Effect of Annealing on Visible-Bubble Formation and Stability Profiles of Freeze-Dried High Concentration Omalizumab Formulations.

In the clinical application of freeze-dried highly concentrated omalizumab formulations, extensive visible bubbles (VBs) can be generated and remain for a long period of time in the reconstitution process, which greatly reduces the clinical use efficiency. It is necessary to understand the forming and breaking mechanism of VBs in the reconstitution process, which is a key factor for efficient and safe administration of biopharmaceutical injection. The effects of different thermal treatments on the volume of VBs and stability of omalizumab, mAb-1, and mAb-2 were investigated. The internal microvoids of the cake were characterized by scanning electron microscopy and mercury intrusion porosimetry. Electron paramagnetic resonance was applied to obtain the molecular mobility of the protein during annealing. A large number of VBs were generated in the reconstitution process of unannealed omalizumab and remained for a long period of time. When annealing steps were added, the volume of VBs was dramatically reduced. When annealed at an aggressive temperature (i.e., -6 °C), although the volume of VBs decreased, the aggregation and acidic species increased significantly. Thus, our observations highlight the importance of setting an additional annealing step with a suitable temperature, which contributes to reducing the VBs while maintaining the stability of the high concentration freeze-dried protein formulation.

Secure RoF system based on key nested polar code and feedback neural network.

With the development of 6 G network, the issue of information security is becoming more and more significant. In this paper, a secure RoF system based on key nested polar code and feedback neural network (FNN) is proposed. For the nested polar code, the original key is randomly selected from the constructed codebook and the index of key is encoded by inner polar code which is placed at the location with better channel quality bit of the frozen bit of outer polar code, for the other part of outer polar code, information bits are encrypted by chaotic sequence generated by 4-D cellular neural network. The polar coded sequence is mapped to the 16-QAM symbol for orthogonal frequency division multiplexing (OFDM) and then the OFDM signal is modulated to the optical pulse, which is delivered to users through 50 km standard single-mode fiber and 5 m wireless channel. In the receiver, successive cancellation list (SCL) decoder is used for decoding outer polar code and FNN is used for decoding inner polar code to reduce the latency. The experimental results show that, compared with the existing scheme, when the bit err rate is 10-3, the received optical power (ROP) gain of the proposed scheme with SCL2 decoder and SCL4 decoder is ∼1.2 dB and ∼1.6 dB, respectively. And compared with the traditional OFDM signal with polar code, when the bit err rate is 10-3, the ROP gain of the proposed scheme with SCL4 decoder is ∼1 dB. What's more, the randomness of the chaotic key sequence, the ability to resist brute-force attacks and the ability to resist chosen-plaintext attacks are elaborated. Therefore, the proposed scheme can greatly improve the security of the system while ensuring the correct transmission of information.

Coordinated-security based on probabilistic shaping and encryption in MMW-RoF system.

A coordinated-security probabilistic shaping (PS) physical layer encryption scheme is proposed for a W-band millimeter-wave radio-over-fiber (MMW-RoF) system. This scheme mainly includes substituting encryption, coordinated encrypted PS, and unequal length grouping scrambling, which can realize the coordination between PS and chaotic encryption. The key space of the proposed scheme is 10103, which can effectively prevent against brute force cracking and chosen-plaintext attacks. The encrypted orthogonal frequency division multiplexing (OFDM) signal is successfully transmitted over 50-km standard single-mode fiber (SSMF) and a 5-m wireless channel. The results show that the proposed scheme achieves 0.8-dB received optical power gain at a bit error rate (BER) of 10-3 compared with a traditional OFDM signal. The superiority of the proposed scheme in security performance and BER performance has been verified.

Porosity Engineering of Dried Smart Poly(N-isopropylacrylamide) Hydrogels for Gas Sensing.

