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Calcium sulphate (plaster of Paris) has been used since 1892 to fill bone defects and as a good bone graft substitute. Calcium sulphate is an osteoconductive, inorganic substance. Following 75 years, many other authors reported variable and a better result in grafting of bone defects and in several cases of immediate and delayed dental implants for good osseointegrations, with no complications attributed to the calcium sulphate. Early results were variable, because of its conflicting crystalline structure, purity, and quality of the calcium sulphate. Apart from this, calcium sulphate also shows predictable resorption rate in vivo, presence of minimal trace elements and extremely uniform crystalline structure. Calcium sulphate is a bio-inert material and get resorbed over a period of weeks and fibrovascular tissue takes its place which eventually allows neovascularization and bone formation within the area. Use During the conventional surgical treatment addition of calcium sulphate as a bone graft of in case of placement of dental implants and pathological bony defects it improves the clinical outcome. Calcium sulphate also act as a barrier and filling material for the treatment of "through and through" bony lesions. Use of calcium sulphate as a bone graft substitute avoids the complications and morbidity associated with autograft like infection, second surgery.

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Objective: To assess the efficacy and safety of colistin sulfate in treating infections caused by carbapenem-resistant organisms (CRO) and to analyze potential factors impacting its effectiveness. Methods: In this retrospective study, medical records of CRO-infected patients from June 2020 to June 2023 were analyzed, divided into effective and ineffective treatment groups, and compared for clinical outcomes and adverse reactions. Multifactorial logistic regression and ROC curve analysis were used to identify influencing factors. Results: The study included 226 patients, with 124 in the effective treatment group and 102 in the ineffective group. A total of 293 CRO strains were cultured. The clinical efficacy rate of colistin sulfate was 54.87%, the microbiological efficacy rate 46.46%, and the hospital mortality rate 20.80%, with nephrotoxicity observed in 11.50% of patients. Multifactorial analysis identified APACHE II scores and vasoactive drug use as independent predictors of ineffective treatment, while treatment duration and albumin levels predicted effective treatment. ROC analysis indicated that albumin levels >34 g/L, APACHE II scores <13, and treatment duration >10 days correlated with better clinical efficacy. Conclusion: Colistin sulfate is both safe and effective in clinical settings. Factors such as treatment duration, albumin levels, APACHE II scores, and vasoactive drug use independently affect its clinical efficacy, providing valuable guidance for its informed clinical application.

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Introduction: during laparoscopic surgery, carbon dioxide (CO2) insufflation to create pneumoperitoneum increases blood pressure, heart rate and systemic vascular resistance. The purpose of our study was to investigate the efficacy of magnesium sulfate in preventing adverse hemodynamic reactions associated with pneumoperitoneum in patients undergoing laparoscopic cholecystectomy. Methods: we conducted a prospective, randomized, double-blind, controlled clinical study of patients scheduled for laparoscopic cholecystectomy and divided into two equal groups: the Mg2+ group received slow intravenous magnesium sulfate 50 mg/kg injection prior to pneumoperitoneum insufflation while the S group received the same volume of 0.9 % saline. Our primary endpoint was intraoperative changes in systolic blood pressure (SBP) related to pneumoperitoneum, in particular at 1 minute after insufflation. The secondary endpoints were the haemodynamic effects of pneumoperitoneum in terms of systolic blood pressure (SP), diastolic blood pressure (DP), mean arterial pressure (MAP) and heart rate (HR) from 2 minutes after insufflation to extubation and postoperatively, and the presence of possible adverse reactions related to the administration of magnesium sulphate. Results: we included 70 patients divided into two groups of 35. SP was significantly higher in the S group at insufflation (T0), 3 min, 4 min and 5 min post-operative, and at 60 min after surgery. HR was significantly higher in patients in the S group compared to the Mg2+ group at 7 min and 8 min after insufflation. No significant differences in DP and MAP measurements were observed between the 2 groups. No adverse reactions related to magnesium administration were reported. Conclusion: magnesium sulfate administered prior to pneumoperitoneum insufflation provided improved intraoperative hemodynamic stability during laparoscopic surgery.

