Cell Burst Research Articles

Placental growth factor alleviates hyperglycemia-induced trophoblast pyroptosis by regulating mitophagy.

Hyperglycemia is closely related to trophoblast dysfunction during pregnancy and results in suppressed invasion, migration, and pro-inflammatory cell death of trophoblasts. Hyperglycemia is a dependent risk factor for gestational hypertension accompanied by decreased placental growth factor (PLGF), which is important for maternal and fetal development. However, there is currently a lack of evidence to support whether PLGF can alleviate trophoblast cell dysfunction caused by high blood sugar. Here, we aim to clarify the effect of hyperglycemia on trophoblast dysfunction and determine how PLGF affects this process. The changes in placental tissue histomorphology from gestational diabetes mellitus (GDM) patients were compared with those of normal placentas. HTR8/SVneo cells were cultured in different amounts of glucose to examine cellular pyroptosis, migration, and invasion as well as PLGF levels. Furthermore, the levels of pyroptosis-related proteins (NLRP3, pro-caspase1, caspase1, IL-1β, and Gasdermin D [GSDMD]) as well as autophagy-related proteins (LC3-II, Beclin1, and p62) were examined by Western blotting. The GFP-mRFP-LC3-II system and transmission electron microscopy were used to detect mitophagy levels, and small interfering RNAs targeting BCL2 Interacting Protein 3 (siBNIP3) and PTEN-induced kinase 1 (siPINK1) were used to determine the role of mitophagy in pyroptotic death of HTR-8/SVneo cells. Our results show that hyperglycemia upregulates NLRP3, pro-caspase1, caspase1, IL-1β at the protein level in GDM patients. High glucose (HG, 25 mM) inhibits viability, invasion, and migration of trophoblast cells while suppressing superoxide dismutase levels and promoting malondialdehyde production, thus leading to a senescence associated beta-gal-positive cell burst. PLGF levels in nucleus and the cytosol are also inhibited by HG, whereas PLGF treatment inhibited pyroptosis-related protein levels of NLRP3, pro-caspase1, caspase1, IL-1β, and GSDMD, Gasdermin D N-terminal domain (GSDMD-N). HG-induced mitochondrial dysfunction and BNIP3 and PINK1/Parkin expression. Knocking down BINP3 and PINK1 abolished the protective role of PLGF by preventing mitophagy. PLGF inhibited hyperglycemia, while PLGF reversed hyperglycemic injury by promoting mitophagy via the BNIP3/PINK1/Parkin pathway. Altogether, these results suggest that PLGF may protect against trophoblast dysfunction in diabetes.

High throughput platform technology for rapid target identification in personalized phage therapy

As bacteriophages continue to gain regulatory approval for personalized human therapy against antibiotic-resistant infections, there is a need for transformative technologies for rapid target identification through multiple, large, decentralized therapeutic phages biobanks. Here, we design a high throughput phage screening platform comprised of a portable library of individual shelf-stable, ready-to-use phages, in all-inclusive solid tablets. Each tablet encapsulates one phage along with luciferin and luciferase enzyme stabilized in a sugar matrix comprised of pullulan and trehalose capable of directly detecting phage-mediated adenosine triphosphate (ATP) release through ATP bioluminescence reaction upon bacterial cell burst. The tablet composition also enhances desiccation tolerance of all components, which should allow easier and cheaper international transportation of phages and as a result, increased accessibility to therapeutic phages. We demonstrate high throughput screening by identifying target phages for select multidrug-resistant clinical isolates of Pseudomonas aeruginosa, Salmonella enterica, Escherichia coli, and Staphylococcus aureus with targets identified within 30-120 min.

Hippocampal cholecystokinin-expressing interneurons regulate temporal coding and contextual learning

Cholecystokinin-expressing interneurons (CCKIs) are hypothesized to shape pyramidal cell-firing patterns and regulate network oscillations and related network state transitions. To directly probe their role in the CA1 region, we silenced their activity using optogenetic and chemogenetic tools in mice. Opto-tagged CCKIs revealed a heterogeneous population, and their optogenetic silencing triggered wide disinhibitory network changes affecting both pyramidal cells and other interneurons. CCKI silencing enhanced pyramidal cell burst firing and altered the temporal coding of place cells: theta phase precession was disrupted, whereas sequence reactivation was enhanced. Chemogenetic CCKI silencing did not alter the acquisition of spatial reference memories on the Morris water maze but enhanced the recall of contextual fear memories and enabled selective recall when similar environments were tested. This work suggests the key involvement of CCKIs in the control of place-cell temporal coding and the formation of contextual memories.

