Revolutionizing Heart Transplantation: A Multidisciplinary Approach to Xenotransplantation, Immunosuppression, Regenerative Medicine, Artificial Intelligence, and Economic Sustainability.

Heart transplantation (HTx) stands as a life-saving intervention for patients with end-stage heart disease, but the field is fraught with numerous challenges that span from the scarcity of donor organs to long-term complications arising from immunosuppressive therapies. This comprehensive review article offers an in-depth exploration of the multifaceted aspects of HTx. The review covers groundbreaking advancements in xenotransplantation, enabled by cutting-edge genetic engineering techniques, and the promising role of stem cell therapies, particularly porcine mesenchymal stem cells, in cardiac regeneration. It also delves into the evolution and limitations of immunosuppressive therapies and the revolutionary potential of artificial intelligence (AI) and machine learning (ML) in enhancing donor-recipient matching and predicting patient outcomes. Economic considerations, especially in the context of rising healthcare costs, are examined to assess the sustainability of these advancements. The article further discusses the significant improvements in patient outcomes over the years, while highlighting persisting challenges, such as graft failure, rejection, and infection. It underscores the importance of experience and specialized training, evidenced by the presence of an institutional learning curve. The review concludes by advocating for a multifaceted, collaborative approach involving clinicians, researchers, and policymakers to overcome existing challenges. Through coordinated efforts that consider medical, ethical, and economic factors, the field of HTx is poised for further evolution, offering renewed hope for improved patient care and outcomes.

Cannulation Strategies in Type A Aortic Dissection: Overlooked Details and Novel Approaches.

Aortic dissection type A is a life-threatening condition that frequently necessitates surgical intervention. This review focuses on central aortic cannulation, arch branch vessel (ABV) cannulation, and proximal arch cannulation as key techniques during aortic surgery. It discusses innovative solutions for addressing these challenges. The review synthesizes findings from recent studies and emphasizes the significance of meticulous planning and execution of cannulation in aortic dissection repair. This review aims to contribute to the advancement of surgical practices and the enhancement of patient outcomes in the management of type A aortic dissection (AAD) by addressing these frequently overlooked details.

Post-COVID-19 Illness Trend in a Local Community in Bangladesh.

BACKGROUND: An infection with coronavirus disease 2019 (COVID-19) might show a wide range of symptoms. Many individuals still experience symptoms after a prolonged period of initial COVID-19. OBJECTIVES: The objective is to find out the prolonged consequences of COVID-19 with their associations. MATERIALS AND METHOD: Two hundred and eighty-six COVID-19 cases were the subject of this cross-sectional investigation, which was carried out in basic and secondary healthcare facilities in Bangladesh. COVID-19-positive participants with consent were interviewed in person about their sociodemographic traits, the nature of their COVID-19 infection, risk factors, present manifestations, etc. We carried out our statistical exploration by use of IBM SPSS Statistics for Windows, Version 22 (Released 2013; IBM Corp., Armonk, New York, United States). To evaluate differences, we utilized the chi-square (χ2) test as well as the unpaired t-test. Our significance threshold level was 0.05. RESULT: In this study, 18.5% of participants reported having post-COVID-19 symptoms. The four main symptom categories were anorexia (26.4%), myalgia (34.8%), fatigue (41.5%), and palpitations (25.5%). The majority of post-COVID-19 syndrome patients (e.g., 40.0%) were over 50 years old. Severe disease (81.8%) was more likely to develop post-COVID-19 illness. CONCLUSION: Fifty-three out of 286 participants (or 18.5%) reported having post-COVID-19 symptoms. The main symptom categories included fatigue, myalgia, anorexia, and palpitations. In order to determine the risk variables our data supports, additional investigation is required.

Effectiveness and Safety of Pembrolizumab in Recurrent and Relapsed Classic Hodgkin Lymphoma: A Systematic Review.

