We report a novel synthetic strategy for tetracyclic heterocycles, specifically 1-thia-4a,11,12-triazatetracenes, representing a previously unreported fused ring system, using enamine 8-amino-3,4-dihydropyrimido[2,1-b][1,3]thiazin-6-one as a versatile building block. This enamine undergoes multicomponent reactions with aldehydes and dimedone in refluxing acetic acid, efficiently affording the target fused heterocycles. Structural elucidation was confirmed via alternative synthetic routes and 2D-HMBC correlations. The resulting compounds possess a rigid, planar, and highly conjugated tetracyclic framework enriched with heteroatoms (N, S, O), features known to enhance binding interactions with biological macromolecules. Such structural characteristics favor interactions within enzyme active sites, particularly nucleic acid-processing enzymes such as DNA-directed RNA polymerase, as a putative target based on molecular docking predictions. Among the synthesized series, compound 9a emerged as a potent broad-spectrum agent, demonstrating strong antibacterial activity against all tested strains, with notable efficacy against S. aureus (MIC = 0.5 mg mL[-1]). Molecular docking studies corroborated its bioactivity, predicting higher binding affinity of 9a against Aspergillus terreus (ΔG = -9.2 kcal mol[-1]) compared to fluconazole, and stronger predicted affinity against the bacterial target than tetracycline (ΔG = -6.7 kcal mol[-1]). These results position 9a as a promising lead for further antimicrobial development.

Thermokarst lakes are biogeochemical hotspots and reservoirs of antibiotic resistance genes (ARGs), yet their vertical organization remains poorly understood. Here, we investigated the vertical stratification of ARGs in sediment cores from thermokarst lakes on the Qinghai-Xizang Plateau, quantifying their distribution and associations with mobile genetic elements (MGEs) and carbohydrate-active enzymes (CAZymes). The results revealed pronounced vertical differentiation, with ARG richness decreasing but β-diversity increasing with depth. A total of 386 ARGs were identified, of which 39% increased and 22% decreased significantly along the depth gradient. Multidrug and glycopeptide resistance genes dominated the profiles, while macrolide, tetracycline, and fluoroquinolone resistance were most abundant overall. MGEs, primarily transposase and recombinase genes, were strongly correlated with ARGs, underscoring horizontal gene transfer as a key mechanism for their persistence and dispersal. Co-occurrence analyses further revealed both positive and negative associations between ARGs and CAZymes, indicating synergistic and antagonistic couplings between antibiotic resistance and microbial carbon metabolism. Genes involved in energy-efficient carbon degradation (e.g. glycoside hydrolases and glycosyltransferases) were positively correlated with resistance genes enhancing stress tolerance, whereas negative interactions reflected trade-offs between carbon utilization and resistance maintenance. These findings demonstrate that ARGs are vertically structured and functionally integrated within microbial metabolic networks, providing new insights into their ecological roles in thermokarst lakes.

Ni1.5Mg1.5Al1-LDH/GO composite was synthesized by the co-precipitation method, and Ni1.5Mg1.5Al1-LDH/GO/g-C3N4 composites (NCG-X, X = 1, 3, 5) with varying mass ratio of GO to Ni1.5Mg1.5Al1-LDH/g-C3N4 were further constructed using electrostatic self-assembly technology. The photocatalytic degradation performance of the NCG-X composites toward ciprofloxacin (CIP) were influenced by the GO dosage, which regulated the microstructure, light-absorbing ability, and photo-electrochemical characteristics of the NCG-X composites. Compared to the pure g-C3N4 nanosheets and Ni1.5Mg1.5Al1-LDH/g-C3N4 composite, all NCG-X composites exhibited better photocatalytic performance. As the GO dosage raising, the photocatalytic performance of NCG-X composites initially improved but subsequently declined, and the NCG-3 composite (with GO dosage of 3 wt%) achieved the optimum photocatalytic performance. After 120 min of irradiation under visible light, 82.96% of CIP molecules (100mL, 10mg/L) were degraded by 0.03g NCG-3 composite, whose reaction rate constant (0.01237 min-1) was 5.11, 2.35 and 1.75 times that of g-C3N4 nanosheets, MgAl-LDH/g-C3N4 composite and Ni1.5Mg1.5Al1-LDH/g-C3N4 composites, respectively. ·O2- and h+ were the predominant active species during the photocatalytic degradation process. Moreover, NCG-3 composite exhibited excellent universality for degrading organic contaminants like methyl orange, crystal violet, tetracycline, and methylene blue. This work provides a novel strategy for synthesizing high performance LDH/g-C3N4 composite photocatalyst via the modification of GO, and demonstrates the good perspective application of Ni1.5Mg1.5Al1-LDH/GO/g-C3N4 composite for the removal of organic pollutants in wastewater.

