Designing Mesoporous Prussian Blue@zinc Phosphate Nanoparticles with Hierarchical Pores for Varisized Guest Delivery and Photothermally-Augmented Chemo-Starvation Therapy.

Background: With the rapid development of nanotechnology, constructing a multifunctional nanoplatform that can deliver various therapeutic agents in different departments and respond to endogenous/exogenous stimuli for multimodal synergistic cancer therapy remains a major challenge to address the inherent limitations of chemotherapy. Methods: Herein, we synthesized hollow mesoporous Prussian Blue@zinc phosphate nanoparticles to load glucose oxidase (GOx) and DOX (designed as HMPB-GOx@ZnP-DOX NPs) in the non-identical pore structures of their HMPB core and ZnP shell, respectively, for photothermally augmented chemo-starvation therapy. Results: The ZnP shell coated on the HMPB core, in addition to providing space to load DOX for chemotherapy, could also serve as a gatekeeper to protect GOx from premature leakage and inactivation before reaching the tumor site because of its degradation characteristics under mild acidic conditions. Moreover, the loaded GOx can initiate starvation therapy by catalyzing glucose oxidation while causing an upgradation of acidity and H2O2 levels, which can also be used as forceful endogenous stimuli to trigger smart delivery systems for therapeutic applications. The decrease in pH can improve the pH-sensitivity of drug release, and O2 can be supplied by decomposing H2O2 through the catalase-like activity of HMPBs, which is beneficial for relieving the adverse conditions of anti-tumor activity. In addition, the inner HMPB also acts as a photothermal agent for photothermal therapy and the generated hyperthermia upon laser irradiation can serve as an external stimulus to further promote drug release and enzymatic activities of GOx, thereby enabling a synergetic photothermally enhanced chemo-starvation therapy effect. Importantly, these results indicate that HMPB-GOx@ZnP-DOX NPs can effectively inhibit tumor growth by 80.31% and exhibit no obvious systemic toxicity in mice. Conclusion: HMPB-GOx@ZnP-DOX NPs can be employed as potential theranostic agents that incorporate multiple therapeutic modes to efficiently inhibit tumors.

Effects of Nitrosyl Iron Complexes with Thiol, Phosphate, and Thiosulfate Ligands on Hemoglobin.

Nitrosyl iron complexes are remarkably multifactorial pharmacological agents. These compounds have been proven to be particularly effective in treating cardiovascular and oncological diseases. We evaluated and compared the antioxidant activity of tetranitrosyl iron complexes (TNICs) with thiosulfate ligands and dinitrosyl iron complexes (DNICs) with glutathione (DNIC-GS) or phosphate (DNIC-PO4-) ligands in hemoglobin-containing systems. The studied effects included the production of free radical intermediates during hemoglobin (Hb) oxidation by tert-butyl hydroperoxide, oxidative modification of Hb, and antioxidant properties of nitrosyl iron complexes. Measuring luminol chemiluminescence revealed that the antioxidant effect of TNICs was higher compared to DNIC-PO4-. DNIC-GS either did not exhibit antioxidant activity or exerted prooxidant effects at certain concentrations, which might have resulted from thiyl radical formation. TNICs and DNIC-PO4- efficiently protected the Hb heme group from decomposition by organic hydroperoxides. DNIC-GS did not exert any protective effects on the heme group; however, it abolished oxoferrylHb generation. TNICs inhibited the formation of Hb multimeric forms more efficiently than DNICs. Thus, TNICs had more pronounced antioxidant activity than DNICs in Hb-containing systems.

Host Cells Upregulate Phosphate Transporter PIT1 to Inhibit Ehrlichia chaffeensis Intracellular Growth.

