Pronounced Activity Research Articles

New gravity field of comet 67P/C-G based on Rosetta’s Doppler and optical data

The gravity field of a celestial body gives valuable insights into its fundamental properties such as its density and internal structure. The Doppler data collected by the Radio-Science Investigation (RSI) experiment of the Rosetta mission were previously used to determine the gravity field of comet 67P/Churyumov–Gerasimenko up to degree 2 (Pätzold et al., 2016). In the present study we re-estimate the gravity field of 67P/C-G using not only RSI data as before, but also images data from Rosetta’s OSIRIS camera. These data, converted into “landmark” observations, are complementary to RSI data. Therefore, the analysis of combined Doppler and optical data results in a significant improvement in the restitution of Rosetta’s orbit and the determination of the comet gravity field with respect to previous work. Some coefficients of the comet’s gravity field are now resolved up to degree 4. The mass and low degrees estimates are in fairly good agreement with those previously published, but the improvement in their accuracy (i.e. lower sigmas) as well as the better resolution (i.e. maximum degree) of the new gravity field suggests that the distribution of mass in the nucleus may not be uniform, contrary to what was previously thought. Moreover, we estimate a change in the mass of the comet attributed to ice sublimation at its orbital perihelion that is almost three times greater than that previously published. The new estimated mass loss is ΔM=28.0±0.29×109kg, corresponding to 0.28% of the total mass of the comet. Thanks to a precise determination of the degree-1 gravity coefficients, we observe for the first time a motion of the center of mass of the comet by ∼35m northward that could be explained by a more pronounced outgassing activity in the south of the comet due to the orientation of its spin axis relative to the Sun. The temporal evolution (before versus after perihelion) of the other estimated gravity coefficients and in particular degree-2 is more modest (0.8% for C20 and 2% for C22, S22).

Allele-specific expression of AP2-like ABA repressor 1 regulates iron uptake by modulating rhizosphere pH in apple.

Genetic variation within a species can result in allelic expression for natural selection or breeding efforts. Here, we identified an iron (Fe) deficiency-inducible gene, AP2-like ABA repressor 1 (MdABR1), in apple (Malus domestica). MdABR1 exhibited differential expression at the allelic level (MdABR131A and MdABR131G) in response to Fe deficiency. The W-box insertion in the promoter of MdABR131A is essential for its induced expression and its positive role under Fe deficiency stress. MdABR1 binds to the promoter of basic helix-loop-helix 105 (MdbHLH105), participating in the Fe deficiency response, and activates its transcription. MdABR131A exerts a more pronounced transcriptional activation effect on MdbHLH105. Suppression of MdABR1 expression leads to reduced rhizosphere acidification in apple, and MdABR131A exhibits allelic expression under Fe deficiency stress, which is substantially upregulated and then activates the expression of MdbHLH105, promoting the accumulation of plasma membrane proton ATPase 8 (MdAHA8) transcripts in response to proton extrusion, thereby promoting rhizosphere acidification. Therefore, variation in the ABR1 alleles results in variable gene expression and enables apple plants to exhibit a wider tolerance capability and Fe deficiency response. These findings also shed light on the molecular mechanisms of allele-specific expression in woody plants.

Raffinocyclicin is a novel plasmid-encoded circular bacteriocin produced by Lactococcus raffinolactis with broad-spectrum activity against many gram-positive food pathogens.

This study describes the discovery and characterization of raffinocyclicin, a novel plasmid-encoded circular bacteriocin, produced by the raw milk isolate Lactococcus raffinolactis APC 3967. This bacteriocin has a molecular mass of 6,092 Da and contains 61 amino acids with a three-amino acid leader peptide. It shows the highest identity to the circular bacteriocins bacicyclicin XIN-1 (42.62%), aureocyclicin 4185 (42.62%), and garvicin ML (41.53%). A broad inhibitory spectrum includes strains from Staphylococcus, Enterococcus, Streptococcus, Micrococcus, Lactobacillus, Leuconostoc, and Listeria, in addition to a pronounced inhibitory effect against Lactococcus and Clostridium. It displays low sensitivity to trypsin, most likely as a result of its circular nature. The raffinocyclicin gene cluster is composed of 10 genes: 6 core genes, genes encoding an accessory three-component ABC transporter (rafCDE), and a putative transcriptional regulator related to the MutR family. A lack of inhibitory activity in the cell-free supernatant combined with the pronounced activity of cell extracts suggests that the majority of raffinocyclicin is associated with the cell rather than being released to the extracellular environment. This is the first report of a bacteriocin produced by the L. raffinolactis species.IMPORTANCEThe present study aimed to characterize raffinocyclicin, a novel circular bacteriocin produced by the lactic acid bacteria Lactococcus raffinolactis APC 3967. Bacteriocins are generally cationic and hydrophobic peptides with antimicrobial activity, which present diverse biotechnological properties of interest for the food industry. Raffinocyclicin inhibits a wide range of bacteria, including foodborne pathogens, and is stable against different treatments which suggest its potential as a natural biopreservative. Whole-genome sequencing and the genetic analysis of the raffinocyclicin gene cluster showed that it is encoded by plasmid that could be used in the future to transfer the ability to produce the bacteriocin to other lactic acid bacteria for industrial applications. These results together highlight the potential of this novel antimicrobial as a biopreservative to be used by the food industry.