Classical Hodgkin lymphoma (cHL) has achieved high cure rates as a result of recent advancements in treatment. However, recurring or relapsed illness still poses a therapeutic challenge. Immune checkpoint inhibitor pembrolizumab, which targets PD-1, is now being commonly used as part of immunotherapy for recurrent and relapsed cHL. We found eight appropriate articles through systematic search and conducted in-depth analysis to find insights into the effectiveness and safety profiles of pembrolizumab by analyzing clinical trial data in patients with recurrent and relapsed cHL. Analysis of the studies shows that response rates, progression-free survival, and patient-reported quality of life have all significantly improved. However, immune-related consequences are among the adverse outcomes. The necessity for continued study is highlighted by the variation in reported adverse events and follow-up times. Clinicians, researchers, and other healthcare professionals can use this study as a resource to provide knowledgeable and individualized patient care in cHL.

Bridging Development and Disruption: Comprehensive Insights into Focal Cortical Dysplasia and Epileptic Management.

Focal cortical dysplasia (FCD) is a prominent neurological disorder characterized by disruptions in localized brain cell organization and development. This narrative review delineates the multi-faceted nature of FCD, emphasizing its correlation with drug-resistant epilepsy, predominantly in children and young adults. We explore the historical context of FCD, highlighting its indispensable role in shaping our comprehension of epilepsy and cortical anomalies. The clinical spectrum of FCD is broad, encompassing diverse seizure patterns, cognitive impairments, and associated neuropsychiatric disorders. We underscore the importance of differential diagnosis, with techniques ranging from electroencephalogram (EEG) interpretations to microscopic evaluations, and discuss advanced diagnostic modalities, such as the 3T magnetic resonance imaging (MRI) epilepsy protocols. Therapeutically, while anti-seizure medications are often first-line interventions, surgically refractory cases necessitate more invasive procedures, underscoring the importance of individualized treatment. Furthermore, the review touches upon the prognostic aspects of FCD, highlighting the importance of personalized care regimens, and provides insights into emerging therapeutic avenues, including the potential of the mammalian target of rapamycin (mTOR) pathway. Conclusively, this review accentuates the complex relationship between brain development and epileptogenicity inherent to FCD and underscores the promise of future research in enhancing patient outcomes.

Programmable all-DNA hydrogels based on rolling circle and multiprimed chain amplification products.

Soft, biocompatible, and tunable materials offer biomedical engineers and material scientists programmable matrices for a variety of biomedical applications. In this regard, DNA hydrogels have emerged as highly promising biomaterials that offer programmable self-assembly, superior biocompatibility, and the presence of specific molecular identifiable structures. Many types of DNA hydrogels have been developed, yet the programmability of the DNA building blocks has not been fully exploited, and further efforts must be directed toward understanding how to finely tune their properties in a predictable manner. Herein, we develop physically crosslinked all-DNA hydrogels with tunable morphology and controllable biodegradation, based on rolling circle amplification and multiprimed chain amplification products. Through molecular engineering of the DNA sequences and their nano-/microscale architectures, the precursors self-assemble in a controlled manner to produce soft hydrogels in an efficient, cost-effective, and highly tunable manner. Notably, we develop a novel DNA microladder architecture that serves as a framework for modulating the hydrogel properties, including over an order of magnitude change in pore size and up to 50% change in biodegradation rate. Overall, we demonstrate how the properties of this DNA-based biomaterial can be tuned by modulating the amounts of rigid double-stranded DNA chains compared to flexible single-stranded DNA chains, as well as through the precursor architecture. Ultimately, this work opens new avenues for the development of programmable and biodegradable soft materials in which DNA functions not only as a store of genetic information but also as a versatile polymeric biomaterial and molecularly engineered macroscale scaffold.

Safety and Efficacy of Efpeglenatide in Patients With Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials.

The aim of this study was to assess the efficacy and safety of efpeglenatide in patients with type 2 diabetes (T2D). The study was reported according to the 2020 guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Web of Science, PubMed, and Scopus databases were searched by two authors independently, with no restriction on language and year of publication, using the following key terms: (efpeglenatide) OR (glucagon-like peptide-1 receptor agonist) AND (type 2 diabetes) OR (diabetes) OR (T2DM) AND (HbA1c) OR (FSG) OR (fasting serum glucose) OR (weight) OR (bodyweight) OR (adverse events) OR (safety) OR (AE). Outcomes assessed in this meta-analysis included change in hemoglobin A1C (HbA1C) from baseline (%), change in weight from baseline (Kg), and change in fasting serum glucose (FSG) from baselines. For the safety analysis, we assessed total adverse events and gastrointestinal (GI) adverse events. A total of four studies fulfilled the inclusion and exclusion criteria and were included in this meta-analysis, encompassing six randomized controlled trials (RCTs). Compared with a control group, efpeglenatide lowered the HbA1c (mean difference (MD): -0.81, 95% confidence interval (CI): -1.01 to -0.60), body weight (MD: -1.15, 95% CI: -1.82 to -0.47), and FSG (MD: -0.98, 95% CI: -1.19 to -0.77). However, the risk of GI-related adverse events was significantly higher in the efpeglenatide group compared to the control group.

