Severe Damage Research Articles

Epitranscriptomic m5C methylation of SARS-CoV-2 RNA regulates viral replication and the virulence of progeny viruses in the new infection.

While the significance of N6-methyladenosine (m6A) in viral regulation has been extensively studied, the functions of 5-methylcytosine (m5C) modification in viral biology remain largely unexplored. In this study, we demonstrate that m5C is more abundant than m6A in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and provide a comprehensive profile of the m5C landscape of SARS-CoV-2 RNA. Knockout of NSUN2 reduces m5C levels in SARS-CoV-2 virion RNA and enhances viral replication. Nsun2 deficiency mice exhibited higher viral burden and more severe lung tissue damages. Combined RNA-Bis-seq and m5C-MeRIP-seq identified the NSUN2-dependent m5C-methylated cytosines across the positive-sense genomic RNA of SARS-CoV-2, and the mutations of these cytosines enhance RNA stability. The progeny SARS-CoV-2 virions from Nsun2 deficiency mice with low levels of m5C modification exhibited a stronger replication ability. Overall, our findings uncover the vital role played by NSUN2-mediated m5C modification during SARS-CoV-2 replication and propose a host antiviral strategy via epitranscriptomic addition of m5C methylation to SARS-CoV-2 RNA.

Safety evaluation of Indocalamus Iatifolius McClure leaves based on acute toxicity, harmful metals, and 9 organochlorine residue determination

To investigate the safety of Indocalamu Iatifolius McClur leaves sold in the market, a study was conducted using Indocalamu Iatifolius McClur leaves randomly collected from an online store and a large supermarket. Acute toxicity experiments were performed on mice, and their body weight was monitored for 14 days after administration. After the observation period, blood samples were collected for biochemical analysis, and organ pathology was examined. Then, the content of copper (Cu), lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As), and the residues of nine organochlorine pesticides in Indocalamu Iatifolius McClur leaves were measured according to the National Food Safety Standard (GB/T5009-2003) and the pesticide residue determination methods in the 2020 edition of the Chinese Pharmacopoeia. The results showed that the mice in the Indocalamu Iatifolius McClur leaves (online store) group experienced mortality and severe liver and lung damage. The levels of lead, cadmium, mercury, arsenic, and the nine organochlorine pesticides met the relevant standards and regulations. However, the copper content in the Indocalamu Iatifolius McClur leaves (online store) group was nearly 80 times higher than that in the supermarket group. Mice in the Indocalamu Iatifolius McClur leaves (supermarket) group remained healthy without any abnormalities, and the levels of harmful metals and organochlorine pesticides complied with the standards and regulations. The study suggests the need for regulatory policies and safety standards for the sale of Indocalamu Iatifolius McClur leaves.

Risk factors of bloodstream infection after allogeneic hematopoietic cell transplantation in children/adolescent and young adults.

Allogeneic hematopoietic cell transplantation (HCT) is a crucial treatment for various diseases, including hematological malignancies, solid tumors, and genetic disorders. Despite its curative potential, HCT is associated with severe complications, notably infections, graft-versus-host disease, and organ damage. Infections, particularly bloodstream infections (BSIs), pose a significant threat in the initial weeks post-HCT, necessitating effective management strategies. This retrospective study aimed to clarify the incidence, pathogens, and risk factors associated with BSI within the first 30 days after allogeneic HCT in children/adolescents and young adults (AYAs). The study included 115 patients aged <31 years who underwent 121 allogeneic HCTs at the Department of Pediatrics, Nagoya University Hospital between January 1, 2018, and March 31, 2022. Data encompassed demographic characteristics, HCT details, and BSI information. Overall, 27 of 121 patients developed BSI with the cumulative incidence of 23.5% (95% confidence intervals [CI]: 17.0%-30.6%) at 30 days after HCT. The median onset time of BSI was 7 (range, 4-26 days) after HCT. Gram-positive bacteria accounted for 89% of pathogens isolated from blood cultures, with Streptococcus mitis/oralis being the most common. In multivariable analysis, tandem HCT (subdistribution hazard ratio [SHR]: 5.67, 95% CI: 2.74-11.7, p < 0.001) and peripherally inserted central catheters (SHR: 2.96, 95% CI: 1.34-6.55, p = 0.007) were identified as independent risk factors for BSI. In patients receiving tandem HCT, the pathogens isolated from blood cultures were all gram-positive bacteria, with Streptococcus mitis/oralis accounting for up to 67% of the isolated pathogens. Tandem HCT and PICCs were identified as independent risk factors for BSI after allogeneic HCT in children/AYAs. The pathogens were commonly gram-positive, and Streptococcus mitis/oralis is important in patients who received tandem HCT. These data can provide valuable information for future studies to consider effective interventions to reduce the risk of BSI in high-risk patients.

