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Tryptophan is an essential amino acid metabolized in the body primarily through enzymatic degradation involving indoleamine and tryptophan 2,3-dioxygenase (IDO and TDO), generating kynurenine as the initial step, and ultimately leads to multiple bioactive metabolites including NAD and quinolinic acid. We have previously shown that kynurenine accumulates with age and contributes to age-induced bone loss, and we hypothesized that knocking out IDO1 might be protective against bone loss in states such as aging by decreasing kynurenine levels in osteoprogenitor cells. To begin to characterize the target cell responsible for this effect, we generated conditional IDO1 knockout (KO) mouse model using floxed mice created by EUCOMM/IMPC and an osteoprogenitor-expressed (Osterix-promoter-driven) Cre possessing a Tet-off element. In an IACUC-approved protocol using male/female conditional IDO1 KO (cKO) C57BL/6 mice, we found sex-dependent differences in changes in bone mass. We report that bone mineral density (BMD) at the femoral (but not spinal) site was significantly higher in 21-month-old cKO male mice compared to wild-type (WT). In contrast, spinal (but not femoral) BMD was higher in 21-month-old female cKO mice versus WT. There were no significant differences in trabecular μCT parameters in female mice; however, male cKO mice showed increased trabecular number and decreased trabecular separation. In contrast, there were no differences between male mice in cortical bone measurements whereas female cKO mice had decreased cortical thickness. These data suggest that there are sex-dependent differences in the role of IDO1 in osteoprogenitor cells with aging.

Low-protein diets (LPD) are recommended in chronic kidney disease (CKD) to reduce disease progression. However, their clinical efficacy and safety are debated due to the risk of protein-energy wasting. A deeper mechanistic understanding is therefore required. Herein, the metabolic effects of LPD in both murine models and a randomized controlled trial in nondiabetic CKD patients were investigated, focusing on glucose homeostasis, plasmatic uremic toxin (UTs) levels, gut microbiota remodeling, and endocrine adaptations. In both experimental and clinical settings, LPD improved glucose tolerance and significantly decreased circulating levels of gut-derived UTs while reducing body weight (-33% weight gain in mice and a decrease in body mass index of ~-0.5 kg/m2 in humans). These metabolic improvements were associated with alterations in gut microbiota composition and function, including the downregulation of microbial pathways involved in aromatic amino acid biosynthesis. In both mice and patients, LPD triggered a significant hepatic induction of fibroblast growth factor 21 (FGF21), an endocrine regulator of amino acid deficiency (+2.9-fold in human and 28-fold in mice) FGF21 levels correlated negatively with lean mass and positively with fat mass and glycemic control, supporting a dual role in metabolic adaptation and catabolic signaling. To mitigate the adverse nutritional effects of LPD, we administered Lactiplantibacillus plantarum WJL (LpWJL), a probiotic previously found to enhance growth of under nutritional stress in CKD mice. LpWJL restored circulating amino acid levels, suppressed FGF21 induction (-26%) and stress-related biosynthetic responses, and preserved body weight (+247% weight gain) and composition, without impairing the benefits of LPD on kidney and metabolic parameters. The present findings identify UTs and FGF21 as crucial factors of the metabolic response to LPD, and support microbiota-targeted strategies, such as LpWJL supplementation, to enhance LPD efficacy. Clinical trials are, however, required to confirm their relevance in CKD management.

