Protein coupled thionine acetate probed silica nanoparticles: An integrated laser-assisted therapeutic approach for treating cancer.

Herein, we report a multifaceted nanoformulation, developed by binding thionine acetate (TA) in silica matrix to form TA loaded silica nanoparticles (STA Nps), which were characterized using various physicochemical techniques. STA NPs were spherical shaped having size 40-50 nm and exhibited good heating efficiency, improved photostability and singlet oxygen production rate than TA alone. In PDT experiment, the rate of degradation for ABDMA was enhanced from 0.1367 min-1 for TA alone to 0.1774 min-1 for STA Nps, depicting an increase in the reactive oxygen species (ROS) generation ability of STA Nps. Further, the cytotoxicity of STA Nps was investigated by carrying out the biophysical studies with Calf thymus DNA (Ct-DNA) and Human Serum Albumin (HSA). The results indicated that the binding of STA Nps to Ct-DNA causes alterations in the double helix structure of DNA and as a result, STA Nps can impart chemotherapeutic effects via targeting DNA. STA Nps showed good binding affinity with HSA without compromising the structure of HSA, which is important for STA Nps sustainable biodistribution and pharmacokinetics. Based on this study, it is suggested that because of the synergistic effect of chemo and phototherapy, STA Nps can be extensively utilized as potential candidates for treating cancer.

A Tumor-Specific Molecular Network Promotes Tumor Growth in Drosophila by Enforcing a Jun N-Terminal Kinase-Yorkie Feedforward Loop.

Cancer cells expand rapidly in response to altered intercellular and signaling interactions to achieve the hallmarks of cancer. Impaired cell polarity combined with activated oncogenes is known to promote several hallmarks of cancer, e.g., activating invasion by increased activity of Jun N-terminal kinase (JNK) and sustained proliferative signaling by increased activity of Hippo effector Yorkie (Yki). Thus, JNK, Yki, and their downstream transcription factors have emerged as synergistic drivers of tumor growth through pro-tumor signaling and intercellular interactions like cell competition. However, little is known about the signals that converge onto JNK and Yki in tumor cells and enable tumor cells to achieve the hallmarks of cancer. Here, using mosaic models of cooperative oncogenesis (RasV12,scrib-) in Drosophila, we show that RasV12,scrib- tumor cells grow through the activation of a previously unidentified network comprising Wingless (Wg), Dronc, JNK, and Yki. We show that RasV12,scrib- cells show increased Wg, Dronc, JNK, and Yki signaling, and all these signals are required for the growth of RasV12,scrib- tumors. We report that Wg and Dronc converge onto a JNK-Yki self-reinforcing positive feedback signal-amplification loop that promotes tumor growth. We found that the Wg-Dronc-Yki-JNK molecular network is specifically activated in polarity-impaired tumor cells and not in normal cells, in which apical-basal polarity remains intact. Our findings suggest that the identification of molecular networks may provide significant insights into the key biologically meaningful changes in signaling pathways and paradoxical signals that promote tumorigenesis.

Seaweed-derived fucoidans and rhamnan sulfates serve as potent anti-SARS-CoV-2 agents with potential for prophylaxis.

Seaweeds represent a rich source of sulfated polysaccharides with similarity to heparan sulfate, a facilitator of myriad virus host cell attachment. For this reason, attention has been drawn to their antiviral activity, including the potential for anti-SARS-CoV-2 activity. We have identified and structurally characterized several fucoidan extracts, including those from different species of brown macroalga, and a rhamnan sulfate from a green macroalga species. A high molecular weight fucoidan extracted from Saccharina japonica (FSjRPI-27), and a rhamnan sulfate extracted from Monostroma nitidum (RSMn), showed potent competitive inhibition of spike glycoprotein receptor binding to a heparin-coated SPR chip. This inhibition was also observed in cell-based assays using hACE2 HEK-293 T cells infected by pseudotyped SARS-CoV-2 virus with IC50 values <1 µg/mL. Effectiveness was demonstrated in vivo using hACE2-transgenic mice. Intranasal administration of FSjRPI-27 showed protection when dosed 6 h prior to and at infection, and then every 2 days post-infection, with 100 % survival and no toxicity at 104 plaque-forming units per mouse vs. buffer control. At 5-fold higher virus dose, FSjRPI-27 reduced mortality and yielded reduced viral titers in bronchioalveolar fluid and lung homogenates vs. buffer control. These findings suggest the potential application of seaweed-based sulfated polysaccharides as promising anti-SARS-CoV-2 prophylactics.