MnO2-based capacitive system enhances ozone inactivation of bacteria by disrupting cell membrane

The application of ozone (O3) disinfection has been hindered by its low solubility in water and the formation of disinfection by-products (DBPs). In this study, capacitive disinfection is applied as a pre-treatment for O3 oxidation, in which manganese dioxide with a rambutan-like hollow spherical structure is used as the electrode to increase the charge density on the electrode surface. When a voltage is applied, the negative-charged microbes are attracted to the electrodes and killed by electrical interactions. The contact between microbes and capacitive electrodes leads to changes in cell permeability and burst of reactive oxygen species, thereby promoting the diffusion of O3 into the cells. After O3 penetrates the cell membrane, it can directly attack the cytoplasmic constituents, accelerating fatal and irreversible damage to pathogens. As a result, the performance of the capacitance-O3 process is proved better than the direct sum of the two individual process efficiencies. The design of capacitance-O3 system is beneficial to reduce the ozone dosage and DBPs with a broader inactivation spectrum, which is conducive to the application of ozone in primary water disinfection.

Radio Frequency (RF) Mediated Hyperthermia of Nickel Ferrites-A Potential Application of Cancer Therapy

We present an invitro study of the hyperthermia application of nanomaterials for the cancer treatment by Radiofrequency (RF). Nickel-ferrite nano materials are synthesized by using microwave hydrothermal method at different pH values under a lower temperature of 160°C for a short holding time of 30 minutes. RF source generator is being used that opeartes at 100 KHz and a temperature regulator monitors the temperature of the solution.The in-vivo experimemnt was conducted with the nanomaterials dispersed in the ferrofluid, and RF energy is appiled when the solution is being placed in a magnetic stirrer. The results shows that the temperature of the nanomaterials has increased beyond 40°C and went up to 45°C with the increase in frequency of the RF under the constant magnetic field of 100 Oe. As the strength of the magnetic field increases the Nanomaterials have shown rapid variation in their temperature Characteristics. The nickel-ferrites have shown linear temperature characteristics under the magnetic field of 100Oe with the RF frequency of 100 KHz. Hence the nickel-ferrites are most suitable for the Hyperthermia application of cancer treatment..The cancerous cells are destroyed by ‘Active cell destruction’ or they are swollen till the cells burst. The superconductivity property of nano particles and Radio Frequency coils used plays the major role in the treatment.

Phage-induced bacterial morphological changes reveal a phage-derived antimicrobial affecting cell wall integrity.

In a looming post-antibiotic era, antibiotic alternatives have become key players in the combat against pathogens. Although recent advances in genomic research allow scientists to fully explore an organism's genome in the search for novel antibacterial molecules, laborious work is still needed in order to dissect each individual gene product for its antibacterial activity. Here, we exploited phage-induced bacterial morphological changes as anchors to explore and discover a potential phage-derived antimicrobial embedded in the phage genome. We found that, upon vibriophage KVP40 infection, Vibrio parahaemolyticus exhibited morphological changes similar to those observed when treated with mecillinam, a cell wall synthesis inhibitor, suggesting the mechanism of pre-killing that KVP40 exerts inside the bacterial cell upon sieging the host. Genome analysis revealed that, of all the annotated gene products in the KVP40 genome that are involved in cell wall degradation, lytic transglycosylase (LT) is of particular interest for subsequent functional studies. A single-cell morphological analysis revealed that heterologous expression of wild-type KVP40-LT induced similar bacterial morphological changes to those treated with the whole phage or mecillinam, prior to cell burst. On the contrary, neither the morphology nor the viability of the bacteria expressing signal-peptide truncated- or catalytic mutant E80A- KVP40-LT was affected, suggesting the necessity of these domains for the antibacterial activities. Altogether, this research paves the way for the future development of the discovery of phage-derived antimicrobials that is guided through phage-induced morphological changes.

