A master regulator of opioid reward in the ventral prefrontal cortex.

In addition to their intrinsic rewarding properties, opioids can also evoke aversive reactions that protect against misuse. Cellular mechanisms that govern the interplay between opioid reward and aversion are poorly understood. We used whole-brain activity mapping in mice to show that neurons in the dorsal peduncular nucleus (DPn) are highly responsive to the opioid oxycodone. Connectomic profiling revealed that DPn neurons innervate the parabrachial nucleus (PBn). Spatial and single-nuclei transcriptomics resolved a population of PBn-projecting pyramidal neurons in the DPn that express µ-opioid receptors (µORs). Disrupting µOR signaling in the DPn switched oxycodone from rewarding to aversive and exacerbated the severity of opioid withdrawal. These findings identify the DPn as a key substrate for the abuse liability of opioids.

Giant left sinus of Valsalva aneurysm as a rare cause of acute myocardial infarction: a case report.

Background: Sinus of Valsalva aneurysm (SVA) is a rare but potentially life-threatening condition. Acute myocardial infarction (MI) is a rare consequence of aneurysmal dilatation of one or more sinuses of Valsalva. We present a case of an unruptured and partially thrombosed left SVA, presenting as anterior MI and congestive heart failure. Case summary: A 55-year-old gentleman was admitted with pulmonary oedema and a late presenting ST-elevation MI with Q wave. After initial treatment on furosemide infusion, a coronary angiography showed significant stenosis in both his left main stem (LMS) and left anterior descending artery (LAD). This is likely a result of external compression, potentially from the enlarged left sinus of Valsalva. A subsequent transthoracic echocardiogram and transoesophageal echocardiogram (TOE) confirmed large SVA involving the left coronary cusp measured 9.9 cm compressing both LMS and LAD. Discussion: Left SVAs are rare and frequently asymptomatic, typically being identified incidentally. Due to the close proximity of the left coronary system, they can present with myocardial ischaemia due to extrinsic compression of the coronary system. We were able to perform a comprehensive multi-modality assessment of left SVA, which helped establish this unusual diagnosis and guide management. Transthoracic echocardiogram and TOE helped assess the SVA and demonstrated the thrombus in situ, aortic valve insufficiency, and cardiac function. The computed tomography scan aided in accurately defining the extent of the aneurysm and the extent of compression of the left coronary system and cardiac magnetic resonance scan was able to demonstrate viability in LAD and circumflex territory.

Percutaneous Left Ventricular Unloading During High-Risk Coronary Intervention: Rationale and Design of the CHIP-BCIS3 Randomized Controlled Trial.

INTRODUCTION: Percutaneous coronary intervention for complex coronary disease is associated with a high risk of cardiogenic shock. This can cause harm and limit the quality of revascularization achieved, especially when left ventricular function is impaired at the outset. Elective percutaneous left ventricular unloading is increasingly used to mitigate adverse events in patients undergoing high-risk percutaneous coronary intervention, but this strategy has fiscal and clinical costs and is not supported by robust evidence. METHODS: CHIP-BCIS3 (Controlled Trial of High-Risk Coronary Intervention With Percutaneous Left Ventricular Unloading) is a prospective, multicenter, open-label randomized controlled trial that aims to determine whether a strategy of elective percutaneous left ventricular unloading is superior to standard care (no planned mechanical circulatory support) in patients undergoing nonemergent high-risk percutaneous coronary intervention. Patients are eligible for recruitment if they have severe left ventricular systolic dysfunction, extensive coronary artery disease, and are due to undergo complex percutaneous coronary intervention (to the left main stem with calcium modification or to a chronic total occlusion with a retrograde approach). Cardiogenic shock and acute ST-segment-elevation myocardial infarction are exclusions. The primary outcome is a hierarchical composite of all-cause death, stroke, spontaneous myocardial infarction, cardiovascular hospitalization, and periprocedural myocardial infarction, analyzed using the win ratio. Secondary outcomes include completeness of revascularization, major bleeding, vascular complications, health economic analyses, and health-related quality of life. A sample size of 250 patients will have in excess of 80% power to detect a hazard ratio of 0.62 at a minimum of 12 months, assuming 150 patients experience an event across all follow-up. CONCLUSIONS: To date, 169 patients have been recruited from 21 National Health Service hospitals in the United Kingdom, with recruitment expected to complete in 2024. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05003817.

