Exploring the role of Müller cells-derived exosomes in diabetic retinopathy.

Exosomes are nanosized vesicles that have been reported as cargo-delivering vehicles between cells. Müller cells play a crucial role in the pathogenesis of diabetic retinopathy (DR). Activated Müller cells in the diabetic retina mediate disruption of barrier integrity and neovascularization. Endothelial cells constitute the inner blood-retinal barrier (BRB). Herein, we aim to evaluate the effect of Müller cell-derived exosomes on endothelial cell viability and barrier function under normal and hyperglycemic conditions. Müller cell-derived exosomes were isolated and characterized using Western blotting, nanoparticle tracking, and electron microscopy. The uptake of Müller cells-derived exosomes by the human retinal endothelial cells (HRECs) was monitored by labeling exosomes with PKH67. Endothelial cell vitality after treatment by exosomes under normo- and hypoglycemic conditions was checked by MTT assay and Western blot for apoptotic proteins. The barrier function of HRECs was evaluated by analysis of ZO-1 and transcellular electrical resistance (TER) using ECIS. Additionally, intracellular Ca+2 in HRECs was assessed by spectrofluorimetry. Analysis of the isolated exosomes showed a non-significant change in the number of exosomes isolated from both normal and hyperglycemic condition media, however, the average size of exosomes isolated from the hyperglycemic group showed a significant rise when compared to that of the normoglycemic group. Müller cells derived exosomes from hyperglycemic condition media markedly reduced HRECs cell count, increased caspase-3 and Annexin V, decreased ZO-1 levels and TER, and increased intracellular Ca+ when compared to other groups. However, treatment of HRECs under hyperglycemia with normo-glycemic Müller cells-derived exosomes significantly decreased cell death, preserved cellular integrity and barrier function, and reduced intracellular Ca+2. Collectively, Müller cell-derived exosomes play a remarkable role in the pathological changes associated with hyperglycemia-induced inner barrier dysfunction in DR. Further in vivo research will help in understanding the role of exosomes as therapeutic targets and/or delivery systems for DR.

Thiadiazole/Thiadiazine Derivatives as Insecticidal Agent: Design, Synthesis, and Biological Assessment of 1,3,4-(Thiadiazine/Thiadiazole)-Benzenesulfonamide Derivatives as IGRs Analogues against Spodoptera littoralis.

In keeping with our investigation, a simple and practical synthesis of novel heterocyclic compounds with a sulfamoyl moiety that can be employed as insecticidal agents was reported. The compound 2-hydrazinyl-N-(4-sulfamoylphenyl)-2-thioxoacetamide 1 was coupled smoothly with triethylorthoformate or a variety of halo compounds, namely phenacyl chloride, chloroacetyl chloride, chloroacetaldehyde, chloroacetone, 1,3-dichloropropane, 1,2-dichloroethane, ethyl chloroformate, 2,3-dichloro-1,4-naphthoquinone, and chloroanil respectively, which afforded the 1,3,4-thiadiazole and 1,3,4-thiadiazine derivatives. The new products structure was determined using elemental and spectral analysis. Under laboratory conditions, the biological and toxicological effects of the synthetic compounds were also evaluated as insecticides against Spodoptera littoralis (Boisd.). Compounds 3 and 5 had LC50 values of 6.42 and 6.90 mg/L, respectively. The investigated compounds (from 2 to 11) had been undergoing molecular docking investigation for prediction of the optimal arrangement and strength of binding between the ligand (herein, the investigated compounds (from 2 to 11)) and a receptor (herein, the 2CH5) molecule. The binding affinity within docking score (S, kcal/mol) ranged between -8.23 (for compound 5), -8.12 (for compound 3) and -8.03 (for compound 9) to -6.01 (for compound 8). These compounds were shown to have a variety of binding interactions within the 2CH5 active site, as evidenced by protein-ligand docking configurations. This study gives evidence that those compounds have 2CH5-inhibitory capabilities and hence may be used for 2CH5-targeting development. Furthermore, the three top-ranked compounds (5, 3, and 9) and the standard buprofezin were subjected to density functional theory (DFT) analysis. The highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) energy difference (ΔE) of compounds 5, 3, and 9 was found to be comparable to that of buprofezin. These findings highlighted the potential and relevance of charge transfer at the molecular level.

