Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 56
Filter
1.
Opt Lett ; 49(15): 4122-4125, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39090873

ABSTRACT

Without the axial component, an annular spatial profile of the first-order Stokes (S1) was observed during the SRS process in low-energy pumped CO2 gas, which is supposed to be generated by a parametric four-wave mixing process (PFWM), i.e., 2ωP = ωAS1 + ωS1. In order to verify such a mechanism, similar experiments were conducted in H2, and the annular S1 intensity distribution was also noticed. Furthermore, simulations of S1 radial intensity distributions were carried out based on the proposed PFWM phase matching geometry. The PFWM has been verified to be a process that directly annihilates two pump photons and simultaneously produces one AS1 photon and one S1 photon.

2.
ACS Appl Mater Interfaces ; 16(32): 42566-42576, 2024 Aug 14.
Article in English | MEDLINE | ID: mdl-39088734

ABSTRACT

The seed method stands out as a straightforward and efficient approach for fabricating high-performance perovskite solar cells (PSCs). In this study, we propose the utilization of an antisolvent as an additive to induce crystal seeding, thereby facilitating the growth of wide-bandgap perovskite grains. Specifically, we introduce three commonly used antisolvents─ethyl acetate (EA), isopropanol (IPA), and chlorobenzene (CB)─directly into the perovskite precursor solution to generate perovskite seeds, which serve to promote subsequent nucleation. This antisolvent-crystal seeding method (ACSM) results in increased grain sizes, reduced film defects, and overall improved film quality. Consequently, the power conversion efficiencies (PCEs) of 1.647 eV PSCs with EA, IPA, and CB additives are recorded at 19.86%, 20.61%, and 20.45%, respectively, surpassing that of the reference device with a PCE of 18.83%. Furthermore, the stability of the PSCs prepared through ACSM is notably enhanced. Notably, PSCs optimized with IPA retain 75% of the original PCE after being stored in ambient air conditions (25 °C, RH ∼ 15%) for 30 days, better than the CB-added (64%) and the EA-added devices (53%), while the reference devices only retain 31% of the initial PCE. Moreover, even after continuous thermal annealing at 50 °C for 200 h, IPA-assisted devices demonstrate the best stability, followed by those with CB and EA, with the reference exhibiting the poorest stability.

4.
Opt Express ; 32(11): 19552-19566, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38859088

ABSTRACT

Besides the scattering structures, the energy transfer (ET) process in the gain medium plays a significant role in the competition between coherent (comprising strongly coherent components) and incoherent (consisting of weakly coherent or "hidden" coherent components) modes of random lasers. In this study, bichromatic emission random lasers were successfully created using polydimethylsiloxane (PDMS) replicas with grooved structures that imitate the inner surface of abalone shells as scattering substrates. The influence mechanism of the ET process from the monomer to dimer in the Rhodamine 640 dye on the competition of random laser modes was thoroughly investigated from both spectral and temporal dimensions. It was confirmed that the ET process can reduce the gain of monomers while amplifying the gain of dimers. By considering the dominant high-efficiency ET processes, an energy transfer factor associated with the pump energy density was determined. Notably, for the first time, it was validated that the statistical distribution characteristics of the time sequence variations in the coherent random laser generated by dimers closely resemble a normal distribution. This finding demonstrates the feasibility of producing high-quality random number sequences.

5.
Opt Express ; 32(11): 19645-19654, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38859094

ABSTRACT

Over the past decade, perovskite solar cells (PSCs) have attracted enormous attention due to their high performance. One key to fabricating high-quality perovskite films lies in controlling the volatilization rate of residual solvents during the annealing process. This study systematically investigates how different protective substrates affect the volatilization rate of residual solvent in perovskite films. By adjusting the direction and rate of evaporation, the supersaturation time of the solution was precisely controlled, leading to effective recrystallization of the grains. Concurrently, the annealing time was optimized to enhance film quality further. This optimization aimed to increase crystallinity, reduce defects, and thereby minimize non-radiative recombination centers. Implementing these methodologies, particularly the use of filter paper as a protective substrate during a 2-minute annealing process, significantly improved the fill factor (FF) and open-circuit voltage (VOC) of the PSCs. This led to a remarkable 5.26% improvement in power conversion efficiency (PCE) compared to control devices. The strategies employed in this work demonstrate significant potential in improving PSC film quality. This approach not only advances our understanding of film formation dynamics but also provides a practical guideline for future PSC fabrication.