Very early invasive strategy in higher risk non-ST-elevation acute coronary syndrome: the RAPID NSTEMI trial.

OBJECTIVE: To investigate whether a very early invasive strategy (IS)±revascularisation improves clinical outcomes compared with standard care IS in higher risk patients with non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: Multicentre, randomised, controlled, pragmatic strategy trial of higher risk patients with NSTE-ACS, defined by Global Registry of Acute Coronary Events 2.0 score of ≥118, or ≥90 with at least one additional high-risk feature. Participants were randomly assigned to very early IS±revascularisation (<90 min from randomisation) or standard care IS±revascularisation (<72 hours). The primary outcome was a composite of all-cause mortality, new myocardial infarction or hospitalisation for heart failure at 12 months. RESULTS: The trial was discontinued early by the funder due to slow recruitment during the COVID-19 pandemic. 425 patients were randomised, of whom 413 underwent an IS: 204 to very early IS (median time from randomisation: 1.5 hours (IQR: 0.9-2.0)) and 209 to standard care IS (median: 44.0 hours (IQR: 22.9-72.6)). At 12 months, there was no significant difference in the primary outcome between the early IS (5.9%) and standard IS (6.7%) groups (OR 0.93, 95% CI 0.42 to 2.09; p=0.86). The incidence of stroke and major bleeding was similar. The length of hospital stay was reduced with a very early IS (3.9 days (SD 6.5) vs 6.3 days (SD 7.6), p<0.01). CONCLUSIONS: A strategy of very early IS did not improve clinical outcomes compared with a standard care IS in higher risk patients with NSTE-ACS. However, the primary outcome rate was low and the trial was underpowered to detect such a difference. TRIAL REGISTRATION NUMBER: NCT03707314.

A dissipative and entropy-optimized MHD nanomaterial mixed convective flow for engineering applications.

Background and objective: Nanomaterials play significant roles in numerous industrial and engineering applications, like nuclear plants, paper production, thermal power plants, glass fibres, manufacturing of medicines, medical instruments, micro-electronics and polymer sheet extrusion. In view of such important applications, in this study, we discuss the magnetohydrodynamic flow of a nanofluid over an inclined surface by employing the Darcy-Forchheimer model. The Buongiorno model is applied to understand the various important aspects of the nanofluid. Radiation, magnetic field, dissipation and entropy generation in a chemically reactive flow are also discussed. Methodology: The governing nonlinear expressions were transformed into a dimensionless system through adequate transformations. The obtained non-dimensional systems were computed by the NDSolve approach. Results: Physical illustrations for the flow, temperature, concentration and entropy rate via emerging variables were examined. Here an enhancement in velocity was seen for the mixed convection variable, while opposite impacts on flow and temperature were noticed through the Hartman number. A higher Eckert number was obtained with a rise in temperature, while a decrease in concentration was noticed for the thermophoresis variable. An augmentation in the entropy rate was detected for radiation, while the thermal transport rate was boosted by thermophoresis.

KHA model comprising MoS4 and CoFe2O3 in engine oil invoking non-similar Darcy-Forchheimer flow with entropy and Cattaneo-Christov heat flux.

Objective: Nanoliquid flows are widely utilized in industrial, petroleum, engineering, and pharmaceutical applications including electric cooling, drug delivery, nuclear reactor cooling, solar collectors, heat exchangers, magnetohydrodynamic power generators, aerospace, porous media, thermal storage systems, and many others. Darcy-Forchheimer magnetized hybrid nanoliquid subjected to a stretchable cylinder was addressed, and the Cattaneo-Christov heat flux analysis was considered. Herein, disulfido (dithioxo) molybdenum (MoS4) and cobalt ferrite (CoFe2O4) were considered as nanoparticles, and engine oil as a conventional liquid. The thermal relationship of heat generation and radiation was discussed, and the influence of the entropy rate was addressed. Methodology: Governing expressions were transformed into dimensionless forms. Simulation by the ND-solve technique was implemented. Conclusions: Features for the entropy rate, liquid flow, and temperature against emerging variables for nanoliquid (MoS4/engine oil) and hybrid nanoliquid (MoS4 + CoFe2O4/engine oil) were explored. The numerical results of the coefficient of skin friction and thermal transport rate for nanoliquid (MoS4/engine oil) and hybrid nanoliquid (MoS4 + CoFe2O4/engine oil) were examined. Reduction in velocity clearly occurred through a magnetic field, whereas the reverse impact held for the entropy rate. The thermal field and entropy rate against the curvature parameter were enhanced. A decrease in liquid flow occurred for higher porosity variables. An enhancement in the entropy rate was witnessed for radiation and porosity parameters. Higher radiation and thermal relaxation time variables resulted in enhancement of the thermal transport rate.

