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Microfluidic capillary zone electrophoresis coupled to mass spectrometry enables improved throughput, resolution, and sensitivity in characterization of 12–40 kDa bispecific antigen-binding biotherapeutic fragments compared to traditional methods.

Acrophobia (fear of heights), a prevalent psychological disorder, elicits profound fear and evokes a range of adverse physiological responses in individuals when exposed to heights, which will lead to a very dangerous state for people in actual heights. In this paper, we explore the behavioral influences in terms of movements in people confronted with virtual reality scenes of extreme heights and develop an acrophobia classification model based on human movement characteristics. To this end, we used wireless miniaturized inertial navigation sensors (WMINS) network to obtain the information of limb movements in the virtual environment. Based on these data, we constructed a series of data feature processing processes, proposed a system model for the classification of acrophobia and non-acrophobia based on human motion feature analysis, and realized the classification recognition of acrophobia and non-acrophobia through the designed integrated learning model. The final accuracy of acrophobia dichotomous classification based on limb motion information reached 94.64%, which has higher accuracy and efficiency compared with other existing research models. Overall, our study demonstrates a strong correlation between people’s mental state during fear of heights and their limb movements at that time.

Aims This study aimed to explore the therapeutic effects of Lactiplantibacillus plantarum HG20 (HG20) on collagen-induced arthritis (CIA) rats and its mechanism. Methods and Results CIA rats were established by injecting bovine type II collagen for 7 days, and treated by intragastric administration HG20 for 21 days. The foot palm temperature and arthritis score were measured once a week. The pathological changes in the knee joint were observed by hematoxylin and eosin staining. The levels of cytokines were detected by enzyme linked immunosorbent assay, and the effects of HG20 on inflammatory and apoptosis pathway of spleen cells were detected by western blot analysis. The results indicated that HG20 reduced the joint swelling degree and foot palm temperature, inhibited the development of joint histopathology, decreased the levels of pro-inflammatory cytokines, down-regulate the expression of pro-inflammatory cytokines by nuclear factor kappa-B pathway, and inhibited the apoptosis of spleen cells by inhibiting phosphatidylinositol 3-kinase/protein kinase B pathway and regulating apoptosis pathways. Conclusions HG20 had an adjuvant therapeutic effect on arthritis in CIA rats, and its mechanism might be related to the inflammatory and apoptosis pathway. Significance and Impact of Study These results revealed that HG20 could be used as a functional probiotic in the field of food and medical, and which played a potential role in the prevention and treatment of arthritis.

The development of a simple and efficient methanol-resistant membrane strategy is of great significance for improvement of the performance of fuel cells, making it an attractive and challenging topic. In this work, sulfonated covalent triazine framework (SCTF) nanosheets are prepared by a micro-interface method and post-sulfonation, which show excellent dispersion in polar solutions, such as water and N, N-Dimethylacetamide (DMAc). Then a series of composite proton exchange membranes (SCTF-x@SPP-co-PAEKs) are prepared by blending these SCTF nanosheets with sulfonated micro-block copolymers (SPP-co-PAEKs) resin. The results show that the appropriate addition of SCTF can significantly improve the proton conductivity (PC), methanol resistance and fuel cell performance of the prepared composite membrane, which can be attributed to the good interfacial compatibility between the SCTF nanosheets and the sulfonated micro-block copolymer matrix. The passive direct methanol fuel cells (DMFCs) with SCTF-x@SPP-3 membrane exhibit power density in the range of 28.0–33.3 mW cm−2 at 25 °C, which is superior to the related values of the pristine membrane and the commercial Nafion® series membranes.

Chemotherapy resistance is a huge challenge in the treatment of hepatocellular carcinoma because resistance to nab-paclitaxel largely affects the efficacy of chemotherapy. An increased expression of fibronectin type III domain containing 5 (FNDC5) in hepatocellular carcinoma cells can predict post-hepatectomy complications in patients with hepatocellular carcinoma and also stimulate proliferation and invasion of hepatocellular carcinoma cells; however, its role in the chemotherapy of hepatocellular carcinoma cells has never been evaluated. Thus, this study aimed to explore whether FNDC5 regulates chemoresistance in hepatocellular carcinoma. We identified by immunohistochemistry that hepatocellular carcinoma tissues had a higher FNDC5 expression than normal tissues adjacent to the cancer cells. Subsequently, knockdown of FNDC5 in hepatocellular carcinoma cells resulted in their diminished resistance to cell death after chemotherapy with nab-paclitaxel. By contrast, overexpression of FNDC5 in hepatocellular carcinoma cells increased the resistance of hepatocellular carcinoma cells to treatment. Moreover, FNDC5 mechanistically promoted autophagy via the AMPK/mTOR signaling pathway, thereby reducing cell death induced by nab-paclitaxel. Finally, we tested our hypothesis by conducting animal experiments. In conclusion, FNDC5 could be used as a biomarker for predicting chemotherapeutic efficacy in hepatocellular carcinoma treated with nab-paclitaxel chemotherapy, and as a therapeutic target to overcome resistance to nab-paclitaxel in hepatocellular carcinoma chemotherapy.

