Long-term Circulation Research Articles

Influences of the Kuroshio on the salinity budget of the Seto Inland Sea, Japan

The Seto Inland Sea (SIS) harbors abundant aquatic biological diversity, while its ecosystem has been affected by climate change in recent years. Previous studies have shown that the residual current in the SIS varies significantly under the influence of the Kuroshio. To isolate the open ocean influences, salinity transport and the associated salinity budget in the SIS were investigated, as a conservative variable characterizing the estuarine hydrodynamics, using a high-resolution, long-term 3D circulation model. Our findings indicate that the fluctuations of salinity fluxes were influenced by the position of the Kuroshio axis and were highly correlated with the associated volume fluxes. The clockwise eastward transport from Bungo to Kii varies seasonally with an increase in winter and a decrease or counterclockwise increase in summer. The total salinity in each of the eight sub-basins of the SIS was also correlated with the salinity fluxes at the straits connecting the sub-basins. The total salinity in the western sub-basins increased with the eastward clockwise transport and decreased with the westward counterclockwise transport, whereas the eastern sub-basins showed less correlations, resulting in a zonal difference of salinity response to the open ocean.

Platelet and Erythrocyte Membranes Coassembled Biomimetic Nanoparticles for Heart Failure Treatment.

Cardiac fibrosis is a prevalent pathological process observed in the progression of numerous cardiovascular diseases and is associated with an increased risk of sudden cardiac death. Although the BRD4 inhibitor JQ1 has powerful antifibrosis properties, its clinical application is extremely limited due to its side effects. There remains an unmet need for effective, safe, and low-cost treatments. Here, we present a multifunctional biomimetic nanoparticle drug delivery system (PM&EM nanoparticles) assembled by platelet membranes and erythrocyte membranes for targeted JQ1 delivery in treating cardiac fibrosis. The platelet membrane endows PM&EM nanoparticles with the ability to target cardiac myofibroblasts and collagen, while the participation of the erythrocyte membrane enhances the long-term circulation ability of the formulated nanoparticles. In addition, PM&EM nanoparticles can deliver sufficient JQ1 with controllable release, achieving excellent antifibrosis effects. Based on these advantages, it is demonstrated in both pressures overloaded induced mouse cardiac fibrosis model and MI-induced mouse cardiac fibrosis that injection of the fusion membrane biomimetic nanodrug carrier system effectively reduced fibroblast activation, collagen secretion, and improved cardiac fibrosis. Moreover, it significantly mitigated the toxic and side effects of long-term JQ1 treatment on the liver, kidney, and intestinal tract. Mechanically, bioinformatics prediction and experimental validation revealed that PM&EM/JQ1 NPs reduced liver and kidney damage via alleviated oxidative stress and mitigated cardiac fibrosis via the activation of oxidative phosphorylation activation. These results highlight the potential value of integrating native platelet and erythrocyte membranes as a multifunctional biomimetic drug delivery system for treating cardiac fibrosis and preventing drug side effects.

Zincophile Zn2+ Conductor Regulation by Ultrathin Nano MoO3 Coating for Dendrite-Free Zn Anode.

Aqueous battery with nonflammable and instinctive safe properties has received great attention. However, issues related to Zn anode such as side reactions and rampant dendrite growth hinder the long-term circulation of AZMBs. Herein, an ultrathin(35nm) MoO3 coating is deposited on the Zn anode by means of vacuum vapor deposition for the first time. Due to the peculiar layer structure of MoO3, insertion of Zn2+ in ZnxMoO3 acts as Zn2+ ion conductor, which regulates Zn2+ deposition in an ordered manner. Additionally, the MoO3 coating can also inhibit the hydrogen evolution and corrosion reactions at the interface. Therefore, both Zn//MoO3@Cu asymmetric battery and Zn symmetric battery cells manage to deliver satisfactory electrochemical performances. The symmetric cell assembled with MoO3@Zn shows a significant long cycle life of more than 1600h at a current density of 2mA cm-2. Meanwhile, the MoO3@Zn//Cu asymmetric cell exhibits an ultrahigh Zn deposition/stripping efficiency of 99.82% after a stable cycling of 650h at 2mA cm-2. This study proposes a concept of "zincophile Zn2+ conductor regulation" to dictate Zn electrodeposition and broadens novel design of vacuum evaporation for nano MoO3 modified Zn anodes.