6.
Infect Drug Resist ; 17: 403-416, 2024.
Article in English | MEDLINE | ID: mdl-38328339

ABSTRACT

Background: China is a country with a burden of high rates of both TB and multidrug-resistant TB (MDR-TB). However, published data on pyrazinamide (PZA) resistance are still limited in Hunan province, China. This study investigated the prevalence, transmission, and genetic diversity of PZA resistance among multidrug-resistant Mycobacterium tuberculosis isolates in Hunan province. Methods: Drug susceptibility testing (DST) with the Bactec MGIT 960 PZA kit and pyrazinamidase (PZase) testing were conducted on all 298 MDR clinical isolates. Moreover, 24-locus MIRU-VNTR and DNA sequencing of pncA, rpsA, and panD genes were conducted on 180 PZA-resistant (PZA-R) isolates. Results: The prevalence of PZA resistance among MDR-TB strains reached 60.4%. Newly diagnosed PZA-R TB patients and clustered isolates with identical pncA, rpsA, and panD mutations showed that transmission of PZA-R isolates played a significant role in the formation of PZA-R TB. Ninety-eight mutation patterns were observed in the pncA among 180 PZA-R isolates, and seventy-one (72.4%) were point mutations. Twenty-four of these mutations are new, including 2 base substitutions (V93G and T153S) and 22 nucleotide deletions or insertions. The W119C was found in PZA-S isolates, on the other hand, F94L and V155A mutations were found in both PZA resistant and susceptible isolates with positive PZase activity, indicating that they were not associated with PZA resistance. This is not entirely in line with the WHO catalogue. Ten novel rpsA mutations were found in 10 PZA-R isolates, which all combined with mutations in pncA. Thus, it is unpredictable whether these mutations in rpsA can impact PZA resistance. No panD mutation was found in all PZA-R isolates. Conclusion: DNA sequencing of pncA and PZase activity testing have great potential in predicting PZA resistance.

7.
Sci Rep ; 14(1): 4612, 2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38409210

ABSTRACT

The violent goods vibration during curve negotiation is a huge threat to the vehicle running safety. Qualified load restraint assemblies that can significantly suppress the cargo vibration are necessary. This study proposes a novel method for evaluating the essential restraint strength, focusing on the relative motion between cargo and wagon. In the beginning, as a comparison, current methods are used to calculate the necessary stiffness of lashings, which are adopted to restrain the cargo vibration on the wagon. Based on the data of the field test, the accuracy of the established wagon-cargo coupled dynamics model is validated. The loaded wagon model negotiates the curve under different running and loading conditions. The simulation results and analysis demonstrate effective strategies for suppressing the vibration of the cargo and reveal the necessary lashing stiffness. The comparison among the results of different evaluation methods shows that the stability of the cargo can be improved by optimizing the lashing stiffness with the method of dynamics simulations. We hope this study will make a positive contribution to the safety of railway freight transportation.

8.
Clin Rehabil ; 38(6): 715-731, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38317586

ABSTRACT

OBJECTIVE: To review the effectiveness of different physical therapies for acute and sub-acute low back pain supported by evidence, and create clinical recommendations and expert consensus for physiotherapists on clinical prescriptions. DATA SOURCES: A systematic search was conducted in PubMed and the Cochrane Library for studies published within the previous 15 years. REVIEW METHODS: Systematic review and meta-analysis, randomized controlled trials assessing patients with acute and sub-acute low back pain were included. Two reviewers independently screened relevant studies using the same inclusion criteria. The Physiotherapy Evidence Database and the Assessment of Multiple Systematic Reviews tool were used to grade the quality assessment of randomized controlled trials and systematic reviews, respectively. The final recommendation grades were based on the consensus discussion results of the Delphi of 22 international experts. RESULTS: Twenty-one systematic reviews and 21 randomized controlled trials were included. Spinal manipulative therapy and low-level laser therapy are recommended for acute low back pain. Core stability exercise/motor control, spinal manipulative therapy, and massage can be used to treat sub-acute low back pain. CONCLUSIONS: The consensus statements provided medical staff with appliable recommendations of physical therapy for acute and sub-acute low back pain. This consensus statement will require regular updates after 5-10 years.


