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Herein we unveil a visible-light-driven transition-metal-free 1,3-bromodifluoroallylation of [1.1.1]propellane. This reactivity is harnessed through organophotocatalysis, providing practical synthetic pathways to 1-brominated-3-gem-difluoroallylic bicyclo[1.1.1]pentane derivatives, particularly derived from readily available α-trifluoromethylalkenes and inexpensive KBr salts utilized as precursors for bromine radicals. Mechanistic investigations reveal that bromide anions quench the excited state of the photocatalyst, leading to the formation of bromine radicals, which react in a strain-release radical addition process rather than hydrogen atom abstraction with [1.1.1]propellane.
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With the development of generative model, the cost of facial manipulation and forgery is becoming lower and lower. Fraudulent data has brought numerous hidden threats in politics, privacy, and cybersecurity. Although many methods of face forgery detection focus on the learning of high frequency forgery traces and achieve promising performance, these methods usually learn features in spatial and frequency independently. In order to combine the information of the two domains, a combined spatial and frequency dual stream network is proposed for face forgery detection. Concretely, a cross self-attention (CSA) module is designed to improve frequency feature interaction and fusion at different scales. Moreover, to augment the semantic and contextual information, frequency guided spatial feature extraction module is proposed to extract and reconstruct the spatial information. These two modules deeply mine the forgery traces via a dual-stream collaborative network. Through comprehensive experiments on different datasets, we demonstrate the effectiveness of proposed method for both within and cross datasets.
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Melanocortin-4 receptor (MC4R) functions as a crucial neuroendocrine G protein-coupled receptor (GPCR) in the central nervous system of mammals, displaying agonist-independent constitutive activity that is mainly determined by its N-terminal domain. We previously reported that zebrafish MC4R exhibited a much higher basal cAMP level in comparison to mammalian MC4Rs. However, the functional evolution of constitutive activities in chordate MC4Rs remains to be elucidated. Here we cloned and compared the constitutive activities of MC4Rs from nine vertebrate species and showed that the additive action of the N-terminus with the extracellular region or transmembrane domain exhibited a combined pharmacological effect on the MC4R constitutive activity. In addition, we demonstrated that four residues of F149, Q156, V163, and K164 of the second intracellular loop played a vital role in determining MC4R constitutive activity. This study provided novel insights into functional evolution and identified a key motif essential for constitutive modulation of MC4R signaling.
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Ultraviolet spectroscopy provides unique insights into the structure of matter with applications ranging from fundamental tests to photochemistry in the Earth's atmosphere and astronomical observations from space telescopes1-8. At longer wavelengths, dual-comb spectroscopy, using two interfering laser frequency combs, has become a powerful technique capable of simultaneously providing a broad spectral range and very high resolution9. Here we demonstrate a photon-counting approach that can extend the unique advantages of this method into ultraviolet regions where nonlinear frequency conversion tends to be very inefficient. Our spectrometer, based on two frequency combs with slightly different repetition frequencies, provides a wide-span, high-resolution frequency calibration within the accuracy of an atomic clock, and overall consistency of the spectra. We demonstrate a signal-to-noise ratio at the quantum limit and an optimal use of the measurement time, provided by the multiplexed recording of all spectral data on a single photon-counter10. Our initial experiments are performed in the near-ultraviolet and in the visible spectral ranges with alkali-atom vapour, with a power per comb line as low as a femtowatt. This crucial step towards precision broadband spectroscopy at short wavelengths paves the way for extreme-ultraviolet dual-comb spectroscopy, and, more generally, opens up a new realm of applications for photon-level diagnostics, as encountered, for example, when driving single atoms or molecules.