Synthesis, Characterization, Antimicrobial and DFT Studies of Novel Quinolino‐Pyrazole Derivatives

AbstractSynthesis of novel (E)‐N‐(4‐(substituted)benzylidene)‐6‐substituted‐1H‐pyrazolo[3,4‐b]quinoline‐1‐carbothioamides/carboxamides was achieved by the condensation of 6‐substituted‐1H‐pyrazolo[3,4‐b]quinoline‐1‐carbothioamides/carboxamides with substituted benzaldehydes in alcoholic medium in the presence of acetic acid. The structures of synthesized compounds are assigned on the basis of FT IR, 1H NMR, 13C NMR and Mass Spectral data. The compounds are subjected for their antibacterial, antifungal and DFT studies. Compounds, (E)‐6‐chloro‐N‐(4‐(dimethylamino)benzylidene)‐1H‐pyrazolo[3,4‐b]quinoline‐1‐carbothioamide (5 b), (E)‐6‐chloro‐N‐(4‐(dimethylamino)benzylidene)‐1H‐pyrazolo[3,4‐b]quinoline‐1‐carboxamide (5 f), and (E)‐6‐chloro‐N‐(4‐hydroxybenzylidene)‐1H‐pyrazolo[3,4‐b]quinoline‐1‐carboxamide (5 j) possessed pronounced antibacterial and antifungal activities due to their chemical structure.

Whistler echo trains triggered by energetic winter lightning

Lightning generated electromagnetic impulses propagating in the magnetospheric plasma disperse into whistlers – several seconds long radio wave signals with decreasing frequency. Sometimes, multiple reflections form long echo trains containing many whistlers with increasing dispersion. On January 3, 2017, two necessary prerequisites – a pronounced lightning activity and a magnetospheric plasma duct – allowed for observations of a large number of whistler echo trains by the high-latitude station in Kannuslehto, Finland. Our investigation reveals that the duct existed for nearly eight hours. We show that causative lightning sferics arrived to the duct entry from three different winter thunderstorms: a small storm at the Norwegian coast, which produced energetic lightning capable to trigger echo trains in 50% of cases, and two large storms at unexpectedly distant locations in the Mediterranean region. Our results show that intense thunderstorms can repetitively feed electromagnetic energy into a magnetospheric duct and form whistler echo trains after subionospheric propagation over distances as large as 4000 km.

Activity of Streptomyces globosus OPF-9 against the important pathogen Alternaria longipes and biocontrol mechanisms revealed by multi-omic analyses

Plant diseases caused by fungal pathogens represent main threats to the yield and quality of agricultural products, and Alternaria longipes is one of the most important pathogens in agricultural systems. Biological control is becoming increasingly prevalent in the management of plant diseases due to its environmental compatibility and sustainability. In the present study, a bacterial strain, designated as OPF-9, was shown to effectively inhibit the pathogen A. longipes, which was identified as Streptomyces globosus. The culture conditions for OPF-9 were optimized through a stepwise approach and the fermentation broth acquired displayed an excellent inhibitory activity against A. longipes in vitro and in vivo. Further investigations suggested that the fermentation broth exhibited strong stability under a range of adverse environmental conditions. To reveal the molecular bases of OPF-9 in inhibiting pathogens, the whole-genome sequencing and assembly were conducted on this strain. It showed that the genome size of OPF-9 was 7.668 Mb, containing a chromosome and two plasmids. Multiple clusters of secondary metabolite synthesis genes were identified by genome annotation analysis. In addition, the fermentation broth of strain OPF-9 was analyzed by LC-MS/MS non-target metabolomic assay and the activity of potential antifungal substances was determined. Among the five compounds evaluated, pyrogallol displayed the most pronounced inhibitory activity against A. longipes, which was found to effectively inhibit the mycelial growth of this pathogen. Overall, this study reported, for the first time, a strain of S. globosus that effectively inhibits A. longipes and revealed the underlying biocontrol mechanisms by genomic and metabolomic analyses.

