Identification of potential JNK3 inhibitors through virtual screening, molecular docking and molecular dynamics simulation as therapeutics for Alzheimer's disease.

Alzheimer's disease (AD) is a complex neurological disorder and no effective drug is available for its treatment. Numerous pathological conditions are believed to be responsible for the initiation and development of AD including c-Jun N-terminal kinases (JNKs). The JNKs are one of the enzymes from the mitogen-activated protein kinase (MAPK) family that controls the phosphorylation of various transcription factors on serine and threonine residues, and hold significant responsibilities in tasks like gene expression, cell proliferation, differentiation, and apoptosis. Since, JNK3 is primarily expressed in the brain hence its increased levels in the brain are associated with the AD pathology promoting neurofibrillary tangles, senile plaques, neuroinflammation, and nerve cell apoptosis. The current research work is focused on the development of novel JNK inhibitors as therapeutics for AD employing a structure-based virtual screening (SBVS) approach. The ZINC database (14634052 compounds) was investigated after employing pan assay interference (PAINs), drug-likeness, and diversity picking filter to distinguish molecules interacting with JNK3 by following three docking precision criteria: High Throughput Virtual Screening (HTVS), Standard Precision (SP), and Extra Precision (XP) & MMGBSA. Five lead molecules showed a better docking score in the range of -13.091 to -14.051 kcal/mol better than the reference compound (- 11.828 kcal/mol). The lead compounds displayed acceptable pharmacokinetic properties and were subjected to molecular dynamic simulations of 100 ns and binding free energy calculations. All the lead molecules showed stable RMSD and hydrogen bond interactions throughout the trajectory. The ∆GMM/PBSA_total score for the lead compounds ZINC220382956, ZINC147071339, ZINC207081127, ZINC205151456, ZINC1228819126, and CC-930 was calculated and found to be - 31.39, - 42.8, - 37.04, - 39.01, - 36.5, - 34.16 kcal/mol, respectively. Thus, it was concluded that the lead molecules identified in these studies have the potential to be explored as potent JNK3 inhibitors.

Design, synthesis, in silico and biological evaluation of new indole based oxadiazole derivatives targeting estrogen receptor alpha.

A series of new indole-oxadiazole derivatives was designed and synthesized to develop potential anti-breast cancer agents. The compounds exhibited significant inhibitory activity with IC50 values ranging from 1.78 to 19.74 µM against ER-positive human breast cancer (BC) cell lines T-47D and MCF-7. Among them, compounds (5a, 5c, 5e-5h, 5j-5o) displayed superior activity against ER-α dominant (ratio of ER-α/ER-ß is 9/1) T-47D cells compared to the standard drug bazedoxifene (IC50 = 12.78 ± 0.92 µM). Compounds 5c and 5o exhibited remarkable anti-proliferative activity with IC50 values of 3.24 ± 0.46 and 1.72 ± 1.67 µM against T-47D cells, respectively. Further, compound 5o manifested 1589-fold higher ER-α binding affinity (213.4 pM) relative to bazedoxifene (339.2 nM) in a competitive ER-α binding assay, while compound 5c showed a binding affinity of 446.6 nM. The Western blot analysis proved that both compounds influenced the ER-α protein's expression, impeding its subsequent transactivation and signalling pathway within T-47D cells. Additionally, a molecular docking study suggests that compounds 5c and 5o bind in such a fashion that induces conformational changes in the protein, culminating in their antagonistic effect. Also, pharmacokinetic profiles showed that all compounds have drug-like properties. Further, molecular dynamic (MD) simulations and density functional theory (DFT) analysis confirmed the stability, conformational behaviour, reactivity, and biological feasibility of compounds 5c and 5o. In conclusion, based on our findings, compounds 5c and 5o, which exhibit significant ER-α antagonistic activity, can act as potential lead compounds for developing anti-breast cancer agents.

Quality of life and symptom burden in hematological cancer patients receiving hematopoietic stem cell transplantation: an observational study at Regional Cancer Centre, India.