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Objective To investigate the effects of collagen peptides on the immune function of mice under the condition of X-ray irradiation combined with simulated weightlessness. Methods Mice were randomly divided into control group, modelling group and collagen peptide group. Mice in collagen peptide group were intraperitoneally injected with collagen peptide (600 mg/kg) once a day from the first day of the experiment, while mice in the other two groups were intraperitoneally injected with normal saline. On the fourth day of the experiment, mice in the modelling group and collagen peptide group were simultaneously exposed to X-ray irradiation (2 Gy) and hindlimb-unloaded simulated weightlessness by tail-suspension. On the 10th day of the experiment, the mice were terminated by cervical dislocation. Automated hematology analyzer was used to detect Leukocyte classification of peripheral blood. Splenic lymphocyte subsets, cell cycle and apoptosis of bone marrow cells were analyzed by flow cytometry. The expressions of 19 plasma cytokines were tested with liquid suspension chips. Results Compared with the control group, the modelling group had a significant reduction in the total number of white blood cells and lymphocytes in the peripheral blood, the total number of splenocyte and the number of T cells, CD4+ and CD8+ T cells, B cells, and natural killer (NK) cells in the spleen, an decrease in 18 cytokines in the plasma, and an increase in myelocyte apoptosis in mice of the modelling group. Compared with the modelling group, most immunological parameters had improved in the mice of the collagen peptide group except some cytokines. Conclusion Collagen peptides can effectively improve the immune function of mice under the condition of X-ray irradiation combined with simulated weightlessness.
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Linfocitos T CD8-positivos , Ingravidez , Animales , Ratones , Rayos X , Citocinas/metabolismo , Células Asesinas Naturales , Colágeno , InmunidadRESUMEN
We propose an optical frequency domain reflectometry (OFDR) with the assistance of a dual electro-optic frequency comb (EOFC), which is intended to improve the system spatial resolution. As the spatial resolution of an OFDR system is inversely proportional to the frequency sweep range, the EOFC acts as a multi-frequency light source for collecting Rayleigh backscattering signals, which are combined to extend the effective frequency sweep range. By utilizing this technique, we have successfully expanded the experimental frequency sweep range to hundreds of gigahertz, achieving a sub-millimeter spatial resolution.
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We undertook this study to investigate the effects and mechanisms of dexamethasone liposome (Dex-Lips) on alleviating destabilization of the medial meniscus (DMM)-induced osteoarthritis (OA) in miR-204/-211-deficient mice. Dex-Lips was prepared by the thin-film hydration method. The characterization of Dex-Lips was identified by the mean size, zeta potential, drug loading, and encapsulation efficiencies. Experimental OA was established by DMM surgery in miR-204/-211-deficient mice, and then Dex-Lips was treated once a week for 3 months. Von Frey filaments was used to perform the pain test. The inflammation level was evaluated with quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Polarization of macrophages was evaluated by immunofluorescent staining. X-ray, micro-CT scanning, and histological observations were conducted in vivo on DMM mice to describe the OA phenotype. We found that miR-204/-211-deficient mice displayed more severe OA symptoms than WT mice after DMM surgery. Dex-Lips ameliorated DMM-induced OA phenotype and suppressed pain and inflammatory cytokine expressions. Dex-Lips could attenuate pain by regulating PGE2. Dex-Lips treatments reduced the expression of TNF-α, IL-1ß, and IL-6 in DRG. Moreover, Dex-Lips could reduce inflammation in the cartilage and serum. Additionally, Dex-Lips repolarize synovial macrophages to M2 phenotypes in miR-204/-211-deficient mice. In conclusion, Dex-Lips inhibited the inflammatory response and alleviated the pain symptoms of OA by affecting the polarization of macrophages.
