Fucoxanthin Loaded in Palm Stearin- and Cholesterol-Based Solid Lipid Nanoparticle-Microcapsules, with Improved Stability and Bioavailability In Vivo.

Fucoxanthin (FX) is a marine carotenoid that has proven to be a promising marine drug due to the multiple bioactivities it possesses. However, the instability and poor bioavailability of FX greatly limit its application in pharmaceuticals or functional foods. In this study, the creative construction of a solid lipid nanoparticle-microcapsule delivery system using mixed lipids of palm stearin and cholesterol wrapped with gelatin/Arabic gum to load lipophilic FX was fabricated, aiming to improve the stability and bioavailability of FX. The results showed that the encapsulated efficiency (EE) and drug loading capacity (LC) of optimized FX microcapsules (FX-MCs) obtained were as high as 96.24 ± 4.60% and 0.85 ± 0.04%, respectively, after single-factor experiments. The average particle size was 1154 ± 54 nm with negative Zeta potential (-20.71 ± 0.93 mV) as depicted with size-zeta potential spectrometer. The differential scanning calorimeter (DSC) and thermogravimetric analyzer (TG) results indicated that FX-MC has a higher Tg and slower weight loss than FX monomers (FX crystal) and blank MCs. Besides, The Fourier transform infrared spectrometer (FTIR) confirmed the good double encapsulation of FX into the solid lipid and composite coacervate. Moreover, the encapsulated FX showed higher storage stability, sustained release (55.02 ± 2.80% release in 8 h), and significantly improved bioavailability (712.33%) when compared to free FX. The research results can provide a principle theoretical basis for the development and application of FX in pharmaceuticals or functional foods.

Effect of silica coating on the bond strength of milled pure titanium to dental porcelain.

The creation of a high bond strength between machined computer-manufactured pure titanium and porcelain remains problematic, and the effects of a silica coating on the bond strength of milled pure titanium bonded to dental porcelain require further investigation. The objective of this study was to evaluate the bond strength of machined pure titanium, with an intermediate coating of silica, to dental porcelain. In this work, 24 specimens of milled pure titanium were prepared and randomly divided into test and control groups, in which the test group was coated with silica using the sol-gel dipping technique. The metal-ceramic bond strength was evaluated, according to ISO 9693 standards, using the three-point bending test, and scanning electron microscopy and energy-dispersive spectroscopy were used to study the microstructure and elemental composition of the specimens. The bonding strength of the silica-coated group was significantly higher than that of the control group, and more residual porcelain on the metal surface could be observed in the silica-coated group. Therefore, the application of a silica intermediate coating produced using the sol-gel method could significantly improve the bond strength between machined pure titanium and porcelain.

Development and Application of a Duplex RT-RPA Assay for the Simultaneous Detection of Cymbidium mosaic virus and Odontoglossum ringspot virus.

Cymbidium mosaic virus (CymMV) and Odontoglossum ringspot virus (ORSV) are among the world's most serious and widespread orchid viruses; they often infect orchids, causing devastating losses to the orchid industry. Therefore, it is critical to establish a method that can rapidly and accurately detect viruses in the field using simple instruments, which will largely reduce the further spread of viruses and improve the quality of the orchid industry and is suitable for mass promotion and application at grassroots agrotechnical service points. In this investigation, we established a rapid amplification method for virus detection at 39 °C for 35 min to detect the presence of CymMV and ORSV simultaneously, sensitively, and specifically in orchids. Primers for the capsid protein (CP)-encoding genes of both viruses were designed and screened, and the reaction conditions were optimized. The experimental amplification process was completed in just 35 min at 39 °C. There were no instances of nonspecific amplification observed when nine other viruses were present. The RPA approach had detection limits of 104 and 103 copies for pMD19T-CymMV and pMD19T-ORSV, respectively. Moreover, the duplex RT-RPA investigation confirmed sensitivity and accuracy via a comparison of detection results from 20 field samples with those of a gene chip. This study presents a precise and reliable detection method for CymMV and ORSV using RT-RPA. The results demonstrate the potential of this method for rapid virus detection. It is evident that this method could have practical applications in virus detection processes.

Bioengineered Neutrophils for Smart Response in Brain Infection Management.