Transcriptome-wide association mapping provides insights into the genetic basis and candidate genes governing flowering, maturity and seed weight in rice bean (Vigna umbellata).

BACKGROUND: Rice bean (Vigna umbellata), an underrated legume, adapts to diverse climatic conditions with the potential to support food and nutritional security worldwide. It is used as a vegetable, minor food crop and a fodder crop, being a rich source of proteins, minerals, and essential fatty acids. However, little effort has been made to decipher the genetic and molecular basis of various useful traits in this crop. Therefore, we considered three economically important traits i.e., flowering, maturity and seed weight of rice bean and identified the associated candidate genes employing an associative transcriptomics approach on 100 diverse genotypes out of 1800 evaluated rice bean accessions from the Indian National Genebank. RESULTS: The transcriptomics-based genotyping of one-hundred diverse rice bean cultivars followed by pre-processing of genotypic data resulted in 49,271 filtered markers. The STRUCTURE, PCA and Neighbor-Joining clustering of 100 genotypes revealed three putative sub-populations. The marker-trait association analysis involving various genome-wide association study (GWAS) models revealed significant association of 82 markers on 48 transcripts for flowering, 26 markers on 22 transcripts for maturity and 22 markers on 21 transcripts for seed weight. The transcript annotation provided information on the putative candidate genes for the considered traits. The candidate genes identified for flowering include HSC80, P-II PsbX, phospholipid-transporting-ATPase-9, pectin-acetylesterase-8 and E3-ubiquitin-protein-ligase-RHG1A. Further, the WRKY1 and DEAD-box-RH27 were found to be associated with seed weight. Furthermore, the associations of PIF3 and pentatricopeptide-repeat-containing-gene with maturity and seed weight, and aldo-keto-reductase with flowering and maturity were revealed. CONCLUSION: This study offers insights into the genetic basis of key agronomic traits in rice bean, including flowering, maturity, and seed weight. The identified markers and associated candidate genes provide valuable resources for future exploration and targeted breeding, aiming to enhance the agronomic performance of rice bean cultivars. Notably, this research represents the first transcriptome-wide association study in pulse crop, uncovering the candidate genes for agronomically useful traits.

Genome-wide discovery of InDels and validation of PCR-Based InDel markers for earliness in a RIL population and genotypes of lentil (Lens culinaris Medik.).

The systematic identification of insertion/deletion (InDel) length polymorphisms from the entire lentil genome can be used to map the quantitative trait loci (QTL) and also for the marker-assisted selection (MAS) for various linked traits. The InDels were identified by comparing the whole-genome resequencing (WGRS) data of two extreme bulks (early- and late-flowering bulk) and a parental genotype (Globe Mutant) of lentil. The bulks were made by pooling 20 extreme recombinant inbred lines (RILs) each, derived by crossing Globe Mutant (late flowering parent) with L4775 (early flowering parent). Finally, 734,716 novel InDels were identified, which is nearly one InDel per 5,096 bp of lentil genome. Furthermore, 74.94% of InDels were within the intergenic region and 99.45% displayed modifier effects. Of these, 15,732 had insertions or deletions of 20 bp or more, making them amenable to the development of PCR-based markers. An InDel marker I-SP-356.6 (chr. 3; position 356,687,623; positioned 174.5 Kb from the LcFRI gene) was identified as having a phenotypic variance explained (PVE) value of 47.7% for earliness when validated in a RIL population. Thus, I-SP-356.6 marker can be deployed in MAS to facilitate the transfer of the earliness trait to other elite late-maturing cultivars. Two InDel markers viz., I-SP-356.6 and I-SP-383.9 (chr. 3; linked to LcELF3a gene) when tested in 9 lentil genotypes differing for maturity duration, clearly distinguished three early (L4775, ILL7663, Precoz) and four late genotypes (Globe Mutant, MFX, L4602, L830). However, these InDels could not be validated in two genotypes (L4717, L4727), suggesting either absence of polymorphism and/or presence of other loci causing earliness. The identified InDel markers can act as valuable tools for MAS for the development of early maturing lentil varieties.