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MicroARNs , Osteoartritis , Ratones , Animales , Liposomas/uso terapéutico , Osteoartritis/metabolismo , Inflamación , Dolor , Dexametasona/farmacología , Dexametasona/uso terapéutico , Macrófagos/metabolismo , MicroARNs/genética , MicroARNs/uso terapéutico , Modelos Animales de EnfermedadRESUMEN
Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterized by synovial hyperplasia. Mir204 and Mir211 are homologous miRNAs with the same gene targeting spectrum. It is known that Mir204/211 play an important role in protecting osteoarthritis development; however, the roles of Mir204/211 in RA disease have not been determined. In the present study, we investigated the effects and molecular mechanisms of Mir204/211 on synovial inflammation and hyperproliferation in RA. The effects of Mir204/211 on the inflammation and abnormal proliferation in primary fibroblast-like synoviocytes (FLSs) were examined by Mir204/211 gain-of-function and loss-of-function approaches in vitro and in vivo. We identified the structure-specific recognition protein 1 (Ssrp1) as a downstream target gene of Mir204/211 based on the bioinformatics analysis. We overexpressed Ssrp1and Mir204/211 in FLS to determine the relationship between Ssrp1 and Mir204/211 and their effects on synovial hyperplasia. We created a collagen-induced arthritis (CIA) model in wild-type as well as Mir204/211 double knockout (dKO) mice to induce RA phenotype and administered adeno-associated virus (AAV)-mediated Ssrp1-shRNA (AAV-shSsrp1) by intra-articular injection into Mir204/211 dKO mice. We found that Mir204/211 attenuated excessive cell proliferation and synovial inflammation in RA. Ssrp1 was the downstream target gene of Mir204/211. Mir204/211 affected synovial proliferation and decelerated RA progression by targeting Ssrp1. CIA mice with Mir204/211 deficiency displayed enhanced synovial hyperplasia and inflammation. RA phenotypes observed in Mir204/211 deficient mice were significantly ameliorated by intra-articular delivery of AAV-shSsrp1, confirming the involvement of Mir204/211-Ssrp1signaling during RA development. In this study, we demonstrated that Mir204/211 antagonize synovial hyperplasia and inflammation in RA by regulation of Ssrp1. Mir204/211 may serve as novel agents to treat RA disease.
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Artritis Experimental , Artritis Reumatoide , Ratones , Animales , Hiperplasia/metabolismo , Células Cultivadas , Artritis Reumatoide/genética , Artritis Reumatoide/metabolismo , Artritis Experimental/genética , Artritis Experimental/metabolismo , Proliferación Celular , Fibroblastos/metabolismo , Inflamación/patologíaRESUMEN
We demonstrate bandwidth measurement and high-speed data transmission of meter-scale connectorized ultra-flexible multimode waveguide links with a maximum length of 180â cm. The pulses propagating through the waveguides broadened linearly with the increase of the length from 20â cm to 240â cm and the estimated mode delay from the pulse broadening was 0.093 ps/cm. The corresponding waveguide bandwidth decreased inversely with the increase of waveguide length, leading to a bandwidth-length product of 42â GHz·m. Degradation in bandwidth due to the introduction of bending or twisting was small when the samples were bent with a bending radius as small as 1â mm for 3 turns or twisted for 4 full turns, respectively. Error-free transmission of 30 Gb/s non-return-to-zero (NRZ) signal was achieved with a record link length up to 140â cm to the best of our knowledge. Our results show that the demonstrated flexible waveguides have both excellent optical and mechanical properties and are ideal for high-speed optical interconnects application especially those have a strict requirement on flexibility.
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Objective: This prospective study is aimed at observing the number of nasal itching and sneezing in rats from the macroscopic level and examine the pathological changes of nasal mucosa, Th1 and Th2-related cytokines, and Treg/Th17 by vitamin D3 administration from the microscopic level, in order to explore the role of vitamin D in allergic rhinitis and to provide theoretical guidance for prevention and treatment. Results: There were significant differences in nasal itching and sneezing between the administration groups and the positive groups. Meanwhile, the level of Th1 and Treg in the administration groups increased, while the level of Th2 and Th17 decreased, indicating that the balance of Th1/Th2 was corrected. Our study revealed that vitamin D3 has preventive and therapeutic effects on allergic rhinitis, which provides theoretical guidance for practical application.