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Geoffroea decorticans, commonly known as Chañar, is a native Chilean plant widely used in folk medicine for its expectorant, pain relief, and antinociceptive properties. This study explored the antioxidant, cytotoxic, and protective effects of its ethanolic (EE) and aqueous (EA) seed extracts against oxidative stress induced by copper sulfate, using both in vitro and in vivo approaches. Phytochemical analyses revealed the presence of phenolic compounds and flavonoids in the extracts. High-Performance Liquid Chromatography (HPLC) coupled with Gas Chromatography-Mass Spectrometry/Mass Spectrometry (GC-MS/MS) identified significant components such as phytol, alpha-tocopherol, vitexin, and rutin, with the EE being particularly rich in phytol and vitexin. Antioxidant assays-measuring the total antioxidant capacity (TAC), reducing power, DPPH radical scavenging, and copper and iron chelation-confirmed their potent antioxidant capabilities. Both extracts were non-cytotoxic and provided protection against CuSO4-induced oxidative stress in the 3T3 cell line. Additionally, the use of Tenebrio molitor as an invertebrate model underscored the extracts' antioxidant and protective potentials, especially that of the EE. In conclusion, this study highlights the significant antioxidant and protective properties of Chañar seed extracts, particularly the ethanolic extract, in both in vitro and in vivo models.

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AIM: This study examined the roles of the laminin and proteoglycan receptor dystroglycan (DG) in extracellular matrix stabilization and cellular mechanosensory processes conveyed through communication between the extracellular matrix (ECM) and cytoskeleton facilitated by DG. Specific functional attributes of HS-proteoglycans (HSPGs) are conveyed through interactions with DG and provide synaptic specificity through diverse interactions with an extensive range of cell attachment and adaptor proteins which convey synaptic plasticity. HSPG-DG interactions are important in phototransduction and neurotransduction and facilitate retinal bipolar-photoreceptor neuronal signaling in vision. Besides synaptic stabilization, HSPG-DG interactions also stabilize basement membranes and the ECM and have specific roles in the assembly and function of the neuromuscular junction. This provides neuromuscular control of muscle systems that control conscious body movement as well as essential autonomic control of diaphragm, intercostal and abdominal muscles and muscle systems in the face, mouth and pharynx which assist in breathing processes. DG is thus a multifunctional cell regulatory glycoprotein receptor and regulates a diverse range of biological and physiological processes throughout the human body. The unique glycosylation of the αDG domain is responsible for its diverse interactions with ECM components in cell-ECM signaling. Cytoskeletal cell regulatory switches assembled by the ßDG domain in its role as a nuclear scaffolding protein respond to such ECM cues to regulate cellular behavior and tissue homeostasis thus DG has fascinating and diverse roles in health and disease.

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Heparan sulphates (HSs), a specific class of glycosaminoglycans (GAGs), are important participants of cellular signalling. Analytical characterization of GAGs requires a complex sample preparation workflow. Although a detailed stability and recovery study is available for the chondroitin sulphate GAG class, the literature concerning HS is incomplete in this regard. Therefore, our aim was to systematically investigate various parameters that could potentially influence the stability and recovery of HS samples when performing disaccharide analysis using high-performance liquid chromatography-mass spectrometry. First, effects concerning vacuum evaporation and freezing were investigated. Next, the storage stability of the HS disaccharides was analysed under several conditions such as temperature, pH, digestion buffers, injection solvents and storage vessels. We have identified several critical parameters influencing the stability and recovery of HS disaccharides. We concluded that major sample loss is expected when Tris-HCl is used as digestion buffer, followed by vacuum evaporation at elevated temperatures, or samples are stored under alkaline conditions. Following the practical considerations of this paper can contribute to increasing the reliability of future analytical measurements.

