Epitope prime editing shields hematopoietic cells from CD123 immunotherapy for acute myeloid leukemia.

Acute myeloid leukemia (AML) is a malignant cancer characterized by abnormal differentiation of hematopoietic stem and progenitor cells (HSPCs). While chimeric antigen receptor T (CAR-T) cell immunotherapies target AML cells, they often induce severe on-target/off-tumor toxicity by attacking normal cells expressing the same antigen. Here, we used base editors (BEs) and a prime editor (PE) to modify the epitope of CD123 on HSPCs, protecting healthy cells from CAR-T-induced cytotoxicity while maintaining their normal function. Although BE effectively edits epitopes, complex bystander products are a concern. To enhance precision, we optimized prime editing, increasing the editing efficiency from 5.9% to 78.9% in HSPCs. Epitope-modified cells were resistant to CAR-T lysis while retaining normal differentiation and function. Furthermore, BE- or PE-edited HSPCs infused into humanized mice endowed myeloid lineages with selective resistance to CAR-T immunotherapy, demonstrating a proof-of-concept strategy for treating relapsed AML.

Elastocaloric Heat Pump by Twist Induced Periodical Non-Linear Stress for Low Hysteresis and High Carnot Efficiency.

Elastocaloric cooling is one of the most promising solid-state cooling approaches to address the issues of energy shortage and global warming. However, the cooling efficiency and cycle life of this technology need to be improved, and the required driving force shall be reduced. Here, a novel elastocaloric heat pump by periodic non-linear stress is developed by employing fiber twisting and separated cooling and heating media. The non-linear stress generated by fiber twisting yields a hierarchical, rigid-yet-flexible architecture and a periodic entropy spatial distribution, which result in a low mechanical hysteresis work and a high cooling efficiency (a maximum material coefficient of performance (COP) of 30.8 and a maximum Carnot efficiency of 82%). The torsional non-linear stress inhibits crack propagation and results in a highly extended cycle life (14752 cycles, more than ten times of fiber stretching). The heat pump exhibits a maximum average temperature span of 25.6 K, a maximum specific cooling power of 1850 W Kg-1, a maximum device COP of 19.5, and a maximum device power of 5.0 W, under each optimal condition.

Bispecific CAR-T cells targeting CD19/20 in patients with relapsed or refractory B cell non-Hodgkin lymphoma: a phase I/II trial.

Non-Hodgkin lymphoma (NHL) is a common malignancy in the hematologic system, and traditional therapy has limited efficacy for people with recurrent/refractory NHL (R/R NHL), especially for patients with diffuse large B cell lymphoma (DLBCL). Chimeric antigen receptor (CAR) T-cell therapy is a novel and effective immunotherapy strategy for R/R hematopoietic malignancies, but relapses can occur due to the loss of CAR-T cells in vivo or the loss of antigen. One strategy to avoid antigen loss after CAR-T cell therapy is to target one more antigen simultaneously. Tandem CAR targeting CD19 and CD22 has demonstrated the reliability of tandem CAR-T cell therapy for R/R B-ALL. This study explores the therapeutic potential of tandem CD19/20 CAR-T in the treatment of R/R B cell NHL. The efficacy and safety of autologous CD19/20 CAR-T cells in eleven R/R B cell NHL adult patients were evaluated in an open-label, single-arm trial. Most patients achieved complete response, exhibiting the efficacy and safety of tandem CD19/20 CAR-T cells. The TCR repertoire diversity of CAR-T cells decreased after infusion. The expanded TCR clones in vivo were mainly derived from TCR clones that had increased expression of genes associated with immune-related signaling pathways from the infusion product (IP). The kinetics of CAR-T cells in vivo were linked to an increase in the expression of genes related to immune response and cytolysis/cytotoxicity.

Jellyfish-Inspired Artificial Spider Silk for Luminous Surgical Sutures.