A recent update on the connection between dietary phytochemicals and skin cancer: Emerging understanding of the molecular mechanism

Constant exposure to harmful substances from both inside and outside the body can mess up the body's natural ways of keeping itself in balance. This can cause severe skin damage, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma. However, plant-derived compounds found in fruits and vegetables have been shown to protect against skin cancer-causing free radicals and other harmful substances. It has been determined that these dietary phytochemicals are effective in preventing skin cancer and are widely available, inexpensive, and well-tolerated. Studies have shown that these phytochemicals possess anti-inflammatory, antioxidant, and anti-angiogenic properties that can aid in the prevention of skin cancers. In addition, they influence crucial cellular processes such as angiogenesis and cell cycle control, which can halt the progression of skin cancer. The present paper discusses the benefits of specific dietary phytochemicals found in fruits and vegetables, as well as the signalling pathways they regulate, the molecular mechanisms involved in the prevention of skin cancer and their drawbacks.

Assessment of the Compound Damping of a System with Parallelly Coupled Anti-Seismic Devices

(1) Background: Romanian earthquakes caused severe damage over time to a significant number of constructions, and that is why efforts are being made to make structural systems safer. (2) Methods: For structural systems with protection against seismic actions or vibrational actions that have linear viscous dissipation devices, the requirement to assess the equivalent modal damping rate for the entire functional assembly related to the other dynamic parameters arises. (3) Results: This article presents the analytical development of formulas for the compound damping and circular frequency when anti-seismic devices have different dynamic characteristics and their application in order to solve some real engineering cases of bridges and viaducts in Romania with distinct viscoelastic supports. In support of this idea, some experimental tests on a beam system resting on two different anti-seismic elastic supports highlighted the fact that the compound damping of the system can be calculated with the relations established in this paper, provided that the displacements in the horizontal direction of excitation are in the linear domain. Also, we determined the seismic response considering the Vrancea 1977 accelerogram for critical damping ratios of 5% and 18.5%, and then we obtained the variation in the factor of transmissibility depending on the frequency, in order to highlight the optimized value of the equivalent amortization/damping. (4) Conclusions: In the specific context of Romanian seismicity, seismic isolation through the use of isolators with different characteristics represents an optimal technical solution, and it is also optimal from an economic point of view, with an appropriate level of dynamic isolation obtained.

Assessing the Predictive Accuracy of the Eaton–Littler Classification in Thumb Carpometacarpal Osteoarthritis: A Comparative Analysis with the Outerbridge Classification in a Cohort of 51 Cases

(1) Background: The objective of this study is to evaluate the predictive value of the Eaton–Littler radiologic classification for thumb carpometacarpal osteoarthritis (CMC OA) relating to intra-articular cartilage damage assessed by the Outerbridge arthroscopic classification. (2) Methods: A total of 51 thumb CMC OA arthroscopies were performed on patients classified as Eaton stages 1, 2, or 3. Post-arthroscopic evaluations of cartilage damage were categorized using the Outerbridge classification. Comparative analyses were conducted between the radiological Eaton stages and the arthroscopic Outerbridge stages. (3) Results: Arthroscopic examination revealed Outerbridge stage 3 and 4 cartilage damage in 26 cases classified as Eaton stage 2 and in 18 cases classified as Eaton stage 3. The detection of severe cartilage damage in patients classified as Eaton stage 2 was unexpected. (4) Conclusions: Arthroscopy demonstrated that many patients with mild radiological degenerative signs exhibited significant cartilage destruction. Although the Eaton classification is widely used for staging thumb CMC OA, it may not accurately reflect the severity of intra-articular damage. The Eaton classification does not reliably predict intra-articular damage in Eaton stage 2 cases.

