ABSTRACT
Background: Chronic lymphocytic leukemia (CLL) is the most frequent B-cell lymphoproliferative disorder in adults. Although its cytogenetic landscape is dominated by 13q deletion, trisomy 12, 11q deletion, and 17p deletion, rarer numerical abnormalities such as trisomy 3 are occasionally identified. The clinical impact and prognostic value of trisomy 3 remain poorly characterized. Case Presentation: A 71-year-old male presented with progressive asthenia and intermittent headaches lasting for several weeks. Physical examination revealed a tumor syndrome combining splenomegaly and peripheral lymphadenopathy. Laboratory evaluation demonstrated major hyperleukocytosis at 180000/µL associated with anemia (hemoglobin 8.0g/dL) and thrombocytopenia (platelets 75000/µL), categorizing the disease as Binet stage C (Rai stage IV). Peripheral blood smear showed a lymphocytosis composed of monotonous mature small lymphocytes with the presence of Gumprecht shadows. Flow cytometry immunophenotyping on whole blood confirmed the diagnosis of classic CLL with a Matutes score of 5. Conventional R-banding karyotype revealed a trisomy of chromosome 3. FISH analysis excluded the presence of targeted deletions of the TP53 (17p13) and ATM (11q22.3) genes. Conclusion: This case illustrates an aggressive initial presentation of CLL associated with an isolated trisomy 3, despite an immunophenotypic profile highly concordant with typical CLL. Systematic investigation and characterization of these rare chromosomal aberrations are essential to better define their pathophysiological role.

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Introduction: The Philadelphia chromosome (Ph), resulting from the t(9;22) (q34;q11) translocation, is the most common cytogenetic abnormality in adult acute lymphoblastic leukemia (ALL). Complex variant translocations (vPh) involving a third chromosome are rare, and the involvement of the 11q13 locus (CCND1) is exceptional. Case Presentation: We report the case of a 67-year-old male presenting with systemic symptoms, splenomegaly, and hyperleukocytosis at 80,000/µL. Bone marrow aspirate and immunophenotyping led to a diagnosis of common B-cell ALL (B-ALL II). Cytogenetic analysis revealed a complex translocation t(9;11;22) (q34;q13;q11). Fluorescence in situ hybridization (FISH) confirmed a rearrangement involving the BCR, ABL1, and CCND1 genes. Unexpectedly, RT-PCR testing for BCR-ABL1 fusion transcripts (p190, p210, and p230) returned negative results. Conclusion: This case illustrates an atypical cytogenetic presentation of B-ALL and underscores the importance of an integrated diagnostic approach. The discordance between FISH and RT-PCR suggests the presence of a cryptic breakpoint or an alternative fusion transcript, highlighting the need for next-generation sequencing (NGS/RNA-Seq) to optimize therapeutic management.

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Novel research is proposed to optimize a pollutant-degrading microbial consortium by employing two state-of-the-art technologies. These technologies will incorporate CRISPR-Cas9-based genome editing in conjunction with molecular dynamics (MD) guided enzyme stabilization methods into one unified product. Both technologies, when used in conjunction, make for a robust and scalable way to engineer a stable, predictable, and efficient microbial system. However, most of the current techniques fail to address the unstable nature of the enzyme structure, which limits their use in real-world applications, and MD provides a detailed method for assessing enzyme stability under variable environmental stresses. MD is performed at the atomic level and can identify the regions of the target enzyme (e.g., cytochrome P450 monooxygenases) with the most structural instability, due to stress from variable pH and salinity conditions. Once an enzyme's stress point is identified, CRISPR-Cas9 is then utilized to design the specific modifications (rigidifying modifications) that enhance the rigidity of the structure while maintaining the enzyme's catalytic property or activity. Additionally, metabolic pathways containing the enzymes of interest will be engineered into the microbe consortium and then evaluated for synergistic interactions and degradation rates using simulated field conditions. The closed-loop approach uniquely combines MD with consortium engineering by providing a system where the MD-derived information will directly affect the genetic modifications of the enzyme(s) and therefore influence the optimization of the metabolic pathways/consortia. Results of experimental testing have shown a 30% increase in the resilient nature of the engineered consortia compared to non-engineered consortia (wild-type), demonstrating the potential of this approach for the construction of scalable environmental bioremediation strategies. Overall, this study significantly advances the current tech

