Caspase-4/11 exacerbates disease severity in SARS-CoV-2 infection by promoting inflammation and immunothrombosis.

Severe acute respiratory syndrome coronavirus 2 (SARS­CoV-2) is a worldwide health concern, and new treatment strategies are needed. Targeting inflammatory innate immunity pathways holds therapeutic promise, but effective molecular targets remain elusive. Here, we show that human caspase-4 (CASP4) and its mouse homolog, caspase-11 (CASP11), are up-regulated in SARS­CoV-2 infections and that CASP4 expression correlates with severity of SARS­CoV-2 infection in humans. SARS­CoV-2­infected Casp11−/− mice were protected from severe weight loss and lung pathology, including blood vessel damage, compared to wild-type (WT) mice and mice lacking the caspase downstream effector gasdermin-D (Gsdmd−/−). Notably, viral titers were similar regardless of CASP11 knockout. Global transcriptomics of SARS­CoV-2­infected WT, Casp11−/−, and Gsdmd−/− lungs identified restrained expression of inflammatory molecules and altered neutrophil gene signatures in Casp11−/− mice. We confirmed that protein levels of inflammatory mediators interleukin (IL)-1ß, IL-6, and CXCL1, as well as neutrophil functions, were reduced in Casp11−/− lungs. Additionally, Casp11−/− lungs accumulated less von Willebrand factor, a marker for endothelial damage, but expressed more Kruppel-Like Factor 2, a transcription factor that maintains vascular integrity. Overall, our results demonstrate that CASP4/11 promotes detrimental SARS­CoV-2­induced inflammation and coagulopathy, largely independently of GSDMD, identifying CASP4/11 as a promising drug target for treatment and prevention of severe COVID-19.

Cyclin-dependent kinase 5 (CDK5) inhibitors in Parkinson disease.

Cyclin-dependent kinase 5 (Cdk5) is a protein expressed in postmitotic neurons in the central nervous system (CNS). Cdk5 is activated by p35 and p39 which are neuron regulatory subunits. Cdk5/p35 complex is activated by calpain protease to form Cdk5/p35 which has a neuroprotective effect by regulating the synaptic plasticity and memory functions. However, exaggerated Cdk5 is implicated in different types of neurodegenerative diseases including Parkinson disease (PD). Therefore, modulation of Cdk5 signalling may mitigate PD neuropathology. Therefore, the aim of the present review was to discuss the critical role of Cdk5 in the pathogenesis of PD, and how Cdk5 inhibitors are effectual in the management of PD. In conclusion, overactivated Cdk5 is involved the development of neurodegeneration, and Cdk5/calpain inhibitors such as statins, metformin, fenofibrates and rosiglitazone can attenuate the progression of PD neuropathology.

How circulating tumor cluster biology contributes to the metastatic cascade: from invasion to dissemination and dormancy.

Circulating tumor cells (CTCs) are known to be prognostic for metastatic relapse and are detected in patients as solitary cells or cell clusters. Circulating tumor cell clusters (CTC clusters) have been observed clinically for decades and are of significantly higher metastatic potential compared to solitary CTCs. Recent studies suggest distinct differences in CTC cluster biology regarding invasion and survival in circulation. However, differences regarding dissemination, dormancy, and reawakening require more investigations compared to solitary CTCs. Here, we review the current state of CTC cluster research and consider their clinical significance. In addition, we discuss the concept of collective invasion by CTC clusters and molecular evidence as to how cluster survival in circulation compares to that of solitary CTCs. Molecular differences between solitary and clustered CTCs during dormancy and reawakening programs will also be discussed. We also highlight future directions to advance our current understanding of CTC cluster biology.

Prediction of Degradation Profiles for Various Sartans under Solvent-Free Mechanochemical Conditions.

For the approval of a drug, the stability data must be submitted to regulatory authorities. Such analyses are often time-consuming and cost-intensive. Forced degradation studies are mainly carried out under harsh conditions in the dissolved state, often leading to extraneous degradation profiles for a solid drug. Oxidative mechanochemical degradation offers the possibility of generating realistic degradation profiles. In this study, a sustainable mechanochemical procedure is presented for the degradation of five active pharmaceutical ingredients (APIs) from the sartan family: losartan potassium, irbesartan, valsartan, olmesartan medoxomil, and telmisartan. High-resolution mass spectrometry enabled the detection of impurities already present in untreated APIs and allowed the elucidation of degradation products. Significant degradation profiles could already be obtained after 15-60 min of ball milling time. Many of the identified degradation products are described in the literature and pharmacopoeias, emphasizing the significance of our results and the applicability of this approach to predict degradation profiles for drugs in the solid state.