Synthesis, Structure, Electrochemical Properties, and Antioxidant Activity of Organogermanium(IV) Catecholate Complexes.

A series of novel organogermanium(IV) catecholates 1-9 of the general formula R'2Ge(Cat), where R' = Ph, Et, have been synthesized. Compounds were characterized by 1H, 13C NMR, IR spectroscopy, and elemental analysis. The molecular structures of 1-3, 6, and 8 in crystal state were established using single-crystal X-ray analysis. The complexes are tetracoordinate germanium(IV) compounds containing a dioxolene ligand in a dianion (catecholato) form. Electrochemical transformations of target germanium(IV) complexes have been studied by cyclic voltammetry. The electro-oxidation mechanism of complexes 1-5, 7, and 10 (the related complex Ph2Ge(3,5-Cat) where 3,5-Cat is 3,5-di-tert-butylcatecholate) involves the consecutive formation of mono- and dicationic derivatives containing the oxidized forms of redox-active ligands. The stability of the generated monocations depends both on the hydrocarbon groups at the germanium atom and on the substituents in the catecholate ring. Compounds 6, 8, and 9 are oxidized irreversibly under the electrochemical conditions with the formation of unstable complexes. The radical scavenging activity and antioxidant properties of new complexes were estimated in the reaction with DPPH radical, ABTS radical cation, and CUPRACTEAC assay. It has been found that compounds 8 and 9 with benzothiazole or phenol fragments are more active in DPPH test. The presence of electron-rich moieties in the catecholate ligand makes complexes 5 and 7-9 more reactive to ABTS radical cation. The value of CUPRACTEAC for organogermanium(IV) catecholates varies from 0.23 to 1.45. The effect of compounds 1-9 in the process of lipid peroxidation of rat liver (Wistar) homogenate was determined in vitro. It was found that most compounds are characterized by pronounced antioxidant activity. A feature of complexes 1, 3, and 5-9 is the intensification of the antioxidant action with the incubation time. In the presence of additives of complexes 3, 5, 6, and 8, an induction period was observed during the process of lipid peroxidation.

The occurrence of Leptospira spp. serogroup Pomona infections in wild boars

Leptospirosis is a worldwide zoonosis caused by different pathogenic serovars of the genus Leptospira, with very complex aetiology and epidemiology. Recent publications suggest that wild boar (Sus scrofa) has an important role in the epizootiology of leptospirosis, representing a potential source of infection. Wild boar populations in urban environments are increasing, posing not only agricultural and ecosystem concerns, but also a public health concern. The aim of this study was to assess the prevalence, temporal patterns and risk factors of Pomona infection in wild boars from areas with pronounced human activity. A total of 159 wild boar serum samples were collected within a health monitoring project in Medvednica Nature Park over a period of six hunting seasons (2012–2016; 2018) and 25.2% samples tested positive. Seropositivity against seven different serogroups was observed, with the highest number of positive reactions to the serogroup Pomona. Annual variation in Pomona reactivity was also detected, and positive reactions were five times more common in females than in males. In most of studies, adults had a higher seroprevalence than younger categories; however, in this study,seroprevalence against Pomona was higher in piglets and subadults. The results indicate that wild boar has the potential of maintaining serovars from the serogroup Pomona in certain natural foci. Due to the expansion of wild boar populations and their intrusion into urban areas, they should be considered a potentially important source of infection for humans and domestic animals.