Pan-inhibition of the three H2S synthesizing enzymes restrains tumor progression and immunosuppression in breast cancer.

BACKGROUND: Hydrogen sulfide (H2S) is a significant endogenous mediator that has been implicated in the progression of various forms of cancer including breast cancer (BC). Cystathionine-ß-synthase (CBS), cystathionine-γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3MST) are the three principal mammalian enzymes responsible for H2S production. Overexpression of CBS, CSE and 3MST was found to be associated with poor prognosis of BC patients. Moreover, H2S was linked to an immune-suppressive tumor microenvironment in BC. Recently it was observed that BC cells, in response to single or dual inhibition of H2S synthesizing enzymes, develop an escape mechanism by overexpressing alternative sources of H2S generation. Thus, the aim of this work is to escape the H2S compensatory mechanism by pan repressing the three enzymes using microRNAs (miRNAs) and to investigate their impact on the oncogenic and immunogenic profile of BC cells. METHODS: BC female patients (n = 25) were recruited. In-silico analysis was used to identify miRNAs targeting CBS, CSE, and 3MST. MDA-MB-231 cells were cultured and transfected using oligonucleotides. Total RNA was extracted using Biazol, reverse transcribed and quantified using qRT-PCR. H2S levels were measured using AzMc assay. BC hallmarks were assessed using trans-well migration, wound healing, MTT, and colony forming assays. RESULTS: miR-193a and miR-548c were validated by eight different bioinformatics software to simultaneously target CBS, CSE and 3MST. MiR-193a and miR-548c were significantly downregulated in BC tissues compared to their non-cancerous counterparts. Ectopic expression of miR-193a and miR-548c in MDA-MB-231 TNBC cells resulted in a marked repression of CBS, CSE, and 3MST transcript and protein levels, a significant decrease in H2S levels, reduction in cellular viability, inhibition of migration and colony forming ability, repression of immune-suppressor proteins GAL3 GAL9, and CD155 and upregulation of the immunostimulatory MICA and MICB proteins. CONCLUSION: This study sheds the light onto miR-193a and miR-548c as potential pan-repressors of the H2S synthesizing enzymes. and identifies them as novel tumor suppressor and immunomodulatory miRNAs in TNBC.

Burden of Ischemic and Hemorrhagic Stroke Across the US From 1990 to 2019.

Importance: Stroke is a leading cause of death and disability in the US. Accurate and updated measures of stroke burden are needed to guide public health policies. Objective: To present burden estimates of ischemic and hemorrhagic stroke in the US in 2019 and describe trends from 1990 to 2019 by age, sex, and geographic location. Design, Setting, and Participants: An in-depth cross-sectional analysis of the 2019 Global Burden of Disease study was conducted. The setting included the time period of 1990 to 2019 in the US. The study encompassed estimates for various types of strokes, including all strokes, ischemic strokes, intracerebral hemorrhages (ICHs), and subarachnoid hemorrhages (SAHs). The 2019 Global Burden of Disease results were released on October 20, 2020. Exposures: In this study, no particular exposure was specifically targeted. Main Outcomes and Measures: The primary focus of this analysis centered on both overall and age-standardized estimates, stroke incidence, prevalence, mortality, and DALYs per 100 000 individuals. Results: In 2019, the US recorded 7.09 million prevalent strokes (4.07 million women [57.4%]; 3.02 million men [42.6%]), with 5.87 million being ischemic strokes (82.7%). Prevalence also included 0.66 million ICHs and 0.85 million SAHs. Although the absolute numbers of stroke cases, mortality, and DALYs surged from 1990 to 2019, the age-standardized rates either declined or remained steady. Notably, hemorrhagic strokes manifested a substantial increase, especially in mortality, compared with ischemic strokes (incidence of ischemic stroke increased by 13% [95% uncertainty interval (UI), 14.2%-11.9%]; incidence of ICH increased by 39.8% [95% UI, 38.9%-39.7%]; incidence of SAH increased by 50.9% [95% UI, 49.2%-52.6%]). The downturn in stroke mortality plateaued in the recent decade. There was a discernible heterogeneity in stroke burden trends, with older adults (50-74 years) experiencing a decrease in incidence in coastal areas (decreases up to 3.9% in Vermont), in contrast to an uptick observed in younger demographics (15-49 years) in the South and Midwest US (with increases up to 8.4% in Minnesota). Conclusions and Relevance: In this cross-sectional study, the declining age-standardized stroke rates over the past 3 decades suggest progress in managing stroke-related outcomes. However, the increasing absolute burden of stroke, coupled with a notable rise in hemorrhagic stroke, suggests an evolving and substantial public health challenge in the US. Moreover, the significant disparities in stroke burden trends across different age groups and geographic locations underscore the necessity for region- and demography-specific interventions and policies to effectively mitigate the multifaceted and escalating burden of stroke in the country.