Optimisation of indole acetic acid production by Neopestalotiopsis aotearoa endophyte isolated from Thymus vulgaris and its impact on seed germination of Ocimum basilicum.

BACKGROUND: Microbial growth during plant tissue culture is a common problem that causes significant losses in the plant micro-propagation system. Most of these endophytic microbes have the ability to propagate through horizontal and vertical transmission. On the one hand, these microbes provide a rich source of several beneficial metabolites. RESULTS: The present study reports on the isolation of fungal species from different in vitro medicinal plants (i.e., Breynia disticha major, Breynia disticha, Duranta plumieri, Thymus vulgaris, Salvia officinalis, Rosmarinus officinalis, and Ocimum basilicum l) cultures. These species were tested for their indole acetic acid (IAA) production capability. The most effective species for IAA production was that isolated from Thymus vulgaris plant (11.16 µg/mL) followed by that isolated from sweet basil plant (8.78 µg/mL). On screening for maximum IAA productivity, medium, "MOS + tryptophan" was chosen that gave 18.02 µg/mL. The macroscopic, microscopic examination and the 18S rRNA sequence analysis indicated that the isolate that given code T4 was identified as Neopestalotiopsis aotearoa (T4). The production of IAA by N. aotearoa was statistically modeled using the Box-Behnken design and optimized for maximum level, reaching 63.13 µg/mL. Also, IAA extract was administered to sweet basil seeds in vitro to determine its effect on plant growth traits. All concentrations of IAA extract boosted germination parameters as compared to controls, and 100 ppm of IAA extract exhibited a significant growth promotion effect for all seed germination measurements. CONCLUSIONS: The IAA produced from N. aotearoa (T4) demonstrated an essential role in the enhancement of sweet basil (Ocimum basilicum) growth, suggesting that it can be employed to promote the plant development while lowering the deleterious effect of using synthetic compounds in the environment.

Characterization, modeling, and anticancer activity of L.arginase production from marine Bacillus licheniformis OF2.

BACKGROUND: L-arginase, is a powerful anticancer that hydrolyzes L-arginine to L-ornithine and urea. This enzyme is widely distributed and expressed in organisms like plants, fungi, however very scarce from bacteria. Our study is based on isolating, purifying, and screening the marine bacteria that can produce arginase. RESULTS: The highest arginase producing bacteria will be identified by using microbiological and molecular biology methods as Bacillus licheniformis OF2. Characterization of arginase is the objective of this study. The activity of enzyme was screened, and estimated beside partial sequencing of arginase gene was analyzed. In silico homology modeling was applied to generate the protein's 3D structure, and COACH and COFACTOR were applied to determine the protein's binding sites and biological annotations based on the I-TASSER structure prediction. The purified enzyme was undergone an in vitro anticancer test. CONCLUSIONS: L-arginase demonstrated more strong anti-cancer cells with an IC50 of 21.4 ug/ml in a dose-dependent manner. L-arginase underwent another investigation for its impact on the caspase 7 and BCL2 family of proteins (BCL2, Bax, and Bax/Bcl2). Through cell arrest in the G1/S phase, L-arginase signals the apoptotic cascade, which is supported by a flow cytometry analysis of cell cycle phases.

Biochemical and proteomic response of the freshwater green alga Pseudochlorella pringsheimii to iron and salinity stressors.

