Search

The advent of cancer immunotherapy has imparted a transformative impact on cancer treatment paradigms by harnessing the power of the immune system. However, the challenge of practical and precise targeting of malignant cells persists. To address this, engineered nanoparticles (NPs) have emerged as a promising solution for enhancing targeted drug delivery in immunotherapeutic interventions, owing to their small size, low immunogenicity, and ease of surface modification. This comprehensive review delves into contemporary research at the nexus of NP engineering and immunotherapy, encompassing an extensive spectrum of NP morphologies and strategies tailored toward optimizing tumor targeting and augmenting therapeutic effectiveness. Moreover, it underscores the mechanisms that NPs leverage to bypass the numerous obstacles encountered in immunotherapeutic regimens and probes into the combined potential of NPs when co-administered with both established and novel immunotherapeutic modalities. Finally, the review evaluates the existing limitations of NPs as drug delivery platforms in immunotherapy, which could shape the path for future advancements in this promising field.

The hole transport layer (HTL) is a crucial component in planar antimony sulfide (Sb2S3) solar cell. However, the issue of high cost, poor environmental stability and toxic benzene-based solvents for preparation represent significant challenges for the efficient organic HTLs. In contrast, low-cost and environmentally friendly inorganic hole transport materials have garnered considerable attention due to their excellent carrier mobility and environmental stability. Herein, thermal evaporated inorganic manganese sulfide (MnS) thin films were prepared as HTL for full inorganic Sb2S3 solar cell. The effects of post-annealing treatment on the structure, photoelectric properties of MnS films and device performance were investigated. The post-annealing treatment enables MnS HTL to exhibit high carrier mobility and suitable energy band matching characteristics, thereby suppressing the internal charge recombination and reducing the voltage loss in the device. This ultimately results in a high photovoltaic conversion efficiency (PCE) of 5.66%, which is more than a twofold increase in efficiency compared to that of device with unannealed MnS HTL. Furthermore, the optimal MnS HTL-based Sb2S3 solar cell demonstrated superior environmental stability (around 5.59% degradation in 30 days), compared to that of device with organic Spiro-OMeTAD HTL (around 20% degradation in 30 days). The study offers a material choice and post-processing solution for the development of high-efficiency all-inorganic Sb2S3 solar cells.

The digital economy now drives China’s new economic growth. However, with various industries’ digital transformation (DT), the consequent environmental pollution problems must be addressed. To achieve a better balance between economic growth and environmental protection, digitalization and carbon dioxide (CO2) emissions reduction targets should be achieved. In promoting the DT of manufacturing, it is essential to consider the industry’s CO2 emissions and the CO2 emission spillover effects (CO2SE). This paper first constructs a model of CO2SE generated and suffered in the DT of industries using input–output techniques, i.e., the perpetrator and victim effects, and measures these effects. Then, the cross-sectional inter-industry differences and vertical time-series characteristics are analyzed based on the measurement results. Finally, the convergence test of CO2 emission spillover effects in the digital transformation (CO2SE-DT) of China’s manufacturing industry is conducted, and the test results are analyzed. The research results show that (1) digital infrastructure-dependent and technology-intensive manufacturing have the largest CO2SE-DT, followed by capital-intensive and labor-intensive manufacturing in that order. (2) The whole victim effect in the DT of China’s manufacturing industry shows an “N” trend. In addition, according to the time-series changes of the perpetrator effect in the DT of China’s manufacturing industry between 2000 and 2014, China’s manufacturing industry can be classified into three types: stable, fluctuating downward, and fluctuating upward, among which the fluctuating upward type is the key industry of concern for CO2 emissions. (3) There is no gradual decrease in the industry differences in CO2SE-DT of China’s manufacturing industry, but manufacturing industries with low CO2SE-DT levels have faster growth rates compared with high-level manufacturing industries and eventually achieve convergence of CO2SE-DT rate of change. However, there is a significant difference in the results of the industry difference analysis for different types of manufacturing industries.