Understanding genetic risks: Computational exploration of human ß-Synuclein nsSNPs and their potential impact on structural alteration.

Synucleins are pivotal in neurodegenerative conditions. Beta-synuclein (ß-synuclein) is part of the synuclein protein family alongside alpha-synuclein (α-synuclein) and gamma-synuclein (γ-synuclein). These proteins, found mainly in brain tissue and cancers, are soluble and unstructured. ß-synuclein shares significant similarity with α-synuclein, especially in their N-terminus, with a 90% match. However, their aggregation tendencies differ significantly. While α-synuclein aggregation is believed to be counteracted by ß-synuclein, which occurs in conditions like Parkinson's disease, ß-synuclein may counteract α-synuclein's toxic effects on the nervous system, offering potential treatment for neurodegenerative diseases. Under normal circumstances, ß-synuclein may guard against disease by interacting with α-synuclein. Yet, in pathological environments with heightened levels or toxic substances, it might contribute to disease. Our research aims to explore potential harmful mutations in the ß-synuclein using computational tools to predict their destabilizing impact on protein structure. Consensus analysis revealed rs1207608813 (A63P), rs1340051870 (S72F), and rs1581178262 (G36C) as deleterious. These findings highlight the intricate relationship between nsSNPs and protein function, shedding light on their potential implications in disease pathways. Understanding the structural consequences of nsSNPs is crucial for elucidating their role in pathogenesis and developing targeted therapeutic interventions. Our results offer a robust computational framework for identifying neurodegenerative disorder-related mutations from SNP datasets, potentially reducing the costs associated with experimental characterization.

Microbiota-brain axis: Exploring the role of gut microbiota in psychiatric disorders - A comprehensive review.

Mental illness is a hidden epidemic in modern science that has gradually spread worldwide. According to estimates from the World Health Organization (WHO), approximately 10% of the world's population suffers from various mental diseases each year. Worldwide, financial and health burdens on society are increasing annually. Therefore, understanding the different factors that can influence mental illness is required to formulate novel and effective treatments and interventions to combat mental illness. Gut microbiota, consisting of diverse microbial communities residing in the gastrointestinal tract, exert profound effects on the central nervous system through the gut-brain axis. The gut-brain axis serves as a conduit for bidirectional communication between the two systems, enabling the gut microbiota to affect emotional and cognitive functions. Dysbiosis, or an imbalance in the gut microbiota, is associated with an increased susceptibility to mental health disorders and psychiatric illnesses. Gut microbiota is one of the most diverse and abundant groups of microbes that have been found to interact with the central nervous system and play important physiological functions in the human gut, thus greatly affecting the development of mental illnesses. The interaction between gut microbiota and mental health-related illnesses is a multifaceted and promising field of study. This review explores the mechanisms by which gut microbiota influences mental health, encompassing the modulation of neurotransmitter production, neuroinflammation, and integrity of the gut barrier. In addition, it emphasizes a thorough understanding of how the gut microbiome affects various psychiatric conditions.

Novel Compound Heterozygous Mutations of LIG4 Gene in an Indian LIG4 Syndrome Patient with Severe Microcephaly: Case Report, In-silico Analysis and Systematic Review.