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Bacteriophages are being cataloged at an accelerating pace and are recognized as key players in nutrient and energy cycling across ecosystems. Yet the bacterial genetic determinants that govern phage-host specificity and infection success remain poorly understood, particularly in clinically and ecologically important genera such as Klebsiella where prior receptor characterization has been almost entirely limited to capsulated strains. Here we used a randomly barcoded, genome-wide, loss-of-function transposon mutant library (RB-TnSeq) of Klebsiella sp. M5al, a naturally acapsular, nitrogen-fixing rhizobacterium, to generate the first systematic, cross-family map of phage receptor gene dependencies in Klebsiella. Challenging the library against 25 double-stranded DNA phages spanning five families in 213 parallel assays, we identified 42 bacterial genes associated with phage infection, of which 15 had no prior association with phage infection in any bacterial system. Disruption of surface receptor biosynthesis genes conferred cross-resistance across multiple phage families, while intracellular gene disruptions had predominantly phage-specific effects. Clonal validation of eight genes confirmed LPS outer core biosynthesis genes as primary receptor determinants alongside additional host factors spanning outer membrane transport, cofactor biosynthesis, and two-component signaling. Comparative analysis across all 25 phages revealed that phage genus rather than family is the stronger predictor of host gene dependency profiles, a finding with direct implications for the functional annotation of uncharacterized phage isolates and rational phage cocktail design. Together, these findings provide a community resource for linking phage genomic diversity to functional host interaction space in this ecologically and clinically important genus.

Endocan and its major catabolite cleaved endocan are reported as potential biomarkers of pneumonia in the setting of critical illness. However, very little is known about their accuracy to discriminate microbiologically confirmed ventilator-associated pneumonia (VAP) at the time of clinical suspicion. The objective of this study was to evaluate the performance of endocan and cleaved endocan for the early discrimination of microbiologically confirmed VAP. In a pre-planned ancillary analysis of the single-center prospective observational SOH-VAP cohort (NCT03434821) which was conducted at the University hospital of Lille from March 2018 to April 2022, patients presenting with a clinical suspicion of VAP leading to microbiological respiratory sampling were included. Endocan and cleaved endocan were measured on EDTA plasma collected on the day of VAP clinical suspicion. The performance of these biomarkers and of the endocan cleavage ratio (ECR) was determined by comparing values obtained in patients with microbiologically confirmed VAP to those without microbiological confirmation, and by establishing ROC curves. We enrolled 47 patients with microbiologically confirmed VAP and 67 patients without microbiological confirmation. No significant differences were found when comparing endocan, cleaved endocan, and ECR values between confirmed and non-confirmed VAP (median [IQR] = 5 [2.7; 9.6] ng/mL vs. 4.7 [2.5; 8.5] ng/mL, p = 0.86 for endocan; 1.2 [0; 2] ng/mL vs. 1 [0; 2] ng/mL, p = 0.71 for cleaved endocan; and 0.06 [0; 0.32] vs. 0.07 [0; 0.29], p = 0.94 for ECR). Areas under the ROC curves for differentiating confirmed and non-confirmed VAP were respectively calculated at 0.51 (95% CI: 0.4-0.62) for endocan, 0.52 (95% CI: 0.43-0.64) for cleaved endocan, and 0.52 (95% CI: 0.41-0.63) for ECR. Our results do not support the use of endocan nor cleaved endocan for the early detection of microbiologically confirmed VAP at the time of clinical suspicion.

Acinetobacter baumannii is a major nosocomial pathogen, and its increasing multidrug-resistant and pandrug-resistant profiles pose a serious challenge to anti-infective therapy. In recent years, heteroresistance to multiple antibiotics in A. baumannii has attracted growing attention. Heteroresistance refers to the presence of low-frequency resistant subpopulations within an isolate that is classified as susceptible by conventional susceptibility testing. These resistant subpopulations can survive under antibiotic selective pressure and subsequently expand, potentially leading to treatment failure. Owing to the lack of standardized and unified detection methods, heteroresistance is often overlooked in clinical practice. Current evidence indicates that heteroresistance in A. baumannii arises through diverse molecular mechanisms, including genetic mutations, gene amplification, efflux pump overexpression, and membrane structural modifications. The mechanisms underlying heteroresistance vary among different classes of antibiotics, and even for a single antibiotic, multiple resistance pathways may coexist. Given this mechanistic complexity, monotherapy is often insufficient to eradicate all heteroresistant subpopulations and may instead promote the enrichment of resistant cells under selective pressure. Combination therapy has therefore been proposed as a promising strategy to suppress heteroresistance, although its efficacy, safety, and clinical applicability require further validation. With the rapid development of emerging technologies, such as single-cell analysis, microfluidic platforms, and high-throughput sequencing, promise for enabling precise and rapid detection of heteroresistance. This review systematically summarizes the definition, detection methods, molecular mechanisms, and therapeutic strategies related to heteroresistance in A. baumannii, with the aim of providing a reference for rational antimicrobial use and the development of novel antibacterial strategies.

