Preparation and Stability of Monodisperse Amorphous CaCO3 Microspheres of High Hardness and Sphericity.

Using amorphous CaCO3 (ACC) to biomimic the crustacean exoskeleton and optimize the physical and chemical properties of the polymeric phase of ACC holds great promise. Controlling the ACC morphology and stability is key in this process. For this article, monodisperse ACC microspheres, with a high sphericity of 0.973 ± 0.001 and a hardness of 0.6755 GPa, were prepared using the gas diffusion method in the presence of Mg2+. Their hardness is 3.58-16 times greater than that ever reported before for ACC microspheres. The stability of ACC is strongly affected by environmental conditions. The liquid phase and high temperature are not conducive to its stability, but ACC microspheres do have high stability under ambient conditions. After 100 days under such conditions, only a small amount of crystallization occurs, and their spherical shape survives intact. This article provides guidance for the preparation of ACC biomimetic composites, sheds light on the biological function of ACC in crustacean exoskeletons, and improves the theoretical understanding of the mechanism of biomineralization.

Identification of Single Yeast Budding Using Impedance Cytometry with a Narrow Electrode Span.

Impedance cytometry is wildly used in single-cell detection, and its sensitivity is essential for determining the status of single cells. In this work, we focus on the effect of electrode gap on detection sensitivity. Through comparing the electrode span of 1 µm and 5 µm, our work shows that narrowing the electrode span could greatly improve detection sensitivity. The mechanism underlying the sensitivity improvement was analyzed via numerical simulation. The small electrode gap (1 µm) allows the electric field to concentrate near the detection area, resulting in a high sensitivity for tiny particles. This finding is also verified with the mixture suspension of 1 µm and 3 µm polystyrene beads. As a result, the electrodes with 1 µm gap can detect more 1 µm beads in the suspension than electrodes with 5 µm gap. Additionally, for single yeast cells analysis, it is found that impedance cytometry with 1 µm electrodes gap can easily distinguish budding yeast cells, which cannot be realized by the impedance cytometry with 5 µm electrodes gap. All experimental results support that narrowing the electrode gap is necessary for tiny particle detection, which is an important step in the development of submicron and nanoscale impedance cytometry.

Percutaneous vertebral augmentation using drill rotation for osteoporotic vertebral compression fractures with intravertebral vacuum cleft.

OBJECTIVE: To evaluate the efficacy of a new technique of percutaneous vertebral augmentation (PVA): drill rotation-cement injected under vacuum aspiration (DR-CIVAS) for vertebral compression fractures (OVCFs) with intravertebral vacuum cleft (IVC) sign. MATERIALS AND METHODS: A retrospective study was conducted in 46 consecutive patients with OVCFs and IVC signs, who underwent PVA using DR-CIVAS (n = 22, DR-CIVAS group) or traditional technique without DR-CIVAS (n = 24, control group). The pre- and postoperative vertebral height and wedge angle change and visual analog scale (VAS), the volume of cement injected, incidences of cement leakage, and subsequent new vertebral compression fractures were evaluated between the two groups. RESULTS: No significant difference was found in cement leakage incidences, pre- and postoperative VAS scores, vertebral height, and wedge angle change between the two groups. The mean cement volume was significantly higher (P < 0.001) in DR-CIVAS group (4.87 mL) than in the control group (3.58 mL). Of the 22 patients in DR-CIVAS group, the subsequent fractures occurred in 2 cases (9.1%) located in the nonadjacent levels. In the control group, the subsequent fractures occurred in 6 cases (25.0%) located in the adjacent level (n = 1) and the augmented levels (n = 5). Although DR-CIVAS group did not demonstrate a statistical reduction of the incidence of subsequent fractures (P = 0.25), the subgroup analysis revealed that subsequent fractures frequently involved the augmented level in the control group (P = 0.04). CONCLUSIONS: PVA with DR-CIVAS technique is effective for OVCFs with IVC sign, with lower incidences of subsequent new vertebral compression fractures in the augmented vertebra.

