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Peptide‐ and polypeptide‐based self‐assembling gene delivery systems have received considerable attention owing to their inherent biocompatibility and bioactivity. Gene carriers based on elastin‐like polypeptides (ELPs) have been extensively studied because of their controllability and unique temperature responsiveness. The (EK)10‐PLGLAG‐Tat polypeptide sequence was selected for tumor gene delivery, with ELP serving as the hydrophobic core. In this sequence, a hydration layer can be formed on the surface of the carrier using the zwitterionic peptide segment (EK)10, which helps prevent the nonspecific adsorption of plasma proteins. Additionally, the MMP‐2 enzyme‐responsive PLGLAG peptide segment is responsible for exposing the cell‐penetrating peptide Tat specifically near tumor cells, facilitating the penetration of tumor cells. To introduce (EK)10‐PLGLAG‐Tat into the self‐assembling carrier while ensuring its bioactivity, a leucine zipper ZR/ZE with opposite charges was used to link it to the ELP. Because of its high specificity and low systemic toxicity, the carrier was named environmentally responsive gene carrier (ERGV). Experimental results demonstrated that the ERGV effectively removed (EK)10 in MMP‐2 overexpressed environments, altering the surface charge from negative to positive and facilitating ssDNA delivery into tumor cells. These findings highlight the potential of ERGVs as a safe and efficient method for targeted gene delivery to tumors. [ABSTRACT FROM AUTHOR]

In recent years, cyclic peptides have attracted much attention due to their chemical and enzymatic stability, low toxicity, and easy modification. In general, the self-assembled nanostructures of cyclic peptides tend to form nanotubes in a cyclic stacking manner through hydrogen bonding. However, studies exploring other assembly strategies are scarce. In this context, we proposed a new assembly strategy based on cyclic peptides with covalent self-assembly. Here, cyclic peptide-(DPDPDP) was rationally designed and used as a building block to construct new assemblies. With cyclo-(DP)3 as the structural unit and 2,2′-diamino-N-methyldiethylamine as the linker, positively charged nanospheres ((CP)6NS) based on cyclo-(DP)3 were successfully constructed by covalent self-assembly. We assessed their size and morphology by scanning electron microscopy (SEM), TEM, and DLS. (CP)6NS were found to have a strong positive charge, so they could bind to siRNA through electrostatic interactions. Confocal microscopy analysis and cell viability assays showed that (CP)6NS had high cellular internalization efficiency and low cytotoxicity. More importantly, real-time polymerase chain reaction (PCR) and flow cytometry analyses indicated that (CP)6NS-siRNA complexes potently inhibited gene expression and promoted tumor cell apoptosis. These results suggest that (CP)6NS may be a potential siRNA carrier for gene therapy. [ABSTRACT FROM AUTHOR]

Void ratios in the different layers of the rock mass. The void ratios in the lower part of the rock mass were found to be between 1.2 and 1.7 times that of the upper part of the rock mass. • Discrete element method was used to study voids in different layers of rock mass. • The stress of the upper rock mass was higher than the stress of the lower rock mass. • The rock blocks in upper rock mass were densely packed than those in lower rock mass. • The void ratios of rock mass decreased from the bottom to the top. The internal stress levels of the crushed rock masses will change the movement states of the rock masses in the gob, and then affect the void distributions of crushed rock mass, and finally change the flow of gas in the gob. In this study, under the Lagrange framework, based on a discrete element method and a Hertz-Mindlin contact model, self-programming was used to simulate the compaction processes of a rock mass in mining gobs. The compression amounts were set as 0%, 5%, 10%, 15%, 20%, and 25%, respectively. The effects on the void distributions of the crushed rock masses of the internal stress levels of the crushed rock masses under the external load conditions were examined by changing the motion state of the rock blocks within in the gobs. The results showed that during the compression processes, the external loads could not be uniformly transmitted from the top of the crushed rock masses to the lower sections. Therefore the stress levels in the upper sections of the crashed rock masses were significantly higher than those of the lower sections. In addition, due to the rock blocks in the upper section of the crushed rock masses experiencing higher degrees of interference from the external forces, the sliding speeds of the upper rock blocks were also larger. At the same time, the rock blocks in the upper sections of the crushed rock masses tended to slide downward down longer. The migration of the rock blocks caused the upper rock blocks to become densely packed, and the coordination numbers of the rock blocks were large. However, the lower rock blocks were loosely distributed, and the coordination numbers of the rock blocks were small. This resulted in the void ratios in the lower sections of the crushed rock masses being higher than the void ratios in other layers of the crushed rock masses, with the void ratios of the lower sections of the rock masses determined to be 1.1–1.4 times that of the upper sections. [ABSTRACT FROM AUTHOR]