Synergid cell calcium oscillations refine understanding of FERONIA/LORELEI signaling during interspecific hybridization

Key messagePollen tubes from closely related species and mutants lacking pollen tube MYB transcription factors are able to initiate FER/LRE-dependent synergid cell calcium oscillations.Reproductive isolation leads to the evolution of new species; however, the molecular mechanisms that maintain reproductive barriers between sympatric species are not well defined. In flowering plants, sperm cells are immotile and are delivered to female gametes by the pollen grain. After landing on the stigmatic surface, the pollen grain germinates a polarized extension, the pollen tube, into floral tissue. After growing via polar extension to the female gametes and shuttling its cargo of sperm cells through its cytoplasm, the pollen tube signals its arrival and identity to synergid cells that flank the egg. If signaling is successful, the pollen tube and receptive synergid cell burst, and sperm cells are released for fusion with female gametes. To better understand cell–cell recognition during reproduction and how reproductive barriers are maintained between closely related species, pollen tube-initiated synergid cell calcium ion dynamics were examined during interspecific crosses. It was observed that interspecific pollen tubes successfully trigger synergid cell calcium oscillations—a hallmark of reproductive success—but signaling fails downstream of key signaling genes and sperm are not released. This work further defines pollen tube–synergid cell signaling as a critical block to interspecific hybridization and suggests that the FERONIA/LORELEI signaling mechanism plays multiple parallel roles during pollen tube reception.

Application of a novel lytic Jerseyvirus phage LPSent1 for the biological control of the multidrug-resistant Salmonella Enteritidis in foods.

Non-typhoidal Salmonella is the tremendously predominant source of acquired foodborne infection in humans, causing salmonellosis which is a global threat to the healthcare system. This threat is even worse when it is combined with the incidence of multidrug-resistant Salmonella strains. Bacteriophage therapy has been proposed as a promising potential candidate to control a diversity of foodborne infective bacteria. The objective of this study designed to isolate and characterize lytic phages infecting zoonotic multi-drug resistant and strong biofilm producer Salmonella enterica serovar Enteritidis EG.SmE1 and then apply the isolated phage/s as a biocontrol agent against infections in ready-to-eat food articles including milk, water, apple juice, and chicken breasts. One lytic phage (LPSent1) was selected based on its robust and stable lytic activity. Phage LPSent1 belonged to the genus Jerseyvirus within the Jerseyvirinae subfamily. The lysis time of phage LPSent1 was 60 min with a latent period of 30 min and each infected cell burst about 112 plaque-forming units. Phage LPSent1 showed a narrow host range. Furthermore, the LPSent1 genome did not encode any virulence or lysogenic genes. In addition, phage LPSent1 had wide pH tolerance, prolonged thermal stability, and was stable in food articles lacking its susceptible host for 48 h. In vitro applications of phage LPSent1 inhibited free planktonic cells and biofilms of Salmonella Enteritidis EG.SmE1 with a lower occurrence to form phage-resistant bacterial mutants which suggests promising applications on food articles. Application of phage LPSent1 at multiplicities of infections of 100 or 1000 showed significant inhibition in the bacterial count of Salmonella Enteritidis EG.SmE1 by 5 log10/sample in milk, water, apple juice, and chicken breasts at either 4°C or 25°C. Accordingly, taken together these findings establish phage LPSent1 as an effective, promising candidate for the biocontrol of MDR Salmonella Enteritidis in ready-to-eat food.

The role of ketamine in major depressive disorders: Effects on parvalbumin-positive interneurons in hippocampus.

Major depressive disorder (MDD) is a complex illness that is arising as a growing public health concern. Although several brain areas are related to this type of disorders, at the cellular level, the parvalbumin-positive cells of the hippocampus interplay a very relevant role. They control pyramidal cell bursts, neuronal networks, basic microcircuit functions, and other complex neuronal tasks involved in mood disorders. In resistant depressions, the efficacy of current antidepressant treatments drops dramatically, so the new rapid-acting antidepressants (RAADs) are being postulated as novel treatments. Ketamine at subanesthetic doses and its derivative metabolites have been proposed as RAADs due to their rapid and sustained action by blocking N-methyl-d-aspartate (NMDA) receptors, which in turn lead to the release of brain-derived neurotrophic factor (BDNF). This mechanism produces a rapid plasticity activation mediated by neurotransmitter homeostasis, synapse recovery, and increased dendritic spines and therefore, it is a promising therapeutic approach to improve cognitive symptoms in MDD.

