Enhancing photocatalytic H2O2 production with Au co-catalysts through electronic structure modification.

Gold-based co-catalysts are a promising class of materials with potential applications in photocatalytic H2O2 production. However, current approaches with Au co-catalysts show limited H2O2 production due to intrinsically weak O2 adsorption at the Au site. We report an approach to strengthen O2 adsorption at Au sites, and to improve H2O2 production, through the formation of electron-deficient Auδ+ sites by modifying the electronic structure. In this case, we report the synthesis of TiO2/MoSx-Au, following selective deposition of Au onto a MoSx surface which is then further anchored onto TiO2. We further show that the catalyst achieves a significantly increased H2O2 production rate of 30.44 mmol g-1 h-1 in O2-saturated solution containing ethanol. Density functional theory calculations and X-ray photoelectron spectroscopy analysis reveal that the MoSx mediator induces the formation of electron-deficient Auδ+ sites thereby decreasing the antibonding-orbital occupancy of Au-Oads and subsequently enhancing O2 adsorption. This strategy may be useful for rationally designing the electronic structure of catalyst surfaces to facilitate artificial photosynthesis.

Reduced DNMT1 levels induce cell apoptosis via upregulation of METTL3 in cardiac hypertrophy.

DNA methylation is also involved in the development and progression of cardiac diseases. Although studies have shown that DNA methylation and RNA m6A methylation play an important role in the development of myocardial hypertrophy, whether DNA methylation and RNA m6A methylation have a coordinated role in the development of myocardial hypertrophy and influence each other is still unknown. Here, we found that DNMT1 expression was downregulated in TAC mice and Ang II-treated NRCMs. Moreover, DNMT1 overexpression inhibited Ang II-induced apoptosis of NRCMs. Furthermore, we found that the expression of METTL3 was up-regulated after inhibiting the expression of DNMT1 by a DNMT1 inhibitor or small interfering RNA. In addition, ectopic expression DNMT1 inhibited METTL3 expression in NRCMs. Furthermore, METTL3 expression was elevated in NRCMs treated with Ang II, and suppression of METTL3 inhibited cell apoptosis induced by Ang II in NRCMs.In addition, this study revealed that the DNMT1/METTL3 pathway affected Ang II-induced apoptosis in NRCMs. Finally, this study found that DNMT1, but not METTL3, might directly regulated the ANP and BNP expression. Collectively, our findings revealed the role of the DNMT1/METTL3 pathway in cardiac hypertrophy and provided a novel molecular mechanism describing the physiological and pathological processes.

Free-Electron Inversive Modulation to Charge Antibonding Orbital of ReS2 Cocatalyst for Efficient Photocatalytic Hydrogen Generation.

The free electron transfer between cocatalyst and photocatalyst has a great effect on the bonding strength between the active site and adsorbed hydrogen atom (Hads), but there is still a lack of effective means to purposely manipulate the electron transfer in a beneficial direction of H adsorption/desorption activity. Herein, when ReSx cocatalyst is loaded on TiO2 surface, a spontaneous free-electron transfer from ReSx to TiO2 happens due to the smaller work function of ReSx, causing an over-strong S-Hads bond. To prevent the over-strong S-Hads bonds of ReSx in the ReSx/TiO2 , a free-electron reversal transfer strategy is developed to weaken the strong S-Hads bonds via increasing the work function of ReSx by incorporating O to produce ReOSx cocatalyst. Research results attest that a larger work function of ReOSx than that of TiO2 can induce reversal transfer of electrons from TiO2 to ReOSx to produce electron-rich S(2+δ)-, causing the increased antibonding-orbital occupancy of S-Hads in ReOSx/TiO2 . Accordingly, the stability of adsorbed H on S sites is availably decreased, thus weakening the S-Hads of ReOSx. In this case, an electron-rich S(2+δ)--mediated "capture-hybridization-conversion" mechanism is raised . Benefiting from such property, the resultant ReOSx/TiO2 photocatalyst exhibits a superior H2-evolution rate of 7168 µmol h-1 g-1 .