BACKGROUND: LIG4 syndrome, characterized by immunodeficiency, sensitivity to ionizing radiations, intrauterine growth retardation, postnatal growth retardation, and microcephaly, is a rare genetic disorder caused by pathogenic variants of the LIG4 gene. Few patients are presented with no immune dysregulation as well. CASE STUDY: We present here a male child of 2 years and 4 months of age with severe microcephaly and short stature. His birth weight was 1.9 Kg, and his current height, weight, and head circumference are 83.2 cm (z score = -2.37), 9.5 Kg (z score = -2.76), and 36 cm (z score = -9.24), respectively. Possible causative pathogenic compound heterozygous variants of the LIG4 gene, which were inherited from the parents, were identified by whole exome sequencing of the DNA of the patient and his parents. A systematic review of the literature is also performed to summarize the patients of LIG4 syndrome reported worldwide and summarize the associated genetic mutations of the LIG4 gene. Compound heterozygous variants (c.597_600delTCAG/ c.342del) of LIG4 gene were identified. The parents were found to be heterozygous carriers of one variant each. CONCLUSION: The in-silico analysis of identified variants explains their effect on the structure and function of the LIG4 protein hence explaining the genotype-phenotype correlation.

Therapeutic Potential of Morin Hydrate Against Rifampicin Induced Hepato and Renotoxicity in Albino Wistar Rats: Modulation of Organ Function, Oxidative Stress and Inflammatory Response.

Tuberculosis (TB) is a challenging public health issue, particularly in poor and developing countries. Rifampicin (RIF) is one of the most common first-line anti-TB drugs but it is known for its adverse effects on the hepato-renal system. The present study investigated the efficacy of morin hydrate (MH) in protecting hepato-renal damage inflicted by RIF in rats. RIF (50 mg/kg), and a combination of RIF (50 mg/kg) and MH (50 mg/kg) were administered orally for 4 weeks in rats. Silymarin (50 mg/kg) was used as a positive control. Increased levels of serological parameters such as AST, ALT, ALP, LDH, GGT, bilirubin, triglyceride, total cholesterol, urea, uric acid, creatinine, TNF-α, IFN-γ, IL-6 along with the decreased level of IL-10, total protein and albumin were used as markers of hepatic and renal injury. Oxidative damage in the tissues was measured by the increase in lipid peroxidation and decline in GSH, SOD and catalase activities. Histopathology of liver slices was used to study hepatic architecture. Four-week RIF treatment produced altered serological parameters with an increase in pro-inflammatory cytokines in serum suggesting hepatotoxicity and nephrotoxicity. The antioxidant status of the liver and kidney (increased lipid peroxidation and decline in GSH, SOD and catalase) was compromised. Cellular damage and necrosis were observed in liver slices. MH supplementation with RIF improved hepato-renal functions by restoring the serum and tissue markers towards normal values. Histological observations authenticated the results. MH supplementation also reduced the production of pro-inflammatory cytokines. Thus, the results revealed that MH provides protection against RIF-induced hepato-renal injury.

Genetic mechanism regulating diversity in the placement of eyes on the head of animals.

Despite the conservation of genetic machinery involved in eye development, there is a strong diversity in the placement of eyes on the head of animals. Morphogen gradients of signaling molecules are vital to patterning cues. During Drosophila eye development, Wingless (Wg), a ligand of Wnt/Wg signaling, is expressed anterolaterally to form a morphogen gradient to determine the eye- versus head-specific cell fate. The underlying mechanisms that regulate this process are yet to be fully understood. We characterized defective proventriculus (dve) (Drosophila ortholog of human SATB1), a K50 homeodomain transcription factor, as a dorsal eye gene, which regulates Wg signaling to determine eye versus head fate. Across Drosophila species, Dve is expressed in the dorsal head vertex region where it regulates wg transcription. Second, Dve suppresses eye fate by down-regulating retinal determination genes. Third, the dve-expressing dorsal head vertex region is important for Wg-mediated inhibition of retinal cell fate, as eliminating the Dve-expressing cells or preventing Wg transport from these dve-expressing cells leads to a dramatic expansion of the eye field. Together, these findings suggest that Dve regulates Wg expression in the dorsal head vertex, which is critical for determining eye versus head fate. Gain-of-function of SATB1 exhibits an eye fate suppression phenotype similar to Dve. Our data demonstrate a conserved role for Dve/SATB1 in the positioning of eyes on the head and the interocular distance by regulating Wg. This study provides evidence that dysregulation of the Wg morphogen gradient results in developmental defects such as hypertelorism in humans where disproportionate interocular distance and facial anomalies are reported.