Long-chain polyunsaturated fatty acids (LC-PUFAs), particularly arachidonic acid (AA, 20:4n-6) and docosahexaenoic acid (DHA, 22:6n-3), are essential for optimal neurodevelopment through their effect on neuronal proliferation, neurite outgrowth and synaptogenesis. Emerging evidence highlights that brain PUFAs are metabolized in oxylipins, the bioactive oxidized PUFA metabolites known to regulate inflammatory processes. Recent data highlighted that both PUFA and oxylipin profiles are modulated in the brains of adult male mice by dietary PUFA content. However, little is known on the impact of maternal dietary n-3 PUFA intake during the perinatal period and the neurodevelopmental profile of brain fatty acids and associated oxylipins in mouse offspring, and whether these effects differ between sexes. To address this question, we first measured fatty acid levels in the placenta and embryonic brain of male and female mice at embryonic day (E)17.5 of mothers fed an n-3 PUFA-sufficient diet (based on canola oil, rich in the n-3 precursor alpha-linolenic acid) or an n-3 PUFA-deficient diet (based on sunflower oil, rich in the n-6 precursor linoleic acid) in n-3 PUFAs starting at E0. Then, fatty acids and oxylipins were measured at different post-natal stages, in the brain at postnatal day (P)0 and P7, and in the hippocampus at P14 and P21, in both male and female mouse offspring. Our results show that maternal n-3 PUFA dietary deficiency alters fatty acid profiles as early as E17.5 in both the placenta and the brain. Furthermore, dietary intervention affects both fatty acid and oxylipin profiles throughout postnatal brain development, with notable sex-specific differences. These findings highlight the importance of maternal n-3 PUFA intake during the perinatal period for establishing and maintaining PUFA and oxylipin profiles in the developing brain.

Despite durable viral suppression with antiretroviral therapy (ART), non-AIDS comorbidities remain frequent in aging people with HIV (PWH). Cerebral small-vessel disease (CSVD), a major contributor to stroke and cognitive decline, is up to twice as prevalent in middle-aged ART-treated PWH. Mechanisms underlying this excess risk remain unclear. This study aims to identify inflammatory, viral, renal, and retinal vascular factors independently associated with CSVD in virologically controlled PWH. The case-control MicroBREAK-2 study (NCT02210130), nested in the PWH group of the MicroBREAK-1 study, included 80 ART-treated (≥5 years) PWH aged ≥50 years with MRI-defined CSVD and 80 matched CSVD-free controls (age ± 5 years, sex, year of HIV diagnosis ± 5 years). Participants underwent brain MRI, renal, carotid, and orbital color Doppler ultrasonography, and comprehensive ophthalmologic assessment. Circulating inflammatory and coagulation biomarkers, Epstein-Barr virus plasma load, and antiretroviral exposure were measured. Independent associations were identified using conditional logistic regression with LASSO selection and bootstrap resampling. Hypertension was the strongest independent correlate of CSVD (OR 4.92, 95% CI 1.23-19.62; P = .02). Markers of persistent inflammatory and coagulative activity were also independently linked to CSVD, including higher white blood cell count (OR 1.58; 1.17-2.14; P = .003) and elevated D-dimer levels (OR 1.52; 1.09-2.12; P = .01). Increased intraocular pressure was independently related to CSVD (OR 6.37; 1.38-29.4; P = .02). In contrast, HIV-specific parameters showed no independent relationship with CSVD. In virologically suppressed PWH, CSVD is primarily associated with hypertension and persistent low-grade inflammation rather than HIV-specific factors, underscoring the need for aggressive cardiovascular risk management.