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Rinitis Alérgica , Linfocitos T Reguladores , Animales , Colecalciferol/farmacología , Colecalciferol/uso terapéutico , Citocinas/uso terapéutico , Modelos Animales de Enfermedad , Estudios Prospectivos , Prurito , Ratas , Rinitis Alérgica/tratamiento farmacológico , Rinitis Alérgica/prevención & control , Estornudo , Vitamina D/farmacología , Vitamina D/uso terapéuticoRESUMEN
The properties of nutraceutical-loaded biopolymer nanoparticles fabricated by antisolvent co-precipitation (ASCP) and precipitation (ASP) were compared. Curcumin-loaded zein-tea saponin nanoparticles were fabricated using both methods and then their structural and physicochemical properties were characterized. The diameter of the nanoparticles prepared by ASCP were smaller (120-130 nm) than those prepared by ASP (140-160 nm). The encapsulation efficiency of the ASCP-nanoparticles (80.0%) was higher than the ASP-ones (71.0%) at a zein-to-curcumin mass ratio of 3:1, which was also higher than previous studies. The storage and light stability of curcumin was higher in zein-saponin nanoparticles than in zein nanoparticles. All nanoparticles had good water dispersibility after freeze-drying and rehydration. This study shows that nanoparticles produced by antisolvent co-precipitation have superior properties to those produced by antisolvent precipitation. The co-precipitation method leads to a higher encapsulation efficiency, smaller particle size, and greater storage stability, which may be advantageous for some applications.
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Curcumina , Nanopartículas , Saponinas , Zeína , Curcumina/química , Nanopartículas/química , Tamaño de la Partícula , Té , Zeína/químicaRESUMEN
There is much uncertainty about how climate warming will impact greenhouse gases (GHG) budget in dry environments due to the lack of available data for desert biocrust soil. We implemented a 2.5-year field measurement of CO2, CH4 and N2O effluxes in cyanobacteria-dominated, moss-dominated and mixed (cyanobacteria, moss and lichen) biocrust soils using open-top-chambers to simulate climate warming (1.2 °C on average). Desert biocrust soils generally acted as a weak sink of atmospheric CH4 and N2O. Although warming effects on daily CO2, CH4, and N2O effluxes varied depending on sampling date and biocrust soil, there was no significant difference in daily, monthly and seasonal average CO2, CH4 and N2O effluxes between warming and control in most cases for three biocrust soils. However, warming caused a marginal (p = 0.06) decrease (14.2%) in annual accumulative CO2 efflux in moss-dominated biocrust soil due to the drought effects caused by warming indirectly and OTC sheltering of precipitation directly, while there was no significant difference between warming and control for cyanobacteria-dominated and mixed biocrust soils, implying a neutral response of GHG effluxes to climate warming. These results suggest that the GHG budget in arid desert biocrust soil would not be significantly changed in the warmer future when the direct negative effects of drought on CO2 effluxes were excluded. Therefore, a marginal decrease of accumulative CO2 effluxes in response to warming coupled with drought for moss-dominated biocrust soil might offer a weak negative feedback to warming and drier climate change pattern.
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Briófitas , Gases de Efecto Invernadero , Dióxido de Carbono/análisis , Clima Desértico , Gases de Efecto Invernadero/análisis , Metano/análisis , Óxido Nitroso/análisis , SueloRESUMEN
BACKGROUND: Early diagnosis and continuous monitoring are the key to emergency treatment and intensive care of patients with acute ischemic stroke (AIS). Nevertheless, there has not been a fully accepted method targeting continuous assessment of AIS in clinical. METHODS: Near-field coupling (NFC) sensing can obtain the conductivity related to the volume of intracranial components with advantages of non-invasiveness, strong penetrability and real-time monitoring. In this work, we built a multi-parameter monitoring system that is able to measure changes of phase and amplitude in the process of electromagnetic wave (EW) reflection and transmission. For investigating its feasibility in AIS detection, 16 rabbits were chosen to establish AIS models by bilateral common carotid artery ligation and then were enrolled for monitoring experiments. RESULTS: During the 6 h after AIS, the reflection amplitude (RA) shows a decline trend with a range of 0.69 dB and reflection phase (RP) has an increased variation of 6.48° . Meanwhile, transmission amplitude (TA) and transmission phase (TP) decrease 2.14 dB and 24.29° , respectively. The statistical analysis illustrates that before ligation, 3 h after ligation and 6 h after ligation can be effectively distinguished by the four parameters individually. When all those parameters are regarded as recognition features in back propagation (BP) network, the classification accuracy of the three different periods reaches almost 100%. CONCLUSION: These results prove the feasibility of multi-parameter NFC sensing to assess AIS, which is promised to become an outstanding point-of-care testing method in the future.