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BACKGROUND: Postoperative atrial fibrillation (POAF) is a common and potentially serious complication post cardiac surgery. Hypomagnesaemia is common after cardiac surgery and recent evidence indicates that supplementation of magnesium may prevent POAF. We aim to investigate the effectiveness of continuous intravenous magnesium sulphate administration in the perioperative period to prevent POAF as compared to placebo. METHODS: The (POMPAE) trial is a phase 2, single-center, double-blinded randomized superiority clinical study. It aims to assess the impact of perioperative continuous intravenous magnesium administration on the occurrence of cardiac surgery-related POAF. A total of 530 patients will be included. Eligible patients will be randomized in 1:1 ratio to the intervention or placebo group with stratification based on the presence of valvular surgery. The objective of the infusion is to maintain ionized magnesium levels between 1.5 and 2.0 mmol/L. DISCUSSION: The primary outcome measure is the incidence of de novo POAF within the first 7 days following surgery, with censoring at hospital discharge. This trial may generate crucial evidence for the prevention of POAF and reduce clinical adverse events in patients following cardiac surgery. TRIAL REGISTRATION: The POMPAE trial was registered at ClinicalTrials.gov under the following identifier NTC05669417, https://clinicaltrials.gov/ct2/show/NCT05669417 . Registered on December 30, 2022. PROTOCOL VERSION: Version 3.3, dated 13-01-2023.

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BACKGROUND: Laryngospasm is sustained closure of the airways and can be a life-threatening condition. Magnesium sulphate is postulated to reduce the incidence of laryngospasm if administered peri-operatively. This systematic review and meta-analysis was performed to assess the efficacy of magnesium sulphate in preventing peri-operative laryngospasm in paediatric patients undergoing non-cardiac surgery. METHODS: Four databases and a trial registry were searched. Inclusion criteria were paediatric patients undergoing general anaesthesia. Exclusion criteria were patients who underwent cardiopulmonary bypass during surgery. The intervention of interest was the peri-operative administration of magnesium sulphate. The intervention was compared to either a placebo or other pharmacological agent. The primary outcome was the incidence of laryngospasm. A meta-analysis of all studies was performed. Sub-group analysis was subsequently performed. RESULTS: A total of 953 patients from 13 trials were included in this study. Nine RCTs administered magnesium intravenously and 4 RCTs administered magnesium locally. Laryngospasm rates were 6% lower in the magnesium group (OR 0.48 [95% CI 0.25-0.96], p = 0.04) compared to control in the pooled data. Subgroup analysis showed laryngospasm rates were lower by 12.5% (Odds Ratio 0.26 [CI 0.09-0.76], p = 0.01) in the local magnesium group. Subgroup analysis of studies that only administered intravenous magnesium did not show a statistically significant difference in the incidence of laryngospasm (OR 0.73 [95% CI 0.33-1.63], p = 0.44). CONCLUSIONS: This review shows a potential role for magnesium in the prevention of laryngospasm in paediatric patients undergoing general anaesthesia. There is a correlation between local administration of magnesium and reduction in laryngospasm rates. Further studies are required to assess the efficacy of intravenous magnesium in prevention of laryngospasm. REGISTRATION: Prospective Register of Systematic Reviews (PROSPERO); PROSPERO ID CRD42022307868 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022307868).

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BACKGROUND: Chondroitin and glucosamine sulphates (CGS) are considered structure-modifying drugs and have been studied in the prevention, delay or reversal of structural morphological changes in joints caused by osteoarthritis. OBJECTIVE: The aim of the present study was to investigate the action of CGS on the progression of chemically induced osteoarthritis in the temporomandibular joint (TMJ) of rabbits by evaluating the serum levels of tumour necrosis factor (TNF-α) and collagen in the articular discs. MATERIALS AND METHODS: A sample of 36 male rabbits was divided into three groups: control (CG), osteoarthritis (OG) and treatment (TG). The disease was induced by intra-articular injection of sodium monoiodoacetate (10 mg/mL) in the OG and TG groups bilaterally. After 10 days, the TG animals received subcutaneous injection of chondroitin sulphates and glucosamine (7.5 mg/kg) and the OG and CG received saline solution (50 µL). Euthanasia times were subdivided into 40 and 100 days. Collagen quantification was performed by biochemical and histological analysis and for the quantification of serum levels of TNF-α, an enzyme immunoassay was used. RESULTS: The TG showed an increase in the collagen area of the articular disc when compared to the CG and the OG. The increase collagen concentration in the discs did not show a statistically significant difference between the groups. Post-treatment TNF-α levels were significantly lower in TG compared to OG. CONCLUSIONS: The results indicate that CGS treatment delayed the degeneration of the collagen in the TMJ articular disc and reduced serum TNF-α levels, indicating a preventive effect on OA progression.

