Molecular force-induced liberation of transforming growth factor-beta remodels the spleen for ectopic liver regeneration.

BACKGROUND & AIMS: Ectopic liver regeneration in the spleen is a promising alternative to organ transplantation for treating liver failure. To accommodate transplanted liver cells, the splenic tissue must undergo structural changes to increase extracellular matrix content, demanding a safe and efficient approach for tissue remodelling. METHODS: We synthesised sulphated hyaluronic acid (sHA) with an affinity for the latent complex of transforming growth factor-ß (TGF-ß) and cross-linked it into a gel network (sHA-X) via click chemistry. We injected this glycan into the spleens of mice to induce splenic tissue remodelling via supraphysiological activation of endogenous TGF-ß. RESULTS: sHA-X efficiently bound to the abundant latent TGF-ß in the spleen. It provided the molecular force to liberate the active TGF-ß dimers from their latent complex, mimicking the 'bind-and-pull' mechanism required for physiological activation of TGF-ß and reshaping the splenic tissue to support liver cell growth. Hepatocytes transplanted into the remodelled spleen developed into liver tissue with sufficient volume to rescue animals with a metabolic liver disorder (Fah-/- transgenic model) or following 90% hepatectomy, with no adverse effects observed and no additional drugs required. CONCLUSION: Our findings highlight the efficacy and translational potential of using sHA-X to remodel a specific organ by mechanically activating one single cytokine, representing a novel strategy for the design of biomaterials-based therapies for organ regeneration. IMPACT AND IMPLICATIONS: Cell transplantation may provide a lifeline to millions of patients with end-stage liver diseases, but their severely damaged livers being unable to accommodate the transplanted cells is a crucial hurdle. Herein, we report an approach to restore liver functions in another organ - the spleen - by activating one single growth factor in situ. This approach, based on a chemically designed polysaccharide that can mechanically liberate the active transforming growth factor-ß to an unusually high level, promotes the function of abundant allogenic liver cells in the spleen, rescuing animals from lethal models of liver diseases and showing a high potential for clinical translation.

Distinguishing the Vaccine Effectiveness of Inactivated BBIBP-CorV Vaccine Booster Against the Susceptibility, Infectiousness, and Transmission of Omicron Stains: A Retrospective Cohort Study in Urumqi, China.

INTRODUCTION: With COVID-19 vaccination rolled out globally, increasing numbers of studies have shown that booster vaccines can enhance an individual's protection against the infection, hospitalization, and death caused by SARS-CoV-2. This study evaluated the effectiveness of COVID-19 vaccine BBIBP-CorV booster against being infected (susceptibility), infecting others (infectiousness), and spreading the disease from one to another (transmission). METHODS: This retrospective cohort study investigated the close contacts of all officially ascertained COVID-19 confirmed cases in Urumqi, China between August 1 and September 7, 2022. Eligible records were divided into four subcohorts based on the vaccination status of both the close contact and their source case: group 2-2, 2-dose contacts seeded by 2-dose source case (as the reference level); group 2-3, 3-dose contacts seeded by 2-dose source case; group 3-2, 2-dose contacts seeded by 3-dose source case; and group 3-3, 3-dose contacts seeded by 3-dose source case. In the four subcohorts, multivariate logistic regression models were used to examine the vaccine effectiveness (VE) for the BBIBP-CorV booster dose. We adjusted for potential confounding variables, including the sex and age of source cases and close contacts, the calendar week of contact history and contact settings. We evaluated the statistical uncertainty using a 95% confidence interval (CI). In addition, we conducted subgroup analyses to evaluate VE by sex. RESULTS: The sample sizes of groups 2-2, 2-3, 3-2, and 3-3 were 1184, 3773, 4723, and 27,136 individuals, respectively. Overall VE against susceptibility (group 2-3 vs 2-2) was 42.1% (95% CI 10.6, 62.5), VE against infectiousness (group 3-2 vs 2-2) was 62.0% (95% CI 37.2, 77.0), and VE against transmission (group 3-3 vs 2-2) was 83.7% (95% CI 75.1, 89.4). In the sex-stratified subgroups, male close contacts showed similar VE compared to the overall. However, among female close contacts, while the booster dose improved VE against infectiousness and VE against susceptibility, the VEs were not significantly different from zero. CONCLUSION: BBIBP-CorV vaccine booster was associated with mild to moderate levels of protection against Omicron susceptibility, infectiousness, and transmission. Real-world assessment of protective performance of COVID-19 vaccines against the risk of Omicron strains is continuously needed, and may provide information that helps vaccination strategy.