A recent study unveiled the potential of acrylamide-based stimulus-responsive hydrogels for volatile organic compound detection in gaseous environments. However, for gas sensing, a large surface area, that is, a highly porous material, offering many adsorption sites is crucial. The large humidity variation in the gaseous environment constitutes a significant challenge for preserving an initially porous structure, as the pores tend to be unstable and irreversibly collapse. Therefore, the present investigation focuses on enhancing the porosity of smart PNiPAAm hydrogels under the conditions of a gaseous environment and the preservation of the structural integrity for long-term use. We have studied the influence of polyethylene glycol (PEG) as a porogen and the application of different drying methods and posttreatment. The investigations lead to the conclusion that only the combination of PEG addition, freeze-drying, and subsequent conditioning in high relative humidity enables a long-term stable formation of a porous surface and inner structure of the material. The significantly enhanced swelling response in a gaseous environment and in the test gas acetone is confirmed by gravimetric experiments of bulk samples and continuous measurements of thin films on piezoresistive pressure sensor chips. These measurements are furthermore complemented by an in-depth analysis of the morphology and microstructure. While the study was conducted for PNiPAAm, the insights and developed processes are general in nature and can be applied for porosity engineering of other smart hydrogel materials for VOC detection in gaseous environments.

State-of-the-art molecular imprinted colorimetric sensors and their on-site inspecting applications.

Molecular imprinted colorimetric sensors can realize visual semi-quantitative analysis without the use of any equipment. With the advantages of low cost, fast response, ease of handling, and excellent recognition ability, the molecular imprinted colorimetric sensor shows great application potential in the field of sample rapid assay. Molecular imprinted colorimetric sensors can be prepared in various forms to meet the needs of different sample determination, such as film, hydrogel, strip, and adsorption coating. In this review, the preparation methods for various types of molecularly imprinted colorimetric sensors are systematically introduced. Their applications in the field of on-site biological sample detection, drug detection, disease treatment, chiral substance detection and separation, environmental analysis, and food safety detection are introduced. The limitations encountered in the practical application are presented, and the future development directions prospect.

Elimination of light chain tailing in reducing capillary electrophoresis with sodium dodecyl sulfate analysis of a monoclonal antibody.

Capillary electrophoresis with sodium dodecyl sulfate (CE-SDS) is a common analytical technique for investigating the purity and molecular size heterogeneity of monoclonal antibody (mAb) drugs. In reducing CE-SDS analysis of mAb-A, the light chain (LC) peak exhibited severe tailing, seriously affecting the purity analysis. The purposes of this investigation are to clarify the source of tailing and develop a more appropriate CE-SDS method to eliminate LC tailing. The degree of LC tailing was closely related to the mAb concentration, SDS concentration, and injection amount, and more hydrophobic detergents, such as sodium hexadecyl sulfate (SHS) and sodium tetradecyl sulfate (STS), could be used instead of SDS to obtain better peak shapes. The results also indicated that the tailing was caused by the binding problem associated with SDS, and SHS/STS could provide a more stable and uniform complexation for the LC. In summary, the method we developed successfully eliminated the LC tailing and provided a robust characterization of mAb-A in reducing CE-SDS analysis.

Security enhancement of a W-band millimeter-wave signal based on 3D Hilbert scrambling and diffusion.

A physical layer enhancement scheme of the W-band millimeter-wave signal based on chaotic grouping and segmentation encryption, 3D Hilbert scrambling, and diffusion is proposed in this paper. Chaotic grouping and segmentation bit-level encryption can enhance the randomness of data and enlarge the key space. 3D Hilbert scrambling and chaotic diffusion are performed in symbol and subcarrier domains. The correlation of data can be effectively reduced after encryption. The analyses show that the key space of the proposed scheme can reach ∼10152. The encrypted W-band millimeter-wave signal can be successfully transmitted in the orthogonal frequency division multiplexing (OFDM) radio-over-fiber (RoF) system of 50-km standard single-mode fiber (SSMF) and 3-m wireless channel, and the experimental results demonstrate that the proposed scheme can enhance the security of the system without negatively affecting transmission performance.

