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This study aimed to evaluate the efficacy and safety of entecavir(ETV) versus ETV maleate in Chinese patients with chronic hepatitis B(CHB). This was a randomized, double-blind, double-dummy, controlled, multicentre study. Patients were randomly assigned to receive 48 weeks of treatment with 0.5 mg/day ETV (group A) or 0.5 mg/day ETV maleate (group B), then, all patients received treatment with 0.5 mg/day ETV maleate from week 49 onwards. Patients were regularly followed up. Serum hepatitis B virus (HBV) markers were detected. Adverse events (AE) were recorded. The primary endpoint was the decline in HBV DNA in each group at the end of treatment. Secondary endpoints included the rate of HBV DNA below the lower limit of detection (LLOD) (20 I U/ml) at the end of treatment, the rate of hepatitis B e antigen (HBeAg) loss, the rate of HBeAg seroconversion and serum alanine aminotransferase (ALT) normalization. One hundred and thirty-seven (71 in group A) patients with HBeAg-positive CHB and 46 (21 in group A) patients with HBeAg-negative CHB completed the 240-week treatment and follow-up. Baseline characteristics were well balanced between the two groups. For the HBeAg-positive CHB patients, the mean HBV DNA level had similarly decreased from baseline in both groups (A: by 6.67 log10 IU/ml vs. B: by 6.74 log10 IU/ml; p > .05) at Week 240. Patients who achieved undetectable levels of serum HBV DNA (<20 IU/ml) at Week 240 were similar between groups (A:91.55% vs. B:87.88%; p > .05). Both groups achieved similar HBeAg seroconversion rates at week 240 (A:26.98% vs. B:20.97%; p > .05). Both groups achieved similar normalization of ALT (A:87.32% vs. B:83.61%; p > .05) at Week 240 (p > .05). For the HBeAg-negative CHB patients, the mean HBV DNA level had similarly decreased from baseline in both groups (A: by 6.05 log10 IU/ml vs. B: by 6.10 log10 IU/ml; p > .05) at Week 240. Patients who achieved undetectable levels of serum HBV DNA at Week 240 were similar between groups (A:100% vs. B:100%). Both groups achieved similar normalization rates (A:90.91% vs. B: 95.45%; p > .05) of ALT at Week 240 (p > .05). In conclusion, long-term ETV maleate treatment was safe and efficient in Chinese CHB predominantly of genotype B or C.
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Hepatitis B Crónica , Antivirales/efectos adversos , China , ADN Viral , Genotipo , Guanina/análogos & derivados , Antígenos e de la Hepatitis B , Virus de la Hepatitis B/genética , Humanos , Maleatos , Resultado del TratamientoRESUMEN
Organic LPL (long-persistent luminescence) materials have sparked extensive research interest due to the ultralong-lived triplet states. Although numerous organic LPL materials have been reported, most of the triplet emission was static and monotonous. Therefore, LPL materials with dynamic triplet emission are urgently required. A triamino-s-triazine derivative 1 with dynamic LPL was fabricated. The single-crystal structure shows that the abundant intermolecular interactions and small free volume restrict the molecular motion and avoid the quenchers. Spectral and theoretical calculations upheld the existence of multiple excited states in 1, and the migration of electrons between multiple excited states is very sensitive to external stimuli. By modulating the stimulus, the residence of electrons in different triplet states can be manipulated to achieve RGB LPL. Importantly, blue LPL was achieved by manipulating the anti-Kasha emission. And the red LPL can still be observed at high temperature.
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The indoor air quality is of prime importance for human daily life and health, for which the adsorbents like zeolites and silica-gels are widely used for air dehumidification and harmful gases capture. Herein, we develop a pore-nanospace post-engineering strategy to optimize the hydrophilicity, water-uptake capacity and air-purifying ability of metal-organic frameworks (MOFs) with long-term stability, offering an ideal candidate with autonomous multi-functionality of moisture control and pollutants sequestration. Through variant tuning of organic-linkers carrying hydrophobic and hydrophilic groups in the pore-nanospaces of prototypical UiO-67, a moderately hydrophilic MOF (UiO-67-4Me-NH2 -38 %) with high thermal, hydrolytic and acid-base stability is screened out, featuring S-shaped water sorption isotherms exactly located in the recommended comfortable and healthy ranges of relative humidity for indoor ventilation (45 %-65 % RH) and adverse health effects minimization (40-60 % RH). Its exceptional attributes of water-uptake working capacity/efficiency, contaminants removal, recyclability and regeneration promise a great potential in confined indoor environment application.