PURPOSE: Hematopoietic stem cell transplant (HSCT) is an intense form of treatment, resulting in major symptom burden but can prove curative. The quality of life (QOL) is a major endpoint for these patients as the survival rate in them has improved over time. The aim of the study is to assess the QOL and symptom burden of hematological malignancy patients at admission to hospital for HSCT, at 1 month and at 3 months following HSCT. METHODS: This prospective observational study was done on hematological malignancy patients who were admitted for HSCT in a regional cancer center. The study subjects were assessed by the Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT Scale), Edmonton Symptom Assessment Scale-revised (r-ESAS), and Depression, Anxiety and Stress Scale-21 Items (DASS-21) at the time of hospital admission for transplantation, on day 30 (~ 1 month) and day100 (~ 3 months) of transplantation. RESULTS: A total of 68 patients were included in this study. FACT-BMT scores have decreased from baseline (F0) to the first follow-up (F1) and then increased in the third follow-up (F2). The maximum r-ESAS mean score was for tiredness among all other symptoms at F0 as well as at F1 and at F2. The DASS 21 scores for depression, anxiety, and stress were maximum during F1 and minimum during F2. CONCLUSION: Symptom burden is maximum during the first month of BMT, which improves later and QOL becomes improved with time.

An Eclectic Review on Dicarboxylic Acid Production Through Yeast Cell Factories and Its Industrial Prominence.

Dicarboxylic acid (DCA) is a multifaceted chemical intermediate, recoursed to produce many industrially important products such as adhesives, plasticizers, lubricants, polymers, etc. To bypass the shortcomings of the chemical methods of synthesis of DCA and to reduce fossil fuel footprints, bio-based synthesis is gaining attention. In pursuit of an eco-friendly sustainable alternative method of DCA production, microbial cell factories, and renewable organic resources are gaining popularity. Among the plethora of microbial communities, yeast is being favored industrially compared to bacterial fermentation due to its hyperosmotic and low pH tolerance and flexibility for gene manipulations. By application of rapidly evolving genetic manipulation techniques, the bio-based DCA production could be made more precise and economical. To bridge the gap between supply and demand of DCA, many strategies are employed to improve the fermentation. This review briefly outlines the advancements in DCA production using yeast cell factories with the exemplification of strain improvement strategies.

KASP: a high-throughput genotyping system and its applications in major crop plants for biotic and abiotic stress tolerance.

Advances in plant molecular breeding have resulted in the development of new varieties with superior traits, thus improving the crop germplasm. Breeders can screen a large number of accessions without rigorous and time-consuming phenotyping by marker-assisted selection (MAS). Molecular markers are one of the most imperative tools in plant breeding programmes for MAS to develop new cultivars possessing multiple superior traits. Single nucleotide polymorphisms (SNPs) are ideal for MAS due to their low cost, low genotyping error rates, and reproducibility. Kompetitive Allele Specific PCR (KASP) is a globally recognized technology for SNP genotyping. KASP is an allele-specific oligo extension-based PCR assay that uses fluorescence resonance energy transfer (FRET) to detect genetic variations such as SNPs and insertions/deletions (InDels) at a specific locus. Additionally, KASP allows greater flexibility in assay design, which leads to a higher success rate and the capability to genotype a large population. Its versatility and ease of use make it a valuable tool in various fields, including genetics, agriculture, and medical research. KASP has been extensively used in various plant-breeding applications, such as the identification of germplasm resources, quality control (QC) analysis, allele mining, linkage mapping, quantitative trait locus (QTL) mapping, genetic map construction, trait-specific marker development, and MAS. This review provides an overview of the KASP assay and emphasizes its validation in crop improvement related to various biotic and abiotic stress tolerance and quality traits.

Collapsing Glomerulopathy in a Patient with Tuberculosis and Poncet's Disease.