Cardiovascular disease (CVD) is a leading cause of mortality worldwide. Emerging lung cancer screening in smokers may offer an opportunity for simultaneous cardiovascular risk evaluation. We developed a mobile CT screening unit and assessed the feasibility of integrating dyslipidemia screening and non-HDL cholesterol-based SCORE2 estimation using the Cobas® b101 point-of-care testing (POCT) analyzer on capillary blood samples. Following a preliminary evaluation of two POCT analyzers, the Cobas® b101 was selected for capillary lipid profiling. Lipid results obtained from capillary samples analyzed in the mobile unit were compared with venous samples analyzed in the central laboratory in 84 screened participants. For total cholesterol and HDL-C, the Passing-Bablok regression were strong, with clinically acceptable differences of -0.81 % and +5.23 %, respectively. Triglycerides showed a clinically unacceptable difference of +29.4 %, but strong agreement with clinical categories was observed (kappa 95 % CI [0.55; 0.82]); this may reflect both matrix effects and the non-fasting status of almost all participants (∼91 % were non-fasting). Calculated LDL-C misclassification rates were 47 %, 37 %, and 32 % using the Friedewald, Sampson, and Martin-Hopkins equations, respectively. Non-HDL-C showed a clinically acceptable bias of -2.83 %, supporting its use for prevention goals and familial hypercholesterolemia screening. Concordance analysis of SCORE2 based on non-HDL-C categories revealed high reliability (95 % CI [0.72; 0.92]). These findings support the use of Cobas® b101 with capillary sampling for population-level screening and preliminary CVD risk assessment using SCORE2, despite reduced analytical performance for TG. Abnormal results should be confirmed by a fasting lipid profile.

Osteogenesis imperfecta (OI) is a rare bone fragility disorder. Previously, in a severe OI mouse model (Col1a1Jrt/+), a sex- and age-dependent metabolic phenotype was observed, correlating with elevated levels of the bone-derived hormone osteocalcin (OCN). This hormone is known to play a crucial role in managing energy metabolism, including glucose regulation and fat mass. In fact, upon high-fat diet (HFD) exposure, OI mice developed a metabolic syndrome linked to sex and OCN. To assess OCN's role in OI, Col1a1Jrt/+ mice were crossed with OCN-deficient mice (Bglap). Under regular chow and HFD conditions, both OCN-dependent and OCN-independent metabolic alterations were identified. OCN-dependent processes were adipose tissue, liver, and insulin metabolism in a sex-, age-, and diet-dependent manner. OCN-independent traits included the pancreas in juvenile mice, HFD-induced pancreatic insulin levels and glucose intolerance, besides overall growth, fertility, and bone phenotype. Notably, increased juvenile energy expenditure was OCN-independent, while HFD-induced changes were OCN-driven. These findings demonstrate OCN's role in shaping the metabolic phenotype while revealing distinct OCN-independent effects, emphasizing the complex genetic regulation of metabolism in OI.

Diagnosing rare muscle diseases can be challenging due to their genetic heterogeneity. The French National Network for Rare Neuromuscular Diseases (FILNEMUS) has previously established a pioneering nationwide strategy based on gene lists organized in 13 phenotype-specific gene panels. We now revise these lists and add recently described genes. Using data collected from all FILNEMUS diagnostic laboratories, we also establish a "Major Muscle Genes" panel that includes genes responsible for the most frequent genetic muscle diseases. The updated diagnostic strategy of the FILNEMUS network will help reduce the turn-around time for genetic results and facilitate rapid access to the French national genome sequencing platforms.