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Estructuras Metalorgánicas/química , Nanopartículas/química , Contaminantes Químicos del Agua/aislamiento & purificación , Adsorción , Contaminación del Aire Interior , Humedad , Estructura Molecular , Tamaño de la Partícula , Propiedades de Superficie , Agua/química , Contaminantes Químicos del Agua/químicaRESUMEN
By designing a tetraphenylethylene (TPE)-based AIEgen-ligand with reduced symmetry, we obtained two alkaline-earth metal-based MOFs (LIFM-102 and LIFM-103) with dense packing structures and low porosity as proved by single-crystal X-ray diffraction and CO2 sorption data. Excitingly, the desolvated MOFs with rigid environment and reduced lattice free solvent exhibit high quantum yields (QY, 64.9 % and 79.4 %) and excellent two-photon excited photoluminescence (TPA cross-sections, 2946.6â GM and 2899.0â GM), while maintaining the external-stimuli-responsive properties suitable for anticounterfeit fields. The effect of ligand conformation was validated by comparing the structure and fluorescence properties of the samples before and after desolvation and further verified by theoretical calculations. This work expands the study on TPE-cored materials to symmetry-reduced ligand and might bring forward novel structures and excellent photoluminescent properties in the future.
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Tumor-infiltrating dendritic cells (TIDCs) are mostly immature and immunosuppressive, usually mediating immune inhibition. The utilization of cytosine-guanine oligodeoxynucleotides (CpG ODNs) to stimulate the activation of TIDCs has been demonstrated to be effective for improving antitumor immunity. However, a series of biological barriers has limited the efficacy of previous nanocarriers for delivering CpG to TIDCs. Herein, we developed a dual-sensitive dendrimer cluster-based nanoadjuvant for delivering CpG ODNs into TIDCs. We show that the tumor acidity triggers the rapid release of CpG conjugated polyamidoamine (PAMAM) dendrimers from the nanoadjuvant, thus facilitating its perfusion deep into tumors and phagocytosis by TIDCs. Thereafter, the reductive condition of the endolysosomes led to the subsequent release of CpG, which promotes the DCs activation and enhances antitumor immunotherapies. Programmable delivery of immune adjuvant efficiently overcomes the barriers for targeted delivery to TIDCs and provides a promising strategy for improving cancer immunotherapy.
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Inmunoterapia , Neoplasias , Adyuvantes Inmunológicos , Células Dendríticas , Guanina , Humanos , Neoplasias/terapiaRESUMEN
Known for excellent stability, porosity and functionality, the high-valent Zr4+ metal-organic frameworks (Zr-MOFs) still meets synthetic challenge in modulating the strength of Zr-Ocarboxylate linkage. Herein we explore the unusual coordination dynamics of fluorinated Zr-MOFs by designing two trifluoromethyl modified ligands with distinct geometry preference to form a family of thermodynamic and kinetic products. The low-connecting kinetic Zr-MOFs possess substitutable coordination sites to endow Zr6 -cluster with extra dynamic behaviors, thus opening a post-synthetic pathway to sequential reassembly/disassembly processes. Comprehensive factors, including ligand geometry, Zr6 -cluster connectivity, acid modulator and reaction temperature/concentration, have been studied for controllable syntheses. The stability, hydrophobicity and gas adsorption/separation properties of obtained Zr-MOFs are explored. This work sheds light on the understanding of the dynamic coordination chemistry of Zr-MOFs beyond strong Zr-O bond, which poses a versatile platform for modification and functionalization of Zr-MOFs.