Ehrlichia chaffeensis infects and proliferates inside monocytes or macrophages and causes human monocytic ehrlichiosis (HME), an emerging life-threatening tick-borne zoonosis. After internalization, E. chaffeensis resides in specialized membrane-bound inclusions, E. chaffeensis-containing vesicles (ECVs), to evade from host cell innate immune responses and obtain nutrients. However, mechanisms exploited by host cells to inhibit E. chaffeensis growth in ECVs are still largely unknown. Here we demonstrate that host cells recognize E. chaffeensis Ech_1067, a penicillin-binding protein, and then upregulate the expression of PIT1, which is a phosphate transporter and transports phosphate from ECVs to the cytosol to inhibit bacterial growth. We found that host cells upregulate the PIT1 expression upon E. chaffeensis infection using transcriptome sequencing, qRT-PCR and Western blotting, and PIT1 is localized on the ECV membrane in infected THP-1 cells using confocal microscopy. Silence of PIT1 using shRNA enhances E. chaffeensis intracellular growth. Finally, we found that E. chaffeensis Ech_1067 induces the upregulation of PIT1 expression through the MyD88-NF-κB pathway using recombinant protein for stimulation and siRNA for silence. Our findings deepen the understanding of the innate immune responses of host cells to inhibit bacterial intracellular growth and facilitate the development of new therapeutics for HME.

Mechanism of phosphate release from actin filaments.

After ATP-actin monomers assemble filaments, the ATP's [Formula: see text]-phosphate is hydrolyzedwithin seconds and dissociates over minutes. We used all-atom molecular dynamics simulations to sample the release of phosphate from filaments and study residues that gate release. Dissociation of phosphate from Mg2+ is rate limiting and associated with an energy barrier of 20 kcal/mol, consistent with experimental rates of phosphate release. Phosphate then diffuses within an internal cavity toward a gate formed by R177, as suggested in prior computational studies and cryo-EM structures. The gate is closed when R177 hydrogen bonds with N111 and is open when R177 forms a salt bridge with D179. Most of the time, interactions of R177 with other residues occlude the phosphate release pathway. Machine learning analysis reveals that the occluding interactions fluctuate rapidly, underscoring the secondary role of backdoor gate opening in Pi release, in contrast with the previous hypothesis that gate opening is the primary event.

Dispersive solid-phase extraction based on zirconium metal-organic framework coupled with gas chromatography-mass spectrometry for determining sugar phosphates in biological samples.

BACKGROUND: Sugar phosphates (SPx) play important role in the metabolism of the organism. SPx such as glycerate 3-phosphate, fructose 6-phosphate and glucose 6-phosphate in biological samples have the poor stability, similar structure and low abundance, which make their separation and detection more challenging. METHOD: UiO-66-NH2 and ZrO2 coated SiO2(SBA-15) hard-core-shell adsorbents (UiO-66-NH2@SBA-15 and ZrO2@SBA-15) were synthesized, which were further used for dispersive solid-phase extraction for enriching the SPx in biological samples. The protocol was developed by UiO-66-NH2@SBA-15 and ZrO2@SBA-15 coupled with gas chromatography-mass spectrometry for the detection of trace SPx. The univariate experiment and response surface methodology were used to optimize the adsorption and desorption conditions. RESULTS: The adsorbents showed excellent adsorption capacity and specificity towards SPx, which were proved by adsorption and selective experiments. Under the optimized conditions, there were good linearity within the range of 5.0-5000.0 ng mL-1, low limits of detection (0.001-1.0 ng mL-1), low limits of quantification (0.005-5.0 ng mL-1) and good precision (relative standard deviation less than 14.7 % for intra-day and inter-day). The satisfactory recoveries (89.1-113.8 %) and precision (0.5-14.6 %) were obtained when the sorbents were used to extract SPx from serum, saliva and cell samples. Moreover, UiO-66-NH2@SBA-15 was applied to the quantitative analysis of SPx from gastric cancer patients, because of a higher adsorption capacity (169.5-196.1 mg g-1). CONCLUSIONS: UiO-66-NH2@SBA-15 showed great potential in the extraction of SPx in biological samples, which was beneficial to find out the metabolic change of SPx and explain the pathogenesis of the disease.

Time Course of High-Energy Phosphate Depletion During Cold Storage of Human Heart Grafts Using the Celsior Solution.