Synthesis and cytotoxic activity investigations of DNA-tropic 4-dimethylaminostyryl derivatives of N-methyl-pyrimidobenzimidazolium iodides

Introduction. The creation of new compounds with pronounced cytotoxic activity is one of the priority goals in modern medicinal chemistry due to the emergence of multidrug resistance (MDR) to existing chemotherapy drugs for many types of tumour diseases.The objective was the synthesis of DNA-tropic heterocyclic systems containing a quaternized nitrogen atom and one or two styryl moieties as side chains. The synthesized compounds must have pronounced cytotoxic activity and moreover bind with DNA macromolecules effectively.Methods and materials. In this paper, 2 new compounds containing a 10-methyl substituted pyrimidobenzimidazolium core and 1 or 2 4-dimethylaminostyryl moieties as side chains were synthesized. The structures of targeting compounds were confirmed using mass spectrometry and NMR spectroscopy methods. The electronic spectra of these compounds were studied in this work. The investigations of targeting compounds proved their ability to bind with DNA macromolecules. The cytotoxicity of the synthesized compounds was studied on four cell lines.Results. The target compounds were obtained in four-stage synthetic procedure. The purity of the target products was confirmed using NMR spectroscopy and mass spectrometry. The synthesized compounds are effective cyanine dyes with absorption maxima in the dark red and dark violet regions of the visible spectrum for mono and bis 4-dimethylaminostyryl derivatives, respectively in the its electronic absorption spectra. Both of the synthesized compounds can form a stable complex with DNA macromolecules with a significant deepening of the colour in the solutions. The compounds showed pronounced cytotoxic activity in in vitro experiments on a number of cancer-transformed cell lines. The target compounds were shown a high cytotoxic activity against triple-negative breast cancer cells, which are extremely resistant to chemotherapy.Conclusion. 4-Dimethylaminostyryl derivatives of N-methyl-pyrimidobenzimidazolium iodides require a further study as new promising compounds with pronounced antitumor activity.

Investigation of a tamoxifen-RACK7/KDM5C-IFN-I axis for ER+ breast cancer immunomodulation.

9 Background: ER+ breast cancer patients generally have good prognosis. However, significant relapse rates (i.e., hormone drugs, Tamoxifen/TMX) and the poor response to immune checkpoint blockade (ICB) remain critical issues to be addressed. Thus, exploration of anti-ICB resistant mechanisms and alternative targets is needed to improve therapeutic efficacy. Methods: To investigate potential cross-resistant mechanisms between hormone and ICB therapy, ER+ cell lines T47D and MCF7 cells were chronically-treated with TMX for 6 months, and subjected to RNA-Seq and pathway enrichment analysis. Dysregulation of identified factors were validated via western blotting, RT-qPCR, and flow cytometry. Target factors were then inhibited or depleted by shRNA knockdown (KD) or small-compound inhibition. Identified ICB resistance mechanisms were further elaborated by in vitro co-culture assays, syngeneic mouse models, and immune-profiling of tumor microenvironment (TME). Results: Chronic exposure to TMX activates Type I interferon (IFN-I) signaling, induces IFN I-stimulated gene (ISG) expression, and downregulates the H3K4 demethylase and ISG repressor complex known as RACK7/KDM5C. Chronic TMX also upregulates CEACAM1, a well-known ligand for the immune checkpoint receptor TIM3. Results prompt us to evaluate whether loss of RACK7 combined with TMX treatment may modulate a lymphocyte-attractive (via IFN-I), but T-cell exhaustive (via CEACAM1-TIM3) TME. Indeed, in vitro treatment of TMX under RACK7-KD conditions triggers STING upregulation, TBK1 hyperphosphorylation, and a more pronounced activation of ISGs and CEACAM1. In vivo, TMX combined with RACK7-KD enhances tumor growth in the TS/A (ER+) syngeneic mouse model, while immune-profiling reveal that this combination promotes lymphocyte infiltration with a higher population of terminally exhausted CD8+ T-cells in the TME. Conclusions: Our data demonstrate that the TMX-induced activation of cGAS/STING pathway and RACK7 downregulation coordinately shape the IFN-I and immune checkpoint signaling axes in ER+ breast cancer. This TMX–RACK7–IFN-I regulatory network promotes a lymphocyte-attractive TME via IFN-I signaling activation, whereas induction of inhibitory ligands renders T-cells to be terminally-exhausted and unable to kill tumors. These findings highlight the potential use of TMX’s STING-agonistic effect in re-shaping the “cold” breast cancer TME, and the use of combined TMX and anti-TIM3 or anti-CEACAM1 blockade to improve ICB therapy.

