ABSTRACT
Garlic cultivars are predominantly characterized by their sterility and reliance on asexual reproduction, which have traditionally prevented the use of hybrid breeding for cultivar improvement in garlic. Our investigation has revealed a notable exception in the garlic line G398, which demonstrates the ability to produce fertile pollen. Notably, at the seventh stage of anther development, callose degradation in the sterile line G390 was impeded, while G398 exhibited normal callose degradation. Transcriptome profiling revealed an enhanced expression of the callose-degrading gene, AsaNRF1, in the mature flower buds of the fertile line G398 compared to the sterile line G390. An insertion in the promoter of AsaNRF1 in G390 was identified, which led to its reduced expression at the tetrad stage and consequently delayed callose degradation, potentially resulting in the male sterility of G390. A discriminatory marker was developed to distinguish between fertile G398 and sterile G390, facilitating the assessment of male fertility in garlic germplasm resources. This study introduces a practical approach to harnessing garlic hybridization, which can further facilitate the breeding of new cultivars and the creation of novel male-fertile garlic germplasm using modern molecular biology methods.
ABSTRACT
Sarcoidosis is a rare disease that severely affects the lungs and superficial lymph nodes. In addition, this disease can also affect the skin, eyes and kidneys to varying degrees. The present report described a 32-year-old male patient who was admitted to Renmin Hospital of Wuhan University (Wuhan, China) due to joint pain in the extremities. He was diagnosed with uncorrectable hypercalcemia. A lymph node biopsy revealed the hypercalcemia to be associated with sarcoidosis, with the patient also demonstrating renal failure and lymph node enlargement. Administration of glucocorticoids provided benefits in terms of both primary and recurrent sarcoidosis, which also improved and preserved renal function. After being prescribed with oral prednisone treatment, blood calcium levels returned to normal, which indicated markedly improving renal function. However, the discontinuation of glucocorticoids for 2 months resulted in increased serum calcium and creatinine levels, both of which returned to abnormal levels. Overall, the present case report suggests that clinicians should actively perform sarcoidosis treatment in clinical practice to overcome any unexpected results associated with organ damage.
ABSTRACT
PURPOSE: This study aims to observe the curative effect of radioactive 125I seed implantation in treating inoperable or refused operation head and neck cancer. METHODS: Data from 132 patients with head and neck malignant tumors underwent computed tomography-guided radioactive 125I seed implantation from April 2004 to August 2020 were analyzed retrospectively. The Kaplan-Meier method was used to calculate the local control and survival rates. The logarithmic rank test and the Cox proportional risk model were used for univariate and multivariate analysis, respectively. RESULTS: A total of 132 patients were enrolled. All tumors were confirmed to be malignant through pathological analysis. Herein, we revealed that the seeds were implanted at the primary tumor site (23 cases, representing 17.4%), recurrent (9 cases, representing 6.8%), or metastatic lymph nodes (100 cases, representing 75.8%). Three months after the operation, 96 patients were evaluated as effective, whereas 36 patients were considered ineffective. The median local control time was 16 months; the local rates at 6, 12, 18, and 24 months were observed to be 75%, 47%, 35%, and 22%, respectively. The study reports a median survival period (OS) of 15 months. Additionally, the survival rates at 6, 12, 18, and 24 months were 61%, 42%, 31%, and 27%, respectively. Regarding side effects, skin or mucosal toxicity occurred in 14 patients. Grade I skin toxicity occurred in seven cases (5.3%), grade IV skin toxicity in one case (0.8%), grade I mucosal ulcer in four cases (3.0%), and grade I dry mouth in four cases (3.0%). The multivariate analysis showed that short-term efficacy and tumor site were independent prognostic factors (P < 0.001, 0.006, respectively). Additionally, the multivariate analysis showed that the independent OS influencing factors included D90, the longest tumor diameter, and short-term efficacy (P = 0.017, 0.001, <0.001). CONCLUSION: Radioactive 125I seed implantation is a safe and effective salvage therapy for patients with inoperable or refused operation head and neck cancer.