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Background and aims Laryngoscopy and intubation cause an increased sympatho-adrenergic pressor response, which can be detrimental to patients with coronary artery disease, hypertension, etc. Various drugs and manoeuvres have been tried to reduce the pressor response with acceptable results but the quest for the ideal drug still continues. Hence, we planned to compare the effects of magnesium sulfate with paracetamol and fentanyl with lignocaine on attenuating the hemodynamic responses due to direct laryngoscopy and intubation and to note the complications of these drugs. Methods We studied 60 adult patients of the American Society of Anaesthesiologists (ASA) physical status I and II of either sex, scheduled for elective surgery under general anaesthesia. The patients were randomly divided into two groups. Group A received 25 mg/kg magnesium sulphate mixed with paracetamol 1 gram IV (100 ml) given over 10 minutes before induction and Group B received 2 mcg/kg fentanyl and 1.5 mg/kg lignocaine, 3 minutes before intubation. All patients were uniformly pre-medicated, induced, and intubated as per standard protocol. Heart rate (HR) and systemic arterial pressures were recorded at baseline, after study drug infusion, after induction, and 1, 3, 5, 10, and 15 mins after intubation. Hemodynamic parameters were compared using repeated measures analysis of variance (ANOVA). In the post-hoc tests, p value < 0.05 was considered statistically significant. Results We observed the mean pre-op HR (p = 0.161) and mean HR one-minute post-induction (p = 0.144). The percentage change from baseline at one-minute post-induction was 9.7 in Group A and 15.2 in Group B. We observed the mean pre-op mean arterial pressure (MAP) (p = 0.119) and mean MAP one minute post-induction (p = 0.585). The percentage change from baseline at one-minute post-induction was 3.3 in Group A and 2.8 in Group B. The percentage change from baseline was found to be within 15%, for HR in Group A and for systolic blood pressure (SBP), diastolic blood pressure (DBP), and MAP in Group B. However, there was no statistically significant difference (p > 0.05) between the mean HR, SBP, DBP, and MAP between the time points. Conclusion In our study, both the combinations of drugs, magnesium sulphate with paracetamol (Group A drugs) and fentanyl with lignocaine (Group B drugs) were found to be equally effective (i.e. neither group was superior to the other) in attenuating the hemodynamic response to laryngoscopy and intubation.

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Glutathione redox cycling is important for cell cycle regulation, but its mechanisms are not well understood. We previously identified a small-sized mutant, suppressor of mat3 15-1 (smt15-1) that has elevated cellular glutathione. Here, we demonstrated that SMT15 is a chloroplast sulphate transporter. Reducing expression of γ-GLUTAMYLCYSTEINE SYNTHETASE, encoding the rate-limiting enzyme required for glutathione biosynthesis, corrected the size defect of smt15-1 cells. Overexpressing GLUTATHIONE SYNTHETASE (GSH2) recapitulated the small-size phenotype of smt15-1 mutant, confirming the role of glutathione in cell division. Hence, SMT15 may regulate chloroplast sulphate concentration to modulate cellular glutathione levels. In wild-type cells, glutathione and/or thiol-containing molecules (GSH/thiol) accumulated in the cytosol at the G1 phase and decreased as cells entered the S/M phase. While the cytosolic GSH/thiol levels in the small-sized mutants, smt15-1 and GSH2 overexpressors, mirrored those of wild-type cells (accumulating during G1 and declining at early S/M phase), GSH/thiol was specifically accumulated in the basal bodies at early S/M phase in the small-sized mutants. Therefore, we propose that GSH/thiol-mediated redox signalling in the basal bodies may regulate mitotic division number in Chlamydomonas reinhardtii. Our findings suggest a new mechanism by which glutathione regulates the multiple fission cell cycle in C. reinhardtii.