Investigation of an Uncommon Artifact during Reducing Capillary Electrophoresis-Sodium Dodecyl Sulfate Analysis of a Monoclonal Antibody with Dynamic Light Scattering and Reversed Phase High-Performance Liquid Chromatography.

PURPOSES: In reducing capillary electrophoresis sodium dodecyl sulfate (CE-SDS) analysis of a monoclonal antibody (mAb-1), the peak area ratio of heavy chain (HC) to light chain (LC) was out of balance, while multiple artifact peaks were observed following the migration of HC. The main purposes of this study were to describe the techniques utilized to eliminate this artifact and clarify the root cause for this interesting phenomenon. METHODS: We optimized the CE-SDS analysis of mAb-1 by a vairety of techniques including changing the concentration of protein or replacing SDS with a more hydrophobic surfactant (i.e., sodium hexadecyl sulfate (SHS) or sodium tetradecyl sulfate (STS) instead of SDS) in sample and/or the sieving gel buffer. Dynamic light scattering (DLS) and reversed phase high-performance liquid chromatography (RP-HPLC) were used to study the protein-surfactant complex. RESULTS: The artifact could be partially mitigated by reducing the protein concentration and replacing SDS with SHS or STS in the sample and/or the sieving gel buffer solutions. Due to replacing a more hydrophobic surfactant, the HC-surfactant complex formed was more resistant to dissociation, preventing additional hydrophobic HC-HC interaction and aggregation, thus eliminating the artifact problem. CONCLUSIONS: DLS and RP-HPLC are powerful supplementary techniques in characterizing the protein-surfactant complex, and hydrophobic surfactants such as SHS and STS could afford more normal electropherograms during the analysis of mAbs.

Probabilistic shaping based constellation encryption for physical layer security in OFDM RoF system.

The physical layer security of radio-over-fiber (RoF) system is a very important problem for future communication. In this paper, a novel probabilistic shaping (PS) based constellation encryption scheme is proposed in which two bit-level encryption operations are firstly performed according to chaotic sequences and hash values. The chaotic sequences are generated by hyperchaotic system and hash values are obtained by SHA-512. Then PS is applied to enhance transmission performance. After PS-16-quadrature amplitude modulation (QAM), constellation encryption is implemented aiming at maintaining overall shaping distribution unchanged and improving security. An encrypted PS-16-QAM orthogonal frequency division multiplexing (OFDM) signal is successfully transmitted over 50 km standard single-mode fiber (SSMF) and 5 m wireless channel in our experiment. The results demonstrate that the key space of 10121 is achieved to defend malicious attacks. Moreover, the proposed PS-based encryption scheme can obtain approximately 2.4 dB gain at a BER of 10-3 compared with traditional OFDM signal. Thus, the proposed scheme has a good application prospect in the future OFDM-RoF system due to the dominant BER and security performance.

Stress-Actuated Spiral Microelectrode for High-Performance Lithium-Ion Microbatteries.

Miniaturization of batteries lags behind the success of modern electronic devices. Neither the device volume nor the energy density of microbatteries meets the requirement of microscale electronic devices. The main limitation for pushing the energy density of microbatteries arises from the low mass loading of active materials. However, merely pushing the mass loading through increased electrode thickness is accompanied by the long charge transfer pathway and inferior mechanical properties for long-term operation. Here, a new spiral microelectrode upon stress-actuation accomplishes high mass loading but short charge transfer pathways. At a small footprint area of around 1 mm2 , a 21-fold increase of the mass loading is achieved while featuring fast charge transfer at the nanoscale. The spiral microelectrode delivers a maximum area capacity of 1053 µAh cm-2 with a retention of 67% over 50 cycles. Moreover, the energy density of the cylinder microbattery using the spiral microelectrode as the anode reaches 12.6 mWh cm-3 at an ultrasmall volume of 3 mm3 . In terms of the device volume and energy density, the cylinder microbattery outperforms most of the current microbattery technologies, and hence provides a new strategy to develop high-performance microbatteries that can be integrated with miniaturized electronic devices.

