Physiological pH Research Articles

Buffering Donor Shuttles in Proton-Coupled Electron Transfer Kinetics for Electrochemical Hydrogenation of Hydroxyacetone to Propylene Glycol.

Electrochemical hydrogenation reactions demand rapid proton-coupled electron transfer at the electrode surface, the kinetics of which depend closely on pH. Buffer electrolytes are extensively employed to regulate pH over a wide range. However, the specific role of buffer species should be taken into account when interpreting the intrinsic pH dependence, which is easily overlooked in the current research. Herein, we report the electrochemical hydrogenation of hydroxyacetone, derived from glycerol feedstock, to propylene glycol with a faradaic efficiency of 56 ± 5% on a polycrystalline Cu electrode. The reaction activities are comparable in citrate, phosphate, and borate buffer electrolytes, encompassing different buffer identities and pH. The electrokinetic profile reveals that citrate is a site-blocking adsorbate on the Cu surface, thereby decreasing buffer concentration and increasing pH will enhance the reaction rate; phosphate is an explicit proton donor, which promotes the interfacial rate by increasing buffer concentration and decreasing pH, while borate is an innocent buffer, which can be used to investigate the intrinsic pH effect. Combined with in situ SEIRAS, we demonstrate that water is the primary proton source in citrate and borate electrolytes, reiterating the rationality of the proposed mechanism based on the microkinetic modeling. Our results emphasize the intrinsic complexity of the buffer system on the kinetic activity for electrocatalysis. It calls for special care when we diagnose the mechanistic pathway in buffer electrolytes convoluted by different buffer identities and pH.

The Respiratory Compensation Point: Mechanisms and Relation to the Maximal Metabolic Steady State.

At a point during the latter third of an incremental exercise protocol, ventilation begins to exceed the rate of clearance of carbon dioxide (CO2) at the lungs ( CO2). The onset of this hyperventilation, which is confirmed by a fall from a period of stability in end-tidal and arterial CO2 tensions (PCO2), is referred to as the respiratory compensation point (RCP). The mechanisms that contribute to the RCP remain debated as does its surrogacy for the maximal metabolic steady state of constant-power exercise (i.e., the highest work rate associated with maintenance of physiological steady state). The objective of this current opinion is to summarize the original research contributions that support and refute the hypotheses that: (i) the RCP represents a rapid, peripheral chemoreceptor-mediated reflex response engaged when the metabolic rate at which the buffering systems can no longer constrain the rise in hydrogen ions ([H+]) associated with rising lactate concentration and metabolic CO2 production is surpassed; and (ii) the metabolic rate at which this occurs is equivalent to the maximal metabolic steady state of constant power exercise. In doing so, we will shed light on potential mechanisms contributing to the RCP, attempt to reconcile disparate findings, make a case for its adoption for exercise intensity stratification and propose strategies for the use of RCP in aerobic exercise prescription.

Central nervous injury risk factors after endovascular repair of a thoracic aortic aneurysm with type B aortic dissection.

Aortic dissection is the deadliest disease of the cardiovascular system. Type B aortic dissection accounts for 30%-60% of aortic dissections and is mainly treated by endovascular repair of thoracic endovascular aneurysm repair (TEVAR). However, patients are prone to various complications after surgery, with central nervous system injury being the most common, which seriously affects their prognosis and increases the risk of disability and death. Therefore, exploring the risk factors of central nervous system injury after TEVAR can provide a basis for its prevention and control. To investigate the risk factors for central nervous system injury after the repair of a thoracic endovascular aneurysm with type B aortic dissection. We enrolled 306 patients with type B aortic dissection who underwent TEVAR at our hospital between December 2019 and October 2022. The patients were categorized into injury (n = 159) and non-injury (n = 147) groups based on central nervous system injury following surgery. The risk factors for central nervous system injury after TEVAR for type B aortic dissection were screened by comparing the two groups. Multivariate logistic regression analysis was performed. The Association between age, history of hypertension, blood pH value, surgery, mechanical ventilation, intensive care unit stay, postoperative recovery times on the first day after surgery, and arterial partial pressure of oxygen on the first day after surgery differed substantially (P < 0.05). Multivariate logistic regression analysis indicated that age, surgery time, history of hypertension, duration of mechanical ventilation, and intensive care unit stay were independent risk factors for central nervous system injury after TEVAR of type B aortic dissection (P < 0.05). For high-risk patients with central nervous system injury after TEVAR of type B aortic dissection, early intervention measures should be implemented to lower the risk of neurological discomfort following surgery in high-risk patients with central nervous system injury after TEVAR for type B aortic dissection.

