CRISPR/Cas9 genome editing of potato StDMR6-1 results in plants less affected by different stress conditions.

Potato is the third most important food crop, but cultivation is challenged by numerous diseases and adverse abiotic conditions. To combat diseases, frequent fungicide application is common. Knocking out susceptibility genes by genome editing could be a durable option to increase resistance. DMR6 has been described as a susceptibility gene in several crops, based on data that indicates increased resistance upon interruption of the gene function. In potato, Stdmr6-1 mutants have been described to have increased resistance against the late blight pathogen Phytophthora infestans in controlled conditions. Here, we present field evaluations of CRISPR/Cas9 mutants, in a location with a complex population of P. infestans, during four consecutive years that indicate increased resistance to late blight without any trade-off in terms of yield penalty or tuber quality. Furthermore, studies of potato tubers from the field trials indicated increased resistance to common scab, and the mutant lines exhibit increased resistance to early blight pathogen Alternaria solani in controlled conditions. Early blight and common scab are problematic targets in potato resistance breeding, as resistance genes are very scarce. The described broad-spectrum resistance of Stdmr6-1 mutants may further extend to some abiotic stress conditions. In controlled experiments of either drought simulation or salinity, Stdmr6-1 mutant plants are less affected than the background cultivar. Together, these results demonstrate the prospect of the Stdmr6-1 mutants as a useful tool in future sustainable potato cultivation without any apparent trade-offs.

Comparative Analysis of Keratometric and Pachymetry Values From Corneal Topography Scans: A Comparison Between Pentacam and Galilei.

Objective The objective of this study was to compare K1, K2, Kmax, and pachymetry values from Pentacam and Galilei scans of corneal topography in order to assess their correlation and interchangeability in clinical practice. Methodology A total of 34 patients (68 eyes) were enrolled in the study. Corneal topography was performed using Pentacam and Galilei devices on the same day. K1, K2, Kmax, and pachymetry readings were obtained from the scans and analyzed using paired t-tests and Bland-Altman plots. Results There were minimal differences in clinical settings between Pentacam and Galilei for K1, K2, Kmax (>0.75 D), and pachymetry values (>15 um). However, there was a statistically significant difference found between Kmax and pachymetry, making their interchangeability questionable. Conclusion Pentacam and Galilei demonstrate a good correlation between corneal keratometric values (K1, K2, and Kmax) and pachymetry values in clinical settings, and they should be used interchangeably with caution.

Loss of YAP in Schwann cells improves HNPP pathophysiology.

Rapid nerve conduction in the peripheral nervous system (PNS) is facilitated by the multilamellar myelin sheath encasing many axons of peripheral nerves. Charcot-Marie-Tooth type 1A (CMT1A), and hereditary neuropathy with liability to pressure palsy (HNPP) are common demyelinating inherited peripheral neuropathies and are caused by mutations in the peripheral myelin protein 22 (PMP22) gene. Duplication of PMP22 leads to its overexpression and causes CMT1A, while its deletion results in PMP22 under expression and causes HNPP. Here, we investigated novel targets for modulating the protein level of PMP22 in HNPP. We found that genetic attenuation of the transcriptional coactivator Yap in Schwann cells reduces p-TAZ levels, increased TAZ activity, and increases PMP22 in peripheral nerves. Based on these findings, we ablated Yap alleles in Schwann cells of the Pmp22-haploinsufficient mouse model of HNPP and identified fewer tomacula on morphological assessment and improved nerve conduction in peripheral nerves. These findings suggest YAP modulation may be a new avenue for treatment of HNPP.

Interaction of base excision repair gene polymorphism and estrogen-DNA adducts in breast cancer risk among East Asian women.

