List prices and clinical value of anticancer drugs in China, Japan, and South Korea: a retrospective comparative study.

Background: High prices of anticancer drugs have raised concerns due to their financial impact on patients and healthcare systems. This study aimed to assess the initial and latest list prices and clinical value of reimbursed anticancer drugs in China, Japan, and South Korea. Methods: We identified anticancer drugs newly approved by the National Medical Products Administration of China from January 2012 to June 2022, and by the Pharmaceuticals and Medical Devices Agency of Japan and the Ministry of Food and Drug Safety of South Korea up until June 2022. We compared initial and latest treatment prices between countries and assessed clinical value using patients' survival, quality of life (QoL), and European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). We calculated Spearman rank correlation coefficients of treatment prices with clinical value for individual countries and employed regression analyses to investigate whether the relationship between prices and clinical value was modified by the country setting. Findings: Our cohort included 91 anticancer drug indications, with 60 listed for reimbursement in China, 91 in Japan, and 87 in South Korea. Median treatment prices were highest in Japan, followed by South Korea, and lowest in China, both for initial prices (US$64082 vs. US$45529 vs. US$19144, p < 0.0001) and latest prices (US$50859 vs. US$31611 vs. US$18666, p < 0.0001). Over time, China (ß = -0.047, p < 0.0001) and South Korea (ß = -0.049, p < 0.0001) witnessed more significant price reductions compared to Japan (ß = -0.013, p = 0.011). The correlations between both initial and latest treatment prices and clinical value (QoL and ESMO-MCBS) were more significant and stronger in China and South Korea than in Japan, although Japan exhibited slightly stronger correlations in terms of survival compared to China and South Korea. The relationship between clinical value and treatment prices may not be modified by the country setting. Interpretation: In comparison, South Korea's list prices and their correlations with clinical value appear reasonable. Policymakers in Japan could enhance efficiency by controlling prices and aligning them with clinical value, while China would need to take substantial steps to expand anticancer drug coverage. Funding: National Natural Science Foundation of China (72374149 and 72074163), and China Center for South Asian Studies, Sichuan University.

CD39+ tumor infiltrating T cells from colorectal cancers exhibit dysfunctional phenotype.

Recent studies revealed that CD39 was highly expressed in tumor-specific CD4+ tumor infiltrating lymphocytes (TILs). However, the divergent function of CD39+ T cells remains to be elucidated in colorectal cancer (CRC). In this study, T cells from CRC patients and tumor-bearing mice were isolated to evaluate the function of CD39 in T cells. We found that CD39 was elevated in intratumoral T cells from CRC patients, and negatively correlated with cytokine secretion capacity. T cell activation induced CD39 expression, and CD39+ T cells produced more IFN-γ in response to CRC tumor antigens. In addition, CD39+ T cells in the spleens of tumor-bearing mice exhibited a stronger anti-tumor activity in vitro than CD39- T cells, but there was no significant difference in the anti-tumor activities between CD39- TILs and CD39+ TILs. Moreover, we found that CD39+ T cells expressed higher checkpoint molecules and contained a higher proportion of Treg cells than CD39- T cells, suggesting that CD39+ T cells may be correlated with an immunosuppressive phenotype. And CD39 expression on T cells could convert pro-inflammatory eATP to immunosuppressive eADO. However, both T cells from the vaccinated-wild-type mice and CD39-/- mice could recognize and eliminate tumor cells in vitro, and adoptive transfer of these T cells resulted in tumor growth inhibition in tumor-bearing mice. In conclusion, our study revealed the divergent functions of CD39+ T cells, which were reactive to tumor antigen but exhibited a dysfunctional phenotype.

A natural biogenic nanozyme for scavenging superoxide radicals.

