Influence of network latency and bandwidth on robot-assisted laparoscopic telesurgery: A pre-clinical experiment.

BACKGROUND: Telesurgery has the potential to overcome spatial limitations for surgeons, which depends on surgical robot and the quality of network communication. However, the influence of network latency and bandwidth on telesurgery is not well understood. METHODS: A telesurgery system capable of dynamically adjusting image compression ratios in response to bandwidth changes was established between Beijing and Sanya (Hainan province), covering a distance of 3000 km. In total, 108 animal operations, including 12 surgical procedures, were performed. Total latency ranging from 170 ms to 320 ms and bandwidth from 15-20 Mbps to less than 1 Mbps were explored using designed surgical tasks and hemostasis models for renal vein and internal iliac artery rupture bleeding. Network latency, jitter, frame loss, and bit rate code were systemically measured during these operations. National Aeronautics and Space Administration Task Load Index (NASA-TLX) and a self-designed scale measured the workload and subjective perception of surgeons. RESULTS: All 108 animal telesurgeries, conducted from January 2023 to June 2023, were performed effectively over a total duration of 3866 min. The operations were completed with latency up to 320 ms and bandwidths as low as 1-5 Mbps. Hemostasis for vein and artery rupture bleeding models was effectively achieved under these low bandwidth conditions. The NASA-TLX results indicated that latency significantly impacted surgical performance more than bandwidth and image clarity reductions. CONCLUSIONS: This telesurgery system demonstrated safety and reliability. A total of 320 ms latency is acceptable for telesurgery operations. Reducing image clarity can effectively mitigate the potential latency increase caused by decreased bandwidth, offering a new method to reduce the impact of latency on telesurgery.

Experiments and machine learning-based modeling for haloacetic acids rejection by nanofiltration: Influence of solute properties and operating conditions.

Because of potential risks to public health, the presence of haloacetic acids (HAAs) in drinking water is a major concern. Nanofiltration (NF) has shown potential for HAAs rejection, and several factors, namely, membrane properties, solute properties, and operating conditions, have been revealed key roles. However, knowledge of NF separation mechanism by quantifying these factors is limited. This study investigated and modeled NF performance on HAAs rejection. NF performance was experimentally investigated under various transmembrane pressure (TMP), cross-flow velocity (CV), temperature, pH, ionic strength (IS), and HAAs initial feed concentration (Cin). We used machine learning (ML) to understand the mechanism from the perspective of HAAs properties and operating conditions. Multiple linear regression (MLR), support vector machine (SVM), multsilayer perceptron (MLP), extreme gradient boosting (XGBoost), and random forest (RF) models were used. The MLP, XGBoost and RF models achieved significant performance with high R2 (0.970, 0.973, and 0.980) and low RMSE (4.71, 4.41, and 3.84). These three models were analyzed using the Shapley Additive explanation (SHAP) to quantify relative contributions of HAAs properties and operating conditions. XGBoost-SHAP produced the most logical results and was the best-performing model for selecting optimal input variables combinations. The results showed that Stokes radius (rs), logarithmic octanol-water partitioning coefficient (logKow), molecular weight (MW), pH, TMP, and temperature are key variables for interpreting NF process. The effects of HAAs properties were ranked as rs > logKow > MW, suggesting significance of size exclusion and hydrophobic interaction. The impact of the operational conditions followed the order pH > TMP > temperature, illustrating that pH was the major influencing operating condition. This study demonstrated significant capacity of ML, which reduced amount of experimental work. In addition, the main operating conditions can be evaluated in terms of their contributions, making ML an efficient tool for risk management and process optimization.

Preparation and in Vitro Evaluation of Osmotic-Pump Lorcaserin-hydrochloride Controlled-Release Tablets.

Long-term and constant-release osmotic-pump lorcaserin hydrochloride controlled-release tablets (OP LH CRTs) were prepared, to investigate the influencing factors of LH release and optimize the formulation. The mechanism of release of LH from OP LH CRTs in vitro was investigated. By establishing a high-efficiency method for measuring LH release in vitro, and optimizing it by single-factor and orthogonal experiments, the best formulation of OP LH CRTs was determined. Then, the optimal prescription of OP LH CRTs was: LH = 20.8 mg; mannitol = 100 mg, microcrystalline cellulose = 125 mg; magnesium stearate = 5 mg; cellulose acetate = 3%; polyethylene glycol 400 = 10%; dibutyl phthalate = 10%; Wetting agent and binder was 3% polyvinyl pyrrolidone (PVP) K30 ethanol solution; aperture diameter = 0.8 mm; the coating gained 3% weight. And finally, prepared OP LH CRTs were released at a constant rate in vitro and sustained for 16 h with good reproducibility between batches. Using an orthogonal experimental design, OP LH CRTs with remarkable zero-order release characteristics within 16 h were obtained, and formulation optimization was realized.