Nature of TiO2–oligonucleotides interactions by atomistic molecular dynamics simulations

We used molecular dynamics simulations to investigate the adsorption behavior of single-stranded deoxyribonucleic acid (ssDNA) segments on the anatase (101) surface. Four different ssDNA oligonucleotides, each consisting of six/twelve adenine (A6 and A12), six guanine (G6), six cytosine (C6) or six/twelve thymine (T6 and T12) nucleobases, were considered. We observed that the initial interaction between the ssDNA and the surface occurs primarily through hydrogen bonding between the nucleobases and the surface, followed by strong chemical bonding between the terminal phosphate group and the anatase surface. The interactions between the nucleobases and the surface varied between the different ssDNA segments. Adenine showed the highest affinity for the surface, whereas thymine showed the lowest affinity. In addition, the purine bases interact more strongly when the surface is negatively charged (as it would be at physiological pH) than in neutral surface (slightly acidic conditions), in agreement with experimental data from fluorescence experiments and ATR-FTIR spectroscopy. Moreover, our study provides mechanistic insights into the dynamic behavior of ssDNA on the anatase surface and comparative analyses on how different conditions (pH, fragment length, composition, etc.) affect DNA/TiO2 interactions. Therefore, we expect that experimental scientists will benefit from our work in the design of optimal nanoconjugates for their specific final goals and applications.

Effects of higher dietary acid load: a narrative review with special emphasis in children.

Metabolic effects of high diet acid load (DAL) have been studied for years in adults, although only recently in children. Contemporary diets, especially those of Western societies, owe their acidogenic effect to high animal-origin protein content and low contribution of base-forming elements, such as fruits and vegetables. This imbalance, where dietary acid precursors exceed the body's buffering capacity, results in an acid-retaining state known by terms such as "eubicarbonatemic metabolic acidosis," "low-grade metabolic acidosis," "subclinical acidosis," or "acid stress". Its consequences have been linked to chronic systemic inflammation, contributing to various noncommunicable diseases traditionally considered more common in adulthood, but now have been recognized to originate at much earlier ages. In children, effects of high DAL are not limited to growth impairment caused by alterations of bone and muscle metabolism, but also represent a risk factor for conditions such as obesity, insulin resistance, diabetes, hypertension, urolithiasis, and chronic kidney disease (CKD). The possibility that high DAL may be a cause of chronic acid-retaining states in children with growth impairment should alert pediatricians and pediatric nephrologists, since its causes have been attributed traditionally to inborn errors of metabolism and renal pathologies such as CKD and renal tubular acidosis. The interplay between DAL, overall diet quality, and its cascading effects on children's health necessitates comprehensive nutritional assessments and interventions. This narrative review explores the clinical relevance of diet-induced acid retention in children and highlights the potential for prevention through dietary modifications, particularly by increasing fruit and vegetable intake alongside appropriate protein consumption.

Tailored amino acid-derived ionic Liquids: Precision chemotherapy for tumors

A set of fourteen imidazolium ionic liquids, each derived from L-amino acids and featuring distinct hydrophobic and hydrophilic components, were synthesized and physicochemically characterized. Thermal analysis showed transition temperatures remaining below 100 °C, being the rigid solid to elastic solid transition temperatures between −27 °C to + 57 °C. The aggregation studies investigated by fluorescence in water and buffered media showed two critical micellar concentrations (CMC) in aqueous media for compounds 7, 8 and 9, with the formation of well-defined aggregates in the second step. The synthesized ILs were assessed for their effects on two cancer cell lines, namely human lung adenocarcinoma A-549 and colon adenocarcinoma HT-29, under both physiological and acidic pH conditions. Furthermore, the influence of the ILs on embryonic kidney cells (HEK-293) was investigated to assess their effect on non-cancerous cells. This study demonstrates that the manipulation of various design vectors allowed for the precise tuning of the structure of ILs, resulting in IC50 values within the micromolar range. ILs featuring a NC12 alkyl side chain in the amide consistently exhibited low IC50 values and a high degree of selectivity against non-tumoral cells under acidic pH conditions. Subsequent investigations were carried out to gain insights into the cellular-level mechanisms of action. These findings provide strong evidence that by meticulously adjusting the molecular structure of these functionalized ILs, it is possible to design potent and selective chemotherapeutic agents.