Magnetic hypercrosslinked polymer microspheres for the detection, spatial distribution, source identification and potential risks assessment of five polycyclic aromatic hydrocarbons in city river of plateau lake, Southwest China.

Polycyclic aromatic hydrocarbons (PAHs) have long been globally distributed, and almost worldwide people are exposed to varying degrees of PAHs. Aqueous medium is an important transmission route of PAHs, but the detection of PAHs in aqueous environment has been a challenge. Herein, a magnetic hypercrosslinked polymer microsphere (Fe3O4@SiO2-PS@HCP) was developed for the effective detection of PAHs. Under the effect of multiple factors (hydrophilicity, intermolecular force and molecular volume), Fe3O4@SiO2-PS@HCP shows excellent performance on the enrichment of five PAHs in aqueous environment. Fe3O4@SiO2-PS@HCP was used to capture PAHs in city river of plateau lake. In-depth data analysis showed that factory activities and traffic emissions are the main pollution sources of PAHs. Ecological, carcinogenic and non-carcinogenic risks are almost within the safe range. The carcinogenic and non-carcinogenic risks of PAHs in children are higher than adults, which needs to be taken seriously. This method breaks the dilemma that it is difficult to enrich weakly hydrophilic pollutants in aqueous media, and complements important pathways for tracing sources of pollutants and assessing associated risks. It brings methodological enlightenment into the development of environmental pollution and human health risk assessment methodology.

Characterization and exploration of an artifact in the reducing capillary electrophoresis-sodium dodecyl sulfate analysis of the 'me-too' drug zuberitamab related to rituximab.

For monoclonal antibody (mAb) drugs, the 'me-too' drug is a pharmacologically active compound that is structurally similar to the first-in-class drugs, acting on the same target and is used for the same therapeutic purposes, but it may differ in drug-drug interactions and adverse drug reactions. Capillary electrophoresis-sodium dodecyl sulfate (CE-SDS) has been widely used for quality evaluation of mAb drugs. The properties of the detected substances can interfere with the credibility and accuracy of the method. In the routine comparison analysis for both innovator rituximab and 'me-too' drug zuberitamab samples, an uncommon artifact related to the heavy chain (HC) of zuberitamab was observed in reducing CE-SDS and interfered with our identification of the purity of samples. In this work, the overall hydrophobicity of the HCs of rituximab, zuberitamab, and several other common mAbs was characterized and determined by reversed-phase high-performance liquid chromatography. Additionally, the local hydrophobicity and surface charge were compared using Expasy ProtScale and PyMOL software simulations. We concluded that noncovalent protein aggregation can be related to strong hydrophobicity and low electrostatic repulsion of local amino acid regions, which complicates drug quality control. These findings shed light on the relationship between protein aggregation and the local hydrophobicity region, and broaden the way to analyze the detection 'artifacts' in reducing CE-SDS studies of therapeutic proteins.

Advances in Molecular Imprinting Technology for the Extraction and Detection of Quercetin in Plants.

Quercetin is a kind of flavonoid compound, which has antioxidative, anti-aging and anti-cancer effects, so it is of great importance to study the efficient extraction and highly sensitive detection of quercetin. Molecular imprinting technology has remarkable selectivity and resistance to complex matrix interference, which is often used for extracting quercetin. The methods of molecular imprinted solid phase extraction, molecularly imprinted microsphere extraction, molecularly imprinted electrochemical sensor recognition and molecularly imprinted composite material extraction of quercetin from plant samples were discussed in detail. This review provides valuable information on efficient and sensitive methods for separating and purifying quercetin in plants. It also provides a technical reference for further investigation of the separation and analysis of active ingredients in natural products.

Monitoring of low-molecular-weight protein aggregation by CE-SDS as a complementary method to SE-HPLC.