A deterministic model for homologous antibody dependant enhancement on influenza infection

Antibody dependant enhancement refers that viral infectivity was unexpectedly enhanced at low antibody concentration compared to when antibodies were absent, such as Dengue, Zika and influenza virus. To mathematically describe switch from enhancement to neutralisation with increase of antibody concentration, one hyperbolic tangent variant is used as switching function in existed models. However, switching function with hyperbolic tangent contains four parameters, and does not always increase with antibody concentration. To address this problem, we proposed a monotonically increasing Logistical function variant as switching function, which only contains position parameter and magnitude parameter. Analysing influenza viral titre estimated from 21 focus reduction assay (FRA) datasets from neutralisation group (viral titre lower than negative control on all serial dilutions) and 20 FRA dataset from enhancement group (viral titre higher than negative control on high serial dilution), switching function with Logistic function performs better than existed model independent of both groups and exhibited different behaviour/character; specifically, magnitude parameter estimated from enhancement group is lower, but position parameter estimated from enhancement group is higher. A lower magnitude parameter refers that enhancement group more rapidly switches from enhancement to neutralisation with increase of antibody concentration, and a higher position parameter indicates that enhancement group provides a larger antibody concentration interval corresponding to enhancement. Integrating estimated neutralisation kinetics with viral replication, we demonstrated that antibody-induced bistable influenza kinetics exist independent of both groups. However, comparing with neutralisation group, enhancement group provides higher threshold value of antibody concentration corresponding to influenza infectivity. This explains the observed phenomenon that antibody dependent enhancement enhances susceptibility, severity, and mortality to influenza infection. On population level, antibody dependant enhancement can promote H1N1 and H3N2 influenza virus cooperate to sustain long-term circulation on human populations according to antigenic seniority theory.

Long circulating liposomal platform utilizing hydrophilic polymer-based surface modification: preparation, characterisation, and biological evaluation

Liposomes are one of the most important drug delivery vectors, nowadays used in clinics. In general, polyethylene glycol (PEG) is used to ensure the stealth properties of the liposomes. Here, we have employed hydrophilic, biocompatible and highly non-fouling N-(2-hydroxypropyl) methacrylamide (HPMA)-based copolymers containing hydrophobic cholesterol anchors for the surface modification of liposomes, which were prepared by the method of lipid film hydration and extrusion through 100 nm polycarbonate filters. Efficient surface modification of liposomes was confirmed by transmission electron microscopy, atomic force microscopy, and gradient ultracentrifugation. The ability of long-term circulation in the vascular bed was demonstrated in rabbits after i.v. application of fluorescently labelled liposomes. Compared to PEGylated liposomes, HPMA-based copolymer-modified liposomes did not induce specific antibody formation and did not activate murine and human complement. Compared with PEGylated liposomes, HPMA-based copolymer-modified liposomes showed a better long-circulating effect after repeated administration. HPMA-based copolymer-modified liposomes thus represent suitable new candidates for a generation of safer and improved liposomal drug delivery platforms.

Roles of heat and stress transfer in triggering fault instability in conjugate faulted reservoirs

The presence of multiple conjugate but non-intersecting faults in geothermal reservoirs presents issues related to fault interaction in the presence of complex coupled thermo-hydro-mechanical (THM) processes in influencing the triggering of seismicity. We examine alternate strategies in stimulating such a conjugate-faulted geothermal reservoir analogous to that hosting the Mw 5.5 Pohang earthquake (2017). We evaluate the response of the reservoir to both short-term stimulation (1y) and long-term production (10y), both with and without thermal effects – for a large fault (F1) adjacent to a non-intersecting smaller fault (F2) and in a reverse faulting stress regime. Results suggest that the slip on either fault impacts the stress state on the other fault through stress transfer. Reactivation of the minor fault (F2) transfers stress towards to the upper part of primary fault (F1), inducing instability. The slip of the major fault is delayed by positioning the location of injection away from the junction between the two faults – decreasing the injection depth from 4087.5 m to 3712.5 m delays the time to slip by 2.61 y. Furthermore, thermal stress plays a decisive role in prompting late-stage fault reactivation for long-term fluid circulation where pore pressures have already reached steady state. The pattern of thermal unloading follows the path of fluid transport and heat transfer along the faults. Overall, this study not only advances our understanding of mechanisms of injection-induced fault instability in EGS reservoirs with multiple and closely-interacting faults, but also provides insights into how different injection strategies can delay or mitigate induced seismicity.