Comparison of percutaneous long bone cementoplasty with or without embedding a cement-filled catheter for painful long bone metastases with impending fracture.

OBJECTIVE: To compare the efficacy of percutaneous long bone cementoplasty (PLBC) with and without embedding a cement-filled catheter in the medullary canal (ECFC) for painful long bone metastases with impending fracture. METHODS: A retrospective study was conducted in 36 consecutive patients undergoing PLBC and ECFC combination (n = 17, group A) or PLBC alone (n = 19, group B). All patients had a high risk of impending fracture in the long bone based on Mirels' scoring system. Clinical effects were evaluated using both a pre- and a postoperative visual analogue scale (VAS) and Karnofsky performance scale (KPS). RESULTS: Overall pain relief rate with excellent (VAS 0-2) and good (VAS 2.5-4.5) results during follow-up was significantly higher in group A than in group B (88.2 % vs. 57.9 %, P<0.05). The average VAS and KPS changes in group A were significantly higher than those in group B at 1, 3 and 6 months postoperatively (P<0.05). Also, the rate of fractures of the treated long bone in group A was significantly lower than that in group B (P<0.05). CONCLUSIONS: Combined PLBC and ECFC is a safe and effective procedure for long bone metastases with impending fracture. KEY POINTS: • Metastases in long bones may cause pain and subsequent pathological fractures. • Cementoplasty resulted in significant pain relief in patients with long bone metastases. • Combination of PLBC and ECFC may reduce the incidence of fractures.

Cementoplasty for managing painful bone metastases outside the spine.

OBJECTIVE: To illustrate the effect of treatment with cementoplasty in patients with painful bone metastases in the extraspinal region. METHODS: A retrospective study was conducted to review 51 consecutive patients who underwent cementoplasty under CT or fluoroscopic guidance, a total of 65 lesions involving the ilium, ischium, pubis, acetabulum, humeral, femur and tibia. In 5 patients with a high risk of impending fracture in long bones based on Mirels' scoring system, an innovative technique using a cement-filled catheter was applied. The clinical effects were evaluated using the visual analogue scale (VAS) preoperatively and postoperatively. RESULTS: All patients were treated successfully with a satisfying resolution of painful symptoms at 3 months' follow-up. Cement leakage was found in 8 lesions without any symptoms. VAS scores decreased from 8.19 ± 1.1 preoperatively to 4.94 ± 1.6 at 3 days, 3.41 ± 2.1 at 1 month and 3.02 ± 1.9 at 3 months postoperatively. There was a significant difference between the mean preoperative baseline score and the mean score at all of the postoperative follow-up points (P < 0.01). CONCLUSIONS: Cementoplasty is an effective technique for treating painful bone metastases in extraspinal regions, which is a valuable, minimally invasive, method that allows reduction of pain and improvement of patients' quality of life. KEY POINTS: • Metastases in long bones may cause pain and subsequent pathological fractures. • Cement-filled catheter resulted in a fixation effect to prevent pathological fractures. • Cementoplasty resulted in significant pain relief in patients with extraspinal metastases.

Percutaneous vertebroplasty for painful spinal metastasis with epidural encroachment.

BACKGROUND AND OBJECTIVES: Spinal metastasis with epidural encroachment is regarded by several authors to be a contraindication to percutaneous vertebroplasty (PVP) because of the risk of increasing symptomatic leakage of cement. This analysis aims to evaluate the safety and efficacy of PVP in patients with painful spinal metastasis and encroachment of epidural space. METHODS: A retrospective study was conducted to review 43 consecutive patients with spinal metastasis that underwent PVP, for a total of 69 affected levels. All patients had at least 1 level associated with epidural encroachment related to metastasis. Among these patients, 14 had signs of spinal cord or cauda equina compression. Pain intensity was scored on a visual-analog scale (VAS). The analgesic efficacy was defined as at least 50% improvement in pain score as compared with the pre-procedure baseline and post-procedure. Clinical improvement of neurological compressive symptoms was defined as a decrease in ASIA impairment scale from baseline of 1 point or more. RESULTS: The analgesic efficacy was achieved in 89.7% of survival patients at 1 month, 87.5% at 3 months, 86.9% at 6 months, and 84.6% at 1 year. Small amount cement leakages were detected in 69.6% of treated levels without clinical complications. No deterioration of spinal cord or cauda equina compression symptoms was observed after a PVP in any patients. The different grade of epidural encroachment of the lesions was not correlated with filling volume or extraosseous leakage (P > 0.05). The treated levels with epidural encroachment showed a statistically significant relationship to spinal-canal leakage (P < 0.05). CONCLUSIONS: PVP can be performed safely and effectively in patients with painful spinal metastasis and epidural encroachment.

