Dependent Way Research Articles

Insights into the structural changes that trigger receptor binding upon proteolytic activation of Bacillus thuringiensis Vip3Aa insecticidal protein.

Bacillus thuringiensis (Bt) bacteria produce different pore forming toxins with insecticidal activity, including Cry and Vip3 proteins. While both Cry and Vip3 cause insect death by forming pores in susceptible lepidopteran larval midgut cells, their mechanisms of action differ. The Vip3Aa protoxin adopts a tetramer-structure, where each monomer has five distinct domains. Upon proteolytic activation, the Vip3 tetramer undergoes a large conformational change forming a syringe like structure that is ready for membrane insertion and pore formation. Here we show that Vip3Aa protoxin had low binding to Spodoptera frugiperda brush border membrane vesicles (BBMV) unlike the activated toxin that bound specifically in a concentration dependent way, suggesting that a structural change upon Vip3Aa proteolytic activation is required for efficient receptor binding. Consistently, the Vip3Aa protoxin showed no toxicity to Sf9 cells compared to the activated toxin. In contrast, Cry1Fa protoxin and its activated toxin, were both highly toxic to Sf9 cells. To identify the region of Vip3 involved in binding to BBMV proteins, different overlapping peptides from Vip3Aa covering domains III, IV and V were expressed, and binding analysis were performed against BBMV, showing that domain III is the primary binding domain. Additionally, domains III, IV and V amino acid residues that become exposed upon activation of Vip3Aa were identified. Mutagenesis of these exposed residues revealed three amino acids (K385, K526 and V529) located in two structural adjacent loops, domain III loop β5-β6 and loop α11-β16 that connects domains III and IV, that are crucial for binding to the midguts of S. frugiperda larvae and for toxicity. Our results demonstrate that proteolytic activation of Vip3Aa exposes a receptor binding region essential for its toxicity.

REsolved ALMA and SMA Observations of Nearby Stars. REASONS: A population of 74 resolved planetesimal belts at millimetre wavelengths

Planetesimal belts are ubiquitous around nearby stars, and their spatial properties hold crucial information for planetesimal and planet formation models. We present resolved dust observations of 74 planetary systems as part of the REsolved ALMA and SMA Observations of Nearby Stars (REASONS) survey and archival reanalysis. We uniformly modelled interferometric visibilities for the entire sample to obtain the basic spatial properties of each belt, and combined these with constraints from multi-wavelength photometry. We report key findings from a first exploration of this legacy dataset: (1) Belt dust masses are depleted over time in a radially dependent way, with dust being depleted faster in smaller belts, as predicted by collisional evolution. (2) Most belts are broad discs rather than narrow rings, with much broader fractional widths than rings in protoplanetary discs. We link broad belts to either unresolved substructure or broad planetesimal discs produced if protoplanetary rings migrate. (3) The vertical aspect ratios ($h=H/R$) of 24 belts indicate orbital inclinations of sim 1-20$^ circ $, implying relative particle velocities of sim 0.1-4 km/s, and no clear evolution of heights with system age. This could be explained by early stirring within the belt by large bodies (with sizes of at least sim 140 km to the size of the Moon), by inheritance of inclinations from the protoplanetary disc stage, or by a diversity in evolutionary pathways and gravitational stirring mechanisms. We release the REASONS legacy multidimensional sample of millimetre-resolved belts to the community as a valuable tool for follow-up multi-wavelength observations and population modelling studies.

Comparison of Adequacy of Reduction of Third Malleolar Fracture in Prone vs. Spine Position in Tri-Malleolar Ankle Fracture a Tertiary Care Experience