DF-1-Derived exosomes mediate transmission of reticuloendotheliosis virus and resist REV-specific antibodies

BackgroundReticuloendotheliosis virus (REV), a member of the family Retroviridae, is a hot area of research, and a previous study showed that exosomes purified from REV-positive semen were not blocked by REV-specific neutralizing antibodies and established productive infections.MethodsTo further verify the infectivity of exosomes from REV-infected cells, we isolated and purified exosomes from REV-infected DF-1 cells and identified them using Western blot and a transmission electron microscope. We then inoculated 7-day-old embryonated eggs, 1-day-old chicks and 23-week-old hens with and without antibody treatment. REV was administered simultaneously as a control.ResultsIn the absence of antibodies, the results indicated that REV-exosomes and REV could infect chicks, resulting in viremia and viral shedding, compared with the infection caused by REV, REV-exosomes reduced the hatching rate and increased mortality after hatching, causing severe growth inhibition and immune organ damage in 1-day-old chicks; both REV and REV-exosomes also could infect hens, however, lead to transient infection. In the presence of antibodies, REV-exosomes were not blocked by REV-specific neutralizing antibodies and infected 7-day-old embryonated eggs. However, REV could not infect 1-day-old chicks and 23-week-old hens.ConclusionIn this study, we compared the infectious ability of REV-exosomes and REV, REV-exosomes could escape from REV-specific neutralizing antibodies in embryonated eggs, providing new insights into the immune escape mechanism of REV.

Molecular Investigations to Improve Fusarium Head Blight Resistance in Wheat: An Update Focusing on Multi-Omics Approaches

Fusarium head blight (FHB) is mainly caused by Fusarium graminearum (Fg) and is a very widespread disease throughout the world, leading to severe damage to wheat with losses in both grain yield and quality. FHB also leads to mycotoxin contamination in the infected grains, being toxic to humans and animals. In spite of the continuous advancements to elucidate more and more aspects of FHB host resistance, to date, our knowledge about the molecular mechanisms underlying wheat defense response to this pathogen is not comprehensive, most likely due to the complex wheat–Fg interaction. Recently, due to climate changes, such as high temperature and heavy rainfall, FHB has become more frequent and severe worldwide, making it even more urgent to completely understand wheat defense mechanisms. In this review, after a brief description of the first wheat immune response to Fg, we discuss, for each FHB resistance type, from Type I to Type V resistances, the main molecular mechanisms involved, the major quantitative trait loci (QTLs) and candidate genes found. The focus is on multi-omics research helping discover crucial molecular pathways for each resistance type. Finally, according to the emerging examined studies and results, a wheat response model to Fg attack, showing the major interactions in the different FHB resistance types, is proposed. The aim is to establish a useful reference point for the researchers in the field interested to adopt an interdisciplinary omics approach.

Dietary therapy of murine primary biliary cholangitis induces hepatocellular steatosis: A cautionary tale.

There is increased interest in utilizing dietary interventions to alter the progression of autoimmune diseases. These efforts are driven by associations of gut microbiota/metabolites with levels of short-chain fatty acids (SCFAs). Propionate is a key SCFA that is commonly used as a food preservative and is endogenously generated by bacterial fermentation of non-digestible carbohydrates in the gut. A thesis has suggested that a diet rich in propionate and other SCFAs can successfully modulate autoimmunity. Herein, we investigated the effect of long-term administration of propionylated high-amylose resistant starches (HAMSP) on the course of murine primary biliary cholangitis. Groups of female ARE-Del mice were fed an HAMSP diet either before or after disease onset. A detailed immunobiological analysis was performed involving autoantibodies and rigorous T-cell phenotyping, including enumeration of T-cell subsets in the spleen, liver, intestinal intraepithelial lymphocytes and lamina propria by flow cytometry. Histopathological scores were used to assess the frequency and severity of liver inflammation and damage to hepatocytes and bile ducts. Our results demonstrate that a long-term propionate-yielding diet re-populated the T-cell pool with decreased naïve and central memory T-cell subsets and an increase in the effector memory T cells in mice. Similarly, long-term HAMSP intake reduced CD4+CD8+ double-positive T cells in intraepithelial lymphocytes and the intestinal lamina propria. Critically, HAMSP consumption led to moderate-to-severe hepatocellular steatosis in ARE-Del mice, independent of the stage of autoimmune cholangitis. Our data suggest that administration of HAMSP induces both regulatory and effector T cells. Furthermore, HAMSP administration resulted in hepatocellular steatosis. Given the interest in dietary modulation of autoimmunity and because propionate is widely used as a food preservative, these data have significant implications. This study also provides new insights into the immunological and pathological effects of chronic propionate exposure.