Ligand-Induced Atomically Segregation-Tunable Alloy Nanoprobes for Enhanced Magnetic Resonance Imaging.

Bimetallic iron-noble metal alloy nanoparticles have emerged as promising contrast agents for magnetic resonance imaging (MRI) due to their biocompatibility and facile control over the element distribution. However, the inherent surface energy discrepancy between iron and noble metal often leads to Fe atom segregation within the nanoparticle, resulting in limited iron-water molecule interactions and, consequently, diminished relaxometric performance. In this study, we present the development of a class of ligand-induced atomically segregation-tunable alloy nanoprobes (STAN) composed of bimetallic iron-gold nanoparticles. By manipulating the oxidation state of Fe on the particle surface through varying molar ratios of oleic acid and oleylamine ligands, we successfully achieve surface Fe enrichment. Under the application of a 9 T MRI system, the optimized STAN formulation, characterized by a surface Fe content of 60.1 at %, exhibits an impressive r1 value of 2.28 mM-1·s-1, along with a low r2/r1 ratio of 6.2. This exceptional performance allows for the clear visualization of hepatic tumors as small as 0.7 mm in diameter in vivo, highlighting the immense potential of STAN as a next-generation contrast agent for highly sensitive MR imaging.

Vertebroplasty in the treatment of symptomatic vertebral haemangiomas without neurological deficit.

OBJECTIVE: To evaluate the effectiveness of vertebroplasty in symptomatic vertebral haemangiomas (VHs) with no neurological deficit, with or without features of aggressiveness in imaging studies. METHODS: A retrospective study was conducted to review 31 consecutive patients with symptomatic VHs that underwent vertebroplasty procedures (13 males, 18 females; mean age, 57.5 years), for a total of 33 affected vertebral levels (range, T4-L5 levels). Pre procedure radiological examinations were reviewed. The presence of predominant soft tissue stroma on CT, low signals on T1W of MRI, epidural tissue, and cortical erosion are considered features of aggressiveness. The clinical effects were evaluated using the visual analogue scale (VAS) and modified Roland-Morris Disability Questionnaire (RDQ) at the pre and each postoperative follow-up time point (mean follow-up of 15.8 months). RESULTS: Symptomatic VHs with no signs of aggressiveness were observed in 26 lesions and those with signs of aggressiveness in 7 lesions. Vertebroplasty was successfully performed under fluoroscopic guidance with a unipedicular approach in 16 levels, a bipedicular approach in 17 levels. VAS scores and RDQ scores were significantly improved after vertebroplasty (P < 0.001). Extraosseous cement leakage was observed in 4 patients without clinical complications. CONCLUSIONS: Vertebroplasty is an optional treatment for symptomatic VHs with no neurological deficit. KEY POINTS: • Vertebral haemangiomas with or without aggressive signs may cause pain. • Radiological signs of aggressiveness include evidence of lesions that contain less fat predominance, evidence of epidural soft tissue and evidence of cortical erosion. • Vertebroplasty provides effective treatment for symptomatic vertebral haemangiomas causing no neurological deficit.

One-pot synthesis of dynamically cross-linked polymers for serum-resistant nucleic acid delivery.