Exploration of Some Heterocyclic Compounds Containing Trifluoromethylpyridine Scaffold as Insecticides Toward Aphis gossypii Insects.

Five types of heterocyclic compounds containing trifloromethylpyridine scaffold namely; 3-cyano-2-(N-phenyl)carbamoylmethylthio-6-(thiophen-2-yl)-4-trifluoromethyl-pyridine (6a), thieno[2,3-b]pyridines 3-5 and 7a-c, pyrido[3',2':4,5]thieno[3,2-d] pyrimidines 8-13 and 15a-c, pyrido[3',2':4,5]thieno[3,2-d][1,2,3]triazines 16a,b, and 9-(thiophen-2-yl)-7-(trifluoromethyl) pyrido [3',2':4,5]thieno[2,3-e][1,2,4]triazolo[1,5-c]pyrimidine (14) were synthesized in excellent yields and very pure state. The structures of these compounds were confirmed by elemental and spectral analyses. Most of the synthesized compounds were evaluated as insecticidal agents toward Aphis gossypii insects and promising results obtained. Among all tested compounds, only 6, 7a, 7c and 15c being the most potent compounds against nymphs and adults of Aphis gossypii and their activities are nearly to that of acetamiprid as a reference. The effect of 6a compounds 7a, 7c and 15c on the Aphis digestive system from histological point of view was also included.

The epidemiological and economic burden of diabetes in Ghana: A scoping review to inform health technology assessment.

Diabetes remains one of the four major causes of morbidity and mortality globally among non-communicable diseases (NCDs. It is predicted to increase in sub-Saharan Africa by over 50% by 2045. The aim of this study is to identify, map and estimate the burden of diabetes in Ghana, which is essential for optimising NCD country policy and understanding existing knowledge gaps to guide future research in this area. We followed the Arksey and O'Malley framework for scoping reviews. We searched electronic databases including Medline, Embase, Web of Science, Scopus, Cochrane and African Index Medicus following a systematic search strategy. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews was followed when reporting the results. A total of 36 studies were found to fulfil the inclusion criteria. The reported prevalence of diabetes at national level in Ghana ranged between 2.80%- 3.95%. At the regional level, the Western region reported the highest prevalence of diabetes: 39.80%, followed by Ashanti region (25.20%) and Central region at 24.60%. The prevalence of diabetes was generally higher in women in comparison to men. Urban areas were found to have a higher prevalence of diabetes than rural areas. The mean annual financial cost of managing one diabetic case at the outpatient clinic was estimated at GHS 540.35 (2021 US $194.09). There was a paucity of evidence on the overall economic burden and the regional prevalence burden. Ghana is faced with a considerable burden of diabetes which varies by region and setting (urban/rural). There is an urgent need for effective and efficient interventions to prevent the anticipated elevation in burden of disease through the utilisation of existing evidence and proven priority-setting tools like Health Technology Assessment (HTA).

High gain antipodal meander line antenna for point-to-point WLAN/WiMAX applications.

This paper introduces a planar antipodal meander line antenna fabricated using RO3003 substrate. The proposed antenna is designed to radiate in the end-fire direction, achieving a maximum measured gain of 10.43 dBi within its working bandwidth, which ranges from 2.24 GHz to 2.7 GHz, covering long-range WLAN/WiMAX applications. A systematic procedure is adopted in the design process to prove its tunability to cover other application requirements in terms of gain and bandwidth. The proposed design steps show that the bandwidth and the gain can independently be controlled by adjusting specific design parameters such as the number of radiators and the scaling factor. The antenna is fine-tuned using sensitivity analysis and parametric study to guarantee optimum operation at the desired bandwidth. Experimental measurements of the fabricated design demonstrate a high degree of correlation with simulations conducted using CST and HFSS. In comparison to other end-fire antennas presented in the literature, the proposed design manifests its capability to provide high gain for WLAN/WiMAX nodes connectivity. The measurements show that the proposed traveling wave antenna exhibits a high radiation efficiency with maximum value of 99.8% at 2.35 GHz. The measured side lobe level is found to be below - 18 dB and - 20 dB at 2.45 GHz along the E - and H -planes, respectively. Apart from its excellent radiation performance, the antenna is characterized by its low profile and fabrication simplicity.