The accuracy of Fiber-Optic Raman Spectroscopy in the detection and diagnosis of head and neck neoplasm in vivo: a systematic review and meta-analysis.

Purpose: The aim of this article was to review and collectively assess the published studies of fiber-optic Raman spectroscopy (RS) of the in vivo detection and diagnosis of head and neck carcinomas, and to derive a consensus average of the accuracy, sensitivity and specificity. Methods: The authors searched four databases, including Ovid-Medline, Ovid-Embase, Cochrane Library, and the China National Knowledge Infrastructure (CNKI), up to February 2023 for all published studies that assessed the diagnostic accuracy of fiber-optic RS in the in vivo detection of head and neck carcinomas. Nonqualifying studies were screened out in accordance with the specified exclusion criteria, and relevant information about the diagnostic performance of fiber-optic RS was excluded. Publication bias was estimated by Deeks' funnel plot asymmetry test. A random effects model was adopted to calculate the pooled sensitivity, specificity and diagnostic odds ratio (DOR). Additionally, the authors conducted a summary receiver operating characteristic (SROC) curve analysis and threshold analysis, reporting the area under the curve (AUC) to evaluate the overall performance of fiber-optic RS in vivo. Results: Ten studies (including 16 groups of data) were included in this article, and a total of 5365 in vivo Raman spectra (cancer = 1,746; normal = 3,619) were acquired from 877 patients. The pooled sensitivity and specificity of fiber-optic RS of head and neck carcinomas were 0.88 and 0.94, respectively. SROC curves were generated to estimate the overall diagnostic accuracy, and the AUC was 0.96 (95% CI [0.94-0.97]). No significant publication bias was found in this meta-analysis by Deeks' funnel plot asymmetry test. The heterogeneity of these studies was significant; the Q test values of the sensitivity and specificity were 106.23 (P = 0.00) and 64.21 (P = 0.00), respectively, and the I2 index of the sensitivity and specificity were 85.88 (95% CI [79.99-91.77]) and 76.64 (95% CI [65.45-87.83]), respectively. Conclusion: Fiber-optic RS was demonstrated to be a reliable technique for the in vivo detection of head and neck carcinoma with high accuracy. However, considering the high heterogeneity of these studies, more clinical studies are needed to reduce the heterogeneity, and further confirm the utility of fiber-optic Raman spectroscopy in vivo.

Anisotropy in the Liquefaction Resistance of Fibre Reinforced Sand.

Adding discrete fibres to sand has been seen as a feasible technique to improve sand's strength as well as liquefaction resistance. Considering the anisotropic distribution of fibre orientations, the anisotropy in the liquefaction resistance of the reinforced sand is also introduced using fibres. Here, the triaxial compression and extension test results of unreinforced and fibre-reinforced sand in different density states are provided, from which the anisotropy in the liquefaction resistance of fibre-reinforced sand is demonstrated. Fibre reinforcement improves the liquefaction resistance of sand by introducing both the densifying effect and the confining effect. The inclusion of fibres increases both the slope and the intercept of the strength envelope in comparison with the unreinforced sand under triaxial compression, while the strength envelope is not affected by fibres under triaxial extension. Stress contribution of fibres makes the ESP of the composite under undrained loading reverse its direction to develop even though the phase transformation is absent. The stress ratio initiating the ESP reversal is irrespective of the fibre content but dependent on the density state under triaxial compression. Under triaxial extension, the stress ratio initiating the ESP reversal remains the same in the samples with varied density states and fibre contents. The mechanism correlating to the strength envelope and ESP reversal of the fibre-reinforced sand was demonstrated following a rule of mixture based constitutive modelling framework. By introducing an alternatively defined pore pressure ratio that incorporates the stress contribution of fibres, the liquefaction state of the fibre reinforced sand is reasonably assessed. Liquefaction remains absent in the sand once the fibres are mixed. The anisotropy in the liquefaction resistance of fibre-reinforced sand arises, as the predominant role played by the fibres to suppress the liquefaction is different when varied loading paths are involved, which is sourced from the anisotropic distribution of fibre orientations.