Cationic polymers used for nucleic acid delivery often suffer from complicated syntheses, undesired intracellular cargo release and low serum stability. Herein, a series of ternary polymers were synthesized via facile green chemistry to achieve efficient plasmid DNA and mRNA delivery in serum. During the one-pot synthesis of the ternary polymer, acetylphenylboric acid (APBA), polyphenol and low-molecular weight polyethyleneimine (PEI 1.8k) were dynamically cross-linked with each other due to formation of an imine between PEI 1.8k and APBA and formation of a boronate ester between APBA and polyphenol. Series of polyphenols, including ellagic acid (EA), epigallocatechin gallate (EGCG), nordihydroguaiaretic acid (NDGA), rutin (RT) and rosmarinic acid (RA), and APBA molecules, including 2-acetylphenylboric acid (2-APBA), 3-acetylphenylboric acid (3-APBA) and 4-acetylphenylboric acid (4-APBA), were screened and the best-performing ternary polymer, 2-PEI-RT, constructed from RT and 2-APBA, was identified. The ternary polymer featured efficient DNA condensation to favor cellular internalization, and the acidic environment in endolysosomes triggered effective degradation of the polymer to promote cargo release. Thus, 2-PEI-RT showed robust plasmid DNA transfection efficiencies in various tumor cells in serum, outperforming the commercial reagent PEI 25k by 1-3 orders of magnitude. Moreover, 2-PEI-RT mediated efficient cytosolic delivery of Cas9-mRNA/sgRNA to enable pronounced CRISPR-Cas9 genome editing in vitro. Such a facile and robust platform holds great potential for non-viral nucleic acid delivery and gene therapy.

A Trained Humanoid Robot can Perform Human-Like Crossmodal Social Attention and Conflict Resolution.

To enhance human-robot social interaction, it is essential for robots to process multiple social cues in a complex real-world environment. However, incongruency of input information across modalities is inevitable and could be challenging for robots to process. To tackle this challenge, our study adopted the neurorobotic paradigm of crossmodal conflict resolution to make a robot express human-like social attention. A behavioural experiment was conducted on 37 participants for the human study. We designed a round-table meeting scenario with three animated avatars to improve ecological validity. Each avatar wore a medical mask to obscure the facial cues of the nose, mouth, and jaw. The central avatar shifted its eye gaze while the peripheral avatars generated sound. Gaze direction and sound locations were either spatially congruent or incongruent. We observed that the central avatar's dynamic gaze could trigger crossmodal social attention responses. In particular, human performance was better under the congruent audio-visual condition than the incongruent condition. Our saliency prediction model was trained to detect social cues, predict audio-visual saliency, and attend selectively for the robot study. After mounting the trained model on the iCub, the robot was exposed to laboratory conditions similar to the human experiment. While the human performance was overall superior, our trained model demonstrated that it could replicate attention responses similar to humans.

[Effects of Low-density Polyethylene Microplastics on the Growth and Physiology Characteristics of Ipomoea aquatica Forsk].

Microplastic pollution in soil and its toxicological effects have attracted increasing attention from researchers, but the mechanisms of microplastics affecting crop growth and physiology remain unclear. A pot experiment was conducted to evaluate the impacts of various mass concentrations (0%, 0.2%, 5%, and 10%) of low-density polyethylene microplastics (LDPE MPs) on the germination rate, photosynthetic pigment content, biomass, antioxidant enzyme activity, soluble protein, and soluble sugar content of water spinach (Ipomoea aquatica Forsk). The results showed that LDPE MPs significantly inhibited (P<0.05) the seed vigor of water spinach, and the inhibitory effect increased with increasing concentration of LDPE MPs. However, the 5% LDPE MPs significantly promoted the aboveground biomass of water spinach. The 0.2% and 10% LDPE MPs significantly improved the superoxide dismutase (SOD) activity and catalase (CAT) and peroxidase (POD) activities, respectively. Further, malondialdehyde (MDA) content decreased with increasing concentration of LDPE MPs, and the reductions reached 15.53%-27.39% in comparison to that in the control. The LDPE MPs also significantly increased the soluble sugar content of water spinach leaves. In summary, LDPE MPs could inhibit the seed vigor and promote biomass accumulation in water spinach. Water spinach could relieve the oxidative stress caused by LDPE MPs by regulating antioxidant enzyme activity and soluble protein content. Therefore, this study may provide basic information for assessing the influences of microplastics on vegetables.