The aim of this study was to provide insight into high-energy phosphate compound concentration dynamics under realistic clinical cold-storage conditions using the Celsior solution in seven heart grafts discarded from transplantation. The hearts of seven local donors (three males, four females, age 37 ± 17 years, height 175 ± 5 cm, weight 75 ± 9 kg) initially considered for transplantation and eventually discarded were submitted to a Magnetic Resonance Spectroscopy observation in a clinical Magnetic Resonance Imaging scanner over at least 9 h. The grafts remained in their sterile container at 4°C during the entire examination. Hence, Phosphocreatine (PCr), adenosine triphosphate (ATP), inorganic phosphate (Pi) and intracellular pH were recorded non-destructively at a 30-minute interval. With the ischemic time Ti, the concentration ratios decreased at PCr/ATP = 1.68-0.0028·Tis, Pi/ATP = 1.38 + 0.0029·Tis, and intracellular pH at 7.43-0.0012·Tis. ATP concentration remained stable for at least 9 h and did not decrease as long as phosphocreatine was detectable. Acidosis remained moderate. In addition to the standard parameters assessed at the time of retrieval, Magnetic Resonance Spectroscopy can provide an assesment of the metabolic status of heart grafts before transplantation. These results show how HEPC metabolites deplete during cold storage. Although many parameters determine graft quality during cold storage, the dynamics of HEPC and intracellular pH may be helpful in the development of strategies aiming at extending the ischemic time.

Sustainable regulation of calcium magnesium phosphate and rapeseed cake on soil-tea system in Mount Lushan, China.

Lushan Yunwu tea quality is limited by soil acidity and sterility. This article examined a 3-year localization experiment at 1100 m altitude to demonstrate the sustainable management of conditioners, calcium magnesium phosphate (P), rapeseed cake (C), and combination application (P + C) by one-time application on the soil-tea system in Mount Lushan. The study found that conditioners (P, C, P + C) reduced soil acidification and maintained a pH of 4.75-5.34, ideal for tea tree development for 3 years. Phosphorus activation coefficient (PAC), nitrogen activation coefficient (NAC), and organic matter (OM) content were significantly higher (P < 0.05) in the first year after conditioner treatment, with P + C being the best. After P + C, PAC, NAC, and OM rose by 31.25%, 47.70%, and 10.06 g kg-1 compared to CK. In comparison to the CK, tea's hundred-bud weight (BW), free amino acids (AA), tea polyphenols (TPC), and chlorophyll (Chl) content of P + C treatment got 29.98%, 14.41%, 22.49%, and 28.85% increase compared to that of the CK, respectively. In the second year, the three treatments of P, C and P + C still had significant moderating effects on the physicochemical properties of the soil and the quality indexes of the tea leaves. The PAC of the soil under the three treatments increased by 0.06%, 0.07% and 0.18%, respectively, as compared to the control.P + C increased BW, AA, TPC and Chl of tea for 2 years. Three conditioners had 2-year regulatory impacts on soil fertility indicators, tea output, and quality. C and P + C both increased soil OM by 18.59% and 21.78% compared to CK in the third year, outperforming P treatment. Redundancy analysis revealed that the primary physicochemical factors influencing tea output and quality were soil OM and pH, with available phosphorus, urease, acid phosphatase, and available nitrogen following closely afterwards.

Phosphate solubilizing Aspergillus Niger PH1 ameliorates growth and alleviates lead stress in maize through improved photosynthetic and antioxidant response.