The development of functional surgical sutures with excellent mechanical properties, good fluorescence, and high cytocompatibility is highly required in the field of medical surgeries. Achieving fibers that simultaneously exhibit high mechanical robustness, good spinnability, and durable fluorescence emission has remained challenging up to now. Taking inspiration from the spinning process of spider silk and the luminescence mechanism of jellyfish, this work reports a luminous artificial spider silk prepared with the aim of balancing the fiber spinnability and mechanical robustness. This is realized by employing highly hydrated segments with aggregation-induced luminescence for enhancing the fiber spinnability and polyhydroxyl segments for increasing the fiber mechanical robustness. Twist insertion during fiber spinning improves the fiber strength, toughness, and fluorescence emission. Furthermore, coating the fiber with an additional polymer layer results in a "sheath-core" architecture with improved mechanical properties and capacity to withstand water. This work provides a new design strategy for performing luminescent and robust surgical sutures.

The History of Classification Systems for Periprosthetic Femoral Fractures: A Literature Review.

Periprosthetic femoral fractures (PPFFs) following total hip arthroplasty (THA) present a significant clinical challenge due to their increasing incidence with an aging population and evolving surgical practices. Historically, classifications were primarily based on anatomical fracture location, the stability of the implant, and bone quality surrounding the implant. We critically analyzed 25 classification systems, highlighting the emergence and adaptations of key systems such as the Vancouver classification system (VCS) and the Unified classification system (UCS), which are lauded for their simplicity and effectiveness yet require further refinement. VCS, developed in 1995, categorizes fractures based on the site, implant stability, and bone quality, and remains widely used due to its robust applicability across different clinical settings. Introduced in 2014, UCS expands the VCS to encompass all periprosthetic fractures with additional fracture types, aiming for a universal application. Despite their widespread adoption, these systems exhibit shortcomings, including the incomplete inclusion of all PPFF types and the imprecise assessment of implant stability and surrounding bone loss. These gaps can result in misclassification and suboptimal treatment outcomes. This paper suggests the necessity for ongoing improvements in classification systems to include emerging fracture types and refined diagnostic criteria, ensuring that they remain relevant to contemporary orthopedic practices and continue to facilitate the precise tailoring of treatment to patient-specific circumstances. This comprehensive historical review serves as a foundation for future innovations in classification systems, ultimately aiming to standardize PPFF treatment and improve patient prognosis.

Regeneration of sedimentary manganese in coastal sediments deciphered by 224Ra/228Th disequilibria.

Manganese (Mn) is a vital micronutrient and participates in multiple biochemical reactions and enzyme catalytic activities. Its cycling is tightly connected with iron (Fe) and nitrogen (N). Although coastal sediments are recognized as an important source of dissolved Mn to marine waters, this contribution remains inadequately quantified. In the summer of 2019 and 2020, we investigated benthic fluxes of dissolved Mn, Fe and ammonia (NH4+) in the Changjiang Estuary and East China Sea shelf using the 224Ra/228Th disequilibrium approach. Our results showed that the availability of reactive Mn oxides (MnD) played a crucial role in sedimentary Mn regeneration, as revealed by the positive correlation (r = 0.75, P < 0.05) between Mn fluxes and MnD contents. In addition, the positive correlation (r = 0.80, P < 0.01) between the decomposition rates of sedimentary organic matter (NH4+ flux) and Mn fluxes suggested that the reduction of MnD was mainly driven by the organic carbon oxidation. Furthermore, NH4+ and Mn fluxes exhibited an exponential increase against the product of dissolved oxygen concentration (DO) and the amplification factor of sediment surface area (ξ). In this context, ξ represents the rate of bottom water DO pumped into the sediment via physical reworking and bio-irrigation. In contrast to the most efficient Fe released from sediment overlain by hypoxic waters (DO <62.5 µM), the maximum Mn flux (63.5 ± 9.4 mmol m-2 d-1) was observed at sediment with oxygenated bottom waters (DO = 158 µM). This implies that the regeneration of Mn was associated with a more permissive redox state compared to that of Fe. We further demonstrated that Mn flux was 1-2 orders of magnitude higher than those estimated through traditional methods. Therefore, coastal sediments may contribute more Mn to ocean waters than previously thought. The precise estimation of Mn release from coastal sediments holds critical significance for research on the global Mn budget.