Tailoring Hyperbranched Poly(ß-amino ester) as a Robust and Universal Platform for Cytosolic Protein Delivery.

Cytosolic protein delivery is a prerequisite for protein-based biotechnologies and therapeutics on intracellular targets. Polymers that can complex with proteins to form nano-assemblies represent one of the most important categories of materials, because of the ease of nano-fabrication, high protein loading efficiency, no need for purification, and maintenance of protein bioactivity. Stable protein encapsulation and efficient intracellular liberation are two critical yet opposite processes toward cytosolic delivery, and polymers that can resolve these two conflicting challenges are still lacking. Herein, hyperbranched poly(ß-amino ester) (HPAE) with backbone-embedded phenylboronic acid (PBA) is developed to synchronize these two processes, wherein PBA enhanced protein encapsulation via nitrogen-boronate (N-B) coordination while triggered polymer degradation and protein release upon oxidation by H2 O2 in cancer cells. Upon optimization of the branching degree, charge density, and PBA distribution, the best-performing A2-B3-C2-S2 -P2 is identified, which mediates robust delivery of various native proteins/peptides with distinct molecular weights (1.6-430 kDa) and isoelectric points (4.1-10.3) into cancer cells, including enzymes, toxins, antibodies, and CRISPR-Cas9 ribonucleoproteins (RNPs). Moreover, A2-B3-C2-S2 -P2 mediates effective cytosolic delivery of saporin both in vitro and in vivo to provoke remarkable anti-tumor efficacy. Such a potent and universal platform holds transformative potentials for protein pharmaceuticals.

Dual-frequency impedance assays for intracellular components in microalgal cells.

Intracellular components (including organelles and biomolecules) at the submicron level are typically analyzed in situ by special preparation or expensive setups. Here, a label-free and cost-effective approach of screening microalgal single-cells at a subcellular resolution is available based on impedance cytometry. To the best of our knowledge, it is the first time that the relationships between impedance signals and submicron intracellular organelles and biomolecules are shown. Experiments were performed on Euglena gracilis (E. gracilis) cells incubated under different incubation conditions (i.e., aerobic and anaerobic) and 15 µm polystyrene beads (reference) at two distinct stimulation frequencies (i.e., 500 kHz and 6 MHz). Based on the impedance detection of tens of thousands of samples at a throughput of about 900 cells per second, three metrics were used to track the changes in biophysical properties of samples. As a result, the electrical diameters of cells showed a clear shrinkage in cell volume and intracellular components, as observed under a microscope. The morphology metric of impedance pulses (i.e., tilt index) successfully characterized the changes in cell shape and intracellular composition distribution. Besides, the electrical opacity showed a stable ratio of the intracellular components to cell volume under the cellular self-regulation. Additionally, simulations were used to support these findings and to elucidate how submicron intracellular components and cell morphology affect impedance signals, providing a basis for future improvements. This work opens up a label-free and high-throughput way to analyze single-cell intracellular components by impedance cytometry.

Reactive oxygen species-responsive branched poly (ß-amino ester) with robust efficiency for cytosolic protein delivery.

