A robot-assisted tracheal intubation system based on a soft actuator?

PURPOSE: Tracheal intubation is the gold standard of airway protection and constitutes a pivotal life-saving technique frequently employed in emergency medical interventions. Hence, in this paper, a system is designed to execute tracheal intubation tasks automatically, offering a safer and more efficient solution, thereby alleviating the burden on physicians. METHODS: The system comprises a tracheal tube with a bendable front end, a drive system, and a tip endoscope. The soft actuator provides two degrees of freedom for precise orientation. It is fabricated with varying-hardness silicone and reinforced with fibers and spiral steel wire for flexibility and safety. The hydraulic actuation system and tube feeding mechanism enable controlled bending and delivery. Object detection of key anatomical features guides the robotic arm and soft actuator. The control strategy involves visual servo control for coordinated robotic arm and soft actuator movements, ensuring accurate and safe tracheal intubation. RESULTS: The kinematics of the soft actuator were established using a constant curvature model, allowing simulation of its workspace. Through experiments, the actuator is capable of 90° bending as well as 20° deflection on the left and right sides. The maximum insertion force of the tube is 2 N. Autonomous tracheal intubation experiments on a training manikin were successful in all 10 trials, with an average insertion time of 45.6 s. CONCLUSION: Experimental validation on the manikin demonstrated that the robot tracheal intubation system based on a soft actuator was able to perform safe, stable, and automated tracheal intubation. In summary, this paper proposed a safe and automated robot-assisted tracheal intubation system based on a soft actuator, showing considerable potential for clinical applications.

Iron accumulation in ovarian microenvironment damages the local redox balance and oocyte quality in aging mice.

Accumulating oxidative damage is a primary driver of ovarian reserve decline along with aging. However, the mechanism behind the imbalance in reactive oxygen species (ROS) is not yet fully understood. Here we investigated changes in iron metabolism and its relationship with ROS disorder in aging ovaries of mice. We found increased iron content in aging ovaries and oocytes, along with abnormal expression of iron metabolic proteins, including heme oxygenase 1 (HO-1), ferritin heavy chain (FTH), ferritin light chain (FTL), mitochondrial ferritin (FTMT), divalent metal transporter 1 (DMT1), ferroportin1(FPN1), iron regulatory proteins (IRP1 and IRP2) and transferrin receptor 1 (TFR1). Notably, aging oocytes exhibited enhanced ferritinophagy and mitophagy, and consistently, there was an increase in cytosolic Fe2+, elevated lipid peroxidation, mitochondrial dysfunction, and augmented lysosome activity. Additionally, the ovarian expression of p53, p21, p16 and microtubule-associated protein tau (Tau) were also found to be upregulated. These alterations could be phenocopied with in vitro Fe2+ administration in oocytes from 2-month-old mice but were alleviated by deferoxamine (DFO). In vivo application of DFO improved ovarian iron metabolism and redox status in 12-month-old mice, and corrected the alterations in cytosolic Fe2+, ferritinophagy and mitophagy, as well as related degenerative changes in oocytes. Thereby in the whole, DFO delayed the decline in ovarian reserve and significantly increased the number of superovulated oocytes with reduced fragmentation and aneuploidy. Together, our findings suggest that aging-related disturbance in ovarian iron homeostasis contributes to excessive ROS production and that iron chelation may improve ovarian redox status, and efficiently delay the decline in ovarian reserve and oocyte quality in aging mice. These data propose a novel intervention strategy for preserving the ovarian reserve function in elderly women.

PLD1 promotes spindle assembly and migration through regulating autophagy in mouse oocyte meiosis.