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Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Animales , Arterias Carótidas , Cuidados Críticos , Humanos , Monitoreo Fisiológico , Conejos , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/terapiaRESUMEN
Multi-wavelength diffraction imaging is a lensless, high-resolution imaging technology. To avoid multiple exposures and enable high-speed data collection, here an innovative setup for the single-exposure multi-wavelength diffraction imaging based on a blazed grating is proposed. Since the blazed angle varies with the wavelength, the diffraction patterns for the individual wavelengths can be separated from each other and recorded in a single measurement at one time. A method of high-precision position alignment between different wavelength patterns is proposed in our system to achieve good image quality and high resolution. Experiments on a phase-only USAF resolution target and biological samples were carried out to verify the effectiveness of our proposed method. This proposed setup has such advantages as a simpler structure, fast recording, and algorithm robustness.
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Diagnóstico por ImagenRESUMEN
BACKGROUND: This study aims to explore whether Fufang Shatai Heji (STHJ), as a mixture collected by a decoction of a variety of Chinese herbal medicines for immune system diseases, can improve the cartilage destruction of rheumatoid arthritis (RA). METHODS: The therapeutic effects of STHJ were studied using collagen induced arthritis (CIA) mice. The improvement effect of STHJ on synovitis and cartilage damage caused by arthritis was studied by joint pathological analysis. The inhibitory effect of STHJ on related degradation enzymes in cartilage was studied by immunohistochemistry and real-time polymerase chain reaction (PCR). The specific targets of STHJ were predicted by molecular docking. RESULTS: After successfully inducing CIA, the paws of the mice showed significant swelling, and athological analysis of the ankle and knee joints also showed significant cartilage destruction and synovial hyperplasia. However, synovial hyperplasia and cartilage destruction were markedly alleviated after administration of STHJ. And after STHJ treatment, the expression of ADAMTS-4, ADAMTS-5, MMP-9 and MMP-13, in the cartilage layer of CIA mice was significantly inhibited. Through molecular docking assays, we proved that acteoside in STHJ could directly bind to the Glu111, Phe110 residues in MMP-9 and glycyrrhizic acid in STHJ bind to the Glu382, Asn433 residues in MMP-13. CONCLUSIONS: Our results suggested that STHJ may alleviate synovial hyperplasia and cartilage destruction in CIA mice and protect cartilage by inhibiting the expression of MMP-9 and other enzymes.
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Artritis Experimental , Medicamentos Herbarios Chinos , Animales , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/patología , Cartílago/metabolismo , Cartílago/patología , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Metaloproteinasas de la Matriz/metabolismo , Metaloproteinasas de la Matriz/farmacología , Metaloproteinasas de la Matriz/uso terapéutico , Ratones , Simulación del Acoplamiento MolecularRESUMEN
Pseudo-inverse learners (PILs) are a kind of feedforward neural network trained with the pseudoinverse learning algorithm, which can be traced back to 1995 originally. PIL is an approach for nongradient descent learning, and its main advantage is the lower computational cost and fast learning procedure, which is especially relevant in the edge computing research field. However, PIL is mostly applied to a deterministic learning problem, while in the real world, the greatest case that is of concern is the uncertainty learning problem. In this work, under the framework of the synergetic learning system (SLS), we introduce an approximated synergetic learning scheme, which can transform uncertainty learning into deterministic learning. We call this new learning framework the Bayesian PIL, and the advantages are also demonstrated in this work.
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Algoritmos , Redes Neurales de la Computación , Teorema de Bayes , IncertidumbreRESUMEN
We demonstrate direct bandwidth measurement of 11-cm-long multimode polymer waveguides based on an optical sampling technique for the first time, to our knowledge. The pulse shape can be recovered after transmission due to the advantages such as high bandwidth and high refresh rate of optical sampling technology. A reduction in averaged bandwidth (bandwidth-length product) from 241 GHz (27 GHz·m) to 180 GHz (20 GHz·m) of straight waveguides is observed when using mode scramblers to fully stimulate the higher-order modes. The effects such as bending and crossing structure of the waveguides on the bandwidth are also investigated. The proposed method is effective for measuring the bandwidth and dispersion of meter- and centimeter-long waveguides, fibers, and optical devices.