Background: Ankle fractures, especially tri-malleolar fractures, are among the most frequent injuries to the lower extremities, affecting about 179 out of 100,000 individuals each year. Because of their complexity, these fractures provide serious complications for orthopedic surgeons. This work therefore analyzes tri-malleolar fractures to know the effect of prone position in relation to supine position while at the same time bearing in mind the characteristics of individual fracture, the surgeon and the patient. Methods: This comparative study was conducted at a tertiary care hospital, involving a cohort of 200 patients with diagnosed trimalleolar ankle fractures. All participants registered to a tertiary care hospital for management of tri-malleolar ankle fractures were included in the study. Having distinguished patients who stayed in supine position during reduction from those in prone position, the authors proceeded to comparing results. In order to assess effectiveness of each position, radiographic assessment, clinical evaluation and surgical issues were reviewed. Results: Third malleolar fractures were effectively reduced in both supine and prone positions. While the prone position continued to be a dependable way to treat posterior malleolus fractures, the supine position offered improved anterior visibility and maybe decreased neurovascular problems. Positive results were obtained using both methods. Conclusion: For the purpose of reducing tri-malleolar fractures, the decision between prone and supine positions should be made individually. Both approaches can produce acceptable results; however, more investigation is required to improve position selection criteria by taking fracture features and patient-specific factors into account. Keywords: Tri-malleolar fracture, posterior malleolus, prone position, supine position, fracture reduction.

12502 Bdnf Production by Kiss1 Neurons Acts in a Sexually Dependent Way to Control Sexual Development and Energy Balance in Female and Male Mice

Abstract Disclosure: A.M. Zanesco: None. D. Cabral: None. J. Ferreira: None. F. Valdivieso-Rivera: None. A.L. Carvalho: None. N. Mendes: None. C. Sponton: None. R. Frazao: None. L.A. Velloso: None. The hypothalamus is a key region in the central nervous system that controls different functions such as energy balance, thermogenesis, and reproduction. Kiss1 neurons integrate two distinct neuronal pathways, reproduction, and energy balance, both essential to species survival and maintenance. Recent studies, identify that the Brain-derived neurotrophic factor, BDNF produced by neurons and astrocytes in the hypothalamus is essential to control homeostatic and hedonic feeding by acting in specific groups of hypothalamic neurons. No studies showed the action of BDNF produced in the arcuate nucleus (ARC) of the hypothalamus. Using single-cell RNA sequencing analysis of data obtained from mice hypothalamus reveals that Kiss1 neurons express BDNF and we confirmed this result by immunofluorescence assay. Curiously, there is more expression of BDNF in the female hypothalamus compared with the male hypothalamus. But, when we selected specifically the BDNF produced by KISS1 neurons, this difference disappears. Based on that, we used a Cre-loxP approach to selectively knockout BDNF in Kiss1 neurons and identify the changes in sexual development and energy balance in female and male mice. All experiments were approved by the Animal Use Ethics Committee of UNICAMP (CEUA: 5591-1/2020 and CIBio 04/2021). All female and male mice were evaluated daily to identify their sexual development. We identified no changes in metabolic parameters, such as body weight and adiposity in male and female mice fed on a chow diet. Additionally, BDNF ablation in Kiss1 neurons (BDNF-KO) leaded to a premature vaginal opening, a decreased in uterus and ovary weight, and compromises the regular cyclicity of the estrus cycle in females. No difference was found in the sexual development of male mice, indicating that this effect is sexually dependent. Based on the fact that BDNF produced in VMH and DMH acts as anorexigenic effects, and Kiss1 neurons integrate the neuronal pathway responsible for energy balance, we decided to investigate the effects of BDNF ablation in Kiss1 neurons in female and male mice fed on high-fat diet. Interestingly, male mice without BDNF production in Kiss neurons were protected from obesity development compared with wild-type mice, both fed on a high-fat diet. When they were fed on a chow diet, male BDNF-KO mice, exhibited hyperphagia compared to control mice, showing a disruption in control of food intake and body weight maintenance. No differences were identified in body weight gain, food intake, and adiposity in BDNF-KO female mice. Based on that, we conclude that BDNF produced by Kiss1 exerts different functions in male and female mice. In females, it is more related to sexual development, and males in control of energy balance. This is the first research showing the BDNF production by Kiss1 neurons and its dimorphism effects on male and female mice. Presentation: 6/2/2024

An Assessment of Hepato-protective Activity of Hygrophila auriculata Root Extract against Hepatic Injured Rodent Model