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Molecular or supramolecular level photoluminescence (PL) modulation combining chemical and photonic input/output signals together in an integrated system can provide potential high-density data memorizing and process functions intended for miniaturized devices and machines. Herein, a PL-responsive supramolecular coordination cage has been demonstrated for complex interactions with redox-active guests. PL signals of the cage can be switched and modulated by adding or retracting Fc derivatives or converting TTF into different oxidation states through chemical or photochemical pathways. As a result, reversible or stepwise PL responses are displayed by these host-guest systems because of the occurrence of photoinduced electron-transfer (PET) or fluorescence resonance energy transfer (FREnT) processes, providing unique nanodevice models bearing off/on logic gates or memristor-like sequential memory and Boolean operation functions.
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In multiphoton excited fluorescence (MPEF), high-energy upconversion emission is obtained from low-energy excitation by absorbance of two or more photons simultaneously. In a pressure-induced fluorochromic process, the emission energy is switched by outer pressure stimuli. Now, five metal-organic frameworks containing the same ligand with simultaneous multiphoton absorption and pressure-induced fluorochromic attributes were studied. One-, two-, and three-photon excited fluorescence (1/2/3PEF) can be achieved in the frameworks, which exhibit pressure-induced blue-to-yellow fluorochromism. The performances are closely dependent with the topologies, flexibilities, and packing states of the frameworks and chromophores therein. The multiphoton upconversion performance can be intensified by pressure-related structural contraction. Over ten-fold increment in the 2PA active cross-section up to 2217â GM is achieved in pressed LIFM-114 compared with the 210â GM for pristine sample at 780â nm.
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Long persistent luminescence (LPL) materials have a unique photophysical mechanism to store light radiation energy for subsequent release. However, in comparison to the common UV source, white-light (WL) and near-infrared (NIR) excited LPL is scarce. Herein we report a metal-organic supramolecular box based on a D-π-A-type ligand. Owing to the integrated one-photon absorption (OPA) and two-photon absorption (TPA) attributes of the ligand, the heavy-atom effect of the metal center, as well as π-stacking and J-aggregation states in the supramolecular assembly, LPL can be triggered by all wavebands from the UV to the NIR region. This novel designed supramolecular kit to afford LPL by both OPA and TPA pathways provides potential applications in anti-counterfeiting, camouflaging, decorating, and displaying, among others.
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Luminescent thermometers have attracted much attention, because of their fast response, high sensitivity, and noninvasive operation, relative to other traditional thermometers. The extensive studies on the temperature-dependent luminescent properties of Cu(I) complexes make this low-cost metal source a promising candidate as a component of thermometers. Herein, we prepared three luminescent phosphinine Cu(I) complexes whose emission lifetimes are precisely dependent on the temperature variations. For practical utilization, sensor films have been fabricated by doping these Cu(I) complexes into the matrices of polyacrylamide. These films not only exhibit excellent linear correlations between the temperature and emission lifetime over the wide range of 77-337 K, but also show high sensitivity (with the best one to -6.99 µs K-1). These are essential factors for the application in luminescent molecular thermometers. Moreover, the emission mechanism for these Cu(I) complexes are rationalized by the combination of experimental and theoretical results.
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A Co-MOF, [Co3(HL)2·4DMF·4H2O] was simply synthesized through a one-pot solvothermal method. With the semiconductor nature, its band gap was determined to be 2.95 eV by the Kubelka-Munk method. It is the first trinuclear Co-MOF employed for photocatalytic hydrogen evolution and CO2 reduction with cobalt-oxygen clusters as catalytic nodes. Hydrogen evolution experiments indicated the activity was related to the photosensitizer, TEOA, solvents, and size of catalyst. After optimization, the best activity of H2 production was 1102 µmol/(g h) when catalyst was ground and then soaked in photosensitizer solution before photoreaction. To display the integrated design of Co-MOF, we used no additional photosensitizer and cocatalyst in the CO2 reduction system. When -NH2 was used for light absorption and a Co-O cluster was used as catalyst, Co-MOF exhibited an activity of 456.0 µmol/(g h). The photocatalytic mechanisms for hydrogen evolution and CO2 reduction were also proposed.