Probing Amyloid-DNA Interaction with Nanofluidics.

Nanofluidics is an emerging methodology to investigate single biomacromolecules without functionalization and/or attachment of the molecules to a substrate. In conjunction with fluorescence microscopy, it can be used to investigate structural and dynamical aspects of amyloid-DNA interaction. Here, we summarize the methodology for fabricating lab-on-chip devices in relatively cheap polymer resins and featuring quasi one-dimensional nanochannels with a cross-sectional diameter of tens to a few hundred nanometers. Site-specific staining of amyloid-forming protein Hfq with a fluorescence dye is also described. The methodology is illustrated with two application studies. The first study involves assembling bacterial amyloid proteins such as Hfq on double-stranded DNA and monitoring the folding and compaction of DNA in a condensed state. The second study is about the concerted motion of Hfq on DNA and how this is related to DNA's internal motion. Explicit details of procedures and workflows are given throughout.

SARS-CoV-2 Spike Protein and Mouse Coronavirus Inhibit Biofilm Formation by Streptococcus pneumoniae and Staphylococcus aureus.

The presence of co-infections or superinfections with bacterial pathogens in COVID-19 patients is associated with poor outcomes, including increased morbidity and mortality. We hypothesized that SARS-CoV-2 and its components interact with the biofilms generated by commensal bacteria, which may contribute to co-infections. This study employed crystal violet staining and particle-tracking microrheology to characterize the formation of biofilms by Streptococcus pneumoniae and Staphylococcus aureus that commonly cause secondary bacterial pneumonia. Microrheology analyses suggested that these biofilms were inhomogeneous soft solids, consistent with their dynamic characteristics. Biofilm formation by both bacteria was significantly inhibited by co-incubation with recombinant SARS-CoV-2 spike S1 subunit and both S1 + S2 subunits, but not with S2 extracellular domain nor nucleocapsid protein. Addition of spike S1 and S2 antibodies to spike protein could partially restore bacterial biofilm production. Furthermore, biofilm formation in vitro was also compromised by live murine hepatitis virus, a related beta-coronavirus. Supporting data from LC-MS-based proteomics of spike-biofilm interactions revealed differential expression of proteins involved in quorum sensing and biofilm maturation, such as the AI-2E family transporter and LuxS, a key enzyme for AI-2 biosynthesis. Our findings suggest that these opportunistic pathogens may egress from biofilms to resume a more virulent planktonic lifestyle during coronavirus infections. The dispersion of pathogens from biofilms may culminate in potentially severe secondary infections with poor prognosis. Further detailed investigations are warranted to establish bacterial biofilms as risk factors for secondary pneumonia in COVID-19 patients.

Near-IR Intramolecular Charge Transfer in Strongly Interacting Diphenothiazene-TCBD and Diphenothiazene-DCNQ Push-Pull Triads.

Three types of phenothiazines dimers (PTZ-PTZ, 1-3), covalently linked with one or two acetylene linkers, were synthesized by copper-mediated Eglinton and Pd-catalyzed Sonogashira coupling reactions in excellent yields. The dimers 1-3 were further engaged in [2+2] cycloaddition-retroelectrocyclization reactions with strong electron acceptors, tetracyanoethylene (TCNE) and 7,7,8,8-tetracyanoquinodimethane (TCNQ) to yield tetracyanobutadiene (TCBD, 1 a-3 a), and dicyanoquinodimethane (DCNQ, 1 b-3 b) functionalized donor-acceptor (D-A) conjugates, respectively. The conjugates were examined by a series of spectral, computational, and electrochemical studies. Strong ground state polarization leading to new optical transitions was witnessed in both series of D-A conjugates. In the case of DCNQ derived D-A system 1 b, the optical coverage extended until 1200 nm in benzonitrile, making this a rare class of D-A ICT system. Multiple redox processes were witnessed in these D-A systems, and the frontier orbitals generated on DFT optimized structures further supported the ICT phenomenon. Photochemical studies performed using femtosecond pump-probe studies confirmed solvent polarity dependent excited state charge transfer and separation in these novel multi-modular D-A conjugates. The charge-separated states lasted up to 70 ps in benzonitrile while in toluene slightly prolonged lifetime of up to 100 ps was witnessed. The significance of phenothiazine dimer in wide-band optical capture all the way into the near-IR region and promoting ultrafast photoinduced charge transfer in the D-A-D configured multi-modular systems, and the effect of donor-acceptor distance and the solvent polarity was the direct outcome of the present study.