PURPOSE: In East Asia, the incidence of breast cancer has been increasing rapidly, particularly among premenopausal women. An elevated ratio of estrogen-DNA adducts was linked to a higher risk of breast cancer. The present study explored the influence of the interaction between base excision repair (BER) gene polymorphisms and estrogen-DNA adducts on breast cancer risk. METHODS: We conducted a case-control study comprising healthy volunteers and individuals with benign breast disease (control arm, n = 176) and patients with invasive carcinoma or carcinoma in situ (case arm, n = 177). Genotyping for BER-related genes, including SMUG1, OGG1, ERCC5, and APEX1, was performed. A logistic regression model, incorporating interactions between gene polymorphisms, estrogen-DNA adduct ratio, and clinical variables, was used to identify the risk factors for breast cancer. RESULTS: Univariate analysis indicated marginal associations between breast cancer risk and APEX1 rs1130409 T > G (P = 0.057) and APEX1 rs1760944 T > G (P = 0.065). Multivariate regression analysis revealed significant associations with increased breast cancer risk for APEX1_rs1130409 (GT/GG versus TT) combined with a natural logarithmic value of the estrogen-DNA adduct ratio (estimated OR 1.164, P = 0.023) and premenopausal status with an estrogen-DNA adduct ratio > 2.93 (estimated OR 2.433, P = 0.001). CONCLUSION: APEX1_rs1130409 (GT/GG versus TT) polymorphisms, which are related to decreased BER activity, combined with an increased ratio of estrogen-DNA adducts, increase the risk of breast cancer in East Asian women.

Assessment of heavy metal levels in polyculture fish farms and their aquatic ecosystems: an integrative study addressing environmental and human health risks associated with dam water usage.

This study examines the levels of heavy metals in polyculture fish (Labeo rohita, Cyprinus carpio, and Catla catla), water, and sediment in Tanda Dam, Kohat, Pakistan, aiming to understand environmental and health risks. Samples of fish, water, and sediment were collected from 3 fish farms, and heavy metal concentrations were measured using a Flame Atomic Absorption Spectrophotometer (AAS). Results reveal that C. catla exhibited significantly higher (p < 0.05) levels of Zn than other fish species. Conversely, C. carpio showed significantly higher (p < 0.05) concentrations of Pb, Cd, Cr, Mn, Cu, As, and Ni than other species. The heavy metal hierarchy in C. carpio was found to be Zn > Cu > Pb > Cr > Cd > Mn > As > Ni. While heavy metal levels in L. rohita and C. catla generally fell within reference ranges, exceptions were noted for Zn, Pb, and Cd. Conversely, in C. carpio, all metals exceeded reference ranges except for Cu and Ni. Principal Component Analysis (PCA) indicated a close relationship between water and sediment. Additionally, cluster analysis suggested that C. catla formed a distinct cluster from L. rohita and C. carpio, implying different responses to the environment. Despite concerns raised by the Geoaccumulation Index (Igeo) and Contamination Factor (CF), particularly for Cd, which exhibited a high CF. Furthermore, Hazard Index (HI) values for all three fish species were below 1, suggesting low health risks. However, elevated Igeo and CF values for Cd suggest significant pollution originating from anthropogenic sources. This study underscores the importance of monitoring heavy metals in water for both environmental preservation and human health protection. Future research efforts should prioritize pollution control measures to ensure ecosystem and public health safety.

Management of extensive portal vein thrombosis via thrombolysis and thrombectomy without underlying liver disease: A case report.

Portal vein thrombosis (PVT) is a rare condition, particularly in non-cirrhotic patients. Anticoagulation remains the mainstay of the treatment. Extensive PVT can lead to variceal bleeding, ascites, bowel ischemia, and hypersplenism. The role of thrombolysis and thrombectomy in these patients remains unclear. However, there is evidence that local thrombolysis and thrombectomy should be considered in those who remain symptomatic on anticoagulation and are at risk of complications with acute PVT.

Pt-N catalytic centres concisely enhance interfacial charge transfer in amines functionalized Pt@MOFs for selective conversion of CO2 to CH4.