This study aimed to assess nutritional status, analyze fatty acid profile, evaluate oxidative stress markers, and examine their associations with sarcopenia in patients with cardiovascular disease. Ninety-five adults over 60 years old with diagnosed CVD were enrolled. Sarcopenia risk was assessed using the SARC-F questionnaire dividing patients into two groups: SARC-F- and SARC-F+. Nutritional status was evaluated using the Mini Nutritional Assessment (MNA&#xae;). Mediterranean Diet Score (MDS) reflects adherence to a Mediterranean-style diet. Sarcopenia risk was identified in 56.84% of participants. Participants at risk of sarcopenia had significantly poorer nutritional status (p = 0.001) and lower MDS (p = 0.01). No significant differences were observed in saturated, monounsaturated, or polyunsaturated fatty acids, whereas trans fatty acids and total omega-3 fatty acids, particularly C18:3 &#x3c9;-3, were elevated in the SARC-F+ group (p = 0.009, 0.005 and 0.009 respectively). Logistic regression identified age, diabetes, poor nutritional status, and elevated omega-3 fatty acids and GPx as significant predictors of sarcopenia, with an inverse association for MDS and GSH. Elevated omega-3 fatty acid levels were associated with sarcopenia independently of age, sex, diabetes, and nutritional status, but this association appeared to be influenced by MDS, GPx and GSH. More else omega-3 fatty acids were positively associated with GPx (&#x3b2; = 0.117; p < 0.001) and negatively associated with GSH (&#x3b2; = -3.486; p = 0.01) only in patients without sarcopenia. These findings provide novel insights into the relationship between omega-3 fatty acids and sarcopenia and may inform future nutritional strategies for its prevention.

The frequency structure of the superconducting correlations in cuprates gives insights on the pairing mechanism. Here we present an exhaustive study of this problem in the two-dimensional Hubbard model with cellular dynamical mean-field theory. To this end, we systematically quantify the dependence on doping &#x3b4; and interaction strength U of the superconducting gap, of the frequency scales where d-wave pairing occurs, and of their relative contribution to pairing. For all values of U and &#x3b4;, we find pair-forming processes confined to frequencies set by the superexchange interaction and followed by pair-breaking processes, ruling out both pair-forming and pair-breaking processes on the scale of U. This suggests that at high frequencies, the effect of U is eliminated by the d-wave paring, and that at small frequencies, U generates the superexchange interaction that leads to low-frequency pair-forming processes providing the net contribution to pairing.

Microalgae are emerging as valuable model systems for studying epigenetic regulation in unicellular eukaryotes and as promising platforms for biotechnological lipid production. In these organisms, DNA and RNA methylation, histone modifications, and non-coding RNAs form interconnected regulatory layers that shape chromatin structure, genome stability, transcriptional responses, and metabolic plasticity. This review synthesizes current knowledge on epigenetic mechanisms in microalgae, with particular emphasis on environmental responsiveness, and links to lipid metabolism. The major epigenetic pathways will be described in model species, including cytosine and adenine DNA methylation, RNA methylation, histone post-translational modifications, and RNA-guided silencing mediated by small and long non-coding RNAs. Then it will be reported how environmental drivers such as salinity, nutrient limitation, light, temperature, and carbon availability remodel the microalgal epigenome. Finally, the evidence connecting epigenetic regulation to lipid accumulation will be presented, including methylation-dependent carbon reallocation, histone-modification dynamics under nutrient stress, and RNA-based regulation of lipid-related genes. Chemical perturbation and emerging epigenome-editing approaches further support the functional relevance of these pathways, although interpretation remains complicated by stress-associated secondary effects and strong lineage dependence. Overall, available studies indicate that epigenetic regulation contributes to both environmental acclimation and metabolic rewiring in microalgae, but direct causal links to lipid productivity remain limited to a small number of systems. A better mechanistic understanding of these processes will be essential for exploiting epigenetic regulation as a lever for strain improvement and sustainable lipid biotechnology.