Objectives: Dog-mediated human rabies remains an important public health problem in China. In this study, we aimed to understand the spatiotemporal variation of rabies and examine its nonmedical ecological factors. Methods: In this study, we used the annual incidence data for rabies at the province level in China to describe the incidence trends for the period 2004-2019 and used a Bayesian hierarchical spatiotemporal model to determine the impacts of environmental, economic, and demographic factors. Results: From 2004 to 2019, there were 26,593 cases reported in 31 provinces in Mainland China, and the annual incidence increased from 0.02 per 100,000 in 2004 to 0.14 in 2007, substantially decreased in 2008, and was gradually declining thereafter. Guizhou, Guangxi, Hunan, and Hainan were four high-risk provinces, and Yunnan and Anhui provinces showed an increased risk in 2018 and 2019. Temperature and per capita gross domestic product were significantly positively correlated with the disease risk. The standardized morbidity ratio of rabies is likely to increase by 28% (relative risk: 1.28, 95% credible interval: 1.13-1.36) for every 1°C rise in temperature, and 17% (relative risk: 1.17, 95% credible interval: 1.01-1.34) for every 10,000 yuan increase in per capita gross domestic product. Conclusion: In most provinces in China, the risk of rabies has been reduced to a persistently low level. However, the progress of rabies control in six provinces have been less than satisfactory. The study highlights interventions, such as enhancing animal vaccination need to be implemented in these priority areas.

Hepatocellular carcinoma is one of the most common gastrointestinal malignancies. Anti-angiogenesis therapies have recently demonstrated promise in the treatment of malignancies, although early treatment benefits may be accompanied by metastasis over time. Additional and more effective anti-angiogenic treatment modalities are therefore needed. We previously found that Yes-associated protein 1 (YAP1) expression is increased in hepatocellular carcinoma (HCC), particularly around tumor-associated blood vessels, suggesting a role in angiogenesis. The YAP1 inhibitor verteporfin is presently in anti-angiogenic clinical trials for the treatment of various cancers. Depleted YAP1 from vascular endothelial cells effectively reduced proliferation and tube formation, validating its utility as an anti-angiogenesis target. We also showed that YAP1 depletion or inhibition in vascular endothelial cells leads to increased release of exosomes containing the long non-coding RNA (lncRNA) MALAT1 into the tumor microenvironment. Direct exosomal transfer of MALAT1 to hepatic cells leads to increased hepatic cell invasion and migration via activation of extracellular signal-regulated kinase 1/2 (ERK1/2) signaling. These observations may explain the occurrence of distant tumor metastasis with YAP1-associated anti-angiogenic therapy over time. It provides insight into new pathways and treatment paradigms that may be targeted to increase the long-term success of anti-angiogenic therapies.

Natural gas depressurization at city gate stations can cause hydrate formation, necessitating preheating before pressure regulation. To reduce the high energy consumption of traditional city gate station preheating processes, this study introduces four novel multi-energy coupled systems: photovoltaic-air source heat pump (PV-ASHP), solar thermal-combined heat and power-ASHP (ST-CHP-ASHP), CHP-ASHP, and ASHP system, with a typical city gate station in Shanghai taken as the research case. Dynamic energy simulation systems were developed in Dymola software to evaluate the proposed systems from energy, environmental, and economic perspectives, conducting a comparison with conventional boiler preheating systems, including sensitivity analysis of energy prices on system economics. Results indicate PV-ASHP has the lowest annual total cost (ATC) and shortest discounted payback period, while ATC values for ST-CHP-ASHP, CHP-ASHP, and ASHP increase by 6.4 %, 9.6 %, and 12.6 %, respectively. ST-CHP-ASHP and PV-ASHP demonstrate advantages in primary energy rate and carbon emissions, with ST-CHP-ASHP performing slightly better than PV-ASHP. Currently, PV-ASHP demonstrates the highest development potential. If photovoltaic feed-in tariffs remain constant, and natural gas prices decrease by over 12.5 % or CHP feed-in tariffs increase by over 38.4 %, ST-CHP-ASHP becomes more economically viable. This research provides valuable insights for retrofitting China's existing city gate station preheating systems.