PLD1 has been implicated in cytoskeletal reorganization and vesicle trafficking in somatic cells; however, its function remains unclear in oocyte meiosis. Herein, we found PLD1 stably expresses in mouse oocytes meiosis, with direct interaction with spindle, RAB11A+ vesicles and macroautophagic/autophagic vacuoles. The genetic or chemical inhibition of PLD1 disturbed MTOC clustering, spindle assembly and its cortical migration, also decreased PtdIns(4,5)P2, phosphorylated CFL1 (p-CFL1 [Ser3]) and ACTR2, and their local distribution on MTOC, spindle and vesicles. Furthermore in PLD1-suppressed oocytes, vesicle size was significantly reduced while F-actin density was dramatically increased in the cytoplasm, the asymmetric distribution of autophagic vacuoles was broken and the whole autophagic process was substantially enhanced, as illustrated with characteristic changes in autophagosomes, autolysosome formation and levels of ATG5, BECN1, LC3-II, SQSTM1 and UB. Exogenous administration of PtdIns(4,5)P2 or overexpression of CFL1 hyperphosphorylation mutant (CFL1S3E) could significantly improve polar MTOC focusing and spindle structure in PLD1-depleted oocytes, whereas overexpression of ACTR2 could rescue not only MTOC clustering, and spindle assembly but also its asymmetric positioning. Interestingly, autophagy activation induced similar defects in spindle structure and positioning; instead, its inhibition alleviated the alterations in PLD1-depleted oocytes, and this was highly attributed to the restored levels of PtdIns(4,5)P2, ACTR2 and p-CFL1 (Ser3). Together, PLD1 promotes spindle assembly and migration in oocyte meiosis, by maintaining rational levels of ACTR2, PtdIns(4,5)P2 and p-CFL1 (Ser3) in a manner of modulating autophagy flux. This study for the first time introduces a unique perspective on autophagic activity and function in oocyte meiotic development.Abbreviations: ACTR2/ARP2: actin related protein 2; ACTR3/ARP3: actin related protein 3; ATG5: autophagy related 5; Baf-A1: bafilomycin A1; BFA: brefeldin A; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GOLGA2/GM130: golgin A2; GV: germinal vesicle; GVBD: germinal vesicle breakdown; IVM: in vitro maturation; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MI: metaphase of meiosis I; MII: metaphase of meiosis II; MO: morpholino; MTOC: microtubule-organizing center; MTOR: mechanistic target of rapamycin kinase; PB1: first polar body; PLA: proximity ligation assay; PLD1: phospholipase D1; PtdIns(4,5)P2/PIP2: phosphatidylinositol 4,5-bisphosphate; RAB11A: RAB11A, member RAS oncogene family; RPS6KB1/S6K1: ribosomal protein S6 kinase B1; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscopy; TUBA/α-tubulin: tubulin alpha; TUBG/γ-tubulin: tubulin gamma; UB: ubiquitin; WASL/N-WASP: WASP like actin nucleation promoting factor.

Loss-of-function mutations in IQCN cause male infertility in humans and mice owing to total fertilization failure.

Fertilization failure is a significant manifestation of unexplained male infertility. Previous work has suggested a genetic origin. In this study, we report on a man with unexplained infertility from a large consanguineous marriage family. Whole-exome sequencing and Sanger sequencing identified a homozygous frameshift variation of the IQ motif containing N (IQCN; GenBank: NM_001145304.1; c.1061_1062delAT; p.Y354Sfs*13) in the proband and one of his two brothers, who also remained infertile. Analyses of spermatozoa by quantitative RT-PCR indicated that the level of IQCN mRNA was significantly reduced compared to fertile men and the protein could not be detected by western blotting and immunofluorescent staining in the proband. Immunofluorescent staining of spermatozoa from fertile men showed that IQCN was located in the acrosomal region and translocated to the equatorial segment after the acrosome reaction. The proband spermatozoa had abnormal morphology and function. Finally, the proband couple underwent IVF with donor sperm and a healthy baby was born. Furthermore, we developed an Iqcn-KO mouse model using the CRISPR/Cas9 technique. Sperm quality, except for sperm motility, and the fertility of male Iqcn-/- mice were consistent with those of the proband. In conclusion, the findings in humans and mice demonstrate that the homozygous frameshift variant of IQCN causes male infertility owing to autosomal-recessive fertilization failure.

Divergent total synthesis of the revised structures of marine anti-cancer meroterpenoids (+)-dysiherbols A-E.

We report here a concise and divergent enantioselective total synthesis of the revised structures of marine anti-cancer sesquiterpene hydroquinone meroterpenoids (+)-dysiherbols A-E (6-10) using dimethyl predysiherbol 14 as a key common intermediate. Two different improved syntheses of dimethyl predysiherbol 14 were elaborated, one starting from Wieland-Miescher ketone derivative 21, which is regio- and diastereoselectively α-benzylated prior to establishing the 6/6/5/6-fused tetracyclic core structure through intramolecular Heck reaction. The second approach exploits an enantioselective 1,4-addition and a Au-catalyzed double cyclization to build-up the core ring system. (+)-Dysiherbol A (6) was prepared from dimethyl predysiherbol 14via direct cyclization, while (+)-dysiherbol E (10) was synthesized through allylic oxidation and subsequent cyclization of 14. Epoxidation of 14 afforded allylic alcohol 45 or unexpectedly rearranged homoallylic alcohol 44. By inverting the configuration of the hydroxy groups, exploiting a reversible 1,2-methyl shift and selectively trapping one of the intermediate carbenium ions through oxy-cyclization, we succeeded to complete the total synthesis of (+)-dysiherbols B-D (7-9). The total synthesis of (+)-dysiherbols A-E (6-10) was accomplished in a divergent manner starting from dimethyl predysiherbol 14, which led to the revision of their originally proposed structures.