Among the several threats to humanity by anthropogenic activities, contamination of the environment by heavy metals is of great concern. Upon entry into the food chain, these metals cause serious hazards to plants and other organisms including humans. Use of microbes for bioremediation of the soil and stress mitigation in plants are among the preferred strategies to provide an efficient, cost-effective, eco-friendly solution of the problem. The current investigation is an attempt in this direction where fungal strain PH1 was isolated from the rhizosphere of Parthenium hysterophorus which was identified as Aspergillus niger by sequence homology of the ITS 1 and ITS 4 regions of the rRNA. The strain was tested for its effect on growth and biochemical parameters as reflection of its potential to mitigate Pb stress in Zea mays exposed to 100, 200 and 500 µg of Pb/g of soil. In the initial screening, it was revealed that the strain has the ability to tolerate lead stress, solubilize insoluble phosphate and produce plant growth promoting hormones (IAA and SA) and other metabolites like phenolics, flavonoids, sugar, protein and lipids. Under 500 µg of Pb/g of soil, Z. mays exhibited significant growth retardation with a reduction of 31% in root length, 30.5% in shoot length, 57.5% in fresh weight and 45.2% in dry weight as compared to control plants. Inoculation of A. niger to Pb treated plants not only restored root and shoot length, rather promoted it to a level significantly higher than the control plants. Association of the strain modulated the physio-hormonal attributes of maize plants that resulted in their better growth which indicated a state of low stress. Additionally, the strain boosted the antioxidant defence system of the maize there by causing a significant reduction in the ascorbic acid peroxidase (1.5%), catalase (19%) and 1,1-diphenyl-2 picrylhydrazyl (DPPH) radical scavenging activity (33.3%), indicating a lower stress condition as compared to their non-inoculated stressed plants. Based on current evidence, this strain can potentially be used as a biofertilizer for Pb-contaminated sites where it will improve overall plant health with the hope of achieving better biological and agricultural yields.

Iron Oxyhydroxide Transformation in a Flooded Rice Paddy Field and the Effect of Adsorbed Phosphate.

The mobility and bioavailability of phosphate in paddy soils are closely coupled to redox-driven Fe-mineral dynamics. However, the role of phosphate during Fe-mineral dissolution and transformations in soils remains unclear. Here, we investigated the transformations of ferrihydrite and lepidocrocite and the effects of phosphate pre-adsorbed to ferrihydrite during a 16-week field incubation in a flooded sandy rice paddy soil in Thailand. For the deployment of the synthetic Fe-minerals in the soil, the minerals were contained in mesh bags either in pure form or after mixing with soil material. In the latter case, the Fe-minerals were labeled with 57Fe to allow the tracing of minerals in the soil matrix with 57Fe Mössbauer spectroscopy. Porewater geochemical conditions were monitored, and changes in the Fe-mineral composition were analyzed using 57Fe Mössbauer spectroscopy and/or X-ray diffraction analysis. Reductive dissolution of ferrihydrite and lepidocrocite played a minor role in the pure mineral mesh bags, while in the 57Fe-mineral-soil mixes more than half of the minerals was dissolved. The pure ferrihydrite was transformed largely to goethite (82-85%), while ferrihydrite mixed with soil only resulted in 32% of all remaining 57Fe present as goethite after 16 weeks. In contrast, lepidocrocite was only transformed to 12% goethite when not mixed with soil, but 31% of all remaining 57Fe was found in goethite when it was mixed with soil. Adsorbed phosphate strongly hindered ferrihydrite transformation to other minerals, regardless of whether it was mixed with soil. Our results clearly demonstrate the influence of the complex soil matrix on Fe-mineral transformations in soils under field conditions and how phosphate can impact Fe oxyhydroxide dynamics under Fe reducing soil conditions.

Titanium-doped phosphate glasses containing zinc and strontium applied in bone regeneration.

Phosphate bioactive glass has been studied for its advanced biodegradability and active ion release capability. Our previous research found that phosphate glass containing (P2O5)-(Na2O)-(TiO2)-(CaO)-(SrO) or (ZnO) showed good biocompatibility with MG63 and hMSCs. This study further investigated the application of 5 mol% zinc oxide or 17.5 mol% strontium oxide in titanium-doped phosphate glass for bone tissue engineering. Ti-Ca-Na-Phosphate glasses, incorporating 5% zinc oxide or 17.5% strontium oxide, were made with melting quenching technology. The pre-osteoblast cell line MC3T3-E1 was cultured for indirect contact tests with graded diluted phosphate glass extractions and for direct contact tests by seeding cells on glass disks. The cell viability and cytotoxicity were analysed in vitro over 7 days. In vivo studies utilized the tibial defect model with or without glass implants. The micro-CT analysis was performed after surgery and then at 2, 6, and 12 weeks. Extractions from both zinc and strontium phosphate glasses showed no negative impact on MC3T3-E1 cell viability. Notably, non-diluted Zn-Ti-Ca-Na-phosphate glass extracts significantly increased cell viability by 116.8% (P < 0.01). Furthermore, MC3T3-E1 cells cultured with phosphate glass disks exhibited no increase in LDH release compared with the control group. Micro-CT images revealed that, over 12 weeks, both zinc-doped and strontium-doped phosphate glasses demonstrated good bone incorporation and longevity compared to the no-implant control. Titanium-doped phosphate glasses containing 5 mol% zinc oxide, or 17.5 mol% strontium oxide have promising application potential for bone regeneration research.