Triggering the Channel-Sulfur Sites in 1T'-ReS2 Cocatalyst toward Splendid Photocatalytic Hydrogen Generation.

Electron density manipulation of active sites in cocatalysts is of great essential to realize the optimal hydrogen adsorption/desorption behavior for constructing high-efficient H2 -evolution photocatalyst. Herein, a strategy about weakening metal-metal bond strength to directionally optimize the electron density of channel-sulfur(S) sites in 1T' Re1- x Mox S2 cocatalyst is clarified to improve their hydrogen adsorption strength (S─H bond) for rapid H2 -production reaction. In this case, the ultrathin Re1- x Mox S2 nanosheet is in situ anchored on the TiO2 surface to form Re1- x Mox S2 /TiO2 photocatalyst by a facial molten salt method. Remarkably, numerous visual H2 bubbles are constantly generated on the optimal Re0.92 Mo0.08 S2 /TiO2 sample with a 10.56 mmol g-1  h-1 rate (apparent quantum efficiency is about 50.6%), which is 2.6 times higher than that of traditional ReS2 /TiO2 sample. Density functional theory and in situ/ex situ X-ray photoelectron spectroscopy results collectively demonstrate that the weakened Re─Re bond strength via Mo introduction can induce the formation of unique electron-deficient channel-S sites with suitable electron density, which yield thermoneutral S─H bonds to realize superior interfacial H2 -generation performance. This work provides fundamental guidance on purposely optimizing the electronic state of active sites by manipulating the intrinsic bonding structure, which opens an avenue for designing efficacious photocatalytic materials.

Study on the thermal stability of nab-paclitaxel during hyperthermic intraperitoneal chemotherapy.

BACKGROUND: Albumin-bound paclitaxel (nab-paclitaxel), as a special targeted preparation of paclitaxel, has the advantages of good curative effect and less side effects in anti-tumor therapy. The existence of the plasma-peritoneal barrier and insufficient blood supply make intravenous drugs hard to reach the peritoneum, while hyperthermic intraperitoneal chemotherapy can solve the difficulty. And compared with systemic medications, HIPEC can also give higher concentrations of chemotherapy drugs in the abdominal cavity, while ensuring lower systemic toxicity. However, at present, there is no relevant report on the clinical study of nab-paclitaxel during intraperitoneal hyperthermic chemotherapy, and its stability under special temperature conditions has not been reported either. METHODS: In this study, We examined three batches of albumin-bound paclitaxel dissolved in saline at different temperatures (25 °C, 37 °C, 41 °C, 42 °C and 43 °C) for the changes of human serum albumin content, human serum albumin polymer content, related substance content, in-vitro release rate, paclitaxel binding rate and paclitaxel content at different temperatures. RESULTS: Our results demonstrated that the indicators including human serum albumin content, human serum albumin polymer content, in-vitro release rate, paclitaxel binding rate and paclitaxel content were stable to the several temperatures, except that Taxane (0.1%) and other individual impurities in the determination of related substance content fluctuated comparatively widely with the change of temperature. In addition, only Taxane (0.1%) and 7-Epitaxol (1%) were detected. CONCLUSIONS: Overall, albumin-bound paclitaxel is relatively stable to different temperatures (25 °C, 37 °C, 41 °C, 42 °C and 43 °C). This study will lay a foundation for further studies on the albumin-bound paclitaxel during hyperthermic intraperitoneal chemotherapy.

Environmental occurrence, toxicity concerns, and biodegradation of neonicotinoid insecticides.

