Single-Photon Deep-Red Light-Triggered Direct Release of an Anticancer Drug: An Investigative Tumor Regression Study on a Breast Cancer Spheroidal Tumor Model.

Breast adenocarcinoma ranks high among the foremost lethal cancers affecting women globally, with its triple-negative subtype posing the greatest challenge due to its aggressiveness and resistance to treatment. To enhance survivorship and patients' quality of life, exploring advanced therapeutic approaches beyond conventional chemotherapies is imperative. To address this, innovative nanoscale drug delivery systems have been developed, offering precise, localized, and stimuli-triggered release of anticancer agents. Here, we present perylenemonoimide nanoparticle-based vehicles engineered for deep-red light activation, enabling direct chlorambucil release. Synthesized via the reprecipitation technique, these nanoparticles were thoroughly characterized. Light-induced drug release was monitored via spectroscopic and reverse-phase HPLC. The efficacy of the said drug delivery system was evaluated in both two-dimensional and three-dimensional spheroidal cancer models, demonstrating significant tumor regression attributed to apoptotic cell death induced by efficient drug release within cells and spheroids. This approach holds promise for advancing targeted breast cancer therapy, enhancing treatment efficacy and minimizing adverse effects.

Site-Specific Conjugation of Bottlebrush Polymers to Therapeutic Protein via Bioorthogonal Chemistry.

Achieving efficient and site-specific conjugation of therapeutic protein to polymer is crucial to augment their applicability in the realms of biomedicine by improving their stability and enzymatic activity. In this study, we exploited tetrazine bioorthogonal chemistry to achieve the site-specific conjugation of bottlebrush polymers to urate oxidase (UOX), a therapeutic protein for gout treatment. An azido-functionalized zwitterionic bottlebrush polymer (N3-ZBP) using a "grafting-from" strategy involving RAFT and ATRP methods was synthesized, and a trans-cyclooctene (TCO) moiety was introduced at the polymer end through the strain-promoted azide-alkyne click (SPAAC) reaction. The subsequent coupling between TCO-incorporated bottlebrush polymer and tetrazine-labeled UOX using a fast and safe bioorthogonal reaction, inverse electron demand Diels-Alder (IEDDA), led to the formation of UOX-ZBP conjugates with a 52% yield. Importantly, the enzymatic activity of UOX remained unaffected following polymer conjugation, suggesting a minimal change in the folded structure of UOX. Moreover, UOX-ZBP conjugates exhibited enhanced proteolytic resistance and reduced antibody binding, compared to UOX-wild type. Overall, the present findings reveal an efficient and straightforward route for synthesizing protein-bottlebrush polymer conjugates without compromising the enzymatic activity while substantially reducing proteolytic degradation and antibody binding.

Inhibition of cancer cells by Quinoline-Based compounds: A review with mechanistic insights.

This article includes a thorough examination of the inhibitory potential of quinoline-based drugs on cancer cells, as well as an explanation of their modes of action. Quinoline derivatives, due to their various chemical structures and biological activity, have emerged as interesting candidates in the search for new anticancer drugs. The review paper delves into the numerous effects of quinoline-based chemicals in cancer progression, including apoptosis induction, cell cycle modification, and interference with tumor-growth signaling pathways. Mechanistic insights on quinoline derivative interactions with biological targets enlightens their therapeutic potential. However, obstacles such as poor bioavailability, possible off-target effects, and resistance mechanisms make it difficult to get these molecules from benchside to bedside. Addressing these difficulties might be critical for realizing the full therapeutic potential of quinoline-based drugs in cancer treatment.

Design of saccharide based organic binder for low-grade iron ore pelletization using atomistic simulations and machine learning methods.

Inorganic binders like bentonite, used for pelletization of low-grade iron ore, generate iron ore slimes with comparatively high silica and alumina content necessitating extra steps for their removal during iron making process. This demands the usage of organic binders as full or partial replacement of bentonite for iron ore pelletization. In this work, adsorption of organic binders with saccharides skeleton and -H, -OH, -CH2OH and -CH2CH2OH as polar substituents, on goethite surface was studied using density functional theory, molecular dynamics and machine learning. It was observed that adsorption energy of binders on goethite surface had weak dependence on number of hydrogen bonds between them. With this favorable interaction in mind, a library containing 64 organic binders was constructed and adsorption energy of 30 of these binders was computed using molecular dynamics, followed by training of a linear regression model, which was then used to predict the adsorption energy of rest of the binders in the library. It was found that the introduction of -CH2CH2OH at R2 position resulted in statistically significant higher adsorption energy. Binder34 and Binder44 were identified as viable candidates for both goethite and hematite ore pelletization and adsorption of their n-mers on goethite and hematite surfaces was also quantified.