Chemotherapy resistance is a huge challenge in the treatment of hepatocellular carcinoma because resistance to nab-paclitaxel largely affects the efficacy of chemotherapy. An increased expression of fibronectin type III domain-containing protein 5 (FNDC5) in hepatocellular carcinoma cells can predict post-hepatectomy complications in patients with hepatocellular carcinoma and also stimulate proliferation and invasion of hepatocellular carcinoma cells; however, its role in the chemotherapy of hepatocellular carcinoma cells has never been evaluated. Thus, this study aimed to explore whether FNDC5 regulates chemoresistance in hepatocellular carcinoma. We identified by immunohistochemistry that hepatocellular carcinoma tissues had a higher FNDC5 expression than normal tissues adjacent to the cancer cells. Subsequently, knockdown of FNDC5 in hepatocellular carcinoma cells resulted in their diminished resistance to cell death after chemotherapy with nab-paclitaxel. By contrast, overexpression of FNDC5 in hepatocellular carcinoma cells increased the resistance of hepatocellular carcinoma cells to treatment. Moreover, FNDC5 mechanistically promoted autophagy via the AMPK/mTOR signaling pathway, thereby reducing cell death induced by nab-paclitaxel. Finally, we tested our hypothesis by conducting animal experiments. In conclusion, FNDC5 could be used as a biomarker for predicting chemotherapeutic efficacy in hepatocellular carcinoma treated with nab-paclitaxel chemotherapy, and as a therapeutic target to overcome resistance to nab-paclitaxel in hepatocellular carcinoma chemotherapy.

The preparation of polyelectrolytes with excellent stability in high alkaline conditions still faces several challenges. In this study, we report a novel imidazolium-ionized monomer PhIM [PF₆], modified by the propylbenzene group on the position of N1/N3, which can be copolymerized with 1,1,1-trifluoroacetone under superacid-catalyzed conditions. The main-chain poly(arylene–imidazolium) polymers with a controllable degree of functionalization, high molecular weight, and good solubility are successfully prepared without further postfunctionalization. Two copolymers (block-like and random) can also be prepared by introducing biphenyl as a comonomer and adjusting the feed order. Due to their different microstructures, the two copolymers exhibit different ion conduction behaviors, water absorption capacities, and mechanical properties. The obtained polymer membranes exhibit high hydroxide conductivities and high chemical stability even after treatment in a 10 M NaOH solution at 80 °C. In summary, we highlight a simple, effective, and low-cost strategy to prepare highly alkaline stable poly(arylene–imidazolium) polymers.

BACKGROUND: Therapeutic hypothermia (TH) is effective to treat adult traumatic brain injury (TBI), but there is still controversy about its safety to treat the children with severe TBI. METHODS: Clinical studies on TH in children with severe TBI from January 2000 to September 2020 were screened in PubMed, Web of Science, Embase, Cochrane Library, Nature, NCKI, and Wanfang online databases. Data were meta-analyzed by Rev Man 5.3. Differences in mortality, adverse outcomes, duration of Pediatric Intensive Care Unit (PICU), incidence of infection, and incidence of arrhythmia were compared between experimental group and control group. The heterogeneity of the results was evaluated by chi-square test and I(2) test in Rev Man 5.3, and publication bias was evaluated by funnel plot. RESULTS: Five articles were included, including 421 children. Cochrane evaluation was B grade or above, and Jadad scale score was over three points. The overall mortality between two groups showed great difference [odds ratio (OR) =1.72, 95% CI: 0.98–3.02, Z=1.87, P=0.04]. The incidence of adverse outcomes (OR =1.39, 95% CI: 0.86–2.25, Z=1.34, P=0.18), the duration of PICU [mean difference (MD) =0.51, 95% CI: −0.33 to 1.35, Z=1.19, P=0.24], the incidence of infection (OR =0.79, 95% CI: 0.51–1.23, Z=1.03, P=0.30), and the incidence of arrhythmia (OR =3.10, 95% CI: 0.77–12.50, Z=1.59, P=0.11) were not considerably different. DISCUSSION: TH significantly reduced overall mortality in children with severe TBI, but did not significantly improve the incidence of adverse outcomes, PICU duration, infection rate, or arrhythmia. These results provided a reference for selecting proper clinical treatment methods for children with severe TBI.