A novel β-1,4-xylosidase was identified from the genome of Bacteroides ovatus strain ATCC 8483 and overexpressed in Escherichia coli BL21 (DE3) cells. The molecular weight of recombinant enzyme named BoXyl43A was calculated to be 37.1 kDa. Using p-nitrophenyl-β-D-xylopyranoside (pNPβXyl) as substrate, BoXyl43A was most active at pH 7.0 and 35 °C. The enzyme could be activated by Mg2+ and Mn2+. The Km and Vmax of BoXyl43A against pNPβXyl were 1.71 ± 0.21 mM, 7.41 ± 0.81 μmol/min/mg, respectively. BoXyl43A hydrolyzed xylooligosaccharide to produce D-xylose as main product, indicating that BoXyl43A acted as an exo-β-1,4-xylosidase. The mixture of BoXyl43A and PoAbf62A (α-L-arabinofuranosidase) exhibited significant synergistic effects on the degradation of arabinoxylan. Therefore, BoXyl43A would be a useful tool to degrade hemicellulose. [ABSTRACT FROM AUTHOR]

The combination of selenium and pillararenes to prepare selenium-containing pillararene-based biomaterials is of great significance for the development of biomedicine. Herein, using a covalent self-assembly strategy, we successfully developed new diselenium-containing ultrathin polymer nanocapsules based on lateral cross-linked pillararenes. The new system exhibited a very potent anticancer effect; additionally, the incorporation of the cleavable redox diselenium bond into the polymer nanocapsules provided a smart nanocarrier for drug delivery. Moreover, the polymer nanocapsules were developed for anticancer drug targeting delivery by loading an anticancer drug and introducing the tumor-penetrating peptide RGD through the host–guest interaction strategy. The targeting DOX-loaded diselenium-containing polymer nanocapsules exhibited enhanced stability, self-anticancer effect, targeted delivery and controlled drug release, resulting in effective combined inhibition of tumor progression. [ABSTRACT FROM AUTHOR]

A new reconfigurable DNA nanocage based on a DNA origami method has been constructed to capture a tobacco mosaic virus (TMV) disk. We used a hairpin to control the transformation of the nanocage and a strand of TMV RNA to attract the TMV disk. Our design could inspire new DNA–protein complex designs. [ABSTRACT FROM AUTHOR]

On the basis of the host–guest molecular recognition interaction between β-cyclodextrin and azobenzene, two kinds of supramolecular self-assemblies (Py-CD⊃Azo-C and Py-CD⊃Azo-C3) were constructed. Owing to the azo group on the guest molecule, supramolecular vesicles could reversibly realize disassembly and reassembly under irradiation with UV and visible light. Because of the existence of terpyridine groups on the surfaces of supramolecular vesicles, addition of metal ions triggers the vesicle–vesicle self-assembly from the nanoscale to the microscale. [ABSTRACT FROM AUTHOR]

This study aims to investigate the neuroprotective effects of Coptis chinensis Franch polysaccharide (CCP) on Aβ 1–42 transgenic CL4176 Caenorhabditis elegans , as well as its mechanism of action. The results in life span experiment showed that CCP could significantly increase the lifespan of C. elegans and the effect is in the descending order of 100 mg/L > 500 mg/L > 200 mg/L. The behavioral experiments also demonstrated that CCP at the concentration of 100 mg/L could delay the paralysis rate of C. elegans , which was significantly different from the control group. In terms of Aβ toxicity in C. elegans , morphological observation using Thioflavin S staining method indicated that the deposition of Aβ protein in the head area of the untreated C. elegans was much more than those in the CCP (100 mg/L)-treated CL4176. In line with this finding, fluorogenic quantitative real-time PCR confirmed that the transcriptional levels of HSP16.2 (Y46H3A.D) and HSP16.41 (Y46H3A.E) in C. elegans was 21 times and 79 times higher than those in untreated control. Thus, these data demonstrate that CCP could reduce Aβ-induced toxicity by delaying the aging, decreasing the rate of paralysis, inhibiting the deposition of Aβ, and increasing the expression levels of HSP genes in transgenic C. elegans . [ABSTRACT FROM AUTHOR]