Surface Charge-Switchable Antifouling Block Copolymer with Bacteriostatic Properties.

Zwitterionic polymers are an emerging family of effective, low-fouling materials that can withstand unintended interactions with biological systems while exhibiting enhanced activity in bacterial matrix deterioration and biofilm eradication. Herein, we modularly synthesized an amphiphilic block copolymer, ZABCP, featuring potential bacteriostatic properties composed of a charge-switchable polyzwitterionic segment and a redox-sensitive pendant disulfide-labeled polymethacrylate block. The leucine-appended polyzwitterionic segment with alternatively positioned cationic amine and anionic carboxylate functionalities undergoes charge alterations (+ve → 0 → -ve) on pH variation. By introducing appropriate amphiphilicity, ZABCP forms distinct vesicles with redox-sensitive bilayer membranes and zwitterionic shielding coronas, enabling switching of surface charge. ZABCP vesicles exhibit 180 ± 20 nm hydrodynamic diameter, and its charge switching behavior in response to pH was confirmed by the change of zeta potential value from -23 to +36 mV. The binding interaction between ZABCP vesicles with lysozyme and pepsin proteins strengthens when the surface charge shifts from neutral (pH 7.4) to either anionic or cationic. This surface-charge-switchable phenomenon paves the way for implementing cationic ZABCP vesicles for bacterial cell growth inhibition, which is shown by the pronounced transition of cellular morphology, including clustering, aggregation, or elongation as well as membrane disruption for both Bacillus subtilis (Gram-positive) and Escherichia coli (Gram-negative). Such enhanced bacteriostatic activity could be ascribed to a strong electrostatic interaction between cationic vesicles and negatively charged bacterial membranes, leading to cell membrane disruption. Overall, this study provides a tailor-made approach to adopt low-fouling properties and potential bacteriostatic activity using zwitterionic polymers through precise control of pH.

Metal catalyst-free selective acetosyringone synthesis from rice straw lignin.

In recent decades, due to abundance (second most abundant natural polymer after cellulose) and sustainability, lignin has attracted much interest from different researchers to use as a raw material for producing various value-added materials such as polymer and fuel. In addition to that, the aromatic structure of lignin makes it a suitable candidate for producing platform chemicals with aromatic rings. As a result, lignin depolymerization has become an interesting process to derive different phenolic monomers like vanillin, acetosyringone, and guaiacol. Among them, due to the bioactive characteristics and efficiency of acetosyringone in plant regulatory systems, the production of acetosyringone from lignin has been presented in this work. A green and cost-effective method was developed for the selective formation of acetosyringone via depolymerization of isolated rice straw lignin (RSL) by using metal catalyst-free conditions in the biphasic medium and described. The RSL was characterized with various spectroscopic techniques such as FT-IR, solid-state 13C NMR, XPS, and TGA. The selectivity of synthesized acetosyringone during depolymerization of RSL was checked from GC-MS analysis. The molecular structure and purity of acetosyringone isolated from preparative thin layer chromatography (TLC) were confirmed with the help of 1H NMR and HRMS, respectively.

Facile fabrication and application of highly efficient reduced graphene oxide (rGO)-wrapped 3D foam for the removal of organic and inorganic water pollutants.

The pace of water contamination is increasing daily due to expanding industrialisation. Finding a feasible solution for effectively remediating various organic and inorganic pollutants from large water bodies remains challenging. However, a nano-engineered advanced hybrid material could provide a practical solution for the efficient removal of such pollutants. This work has reported the development of a highly efficient and reusable absorbent comprising a porous polyurethane (PU) and reduced graphene oxide (rGO) nanosheets (rGOPU) for the removal of different organic oils (industrial oil, engine oil and mustard oil), dyes (MB, MO, RB, EY and MV) and heavy metals (Pb(II), Cr(VI), Cd(II), Co(II) and As(V)). The structure, morphology and properties of the rGOPU hybrid absorbents were analysed by using Raman spectroscopy, field emission scanning electron microscopy (FESEM), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA) and Brunner-Emitte-Teller (BET) analysis. The rGOPU possessed both superhydrophobicity and superoleophilicity with water and oil contact angles of about 164° and 0°, respectively. The prepared rGOPU has demonstrated an excellent oil-water separation ability (up to 99%), heavy metals removal efficiency (more than 75%), toxic dye adsorption (more than 55%), excellent recyclability (> 500 times for oils), extraordinary mechanical stability (90% compressible for > 1000 cycles) and high recoverability. This work presents the first demonstration of rGOPU's multifunctional absorbent capacity in large-scale wastewater treatment for effectively removing a wide variety of organic and inorganic contaminants.