Synthesis and Insecticidal Evaluation of 3,5-Dicyanopyridines Against Cotton Aphids via Microwave-Assisted Multicomponent Reactions.

Certain 2-amino-6-alkoxy-4-arylpyridine-3,5-dicyanide 1a-e were prepared via a straightforward process using microwave technology rather than conventional methods. This involved reaction of arylidenemalononitrile thru propanedinitrile in the occurrence of sodium alkoxide under MW. While, their positional isomer 4-amino-6-alkoxy-2-arylpyridine-3,5-dicyanide 3a-j have been separated from the reaction of aryl aldehydes with 2-aminoprop-1-ene-1,1,3-tricarbonitrile 2 in the presence of sodium alkoxide using microwave technic. Furthermore, the insecticidal properties of all synthesized compounds were observed with respect to Cotton aphid nymphs and adults. Neonicotinoid pesticides are indicated as the most effective pesticides toward aphids and many other pests. Many insecticides are discovered as novelties. As a result, several pyridine compounds were chemical method synthesized to serve as equivalents of neonicotinoids, a broad class of insecticides. With LC50 value of 0.03 mg/L, components 3g exhibit the highest insecticidal bioactivity. This work discusses how to find new chemicals that could be used as insecticidal agents in the future.

A tolerant hydrologic technique for real-time selection of optimum QPFs from NWPMs for flood warning applications.

The most important information required to successfully issue a flood warning is the quantitative precipitation forecasts (QPFs). This is important to run subsequent rainfall-runoff simulations. A rainfall-runoff simulation derives its accuracy mainly from the accuracy of the input QPFs. The dynamically based global numerical weather prediction models (NWPMs) are strong candidate sources of QPFs. A main problem is the real-time selection of which NWPM should be used to provide the QPFs for flood warning simulations. This paper develops an automated technique to solve this problem. The technique performs real-time comparisons with measured rainfall fields using a novel 'tolerant' hydrologic approach. The 'tolerant' approach performs the comparison on the basin scale and allows for timing shifts in the forecasts. This is because QPFs can be good but only a few hours early or late. Two events are used for illustration, and the proposed real-time application in flood warning is presented. The developed technique, employing the tolerant approach, could eliminate the effects of the timing shifts and, accordingly, succeeded to select the QPFs to be used. A Python package was developed for automation. The developed technique is expected to also be useful for offline assessments of historical performances of NWPMs.

Role of Hydrogen Sulfide in Oncological and Non-Oncological Disorders and Its Regulation by Non-Coding RNAs: A Comprehensive Review.

Recently, myriad studies have defined the versatile abilities of gasotransmitters and their synthesizing enzymes to play a "Maestro" role in orchestrating several oncological and non-oncological circuits and, thus, nominated them as possible therapeutic targets. Although a significant amount of work has been conducted on the role of nitric oxide (NO) and carbon monoxide (CO) and their inter-relationship in the field of oncology, research about hydrogen sulfide (H2S) remains in its infancy. Recently, non-coding RNAs (ncRNAs) have been reported to play a dominating role in the regulation of the endogenous machinery system of H2S in several pathological contexts. A growing list of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are leading the way as upstream regulators for H2S biosynthesis in different mammalian cells during the development and progression of human diseases; therefore, their targeting can be of great therapeutic benefit. In the current review, the authors shed the light onto the biosynthetic pathways of H2S and their regulation by miRNAs and lncRNAs in various oncological and non-oncological disorders.

Green synthesis and bioefficacy screening of new insect growth regulators as eco-friendly insecticides against the cotton mealybug Phenacoccus solenopsis.