Subject(s)
Brachytherapy , Head and Neck Neoplasms , Iodine Radioisotopes , Humans , Iodine Radioisotopes/therapeutic use , Male , Female , Middle Aged , Head and Neck Neoplasms/radiotherapy , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/mortality , Aged , Adult , Retrospective Studies , Brachytherapy/methods , Brachytherapy/adverse effects , Survival Rate , Aged, 80 and over , Treatment Outcome , Follow-Up Studies , Tomography, X-Ray Computed , Neoplasm Recurrence, Local/radiotherapy , Neoplasm Recurrence, Local/pathology , PrognosisABSTRACT
Nano/microfluidic-based nucleic acid tests have been proposed as a rapid and reliable diagnostic technology. Two key steps for many of these tests are target nucleic acid (NA) immobilization followed by an enzymatic reaction on the captured NAs to detect the presence of a disease-associated sequence. NA capture within a geometrically confined volume is an attractive alternative to NA surface immobilization that eliminates the need for sample pre-treatment (e.g. label-based methods such as lateral flow assays) or use of external actuators (e.g. dielectrophoresis) that are required for most nano/microfluidic-based NA tests. However, geometrically confined spaces hinder sample loading while making it challenging to capture, subsequently, retain and simultaneously expose target NAs to required enzymes. Here, using a nanofluidic device that features real-time confinement control via pneumatic actuation of a thin membrane lid, we demonstrate the loading of digital nanocavities by target NAs and exposure of target NAs to required enzymes/co-factors while the NAs are retained. In particular, as proof of principle, we amplified single-stranded DNAs (M13mp18 plasmid vector) in an array of nanocavities via two isothermal amplification approaches (loop-mediated isothermal amplification and rolling circle amplification).
Subject(s)
Lab-On-A-Chip Devices , Nucleic Acid Amplification Techniques , DNA, Single-Stranded/chemistry , Microfluidic Analytical Techniques/instrumentation , Nanotechnology/instrumentation , Nucleic Acids/analysis , DNA/chemistry , DNA/analysisABSTRACT
We use molecular dynamics (MD) simulation and nanofluidic experiments to probe the non-equilibrium transient physics of two nanochannel-confined polymers driven against a permeable barrier in a flow field. For chains with a persistence length P smaller than the channel diameter D, both simulation and experiment with dsDNA reveal nonuniform mixing of the two chains, with one chain dominating locally in what we term "aggregates." Aggregates undergo stochastic dynamics, persisting for a limited time, then disappearing and reforming. Whereas aggregate-prone mixing occurs immediately at sufficiently high flow speeds, chains stay segregated at intermediate flow for some time, often attempting to mix multiple times, before suddenly successfully mixing. Observation of successful mixing nucleation events in nanofluidic experiments reveal that they arise through a peculiar "back-propagation" mechanism whereby the upstream chain, closest to the barrier, penetrates and passes through the downstream chain (farthest from the barrier) moving against the flow direction. Simulations suggest that the observed back-propagation nucleation mechanism is favored at intermediate flow speeds and arises from a special configuration where the upstream chain exhibits one or more folds facing the downstream chain, while the downstream chain has an unfolded chain end facing upstream.
ABSTRACT
Diabetic kidney disease (DKD) is one of the leading causes to develop end-stage kidney disease worldwide. Pericytes are implicated in the development of tissue fibrosis. However, the underlying mechanisms of pericytes in DKD remain largely unknown. We isolated and cultured primary pericytes and rat mesangial cells (HBZY-1). Western blot and qRT-PCR analysis were used to explore the role and regulatory mechanism of Integrin ß8/transforming growth factor beta 1 (TGF-ß1) pathway. We also constructed pericyte-specific Integrin ß8 knock-in mice as the research objects to determine the role of Integrin ß8 in vivo. We discovered that reduced Integrin ß8 expression was closely associated with pericyte transition in DKD. Overexpressed Integrin ß8 in pericytes dramatically suppressed TGF-ß1/TGF beta receptor 1 (TGFBR1)/Smad3 signaling pathway and protected glomerular endothelial cells (GECs) in vitro. In vivo, pericyte-specific Integrin ß8 knock-in ameliorated pericyte transition, endothelium injury and renal fibrosis in STZ-induced diabetic mice. Mechanistically, Murine double minute 2 (MDM2) was found to increase the degradation of Integrin ß8 and caused TGF-ß1 release and activation. Knockdown MDM2 could partly reverse the decline of Integrin ß8 and suppress pericytes transition. In conclusion, the present findings suggested that upregulated MDM2 expression contributes to the degradation of Integrin ß8 and activation of TGF-ß1/TGFBR1/Smad3 signaling pathway, which ultimately leads to pericyte transition during DKD progression. These results indicate MDM2/Integrin ß8 might be considered as therapeutic targets for DKD.