Genome-Wide Comparative Analysis of Five Amaranthaceae Species Reveals a Large Amount of Repeat Content.

Amaranthus is a genus of C4 dicotyledonous herbaceous plant species that are widely distributed in Asia, Africa, Australia, and Europe and are used as grain, vegetables, forages, and ornamental plants. Amaranth species have gained significant attention nowadays as potential sources of nutritious food and industrial products. In this study, we performed a comparative genome analysis of five amaranth species, namely, Amaranthus hypochondriacus, Amaranthus tuberculatus, Amaranthus hybridus, Amaranthus palmeri, and Amaranthus cruentus. The estimated repeat content ranged from 54.49% to 63.26% and was not correlated with the genome sizes. Out of the predicted repeat classes, the majority of repetitive sequences were Long Terminal Repeat (LTR) elements, which account for about 13.91% to 24.89% of all amaranth genomes. Phylogenetic analysis based on 406 single-copy orthologous genes revealed that A. hypochondriacus is most closely linked to A. hybridus and distantly related to A. cruentus. However, dioecious amaranth species, such as A. tuberculatus and A. palmeri, which belong to the subgenera Amaranthus Acnida, have formed their distinct clade. The comparative analysis of genomic data of amaranth species will be useful to identify and characterize agronomically important genes and their mechanisms of action. This will facilitate genomics-based, evolutionary studies, and breeding strategies to design faster, more precise, and predictable crop improvement programs.

In silico and network pharmacology analysis of fucosterol: a potent anticancer bioactive compound against HCC.

The Fucaceae family of marine brown algae includes Ascophyllum nodosum. Fucosterol (FSL) is a unique bioactive component that was identified through GC-MS analysis of the hydroalcoholic extract of A. nodosum. Fucosterol's mechanism of action towards hepatocellular cancer was clarified using network pharmacology and docking study techniques. The probable target gene of FSL has been predicted using the TargetNet and SwissTargetPred databases. GeneCards and the DisGNet database were used to check the targeted genes of FSL. By using the web programme Venny 2.1, the overlaps of FSL and HCC disease demonstrated that 18 genes (1.3%) were obtained as targeted genes Via the STRING database, a protein-protein interaction (PPI) network with 18 common target genes was constructed. With the aid of CytoNCA, hub genes were screened using the Cytoscape software, and the targets' hub genes were exported into the ShinyGo online tool for study of KEGG and gene ontology enrichment. Using the software AutoDock, a hub gene molecular docking study was performed. Ten genes, including AR, CYP19A1, ESR1, ESR2, TNF, PPARA, PPARG, HMGCR, SRC, and IGF1R, were obtained. The 10 targeted hubs docked with FSL successfully. The active components FSL of ASD, the FSL, are engaged in fatty liver disease, cancer pathways, and other signalling pathways, which could prove beneficial for the management of HCC.

Cyclic AMP binding to a universal stress protein in Mycobacterium tuberculosis is essential for viability.