Follow-up from the A041202 study shows continued efficacy of ibrutinib regimens for older adults with CLL.

ABSTRACT: A041202 (NCT01886872) is a phase 3 study comparing bendamustine plus rituximab (BR) with ibrutinib and the combination of ibrutinib plus rituximab (IR) in previously untreated older patients with chronic lymphocytic leukemia (CLL). The initial results showed that ibrutinib-containing regimens had superior progression-free survival (PFS) and rituximab did not add additional benefits. Here we present an updated analysis. With a median follow-up of 55 months, the median PFS was 44 months (95% confidence interval [CI], 38-54) for BR and not yet reached in either ibrutinib-containing arm. The 48-month PFS estimates were 47%, 76%, and 76% for BR, ibrutinib, and IR, respectively. The benefit of ibrutinib regimens over chemoimmunotherapy was consistent across subgroups of patients defined by TP53 abnormalities, del(11q), complex karyotype, and immunoglobulin heavy chain variable region (IGHV). No significant interaction effects were observed between the treatment arm and del(11q), the complex karyotype, or IGHV. However, a greater difference in PFS was observed among the patients with TP53 abnormalities. There was no difference in the overall survival. Notable adverse events with ibrutinib included atrial fibrillation (afib) and hypertension. Afib was observed in 11 patients (pts) on BR (3%) and 67 pts on ibrutinib (18%). All-grade hypertension was observed in 95 pts on BR (27%) and 263 pts on ibrutinib (55%). These data show that ibrutinib regimens prolong PFS compared with BR for older patients with treatment-naïve CLL. These benefits were observed across subgroups, including high-risk groups. Strikingly, within the ibrutinib arms, there was no inferior PFS for patients with abnormalities in TP53, the highest risk feature observed in CLL. These data continue to demonstrate the efficacy of ibrutinib in treatment-naïve CLL.

FindDNAFusion: An Analytical Pipeline with Multiple Software Tools Improves Detection of Cancer-Associated Gene Fusions from Genomic DNA.

Detection of cancer-associated gene fusions is crucial for diagnosis, prognosis, and treatment selection. Many bioinformatics tools are available for the detection of fusion transcripts by RNA sequencing, but there are fewer well-validated software tools for DNA next-generation sequencing (NGS). A 542-gene solid tumor NGS panel was designed, with exonic probes supplemented with intronic bait probes against genes commonly involved in oncogenic fusions, with a focus on lung cancer. Three software tools for the detecting gene fusions in this DNA-NGS panel were selected and evaluated. The performance of these tools was compared after a pilot study, and each was configured for optimal batch analysis and detection rate. A blacklist for filtering common tool-specific artifacts, and criteria for selecting clinically reportable fusions, were established. Visualization tools for annotating and confirming somatic fusions were applied. Subsequently, a full clinical validation was used for comparing the results to those from in situ hybridization and/or RNA sequencing. With JuLI, Factera, and GeneFuse, 94.1%, 88.2%, and 66.7% of expected fusions were detected, respectively. With a combinatorial pipeline (termed FindDNAFusion), developed by integrating fusion-calling tools with methods for fusion filtering, annotating, and flagging reportable calls, the accuracy of detection of intron-tiled genes was improved to 98.0%. FindDNAFusion is an accurate and efficient tool in detecting somatic fusions in DNA-NGS panels with intron-tiled bait probes when RNA is unavailable.

Favorable response of a patient with primary B/myeloid mixed phenotype acute Leukemia to CD19-CAR-T: Case report and literature review.