Synergistic Effect of Huangqin Decoction Combined Treatment With Radix Actinidiae chinensis on DSS and AOM-Induced Colorectal Cancer.

Objective: To demonstrate the effectiveness of Huangqin decoction (Huangqin Tang in Chinese, HQT) combined with Radix Actinidiae chinensis (Tengligen in Chinese, TLG) under the guidance of "dampness-heat theory" in preventing and treating colorectal cancer (CRC) with dampness-heat accumulation and to preliminarily reveal its mechanism. Methods: The mice model of CRC was established by intraperitoneal injection of AOM combined with consumption of 2.5% DSS solution, and celecoxib, HQT, TLG, and their combination (HQT + TLG) were administered at the same time. The physical signs and death of the mice were observed daily. At the end of the experiment, the colorectal tissue was dissected, and the tumor was observed and counted. HE staining and Masson's staining were used to observe the histopathological changes of colon. Expression levels of TNF-α, IL-6, and IL-10 in colorectal tissue were detected by ELISA, and the expression of TNF-α was observed by immunofluorescence. TUNEL assay was used to observe the apoptosis of tumor tissues, and immunohistochemistry was used to observe the expression of Ki-67 and occludin. The mRNA expression levels of claudin-1, occludin, ZO-1, and IL-6 and IL-17 were detected by RT-PCR, and occludin, ZO-1, NF-κB, and STAT3 protein levels were detected by Western blot. The composition of intestinal flora was analyzed by 16S rRNA. Results: HQT + TLG could significantly reduce the mortality of model mice and improve the intestinal mucosal inflammatory cell infiltration and high-grade intraepithelial neoplasia in model mice. All administration groups show a great reduction in the levels of IL-6 and TNF-α in the colorectal tissues of model mice, and increase in the level of IL-10, the total number of CD3+ T cells, the proportion of CD3+CD4+ T cells, and the ratio of CD4/CD8. HQT and HQT + TLG could significantly change the composition of intestinal flora and increase the abundance of Firmicutes and Patescibacteria. Conclusion: HQT and TLG combination has a good effect on inhibiting AOM-DSS-induced CRC. This function may be related to improving the composition of the intestinal flora, regulating the proportion of T-cell subsets in colorectal lymphoid tissue to improve inflammatory response, and downregulating the expression of claudin-1, inhibiting the activation of IL-6/STAT3 signaling pathway to improving abnormal hyperplasia.

Hydrothermal in situ growth and application of a novel flower-like phosphorous-doped titanium oxide nanoflakes on titanium alloy substrate for enhanced solid-phase microextraction of polycyclic aromatic hydrocarbons in water samples.

A novel flower-like phosphorous-doped titanium oxide nanocomposite coating was in situ grown on nickel-titanium alloy (NiTi) fiber by hydrothermal treatment in phosphoric acid solution. The experimental results demonstrated that phosphorous-doped titanium oxide nanoflakes (P-TiONFs) with an average thickness of 80 nm were formed on the NiTi fiber substrate in 0.1 mol L-1 H3PO4 at 150 °C for 6 h. Thereafter, the resulting P-TiONFs were used as SPME fiber coatings for the adsorption of typical aromatic analytes from environmental water samples, which were determined by HPLC-UV. These P-TiONFs exhibited good adsorption selectivity for hydrophobic PAHs. After optimizing microextraction conditions, linear responses were achieved in the ranges of 0.05-200 µg L-1 for the determination of PAHs with determination coefficients higher than 0.999. LODs (S/N = 3) ranged from 0.009 to 0.132 µg L-1, while LOQs (S/N = 10) ranged from 0.030 to 0.441 µg L-1. RSDs for intra-day and inter-day analyses with a single fiber varied from 4.46% to 5.56% and 5.14%-6.75%, respectively. The relative recoveries of 83.60%-119.0% were achieved for the determination of PAHs in real water samples spiked at the concentration levels of 5.0 µg L-1 and 10.0 µg L-1 with RSDs below 7.38%. In addition, the fibers exhibited no significant decrease in adsorption efficiency after being used 240 adsorption and desorption cycles. The proposed method was successfully applied to the selective enrichment and determination of target PAHs in different water samples.