A 39-year-old woman presented with inflammatory polyarthritis, low-grade fever, progressive pedal edema, and frothy urination of three weeks duration. She had nephrotic range proteinuria and elevated creatinine. Kidney biopsy showed collapse of capillary tuft in the glomeruli and proliferation, hyperplasia, and hypertrophy of the overlying podocytes suggestive of collapsing glomerulopathy. Histology of the cervical lymph node showed necrotizing granulomatous inflammation suggestive of tuberculosis. With all other possible causes of polyarthritis ruled out, a diagnosis of Poncet's disease-a form of polyarthritis observed in patients suffering from an active form of extrapulmonary tuberculosis (TB)-was considered. Association between TB lymphadenitis and collapsing glomerulopathy (CG) is very rare, and the patient had partial remission of the disease after being started on anti-tuberculosis therapy (ATT) along with steroids.

Urbanisation negatively impacts sleep health and mood in adolescents: a comparative study of female students from city and rural schools of North India.

This study investigated the impact of social settings on sleep, physical and mental health in female adolescents of North India (latitude 29.5 oN; longitude 77.5 oE). Using a battery of questionnaires, we compared the chronotype, sleep-wake pattern, sleep health (e.g. sleep quality, daytime sleepiness and fatigue) and mood (via depression, anxiety and stress symptoms) in female students (age 14-18 years) from rural (N = 719) and urban (N = 1033) schools separated by about 35 km, but families had almost similar socio-demographic details. The morning type was prevalent amongst rural, whilst the evening type was prevalent amongst urban students who also had access to smart phones, suggesting a possible greater use of the internet. There were greater negative sleep effects, daytime sleepiness, overall poor sleep quality, higher fatigue and anxiety levels in urban than the rural cohort. Interestingly, these measures also differed between school days and free days, suggesting an impact of the conflict between internal biological and social timings (= social jet lag). We also found a significant relationship between chronotype, internet addiction, mood-related parameters and measures of sleep health. Overall, these results suggest a possible impact of social settings on sleep health and mood-related behaviours in female adolescents.

Poly(acrylamide)-co-poly(hydroxyethyl)methacrylate-co-poly(cyclohexyl methacrylate) hydrogel platform for stability, storage and biocatalytic applications of urease.

In our present work, an explicit crosslinked thermo-responsive hydrogel platform has been developed, by using polyacrylamide (PAAm), poly(2-hydroxyethyl methacrylate) (PHEMA) and poly(cyclohexyl methacrylate) (PCHMA), and then coupled with urease to yield bioconjugates (BCs). Synergic effect of these polymer units provides thermoresponsive nature, optimum crosslinking with desired swelling behaviour, and stability and improved catalytic to Urease in the resultant BCs. Synthesis of the terpolymer has been achieved by employing HEMA (monomer as well as crosslinker), instead of using the conventional crosslinkers, through free radical solution polymerization technique. Various grades of TRPUBs have been fabricated by varying HEMA and CHMA contents while keeping fixed amounts of AAm. Further, the structural analysis of BCs has been done by fourier transform infra-red spectroscopic study and their thermal stabilities have been studied by thermogravimetric analysis. Urea present in TRPUBs has beenanalysed for its hydrolysis atdifferent temperatures viz., 25 °C, 45 °C and 70 °C. Further, the effect of crosslinking, temperature and reaction time on catalytic activities of TRPUBs has been studied. TRPUBs grades have showna maximum swelling capacity up to 5200 %; excellent catalytic activity even at 70 °C; and 85 % activity retention after 18 days storage in buffer medium.

Constant light and pinealectomy disrupt daily rhythm in song production and negatively impact reproductive performance in zebra finches.