The Extraction and Impact of Essential Oils on Bioactive Films and Food Preservation, with Emphasis on Antioxidant and Antibacterial Activities-A Review.

Essential oils, consisting of volatile compounds, are derived from various plant parts and possess antibacterial and antioxidant properties. Certain essential oils are utilized for medicinal purposes and can serve as natural preservatives in food products, replacing synthetic ones. This review describes how essential oils can promote the performance of bioactive films and preserve food through their antioxidant and antibacterial properties. Further, this article emphasizes the antibacterial efficacy of essential oil composite films for food preservation and analyzes their manufacturing processes. These films could be an attractive delivery strategy for improving phenolic stability in foods and the shelf-life of consumable food items. Moreover, this article presents an overview of current knowledge of the extraction of essential oils, their effects on bioactive films and food preservation, as well as the benefits and drawbacks of using them to preserve food products.

Recent Updates on Multifunctional Nanomaterials as Antipathogens in Humans and Livestock: Classification, Application, Mode of Action, and Challenges.

Pathogens cause infections and millions of deaths globally, while antipathogens are drugs or treatments designed to combat them. To date, multifunctional nanomaterials (NMs), such as organic, inorganic, and nanocomposites, have attracted significant attention by transforming antipathogen livelihoods. They are very small in size so can quickly pass through the walls of bacterial, fungal, or parasitic cells and viral particles to perform their antipathogenic activity. They are more reactive and have a high band gap, making them more effective than traditional medications. Moreover, due to some pathogen's resistance to currently available medications, the antipathogen performance of NMs is becoming crucial. Additionally, due to their prospective properties and administration methods, NMs are eventually chosen for cutting-edge applications and therapies, including drug administration and diagnostic tools for antipathogens. Herein, NMs have significant characteristics that can facilitate identifying and eliminating pathogens in real-time. This mini-review analyzes multifunctional NMs as antimicrobial tools and investigates their mode of action. We also discussed the challenges that need to be solved for the utilization of NMs as antipathogens.

Therapeutic potential of natural products and antibiotics against bovine mastitis pathogen of cows and buffaloes.

The present study aims to evaluate the prevalence and antimicrobial sensitivity of Staphylococcus aureus associated with bovine mastitis to selected antibiotics and plant extracts. In the current study, 140 milk samples were collected from cows and buffaloes. Among the 140 samples, 93 samples were positive for sub-clinical mastitis based on the California Mastitis Test (CMT). Out of the total positive samples, 45 were confirmed for S. aureus on a Mannitol salt agar media. The antimicrobial susceptibility test revealed that 44.82% of the isolates were resistant to cefoxitin (oxacillin) confirming methicillin-resistant S. aureus (MRSA) with a higher percentage (51.61%) in the buffalo than in the cow samples. Furthermore, the PCR assay confirmed the presence of the mecA gene in all the MRSA isolates. Among the seven tested antibiotics, sulfamethoxazole + trimethoprim showed high efficacy (71.1%) against methicillin-susceptible S. aureus isolates (MSSA). Oxytetracycline and sulfamethoxazole + trimethoprim showed 20% efficacy against MRSA followed by enrofloxacin (10%). On the other hand, the tested samples from Pistacia chinensis revealed that the ethyl acetate extract of bark showed a maximum zone of inhibition of 21.3 mm against MSSA and MRSA isolates at 3 000 µg/disc. Moreover, the methanol extract of Cotoneaster microphyllus formed a 12.3 mm and 9.1 mm zone of inhibition against the MSSA and MRSA isolates, respectively.

Unfolding the reality of the smoking paradox in a South Asian cohort of patients presenting with ST-elevation acute coronary syndrome undergoing primary percutaneous coronary intervention.