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Human communities need water and mineral resources, the supply of which requires the implementation of recycling and saving strategies. Both closed and active mining sites could beneficiate of the implementation of nature-based solutions, including bioreactors involving sulphate-reducing prokaryotes (SRP), in order to separate and recover arsenic (As) and metals from aqueous stream while producing clean water. Selective precipitation strategies can be designed based on the selection of microbial communities adapted to the pH conditions, generally acidic, and to available low-cost electron donors. Laboratory batch and continuous experiments must be implemented for each type of mine water in order to determine the optimal flow-sheet in which As could be precipitated as sulphides (orpiment or realgar), inside the bioreactor or offline, through stripping of biologically produced hydrogen sulphides (H2S). The respective concentrations and proportions of As and metals and the initial acid mine drainage pH are key parameters that will influence the feasibility of efficient selective precipitation. SRP-based bioreactors could be combined with complementary treatment steps in optimised mine water management solutions that will minimise the production of As-contaminated end-solid waste.

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Examining the critical role of anticoagulants in medical practice, particularly their central function in preventing abnormal blood clotting, is of the utmost importance. However, the study of interactions between blood proteins and alternative anticoagulant nano-surfaces is still understood poorly. In this study, novel approach involving direct functionalisation of magnetic iron oxide nanoparticles (MNPs) as carriers with sulphated dextran (s-dext) is presented, with the aim of evaluating the potential of magnetically-responsive MNPs@s-dext as anticoagulants. The physicochemical characterisation of the synthesised MNPs@s-dext includes crystal structure analysis, morphology study, surface and electrokinetic properties, thermogravimetric analysis and magnetic properties` evaluation, which confirms the successful preparation of the nanocomposite with sulfonate groups. The anticoagulant potential of MNPs@s-dext was investigated using a standardised activated partial thromboplastin time (APTT) test and a modified APTT test with a quartz crystal microbalance with dissipation (QCM-D) which confirmed the anticoagulant effect. Time-resolved solid-liquid interactions between the MNPs@s-dext and model blood proteins bovine serum albumin and fibrinogen were also investigated, to gain insight into their hemocompatibility, and revealed protein-repellence of MNPs@s-dext against blood proteins. The study also addressed comprehensive cytotoxicity studies of prepared nanocomposites, and provided valuable insights into potential applicability of MNPs@s-dext as a promising magnetic anticoagulant in biomedical contexts.

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Polysaccharides like hyaluronan (HA) and chondroitin sulfate (CS) are native of the brain's extracellular matrix crucial for myelination and brain maturation. Despite extensive research on HA and CS as drug delivery systems (DDS), their high water solubility limits their application as drug carriers. This study introduces an injectable DDS using aldehyde-modified hyaluronic acid (HAOX) hydrogel containing polyelectrolyte complexes (PEC) formed with calcium, gelatin, and either CS or aldehyde-modified CS (CSOX) to deliver minocycline for Multiple Sclerosis therapy. PECs with CSOX enable covalent crosslinking to HAOX, creating immobilized PECs (HAOX_PECOX), while those with CS remain unbound (HAOX_PECS). The in situ forming DDS can be administered via a 20 G needle, with rapid gelation preventing premature leakage. The system integrates into an implanted device for minocycline release through either Fickian or anomalous diffusion, depending on PEC immobilization. HAOX_PECOX reduced burst release by 88 %, with a duration of 127 h for 50 % release. The DDS exhibited an elastic modulus of 3800 Pa and a low swelling ratio (0-1 %), enabling precise control of minocycline release kinetics. Released minocycline reduced IL-6 secretion in the Whole Blood Monocytes Activation Test, suggesting that DDS formation may not alter the biological activity of the loaded drug.