Overcoming or reducing the majority of difficulties caused by the use of common pesticides requires the use of developed, secure, unique and selective organic compounds. Due to their clear mechanism of action on pests and lower poisonousness towards vertebrates than conventional insecticides, juvenile hormone analogues as an example of insect growth regulators appear promising. Thus, a unique set of pure insect growth regulators has been synthesized. The structure of these synthesized compounds, which were related to the most well-known insect growth regulator insecticides, was confirmed by elemental and contemporary spectroscopic investigations (IR, UV, 1 H-NMR, 13 C NMR, and Dept 135 spectrum). Under laboratory conditions, the effectiveness of a chemically newly synthesized products was tested against the cotton mealybug, Phenacoccus solenopsis, and compared with Fenoxycarb as a reference insecticide. Compound 7 was discovered to be more effective than the other synthetic compounds, with LC50 values of 0.907 mg/L for adult female P. solenopsis and 0.377 mg/L for third instar nymphs. Furthermore, this results concluded that the adult female's stage of P. solenopsis was less sensitive to the checked treatments as matched to the third instar nymphs.

Efficacy of chitosan nanoparticles and wax coatings on maintaining post-harvest quality of "Murcott" mandarins.

Because of its high degree of biodegradability, chitosan is widely used as a component in food packaging. However, its poor physical properties, such as permeability, limit its applicability. Consequently, applying nano chitosan is regarded as the most effective solution to this issue. In the current study, we studied the effect of using different materials in the coating process on the quality of "Murcott" mandarin during cold storage. We used different concentrations of nano chitosan (50 and 100 ppm) without wax and 100 ppm nano chitosan with wax. We investigated the impact of these compounds on the chemical composition and quality of fruits. The most successful treatment for preventing weight loss from discarded fresh fruit was a combination of wax and 100 ppm nano chitosan. This combination also prevented the deterioration of vitamin C, maintained the fruit pulp, and preserved the fruit's superior taste during cold storage and shelf life. It also maintains a better total soluble solids and total acidity level than other treatments. In addition, the activity of antioxidant enzymes and the total number of antioxidants indicates no degradation of plant tissues compared to those not coated with nano chitosan. It also reduces the microbial load on the coated fruits. Consequently, this coating combination could suggest prolonging post-harvest life and increasing the marketing period of mandarin fruits.

Design, Characterization and SAR Studies of Novel Bioactive Benzylideneacetophenone Derivatives as Insecticidal Agents against Spodoptera frugiperda (Lepidoptera: Noctuidae).

Unintentional environmental effects brought on by insecticides encourage the creation of safer substitutes. A very polyphagous migrating lepidopteran pest species in Africa called S. Frugiperda causes terrible damage. In the current paper, treatment of 4-acetylphenyl 4-methylbenzenesulfonate with different aromatic aldehydes in the presence of NaOH afforded benzylideneacetophenones. The structure of the newly prepared compounds were proved by different spectroscopic techniques such as IR, 1 H-NMR, 13 C NMR, and elemental analysis. We looked at the association between contact with S. frugiperda and stricture reaction to examine their harmful effect. Additionally, S. frugiperda was used for testing the newly created compounds for their ability to kill insects. The majority of substances have been proven to be effective and promising. It has been found that 4-[3-(4-Methylphenyl)prop-2-enoyl]phenyl-4-methyl benzenesulfonate (4) was the most active with an LC50 =3.46 mg/L of 2nd instar larvae and LC50 =9.45 mg/L of 4th instar larvae. Moreover, some of biological and histopathological aspects of the synthesized products were investigated under laboratory conditions.

Antibacterial and in vitro anticancer activities of the antimicrobial peptide NRC-07 encapsulated in chitosan nanoparticles.

Antimicrobial peptides (AMPs) are promising alternatives to conventional antibiotics and chemotherapy in the treatment of multidrug-resistant pathogens and drug-resistant cancers. Clinical application of AMPs is limited due to low stability and inefficient transport. Encapsulation in nanocarriers may improve their therapeutic potential. Chitosan nanoparticles (CS-NPs) are efficient carriers for proteins and peptides, improving the treatment of microbial infections and targeted drug delivery. We examined toxicity against cancer cell lines and antibacterial activities of the pleurocidin-like AMP NRC-07 upon encapsulation in CS-NPs by ionotropic gelation. The biological activities of various formulations of free and encapsulated NRC-07 and free nanoparticles were evaluated against Pseudomonas aeruginosa and breast cancer cells, using assays for cell viability and lactate dehydrogenase cytolysis with non-cancer cell lines as controls. NRC-07-containing nanoparticles decreased the bacterial and cancer cell viability in a concentration-dependent manner. Activities of encapsulated peptide were >2-fold higher than those of free NRC-07 peptide. Unloaded CS-NPs and free peptide were not cytotoxic against control cells. Encapsulation of NRC-07 into CS-NPs enhanced the antibacterial and selective cytotoxicity of the peptide, possibly enhancing anticancer activities. Encapsulation presents a promising tool for the development of efficient drug delivery systems.