Evaluation of Shifts of Gene Transcription Levels of Unicellular Green Alga Chlamydomonas reinhardtii Due to UV-C Irradiation

Green algae produce valuable lipids as carbon-recycling resources. Collecting whole cells with the intracellular lipids could be efficient without cell burst; however, direct use of the cells causes microbial contamination in environments. Then, UV-C irradiation was selected to satisfy the requirements of avoiding the cell burst and sterilizing cells with Chlamydomonas reinhardtii. UV-C irradiation with 1.209 mW·cm-2 showed enough sterilization activity for 1.6 × 107 cells·mL-1 of C. reinhardtii in a depth of 5 mm for 10 min. The irradiation showed no effects to composition and contents of the intracellular lipids. From the viewpoint of transcriptomic analysis, the irradiation displayed possibilities of (i) inhibition of the synthesis of lipids due to decrement of the transcription of related genes, such as diacylglycerol acyl transferase and cyclopropane fatty acid synthase, and (ii) activation of lipid degradation and the production of NADH2+ and FADH2 due to increment of the transcription of related genes, such as isocitrate dehydrogenase, dihydrolipoamide dehydrogenase and malate dehydrogenase. Irradiation until cell death could be insufficient to shift the metabolic flows even though the transcriptions were already shifted to lipid degradation and energy production. This paper is the first report of the response of C. reinhardtii to UV-C irradiation on the transcription level.

Modeling cholinergic retinal waves: starburst amacrine cells shape wave generation, propagation, and direction bias

Stage II cholinergic retinal waves are one of the first instances of neural activity in the visual system as they are present at a developmental timepoint in which light-evoked activity remains largely undetectable. These waves of spontaneous neural activity sweeping across the developing retina are generated by starburst amacrine cells, depolarize retinal ganglion cells, and drive the refinement of retinofugal projections to numerous visual centers in the brain. Building from several well-established models, we assemble a spatial computational model of starburst amacrine cell-mediated wave generation and wave propagation that includes three significant advancements. First, we model the intrinsic spontaneous bursting of the starburst amacrine cells, including the slow afterhyperpolarization, which shapes the stochastic process of wave generation. Second, we establish a mechanism of wave propagation using reciprocal acetylcholine release, synchronizing the bursting activity of neighboring starburst amacrine cells. Third, we model the additional starburst amacrine cell release of GABA, changing the spatial propagation of retinal waves and in certain instances, the directional bias of the retinal wave front. In total, these advancements comprise a now more comprehensive model of wave generation, propagation, and direction bias.

IL-17 Imbalance Promotes the Pyroptosis in Immune-Mediated Liver Injury Through STAT3-IFI16 Axis.

Autoimmune hepatitis (AIH) affects all age group and occurs mainly in women. Pyroptosis is a novel programmed cell death featured with cell bursting and release of proinflammatory cytokines. A deeper understanding of AIH pathogenesis will contribute to novel therapy for AIH patients. Here, we aimed to investigate the role of IL-17 in immune-mediated liver injury. The levels of cytokines were measured by ELISA, and mRNA levels of STAT3 and IFN gamma-inducible protein 16 (IFI16) were detected by PCR. Expressions of STAT3, IFI16, gasdermin D and cleaved caspase-1 were measured by western-blotting. Immunohistochemical staining and transmission electron microscopy were applied to evaluate liver histopathological changes of the treated mice. Our results showed that the levels of IFI16 was increased in hepatocytes treated with IL-17 protein, and further elevated after STAT3-overexpressed (STAT3-OE) lentivirus treatment. The levels of IFI16 were reduced in hepatocytes treated with IL-17 neutralizing Ab (nAb), but were significantly increased after STAT3-OE treatment. Pyroptosis was observed in hepatocytes treated with IL-17 protein, and further cell damage was observed after STAT3-OE lentivirus treatment. Liver damage was alleviated in mice treated with IL-17 nAb, however sever damage was experienced after STAT3-OE lentivirus treatment. A binding interaction between IFI16 and STAT3 was detected in IL-17 treated hepatocytes. Glutathione transaminase activity was enhanced in concanavalin A-induced AIH mice compared to the control group (p<0.01). IL-17 plays an important role in activating STAT3 and up-regulating IFI16, which may promote the pyroptosis in AIH-related liver injury through STAT3-IFI16 axis.