Brain infections, frequently accompanied by significant inflammation, necessitate comprehensive therapeutic approaches targeting both infections and associated inflammation. A major impediment to such combined treatment is the blood-brain barrier (BBB), which significantly restricts therapeutic agents from achieving effective concentrations within the central nervous system. Here, a neutrophil-centric dual-responsive delivery system, coined "CellUs," is pioneered. This system is characterized by live neutrophils enveloping liposomes of dexamethasone, ceftriaxone, and oxygen-saturated perfluorocarbon (Lipo@D/C/P). CellUs is meticulously engineered to co-deliver antibiotics, anti-inflammatory agents, and oxygen, embodying a comprehensive strategy against brain infections. CellUs leverages the intrinsic abilities of neutrophils to navigate through BBB, accurately target infection sites, and synchronize the release of Lipo@D/C/P with local inflammatory signals. Notably, the incorporation of ultrasound-responsive perfluorocarbon within Lipo@D/C/P ensures the on-demand release of therapeutic agents at the afflicted regions. CellUs shows considerable promise in treating Staphylococcus aureus infections in mice with meningitis, particularly when combined with ultrasound treatments. It effectively penetrates BBB, significantly eliminates bacteria, reduces inflammation, and delivers oxygen to the affected brain tissue, resulting in a substantial improvement in survival rates. Consequently, CellUs harnesses the natural chemotactic properties of neutrophils and offers an innovative pathway to improve treatment effectiveness while minimizing adverse effects.

Pegylated filgrastim is comparable with filgrastim as support for commonly used chemotherapy regimens: a multicenter, randomized, crossover phase 3 study.

The purpose of this study was to compare the efficacy and safety of a single subcutaneous injection of pegylated filgrastim with daily filgrastim as a prophylaxis for neutropenia induced by commonly used chemotherapy regimens. Fifteen centers enrolled 337 chemotherapy-naive cancer patients with normal bone marrow function. All patients randomized into AOB and BOA arms received two cycles of chemotherapy. Patients received a single dose of pegylated filgrastim 100 µg/kg in cycle 1 (AOB) or cycle 2 (BOA) and daily doses of filgrastim 5 µg/kg/day in cycle 1 (BOA) or cycle 2 (AOB). Efficacy and safety parameters were recorded. The primary end point was the rate of protection against grade 4 neutropenia after chemotherapy [defined as the rate at which the absolute neutrophil count (ANC) remained >0.5×10(9)/l throughout the entire cycle]. Ninety-four percent of patients receiving pegylated filgrastim or filgrastim did not develop grade 4 neutropenia. The incidence of ANC<1.0×10(9)/l was 16.0% (50/313) after support with either pegylated filgrastim or filgrastim. The incidences of febrile neutropenia and antibiotic administration were similar in both groups. Notably, faster ANC recovery was observed with pegylated filgrastim support. The ANC nadir was also earlier with pegylated filgrastim (day 7) support than with filgrastim support (day 9), although the depth of nadir was not significantly different. A single subcutaneous injection of pegylated filgrastim 100 µg/kg provided adequate and safe neutrophil support comparable with daily subcutaneous injections of unmodified filgrastim 5 µg/kg/day in patients receiving commonly used standard-dose mild-to-moderate myelosuppressive chemotherapy regimens.

Effect of titanium preoxidation on wrought pure titanium to ceramic bond strength.

STATEMENT OF PROBLEM: The creation of high bond strength between machined computer-manufactured pure titanium and porcelain remains a problem. However, machined titanium does not form the thick titanium oxide film found in cast titanium. PURPOSE: The purpose of this study was to investigate the effects of different preoxidation treatments on the bond strength of a machined pure titanium ceramic system. MATERIAL AND METHODS: Specimens of commercially pure titanium (25 × 3 × 0.5 mm) were divided equally into 6 groups (n=8), which received different preoxidation treatments (3 hour natural oxidation; 600°C, 650°C, 700°C, 750°C, and 800°C for 3 minutes). Bond strengths were evaluated by using a 3-point bend test. The results were analyzed by using 1-way ANOVA and the least significant difference test. Twelve additional specimens of commercially pure titanium (15 × 3 × 0.5 mm) were cut for interface observation and divided equally into 6 groups that received the preoxidation treatments described previously. Scanning electron microscopy and energy dispersive spectrum were used to observe microscopic features of the interface between Ti and ceramic. RESULTS: The bond strength values of the 6 groups ranged from 23.72 ±2.53 MPa to 36.99 ±3.92 MPa, with significant differences (P<.05). The specimen that received 750°C preoxidation had the highest bond strength. The main interface elements of the 6 groups were O, Si, Ti, Sn, Al, Na, and K. Ti showed a sigmoidal diffusion curve in each group, and Si showed a sigmoidal diffusion curve in most groups. Sn was enriched in each group's interface. CONCLUSIONS: Preoxidation under vacuum before porcelain firing can effectively improve the bond strength of machined pure titanium-porcelain systems.

