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1.
J Med Chem ; 67(17): 15476-15493, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39190821

ABSTRACT

Hepatobiliary-specific magnetic resonance imaging contrast agents (MRI CAs) play a crucial role in the early diagnosis of hepatocellular carcinoma (HCC). However, only two acyclic CAs, Gd-BOPTA and Gd-EOB-DTPA, exhibit unfavorable kinetic inertness. Our study focused on the development of superior stable innovative macrocyclic CAs. By introducing a lipophilic benzyloxy group (OBn) into the H4DOTA ring (Gd-L1), we achieved significant enhancement in kinetic inertness. In vivo experiments in mice demonstrated that 40% of the dosage was distributed to the liver at 5 min, providing sustained hepatic enhancement for over 35 min. We also developed an MPO-responsive MRI CA (Gd-L3), which can participate in the "peroxidase cycle" as the substrate, generating oligomers with a 3.8-fold increase in relaxivity, and selectively enhance the lesion in an acute gout mouse model. Overall, our work represents a significant advancement in the field of hepatic and inflammatory MRI, offering promising avenues for early diagnosis and improved imaging outcomes.


Subject(s)
Contrast Media , Liver , Magnetic Resonance Imaging , Organometallic Compounds , Contrast Media/chemistry , Contrast Media/chemical synthesis , Animals , Magnetic Resonance Imaging/methods , Mice , Organometallic Compounds/chemistry , Organometallic Compounds/chemical synthesis , Liver/diagnostic imaging , Liver/metabolism , Drug Design , Humans , Inflammation/diagnostic imaging , Male , Liver Neoplasms/diagnostic imaging , Carcinoma, Hepatocellular/diagnostic imaging , Heterocyclic Compounds
2.
Acta Pharmacol Sin ; 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39160244

ABSTRACT

Pulmonary fibrosis (PF) is a chronic, progressive and irreversible interstitial lung disease characterized by unremitting pulmonary myofibroblasts activation, extracellular matrix (ECM) deposition and inflammatory recruitment. PF has no curable medication yet. In this study we investigated the molecular pathogenesis and potential therapeutic targets of PF and discovered drug lead compounds for PF therapy. A murine PF model was established in mice by intratracheal instillation of bleomycin (BLM, 5 mg/kg). We showed that the protein level of pulmonary protein phosphatase magnesium-dependent 1A (PPM1A, also known as PP2Cα) was significantly downregulated in PF patients and BLM-induced PF mice. We demonstrated that TRIM47 promoted ubiquitination and decreased PPM1A protein in PF progression. By screening the lab in-house compound library, we discovered otilonium bromide (OB, clinically used for treating irritable bowel syndrome) as a PPM1A enzymatic activator with an EC50 value of 4.23 µM. Treatment with OB (2.5, 5 mg·kg-1·d-1, i.p., for 20 days) significantly ameliorated PF-like pathology in mice. We constructed PF mice with PPM1A-specific knockdown in the lung tissues, and determined that by targeting PPM1A, OB treatment suppressed ECM deposition through TGF-ß/SMAD3 pathway in fibroblasts, repressed inflammatory responses through NF-κB/NLRP3 pathway in alveolar epithelial cells, and blunted the crosstalk between inflammation in alveolar epithelial cells and ECM deposition in fibroblasts. Together, our results demonstrate that pulmonary PPM1A activation is a promising therapeutic strategy for PF and highlighted the potential of OB in the treatment of the disease.