Neonicotinoids (NEOs) are fourth generation pesticides, which emerged after organophosphates, pyrethroids, and carbamates and they are widely used in vegetables, fruits, cotton, rice, and other industrial crops to control insect pests. NEOs are considered ideal substitutes for highly toxic pesticides. Multiple studies have reported NEOs have harmful impacts on non-target biological targets, such as bees, aquatic animals, birds, and mammals. Thus, the remediation of neonicotinoid-sullied environments has gradually become a concern. Microbial degradation is a key natural method for eliminating neonicotinoid insecticides, as biodegradation is an effective, practical, and environmentally friendly strategy for the removal of pesticide residues. To date, several neonicotinoid-degrading strains have been isolated from the environment, including Stenotrophomonas maltophilia, Bacillus thuringiensis, Ensifer meliloti, Pseudomonas stutzeri, Variovorax boronicumulans, and Fusarium sp., and their degradation properties have been investigated. Furthermore, the metabolism and degradation pathways of neonicotinoids have been broadly detailed. Imidacloprid can form 6-chloronicotinic acid via the oxidative cleavage of guanidine residues, and it is then finally converted to non-toxic carbon dioxide. Acetamiprid can also be demethylated to remove cyanoimine (=N-CN) to form a less toxic intermediate metabolite. A few studies have discussed the neonicotinoid toxicity and microbial degradation in contaminated environments. This review is focused on providing an in-depth understanding of neonicotinoid toxicity, microbial degradation, catabolic pathways, and information related to the remediation process of NEOs. Future research directions are also proposed to provide a scientific basis for the risk assessment and removal of these pesticides.

Novel mechanism and degradation kinetics of allethrin using Bacillus megaterium strain HLJ7 in contaminated soil/water environments.

As a common pyrethroid insecticide, allethrin is widely used for various purposes in agriculture and home applications. At present, allethrin residues have been frequently detected worldwide, yet little is known about the kinetics and degradation mechanisms of this insecticide. In this study, a highly efficient allethrin-degrading bacterium, Bacillus megaterium strain HLJ7, was obtained through enrichment culture technology. Strain HLJ7 can remove 96.5% of 50 mg L-1 allethrin in minimal medium within 11 days. The first-order kinetic analysis of degradation demonstrated that the half-life of allethrin degradation by strain HLJ7 was 3.56 days, which was significantly shorter than the 55.89 days of the control. The Box-Behnken design of the response surface method optimized the degradation conditions for strain HLJ7: temperature 32.18 °C, pH value 7.52, and inoculation amount 1.31 × 107 CFU mL-1. Using Andrews equation, the optimal concentration of strain HLJ7 to metabolize allethrin was determined to be 21.15 mg L-1, and the maximum specific degradation rate (qmax), half-rate constant (Ks) and inhibition coefficient (Ki) were calculated to be 1.80 d-1, 1.85 mg L-1 and 68.13 mg L-1, respectively. Gas chromatography-mass spectrometry identified five intermediate metabolites, suggesting that allethrin could be degraded firstly by cleavage of its carboxylester bond, followed by degradation of the five-carbon ring and subsequent metabolism. The results of soil remediation experiments showed that strain HLJ7 has excellent bioremediation potential in the soils. After 15 days of treatment, about 70.8% of the initial allethrin (50 mg kg-1) was removed and converted into nontoxic intermediate metabolites, and its half-life was significantly reduced in the soils. Taken together, these findings shed light on the degradation mechanisms of allethrin and also highlight the promising potentials of B. megaterium HLJ7 in bioremediation of allethrin-comtaminated environment.

The Effects of Fiber Inclusion on the Evolution of Desiccation Cracking in Soil-Cement.

