sun protection and antioxidant potential using polymeric mixed micelles (PMMs) are nanocarriers. PMMs of Pluronic F127 and Pluronic F68 loaded with curcumin and quercetin were optimized by 32 factorial designs. Responses studied were vesicle size, SPF, entrapment efficiency of curcumin and quercetin and antioxidant activity. Droplet size ranged from 300 to 500 nm with PDI in between 0.248 and 0.584. Combination of curcumin and quercetin showed enhanced sun protection and antioxidant activity. Pluronics played a significant positive role in various parameters. In present studies vesicle size of factorial batches was found to be between 387 and 527 nm, and SPF was found to be between 18.86 and 28.32. Transmission electron microscopy revealed spherical morphology of micelles. Optimized micelles were incorporated into Carbopol 940. Optimized PDG was evaluated for pH, drug content, spreadability, rheology, syneresis, ex vivo permeation, and skin retention. Hysteresis loop in the rheogram suggested thixotropy of PDG. Syneresis for gels from day 0–30 days was found to be between 0% and 12.46% w/w. SPF of optimized PDG was 27±0.5. Optimized PDG showed no signs of erythema and edema on Wistar rats. PMMs thus effectively enhanced antioxidant and skin protective effect of curcumin and quercetin.

Coordinated Control of Carbon Emission Reduction and Air Quality Improvement in the Industrial Sector in Hunan Province

Climate warming and air pollution are the main environmental problems in China. This study used China's Carbon Accounting Database, energy economic model, and air quality model to analyze the potential carbon emission peaking path and synergistic air quality improvement gain in the industrial sector in Hunan Province. Based on China's Carbon Accounting Database and the local industry/energy statistical yearbooks in Hunan, the total CO2 emissions in Hunan Province in 2019 were 310.6 Mt, of which the industrial sector accounted for over 70% of the emissions, mainly from the production and supply of electricity, steam, and heat; the production of non-metallic minerals; and the smelting and pressing of ferrous metals. Three potential industrial carbon emission peaking scenarios were analyzed using the LEAP energy economic model, including the business-as-usual scenario (peaking by 2030), moderate emission reduction scenario (peaking by 2028), and aggressive emission reduction scenario (peaking by 2025), by employing different economic growth rates, energy technology progress, and energy structures of the industrial sector. Furthermore, by combining the anthropogenic air pollutant emission inventory and the regional air quality model WRF-Chem, we analyzed the air quality improvement associated with various carbon emission peak paths. The results showed that the annual mean concentrations of major air pollutants had decreased in the three scenarios, especially in the Chang-Zhu-Tan Region. The aggressive emission reduction scenario was the most effective scenario, followed by the moderate emission reduction scenario and the business-as-usual scenario. Manufacturing was the sector with the most significant synergistic effect of pollution and carbon reduction. When carbon emission peaks were achieved, the annual average concentrations of PM2.5 and PM10 in Hunan Province could be synergistically reduced by 0.6-1.8 μg·m-3 and 1.8-8.9 μg·m-3, respectively. Our findings offer important insights into carbon emission peaking and can provide useful information for potential mitigation actions.

Liposomal nanoformulations with trans-caryophyllene and caryophyllene oxide: do they have an inhibitory action on the efflux pumps NorA, Tet(K), MsrA, and MepA?