Biominerals, the inorganic minerals of organisms, are known mainly for their physical property-related functions in modern living organisms. Our recent discovery of the enzyme-like activities of nanomaterials, coined as nanozyme, inspires the hypothesis that nano-biominerals might function as enzyme-like catalyzers in cells. Here we report that the iron cores of biogenic ferritins act as natural nanozymes to scavenge superoxide radicals. Through analyzing eighteen representative ferritins from three living kingdoms, we find that the iron core of prokaryote ferritin possesses higher superoxide-diminishing activity than that of eukaryotes. Further investigation reveals that the differences in catalytic capability result from the iron/phosphate ratio changes in the iron core, which is mainly determined by the structures of ferritins. The phosphate in the iron core switches the iron core from single crystalline to amorphous iron phosphate-like structure, resulting in decreased affinity to the hydrogen proton of the ferrihydrite-like core that facilitates its reaction with superoxide in a manner different from that of ferric ions. Furthermore, overexpression of ferritins with high superoxide-diminishing activities in E. coli increases the resistance to superoxide, whereas bacterioferritin knockout or human ferritin knock-in diminishes free radical tolerance, highlighting the physiological antioxidant role of this type of nanozymes.

A Thrombin-Activated Peptide-Templated Nanozyme for Remedying Ischemic Stroke via Thrombolytic and Neuroprotective Actions.

Ischemic stroke (IS) is one of the most common causes of disability and death. Thrombolysis and neuroprotection are two current major therapeutic strategies to overcome ischemic and reperfusion damage. In this work, a novel peptide-templated manganese dioxide nanozyme (PNzyme/MnO2 ) is designed that integrates the thrombolytic activity of functional peptides with the reactive oxygen species scavenging ability of nanozymes. Through self-assembled polypeptides that contain multiple functional motifs, the novel peptide-templated nanozyme is able to bind fibrin in the thrombus, cross the blood-brain barrier, and finally accumulate in the ischemic neuronal tissues, where the thrombolytic motif is "switched-on" by the action of thrombin. In mice and rat IS models, the PNzyme/MnO2 prolongs the blood-circulation time and exhibits strong thrombolytic action, and reduces the ischemic damages in brain tissues. Moreover, this peptide-templated nanozyme also effectively inhibits the activation of astrocytes and the secretion of proinflammatory cytokines. These data indicate that the rationally designed PNzyme/MnO2 nanozyme exerts both thrombolytic and neuroprotective actions. Giving its long half-life in the blood and ability to target brain thrombi, the biocompatible nanozyme may serve as a novel therapeutic agent to improve the efficacy and prevent secondary thrombosis during the treatment of IS.

Inhibition of OTUB2 suppresses colorectal cancer cell growth by regulating ß-Catenin signaling.

In the effort to identify deubiquitinating enzymes required for the growth of colorectal cancer (CRC) cells, we found that OTUB2 knockdown markedly inhibited the viability of these cancer cells in culture and in xenografted mice. It was also found that the level of OTUB2 was elevated in primary CRCs, and its high expression was a poor prognostic indicator for the patients. Interestingly, immunoprecipitation and LC-MS/MS analyses suggested that ß-Catenin was an OTUB2-interacting protein, and there was a positive correlation between OTUB2 and ß-Catenin expression in both CRC tissues and cell lines. We then performed reciprocal co-immunoprecipitations and demonstrated that OTUB2 and ß-Catenin bound to each other. Enforced expression of OTUB2 decreased ubiquitination of ß-Catenin and increased the half-life and intracellular level of ß-Catenin, whereas the catalytic inactive OTUB2 did not. OTUB2 also enhanced ß-Catenin-mediated transactivation as measured by TCF-luciferase and expression of endogenous CCND1 and MYC in CRC cells. These results indicated that OTUB2 was a potential target for therapeutic intervention for CRC.

Astragaloside IV derivative HHQ16 ameliorates infarction-induced hypertrophy and heart failure through degradation of lncRNA4012/9456.