Subject(s)
Diabetes Mellitus, Experimental , Diabetic Nephropathies , Integrin beta Chains , Animals , Mice , Rats , Diabetes Mellitus, Experimental/metabolism , Diabetic Nephropathies/metabolism , Endothelial Cells/metabolism , Fibrosis , Kidney/pathology , Myofibroblasts/pathology , Pericytes/metabolism , Pericytes/pathology , Receptor, Transforming Growth Factor-beta Type I/metabolism , Transforming Growth Factor beta1/metabolismABSTRACT
BACKGROUND: The discovery of antigen phospholipase A2 receptor (PLA2R) in 2009 ushered in the antigen-based study of membranous nephropathy. The further putative antigen exostosin 1/2 (EXT1/2) was described in 2019. However, the distribution spectrum of glomerular EXT1 deposits in membranous nephropathy has not been fully elucidated. METHODS: We conducted a retrospective cohort study of biopsy-proven membranous nephropathy patients. Patients with complete baseline data and adequate tissue specimens were included in this study. Tests for glomerular expression of PLA2R and EXT1 and circulating anti-PLA2R antibodies were performed. Clinicopathological and outcome data were reviewed. RESULTS: We included 626 patients, namely, 487 (77.8%) PLA2R-positive patients and 54 (8.6%) EXT1-positive patients; 32 (5.1%) patients were dual-positive for PLA2R and EXT1 (PLA2R + /EXT1 +). A higher percentage of dual-positive patients had low C3 levels (P < 0.001) and were more likely to have autoimmune diseases (P = 0.013) than PLA2R-positive and EXT1-negative (PLA2R + /EXT1-) patients. Kidney biopsy findings revealed that there was a higher percentage of glomerular IgG1, IgG2, IgA, C4, and C1q deposits (P < 0.05), "full-house" staining (P < 0.001), and stronger intensity of C1q staining (P = 0.002) in PLA2R + /EXT1 + patients. Based on Kaplan-Meier analysis, a higher percentage of PLA2R + /EXT1 + patients exhibited partial or complete remission of proteinuria. Furthermore, EXT1-positive expression was a favourable predictor for proteinuria remission, whereas interstitial fibrosis/tubular atrophy was an unfavourable predictor. A complement C3 level < 0.79 g/L was independently associated with EXT1 positivity in PLA2R-positive membranous nephropathy. CONCLUSIONS: We describe a subgroup of PLA2R and EXT1 dual-positive patients. Patients in this subset exhibited more signs of autoimmunity and more frequent clinical remission. In PLA2R-positive membranous nephropathy, a complement C3 level < 0.79 g/L was independently associated with EXT1 positivity, which was a favourable predictor for proteinuria remission.
Subject(s)
Glomerulonephritis, Membranous , Humans , Glomerulonephritis, Membranous/pathology , Receptors, Phospholipase A2 , Complement C3 , Retrospective Studies , Clinical Relevance , Complement C1q , Proteinuria , AutoantibodiesABSTRACT
It is well established that a thin silica-like surface layer is formed when a cross-linked PDMS structure is subjected to ultraviolet/ozone treatment. Due to surface geometry, especially near the corners, this silica-like surface layer has non-uniform thickness, which can impact many mechanical properties, including adhesion and fracture strength. Here we use a simple analytic model based on diffusion of reactive species to predict the thickness of the oxidized surface layer near the corners. We demonstrate that these corner solutions can be patched together to determine the thickness of the oxidized layer in complex geometries.