Selective solid-phase microextraction of polycyclic aromatic hydrocarbons in water based on oriented phosphorus-containing titanium oxide nanofibers grown on titanium support prior to high-performance liquid chromatography with ultraviolet detection.

A novel solid-phase microextraction coating of phosphorous-containing titanium oxide composite was developed using titanium fiber as a support and a titanium source by hydrothermal oxidation in a phosphoric acid solution containing hydrogen peroxide. The morphology of the fiber coatings was controlled by the conditions of the hydrothermal oxidation reaction. The oriented nanofiber coating was employed to extract several types of representative aromatic analytes. The experimental results demonstrated that the as-prepared fiber exhibited excellent extraction efficiency toward polycyclic aromatic hydrocarbons. Combined with high-performance liquid chromatography with ultraviolet detection, main extraction conditions were optimized, including pH, ionic strength, extraction temperature, stirring rate, extraction time and desorption time. The established method presented good linearity from 0.05 to 200 µg/L with limit of detection ranging from 0.012 to 0.126 µg/L. This convenient and green procedure was suitable for the selective extraction and determination of typical polycyclic aromatic hydrocarbons in environmental water samples. The relative recoveries of 85.8-112% were obtained for the determination of target polycyclic aromatic hydrocarbons in water samples spiked with 5.0 and 15.0 µg/L. Moreover, the as-prepared fiber showed at least 210 extraction/desorption cycles due to its high mechanical and chemical stability.

Controllable growth of flower-like hierarchical CoNiO2 nanoflakes anchored on Nitinol fiber substrate with good selectivity for highly efficient solid-phase microextraction of polycyclic aromatic hydrocarbons in water.

The flower-like hierarchical cobalt nickel oxide nanoflakes (CoNiO2NFs) with a porous structure were fabricated on Nitinol (NiTi) fiber substrate by a hydrothermal reaction and subsequent annealing treatment. The morphology affected by the molar ratios of Ni to Co and counter ions in starting precursors as well as hydrothermal reaction temperature and time was investigated in detail. The obtained CoNiO2NFs coating exhibited outstanding performance for the selective extraction of PAHs. After optimizing the main parameters that affected extraction through orthogonal experiments, the developed method showed good linearity in the ranges of 0.05 µg L-1 - 200 µg L-1 with the determination coefficient >0.999. LODs were between 0.006 µg L-1 and 0.114 µg L-1, LOQs were in the ranges of 0.020-0.376 µg L-1 and RSDs were below 5.19% and 5.71% for intra-day and inter-day analyses, respectively. The developed method was successfully applied to selective enrichment and determination of target PAHs in real water samples. Moreover, the fabricated fiber exhibited high chemical and mechanical stability, and could withstand more than 260 extraction-desorption cycles without loss of its extraction efficiency.

On the accuracy of displacement-based wave intensity analysis: Effect of vessel wall viscoelasticity and nonlinearity.

Recent studies showed that wave intensity analysis (WIA) provides clinically valuable information about local and global cardiovascular function. Wave intensity (WI) is computed as the product of the pressure change and the velocity change during short time intervals. The major limitation of WIA in clinical practice is the need for invasive pressure measurement. Since vessel wall displacement can be measured non-invasively, the usage of WI will be expanded if the vessel wall dilation is used instead of pressure in derivation of WI waveform. Our goal in this study is to investigate the agreement between wall displacement-based WI and the pressure-based WI for different vessel wall models including linear elastic, nonlinear and viscoelastic cases. The arbitrary Eulerian Lagrangian finite element method is employed to solve the coupled fluid-structure interaction (FSI). Our computational models also include two types of vascular disease-related cases with geometrical irregularities, aneurysm and stenosis. Our results show that for vessels with linear elastic wall, the displacement-based WI is almost identical to the pressure-based WI. The existence of vessel irregularities does not impact the accuracy of displacement-based WI. However, in a viscoelastic wall where there is a phase difference between pressure and vessel wall dilation, displacement-based WI deviated from pressure-based WI. The error associated with this phase difference increased nonlinearly with increasing viscosity. This results in a maximum error of 6.8% and 7.13% for a regular viscoelastic vessel wall and an irregular viscoelastic vessel wall, respectively. A separate analysis has also been performed on the agreement of backward and forward running waves extracted from a decomposition of the displacement-based and pressure-based WI. Our findings suggest that displacement-based WI is a reliable method of WIA for large central arteries that do not show viscoelastic behaviors. This can be clinically significant since the required information can be measured non-invasively.