BACKGROUND: Pseudochlorella pringsheimii (Ppr) is a green unicellular alga rich with chlorophyll, carotenoids, and antioxidants. As a widespread organism, Ppr must face, and adapt to, many environmental stresses and these are becoming more frequent and more extreme under the conditions of climate change. We therefore focused on salinity induced by NaCl and iron (Fe) variation stresses, which are commonly encountered by algae in their natural environment. RESULTS: The relatively low stress levels improved the biomass, growth rate, and biochemical components of Ppr. In addition, the radical-scavenging activity, reducing power, and chelating activity were stimulated by lower iron concentrations and all NaCl concentrations. We believe that the alga has adapted to the stressors by increasing certain biomolecules such as carotenoids, phenolics, proteins, and carbohydrates. These act as antioxidants and osmoregulators to protect cell membranes and other cellular components from the harmful effects of ions. We have used SDS-PAGE and 2D-PAGE in combination with tandem mass spectrometry to identify responsive proteins in the proteomes of stressed vs. non-stressed Ppr. The results of 2D-PAGE analysis showed a total of 67 differentially expressed proteins, and SDS-PAGE identified 559 peptides corresponding to 77 proteins. Of these, 15, 8, and 17 peptides were uniquely identified only under the control, iron, and salinity treatments, respectively. The peptides were classified into 12 functional categories: energy metabolism (the most notable proteins), carbohydrate metabolism, regulation, photosynthesis, protein synthesis, stress proteins, oxido-reductase proteins, transfer proteins, ribonucleic-associated proteins, hypothetical proteins, and unknown proteins. The number of identified peptides was higher under salinity stress compared to iron stress. CONCLUSIONS: A proposed mechanism for the adaptation of Ppr to stress is discussed based on the collected data. This data could serve as reference material for algal proteomics and the mechanisms involved in mediating stress tolerance.

Ameliorative impacts of gamma-aminobutyric acid (GABA) on seedling growth, physiological biomarkers, and gene expression in eight wheat (Triticum aestivum L.) cultivars under salt stress.

Plants spontaneously accumulate γ-aminobutyric acid (GABA), a nonprotein amino acid, in response to various stressors. Nevertheless, there is limited knowledge regarding the precise molecular mechanisms that plants employ to cope with salt stress. The objective of this study was to investigate the impact of GABA on the salt tolerance of eight distinct varieties of bread wheat (Triticum aestivum L.) by examining plant growth rates and physiological and molecular response characteristics. The application of salt stress had a detrimental impact on plant growth markers. Nevertheless, the impact was mitigated by the administration of GABA in comparison to the control treatment. When the cultivars Gemmiza 7, Gemmiza 9, and Gemmiza 12 were exposed to GABA at two distinct salt concentrations, there was a substantial increase in both the leaf chlorophyll content and photosynthetic rate. Both the control wheat cultivars and the plants exposed to salt treatment and GABA treatment showed alterations in stress-related biomarkers and antioxidants. This finding demonstrated that GABA plays a pivotal role in mitigating the impact of salt treatments on wheat cultivars. Among the eight examined kinds of wheat, CV. Gemmiza 7 and CV. Gemmiza 11 exhibited the most significant alterations in the expression of their TaSOS1 genes. CV. Misr 2, CV. Sakha 94, and CV. Sakha 95 exhibited the highest degree of variability in the expression of the NHX1, DHN3, and GR genes, respectively. The application of GABA to wheat plants enhances their ability to cope with salt stress by reducing the presence of reactive oxygen species (ROS) and other stress indicators, regulating stomatal aperture, enhancing photosynthesis, activating antioxidant enzymes, and upregulating genes involved in salt stress tolerance.

UltraAIGenomics: Artificial Intelligence-Based Cardiovascular Disease Risk Assessment by Fusion of Ultrasound-Based Radiomics and Genomics Features for Preventive, Personalized and Precision Medicine: A Narrative Review.

Cardiovascular disease (CVD) diagnosis and treatment are challenging since symptoms appear late in the disease's progression. Despite clinical risk scores, cardiac event prediction is inadequate, and many at-risk patients are not adequately categorised by conventional risk factors alone. Integrating genomic-based biomarkers (GBBM), specifically those found in plasma and/or serum samples, along with novel non-invasive radiomic-based biomarkers (RBBM) such as plaque area and plaque burden can improve the overall specificity of CVD risk. This review proposes two hypotheses: (i) RBBM and GBBM biomarkers have a strong correlation and can be used to detect the severity of CVD and stroke precisely, and (ii) introduces a proposed artificial intelligence (AI)-based preventive, precision, and personalized ( aiP 3 ) CVD/Stroke risk model. The PRISMA search selected 246 studies for the CVD/Stroke risk. It showed that using the RBBM and GBBM biomarkers, deep learning (DL) modelscould be used for CVD/Stroke risk stratification in the aiP 3 framework. Furthermore, we present a concise overview of platelet function, complete blood count (CBC), and diagnostic methods. As part of the AI paradigm, we discuss explainability, pruning, bias, and benchmarking against previous studies and their potential impacts. The review proposes the integration of RBBM and GBBM, an innovative solution streamlined in the DL paradigm for predicting CVD/Stroke risk in the aiP 3 framework. The combination of RBBM and GBBM introduces a powerful CVD/Stroke risk assessment paradigm. aiP 3 model signifies a promising advancement in CVD/Stroke risk assessment.