Desiccation cracking frequently occurs in mud, clay, and pavement. Understanding the evolution of desiccation cracking may facilitate the development of techniques to mitigate cracking and even prevent it from developing altogether. In this study, experimental investigations were performed focusing on the effects of fibers on the evolution of desiccation cracking in soil-cement. Varied types of fibers (i.e., jute fiber and polyvinyl alcohol fiber (PVA)) and fiber contents (i.e., 0%, 0.25%, 0.5%, and 1%) were involved. The digital image correlation (DIC) method was employed to capture the evolution and propagation of cracks in the soil-cement specimens when subjected to desiccation. The results show that the presence of fibers imposes significant effects on the crack propagation pattern as well as the area and length of the cracks in the soil-cement during shrinkage. The addition of fibers, however, insignificantly affects the evaporation rate of the specimens. The crack area and crack length of the specimens decreased significantly when more fibers were included. There were no macroscopic cracks observed in the specimens where the fiber content was 1%. The DIC method effectively helped to determine the evolution of displacement and strain field on the specimens' surface during the drying process. The DIC method is therefore useful for crack monitoring.

Photodepositing CdS on the Active Cyano Groups Decorated g-C3 N4 in Z-Scheme Manner Promotes Visible-Light-Driven Hydrogen Evolution.

g-C3 N4 /CdS heterojunctions are potential photocatalysts for hydrogen production but their traditional type-II configuration generally leads to weak oxidative and reductive activity. How to construct the novel Z-scheme g-C3 N4 /CdS counterparts to address this issue remains a great challenge in this field. In this work, a new direct Z-scheme heterojunction of defective g-C3 N4 /CdS is designed by introducing cyano groups (NC-) as the active bridge sites. Experimental observations in combination with density functional theory (DFT) calculations reveal that the unique electron-withdrawing feature of cyano groups in the defective g-C3 N4 /CdS heterostructure can endow this photocatalyst with numerous advantageous properties including high light absorption ability, strong redox performance, satisfactory charge separation efficiency, and long lifetime of charge carriers. Consequently, the resultant photocatalytic system exhibits more active performance than CdS and g-C3 N4 under visible light and reaches an excellent hydrogen evolution rate of 1809.07 µmol h-1 g-1 , which is 6.09 times higher than pristine g-C3 N4 . Moreover, the defective g-C3 N4 /CdS photocatalyst maintains good stability after 40 h continuous test. This work provides new insights into design and construction of Z-scheme heterojunctions for regulating the visible-light-induced photocatalytic activity for H2 evolution.

Spatial Distribution and Source Apportionment of Agricultural Soil Heavy Metals in a Rapidly Developing Area in East China.

We collected 682 topsoil samples (0-20cm) from agricultural lands of Luhe County in East China, and analyzed the spatial distribution patterns and potential sources of four major heavy metals. High Pb and Cr were mainly in the southeast adjacent to the Yangtze River, and Cd were characterized by an increasing trend from northwest to southeast, while high Hg mainly occurred in the areas near downtown. Spatially-continuous sources dominated the soil heavy metal concentrations. Contributions of spatially-continuous natural source (soil parent material) to Cr and Cd were 97.0% and 77.7%, respectively, whereas contributions of spatially-continuous anthropogenic source such as diffuse pollution to Pb and Hg were 75.7% and 86.7%, respectively. The distance to factories was the most influential anthropogenic factor for localized anomaly patterns of Pb, Cd, and Cr, while the intensive agricultural land uses associated with the rapid urban expansion were particularly relevant to the anomaly patterns of Hg.

Synthesis of multifunctional rare-earth fluoride/Ag nanowire nanocomposite for efficient therapy of cancer.

