Evaluation of the effectiveness of alginate-based hydrogels in preventing peritoneal adhesions.

Infertility and intestinal blockage are just two examples of the postoperative consequences that can arise from peritoneal damage, which can also result in severe peritoneal fibrosis and peritoneal adhesions. Peritoneal adhesions are still not effectively treated, and both pharmaceutical therapy and biomaterial barriers have only had modest preventative effects. In this work, we looked into the effectiveness of in-place injectable sodium alginate hydrogel for peritoneal adhesion prevention. The findings demonstrated that sodium alginate hydrogel promoted human peritoneal mesothelial cell proliferation and migration, prevented peritoneal fibrosis by suppressing the production of transforming growth factor-ß1, and, most importantly, promoted mesothelium self-repair. These findings imply that this brand-new sodium alginate hydrogel is a good candidate material for peritoneal adhesion prevention.

The mechanosensitive ion channel Piezo1 modulates the migration and immune response of microglia.

Microglia are the brain's resident immune cells, performing surveillance to promote homeostasis and healthy functioning. While microglial chemical signaling is well-studied, mechanical cues regulating their function are less well-understood. Here, we investigate the role of the mechanosensitive ion channel Piezo1 in microglia migration, pro-inflammatory cytokine production, and stiffness sensing. In Piezo1 knockout transgenic mice, we demonstrated the functional expression of Piezo1 in microglia and identified genes whose expression was consequently affected. Functional assays revealed that Piezo1 deficiency in microglia enhanced migration toward amyloid ß-protein, and decreased levels of pro-inflammatory cytokines produced upon stimulation by lipopolysaccharide, both in vitro and in vivo. The phenomenon could be mimicked or reversed chemically using a Piezo1-specific agonist or antagonist. Finally, we also showed that Piezo1 mediated the effect of substrate stiffness-induced migration and cytokine expression. Altogether, we show that Piezo1 is an important molecular mediator for microglia, its activation modulating microglial migration and immune responses.

Thoracic Jia-Ji electro-acupuncture mitigates low skeletal muscle atrophy and improves motor function recovery following thoracic spinal cord injury in rats.

OBJECTIVES: The goal of this study was to determine whether electro-acupuncture (EA) stimulation might protect the motor endplate, minimize muscle atrophy in the hind limbs, and enhance functional recovery of rats with spinal cord injury (SCI). METHODS: Sprague-Dawley adult female rats (n = 30) were randomly assigned into Sham, SCI, and EA + SCI groups (n = 10 each). Rats in the Sham and SCI groups were bound in prone position only for 30 min, and rats in the EA + SCI group were treated with electro-acupuncture. The EA was conducted from the first day after surgery, lasted for 30 mins, once every day for 28 consecutive days. RESULTS: EA significantly prevented motor endplate degeneration, improved electrophysiological function, and ameliorated hindlimb muscle atrophy after SCI. Meanwhile, EA upregulated Tuj-1 expression, downregulated GFAP expression, and reduced glial scar formation. Additionally, after 4 weeks of EA treatment, the serum of SCI rats exhibited a reduced inflammatory response. CONCLUSION: These findings suggest that EA can preserve the motor endplate and reduce muscular atrophy. In addition, EA has been shown to improve the function of upper and lower neurons, reduce glial scar formation, suppress systemic inflammation, and improve axon regeneration.

SN-38 Sensitizes BRCA-Proficient Ovarian Cancers to PARP Inhibitors through Inhibiting Homologous Recombination Repair.

As a multifunctional protein posttranslational modification enzyme in eukaryotic cells, Poly-ADP-ribose polymerase (PARP) acts as a DNA damage sensor, which helps to repair DNA damage through recruiting repair proteins to the DNA break sites. PARP inhibitors offer a significant clinical benefit for ovarian cancer with BRCA1/2 mutations. However, the majority of ovarian cancer patients harbor wild-type (WT) BRCA1/2 status, which narrows its clinical application. Here, we identified a small compound, SN-38, a CPT analog, which sensitizes BRCA-proficient ovarian cancer cells to PARP inhibitor treatment by inhibiting homologous recombination (HR) repair. SN-38 treatment greatly enhanced PARP inhibitor olaparib induced DNA double-strand breaks (DSBs) and DNA replication stress. Meanwhile, the combination of SN-38 and olaparib synergistically induced apoptosis in ovarian cancer. Furthermore, combination administration of SN-38 and olaparib induced synergistic antitumor efficacy in an ovarian cancer xenograft model in vivo. Therefore, our study provides a novel therapeutic strategy to optimize PARP inhibitor therapy for patients with BRCA-proficient ovarian cancer.