Objectives: Smoking is a potent risk factor for coronary artery disease, but there is controversy about its protective nature in terms of prognosis in ST-elevation acute coronary syndrome patients undergoing primary percutaneous coronary intervention. So, the main objective of this study is to unfold this controversy in a South Asian population in terms of clinical angiographic parameters and its in-hospital outcomes. Methods: In this study, we included 1756 consecutive patients diagnosed with ST-elevation acute coronary syndrome undergoing primary percutaneous coronary intervention. Patients were classified into smokers and non-smokers, and the in-hospital mortality rate was compared. Multivariable logistic regression analysis was performed to evaluate the paradoxical role of smoking. Results: Smokers were younger (53.78 ± 11.16 years vs 56.43 ± 11.17 years; p < 0.001) and more frequently men (98.7% vs 69.9%; p < 0.001) and had less diabetes (19.6% vs 44.8%; p < 0.001) and hypertension (38.5% vs 64.9%; p < 0.001). Smokers presented less frequently in Killip III (5.6% vs 8.1%; p < 0.001) and Killip IV (2.5% vs 4.8%; p < 0.001). Smokers mostly had single vessel disease (41.7% vs 34.4%; p = 0.013), whereas non-smokers had the multi-vessel disease and frequently presented with total occlusion of the culprit vessel (64.6% vs 58.8%; p = 0.040). Smokers have significantly lesser mortality (1.8% vs 4.3%; p = 0.009) compared to non-smokers with an odds ratio of 0.41 (95% confidence interval (CI): 0.21-0.82, p = 0.011); however, adjusted odds ratio on multivariable analysis was 0.67 (95% CI: 0.31-1.41, p = 0.290). Conclusions: The paradoxical protective role of smoking is the confounding effect of mainly younger age, less coronary artery disease burden, lower prevalence of diabetes and hypertension, and lower Killip III/IV at presentation.

Intercomparison of SWAT and ANN techniques in simulating streamflows in the Astore Basin of the Upper Indus.

The current research work was carried out to simulate monthly streamflow historical record using Soil and Water Assessment Tool (SWAT) and Artificial Neural Network (ANN) at the Astore Basin, Gilgit-Baltistan, Pakistan. The performance of SWAT and ANN models was assessed during calibration (1985-2005) and validation (2006-2010) periods via statistical indicators such as coefficient of determination (R2), Nash-Sutcliffe efficiency (NSE), percent bias (PBIAS), and root-mean-square error (RMSE). R2, NSE, PBIAS, and RMSE values for SWAT (ANN with Architecture (2,27,1)) models during calibration are 0.80 (0.88), 0.73 (0.82), 15.7 (0.008), and 79.81 (70.34), respectively, while during validation, the corresponding values are 0.71 (0.86), 0.66 (0.95), 17.3 (0.10), and 106.26 (75.92). The results implied that the ANN model is superior to the SWAT model based on the statistical performance indicators. The SWAT results demonstrated an underestimation of the high flow and overestimation of the low flow. Comparatively, the ANN model performed very well in estimating the general and extreme flow conditions. The findings of this research highlighted its potential as a valuable tool for accurate streamflow forecasting and decision-making. The current study recommends that additional machine learning models may be compared with the SWAT model output to improve monthly streamflow predictions in the Astore Basin.

Entropy generation in bioconvection hydromagnetic flow with gyrotactic motile microorganisms.

Here, the magnetohydrodynamic bioconvective flow of a non-Newtonian nanomaterial over a stretched sheet is scrutinized. The characteristics of convective conditions are analyzed. Irreversibility analysis in the presence of gyrotactic micro-organisms is discussed. Energy expression is assisted with thermal radiation, heat generation and ohmic heating. Buongiorno's model is employed to discuss the characteristics of the nanoliquid through thermophoresis and random diffusions. Nonlinear expressions of the given model are transformed through adequate transformations. The obtained expressions have been computed by the Newton built in-shooting technique. Results of influential variables for velocity, concentration, microorganism field, temperature and entropy rate are graphically studied. Clearly, velocity reduction is witnessed for the bioconvection Rayleigh number and magnetic variable. A higher heat generation variable leads to augmentation of temperature. An increase in the magnetic variable results in entropy and temperature enhancement. A higher Peclet number results in microorganism field reduction. Temperature distribution rises for radiation and the thermal Biot number. A higher solutal Biot number intensifies the concentration. The entropy rate for radiation and diffusion variables is enhanced.