ABSTRACT
Background: The treatment of local-regional recurrent breast cancer (BC) after external beam radiotherapy is challenging. We aim to evaluate the effectiveness and safety of computed tomography (CT)-guided percutaneous iodine-125 brachytherapy for local recurrent BC. Methods: We retrospectively analyzed 15 patients with local recurrent BC treated with CT-guided interstitial implantation of iodine-125 seeds. Regular contrast-enhanced CT was conducted to evaluate the tumor response. Follow-up survival, quality of life, and adverse events were analyzed. Results: Among the 15 patients, five were elderly patients (older than 80 years) and six were complicated with chronic underlying diseases. The median number of 125I seeds implantation was 33 (range: 20-130) with median dose 90 (D90, the minimum dose covering 90% of the target volume) of 108 Gy (range: 60-120 Gy). There was no significant difference in D90, V100 (the volume of the target receiving 100% of the prescription dose), and V150 (the volume of the target receiving 150% of the prescription dose) before and after operation (p > 0.05). The median follow-up was 14 months (range: 6-18 months). Six months after operation, the ORR was 66.7% (10/15) and the LCR was 93.3% (14/15). The 6- and 12-month survival rates were 100 and 41.6%, respectively, and the median survival time was 12.5 months. PS score decreased from 1.53 ± 0.81 to 0.53 ± 0.49. The pain score decreased from 2.87 ± 1.67 before operation to 1.07 ± 1.18 after operation, and the differences were statistically significant (p< 0.05). No severe complications occurred. Conclusions: CT-guided iodine-125 brachytherapy provided a safe and effective choice for recurrent BC with significant local therapeutic effects and minor complications, especially for elderly patients with chronic underlying disease and those who were not eligible for surgical resection and had failed to benefit from systemic therapy.
ABSTRACT
Bacteria have numerous large dsDNA molecules that freely interact within the cell, including multiple plasmids, primary and secondary chromosomes. The cell membrane maintains a micron-scale confinement, ensuring that the dsDNA species are proximal at all times and interact strongly in a manner influenced by the cell morphology (e.g. whether cell geometry is spherical or anisotropic). These interactions lead to non-uniform spatial organization and complex dynamics, including segregation of plasmid DNA to polar and membrane proximal regions. However, exactly how this organization arises, how it depends on cell morphology and number of interacting dsDNA species are under debate. Here, using an in vitro nanofluidic model, featuring a cavity that can be opened and closed in situ, we address how plasmid copy number and confinement geometry alter plasmid spatial distribution and dynamics. We find that increasing the plasmid number alters the plasmid spatial distribution and shortens the plasmid polar dwell time; sharper cavity end curvature leads to longer plasmid dwell times.
Subject(s)
DNA , DNA/genetics , Plasmids/genetics , Anisotropy , Cell MembraneABSTRACT
Solitary fibrous tumor (SFT) is a rare spindle cell tumor, benign or low-grade malignant, with an extremely low possibility of occurrence of malignant solitary fibrous tumor (MSFT). Surgery is an effective way for treating SFT, but it is often difficult to resect completely due to a large size, with a high recurrence rate and mortality rate after operation. Additionally, SFT is relatively resistant to chemotherapy, and there is a lack of effective systemic drug treatment. These lead to certain difficulties in the treatment of SFT. We report a case of a rare MSFT in the pelvic cavity. With a history of recurrence after two surgeries, this patient underwent surgical removal combined with 125I seed implantation at our hospital in the context that the tumor could not be completely removed because it was large and adhered to surrounding tissues; after up to 43 months of progression-free survival (PFS), the patient underwent 125I seed implantation alone, and achieved a complete remission, with a PFS up to 35 months. 125I seed implantation can be a safe and effective treatment option for unresectable MSFT as well as a potential solution to repeated local recurrence.