Curcumin protects against lamotrigine-induced chronic ovarian and uterine toxicity in rats by regulating PPAR-γ and ROS production.

Lamotrigine (LTG) is an antiepileptic drug with possible adverse effects on the female reproductive system. Curcumin was declared to improve ovarian performance. Therefore, this study aimed to clarify ovulatory dysfunction (OD) associated with LTG and the role of curcumin in ameliorating this dysfunction. Adult female Wister albino rats were assigned into four groups: negative control (received saline), positive control (received curcumin only), LTG, and LTG with curcumin groups. Drugs were administered for 90 days. The hormonal profile, including testosterone, estrogen, progesterone, luteinizing hormone, and follicle-stimulating hormone, in addition to the lipid profile and glycemic analysis, were tested. Oxidative stress biomarkers analysis in the ovaries and uterus and peroxisome proliferator-activated receptor-γ (PPAR-γ) gene expression were also included. Histopathological examination of ovarian and uterine tissues and immunohistochemical studies were also performed. Curcumin could improve the OD related to chronic LTG intake. That was proved by the normalization of the hormonal profile, glycemic control, lipidemic status, oxidative stress markers, and PPAR-γ gene expression. The histopathological and immunohistochemical examination of ovarian and uterine tissues revealed an improvement after curcumin administration. The results describe an obvious deterioration in ovarian performance with LTG through the effect on lipidemic status, PPAR-γ gene, and creating an oxidative stress condition in the ovaries of chronic users, with a prominent improvement with curcumin addition to the treatment protocol.

Novel quinazoline sulfonamide-based scaffolds modulate methicillin-resistant Staphylococcus aureus (MRSA) pneumonia in immunodeficient irradiated model: Regulatory role of TGF-ß.

A library of new quinazoline pharmacophores bearing benzenesulfonamide moiety was designed and synthesized. Compounds 3a-n were screened for their in vitro antimicrobial activity against eight multidrug-resistant clinical isolates. Compounds 3d and 3n exhibited prominent antibacterial activity, specifically against MRSA. After exhibiting relative in vitro and in vivo safety, compound 3n was selected to assess its anti-inflammatory activity displaying promising COX-2 inhibitory activity compared to Ibuprofen. In vivo experimental MRSA pneumonia model was conducted on immunodeficient (irradiated) mice to reveal the antimicrobial and anti-inflammatory responses of compound 3n compared to azithromycin (AZ). Treatment with compound 3n (10 and 20 mg/kg) as well as AZ resulted in a significant decrease in bacterial counts in lung tissues, suppression of serum C-reactive protein (CRP), lung interleukin-6 (IL-6), myeloperoxidase activity (MPO) and transforming growth factor-ß (TGF-ß). Compound 3n showed a non-significant deviation of lung TGF-ß1 from normal values which in turn controlled the lung inflammatory status and impacted the histopathological results. Molecular docking of 3n showed promising interactions inside the active sites of TGF-ß and COX-2. Our findings present a new dual-target quinazoline benzenesulfonamide derivative 3n, which possesses significant potential for treating MRSA-induced pneumonia in an immunocompromised state.

Utility of sulfachloropyridazine in the synthesis of novel anticancer agents as antiangiogenic and apoptotic inducers.

In a search for new anticancer agents with better activity and selectivity, the present work described the synthesis of several new series of sulfachloropyridazine hybrids with thiocarbamates 3a-e, thioureids 4a-h, 5a-e and 4-substituted sulfachloropyridazines 6a, b, 7a, b and 8. The synthesized compounds were screened in vitro against a panel of 60 cancer cell lines in one dose assay. The most potent derivatives 3a, 3c, 4c, 4d, 5e, 7a and 7b were tested for their antiangiogenic activity by measuring their ability to inhibit VEGFR-2. The most potent compounds in VEGFR-2 inhibitory assay were further evaluated for their ability to inhibit PDGFR. In addition, the ability of 4c compound to inhibit cell migration on HUVEC cells and cell cycle effect on UO-31 cells has been studied. The pro-apoptotic effect of compound 4c was studied by the evaluation of caspase-3, Bax and BCl-2. Alternatively, the IC50 of compounds 3a, 3c, 4c, 5e, 7a and 7b against certain human cancer cell lines were determined. Re-evaluation in combination with γ-radiation was carried out for compounds 4c, 5e and 7b to study the possible synergistic effect on cytotoxicity. Docking studies of the most active compounds were performed to give insights into the binding mode within VEGFR-2 active site.