MANIFESTATIONS OF ENDOGENOUS INTOXICATION SYNDROME DEPENDING ON ITS ACTIVITY ACCORDING THE LEVEL OF MEDIUM-MASS MOLECULES

Substances of endogenous intoxication syndrome (EIS), which belong to medium-mass molecules (MMM), have cardiovascular toxicity; their content is increased in conditions of chronic heart failure. However, the influence of EIS activity has been studied not enough, which determined the relevance and expediency of our study.Aim. In order to compare the laboratory-instrumental features of the course of metabolically associated liver steatosis (LS) under the conditions of pronounced and insignificant activity of EIS, 19 patients (10 men, 9 women; average age 61,8 years) with coronary artery disease (CAD), atherosclerotic cardiosclerosis, HF of I-II FC and sonographically diagnosed LS were examined. Depending on the level of MMM, patients were divided into two groups with pronounced EIS (MMM >0,6 units) and moderate activity (MMM <0,6 units), which were identical in gender and age composition, hemodynamic indicators, body mass index and area body surface. Photometric determination of MMM total and at wave lengths of 238, 254, 266, 282 nm in blood and urine was carried out; determination of blood L-arginine and urine nitrites, leptin were provided; aromaticity coefficient 238/282, hepato-steatosis index, AST/platelet ratio, nuclear intoxication index (NII), the ratio of lymphocytes and neutrophils to monocytes were calculated. All results were calculated statistically, the level of significance was taken as p<0.05.The results. Among the examined patients, 36.8% had high EIS activity (grades 2-3), and in 63.2% it was moderate (grade 1). Patients with pronounced EIS activity were characterized by hypoalbuminemia, dyslipidemia, low leptin content and higher arginine level, peripheral blood lymphopenia, and relative thinning of the heart walls. The content of MMM254,266,282 in blood was correlated with the size of the left ventricle in diastole, MMM266,282 in urine - with total cholesterol, low and very low density its particles and triglycerides, the aromaticity coefficient - with urinary nitrites. Integral hematological NII was directly proportional to diastolic pressure, and the lymphocyte/monocyte ratio - to systolic pressure. The ratio of neutrophils to monocytes and AST/platelets were correlated with the content of total bilirubin; and the hepato-steatosis index - with high-density lipoproteins and the coefficient of atherogenicity.Conclusion. Patients with concomitant metabolic-associated steatosis of the liver and a high level of EIS were characterized by metabolic disorders. Specific indicators of EIS correlated with parameters of lipid metabolism and hemodynamics.

Консервативная тактика ведения врожденного и инфантильного нефротического синдрома: опыт одного центра

Treatment tactics for patients with congenital nephrotic syndrome (CNS) varies from aggressive kinds, such as early nephrectomy, to conservative ones that include diuretic and nutritional support. The purpose of this research was to assess the effectiveness of conservative treatment of children with congenital and infantile nephrotic syndromes. Materials and methods used: a single-center retrospective study of 11 pediatric patients who had been manifested with NS within their first year of life and had required diuretic therapy, was conducted. The effectiveness of conservative therapy was assessed as preservation of the renal function according to glomerular filtration and satisfactory weight/height and height alone parameters’ dynamics that ensure the safety of kidney transplantation. Results: despite the molecular genetic study was conducted in all 250 children with NS, the described 11 have had verified pathogenic variants as follows: in the NPHS1 gene in 5 (45.5%, CI 16.8-76.6%), in the NPHS2 gene in another 5 (45.5%, CI 16.8-76.6%) and a single patient with none of a kind. It was revealed that despite the persistence of pronounced NS laboratory activity, the edema gradually disappeared against the background of conservative therapy, which in its turn had made it possible to refrain from early nephrectomy as well as to begin the renal replacement therapy over the age of 3 (4) y/o. 9 (81.8%, CI 48.2-97.7%) had satisfactory weight and height parameters at the age of 3 y/o. Only a single patient had undergone the early nephrectomy at the age of 4 months old, that was then followed by a successful kidney transplant at the age of 1 year and 4 months old, which, however, did not affect the then positive height prognosis. Conclusion: thus, reasonably selected conservative therapy for CNS can be effective against edematous syndrome and contribute to satisfactory weight/height growth parameters without early nephrectomy and, accordingly, the start of dialysis during the first year of life.