3.
Bioinspir Biomim ; 19(5)2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39025108

ABSTRACT

The reef ecosystem plays a vital role as a habitat for fish species with limited swimming capabilities, serving not only as a sanctuary and food source but also influencing their behavioral tendencies. Understanding the intricate mechanism through which fish adeptly navigate the moving targets within reef environments within complex water flow, all while evading obstacles and maintaining stable postures, has remained a challenging and prominent subject in the realms of fish behavior, ecology, and biomimetics alike. An integrated simulation framework is used to investigate fish predation problems within intricate environments, combining deep reinforcement learning algorithms (DRL) with high-precision fluid-structure interaction numerical methods-immersed boundary lattice Boltzmann method (lB-LBM). The Soft Actor-Critic (SAC) algorithm is used to improve the intelligent fish's capacity for random exploration, tackling the multi-objective sparse reward challenge inherent in real-world scenarios. Additionally, a reward shaping method tailored to its action purposes has been developed, capable of capturing outcomes and trend characteristics effectively. The convergence and robustness advantages of the method elucidated in this paper are showcased through two case studies: one addressing fish capturing randomly moving targets in hydrostatic flow field, and the other focusing on fish counter-current foraging in reef environments to capture drifting food. A comprehensive analysis was conducted of the influence and significance of various reward types on the decision-making processes of intelligent fish within intricate environments.


Subject(s)
Coral Reefs , Fishes , Predatory Behavior , Animals , Predatory Behavior/physiology , Fishes/physiology , Algorithms , Deep Learning , Computer Simulation , Reinforcement, Psychology , Avoidance Learning/physiology , Swimming/physiology , Ecosystem , Biomimetics/methods , Models, Biological
4.
Nature ; 632(8024): 267-272, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38987606

ABSTRACT

The fermionic Hubbard model (FHM)1 describes a wide range of physical phenomena resulting from strong electron-electron correlations, including conjectured mechanisms for unconventional superconductivity. Resolving its low-temperature physics is, however, challenging theoretically or numerically. Ultracold fermions in optical lattices2,3 provide a clean and well-controlled platform offering a path to simulate the FHM. Doping the antiferromagnetic ground state of a FHM simulator at half-filling is expected to yield various exotic phases, including stripe order4, pseudogap5, and d-wave superfluid6, offering valuable insights into high-temperature superconductivity7-9. Although the observation of antiferromagnetic correlations over short10 and extended distances11 has been obtained, the antiferromagnetic phase has yet to be realized as it requires sufficiently low temperatures in a large and uniform quantum simulator. Here we report the observation of the antiferromagnetic phase transition in a three-dimensional fermionic Hubbard system comprising lithium-6 atoms in a uniform optical lattice with approximately 800,000 sites. When the interaction strength, temperature and doping concentration are finely tuned to approach their respective critical values, a sharp increase in the spin structure factor is observed. These observations can be well described by a power-law divergence, with a critical exponent of 1.396 from the Heisenberg universality class12. At half-filling and with optimal interaction strength, the measured spin structure factor reaches 123(8), signifying the establishment of an antiferromagnetic phase. Our results provide opportunities for exploring the low-temperature phase diagram of the FHM.

5.
Anal Chem ; 96(24): 9975-9983, 2024 06 18.
Article in English | MEDLINE | ID: mdl-38830231

ABSTRACT

The emergence of lipid droplets (LDs) has been recognized as cellular markers of ocular surface hyperosmosis, which is recognized as a fundamental mechanism driving dry eye disease (DED), while their dynamics during DED progression and therapy remains unlocked. For this purpose, an LD-specific fluorescent probe P1 is presented in this work that exhibits highly selective and sensitive emission enhancement in response to a decreased ambient polarity (Δf) from 0.209 to 0.021. The hydrophobic nature of P1 enables specific staining of LDs, facilitating visualization of changes in polarity within these cellular structures. Utilizing P1, we observe a decrease in polarity accompanied by an increase in the size and number of LDs in hyperosmotic human corneal epithelial cells (HCECs). Furthermore, interplays between LDs and cellular organelles such as mitochondria and the Golgi apparatus are visualized, suggesting the underlying pathogenesis in DED. Notably, the variations of LDs are observed after the inhibition of ferroptosis or activation of autophagy in hyperosmotic HCECs, implying the great potential of LDs as indicators for the design and efficacy evaluation of DED drugs regarding ferroptosis or autophagy as targets. Finally, LDs are confirmed to be overproduced in corneal tissues from DED mice, and the application of clinical eye drops effectively impedes these changes. This detailed exploration underscores the significant roles of LDs as an indicator for the deep insight into DED advancement and therapy.