Mobility of Bacterial Protein Hfq on dsDNA: Role of C-Terminus-Mediated Transient Binding.

The mobility of protein is fundamental in the machinery of life. Here, we have investigated the effect of DNA binding in conjunction with DNA segmental fluctuation (internal motion) of the bacterial Hfq master regulator devoid of its amyloid C-terminus domain. Hfq is one of the most abundant nucleoid associated proteins that shape the bacterial chromosome and is involved in several aspects of nucleic acid metabolism. Fluorescence microscopy has been used to track a C-terminus domain lacking mutant form of Hfq on double-stranded DNA, which is stretched by confinement to a rectangular nanofluidic channel. The mobility of the mutant is strongly accelerated with respect to the wild-type variant. Furthermore, it shows a reverse dependence on the internal motion of DNA, in that slower motion results in slower protein diffusion. The results demonstrate the subtle role of DNA internal motion in controlling the mobility of a nucleoid associated protein, and, in particular, the importance of transient binding and moving DNA strands out of the way.

Amyloid-like Hfq interaction with single-stranded DNA: involvement in recombination and replication in Escherichia coli.

Interactions between proteins and single-stranded DNA (ssDNA) are crucial for many fundamental biological processes, including DNA replication and genetic recombination. Thus, understanding detailed mechanisms of these interactions is necessary to uncover regulatory rules occurring in all living cells. The RNA-binding Hfq is a pleiotropic bacterial regulator that mediates many aspects of nucleic acid metabolism. The protein notably mediates mRNA stability and translation efficiency by using stress-related small regulatory RNA as cofactors. In addition, Hfq helps to compact double-stranded DNA. In this paper, we focused on the action of Hfq on ssDNA. A combination of experimental methodologies, including spectroscopy and molecular imaging, has been used to probe the interactions of Hfq and its amyloid C-terminal region with ssDNA. Our analysis revealed that Hfq binds to ssDNA. Moreover, we demonstrate for the first time that Hfq drastically changes the structure and helical parameters of ssDNA, mainly due to its C-terminal amyloid-like domain. The formation of the nucleoprotein complexes between Hfq and ssDNA unveils important implications for DNA replication and recombination.

Phase Transition of Catenated DNA Networks in Poly(ethylene glycol) Solutions.

Conformational phase transitions of macromolecules are an important class of problems in fundamental polymer physics. While the conformational phase transitions of linear DNA have been extensively studied, this feature of topologically complex DNA remains unexplored. We report herein the polymer-and-salt-induced (Ψ) phase transition of 2D catenated DNA networks, called kinetoplasts, using single-molecule fluorescence microscopy. We observe that kinetoplasts can undergo a reversible transition from the flat phase to the collapsed phase in the presence of NaCl as a function of the crowding agent poly(ethylene glycol). The nature of this phase transition is tunable through varying ionic strengths. For linear DNA, the coexistence of coil and globule phases was attributed to a first order phase transition associated with a double well potential in the transition regime. Kinetoplasts, however, navigate from the flat to the collapsed phase by passing through an intermediate regime, characterized by the coexistence of a multipopulation with varying shapes and sizes. Conformations of individual molecules in the multipopulation are long-lived, which suggests a rugged energy landscape.

Internal Motion of Chromatin Fibers Is Governed by Dynamics of Uncompressed Linker Strands.