Improving ligand-to-active metal charge transfer (LAMCT) by finely tuning the organic ligand is a decisive strategy to enhance charge transfer in metal organic frameworks (MOFs)-based catalysts. However, in most MOFs loaded with active metal catalysts, electron transmission encounters massive obstacle at the interface between the two constituents owing to poor LAMCT. Herein, amines (-NH2) functionalized MOFs (NH2-MIL-101(Cr)) encapsulated active metal Pt nanoclusters (NCs) catalysts are synthesized by the polyol reduction method and utilized for the photoreduction of CO2. Surprisingly, the introduction of -NH2 (electron donating) groups within the matrix of MIL-101(Cr) improved the electron migration through the LAMCT process, fostering a synergistic interaction with Pt. The combined experimental analysis exposed the high number of metallic Pt (Pt0) in Pt@NH2-MIL-101(Cr) catalyst through seamless electron shuttling from N of -NH2 group to excited Pt generating versatile hybrid Pt-N catalytic centres. Consequently, these versatile hybrid catalytic centres act as electro-nucleophilic centres, which enable the efficient and selective conversion of CO bond in CO2 to harvest CH4 (131.0 µmol.g-1) and maintain excellent stability and selectivity for consecutive five rounds, superior to Pt@MIL-101(Cr) and most reported catalysts. Our study verified that the precise tuning of organic ligands in MOFs immensely improves the surface-active centres, electron migration, and catalytic selectivity of the excited Pt NCs catalysts encaged inside MOFs through an improved LAMCT pathway.

Sculpting the future: A narrative review of 3D printing in plastic surgery and prosthetic devices.

Background and Aims: The advent of 3D printing has revolutionized plastic surgery and prosthetic devices, providing personalized solutions for patients with traumatic injuries, deformities, and appearance-related conditions. This review offers a comprehensive overview of 3D printing's applications, advantages, limitations, and future prospects in these fields. Methods: A literature search was conducted in PubMed, Google Scholar, and Scopus for studies on 3D printing in plastic surgery. Results: 3D printing has significantly contributed to personalized medical interventions, with benefits like enhanced design flexibility, reduced production time, and improved patient outcomes. Using computer-aided design (CAD) software, precise models tailored to a patient's anatomy can be created, ensuring better fit, functionality, and comfort. 3D printing allows for intricate geometries, leading to improved aesthetic outcomes and patient-specific prosthetic limbs and orthoses. The historical development of 3D printing, key milestones, and breakthroughs are highlighted. Recent progress in bioprinting and tissue engineering shows promising applications in regenerative medicine and transplantation. The integration of AI and automation with 3D printing enhances surgical planning and outcomes. Emerging trends in patient-specific treatment planning and precision medicine are potential game-changers. However, challenges like technical considerations, economic implications, and ethical issues exist. Addressing these challenges and advancing research in materials, design processes, and long-term outcomes are crucial for widespread adoption. Conclusion: The review underscores the increasing adoption of 3D printing in healthcare and its impact on plastic surgery and prosthetic devices. It emphasizes the importance of evaluating the current state and addressing knowledge gaps through future research to foster further advancements.

Enhanced stress resilience in potato by deletion of Parakletos.

Continued climate change impose multiple stressors on crops, including pathogens, salt, and drought, severely impacting agricultural productivity. Innovative solutions are necessary to develop resilient crops. Here, using quantitative potato proteomics, we identify Parakletos, a thylakoid protein that contributes to disease susceptibility. We show that knockout or silencing of Parakletos enhances resistance to oomycete, fungi, bacteria, salt, and drought, whereas its overexpression reduces resistance. In response to biotic stimuli, Parakletos-overexpressing plants exhibit reduced amplitude of reactive oxygen species and Ca2+ signalling, and silencing Parakletos does the opposite. Parakletos homologues have been identified in all major crops. Consecutive years of field trials demonstrate that Parakletos deletion enhances resistance to Phytophthora infestans and increases yield. These findings demark a susceptibility gene, which can be exploited to enhance crop resilience towards abiotic and biotic stresses in a low-input agriculture.

A descriptive analysis of skin-only closure and Bogota bag techniques for achieving complete fascial closure in damage control abdominal surgery.