Subject(s)
Dry Eye Syndromes , Fluorescent Dyes , Lipid Droplets , Dry Eye Syndromes/metabolism , Dry Eye Syndromes/pathology , Lipid Droplets/metabolism , Lipid Droplets/chemistry , Humans , Animals , Mice , Fluorescent Dyes/chemistry , Autophagy , Fluorescence
6.
J Org Chem ; 89(7): 5049-5059, 2024 Apr 05.
Article in English | MEDLINE | ID: mdl-38491018

ABSTRACT

A green and practical protocol of defluoroborylation of polyfluoroarenes with stable and readily accessible NHC-borane was developed, using 1,2-diphenyldisulfane as a hydrogen atom transfer (HAT) and single electron transfer (SET) reagent precursor under visible-light irradiation, leading to the concise formation of value-added fluorinated organoboron scaffolds. Mechanism studies revealed the method underwent a boryl radical addition reaction with polyfluoroarene, followed by successive single electron transfer pathways and defluorination of the C-F bond to offer the targeted product. This unprecedented platform relies on 1,2-diphenyldisulfane and base without using expensive photocatalysts, highlighting the methodology has promising application value to prepare borylated polyfluoroarene compounds.

7.
IEEE Trans Pattern Anal Mach Intell ; 46(5): 3796-3812, 2024 May.
Article in English | MEDLINE | ID: mdl-38170661

ABSTRACT

Successful point cloud registration relies on accurate correspondences established upon powerful descriptors. However, existing neural descriptors either leverage a rotation-variant backbone whose performance declines under large rotations, or encode local geometry that is less distinctive. To address this issue, we introduce RIGA to learn descriptors that are Rotation-Invariant by design and Globally-Aware. From the Point Pair Features (PPFs) of sparse local regions, rotation-invariant local geometry is encoded into geometric descriptors. Global awareness of 3D structures and geometric context is subsequently incorporated, both in a rotation-invariant fashion. More specifically, 3D structures of the whole frame are first represented by our global PPF signatures, from which structural descriptors are learned to help geometric descriptors sense the 3D world beyond local regions. Geometric context from the whole scene is then globally aggregated into descriptors. Finally, the description of sparse regions is interpolated to dense point descriptors, from which correspondences are extracted for registration. To validate our approach, we conduct extensive experiments on both object- and scene-level data. With large rotations, RIGA surpasses the state-of-the-art methods by a margin of 8 ° in terms of the Relative Rotation Error on ModelNet40 and improves the Feature Matching Recall by at least 5 percentage points on 3DLoMatch.

8.
Adv Mater ; 36(4): e2307218, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37972344

ABSTRACT

Costly data movement in terms of time and energy in traditional von Neumann systems is exacerbated by emerging information technologies related to artificial intelligence. In-memory computing (IMC) architecture aims to address this problem. Although the IMC hardware prototype represented by a memristor is developed rapidly and performs well, the sneak path issue is a critical and unavoidable challenge prevalent in large-scale and high-density crossbar arrays, particularly in three-dimensional (3D) integration. As a perfect solution to the sneak-path issue, a self-rectifying memristor (SRM) is proposed for 3D integration because of its superior integration density. To date, SRMs have performed well in terms of power consumption (aJ level) and scalability (>102  Mbit). Moreover, SRM-configured 3D integration is considered an ideal hardware platform for 3D IMC. This review focuses on the progress in SRMs and their applications in 3D memory, IMC, neuromorphic computing, and hardware security. The advantages, disadvantages, and optimization strategies of SRMs in diverse application scenarios are illustrated. Challenges posed by physical mechanisms, fabrication processes, and peripheral circuits, as well as potential solutions at the device and system levels, are also discussed.