Convallatoxin is widely used as a cardiac glycoside in acute and chronic congestive heart-failure and paroxysmal tachycardia, with many effects and underlying protective mechanisms on inflammation and cellular proliferation. However, convallatoxin has not been investigated in its antioxidant effects and lifespan extension in Caenorhabditis elegans. In this study, we found that convallatoxin (20 μM) could significantly prolong the lifespan of wild-type C. elegans up to 16.3% through daf-16, but not sir-2.1 signalling and increased thermotolerance and resistance to paraquat-induced oxidative stress. Convallatoxin also improved pharyngeal pumping, locomotion, reduced lipofuscin accumulation and reactive oxygen species levels in C. elegans, which were attributed to hormesis, free radical-scavenging effects in vivo, and up-regulation of stress resistance-related proteins, such as SOD-3 and HSP-16.1. Furthermore, aging-associated genes daf-16, sod-3, and ctl-2 also appeared to contribute to the stress-resistance effect of convallatoxin. In summary, this study demonstrates that convallatoxin can protect against heat and oxidative stress and extend the lifespan of C. elegans, pointing it as a potential novel drug for retarding the aging process in humans. [ABSTRACT FROM AUTHOR]

Previous studies demonstrated that the CXCL12 peptide analogue CTCE- 0214 (CTCE) has beneficial effects in experimental sepsis induced by caecal ligation and puncture (CLP). We examined the hypothesis that CTCE recruits neutrophils (polymorphonuclear leucocytes; PMN) to the site of infection, enhances PMN function and improves survival of mice in CLPinduced sepsis with antibiotic treatment. Mice with sepsis (n = 15) were administered imipenem (25 mg/kg) and CTCE (10 mg/kg) subcutaneously versus vehicle control at designated intervals post-CLP. CTCE treatment increased PMN recruitment in CLP-induced sepsis, as evidenced by increased PMN in blood, by 2.4 ± 0.6 fold at 18 hr, 2.9 ± 0.6 fold at 24 hr, and in peritoneal fluid by 2.0 ± 0.2 fold at 24 hr versus vehicle control. CTCE treatment reduced bacterial invasion in blood [colonyforming units (CFU) decreased 77 ± 11%], peritoneal fluid (CFU decreased 78 ± 9%) and lung (CFU decreased 79 ± 8% versus CLP vehicle). The improved PMN recruitment and bacterial clearance correlated with reduced mortality with CTCE treatment (20% versus 67% vehicle controls). In vitro studies support the notion that CTCE augments PMN function by enhancing phagocytic activity (1.25 ± 0.02 fold), increasing intracellular production of reactive oxygen species (32 ± 4%) and improving bacterial killing (CFU decreased 27 ± 3%). These composite findings support the hypothesis that specific CXCL12 analogues with ancillary antibiotic treatment are beneficial in experimental sepsis, in part, by augmenting PMN recruitment and function. [ABSTRACT FROM AUTHOR]

Earlier studies have demonstrated that Deuterohaemin-AlaHisThrValGluLys (DhHP-6), a novel porphyrin-peptide, increases lifespan and enhances stress resistance of Caenorhabditis elegans. To explore the possible mechanisms, in this study we investigated the roles of SIR-2.1 and DAF-16 in DhHP-6's function using wild-type and various other mutant strains of C. elegans. DhHP-6's effect was dependent upon DAF-16, and it did not extend the lifespan of the loss-of-function daf-16 mutant strain ( daf-16(mu86) I). DhHP-6 enhanced DAF-16 translocation from cytoplasm to nuclei; and it increased DAF-16's transcriptional activity, likely by activating the SIR-2.1/DAF-16 complex. DhHP-6's effect was also dependent upon SIR-2.1, and it did not increase the lifespan of the worms with SIR-2.1 deacetylase activity inhibited by niacin amide (SIR-2.1 inhibitor) and SIR-2.1 RNA interference (RNAi). Niacin amide and RNAi increased DAF-16's nuclear localization; but they decreased DAF-16's transcriptional activity, likely by preventing the formation of the SIR-2.1/DAF-16 complex. These results suggest that DhHP-6 extends the lifespan of C. elegans via SIR 2.1 and DAF-16, and they provide new insights into the molecular mechanisms of aging. [ABSTRACT FROM AUTHOR]