Comparing Pharmacological Potential of Freshwater Microalgae Carotenoids Towards Antioxidant and Anti-proliferative Activity on Liver Cancer (HUH7) Cell Line.

Chemical-based carotenoids have large implications to health as they may cause adverse side effects. Naturally occurring carotenoids mainly from microalgal sources are emerging as excellent substitute to combat cancer diseases. Astaxanthin is the most powerful antioxidant that derived from selected established microalgae with limited yield. Microalgal bioprospecting may provide the high-yielding sources for astaxanthin production. Hence, in the present research, freshwater microalgae Monoraphidium sp. (NCM no. 5585) and Scenedesmus obliquus (NCM no. 5586) were chosen to explore the unique potential of producing astaxanthin. Identification of bioactive metabolites in extracted carotenoid was analyzed through HPLC. Astaxanthin is identified as a major bioactive metabolite in both carotenoid fraction and ß carotene only in Scenedesmus obliquus. Antioxidant potential of microalgal carotenoids was obtained by 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and Ferric-reducing antioxidant power (FRAP) assay. The anti-proliferation activity of the extracted carotenoid from Monoraphidium sp. and Scenedesmus obliquus was evaluated against hepatocellular liver carcinoma cell line HUH7 by 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) colorimetric assay. Higher astaxanthin in Monoraphidium sp. leads to boosted antioxidant and anti-proliferation activity contrary to Scenedesmus obliquus that possess both astaxanthin and ß carotene. Though freshwater microalgae have a huge potential to create beneficial metabolites like carotenoids, they are rarely studied in the pharmaceutical industry. This work was the first to investigate the anti-proliferative activity of Monoraphidium sp. and Scenedesmus obliquus carotenoid fraction on the HUH7 hepatocarcinoma cell line.

Development of silver nanoparticles and aptamer conjugated biosensor for rapid detection of E. coli in a water sample.

A simple, rapid, and sensitive electrochemical biosensor based on a screen-printed carbon electrode (SPCE) was developed for onsite detection of E. coli in real time. This work analyzed the effect of aptamer conjugation and PBS buffer solution on the colloidal stability of the silver nanoparticles (AgNPs). Aggregations of the AgNPs after aptamer conjugation in PBS buffer were observed from the particle size distribution analysis. The AgNP-aptamer conjugation and its affinity towards E. coli (DH5α) were confirmed by UV-visible spectrophotometry, which showed a linear increment in the absorption with increasing E.coli concentration. The screen-printed carbon electrodes were modified by drop-casting of AgNPs, which were used as an effective immobilization platform for E. coli-specific aptamers. The modified electrode's surface modification and redox behavior were characterized using cyclic voltammetry. Finally, E. coli was detected using differential pulse voltammetry with an optimized incubation time of 15 min. The developed biosensors showed a linear decrease in current intensity with an increase in the concentration of E. coli. The biosensor had a relative standard deviation (RSD) of 6.91% (n = 3), which showed good reproducibility. The developed biosensors are highly sensitive and have a limit of detection (LOD) as low as 150 CFU/ml. The biosensor showed good selectivity for E.coli coli when comparing the signal response obtained for bacteria other than E.coli. Also, the biosensor was found stable for four weeks at room temperature and showed high recoveries from 95.27% to 107% during the tap water sensitivity validation.

Multifunctional CdS Nanoparticle-Decorated CeO2 as Efficient Visible Light Photocatalysts and Toxic Cr(VI) Sensors.

Several one-dimensional and three-dimensional CdS@CeO2 nanocomposites were synthesized by a solvothermal route. A nanoflower-shaped CdS@CeO2 nanocomposite (CdS-NF@CeO2) was selected as the model catalyst after various characterizations. It was, then, employed directly as a luminescent sensor for Cr(VI) detection in an aqueous medium. A good linear quenching was observed in the range of 0-0.5 µM with a detection limit of 0.04 µM. The quantum yield of the catalyst was found to be 73%. Moreover, our catalyst is highly selective toward Cr(VI) and can be applied as an efficient sensor for real water analysis. The efficiency of the catalyst was also tested in controlling the photocatalytic activity for oxidation of benzylamine to N-benzylidenebenzylamine under a domestic LED bulb with molecular O2 as a sole, green oxidant. Conversion (>99.9%) and selectivity as high as 100% were observed for the CdS-NF@CeO2 photocatalyst. These results show the potential applications of CdS-NF@CeO2 nanocomposites as an efficient photocatalyst for organic transformation and environmental remediation.