9.
Gels ; 9(10)2023 Oct 06.
Article in English | MEDLINE | ID: mdl-37888377

ABSTRACT

Fractured-vuggy reservoirs are mainly composed of three types: underground rivers, vugs, and fractured-vuggy structures. Based on the similarity criterion, a 3D model can truly reflect the characteristics of the multi-scale space of a fractured-vuggy reservoir, and it can reflect fluid flow laws in the formation. Water flooding, gas flooding, and gel foam flooding were carried out in the model sequentially. Based on gas flooding, the enhanced recovery ratio of gel foam flooding in the underground river was approximately 12%. By changing the injection rate, the average recovery ratio of nitrogen flooding was 6.84% higher than that of other injection rates at 5 mL/min, and that of gel foam flooding was 1.88% higher than that of other injection rates at 5 mL/min. The experimental results showed that the gel foam induced four oil displacement mechanisms, which selectively plugged high-permeability channels, controlled the mobility ratio, reduced oil-water interfacial tension, and changed the wettability of rock surfaces. With different injection-production methods, gel foam flooding can spread across two underground river channels. Two cases of nitrogen flooding affected one underground river channel and two underground river channels. By adjusting the injection rate, it was found that after nitrogen flooding, there were mainly four types of residual oil, and gel foam flooding mainly yielded three types of remaining oil. This study verified the influencing factors of extracting residual oil from an underground river and provides theoretical support for the subsequent application of gel foam flooding in underground rivers.

10.
Bioorg Chem ; 141: 106905, 2023 12.
Article in English | MEDLINE | ID: mdl-37832222

ABSTRACT

As an important member of dyes, small-molecule fluorescent dyes show indispensable value in biomedical fields. Although various molecular dyes have been developed, full-color dyes covering blue to red region derived from a single chromophore are still in urgent demand. In this work, a series of dyes based on C2-alkenyl indole skeleton were synthesized, namely AI dyes, and their photophysical properties, cytotoxicity, and imaging capacity were verified to be satisfactory. Particularly, the maximal emission wavelengths of these dyes could cover a wide range from visible to NIR light with large Stokes shifts. Besides, the optical and structural discrepancies between the C2- and C3- alkenyl AI dyes were discussed in detail, and the theoretical calculations were conducted to provide insights on such structure-activity relationship. Finally, as a proof-of-concept, a fluorescent probe AI-Py-B capable of imaging endogenous ONOO- was presented, demonstrating the bioimaging potentials of these alkenyl indole dyes. This work is anticipated to open up new possibilities for developing dye engineering and bio-applications of natural indole framework.


Subject(s)
Fluorescent Dyes , Indoles , Optical Imaging/methods , Radiopharmaceuticals
11.
ACS Sens ; 8(10): 3882-3891, 2023 10 27.
Article in English | MEDLINE | ID: mdl-37737091

ABSTRACT

Diabetic cataract (DC) surgery carries risks such as slow wound healing, macular edema, and progression of retinopathy and is faced with a deficiency of effective drugs. In this context, we proposed a protocol to evaluate the drug's efficacy using lipid droplets (LDs) as the marker. For this purpose, a fluorescent probe PTZ-LD for LDs detection is developed based on the phenothiazine unit. The probe displays polarity-dependent emission variations, i.e., lower polarity leading to stronger intensity. Especially, the probe exhibits photostability superior to that of Nile Red, a commercial LDs staining dye. Using the probe, the formation of LDs in DC-modeled human lens epithelial (HLE) cells is validated, and the interplay of LDs-LDs and LDs-others are investigated. Unexpectedly, lipid transfer between LDs is visualized. Moreover, the therapeutic efficacy of various drugs in DC-modeled HLE cells is assessed. Ultimately, more LDs were found in lens epithelial tissues from DC patients than in cataract tissues for the first time. We anticipate that this work can attract more attention to the important roles of LDs during DC progression.


Subject(s)
Cataract , Diabetes Mellitus , Humans , Lipid Droplets , HeLa Cells , Epithelial Cells , Optical Imaging
12.
J Am Chem Soc ; 145(6): 3577-3587, 2023 Feb 15.
Article in English | MEDLINE | ID: mdl-36744315