Effects of low-molecular-weight organic acids on the transformation and phosphate retention of iron (hydr)oxides.

The retention and mobilization of phosphate in soils are closely associated with the adsorption of iron (hydr)oxides and root exudation of low-molecular-weight organic acids (LMWOAs). This study investigated the role of LMWOAs in phosphate mobilization under incubation and field conditions. LMWOAs-mediated iron (hydr)oxide transformation and phosphate adsorption experiments revealed that the presence of LMWOAs decreased the phosphate adsorption capacity of iron (hydr)oxides by up to ~74 % due to the competition effect, while LMWOAs-induced iron mineral transformation resulted in an approximately six-fold increase in phosphate retention by decreasing the crystallinity and increasing the surface reactivity. Root simulation in rhizobox experiments demonstrated that LMWOAs can alter the contents of different extractable phosphate species and iron components, leading to 10 % ~ 30 % decreases in available phosphate in the near root region of two tested soils. Field experiments showed that crop covering between mango tree rows promoted the exudation of LMWOAs from mango roots. In addition, crop covering increased the contents of total phosphate and available phosphate by 9.08 % ~ 61.20 % and 34.33 % ~ 147.33 % in the rhizosphere soils of mango trees, respectively. These findings bridge the microscale and field scale to understand the delicate LMWOAs-mediated balance between the retention and mobilization of phosphate on iron (hydr)oxide surface, thereby providing important implications for mitigating the low utilization efficiency of phosphate in iron-rich soils.

Unlocking the potential of surface modification with phosphate on ball milled zero-valent iron reactivity:Implications for radioactive metal ions removal.

Numerous investigations have illuminated the profound impact of phosphate on the adsorption of uranium, however, the effect of phosphate-mediated surface modification on the reactivity of zero-valent iron (ZVI) remained enigmatic. In this study, a phosphate-modified ZVI (P-ZVIbm) was prepared with a facile ball milling strategy, and compared with ZVIbm, the U(VI) removal amount (435.2 mg/g) and efficiency (3.52×10-3 g·mg-1·min-1) of P-ZVIbm were disclosed nearly 2.0 and 54 times larger than those of ZVIbm respectively. The identification of products revealed that the adsorption mechanism dominated the removal process for ZVIbm, while the reactive modified layer strengthened both the adsorption pattern and reduction performance on P-ZVIbm. DFT calculation result demonstrated that the binding configuration shifted from bidentate binuclear to multidentate configuration, further shortening the Fe-U atomic distance. More importantly, the electron transferred is more accessible through the surface phosphate layer, and selectively donated to U(VI), accounting for the elevated reduction performance of P-ZVIbm. This investigation explicitly underscores the critical role of ZVI's surface microenvironment in the domain of radioactive metal ion mitigation and introduces a novel methodology to amplify the sequestration of U(VI) from aqueous environments.

Endogenous activation of peroxisome proliferator-activated receptor-α in proximal tubule cells in counteracting phosphate toxicity.