Clinical Outcomes of Concomitant Secondary Chordal Cutting to Surgical Myectomy in HOCM.

OBJECTIVES: In patients who underwent surgical septal myectomy for hypertrophic obstructive cardiomyopathy (HOCM), additional mitral valve repair may offer additional benefits in terms of further reducing left ventricle outflow tract (LVOT) gradients, systolic anterior motion (SAM) and mitral regurgitation (MR). We performed a systematic review of the literature to evaluate the evidence of surgical myectomy with additional secondary chordal cutting in patients with HOCM. METHODS: A systematic literature search in MEDLINE and EMBASE was performed until April 2024. The primary outcome studied was postoperative echocardiographic LVOT-gradient. A random effects meta-analysis of means was performed for the primary outcome. The secondary outcomes studied were postoperative residual MR-grade, 30-day new permanent pacemaker implantation, and in-hospital mortality. RESULTS: From 1911 unique publications, a total of 6 articles fulfilled the inclusion criteria and comprised 471 patients with a pooled mean preoperative resting LVOT gradient of 84 mmHg (95% CI: 76-91). The postoperative pooled mean LVOT-gradient was 11 mmHg (95% CI: 10 - 12) with a low heterogeneity (I2 = 44%). The residual LVOT gradient exceeding 30 mmHg was present in 9 (1%) patients. MR-grade 3 or 4 at hospital discharge was present in 7 (1%) patients. The 30-day new permanent pacemaker implantation rate was 7% and the in-hospital mortality was 0.4%. CONCLUSION: This systematic review and meta-analysis demonstrate that combining surgical septal myectomy with secondary chordal cutting can be performed safely and effectively eliminate LVOT obstruction in HOCM patients. Further studies are needed to determine the additive effectiveness of additional secondary chordal cuttings.

Pediatric retroclival hematomas.

BACKGROUND: Traumatic retroclival hematomas (RCHs) are infrequent occurrences among the pediatric population. The existing body of research pertaining to these hematomas primarily consists of case reports or small case series, which do not provide adequate guidance for managing this condition. OBJECTIVE: This study aims to present a report on four cases of RCHs. Additionally, we aim to conduct a systematic review to consolidate the existing literature on pediatric RCHs. METHODS: The authors conducted a systematic review in accordance with the PRISMA and CARE guidelines. A multivariate logistic regression model was developed to evaluate the potential impact of various clinical variables on clinical outcomes. The study also documented four of our cases, one of which was a rare occurrence of spontaneous subdural RCH. RESULTS: A total of 62 traumatic RCHs have been documented in the literature. We documented three cases of traumatic RCHs and one case of spontaneous RCH. A systematic analysis of 65 traumatic RCHs was performed. Of trauma cases, 64.6% demonstrated craniocervical junction instability with 83.3% ligamentous involvement. Thirty-five patients were males. 50.7% were aged between 5 and 9 years. Cranial nerve palsies occurred in 29 patients (27 had abducent palsy), 26 of which resolved within 6 months of trauma. 23.5% underwent surgery, and 76.5% were conservatively managed. Surgeries targeted hematomas, hydrocephalus, or craniocervical instability. Approaches to hematomas included transclival and far/extreme lateral suboccipital approaches. Clinical outcome was good in 75.4% and intermediate or poor in 24.6%. Logistic regression suggested an association between craniocervical junction injuries and poor or intermediate outcomes (OR 4.88, 95% CI (1.17, 27.19), p = 0.04). CONCLUSION: Pediatric RCHs are mostly traumatic and extradural. Children between 5 and 9 years old are most vulnerable. Craniocervical junction injuries, mainly ligamentous, are common in RCHs and are associated with intermediate or poor outcomes. Cervical MRI could be important in cases of trauma to rule out ligamentous injuries of the craniocervical junction. The small size of RCHs should not exempt the careful assessment of craniocervical junction instability. Cranial nerve palsies are common and usually resolve within 6 months. Conservative treatment is typical unless brainstem compression, hydrocephalus, or craniocervical junction instability exists.