Protein therapy targeting the intracellular machinery holds great potentials for disease treatment, and therefore, effective cytosolic protein delivery technologies are highly demanded. Herein, we developed reactive oxygen species (ROS)-degradable, branched poly(ß-amino ester) (PBAE) with built-in phenylboronic acid (PBA) in the backbone and terminal-pendent arginine for the efficient cytosolic protein delivery. The PBAE could form stable and cell-ingestible nanocomplexes (NCs) with proteins via electrostatic interaction, nitrogen-boronate (N-B) coordination, and hydrogen bonding, while it can be degraded into small segments by the over-produced H2O2 in tumor cells to enable cytoplasmic protein release. As thus, PBAE exhibited high efficiency in delivering varieties of proteins with distinct molecular weights (12.4-430 kDa) and isoelectric points (4.7-10.5) into tumor cells, including enzymes, toxins, and antibodies. Moreover, PBAE mediated efficient delivery of saporin into tumor cells in vivo, provoking pronounced anti-tumor outcomes. This study provides a robust and versatile platform for cytosolic protein delivery, and the elaborately tailored PBAE may find promising applications for protein-based biological research and disease management. STATEMENT OF SIGNIFICANCE: Cytosolic delivery of native proteins holds great therapeutic potentials, which however, is limited by the lack of robust delivery carriers that can simultaneously feature strong protein encapsulation yet effective intracellular protein release. Herein, ROS-degradable, branched poly(ß-amino ester) (PBAE) with backbone-embedded phenylboronic acid (PBA) and terminal-pendent arginine was developed to synchronize these two processes. PBA and arginine moieties allowed PBAE to encapsulate proteins via N-B coordination, electrostatic interaction, hydrogen bonding, and salt bridging, while PBA could be oxidized by over-produced H2O2 inside cancer cells to trigger PBAE degradation and intracellular protein release. As thus, the top-performing PBAE mediated efficient cytosolic delivery of various proteins including enzymes, toxins, and antibodies. This study provides a powerful platform for cytosolic protein delivery, and may find promising utilities toward intracellular protein therapy against cancer and other diseases such as inflammation.

Parallel Impedance Cytometry for Real-Time Screening of Bacterial Single Cells from Nano- to Microscale.

The benefits of impedance cytometry include high-throughput and label-free detection, while long-term calibration is required to remove the effects of the detection circuits. This study presents a novel impedance cytometry system, called parallel impedance cytometry, to simplify the calibration and analysis of the impedance signals. Furthermore, target objects can be detected even when benchmarked against similar objects. Parallel dual microchannels allow the simultaneous detection of reference and target particles in two separate microchannels, without the premixing of reference and target suspensions. The impedance pulses of both can appear separately on the opposite sides of the same time series, which have been verified via simulation and experimental results. Raw impedance signals can easily distinguish target particles from reference ones. Polystyrene beads with different sizes ranging from nano- to microscale (e.g., 500, 750 nm, 1, 2, 3, and 4.5 µm) confirm the nanosensitivity of the system. In addition, the detection of antibiotic-treated Escherichia coli cells demonstrates that our system can be used for the quantitative assessment of the dielectric properties of individual cells, as well as for the proportion of susceptible cells. Through benchmarking against untreated E. coli cells in the other channel, our method enables the discrimination of susceptible cells from others and the comparison of susceptible and insusceptible cells in the target suspension. Those findings indicate that the parallel impedance cytometry can greatly facilitate the measurement and calibration of the impedances of various particles or cells and provide a means to compare their dielectric properties.

Height restoration and wedge angle correction effects of percutaneous vertebroplasty: association with intraosseous clefts.

OBJECTIVE: To evaluate effects of vertebroplasty on restoration of vertebral body height and wedge angle and relief from pain in patients with osteoporotic compression fractures. METHODS: A retrospective study of 156 patients (232 levels) who had undergone vertebroplasty was conducted. Treated vertebrae with cleft included 49 patients (49 levels) and that without cleft 107 patients (183 levels). Effects on restoration of vertebral body height and wedge angle, and pain scores between pre- and post-procedure were statistically analyzed by using a paired-sample t test, and Kruskal Wallis test. RESULTS: The height and wedge angle of the fractured vertebral body, and pain score, improved significantly after vertebroplasty. On a vertebra-by-vertebra analysis, the vertebral body height and wedge angle in the cleft group, were statistically significantly better post-procedure (P < 0.01); in the non-cleft group, there was nosignificant improved (P > 0.05). Pain relief was not statistically significant different between the two groups (P > 0.05). CONCLUSION: Most patients experienced pain relief after vertebroplasty. After vertebroplasty, the height and wedge angle were significantly improved in the cleft group (p < 0.01), with no significant improvement in the non-cleft group (p > 0.05). Key Points • Vertebra with cleft is attributed to improvement of the spinal deformity • Vertebra without cleft was not associated with improvement of the spinal deformity • Vertebroplasty is an effective treatment strategy for osteoporotic compression fractures.