In Vitro and In Vivo Investigation on the Effectiveness of Alginate-Based Gastric Mucosal Protective Gel.

Objective: To investigate the feasibility and effectiveness of an alginate-based gastric mucosal protective gel on the gastric ulcer. Methods: (1) In the physical protection model, after GES-1 cell attachment add the gel to transwell chamber, add different concentrations of HCl to the gel. Absorbance was measured to assess proliferation and images of the cells migrating into the wound were taken; then the migration rate of the cells was quantified by comparing images. (2) In the gastric ulcer model, excise the gastric mucosal of SD rats; the gel and fixative were applied on the artificial ulcer immediately. Dissect rats after 10 days, and calculate the wound healing rate and analyzed histology changes. Results: The effect of hydrochloric acid on cells in the lower layer was significantly reduced after the use of gastric mucosal protection gel. The protective gel had an isolation effect on different concentrations of acid. A number of GES-1 were significantly higher than those in the control group at 24 h to 72 h (P < 0.01). The migration was observed compared with the control group. The average healing rate of ulcer in the gel group was about 50%, and the control group was about 30%. Inflammation occurred in all wound regions after ten days. In the gel group, inflammatory infiltration depth was lower than that of the control, and part of SD rats' new muscle layer appeared without inflammatory infiltration. The connective tissue proliferation promoted tissue repair. In the control group, necrosis marginal, mucosal hyperplasia, marginal lymphocyte aggregation, and bleeding were observed. Conclusion: This novel gel mainly has an isolating and shielding effect to prevent the wound from being exposed to gastric acid for a long time, and it can reduce the inflammatory reaction on the wounds to promote the healing of the ulcer. The gastric mucosal protective gel cannot only promote the speed of wound healing but also improve the quality of wound healing.

Case Report: A Novel Homozygous Frameshift Mutation of the SKIV2L Gene in a Trichohepatoenteric Syndrome Patient Presenting With Short Stature, Premature Ovarian Failure, and Osteoporosis.

Background: Trichohepatoenteric syndrome (THES) is a rare Mendelian autosomal recessive genetic disease characterized by intractable diarrhea, woolly hair, facial abnormality, immune dysfunction, and intrauterine growth restriction. THES mutations are found in the TTC37 and SKIV2L genes, which encode two components of the human superkiller (SKI) complex. Methods and results: We report one case of a 32-year-old woman of Chinese descent with THES, who was born with a low weight (2000 g). She had intractable diarrhea during the neonatal period and was allergic to cow's milk and condensed milk, but did not require total parenteral nutrition. She experienced menarche at age 12 and amenorrhea at age 28. In May 2019, the patient presented with a left fibular head fracture and was diagnosed with osteoporosis. Genetic testing showed a novel mutation in exon1 [p.E5Afs∗37 (c.12_13del)] of SKIV2L, which is composed of 28 exons. After the diagnosis, hormone replacement therapy was prescribed, in addition to the routine calcium and vitamin D supplements. Conclusion: This case expands the clinical characteristic and phenotype spectrum of THES, providing further understanding of SKIV2L and its autoimmune influence.

Association of serum C1Q/TNF-related protein 4 levels with carotid atherosclerosis in subjects with type 2 diabetes mellitus: A cross-sectional study.

BACKGROUND: Carotid atherosclerosis (CAS) is a common manifestation of macroangiopathy in type 2 diabetes mellitus (T2DM). C1Q/TNF-related protein 4 (CTRP4) was found to be involved in regulation of food intake behaviors and glucolipid metabolism, which were also key factors in the development of CAS. However, the relationship between serum CTRP4 and CAS in T2DM remains unclear. METHODS: A total of 111 participants with T2DM were enrolled in the study and were divided into 2 groups (T2DM group and T2DM + CAS group) according to the result of carotid ultrasound examinations. Serum CTRP4 levels were measured by enzyme linked immunosorbent assay (ELISA). Trend χ2 test and binary stepwise logistic regression were conducted to assess the association between serum CTRP4 and the risk of CAS in T2DM. RESULTS: Serum CTRP4 concentrations in T2DM + CAS group were significantly lower compared with those in T2DM group [7.98 (5.53) vs. 11.29 (7.36) ng/ml, P < 0.01]. The risk of CAS in T2DM decreased with the increasing of CTRP4 quartiles (P for trend < 0.01). Binary stepwise logistic regression suggested that serum CTRP4 might be an independent influence factor for CAS in patients with T2DM (P < 0.01) and high concentrations of serum CTRP4 were related to low risk of CAS in T2DM. CONCLUSIONS: The concentrations of serum CTRP4 are lower in T2DM patients with CAS compared to those without CAS. Serum CTRP4 levels are negatively related to the risk of CAS in T2DM.