Increased dietary phosphate consumption intensifies renal phosphate burden. Several mechanisms for phosphate-induced renal tubulointerstitial fibrosis have been reported. Considering the dual nature of phosphate as both a potential renal toxin and an essential nutrient for the body, kidneys may possess inherent protective mechanisms against phosphate overload, rather than succumbing solely to injury. However, there is limited understanding of such mechanisms. To identify these mechanisms, we conducted single-cell RNA sequencing (scRNA-seq) analysis of the kidneys of control and dietary phosphate-loaded (Phos) mice at a time point when the Phos group had not yet developed tubulointerstitial fibrosis. scRNA-seq analysis identified the highest number of differentially expressed genes in the clusters belonging to proximal tubular epithelial cells (PTECs). Based on these differentially expressed genes, in silico analyses suggested that the Phos group activated peroxisome proliferator-activated receptor-α (PPAR-α) and fatty acid ß-oxidation (FAO) in the PTECs. This activation was further substantiated through various experiments, including the use of an FAO activity visualization probe. Compared with wild-type mice, Ppara knockout mice exhibited exacerbated tubulointerstitial fibrosis in response to phosphate overload. Experiments conducted with cultured PTECs demonstrated that activation of the PPAR-α/FAO pathway leads to improved cellular viability under high-phosphate conditions. The Phos group mice showed a decreased serum concentration of free fatty acids, which are endogenous PPAR-α agonists. Instead, experiments using cultured PTECs revealed that phosphate directly activates the PPAR-α/FAO pathway. These findings indicate that noncanonical metabolic reprogramming via endogenous activation of the PPAR-α/FAO pathway in PTECs is essential to counteract phosphate toxicity.NEW & NOTEWORTHY This study revealed the activation of peroxisome proliferator-activated receptor-α and fatty acid ß-oxidation in proximal tubular epithelial cells as an endogenous mechanism to protect the kidney from phosphate toxicity. These findings highlight noncanonical metabolic reprogramming as a potential target for suppressing phosphate toxicity in the kidneys.

Homeostatic coordination of cellular phosphate uptake and efflux requires an organelle-based receptor for the inositol pyrophosphate IP8.

Phosphate (Pi) serves countless metabolic pathways and is involved in macromolecule synthesis, energy storage, cellular signaling, and bone maintenance. Herein, we describe the coordination of Pi uptake and efflux pathways to maintain mammalian cell Pi homeostasis. We discover that XPR1, the presumed Pi efflux transporter, separately supervises rates of Pi uptake. This direct, regulatory interplay arises from XPR1 being a binding partner for the Pi uptake transporter PiT1, involving a predicted transmembrane helix/extramembrane loop in XPR1, and its hitherto unknown localization in a subset of intracellular LAMP1-positive puncta (named "XLPVs"). A pharmacological mimic of Pi homeostatic challenge is sensed by the inositol pyrophosphate IP8, which functionalizes XPR1 to respond in a temporally hierarchal manner, initially adjusting the rate of Pi efflux, followed subsequently by independent modulation of PiT1 turnover to reset the rate of Pi uptake. These observations generate a unifying model of mammalian cellular Pi homeostasis, expanding opportunities for therapeutic intervention.

Specific and efficient knockdown of intracellular miRNA using partially neutralized phosphate-methylated DNA oligonucleic acid-loaded mesoporous silica nanoparticles.

Antisense oligonucleotides (ASOs) are molecules used to regulate RNA expression by targeting specific RNA sequences. One specific type of ASO, known as neutralized DNA (nDNA), contains site-specific methyl phosphotriester (MPTE) linkages on the phosphate backbone, changing the negatively charged DNA phosphodiester into a neutralized MPTE with designed locations. While nDNA has previously been employed as a sensitive nucleotide sequencing probe for the PCR, the potential of nDNA in intracellular RNA regulation and gene therapy remains underexplored. Our study aims to evaluate the regulatory capacity of nDNA as an ASO probe in cellular gene expression. We demonstrated that by tuning MPTE locations, partially and intermediately methylated nDNA loaded onto mesoporous silica nanoparticles (MSNs) can effectively knock down the intracellular miRNA, subsequently resulting in downstream mRNA regulation in colorectal cancer cell HCT116. Additionally, the nDNA ASO-loaded MSNs exhibit superior efficacy in reducing miR-21 levels over 72 hours compared to the efficacy of canonical DNA ASO-loaded MSNs. The reduction in the miR-21 level subsequently resulted in the enhanced mRNA levels of tumour-suppressing genes PTEN and PDCD4. Our findings underscore the potential of nDNA in gene therapies, especially in cancer treatment via a fine-tuned methylation location.

