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Cell Dec 2023Cancer cells are regulated by oncogenic mutations and microenvironmental signals, yet these processes are often studied separately. To functionally map how...
Cancer cells are regulated by oncogenic mutations and microenvironmental signals, yet these processes are often studied separately. To functionally map how cell-intrinsic and cell-extrinsic cues co-regulate cell fate, we performed a systematic single-cell analysis of 1,107 colonic organoid cultures regulated by (1) colorectal cancer (CRC) oncogenic mutations, (2) microenvironmental fibroblasts and macrophages, (3) stromal ligands, and (4) signaling inhibitors. Multiplexed single-cell analysis revealed a stepwise epithelial differentiation phenoscape dictated by combinations of oncogenes and stromal ligands, spanning from fibroblast-induced Clusterin (CLU) revival colonic stem cells (revCSCs) to oncogene-driven LRIG1 hyper-proliferative CSCs (proCSCs). The transition from revCSCs to proCSCs is regulated by decreasing WNT3A and TGF-β-driven YAP signaling and increasing KRAS or stromal EGF/Epiregulin-activated MAPK/PI3K flux. We find that APC loss and KRAS collaboratively limit access to revCSCs and disrupt stromal-epithelial communication-trapping epithelia in the proCSC fate. These results reveal that oncogenic mutations dominate homeostatic differentiation by obstructing cell-extrinsic regulation of cell-fate plasticity.
Topics: Cell Differentiation; Oncogenes; Proto-Oncogene Proteins p21(ras); Signal Transduction; Stem Cells; Humans; Animals; Mice; Cell Lineage
PubMed: 38065080
DOI: 10.1016/j.cell.2023.11.004 -
Cell Dec 2023Patient-derived organoids (PDOs) can model personalized therapy responses; however, current screening technologies cannot reveal drug response mechanisms or how tumor...
Patient-derived organoids (PDOs) can model personalized therapy responses; however, current screening technologies cannot reveal drug response mechanisms or how tumor microenvironment cells alter therapeutic performance. To address this, we developed a highly multiplexed mass cytometry platform to measure post-translational modification (PTM) signaling, DNA damage, cell-cycle activity, and apoptosis in >2,500 colorectal cancer (CRC) PDOs and cancer-associated fibroblasts (CAFs) in response to clinical therapies at single-cell resolution. To compare patient- and microenvironment-specific drug responses in thousands of single-cell datasets, we developed "Trellis"-a highly scalable, tree-based treatment effect analysis method. Trellis single-cell screening revealed that on-target cell-cycle blockage and DNA-damage drug effects are common, even in chemorefractory PDOs. However, drug-induced apoptosis is rarer, patient-specific, and aligns with cancer cell PTM signaling. We find that CAFs can regulate PDO plasticity-shifting proliferative colonic stem cells (proCSCs) to slow-cycling revival colonic stem cells (revCSCs) to protect cancer cells from chemotherapy.
Topics: Humans; Apoptosis; Cancer-Associated Fibroblasts; Organoids; Signal Transduction; Single-Cell Analysis; Drug Evaluation, Preclinical; Algorithms; Stem Cells
PubMed: 38065081
DOI: 10.1016/j.cell.2023.11.005 -
Biomedical Engineering Letters Mar 2024This research was conducted to apply polyimide tape, which has the advantages of low price ans strong adhesive strength, to the neural electrode process. In addition, to...
This research was conducted to apply polyimide tape, which has the advantages of low price ans strong adhesive strength, to the neural electrode process. In addition, to maximize the low-cost characteristics, a fabrication process based on UV laser patterning rather than a photolithography process was introduced. The fabrication process started by attaching the gold sheet on the conductive double-sided tape without being torn or crushed. Then, the gold sheet and the double-sided tape were patterned together using UV laser. The patterned layer was transferred to the single-side polyimide tape. For insulation layer, electrode site opened single-sided polyimide tape was prepared. Polydimethylsiloxane was used as an adhesion layer, and alignment between electrode sites and opening sites was processed manually. The minimum line width achieved through the proposed fabrication process was approximately 100 m, and the sheet resistance of the conductive layer was 0.635 /sq. Measured cathodal charge storage capacity was 0.72 mC/cm and impedance at 1 kHz was 4.07 k/cm. Validation of fabricated electrode was confirmed by conducting 30 days accelerated soak test, flexibility test, adhesion test and ex vivo stimulation test. The novel flexible neural electrodes based on single-sided polyimide tape and UV laser patterned gold sheet was fabricated successfully. Conventional neural electrode fabrication processes based on polyimide substrate has a disadvantages such as long fabrication time, expensive costs, and probability of delamination between layers. However, the novel fabrication process which we introduced can overcome many shortcomings of existing processes, and offers great advantages such as simplicity of fabrication, inexpensiveness, flexibility and long-term reliability.