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We propose and experimentally demonstrate a novel method for photonic-assisted microwave frequency measurement based on whispering-gallery mode (WGM) barcode, which is a dense spectrum generated by a micro-resonator that supports a large number of optical modes. The measurement relies on the relation between the microwave frequency and its unique barcode. The proposed system has the advantages of wide bandwidth, high accuracy, and multiple-frequency measurement capability. Microwave frequency measurement from 1 to 20 GHz is experimentally demonstrated with a measurement error of 40 kHz. For multi-tone signals, the frequency resolution is demonstrated to be less than 20 MHz. A dynamic multi-tone microwave signal consists of a 16-20 GHz linear frequency-modulated (LFM) signal, and a 10 GHz signal is measured to show the capability of multiple-frequency measurement. The system stability is also evaluated, and a self-reference method is proposed to maintain a long-term high-accuracy measurement.
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In this Letter, we propose a real-time machine learning scheme of a tracking optical intensity-modulation and direct-detection (IMDD) system's conditional distribution using linear optical sampling and inline Gaussian mixer modeling (GMM) programming. End-to-end conditional distribution tracking enables an adaptive decoding of optical IMDD signals, with robustness to the bias point shift of the optical intensity modulator. Experimental demonstration is conducted over a 20-Gbits/s optical pulse amplitude modulation-4 (PAM-4) modulation system. Optical PAM-4 signals are optically down-sampled by short pulses to 250 Msa/s. Then, statistical characters of signal distribution can be estimated using inline GMM processing. Due to the real-time learned distribution, intelligent decoding of received signals exhibits a perfect adaptation to the changing bias point of a Mach-Zendner intensity modulator, enhancing the communication reliability with bit error rate (BER) below 3.8â 10-3. In addition, the proposed scheme also provides the possibility of practical implementation to other machine learning signal decoding methods.
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BACKGROUND: We utilized the destabilization of medial meniscus (DMM)-induced mice to illustrate the osteoarthritis (OA) suppressing and pain-relieving effects of a novel prolonged-release intra-articular (IA)-dexamethasone-loaded thermo-sensitive hydrogel (DLTH). METHODS: The effects of temperature and pH on DLTH formation and in vitro DLTH release profile were assessed. C57BL/6J mice were randomly divided into three groups: Ctrl group, Model group and DLTH group. The DLTH group received joint injections of 10 µL DLTH (1 mg/kg) into the right knee once a week from week 2 to week 11. We performed micro-computed tomography (Micro-CT) and histological analyses of safranin O-fast green, hematoxylin and eosin, and tartrate-resistant acid phosphatase in knee joints. We also carried out immunohistochemical (IHC) staining for matrix metalloproteinase-9 (MMP-9), MMP-13, and a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5) in cartilage and Ki-67 in synovia. Pain behavioral testing was carried out in all mice. The serum content of prostaglandin E2 (PGE2) and real-time polymerase chain reaction (PCR) of inflammatory cytokines and pain-related factors in dorsal root ganglia (DRGs) were evaluated. RESULTS: It took 20 minutes to form DLTH at pH 7.0 and 37 °C. The cumulative release profiles of dexamethasone (Dex) from DLTH at 37 °C revealed a rapid release in the first 24 h and a sustained slow release for 7 days. In vivo study illustrated that DLTH attenuated OA bone destruction and ameliorated synovitis and progression of OA in DMM-induced mice. The chondroprotective effects of DLTH were mediated by decreased expressions of MMP-9, MMP-13, and ADAMTS-5. The results showed that IA-DLTH exerted pain-relieving effects in OA mice. Upregulation of nociceptive response time (NRT) and downregulations of serum PGE2, inflammatory factors, and pain-related mediators in DRGs of mice in the DLTH group were recorded. CONCLUSIONS: Data presented in this study elucidated that DLTH exhibited a long and lasting Dex release and it is a potential sustainable drug delivery system (DDS) to treat OA locally. IA-DLTH injection exerted chondroprotective and pain-relieving effects in DMM-induced arthritis. The involvement of MMP-9, MMP-13, ADAMTS-5, and inflammatory and pain-related factors, may account for the suppression of OA progression and pain.