Establishment of a triplex TaqMan quantitative real-time PCR assay for simultaneous detection of Cymbidium mosaic virus, Odontoglossum ringspot virus and Cymbidium ringspot virus.

Orchids are significant ornamental plants whose viral infection results in substantial economic damage. Cymbidium mosaic virus (CymMV), Odontoglossum ringspot virus (ORSV), and Cymbidium ringspot virus (CymRSV) represent three important and prevalent orchid viruses. The detection system proposed in this study uses a triplex TaqMan quantitative real-time PCR assay to identify CymMV, ORSV, and CymRSV in a simultaneous manner. We designed specific primers and probes for CymMV, ORSV, and CymRSV, with amplified sequences of 156 bp, 148 bp, and 145 bp, respectively. The minimum detection limit of the triplex qRT-PCR assay for CymMV and CymRSV was 1 copy/assay, and the minimum detection limit was 10 copies/assay for ORSV. The minimum stable detection limits for CymMV, ORSV, and CymRSV were 10, 102, and 102 copies/assay, respectively. Therefore, this system exhibited higher sensitivity (approximately 10 to 104-fold) than RT-PCR. The intra-and interassay CVs of Cq values are less than 0.55 and 0.95%, respectively, indicating that the triplex assay is highly reliable and accurate. In addition, 66 samples from five different orchid genera were analyzed using the established assay and gene chip. The detection results demonstrated that the triplex probe qRT-PCR demonstrated higher sensitivity than the gene chip, indicating that the triplex real-time PCR assay could be used for the detection of field samples. Our findings suggest that the triplex real-time RT-PCR detection system represents a rapid, simple, and accurate tool for detecting CymMV, ORSV, and CymRSV on orchids.

Phenyllactic acid application to control Listeria monocytogenes biofilms and its growth in milk and spiced beef.

Listeria monocytogenes, as a food-associated pathogen, is able to develop biofilms on different surfaces of food contact, which seriously threatens food safety. Phenyllactic acid (PLA) exhibits excellent inhibitory effects on many bacterial strains including L. monocytogenes. Our study aimed to investigate effects of PLA on L. monocytogenes biofilms and its growth in milk and on spiced beef. Biofilm biomass was measured by the microplate method and biofilm structure was observed by electron microscopy. Growth of L. monocytogenes in food samples was determined by colony counting. Results from the agar dilution method demonstrated that L. monocytogenes 10403S had a PLA minimum inhibitory concentration (MIC) value of 6 mg/ml. Sub-inhibitory concentrations of PLA could inhibit biofilm formation by reducing the secretion of exopolysaccharides and extracellular proteins in L. monocytogenes. PLA at concentrations above 1/2MIC could destroy mature biofilms of L. monocytogenes by decreasing the exopolysaccharides and extracellular proteins in the biofilm framework. Both swimming and swarming motilities of L. monocytogenes were inhibited by PLA. The hemolytic activity of L. monocytogenes was inactivated by PLA. However, the capacity to attach and invade Caco-2 cells was not affected by PLA. The results displayed that PLA had no effect on the expression of genes associated with motility, but reduced the expression level of the hly gene encoding Listeria hemolysin. When added to ultra-high temperature (UHT) whole and pasteurized milk, PLA at 3 mg/ml inhibited L. monocytogenes growth through 14 days of storage at 4 °C. PLA at concentrations ≥3 mg/ml significantly reduced L. monocytogenes counts on spiced beef samples during storage. PLA has potential as an alternative antimicrobial to control L. monocytogenes contamination and its biofilms in food industry.

Transhemispheric cortex remodeling promotes forelimb recovery after spinal cord injury.

