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The ASCENT trial demonstrated the efficacy of sacituzumab govitecan for the treatment of advanced or metastatic triple-negative breast cancer (TNBC). The current study evaluated the cost-effectiveness of receiving sacituzumab govitecan compared with standard of care chemotherapy from the United States payer perspective. A partitioned survival approach was used to project the disease course of advanced or metastatic TNBC. Two survival modes were applied to analyze two groups of patients. The survival data were gathered from the ASCENT trial. Direct medical costs were derived from the data of Centers for Medicare & Medicaid Services. Utility data was collected from the published literature. The incremental cost-utility ratio (ICUR) was the primary outcome that measured the cost-effectiveness of therapy regimen. One-way sensitivity and probabilistic sensitivity analysis were implemented to explore the uncertainty and validate the stability of results. In the base-case, the ICUR of sacituzumab govitecan versus chemotherapy is $ 778,771.9/QALY and $ 702,281/QALY for full population group and brain metastatic-negative (BMN) group with the setting of classic survival mode. And in the setting of cure survival mode, the ICUR is $ 506,504.5/QALY for the full population group and $ 274,232.0/QALY for BMN population group. One-way sensitivity analyses revealed that the unit cost of sacituzumab govitecan and body weight were key roles that lower the ICUR value. Probabilistic sensitivity analyses also showed that reducing the unit price of sacituzumab govitecan can improve the likelihood of becoming cost-effective. The cost-effectiveness analysis suggested that from a US payer perspective, sacituzumab govitecan at current price is unlikely to be a preferred option for patients with advanced or metastatic TNBC at a threshold of $ 150,000/QALY. • Sacituzumab govitecan was better in the brain metastases-negative group than in the full population. • The survival benefit is more significant in the cure mode than in the classic mode. • The unit price of sacituzumab govitecan and the body weight could have a significant impact on the reduction in ICUR. • From a US payer perspective, sacituzumab govitecan is unlikely to be a preferred option for patients with advanced or metastatic TNBC. [ABSTRACT FROM AUTHOR]

Photocatalytic oxalic acid (OA) activation for pharmaceutical wastewater degradation based on Fe-based catalysts are usually limited by the cycle of Fe3+/Fe2+ and low conversion efficiency of OA. Herein, an effective OA activator, FeOOH loaded FeWO 4 /WO 3 (FFW) heterojunction photocatalyst, were fabricated by electrostatic self-assembly for tetracycline (TC) degradation. Experimental results revealed that the introduction of FeOOH can greatly enhance the optical absorption and separation efficiency of photogenerated carriers of the FeWO 4 /WO 3 (FW) composite. Moreover, optimized FFW heterojunction exhibited the excellent photocatalytic OA activation activity and the highest OA conversion rate for TC degradation, which exhibited 97.3% photocatalytic performance for TC within 30 min under 420 nm light irradiation. The FFW heterojunction still revealed high photocatalytic OA activation activity for TC degradation even after six cycles. The possible degradation pathway of TC and photocatalytic OA activation mechanism of FFW heterojunction were also presented by ESR spectroscopy results, quenching tests, and LC-MS analysis. This work not only provides a fresh perspective on the surface photo-Fenton chemistry of catalytic redox processes, but also presents a valid reference for designing highly efficient photocatalytic OA-activation systems for pharmaceutical wastewater treatment. [Display omitted] • FeOOH loaded FeWO 4 /WO 3 heterojunction was fabricated for TC degradation via oxalic acid activation. • The introduced FeOOH can greatly enhance the separation efficiency of photogenerated carriers. • FeOOH loaded FeWO 4 /WO 3 heterojunction showed high activity, stability and adaptability. • The mechanism of oxalic acid activation was proposed. [ABSTRACT FROM AUTHOR]

In this study, the effects of enzymatic hydrolysis of tallow and addition of sodium chloride (NaCl) were evaluated on the formation of 3-monochloropropane-1,2-diol (3-MCPD) esters and sensory characteristic of beef flavors. The enzymatic hydrolysis condition had significant effects on 3-MCPD mono/di-esters formation during the beef flavor preparation. Considering the safety and sensory characteristics of beef flavors, the optimal enzymatic hydrolysis conditions were selected as: lipase concentration 75 U/g tallow, tallow concentration 80% (w/v) and pH 7.0 at 47.5 °C for 9.5 h. Using the optimal enzymatic hydrolysis conditions, no 3-MCPD monoesters were detected and 3-MCPD-diesters concentration was strongly dependent on NaCl concentration and its addition moment (before or after thermal reaction) at different temperatures. In conclusion, beef flavor was prepared using the optimal hydrolysis conditions and heated at 110 °C for 100 min, then 10% NaCl was added when the system was cooled to 60 °C. [ABSTRACT FROM AUTHOR]