PubMed: 38374899
DOI: 10.1007/s13534-023-00345-0 -
The American Journal of Sports Medicine Dec 2023Reconstruction using autograft remains the gold standard surgical treatment for anterior cruciate ligament (ACL) injuries. However, up to 10% to 15% of patients will...
BACKGROUND
Reconstruction using autograft remains the gold standard surgical treatment for anterior cruciate ligament (ACL) injuries. However, up to 10% to 15% of patients will suffer a graft failure in the future. Cadaveric studies have demonstrated that the addition of suture tape augmentation to ACL autograft constructs can increase graft strength and reduce elongation under cyclical loading.
PURPOSE/HYPOTHESIS
This study aimed to investigate the clinical outcomes and rerupture rates after ACL reconstruction (ACLR) with suture tape augmentation. We hypothesized that augmentation with suture tape would lead to lower rerupture rates.
STUDY DESIGN
Case series; Level of evidence, 4.
METHODS
Patients undergoing primary ACLR using hamstring or patellar tendon autografts augmented with suture tape between 2015 and 2019 were recruited prospectively. Patients with multiligament injuries or a concomitant lateral extra-articular procedure were excluded. Patients were observed in person for 6 months, and patient-reported outcome measures (PROMs) were collected at 2 and 5 years postoperatively. All patients were contacted, and records were reviewed to determine the incidence of graft failure. PROMs collected were as follows: Knee injury and Osteoarthritis Outcome Score (KOOS), Veterans RAND 12-Item Health Survey (VR-12), Tegner and Marx activity scores, and visual analog scale for pain (VAS).
RESULTS
A total of 97 patients, with a mean age of 34.7 (±13.4) years, were included (76% men; 52 hamstring and 45 patellar tendon grafts). The mean graft diameter was 8 (±1) mm. There was 1 rerupture (1.1%) out of the 90 patients who were contactable at a mean of 5 years postoperatively. Median KOOS scores at 2 years were as follows: Pain, 94; Symptoms, 86; Activities of Daily Living, 99; Sport and Recreation, 82; and Quality of Life, 81. The postoperative scores were significantly higher than the preoperative scores ( < .001). The VR-12 Physical score improved from 43 preoperatively to 55 at 2 years and remained at 56 at 5 years. The VAS pain, Tegner, and Marx scores were 0, 6, and 9, respectively, at 2 years postoperatively. There was no difference in PROMs between graft types.
CONCLUSION
This study demonstrates encouraging results of suture tape augmentation of autograft ACLR for both hamstring and patellar tendon grafts. The failure rate of 1.1% at a mean follow-up of 5 years is lower than published rates for reconstruction, and PROMs results are satisfactory. The technique is safe to use and may permit a return to the preinjury sporting level with a lower chance of reinjury.
Topics: Male; Humans; Adult; Female; Follow-Up Studies; Activities of Daily Living; Quality of Life; Anterior Cruciate Ligament Reconstruction; Anterior Cruciate Ligament Injuries; Sutures; Autografts; Pain; Hamstring Tendons
PubMed: 37975527
DOI: 10.1177/03635465231207623 -
Heliyon Sep 2023Wireless devices have become extremely inexpensive and popular in recent years. The two most significant advantages of wireless devices over wired ones are convenience...