BACKGROUND: Temporary abdominal closure (TAC) techniques are essential in managing open abdomen cases, particularly in damage control surgery. Skin-only closure (SC) and Bogota bag closure (BBC) are commonly used methods for TAC, but their comparative effectiveness in achieving primary fascial closure (PFC) remains unclear. The objective of this study was to evaluate the rates of PFC between patients undergoing SC and BBC techniques for TAC in peritonitis or abdominal trauma cases at a tertiary care hospital. METHODS: A retrospective cross-sectional study was conducted at the Surgical A Unit of Hayatabad Medical Complex, Peshawar, from January 2022 to July 2023. Approval was obtained from the institutional review board, and patient consent was secured for data use. Patients undergoing temporary abdominal closure using either skin-only or Bogota bag techniques were included. Exclusions comprised patients younger than 15 or older than 75 years, those with multiple abdominal wall incisions, and those with prior abdominal surgeries. Data analysis utilized SPSS version 25. The study aimed to assess outcomes following damage control surgery, focusing on primary fascial closure rates and associated factors. Closure techniques (skin-only and Bogota bag) were chosen based on institutional protocols and clinical context. Indications for damage control surgery (DCS) included traumatic and non-traumatic emergencies. Intra-abdominal pressure (IAP) was measured using standardized methods. Patients were divided into SC and BBC groups for comparison. Criteria for reoperation and primary fascial closure were established, with timing and technique determined based on clinical assessment and multidisciplinary team collaboration. The decision to leave patients open during the index operation followed damage control surgery principles. RESULTS: A total of 193 patients were included in this study, with 59.0% undergoing skin-only closure (SC) and 41.0% receiving Bogota bag closure (BBC). Patients exhibited similar demographic characteristics across cohorts, with a majority being male (73.1%) and experiencing acute abdomen of non-traumatic origin (58.0%). Among the reasons for leaving the abdomen open, severe intra-abdominal sepsis affected 51.3% of patients, while 42.0% experienced hemodynamic instability. Patients who received SC had significantly higher rates of primary fascial closure (PFC) compared to BBC (85.1% vs. 65.8%, p = 0.04), with lower rates of fascial dehiscence (1.7% vs. 7.6%, p = 0.052) and wound infections (p = 0.010). Multivariate regression analysis showed SC was associated with a higher likelihood of achieving PFC compared to BBC (adjusted OR = 1.7, 95% CI: 1.3-3.8, p < 0.05). CONCLUSION: In patients with peritonitis or abdominal trauma, SC demonstrated higher rates of PFC compared to BBC for TAC in our study population. However, further studies are warranted to validate these results and explore the long-term outcomes associated with different TAC techniques.

Assessing soil pollution concerns in proximity to Fence-type solar photovoltaic system installations.

This study conducted in the Kyungpook National University Eco-friendly Agriculture Research Centre between 2022 and 2023 investigates the environmental implications of fence-type solar photovoltaic (PV) systems in diverse agricultural settings. Despite the increasing adoption of solar energy for climate change mitigation, there is a noticeable gap in research regarding the potential environmental impact of these specific PV systems. Focusing on heavy metal concentrations, including Cadmium (Cd), Copper (Cu), Arsenic (As), Mercury (Hg), Lead (Pb), Hexavalent Chromium (Cr+6), Zinc (Zn), and Nickel (Ni), across distinct fields, the study reveals significant fluctuations. Notably, the Rice Field experienced a substantial increase in Cd levels from 0.47 mg/kg in 2022 to 1.55 mg/kg in 2023, while Cu and Pb concentrations decreased to acceptable levels in 2023. The findings underscore the dynamic nature of heavy metal concentrations, emphasizing the importance of continuous soil quality monitoring to prevent contamination. This research provides valuable insights into the impact of fence-type solar PV system installations on agricultural soil quality, emphasizing the urgent need to secure these ecosystems through vigilant monitoring and environmental management practices.