Modeling and simulation for Cattaneo-Christov heat analysis of entropy optimized hybrid nanomaterial flow.

Here, the hydromagnetic entropy optimized flow of a hybrid (Pb + Fe2O3/C2H6O2) nanoliquid by a curved stretchable surface is addressed. The Darcy-Forchheimer model is utilized for porous space. Lead (Pb) and ferric oxide (Fe2O3) are considered the nanoparticles and ethylene glycol (C2H6O2) as the base liquid. Thermal expression consists of dissipation and ohmic heating. Entropy generation is under consideration. The Cattaneo-Christov heat flux impact is discussed. Non-dimensional partial expressions by adequate transformations have been reduced to ordinary differential systems. The ND-solve technique is implemented for numerical solutions of dimensionless systems. Graphical illustrations of velocity, thermal field and entropy against influential variables for both nanoliquid (Pb/C2H6O2) and hybrid nanoliquid (Pb + Fe2O3/C2H6O2) are presented. Graphical illustrations of velocity, thermal field and entropy against sundry variables for both nanoliquid (Pb/C2H6O2) and hybrid nanoliquid (Pb + Fe2O3/C2H6O2) are presented. Influences of sundry variables on the Nusselt number and drag force for both nanoliquid (Pb/C2H6O2) and hybrid nanoliquid (Pb + Fe2O3/C2H6O2) are examined. A higher thermal relaxation time tends to intensify the heat transport rate and temperature. An increment in the magnetic variable leads to an enhancement of the entropy and thermal field. An improvement in liquid flow is seen for volume fraction variables. Velocity against the porosity variable and Forchheimer number is reduced. The Brinkman number leads to maximization of entropy generation.

Acute hyperglycemia, a rabble-rouser or innocent bystander? A prospective analysis of clinical implications of acute hyperglycemia in STE-ACS patients.

BACKGROUND: Acute hyperglycemia is considered an independent prognosticator of both in-hospital and long-term outcomes in patients with acute coronary syndrome (ACS). This study aimed To analyze the incidence of acute hyperglycemia and its impact on the adverse in-hospital outcome in patients with STE-ACS undergoing primary percutaneous coronary intervention (PCI). METHODS: In this study, we enrolled patients presenting with STE-ACS and undergoing primary PCI at a tertiary care cardiac center. Acute hyperglycemia was defined as random plasma glucose (RBS) > 200 mg/dl at the time of presentation to the emergency room. RESULTS: Of the 4470 patients, 78.8% were males, and the mean age was 55.52 ± 11 years. In total, 39.4% (1759) were found to have acute hyperglycemia, and of these, 59% (1037) were already diagnosed with diabetes. Patients with acute hyperglycemia were observed to have a higher incidence of heart failure (8.2% vs. 5.5%; p < 0.001), contrast-induced nephropathy (10.9% vs. 7.4%; p < 0.001), and in-hospital mortality (5.7% vs. 2.5%; p < 0.001). On multivariable analysis, acute hyperglycemia was found to be an independent predictor of mortality with an adjusted odds ratio of 1.81 [1.28-2.55]. Multi-vessel disease (1.73 [1.17-2.56]), pre-procedure left ventricular end-diastolic pressure (LVEDP) (1.02 [1.0-1.03]), and Killip class III/IV (4.55 [3.09-6.71]) were found to be the additional independent predictors of in-hospital mortality. CONCLUSIONS: Acute hyperglycemia, regardless of diabetic status, is an independent predictor of in-hospital mortality among patients with STE-ACS undergoing primary PCI. Acute hyperglycemia, along with other significant predictors such as multi-vessel involvement, LVEDP, and Killip class III/IV, can be considered for the risk stratification of these patients.

Role of Optical Coherence Tomography in Chronic Spontaneous Coronary Artery Dissection-Diagnosis and Management.

Spontaneous coronary artery dissection is an underdiagnosed cause of acute coronary syndrome, often occurring in younger females. Such a diagnosis should always be considered in this demographic. In this case report, we focus on the importance of optical coherence tomography in the diagnosis and management of this condition in the elective setting.