Investigation of thermal cooling effect of long-term circulation in Raft River enhanced geothermal system

The Raft River Enhanced Geothermal System (EGS) demonstration project incorporated three hydraulic stimulations in well RRG-9 ST1 to improve geothermal production. This study investigated the injectivity index (injection rate divided by injection pressure) increase during long-term injection into RRG-9-ST1 after the stimulations from the perspective of thermoelasticity. We have used a one-dimensional approximate solution to estimate the injectivity/aperture change due to thermal cooling. The inferred aperture change vs. square root of time falls along a linear trend. The thermal coefficient (a combination of rock thermal properties, rock initial temperature, and injected fluid temperature) back-calculated by fitting the field injection data is in the same order of magnitude as the value directly calculated from these parameters. We have conducted fully-coupled thermal-hydro-mechanical modeling to simulate long-term circulation (cold water injection). The simulated injectivity index increased by 1.7 × 10−8 m3/(Pa·s) after 272 days of cold-water injection, similar to the field data, which increased by 2.5 × 10−8 m3/(Pa·s). Both the trend and the magnitude of the simulated injectivity change match with the field data recorded at Raft River. The injectivity index increased faster at the beginning and then the rate of increase became smaller with time. The injectivity index increase is hypothesized to be the result of fracture aperture increase due to cooling effects. The simulated fracture aperture at the injection well increased by 0.64 mm, and the simulated maximum fracture aperture increased by 1.93 mm. The trend of the simulated aperture change also matches the value interpreted from the field data using the 1D approximate solutions. The study suggests that cooling is the major reason for the injectivity increase at Raft River EGS during the long-term injection. More broadly, cold water injection could serve as a method to increase the injectivity in other settings after high-volume and high rate/pressure hydraulic stimulation

Chitosan in cancer therapy: a dual role as a therapeutic agent and drug delivery system.

Although chemotherapy is still the most preferred treatment for cancer, most chemotherapeutic agents target both cancer cells and healthy cells and cause serious sideeffects due to high toxicity. Improved drug delivery systems (DDSs), which enhance the efficacy of current chemotherapeutic drugs while reducing their toxicity, offer potential solutions to these challenges. Chitosan (CS) and its derivatives are biopolymers with biodegradable, biocompatible, and low-toxicity properties, and their structure allows for convenient chemical and mechanical modifications. In its role as a therapeutic agent, CS can impede the proliferation of tumor cells through the inhibition of angiogenesis and metastasis, as well as by triggering apoptosis. CS and its derivatives are also frequently preferred as DDSs due to their properties such as high drug-carrying capacity, polycationic structure, long-term circulation, and direct targeting of cancer cells. Various therapeutic agents linked to CS and its derivatives demonstrate potent anticancer effects with advantages such as reduced side effects compared to the original drugs, owing to factors like targeted distribution within cancer tissues and sustained release. This review emphasizes the utilization of CS and its derivatives, both as therapeutic agents and as carriers for established chemotherapeutic drugs.

Origin and dispersal of the Mycobacterium tuberculosis Haarlem genotype: Clues from its phylogeographic landscape and human migration

The Haarlem family belongs to the Euro-American phylogenetic lineage of Mycobacterium tuberculosis and is one of the globally spread genotypes of this important human pathogen. In spite of the sporadic observations on drug resistance and peculiar virulence profile, Haarlem remains in the shade of other M. tuberculosis genotypes. I analyzed genotyping data of the Haarlem genotype in light of its pathogenic properties and relevant human migration, to gain insight into its origin, evolutionary history, and current spread. Central Europe is marked with a very high prevalence of both major Haarlem subclades ancestral H3/SIT50 and derived H1, jointly making 33–41% in Czechia, Austria, and Hungary. There is a declining gradient of Haarlem beyond central Europe with 10–18% in Italy, France, Belgium, 10–13% in the Balkan countries and Turkey. Placing the available genetic diversity and ancient DNA data within the historical context, I hypothesize that M. tuberculosis Haarlem genotype likely originated in Central Europe and its primary long-term circulation occurred within the area of the former Austria/Austria-Hungary Empire in the 14th-19th centuries. The genotype is not highly transmissible and its spread was driven by long-term human migration. The European colonial expansion (when accompanied by a sufficient volume of migration) was a vehicle of its secondary dissemination. I conclude that human migration and its lack thereof (but not strain pathobiology) was a major driving force that shaped the population structure of this global lineage of M. tuberculosis. At the same time, Haarlem strains appear over-represented in some ethnic groups which warrants in-depth experimental research.