Mycobacterial genomes encode multiple adenylyl cyclases and cAMP effector proteins, underscoring the diverse ways these bacteria utilize cAMP. We identified universal stress proteins, Rv1636 and MSMEG_3811 in Mycobacterium tuberculosis and Mycobacterium smegmatis, respectively, as abundantly expressed, novel cAMP-binding proteins. Rv1636 is secreted via the SecA2 secretion system in M. tuberculosis but is not directly responsible for the efflux of cAMP from the cell. In slow-growing mycobacteria, intrabacterial concentrations of Rv1636 were equivalent to the concentrations of cAMP present in the cell. In contrast, levels of intrabacterial MSMEG_3811 in M. smegmatis were lower than that of cAMP and therefore, overexpression of Rv1636 increased levels of "bound" cAMP. While msmeg_3811 could be readily deleted from the genome of M. smegmatis, we found that the rv1636 gene is essential for the viability of M. tuberculosis and is dependent on the cAMP-binding ability of Rv1636. Therefore, Rv1636 may function to regulate cAMP signaling by direct sequestration of the second messenger. This is the first evidence of a "sponge" for any second messenger in bacterial signaling that would allow mycobacterial cells to regulate the available intrabacterial "free" pool of cAMP.

Clinical and CBCT Assessment of Role of Bisphosphonate on Osteotomy Site and Implant Surface.

Objectives: To assess the role of bisphosphonate on osteotomy site and implant surface. Materials and Methods: Twenty patients with adequate width and height of edentulous space and a single missing posterior tooth between the ages of 25 and 55 were incorporated in this research. Ten participants received implant therapy alone; the other ten patients received implant therapy and bisphosphonate application to osteotomy site and the implant surface. Result: Changes in the crestal bone level were seen in both the study and control groups. At 1 year, crestal bone loss was less in the bisphosphonate-treated group than in the control group. Conclusion: The quantity of crestal bone loss was reduced when bisphosphonate (sodium alendronate) was applied locally near the implant and osteotomy site.

Protocol for preparing formalin-fixed paraffin-embedded musculoskeletal tissue samples from mice for spatial transcriptomics.

Here, we present a protocol for using spatial transcriptomics in bone and multi-tissue musculoskeletal formalin-fixed paraffin-embedded (FFPE) samples from mice. We describe steps for tissue harvesting, sample preparation, paraffin embedding, and FFPE sample selection. We detail procedures for sectioning and placement on spatial slides prior to imaging, decrosslinking, library preparation, and final analyses of the sequencing data. The complete protocol takes ca. 18 days for mouse femora with adjacent muscle; of this time, >50% is required for mineralized tissue decalcification. For complete details on the use and execution of this protocol, please refer to Wehrle et al.1 and Mathavan et al.2.

Insights into the genomic features and lifestyle of B1 subcluster mycobacteriophages.

Bacteriophages infecting Mycobacterium smegmatis mc2155 are numerous and, hence, are classified into clusters based on nucleotide sequence similarity. Analyzing phages belonging to clusters/subclusters can help gain deeper insights into their biological features and potential therapeutic applications. In this study, for genomic characterization of B1 subcluster mycobacteriophages, a framework of online tools was developed, which enabled functional annotation of about 55% of the previously deemed hypothetical proteins in B1 phages. We also studied the phenotype, lysogeny status, and antimycobacterial activity of 10 B1 phages against biofilm and an antibiotic-resistant M. smegmatis strain (4XR1). All 10 phages belonged to the Siphoviridae family, appeared temperate based on their spontaneous release from the putative lysogens and showed antibiofilm activity. The highest inhibitory and disruptive effects on biofilm were 64% and 46%, respectively. This systematic characterization using a combination of genomic and experimental tools is a promising approach to furthering our understanding of viral dark matter.

Impact of surgical timing and type of operative procedure on outcomes in periprosthetic hip fractures: an observational study at an NHS trust centre in the UK.