This group has invented a novel deuterohemin containing peptide deuterohemin-AlaHisThrValGluLys (DhHP-6), which has various biological activities including protection of murine ischemia reperfusion injury, improving cell survival and preventing apoptosis. It was hypothesized that DhHP-6 is beneficial on the lifespan of Caenorhabditis elegans ( C. elegans) and increases their resistance to heat and oxidative stress. C. elegans were treated with different concentrations of DhHP-6. Survival time and sensitivity to heat and paraquat were investigated. The data demonstrated that the mean survival time of C. elegans was significantly increased ( p < 0.05) in the DhHP-6 treated group compared with the control group. The maximum lifespan was not affected by DhHP-6 treatment. DhHP-6 improved the survival rate of C. elegans in the acute heat stress (35°C) and rescued the C. elegans' sensitivity to paraquat in acute oxidative stress. Superoxide dismutase 3 (SOD-3) protein was up-regulated by DhHP-6 treatment. It was further demonstrated that stress resistance genes such as hsp-16.1, hsp-16.49 and sir-2.1 were regulated by DhHP-6. DAF-16 and SIR-2.1 genes are essential for the beneficial effect of DhHP-6. Therefore, the investigation into the beneficial effect of DhHP-6 on C. elegans' lifespan has the potential to develop novel drugs to prevent ageing. [ABSTRACT FROM AUTHOR]

Panax ginseng is a valuable traditional Chinese medicine in Northeast China. Ginsenoside, the active component of ginseng, has not been investigated much for its effects on aging and its underlying mechanism(s) of action. Here, we investigated the effects of total ginsenoside (TG), a mixture of the primary active ginsenosides from Panax ginseng, on the lifespan of Caenorhabditis elegans (C. elegans). We found that TG extended the lifespan of C. elegans and reduced lipofuscin accumulation. Moreover, TG increased the survival of C. elegans in response to heat and oxidative stress via the reduction of ROS. Next, we used RNA-seq to fully define the antiaging mechanism(s) of TG. The KEGG pathway analysis showed that TG can prolong the lifespan and is involved in the longevity regulating pathway. qPCR showed that TG upregulated the expression of nrh-80, daf-12, daf-16, hsf-1 and their downstream genes. TG also reduced the fat accumulation and promoted lipid metabolism. Moreover, TG failed to extend the lifespan of daf-16 and hsf-1 mutants, highlighting their role in the antiaging effects of TG in C. elegans. The four main constitution of TG were then confirmed by HPLC and included ginsenoside Re, Rg1, Rg2 and Rd. Of the ginsenosides, only ginsenoside Rd prolonged the lifespan of C. elegans to levels comparable to TG. These findings provided mechanistic insight into the antiaging effects of ginsenoside in C. elegans. [ABSTRACT FROM AUTHOR]