Chromatin compaction and internal motion are fundamental aspects of gene expression regulation. Here, we have investigated chromatin fibers comprising recombinant histone octamers reconstituted with double-stranded bacteriophage T4-DNA. The size of the fibers approaches the typical size of genomic topologically associated domains. Atomic force and fluorescence (correlation) microscopy have been used to assess the structural organization, histone-induced compaction, and internal motion. In particular, the fibers are stretched on arrays of nanochannels, each channel with a diameter of 60 or 125 nm. Major intrafiber segregation and fast internal fluctuations are observed. Full compaction was only achieved by triggering an attractive nucleosome interaction through the addition of magnesium cations. Besides compaction, histone complexation results in a dramatic decrease in the fiber's relaxation time. The relaxation times are similar to those of naked DNA with a comparable stretch, which indicates that internal motion is governed by the dynamics of uncompressed linker strands. Furthermore, the main reorganization process is association-dissociation of individually compacted regions. We surmise that the modulation of chromatin's internal motion by histone complexation might have implications for transcriptional bursting.

Role of Internal DNA Motion on the Mobility of a Nucleoid-Associated Protein.

Protein transport on DNA is at the core of the machinery of life. Here we investigated the influence of DNA internal motion on the mobility of Hfq, which is involved in several aspects of nucleic acid metabolism and is one of the nucleoid-associated proteins that shape the bacterial chromosome. Fluorescence microscopy was used to follow Hfq on double-stranded DNA that was stretched by confinement to a channel with a diameter of 125 nm. The protein mobility shows a strong dependence on the internal motion of DNA in that slower motion results in faster protein diffusion. A model of released diffusion is proposed that is based on three-dimensional diffusion through the interior of the DNA coil interspersed by periods in which the protein is immobilized in a bound state. We surmise that the coupling between DNA internal motion and protein mobility has important implications for DNA metabolism and protein-binding-related regulation of gene expression.

Interactions between DNA and the Hfq Amyloid-like Region Trigger a Viscoelastic Response.

Molecular transport of biomolecules plays a pivotal role in the machinery of life. Yet, this role is poorly understood due the lack of quantitative information. Here, the role and properties of the C-terminal region of Escherichia coli Hfq is reported, involved in controlling the flow of a DNA solution. A combination of experimental methodologies has been used to probe the interaction of Hfq with DNA and to measure the rheological properties of the complex. A physical gel with a temperature reversible elasticity modulus is formed due to the formation of noncovalent cross-links. The mechanical response of the complexes shows that they are inhomogeneous soft solids. Our experiments indicate that the Hfq C-terminal region could contribute to the genome's mechanical response. The reported viscoelasticity of the DNA-protein complex might have implications for cellular processes involving molecular transport of DNA or segments thereof.

Charge stabilization via electron exchange: excited charge separation in symmetric, central triphenylamine derived, dimethylaminophenyl-tetracyanobutadiene donor-acceptor conjugates.

Photoinduced charge separation in donor-acceptor conjugates plays a pivotal role in technology breakthroughs, especially in the areas of efficient conversion of solar energy into electrical energy and fuels. Extending the lifetime of the charge separated species is a necessity for their practical utilization, and this is often achieved by following the mechanism of natural photosynthesis where the process of electron/hole migration occurs distantly separating the radical ion pairs. Here, we hypothesize and demonstrate a new mechanism to stabilize the charge separated states via the process of electron exchange among the different acceptor entities in multimodular donor-acceptor conjugates. For this, star-shaped, central triphenylamine derived, dimethylamine-tetracyanobutadiene conjugates have been newly designed and characterized. Electron exchange was witnessed upon electroreduction in conjugates having multiple numbers of electron acceptors. Using ultrafast spectroscopy, the occurrence of excited state charge separation, and the effect of electron exchange in prolonging the lifetime of charge separated states in the conjugates having multiple acceptors have been successfully demonstrated. This work constitutes the first example of stabilizing charge-separated states via the process of electron exchange.

Evolution of Interactions in the Protein Solution As Induced by Mono and Multivalent Ions.