Owing to incurable castration-resistant prostate cancer (CRPC) ultimately developing after treating with androgen deprivation therapy (ADT), it is vital to devise new therapeutic strategies to treat CRPC. Treatments that target programmed cell death protein 1 (PD-1) and programmed death ligand-1 (PD-L1) have been approved for human cancers with clinical benefit. However, many patients, especially prostate cancer, fail to respond to anti-PD-1/PD-L1 treatment, so it is an urgent need to seek a support strategy for improving the traditional PD-1/PD-L1 targeting immunotherapy. In the present study, analyzing the data from our prostate cancer tissue microarray, we found that PD-L1 expression was positively correlated with the expression of heterogeneous nuclear ribonucleoprotein L (HnRNP L). Hence, we further investigated the potential role of HnRNP L on the PD-L1 expression, the sensitivity of cancer cells to T-cell killing and the synergistic effect with anti-PD-1 therapy in CRPC. Indeed, HnRNP L knockdown effectively decreased PD-L1 expression and recovered the sensitivity of cancer cells to T-cell killing in vitro and in vivo, on the contrary, HnRNP L overexpression led to the opposite effect in CRPC cells. In addition, consistent with the previous study, we revealed that ferroptosis played a critical role in T-cell-induced cancer cell death, and HnRNP L promoted the cancer immune escape partly through targeting YY1/PD-L1 axis and inhibiting ferroptosis in CRPC cells. Furthermore, HnRNP L knockdown enhanced antitumor immunity by recruiting infiltrating CD8+ T cells and synergized with anti-PD-1 therapy in CRPC tumors. This study provided biological evidence that HnRNP L knockdown might be a novel therapeutic agent in PD-L1/PD-1 blockade strategy that enhanced anti-tumor immune response in CRPC.

Sorafenib is a first-line molecular-target drug for advanced hepatocellular carcinoma (HCC), and reducing sorafenib resistance is an important issue to be resolved for the clinical treatment of HCC. In the current study, we identified that ABCC5 is a critical regulator and a promising therapeutic target of acquired sorafenib resistance in human hepatocellular carcinoma cells. The expression of ABCC5 was dramatically induced in sorafenib-resistant HCC cells and was remarkably associated with poor clinical prognoses. The down-regulation of ABCC5 expression could significantly reduce the resistance of sorafenib to HCC cells. Importantly, activation of PI3K/AKT/NRF2 axis was essential for sorafenib to induce ABCC5 expression. ABCC5 increased intracellular glutathione (GSH) and attenuated lipid peroxidation accumulation by stabilizing SLC7A11 protein, which inhibited ferroptosis. Additionally, the inhibition of ABCC5 enhanced the anti-cancer activity of sorafenib in vitro and in vivo. These findings demonstrate a novel molecular mechanism of acquired sorafenib resistance and also suggest that ABCC5 is a new regulator of ferroptosis in HCC cells.

Mercury ion (Hg2+) is a toxic heavy metal ion and Hg2+ is convertible to methylmercury (MeHg) by many aquatic microorganisms, leading to bioaccumulation and biomagnification in aquatic organisms, which can interfere with brain development and function in humans. This study employs a newly developed AIEgen (Aggregation-induced emission fluorogen) to quantify and visualise the process of MeHg bioaccumulation in vivo on the species of water flea Daphnia carinata. Two approaches to MeHg absorption were taken, either by direct incubation in a MeHg solution or by indirect consumption of algae contaminated with MeHg. We analysed the relationship between the ratio of photoluminescence (PL) intensities (I585/I480) and MeHg concentration (CMeHg) and generated a master curve for determining MeHg concentration based on the measurement of PL intensities. Fluorescent image analysis showed the occurrence of MeHg in D. carinata to be mainly in the compound eyes, optic nerve and carapace. This study indicates that MeHg absorption can be quantified and visualised in the body of zooplankton, and the MeHg transfer to zooplankton is more likely through direct exposure than via indirect food intake. The accumulation of MeHg in the eye and the nervous system could be the cause of the high mortality of D. carinata exposed to MeHg in water.