Vitamin D plays critical roles in maternal and fetal skeletal health; its deficiency during pregnancy is common worldwide but the interest of its supplementation is not clearly established. This review aims to synthesize current evidence on vitamin D supplementation during pregnancy, with a focus on safety, efficacy, maternal and neonatal outcomes, and to revisit current French GRIO recommendations. A narrative review of mostly recent meta-analyses of clinical trials aimed to identify skeletal and extra-skeletal effects of supplementation, as well as dosage and safety considerations. Vitamin D supplementation during pregnancy has been shown to improve neonatal bone mineralization and decrease the incidence of neonatal hypocalcemia and rickets. Evidence also suggests a protective role against preeclampsia and possibly gestational diabetes, although findings remain heterogeneous across populations. Recommended daily vitamin D intakes vary widely between international authorities, from 400 IU to 4,000 IU. In pregnant women, vitamin D supplementation may help reduce skeletal and extra skeletal risk, is associated with improved outcomes in some studies, with strongest evidence for skeletal outcomes and should be implemented as soon as possible during pregnancy. Further high-quality studies are however warranted to refine optimal dosing strategies and long-term outcomes.

Inguinal WAT (IngWAT) quickly adapts its metabolism to body energy status variations, including uncoupling protein 1 (UCP1) expression. However, its long-term metabolic response to long-term sedentary and exercise training has not been fully characterized. This study investigated IngWAT's long-term response to sedentary (SED, restricted cage) vs. exercise (EXER, treadmill running with a defined protocol) conditions in mice. EXER mice showed increased expression of Sarcoendoplasmic Reticulum Calcium ATPase (SERCA)2b and UCP1, along with a reduction in adipocyte size, indicating activation of thermogenesis. Fascinatingly, exercise elevated the expression of CIDEA in tiny adipocytes and promoted a beiging effect in mice. Elevated OXPHOS complex proteins expression and NMR-based metabolite profiling in IngWAT revealed that exercise profoundly reprogrammed energy metabolism by strengthening phosphocreatine-creatine buffering, regulating TCA cycle metabolite cycling (citrate and succinate), and increasing ketone body formation (3-hydroxybutyrate and acetone). Elevated glycerol level, a higher glycerol-lactate ratio, and reduced carnitine in IngWAT of EXER mice reflected improved fatty acid uptake and &#x3b2;-oxidation, in contrast to the metabolic inefficiency observed during sedentariness. Moreover, increased vascularization was accomplished by upregulated expression of vascular endothelial growth factor 1a (VEGF1a), angiopoietins (ANG)1&2, supports elevated metabolic state in exercise. Conversely, SED mice showed larger adipocytes with uniform CIDEA expression, but a downregulation of thermogenic proteins. Interestingly, a significant downregulation of mitochondrial complex III was also observed, which indicates altered mitochondrial physiology in SED mice. Data presented here suggest that IngWAT is metabolically flexible and can undergo both structural and metabolic adaptations in accordance with physical activity level.