ABSTRACT

Aromatic polycyclic systems have been extensively utilized as structural subunits for the preparation of various functional molecules. Currently, aromatics-based polycyclic systems are predominantly generated from the extension of two-dimensional (2D) aromatic rings. In contrast, polycyclic compounds based on the extension of three-dimensional (3D) aromatics such as boron clusters are less studied. Here, we report three types of boron cluster-cored tricyclic molecular systems, which are constructed from a 2D aromatic ring, a 3D aromatic nido-carborane, and an alkyne. These new tricyclic compounds can be facilely accessed by Pd-catalyzed B-H activation and the subsequent cascade heteroannulation of carborane and pyridine with an alkyne in an isolated yield of up to 85% under mild conditions without any additives. Computational results indicate that the newly generated ring from the fusion of the 3D carborane, the 2D pyridyl ring, and an alkyne is non-aromatic. However, such fusion not only leads to a 1H chemical shift considerably downfield shifted owing to the strong diatropic ring current of the embedded carborane but also devotes to new/improved physicochemical properties including increased thermal stability, the emergence of a new absorption band, and a largely red-shifted emission band and enhanced emission efficiency. Besides, a number of bright, color-tunable solid emitters spanning over all visible light are obtained with absolute luminescence efficiency of up to 61%, in contrast to aggregation-caused emission quenching of, e.g., Rhodamine B containing a 2D-aromatics-fused structure. This work demonstrates that the new hybrid conjugated tricyclic systems might be promising structural scaffolds for the construction of functional molecules.

13.
Front Chem ; 11: 1126309, 2023.
Article in English | MEDLINE | ID: mdl-36778034

ABSTRACT

Hydrogen sulfide (H2S), as an important endogenous signaling molecule, plays a vital role in many physiological processes. The abnormal behaviors of hydrogen sulfide in organisms may lead to various pathophysiological processes. Monitoring the changes in hydrogen sulfide is helpful for pre-warning and treating these pathophysiological processes. Fluorescence imaging techniques can be used to observe changes in the concentration of analytes in organisms in real-time. Therefore, employing fluorescent probes imaging to investigate the behaviors of hydrogen sulfide in pathophysiological processes is vital. This paper reviews the design strategy and sensing mechanisms of hydrogen sulfide-based fluorescent probes, focusing on imaging applications in various pathophysiological processes, including neurodegenerative diseases, inflammation, apoptosis, oxidative stress, organ injury, and diabetes. This review not only demonstrates the specific value of hydrogen sulfide fluorescent probes in preclinical studies but also illuminates the potential application in clinical diagnostics.

14.
Animals (Basel) ; 12(22)2022 Nov 20.
Article in English | MEDLINE | ID: mdl-36428445

ABSTRACT

The present study investigated the effects of dietary riboflavin on growth performance, body composition and anti-oxidative capacity of coho salmon (Oncorhynchus kisutch) post-smolts. Seven experimental diets were formulated with graded riboflavin levels of 0.00, 3.96, 8.07, 16.11, 31.81, 63.67 and 126.69 mg/kg, respectively. Each diet was fed to triplicate groups of 10 fish with an individually initial mean body weight of 186.22 ± 0.41 g in 21 cages (water volume, 1000-L/cage) and fed three times daily (7:30, 12:30 and 17:30) to apparent satiation for 12 weeks. Fish fed a diet with 31.81 mg/kg riboflavin had the highest specific growth rate (SGR), which was significantly higher than fish-fed diets with 0.00, 3.96, 8.07 and 126.69 mg/kg riboflavin (p < 0.05). Feed conversion ratio showed an inverse trend with SGR. No significant differences were observed in condition factor, hepatosomatic index, viscerosomatic index, muscle moisture, crude protein and ash contents among dietary groups. Muscle lipid had the highest content in the 31.81 mg/kg group and was significantly higher (p < 0.05) than those in the 0.00, 3.96 and 8.07 mg/kg groups. The alanine aminotransferase, aspartate aminotransferase and malondialdehyde contents in the liver and serum of fish were significantly decreased with the increase in dietary riboflavin level up to 31.81 mg/kg, and then increased as dietary riboflavin level further increased. An inverse trend was observed for total superoxide dismutase and catalase activities. Serum total cholesterol and triglyceride levels were significantly decreased with the dietary of riboflavin levels up to 31.81 and 63.67 mg/kg, respectively. The cubic curve regression analysis based on SGR indicated that the optimum dietary riboflavin level was estimated to be 35.26 mg/kg for coho salmon post-smolts.