Aortic cusp perforation during rotational atherectomy: a case report.

Background: Rotational atherectomy has become increasingly utilised over the past decade. Although a relatively safe procedure in appropriately trained physicians' hands, there are a number of recognised complications. Case summary: We describe the case of a 64-year-old female who presented with chest pain and was diagnosed with non-ST-segment elevation acute coronary syndrome. A transthoracic echocardiogram (TTE) showed normal biventricular function and no valve disease. Invasive coronary angiogram was performed which revealed a severely calcified ostial right coronary artery (RCA) disease which was felt to be the culprit of the presentation. Balloon dilatation was unsuccessful, therefore, rotational atherectomy with an Amplatz left 0.75 guide and a 1.5 mm rota-burr was utilised and improved calcium burden. This was complicated by ostial dissection, treated with stenting. A TTE following the procedure revealed moderate aortic regurgitation (AR). The patient was discharged as she remained asymptomatic. An outpatient transoesophageal echocardiogram performed eight months later showed evidence of severe eccentric AR. Cardiac magnetic resonance imaging confirmed severe AR with left ventricular dilatation. Repeat angiogram 10 months after index procedure revealed in-stent restenosis, and the patient was accepted by heart multidisciplinary team for aortic valve replacement and grafting of RCA. Discussion: As the field of rotational atherectomy continues to expand, we propose that novel complications such as reported in this case may become recognised. Finally, we stress the importance of multi-modality imaging in the investigation and timely planning of interventions in the management of these patients.

Prevalence and Prognostic Implications of Amyloidosis in Valvular Heart Disease.

There has been less emphasis on the prognostic impact of amyloidosis in patients with valvular heart disease (VHD). We aimed to determine the prevalence of amyloidosis in VHD and its clinical implications in terms of mortality. Patients hospitalized for VHD were identified using National Inpatient Sample 2016-2020 which were divided into 2 cohorts: with and without amyloidosis. Among 5,728,873 patients hospitalized with VHD, 11,715 patients had amyloidosis in which mitral valve disease has the highest prevalence (7.6%) followed by aortic (3.6%), and tricuspid valve disease (1%). Underlying amyloidosis is associated with higher mortality in VHD (OR 1.45, CI 1.2-1.7, P<0.001), mainly mitral valve disease (OR 1.44, CI 1.1-1.9, P<0.01). Patients with amyloidosis have higher adjusted mortality rates (5-6% vs 2.6%, P<0.01), longer mean length of stay (7.1 vs 5.7 days, P<0.001), but they have lower valvular intervention rates. In hospitalized VHD patients, underlying amyloidosis is associated with higher in-hospital mortality.

Recommendations for developing effective and safe paediatric and congenital heart disease services in low-income and middle-income countries: a public health framework.

The global burden of paediatric and congenital heart disease (PCHD) is substantial. We propose a novel public health framework with recommendations for developing effective and safe PCHD services in low-income and middle-income countries (LMICs). This framework was created by the Global Initiative for Children's Surgery Cardiac Surgery working group in collaboration with a group of international rexperts in providing paediatric and congenital cardiac care to patients with CHD and rheumatic heart disease (RHD) in LMICs. Effective and safe PCHD care is inaccessible to many, and there is no consensus on the best approaches to provide meaningful access in resource-limited settings, where it is often needed the most. Considering the high inequity in access to care for CHD and RHD, we aimed to create an actionable framework for health practitioners, policy makers and patients that supports treatment and prevention. It was formulated based on rigorous evaluation of available guidelines and standards of care and builds on a consensus process about the competencies needed at each step of the care continuum. We recommend a tier-based framework for PCHD care integrated within existing health systems. Each level of care is expected to meet minimum benchmarks and ensure high-quality and family centred care. We propose that cardiac surgery capabilities should only be developed at the more advanced levels on hospitals that have an established foundation of cardiology and cardiac surgery services, including screening, diagnostics, inpatient and outpatient care, postoperative care and cardiac catheterisation. This approach requires a quality control system and close collaboration between the different levels of care to facilitate the journey and care of every child with heart disease. This effort was designed to guide readers and leaders in taking action, strengthening capacity, evaluating impact, advancing policy and engaging in partnerships to guide facilities providing PCHD care in LMICs.