Targeting the PAC1 receptor mitigates degradation of myelin and synaptic markers and diminishes locomotor deficits in the cuprizone demyelination model.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system with a strong neuroinflammatory component. Current treatments principally target the immune system but fail to preserve long-term myelin health and do not prevent neurological decline. Studies over the past two decades have shown that the structurally related neuropeptides VIP and PACAP (vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide, respectively) exhibit pronounced anti-inflammatory activities and reduce clinical symptoms in MS disease models, largely via actions on their bivalent VIP receptor type 1 and 2. Here, using the cuprizone demyelination model, we demonstrate that PACAP and VIP, and strikingly the PACAP-selective receptor PAC1 agonist maxadilan, prevented locomotor deficits in the horizontal ladder and open field tests. Moreover, only PACAP and maxadilan were able to prevent myelin deterioration, as assessed by a reduction in the expression of the myelin markers proteolipid protein 1, oligodendrocyte transcription factor 2, quaking-7 (APC) and Luxol Fast Blue staining. Furthermore, PACAP and maxadilan (but not VIP), prevented striatal synaptic loss and diminished astrocyte and microglial activation in the corpus callosum of cuprizone-fed mice. Invitro, PACAP or maxadilan prevented lipopolysaccharide (LPS)-induced polarisation of primary astrocytes at 12-24 h, an effect that was not seen with maxadilan in LPS-stimulated microglia. Taken together, our data demonstrates for the first time that PAC1 agonists provide distinctive protective effects against white matter deterioration, neuroinflammation and consequent locomotor dysfunctions in the cuprizone model. The results indicate that targeting the PAC1 receptor may provide a path to treat myelin-related diseases in humans.

Influence of the Extraction Method on the Biological Potential of Solidago virgaurea L. Essential Oil and Hydrolates.

Solidago virgaurea L., or European goldenrod, has a long tradition in folk medicine due to the wide range of its biological activity. This paper aimed to investigate the antimicrobial and antioxidative potential of S. virgaurea essential oil and hydrolates obtained by traditional and novel extraction techniques. For that purpose, hydrodistillation, microwave-assisted hydrodistillation and solvent-free extraction were performed. Analysis of the composition of essential oils indicated the presence of 59 different compounds with cyclocolorenone, germacrene D and spathulenol being the dominant in all essential oil samples. Antimicrobial activity was detected in all the analyzed samples, with higher effect on Gram-positive microorganisms compared to Gram-negative. Regarding the type of performed extraction process, the introduction of microwaves induced higher antimicrobial and antioxidative potential in both essential oils and hydrolates. Hydrolates obtained in microwave-assisted processes had pronounced antioxidative activity, which creates a good basis for further investigation of this side product's potential use in the food, cosmetic and pharmaceutical industries.

Worse fibro-inflammatory activity on diagnostic liver biopsy adversely impacts biochemical remission in autoimmune hepatitis

BackgroundAutoimmune hepatitis (AIH) patients can present with advanced fibrosis at diagnosis or may progress to the same if biochemical remission on treatment is not achieved. MethodsWe conducted a single-center retrospective analysis of 34 pediatrics and 39 adult AIH patients. Three pathologists, blinded to clinical information, reviewed the diagnostic liver biopsy (DLB) slides of AIH patients. We evaluated the impact of clinical, laboratory, and histopathologic parameters on outcomes including biochemical remission (BR). ResultsIncidence of advanced (Ludwig stage 3 or 4) fibrosis on DLB was 45.2 %. AIH patients with advanced fibrosis had higher median Ishak score (p < 0.001) and higher IgG level (p = 0.01) at diagnosis. The incidence of BR at 6-month (31.2% vs. 88.6 %, p = 0.001) and 1-year (68.8% vs. 88.6 %, p = 0.04) post-diagnosis was significantly lower in AIH patients with advanced fibrosis. Although not statistically significant, a higher proportion of AIH patients with advanced fibrosis were on high dose of steroids (58% vs. 37.9 %, p = 0.1) at 1 year post diagnosis. Higher serum IgG level at diagnosis was associated with lower odds of achieving BR at 6-month (p = 0.004) and 1-year (p = 0.03) post-diagnosis in multivariate analysis. Pediatric age at diagnosis (p = 0.02) was associated with higher steroid dose at 1-year post-diagnosis in univariate analysis. ConclusionsFindings of advanced fibrosis on DLB of AIH patients was accompanied by more pronounced necro-inflammatory activity and higher serum IgG level, which translated to lower rates of BR and higher exposure to steroids during the first year after diagnosis.