A facile one-step self-assembly strategy for constructing biocompatible and pH-sensitive polyphenol-based nanoparticles for high-efficiency tumor therapy

Self-assembled supramolecular nanoparticles possess several advantages, including convenient preparation process, high controllability, stability, and multifunctionality, which make them highly beneficial as drug-carriers in field of drug delivery. Size of nano-carriers plays a crucial role in their performance, affecting their ability for long-term circulation and deep penetration into tumor tissues within biological systems. In this study, we present a simple one-step self-assembly strategy for constructing biocompatible and pH-sensitive polyphenol-based nanoparticles for high-efficiency tumor therapy. The self-assembled DOX@F127-TA nanoparticles are achieved through a combination of hydrogen bonding and hydrophobic interactions. The Pluronic F127 (F127) and tannic acid (TA) endow high biocompatibility and satisfactory safety to nano-drug carriers. By adjusting DOX content, DOX@F127-TA nanoparticles are successfully prepared with advantages of high drug content, pH-sensitive, high stability and small size. Additionally, the nanoparticles exhibit low hemolysis performance and electronegativity, which contribute to their long-term circulation stability in vivo. Furthermore, in vitro cytotoxicity, cellular uptake and patient-derived organoids were utilized to evaluate the efficacy of the DOX@F127-TA. The results demonstrate efficient endocytosis, successful organoid drug delivery, and remarkable anti-tumor effects, while exhibiting minimal toxicity to normal cells. Overall, DOX@F127-TA nanoparticles demonstrate great potential as a promising drug delivery platform for high-efficient cancer therapy and practical application.

Genomic epidemiology of third-generation cephalosporin-resistant Escherichia coli from Argentinian pig and dairy farms reveals animal-specific patterns of co-resistance and resistance mechanisms.

Little is known about the ecology of critically important antibiotic resistance among bacteria with the potential to be opportunistic human pathogens (e.g., Escherichia coli) on South American farms. By studying 70 pig and dairy cattle farms in central-eastern Argentina, we identified that third-generation cephalosporin resistance (3GC-R) in E. coli was mediated by mechanisms seen more often in certain species and that 3GC-R pig E. coli were more likely to be co-resistant to florfenicol and amoxicillin/clavulanate. This suggests that on-farm antibiotic usage is key to selecting the types of E. coli present on these farms. 3GC-R E. coli and 3GC-R plasmids were diverse, suggestive of long-term circulation in this region. We identified the de novo mobilization of the resistance gene blaROB from pig pathogens into E. coli on a novel mobile genetic element, which shows the importance of surveying poorly studied regions for antibiotic resistance that might impact human health.

Multi-century (635-year) spring season precipitation reconstruction from northern Pakistan revealed increasing extremes

The Hindu Kush Himalaya region is experiencing rapid climate change with adverse impacts in multiple sectors. To put recent climatic changes into a long-term context, here we reconstructed the region’s climate history using tree-ring width chronologies of climate-sensitive Cedrus deodara and Pinus gerardiana. Growth-climate analysis reveals that the species tree-growth is primarily limited by moisture stress during or preceding the growing season, as indicated by a positive relationship between the chronology and precipitation and scPDSI, and a negative one with temperature. We have reconstructed 635 years (1384–2018 CE) of February–June precipitation using a robust climate reconstruction model that explains about 53% variance of the measured precipitation data. Our reconstruction shows several dry and wet episodes over the reconstruction period along with an increase in extreme precipitation events during recent centuries or years. Long, very wet periods were observed during the following years: 1392–1393, 1430–1433, 1456–1461, 1523–1526, 1685–1690, 1715–1719, 1744–1748, 1763–1767, 1803–1806, 1843–1846, 1850–1855, 1874–1876, 1885–1887, 1907–1909, 1921–1925, 1939–1944, and 1990–1992, while long dry periods were observed during the following years: 1398–1399, 1464–1472, 1480–1484, 1645–1649, 1724–1727, 1782–1786, 1810–1814, 1831–1835, 1879–1881, 1912–1918, 1981–1986, 1998–2003, and 2016–2018 CE. We found predominantly short-term periodicity cycles of 2.0, 2.2, 2.3, 2.4, 2.6–2.7, 2.9, 3.3, 4.8, 8.1–8.3, and 9.4–9.6 years in our reconstruction. Spatial correlation analyses reveal that our reconstruction is an effective representation of the precipitation variability in the westerly climate-dominated areas of Pakistan and adjacent regions. In addition to the influence of regional circulation systems like western disturbances, we found possible teleconnections between the precipitation variability in northern Pakistan and broader-scale climate modes or phases like AMO and ENSO. The study also highlights the prospects of tree-ring application to explore linkages between western disturbance, increasing intensity and frequency of extreme climate events, and analysis of long-term atmospheric circulation over the western Himalayan region.