ABSTRACT
Ethyl carbamate (EC), a Group 2A carcinogen, is unavoidably formed during fermentation and poses a persistent safety concern in alcoholic beverages and fermented foods. Although enzymatic degradation offers a mild and substrate-specific strategy, EC hydrolases suitable for brewing environments remain scarce, and heterologous expression of known candidates often results in inactive inclusion bodies. In this study, we mined amidase genes from three brewing-associated microorganisms—Bacillus velezensis, Clavispora lusitaniae, and Saccharomyces cerevisiae—based on the conserved GGSSGG motif of the AS-family amidases. Three full-length genes, amiE (1458 bp), amdA (1632 bp), and amd08 (1665 bp), were successfully cloned into pET-28a vectors. Prokaryotic expression revealed that AmiE (52.63 kDa) and AmdA (60.76 kDa) were predominantly deposited as insoluble inclusion bodies, while Amd08 (61.39 kDa) was not detected due to apparent gene silencing. To circumvent these expression barriers, we performed comprehensive bioinformatic analyses. All three proteins were predicted as stable, hydrophilic molecules with theoretical pI values of 5.12–5.47 and negative GRAVY indices. Secondary structures were dominated by α-helices and random coils, and homology modeling confirmed the presence of intact GGSSGG motifs and Lys-Ser-Ser catalytic triads in each protein. Multidimensional model validation further supported their stereochemical reliability. Collectively, this study enriches the genetic reservoir of brewing-origin EC hydrolases and provides essential molecular and structural foundations for future solubility engineering and enzyme preparation development.

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The effectiveness of conventional antibiotic regimens has been severely compromised by the rapid dissemination of the multidrug-resistant (MDR) Pseudomonas aeruginosa, a critical ESKAPE pathogen characterized by impermeable outer membranes, active efflux mechanism, and robustbiofilm matrix production. Lytic bacteriophages therapy represents a highly promising alternative treatment approach. In this study, we isolated and characterized virulent bacteriophages targeting a MDR P.aeruginosahost from hospital sewage water and the River Ganges, and for this we adapted the host-mediated selective enrichment and double layer agar typing methodologies that was first developed by Dr. Sachindranath Mukherjee. The isolated phages generated homogenous, transparent plaques ranging from 2.5 to 4.5 mm in a diameter. The absence of central turbidity or peripheral halo zones confirms a lytic, obligate lifecycle. These findings demonstrates that bioprospecting geographically diverse environmental reservoirs to produce lytic phages for downstream lyophilization, encapsulation against chronic nosocomial infections.

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Inflammatory skin allergies, including atopic dermatitis, allergic contact dermatitis, and urticaria, represent a significant global health burden affecting millions of individuals worldwide. The Janus kinase 3 (JAK3), a critical member of the JAK-STAT signaling pathway, has emerged as a promising therapeutic target due to its selective expression in immune cells and its pivotal role in mediating cytokine-driven inflammation. While synthetic JAK inhibitors have demonstrated clinical efficacy, their systemic immunosuppressive effects, hepatotoxicity, and high costs limit their widespread application. This study presents a comprehensive in silico approach to identify, characterize, and evaluate natural product-based JAK3 inhibitors as safer alternatives for topical management of skin allergies. Using the Protein Data Bank (PDB ID: 7C3N) as the target receptor, we performed database screening via IMPPAT and Dr. Duke's Phytochemical and Ethnobotanical Databases to identify medicinal plants with established anti-allergic and anti-inflammatory properties. From an initial pool of over 1,500 plants, seven medicinally important species—Aloe vera, Ocimum sanctum, Cucumis sativus, Azadirachta indica, Withania somnifera, Cocos nucifera, and Lawsonia inermis—were selected based on local availability and accessibility. Phytochemical profiling yielded 92 phytoconstituents, which were subjected to molecular docking analysis using Schrodinger Maestro 12.5 against the delgocitinib binding site of JAK3. The docking results revealed cucurbitacin-C (docking score: -12.406), quercetin (-9.98), luteolin (-9.243), and chrysophanic acid (-9.015) as top-scoring candidates with binding affinities comparable to the standard drug delgocitinib (-12.406). ADMET and physicochemical profiling via pKCSM and SwissADME demonstrated that all lead compounds adhered to Lipinski's Rule of Five and Veber's rules, indicating favorable drug-likeness, oral bioavailability, and safety profiles. The identified

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Secondary bacterial infections in intensive cardiac care settings necessitate a transition toward automated bedside screening systems. To understand the mechanics behind these devices, this paper reviews the foundational physics of light-guiding pathways, solid-state circuits, and nanoscale layers. Integrating these engineering frameworks enables clinical teams to clearly track sensitive patient immune responses. In practice, the platform evaluates a patient's host defense status by measuring local C-reactive protein (CRP) and procalcitonin levels. Time is critical; traditional laboratory cultures require two full days to yield results, thereby squandering the narrow therapeutic window available during sudden coronary emergencies. Rapid-onset sepsis poses a severe threat to vulnerable cardiac patients, directly increasing hospital mortality rates. While high production costs and sensor fouling from whole-blood samples remain engineering bottlenecks that slow widespread clinical deployment, their potential is significant. Ultimately, linking decentralized electronic networks with localized testing instruments simplifies hospital logistics and protects at-risk patients during acute medical crises.