Current development of ß-carboline derived potential antimalarial scaffolds.

ß-Carboline alkaloids are an eminent class of nitrogen-based natural alkaloids and therapeutic molecules which exert various pharmacological activities through diverse mechanisms. A lot of attention has recently been directed towards this moiety in order to develop effective antimalarial drugs. "Malaria", an acute febrile illness caused by diverse Plasmodium parasites, is a continuing and escalating problem that devastates economically less developed countries by significantly increased morbidity and mortality rates. The mounting parasite resistance towards the antimalarial drugs and augmenting the 'habitat of the insect vector' are creating a catastrophe, indicating an urgent need for new efficacious therapeutics to combat this tropical disease. This article comprehensively encapsulates the clinical and preclinical antimalarial scaffolds comprising ß-carboline moiety in their structure. Herein, various classes of natural and semi-synthetic analogues of ß-carbolines reported in the last decade (2011-2021) have been extensively studied and illustrated. This review will help the readers to develop an insight into the ß-carboline based antimalarials and molecular mechanisms lying behind their mode of action, which is anticipated to be beneficial for the future development of new ß-carboline based therapeutics.

An Inbuilt Electronic Pawl Gates Orbital Information Processing and Controls the Rotation of a Double Ratchet Rotary Motor.

A direct external input energy source (e.g., light, chemical reaction, redox potential, etc.) is compulsory to supply energy to rotary motors for accomplishing rotation around the axis. The stator leads the direction of rotation, and a sustainable rotation requires two mutual input energy supplies (e.g., light and heat, light and pH or metal ion, etc.); however, there are some exceptions (e.g., covalent single bond rotors and/or motors). On the contrary, our experiment suggested that double ratchet rotary motors (DRMs) can harvest power from available thermal noise, kT, for sustainable rotation around the axis. Under a scanning tunneling microscope, we have imaged live thermal noise movement as a dynamic orbital density and resolved the density diagram up to the second derivative. A second input energy can synchronize multiple rotors to afford a measurable output. Therefore, we hypothesized that rotation control in a DRM must be evolved from an orbital-level information transport channel between the two coupled rotors but was not limited to the second input energy. A DRM comprises a Brownian rotor and a power stroke rotor coupled to a -C≡C- stator, where the transport of information through coupled orbitals between the two rotors is termed the vibrational information flow chain (VIFC). We test this hypothesis by studying the DRM's density functional theory calculation and variable-temperature 1H nuclear magnetic resonance. Additionally, we introduced inbuilt pawl-like functional moieties into a DRM to create different electronic environments by changing proton intercalation interactions, which gated information processing through the VIFC. The results show the VIFC can critically impact the motor's noise harvesting, resulting in variable rotational motions in DRMs.

Optimized EEG based mood detection with signal processing and deep neural networks for brain-computer interface.

Electroencephalogram (EEG) is a very promising and widely implemented procedure to study brain signals and activities by amplifying and measuring the post-synaptical potential arising from electrical impulses produced by neurons and detected by specialized electrodes attached to specific points in the scalp. It can be studied for detecting brain abnormalities, headaches, and other conditions. However, there are limited studies performed to establish a smart decision-making model to identify EEG's relation with the mood of the subject. In this experiment, EEG signals of 28 healthy human subjects have been observed with consent and attempts have been made to study and recognise moods. Savitzky-Golay band-pass filtering and Independent Component Analysis have been used for data filtration.Different neural network algorithms have been implemented to analyze and classify the EEG data based on the mood of the subject. The model is further optimised by the usage of Blackman window-based Fourier Transformation and extracting the most significant frequencies for each electrode. Using these techniques, up to 96.01% detection accuracy has been obtained.

A novel, efficient and economical alternative for the removal of toxic organic, inorganic and pathogenic water pollutants using GO-modified PU granular composite.