RATIONALE: Mixed phenotype acute leukemia (MPAL) is a rare and heterogeneous type of leukemia known for its poor prognosis. The optimal treatment strategy for this condition currently lacks consensus, leaving uncertainty in its management. Nonetheless, a potential therapeutic option for patients with refractory MPAL who express target antigens is donor-derived chimeric antigen receptor T (CAR-T) cell therapy. PATIENT CONCERNS: We recently reported a 61-year-old woman with MPAL and elucidated its diagnosis and treatment. DIAGNOSIS: The diagnosis of MPAL was established based on the classification of World Health Organization in 2016. INTERVENTIONS: Despite undergoing 3 different acute lymphoblastic leukemia (ALL) regimens and 1 acute myelogenous leukemia (AML) regimen, the patient did not achieve remission. Subsequently, the patient received human CD19-targeted CAR-T cell therapy. OUTCOMES: The patient achieved a successful and complete remission after CAR-T cell therapy. Tragically, 8 months after CAR-T infusion, the patient experienced a relapse characterized by CD19-negative disease and ultimately passed away. LESSONS: This case underscores the potential efficacy and safety of human-derived CD19 CAR-T cell therapy in treating refractory MPAL. While this particular patient outcome was unfortunate, it suggests that CAR-T cell therapy may still hold promise as a viable treatment option for MPAL patients unresponsive to other therapies. Further research in this field is warranted to determine the most effective treatment strategies for managing this challenging disease.

High Cycle-Life Twistocaloric Cooling of Poly-p-Phenylene Benzodioxole Fibers.

It is an urgent need to develop efficient solid state cooling technologies and materials with high cycle life. Poly-p-phenylene benzodioxole (PBO) is a high performance fiber with excellent mechanical properties. In this work, for the first time, elasto- and twistocaloric cooling of PBO fibers by stretching and twisting of the PBO fiber bundles is reported. The cooling temperature reaches -0.4 and -1.3 K, for fiber stretching and twisting, respectively. A self-coiled PBO fiber achieves maximum cooling of -3.7 K upon stretching by 35% strain, with an exceptionally high cycle life of 200 000 times. During the twisting of the PBO fibers, reversible changes in the intensity of the diffraction peaks in X-ray diffraction patterns are observed. A strain-sensitive color change application is realized by coating a self-coiled PBO fiber with liquid crystallite dyes. This work provides new perspectives for PBO fibers as a high cycle-life solid-state refrigeration material.

Surgical treatment of specific Unified Classification System B fractures: potentially destabilising lesser trochanter periprosthetic fractures.

To investigate the clinical effects of specific Unified Classification System B (UCS B)-lesser trochanter periprosthetic fractures and determine whether they occur only with non-cemented stems. A retrospective analysis of 28 patients with specific UCS B2 fractures who underwent two surgical treatments, longer stem revision and internal fixation (LSRIF) and open reduction and internal fixation (ORIF), was performed. The patients were assessed at 1, 3, 6, 12, and 24 months and annually thereafter. Fracture healing, complications, Harris Hip Score (HHS), and the Short Form Health Survey questionnaire (SF-36) quality of life score were assessed at each follow-up. At the time of the last follow-up, seven patients had been lost: three were lost to contact, two died, and two were hospitalised elsewhere and unavailable for follow-up. The remaining 21 patients were followed for an average of 49.3 ± 15.4 (range: 24-74.4) months. Their average fracture healing time was 13.5 ± 1.1 (12-15.4) weeks. Complications included three cases (10.71%) of thrombus, one (3.57%) of heart failure, and one (3.57%) of pulmonary infection. There were no revisions due to prosthesis loosening, subsidence, or infection. At the last follow-up, the HHS, SF-36 mental score, and SF-36 physical score were recorded, LSRIF vs. ORIF (82.9 ± 6.6 vs. 74.7 ± 3.9, p = 0.059; 50.9 ± 7.6 vs. 38 ± 1.4, p = 0.012, and 51.7 ± 8.4 vs. 39.7 ± 3.4, p = 0.032, respectively). Specific UCS B2 fractures mostly occur with non-cemented stems. LSRIF with cables is the main treatment, while ORIF is an option for those elderly in poor condition.

Reverse traction with Kirschner wires and bilateral external fixation device combined with minimally invasive plate oseoynthesis technique for tibial plateau fractures of type Schatzker V and VI.