Vegetation’s Dynamic Changes, Spatial Trends, and Responses to Drought in the Yellow River Basin, China

Drought is a complex and recurrent natural disaster that can have devastating impacts on economies, societies, and ecosystems around the world. In light of climate change, the frequency, duration, and severity of drought events worldwide have increased, and extreme drought events have caused more severe and irreversible damage to terrestrial ecosystems. Therefore, estimating the resilience of different vegetation to drought events and vegetation’s response to damage is crucial to ensuring ecological security and guiding ecological restoration. Based on meteorological and remote-sensing datasets from 1982 to 2022, the spatial distribution characteristics and temporal variability of vegetation were identified in the Yellow River Basin (YRB), the dynamic changes and recurrence periods of typical drought events were clarified, and the driving effects of different drought types on vegetation were revealed. The results indicated that (1) during the research period, the standardized vegetation water-deficit index (SVWI) showed a downward trend in the YRB, with a 99.52% probability of abrupt seasonal changes in the SVWI occurring in January 2003; (2) the characteristic values of the grid trend Zs were −1.46 and 0.20 in winter and summer, respectively, indicating a significant downward trend in the winter SVWI; (3) the drought with the highest severity (6.48) occurred from September 1998 to February 1999, with a recurrence period of 8.54 years; and (4) the growth of vegetation was closely related to drought, and as the duration of drought increased, the sensitivity of vegetation to drought events gradually weakened. The research results provide a new perspective for identifying vegetation’s dynamic changes and responses to drought, which is of great significance in revealing the adaptability and potential influencing factors of vegetation in relation to climate.

Exploring the mechanism of intestinal injury induced by Bisphenol S in freshwater crayfish (Procambarus clarkii): Molecular and biochemical approaches

Bisphenol S (BPS) is extensively utilized in various industries such as plastic manufacturing, food packaging, and electronics. The release of BPS into aquatic environments has been observed to have negative impacts on aquatic ecosystems. Research has shown that exposure to BPS can have adverse effects on the health of aquatic animals. This study aimed to explore the mechanism of oxidative stress and endoplasmic reticulum stress induced in freshwater crayfish (Procambarus clarkii) by exposure to BPS (0 µg/L, 1 µg/L, 10 µg/L, and 100 µg/L) for 14 days. The results showed that BPS exposure resulted in elevated levels of reactive oxygen species (ROS) and malondialdehyde (MDA) and severe intestinal histological damage. In addition, oxidative stress can occur in the body by inhibiting the activity of antioxidant enzymes and the expression of related genes. BPS exposure induced a significant increase in the relative mRNA expression levels of inflammatory cytokines (NF-κB and TNF-α) and key unfolded protein response (UPR) related genes (Bip, Ire1, and Xbp1). At the same time, BPS exposure also induced up-regulation of apoptosis genes (Cytc and Casp3), suggesting that UPR and Nrf2-Keap1 signaling pathways may play a protective role in the process of apoptosis and oxidative stress. In conclusion, Our findings present the initial evidence that exposure to environmentally relevant levels of BPS can lead to intestinal injury through various pathways, highlighting concerns about the potential harm at a population level from BPS and other bisphenol analogs.

Discovery of Novel Imidazo[1,2-a]pyridine-Based HDAC6 Inhibitors as an Anticarcinogen with a Cardioprotective Effect.