Inhibition of acid rock drainage with iron-silicate or phosphate film: in rainy and submerged environments.

Iron phosphate-based coating and iron silicate-based coating were used to inhibit the oxidation of sulfide minerals in rainy and submerged environments. The inhibiting effectiveness of coating agents on the oxidation of iron sulfide minerals was investigated using pyrite and rock samples resulting from acid drainage. The film formed with both surface-coating agents was identified by pyrite surface analysis. It was also confirmed that the formation of coatings varies depending on the crystallographic orientation. The inhibitory effects under rainy and submerged conditions were investigated using column experiments. Submerged conditions accelerated deterioration compared to that under rainy conditions. Iron phosphate coating had a significantly better oxidation-inhibitory effect (84.86-98.70%) than iron silicate coating (56.80-92.36%), and at a concentration of 300 mM, H+ elution was inhibited by more than 90% throughout the experiment. Furthermore, methods for effective film formation were investigated in terms of producing Fe3+; (1) application of coating agents mixed with oxidant (H2O2), (2) application of coating agent after the use of the oxidant. In a rainy environment, applying iron phosphate-based coating using the sequential method showed oxidation inhibition effects for cycles 1-9, whereas applying the mixed material showed effects for cycles 9-13. The use of a surface-coating agent after applying an oxidant did not inhibit oxidation. The surface coating agent and the oxidizing agent should be applied as a mixture to form a film.

The Association Between Low Preoperative Phosphate Levels and Postliver Surgery Outcomes-A Single Center Experience.

INTRODUCTION: Previous research has demonstrated the impact of postoperative phosphate levels on liver regeneration and outcomes after liver resection surgeries, a potential predictor for regenerative success and liver failure. However, little is known about the association between low preoperative serum phosphate levels and outcomes in liver resections. METHODS: We performed a retrospective analysis of liver resections performed at our institution. Patients were categorized based on preoperative phosphate levels (low versus normal). Our primary outcome measure was posthepatectomy liver failure. RESULTS: A total of 265 cases met the study criteria. 71 patients (26.7%) had low preoperative phosphate levels. The incidence of posthepatectomy liver failure was higher in the low preoperative phosphate group (19.2% versus 12.4%). However, after propensity score matching, rates of posthepatectomy liver failure were similar between low and normal preoperative phosphate cohorts (13% versus 14%, P = 0.83). CONCLUSIONS: Low preoperative phosphate levels were not associated with worse postoperative outcomes in this study. Further studies are warranted to investigate this association and its relevance as a clinical prognostic factor for postoperative liver failure.

Pollution, spatial distribution, and health risks assessment of nutrient concentration in surface water resources of Maroon-Jarahi Basin in southwestern Iran.

Nowadays, the introduction of nutrients caused by human activities is considered an environmental issue and a significant problem in river basins and coastal ecosystems. In this study, the concentration of nutrients ( NO 3 - and PO 4 3 - ) in the surface water sources of the Maroon-Jarahi watershed in the southwest of Iran was determined, and the pollution status and health risk assessment were done. The average concentration of nitrate and phosphate in Ludab, Maroon, Zard, Allah, Jarahi rivers, and Shadegan wetland were obtained at 2.25-0.59, 4.59-1.84, 4.07-2.02, 5.40-2.81, 11.51-4.67, 21.63 and 6.20 (mg/l), respectively. A comparison of the results with the World Health Organization (WHO) limit showed that nitrate was lower than in all stations, but phosphate was higher than the limit in some stations of the Maroon, Allah, Jarahi rivers, and Shadegan wetland. Calculation of linear regression analysis showed significant positive relationships between nitrate and phosphate in all surface water sources (except Ludab) and based on the N/P ratio, nitrogen was estimated as the limiting factor in phytoplankton growth (N/P < 16). The evaluation of the status of the Nutrient pollution index (NPI) was observed as: Shadegan > Jarahi > Allah > Maroon > Zard > Ludab that the Jarahi River and Shadegan wetland were in the medium pollution class (1 < NPI ≤ 3) and other waterbodies were in the non-polluted to low pollution state (NPI < 1). Calculation of the chronic daily intake (CDI) showed that water body nutrients cause more non-carcinogenic health risks through the oral route than dermal exposure, and according to HI, children's health is more at risk than adults. Findings showed that surface water resources especially downstream of the Maroon-Jarahi watershed are at eutrophication risk, and to control the nearby human activities and as a result increase the nutrients in these water resources, measures should be taken.