Fuzzy fixed point approach to study the existence of solution for Volterra type integral equations using fuzzy Sehgal contraction.

In this manuscript, we present a novel concept known as the fuzzy Sehgal contraction, specifically designed for self-mappings defined in the context of a fuzzy metric space. Our primary objective is to explore the existence and uniqueness of fixed points for self-mappings in fuzzy metric space. To support our conclusions, we present a detailed illustrative case that demonstrates the superiority of the convergence obtained with our suggested method to those currently recorded in the literature. Moreover, we provide graphical depictions of the convergence behavior, which makes our study more understandable and transparent. Additionally, we extend the application of our results to address the existence and uniqueness of solutions for Volterra integral equations.

Clinical and genetic investigation of 14 families with various forms of short stature syndromes.

Skeletal dysplasias are a heterogeneous group of disorders presenting mild to lethal defects. Several factors, such as genetic, prenatal, and postnatal environmental may contribute to reduced growth. Fourteen families of Pakistani origin, presenting the syndromic form of short stature either in the autosomal recessive or autosomal dominant manner were clinically and genetically investigated to uncover the underlying genetic etiology. Homozygosity mapping, whole exome sequencing, and Sanger sequencing were used to search for the disease-causing gene variants. In total, we have identified 13 sequence variants in 10 different genes. The variants in the HSPG2 and XRCC4 genes were not reported previously in the Pakistani population. This study will expand the mutation spectrum of the identified genes and will help in improved diagnosis of the syndromic form of short stature in the local population.

Next-generation sequencing to genetically diagnose a diverse range of inherited eye disorders in 15 consanguineous families from Pakistan.

Inherited retinal dystrophies (IRDs) are characterized by photoreceptor dysfunction or degeneration. Clinical and phenotypic overlap between IRDs makes the genetic diagnosis very challenging and comprehensive genomic approaches for accurate diagnosis are frequently required. While there are previous studies on IRDs in Pakistan, causative genes and variants are still unknown for a significant portion of patients. Therefore, there is a need to expand the knowledge of the genetic spectrum of IRDs in Pakistan. Here, we recruited 52 affected and 53 normal individuals from 15 consanguineous Pakistani families presenting non-syndromic and syndromic forms of IRDs. We employed single molecule Molecular Inversion Probes (smMIPs) based panel sequencing and whole genome sequencing to identify the probable disease-causing variants in these families. Using this approach, we obtained a 93% genetic solve rate and identified 16 (likely) causative variants in 14 families, of which seven novel variants were identified in ATOH7, COL18A1, MERTK, NDP, PROM1, PRPF8 and USH2A while nine recurrent variants were identified in CNGA3, CNGB1, HGSNAT, NMNAT1, SIX6 and TULP1. The novel MERTK variant and one recurrent TULP1 variant explained the intra-familial locus heterogeneity in one of the screened families while two recurrent CNGA3 variants explained compound heterozygosity in another family. The identification of variants in known disease-associated genes emphasizes the utilization of time and cost-effective screening approaches for rapid diagnosis. The timely genetic diagnosis will not only identify any associated systemic issues in case of syndromic IRDs, but will also aid in the acceleration of personalized medicine for patients affected with IRDs.

Implications of Heavy Metal Accumulation in Fish Feed, Water, Sediment, and Different Fish Species in a Polyculture System.