A comprehensive review of engineered exosomes from the preparation strategy to therapeutic applications.

Exosomes exhibit high bioavailability, biological stability, targeted specificity, low toxicity, and low immunogenicity in shuttling various bioactive molecules such as proteins, lipids, RNA, and DNA. Natural exosomes, however, have limited production, targeting abilities, and therapeutic efficacy in clinical trials. On the other hand, engineered exosomes have demonstrated long-term circulation, high stability, targeted delivery, and efficient intracellular drug release, garnering significant attention. The engineered exosomes bring new insights into developing next-generation drug delivery systems and show enormous potential in therapeutic applications, such as tumor therapies, diabetes management, cardiovascular disease, and tissue regeneration and repair. In this review, we provide an overview of recent advancements associated with engineered exosomes by focusing on the state-of-the-art strategies for cell engineering and exosome engineering. Exosome isolation methods, including traditional and emerging approaches, are systematically compared along with advancements in characterization methods. Current challenges and future opportunities are further discussed in terms of the preparation and application of engineered exosomes.

Enhancing oncolytic virus efficiency with methionine and N-(3-aminoprolil)methacrylamide modified acrylamide cationic block polymer.

Oncolytic virus ablation of tumor cells has the advantages of high tumor selectivity, strong immunogenicity, and low side effects. However, the recognition and clearance of oncolytic viruses by the immune system are the main factors limiting their anti-tumor efficiency. As a highly biosafe and highly modifiable oncolytic virus vector, acrylamide can improve the long-term circulation of oncolytic viruses. Still, it is limited in its uptake efficiency by tumor cells. Herein, we constructed an N-hydroxymethyl acrylamide-b-(N-3-aminopropyl methacrylamide)-b-DMC block copolymer (NMA-b-APMA-b-DMA, NAD) as an oncolytic virus carrier, which not only improves the long-term circulation of oncolytic viruses in the body but also shows excellent stability for loading an oncolytic virus. The data shows that there was no obvious difference in the transfection effect of the NAD/Ad complex with or without neutralizing antibodies in the medium, which meant that the cationic carrier mediated by NAD/Ad had good serum stability. Only 10 micrograms of NAD carrier are needed to load the oncolytic virus, which can increase the transfection efficiency by 50 times. Cell experiments and mouse animal experiments show that NAD vectors can significantly enhance the anti-tumor effect of oncolytic viruses. We hope that this work will promote the application of acrylamide as an oncolytic virus vector and provide new ideas for methods to modify acrylamide for biomedical applications.

Conflicting Evidence between Clinical Perception and Molecular Epidemiology: The Case of Fowl Adenovirus D.

Fowl adenoviruses (FAdVs, species FAdV-A/-E) are responsible for several clinical syndromes reported with increasing frequency in poultry farms in the last decades. In the present study, a phylodynamic analysis was performed on a group of FAdV-D Hexon sequences with adequate available metadata. The obtained results demonstrated the long-term circulation of this species, at least several decades before the first identification of the disease. After a period of progressive increase, the viral population showed a high-level circulation from approximately the 1960s to the beginning of the new millennium, mirroring the expansion of intensive poultry production and animal trade. At the same time, strain migration occurred mainly from Europe to other continents, although other among-continent connections were estimated. Thereafter, the viral population declined progressively, likely due to the improved control measures, potentially including the development and application of FAdV vaccines. An increase in the viral evolutionary rate featured this phase. A role of vaccine-induced immunity in shaping viral evolution could thus be hypothesized. Accordingly, several sites of the Hexon, especially those targeted by the host response were proven under a significant pervasive or episodic diversifying selection. The present study results demonstrate the role of intensive poultry production and market globalization in the rise of FAdV. The applied control strategies, on the other hand, were effective in limiting viral circulation and shaping its evolution.