Evaluation of mechanical properties and potential environmental applications of biomimetic mineralized composites

With the growing emphasis on environmental protection, there has been extensive research on new green cementitious materials suitable for different conditions. This study focuses on the influence of key environmental factors on proposed biomimetic mineralized composites (BMC) using polyacrylic acid (PAA) as a modifier, based on the biomimetic chemistry induced carbonate precipitation (BCICP) method. The environmental factors examined include the cementing matrices type, the magnesium ions concentration, and the cementing solution pH. The samples treated under various conditions were evaluated for their unconfined compressive strength (UCS) and calcium carbonate content, and their microstructure was characterized using scanning electron microscopy (SEM) and X-ray diffraction (XRD). The results demonstrate that the BMC treatment could achieve high-strength cementation for both Toyoura sand and Fujian quartz sand, with a more pronounced enhancement observed for Toyoura sand. Magnesium ions reduce the cementation effect, and they cannot fully replace calcium ions in participating in the cementation process. Moreover, the cementing solution pH significantly influences the cementation effect, with the best acid-base condition for PAA to modify BMC sand samples found at a pH of 11.5. Overall, the BMC exhibits high performance under various environmental conditions. These findings could provide valuable insights into the influence of environmental factors and the potential applications of BMC in diverse environments.

Therapeutic efficacy of Strobilanthes urticifolia-infused pectin/polyacrylic acid hydrogel for targeted hepatorenal fibrosis mitigation: A multifaceted biomaterial approach.

Pectin/polyacrylic acid (PPAA) hydrogel is a unique and versatile biomaterial with applications in drug delivery, wound healing, tissue engineering, and agriculture, owing to its tailored properties and multifunctional attributes. This study aims to harness the therapeutic potential of Strobilanthes urticifolia extract within a PPAA hydrogel matrix to attenuate liver and kidney fibrosis through targeted and sustained delivery of biologically active substances. PPAA hydrogel was prepared by free radical polymerization, followed by its porosity and swelling determination. The results depicted the porous nature of PPAA hydrogel and improved swelling properties at pH 7.4, confirming its drug delivery promise. The polyphenolic-enriched S. urticifolia extracts of leaf and flower were loaded onto PPAA hydrogel, and the loading efficiency was 87% (leaf) and 62.5% (flower). Moreover, slow-release studies showed controlled and prolonged release of polyphenols for 7 days. The polyphenolic-enriched hydrogel's microstructure was characterized using SEM, FTIR, and thermogravimetric analysis (TGA). SEM results revealed a highly porous structure of polyphenol enriched PPAA hydrogel, while FTIR analysis confirmed the presence of functional groups such as OH group of carboxylic acid, aliphatic CH2 stretching due to acrylic acid grafting with pectin, CO stretching due to acid linkage with pectin, CH of aromatic ring, and CH of carboxylate salt in PPAA hydrogel. TGA of PPAA hydrogel showed its stability up to 488°C. Additionally, the S. urticifolia extract loaded PPAA hydrogel displayed significant antibacterial properties and minimum inhibitory concentrations against both Gram-positive and Gram-negative bacteria. In vivo studies carried out on rats demonstrated that polyphenolic enriched PPAA hydrogel significantly attenuates liver and kidney fibrosis. Therefore, it is concluded from the present study that loading of polyphenolic enriched extract from leaves and flower of S. urticifolia enhanced the biomedical applications of PPAA hydrogel. RESEARCH HIGHLIGHTS: The PPAA hydrogel developed in this study exhibits a highly porous structure and improved swelling properties at physiological pH (7.4), making it an excellent candidate for drug delivery systems. S. urticifolia extracts, rich in polyphenols, were successfully incorporated into the PPAA hydrogel with high loading efficiencies of 87% for leaf and 62.5% for flower extracts. Loading of polyphenolic enriched extracts of S. urticifolia onto PPAA enhanced its biological activities such as antibacterial, hepatoprotective, and reno-protective activities as depicted by in vitro and in vivo studies.

One-Pot Detection of Proteins Using a Two-Way Extension-Based Assay with Cas12a.