Liver is a crucial organ that is susceptible to several hepatotoxins causing hepato-toxicities. These days, medicinal plants have been considered to be more promising compared with the conventionally utilized medications for hepatic treatments. In light of the dire circumstances affecting worldwide currently, Hygrophila auriculata is a vital plant with an abundance of health advantages and hepatoprotective properties. In this experiment, carbon tetrachloride (CCl4) was utilized to cause hepatotoxicity in rats and this plant's anti-hepatotoxic activity was evaluated through assessing the outcomes of several parameters (Liver functioning tests, kidney functioning tests and lipid profiles). Subsequent research revealed that the plant may, to varying degrees and in a dependent way, successfully restore the disrupted pathological state to healthy status. To interpret statistical analysis, the "One-way Anova test" was conducted using the SPSS 16 software. In the case of SGPT, the medium and high dose produced statistically significant (p<0.05) outcomes as compared to the negative control group and for SGOT decrease in all three groups were non-significant (p>0.05). Then for creatinine levels, the outcome for medium, and high dosages were statistically significant (p<0.05) whereas in case of urea level only the high dose imparted significant (p<0.05) decrease. However, none of the dosages for total cholesterol and triglyceride level produced statistically significant (p<0.05) effects. Only in the medium and high doses, HDL levels improved statistically significantly (p<0.05) whereas only the high dosages reduced reduce the LDL quantity in the blood significantly (p<0.05). As a result, Hygrophila auriculata is thought to possess a significant capacity for liver protection and may serve as a more secure and effective substitute for the commercially available synthetic medication, silymarin. To sum up, additional research is required in the future before this appealing plant could get utilized in the arena of hepatotoxic treatments.

Flavopiridol inhibits oocyte maturation, reduces oocyte quality and blocks cumulus cell function

Flavopiridol (FP) is a plant-derived flavonoidis and used to treat cancers, fungal infections and inflammation-related diseases. However, it is not clear whether it has side effects on the female reproductive system. In this study, we aimed to investigate the toxic effects and potential underlying mechanisms of FP on oocyte maturation and cumulus cell expansion in mice. Cumulus-oocyte complexes (COCs) were cultured in vitro with FP of gradient concentration (50–1000 nM), according to the plasma concentration of FP in the clinical trial. The maturation rate and cumulus expansion index of oocytes were counted and studied by immunofluorescence staining, qRT-PCR, oocyte chromosome preparation and so on. The results showed that the FP-exposed COCs inhibited the oocyte maturation and cumulus cell expansion, leading to cell apoptosis in a dose dependent way. Oocytes exposed to 500 nM FP showed abnormalities in the spindle structure and chromosome arrangement, ultimately leading to the oocyte maturation arrest and aneuploidy. This may be due to the excessive oxidative stress caused by mitochondrial membrane potential damage and mislocalization. Therefore, when FP is used for cancer treatment, its side effects on the female reproductive system should be seriously considered.

Blood biomarkers for cardiac damage during and after radiotherapy for esophageal cancer: A prospective cohort study

PurposeThe aim of this study was to test the hypothesis that the levels of High Sensitive Troponin T (HS-TNT) and N-terminal Brain Natriuretic Peptide (NT-ProBNP) increase after radiation therapy in a dose dependent way and are predictive for clinical cardiac events. Materials and MethodsBlood samples during and after radiotherapy of 87 esophageal cancer patients were analysed regarding the course of HS-TNT and NT-ProBNP levels and their relationship with clinical toxicity endpoints and radiation dose volume parameters. ResultsHS-TNT values at the end of treatment correlated with the mean heart dose (p = 0.02), whereas the rise of NT-ProBNP correlated with the mean lung dose (p = 0.01). Furthermore, the course of both HS-TNT (p < 0.001) and NT-ProBNP (p < 0.01) levels were significantly different for patients who developed new cardiac events as opposed to those without new cardiac events. ConclusionSignificant correlations were found for both biomarkers with radiation dose and clinical toxicity endpoints after treatment. Therefore, these markers might be of additional value in NTCP models for cardiac events and might help us unravelling the mechanisms behind these toxicity endpoints.