Mean circulation and its seasonal cycle on the West Florida Shelf as evidenced by multi-decadal time series of moored currents and winds

Time series from a moored array of current velocity and surface meteorological sensors, some with record lengths as long as 25 years, are used to describe both the long-term mean circulation and its seasonal variations on the West Florida Continental Shelf (WFS). The moorings are part of the University of South Florida's Coastal Ocean Monitoring and Prediction System (USF-COMPS), a network of ocean observing assets along with numerical circulation models, all used to describe and understand physical and ecological processes on the WFS. These USF-COMPS observations reveal a coherent, shelf-wide mean circulation pattern with depth-averaged flow directed alongshore and down-coast. The vertical structure and the seasonal variations further describe an inner-shelf, wind-driven upwelling region separated from a deeper-ocean influenced offshore downwelling region by a coastal jet. By adding to the record lengths from previous analyses, the statistics are shown to be robust, with the inferences drawn from shorter records being borne out by the present longer-term analyses.

Application of a Core-Shell Structure Nano Filtration Control Additive in Salt-Resistant Clay-Free Water-Based Drilling Fluid

When drilling into a reservoir, the drilling fluid containing bentonite is prone to solid phase invasion, causing serious damage to the reservoir, and the conventional API barite suspension stability is poor, which makes it easy to cause sedimentation and blockage. Therefore, in order to avoid accidents, we use ultrafine barite to obtain a good suspension stability. More importantly, the method of modifying zwitterionic polymers on the surface of nano-silica is used to develop a temperature-resistant and salt-resistant fluid loss reducer FATG with a core-shell structure, and it is applied to ultra-fine clay-free water-based drilling fluid (WBDF). The results show that the filtration loss of clay-free drilling fluid containing FATG can be reduced to 8.2 mL, and AV can be reduced to 22 mPa·s. Although the viscosity is reduced, FATG can reduce the filter loss by forming a dense mud cake. The clay-free drilling fluid system obtained by further adding sepiolite can reduce the filtration loss to 3.8 mL. After aging at 220 °C for 15 d, it still has significant salt tolerance, the filtration loss is only 9 mL, the viscosity does not change much, a thinner and denser mud cake is formed, and the viscosity coefficient of the mud cake is smaller. The linear expansion test and permeability recovery evaluation were carried out. The hydration expansion inhibition rate of bentonite can reach 72.5%, and the permeability recovery rate can reach 77.9%, which can meet the long-term drilling fluid circulation work in the actual drilling process. This study can provide guidance for technical research in related fields such as reservoir protection.

Epidemiological and Molecular Genetic Analysis of Outbreaks of Acute Intestinal Infections in the Khabarovsk Krai in 2022

Introduction: Acute intestinal infections are amongst the most important health concerns worldwide. The majority of them are caused by viruses spread through environmental objects contaminated with feces. A high incidence of intestinal infections is registered annually in the Far Eastern Federal District of the Russian Federation. Over 50 % of cases of established etiology are induced by rota- and noroviruses. Moreover, outbreaks of viral intestinal infections are registered annually in almost all regions of the Far Eastern Federal District, including the Khabarovsk Krai. Objective: To analyze the incidence of acute intestinal infections and the results of molecular genetics testing of intestinal viruses that caused the outbreaks in the Khabarovsk Krai in the year 2022. Materials and methods: We used epidemiological and statistical methods to analyze the incidence and conducted molecular genetics testing of samples obtained from patients with acute intestinal infections and their contacts in the foci of the disease in the Khabarovsk Krai. Results: The acute intestinal infection situation in the Khabarovsk Krai in 2022 was unfavorable. The regional incidence rate was 20.6 % higher than that in the Far Eastern Federal District, with most diseases induced by intestinal viruses and numerous outbreaks registered. Our epidemiological investigation of six outbreaks revealed the fecal-oral transmission route of infection through contaminated food, household contacts and, probably, water. Molecular genetics testing of the causes of outbreaks showed circulation of norovirus genotypes GII.4Sydney[P16], GII.4Sydney[P31], GII.17[P17], and GII.6[P7] as well as rotavirus A genotypes G9P[8], G4P[8] and G3P[8] in the Khabarovsk Krai. Some of the identified norovirus genotypes had already caused outbreaks in the Khabarovsk Krai: GII.17[P17] – back in 2015 among the population of the Mnogovershinny village, GII.6[P7] – in the years 2018 and 2019 in the city of Khabarovsk, thus indicating long-term circulation of these genotypes. Conclusion: Surveillance over changes in genetic diversity of the viral population is required to evaluate contribution of various gene variants of rota- and noroviruses to the incidence of acute intestinal infections. In this regard, molecular typing of rota- and noroviruses should be performed not only when investigating disease outbreaks, but also when sporadic cases are registered.