PURPOSE: There is a global trend of increased periprosthetic fractures due to the growing number of arthroplasty procedures. The present study assessed the impact of factors such as time to surgery and type of surgery on the outcomes, which have been seldom evaluated for periprosthetic fractures. METHODS: An observational study was conducted on consecutive 87 patients within an NHS district hospital trust in the UK. Patients who underwent a complete hip replacement prior to the fracture, received fixation therapy, or underwent revision surgery within the specified time were screened. Patients were grouped in two ways: based on time to surgery and based on surgery type. Logistic regression models were performed to assess for statistically significant differences in post-operative complication, 30-day, and 1-year mortality rates between groups, whilst adjusting for age, gender, and ASA grade. RESULTS: Forty-one patients underwent open reduction and internal fixation (ORIF), 29 patients underwent revision arthroplasty, and 17 patients were subjected to both, ORIF and revision arthroplasty. Sixty of the 87 patients were operated on > 48 h of injury. The median hospital stay was significantly lower in the ORIF plus revision arthroplasty group, versus other surgical groups (p < 0.05) whilst it was significantly higher in the group of patients who underwent surgery after 48 h of injury (p < 0.05). Numerically higher mortality was noted in the revision arthroplasty group (31.03%, p > 0.05). The group that was operated after 48 h of injury showed greater mortality but was comparable to the other group (25% vs. 14.81%, p > 0.05). For post-operative complications, none of the variables were significantly predictive (p > 0.05). However, for 30-day mortality, ASA grade (p = 0.04) and intra-operative complications (p = 0.0001) were significantly predictive. Additionally, for 1-year mortality, ASA grade (p = 0.004) was noted to be significantly predictive. CONCLUSION: Revision and delayed periprosthetic fracture management (> 48 h after injury) group showed a numerically greater mortality risk; however, this finding was not statistically significant. ASA grading at baseline is predictive of mortality for periprosthetic fractures.

Evaluation of hydrogeochemical processes and saltwater intrusion in the coastal aquifers in the southern part of Puri District, Odisha, India.

Groundwater is widely regarded as being among the freshwater natural resources with the lowest levels of contamination. Nevertheless, the saltwater intrusion has resulted in the contamination of groundwater in coastal regions with lower elevation. The rationale of the present work is to investigate the chemistry of groundwater, to identify the various facies of groundwater, to identify the processes that influence groundwater chemistry and saltwater intrusion, and to evaluate the groundwater's aptness for use in drinking and farming. In order to gain an understanding of the groundwater quality as well as the salinization process that occurs in coastal aquifers as a result of hydrogeochemical processes, a total of 108 groundwater samples (54 each in pre- and post-monsoon) were taken and analyzed for several physiochemical parameters in the southern part of the Puri district in the Indian state of Odisha. The data has undergone analysis and examination to identify the factors (such as hydrological facies, potential solute source in water, and salinization process) that contribute to groundwater salinity. The result showed the chemistry controlling processes of rock-water interaction as per Gibbs diagram. The majority of shallow aquifers exhibit the Na-Cl type of facies as per the Piper plot. A total of 37% pre-monsoon and 33% post-monsoon samples having Na+/Cl- ratio below the threshold of 0.86 indicating the influence of saltwater intrusion. In both seasons, it was observed that 74% of the samples exhibited a Na+ concentration that exceeded the permissible limit set by the World Health Organization (WHO) for drinking purposes. The findings indicate that most groundwater failed to pass safe drinking water and irrigation standards due to saltwater intrusion. Consequently, the monitoring of coastal aquifer quality has become imperative in order to ensure the sustainability of aquifers and the development of groundwater resources. This is because coastal aquifers are highly vulnerable to saltwater intrusion, primarily as a result of the extensive extraction of groundwater for diverse purposes.

Novel approach of plate assisted buttressing in Hoffa fracture.