Reversing ventricular remodeling represents a promising treatment for the post-myocardial infarction (MI) heart failure (HF). Here, we report a novel small molecule HHQ16, an optimized derivative of astragaloside IV, which effectively reversed infarction-induced myocardial remodeling and improved cardiac function by directly acting on the cardiomyocyte to reverse hypertrophy. The effect of HHQ16 was associated with a strong inhibition of a newly discovered Egr2-affiliated transcript lnc9456 in the heart. While minimally expressed in normal mouse heart, lnc9456 was dramatically upregulated in the heart subjected to left anterior descending coronary artery ligation (LADL) and in cardiomyocytes subjected to hypertrophic stimulation. The critical role of lnc9456 in cardiomyocyte hypertrophy was confirmed by specific overexpression and knockout in vitro. A physical interaction between lnc9456 and G3BP2 increased NF-κB nuclear translocation, triggering hypertrophy-related cascades. HHQ16 physically bound to lnc9456 with a high-affinity and induced its degradation. Cardiomyocyte-specific lnc9456 overexpression induced, but knockout prevented LADL-induced, cardiac hypertrophy and dysfunction. HHQ16 reversed the effect of lnc9456 overexpression while lost its protective role when lnc9456 was deleted, further confirming lnc9456 as the bona fide target of HHQ16. We further identified the human ortholog of lnc9456, also an Egr2-affiliated transcript, lnc4012. Similarly, lnc4012 was significantly upregulated in hypertrophied failing hearts of patients with dilated cardiomyopathy. HHQ16 also specifically bound to lnc4012 and caused its degradation and antagonized its hypertrophic effects. Targeted degradation of pathological increased lnc4012/lnc9456 by small molecules might serve as a novel promising strategy to regress infarction-induced cardiac hypertrophy and HF.

Protein-Nanocaged Selenium Induces t(8;21) Leukemia Cell Differentiation via Epigenetic Regulation.

The success of arsenic in degrading PML-RARα oncoprotein illustrates the great anti-leukemia value of inorganics. Inspired by this, the therapeutic effect of inorganic selenium on t(8; 21) leukemia is studied, which has shown promising anti-cancer effects on solid tumors. A leukemia-targeting selenium nanomedicine is rationally built with bioengineered protein nanocage and is demonstrated to be an effective epigenetic drug for inducing the differentiation of t(8;21) leukemia. The selenium drug significantly induces the differentiation of t(8;21) leukemia cells into more mature myeloid cells. Mechanistic analysis shows that the selenium is metabolized into bioactive forms in cells, which drives the degradation of the AML1-ETO oncoprotein by inhibiting histone deacetylases activity, resulting in the regulation of AML1-ETO target genes. The regulation results in a significant increase in the expression levels of myeloid differentiation transcription factors PU.1 and C/EBPα, and a significant decrease in the expression level of C-KIT protein, a member of the type III receptor tyrosine kinase family. This study demonstrates that this protein-nanocaged selenium is a potential therapeutic drug against t(8;21) leukemia through epigenetic regulation.

Location-allocation modelling for rational health planning: Applying a two-step optimization approach to evaluate the spatial accessibility improvement of newly added tertiary hospitals in a metropolitan city of China.

The inequity of access to healthcare services is still one of the most long-lasting problems confronted by worldwide countries. Under such context where maldistributed healthcare resources have posed huge challenges in achieving cross-regional efficiency and equity of healthcare services, rational allocation of newly added healthcare resources has become rather critical to policy makers. To address this issue, we applied a two-step optimization approach to investigate the spatial allocation of newly added tertiary general healthcare resources in Chengdu, a metropolitan city of China. The case study of Chengdu was utilized as an example to illustrate the feasibility of such spatial optimization approach in practice in terms of supporting regional health planning related decision-making procedures in China, as well as evaluating the performance of healthcare resource allocation related strategies actually implemented. Using current and historical health planning data, we sought to optimize tertiary general hospitals' locations to maximize population coverage of healthcare services in the first step, and to achieve equitable access to healthcare services among different residential locations via assigning the capacity (beds) to each hospital in the second step. Results suggested that the spatial optimization of newly added healthcare resources would theoretically enhance both efficiency and equity substantially. Specifically, if implemented in practice, such optimized spatial allocation of healthcare resources would theoretically contribute to improved efficiency as reflected by a 5% increase and a 15% increase in population coverage and the weighted median value of spatial accessibility, respectively. In addition, this would contribute to achieve enhanced equity as reflected by a 27% decrease in the weighted standard deviation of spatial access. These findings are anticipated to offer valuable policy implications to inform the spatial allocation decisions of healthcare resources in China as well as other countries confronted with similar challenges, and the two-step optimization approach could be applied to facilitate future rational health plannings.