Wireless devices have become extremely inexpensive and popular in recent years. The two most significant advantages of wireless devices over wired ones are convenience and flexibility. Considering this, a wireless mouse pad prototype for access has been developed in this study. A capacitive sensors-based mouse pad with basic operations and conventional features has been developed using sensing arrays on paper. A facile, do-it-yourself fabrication process was utilized to develop a cost-effective, thin, wearable, and cleanroom-free wireless mouse cursor control (MCC) pad. The ablation process was used to cut the traces of conductive tape and paste them onto the paper to develop the MCC pad. The pad was connected with Espressif Systems (ESP)32 to wirelessly control the cursor of mobile and laptop. The capacitive touch sensor array-based pad is easy to reproduce and recycle. This pad can contribute to future advancements in thin human-machine interfaces, soft robotics, and medical and healthcare applications.
PubMed: 37681176
DOI: 10.1016/j.heliyon.2023.e19447 -
Heliyon Jun 2023Heat transfer in water with the help of solar energy is an effective way to harness renewable energy and reduce reliance on non-renewable sources of energy. The... (Review)
Review
Heat transfer in water with the help of solar energy is an effective way to harness renewable energy and reduce reliance on non-renewable sources of energy. The utilization of turbulent promoters is an efficient solution to ameliorate the performance of heat exchangers (HE). The current work summarizes the experimental and numerical behaviour of HE reported in the literature, including the thermal examinations of HT and fluid flow characteristics with various turbulent promoters and tube arrangements. This article reviews multiple studies in which different twisted tape (TT) geometry enhances the HT rate in various HE tubes. The current work also compares the thermal performance (η) of TT configurations in HE tubes using correlations developed by different investigators. Maximum heat transfer and minimum friction factor concerning fluid utilized in the system may also produce the optimal form for twisted tapes.
PubMed: 37274726
DOI: 10.1016/j.heliyon.2023.e16390 -
Biosensors & Bioelectronics Oct 2023Glucose is the primary energy source of human cells. Therefore, monitoring glucose inside microphysiological systems (MPS) provides valuable information on the viability...
Glucose is the primary energy source of human cells. Therefore, monitoring glucose inside microphysiological systems (MPS) provides valuable information on the viability and metabolic state of the cultured cells. However, continuous glucose monitoring inside MPS is challenging due to a lack of suitable miniaturized sensors. Here we present an enzymatic, optical glucose sensor element for measurement inside microfluidic systems. The miniaturized glucose sensor (Ø 1 mm) is fabricated together with a reference oxygen sensor onto biocompatible, pressure-sensitive adhesive tape for easy integration inside microfluidic systems. Furthermore, the proposed microfluidic system can be used as plug and play sensor system with existing MPS. It was characterized under cell culture conditions (37 °C and pH 7.4) for five days, exhibiting minor drift (3% day). The influence of further cell culture parameters like oxygen concentration, pH, flow rate, and sterilization methods was investigated. The plug-and-play system was used for at-line measurements of glucose levels in (static) cell culture and achieved good agreement with a commercially available glucose sensor. In conclusion, we developed an optical glucose sensor element that can be easily integrated in microfluidic systems and is able to perform stable glucose measurements under cell culture conditions.
Topics: Humans; Microfluidics; Microfluidic Analytical Techniques; Blood Glucose Self-Monitoring; Biosensing Techniques; Blood Glucose; Cell Culture Techniques; Glucose; Oxygen
PubMed: 37413826
DOI: 10.1016/j.bios.2023.115491 -
Journal of ISAKOS : Joint Disorders &... Dec 2023Anterior cruciate ligament (ACL) repair for proximal tears, where the ligament is re-attached and augmented with suture tape, can negate the need for graft harvest,...
OBJECTIVES
Anterior cruciate ligament (ACL) repair for proximal tears, where the ligament is re-attached and augmented with suture tape, can negate the need for graft harvest, thereby maintaining native anatomy. Autograft harvest has been associated with persistent deficits in lower limb muscle strength after recovery from ACL reconstruction. The aim of this study is to compare lower limb muscle strength following ACL repair and reconstruction.
METHODS
Nineteen ACL repair patients augmented with suture tape and nineteen ipsilateral semitendinosus-gracilis autograft ACL reconstruction patients (both mean 4 years postoperatively) were recruited, along with twenty healthy volunteers. Patient-reported outcome measures (PROMs) were obtained using the Knee Injury and Osteoarthritis Outcome Score (KOOS), Lysholm, and Tegner scores. Maximal isometric quadriceps and hamstring strength at 90° knee flexion were measured using a fixed Myometer after a warm-up and three maximal-effort contractions.