Ferulic acid (FA) is a naturally-occurring well-known potent antioxidant and free radical scavenger. FA supplementation is an effective strategy to delay aging, but the underlying mechanism remains unknown. In the present study, we examined the effects of FA on lifespan extension and its mechanism of FA in Caenorhabditis elegans (C. elegans). Results suggested that FA increased the lifespan of C. elegans, rather than altering the growth of E. coli OP50. Meanwhile, FA promoted the healthspan of C. elegans by improving locomotion and reducing fat accumulation and polyQ aggregation. FA increased the resistance to heat and oxidative stress through reducing ROS. The upregulating of the expression of the hlh-30, skn-1, and hsf-1 were involved in the FA-mediated lifespan extension. Furthermore, FA treatment had no impact on the lifespan of daf-2, hlh-30, skn-1, and hsf-1 mutants, confirming that insulin/IGF-1 signaling pathway and multiple longevity mechanisms were associated with the longevity mechanism of FA. We further found that mitochondrial signaling pathway was modulation involved in FA-mediated lifespan extension. With the results from RNA-seq results and mutants lifespan assay. These findings contribute to our knowledge of the lifespan extension and underlying mechanism of action of FA in C. elegans. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common neurodegenerative disorder in the elderly, which is characterized by the accumulation of amyloid β (Aβ) plaques, oxidative stress, and neuronal loss. Therefore, clearing Aβ aggregates and reducing oxidative stress could be an effective therapeutic strategy for AD. Deuterohemin-AlaHisThrValGluLys (DhHP-6), a novel deuterohemin-containing peptide mimetic of the natural microperoxidase-11 (MP-11), shows higher antioxidant activity and stability compared to the natural microperoxidases. DhHP-6 possesses the ability of extending lifespan and alleviating paralysis in the Aβ1-42 transgenic Caenorhabditis elegans CL4176 model of AD, as shown in our previous study. Therefore, this study was aimed at exploring the neuroprotective effect of DhHP-6 in the APPswe/PSEN1dE9 transgenic mouse model of AD. DhHP-6 reduced the diameter and fiber structure of Aβ1-42 aggregation in vitro, as shown by dynamic light scattering and transmission electron microscope. DhHP-6 exerted its neuroprotective effect by inhibiting Aβ aggregation and plaque formation, and by reducing Aβ1-42 oligomers-induced neurotoxicity on HT22 (mouse hippocampal neuronal) and SH-SY5Y (human neuroblastoma) cells. In the AD mouse model, DhHP-6 significantly ameliorated cognitive decline and improved spatial learning ability in behavioral tests including the Morris water maze, Y-maze, novel object recognition, open field, and nest-building test. Moreover, DhHP-6 reduced the deposition of Aβ plaques in the cerebral cortex and hippocampus. More importantly, DhHP-6 restored the morphology of astrocytes and microglia, and significantly reduced the levels of pro-inflammatory cytokines. Our findings provide a basis for considering the non-toxic, peroxidase mimetic DhHP-6 as a new candidate drug against AD. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • DhHP-6 inhibits the aggregation of Aβ 1–42 in vitro. • DhHP-6 binds to Aβ 1–42 closely at the α-helix and β-sheet structures. • DhHP-6 efficiently protects a transgenic C. elegans model of Alzheimer's disease. Abstract Alzheimer's disease (AD) is a progressive neurodegenerative brain disease and is the most common cause of dementia in the elderly. The main hallmark of AD is the deposition of insoluble amyloid (Aβ) outside the neuron, leading to amyloid plaques and neurofibrillary tangles in the brain. Deuterohemin-Ala-His-Thr-Val-Glu-Lys (DhHP-6), a novel porphyrin-peptide, has both microperoxidase activity and cell permeability. In the present study, DhHP-6 efficiently inhibited the aggregation of Aβ and reduced the β-sheet percentage of Aβ from 89.1% to 78.3%. DhHP-6 has a stronger affinity (K D = 100 ± 12 μM) for binding with Aβ at Phe4, Arg5, Val18, Glu11 and Glu22. In addition, DhHP-6 (100 μM) significantly prolonged lifespan, alleviated paralysis and reduced Aβ plaque formation in the Aβ 1–42 transgenic Caenorhabditis elegans CL4176 model of AD. Our results demonstrate that DhHP-6 is a potential drug candidate that efficiently protects a transgenic C. elegans model of Alzheimer's disease by inhibiting Aβ aggregation. [ABSTRACT FROM AUTHOR]

Abstract: In this study, three chemically sulfated polysaccharides (SPAPs) were derived from one water-soluble polysaccharide (PAP) of Polyporus albicans mycelia by chlorosulfonic acid-pyridine method. The effects of polysaccharides on the immune function were examined after the mice were intragastrical administrated with polysaccharides at three doses of 100, 200, and 300mg/kg body weight for 7 days. The results showed that both the lymphocytes proliferation and macrophage function were significantly enhanced by SPAP in all groups along with the increase of the substitution degree and dose (P <0.01). It indicated that SPAP could be a potential immunostimulants used in the food and pharmaceutical industry. [Copyright &y& Elsevier]

• PEGylation improved water solubility and stability. • Arginine improved penetration efficiency. • Apoptosis of MCF-7 cells after transfection with survivin -siRNA. • PEGylated phenylalanine dipeptides can be used as a novel siRNA vector. Polypeptide carriers have a good cell compatibility, rich functionality, and facile synthesis and modification, make them promising materials as siRNA vectors. Phenylalanine dipeptide (FF) has been previously assessed as an siRNA vector and showed to have two major drawbacks, namely poor water solubility and poor serum stability. Herein, the FF backbone was modified by ligating a PEG-Arg-Ala (PEG-RA) sequence at the N-terminus to increase its hydrophilicity and serum stability. Arg is a typical amino acid in the cell penetrating peptide, which can increase the efficiency of cell internalization. Ala acts as a spacer to avoid steric hindrance. The target sequence PEG-RAFF was synthesized by a solid phase peptide synthesis. The morphology, particle size, and siRNA ratio were assessed by SEM, TEM, DLS, and gel electrophoresis. Further, MCF-7 cells were used as a model and survivin -siRNA as a passenger to assess cell internalization, inhibition of gene expression rate, and apoptosis rate using confocal microscopy, real-time PCR, and flow cytometry. At a concentration of 1 mg/mL, PEG-RAFF took the form of nanovesicles with a diameter of 154.74 ± 14.36 nm. The optimal PEG-RAFF to siRNA ratio was N/P = 100:1. Compared with the control group, the red fluorescence of TAMRA(Carboxytetramethylrhodamine, Red fluorescence)-siRNA transfected into cells was clearly visible in the confocal microscope image. The inhibition rate of survivin was 67.99 ± 10.31%, and the apoptotic rate was 16.07%. Therefore, PEG-RAFF has potential as an siRNA carrier in cancer treatment. [ABSTRACT FROM AUTHOR]