Joint injuries, such as rupture of the anterior cruciate ligament (ACL), are associated with the development of post-traumatic osteoarthritis (PTOA). ACL rupture can lead to disruption of metabolic pathways, including the conversion of tryptophan to kynurenine, which is associated with a sustained inflammatory response. An in vivo study was undertaken to determine the acute effects of intra-articular administration of liposomes loaded with the tryptophan-catabolizing enzyme indoleamine 2,3-dioxygenase-1 (IDO-1) following ACL rupture. Using a rat model of non-surgical ACL injury, male and female rats underwent a single intra-articular injection of empty liposomes, or liposomes loaded with IDO-1 and were subsequently randomized to 1- or 2-week endpoints. IDO-1 treatment after ACL injury was associated with a significant reduction in synovial fluid concentration of tryptophan at both 1- and 2-week endpoints. In addition to reduced tryptophan, IDO-1 treatment led to significantly lower synovial fluid concentrations of IL-1&#x3b2; and TNF-&#x3b1;. IDO-1-loaded liposomes also increased the ratio of regulatory T lymphocytes (Tregs) to IL-17-secreting helper T lymphocytes (Th17 cells). Similarly, IDO-1 treatment increased the number of CTLA4+ cells relative to IL-17 A+ cells that infiltrated joint tissues. Contrast-enhanced micro-computed tomography (CE-&#x3bc;CT) was used to quantify treatment-based effects on articular cartilage thickness and surface roughness at 2-week endpoint. In addition to sex-based differences, IDO-1-loaded liposome treatment was associated with increased cartilage thickness, with no significant effects on surface roughness. Later endpoints and more thorough histologic characterization is needed to determine whether this increased cartilage thickness represents a chondroprotective effect, or an anabolic effect.

This article formally describes Craticula vanensis sp. nov., a new species of diatom from Lake Van, the largest soda lake in the world, and the fifth new species identified in the lake following an 81-years gap in investigations. A genomic approach based on short reads allowed the complete cluster of nuclear rRNA genes to be retrieved alongside the complete plastome, both later used in several single or multigene phylogenies, which surprisingly tended to associate C. vanensis to species of the genus Dorofeyukea. The complex structure of the mitogenome could only be resolved by long-read sequencing. It is characterized by its large size (116,698&#xa0;bp), the presence of several introns in the cox1 gene, the use of an alternative genetic code with the putative reassignment of the UGA codon to arginine and the unexpected presence of six copies of the rRNA genes and nine copies of truncated nad2 sequences. A survey of published metabarcoding datasets suggested the presence of C. vanensis in a soda lake from Central Europe (Kakassz&#xe9;ki, Hungary), which was later confirmed by microscopy and suggests an extended distribution of this taxon.

In the discovery of novel antibiotics, a new series of Schiff base purine derivatives (7-11) was synthesized from two newly prepared purine ring-containing aldehydes (6a) and (6b). The newly synthesized compounds incorporated three bioactive fragments, namely purine, triazole, and the azomethine group. The structures of the synthesized Schiff bases and their corresponding aldehyde precursors were elucidated and confirmed using 1H and 13C NMR spectra and HRMS. The antibacterial activity of the newly synthesized compounds was evaluated against four bacteria: two gram-positive (Staphylococcus Aureus and Enterococcus faecalis) and two gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa). Among the tested compounds, aldehyde (6b) exhibited the most potent activity against S. aureus (MIC&#xa0;=&#xa0;200&#xa0;&#x3bc;g/mL), while Schiff bases (8-10) were most effective against P. aeruginosa (MIC&#xa0;=&#xa0;200&#xa0;&#x3bc;g/mL). Additionally, compound (11) demonstrated notable activity against E. coli and E. faecalis (MIC&#xa0;=&#xa0;390&#xa0;&#x3bc;g/mL and 200&#xa0;&#x3bc;g/mL, respectively). To gain further insight into the antibacterial potential of these compounds, molecular docking studies were conducted to investigate their interactions with key bacterial proteins essential for their viability. As a result, compounds 6a and 7 exhibited the highest binding affinities among all tested molecules, showing strong interactions with almost all selected target proteins, including E. coli (4URO), S. aureus (4CJN), and E. faecalis (2Z1P and 6ORI). Compound 6a demonstrated remarkable binding, with affinities of -8.7&#xa0;kcal/mol for E. faecalis (2Z1P) and&#xa0;-&#xa0;9.9&#xa0;kcal/mol for E. faecalis (6ORI). Similarly, compound 7 displayed high affinities of -8.4&#xa0;kcal/mol with E. faecalis (2Z1P) and&#xa0;-&#xa0;9.0&#xa0;kcal/mol with P. aeruginosa (2UV0).