Protein biomarkers are an important class of biomarkers in disease diagnosis and are traditionally detected by enzyme-linked immunosorbent assay and mass spectrometry, which involve multiple steps and a complex workflow. In recent years, many CRISPR-Cas12a-based methods for protein detection have been developed; however, most of them have not overcome the workflow complications observed in traditional assays, limiting their applicability in point-of-care testing. In this work, we designed a single-step, one-pot, and proximity-based isothermal immunoassay integrating CRISPR Cas12a for homogeneous protein target detection with a simplified workflow and high sensitivity. Probes consisting of different binders (small molecule, aptamer, and antibody) conjugated with oligonucleotides undergo two-way extension upon binding to the protein targets, leading to downstream DNA amplification by a pair of nicking enzymes and polymerases to generate target sequences for Cas12a signal generation. We used the streptavidin-biotin model to demonstrate the design of our assay and proved that all three elements of protein detection (target protein binding, DNA amplification, and Cas12a signal generation) could coexist in one pot and proceed isothermally in a single buffer system at a low reaction volume of 10 μL. The plug-and-play applicability of our assay has been successfully demonstrated using four different protein targets, streptavidin, PDGF-BB, antidigoxigenin antibody, and IFNγ, with the limit of detection ranging from fM to pM.

Storage Media for Dental Avulsion: A Literature Review

Tooth avulsion is a critical dental emergency where immediate and appropriate management is essential for the successful reimplantation of the tooth. The choice of storage medium during the extra-alveolar period significantly impacts the viability of periodontal ligament (PDL) cells, crucial for the long-term retention of the replanted tooth. This review examines various storage media proposed for avulsed teeth, assessing their pH, osmolality, and overall efficacy in maintaining PDL cell viability. A comprehensive literature search was conducted across databases including PubMed, Scopus, and Google Scholar, identifying media such as Hank’s Balanced Salt Solution (HBSS), milk, saline, propolis, coconut water, and more. Ideal storage media should exhibit antimicrobial properties, maintain physiological osmolality and pH, support PDL cell viability, and be readily available. HBSS is highlighted as the gold standard, with its ability to preserve PDL cells for up to 48 hours. Other effective media like milk, soy milk, and oral rehydration solutions are discussed for their accessibility and performance. Emerging media such as propolis and epigallocatechin-3-gallate show promise but require further research. This review emphasizes the importance of public awareness and accessibility to effective storage media to improve the prognosis of avulsed teeth. Keywords: Storage Media, Dental Avulsion, PDL viability.

A Water-Soluble Multifunctional Probe for Colorimetric Copper Sensing, Lysosome Labelling and Live-Cell Imaging.

We report a water-soluble fluorescence and colorimetric copper probe (LysoBC1); this system can also serve for lysosome labeling and for the dynamic tracking of Cu2+ in living cells. The sensing mechanism takes advantage of the synergic action by the following three components: i) a lysosome targeting unit, ii) the spirolactam ring-opening for the selective copper chelation and iii) the metal-mediated hydrolysis of the rhodamine moiety for fluorescence enhancement. In aqueous environment the molecule acts as a fluorescent reversible pH sensor and as colorimetric probe for Cu2+ at physiological pH; the hydrolysis of the copper targeting unit resulted in a 50-fold increase of the fluorescence intensity. Most importantly, in vitro cell analyses in undifferentiated (SH SY5Y) and differentiated (d-SH SY5Y) neuroblastoma cells, LysoBC1 is able to selectively accumulate into lysosome while the copper binding ability allowed us to monitor intracellular copper accumulation into lysosome.

Cord Blood pH and Lactate- A Step Ahead in Diagnosis of Fetal Acidaemia in Patients with Abnormal Cardiotocography

OBJECTIVES: Electronic fetal monitoring (EFM) is used to identify early signs of fetal deterioration. However, caution is advised when interpreting cardiotocographic parameters. A promising alternative is umbilical cord blood sampling. The analysis of blood gases and lactate levels in the cord within the ini-tial minutes of life is a recommended approach. STUDY DESIGN: This prospective cohort study, conducted over eighteen months from June 2021 to December 2022, enrolled 70 patients with non-reactive and 70 with reactive cardiotocograph (CTG) pat-terns. APGAR scores were recorded at 1 and 5-minute intervals. 1 ml of umbilical artery blood was as-sessed in an arterial blood gas machine and fetal acidosis was defined as pH &lt;7.0 and a lactate con-centration exceeding 4 mmol/L. RESULTS: In the non-reactive CTG group, 35.7% had early decelerations, 37.1% had variable decel-erations, and 17.1% had late decelerations (p&lt;0.001). The mean cord blood lactate was 5.220±1.970 mmol/L in the non-reactive CTG group and 3.400±0.228 mmol/L in the reactive CTG group. Similarly, the mean cord blood pH was 7.030±0.007 in the non-reactive CTG group and 7.170±0.076 in the reac-tive CTG group (p&lt;0.001). 14.3% of cases in the non-reactive CTG group had a 5-minute APGAR &lt;7, with a higher APGAR score in the reactive group. CONCLUSION: The study suggests that abnormal or indeterminate CTG readings are linked to a higher risk of intrapartum fetal acidosis. Non-reactive CTG results were associated with higher mean cord blood lactate and pH levels and more number of Neonatal Intensive Care Unit (NICU) admissions. There is a definite correlation between abnormal CTG patterns and poorer neonatal outcomes.