Heavy metal bioaccumulation in organisms is primarily a result of dietary uptake. The current study examines the concentrations of heavy metals (Pb, Cd, Cr, and Cu) in fish feed, water, sediment, and three fish species (Catla catla, Labeo rohita, and Cyprinus carpio) from different feeding zones in a polyculture pond system. Furthermore, associated human health risks were also evaluated. The fish samples (n = 25 for each species) were collected from 10 different fish ponds in the Kohat district, Pakistan. Heavy metals were determined using an atomic absorption spectrometer. Results revealed higher concentrations of heavy metals in sediment, followed by water. However, the concentration of heavy metals in fish feed was lower than the standard limits. In the case of fish, the bottom feeder (C. carpio) notably exhibited higher (P < 0.05) levels of heavy metals than the column feeder (L. rohita) and surface feeder (C. catla) fish. Moreover, in the liver of all fish species, the bioaccumulation of heavy metals was higher, followed by the gills. Principal component analysis (PCA) demonstrated a strong correlation of heavy metals in C. carpio gills, flesh, feed, and pond water, while the heavy metals in the liver correlated with the detected metals in sediment. The human health risk analysis shows that bottom feeder fish had higher estimated daily intake (EDI), target hazard quotient (THQ), and hazard index (HI) values (> 1). Consequently, the exposed population may experience adverse health effects. The findings of this study suggest that the bottom feeder (C. carpio) bioaccumulates a higher concentration of heavy metals than column (L. rohita) and surface feeder (C. catla) in the polyculture system.

Ischemic stroke as an initial presentation of neurosyphilis in a newly diagnosed HIV patient: A case report and literature review.

With syphilis resurgence, physicians should be more vigilant to infection-induced cerebral vasculitis in high-risk patients presenting with neurological symptoms. In this case, neurosyphilis should not be missed. Thorough serologic screening and lumbar puncture are crucial for diagnosis, and further research is needed for safe and effective treatments in these populations.

Eating Disorders and Disordered Eating Behaviors Among Undergraduate Students in Pakistan as Measured by Eating Disorder Examination Questionnaire (EDE-Q).

Objectives Eating disorders (ED) are an emerging public health issue globally, especially in young adults studying at the undergraduate level. This study aims to assess the frequency of eating disorders, their types, and disordered eating behaviors among such students. Moreover, it aims to identify factors like weight concern, shape concern, eating concern, and restraint, along with assessing the shifting trend of BMI impact on eating disorders using a standardized Eating Disorder Examination Questionnaire (EDE-Q). Methods In this cross-sectional study, 400 undergraduate students (aged 18-25) from four public universities participated from July 2022 to November 2023. Data was collected using the Eating Disorder Examination Questionnaire (EDE-Q). The frequency of eating disorders was computed using SPSS version 27. Results Among the participants, 21.75% (n=84) were identified as having a score surpassing the clinical cut-off. This group comprised 5.5% males (n=22) and 16% females (n=64). The highest prevalence among the four subscales was observed in the Shape Concern subscale (10.5%). Objective binge episodes (19.3%) emerged as the most notable disordered eating attitude. Atypical anorexia nervosa accounted for 13.8% of different eating disorders, while disordered eating was noted in 19.5% (n=78) of individuals. Discussion This study offers critical insights into eating disorders among Pakistan undergraduate students, utilizing the EDE-Q 6.0. Disordered eating behaviors, particularly shape concern and objective binge eating, exhibit significant correlations with these disorders. Weight dissatisfaction emerges as a prominent predictor, suggesting societal influence. The study also reveals a moderate correlation between BMI and eating disorders, challenging conventional assumptions. Furthermore, a changing trend in the prevalence of eating disorders is observed among the male population.

Enhancing the Photocatalytic Degradation of Methylene Blue with Graphene Oxide-Encapsulated g-C3N4/ZnO Ternary Composites.