Capillary electrophoresis with sodium dodecyl sulfate (CE-SDS) has long been proven to have excellent performance in the analysis and characterization of therapeutic proteins. However, it is rarely used for the detection of low-molecular-weight proteins or peptides. Our research has proved the ability of CE-SDS to characterize the purity of low-molecular-weight proteins (i.e., <10 kDa) and even polypeptides. In this article, insulin glargine was used as a model protein, and CE-SDS was used to analyze the samples damaged by heating and light exposure. The monomers, dimers, and trimers of insulin glargine were effectively separated, and the results of the mass spectrometry also confirmed the existence of two kinds of insulin aggregates. For comparison, the size-exclusion high-performance liquid chromatography (SE-HPLC) only showed a single aggregate peak. In addition, the denaturation conditions caused only the covalent aggregates to appear in the CE-SDS analysis. These advantages also make CE-SDS an excellent supplementary technology to the traditional SE-HPLC, providing biopharmaceutical analysts with more information.

Multitarget Reactive Magnetron Sputtering towards the Production of Strontium Molybdate Thin Films.

X-ray photoelectron spectroscopy was used to study the direct synthesis of strontium and molybdenum oxide thin films deposited by multitarget reactive magnetron sputtering (MT-RMS). Sr and Mo targets with a purity of 99.9% and 99.5%, respectively, were co-sputtered in an argon-oxygen gas mixture. The chamber was provided with an oxygen background flow plus an additional controlled oxygen supply to each of the targets. We demonstrate that variation in the power applied to the Mo target during MT-RMS enables the production of strontium and molybdenum oxide films with variable concentrations of Mo atoms. Both molybdenum and strontium were found in the oxidized state, and no metallic peaks were detected. The deconvoluted high-resolution XPS spectra of molybdenum revealed the presence of several Mo 3d peaks, which indicates molybdenum bonds in a lower valence state. Contrary to the Mo spectra, the high-resolution strontium Sr 3d spectra for the same samples were very similar, and no additional peaks were detected.

Establishment of a Spontaneous Liver Fibrosis Model in NOD/SCID Mice Induced by Natural Aging.

Liver fibrosis, a critical pathological feature of chronic liver diseases, arises from a multitude of pathogenic factors. Consequently, establishing an appropriate animal model to simulate liver fibrosis holds immense significance for comprehending its underlying pathogenesis. Despite the numerous methodologies available for generating liver fibrosis models, they often deviate substantially from the spontaneous age-related liver fibrosis process. In this study, compared with young (12 weeks) and middle-aged NOD/SCID mice (32 weeks), there were a large number of fibrous septum and collagen in the liver tissue of old NOD/SCID mice (43 weeks, 43 W). Immunohistochemical analysis unequivocally indicated heightened α-SMA content within the liver tissue of the 43 W mice, thereby underscoring aging's role in triggering the epithelial-to-mesenchymal transition. In addition, SA-ß-gal staining as well as P21 expression were increased, and SIRT1 and SIRT3 expression were decreased in 43 W mice. A comprehensive evaluation encompassing transmission electron microscopy and fluorescence quantitative analysis elucidated compromised mitochondrial function and reduced antioxidant capacity in hepatocytes of the 43 W mice. Furthermore, the aging process activated the pro-fibrotic TGF-ß-SMAD pathway, concurrently inducing hepatocellular inflammation. The results of the present study not only validate the successful construction of a spontaneous liver fibrosis mouse model through natural aging induction but also provide initial insights into the mechanisms underpinning age-induced liver fibrosis.

Myc induced miR-144/451 contributes to the acquired imatinib resistance in chronic myelogenous leukemia cell K562.

Imatinib resistance remains the big hurdle for CML therapy. Previous study reveals that c-myc is important for bcr-abl CML cell proliferation, while its role in imatinib resistance is largely unknown. In this study, we first found that c-myc expression is upregulated in imatinib resistant K562R cells, which in turn enhances the expression of miR-144/451. Knockdown of c-myc or restoration of miR-144/451 in the K562R cells sensitizes K562R cells to imatinib therapy. Our study here reveals an regulatory pathway between myc and miR-144/451 and highlights that targeting either myc or miR-144/451 might be valuable for eliminating the imatinib resistant CML cells.