Multicomponent wastewater treatment utilising simple and cost-effective materials and methods is an important research topic. This study has reported the fabrication and utilisation of graphene oxide (GO) embedded granular Polyurethane (PU) (GOPU) adsorbent for the treatment of lead ion (Lead ion (Pb(II)), Methylene blue (MB), and E. coli. PU granules were wrapped with GO flakes to improve hydrophilicity, interaction with polluted water, cation-exchange reaction, and binding of pollutants on its surface. Synthesised GOPU granules were characterised by X-Ray Diffraction (XRD), Raman, Fourier transform infrared (FTIR) spectroscopy, and Scanning electron microscopy (SEM) analysis to ensure the successful synthesis of GO and fabrication of GOPU granules. Further, batch and continuous adsorption processes were studied in different operating conditions to evaluate the performance of GOPU granules in practical applications. The kinetic and isotherm analyses revealed that the adsorption of Lead (Pb(II)) ion and Methylene Blue (MB) dye followed the Freundlich and Langmuir isotherm models, respectively, and they showed good agreement with the Pseudo-second-order kinetic model. The adsorption capacities of GOPU granules for the elimination of Pb(II) and MB dye were about 842 mg/g and 899 mg/g, respectively. Additionally, investigations into the fixed bed column revealed that the adsorption column performed best at a flow rate of 5 mL/min and a bed height of 6 cm. Pb(II) adsorption had a bed uptake capacity (qbed) of 88 mg/g and percentage removal efficiency (%R) of 76%. Similarly, MB adsorption had a bed uptake capacity of 202 mg/g and a percentage removal efficiency of 71%. A systematic invention on antibacterial activity toward E. coli showed that The GOPU granules have a removal efficiency of about 100% at an exposure of 24 h. These findings indicated the possible use of GOPU granules as promising adsorbents for various water pollutants.

Synthesis of fused polycyclic ß-carboline derivatives using Ugi-4CR followed by cascade cyclization.

Ugi-four component reaction (Ugi-4CR) is extremely attractive for diversity-oriented and step economical synthesis as evident from past applications. Here we report the synthesis of fused polycyclic ß-carboline derivatives by sequential Pictet-Spengler's and Ugi-4CR multi-component reaction followed by cascade cyclization. The post cyclisation of Ugi product provides conformationally stable heterocyclic molecule that is expected to be suitable for interaction with different biological targets. The methodology provides a simple and facile access to heterocycles embedded in polycyclic framework which otherwise seems difficult to synthesize by conventional methods. Synthesis of fused Polycyclic ß-Carboline Derivatives Using Ugi-4CR Followed by Cascade Cyclization.

Ammonia from dinitrogen at ambient conditions by organometallic catalysts.

Fixation of atmospheric dinitrogen in plants by [Mo-Fe] cofactor of nitrogenase enzyme takes place efficiently under atmospheric pressure and normal temperature. In search for an alternative methodology for the highly energy intensive Haber-Bosch process, design and synthesis of highly efficient inorganic and organometallic complexes by mimicking the structure and function of [Mo-Fe] cofactor system is highly desirable for ammonia synthesis from dinitrogen. An ideal catalyst for ammonia synthesis should effectively catalyse the reduction of dinitrogen in the presence of a proton source under mild to moderate conditions, and thereby, significantly reducing the cost of ammonia production and increasing the energy efficacy of the process. In the light of current research, it is evident that there is a plenty of scope for the development and enhanced performance of the inorganic and organometallic catalysts for ammonia synthesis under ambient temperature and pressure. The review furnishes a comprehensive outlook of numerous organometallic catalysts used in the synthesis of ammonia from dinitrogen in the past few decades.

Inhibition and eradication of bacterial biofilm using polymeric materials.

Biofilms, ubiquitous in nature, are three-dimensional complex microbial communities sheathed in a self-secreted extracellular polymeric matrix. Infections caused by these communities have sprouted as serious threats to global healthcare systems due to their intrinsic tolerance toward conventional antibiotics. There is a huge demand for alternative "cutting-edge" materials featuring strong antibiofilm abilities to mitigate and/or exterminate pre-matured biofilms. Natural or synthetic macromolecule-based compounds have evolved as one of the most sought-after materials because of their unique stimulus-directed selective targeting efficiency to the bacterial cell, antibiotic-encapsulation ability endowing them with a synergistic effect, and highly dense embedded cationic functionalities that promote accumulation within the biofilm. In this comprehensive review, we aim to highlight the progress made in inhibiting or eradicating bacterial biofilms using various forms of polymeric material including cationic and charge-switchable macromolecules, conjugated polymers, polymeric metal nanocomposites, hydrogels, and supramolecular polymers. We particularly emphasize understanding the underlying antibiofilm mechanisms of each presented example ushered in by state-of-the-art synthetic strategies. Lastly, focusing on bench-to-bedside, the review is concluded by providing some forthcoming aspects and possible future development directions to expand polymer-based antibiofilm research, keeping their clinical translations in mind.