Kigelia pinnata fruit extract mediated green synthesis of Ce11O20/CeCu/CuO nanocomposites and their anticancer and antibacterial properties

In the current study, we used green synthesis techniques to conjugate additional metals into native nanoparticles, with an emphasis on how this altered its surface morphology and biological capabilities. It is an important turning point in the field of nanotechnology since it opens up new, dependable, environmentally friendly and manageable ways to prepare nanocomposites. This work employs a green synthetic technique to synthesize CuO nanparticles (KpCuO NPs), Ce11O20/CeCu/CuO nanocomposites (KpCe@CuO-5 and KpCe@CuO-10 NCs) using aqueous extract of Kigelia pinnata fruit. The materials were characterized by Fourier-Transform Infrared Spectroscopy (FTIR), surface area and porosity of nanocomposites analyzed with the Scanning Electronic Microscopy (SEM), Energy-dispersive X-ray spectroscopy (EDX), UV-visible spectroscopy (UV–visible), X-ray Powder Diffraction (XDR), XPS (X-ray photoelectron spectroscopy), and High-Resolution Transmission Electron Microscopy (HRTEM). The synthesized KpCuO NPs, KpCe@CuO-5 and KpCe@CuO-10 nanocomposites exhibited anticancerous activity against MDA-MB-231, HEK-293 and antimicrobial properties against E. Coli bacteria. These samples also demonstrated their bio-potency by preventing the migration and proliferation of cells, decreasing the number of colonies, and triggering cell cycle arrest and programmed cell death. All of these findings suggest that KpCuO NPs and KpCe@CuO NCs have therapeutic potential to treat triple negative breast cancer (TNBC).

Functional and metabolic effects of omega-3 polyunsaturated fatty acid supplementation and the role of β-hydroxy-β-methylbutyrate addition in chronic obstructive pulmonary disease: A randomized clinical trial

IntroductionShort-term (4 weeks) supplementation with n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has recently been shown to improve protein metabolism in a dose dependent way in normal weight patients with Chronic Obstructive Pulmonary Disease (COPD). Furthermore, EPA/DHA supplementation was able to increase extremity lean soft tissue but not muscle function. No studies are available combining n-3 PUFAs and the leucine metabolite β-hydroxy-β-methylbutyrate (HMB) supplementation in chronic clinical conditions. Whether adding HMB to daily EPA/DHA supplementation for 10 weeks enhances muscle and brain health, daily functional performance, and quality of life of patients with COPD by further improving their protein and amino acid homeostasis remains unknown. MethodsPatients with COPD (GOLD: II-IV, n=46) received daily for 10 weeks, according to a randomized double-blind placebo-controlled three-group design, EPA/DHA (n=16), EPA/DHA to which HMB was added (n=14), or placebo (n=16). The daily dose of 2.0 g of EPA/DHA or soy + corn oil as the placebo was provided via gel capsules, and 3.0 g of Ca-HMB or maltodextrin as placebo as powders. At pre- and post-intervention, a pulse mixture of multiple amino acids was administered to measure postabsorptive net protein breakdown (netPB as primary endpoint) and whole body production (WBP) and conversion rates of the amino acids. As secondary endpoints, lean soft tissue, and fat mass were assessed by dual-energy X-ray absorptiometry, upper and lower muscle function by handgrip and single leg isokinetic dynamometry, brain (cognitive, wellbeing) health by assessments, daily functional performance by measuring 6-minute walk distance, 4-meter gait speed, and postural balance, and quality of life by questionnaire. Plasma enrichments and concentrations were analyzed by LC-MS/MS, and systemic inflammatory profile and metabolic hormones by Luminex. ResultsHMB + EPA/DHA but not EPA/DHA supplementation increased postabsorptive netPB (p=0.028), and WBPs of glutamine (p=0.024), taurine (p=0.039), and tyrosine (p=0.036). Both EPA/DHA and HMB + EPA/DHA supplementation resulted in increased WBP of phenylalanine (p<0.05). EPA/DHA but not HMB + EPA/DHA was able to increase WBP of arginine (p=0.030), citrulline (p=0.008), valine (p=0.038), and conversion of citrulline to arginine (p=0.009). Whole body and extremity fat mass were reduced after HMB + EPA/DHA supplementation only, whereas lean soft tissue was increased after EPA/DHA (p=0.049) and HMB + EPA/DHA (p=0.073). No other significant findings were observed. Reductions in several proinflammatory cytokines were observed in the HMB + EPA/DHA group including IL-2, IL-17, IL-6, IL-1 receptor antagonist, IL-12P40, and TNF-β (p<0.05). ConclusionsTen weeks of supplementation with 2 g of EPA/DHA daily is sufficient to induce muscle gain in COPD but HMB is needed to induce fat loss. Whether HMB is solely responsible for the fat mass loss or has a synergistic effect with EPA/DHA remains unclear. The increase in net protein breakdown observed with HMB + EPA/DHA supplementation may not indicate harmful muscle catabolism but rather a beneficial enhanced protein turnover cycling associated with increased lean soft tissue. Clinical Trial RegistryClinicalTrials.gov; NCT03796455