Synthesis of highly active enzyme-metal nanohybrids and uncovering the design rules.

Nanobiohybrid CAL-B/MNPs were synthesized through enzyme in situ reduction of metal ions, including noble and non-noble metals. Lipase CAL-B acted as multifunctional reagents (reducing and supporting agents). The hybrid catalysts were systematically characterized by HRTEM, EDX, MALDI-TOF-MS, and XPS analysis, confirming that highly dispersed 3-5 nm nanoparticles were evenly dispersed on lipase matrix without agglomeration. The mechanism of CAL-B reducing metal ions was investigated, revealing that AGLFFSSKDL in the amino acid sequence of CAL-B from 111 to 128 formed a stable spatial structure through hydrogen bonding, which was the key factor for enzyme in situ reduction of metal ions into highly dispersed nanoparticles.

AITC induces MRP1 expression by protecting against CS/CSE-mediated DJ-1 protein degradation via activation of the DJ-1/Nrf2 axis.

The present study aimed to examine the effect of allyl isothiocyanate (AITC) on chronic obstructive pulmonary disease and to investigate whether upregulation of multidrug resistance-associated protein 1 (MRP1) associated with the activation of the PARK7 (DJ-1)/nuclear factor erythroid 2-related factor 2 (Nrf2) axis. Lung function indexes and histopathological changes in mice were assessed by lung function detection and H&E staining. The expression levels of Nrf2, MRP1, heme oxygenase-1 (HO-1), and DJ-1 were determined by immunohistochemistry, Western blotting and reverse transcription-quantitative polymerase chain reaction. Next, the expression of DJ-1 in human bronchial epithelial (16HBE) cells was silenced by siRNA, and the effect of DJ-1 expression level on cigarette smoke extract (CSE)-stimulated protein degradation and AITC-induced protein expression was examined. The expression of DJ-1, Nrf2, HO-1, and MRP1 was significantly decreased in the wild type model group, while the expression of each protein was significantly increased after administration of AITC. Silencing the expression of DJ-1 in 16HBE cells accelerated CSE-induced protein degradation, and significantly attenuated the AITC-induced mRNA and protein expression of Nrf2 and MRP1. The present study describes a novel mechanism by which AITC induces MRP1 expression by protecting against CS/CSEmediated DJ-1 protein degradation via activation of the DJ-1/Nrf2 axis.

Allyl isothiocyanate upregulates MRP1 expression through Notch1 signaling in human bronchial epithelial cells.

Multidrug resistance associated protein-1 (MRP1) and Notch signaling are closely related and both play a critical role in chronic obstructive pulmonary disease (COPD) establishment and progression. The aim of our work was to test whether Notch1 is involved in allyl isothiocyanate (AITC) induced MRP1 expression. We used cigarette smoke extract (CSE) to simulate the smoking microenvironment in vitro. The results demonstrated that CSE led to apoptosis as well as reduced the expression of Notch1, Hes1, and MRP1, while AITC significantly reversed this downregulation. Transfected with Notch1 siRNA downregulated MRP1 expression and activity, aggravated the suppression effect by CSE, and abolished the AITC-induced Notch1, Hes1, and MRP1 expression. Validation of the correlation between Notch1 and MRP1 was implemented by gel-shift assays (electrophoretic mobility shift assay). The result revealed an interaction between a specific promoter region of MRP1 and the intracellular domain of Notch1. In conclusion, Notch1 signaling positively regulated MRP1 in 16HBE cells and AITC induced MRP1 expression and function may be attributed to Notch1 signaling. These findings show that Notch1 and MRP1 might have a potential protective effect in the COPD process and become a new therapeutic target for COPD or other lung diseases. It also provides a theoretical basis for the therapeutic effects of AITC.

Preparation and in vitro/in vivo evaluation of azilsartan osmotic pump tablets based on the preformulation investigation.

The objective of this study was to design and evaluate azilsartan osmotic pump tablets. Preformulation properties of azilsartan were investigated for formulation design. Azilsartan osmotic pump tablets were prepared by incorporation of drug in the core and subsequent coating with cellulose acetate and polyethylene glycol 4000 as semi-permeable membrane, then drilled an orifice at the center of one side. The influence of different cores, compositions of semipermeable membrane and orifice diameter on azilsartan release were evaluated. The formulation of core tablet was optimized by orthogonal design and the release profiles of various formulations were evaluated by similarity factor (f2). The optimal formulation achieved to deliver azilsartan at an approximate zero-order up to 14 h. The pharmacokinetic study was performed in beagle dogs. The azilsartan osmotic pump tablets exhibited less fluctuation in blood concentration and higher bioavailability compared to immediate-release tablets. Moreover, there was a good correlation between the in vitro dissolution and in vivo absorption of the tablets. In summary, azilsartan osmotic pump tablets presented controlled release in vitro, high bioavailability in vivo and a good in vitro-in vivo correlation.