Unusual norcucurbitacin glycosides from the roots of Siraitia grosvenorii

Siraitia grosvenorii Swingle is one of the first approved medicine food homology species in China, and it has been used as a natural sweetener in the food industry and as a traditional medicine to relieve cough and reduce phlegm. However, many S. grosvenorii roots are discarded yearly, which results in a great waste of resources. Twelve undescribed norcucurbitacin-type triterpenoid glycosides, siraitiaosides A-L (1–12), and six known analogs (13–18) were isolated from the roots of S. grosvenorii. The structures of isolated norcucurbitacin glycosides were elucidated by comprehensive data analyses, including HRESIMS, UV, IR, NMR, ECD calculations, and X-ray crystallography analysis. Siraitiaosides A-E (1–5) featured an unusual 19,29-norcucurbitacin framework while siraitiaosides F-L (6–12) featured a rare 29-norcucurbitacin framework. Notably, compound 4 displayed moderate anti-acetylcholinesterase (AChE) activity with an IC50 of 21.0 μM, meanwhile, compounds 16 and 18 exhibited pronounced cytotoxic activities against MCF-7, CNE-1, and HeLa cancer cell lines with IC50 values of 2.1–15.2 μM. In silico studies showed that compound 4 bound closely to AChE with a binding energy of −5.04 kcal/mol, and compound 18 could tightly bind to PI3K, AKT1, ERK2, and MMP9 proteins that related to autophagy, apoptosis, migration/invasion, and growth/proliferation. In summary, the roots of Siraitia grosvenorii have potential medicinal values due to the multiple bioactive components.

Synthesis of antibacterial fluorescent carbon dots and green coal-like hydrochar from tea Industry byproducts via hydrothermal carbonization

This study introduces an experimental framework employing hydrothermal carbonization (HTC) for the valorisation of factory tea waste as a solid fuel. Employing a centre composite design and response surface methodology, the investigation systematically assesses the influence of two critical process parameters, temperature (180–220 °C) and time (0–240 min), on higher heating value (HHV), hydrochar yield, and energy yield. The study identifies an optimized HTC condition (220°C, 55 min) resulting in the recorded HHV of 22.26±1.10 Mj/Kg. Combustion characteristics and kinetics of the factory tea waste-derived hydrochar (TW-hydrochar) is analysed through TGA and DTG, complemented by structural elucidation via FTIR and FE-SEM. Concurrently, the study reports the observation of carbon dots (TW-CDs) generation during TW-hydrochar production, characterized comprehensively through UV–visible spectroscopy, TEM, XRD, XPS, Zeta potential, and fluorescence methods. Further, antimicrobial properties of TW-CDs are rigorously investigated against Bacillus subtilis and Escherichia coli, manifesting pronounced antibacterial activity against B. subtilis and E. coli as evidenced by a 12 mm and 11 mm inhibition zone, respectively. This research contributes to the scientific understanding of tea waste valorization through HTC, providing insights into cleaner fuel options and the emergence of carbon dots with potential antibacterial applications.

Antiplasmodial action of 4-nitrobenzenesulfonamide chalcones: Design, synthesis, characterisation, in vitro and in silico evaluation against blood stages of Plasmodium falciparum 3D7.

Malaria is an intracellular protozoan parasitic disease caused by Plasmodium species with significant morbidity and mortality in endemic regions. The complex lifecycle of the parasite and the emergence of drug-resistant Plasmodium falciparum have hampered the efficacy of current anti-malarial agents. To circumvent this situation, the present study attempts to demonstrate the blood-stage anti-plasmodial action of 26 hybrid compounds containing the three privileged bioactive scaffolds (sulfonamide, chalcone, and nitro group) with synergistic and multitarget action. These three parent scaffolds exhibit divergent activities, such as antibacterial, anti-malarial, anti-fungal, anti-inflammatory, and anticancer. All the synthesised compounds were characterised using various spectroscopic techniques. The in vitro blood-stage inhibitory activity of 26 hybrid compounds was evaluated against mixed-stage culture (asynchronize) of human malarial parasite P. falciparum, Pf 3D7 at different concentrations ranging from 25.0 µg/mL to 0.78 µg/mL using SYBR 1 green assay, with IC50 values determined after 48 h of treatment based on the drug-response curves. Two potent compounds (11 and 10), with 2-Br and 2,6-diCl substitutions, showed pronounced activity with IC50 values of 5.4 µg/mL and 5.6 µg/mL, whereas others displayed varied activity with IC50 values ranging from 7.0 µg/mL to 22.0 µg/mL. Both 11 and 10 showed greater susceptibility towards mature-stage trophozoites than ring-stage parasites. The hemolytic and in vitro cytotoxicity assays revealed that compounds 11 and 10 did not cause any toxic effects on host red blood cells (uninfected), human-derived Mo7e cells, and murine-derived BA/F3 cells. The in vitro observations are consistent with the in silico studies using P. falciparum-dihydrofolate reductase, where 11 and 10 showed a binding affinity of -10.4 Kcal/mol. This is the first report of the hybrid scaffold, 4-nitrobenzenesulfonamide chalcones, demonstrating its potential as an anti-plasmodial agent.