Clinical implications of a Couvelaire uterus with placental abruption: A retrospective study.

This study aimed to clarify the maternal and neonatal outcomes based on the presence or absence of a Couvelaire uterus with placental abruption. This single-center retrospective study was conducted at a tertiary perinatal center in Japan, including patients diagnosed with acute placental abruption who delivered live births via cesarean section between 2016 and 2023. Patients were divided into two groups based on the presence or absence of a Couvelaire uterus during surgery: the Couvelaire and normal uterus groups. Maternal and neonatal outcomes were assessed. This study included 76 patients: 24 in the Couvelaire group and 52 in the normal uterus group. No patients underwent hysterectomies. The Couvelaire group had significantly higher intraoperative blood loss (median 1152 vs 948 g, P = 0.010), blood transfusion rates (58% vs 31%, P = 0.022), fibrinogen administration rates (38% vs 13%, P = 0.038), intensive care unit/high care unit admission rates (29% vs 7.7%, P = 0.013), and disseminated intravascular coagulation complication rates (25% vs 7.7%, P = 0.038). There were no differences in birth weight, gestational age (median 2387 vs 2065 g, P = 0.082), Apgar score <4 at 5 min (4.2% vs 3.9%, P = 0.95), umbilical artery blood pH <7.1 (25% vs 22%, P = 0.82), and neonatal death (4.2% vs 1.9%, P = 0.57). A Couvelaire uterus indicated adverse maternal outcomes but not neonatal ones. Its presence necessitates preparation for blood transfusions and/or intensive patient follow-up.

Dual Mode Ratiometric Analysis of Cu2+ and Ni2+ Ions at Physiological pH: Effect of Signalling Units on Analytical Efficacy

AbstractHerein, we report the metal ion sensing property of two 2,2’‐bis (pyridylmethyl) amine‐based chromogenic probes at physiological pH in buffered media. The binding of metal ions to the bispicolyl site alters its electronic property, which subsequently influences the optical property of the covalently‐linked signaling unit. The compound experienced a change in the solution color from red to deep and light yellow respectively upon the addition of Cu2+ and Ni2+ ions. Further, it is observed that by modifying the signaling unit, one can tune the mode of metal ion binding and sensitivity. The compound with an electron‐deficient quinolinium unit as the signaling moiety, showed 2 : 1 stoichiometry of binding with metal ions, while the compound functionalized with a pyrene unit formed complexes with 1 : 1 stoichiometry. It was conferred that changes in the signaling moiety not only alter the basicity/nucleophilicity of the pyridine nitrogen ends but also influence their aggregation properties. Such kind of studies will be beneficial for engineering new optical probes with tuneable sensitivity.

Pathophysiological role of ion channels and transporters in hepatocellular carcinoma.

The incidence of hepatocellular carcinoma (HCC) has continued to increase annually worldwide, and HCC has become a common cause of cancer-related death. Despite great progress in understanding the molecular mechanisms underlying HCC development, the treatment of HCC remains a considerable challenge. Thus, the survival and prognosis of HCC patients remain extremely poor. In recent years, the role of ion channels in the pathogenesis of diseases has become a hot topic. In normal liver tissue, ion channels and transporters maintain water and electrolyte balance and acid‒base homeostasis. However, dysfunction of these ion channels and transporters can lead to the development and progression of HCC, and thus these ion channels and transporters are expected to become new therapeutic targets. In this review, ion channels and transporters associated with HCC are reviewed, and potential targets for new and effective therapies are proposed.