PURPOSE: Complex bicondylar tibial plateau fracture (TPF) has always been a tricky problem for surgeons. We created a novel external device used intraoperatively consisting of Kirschner wires, and combined with minimally invasive plate oseoynthesis (MIPO) technique to treat complex bicondylar TPFs, and the clinical effect and feasibility were further evaluated. METHODS: From March 2016 to February 2021, 49 cases (29 males and 20 females) were identified as bicondylar TPF, the mean age 47.2 (27-69). All patients adopted the device and MIPO technique. A series of score, complications, and radiographs in the follow-up period, from three months, six months, one year, and two years and the last follow-up, were recorded, from visual analogue score (VAS), hospital for special surgery (HSS), and Short-Form 36 (SF-36), containing physical (PCS) and mental (MCS), and Rasmussen score. RESULTS: Forty-seven patients showed good functional recovery. No patients were lost, mean follow-up time was 28.17 ± 2.81 (24.2-35.4) months. Operation time was 89.80 ± 13.46 (58-110) min. At the last follow-up, VAS was 1.3 ± 0.92 (0-4), HHS was 93.10 ± 2.63 (89-99), PCS was 49.20 ± 7.40 (38-65), and MCS was 50.08 ± 4.77 (43-62). Complications were as follows: cutaneous necrosis (3, 6%), asymptomatic arthritis (3, 6%), symptomatic arthritis (1, 2%), and deep venous thrombosis (1, 2%). Mean fracture healing time was 11.82 ± 1.5 (10-15.4) weeks. All patients got recovery without extra surgery and removed the implants at 12.85 ± 0.76 (11.2-15.4) months. CONCLUSION: Temporary traction device of bilateral external fixator combined with MIPO technique was simple and convenient, with a smaller soft-tissue damage, an easier operational approach, and its worth being promoted.

Samples from patients with AML show high concordance in detection of mutations by NGS at local institutions vs central laboratories.

Next-generation sequencing (NGS) to identify pathogenic mutations is an integral part of acute myeloid leukemia (AML) therapeutic decision-making. The concordance in identifying pathogenic mutations among different NGS platforms at different diagnostic laboratories has been studied in solid tumors but not in myeloid malignancies to date. To determine this interlaboratory concordance, we collected a total of 194 AML bone marrow or peripheral blood samples from newly diagnosed patients with AML enrolled in the Beat AML Master Trial (BAMT) at 2 academic institutions. We analyzed the diagnostic samples from patients with AML for the detection of pathogenic myeloid mutations in 8 genes (DNMT3A, FLT3, IDH1, IDH2, NPM1, TET2, TP53, and WT1) locally using the Hematologic Neoplasm Mutation Panel (50-gene myeloid indication filter) (site 1) or the GeneTrails Comprehensive Heme Panel (site 2) at the 2 institutions and compared them with the central results from the diagnostic laboratory for the BAMT, Foundation Medicine, Inc. The overall percent agreement was over 95% each in all 8 genes, with almost perfect agreement (κ > 0.906) in all but WT1, which had substantial agreement (κ = 0.848) when controlling for site. The minimal discrepancies were due to reporting variants of unknown significance (VUS) for the WT1 and TP53 genes. These results indicate that the various NGS methods used to analyze samples from patients with AML enrolled in the BAMT show high concordance, a reassuring finding given the wide use of NGS for therapeutic decision-making in AML.

Neuron-Inspired Sticky Artificial Spider Silk for Signal Transmission.

Neurons exhibit excellent signal transmission capacity, which inspire artificial neuron materials for applications in the field of wearable electronics and soft robotics. In addition, the neuron fibers exhibit good mechanical robustness by sticking to the organs, which currently has rarely been studied. Here, a sticky artificial spider silk is developed by employing a proton donor-acceptor (PrDA) hydrogel fiber for application as artificial neuron fibers. Tuning the molecular electrostatic interactions by modulating the sequences of proton donors and acceptors, enables combination of excellent mechanical properties, stickiness, and ion conductivity. In addition, the PrDA hydrogel exhibits high spinning capacity for a wide range of donor-acceptor combinations. The PrDA artificial spider silk would shed light on the design of new generation of artificial neuron materials, bio-electrodes, and artificial synapses.