ABSTRACT
There is growing appreciation for the role phase transition based phenomena play in biological systems. In particular, self-avoiding polymer chains are predicted to undergo a unique confinement dependent demixing transition as the anisotropy of the confined space is increased. This phenomenon may be relevant for understanding how interactions between multiple dsDNA molecules can induce self-organized structure in prokaryotes. While recent in vivo experiments and Monte Carlo simulations have delivered essential insights into this phenomenon and its relation to bacteria, there are fundamental questions remaining concerning how segregated polymer states arise, the role of confinement anisotropy and the nature of the dynamics in the segregated states. To address these questions, we introduce an artificial nanofluidic model to quantify the interactions of multiple dsDNA molecules in cavities with controlled anisotropy. We find that two dsDNA molecules of equal size confined in an elliptical cavity will spontaneously demix and orient along the cavity poles as cavity eccentricity is increased; the two chains will then swap pole positions with a frequency that decreases with increasing cavity eccentricity. In addition, we explore a system consisting of a large dsDNA molecule and a plasmid molecule. We find that the plasmid is excluded from the larger molecule and will exhibit a preference for the ellipse poles, giving rise to a non-uniform spatial distribution in the cavity that may help explain the non-uniform plasmid distribution observed during in vivo imaging of high-copy number plasmids in bacteria.
Subject(s)
DNA , Polymers , Anisotropy , DNA/chemistry , Monte Carlo Method , Polymers/chemistryABSTRACT
PURPOSE: The purpose of this research was to evaluate the feasibility and efficacy of 125I seed brachytherapy as salvage treatment for recurrence from non-anaplastic thyroid cancer refractory to other modalities. METHODS: Between June 2006 and September 2019, fifteen patients with recurrent non-anaplastic thyroid cancer were treated with 125I seed brachytherapy. 125I seeds were implanted into the tumor under the guidance of CT and/or ultrasound images with the median prescription dose of 120 Gy (range, 100-140 Gy). The median seed number was 80 (range 10-214). Clinical efficacy was evaluated with Response Evaluation Criteria in Solid Tumors. FINDINGS: Fifteen patients were selected, eleven of whom had papillary carcinoma, two suffered from follicular carcinoma, and two were diagnosed with medullary carcinoma. These patients had twenty-four nodes in total. After they received salvage surgery and/or radioactive iodine (RAI) therapy, local recurrence was detected in all of them. No less than one node was observed in everyone's cervical or supraclavicular areas, and four patients had lung metastatic. The median follow-up period lasted 48 months (range, 5-93 months). All patients did not develop locoregional recurrence after experiencing 125I seed brachytherapy. Only three of them formed new metastases in nontarget regional nodes after brachytherapy, and additional brachytherapy can solve all regional failure problems. No significant adverse events were observed in any patient. IMPLICATIONS: For the chosen patients, 125I seed brachytherapy is feasible for treating refractory local recurrence from non-anaplastic thyroid cancer. Further studies are required to determine the role of 125I seed brachytherapy in the treatment of thyroid cancer.
ABSTRACT
An important problem in lubrication is the squeezing of a thin liquid film between a rigid sphere and an elastic substrate under normal contact. Numerical solution of this problem typically uses iteration techniques. A difficulty with iteration schemes is that convergence becomes increasingly difficult under increasingly heavy loads. Here we devise a numerical scheme that does not involve iteration. Instead, a linear problem is solved at every time step. The scheme is fully automatic, stable and efficient. We illustrate this technique by solving a relaxation test in which a rigid spherical indenter is brought rapidly into normal contact with a thick elastic substrate lubricated by a liquid film. The sphere is then fixed in position as the pressure relaxes. We also carried out relaxation experiments on a lubricated soft PDMS (polydimethysiloxane) substrate under different conditions. These experiments are in excellent agreement with the numerical solution.
ABSTRACT
BACKGROUND: Papillary thyroid carcinoma (PTC) is typically treated with surgical resection, even in recurrent cases. However, some cases of recurrent PTC are refractory to the conventionally used locoregional radiotherapy and resection methods. 125I seed permanent brachytherapy has emerged as a promising alternative for such PTCs, but no effective brachytherapy protocol has been reported for tumors with a huge volume, liquefaction, necrosis, and skin invasion. CASE PRESENTATION: A 47-year-old man presented with recurrence 8 years after 2 thyroidectomy procedures for PTC and recurrent PTC. The tumor measured 6 × 7 × 8 cm3 and exhibited liquefaction, necrosis, and skin invasion. The patient was treated at our hospital from December 2017 to November 2018. He received one round of 125I seed temporary brachytherapy and 4 rounds of 125I seed permanent implantation. The activity of the seeds was 0.3-3.0 mCi, and the total dose delivered to the tumor was 145 Gy. The recurrent tumor was successfully removed by 125I seed brachytherapy guided with a 3D-printed template and ultrasound and CT scanning. The refractory tumor healed uneventfully after 125I seed brachytherapy without recurrence over the 25-month follow-up. CONCLUSIONS: To the best of our knowledge, this is the first reported case of a large thyroid carcinoma that was effectively treated by 3D-printed template-guided 125I seed brachytherapy.