Development of tissue-engineered in vitro human bone defect models for evaluation of bone repair materials (BRMs) is a promising approach for addressing both translational and ethical concerns regarding animal models. In this study, human bone marrow mesenchymal stem cell sheets were stacked to form a periosteum like tissue. HE staining showed a cell-dense, multilayered structure. BRMs were implanted in the defect area of the three-dimensional (3D) model. The CCK-8 test demonstrated that the 3D model was stronger in resisting the cytotoxicity of three kinds of commercial BRMs than the 2D culture model, which was consistent with in vivo results. After 28 d implantation in the 3D model, western blot and RT-qPCR showed that three materials induced increased expressions of RUNX2, OSX, OCN, OPN, while Materials B and C seemed to have stronger osteoinductivity than A. In vivo experiments also confirmed the osteoinductivity of the BRMs after 28 and 182 d implantation. Alizarin red staining proved that the mineralized nodules of Materials B and C were more than that of A. The differences of osteogenic properties among three BMRs might be attributed to calcium ion release. This cell sheet-based bone tissue model can resist cytotoxicity of BRMs, demonstrating the priority of long-term evaluation of osteoinductivity of BRMs. Further, the osteoinduction results of the 3D model corresponded to that of in vivo experiments, suggesting this model may have a potential to be used as a novel tool for rapid, accurate evaluation of BRMs, and thus shorten their research and development process., (© 2023 IOP Publishing Ltd.)

Study Objectives: To investigate the feasibility and effectiveness of nasopharyngeal tube (NPT) insertion in alleviating sleep hypoxemia during the first night after velopharyngeal surgery in patients with obstructive sleep apnea syndrome (OSAS)., Methods: In this prospective nonblinded, randomized, controlled study, 46 patients with obstructive sleep apnea syndrome (OSAS) who underwent velopharyngeal surgery were enrolled and randomly allocated to the control group (with no NPT insertion) and the NPT insertion group. Both groups underwent overnight pulse oximetry tests during the first postoperative night., Results: One patient in the NPT insertion group was excluded because of involuntary self-removal of NPT during sleep. A total of 45 patients with OSAS were included for analysis, with 23 in the control group and 22 in the NPT insertion group. No significant differences in preoperative baseline information were found between the two groups. Compared with the patients in the control group, those patients in the NPT insertion group showed a significantly higher value of the lowest oxygen saturation of oximetry during the first postoperative night (85.0 ± 4.0% vs 79.3 ± 8.0%) ( P = .005). The percentage of patients with lowest oxygen saturation of oximetry < 80% in the NPT insertion group was only 9.1% (2 of 22), which was significantly lower than 39.1% (9 of 23) in the control group ( P = .035). No patient reported unbearable discomfort related to NPT insertion. The most common mild discomfort was occasional pharyngeal foreign body sensation (6 of 22, 27.3%)., Conclusions: NPT insertion could lessen the severity of sleep hypoxemia during the first night after velopharyngeal surgery in patients with OSAS and showed excellent compliance. This method could be a potential alternative option for decreasing the risks of complications related to severe sleep hypoxemia during the early postoperative days., Citation: Zhang J, Guan S, Zhang C, Du X, Li T, Xiao S. Nasopharyngeal tube effects on alleviating sleep hypoxemia during the first night following velopharyngeal surgery in patients with obstructive sleep apnea syndrome. J Clin Sleep Med . 2023;19(2):303-308., (© 2023 American Academy of Sleep Medicine.)