Genotypic Characteristics of CTX–VPI<sup>+</sup> Clonal Complexes of <i>Vibrio cholerae</i> O1 Found in Water Bodies of the Rostov Region

The aim of the work was to identify genotypic features of clonal complexes formed by CTX–VPI+ strains of Vibrio cholerae isolated from water bodies of the Rostov Region in different years, based on bioinformatics analysis of their whole genome sequences (WGSs).Materials and methods. Whole genome sequencing was performed on the MiSeq (Illumina) platform; identification of genetic determinants in WGSs and bioinformatics analysis – by means of BioEdit, BLASTN, BLASTP, CARD, Vector NTI software packages.Results and discussion. The strains were almost identical in each group of 2002-, 2005-, 2007-, 2020-, 2021-, and 2022-isolates and were found at different points of water sampling over a longer or shorter periods of time (from 3 weeks to 2 months). Bioinformatics analysis of WGSs of representative strains divided them into 4 clusters, which can be considered as separate clonal complexes sharing a number of characteristic genetic markers: 1) 2002-isolates containing one SNP in regulatory rpoS gene; 2) 2007-strains carrying tandemly duplicated preCTX prophage; 3) strains isolated in 2020 in Rostov-on-Don and in 2005, during epidemiological complications in the Kamensk district of the Rostov Region, which had a “hybrid” pathogenicity island including the cluster of type 3 secretion system and the nan-nag region of the VPI-2 island, and 9 SNPs in rpoS gene; 4) 2021- and 2022-strains and a single 2018-isolate containing a 9 bp deletion in vchC collagenase gene. Despite the revealed differences, representatives of all clonal complexes possessed sufficient sets of intact determinants of pathogenicity/persistence factors to realize virulent properties and ability to survive in water bodies. Detection of clonal complexes of potentially pathogenic strains in surface water bodies indicates occasional emergence of favorable conditions for their long-term circulation, which emphasizes the importance of constant monitoring of V. cholerae in the territory of Russia.

RHEOLOGICAL PARAMETERS OPTIMIZATION OF HYDROCARBON-BASED DRILLING FLUID DEPENDING ON THE MINING AND GEOLOGICAL CONDITIONS OF THEIR APPLICATION

Hydrocarbon-based solutions (HCBS) today are capable ofperforming tasks that water-based muds cannot do. First of all — theability to keep the well walls at a lower density, their insensitivity to clayand salt deposits, the similar nature of the hydrocarbon base and reservoirfluids. These advantages make it possible to use HCBS in the constructionof wells characterized by intensive caving, with high zenithangles and extended horizontal sections. HCBS is successfully appliedat the fields located beyond the Arctic Circle when opening, for example,Devonian deposits. But in addition to the indisputable positive aspects,HCBS also have disadvantages. Among their main disadvantages, highcost is distinguished, which increases the requirements for the quality ofthe solution for trouble-free and fast well drilling, the impossibility ofusing HCBS in absorbing horizons. In addition to the high cost, hydrocarbon-based fluids, due to their nature, are characterized by compressibilityand a non-linear dependence of viscosity on temperature. Simplyput, under the influence of high temperatures, the rheological parametersof the solution decrease, and under the influence of low temperatures,they increase. And if solutions are constantly being found for the firstproblem, improving and developing new viscosity modifiers, emulsifiersand additives, then the second problem has long gone unnoticed. But forthe deposits of the Arctic, characterized by vast zones of permafrost, thesolution of this problem is more relevant than ever. An increase in plasticviscosity when the solution is cooled (for example, in permafrost zones)is possible during long-term circulation stops: during tripping operationsor running casing, etc. This increase in rheology can cause circulationloss, fluid loss, increased timewell construction, and hydraulic fracturing.In this work, we decided to investigate the dependence of the HCBSrheology on temperature and to choose the concentration of reagents thatwill allow leveling this dependence, since, due to the nature of theHCBS, it is impossible to eliminate it completely.