Hepatoprotective effect of date fruit extract against ethanol-induced apoptosis in human hepatoma (HepG2) cells

Ethanol is a well-known hepatotoxic agent and date fruits have been associated with their biological actions. In current study, we have investigated the hepatoprotective potential of DFE on ethanol-induced cellular damages in human hepatoma (HepG2) cells. The hepatoprotective potential was assessed by exposing the HepG2 cells to non-toxic concentrations (15, 30, and 60 μg/mL) of DFE for 24 h; then toxic concentration (500 μM) of ethanol. Our results demonstrated that pretreatment with DFE significantly prohibited ethanol-induced hepatotoxicity in HepG2 cells. We observed that DFE treatment increased cell viability, reduced LDH leakage, restored cellular morphology, and inhibited caspase-3 enzyme activity in a dose dependent way, induced by ethanol. Further DFE was also effective in restoring the LPO, GSH, and catalase levels towards normal altered by ethanol. Our results also revealed that ethanol-induced ROS generation was significantly inhibited by DFE. The ethanol-induced mRNA expression of apoptotic related genes (p53, caspase-3, caspase-7, Bax, and Bcl-2) were also normalized by pretreatment with DFE. The findings from this study indicated that DFE can significantly protect HepG2 cells against ethanol-induced hepatotoxicity. Our study also provides scientific validation for the traditional use of DFE, aiming to understand its hepatoprotective potential. Altogether, to the best of our knowledge, this is the first study demonstrated that ethanol-induced hepatotoxicity can be prohibited by the DFE. Thus, DFE has a potential application in nutraceuticals as a therapeutic agent to prevent liver diseases.

Remediation Strategies of Xenobiotics in Urban Soils and Water: A Review

Xenobiotic substances are synthetic chemicals that are not native to a specificecological system yet have biological activity. Drugs, industrial chemicals, naturally occurring toxins, and environmental contaminants are all examples of xenobiotics. By disrupting or interfering with many cellular communication routes that control growth, development, and normal physiological function, xenobiotics can have a negative impact on human health. These chemicals are extremely poisonous in nature and can harm both lower and higher eukaryotes. These substances are persistent, allowing for bioaccumulation or biomagnification in the environment over time. They also find their way into food chains, where their concentrations are found to be high even in creatures that do not come into direct contact with xenobiotics. Industries regularly release xenobiotics into the environment, increasing the danger of human and other biota exposure. Despite the use of a variety of traditional and modern environment remediation technologies, some of them are unsuccessful at eliminating xenobiotics, while others are too expensive to use on a wide scale. Maize Stover and Rice Husk are abundantly generated across the world, making them attractive and cost-effective feedstocks for large scale biochar synthesis for environmental clean-up. Because virgin Maize Stover and Rice Husk biochar may not be successful in removing some xenobiotics, adding modifiers to MS/RH biochar can help to generate composite MS/RH biochar, which can aid to disinfect water and soil more effectively. Some microbes have the ability to partially or completely break down xenobiotic substances. The most dependable ways for degrading these chemicals are biological and non-biological remediation procedures. Bacterial biodegradation is a cost-effective approach for land filling and composting that employs both wild type and genetically engineered bacterial strains. Many non-biological approaches that are suited for xenobiotic degradation have been categorised under thermal and non-thermal procedures.