PYR-41, an inhibitor of ubiquitin-activating enzyme E1, attenuates 2,4-dinitrochlorobenzene-induced atopic dermatitis-like skin lesions in mice.

PYR-41 is an irreversible and cell permeable inhibitor of ubiquitin-activating enzyme E1, and has been reported to inhibit the degradation of IκB protein. Previous studies have shown that PYR-41 has effects on anti-inflammatory, but whether it has therapeutic effects on allergic dermatitis is unclear. The aim of this research was to explore the therapeutic effects of PYR-41 on atopic dermatitis. The effects of PYR-41 on the activation of NF-κB signaling pathway and the expression of inflammatory genes in HaCat cells were tested by western blot and qPCR. A mouse model was built, and the AD-like skin lesions were induced by 2,4-dinitrochlorobenzene (DNCB). Then, the treatment effects of PYR-41 were examined by skin severity score, ear swelling, ELISA, and qPCR. The results showed that PYR-41 can significantly reduce the K63-linked ubiquitination level of nuclear factor-κB essential modulator (NEMO) and tumor necrosis factor receptor associated factor 6 (TRAF6), inhibit the proteasomal degradation of IκBα, thereby activate TNF-α-induced NF-κB signaling pathway in HaCat cells. In addition, DNCB-treated mice have significant reduction in symptoms after treated by PYR-41, including reduced ear thickening and reduced skin damage. Serum tests showed that PYR-41 significantly reduced the expression of IgE, IFN-γ, and TNF-α. In conclusion, the current results suggest that PYR-41 has potential to reduce the symptoms of atopic dermatitis.

The development and application of a two-step surveillance process for Healthy China Initiative based on wide coverage interagency data.

BACKGROUND: Healthy China is a nationwide health strategy aiming at improving health from diverse dimensions, and strengthening high-quality assessment is essential for its stimulation. However, there is limited evidence in the surveillance of the actual performance of the initiative at regional levels. This study innovatively proposes a two-step surveillance process which comprehensively monitors Healthy China Initiative based on regional realities, thus provides guidance for policymaking. METHODS: A flexible indicator system was firstly developed basing on Delphi survey and focus group discussions. And then the Analysis Hierarchical Process and the TOPSIS method were used to determine the weights of indicators and calculate comprehensive indexes as the surveillance outcomes. A pilot study was conducted in a typical area in China to verify the applicability of the process. RESULTS: Following the surveillance process and basing on the implementation of Healthy China Initiative in the target region, an indicator system comprised of 5 domains and 23 indicators with weights was first developed specifically for the pilot area. Then 1848 interagency data of the study area were collected from 8 provincial institutions/departments to calculate the indexes and ranks of the five domains which were health level, healthy living, disease prevention and control, health service, and healthy environment. The outcomes showed that Healthy China Initiative in the pilot area had been constantly improved since the strategy proposed, while there were still issues to be tackled such as the deficient monitoring mechanisms and unevenly development progress. CONCLUSIONS: This study proposed a pragmatic surveillance process with indicators which could be tailored for specific context of target regions and produce meaningful surveillance outcomes to inform decision-making for policymakers, and also provided a theoretical foundation as well as empirical evidence for further health strategies and plannings assessment studies.

Physicochemical and Functional Similarity Assessment Between Proposed Bevacizumab Biosimilar BAT1706 and Reference Bevacizumab.