HIV-1-negative factor (Nef) protein antagonizes serine incorporator 5 (SERINC5) by redirecting this potent restriction factor to the endosomes and lysosomes for degradation. However, the precise mechanism remains unclear. Using affinity purification/mass spectrometry, we identify cyclin K (CycK) and cyclin-dependent kinase 13 (CDK13) as a Nef-associated kinase complex. CycK/CDK13 phosphorylates the serine at position 360 (S360) in SERINC5, which is required for Nef downregulation of SERINC5 from the cell surface and its counteractivity of the SERINC5 antiviral activity. To understand the role of S360 phosphorylation, we generate chimeric proteins between CD8 and SERINC5 to study their response to Nef. Nef not only downregulates but, importantly, also binds to this chimera in an S360-dependent manner. Thus, S360 phosphorylation increases interactions between Nef and SERINC5 and initiates the destruction of SERINC5 by the endocytic machinery. [Display omitted] • HIV-1 Nef interacts with SERINC5 and the CycK/CDK13 kinase complex • CycK/CDK13 phosphorylates S360 in intracellular loop 4 (ICL4) of SERINC5 • S360 phosphorylation enhances SERINC5 binding to the Nef/AP-2 complex • SERINC5 is then targeted to endosomes and lysosomes for degradation Chai et al. show that CycK/CDK13 is a Nef-associated serine kinase complex. They provide additional insights into how Nef antagonizes SERINC5 via the endocytic machinery for optimal HIV-1 infectivity by identifying S360 as the SERINC5 phosphorylation site, which is required for its binding to Nef and its subsequent downregulation. [ABSTRACT FROM AUTHOR]

This study evaluated the rheological, textural, and microstructural characteristics of CaSO 4 -induced soy protein isolate (SPI) gels in the presence of various sesbania gum (SG) concentrations. The results showed that SG significantly increased the storage modulus (G′), loss modulus (G″), and mechanical strength, especially, in adding 0.3 wt% SG. Furthermore, the gel microstructures varied from homogenous to slight phase separation with a continuous protein phase followed by significant phase separation, depending on SG concentration. The fractal dimension of the gels calculated from confocal laser scanning microscopy (CLSM) images decreased gradually with increased SG concentrations. The denser microstructure in the local regions is related to improving the water-holding capacity (WHC). Fourier transform infrared spectroscopy (FTIR) spectra confirmed that hydrogen bonds are crucial in maintaining the three-dimensional network structure of the SPI-SG gels. A lower concentration (0.1–0.3 wt%) of SG facilitates the formation of the gel; however, if the concentration of SG becomes 0.4 wt% or 0.5 wt%, SPI-SG interactions are inhibited by the entangled galactomannan chains, resulting in significant phase separation. Our findings suggested the great potential of SG in modulating the properties and structure of CaSO 4 -induced SPI gels, obtaining novel SPI-based food gel products with improved texture. [Display omitted] • Adding SG improves the viscoelastic properties and promotes soy protein isolate (SPI) gel formation. • Incorporating 0.3 wt% SG can create a denser gel with a higher WHC. • The microstructure of SPI-SG gels varied depending on the SG concentration. • SG interacts with SPI via stronger hydrogen bonds, increasing gel hardness. [ABSTRACT FROM AUTHOR]

With ever-growing demand for eco-friendly materials for wearable electronics, biopolymer-based hydrogels have drawn significant attention. As one of the most abundant and biodegradable biopolymers, starch-based hydrogels have a great potential for wearable electronics. However, mechanical fragility, low conductivity and subzero freeze restrict their applications. Here, a multifunctional hydrogel was facilely fabricated by integrating ionic liquid and graphene oxide into potato starch/polyvinyl alcohol skeleton via a green physical-crosslinking method. The abundant hydrogen-bond and electrostatic interactions endowed the hydrogel with excellent stretchability (657.5 %), strength (0.64 MPa), high conductivity (1.98 S·m−1) and good anti-freezing property (< −20 °C). Multiple characterizations and theoretical simulation (DFT) were combined to understand and confirm the interactions among different components. Taking advantage of these properties, multimodal wearable sensors were constructed for sensing tension (gauge factor: 6.04), compression (gauge factor: 3.27) and temperature (sensitivity: 0.71 %/°C), which are applied for monitoring human motion, daily-life pressure and body temperature. The sensor had a good anti-fatigue property with stable signals during 2000 cycles. Moreover, the sensor can effectively recognize handwriting and perform human-computer interaction. This work provides a promising route to develop sustainable and multifunctional biopolymer hydrogels for wearable sensors with versatile applications in human health, exercise monitors and soft robots. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract In this work, nanosheet-shaped CuS (NS CuS) is successfully grown on carbon cloth (CC) by a two-step route in combination with electrodeposition and hydrothermal treatment via in situ sulfidations of Cu 2 O and Cu with exposure to thiourea at 120 °C or 24 h. Transmission electron microscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, and X-ray diffractometry are performed to characterize the microstructure, morphology, composition, and crystal structure of the NS CuS CC samples. The electrochemical measurements demonstrate that the synthesized NS CuS CC electrocatalysts possess outstanding oxygen evolution reaction (OER) performance and superior long-term durability in 1 M KOH electrolyte. In particular, the NS CuS CC synthesized via the electrodeposition process at an applied current of 1.5 mA shows a low overpotential for the OER (358 mV at 10 mA/cm2), which is close to that of commercial IrO 2 (346 mV at 10 mA/cm2). The exceptional OER property is ascribed to the NS CuS having a large surface area to offer abundant reaction active sites and to the CC network structures supplying more ions and charge transfer channels during the electrocatalytic process. [ABSTRACT FROM AUTHOR]