Objective: This study aims to evaluate the effect of bilateral nasal packing on sleep oxygen saturation and its influencing factors on the first night after general anesthesia., Method: A total of 36 adult patients who underwent bilateral nasal packing with a nonabsorbable expanding sponge after general anesthesia surgery were prospectively studied. All these patients underwent overnight oximetry tests before and the first night after surgery. The following oximetry variables were collected for analysis: the lowest oxygen saturation (LSAT), the average oxygen saturation (ASAT), the oxygen desaturation index of ≥4% (ODI4), and the percentage of time with oxygen saturation below 90% (CT90)., Results: Among the 36 patients, the incidences of both sleep hypoxemia and moderate-to-severe sleep hypoxemia increased with bilateral nasal packing after general anesthesia surgery. All the pulse oximetry variables we studied deteriorated significantly after surgery: both LSAT and ASAT decreased significantly ( P  < 0.05), while both ODI4 and CT90 increased significantly ( P  < 0.05). In a multiple logistic regression analysis, body mass index (BMI), LSAT, and modified Mallampati grade were found to be independently predictive for a larger decrease in LSAT (≥5%) after surgery (all P 's < 0.05)., Conclusion: Bilateral nasal packing after general anesthesia could induce or aggravate sleep hypoxemia, especially in patients with obesity, relatively normal sleep oxygen saturation, and high modified Mallampati grades., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Guan, Zhao, Ye and Zhang.)

The evidence shows that there is an associated relationship between hepatosteatosis and insulin resistance. While some existing genetic induction animal and patient models challenge this relationship, indicating that hepatosteatosis is dissociated from insulin resistance. However, the molecular mechanisms of this dissociation remain poorly understood due to a lack of available, reliable, and simplistic setup models. Currently, we used primary rat hepatocytes (rHPCs), co-cultured with rat hepatic stellate cells (HSC-T6) or human foreskin fibroblast cells (HFF-1) in stimulation with high insulin and glucose, to develop a model of steatosis charactered as dissociated lipid accumulation from insulin resistance. Oil-Red staining significantly showed intracellular lipid accumulated in the developed model. Gene expression of sterol regulatory element-binding protein 1c (SREBP1c) and elongase of very-long-chain fatty acids 6 (ELOVL6), key genes responsible for lipogenesis, were detected and obviously increased in this model. Inversely, the insulin resistance related genes expression included phosphoenolpyruvate carboxykinase 1 (PCK1), pyruvate dehydrogenase lipoamide kinase isozyme 4 (PDK4), and glucose-6-phosphatase (G6pase) were decreased, suggesting a dissociation relationship between steatosis and insulin resistance in the developed model. As well, the drug metabolism of this developed model was investigated and showed up-regulation of cytochrome P450 3A (CYP3A) and down-regulation of cytochrome P450 2E1 (CYP2E1) and cytochrome P450 1A2 (CYP1A2). Taken together, those results demonstrate that the in vitro model of dissociated steatosis from insulin resistance was successfully created by our co-cultured cells in high insulin and glucose medium, which will be a potential model for investigating the mechanism of insulin resistance dissociated steatosis, and discovering a novel drug for its treatment.

Herein, a new reductive-responsive pillar[5]arene-based, single-molecule-layer polymer nanocapsule is constructed for drug delivery. The functionalized system shows good biocompatibility, efficient internalization into targeted cells and obvious triggered release of entrapped drugs in a reducing environment such as cytoplasm. Besides, this smart vehicle loaded with anticancer drug shows excellent inhibition for tumor cell proliferation and exhibits low side effect on normal cells. This work not only demonstrates the development of a new reductive-responsive single molecular layer polymer nanocapsule for anticancer drug targeting delivery but also extends the design of smart materials for biomedical applications.

Uniform and hydrophilic carbon quantum dots (C-QDs) were synthesized by calcination and NaOH treatment from an organo-templated zeolite precursor. The color of luminescence was determined by the concentration of C-QDs. These variable-color C-QDs were applied for the first time in the imaging of Caenorhabditis elegans (C. elegans) as a model organism. The effects of C-QDs and possible behavioral changes in C. elegans were evaluated under treatment conditions. We could clearly observe distribution of C-QDs in C. elegans from the fluorescence images. Furthermore, we observed significant and detectable fluorescence quenching of the C-QDs by free radicals in C. elegans. Our work affirms that C-QDs can be developed as imaging probes and as potential fluorescent quantitative probes for detecting free radicals.