15.
Chem Sci ; 13(37): 11074-11082, 2022 Sep 28.
Article in English | MEDLINE | ID: mdl-36320483

ABSTRACT

The efficient transformation of nitroaromatics to functional molecules such as N-heterocycles has been an attractive and significant topic in synthesis chemistry. Herein, a photoexcited nitro-induced strategy for switchable annulations of 2-nitroarylethanols was developed to construct N-heterocycles including indoles, N-hydroxyl oxindoles and N-H oxindoles. The metal- and photocatalyst-free reaction proceeds through intramolecular redox C-N coupling of branched hydroxyalkyl and nitro units, which is initiated by a double hydrogen atom abstraction (d-HAA) process. The key to the switchable reaction outcomes is the mediation of a diboron reagent by its favorable oxy-transfer reactivity to in situ generated nitroso species. The utility of this protocol was well demonstrated by broad substrate scope, excellent yields, functional group tolerance and wide applications. Finally, detailed mechanistic studies were performed, and kinetic isotope effect (KIE) experiments indicate that the homolysis of the C-H bond is involved in the rate-determining step.

16.
Phys Rev E ; 106(3-1): 034131, 2022 Sep.
Article in English | MEDLINE | ID: mdl-36266910

ABSTRACT

The Mpemba effect is the phenomenon in which the system with high initial temperature cools faster than the system with low initial temperature when all other conditions are the same. A theoretical model of the Mpemba effect through the canonical first-order phase transition is proposed in this paper, which shows that in the cooling processes, the path of the first-order phase transition of the system with the high initial temperature does not pass through any metastable state, while the path of the first-order phase transition of the system with the low initial temperature passes through a metastable state, which leads to the occurrence of the Mpemba effect. Then an example of the theoretical model is given in the Blume-Emery-Griffiths model. The Monte Carlo algorithm is adopted to calculate the estimated times for both systems with different initial temperature to cool down and undergo a first-order phase transition. The simulation results demonstrate a Mpemba effect in the system. Moreover, the evolution paths of the first-order phase transitions of the systems with high and low initial temperatures are given, respectively. The theoretical model presented here may help explain the Mpemba effect in water.

17.
Chem Commun (Camb) ; 58(85): 11933-11936, 2022 Oct 25.
Article in English | MEDLINE | ID: mdl-36197032

ABSTRACT

The cage-opening functionalization of stable closo-B10H102- salts is a great way to get various boron clusters. However, the known methods to mediate cage-opening functionalization rely on the use of strong acids, which suffer from low efficiency and narrow substrate scope. Herein, an efficient method to synthesize 6-substituted decaboranyl ethers and sulfides has been developed. The reaction was mediated by trimethylsilyl trifluoromethanesulfonate (TMSOTf) and occurred at room temperature. Six 6-substituted ethers were obtained in 65-92% yields and five 6-substituted sulfides were prepared in 38-58% yields. The reaction had excellent regioselectivity, affording the single B(6) regioisomer in all cases. The interaction between the B-H bonds of the boron cage and the silylium ion was believed to be the key factor in the reaction.

18.
Anal Chem ; 94(32): 11159-11167, 2022 08 16.
Article in English | MEDLINE | ID: mdl-35916489

ABSTRACT

Pancreatic cancer (PC) is one of the most lethal cancers worldwide, which is usually diagnosed in the advanced stage and is highly resistant to traditional chemotherapy, radiotherapy, and immunotherapy. Therefore, there is an urgent need for developing new PC-specific imaging and treatment. In this study, an quinone oxidoreductase 1 (NQO-1)-activated near-infrared (NIR) agent, ICy-Q, was synthesized. ICy-Q is almost nonemissive, while its NIR emission at 705 nm is triggered by NQO-1-induced reduction in the PC cells. In addition, the reduction product, ICy-OH, is specifically enriched in mitochondria and lysosomes and acts as an effective chemotherapeutic agent to selectively induce pancreatic cancer cell death via the cell pyroptosis pathway. Further studies have shown that ICy-Q is suitable for ex vivo imaging of clinical PC sections and solid tumors from patients. We expect this study will be helpful in the future for the design of targeted theranostic agents for PC.