Pyridine Derivatives as Insecticides─Part 4: Synthesis, Crystal Structure, and Insecticidal Activity of Some New Thienylpyridines, Thienylthieno[2,3-b]pyridines, and Related Heterocyclic Derivatives.

The reaction of ethyl 5-cyano-2-methyl-4-(thiophen-2-yl)-6-thioxo-1,6-dihydropyridine-3-carboxylate (1) with 2-chloroacetamide or its N-aryl derivatives gave ethyl 6-((2-amino-2-oxoethyl)thio)-5-cyano-2-methyl-4-(thiophen-2-yl) nicotinate (2a) or its N-aryl derivatives 2b-f, respectively. Cyclization of 2a-f into their isomers 3a-f was carried out by heating in absolute ethanol in the presence of a catalytic amount of sodium ethoxide. The o-aminoamide 3a was reacted with some aryl aldehydes in refluxing ethanol containing a few drops of conc. HCl to afford the corresponding tetrahydropyrimidinones 4a-d. The cyclocondensation reaction of 3a with some cycloalkanones such as cyclopentanone and cyclohexanone gave the corresponding spiro compounds 5a,b. The crystal structures of compounds 2a and 2d were determined by single-crystal X-ray diffraction techniques. All new compounds were evaluated for their insecticidal activity toward nymphs and adults of Aphis gossypi.

Dual targeting of H2S synthesizing enzymes; cystathionine ß-synthase and cystathionine γ-lyase by miR-939-5p effectively curbs triple negative breast cancer.

Introduction: Hydrogen sulfide (H2S) has been recently scrutinized for its critical role in aggravating breast cancer (BC) tumorigenicity. Several cancers aberrantly express H2S synthesizing enzymes; Cystathionine-ß-synthase (CBS) and cystathionine-γ-lyase (CSE). However, their levels and interdependence in BC require further studies. Objectives: Firstly, this study aimed to demonstrate a comparative expression profile of H2S synthesizing enzymes in BC vs normal tissue. Moreover, to investigate the reciprocal relationship between CBS and CSE and highlight the importance of dual targeting. Finally, to search for a valid dual repressor of the H2S synthesizing enzymes that could cease H2S production and reduce TNBC pathogenicity. Methods: Pairwise analysis of tumor vs. normal tissues of 40 BC patients was carried out. The TNBC cell line MDA-MB-231 was transfected with oligonucleotides to study the H2S mediated molecular mechanisms. In silico screening was performed to identify dual regulator(s) for CBS and CSE. Gene expression analysis was performed using qRT-PCR and was confirmed on protein level using Western blot. TNBC hallmarks were evaluated using MTT, migration, and clonogenicity assays. H2S levels were detected using a AzMc fluorescent probe. Results: BC tissues exhibited elevated levels of both CBS and CSE. Interestingly, upon CBS knockdown, CSE levels increased compensating for H2S production in TNBC cells, underlining the importance of dually targeting both enzymes in TNBC. In silico screening suggested miR-939-5p as a regulator of both CBS and CSE with high binding scores. Low expression levels of miR-939-5p were found in BC tissues, especially the aggressive subtypes. Ectopic expression of miR-939-5p significantly repressed CBS and CSE transcript and protein levels, diminished H2S production and attenuated TNBC hallmarks. Moreover, it improved the immune surveillance potency of TNBC cells through up regulating the NKG2D ligands, MICB and ULBP2 and reducing the immune suppressive cytokine IL-10. Conclusion: This study sheds light on the reciprocal relationship between CBS and CSE and on the importance of their dual targeting, particularly in TNBC. It also postulates miR-939-5p as a potent dual repressor for CBS and CSE overcoming their redundancy in H2S production, a mechanism that can potentially attenuate TNBC oncogenicity and improves the immunogenic response.