Ozone-high-doses ACC. to Dr. Lahodny and the latest scientific results.

Self-funding his own work on the so-called therapeutic effects of medical ozone with respect to its alleged potential impacts on mitochondria and stem cells, he has been focusing since 2010 on an innovative form of ozone therapy called OHT—“Ozonhochdosistherapie”— commonly known as “10 pass” in the USA. Through a specific process involving 10 repeated interactive transits incurred via autohemotherapy, the blood is “fused” with 200 ml of ozone gas respectively brought to a concentration of 70 mcg/ml, thus providing a cumulative ozone intake of 140,000 mcg.&#x0D; The evolution of the ozonotherapeutic treatment promoted by Lahodny would then consist, in a way, in breaking the restrictive rules relating to pragmatic dosage which tended to prevail until now with regard to a usual protocol which still remains well anchored in traditional customs and habits. Indeed, any former procedure usually involved a single injection of ozonated autologous blood therapy containing 200 ml of ozone at a concentration of 40 mcg, after which the session would end. This conceptual limit was based on an arbitrary credo that exceeding&#x0D; this dose boundary—in terms of both quantity and concentration administered—would be likely to result in cell bursting by blood dissolution, a supputive risk whose consequences had previously been considered hypothetically lethal.&#x0D; In 2014, he discovered and refined a new dosage—L1—that he believes would activate the growth of stem cells and the production of adenosine triphosphate (ATP). Its application can be summed up as a major autologous blood therapy combined with massive doses of ozone injections both in terms of concentration — up to 70 mcg/ml in ozon IV or even 80 mcg/ml in rectal insufflation - and quantity: which generally implied 140,000 mcg, but sometimes up to 280,000 mcg in the treatment of more complex conditions. Thanks to this innovative approach, Lahodny claimed to obtain therapeutic results that he described as “exceptional” in the treatment of a number of chronic pathologies as well as several other morbid conditions which are generally considered difficult to treat.

Amoebal Tubulin Cleavage Late during Infection Is a Characteristic Feature of Mimivirus but Not of Marseillevirus.

Mimivirus and Marseillevirus infections of Acanthamoeba castellanii, like most other viral infections, induce cytopathic effects (CPE). The details of how they bring about CPE and to what extent and how they modify the host cytoskeletal network are unclear. In this study, we compared the rearrangement of the host cytoskeletal network induced by Mimivirus and Marseillevirus upon infection. We show that while both Mimivirus and Marseillevirus infections of A. castellanii cells cause retraction of acanthopodia and depolymerization of the host actin filament network, the Mimivirus infection also results in characteristic cleavage of the host tubulin, a phenomenon not previously reported with any intracellular pathogens. Furthermore, we show that the amoebal tubulin cleavage during Mimivirus infection is a post-replicative event. Because time-lapse microscopy showed that Mimivirus infection leads to the bursting of cells, releasing the virus, we hypothesize that tubulin cleavage together with actin depolymerization during the later stages of Mimivirus assembly is essential for cell lysis due to apoptotic/necrotic cell death. We also characterize the Mimivirus-encoded gp560, a Zn metalloprotease, however, the purified gp560 protein was unable to cleave the commercially available porcine brain tubulin. While protein synthesis is essential for causing the morphological changes in the case of Mimivirus, the proteins which are packaged in the viral capsid along with the genome are sufficient to induce CPE in the case of Marseillevirus. IMPORTANCE In general, intracellular pathogens target the cytoskeletal network to enable their life cycle inside the host. Pathogen-induced changes in the host cell morphology usually accompany global changes in the cytoskeleton resulting in cytopathic effects. While viruses have been shown to use the host actin cytoskeleton for entry and transport during early infection, the role of microtubules in the viral life cycle is only beginning to emerge. Here, we show that the giant viruses Mimivirus and Marseillevirus both induce depolymerization of the actin filament, Mimivirus also causes a characteristic cleavage of tubulin not previously reported for any intracellular pathogen. Because tubulin cleavage occurs late during infection, we hypothesize that tubulin cleavage aids in cell death and lysis rather than establishing infection. The different strategies used by viruses with similar host niches may help them survive in competition.