The evolution of interactions in the bovine serum albumin (BSA) protein solution on addition of mono and multivalent (di, tri and tetra) counterions has been studied using small-angle neutron scattering (SANS), dynamic light scattering (DLS) and ζ-potential measurements. It is found that in the presence of mono and divalent counterions, protein behavior can be well explained by DLVO theory, combining the contributions of screened Coulomb repulsion with the van der Waals attraction. The addition of mono or divalent salts in protein solution reduces the repulsive barrier and hence the overall interaction becomes attractive, but the system remains in one-phase for the entire concentration range of the salts, added in the system. However, contrary to DLVO theory, the protein solution undergoes a reentrant phase transition from one-phase to a two-phase system and then back to the one-phase system in the presence of tri and tetravalent counterions. The results show that tri and tetravalent (unlike mono and divalent) counterions induce short-range attraction between the protein molecules, leading to the transformation from one-phase to two-phase system. The two-phase is characterized by the fractal structure of protein aggregates. The excess condensation of these higher-valent counterions in the double layer around the BSA causes the reversal of charge of the protein molecules resulting into reentrant of the one-phase, at higher salt concentrations. The complete phase behavior with mono and multivalent ions has been explained in terms of the interplay of electrostatic repulsion and ion-induced short-range attraction between the protein molecules.

Structure and Interaction of Nanoparticle-Protein Complexes.

The integration of nanoparticles with proteins is of high scientific interest due to the amazing potential displayed by their complexes, combining the nanoscale properties of nanoparticles with the specific architectures and functions of the protein molecules. The nanoparticle-protein complexes, in particular, are useful in the emerging field of nanobiotechnology (nanomedicine, drug delivery, and biosensors) as the nanoparticles having sizes comparable to that of living cells can access and operate within the cell. The understanding of nanoparticle interaction with different protein molecules is a prerequisite for such applications. The interaction of the two components has been shown to result in conformational changes in proteins and to affect the surface properties and colloidal stability of the nanoparticles. In this feature article, our recent studies exploring the driving interactions in nanoparticle-protein systems and resultant structures are presented. The anionic colloidal silica nanoparticles and two globular charged proteins [lysozyme and bovine serum albumin (BSA)] have been investigated as model systems. The adsorption behavior of the two proteins on nanoparticles is found to be completely different, but they both give rise to similar phase transformation from one phase to two phase in respective nanoparticle-protein systems. The presence of protein induces the short-range and long-range attraction between the nanoparticles with lysozyme and BSA, respectively. The observed phase behavior and its dependence on various physiochemical parameters (e.g., nanoparticle size, ionic strength, and solution pH) have been explained in terms of underlying interactions.

Enhancement in Elastic Bending Rigidity of Polymer Loaded Reverse Microemulsions.

Elastic bending rigidity of the surfactant shell is a crucial parameter which determines the phase behavior and stability of microemulsion droplets. For water-in-oil reverse microemulsions stabilized by AOT (sodium 1,4-bis(2-ethylhexoxy)-1,4-dioxobutane-2-sulfonate) surfactant, the elastic bending rigidity is close to thermal energy at room temperature (kBT) and can be modified by the presence of hydrophilic polymers. Here, we explore the influence of two polymers polyethylene glycol (PEG) and polyvinylpyrrolidone (PVP), both having nearly same size (radius of gyration, Rg) but different dipole moment, on elastic bending rigidity of water-AOT-n-decane reverse microemulsions via estimating the percolation temperatures (TP) and droplet radii using dielectric relaxation spectroscopy (DRS) and small-angle neutron scattering (SANS) techniques. Notably, an increase in TP is observed on introducing PEG and PVP polymers and is attributed to the adsorption of polymer chains onto the surfactant monolayer. The stability of the droplet phase of microemulsion after the incorporation of PEG and PVP polymers is confirmed by contrast matching SANS experiments. An enhancement in elastic bending rigidity of AOT surfactant shell amounting to ∼46% is observed upon incorporation of PVP into the droplet core, whereas for PEG addition, a smaller increase of about 17% is recorded. We conjecture that the considerable increase in elastic bending rigidity of the surfactant monolayer upon introducing PVP is because of the strong ion-dipole interaction between anionic AOT and dipoles present along the PVP polymer chains. Scaling exponents extracted from the temperature dependent electrical conductivity measurements and the frequency dependent scaling of conductivity at percolation indicate the dynamic nature of percolation for both pure and polymer loaded reverse microemulsions. The decrease in activation energy of percolation upon incorporating PEG and PVP polymer molecules also reflects the increased stability of microemulsion droplets against thermal fluctuations.