Does new-type urbanization curb haze pollution? A case study from China.

The rapid urbanization process has led to a high concentration of population and economic activities in urban space, thus leading to severe environmental pollution. The concept of new-type urbanization has been proposed in China to combat the pollution associated with urbanization. This study analyzes the interaction effect of new-type urbanization with land, industry, and technology on haze pollution, using Chinese provincial-level panel data, and employs a STIRPAT model with interaction terms for empirical testing. The results find that new-type urbanization can significantly reduce the national haze pollution level; meanwhile, the optimization of intensive urban land use level, industrial structure, and technological innovation can interact with it to promote haze reduction, and there is regional heterogeneity. The improvement of intensive urban land use and industrial structure in the central region will significantly enhance the haze reduction effect of new-type urbanization, while the improvement of technological innovation in the west will instead weaken its haze reduction effect, and the interaction in the eastern region is not significant. This research provides a theoretical basis for better implementation of new-type urbanization construction and effective promotion of green and sustainable urban development.

Research on Microstructure and Properties of AlSi10Mg Fabricated by Selective Laser Melting.

In order to obtain high-performance aluminum alloy parts fabricated by selective laser melting, this paper investigates the relationship between the process parameters and microstructure properties of AlSi10Mg. The appropriate process parameters are obtained: the layer thickness is 0.03 mm, the laser power is 370 W, the scanning speed is 1454 mm/s, and the hatch spacing is 0.16 mm. With these process parameters, the ultimate tensile strength of the as-printed status is 500.7 ± 0.8 MPa, the yield strength is 311.5 ± 5.9 MPa, the elongation is 7.7 ± 0.5%, and the relative density is 99.94%. After annealing treatment at 275 °C for 2 h, the ultimate tensile strength is 310.8 ± 1.3 MPa, the yield strength is 198.0 ± 2.0 MPa, and the elongation is 13.7 ± 0.6%. The mechanical properties are mainly due to the high relative density, supersaturate solid solution, and fine dispersed Si. The supersaturate solid solution and nano-sized Si formed by the high cooling rate of SLM. After annealing treatment, the Si have been granulated and grown significantly. The ultimate tensile strength and yield strength are reduced, and the elongation is significantly improved.

Air pollution particles hijack peroxidasin to disrupt immunosurveillance and promote lung cancer.

Although fine particulate matter (FPM) in air pollutants and tobacco smoke is recognized as a strong carcinogen and global threat to public health, its biological mechanism for inducing lung cancer remains unclear. Here, by investigating FPM's bioactivities in lung carcinoma mice models, we discover that these particles promote lung tumor progression by inducing aberrant thickening of tissue matrix and hampering migration of antitumor immunocytes. Upon inhalation into lung tissue, these FPM particles abundantly adsorb peroxidasin (PXDN) - an enzyme mediating type IV collagen (Col IV) crosslinking - onto their surface. The adsorbed PXDN exerts abnormally high activity to crosslink Col IV via increasing the formation of sulfilimine bonds at the NC1 domain, leading to an overly dense matrix in the lung tissue. This disordered structure decreases the mobility of cytotoxic CD8+ T lymphocytes into the lung and consequently impairs the local immune surveillance, enabling the flourishing of nascent tumor cells. Meanwhile, inhibiting the activity of PXDN abolishes the tumor-promoting effect of FPM, indicating the key impact of aberrant PXDN activity on the tumorigenic process. In summary, our finding elucidates a new mechanism for FPM-induced lung tumorigenesis and identifies PXDN as a potential target for treatment or prevention of the FPM-relevant biological risks.