Terbium doping of graphitic carbon nitride endows a highly sensitive ratiometric fluorescence assay of alkaline phosphatase.

Terbium doped graphitic carbon nitride (g-C3N4:Tb) gives rise to two exceptional emissions at λex/λem = 290/490 nm and 290/546 nm, with extremely narrow peak widths of FWHM < 12 nm as well as a large Stokes shift of >200 nm. The modification of g-C3N4:Tb with HOOC-PEG-COOH provides a ratiometric fluorescent probe which ensures highly sensitive detection of alkaline phosphatase (ALP) activity based on the inner filter effect (IFE).

Microscopic impedance cytometry for quantifying single cell shape.

In this work, we investigated the ability of impedance flow cytometry to measure the shape of single cells/particles. We found that the impedance pulses triggered by micro-objects that are asymmetric in morphology show a tilting trend, and there is no such a tilting trend for symmetric ones. Therefore, we proposed a new metric, tilt index, to quantify the tilt level of the impedance pulses. Through simulation, we found that the value of tilt index tends to be zero for perfectly symmetrical objects, while the value is greater than zero for asymmetrical ones. Also, this metric was found to be independent on the trajectories (i.e., lateral, and z-direction shift) of the target micro-object. In experiments, we adopted a home-made lock-in amplifier and performed experiments on 10 µm polystyrene beads and Euglena gracilis (E. gracilis) cells with varying shapes. The experimental results coincided with the simulation results and demonstrated that the new metric (tilt index) enables the impedance cytometry to characterize the shape single cells/particles without microscopy or other optical setups.

Brij-58, a potential injectable protein-stabilizer used in therapeutic protein formulation.

Polysorbates (PSs) are common protein stabilizers used in biotherapeutic formulations. However, PSs are heterogeneous and unstable in liquid protein formulations [1,2]. The purpose of this work is to explore possible alternatives for polysorbate replacements that demonstrate superior protein protection, superior self-stability, low toxicity, and wide applicability. For this purpose, 8 non-ionic surfactants that have not yet been used as excipients in marketed biotherapeutic products were investigated with PS20/80 as the benchmark. Compared with PS20/80, Brij-58 showed better protein protection ability in the mAb1 formulation under forced degradation conditions when examined by visual inspection, SEC, and dynamic lighting scanning. Additionally, Brij-58 has a better inherent stability than PS20/80 in the protein formulation when detected by UPLC-CAD. Moreover, Brij-58 is an inert excipient that does not affect protein bioactivity and conformation. In addition, the LD50 and hemolysis concentration of Brij-58 were determined, which is relatively safe when used as a parenteral injection. Furthermore, Brij-58 was also an effective protein stabilizer for the other two antibody products (IgG4 subtype and bispecific antibody) in the shaking study. In summary, Brij-58 stands out as a promising PS replacement in biotherapeutic formulations with a safe, stable and effective protein-protection profile among candidate surfactants.

Robust All-Cellulose Nanofiber Composite from Stack-Up Bacterial Cellulose Hydrogels via Self-Aggregation Forces.

All-cellulose composites are usually prepared by removing impurities and using a surface-selective dissolution approach, which detract significantly from their environment-friendly properties. In this paper, we report an environment-friendly approach to fabricate all-cellulose nanofiber composites from stack-up bacterial cellulose (BC) hydrogels via self-aggregation forces of the hydrogen bond by water-based processing. Structural and mechanical properties of BC-laminated composites have been investigated. The results indicated that BC composites possess the structure of all nanofibers, a tensile strength of 116 MPa, and a storage modulus of 25 GPa. Additionally, the interfacial shear strength and tensile strength of piece-hot-press BC demonstrate the strong self-aggregation forces of BC nanofibers. Thus, BC-laminated composites will be attractive in structural material.