The epidermal growth factor receptor (EGFR), a receptor tyrosine kinase, regulates basic cellular functions and is a major target for anticancer therapeutics. The carboxyl-terminus domain is a disordered region of EGFR that contains the tyrosine residues, which undergo autophosphorylation followed by docking of signaling proteins. Local phosphorylation-dependent secondary structure has been identified and is thought to be associated with the signaling cascade. Deciphering and distinguishing the overall conformations, however, have been challenging because of the disordered nature of the carboxyl-terminus domain and resultant lack of well-defined three-dimensional structure for most of the domain. We investigated the overall conformational states of the isolated EGFR carboxyl-terminus domain using single-molecule Förster resonance energy transfer and coarse-grained simulations. Our results suggest that electrostatic interactions between charged residues emerge within the disordered domain upon phosphorylation, producing a looplike conformation. This conformation may enable binding of downstream signaling proteins and potentially reflect a general mechanism in which electrostatics transiently generate functional architectures in disordered regions of a well-folded protein.

Membrane proteins participate in a broad range of cellular processes and represent more than 60% of drug targets. A new approach to their structural analyses is mass spectrometry (MS)-based footprinting including hydrogen/deuterium exchange (HDX), fast photochemical oxidation of proteins (FPOP), and residue-specific chemical modification. Studying membrane proteins usually requires their isolation from the native lipid environment, after which they often become unstable. To overcome this problem, we are pursuing a novel methodology of incorporating membrane proteins into saposin A picodiscs for MS footprinting. We apply different footprinting approaches to a model membrane protein, mouse ferroportin, in picodiscs and achieve high coverage that enables the analysis of the ferroportin structure. FPOP footprinting shows extensively labeling of the extramembrane regions of ferroportin and protection at its transmembrane regions, suggesting that the membrane folding of ferroportin is maintained throughout the labeling process. In contrast, an amphipathic reagent, N-ethylmaleimide (NEM), efficiently labels cysteine residues in both extramembrane and transmembrane regions, thereby affording complementary footprinting coverage. Finally, optimization of sample treatment gives a peptic-map of ferroportin in picodiscs with 92% sequence coverage, setting the stage for HDX. These results, taken together, show that picodiscs are a new platform broadly applicable to bottom-up mass spectrometry studies of membrane proteins.

BACKGROUND The aim of this study was to explore the curative effects of cardiothoracic surgery (CTS) for critical patients in the intensive care unit (ICU) using meta-analysis. METHODS Literature was searched using the following search terms: "cardiothoracic surgery", "intensive care unit", "critical patients", "post-operation", and "curative effects". Rev Man 5.3 was used for meta-analysis. RESULTS A total of 15 randomized controlled trials (RCTs) were included, all of which had a low risk of bias, indicating medium and high quality. At 30 days after CTS, the number of patients with grade III and IV cardiac function was reduced by 76.84%, and the overall heterogeneity test results revealed that Tau2=0.09, Chi2=17.08, df=5, I2=71%, P=0.004

Because children with autism cannot carry out normal language and social activities, parents and teachers cannot fully understand their specific interests. But the eyes can express their thoughts and feelings and subtle feelings that are difficult to express with words. By tracking children's eye trajectories in real time, they can perform natural eye movement interactions in contextual classified scenes, and perform interest screening and analysis based on the gaze data of the hierarchical interest screening content. After a comparative experiment, the subjects' real eye movement intentions are consistent with the test intentions. According to this method, the children with autism can communicate effectively with their points of interest.

With the development of human-computer interaction technology, due to the advantages of virtual interaction and the quantification of motion capture data, gesture recognition controllers such as LeapMotion have been introduced into hand function rehabilitation training. However, when used individually, its measuring angle and measuring range are limited and cannot be applied in a large space. In this paper, the dual LeapMotion combination is used to unify the data in the two coordinate systems into the same coordinate system, thereby increasing the acquisition space range and space field of view. Through coordinate system conversion, the converted data is consistent with the actual test action. This method can be extended to multiple LeapMotion combinations.