In order to solve the problem of compound pollution of antibiotics and heavy metals in water, AT-PDI/Bi4O5Br2 (AT-PDI/BOB) composites with strong interfacial electric field (IEF) were prepared by hydrothermal method. In the coexistence system containing Tetracycline (TC) and Cr(VI), the material shows obvious synergistic degradation effect, with a degradation rate of 88.9% for TC and 98.2% for Cr(VI). The 10-hour flow experiment validated its stability, maintaining the degradation rates of TC and Cr(VI) at approximately 73% and 86%. The enhanced IEF largely illustrates a significant performance improvement because it successfully drives the directional separation and migration of light-induced carriers. Free radical extinction experiments show that the main active substances involved in degradation are •O2-, h+, and e-. TC effectively consumes h+ and •O2- in the system, thereby facilitating e- extraction and accelerating the degradation of Cr(VI). The present study provides new ideas for the design of high-performance photocatalysts that utilize the IEF to treat water pollution containing both antibiotics and heavy metals.

Hemoglobin Bart's hydrops fetalis syndrome (BHFS) is the most severe form of α-thalassemia and is highly prevalent in Southeast Asia. It is most commonly caused by homozygosity for the α[0]-thalassemia Southeast Asian deletion (--[SEA]/--[SEA]), which eliminates α-globin production and results in profound fetal anemia. Current management is limited to intrauterine transfusions with only transient benefit, and no pharmacological or gene-based therapies are available. Progress toward therapy has been hampered by the lack of disease-relevant in vitro models. Here, we established Chery-Bart's, an immortalized erythroid progenitor cell line derived from umbilical cord blood CD34[+] hematopoietic stem and progenitor cells of a fetus with --[SEA]/--[SEA] and β[IVS I-1 (G> T)]/β using a tetracycline-inducible HPV16 E6/E7 system. Chery-Bart's cells exhibit sustained proliferation beyond the Hayflick limit, stable recovery after cryopreservation, and enrichment in the basophilic erythroblast stage. In vitro erythropoiesis assays showed that the cell line retains key features of the parental cells, including the capacity for erythroid maturation, expression of fetal globin transcripts, and robust production of Hb Bart's (γ4), the hallmark pathological hemoglobin of BHFS. Although Chery-Bart's carries a β-thalassemia mutation, this is unlikely to modify disease severity, as γ-globin predominates in this model. Collectively, Chery-Bart's represents the first durable and disease-specific cellular model of BHFS with --[SEA]/--[SEA] genotype. This platform provides a scalable resource for mechanistic studies and preclinical evaluation of therapeutic approaches, including drug discovery, gene therapy, and α-like globin chain induction. Beyond BHFS, Chery-Bart's may also serve as a model for investigating severe α-thalassemia syndromes associated with the --[SEA] allele, such as deletional and non-deletional HbH disease.

The release of rehabilitated wildlife can introduce antimicrobial resistance (AMR) into wild ecosystems. We examined AMR in Escherichia coli isolated from 44 Bolivian red howler monkeys (Alouatta sara) at a rescue center in Madre de Dios, Peru. Fecal samples were collected noninvasively and processed for E. coli isolation. Antimicrobial susceptibility testing against 12 antibiotics was performed and extended-spectrum beta-lactamase (ESBL) production was phenotypically confirmed. Multidrug resistance (MDR) and the multiple antibiotic resistance (MAR) index were calculated. We isolated E. coli from 43/44 sampled monkeys (98%). Only 1/85 (1%) E. coli isolates was an ESBL producer, and this isolate exhibited MDR to eight antibiotics across five classes. Non-ESBL isolates (n = 84) showed the highest resistance to tetracycline (13%), sulfamethoxazole-trimethoprim (10%), and chloramphenicol (5%). Five isolates (6%) were MDR, and seven (8%) had a MAR index ≥0.2. Although ESBL prevalence was low, the presence of MDR and critical AMR profiles emphasizes the importance of surveillance, following the One Health approach, in primate rehabilitation programs to help prevent potential AMR spread during wildlife release.