Analysis of data on phytophotodermatitis caused by contact with the sap of plants of the genus Hogweed (&lt;i&gt;Heracleum&lt;/i&gt; L.)

The rapid spread of overgrowth of plants of the genus Hogweed, associated with their use as an agricultural fodder crop, is currently a serious problem for the Russian Federation. This process has a negative impact on the biodiversity of the vegetation cover, destroying natural ecosystems and causing significant economic damage. However, the active spread of hogweeds on the territory of the Russian Federation would not be so catastrophic if it were not for their aggressive properties: in contact with the skin, plant sap causes phytophotodermitis, which is a burn similar to thermal burns of I, II and III degrees. The article considers qualitative and quantitative composition of the main biologically active substances of hogweeds sap and shows that the biologically active substances causing phytophotodermatitis are furanocoumarins. It has been established that the pronounced photosensitizing activity of furanocoumarins is determined by the presence of a furan ring at positions 6,7 and 7,8 of coumarin. Such compounds include psoralen and its main derivatives: xanthotoxin, bergapten, bergamotin, imperatorin, isopimpinellin and angelicin (isopsoralen) and its main derivatives: sfondin, pimpinellin, isobergapten. Substitution of furan ring condensed with coumarin ring as well as change of its position leads to loss of photosensitizing activity. It was determined that the activity of plant sap of the genus Hogweed is in direct dependence on such factors as qualitative and quantitative content of furanocoumarins in the plant sap, the amount of sap and the area of the skin lesion zone, the time of contact of the affected skin areas with the plant sap, the intensity of ultraviolet irradiation and the time of its effect on the affected areas, as well as the peculiarities of each person (e.g., age, skin phototype). The methods of standard therapy of three clinical forms of phytophotodermatitis were analyzed. It was found that currently no specific clinical recommendations for the diagnostics and treatment of phytophotodermatitis resulting from contact with the sap of hogweeds. At the end of the article, the conclusion is formulated that one of current and promising tasks of pharmaceutical technology may be the development of drugs used in the treatment of burns caused by the sap of plants of the genus Hogweed, taking into account the mechanism of action of furanocoumarins.

Valorizing recycled paper through chitosan and glyoxal-chitosan treatments: Synergistic effects on mechanical and physical properties

The present study investigates the efficacy of chitosan and glyoxal-crosslinked chitosan (Chi-Gly) as reinforcing agents for enhancing the mechanical, physical, and functional properties of recycled paper. The research aims to evaluate the comparative performance of these two forms of chitosan in imparting strength characteristics and improved functionality to recycled paper substrates. Chitosan and Chi-Gly solutions prepared via glyoxal crosslinking were incorporated into recycled pulp suspensions at varying dosages. Laboratory handsheets were fabricated, and their properties were systematically evaluated through mechanical testing, morphological analysis, wettability measurements, and antibacterial assays. The results demonstrated significant improvements in the tensile index, burst index, and bending resistance for the chitosan and Chi-Gly treated papers, with the Chi-Gly exhibiting superior reinforcement. Notably, the Chi-Gly treated paper exhibited a higher wet tensile index and lower water absorption capacity than the control. SEM analysis revealed a denser, more cohesive fiber network facilitated by chitosan and Chi-Gly, aiding the reinforcement. The treated papers exhibited reduced hydrophobicity and pronounced antibacterial activity against E. coli (a gram-negative bacterium) and S. aureus (a gram-positive bacterium), with the Chi-Gly treatment outperforming chitosan. Notably, the treatments improved the functional properties without negatively impacting optical brightness. The findings highlight the synergistic effects of glyoxal crosslinking on chitosan’s reinforcing ability and the potential of these biopolymers as sustainable and multifunctional additives for the recycled paper industry.