Pyroptosis: A Newly Discovered Therapeutic Target for Ischemia-Reperfusion Injury.

Ischemia-reperfusion (I/R) injury, uncommon among patients suffering from myocardial infarction, stroke, or acute kidney injury, can result in cell death and organ dysfunction. Previous studies have shown that different types of cell death, including apoptosis, necrosis, and autophagy, can occur during I/R injury. Pyroptosis, which is characterized by cell membrane pore formation, pro-inflammatory cytokine release, and cell burst, and which differentiates itself from apoptosis and necroptosis, has been found to be closely related to I/R injury. Therefore, targeting the signaling pathways and key regulators of pyroptosis may be favorable for the treatment of I/R injury, which is far from adequate at present. This review summarizes the current status of pyroptosis and its connection to I/R in different organs, as well as potential treatment strategies targeting it to combat I/R injury.

Single viable fungal aerosol particle discerning using naked eye assisted with laser trapping and microwaving

Viable microbial aerosol detection remains a grand challenge. Here, we pioneered a new system that integrates laser trapping and microwave irradiation for online discerning of single viable microbial aerosol particle through naked eye. To test the system, three fungal species Aspergillus niger, Aspergillus oryzae, and Trichoderma harzianum and three non-biological particles such as MnO2, active carbon, and Fe3O4 were suspended and laser trapped in the air inside a house-made glass cube. When microwave irradiated, some fungal spores were observed to rapidly escape from the trapping and even burst with abrupt morphology changes under a longer irradiation. In contrast, others similar to those non-biological particles were shown to behave differently with little morphology change without the cell burst. For all particles tested, microwave irradiation resulted in particle movement within the trapping region, and a particle trapping was then re-established in a new location. Depending on particle type and irradiation time, light scattering properties also differed between biological and non-biological particles when irradiated. Terminating the microwave irradiation was observed to render the non-biological particles to return where they were being laser trapped. Using the developed system, we have demonstrated the viable microbial aerosol detection using naked eye by simply observing the morphology changes and cell burst upon the laser trapping and microwave irradiation. A portable version of the system was further developed and successfully tested for discerning viable aerosol cells from non-biological ones. Further efforts on this development could lead to a new generation of bioaerosol detection strategy.

Novel effective bioprocess for optimal CO2 fixation via microalgae-based biomineralization under semi-continuous culture

In this study, the effects of microalgae-based biomineralization in a semi-continuous process (M-BSP) on biomass productivity and CO2 fixation rate were investigated. M-BSP significantly improved biomass production and CO2 fixation rate at the second stage of induction by sustaining relatively high photosynthetic rate without exposure to toxic substances (e.g., chlorellin) from aging cells using the microalgae Chlorella HS2. In conventional systems, cells do not receive irradiated light evenly, and many cells age and burst because of the long culture period. In contrast, in the M-BSP, the photosynthesis efficiency increases and biomass production is not inhibited because most of the cells can be harvested during shorter culture period. The accumulated biomass production and CO2 fixation rate of the HS2 cells cultured under M-BSP increased by 4.67- (25 ± 1.09 g/L) and 10.9-fold (30.29 ± 1.79 g/L day−1), respectively, compared to those cultured without the CaCl2 treatment.

Effects of Salinity on Growth and In Vitro Ichthyotoxicity of Three Strains of Karenia mikimotoi