Subject(s)
Antineoplastic Agents , Pancreatic Neoplasms , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Cell Line, Tumor , Humans , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/drug therapy , Precision Medicine , Theranostic Nanomedicine/methods , Pancreatic Neoplasms
19.
Ann Palliat Med ; 11(5): 1762-1773, 2022 May.
Article in English | MEDLINE | ID: mdl-35672893

ABSTRACT

BACKGROUND: The proteinuria remission in hepatitis B virus-associated glomerulonephritis (HBV-GN) patients with massive proteinuria treated with antiviral therapy was low. Tacrolimus (TAC) is effective in primary nephropathy and can inhibit HBV infection by inhibiting HBV binding to sodium taurocholate cotransporting polypeptide on liver cells. This study evaluated the efficacy and safety of TAC combined with ETV compared with entecavir (ETV) monotherapy in HBV-GN. METHODS: Patients diagnosed with HBV-GN were recruited for this prospective, randomized, controlled, multicenter, single-blinded study in China. Patients were given TAC and ETV therapy (the TAC+ETV group) or placebo and ETV therapy (the ETV group) for 26 weeks. The efficacy endpoints included proteinuria remission, including complete and partial remission (CR and PR), the change of 24-hour proteinuria (24 h UP) and HBV DNA titer. The safety endpoints were the incidence of HBV virologic breakthrough and adverse events. RESULTS: There were 14 patients in the TAC+ETV group and 17 patients in the ETV group. In the intention-to-treat analyses, 64.3% (9/14) of patients in the TAC+ETV group and 58.8% (10/17) in the ETV group achieved PR or CR at 26 weeks (P=0.38). At week 14, 42.9% (6/14) and 41.2% (7/17) of patients in the TAC+ETV group and the ETV group, respectively, achieved PR or CR (P=0.23). At week 26, the 24 h UP had decreased by 2.63±6.33 g from baseline in the TAC+ETV group and 1.42±4.34 g in the ETV group (P=0.55). The serum albumin increased by 11.1±7.30 g/L from baseline in the TAC+ETV group and 3.81±5.09 g/L in the ETV group (P<0.001). Log10 HBV DNA decreased by 1.49±2.04 from baseline in the TAC+ETV group and 2.47±2.08 in the ETV group (P=0.37); 28.6% (4/14) patients had HBV DNA virologic breakthrough in the ETV group, while none in the TAC+ETV group (P=0.29). CONCLUSIONS: In adult HBV-GN patients, TAC and ETV combination therapy may significantly improve serum albumin levels without increasing the risk of HBV reactivation compared with entecavir monotherapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT03062813.


Subject(s)
Glomerulonephritis , Hepatitis B, Chronic , Adult , Antiviral Agents/therapeutic use , DNA, Viral/pharmacology , DNA, Viral/therapeutic use , Glomerulonephritis/chemically induced , Glomerulonephritis/drug therapy , Guanine/analogs & derivatives , Hepatitis B virus/genetics , Hepatitis B, Chronic/drug therapy , Humans , Prospective Studies , Proteinuria/chemically induced , Proteinuria/drug therapy , Serum Albumin/pharmacology , Serum Albumin/therapeutic use , Single-Blind Method , Tacrolimus/pharmacology , Tacrolimus/therapeutic use , Treatment Outcome
20.
Angew Chem Int Ed Engl ; 61(33): e202207125, 2022 Aug 15.
Article in English | MEDLINE | ID: mdl-35665583

ABSTRACT

The classical aggregation-induced emission (AIE)-active luminogens (AIEgens) usually include two-dimensional aromatic systems such as tetraphenylethenes, which are synthesized in several steps by using toxic additives. Here, we proposed a new molecular design strategy for the realization of AIE properties by combining three-dimensional aromatic boron clusters of carboranes with vinyl group(s). To obtain a library of the boron cluster-based AIEgens, a Pd-catalyzed hydroboration of alkynes with carboranes is reported. This reaction protocol proceeds in one step under mild conditions with rapid reaction rate, excellent yields and regioselectivity. Photophysical property studies demonstrate that the facile molecular motions in solution can be inhibited in the solid state for these molecules, which leads to interesting AIE properties. This work provides not only a general design principle for AIEgens but also an efficient methodology to synthesize boron cluster-based photo-functional molecules.

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