Pharmacokinetics, Tissue Distribution, Plasma Protein Binding Studies of 10-Dehydroxyl-12-Demethoxy-Conophylline, a Novel Anti-Tumor Candidate, in Rats.

10-Dehydroxyl-12-demethoxy-conophylline is a natural anticancer candidate. The motivation of this study was to explore the pharmacokinetic profiles, tissue distribution, and plasma protein binding of 10-dehydroxyl-12-demethoxy-conophylline in Sprague Dawley rats. A rapid, sensitive, and specific ultra-performance liquid chromatography (UPLC) system with a fluorescence (FLR) detection method was developed for the determination of 10-dehydroxyl-12-demethoxy-conophylline in different rat biological samples. After intravenous (i.v.) dosing of 10-dehydroxyl-12-demethoxy-conophylline at different levels (4, 8, and 12 mg/kg), the half-life t1/2α of intravenous administration was about 7 min and the t1/2ß was about 68 min. The AUC0→∞ increased in a dose-proportional manner from 68.478 µg/L·min for 4 mg/kg to 305.616 mg/L·min for 12 mg/kg. After intragastrical (i.g.) dosing of 20 mg/kg, plasma levels of 10-dehydroxyl-12-demethoxy-conophylline peaked at about 90 min. 10-dehydroxyl-12-demethoxy-conophyllinea absolute oral bioavailability was only 15.79%. The pharmacokinetics process of the drug was fit to a two-room model. Following a single i.v. dose (8 mg/kg), 10-dehydroxyl-12-demethoxy-conophylline was detected in all examined tissues with the highest in kidney, liver, and lung. Equilibrium dialysis was used to evaluate plasma protein binding of 10-dehydroxyl-12-demethoxy-conophylline at three concentrations (1.00, 2.50, and 5.00 µg/mL). Results indicated a very high protein binding degree (over 80%), reducing substantially the free fraction of the compound.

A Novel Paclitaxel-Loaded Polymeric Micelle System with Favorable Biocompatibility and Superior Antitumor Activity.

BACKGROUND/AIM: Polymeric micelles are promising vehicles for paclitaxel delivery. Further improvement in the stability of the micelle formulation is desirable. MATERIALS AND METHODS: Monomethoxy poly(ethylene glycol)-block-poly(D,L-lactide)-9-fluorenylmethoxycarbonyl-L-phenylalanine (mPEG-PDLLA-Phe(Fmoc)) was synthesized through a classical esterification reaction. Paclitaxel-loaded mPEG-PDLLA-Phe(Fmoc) micelles (PTX-PheMs) were prepared by the self-assembly method. Composition, structure and physicochemical properties were characterized. Pharmacokinetics were evaluated in rats. Therapeutic effect was evaluated in tumor-bearing mice. Safety profile was assessed by a hemolysis assay and an acute-toxicity study. RESULTS: The average size of PTX-PheMs was about 45 nm. The hemolysis and acute-toxicity tests confirmed its biocompatibility and safety. The pharmacokinetics and therapeutic effect experiments demonstrated its long circulation property and superior antitumor effect. CONCLUSION: mPEG-PDLLA-Phe(Fmoc) micelle is a biocompatible and effective drug delivery system for hydrophobic drugs such as PTX.

Effect of carboxyethylation degree on the adsorption capacity of Cu(II) by N-(2-carboxyethyl)chitosan from squid pens.

Chitosan was prepared by N-deacetylation of squid pens ß-chitin, and N-carboxyethylated chitosan (N-CECS) with different degrees of substitution (DS) were synthesized. DS values of N-CECS derivatives calculated by (1)H nuclear magnetic resonance (NMR) spectroscopy were 0.60, 1.02 and 1.46, respectively. The adsorption capacity of Cu(II) by N-CECS correlated well with the DS and pH ranging from 3.2 to 5.8. The maximum Cu(II) adsorption capacity (qm) of all three N-CECS at pH 5.4 was 207.5mg g(-1), which was 1.4-fold higher than that of chitosan. The adsorption equilibrium process was better described by the Langmuir than Freundlich isotherm model. Adsorption of Cu(II) ion onto N-CECS followed a pseudo-second order mechanism with chemisorption as the rate-limiting step. In a ternary adsorption system, the adsorption capacity of Cu(II) by N-CECS also presented high values, and qm for Cu(II), Cd(II), and Pb(II) were 150.2, 28.8, and 187.9mg g(-1), respectively.