ABSTRACT
When a poroelastic gel is released from a patterned mold, surface stress drives deformation and solvent migration in the gel and flattens its surface profile in a time-dependent manner. Specifically, the gel behaves like an incompressible solid immediately after removal from the mold, and becomes compressible as the solvent is able to squeeze out of the polymer network. In this work, we use the finite element method (FEM) to simulate this transient surface flattening process. We assume that the surface stress is isotropic and constant, the polymer network is linearly elastic and isotropic, and that solvent flow obeys Darcy's law. The short-time and long-time surface profiles can be used to determine the surface stress and drained Poisson's ratio of the gel. Our analysis shows that the drained Poisson's ratio and the diffusivity of the gel can be obtained using interferometry and high-speed video microscopy, without mechanical measurement.
ABSTRACT
Extracellular vesicles (EVs) are cell-derived membrane structures that circulate in body fluids and show considerable potential for noninvasive diagnosis. EVs possess surface chemistries and encapsulated molecular cargo that reflect the physiological state of cells from which they originate, including the presence of disease. In order to fully harness the diagnostic potential of EVs, there is a critical need for technologies that can profile large EV populations without sacrificing single EV level detail by averaging over multiple EVs. Here we use a nanofluidic device with tunable confinement to trap EVs in a free-energy landscape that modulates vesicle dynamics in a manner dependent on EV size and charge. As proof-of-principle, we perform size and charge profiling of a population of EVs extracted from human glioblastoma astrocytoma (U373) and normal human astrocytoma (NHA) cell lines.
Subject(s)
Extracellular Vesicles , Glioblastoma , Cell Line , HumansABSTRACT
Agitated strings serve as macroscale models of spontaneous knotting, providing valuable insight into knotting dynamics at the microscale while allowing explicit analysis of the resulting knot topologies. We present an experimental setup for confined macroscale knot formation via tumbling along with a software interface to process complex knot data. Our setup allows characterization of knotting probability, knot complexity, and knot formation dynamics for knots with as many as 50 crossings. We find that the probability of knotting saturates below 80% within 100 s of the initiation of tumbling and that this saturation probability does not increase for chains above a critical length, an indication of nonequilibrium knot-formation conditions in our experiment. Despite the saturation in knot formation, we show that longer chains, while being more confined, will always tend to form knots of higher complexity since the free end can access a greater number of loops during tumbling.
ABSTRACT
The interface between two surfaces patterned with complementary shapes such as arrays of ridge-channel structures or pillars accommodates relative misorientation and lattice mismatch by spontaneous production of dislocation arrays. Here, we show that the relative sliding of such an interface is accomplished by dislocation glide on the interfacial plane. An exception is the singular case where the lattices are perfectly matched across the sample dimension, in which case sliding is accompanied by motion of edge-nucleated defects. These are meso-scale analogues of molecular sliding friction mechanisms between crystalline interfaces. The dislocations, in addition to the long-range elastic energy associated with their Burgers vectors, also cause significant out-of-plane dilation, which props open the interface locally. For this reason, the sliding friction is strongly pressure dependent; it also depends on the relative orientation of the patterns. Sliding friction can be strongly enhanced compared with a control, showing that shape-complementary interfaces can be engineered for strongly enhanced pressure- and orientation-dependent frictional properties in soft solids.
Subject(s)
Friction , Motion , Surface PropertiesABSTRACT
The surface of soft solids carries a surface stress that tends to flatten surface profiles. For example, surface features on a soft solid, fabricated by moulding against a stiff-patterned substrate, tend to flatten upon removal from the mould. In this work, we derive a transfer function in an explicit form that, given any initial surface profile, shows how to compute the shape of the corresponding flattened profile. We provide analytical results for several applications including flattening of one-dimensional and two-dimensional periodic structures, qualitative changes to the surface roughness spectrum, and how that strongly influences adhesion.