All-in-one strategy to develop a near-infrared triggered multifunctional bioactive magnesium phosphate bone cement for bone repair.

Bone cement is widely used in clinical with optimistic filling and mechanical properties. However, the setting time of bone cement is difficult to accurately control, and the existing bone cements exhibit limited therapeutic functionalities. In response to these challenges, we designed and synthesized Nd-doped whitlockite (Nd-WH), endowing bone cement with photothermal-responsive and fluorescence imaging capabilities. The doping amount and photothermal properties of Nd-doped whitlockite were studied, and the composite bone cement was prepared. The results showed that the setting time of bone cement could be regulated by near infrared irradiation, and the multiple functions of promoting osteogenic differentiation, antibacterial and anti-tumor could be realized by adjusting the power and irradiation time of near infrared. By incorporating Nd-doped whitlockite and bone cement, we developed an all-in-one strategy to achieve setting time control, enhanced osteogenic ability, tumor cell clearance, bacterial clearance, and bone tissue regeneration. The optimized physical and mechanical properties of composite bone cement ensure adaptability and plasticity. In vitro and in vivo experiments validated the effectiveness of this bone cement platform for bone repair, tumor cell clearance and bacterial clearance. The universal methods to regulate the setting time and function of bone cement by photothermal effect has potential in orthopedic surgery and is expected to be a breakthrough in the field of bone defect repair. Further research and clinical validation are needed to ensure its safety, efficacy and sustainability. STATEMENT OF SIGNIFICANCE: Bone cement is a valuable clinical material. However, the setting time of bone cement is difficult to control, and the therapeutic function of existing bone cement is limited. Various studies have shown that the bone repair capacity of bone cements can be enhanced by synergistic stimulatory effects in vivo and ex vivo. Unfortunately, most of the existing photothermal conversion materials are non-degradable and poorly biocompatible. This study provides a bone-like photothermal conversion material with photothermal response and fluorescence imaging properties, and constructed a platform for integrated regulation of the setting time of bone cement and diversification of its functions. Therefore, it helps to design multi-functional bone repair materials that are more convenient and effective in clinical operation.

Continuous and autonomous-flow separation of laccase enzyme utilizing functionalized aqueous two-phase system with computer vision control.

Downstream processing of biomolecules, particularly therapeutic proteins and enzymes, presents a formidable challenge due to intricate unit operations and high costs. This study introduces a novel cysteine (cys) functionalized aqueous two-phase system (ATPS) utilizing polyethylene glycol (PEG) and potassium phosphate, referred as PEG-K3PO4/cys, for selective extraction of laccase from complex protein mixtures. A 3D-baffle micro-mixer and phase separator was meticulously designed and equipped with computer vision controller, to enable precise mixing and continuous phase separation under automated-flow. Microfluidic-assisted ATPS exhibits substantial increase in partition coefficient (Kflow = 16.3) and extraction efficiency (EEflow = 88 %) for laccase compared to conventional batch process. Integrated and continuous-flow process efficiently partitioned laccase, even in low concentrations and complex crude extracts. Circular dichroism spectra of laccase confirm structural stability of enzyme throughout the purification process. Eventually, continuous-flow microfluidic bioseparation is highly useful for seamless downstream processing of target biopharmaceuticals in integrated and autonomous manner.