Preparation, characterization, and biochemical activities of N-(2-Carboxyethyl)chitosan from squid pens.

Chitosan was prepared by alkaline N-deacetylation of ß-chitin from squid pens, and N-carboxyethylated derivatives (N-CECS) with different degrees of substitution (DS) were synthesized. The carboxyethylation of the polysaccharide was identified by Fourier transform infrared, (1)H and (13)C nuclear magnetic resonance (NMR), and X-ray diffraction analyses. The DS of the derivatives was calculated by (1)H NMR and elemental analysis. All three N-CECS samples showed good water solubility at pH > 6.5. The antioxidant properties and bile acid binding capacity of the derivatives were studied in vitro. The highest bile acid binding capacity of all N-CECS reached 36.9 mg/g, which was 2.6-fold higher than that of chitosan. N-CECS showed a stronger scavenging effect on 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical ability, and EC50 values were below 2 mg/mL. The scavenging ability of N-CECS against superoxide radicals correlated well with the DS and concentration of N-CECS. These results indicated that N-carboxyethylation is a possible approach to prepare chitosan derivatives with desirable in vitro biochemical properties.

Deoxycholic acid-modified chitooligosaccharide/mPEG-PDLLA mixed micelles loaded with paclitaxel for enhanced antitumor efficacy.

Poly(ethylene glycol) (PEG) as a block in polymeric micelles can prolong circulation life and reduce systemic clearance but decrease the cellular uptake. To overcome this limitation, a mixed micelle composed of deoxycholic acid-modified chitooligosaccharide (COS-DOCA) and methoxy poly(ethylene glycol)-polylactide copolymer (mPEG-PDLLA) was designed to load paclitaxel (PTX). The PTX-loaded mixed micelles was prepared by nanoprecipitation method with high drug-loading efficiency of 8.03% and encapsulation efficiency of 97.09% as well as small size (∼40 nm) and narrow size distribution. COS-DOCA/mPEG-PDLLA mixed micelles exhibited the sustained release property. Due to the positive charge and bioadhesive property of COS-DOCA, the cellular uptake of PTX in mixed micelles was higher in cancer cells but lower in macrophage cells compared to the mPEG-PDLLA micelles. The systemic toxicity of PTX in mixed micelles was much lower than Taxol using zebrafish as a toxicological model. Furthermore, the PTX-loaded COS-DOCA/mPEG-PDLLA mixed micelles can prolong the blood circulation time of PTX and enhance the antitumor efficacy in A549 lung xenograft model. Our findings indicate that COS-DOCA/mPEG-PDLLA mixed micelles could be a potential vehicle for enhanced delivery of anticancer drugs.

Effects of hydroxypropyl degree on physiochemical activities of chitosan from squid pens.

Chitosan was prepared by alkaline N-deacetylation of ß-chitin and hydroxypropyl derivatives with different degrees of substitution (DS) were synthesized. It was characterized by Fourier transform infrared (FT-IR) and elemental analysis. The DS of hydroxypropyl chitosan (HPCS) calculated by an element analyzer were 0.42, 0.75, 1.20, 1.82 and 2.25. HPCS showed better foam capacity and stability than that of chitosan, and the effectiveness correlated well with the DS of HPCS. The highest bile acid-binding capacity of all five HPCS reached 56.02 mg/g, which was 4.0-fold higher than that of chitosan. The scavenging ability of HPCS against hydroxyl and ABTS radicals improved with increasing concentration. The correlation between the hydroxypropyl content (DS) of HPCS and scavenging ABTS radical ability was positive. The hydroxyl radicals scavenging activity of HPCS correlated well with its increasing concentration, and EC50 values were below 12.5 mg/mL. These results indicated that hydroxypropylation is a possible approach to obtain chitosan derivatives with desirable physiochemical properties.

Hydrogenation of ortho-nitrochlorobenzene on activated carbon supported platinum catalysts.

Platinum/carbon catalyst is one of the most important catalysts in hydrogenation of ortho-nitrochlorobenzene to 2,2'-dichlorohydrazobenzene. The preparation process and the supports of catalysts are studied in this paper. Raw materials and preparation procedure of the activated carbon have great influences on the compositions and surface structure of platinum/carbon catalysts. Platinum catalysts supported on activated carbon with high purity, high surface area, large pore volume and appropriate pore structure usually exhibit higher activities for hydrogenation of ortho-nitrochlorobenzene to 2,2'-dichlorohydrazobenzene. The catalyst prepared from H(2)PtCl(6) with pH=3 shows greater catalytic performance than those prepared under other conditions.