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Core-shell or striped heteroatomic lanthanide metal-organic framework hierarchical single crystals were obtained by liquid-phase anisotropic epitaxial growth, maintaining identical periodic organization while simultaneously exhibiting spatially segregated structure. Different types of domain and orientation-controlled multicolor photophysical models are presented, which show either visually distinguishable or visible/near infrared (NIR) emissive colors. This provides a new bottom-up strategy toward the design of hierarchical molecular systems, offering high-throughput and multiplexed luminescence color tunability and readability. The unique capability of combining spectroscopic coding with 3D (three-dimensional) microscale spatial coding is established, providing potential applications in anti-counterfeiting, color barcoding, and other types of integrated and miniaturized optoelectronic materials and devices.
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We demonstrate that the conformation, packing mode, and blue fluorescence of a soft piezofluorochromic compound can be preserved by structurally fixing it into a solid calcium metal-organic framework (Ca-MOF, LIFM-40), which can survive pressures up to 8 MPa. DFT calculations have been combined with experimental results to indicate that the ligands adopting a specific conformation and packing without π···π interactions are the reasons for its rigidified blue emission.
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Objective: To compare the effects of Morinda officinalis root and its salt-processing prodduct on rats with kidney yang deficiency from the viewpoint of energetic metabolism. Methods: The rat models for the kidney yang deficiency were established through the perfusion of methimazole. The models were treated with different dosages of Morinda officinalis root without woods and its salt-processing products extracts. The activity of liver glycogen,muscle glycogen,free fatty acid( NEFA),lipoprotein lipase( LPL),hepatic lipase( HL),liver and skeletal muscle Na+,K+ATPase,Ca2 +,Mg2 +ATPase,succinodehydrogenase( SDH) were measured by colormetric methods,and the coefficient of body fat were observed by weighing method. Results: Morinda officinalis root without woods and its saltprocessing products could improve the energetic metabolism of kidney yang deficiency of rats. The effects of salt-processing products were better than Morinda officinalis root without woods in the same dosage. Conclusion: The effect of invigorating the kidney and strengthening yang of Morinda officinalis were correlated with energetic metabolism. The correct processing-products of Morinda officinalis root should be chosen with the suitable measurements in clinic.
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Metabolismo Energético , Morinda , Deficiencia Yang , Animales , Riñón , RatasRESUMEN
The widespread use of herbicides impacts non-target organisms, promotes weed resistance, posing a serious threat to the global goal of green production in agriculture. Although the herbicide residues have been widely reported in individual environmental medium, their presence across different media has received scant attention, particularly in Mollisols regions with intensive agricultural application of herbicides. A systematic investigation was conducted in this study to clarify the occurrence of herbicide residues in soil, surface water, sediments, and grains from a typical agricultural watershed in the Mollisols region of Northeast China. Concentrations of studied herbicides ranged from 0.30 to 463.49 µg/kg in soil, 0.31-29.73 µg/kg in sediments, 0.006-1.157 µg/L in water, and 0.32-2.83 µg/kg in grains. Among these, Clomazone was the most priority herbicide detected in soil, sediments, and water, and Pendimethalin in grains. Crop types significantly affected the residue levels of herbicides in grains. Clomazone posed high ecological risks in soil and water, with 86.4 % of water samples showing high risks from herbicide mixtures (RQ > 1). These findings aid in enhancing our comprehension of the pervasive occurrence and potential ecological risks of herbicides in different media within typical agricultural watersheds, providing detailed data to inform the development of targeted mitigation strategies.
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Agricultura , Monitoreo del Ambiente , Herbicidas , Contaminantes Químicos del Agua , Herbicidas/análisis , China , Contaminantes Químicos del Agua/análisis , Medición de Riesgo , Suelo/química , Contaminantes del Suelo/análisis , Residuos de Plaguicidas/análisisRESUMEN
The functions of natural killer (NK) and T cells in innate and adaptive immunity, as well as their functions in tumor eradication, are complementary and intertwined. Here we show that utilization of multi-specific antibodies or nano-antibodies capable of simultaneously targeting both NK and T cells could be a valuable approach in cancer immunotherapy. Here, we introduce a tri-specific Nano-Antibody (Tri-NAb), generated by immobilizing three types of monoclonal antibodies (mAbs), using an optimized albumin/polyester composite nanoparticle conjugated with anti-Fc antibody. This Tri-NAb, targeting PDL1, 4-1BB, and NKG2A (or TIGIT) simultaneously, effectively binds to NK and CD8+ T cells, triggering their activation and proliferation, while facilitating their interaction with tumor cells, thereby inducing efficient tumor killing. Importantly, the antitumor efficacy of Tri-NAb is validated in multiple models, including patient-derived tumor organoids and humanized mice, highlighting the translational potential of NK and T cell co-targeting.