Well-dispersed Ag nanowires and PVP-modified BaGdF5: Yb3+, Er3+ spherical nanoparticles were prepared by simple solvothermal and hydrothermal method, and they were further combined to obtain photo-thermal-magnetic multifunctional Ag/BaGdF5: Yb3+, Er3+ nanocomposites. Under NIR laser irradiation, monodispersed rare-earth fluoride BaGdF5: Yb3+, Er3+ in nanocomposite exhibit good upconversion fluorescent. Meanwhile, under the action of an external magnetic field, the nanocomposite also exhibits good magnetic properties and excellent contrast efficiency by CT/MR imaging. The NCs possess good structure and photothermal stability at multiple cycles due to that Ag nanowires are modified by polyvinyl pyrrolidone and sodium citrate. The biocompatibility and low toxicity of NCs are also remarkable. Importantly, the unique linear morphology of Ag particles can achieve high efficiency conversion between light and heat. Furthermore, in vitro tests also confirm the high efficiency of photothermal therapy for cancer cells.

Effects of Phosphorus on Interspecific Competition between two cell-size Cyanobacteria: Synechococcus sp. and Microcystis aeruginosa.

Pico-cyanobacteria and micro-cyanobacteria coexist ubiquitously in many lakes. Differences in cell size and abilities to utilize nutrients may influence their distribution patterns. In this study, Synechococcus sp. and Microcystis aeruginosa were chosen as pico- and micro-cyanobacteria, respectively. Gradient phosphorus treatments (0.002, 0.01, 0.05, and 0.25 mg P L-1) were designed in mono- and co-cultures. Growth curves were recorded and fitted by the Monod equation. Moreover, the interspecific competition was analyzed by the Lotka-Volterra model. When mono-cultured in lower P conditions (≤ 0.01 mg P L-1), Synechococcus sp. obtained much higher biomass than M. aeruginosa. But, M. aeruginosa grew faster than Synechococcus sp. in higher P groups (≥ 0.05 mg P L-1) (p < 0.05). Synechococcus sp. has abilities to thrive in low-phosphorus environments, whereas M. aeruginosa favored high-phosphorus conditions. In co-cultures, Synechococcus sp. strongly inhibited M. aeruginosa at each P treatment.

Functional Sensing Interfaces of PEDOT:PSS Organic Electrochemical Transistors for Chemical and Biological Sensors: A Mini Review.

Organic electrochemical transistors (OECTs) are promising devices for applications in in vitro and in vivo measurements. OECTs have two important sensing interfaces for signal monitoring: One is the gate electrode surface; the other is the channel surface. This mini review introduced the new developments in chemical and biological detection of the two sensing interfaces. Specific focus was given on the modification technological approaches of the gate or channel surface. In particular, some unique strategies and surface designs aiming to facilitate signal-transduction and amplification were discussed. Several perspectives and current challenges of OECTs development were also briefly summarized.

Actuation of adaptive liquid microlens droplet in microfluidic devices: A review.

A significant growth of research on adaptive liquid lens is achieved over the past decades, and the field is still attracting increasing attentions, focusing on the transition from the current stage to the commercialized stage. The challenges faced are not limited to fabrication, material, small tuning range in focal lengths, additional control systems, limitations in special actuation methods and so on. In addition, the use of external driving parts or systems induce extra problem on bulky appearance, high cost, low reliability etc. Therefore, adaptive liquid lens will be an interesting research focus in both microfluidics and optofluidics science. This review attempts to summarize and focus on the droplet profile deformation under different driving mechanisms in tunable liquid microlens as well as the application in cameras, cell phone and so on. The driving techniques are generally categorized in terms of mechanisms and driving sources.

Effects of Low-Frequency Ultrasound on Microcystis aeruginosa from Cell Inactivation to Disruption.