Selective recognition and extraction of arsenate by a urea-functionalized tripodal receptor from competitive aqueous media.

A second-generation hydrogen bond donor (HBD) anion receptor with an inner amide cavity and an outer urea cavity can selectively and efficiently extract arsenate (AsO43-) from water in the presence of competitive oxoanions and halides. The X-ray structure showed encapsulation of AsO43- in a π-stacked dimeric capsular assembly of the receptor, the first crystallography-based example of pentavalent AsO43- trianion recognition by a HBD receptor.

Stimuli-Responsive Aggregation-Induced Emission (AIE)-Active Polymers for Biomedical Applications.

At high concentration or in the aggregated state, most of the traditional luminophores suffer from the general aggregation-caused quenching (ACQ) effect, which significantly limits their biomedical applications. On the contrary, a few fluorophores exhibit an aggregation-induced emission (AIE) feature which is just the opposite of ACQ. The luminophores with aggregation-induced emission (AIEgens) have exhibited noteworthy advantages to get tunable emission, excellent photostability, and biocompatibility. Incorporating AIEgens into polymer design has yielded diversified polymer systems with fascinating photophysical characteristics. Again, stimuli-responsive polymers are capable of undergoing chemical and/or physical property changes on receiving signals from single or multiple stimuli. The combination of the AIE property and stimuli responses in a single polymer platform provides a feasible and effective strategy for the development of smart polymers with promising biomedical applications. Herein, the advancements in stimuli-responsive polymers with AIE characteristics for biomedical applications are summarized. AIE-active polymers are first categorized into conventional π-π conjugated and nonconventional fluorophore systems and then subdivided based on various stimuli, such as pH, redox, enzyme, reactive oxygen species (ROS), and temperature. In each section, the design strategies of the smart polymers and their biomedical applications, including bioimaging, cancer theranostics, gene delivery, and antimicrobial examples, are introduced. The current challenges and future perspectives of this field are also stated at the end of this review article.

A Novel Therapeutic Approach With Sodium Pyruvate on Vital Signs, Acid-Base, and Metabolic Disturbances in Rats With a Combined Blast and Hemorrhagic Shock.

Background: Blast injuries from improvised explosive devices (IEDs) are known to cause blast traumatic brain injuries (bTBIs), hemorrhagic shock (HS), organ damage, mitochondrial dysfunction, and subsequent free radical production. A pre-citric acid cycle reagent, pyruvate, is suggested to improve mitochondrial ATP production through the activation of the mitochondrial gatekeeper enzyme "pyruvate dehydrogenase complex (PDH)." Our study aimed to investigate the role of physiologic, metabolic, and mitochondrial effects of hypertonic sodium pyruvate resuscitation in rats with a combined blast and HS injury. Methods: A pre-clinical rat model of combined injury with repetitive 20 PSI blast exposure accompanied with HS and fluid resuscitation (sodium pyruvate as metabolic adjuvant or hypertonic saline as control), followed by transfusion of shed blood was used in this study. Control sham animals (instrumental and time-matched) received anesthesia and cannulation, but neither received any injury nor treatment. The mean arterial pressure and heart rate were recorded throughout the experiment by a computerized program. Blood collected at T0 (baseline), T60 (after HS), and T180 (end) was analyzed for blood chemistry and mitochondrial PDH enzyme activity. Results: Sodium pyruvate resuscitation significantly improved the mean arterial pressure (MAP), heart rate (HR), pulse pressure (PP), hemodynamic stability (Shock index), and autonomic response (Kerdo index) after the HS and/or blast injury. Compared with the baseline values, plasma lactate and lactate/pyruvate ratios were significantly increased. In contrast, base excess BE/( HCO 3 - ) was low and the pH was also acidotic <7.3, indicating the sign of metabolic acidosis after blast and HS in all animal groups. Sodium pyruvate infusion significantly corrected these parameters at the end of the experiment. The PDH activity also improved after the sodium pyruvate infusion. Conclusion: In our rat model of a combined blast and HS injury, hypertonic sodium pyruvate resuscitation was significantly effective in hemodynamic stabilization by correcting the acid-base status and mitochondrial mechanisms via its pyruvate dehydrogenase enzyme.