E-WASTE MANAGEMENT THROUGH DEEP LEARNING: A SEQUENTIAL NEURAL NETWORK APPROACH

The goal of this research is to improve the management of electronic trash (e-waste) by using a Sequential Neural Network (SNN) with TensorFlow and Keras as part of an advanced deep learning technique. In order to address the growing problem of e-waste, the research collects a large amount of data from images of e-waste and then carefully preprocesses and augments those images. With precision, recall, and F1 scores of 87%, 86%, and 86%, respectively, the SNN architecture—which incorporates dropout, pooling, and convolutional layers—achieved an amazing 100% classification accuracy. These outstanding outcomes show how well the model can classify e-waste components, suggesting that it has the potential to be used in real-world scenarios. The results indicate that the SNN-based approach greatly improves the accuracy and efficiency of e-waste sorting, promoting environmental sustainability and resource conservation. By automating the sorting process, the suggested system decreases the need for manual labor, minimizes human error, and speeds up processing. The study emphasizes the model's suitability for integration into current e-waste management workflows, providing a scalable and dependable way to expedite the recycling process. Additionally, the model's real-time applicability highlights its potential to revolutionize current e-waste management practices, making a positive ecological impact. . Future research endeavors will center on broadening the dataset to include a wider range of e-waste image categories, investigating more advanced deep learning architectures, and incorporating the system with Internet of Things (IoT) devices to improve real-time monitoring and management.

CO2 Concentration Assessment for Infection Monitoring and Occupancy Analysis in Tanzanian COVID-19 Isolation Centers

Monitoring of IAQ is one of the foundations of the preventative actions prompted by the worldwide recognition of COVID-19 transmission. The measurement of CO2 has emerged as one of the most popular, dependable, and easy ways to indirectly evaluate the state of indoor air renewal. Reducing the risk of respiratory diseases transmitted by aerosols is attainable through implementing and validating prevention measures made possible by CO2 control. Isolation centers are like health facilities in that they are linked to IAQ, and the presence of natural ventilation can significantly improve the circulation of fresh air, which speeds up the removal of contaminants. This is true even though healthcare facilities are among the environments with the highest rate of COVID-19 propagation. Our investigation revealed, however, that no substantial critical data on air quality in Tanzanian isolation centers is presently available. The process of metabolic CO₂ creation and accumulation within health isolation center cubicles was investigated in this study. Crucially, we suggest comparing settings under various conditions using the indicator ppm/patient. In this research, we experimentally assessed the value of changing a few HVAC system characteristics. We looked at the data to see how well the filtration system worked concerning the submicron particle concentration. Study recommendations for CO2 detectors and ways to reduce infection risk in shared isolation center cubicles are provided. We also show the correlation between particle size and CO2 concentration, the correlation between CO2 concentration derivatives and air volume presented per patient in isolation cubicles, the correlation between patient occupancy and CO2 concentration levels in isolation cubicles, and how to improve air quality by adjusting the patient’s bed position. The study also found that for exposure lengths of two to three hours, a typical hospital cubicle with fifty to one hundred people should have an average interior CO₂ value of less than 900 ppm. Carers’ length of stay in the hospital substantially impacted the permissible CO2 concentration. By establishing a connection between indoor air monitoring and healthcare goals, this study will aid in determining the feasibility of establishing regulations for interior CO2 content depending on occupancy settings, strengthening preventive efforts against COVID-19. In the post-pandemic era, it will be essential to find ways to make health facilities air cleaner so that infectious diseases cannot spread in the future.

Progress on the role of LIN28A/B in tumor development and progression.

LIN28A and its homolog LIN28B are highly conserved RNA-binding proteins that play important roles in early embryonic development, somatic cell reprogramming, metabolism and tumorigenesis. LIN28A/B are highly expressed in a variety of malignant tumors such as breast cancer. They play important roles in the initiation, maintenance, and metastasis of tumors and are associated with poor prognosis. Previous studies have shown that the main regulatory mechanisms of LIN28A/B include let-7s dependent ways and let-7s independent ways, such as directly targeting mRNA. In this review, we summarize the function and molecular regulatory mechanisms of LIN28A/B in malignant tumors such as liver cancer, breast cancer and colorectal cancer, in order to provide references for further exploring the function and mechanism of LIN28A/B and their possible roles in clinical applications.