Subject(s)
Low Back Pain , Physical Therapy Modalities , Humans , Low Back Pain/rehabilitation , Low Back Pain/therapy , Consensus , Randomized Controlled Trials as Topic , Female , Acute Pain/therapy , Acute Pain/rehabilitation , Male
9.
Appl Opt ; 63(2): 543-548, 2024 Jan 10.
Article in English | MEDLINE | ID: mdl-38227252

ABSTRACT

Laser-induced breakdown (LIB) and the competition of other Raman processes are major reasons restricting photon conversion efficiency (PCE) of Raman lasers. In this work, 1064 nm was used as the pump source, and stimulated rotational Raman scattering of hydrogen was investigated. The configuration of zooming out and focusing pump beam was applied, and the dimension of the pump beam at the focus spot increased significantly; consequently, LIB was suppressed, and Raman PCE was improved dramatically. With the help of the Raman gas pressure optimization, vibrational Raman could be fully suppressed, and other competition Raman processes could be well controlled. The optimal PCEs of different rotational Raman lasers could be achieved under different conditions. The maximum PCE of the first rotational Stokes (RS1) was improved to 60.7%, and the maximum energy of RS1 reached 204.5 mJ. With the increment of hydrogen pressure, the maximum PCE of the second rotational Stokes (RS2) was improved to 28.2%, and the maximum energy of RS2 reached 123.9 mJ. Furthermore, a 2.1 µm Raman laser was also generated, the maximum PCE of 2.1 µm reached 44.8%, and its pulse energy reached 106.1 mJ.

10.
J Back Musculoskelet Rehabil ; 37(2): 347-354, 2024.
Article in English | MEDLINE | ID: mdl-37781791

ABSTRACT

BACKGROUND: Studies have shown that core muscle training can accelerate the recovery of motor function in stroke patients. However, there are no relevant reports to show the effect of core muscle training combined with functional electrical stimulation (FES) on the rehabilitation of stroke patients. OBJECTIVE: This study aimed to observe the efficacy of core muscle training combined with FES on motor and balance functions of lower limbs in stroke patients. METHODS: This study selected and divided 120 stroke patients with hemiplegia admitted to our hospital into the control and observation groups. Patients in the control group just received core muscle training; while patients in the observation group were treated by core muscle training combined with FES. Both groups were treated for 8 weeks. Subsequently, the clinical data and information of all patients were collected and counted. Muscle strength changes were observed by detecting paralytic dorsiflexor (pDF), plantar flexor (pPF), knee extensor (pKE), and knee flexor (pKF) before and after treatment. Motor and balance abilities of both groups were scored through the 10-meter walking test (10 MWT), Berg balance scale (BBS), functional ambulation category (FAC) scale, timed up and go (TUG) test, and lower extremity motricity index (MI-Lower). RESULTS: No significant difference was found in clinical data between the two groups. The intensity of pDF, pPF, pKE, and pKF significantly increased in both groups after treatment, and the intensity of these parameters was higher in the observation group relative to the control group. Additionally, 10 MWT and TUG test scores of patients in the observation group were notably decreased while the BBS and MI-Lower scores were significantly increased after treatment compared with those in the control group. CONCLUSION: Core muscle training combined with FES can significantly improve the rehabilitation effect of lower limb motor and balance functions in stroke patients.


Subject(s)
Electric Stimulation Therapy , Stroke Rehabilitation , Stroke , Humans , Stroke/complications , Lower Extremity , Muscle, Skeletal , Electric Stimulation , Treatment Outcome
11.
Adv Mater ; 36(7): e2308979, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38009644

ABSTRACT

Colloidal quantum-dot (QD) lasing is normally achieved in close-packed solid-state films, as a high QD volume fraction is required for stimulated emission to outcompete fast Auger decay of optical-gain-active multiexciton states. Here a new type of liquid optical-gain medium is demonstrated, in which compact compositionally-graded QDs (ccg-QDs) that feature strong suppression of Auger decay are liquefied using a small amount of solvent. Transient absorption measurements of ccg-QD liquid suspensions reveal broad-band optical gain spanning a wide spectral range from 560 (green) to 675 nm (red). The gain magnitude is sufficient to realize a two-color amplified spontaneous emission (ASE) at 637 and 594 nm due to the band-edge (1S) and the excited-state (1P) transition, respectively. Importantly, the ASE regime is achieved using quasicontinuous excitation with nanosecond pulses. Furthermore, the ASE is highly stable under prolonged excitation, which stands in contrast to traditional dyes that exhibit strong degradation under identical excitation conditions. These observations point toward a considerable potential of high-density ccg-QD suspensions as liquid, dye-like optical gain media that feature readily achievable spectral tunability and stable operation under intense photoexcitation.