PURPOSE: Hoffa fracture is a femoral condyle fracture in the coronal plane. The lateral condyle is more commonly involved. The diagnosis is often difficult to detect with routine radiographs. Conservative management in this type of fracture resulted in nonunion, malunion, and other complications, such as stiff knee. Therefore, surgical management is mandatory in displaced fractures. Previous studies suggest only application of cancellous screw fixation, but these are not enough to counter vertical shear stress. Therefore, this study will evaluate the clinical outcomes of open reduction and internal fixation of Letenneur type I Hoffa fracture using cancellous screws with posterior buttressing plate. METHOD: This was a prospective cohort study conducted from March 2017 to July 2022 in orthopaedics department of tertiary care center after approval of institutional ethical committee. The study included 36 patients with Letenneur type I fractures treated by open reduction and internal fixation using posterior buttress plate and cancellous screws. Radiographs and clinical outcomes, range of movement (ROM), bone union, and knee society score (KSS) of patients were assessed at the end of 4 and 12 months in the follow-ups. All statistical analysis was done using Epi info version 7.2.1.0. RESULTS: In the 36 patients with Letenneur type I fracture, the majority belong to younger age group between 25 and 54 years with 22 males and 14 females. The modes of injury were road traffic accidents in 25 patients and fall from height in 11 patients. The right knee was involved in 21 cases and left was involved in 15 cases. Lateral condyle involvement was seen in 27 cases and medial condyle in 9 cases. All 36 patients with Letenneur type I Hoffa fracture were evaluated 4 months after surgical intervention. The notable improvements were observed in terms of ROM 120.4° ± 5.0° and KSS 85.0 ± 4.2. At the 12-month follow-up, considerably better outcomes were maintained regarding ROM 128.1° ± 5.2° and KSS 89.3 ± 4.8 with p < 0.05 which was statistically significant. At the final follow-up, all patients had routine fracture healing with a union time of (3.2 ± 3.4) months. CONCLUSIONS: Fixation of Letenneur type I Hoffa fracture with cancellous screws and posterior buttress plate is effective, reliable and capable of providing adequate stability. Buttress plate assisted fixation is a valuable enhancement of the conventional technique of lag screw fixation of Hoffa fractures.

In silico strategies for identifying therapeutic candidates against Acinetobacter baumannii: spotlight on the UDP-N-acetylmuramoyl-L-alanine-D-glutamate:meso-diaminopimelate ligase (MurE).

The opportunistic bacterium Acinetobacter baumannii, which belongs to ESKAPE group of pathogenic bacteria, is leading cause of infections associated with gram-negative bacteria. Acinetobacter baumannii causes severe diseases, such as VAP (ventilator-associated pneumonia), meningitis, and UTI (urinary tract infections) among the nosocomial infections contracted in hospitals. The high infection rate and growing resistance to the vast array of antibiotics makes it paramount to look for new therapeutic strategies against this pathogen. The most promising therapeutic targets are the proteins involved in the synthesis of peptidoglycan which is chief component of bacterial cell wall, MurE is one of those enzymes and is responsible for the addition of one unit of meso-diaminopimelic acid (meso-A2pm) to the nucleotide precursor, UDPMurNAc-L-Ala-D-Glu, and aids in the formation of crosslinker pentapeptide chain. The three-dimensional structure of MurE was modelled using homology modelling technique and then vHTS was performed using this model against Approved Drug Library on DrugRep server using AutoDock Vina. Out of 500 drug molecules, two were selected based on estimated binding affinity, interaction pattern, interacting residues, etc. The selected drug molecules are DB12887 (Tazemetostat) and DB13879 (Glecaprevir). Then, MD simulations were performed on native MurE and its complexes with ligands to examine their dynamical behaviour, stability, integrity, compactness, and folding properties. The protein-ligand complexes were then subjected to binding free energy calculations using the MM/PBSA-based binding free energy analysis and the values are -109.788 ± 8.03 and -152.753 ± 11.98 kcal for MurE-DB12887 and MurE-DB13879 complex, respectively. All the analysis performed on MD trajectories for the complexes of these ligands with protein provided plenty of dependable evidences to consider these molecules for inhibition of MurE enzyme from A. baumannii. Communicated by Ramaswamy H. Sarma.