Understanding the reorganization of neural circuits spared after spinal cord injury in the motor cortex and spinal cord would provide insights for developing therapeutics. Using optogenetic mapping, we demonstrated a transhemispheric recruitment of neural circuits in the contralateral cortical M1/M2 area to improve the impaired forelimb function after a cervical 5 right-sided hemisection in mice, a model mimicking the human Brown-Séquard syndrome. This cortical reorganization can be elicited by a selective cortical optogenetic neuromodulation paradigm. Areas of whisker, jaw, and neck, together with the rostral forelimb area, on the motor cortex ipsilateral to the lesion were engaged to control the ipsilesional forelimb in both stimulation and nonstimulation groups 8 weeks following injury. However, significant functional benefits were only seen in the stimulation group. Using anterograde tracing, we further revealed a robust sprouting of the intact corticospinal tract in the spinal cord of those animals receiving optogenetic stimulation. The intraspinal corticospinal axonal sprouting correlated with the forelimb functional recovery. Thus, specific neuromodulation of the cortical neural circuits induced massive neural reorganization both in the motor cortex and spinal cord, constructing an alternative motor pathway in restoring impaired forelimb function.

Clinical efficacy and safety of mecapegfilgrastim in small cell lung cancer as primary prophylaxis of neutropenia post chemotherapy: a retrospective analysis.

BACKGROUND: Neutropenia is the most common adverse reaction seen in small cell lung cancer after chemotherapy. Febrile neutropenia (FN) leads to an increase in hospitalizations and may even be life-threatening. This paper aims to investigate the efficacy and adverse reactions of mecapegfilgrastim in the primary prophylaxis of neutropenia in patients with small cell lung cancer after receiving intermediate risk chemotherapy with at least one patient risk factor. METHODS: The clinical records of 106 patients with small cell lung cancer admitted to Zhejiang Cancer Hospital from June 2019 to January 2021 were retrospectively analyzed. Patients were divided into a mecapegfilgrastim [pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF)] group and control group, each with 53 patients. The mecapegfilgrastim group received subcutaneous injection of mecapegfilgrastim 24 hours after the first cycle of chemotherapy, while the control group did not receive this. The Chi-square (χ2) test or Fisher exact test were used to compare the incidence of neutropenia, FN, and the proportion of patients administrated with full dose chemotherapy in the two groups after the first cycle of chemotherapy. Data on adverse events after mecapegfilgrastim were also collected. RESULTS: After the first cycle of chemotherapy, the incidence of neutropenia in the mecapegfilgrastim group was significantly lower than that in the control group (P=0.001) and the incidence of FN in the mecapegfilgrastim group was lower than that in the control group (P=0.118). The proportion of patients administrated with full-dose chemotherapy in the mecapegfilgrastim group was significantly higher than that in the control group (P=0.001). The main adverse reactions to mecapegfilgrastim were muscle pain, fever, and fatigue. CONCLUSIONS: After receiving intermediate risk chemotherapy, the incidence of neutropenia was significantly reduced by the primary prophylaxis of mecapegfilgrastim in patients with small cell lung cancer. The adverse events of mecapegfilgrastim were mild and tolerable, and included muscle pain, fever, and fatigue.

A comparative analysis for the development and recovery processes of different types of clogging in lab-scale vertical flow constructed wetlands.

Clogging is a major operational and maintenance issue associated with the use of constructed wetlands. In this study, four lab-scale vertical flow constructed wetlands (VFCW) were used to fully understand the development mechanisms of various types of clogging and their recovery characteristics. The VFCWs were fed with glucose solution, starch suspension with and without bacteriostat, glucose, and starch mixed solution, respectively, to simulate Bio-clogging, organic particle clogging (Op-clogging), inert particle clogging (Ip-clogging), and the combination of Bio-clogging and Op-clogging (C-clogging). Resting operations with water decline were applied to relieve the clogging in the VFCWs. The results indicate that Op-clogging occurred first, followed by C-clogging and Bio-clogging. Ip-clogging took the longest time to develop and did not occur by the end of this study. The microscope analysis found that the extracellular polymeric substances (EPS) bonded the starch particles together to form a dense membrane-like structure and promoted the clogging process. In addition, surface clogging was observed in all four experimental beds. Op-clogging occurred much closer to the surface than those caused by soluble organic matter and inert particles. Furthermore, the growth of biofilm caused significant decline in hydraulic conductivity, whereas its influence on porosity was relatively slight. Moreover, applying resting operation with water decline was effective for recovery from Bio-clogging, Op-clogging, and C-clogging in VFCWs except for Ip-clogging. The results also implied the recovery rates through applying resting operation with water decline were much higher than that with constant water level.

A Rapid LC-HRMS Method for the Determination of Domoic Acid in Urine Using a Self-Assembly Pipette Tip Solid-Phase Extraction.