12.
Int J Mol Sci ; 24(17)2023 Sep 04.
Article in English | MEDLINE | ID: mdl-37686448

ABSTRACT

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the digestive tract and originate from the interstitial cells of Cajal (ICC), which is the pacemaker for peristaltic movement in the gastrointestinal tract. Existing GIST cell lines are widely used as cell models for in vitro experimental studies because the mutation sites are known. However, the immortalization methods of these cell lines are unknown, and no Chinese patient-derived GIST cell lines have been documented. Here, we transfected simian virus 40 large T antigen (SV40LT) into primary GIST cells to establish an immortalized human GIST cell line (ImGIST) for the first time. The ImGIST cells had neuronal cell-like irregular radioactive growth and retained the fusion growth characteristics of GIST cells. They stably expressed signature proteins, maintained the biological and genomic characteristics of normal primary GIST cells, and responded well to imatinib, suggesting that ImGIST could be a potential in vitro model for research in GIST to explore the molecular pathogenesis, drug resistance mechanisms, and the development of new adjuvant therapeutic options.


Subject(s)
Gastrointestinal Stromal Tumors , Humans , Gastrointestinal Stromal Tumors/genetics , Simian virus 40/genetics , Antigens, Viral, Tumor , Cell Line
13.
Micromachines (Basel) ; 14(7)2023 Jun 22.
Article in English | MEDLINE | ID: mdl-37512592

ABSTRACT

A novel split-gate SiC MOSFET with an embedded MOS-channel diode for enhanced third-quadrant and switching performances is proposed and studied using TCAD simulations in this paper. During the freewheeling period, the MOS-channel diode with a low potential barrier constrains the reverse current flow through it. Therefore, the suggested device not only has a low diode cut-in voltage but also entirely suppresses the intrinsic body diode, which will cause bipolar deterioration. In order to clarify the barrier-lowering effect of the MOS-channel diode, an analytical model is proposed. The calibrated simulation results demonstrate that the diode cut-in voltage of the proposed device is decreased from the conventional voltage of 2.7 V to 1.2 V. In addition, due to the split-gate structure, the gate-to-drain charge (QGD) of the proposed device is 20 nC/cm2, and the reverse-transfer capacitance (CGD) is 14 pF/cm2, which are lower than the QGD of 230 nC/cm2 and the CGD of 105 pF/cm2 for the conventional one. Therefore, a better high-frequency figure-of-merit and lower switching loss are obtained.

14.
Phys Chem Chem Phys ; 25(14): 10054-10062, 2023 Apr 05.
Article in English | MEDLINE | ID: mdl-36970935

ABSTRACT

Dielectric/plasmonic lattice relaxation spectroscopy is theoretically discussed in this work. A lattice relaxation effect generally occurs in nanocrystals, which means that from the bulk phase to the crystal surface, lattice parameters show a gradual shift. Here, lattice relaxation is introduced into finite polarizable point arrays or rod arrays as an adjusting tool, and its effect on lattice resonance extinction spectrum peaks is calculated. DDA (discrete dipole approximation) and FDTD (finite difference time domain) methods are applied. Different from an ideal infinite array, a finite array exhibits a broad, rippled extinction spectral peak. The application of an expanded/contracted lattice relaxation to the finite array can compress the ripple on one shoulder of the peak, as a cost, and the other shoulder of the peak gets more rippled, showing a "ripple transfer" effect. The strategy introduced in this work can contribute to the micro/nano optical measurement, on-chip adjustable optical cavity for OPOs (optical parameter oscillators)/lasers and controlling of fluorescence or hot-electron chemistry.

15.
Appl Opt ; 62(5): 1274-1278, 2023 Feb 10.
Article in English | MEDLINE | ID: mdl-36821227

ABSTRACT

A ∼2.1-µm laser is within an atmospheric transmission window and can be used in remote sensing. In this work, a 1064-nm laser was used as the pump source, pressurized hydrogen was used as the Raman active medium, and a dual-wavelength ∼2.1-µm Raman laser was generated. The 2147-nm laser was generated by a combination processes of stimulated vibrational Raman scattering and stimulated rotational Raman scattering, while a 2132-nm laser was generated by stimulated S-branch vibrational Raman scattering. Optimizing experimental conditions yielded a maximum pulse energy of 76.1 mJ, a peak power of ∼9.2M W, and a photon conversion efficiency of 29.8%.