Cardiotoxicity associated with chemotherapy has gradually become the major cause of death in cancer patients. The development of bifunctional drugs with both cardioprotective and antitumor effects has become the future direction. HDAC6 plays important roles in the progression, treatment, and prognosis of cancer and cardiovascular diseases, but bifunctional inhibitors have not been reported. Herein, structure-activity relationship studies driven by pharmacophore-based remodification and fragment-based design were performed to yield highly potent HDAC6 inhibitor I-c4 containing imidazo[1,2-a]pyridine. Importantly, I-c4 effectively suppressed the growth of MGC-803 xenografts in vitro and in vivo by inhibiting the deacetylation pathway without causing myocardial damage after long-term administration. Meanwhile, I-c4 could mitigate severe myocardial damage against H2O2 or myocardial ischemia/reperfusion in vitro and in vivo. Further studies revealed that the cardioprotective effect of I-c4 was associated with reduction of inflammatory cytokines. Taken together, I-c4 may represent a novel lead compound for further development of an anticarcinogen with a cardioprotective effect.

The Number of Patellar Dislocation Events Is Associated With Increased Chondral Damage of the Trochlea.

Patellofemoral instability is associated with chondral injuries to the patella, trochlea, and lateral femoral condyle. Although studies have demonstrated an association between patellar dislocations and chondral injuries, the influence of the number of dislocations on chondrosis is not established. To elucidate the precise association between the number of patellar dislocation events and the severity of chondral injuries in a multicenter cohort study at the time of patellar stabilization procedures. Cross-sectional study; Level of evidence, 2. A prospective multicenter cohort study (JUPITER [Justifying Patellar Instability Treatment by Early Results]) database was queried for cases of primary patellofemoral instability procedures from December 2016 to September 2022. Cartilage lesions were classified using the International Cartilage Repair Society (ICRS) classification system during an arthroscopic or open evaluation (direct visualization), with grades 2 to 4 considered abnormal. The number of dislocations was categorized as 1, 2-5, and >5. Categorical variables were compared with the chi-square test, and binary logistic regression was performed to identify predictors of the presence of chondral lesions. A total of 938 knees (mean age, 16.2 ± 3.8 years; 61.4% female) were included, with 580 (61.8%) demonstrating a chondral injury. The most affected region was the patella (n = 498 [53.1%]), followed by the lateral femoral condyle (n = 117 [12.5%]) and trochlea (n = 109 [11.6%]). There were no differences in the presence (P = .17) or grade (P = .63) of patellar lesions by the number of dislocations. Patients with >5 dislocations more frequently had trochlear chondral lesions (19.8%) compared with those with fewer dislocations (1, 7.6%; 2-5, 11.0%; P < .001). More dislocations were also associated with a higher proportion of ICRS grade 2 to 4 trochlear lesions (>5, 15.3%; 2-5, 10.0%; 1, 6.9%; P = .015). Combined patellar and trochlear lesions were also more common in those with >5 dislocations (P = .001). In multivariable regression, >5 dislocations was the only variable predictive of a trochlear lesion (odds ratio, 3.03 [95% CI, 1.65-5.58]; P < .001). This large prospective cohort study demonstrated that recurrent patellar dislocations can lead to more severe chondral damage in specific locations in the knee. More than 5 dislocations was associated with a >3-fold increase in the incidence and severity of trochlear chondral injuries. There were no differences in the presence or grade of patellar lesions by the number of dislocations. These findings should caution surgeons regarding prolonged nonoperative treatment.

Shaking table tests on concrete blocks anchored at the bottom of hydrogen storage vessels considering field installation conditions

ABSTRACT In this study, a scale model was created based on field investigation and design standards to evaluate the structural safety of a vertical hydrogen storage vessel stored in gas and liquid form during an earthquake, and a shaking table test was performed. Through testing, it was recognized that fixed anchors were also vulnerable to earthquakes, and additional seismic performance tests were conducted. In Set 1, where gas was stored, no damaged areas were observed during the maximum input seismic motion (EQ 200 %). In Set 2, where liquid was stored, cracks began to appear between the concrete block and the foundation at EQ 100 %, corresponding to the seismic design standard, and progressed to complete destruction at EQ 150 %. Cracks between the concrete block and the foundation led to a decrease in resonant frequency, accompanied by an amplification in acceleration. A reduction in resonant frequency by more than 15 % is anticipated to result in severe damage to the substructure, indicating a potential for brittle failure due to concrete damage prior to anchor failure. The anchors exhibited residual loads of over 80 % of the design load on average, confirming the use of anchors meeting seismic performance requirements.

Morphological characterization and distribution of antennal sensilla of Spodoptera frugiperda (Lepidoptera: Noctuidae) using scanning electron microscopy.