We assessed the circadian clock control of singing and reproductive performance in zebra finches. Experiment 1 examined changes in body mass, testis size, and plasma corticosterone and testosterone levels in male birds exposed to constant light (LL, 100 lx) and constant darkness (DD, 0.5 lx), with controls on 12L:12D (L = 100 lx, D = 0.5 lx). There was a significant increase in the body mass and testis size under LL and a decrease in testis size under the DD. Using a similar design, experiment 2 assessed the persistence of the circadian rhythm in singing along with activity-rest pattern in cohort I birds that were entrained to 12L:12D and subsequently released in DD or LL, and in cohort II birds that were entrained to 12L:12D and following pinealectomy were released in DD. Both activity and singing patterns were synchronized with the light phase under 12L:12D, free-ran with a circadian period under DD, and were arrhythmic under the LL. There was an overall decreased and increased effect on singing under DD and LL, respectively, albeit with differences in various song parameters. The pinealectomy disrupted both activity and singing rhythms but did not affect singing or the overall song features. Pinealectomized bird pairs also exhibited a significant reduction in their nest-building and breeding efforts, resulting in a compromised reproductive performance. These results suggest a circadian clock control of singing and more importantly demonstrate a role of the pineal clock in breeding behaviors, leading to a compromised reproductive performance in diurnal zebra finches.

Evaluation of prone vs supine positioning in fresh rhegmatogenous retinal detachment treated with pars plana vitrectomy and gas.

PURPOSE: To compare Supine versus Prone positioning in fresh rhegmatogenous retinal detachments (RRDs) treated with vitrectomy and gas tamponade. METHODS: This was a prospective randomized controlled trial of 72 eyes with fresh RRD who underwent 25-gauge vitrectomy. 37 eyes were allotted supine position and 35 were allotted prone position. Cases were evaluated for single surgery reattachment rates, best corrected visual acuity (BCVA), intraocular pressure (IOP), cataract formation and any complications. The patients were followed up for a period of 3 months. RESULTS: Both groups had similar demographics, and no significant difference was found between the two groups in terms of extent of retinal detachment, position and number of breaks. The anatomical success after single surgery was 97.3% in Supine group and 94.3% in Prone group (p=0.609). The BCVA at the end of 3 months was 0.44 ± 0.27 in Supine group and 0.35 ± 0.27 in Prone group (p=0.119) with a significant increase in BCVA preoperatively from 0.11 ± 0.22 and 0.13 ± 0.22 in Supine and Prone group respectively (p=<0.001). The IOP in the two groups was comparable at each follow up. The rates of cataract formation were also similar in the two groups - 60% and 53.8% in Supine and Prone group respectively(p=1.00). Complications such as spikes in IOP, epiretinal membrane formation, cystoid macular oedema etc were similar in both groups. CONCLUSION: Rates of retinal reattachment were comparable in both groups, showing that supine position is equally safe and effective for adequate tamponade.

Unified deep learning models for enhanced lung cancer prediction with ResNet-50-101 and EfficientNet-B3 using DICOM images.

Significant advancements in machine learning algorithms have the potential to aid in the early detection and prevention of cancer, a devastating disease. However, traditional research methods face obstacles, and the amount of cancer-related information is rapidly expanding. The authors have developed a helpful support system using three distinct deep-learning models, ResNet-50, EfficientNet-B3, and ResNet-101, along with transfer learning, to predict lung cancer, thereby contributing to health and reducing the mortality rate associated with this condition. This offer aims to address the issue effectively. Using a dataset of 1,000 DICOM lung cancer images from the LIDC-IDRI repository, each image is classified into four different categories. Although deep learning is still making progress in its ability to analyze and understand cancer data, this research marks a significant step forward in the fight against cancer, promoting better health outcomes and potentially lowering the mortality rate. The Fusion Model, like all other models, achieved 100% precision in classifying Squamous Cells. The Fusion Model and ResNet-50 achieved a precision of 90%, closely followed by EfficientNet-B3 and ResNet-101 with slightly lower precision. To prevent overfitting and improve data collection and planning, the authors implemented a data extension strategy. The relationship between acquiring knowledge and reaching specific scores was also connected to advancing and addressing the issue of imprecise accuracy, ultimately contributing to advancements in health and a reduction in the mortality rate associated with lung cancer.