Early surgical treatment of closed reduction and internal fixation for a 30-day old intertrochanteric fracture with hemiplegia after acute stroke: A case report.

RATIONALE: Currently, there are no clear guidelines to determine whether and when to perform surgical hip repair in patients with acute stroke and hip fracture. PATIENT CONCERNS: In this case report, we report a case of 75-year-old woman admitted with left hip pain and limited mobility for 1 month. DIAGNOSES: Patient had a history of acute cerebral infarction 42 days ago, and diagnosed with a left intertrochanteric fracture at another hospital 30 days ago. INTERVENTION: Patient was treated with closed reduction and internal fixation with proximal femoral nail anti-rotation. OUTCOMES: At 2-year follow-up, the patient's basic function was restored. The fracture healed well, and the Harris hip score was 75. LESSONS: Without consistent guidelines, individualized treatment strategies including surgical methods and timing of surgery should be made to weigh the risks and benefits for patients with acute stroke and intertrochanteric fractures.

Refining prognosis in chronic lymphocytic leukemia with normal Fluorescence in situ hybridization results.

Fluorescence in situ hybridization (FISH) to detect the recurrent cytogenetics abnormalities deletion 13q, trisomy 12, deletion 11q, and deletion 17p is important for prognostication in chronic lymphocytic leukemia (CLL). A subset of patients are negative for each of these abnormalities (normal 12/13/11/17 FISH), and outcomes are heterogenous within this group. To elucidate variables important for prognostication in this subgroup we conducted a retrospective analysis of 280 treatment-naïve CLL patients with normal standard CLL FISH results. In a multivariable model, advanced Rai stage (p = 0.04, hazard ratio [HR] 1.24 (95% confidence interval [CI] 1.01-1.53)), unmutated immunoglobulin heavy chain gene (IGHV) (p < 0.0001, HR 5.59 (95% CI 3.63-8.62)) and IGH rearrangement by FISH (p = 0.02, HR 2.56 (95% CI 1.20-5.48)) were significantly associated with shorter time to first treatment. In a multivariable model for overall survival, increasing age at 5-year increments (p < 0.0001, HR 1.55 (95% CI 1.25-1.93)), unmutated IGHV (p = 0.01, HR 5.28 (95% CI 1.52-18.35)) and gain of REL (p = 0.01, HR 4.08 (5% CI 1.45-11.49)) were significantly associated with shorter survival. Our study identifies variables important for refining prognosis for CLL patients with normal standard CLL FISH results.

Incidence, Clinicopathologic Features, HER2 Fluorescence In Situ Hybridization Profile, and Oncotype DX Results of Human Epidermal Growth Factor Receptor 2-Low Breast Cancers: Experience From a Single Academic Center.

Human epidermal growth factor receptor 2 (HER2)-low breast cancer, defined by an immunohistochemical (IHC) score of 1+ or 2+ with negative in situ hybridization, is emerging as a predictive marker for the use of the antibody-drug conjugate. To understand how this category differs from HER2-zero cases, we investigated clinicopathological characteristics and HER2 fluorescence in situ hybridization results in a large cohort of 1309 continuous HER2-negative invasive breast carcinomas from 2018 to 2021 evaluated by the Food and Drug Administration-approved HER2 IHC test. Additionally, we compared Oncotype DX recurrence scores and HER2 mRNA expression between HER-low and HER2-zero cases in a separate cohort of 438 estrogen receptor-positive (ER+) early-stage breast carcinoma cases from 2014 to 2016. Based on the cohort from 2018 to 2021, the incidence of HER2-low breast cancers was approximately 54%. HER2-low cases had less frequent grade 3 morphology, less frequent triple-negative results, ER and progesterone receptor negativity, and a higher mean HER2 copy number and HER2/CEP17 ratio than HER2-zero cases (P < .0001). Among ER+ cases, HER2-low cases showed significantly less frequent Nottingham grade 3 tumors. In the cohort from 2014 to 2016, HER2-low cases showed significantly higher ER+ percentages, fewer progesterone receptor-negative cases, lower Oncotype DX recurrence scores, and higher HER2 mRNA expression scores than HER2-zero cases. In summary, this is the first study, to our knowledge, using a large cohort of continuous cases evaluated by the Food and Drug Administration-approved HER2 IHC companion diagnostic test for HER2-low expression and HER2 fluorescence in situ hybridization profile in a real-world setting. Although HER2-low cases showed a higher HER2 copy number, ratio, and mRNA level than HER2-zero cases statistically, such small differences are unlikely to be biologically or clinically meaningful. However, our study suggests that HER2-low/ER+ early-stage breast carcinoma may represent a less aggressive group of breast carcinoma, given its association with a lower Nottingham grade and Oncotype DX recurrence score.