This study aimed to evaluate the antibacterial and inhibitory action of NorA, Tet(K), MsrA and MepA efflux pumps in S. aureus strains using the sesquiterpenes named trans-caryophyllene and caryophyllene oxide, both isolated and encapsulated in liposomes. The antibacterial and inhibitory action of these efflux pumps was evaluated through the serial microdilution test in 96-well microplates. Each sesquiterpene and liposome/sesquiterpene was combined with antibiotics and ethidium bromide (EtBr). The antibiotics named norfloxacin, tetracycline and erythromycin were used. The 1199 B, IS-58, RN4220 and K2068 S. aureus strains carrying NorA, Tet(K), MsrA and MepA, respectively, were tested. In the fluorescence measurement test, K2068 S. aureus was incubated with the sesquiterpenes and EtBr, and the fluorescence emission by EtBr was measured. The tested substances did not show direct antibacterial activity, with MIC >1024 μg/mL. Nonetheless, the isolated trans-caryophyllene and caryophyllene oxide reduced the MIC of antibiotics and EtBr, indicating inhibition of NorA, Tet(K) and MsrA. In the fluorescence test, these same sesquiterpenes increased fluorescence emission, indicating inhibition of MepA. Therefore, the sesquiterpenes named trans-caryophyllene and caryophyllene oxide did not show direct antibacterial action; however, in their isolated form, they showed possible inhibitory action on NorA, Tet(K), MsrA and MepA efflux pumps. They may also act in antibiotic potentiation. Further studies are needed to identify the mechanisms involved in antibiotic potentiation and efflux pump inhibitory action.

HD\,7977 and its possible influence on Solar System bodies

In the latest Gaia third data release, one can find extremely small proper motion components for the star HD\,7977. This, together with the radial velocity measurement lead to the conclusion that this star passed very close to the Sun in the recent past. Such a very close approach of a one solar mass star must have resulted in noticeable changes in the motion of all Solar System bodies, especially those on less tight orbits, namely long-period comets (LPCs) and transneptunian objects (TNOs). We estimate and discuss these effects. Our current knowledge on the solar neighbourhood found in the latest Gaia catalogues allowed us to perform numerical integrations and prepare a list of potential stellar perturbers of LPCs. We used this list, made available in the StePPeD database. To study the past motion of LPCs under the simultaneous action of the Galactic potential and passing stars, we used precise original cometary orbits taken from the current CODE catalogue. We examined the reliability of the extremely small proper motion of HD\,7977 and conclude that this star can be an unresolved binary; however, according to the astrometry covering more than a century, the current Gaia data cannot be ruled out. We present the parameters of a very close passage of this star near the Sun. We also show examples of the strong influence of this passage on the past motion of some LPCs. We also discuss the possible influence of this perturber on other Solar System bodies. It is possible that 2.47 Myr ago the one solar mass star HD\,7977 passed as close as 1000 au from the Sun. Such an event constitutes a kind of dynamical horizon for all studies of the past Solar System bodies' dynamics.

Diagnosis of the Condition of Aquatic Ecosystems Using a Partial Assessment of Ecological and Trophic States: An Example of Small Lakes in Northern Poland

The current state of aquatic ecosystems was assessed for lakes in two river–lake systems: Święta Struga (Święte and Ocypelek) and Kałębnica (Czarne Południowe and Kałębie). Trophic states were determined using the Vollenweider, Nürnberg, and Carlson methods. Additionally, shoreline changes were analyzed for all lakes concerning their natural character, and physicochemical parameters were utilized as auxiliary elements in the assessment of the ecological state following the guidelines of Directive 2000/60/EC. Supplementary to these methods, the ecological evaluation of the littoral zone utilized meiobenthic organism grouping as an indicator. The results indicate significant differences among the studied reservoirs. Lake Święte is a reservoir bordering mesotrophy and eutrophy, with the ecological state of the littoral zone showing ongoing trophic development. Lake Ocypelek exemplifies a eutrophic reservoir undergoing progressive degradation. The lakes in the Kałębnica system also exhibit advanced trophic conditions, with Lake Kałębie being a eutrophic reservoir. Its shoreline has been significantly altered due to the development of the direct catchment area. In contrast, Lake Czarne Południowe serves as an example of a mesotrophic reservoir, with a substantially changed shoreline. Considering physicochemical elements and chlorophyll a concentration, the water quality for all examined lakes was found to be below the good category. The diagnosis of the condition of lake aquatic ecosystems requires an individualized approach to each of them. Therefore, employing various methods for their assessment, encompassing physico-chemical, biological, and morphological parameters, provides the opportunity to initiate potential remedial actions that will effectively contribute to their improvement. Conducting low-cost research involving a multidisciplinary approach to diagnose the state of aquatic ecosystems is becoming a crucial element in lake monitoring.