Ultrasound can be used to induce cell resonance and cavitation to inhibit cyanobacterial growth, but it can also lead to increase in dissolved nutrients because of cell disruption. This study investigated the process from cell inactivation to disruption of Microcystis aeruginosa. Algal cells were sonicated (at 35 kHz) under various intensities and durations. Results showed that chlorophyll a content and Fv/Fm values decreased slightly within the first 5 min. Superoxide dismutase activity was stimulated and its peak value appeared at the fifth minute. After 20 min, considerable number of ruptured cells were observed and the concentrations of dissolved nitrogen and phosphorus increased rapidly. Finally, ammonia and nitrate merely composed a small portion of dissolved nitrogen. This study demonstrated that excessive ultrasound treatment can significantly rupture algal cells and lead to the release of cellular inclusions, which may cause ecological issues or public health problems. Based on our findings, ultrasonic intensity controlled at 0.035 W/mL and applied for a duration of 20 min delivers the optimal result in effectively inhibiting physiological activities of Microcystis aeruginosa without marked cell disruption. This will ultimately help to achieve algal control, while conserving energy and preserving the environment and human health.

Phosphoinositide kinases play key roles in norepinephrine- and angiotensin II-induced increase in phosphatidylinositol 4,5-bisphosphate and modulation of cardiac function.

The seemly paradoxical Gq agonist-stimulated phosphoinositide production has long been known, but the underlying mechanism and its physiological significance are not known. In this study, we studied cardiac phosphoinositide levels in both cells and whole animals under the stimulation of norepinephrine (NE), angiotensin II (Ang II), and other physiologically relevant interventions. The results demonstrated that activation of membrane receptors related to NE or Ang II caused an initial increase and a later fall in phosphatidylinositol 4,5-bisphosphate (PIP2) levels in the primary cultured cardiomyocytes from adult rats. The possible mechanism underlying this increase in PIP2 was found to be through an enhanced activity of phosphatidylinositol 4-kinase IIIß, which was mediated by an up-regulated interaction between phosphatidylinositol 4-kinase IIIß and PKC; the increased activity of phosphatidylinositol 4-phosphate 5-kinase γ was also involved for NE-induced increase of PIP2. When the systolic functions of the NE/Ang II-treated cells were measured, a maintained or failed contractility was found to be correlated with a rise or fall in corresponding PIP2 levels. In two animal models of cardiac hypertrophy, PIP2 levels were significantly reduced in hypertrophic hearts induced by isoprenaline but not in those induced by swimming exercise. This study describes a novel mechanism for phosphoinositide metabolism and modulation of cardiac function.

[Modulation of non-ion channel proteins by membrane potential].

The different concentration of specific ion species and the electrodiffusion of the ions down their electrochemical gradient generate transmembrane potential. The regulation of membrane potential for the function of numerous membrane proteins such as ion channels, transporters, pumps and enzymes plays primary role in the conversion of extracellular electric stimulation into a sequence of intracellular biochemical signals. Some ion channels regulated by membrane potential are well known, and the membrane non-ion channels protein is also modulated physiologically by membrane potential.

[Effects of Smad4 on liver fibrosis and hepatocarcinogenesis in mice treated with CCl4/ethanol].

To study the effects of Smad4 on liver fibrosis and hepatocarcinogenesis in mice treated with CCl(4)/ethanol. The wild-type mice (Smad4 +/+) and the Smad4 knockout mice (Smad4 +/-) were injected subcutaneously with carbon tetrachloride(CCl(4))/ethanol twice a week for twenty weeks. The expression of Smad4, TGFbeta1, Smad2, Smad3, Smad6, TIMP1, MMP2 and MMP9 was detected by RT-PCR. In the cirrhotic liver, the expression of Smad4 mRNA was significantly higher than that in the normal liver. Comparing with wild-type mice (Smad4 +/+), the TGFbeta1-Smad4 signaling was markedly attenuated in the Smad4 knockout mice (Smad4 +/-). After induction by CCl(4)/ethanol, the hepatic fibrosis in the Smad4 knockout mice (Smad4 +/-) was obviously alleviated compared with the wild-type mice (Smad4 +/+), and the incidence rate of hepatocarcinogenesis of the former was also lower than that of the latter(32.0% vs 41.9%). These results indicate that knocking out Smad4 can delay the progression of liver fibrosis and liver cancer.