The fall armyworm (FAW), Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae), is a globally significant agricultural pest, causing severe damage to corn production in China. Chemical odor-based trapping is a major approach for FAW control, making it essential to understand the FAW antennal sensillum types to enhance development of effective chemical odor attractants. In this study, we comprehensively examined the antennal sensilla types of FAW, identifying eight types and two subtypes, including Böhm's bristles, sensilla trichoidea, sensilla chaetica (I and II), sensilla coeloconica, sensilla styloconica, sensilla squamiformia (I and II), sensilla auricillica, and sensilla basiconica. Sensilla chaetica II, and sensilla squamiformia II are reported for the first time for FAW in this study. Detailed low-voltage field emission scanning electron microscope (LVSEM) images and descriptions are provided for each sensillum type. This study provides the morphological information to aid in conducting antennal sensillum neurophysiological tests on FAW. RESEARCH HIGHLIGHTS: The types of sensilla of fall armyworm were examined, identifying eight types and two subtypes, including Böhm's bristles, sensilla trichoidea, sensilla chaetica (I and II), sensilla coeloconica, sensilla styloconica, sensilla squamiformia (I and II), sensilla auricillica, and sensilla basiconica. Detailed low-voltage field emission scanning electron microscope images and descriptions were provided for each sensillum type.

Laser-assisted Belt Grinding with Creep Feed for Enhanced Surface Integrity and Abrasive wear Reduction

Creep feed belt grinding (CFBG) is a vital machining technique used for intricate curved parts like aero-engine blades and flaps. CFBG effectively removes material by using larger depths of cut and lower feed rates, but high loads can lead to severe belt wear and thermal damage defects in the process. Laser-assisted processing technology can mitigate tool wear and enhance machining quality. This research compared and analyzed belt wear behavior and its impact on the surface integrity of titanium alloys in laser-assisted creep feed belt grinding (LCFBG) and CFBG processes. The following conclusions were drawn: The local thermal effect of the laser softened the material, reduced the grinding force. The wear pattern of the abrasive grains changed from abrasive fracture and stripping to steady abrasive wear. The effective life of the belt increased by about 33 %. In addition, due to reduction in grinding force, the thermo-mechanical coupling effect caused by material removal is reduced, and the grinding temperature is lowered. As a result of the reduction in grinding force and temperature, the mechanical and thermal stresses are reduced, the oxidation reaction on the surface of the titanium alloy is weakened, and the residual stress is lowered, leading to an improvement in surface quality.

Advancing cybersecurity: a comprehensive review of AI-driven detection techniques

As the number and cleverness of cyber-attacks keep increasing rapidly, it's more important than ever to have good ways to detect and prevent them. Recognizing cyber threats quickly and accurately is crucial because they can cause severe damage to individuals and businesses. This paper takes a close look at how we can use artificial intelligence (AI), including machine learning (ML) and deep learning (DL), alongside metaheuristic algorithms to detect cyber-attacks better. We've thoroughly examined over sixty recent studies to measure how effective these AI tools are at identifying and fighting a wide range of cyber threats. Our research includes a diverse array of cyberattacks such as malware attacks, network intrusions, spam, and others, showing that ML and DL methods, together with metaheuristic algorithms, significantly improve how well we can find and respond to cyber threats. We compare these AI methods to find out what they're good at and where they could improve, especially as we face new and changing cyber-attacks. This paper presents a straightforward framework for assessing AI Methods in cyber threat detection. Given the increasing complexity of cyber threats, enhancing AI methods and regularly ensuring strong protection is critical. We evaluate the effectiveness and the limitations of current ML and DL proposed models, in addition to the metaheuristic algorithms. Recognizing these limitations is vital for guiding future enhancements. We're pushing for smart and flexible solutions that can adapt to new challenges. The findings from our research suggest that the future of protecting against cyber-attacks will rely on continuously updating AI methods to stay ahead of hackers' latest tricks.