Microfluidic aerosol-assisted synthesis of gefitinib anticancer drug nanocarrier based on chitosan natural polymer

An aerosol-assisted approach was devised to synthesize gefitinib anticancer drug-loaded chitosan nanocarriers (GefNCs). The nanocarrier synthesis involves mixing and interacting gefitinib molecules with chitosan natural polymer within a microfluidic chip. The combination was nebulized with an on-chip integrated micropneumatic nebulizer with N2 as the nebulizer gas. The aerosol was collected in a beaker containing a glutaraldehyde cross-linking agent while magnetically stirring. The chip was created by CO2 laser engraving on polymethyl methacrylate sheets. The synthesized GefNCs were characterized using FTIR, DLS, FESEM, and TEM. The FESEM images revealed a nanoparticle size distribution of 18.5 ± 4.6 nm. After adjusting numerous experimental parameters such as chip design, polymer concentration, solution flow rate, and nebulizer gas flow rate, the synthesized nanocarrier's release mechanism was investigated using various kinetic models. The results demonstrated that the release behavior of GefNCs is pH-sensitive and greater at acidic pH values than physiological pH, making the synthesized nanocarrier a potential for targeted gefitinib delivery to cancer cells. Furthermore, the kinetic studies revealed that the drug's release mechanism best matches Fick's diffusion rule. Under optimal conditions, the encapsulation efficiency was 77.8 %. The cytotoxicity of the produced nanocarrier was investigated on the A549 non-small cell lung carcinoma. The MTT test revealed that the produced nanocarrier had a lower IC50 than the free medication. Furthermore, cytotoxicity experiments on empty nanocarriers revealed that the materials utilized to synthesize nanocarriers have no appreciable cytotoxicity. The developed microfluidic-assisted approach provides a quicker synthesis procedure with a high encapsulation efficiency.

Nanodroplets Engineered with Folate Carbon Dots for Enhanced Cancer Cell Uptake toward Theranostic Application.

The research in nanotherapeutics is rapidly advancing, particularly in the realm of nanoconstructs for drug delivery. This study introduces folate-based carbon dot-decorated nanodroplets (f-Dnm), synthesized from a binary mixture of negatively charged folic acid carbon dots (f-CDs) and cationic-branched polyethylenimine (PEI). The uniformly spherical nanodroplets with an average diameter of 115 ± 15 nm exhibit notable photoluminescence. Surface potential analysis reveals a significant change upon coacervation, attributed to strong electrostatic interactions between f-CD and PEI. The engineered nanodroplets show excellent colloidal and photostability even after 6 months of storage at room temperature. The pH-dependent self-assembly and disassembly properties of f-Dnm are explored for drug loading and release studies using doxorubicin (DOX) as a model anticancer drug. Moreover, the f-Dnm nanocarrier demonstrates significantly higher drug loading capabilities (∼90%). In vitro release studies of doxorubicin-loaded f-Dnm [f-Dnm(DOX)] reveal 5 times higher drug release at lysosomal pH 5.4 compared to that at physiological blood pH 7.4. Cytocompatibility assessments using the MTT assay on HeLa, A549, and NIH-3T3 cells confirm the nontoxic nature of f-Dnm, even at high concentrations. Additionally, f-Dnm(DOX) exhibits higher cytotoxicity in HeLa cells compared to f-CD(DOX) at similar DOX concentrations. Cellular uptake studies show an increased uptake of f-Dnm in folate receptor-positive HeLa and MDA-MB 231 cells. Hemolysis assay validated the biocompatibility of the developed formulation. Overall, these engineered nanodroplets represent a class of nontoxic nanocarriers that offer promising potential as nanotherapeutics for folate receptor-positive cells.

Negative dietary cation and anion difference supplementation of twin-bearing Merino ewes grazing pasture in late gestation did not affect lamb growth or survival.