Exogenous GABA supplementation to facilitate Cr (III) tolerance and lipid biosynthesis in Chlorella sorokiniana.

Microalgae possess the prospective to be efficiently involved in bioremediation and biodiesel generation. However, conditions of stress often restrict their growth and diminish different metabolic processes. The current study evaluates the potential of GABA to improve the growth of the microalga Chlorella sorokiniana under Cr (III) stress through the exogenous administration of GABA. The research also investigates the concurrent impact of GABA and Cr (III) stress on various metabolic and biochemical pathways of the microalgae. In addition to the control, cultures treated with Cr (III), GABA, and both Cr (III) and GABA treated were assessed for accurately analysing the influence of GABA. The outcomes illustrated that GABA significantly promoted growth of the microalgae, resulting in higher biomass productivity (19.14 mg/L/day), lipid productivity (3.445 mg/L/day) and lipid content (18%) when compared with the cultures under Cr (III) treatment only. GABA also enhanced Chl a content (5.992 µg/ml) and percentage of protein (23.75%). FAMEs analysis by GC-MS and total lipid profile revealed that GABA treatment can boost the production of SFA and lower the level of PUFA, a distribution ideal for improving biodiesel quality. ICP-MS analysis revealed that GABA supplementation could extend Cr (III) mitigation level up to 97.7%, suggesting a potential strategy for bioremediation. This novel study demonstrates the merits of incorporating GABA in C. sorokiniana cultures under Cr (III) stress, in terms of its potential in bioremediation and biodiesel production without disrupting the pathways of photosynthesis and protein production.

Normative modeling of thalamic nuclear volumes.

Thalamic nuclei have been implicated in neurodegenerative and neuropsychiatric disorders. Normative models for thalamic nuclear volumes have not been proposed thus far. The aim of this work was to establish normative models of thalamic nuclear volumes and subsequently investigate changes in thalamic nuclei in cognitive and psychiatric disorders. Volumes of the bilateral thalami and 12 nuclear regions were generated from T1 MRI data using a novel segmentation method (HIPS-THOMAS) in healthy control subjects (n=2374) and non-control subjects (n=695) with early and late mild cognitive impairment (EMCI, LMCI), Alzheimer's disease (AD), Early psychosis and Schizophrenia, Bipolar disorder, and Attention deficit hyperactivity disorder. Three different normative modelling methods were evaluated while controlling for sex, intracranial volume, and site. Z-scores and extreme z-score deviations were calculated and compared across phenotypes. GAMLSS models performed the best. Statistically significant shifts in z-score distributions consistent with atrophy were observed for most phenotypes. Shifts of progressively increasing magnitude were observed bilaterally from EMCI to AD with larger shifts in the left thalamic regions. Heterogeneous shifts were observed in psychiatric diagnoses with a predilection for the right thalamic regions. Here we present the first normative models of thalamic nuclear volumes and highlight their utility in evaluating heterogenous disorders such as Schizophrenia.

TWIST1 is a critical downstream target of the HGF/MET pathway and is required for MET driven acquired resistance in oncogene driven lung cancer.

MET amplification/mutations are important targetable oncogenic drivers in NSCLC, however, acquired resistance is inevitable and the majority of patients with targetable MET alterations fail to respond to MET tyrosine kinase inhibitors (TKIs). Furthermore, MET amplification is among the most common mediators of TKI resistance. As such, novel therapies to target MET pathway and overcome MET TKI resistance are clearly needed. Here we show that the epithelial-mesenchymal transition (EMT) transcription factor, TWIST1 is a key downstream mediator of HGF/MET induced resistance through suppression of p27 and targeting TWIST1 can overcome resistance. We found that TWIST1 is overexpressed at the time of TKI resistance in multiple MET-dependent TKI acquired resistance PDX models. We have shown for the first time that MET directly stabilized the TWIST protein leading to TKI resistance and that TWIST1 was required for MET-driven lung tumorigenesis as well as could induce MET TKI resistance when overexpressed. TWIST1 mediated MET TKI resistance through suppression of p27 expression and genetic or pharmacologic inhibition of TWIST1 overcame TKI resistance in vitro and in vivo. Our findings suggest that targeting TWIST1 may be an effective therapeutic strategy to overcome resistance in MET-driven NSCLC as well as in other oncogene driven subtypes in which MET amplification is the resistance mechanism.