16.
Plant Dis ; 2023 Jan 23.
Article in English | MEDLINE | ID: mdl-36691265

ABSTRACT

Humulus scandens, (Lour.) Merr., is a climbing herb which are used as traditional Chinese medicine, a raw material for papermaking, making soap, and replacing hops H. lupulus. This herb is distributed in many provinces of China, including Sichuan province. During March and June 2022, powdery mildew was found on leaves of H. scandens in the modern agricultural high-tech demonstration garden of Sichuan Academy of Agricultural Science, Chengdu, Sichuan Province, China. Abundant white or grayish powdery colonies could be seen on the surface of leaves, and 30%-100% of leaf areas were affected. Some of the infected leaves were either chlorotic or senescent. About 90% of the observed plants showed powdery mildew symptoms. Conidiophores (n = 25) were 74.0 to 160.1 µm × 8.7 to 12.7 µm (on average 120.9 × 10.4 µm) and composed of cylindrical foot cells (length 31.9-72.9 µm, average 50.1 µm) and conidia (mostly 10 conidia) in chains. Barrel-shaped conidia with fibrosin bodies (n = 30) were 12.8 to 21.0 µm × 7.9 to 15 µm, on average 16.7 × 11.3 µm, with a length/width ratio of 1.5. Chasmothecia were not found. Based on these morphologic characteristics, the pathogen was initially identified as Podosphaera macularis (Braun and Cook 2012; Mahaffee et al. 2009). To confirm the identification, two isolates (PDLC0315 and PDLC0412) of P. macularis mycelia and conidia were collected, and mycelia and conidia were combined for a single DNA extraction from each isolate. With the total genomic DNA, the sequences of the internal transcribed spacer (ITS), 5.8S rRNA, the 18S and 28S large subunit ribosomal DNA (LSU) (Bradshaw and Tobin 2020; White et al. 1990), were bi-directionally sequenced and deposited in GenBank (ON862625.1 and ON862630.1). The ON862625.1 and ON862630.1 showed 100% similarity with sequences of P. macularis isolate CT1 (MH687414.1). Phylogenetic analyses based on the combined ITS and 28S rDNA sequences indicated that the two specimens, PDLC0315 and PDLC0412 formed a monophyletic clade together with sequences retrieved from Podosphaera macularis CT1 and Head quarter 31 (KX842348.1). The pathogenicity test with the fungus was confirmed by gently pressing the infected leaves onto three healthy wild plants from the same geographical location. Three uninoculated wild plants served as controls. Six inoculated and non-inoculated plants were placed in different growth chambers with a 16-h photoperiod at 22±2°C and 70% of relative humidity. After 10 to 14 days, powdery mildew colonies developed on inoculated plants. Non-inoculated control plants did not show any symptoms. The fungus on inoculated leaves was morphologically identical to that first observed in the garden. As far as we know, this study is the first report of powdery mildew disease in Humulus scandens caused by Podosphaera macularis in China. Rapid expansion and wild distribution of H. scandens could lead to increased powdery mildew risk in outdoor cultivation. Due to the invasive potential of the powdery mildew fungi, this record is important in the context of the range extension of Podosphaera macularis.

17.
Heliyon ; 8(12): e12008, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36506366

ABSTRACT

Tendinopathy refers to a type of tendon disease with a multifactorial spectrum. Recent research has begun to reveal the effects of inflammation on the tendinopathic process, especially in the first stage of tendinopathy. Radial extracorporeal shock wave therapy (rESWT) has been successfully used to treat orthopedic diseases. However, the molecular mechanisms underlying the anti-inflammatory effects of rESWT on tumor necrosis factor-α treated tenocytes have not been fully elucidated. In this study, we applied total protein tandem mass tag-labeled quantitative proteomics with liquid chromatography-mass spectrometer/mass spectrometer technology to identify differentially expressed proteins (DEPs) among inflammatory tenocytes, rESWT inflammatory tenocytes, and controls using three biological replicates. Human tenocytes were used and they were cultured in vitro. In total, 1028 and 40 DEPs were detected for control versus inflammatory tenocytes and for inflammatory tenocytes versus rESWT inflammatory tenocytes, respectively. Further, we identified integrin α2, selenoprotein S, and NLR family CARD domain-containing protein 4 as pivotal molecular targets of the anti-inflammatory effects of rESWT. This is the first study to provide a reference proteomic map for inflammatory tenocytes and rESWT inflammatory tenocytes. Our findings provide crucial insight into the molecular mechanisms underscoring the anti-inflammatory effects of rESWT in tendinopathy.