Deciphering the biodesulfurization pathway employing marine mangrove Bacillus aryabhattai strain NM1-A2 according to whole genome sequencing and transcriptome analyses.

In the biogeochemical cycle, sulfur oxidation plays a vital role and is typically referred to as the elemental sulfur or reductive sulfide oxidation process. This study aimed to characterize a subtropical mangrove-isolated bacterial strain using biochemical, whole-genome, and transcriptome sequencing analyses to enhance our understanding of sulfur metabolism and biodegradation from a molecular genetic perspective. Strain NM1-A2 was characterized as Gram-positive and found to have a close molecular phylogenetic relationship with Bacillus aryabhattai. NM1-A2 efficiently converted dibenzothiophene (DBT) into 2-hydroxybiphenyl (2-HBP) via a 4S pathway with 95% efficiency, using enzymes encoded by the dsz operon (dszA, dszB, and dszC), which determine monooxygenases (DszA & DszC) and desulfinase (DszB). The whole-genome sequence of NM1-A2 had a length of approximately 5,257,678 bp and included 16 sulfur metabolism-related genes, featuring the ABC transport system, small subunit (ssu) and cysteine (cys) gene families, and adenosine 5'-phosphosulfate (APS) and 3'-phosphoadenosine-5'-phosphosulfate (PAPS) biosynthesis-related genes. Transcriptomic analysis of NM1-A2 using three sulfur groups-magnesium sulfate (MS), sulfur powder (SP), and sodium thiosulfate (ST) resulted in a significant number of differentially expressed genes (1200, 2304, and 2001, respectively). This analysis revealed that intracellular cysteine concentration directly regulated the expression of cys and ssu genes. Sulfate did not directly affect cys gene expression but repressed ssu gene expression. The cys gene expression levels decreased during the conversion of sulfate to sulfide and cysteine. The transcriptomic data was validated by analyzing the expression patterns of NM1-A2 using real-time quantitative PCR validation analysis. The expression levels of cysl, mccB, and nrnA were significantly upregulated, while cysH, metB, and sat were downregulated in the SP, ST, and MS groups, respectively. This research contributes to our understanding of marine mangrove microorganisms' bacterial efficiency through characterization, whole-genome, and transcriptome sequencing-based molecular degradation of organic compounds in the mangrove ecosystem, which may enhance nutrient availability.

Pseudomonas aeruginosa virulence attenuation by inhibiting siderophore functions.

Pseudmonas aeruginosa is a Gram-negative bacterium known to be ubiquitous and recognized as one of the leading causes of infections such as respiratory, urinary tract, burns, cystic fibrosis, and in immunocompromised individuals. Failure of antimicrobial therapy has been documented to be attributable due to the development of various resistance mechanisms, with a proclivity to develop additional resistance mechanisms rapidly. P. aeruginosa virulence attenuation is an alternate technique for disrupting pathogenesis without impacting growth. The iron-scavenging siderophores (pyoverdine and pyochelin) generated by P. aeruginosa have various properties like scavenging iron, biofilm formation, quorum sensing, increasing virulence, and toxicity to the host. As a result, developing an antivirulence strategy, specifically inhibiting the P. aeruginosa siderophore, has been a promising therapeutic option to limit their infection. Several natural, synthetic compounds and nanoparticles have been identified as potent inhibitors of siderophore production/biosynthesis, function, and transport system. The current review discussed pyoverdine and pyochelin's synthesis and transport system in P. aeruginosa. Furthermore, it is also focused on the role of several natural and synthetic compounds in reducing P. aeruginosa virulence by inhibiting siderophore synthesis, function, and transport. The underlying mechanism involved in inhibiting the siderophore by natural and synthetic compounds has also been explained. KEY POINTS: • Pseudomonas aeruginosa is an opportunistic pathogen linked to chronic respiratory, urinary tract, and burns infections, as well as cystic fibrosis and immunocompromised patients. • P. aeruginosa produces two virulent siderophores forms: pyoverdine and pyochelin, which help it to survive in iron-deficient environments. • The inhibition of siderophore production, transport, and activity using natural and synthesized drugs has been described as a potential strategy for controlling P. aeruginosa infection.