Green synthesis, biological and molecular docking of some novel sulfonamide thiadiazole derivatives as potential insecticidal against Spodoptera littoralis.

Although crop plants provide the majority of human food, pests and insects frequently cause huge economic losses. In order to develop innovative insecticidal compounds with low toxicity and a positive environmental impact, we developed new N-(4-sulfamoylphenyl)-1,3,4-thiadiazole-2-carboxamide derivatives (2-12). With the use of spectroscopic techniques and elemental data, the chemical structure of these new compounds was meticulously clarified. The toxicological and biological effects of the synthesized compound of the cotton leafworm Spodoptera littoralis (Boisduval, 1833) under laboratory conditions were also investigated. Regarding the determined LC50 values, compounds 3, 7, 8, and 10 showed the most potent toxic effect with LC50 values of 29.60, 30.06, 27.65 and 29.01 ppm, respectively. A molecular docking investigation of twelve synthetic compounds (from compound 2 to compound 12) was performed against AChE (Acetylcholinesterase). There was a wide range of binding affinities shown by these compounds. This work suggests that these substances may have insecticidal and AChE inhibitory properties, and it may be possible to further explore them in the process of creating pesticides that target AChE.

Successful Management of an Inadvertent Placement of a Nephrostomy Tube Into the Inferior Vena Cava Following Percutaneous Nephrolithotomy: A Case Discussion and Literature Review of a Rare Complication.

In a percutaneous nephrolithotomy (PCNL) procedure, the placement of the nephrostomy tube is usually inserted last to monitor and maintain urine drainage, avoid potential urine extravasation, and ensure hemostasis. In this report, we provide a clinical case involving the misplacement of a nephrostomy tube, resulting in direct perforation of the inferior vena cava (IVC) after undergoing one-sided PCNL that was successfully treated conservatively, and investigate the current management censuses from the literature for intravenous misplacement of a nephrostomy tube. In our patient, the tip of the nephrostomy catheter was located in the IVC. It was successfully managed using a one-step catheter withdrawal with the surgical vascular team on standby for any potential encounters with massive uncontrollable bleeding. An enhanced CT angiogram on day 14 post-PCNL revealed a lower polar renal arteriovenous pseudoaneurysm which required our patient to undergo selective angioembolization, resulting in maximal parenchymal preservation. The patient was successfully managed and discharged uneventfully. Thirteen cases that have reported inadvertent misplacements in the PubMed database have been discussed in this review. Our case would be the first documented report where a percutaneous nephrostomy drainage tube pierced through the IVC directly. Our case provides an argument for patients to be managed by tube withdrawal under one-step fluoroscopic guidance. Intensive care measures and ultrasound monitoring for two hours followed by another CT angiogram proved effective successful conservative management in a high-volume urologic practice.

Health technology assessment (HTA) readiness in Uganda: stakeholder's perceptions on the potential application of HTA to support national universal health coverage efforts.

INTRODUCTION: Health technology assessment (HTA) is an area that remains less implemented in low- and lower middle-income countries. The aim of the study is to understand the perceptions of stakeholders in Uganda toward HTA and its role in decision making, in order to inform its potential implementation in the country. METHODS: The study takes a cross-sectional mixed methods approach, utilizing an adapted version of the International Decision Support Initiative questionnaire with both semi-structured and open-ended questions. We interviewed thirty key informants from different stakeholder institutions in Uganda that support policy and decision making in the health sector. RESULTS: All participants perceived HTA as an important tool for decision making. Allocative efficiency was regarded as the most important use of HTA receiving the highest average score (8.8 out of 10), followed by quality of healthcare (7.8/10), transparency (7.6/10), budget control (7.5/10), and equity (6.5/10). There was concern that some of the uses of HTA may not be achieved in reality if there was political interference during the HTA process. The study participants identified development partners as the most likely potential users of HTA (66.7 percent of participants), followed by Ministry of Health (43.3 percent). CONCLUSION: Interviewed stakeholders in Uganda viewed the role of HTA positively, suggesting that there exists a promising environment for the establishment and operationalization of HTA as a tool for decision making within the health sector. However, sustainable development and application of HTA in Uganda will require adequate capacity both to undertake HTAs and to support their use and uptake.