18.
Micromachines (Basel) ; 13(10)2022 Oct 14.
Article in English | MEDLINE | ID: mdl-36296094

ABSTRACT

In this paper, a 650 V 4H-SiC trench Metal-Oxide-Semiconductor Field-Effect Transistor (MOSFET) with a hetero-junction diode (HJD) and double current spreading layers (CSLs) is proposed and studied based on Sentaurus TCAD simulation. The HJD suppresses the turn-on of the parasitic body diode and improves the performance in the third quadrant. CSLs with different doping concentrations help to lower the on-state resistance as well as the gate-drain capacitance. As a result, the on-state resistance is decreased by 47.82% while the breakdown voltage remains the same and the turn-on and turn-off losses of the proposed structure are reduced by 83.39% and 68.18% respectively, compared to the conventional structure.

19.
Front Plant Sci ; 13: 971927, 2022.
Article in English | MEDLINE | ID: mdl-36092447

ABSTRACT

Breeders agree that leaf senescence is a favorable process for wheat seed yield improvement due to the remobilization of leaf nutrients. However, several studies have suggested that staying green may be an important strategy for further increasing wheat yields. In this study, we performed a comparative transcriptome analysis between wheat cultivars CN17 and CN19 after heading and also measured photosynthetic parameters, chlorophyll (Chl) contents, and antioxidant enzyme activities at various time points after heading. The physiological and biochemical indexes revealed that CN17 exhibited a functionally stay-green phenotype while CN19 did not. We identified a total of 24,585 and 34,410 differential expression genes between genotypes at two time-points and between time-points in two genotypes, respectively, and we also found that 3 (37.5%) genes for leaf senescence, 46 (100%) for photosynthesis - antenna protein, 33 (70.21%) for Chl metabolism and 34 (68%) for antioxidative enzyme activity were upregulated in CN17 compared with CN19 during leaf senescence, which could be regulated by the differential expression of SAG39 (senescence-associated gene 39), while 22 (100%) genes for photosynthesis - antenna proteins, 6 (46.15%) for Chl metabolism and 12 (80%) for antioxidative enzyme activity were upregulated in CN17 compared with CN19 before the onset of leaf senescence. Here, we further clarified the expression profiles of genes associated with a functional stay-green phenotype. This information provides new insight into the mechanism underlying delayed leaf senescence and a new strategy for breeders to improve wheat yields.

20.
Nat Commun ; 13(1): 5700, 2022 09 28.
Article in English | MEDLINE | ID: mdl-36171212

ABSTRACT

Given the complex nature of ulcerative colitis, combination therapy targeting multiple pathogenic genes and pathways of ulcerative colitis may be required. Unfortunately, current therapeutic strategies are usually based on independent chemical compounds or monoclonal antibodies, and the full potential of combination therapy has not yet been realized for the treatment of ulcerative colitis. Here, we develop a synthetic biology strategy that integrates the naturally existing circulating system of small extracellular vesicles with artificial genetic circuits to reprogram the liver of male mice to self-assemble multiple siRNAs into secretory small extracellular vesicles and facilitate in vivo delivery siRNAs through circulating small extracellular vesicles for the combination therapy of mouse models of ulcerative colitis. Particularly, repeated injection of the multi-targeted genetic circuit designed for simultaneous inhibition of TNF-α, B7-1 and integrin α4 rapidly relieves intestinal inflammation and exerts a synergistic therapeutic effect against ulcerative colitis through suppressing the pro-inflammatory cascade in colonic macrophages, inhibiting the costimulatory signal to T cells and blocking T cell homing to sites of inflammation. More importantly, we design an AAV-driven genetic circuit to induce substantial and lasting inhibition of TNF-α, B7-1 and integrin α4 through only a single injection. Overall, this study establishes a feasible combination therapeutic strategy for ulcerative colitis, which may offer an alternative to conventional biological therapies requiring two or more independent compounds or antibodies.


Subject(s)
Colitis, Ulcerative , Animals , Antibodies, Monoclonal/pharmacology , Antibodies, Monoclonal/therapeutic use , Colitis, Ulcerative/drug therapy , Colitis, Ulcerative/therapy , Inflammation/genetics , Integrin alpha4 , Male , Mice , RNA, Small Interfering , Tumor Necrosis Factor-alpha/genetics , Tumor Necrosis Factor-alpha/therapeutic use
SELECTION OF CITATIONS
SEARCH DETAIL