An experimental and prediction modeling study on water lettuce (Pistia stratiotes L.) assisted heavy metals removal from glass industry effluent.

The glass manufacturing industry produces hazardous effluent that is difficult to manage and causes numerous environmental problems when disposed of in the open. In this study, an attempt was made to study the phytoremediation feasibility of water lettuce (Pistia stratiotes L.), a free-floating aquatic macrophyte, for the removal of six heavy metals from glass industry effluent (GIE) at varying concentrations (0, 25, 50, 75, and 100%). After a 40-day experiment, the results showed that 25% GIE dilution showed maximum removal of heavy metals i.e., Cu (91.74%), Cr (95.29%), Fe (86.47%), Mn (92.95%), Pb (87.10%), and Zn (91.34%), respectively. The bioaccumulation, translocation, and Pearson correlation studies showed that the amount of heavy metals absorbed by vegetative parts of P. stratiotes was significantly correlated with concentrations. The highest biomass production, chlorophyll content, relative growth rate, and biomass productivity were also noted in the 25% GIE treatment. Moreover, the multiple linear regression models developed for the prediction of heavy metal uptake by P. stratiotes also showed good performance in determining the impact of GIE properties. The models showed a high coefficient of determination (R2 > 0.99), low mean average normalizing error (MANE = 0.01), and high model efficiency (ME > 0.99) supporting the robustness of the developed equations. This study outlined an efficient method for the biological treatment of GIE using P. stratiotes to reduce risks associated with its unsafe disposal.

Comparison of lung aeration loss in open abdominal oncologic surgeries after ventilation with electrical impedance tomography-guided PEEP versus conventional PEEP: a pilot feasibility study.

Background: Existing literature lacks high-quality evidence regarding the ideal intraoperative positive end-expiratory pressure (PEEP) to minimize postoperative pulmonary complications (PPCs). We hypothesized that applying individualized PEEP derived from electrical impedance tomography (EIT) would reduce the severity of postoperative lung aeration loss, deterioration in oxygenation, and PPC incidence. Methods: A pilot feasibility study was conducted on 36 patients who underwent open abdominal oncologic surgery. The patients were randomized to receive individualized PEEP or conventional PEEP at 4 cm H2O. The primary outcome was the impact of individualized PEEP on changes in the modified lung ultrasound score (MLUS) derived from preoperative and postoperative lung ultrasonography. A higher MLUS indicated greater lung aeration loss. The secondary outcomes were the PaO2/FIO2 ratio and PPC incidence. Results: A significant increase in the postoperative MLUS (12 ± 3.6 vs 7.9 ± 2.1, P < 0.001) and a significant difference between the postoperative and preoperative MLUS values (7.0 ± 3.3 vs 3.0 ± 1.6, P < 0.001) were found in the conventional PEEP group, indicating increased lung aeration loss. In the conventional PEEP group, the intraoperative PaO2/FIO2 ratios were significantly lower but not the postoperative ratios. The PPC incidence was not significantly different between the groups. Post-hoc analysis showed the increase in lung aeration loss and deterioration of intraoperative oxygenation correlated with the deviation from the individualized PEEP. Conclusions: Individualized PEEP appears to protect against lung aeration loss and intraoperative oxygenation deterioration. The advantage was greater in patients whose individualized PEEP deviated more from the conventional PEEP.

Augmented mannose-binding lectin levels in primary membranous nephropathy: A pilot study.