Each year in Australia, 53% of lamb mortalities are attributed to dystocia, with subclinical maternal calcium deficiencies likely contributing to dystocia rates. A negative dietary cation and anion difference (DCAD) diet has increased circulating calcium in sheep. Therefore, this study aimed to investigate the effects of supplementing twin-bearing, grazing ewes with a negative DCAD partial mixed ration (PMR) during late gestation on ewe calcium and magnesium concentrations and subsequent lamb growth and survival. On day 120 of gestation (dG), blood samples were collected from 115 twin-bearing Merino ewes and analysed for glucose, ketone bodies, pH, ionised calcium, and serum calcium and magnesium. On dG 130, ewes were moved into lambing paddocks and placed in the following two treatment groups; ewes receiving a positive DCAD PMR (DCAD = 287 mEq/kg DM; n = 58) and ewes receiving a negative DCAD PMR (DCAD = - 125 mEq/kg DM; n = 57) fed as a partial mixed ration. On dG 140, a blood and urine sample were collected. The urine was tested for pH. Pasture samples were taken on dG 133 and 149 and tested for DCAD and mineral content. When a lamb was 6 - 18h old, survival, vigour score, liveweight, rectal temperature, blood glucose and body morphology were recorded. At 10 d of age, lamb liveweight and survival were recorded and a milk sample was collected from ewes. At 44 d of age, lamb liveweight and survival were recorded. The DCAD of the pastures across the six paddocks ranged from 598 - 893 mEq/kg DM. There were no differences in lamb survival, weight or viability at any timepoint (P > 0.05). There were no differences in mineral status, metabolic state or acid-bae balance between the positive and negative DCAD supplemented ewes (P > 0.05) during supplementation (dG 140). Supplementing a negative DCAD diet to ewes grazing pasture during late gestation did not improve lamb survival. The blood and urine pH of the negative DCAD supplemented ewes indicated a mild metabolic acidosis was not reached due to the high DCAD of the pastures. Further research needs to take careful consideration of the DCAD of pasture when designing a negative DCAD supplement in order for it to be effective.

Enhancing Therapeutic Efficacy of Cerium Oxide Nanoparticles (CNP) Conjugated with S-Nitroso-N-acetyl Penicillamine for Multifunctional Biomedical Applications

Nanoparticles are extensively used because their small size, unique orientation, and distinct physical properties can significantly modify the behavior of the materials they interact with. Cerium oxide nanoparticles (CNP) also known as nanoceria are gaining popularity in a multitude of sectors, including Biomedical science as drug delivery, therapeutics, and enzyme mimetics. Nanoceria are preferred over typical antioxidants or enzymes because they can scavenge numerous types of free radicals. Studies such as In vitro and in vivo methods have shown that nanoceria may be employed as a carrier for targeted medication and gene delivery. Nanoceria works as an antioxidant therapeutics in healthy cells by scavenging ROS (at physiological pH) free radicals. Furthermore, S-Nitroso-N-acetyl penicillamine (SNAP), a nitroso thiol derivative, releases nitric oxide (NO) under physiological conditions. This makes SNAP a valuable tool for researching the pharmacological and physiological effects of NO. The conjugation of CNP and SNAP along with bacterial cellulose enhances its antimicrobial, SOD, and antidiabetic activities. CNP was synthesized using the Wet chemistry method and optimized using a UV/Vis Spectrophotometer. Further, the conjugate solution was characterized by UV-Vis (i.e., within the range of 230-280 nm) and SEM shows a perfect conjugate solution by its morphology and elements. The anti-microbial activity was administered, and a moderate zone was observed. The zone of inhibition activity was shown 4 mm against gram-negative bacteria and 7 mm against gram-positive bacteria. The conjugate solution examined cellular viability of approximately 50.6 % in HACAT cells which shows less toxicity. These observations concluded that the procedure for nanoparticle synthesis is advantageous and synthesized nanomaterial was found to be highly Antioxidative.

Electrochemical Determination of Cyclobenzaprine Hydrochloride Muscle Relaxant Using Novel S-GCN/TiO2-Based Carbon Electrode.

We have successfully prepared the titanium dioxide (TiO2) nanoparticles (NPs) and sulfur-incorporated graphitic carbon nitride (S-GCN)-modified carbon paste electrode (CPE). The CPEs modified with TiO2 NPs and S-GCN were employed for detecting and quantifying the skeletal muscle relaxant cyclobenzaprine hydrochloride (CBP) using cyclic voltammetry and square wave voltammetry (SWV) techniques. Optimal electrochemical conditions were indicated by the pH study results, with the highest peak current observed at a physiological pH of 7.4. The electrochemical process was determined to involve an equivalent number of protons (H+) and electrons (e-). The concentration variation of CBP (ranging from 0.06 to 10 × 10-7 mol L-1) was explored using SWV. The limits of detection and quantification were determined as 6.4 × 10-9 and 2.1 × 10-8 M, respectively. The proposed electrode configuration was applied to analyze real samples, including water, biomedical, and pharmaceutical specimens.