Precise Ultrasound Neuromodulation in a Deep Brain Region Using Nano Gas Vesicles as Actuators.

Ultrasound is a promising new modality for non-invasive neuromodulation. Applied transcranially, it can be focused down to the millimeter or centimeter range. The ability to improve the treatment's spatial resolution to a targeted brain region could help to improve its effectiveness, depending upon the application. The present paper details a neurostimulation scheme using gas-filled nanostructures, gas vesicles (GVs), as actuators for improving the efficacy and precision of ultrasound stimuli. Sonicated primary neurons display dose-dependent, repeatable Ca2+ responses, closely synced to stimuli, and increased nuclear expression of the activation marker c-Fos in the presence of GVs. GV-mediated ultrasound triggered rapid and reversible Ca2+ responses in vivo and could selectively evoke neuronal activation in a deep-seated brain region. Further investigation indicate that mechanosensitive ion channels are important mediators of this effect. GVs themselves and the treatment scheme are also found not to induce significant cytotoxicity, apoptosis, or membrane poration in treated cells. Altogether, this study demonstrates a simple and effective method to achieve enhanced and better-targeted neurostimulation with non-invasive low-intensity ultrasound.

The Psychological Impact of the COVID-19 Pandemic on Teenagers in China.

PURPOSE: The 2019 COVID-19 pandemic poses a challenge to adolescent psychological health. The aim of this study was to survey junior high and high school students in China to better understand the psychological consequences, such as anxiety, depression, and stress, of the COVID-19 pandemic. METHODS: A cross-sectional online survey using structural questionnaires was conducted from April 7, 2020, to April 24, 2020. Demographic information and general information related to the pandemic were collected. Psychological consequences were assessed by the Impact of Event Scale-Revised and the Depression, Anxiety and Stress Scale. Influencing factors were assessed by the Brief Resilience Scale and Coping Style Questionnaire. RESULTS: Our sample comprised 493 junior high school students (male = 239, mean age = 13.93 years) and 532 high school students (male = 289, mean age = 17.08 years). Resilience and positive coping were protective factors for the occurrence of depressive, anxiety, and stress symptoms in junior high and high school students (p < .05). Positive coping was a protective factor for trauma-related distress in junior high school students (p < .05). Negative coping is a risk factor for depression, anxiety, stress symptoms, and trauma-related distress in junior high and high school students (p < .05). CONCLUSIONS: During the COVID-19 pandemic in China, more than one fifth of junior high and high school students' mental health was affected. Our findings suggested that resilience and positive coping lead to better psychological and mental health status among students. In contrast, negative coping is a risk factor for mental health.

Targeted Neurostimulation in Mouse Brains with Non-invasive Ultrasound.

Recently developed brain stimulation techniques have significantly advanced our ability to manipulate the brain's function. However, stimulating specific neurons in a desired region without significant surgical invasion remains a challenge. Here, we demonstrate a neuron-specific and region-targeted neural excitation strategy using non-invasive ultrasound through activation of heterologously expressed mechanosensitive ion channels (MscL-G22S). Low-intensity ultrasound is significantly better at inducing Ca2+ influx and neuron activation in vitro and at evoking electromyogram (EMG) responses in vivo in targeted cells expressing MscL-G22S. Neurons in the cerebral cortex or dorsomedial striatum of mice are made to express MscL-G22S and stimulated ultrasonically. We find significant upregulation of c-Fos in neuron nuclei only in the regions expressing MscL-G22S compared with the non-MscL controls, as well as in various other regions in the same brain. Thus, we detail an effective approach for activating specific regions and cell types in intact mouse brains by sensitizing them to ultrasound using a mechanosensitive ion channel.