Methylene blue (MB) is a toxic contaminant present in wastewater. Here, we prepared various composites of graphene oxide (GO) with graphitic carbon nitride (g-C3N4) and zinc oxide (ZnO) for the degradation of MB. In comparison to ZnO (22.9%) and g-C3N4/ZnO (76.0%), the ternary composites of GO/g-C3N4/ZnO showed 90% photocatalytic degradation of MB under a light source after 60 min. The experimental setup and parameters were varied to examine the process and effectiveness of MB degradation. Based on the results of the experiments, a proposed photocatalytic degradation process that explains the roles of GO, ZnO, and g-C3N4 in improving the photocatalytic efficacy of newly prepared GO/g-C3N4/ZnO was explored. Notably, the g-C3N4/ZnO nanocomposite's surface was uniformly covered with ZnO nanorods. The images of the samples clearly demonstrated the porous nature of GO/g-C3N4/ZnO photocatalysts, and even after being mixed with GO, the g-C3N4/ZnO composite retained the layered structure of the original material. The catalyst's porous structure plausibly enhanced the degradation of the contaminants. The high-clarity production of g-C3N4 and the effectiveness of the synthesis protocol were later validated by the absence of any trace contamination in the energy-dispersive X-ray spectroscopy (EDS) results. The composition of the ZnO elements and their spectra were revealed by the EDS results of the prepared ZnO nanorods, g-C3N4/ZnO, and GO/g-C3N4/ZnO. The outcomes indicated that the nanocomposites were highly uncontaminated and contained all necessary elements to facilitate the transformative process. The results of this experiment could be applied at a large scale, thus proving the effectiveness of photocatalysts for the removal of dyes.

Microalgal and activated sludge processing for biodegradation of textile dyes.

The textile industry contributes substantially to water pollution. To investigate bioremediation of dye-containing wastewater, the decolorization and biotransformation of three textile azo dyes, Red HE8B, Reactive Green 27, and Acid Blue 29, were considered using an integrated remediation approach involving the microalga Chlamydomonas mexicana and activated sludge (ACS). At a 5 mg L-1 dye concentration, using C. mexicana and ACS alone, decolorization percentages of 39%-64% and 52%-54%, respectively, were obtained. In comparison, decolorization percentages of 75%-79% were obtained using a consortium of C. mexicana and ACS. The same trend was observed for the decolorization of dyes at higher concentrations, but the potential for decolorization was low. The toxic azo dyes adversely affect the growth of microalgae and at high concentration 50 mg L-1 the growth rate inhibited to 50-60% as compared to the control. The natural textile wastewater was also treated with the same pattern and got promising results of decolorization (90%). Moreover, the removal of BOD (82%), COD (72%), TN (64%), and TP (63%) was observed with the consortium. The HPLC and GC-MS confirm dye biotransformation, revealing the emergence of new peaks and the generation of multiple metabolites with more superficial structures, such as N-hydroxy-aniline, naphthalene-1-ol, and sodium hydroxy naphthalene. This analysis demonstrates the potential of the C. mexicana and ACS consortium for efficient, eco-friendly bioremediation of textile azo dyes.

Investigating the role of functional mutations in leucine binding to Sestrin2 in aging and age-associated degenerative pathologies using structural and molecular simulation approaches.

Leucine is the native known ligand of Sestrin2 (Sesn2) and its interaction with Sesn2 is particularly important, as it influences the activity of mTOR in aging and its associated pathologies. It is important to find out how leucine interacts with Sesn2 and how mutations in the binding pocket of leucine affect the binding of leucine. Therefore, this study was committed to investigating the impact of non-synonymous mutations by incorporating a broad spectrum of simulation techniques, from molecular dynamics to free energy calculations. Our study was designed to model the atomic-scale interactions between leucine and mutant forms of Sesn2. Our results demonstrated that the interaction paradigm for the mutants has been altered thus showing a significant decline in the hydrogen bonding network. Moreover, these mutations compromised the dynamic stability by altering the conformational flexibility, sampling time, and leucine-induced structural constraints that consequently caused variation in the binding and structural stability. Molecular dynamics-based flexibility analysis revealed that the regions 217-339 and 371-380 demonstrated a higher fluctuation. Noteworthy, these regions correspond to a linker (217-339) and a loop (371-380) that cover the leucine binding cavity that is critical for the 'latch' mechanism in the N-terminal, which is essential for leucine binding. Further validation of reduced binding and modified internal motions caused by the mutants was obtained through binding free energy calculations, principal components analysis (PCA), and free energy landscape (FEL) analysis. By unraveling the molecular intricacies of Sesn2-leucine interactions and their mutations, we hope to pave the way for innovative strategies to combat the inevitable tide of aging and its associated diseases.Communicated by Ramaswamy H. Sarma.