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BACKGROUND: Over the last two decades, a large body of literature has focused on studying the prevalence and outcome of the postoperative delirium and sleep disturbance. The aim of this work was to evaluate the effect of intraoperative administration of Magnesium sulphate on the occurrence of post-operative delirium and insomnia in patients undergoing lumbar fixation. METHODS: This prospective randomized controlled trial was carried out on 80 patients indicated for lumbar fixation; 40 of them received conventional general anesthesia with extra administration of intraoperative magnesium sulphate (Mg sulphate group), and the other 40 received conventional general anesthesia only (control group). Both groups were submitted to pre-operative assessment of depression using Beck Depression inventory (BDI) scale, pre-operative assessment of fatigue using a fatigue questionnaire, pre- and post-operative assessment of insomnia using Insomnia severity index (ISI), post-operative assessment of delirium using Memorial delirium assessment scale (MDAS), post-operative assessment of pain using Visual Analogue Scale (VAS), and pre- and post-operative Quantitative electroencephalography (QEEG). RESULTS: Mg sulphate administration, age, pre-operative BDI, pre-operative ISI, and post-operative VAS were independent predictors of post-operative ISI (P-value < 0.001, 0.047, 0.021, < 0.001, and < 0.001 respectively). Age and post-operative VAS were independent predictors of post-operative MDAS (P-value = 0.008, 0.013 respectively). Mg sulphate administration and pre-operative ISI were independent predictors of post-operative VAS (P-value = 0.010, 0.006 respectively). CONCLUSION: There was a significant relationship between intraoperative Mg sulphate administration and both post-operative insomnia and pain in unadjusted and adjusted analysis.

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The deformulation stage of original drug products, which includes the quantification of critical excipients, is crucial for the successful development of generic drug products of solid dosage form. Sodium lauryl sulphate (SLS) belongs to the group of critical excipients due to its influence on the bioavailability of drugs, such as metformin. The purpose of this work is to carry out a feasibility study in order to develop a simple, economical, and robust analytical method for the quantification of SLS in metformin-containing tablets after their dissolution in water. Firstly, SLS is extracted with chloroform in acidic conditions, followed by the addition of methylene blue (MB) in order to form a SLS-MB ion pair, which is then measured photometrically at a wavelength of 651 nm. Additionally, interference from matrix components (excipients and APIs) was assessed, and it was found that metformin also forms a blue complex; therefore, this specific extraction method was developed. Other matrix components did not interfere with SLS determination. This method shows a well-estimated precision of 3.3% and accuracy of 5%, a calibration linearity of R2 = 0.99990, and a working range of 0.38 µg/mL to 10 µg/mL of SLS in water. The midpoint of the calibration graph corresponds to the concentration of SLS obtained by dissolving a single tablet in 1 L of water. This method seems appropriate for total SLS determination in tablets and can be applicable for deformulation.

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Efficient recovery of valuable metals from copper smelting slag (CSS) can not only alleviate the pressure from resource scarcity, but also has important practical significance for the realization of green and sustainable production in the copper smelting industry. In this paper, a composite medium of FeS-O2 is used as a synergistic modifier to transform the solid-state valuable metals in CSS into leachable state of sulphates, and achieves efficient and comprehensive recovery of zinc and copper through neutral leaching. XRD, FTIR, XPS, etc and comparative analysis methods are used to deeply analyze the characteristics of occurrence phase and transformation rules of valuable metal in CSS, roasted slag and leached slag. The results show under the optimal roasting conditions of TRoasting = 650 °C, M(copper slag): M(FeS) = 1:1, V(O2): V(Ar) = 1:6 and tHolding = 90 min, the recovery rate for zinc is approximately 95.1 %, and that for copper is 99.3 %, almost all of which is recovered. These findings provide a new method and process foundation and theoretical support for the efficient resource utilization of CSS.

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The separation and utilization of cellulose, hemicellulose, and lignin in lignocellulosic biorefineries present significant challenges. This study proposes a pretreatment method for biomass refining by combining acid and kraft pulping. Firstly, the biomass was pretreated by malic acid, resulting in the isolation of xylo-oligosaccharides (XOS) with a yield of 86.26 % with optimized conditions of 180 °C, 1 wt% concentration, 40 min. Secondly, a mixture of 12.98 wt% NaOH and 1.043 wt% Na2S is employed to achieve lignin removal efficiency up to 63.42 %. Physical refinement techniques are then applied to enhance the enzyme digestion efficiency of cellulose, resulting in an increase from 55.03 % to 91.4 % for efficient cellulose conversion. The reacted samples exhibit a lignin composition rich in ß-O-4 ether bonds, facilitating their high-value utilization. The results indicated that the combined pretreatment approach demonstrates high efficiency in separating cellulose, hemicellulose, and lignin while obtaining XOS, highly active lignin, and enzyme-digested substrates.