Positive roles of the Ca2+ sensors GbCML45 and GbCML50 in improving cotton Verticillium wilt resistance.

As a universal second messenger, cytosolic calcium (Ca2+) functions in multifaceted intracellular processes, including growth, development and responses to biotic/abiotic stresses in plant. The plant-specific Ca2+ sensors, calmodulin and calmodulin-like (CML) proteins, function as members of the second-messenger system to transfer Ca2+ signal into downstream responses. However, the functions of CMLs in the responses of cotton (Gossypium spp.) after Verticillium dahliae infection, which causes the serious vascular disease Verticillium wilt, remain elusive. Here, we discovered that the expression level of GbCML45 was promoted after V. dahliae infection in roots of cotton, suggesting its potential role in Verticillium wilt resistance. We found that knockdown of GbCML45 in cotton plants decreased resistance while overexpression of GbCML45 in Arabidopsis thaliana plants enhanced resistance to V. dahliae infection. Furthermore, there was physiological interaction between GbCML45 and its close homologue GbCML50 by using yeast two-hybrid and bimolecular fluorescence assays, and both proteins enhanced cotton resistance to V. dahliae infection in a Ca2+-dependent way in a knockdown study. Detailed investigations indicated that several defence-related pathways, including salicylic acid, ethylene, reactive oxygen species and nitric oxide signalling pathways, as well as accumulations of lignin and callose, are responsible for GbCML45- and GbCML50-modulated V. dahliae resistance in cotton. These results collectively indicated that GbCML45 and GbCML50 act as positive regulators to improve cotton Verticillium wilt resistance, providing potential targets for exploitation of improved Verticillium wilt-tolerant cotton cultivars by genetic engineering and molecular breeding.

Role of Artificial Intelligence in Diabetic Wound Screening and Early Detection

: The morbidity and death rates linked to diabetes mellitus are substantially increased by foot ulcers, a prevalent consequence of the disease. Proper wound management is essential for controlling foot ulcers. This includes monitoring the ulcers' healing progress through clinical reviews, changing dressings as needed, treating infections with the right medications, and ensuring that the ulcer is offloaded correctly. Taking pictures of the ulcer was a dependable way to track how diabetic foot ulcers were healing in the past. Images of foot ulcers have recently experienced a tremendous change due to the emergence of digital cameras in cell phones. Artificial intelligence (AI) and other recent developments in digital health technology present a great chance to improve the efficiency of diabetes care, which might reduce the growth in healthcare costs associated with diabetes. Patients with diabetes can alleviate the burden on clinics and patients' transportation demands by electronically sharing photos of their ulcers, which diabetes care providers can remotely monitor. Improved remote monitoring of diabetic foot ulcers using smartphone apps is now possible with the help of a new generation of AI-powered solutions. This clinical update review aims to gather information on this trending topic so that medical professionals can be current on all the latest advancements in the field.

Law Grit - One Stop Legal Solution

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Single Stage Autonomous Solar Water Pumping System Using PMSM Drive

Water supply technology has advanced significantly with the development of autonomous solar water pumping devices. These solar-powered systems offer a dependable and sustainable way to pump water in remote and off-grid areas. They are the perfect solution for solving problems with water delivery in places with restricted access to power because of their capacity to function independently and without the requirement for grid electricity. Autonomous solar water pumping systems present a viable and creative approach to a sustainable water supply at a time when demand for renewable energy solutions is only expected to increase. Sustainable and effective agricultural techniques have advanced significantly with the introduction of autonomous solar water pumping equipment. These solar-powered devices provide an economical and environmentally responsible way to address the problems of declining water supplies and growing energy expenses. Adoption of autonomous solar water pumping devices will be essential to maintaining the productivity and long-term sustainability of our world's food supply as the agricultural sector develops.

Emerging evidence of context-dependent synapse elimination by phagocytes in the CNS.