There is evidence to suggest that M-type phospholipase A2 (PLA2R) antibodies activate the mannose-binding lectin (MBL) cascade, resulting in glomerular damage and proteinuria in patients with primary membranous nephropathy (PMN). Furthermore, there are few reports indicating that aberrant MBL activation is associated with endothelial dysfunction and accelerated atherosclerosis. While PMN is a common cause of adult nephrotic syndrome, and patients are at increased risk of cardiovascular disease (CVD), there is a lack of research that explores the factors that contribute to this condition. This study aims to determine the MBL levels in PMN and their relation to the clinical activity and endothelial dysfunction in PMN. The MBL levels of 22 biopsy-confirmed PMN patients were assessed at baseline and after 6 months of immunosuppressive therapy. In order to evaluate endothelial dysfunction in PMN patients, flow-mediated vasodilation (FMD) was measured at baseline and after treatment. A total of 22 healthy controls were included in this study to measure MBL levels and FMD. A significant difference was observed between MBL levels in PMN patients and healthy controls (p < .01). MBL levels decreased significantly after immunosuppressive therapy (p = .04). The baseline MBL levels and FMD levels exhibited a strong correlation (Spearman correlation coefficient [ρ] = 0.51: p = .01). In conclusion, the study signals the activation of the MBL cascade and its association with endothelial dysfunction in PMN patients.

Transcription factor-based biosensor: A molecular-guided approach for advanced biofuel synthesis.

As a sustainable and renewable alternative to petroleum fuels, advanced biofuels shoulder the responsibility of energy saving, emission reduction and environmental protection. Traditional engineering of cell factories for production of advanced biofuels lacks efficient high-throughput screening tools and regulating systems, impeding the improvement of cellular productivity and yield. Transcription factor-based biosensors have been widely applied to monitor and regulate microbial cell factory products due to the advantages of fast detection and in-situ screening. This review updates the design and application of transcription factor-based biosensors tailored for advanced biofuels and related intermediates. The construction and genetic parts selection principle of biosensors are discussed. Strategies to enhance the performance of biosensor, including regulating promoter strength and RBS strength, optimizing plasmid copy number, implementing genetic amplifier, and modulating the structure of transcription factor, have also been summarized. We further review the application of biosensors in high-throughput screening of new metabolic engineering targets, evolution engineering, confirmation of protein function, and dynamic regulation of metabolic flux for higher production of advanced biofuels. At last, we discuss the current limitations and future trends of transcription factor-based biosensors.

Landfill bacteriology: Role in waste bioprocessing elevated landfill gaseselimination and heat management.

This study delves into the critical role of microbial ecosystems in landfills, which are pivotal for handling municipal solid waste (MSW). Within these landfills, a complex interplay of several microorganisms (aerobic/anaerobic bacteria, archaea or methanotrophs), drives the conversion of complex substrates into simplified compounds and complete mineralization into the water, inorganic salts, and gases, including biofuel methane gas. These landfills have dominant biotic and abiotic environments where various bacterial, archaeal, and fungal groups evolve and interact to decompose substrate by enabling hydrolytic, fermentative, and methanogenic processes. Each landfill consists of diverse bio-geochemical environments with complex microbial populations, ranging from deeply underground anaerobic methanogenic systems to near-surface aerobic systems. These kinds of landfill generate leachates which in turn emerged as a significant risk to the surrounding because generated leachates are rich in toxic organic/inorganic components, heavy metals, minerals, ammonia and xenobiotics. In addition to this, microbial communities in a landfill ecosystem could not be accurately identified using lab microbial-culturing methods alone because most of the landfill's microorganisms cannot grow on a culture medium. Due to these reasons, research on landfills microbiome has flourished which has been characterized by a change from a culture-dependent approach to a more sophisticated use of molecular techniques like Sanger Sequencing and Next-Generation Sequencing (NGS). These sequencing techniques have completely revolutionized the identification and analysis of these diverse microbial communities. This review underscores the significance of microbial functions in waste decomposition, gas management, and heat control in landfills. It further explores how modern sequencing technologies have transformed our approach to studying these complex ecosystems, offering deeper insights into their taxonomic composition and functionality.