Imparting aromaticity to 2-pyridone derivatives by O-alkylation resulted in new competitive and non-competitive PIM-1 kinase inhibitors with caspase-activated apoptosis.

New aromatic O-alkyl pyridine derivatives were designed and synthesised as Proviral Integration Moloney (PIM)-1 kinase inhibitors. 4c and 4f showed potent in vitro anticancer activity against NFS-60, HepG-2, PC-3, and Caco-2 cell lines and low toxicity against normal human lung fibroblast Wi-38 cell line. Moreover, 4c and 4f induced apoptosis in the four tested cancer cell lines with high percentage. In addition, 4c and 4f significantly induced caspase 3/7 activation in HepG-2 cell line. Furthermore, 4c and 4f showed potent PIM-1 kinase inhibitory activity with IC50 = 0.110, 0.095 µM, respectively. Kinetic studies indicated that 4c and 4f were both competitive and non-competitive inhibitors for PIM-1 kinase enzyme. In addition, in silico prediction of physiochemical properties, pharmacokinetic profile, ligand efficiency, ligand lipophilic efficiency, and induced fit docking studies were consistent with the biological and kinetic studies, and predicted that 4c and 4f could act as PIM-1 kinase competitive non-adenosine triphosphate (ATP) mimetics with drug like properties.

Discovery of new thymol-3,4-disubstituted thiazole hybrids as dual COX-2/5-LOX inhibitors with in vivo proof.

New thymol-3,4-disubstitutedthiazole hybrids were synthesised as dual COX-2/5-LOX inhibitors. Compounds 6b, 6d, 6e, and 6f displayed in vitro inhibitory activity against COX-2 (IC50= 0.037, 0.042, 0.046, and 0.039 µM) nearly equal to celecoxib (IC50= 0.045 µM). 6b, 6d, and 6f showed SI (379, 341, and 374, respectively) higher than that of celecoxib (327). 6a-l elicited in vitro 5-LOX inhibitory activity higher than quercetin. 6a-f, 6i-l, 7a, and 7c possessed in vivo inhibition of formalin induced paw edoema higher than celecoxib. 6a, 6b, 6f, 6h-l, and 7b showed gastrointestinal safety profile as celecoxib and diclofenac sodium in the population of fasted rats. Induced fit docking and molecular dynamics simulation predicted good fitting of 6b and 6f without changing the packing and globularity of the apo protein. In conclusion, 6b and 6f achieved the target goal as multitarget inhibitors of inflammation.

How does vertical laminar fracture impact the decision-making in thoracolumbar fractures? A systematic scoping review and meta-analysis.

OBJECTIVE: Although vertical laminar fracture (VLF) is generally considered a severity marker for thoracolumbar fractures (TLFs), its exact role in decision-making has never been established. This scoping review aims to synthesize the research on VLF's role in the decision-making of TLFs. METHODS: A systematic review was conducted following PRISMA guidelines. We searched PubMed, Scopus, and Web of Science from inception to  June 11, 2023, for studies examining the association of VLF in thoracolumbar fractures with dural lacerations, neurological deficits, radiographic parameters, or treatment outcomes. Additionally, experimental studies that analyze the biomechanics of burst fractures with VLF were included. The studies extracted key findings, objectives, and patient population. A meta-analysis was performed for the association of VLF with dural laceration and neurological deficit, and ORs were pooled with a 95% confidence interval (CI). RESULTS: Twenty-eight studies were included in this systematic review, encompassing 2021 patients, and twelve were included in the meta-analysis. According to the main subject of the study, the association of VLF with a dural laceration (n = 14), neurological deficit (n = 4), radiographic parameters (n = 3), thoracolumbar fracture classification (n = 2), and treatment outcome (n = 2). Seven studies with a total of 1010 patients reported a significant association between VLF and neurological deficit (OR = 7.35, 95% CI [3.97, 14.25]; P < 0.001). The pooled OR estimates for VLF predicting dural lacerations were 7.75, 95% CI [2.41, 24.87]; P < 0.001). CONCLUSION: VLF may have several important diagnostic and therapeutic implications in managing TLFs. VLF may help to distinguish AO type A3 from A4 fractures. VLF may help to predict preoperatively the occurrence of dural laceration, thereby choosing the optimal surgical strategy. Clinical and biomechanical data suggest VLF may be a valuable modifier to guide the decision-making in burst fractures; however, more studies are needed to confirm its prognostic importance regarding treatment outcomes.