Neisseria gonorrhoeae remains a high-priority pathogen according to the World Health Organisation Bacterial Priority Pathogens List. In South Africa, increasing antimicrobial resistance to tetracycline, ciprofloxacin, and penicillin is limiting available treatment options for N. gonorrhoeae infections. This challenge necessitates the exploration of alternative therapeutics, with natural products representing a promising source of novel scaffolds. This study employed a metabolomics-guided approach to tentatively identify antigonorrhoeal compounds from South African medicinal plants. Sixteen crude extracts prepared by ultrasonic extraction, and 112 solid-phase extraction (SPE) fractions, were screened against N. gonorrhoeae ATCC 49981 using broth microdilution. Leaves from Helichrysum odoratissimum (L.) Sweet and leaves and twigs from Terminalia phanerophlebia Engl. & Diels yielded the most active samples, with minimum inhibitory concentrations (MICs) as low as 6.25 µg/mL. SPE fractions from both plants were analysed by Ultra-Performance Liquid Chromatography-High-Resolution Mass Spectrometry (UPLC-HRMS). Data were processed using the Waters UNIFI[®] platform and analysed by Principal Component Analysis (PCA) and Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA) in MetaboAnalyst 6.0. Putative compounds were annotated using in silico tool, including SIRIUS, complemented by MassLynx, and a literature search, enabling tentative annotation of 23 compounds. Of these, 12 were prioritised by the Neisseria Bayesian model (score ≥ 0.5), including kaempferol and carvacrol in H. odoratissimum, and vitexin and isoscopoletin in T. phanerophlebia. Tanimoto similarity analysis revealed low structural similarity to ciprofloxacin (< 0.30), indicating novelty relative to fluoroquinolone scaffolds. These findings provide candidate compounds for further validation and demonstrate that integrating metabolomics with computational prediction can accelerate antigonorrhoeal discovery.

Tetracycline is an emerging environmental threat, as its presence in water may contribute to antibiotic resistance in microorganisms. In this study, starch and activated carbon were extracted from potato peels and subsequently modified via free-radical polymerization using acrylic acid to develop a novel, green composite hydrogel for efficient tetracycline removal. Various adsorption parameters were optimized using the Taguchi method, including initial contaminant concentration, pH, adsorbent dosage, and contact time. The optimal conditions for tetracycline adsorption by the starch-acrylic acid/activated carbon biocomposite hydrogel identified were an initial concentration of 10 mg/L, a pH of 7, an adsorbent dosage of 2.5 g/L, and a contact time of 80 min. The incorporation of activated carbon significantly enhanced the adsorption capacity from 29.58 mg/g (for the starch-acrylic acid hydrogel) to 52.63 mg/g (for the starch-acrylic acid/activated carbon biocomposite hydrogel). Adsorption equilibrium was best described by the Temkin isotherm model, while kinetic studies confirmed that the process follows the pseudo-second-order model for starch-acrylic acid/activated carbon biocomposite hydrogel. Additionally, thermodynamic evaluations indicated that the process was both spontaneous and exothermic. Despite a moderate loss in efficiency over 8 reuse cycles from 99.99% to 58.06%, the developed starch-acrylic acid/activated carbon biocomposite hydrogel demonstrates a highly favorable adsorption capacity compared to previously reported green adsorbents, establishing it as a promising candidate for sustainable tetracycline removal.

The tetracycline class of antibiotics is widely used for treating bacterial diseases including Lyme disease, anthrax, acne vulgaris, and pneumonia. Using a series of high-resolution cryo-electron microscopy (cryo-EM) structures, we show that tetracyclines can simultaneously target the mRNA decoding center in the 30S subunit and the nascent peptide exit tunnel (NPET) in the 50S subunit of the bacterial ribosome. Among the tested tetracyclines, Doxycycline was distinct in its ability to dimerize and bind the NPET at multiple locations. Structural comparison of Doxycycline, Minocycline, and Sarecycline bound to the Escherichia coli and Cutibacterium acnes 70S ribosome revealed species-specific differences affecting drug interaction and occupancy. Our results reveal a dual site mechanism of action for tetracyclines and provide a structural basis for rational design of narrow spectrum tetracyclines to overcome the rising threat of antibiotic resistance.