Foreign direct investment, environmental regulation, and haze pollution: empirical evidence from China.

As China's economy continues to grow, more and more attention is being paid to environmental pollution issues, including haze pollution, which is the most prominent of the air problems. In order to alleviate the haze pollution problem while ensuring the normal operation of the economy, the government has adopted an environmental regulation policy along with the introduction of foreign direct investment. This study uses a fixed effects model and two-stage least squares to examine the correlation of foreign direct investment and environmental regulation to the haze pollution level by using the Chinese provincial panel data from 2008 to 2019. We found a positive interaction between the foreign direct investment and environmental regulation, where a high-quality investment promotes the haze reduction, and the environmental regulation can enhance this effect. The results approve the possibilities that China can bring the merit investment and reduce its air pollution simultaneously, but how to balance the interaction between environmental regulation and the investment needs to draw attention.

Haze management: is urban public transportation priority effective?

Public transportation is often considered as a green travel mode to alleviate the negative externalities such as traffic congestion and haze pollution generated from transport. However, is prioritizing urban public transportation actually conducive to haze emission reduction? In this study, considering special emphasis on the cumulative effect of haze, a dynamic panel model is constructed to analyze and quantify the impact of public transportation on haze pollution by using the data of 284 cities in China, and the heterogeneity of the impact in cities with different pollution levels is examined. Several interesting findings are derived from the empirical results. First, the development of urban public transportation can significantly alleviate urban haze pollution. Second, the haze reduction effect of public transportation in cities with different pollution levels is non-universal. Comparatively speaking, the haze reduction effect of public transportation in lightly polluted cities is more evident than that in heavily polluted cities. Therefore, in order to reduce haze pollution in a more effective manner, China should continue to promote urban public transportation priority strategy. Moreover, the government should also formulate differentiated traffic development strategies to effectively alleviate the urban traffic burdens.

O2-(2,4-dinitrophenyl) diazeniumdiolate derivative induces G2/M arrest via PTEN-mediated inhibition of PI3K/Akt pathway in hepatocellular carcinoma cells.

OBJECTIVES: The study aimed to investigate whether G2/M arrest caused by O2-(2,4-dinitrophenyl) diazeniumdiolate derivative (JS-K) was related to PTEN-mediated inhibition of PI3K/Akt pathway in hepatocellular carcinoma cells. METHODS: The cell apoptosis was detected by DAPI staining and Annexin V-FITC/PI dual staining. The cell cycle was analysed by PI staining. The expressions of cell cycle-related proteins, PTEN and PI3K/AKT pathway were measured by Western blot. The rat model of primary hepatic carcinoma was established with diethylnitrosamine to verify the antitumour effects of JS-K. KEY FINDINGS: The morphological features of apoptosis were obviously reversed when the cells were pre-treated with bpv(pic), followed by treatment with JS-K. JS-K mediated G2/M arrest and down-regulated expressions of cyclin B1. Meanwhile, it up-regulated the expression of p-Cdk1, p-Chk2 and p-CDC25C while down-regulated that of Cdk1 and CDC25C. Furthermore, JS-K also enhanced the expressions of p21 and p27, PTEN and p53 while decreased the expressions of p-PTEN, PI3K and p-AKT. However, bpv(pic) and Carboxy-PTIO could reverse JS-K-induced G2/M cell arrest and PTEN-mediated inhibition of the PI3K/AKT pathway. The same results were also testified in the rat model of primary hepatic carcinoma. CONCLUSIONS: JS-K caused G2/M arrest through PTEN-mediated inhibition of the PI3K/AKT pathway involving Chk2/CDC25C/Cdk1 checkpoint.