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Anticuerpos Monoclonales , Linfocitos T CD8-positivos , Células Asesinas Naturales , Nanopartículas , Células Asesinas Naturales/inmunología , Animales , Humanos , Ratones , Nanopartículas/química , Anticuerpos Monoclonales/inmunología , Línea Celular Tumoral , Linfocitos T CD8-positivos/inmunología , Inmunoterapia/métodos , Neoplasias/inmunología , Neoplasias/terapia , Antígeno B7-H1/inmunología , Subfamília C de Receptores Similares a Lectina de Células NK/inmunología , Femenino , Miembro 9 de la Superfamilia de Receptores de Factores de Necrosis Tumoral/inmunología , Ratones Endogámicos NODRESUMEN
Immune cells are indispensable defenders of the human body, clearing exogenous pathogens and toxicities or endogenous malignant and aging cells. Immune cell dysfunction can cause an inability to recognize, react, and remove these hazards, resulting in cancers, inflammatory diseases, autoimmune diseases, and infections. Immune cells regulation has shown great promise in treating disease, and immune agonists are usually used to treat cancers and infections caused by immune suppression. In contrast, immunosuppressants are used to treat inflammatory and autoimmune diseases. However, the key to maintaining health is to restore balance to the immune system, as excessive activation or inhibition of immune cells is a common complication of immunotherapy. Nanoparticles are efficient drug delivery systems widely used to deliver small molecule inhibitors, nucleic acid, and proteins. Using nanoparticles for the targeted delivery of drugs to immune cells provides opportunities to regulate immune cell function. In this review, we summarize the current progress of nanoparticle-based strategies for regulating immune function and discuss the prospects of future nanoparticle design to improve immunotherapy.
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Soil environmental capacity (EC) of heavy metals (HMs) can be used as an index to evaluate the pollution status of HMs and to provide basic data for HM remediation. However, the commonly used soil EC for HMs usually are prone to bias due to the lack of local background values (BVs) and the consideration of the contribution from various HM sources. Here, a modified method was proposed to estimate the soil EC by integrating the establishment of local BVs and the quantitative evaluation of contributions from HM sources in an intensive agricultural area of Shouguang city, China. The local BVs of HMs were established using the relative cumulative frequency distribution method. The source-specific EC was quantified based on the local BVs and the contributions of HM sources identified by receptor model and variable importance analysis. Results showed that the average BV values of As, Cd, Cr, Cu, Hg, Ni, Pb, and Zn were 7.67, 0.10, 62.84, 21.17, 0.031, 28.38, 19.25, and 59.60 mg kg-1, respectively, in the study area. The source-specific EC of Cd, Cu, Hg, and Zn were higher than their current EC, indicating an underestimation of soil capacity of HMs by the traditional method. The EC of HMs in these soils was generally medium indicated by their comprehensive EC index (PI) (PI >0.7), suggesting a low risk level of the targeted HMs. According to indexes such as the individual metal index (Pi) and enrichment factor (EF), special attention should be paid to Cd and Zn due to their low capacity (Pi <0.7) and high accumulation (EF > 2) in some points across this area. Altogether, our findings suggested that the modified method had a better capability for evaluating and predicting the enrichment status of soil HMs, which can be helpful for formulating the targeted measures to control HM pollution in such intensive agricultural areas.