RESULTS
Mean hamstring strength of the reconstructed legs was lower than that of healthy volunteers by 0.29 Nm/kg. The hamstring strength ratio of the operated side to the uninjured side was greater in the repair (95% ± 13) than in the reconstruction (81% ± 18) group. There were no statistically significant differences between sides for quadriceps peak torque or for hamstrings in the volunteer or repair group. PROMs scores for the reconstruction group were significantly lower than volunteers across all domains and lower than repair for KOOS activities of daily living and Lysholm scores.
CONCLUSION
Hamstring weakness seen following ACL reconstruction is not evident following ACL repair with suture tape augmentation. Strength asymmetry could contribute to re-injury risk and influence functional performance, while altered loads affect knee biomechanics and may lead to osteoarthritis progression. The absence of these deficits in the repair group demonstrates a potential benefit of this technique when used in appropriate patients.
LEVEL OF EVIDENCE
II.
Topics: Humans; Anterior Cruciate Ligament Injuries; Activities of Daily Living; Anterior Cruciate Ligament; Osteoarthritis; Muscle Strength
PubMed: 37775044
DOI: 10.1016/j.jisako.2023.09.008 -
Sensors (Basel, Switzerland) Nov 2023This work presents the fabrication and characterization of a triple-layered biomimetic muscle constituted by polypyrrole (PPy)-dodecylbenzenesulfonate (DBS)/adhesive...
This work presents the fabrication and characterization of a triple-layered biomimetic muscle constituted by polypyrrole (PPy)-dodecylbenzenesulfonate (DBS)/adhesive tape/PPy-DBS demonstrating simultaneous sensing and actuation capabilities. The muscle was controlled by a neurobiologically inspired cortical neural network sending agonist and antagonist signals to the conducting polymeric layers. Experiments consisted of controlled voluntary movements of the free end of the muscle at angles of ±20°, ±30°, and ±40° while monitoring the muscle's potential response. Results show the muscle's potential varies linearly with applied current amplitude during actuation, enabling current sensing. A linear dependence between muscle potential and temperature enabled temperature sensing. Electrolyte concentration changes also induced exponential variations in the muscle's potential, allowing for concentration sensing. Additionally, the influence of the electric current density on the angular velocity, the electric charge density, and the desired angle was studied. Overall, the conducting polymer-based soft biomimetic muscle replicates properties of natural muscles, permitting simultaneous motion control, current, temperature, and concentration sensing. The integrated neural control system exhibits key features of biological motion regulation. This muscle actuator with its integrated sensing and control represents an advance for soft robotics, prosthetics, and biomedical devices requiring biomimetic multifunctionality.
Topics: Polymers; Biomimetics; Robotics; Pyrroles; Muscles
PubMed: 38005519
DOI: 10.3390/s23229132 -
Materials (Basel, Switzerland) Oct 2023Microfluidic chips have shown their potential for applications in fields such as chemistry and biology, and 3D printing is increasingly utilized as the fabrication...
Microfluidic chips have shown their potential for applications in fields such as chemistry and biology, and 3D printing is increasingly utilized as the fabrication method for microfluidic chips. To address key issues such as the long printing time for conventional 3D printing of a single chip and the demand for rapid response in individualized microfluidic chip customization, we have optimized the use of DLP (digital light processing) technology, which offers faster printing speeds due to its surface exposure method. In this study, we specifically focused on developing a fast-manufacturing process for directly printing microfluidic chips, addressing the high cost of traditional microfabrication processes and the lengthy production times associated with other 3D printing methods for microfluidic chips. Based on the designed three-dimensional chip model, we utilized a DLP-based printer to directly print two-dimensional and three-dimensional microfluidic chips with photosensitive resin. To overcome the challenge of clogging in printing microchannels, we proposed a printing method that combined an open-channel design with transparent adhesive tape sealing. This method enables the rapid printing of microfluidic chips with complex and intricate microstructures. This research provides a crucial foundation for the development of microfluidic chips in biomedical research.
PubMed: 37959581
DOI: 10.3390/ma16216984