Karenia mikimotoi is one of the most damaging ichthyotoxic dinoflagellate species commonly found in China. However, its growth and ichthyotoxicity responses to salinity changes are still largely unknown. In this study, the growth and ichthyotoxicity of three K. mikimotoi strains, Hong Kong strain KMHK, Japanese strain NIES2411 and New Zealand strain CAWD133, under different salinities (25 to 35 ppt), initial algal densities (5 to 40 thousand cells) and growth phases were investigated. Results indicated that the optimum salinity for all three strains was 30 ppt. The Japanese strain achieved the highest maximum cell densities (cells mL−1) and the New Zealand strain achieved the highest specific growth rate. The Hong Kong and New Zealand strains could not tolerate the low salinity at 25 ppt and the algal cells burst after 3 days of exposure. The average cell widths of all three algal strains in 35 ppt salinity were significantly larger than that in 30 ppt. The acute toxicity test performed on Oncorhynchus mykiss gill cell line RTgill-W1 revealed that the median lethal times for KMHK and NIES2411 were 66.9 and 31.3 min, respectively, and their ichthyotoxicity was significantly affected by algal cell density and growth phase. Nevertheless, CAWD133 did not pose any ichthyotoxicity. The gill cell viability levels at 30 min were reduced from 96 to 61% and 95 to 39% for KMHK and NIES2411, respectively, when the algal cell density increased from 5 × 103 to 4 × 104 algal cells mL−1. Both KMHK and NIES2411 at stationary phase also had higher toxicity than at log phase, with a 27% reduction of gill cell viability, and exerted higher toxicity to the gill cells under extremely low (28 ppt) or high (35 ppt) salinity. These findings demonstrated that the growth–ichthyotoxicity response of Karenia mikimotoi to salinity was not only strain-specific but also depended on its density and growth phase. Study on the effects of salinity on the growth and toxicity of K. mikimotoi is greatly limited. Results from the present study provide valuable insight on the growth and toxicity of different K. mikimotoi strains, which is important in understanding their occurrence of algal bloom and fish-killing action.

The computational study, thermodynamic parameters, and partial inhibition of spermatogenesis exhibited by toxicophores scaffolds of an organic–inorganic hybrid complex of tributyltin (IV)

The present investigation focused on the structure and demonstration of partial inhibition of spermatogenesis in male albino rats through pentacoordinate tributyltin (IV) complex of sterically blocked Schiff base of heterocyclic β‐diketone having the general formula Bu3SnL (where ). The aid of physicochemical and spectral analysis suggested the plausible structure of this complex. The density functional theory (DFT) provides the optimized structure of the tributyltin (IV) complex. The computational study of the tributyltin (IV) complex evaluated the thermodynamic parameters, molecular orbitals, principal quantum chemical descriptors, and chemical reactivity. The experimental animals contain three groups, each consisting of nine animals. The male fertility of albino rats of groups II and III treated with tributyltin (IV) complex of sterically blocked Schiff base of heterocyclic β ‐diketone at 10 and 20 mg/kg body wt/day compared with group I during 90 days of the investigation was impaired consistently. Accordingly, the quality and quantity of sperms obtained from cauda epididymis deteriorated in both treatment groups compared with control animals. Blood testes barrier ruptured in the seminiferous tubules as a result of disordered germinal epithelium, substantial loss of germ cells, and remaining germ cell bursting, which stopped spermatogenesis at stage 13 of spermiogenesis. The findings of the study suggest that this complex partially inhibits spermatogenesis. Identifying some toxicophores scaffolds of the complex appears to be a significant contributor to the complete inhibition of spermatogenesis.

K1 Escherichia coli form foci in the brain at 24h post infection

K1 capsule type Escherichia coli is the predominant cause of neonatal meningitis. In an intravenous (IV) infection model with a clinical K1 isolate IHE 3034 adult mice die of sepsis within 24 hours. However, by utilising cefazolin, a first-generation cephalosporin known for its inability to pass through the blood brain barrier, it is possible to prevent bacteraemia and study the early phases of E. coli meningitis in the brain. Mice were infected IV with E. coli IHE 3034 and treated with cefazolin at 12 and 24h intraperitoneal to ensure the survival of animals to the determined end points. The results of the experiment show IHE 3034 is present in the brain as early as 12h and it remains in the tissue 72h post infection even if blood is clear. Despite this, at the cellular level, clear foci formation can be observed in the meninges and the choroid plexus around the vascular endothelial cells at 48h, showing IHE 3034’s ability for intracellular replication inside the meningeal region The foci do not appear to be present at 24 or 72h, indicating for a secondary replication site around the major vascular endothelia sites of the brain. This further promotes the bacterial load increase through cell bursting in the tissue with or without a sustained bacterial influx from the blood. These findings show that K1 E. coli can form foci in the brain which may lead to escalated disease progression and severe morbidity following an initially successful clearance of bloodborne bacteria during sepsis.