In this study, we developed a self-assembly pipette tip solid-phase extraction (PTSPE) method using a high molecular weight polymer material (PAX) as the adsorbent for the determination of domoic acid (DA) in human urine samples by liquid chromatography high-resolution mass spectrometry (LC-HRMS) analysis. The PTSPE cartridge, assembled by packing 9.1 mg of PAX as sorbent into a 200 µL pipette tip, showed high adsorption capacity for DA owing to the strong cationic properties of PAX. Compared with conventional SPE, the PTSPE is simple and fast, and shows some advantages in the aspects of less solvent consumption, low cost, the absence of the evaporation step, and short time requirement. All the parameters influencing the extraction efficiency such as pH, the amount of sorbent, the number of aspirating/dispensing cycles, and the type and volume of eluent in PTSPE were carefully investigated and optimized. Under the optimized conditions, the limit of detection (LOD) and limit of quantification (LOQ) values of DA were 0.12 µg/L and 0.37 µg/L respectively. The extraction recoveries of DA from the urine samples spiked at four different concentrations were in a range from 88.4% to 102.5%. The intra- and inter-day precisions varied from 2.1% to 7.6% and from 2.6% to 12.7%, respectively. The accuracy ranged from -1.9% to -7.4%.

Effect of pretreatments on the metal-ceramic bonding strength of a Pd-Ag alloy.

OBJECTIVES: The purpose of this study was to evaluate the efficacy of surface treatments on the bonding properties between a metal and ceramic. METHODS: Sixty metal specimens were divided equally into four groups of 15 samples each. These groups received different treatments (Gr1: 250µm Al2O3+preoxidation; Gr2: 250µm Al2O3+degassing; Gr3: 120µm Al2O3+preoxidation; Gr4: 120µm Al2O3+degassing). Bond strengths were evaluated using a three-point bending test. The results were analyzed using 2-way ANOVA and Tukey's test. Scanning electron microscopy and energy dispersive spectroscopy were used to observe the microscopic features, elemental compositions and distributions, and diffusion in the specimens. Mechanical profiler was used to measure the roughness of metal surface. RESULTS: The bond strengths of the four groups ranged from 45.00±3.63MPa to 51.61±5.91MPa, with significant differences (P<.05). The specimen that received the pretreatment of 250µm Al2O3 air-particle abrasion+degassing had the highest bond strength. Heating under different oxygen partial pressures caused the final Pd-Ag alloys to have varying degrees of internal oxidation and different quantities of metallic nodules. None of the elements in either the ceramic or the Pd-Ag alloy layer diffused into the other layer. CONCLUSIONS: The metal-ceramic specimen subjected to air-particle abrasion with 250µm Al2O3 and degassed before porcelain firing had significantly higher bond strength than specimens treated differently.

[Effect of different heat treatment on the bonding strength of porcelain and Co-Cr alloy].

PURPOSE: To investigate and compare the effect of different heat treatment on the metal- ceramic bonding strength and the interfacial microstructure of the Co-Cr alloy. METHODS: Thirty specimens were made according to ISO 9693,and then divided into 3 groups (n=10) through the measurements .Group A(degassed 60s):degassed and then maintained 60s in 980 degrees centigrade Group B(degassed 60s and preoxidation 60s): degassed and maintained 60s in 980 degrees centigrade, then were maintained continuously for 60s in 980 degrees centigrade after re-gassed,Group C(degassed 120s): degassed and maintained 120s in 980 degrees centigrade. The bonding strengths of the three groups were evaluated through three point bending test. Six specimens divided into 3 group were made in the same method to observe the metal-ceramic interface through scanning electronic microscope(SEM) and energy dispersive spectrum(EDS).The bonding strength data were analyzed using ANOVA and Bonferroni's test by SPSS13.0 software package. RESULTS: The mean value of bonding strength was (39.03±2.70)MPa for group A, (34.43±2.36)MPa for group B, (31.65±1.49)MPa for group C, respectively. There were significant difference between every two groups (P<0.05). SEM demonstrated that the width of interfacial transition layer was 12.3-16.4µm in group A, 15.2-21.8µm in group B and 26.3-32.2µm in group C. CONCLUSIONS: Higher metal-ceramic bonding strength for Co-Cr alloy will be formed under the situation of degassed,and maintained 60s in 980 degrees centigrade ; while extending degassed time, prolonging the heat maintained time and preoxidation after degassing will reduce metal-ceramic bonding strength.