Author Correction: Three-Dimensional Printed Model-Assisted Screw Installation in Treating Posterior Atlantoaxial Internal Fixation.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Three-Dimensional Printed Model-Assisted Screw Installation in Treating Posterior Atlantoaxial Internal Fixation.

The aim of this study was to evaluate the efficacy and feasibility of a life-size 3-dimensional printing assisted posterior internal fixation. We performed a retrospective review of 138 patients who received posterior atlantoaxial internal fixation from October 2009 to March 2015 with a minimum follow-up period of 12 months. Group A included 76 patients who received the conventional free-hand technique. Group B included 62 patients who were treated with internal fixation assisted by 3D printing. The placement accuracy of the screw was evaluated in the computed tomography images according to the methods of Hojo and clinical outcomes were evaluated using the visual analogue scale, the Japanese Orthopedic Association Score, and the Neck Disability Index score. There were no significant differences in the clinical results at any of the follow-up time points regarding the JOA, VAS, or NDI scores between two group. However, compared to Group A, Group B had better results for screw installation (P = 0.003), shorter surgery time (P = 0.001), and less blood loss (P = 0.037). Compared to the conventional free-hand technique, 3D printed model-assisted is helpful to screw placement in atlantoaxial internal fixation, which can be used as a common tool to provides important guidance for upper cervical surgery.

Seed-Mediated Growth of Silver Nanocubes in Aqueous Solution with Tunable Size and Their Conversion to Au Nanocages with Efficient Photothermal Property.

Two seed-mediated approaches for the growth of silver nanocubes in aqueous solution have been developed. Addition of a silver-seed solution to a mixture of cetyltrimethylammonium chloride (CTAC), silver trifluoroacetate, and ascorbic acid and heating the solution at 60 °C for 1.5 h produces uniform Ag nanocubes with tunable sizes from 23 to 60 nm by simply adjusting the volume of silver-seed solution introduced. Alternatively, the silver-seed solution can be injected into a mixture of cetyltrimethylammonium bromide (CTAB), silver nitrate, copper sulfate, and ascorbic acid and heated to 80 °C for 2 h to generate 46 nm silver nanocubes. Plate-like Ag nanocrystals exposing {111} surfaces can be synthesized by reducing Ag(NH3 )2 (+) with ascorbic acid in a CTAC solution. Relatively large Ag nanocubes were converted to cuboctahedral Au/Ag and Au nanocages and nanoframes with empty {111} faces through a galvanic replacement reaction. The nanocages showed a progressive plasmonic band red-shift with increasing Au content. The nanocages exhibited high and stable photothermal efficiency with solution temperatures quickly reaching beyond 100 °C when irradiated with an 808 nm laser for large heat and water vapor generation.

Facile synthesis of Au-Pd core-shell nanocrystals with systematic shape evolution and tunable size for plasmonic property examination.

A facile synthetic method has been developed for the formation of Au-Pd core-shell nanocrystals in aqueous solution in just 0.5-2 h at 50 °C with systematic shape evolution from cubic to truncated cubic, cuboctahedral, truncated octahedral, and octahedral structures using octahedral gold cores. By adjusting the amounts of H2PdCl4, ascorbic acid, and sometimes surfactants and gold cores added, the particle morphology can be finely tuned, and Pd shells with ultrathin thicknesses have been achieved. Gold cores of three different sizes (35, 45, and 74 nm in opposite corner distance) were used to obtain a full range of particle sizes and shapes for a most complete examination of their plasmonic properties. Visual observations made during particle synthesis reveal that Au-Pd cubes are formed at a faster rate than that for the growth of octahedra. For the smaller cubes, cuboctahedra, and truncated octahedra prepared using 35 and 45 nm gold cores, the surface plasmon resonance (SPR) absorption band from the gold cores can be seen only when the Pd shell thickness is just 1 nm at the thinnest points of the particles. For small-sized Au-Pd octahedra, this band is observable at a Pd shell thickness of around 5 nm. For larger Au-Pd nanocrystals synthesized from 74 nm gold cores, the Au SPR band is more recognizable for all particle shapes, although octahedra still exhibit the most obvious band. The band shifts slightly to the red going from cubes to octahedra. Simulation spectra have been performed, and they roughly match with the experimental spectra. Au-Pd octahedra with two different core sizes and shell thicknesses have been used for hydrogen sensing by comparing their UV-vis spectra before and after hydrogen incorporation forming PdH. The results show that the shell thickness is more important in producing a larger spectral red-shift after hydrogen absorption.