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Metales Pesados , Contaminantes del Suelo , China , Monitoreo del Ambiente/métodos , Metales Pesados/análisis , Medición de Riesgo , Suelo , Contaminantes del Suelo/análisisRESUMEN
The Yangtze River Economic Belt is one of the major strategic development regions in China. It is of great significance to clarify the characteristics and sources of heavy metal pollution in farmland soil of the Yangtze River Economic Belt for the prevention and control of heavy metal pollution and to ensure safe agricultural production. After collecting extensive literature data, we analyzed the pollution characteristics, environmental risk, and potential sources of heavy metals (Cd, Cr, Hg, As, Pb, Cu, Zn, and Ni) in farmland soil of the Yangtze River Economic Belt through the integrated use of spatial and geo-accumulation index analyses. The results showed that:â the proportion of soil samples exceeding the risk screening values for soil contamination of agricultural land of Cd, Cu, Pb, Hg, Zn, and As were 39.8%, 18.5%, 8.3%, 6.9%, 6.9%, and 6.4%, respectively. Compared with the risk standard, soil Cd had the highest rate of exceeding the standard. â¡ The contents of Cr, Cu, Zn, and Ni in the upper reaches were higher than those in the middle and lower reaches, and the contents of Cd, As, and Pb in the middle reaches were higher than those in the upper and lower reaches. ⢠The results of the geo-accumulation index analysis showed that the contamination degree of the eight heavy metals decreased in the order of Cd(0.42)>Hg(-0.28)>Pb(-0.32)>Zn(-0.39)>Cu(-0.42)>Cr(-0.7)>As(-0.81)>Ni(-0.73), where the accumulation risk of soil Cd and Hg was relatively higher. ⣠Higher environmental background and mining activities were the main factors affecting the accumulation of heavy metals in soils in the upper and middle reaches. By contrast, rapid urbanization, industrial production, and intensive agricultural activities were the main factors affecting the heavy metal accumulation in soils in the middle and lower reaches. In view of the current status and control needs of heavy metal pollution in the Yangtze River Economic Belt, it is recommended to strengthen source prevention and control and to also carry out hierarchical control and regional classification management of heavy metal pollution in farmland soils according to the degree of heavy metal pollution, geological background, and quality of agricultural products. The ultimate objective of this research was to archive the farmland soil environmental quality safety and agricultural green sustainable production in the Yangtze River Economic Belt.
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Mercurio , Metales Pesados , Suelo , Granjas , Ríos , Cadmio , Plomo , BibliometríaRESUMEN
Phthalate pollution in plastic greenhouses (PGs) has aroused concerns. However, mechanisms and factors of vegetables planted in PGs (VPGs) accumulating phthalates from soil and air are unclear. To fill the gap, 19 PGs in Shaanxi, the largest vegetable production province in northwestern China, were selected to probe this issue. 35 soil samples, 48 air samples, and 26 VPG samples were collected in winter and summer. Medians of sum of 7 phthalate concentrations (∑7 PAEs) in PG soil, air, and VPGs were 73.9 µg kg-1, 5300 ng m-3, and 1053 µg kg-1 dry weight, respectively. ∑7 PAE concentrations in PG environmental media in winter were higher than summer, with the significant difference in VPGs. Sum concentrations of bis (2-ethylhexyl) phthalate (DEHP) and di-n-butyl phthalate (DnBP) accounted for 76.8% and 82.3% of the ∑7 PAEs in soil and VPGs. DnBP and DEHP concentrations in VPGs were significantly correlated to those in air and soil, with correlation coefficients (R) of 0.89 and 0.96 to air and 0.68 and 0.59 to soil. Log-transformed soil-air partition coefficient (log KSA) and fugacity fraction (log ff) of DnBP decreased while log KSA and log ff of DEHP increased from winter to summer, though DnBP in soil volatilized to air while DEHP in air sank to soil within the year. These issues were caused by air temperature changes and the application of plastic films. Furthermore, DnBP concentrations in VPGs were positively correlated to KSA values of DnBP (R = 0.87) while those of DEHP were negative (R = -0.82). Therefore, VPGs could uptake more phthalates from air than from soil, especially for edible parts of leafy and solanaceous VPGs. Applying phthalates free agricultural films and precision management such as adjusting air temperature in PGs could be considered to ensure VPG safeties.