Micro-/nano-plastics as vectors of heavy metals and stress response of ciliates using transcriptomic and metabolomic analyses

The escalating presence of microplastics and heavy metals in marine environments significantly jeopardizes ecological stability and human health. Despite this, research on the combined effects of microplastics/nanoplastics (MPs/NPs) and heavy metals on marine organisms remains limited. This study evaluated the impact of two sizes of polystyrene beads (approximately 2 μm and 200 nm) combined with cadmium (Cd) on the ciliate species Euplotes vannus. Results demonstrated that co-exposure of MPs/NPs and Cd markedly elevated reactive oxygen species (ROS) levels in ciliates while impairing antioxidant enzyme activities, thus enhancing oxidative damage and significantly reducing carbon biomass in ciliates. Transcriptomic profiling indicated that co-exposure of MPs/NPs and Cd potentially caused severe DNA damage and protein oxidation, as evidenced by numerous differentially expressed genes (DEGs) associated with mismatch repair, DNA replication, and proteasome function. Integrated transcriptomic and metabolomic analysis revealed that DEGs and differentially accumulated metabolites (DAMs) were significantly enriched in the TCA cycle, glycolysis, tryptophan metabolism, and glutathione metabolism. This suggests that co-exposure of MPs/NPs and Cd may reduce ciliate abundance and carbon biomass by inhibiting energy metabolism and antioxidant pathways. Additionally, compared to MPs, the co-exposure of NPs and Cd exhibited more severe negative effects due to the larger specific surface area of NPs, which can carry more Cd. These findings provide novel insights into the toxic effects of MPs/NPs and heavy metals on protozoan ciliates, offering foundational data for assessing the ecological risks of heavy metals exacerbated by MPs/NPs.

Investigation of the toxicity of Cr (VI) against cyanobacteria and the mechanism of tolerance of the cyanobacterial consortia: a quantum mechanical approach.

Hexavalent chromium (Cr (VI)) is a heavy metal that is distributed globally and poses a significant threat to the environment through various mechanisms. It can react with soil and water, leading to severe environmental damage. In this study, the toxicity of Cr (VI) was investigated by analyzing two major cyanobacteria species, Nostoc commune and Anabaena variabilis, commonly found in soil along with their consortia. The findings revealed that the toxicity mechanisms of Cr (VI) differed in individual monocultures, with Cr (VI) competing with various components. However, when the cyanobacteria species were combined, i.e., in consortia, they demonstrated an impressive retention of their functioning even in Cr (VI) concentration at 10ppm. The study also concluded that non-photochemical quenching played a critical role in minimizing Cr (VI) toxicity. Furthermore, the research examined the role of the S-cycle in the process. The quantum yield of electron flux revealed that the Cr (VI) was competing with Qa in A. variabilis and with Qb in N. commune, albeit the photosystem dysfunction is only visible in the latter. The mechanism seemed to be quantum tunneling alteration because of the Cr (VI) having different energized quantum wells. The consortia proved to be behaving in a better manner as compared to the control. Overall, this study reveals the mode of toxicity of Cr (VI) in these two important cyanobacterial strains as well as it also discusses the mechanism of tolerance of consortia against Cr (VI) toxicity.

Cardioprotective effect of Robinin ameliorates Endoplasmic Reticulum Stress and Apoptosis in H9c2 cells.

Robinin is one of the glycosyloxyflavones that has been less explored for its therapeutic application, especially in the field of CVD. Herein, we explored the cardioprotective efficacy of Robinin by using H2O2 and Doxorubicin (DOX) - treated H9c2 cells as an in vitro model. H2O2 and DOX treatment resulted in severe cellular damage to the cardiomyocytes, which was followed by apoptosis. Apoptosis and nuclear morphology were analysed through Hoechst 33342 and AO/EB staining. qPCR was employed to detect the expression of apoptosis as well as ERS-related markers. Reactive oxygen species (ROS) generation was observed using DCFH-DA staining and FACS analysis. Signaling pathways involved were analysed using Western blot. Robinin pre-treatment considerably decreased the apoptotic rate by boosting the endogenous anti-oxidative activity and lowering the activity of Malonaldehyde and Lactate dehydrogenase enzyme. Robinin also inhibited the generation of ROS. Robinin reduced the expression of ERS-associated genes and proteins, thereby decreasing apoptosis-related proteins. Upon comparing the cardioprotective effect of Robinin with a known cardioprotective agent Dexrazoxane (DEX) it was revealed that DEX has more cardioprotective effect against DOX than H2O2-induced stress, while Robinin showed a significant protective effect against both H2O2 and DOX induced stress.