Understanding the phase separation behavior and the interaction mechanism under different conditions is important for the microstructure regulation of macromolecule systems via the induction or inhibition of phase separation. NaCl is widely used to flavor foods and urea is often used as a plasticizer in food packaging materials. In this work, the combined effects of NaCl-pH and urea-pH on phase separation of the model system of type-A gelatin-dextran (GE/DE, 4.0 wt%/4.0 wt%) were investigated. The macroscopic and microscopic structures and phase separation rate of GE/DE with different concentrations of NaCl or urea at pH 3.00, 4.00, 5.00 and 8.00 were investigated using static multiple light scattering (S-MLS), fluorescence microscopy and macroscopic observations. The results showed that NaCl promoted GE/DE phase separation at the above four pHs, and the phase separation rates were significantly increased at pH 5.00 and 8.00 even at quite low concentration of NaCl (5.0 mM). Urea seemed to inhibit the phase separation at all urea concentrations at pH 3.00–5.00 and at high urea concentration of 6.0 M at pH 8.00, while promoted the phase separation only at low concentrations of 0.5–4.0 M at pH 8.00. The effects of NaCl and urea on GE/DE phase separation at different pHs might be related with the zeta potential and transparency of gelatin. This work quantitatively characterized the induction or inhibition effect of NaCl and urea on GE/DE phase separation at different pHs, which was useful for the stability of mixed macromolecules added with NaCl or urea. [Display omitted] • Phase separation rates of type A gelatin/dextran were quantitatively characterized. • The combined effects of NaCl-pH and urea-pH on the phase separation were studied. • NaCl promoted the phase separation even at quite low concentration of 5 mM. • Urea promoted or inhibited the phase separation at different concentrations. • Zeta potential and transparency of gelatin might explain effects of NaCl and urea. [ABSTRACT FROM AUTHOR]

• The D-M ICGA shortened detection time and increased limits. • Signal amplification and flow rate control enhance ICGA sensitivity. • 1000-fold higher sensitivity was achieved by using the D-M ICGA. Application of the traditional immunochromatographic assay (ICGA) has been limited by its poor sensitivity. The objective of this study was to increase the sensitivity of the traditional ICGA. A dual-mode ICGA (D-M ICGA) was developed by combining a nanozyme-assisted signal-amplification strategy with a magnetic-nanoparticle-based flow-speed-control strategy. Salmonella typhimurium can be detected simultaneously based on color and magnetic signals in the detection area of the D-M ICGA strip. The calculated limits of detection of 50 cfu·mL−1 and 75 cfu·mL−1 in the color and magnetic modes, respectively, were approximately 1000 times lower than those of the traditional ICGA. The selectivity and practical applicability of the D-M ICGA were also confirmed in this study. The results prove that the D-M ICGA is an assay that could be used for Salmonella typhimurium detection and can be easily adapted to detect other pathogenic bacteria. [ABSTRACT FROM AUTHOR]

Rabies virus (RABV) is a neurotropic virus that causes fatal disease in humans and animals. Currently there is no cure for rabies once clinical signs appear. It is believed that once RABV enters the central nervous system (CNS), virus neutralizing antibodies (VNAs) in the periphery cannot pass through the blood–brain barrier (BBB) and into the CNS. Furthermore, it has been hypothesized that VNAs produced in the CNS by invading B cells, rather than those produced in the periphery and then transported into the CNS, are important in clearing RABV from the CNS. In the present study, mouse serum containing VNA was administered intravenously into mice after infection with wild-type RABV. Our studies demonstrate that exogenous administration of VNAs is crucial in the clearance of RABV from the brain and prevent the development of rabies in both immunocompetent and immunocompromised mice as long as the BBB permeability remains enhanced. This present study therefore provides a foundation for the possibility of developing VNA therapy for clinical rabies in humans. [ABSTRACT FROM AUTHOR]