Precise synapse elimination is essential for the establishment of a fully developed neural circuit during brain development and higher function in adult brain. Beyond immune and nutrition support, recent groundbreaking studies have revealed that phagocytic microglia and astrocytes can actively and selectively eliminate synapses in normal and diseased brains, thereby mediating synapse loss and maintaining circuit homeostasis. Multiple lines of evidence indicate that the mechanisms of synapse elimination by phagocytic glia are not universal but rather depend on specific contexts and detailed neuron-glia interactions. The mechanism of synapse elimination by phagocytic glia is dependent on neuron-intrinsic factors and many innate immune and local apoptosis-related molecules. During development, microglial synapse engulfment in the visual thalamus is primarily influenced by the classic complement pathway, whereas in the barrel cortex, the fractalkine pathway is dominant. In Alzheimer's disease, microglia employ complement-dependent mechanisms for synapse engulfment in tauopathy and early β-amyloid pathology, but microglia are not involved in synapse loss at late β-amyloid stages. Phagocytic microglia also engulf synapses in a complement-dependent way in schizophrenia, anxiety, and stress. In addition, phagocytic astrocytes engulf synapses in a MEGF10-dependent way during visual development, memory, and stroke. Furthermore, the mechanism of a phenomenon that phagocytes selectively eliminate excitatory and inhibitory synapses is also emphasized in this review. We hypothesize that elucidating context-dependent synapse elimination by phagocytic microglia and astrocytes may reveal the molecular basis of synapse loss in neural disorders and provide a rationale for developing novel candidate therapies that target synapse loss and circuit homeostasis.

Abstract PO3-24-10: Losartan enhances the radiosensitivity of triple-negative breast cancer by reshaping the tumor immune microenvironment

Abstract Triple-negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer, and the therapeutic options available for TNBC are limited. In addition to surgery and chemotherapy, radiotherapy (RT) is a primary treatment modality for TNBC. However, radio-resistance poses significant challenges to TNBC treatment. Prior research has shown that losartan, an angiotensin receptor blocker, can improve vessel perfusion and drug delivery, thereby enhancing the efficacy of chemotherapy or radiotherapy in cancer. However, in our study, we found that losartan could enhance the radiosensitivity of TNBC in immunocompetent mice model, but not in immunodeficient mice model and TNBC cells. It suggested that losartan might enhance the radiosensitivity of TNBC in an immune system dependent way. Previous studies had noted that tumor immune microenvironment (TIME) played an important role in radio-resistance. Therefore, we focused on the TIME in our further study. For immune cells, it had reported that the recruitment and activation of immunosuppressive cells such as M2 phenotype tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), could lead to the establishment of and immunosuppressive TIME and decreased the radiosensitivity. In this study, we found losartan facilitated the polarization of TAMs towards the M1 phenotype, and impeded the immunosuppressive function of MDSCs after RT in 4T1 TNBC mice model. Additionally, losartan also caused a significant increase of CD8+ T lymphocytes in the TIME, and also markedly enhanced the activity of infiltrated T cell. When the CD8+ T cells were eliminated by anti-CD8α antibody, the radiosensitization effect of losartan was significantly decreased. Therefore, T-cell mediated tumor suppression is essential for the radiosensitization caused by losartan in TNBC. For immune factors, we found that TNBC exhibited an increase in the expression of programmed death-ligand (PD-L1) and indoleamine-2,3-dioxygenase (IDO) upon exposure to irradiation, and the combination of losartan resulted in a significant reduction in their expression in vitro and in vivo. At the same time, the 4T1 TNBC transplantation tumors were significantly inhibited by losartan combined with PD-1 inhibitor after RT, which indicated that losartan might amplify the efficacy of radio-immunotherapy. Collectively, these findings suggest that losartan could reshape the TIME of TNBC through regulating immune cells (TAMs, MDCSs and CD8+ T cells) and immune factors (PD-L1 and IDO), which result in the enhancement of radiosensitivity of TNBC. In our investigation, losartan was innovatively found to increase the radiosensitivity of TNBC by reshaping the TIME rather than on the tumor stroma. As one of the most commonly prescribed drugs for hypertension, the safety and affordability of losartan have been extensively confirmed. In the future, losartan combined with radiotherapy might be a promising strategy for TNBC treatment. Citation Format: Cuiwei Liu, Xu Wang, Zihan Xia, Yuxi Ma, Yanxia Zhao. Losartan enhances the radiosensitivity of triple-negative breast cancer by reshaping the tumor immune microenvironment [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-24-10.