An Innovative Model of ISS-Based Multiple Fractures and Gastrointestinal Dysfunction Related to c-Kit Protein Expression on Interstitial Cells of Cajal.

OBJECTIVE: Gastrointestinal dysfunction seriously affects the prognosis and quality of life of patients with multiple fractures. However, experimental evidence of this relationship is lacking. Here we describe a newly developed mouse model of postoperative gastrointestinal dysfunction after multiple fractures. METHODS: Trauma severity was assessed using the injury severity score (ISS). Based on the ISS, a multiple fracture model was established in mice as follows: limb fractures with pelvic fractures and multiple rib fractures; limb fractures with multiple rib fractures; closed fracture of both forelegs with pelvic fracture and rib fractures; closed limb fractures; limb fracture with pelvic fracture; spinal fractures; hind leg fractures with pelvic fractures; pelvic fracture with multiple rib fractures; closed fracture of both fore legs with pelvic fracture; and closed fracture of both fore legs with multiple rib fractures. In each model group, gastrointestinal motility was assayed and the histopathology of the small intestine was examined. Western blot and immunohistochemical analyses of jejunal tissue were performed to detect c-kit protein expression, the level of which was compared with that of a control group. The results of ANOVA are expressed as mean ± standard deviation. RESULTS: In mice with multiple fractures, food intake was greatly reduced, consistent with histopathological evidence of an injured intestinal epithelium. The jejunal tissue of mice in groups a, c, f, and h was characterized by extensively necrotic and exfoliated intestinal mucosal epithelium and inflammatory cell infiltration in the lamina propria. In the gastrointestinal function assay, gastrointestinal motility was significantly reduced in groups a, b, c, f, and g; these group also had a higher ISS (p < 0.01). The expression of c-kit protein in groups with gastrointestinal dysfunction was significantly up-regulated (p < 0.001) compared with the control group. The close correlation between c-kit expression and the ISS indicated an influence of trauma severity on gastrointestinal motility. CONCLUSION: Gastrointestinal dysfunction after multiple fractures was successfully reproduced in a mouse model. In these mice, c-kit expression correlated with gastrointestinal tissue dysfunction and might serve as a therapeutic target.

Morphology modulation of artificial muscles by thermodynamic-twist coupling.

Human muscles can grow and change their length with body development; therefore, artificial muscles that modulate their morphology according to changing needs are needed. In this paper, we report a strategy to transform an artificial muscle into a new muscle with a different morphology by thermodynamic-twist coupling, and illustrate its structural evolution during actuation. The muscle length can be continuously modulated over a large temperature range, and actuation occurs by continuously changing the temperature. This strategy is applicable to different actuation modes, including tensile elongation, tensile contraction and torsional rotation. This is realized by twist insertion into a fibre to produce torsional stress. Fibre annealing causes partial thermodynamic relaxation of the spiral molecular chains, which serves as internal tethering and inhibits fibre twist release, thus producing a self-supporting artificial muscle that actuates under heating. At a sufficiently high temperature, further relaxation of the spiral molecular chains occurs, resulting in a new muscle with a different length. A structural study provides an understanding of the thermodynamic-twist coupling. This work provides a new design strategy for intelligent materials.