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This study investigated the transcriptomic mechanisms underlying melatonin accumulation and the enhancement of salt tolerance in hull-less barley seeds subjected to zinc sulphate stress. Following zinc sulphate treatment, hull-less barley seeds demonstrated increased melatonin accumulation and improved salt tolerance. Through transcriptome analysis, the study compared gene expression alterations in seeds (using the first letter of seed, this group is marked as 'S'), seeds treated with pure water (as the control group, is marked as 'C'), and germinated seeds exposed to varying concentrations of zinc sulphate (0.2 mM and 0.8 mM, the first letter of zinc sulphate, 'Z', is used to mark groups 'Z1' and 'Z2'). The analysis revealed that 8176, 759, and 622 differentially expressed genes (DEGs) were identified in the three comparison groups S.vs.C, C.vs.Z1, and C.vs.Z2, respectively. Most of the DEGs were closely associated with biological processes, including oxidative-stress response, secondary metabolite biosynthesis, and plant hormone signaling. Notably, zinc sulphate stress influenced the expression levels of Tryptophan decarboxylase 1 (TDC1), Acetylserotonin O-methyltransferase 1 (ASMT1), and Serotonin N-acetyltransferase 2 (SNAT2), which are key genes involved in melatonin synthesis. Furthermore, the expression changes of genes such as Probable WRKY transcription factor 75 (WRKY75) and Ethylene-responsive transcription factor ERF13 (EFR13) exhibited a strong correlation with fluctuations in melatonin content. These findings contribute to our understanding of the mechanisms underlying melatonin enrichment in response to zinc sulphate stress.

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BACKGROUND: Cancer treatment often involves the use of potent antineoplastic drugs like Capecitabine [CAP], which can lead to serious toxicities. There is a need for dosage forms to manage these toxicities that can deliver the medication effectively to the target site while maintaining therapeutic efficacy at lower doses. To achieve the aforesaid objective, NLC containing capecitabine [NANOBIN] was prepared and evaluated. Different formulations of NANOBIN, denoted as CaTS, CaT1S, CaT2S, CaTS1, and CaTS2, were designed and evaluated to improve drug delivery and therapeutic outcomes. METHODS: The NANOBIN formulations were prepared using the hot homogenization method. The characterization of these formulations was conducted based on various parameters such as particle size, Polydispersity Index [PDI], Zeta Potential [ZP], Transmission Electron Microscopy [TEM] imaging, and Encapsulation Efficiency [EE]. In vitro evaluations included stability testing, release studies to assess drug release kinetics, and a cytotoxicity assay [MTT assay] to evaluate the efficacy of these formulations against human breast cancer cells [MCF-7]. RESULTS: The characterization results revealed that all NANOBIN formulations exhibited particle sizes ranging from 65 to 193 nm, PDI values within the range of 0.26-0.37, ZP values between 46.47 to 61.87 mV [-ve], and high EE percentages ranging from 94.121% to 96.64%. Furthermore, all NANOBIN formulations demonstrated sustained and slow-release profiles of CAP. The MTT assay showed that the NANOBINs exhibited significantly enhanced cytotoxic efficacy, approximately 10 times greater than free CAP when tested on MCF-7 cells. These findings indicate the potential of NANOBINs to deliver CAP effectively to the target site, enabling prolonged drug availability and enhanced therapeutic effects at lower doses. CONCLUSION: The study demonstrates that NANOBINs can effectively deliver CAP to target sites, prolonging drug exposure and enhancing therapeutic efficacy while reducing the required dose. Further studies are necessary to validate these findings and establish NANOBINs as a preferred treatment option for cancer therapy.