Development and evaluation of 2,4-disubstituted-5-aryl pyrimidine derivatives as antibacterial agents.

Designing novel candidates as potential antibacterial scaffolds has become crucial due to the lack of new antibiotics entering the market and the persistent rise in multidrug resistance. Here, we describe a new class of potent antibacterial agents based on a 5-aryl-N2,N4-dibutylpyrimidine-2,4-diamine scaffold. Structural optimization focused on the 5-aryl moiety and the bioisosteric replacement of the side chain linker atom. Screening of the synthesized compounds focused on a panel of bacterial strains, including gram-positive Staphylococcus aureus strains (Newman MSSA, methicillin- and vancomycin-resistant), and the gram-negative Escherichia coli (ΔAcrB strain). Several compounds showed broad-spectrum antibacterial activity with compound 12, bearing a 4-chlorophenyl substituent, being the most potent among this series of compounds. This frontrunner compound revealed a minimum inhibitory concentration (MIC) value of 1 µg/mL against the S. aureus strain (Mu50 methicillin-resistant S. aureus/vancomycin-intermediate S. aureus) and an MIC of 2 µg/mL against other tested strains. The most potent derivatives were further tested against a wider panel of bacteria and evaluated for their cytotoxicity, revealing further potent activities toward Streptococcus pneumoniae, Enterococcus faecium, and Enterococcus faecalis. To explore the mode of action, compound 12 was tested in a macromolecule inhibition assay. The obtained data were supported by the safety profile of compound 12, which possessed an IC50 of 12.3 µg/mL against HepG2 cells. The current results hold good potential for a new class of extended-spectrum antibacterial agents.

Encapsulation of Candida antarctica lipase B in metal-organic framework under ultrasound and using it to one-pot synthesis of 1,3,4,5-tetrasubstituted pyrazoles.

Encapsulating the enzyme in metal-organic frameworks (MOFs) is a convenient method to prepare MOF-enzyme biocomposite. In this study, Candida antarctica lipase B (CAL-B) was chosen to immobilize in Cu-BTC MOF under ultrasound irradiation. CAL-B was immobilized in Cu-BTC under ultrasound at 21 kHz and 11.4 W/cm2 and incubation. 98% of CAL-B was immobilized in Cu-BTC with 99 U/mg activity (threefold more active than the free CAL-B). The prepared biocomposite was characterized using FT-IR, XRD, TGA, SEM, EDX, and BET. The thermal and solvent stability of CAL-B@Cu-BTC was investigated. It was found that at a temperature of 55 â„ƒ, CAL-B@Cu-BTC maintains its activity even after 2 h of incubation. Furthermore, in the presence of 20% and 50% concentrations of MeCN, THF, and DMF, CAL-B@Cu-BTC was found to have an activity of over 80%. A prepared biocatalyst was used to synthesize 1,3,4,5-tetrasubstituted pyrazole derivatives (50-75%) in a one-pot vessel, by adding phenyl hydrazine hydrochlorides, benzaldehydes, and dimethyl acetylenedicarboxylate.

Performance Evaluation of Sinusoidal Power Supplies for Ozone Generation in Water Purification Applications.

Ozone generation is a water disinfection method, superior to chlorine in terms of fewer byproducts and no residual taste. However, its high production cost limits its widespread adoption. This paper designs an ozone generation sinusoidal power supply for water treatment. Ozone generation requires a high-frequency and high-voltage power supply to produce ozone from oxygen molecules. The study evaluates two power supply topologies, one with a parallel LC filter and the other with an LCL filter, assessing their feasibility, effectiveness, and reliability. Theoretically, the LCL filter achieves higher gains than the parallel LC filter. The larger inductance in the parallel LC filter reduces gain, while the larger inductance in the LCL filter increases gain. Simulation and practical results validate these findings, achieving gains of 40 for the parallel LC filter and 150 for the LCL filter.