BACKGROUND: BAT1706 is a proposed biosimilar of bevacizumab, a vascular endothelial growth factor A (VEGF-A)-targeting biologic used to treat several different cancers, including metastatic colorectal cancer. A comprehensive physicochemical and functional similarity assessment is a key component of demonstrating biosimilarity between a reference biologic and a proposed biosimilar. Here we report the physicochemical and functional similarity of BAT1706 and reference bevacizumab sourced from both the United States (US-bevacizumab) and the European Union (EU-bevacizumab). METHOD: A large range of product attributes, including primary and higher order structure, post-translational modifications, purity, stability, and potency, were characterized for BAT1706 and EU/US-bevacizumab using sensitive state-of-the-art analytical techniques. Up to 18 lots of US- and 29 lots of EU-bevacizumab, and 10 unique drug substance lots of BAT1706, were assessed. RESULT: BAT1706 was shown to have an identical amino acid sequence and an indistinguishable higher-order structure compared with EU/US-bevacizumab. BAT1706 and EU/US-bevacizumab also exhibited similar post-translational modifications, glycan profiles, and charge variants. Potency, assessed using a wide range of bioassays, was also shown to be comparable between BAT1706 and EU/US-bevacizumab, with statistical equivalence demonstrated for VEGF-A binding and neutralizing activity. CONCLUSION: Overall, this extensive comparability exercise demonstrated BAT1706 to match EU/US-bevacizumab in terms of all physicochemical and functional attributes assessed.

SARS-Cov-2 Spike-S1 Antigen Test Strip with High Sensitivity Endowed by High-Affinity Antibodies and Brightly Fluorescent QDs/Silica Nanospheres.

The extensive research into developing novel strategies for detecting respiratory syndrome coronavirus 2 (SARS-CoV-2) antigens in clinical specimens, especially the sensitive point-of-care testing method, is still urgently needed to reach rapid screening of viral infections. Herein, a new lateral flow immunoassay (LFIA) platform was reported for the detection of SARS-CoV-2 spike-S1 protein antigens, in which four sensitive and specific SARS-CoV-2 mouse monoclonal antibodies (MmAbs) were tailored by using quantum dot (QD)-loaded dendritic mesoporous silica nanoparticles modified further for achieving the -COOH group surface coating (named Q/S-COOH nanospheres). Importantly, compact QD adsorption was achieved in mesoporous channels of silica nanoparticles on account of highly accessible central-radial pores and electrostatic interactions, leading to significant signal amplification. As such, a limit of detection for SARS-CoV-2 spike-S1 testing was found to be 0.03 ng/mL, which is lower compared with those of AuNPs-LFIA (traditional colloidal gold nanoparticles, Au NPs) and enzyme-linked immunosorbent assay methods. These results show that optimizing the affinity of antibody and the intensity of fluorescent nanospheres simultaneously is of great significance to improve the sensitivity of LFIA.

How nursing students' risk perception affected their professional commitment during the COVID-19 pandemic: the mediating effects of negative emotions and moderating effects of psychological capital.

Nurses play a pivotal role in the delivery of medical services. Professional commitment is crucial for nursing professionals' long-term, healthy, and sustainable development. However, nursing students' professional commitment levels are currently unsatisfactory in China, especially given that the COVID-19 pandemic has posed unprecedented challenges to the profession. Therefore, studies investigating the professional commitment levels of nursing students and the underlying influencing factors are urgently required. This study explored how nursing students' risk perceptions, negative emotions, and psychological capital affected their professional commitment during the COVID-19 pandemic. A cross-sectional study was conducted among nursing students using risk perception, professional commitment, negative emotions, and psychological capital scales. An analysis of 1142 Chinese nursing students suggested that nursing students' risk perception positively impacted professional commitment and that negative emotions mediated this association. Importantly, psychological capital moderates the mediating effect of negative emotions and can buffer the negative emotions caused by risk perception. This study demonstrated that effective intervention strategies should be implemented in multiple dimensions such as education, individual, public and society to improve the professional commitment of nursing students.

Hydrothermal treatment enhances energy recovery from pig manure digestate and improves the properties of residues.

Energy recovery from biowaste is of high significance for a sustainable society. Herein, hydrothermal treatment (HT) was applied to valorize pig manure digestate. The effects of hydrothermal operational parameters, including temperature (130-250 °C), residence time (15-90 min), and total solid (TS) concentration (10%-20%), on reducing sugar yield were investigated in this study. Among them, hydrothermal temperature was identified as the most important factor influencing reducing sugar yield, followed by the TS concentration and time. The optimal hydrothermal conditions for the pig manure digestate were 175.6 °C, 35.4 min and a TS concentration of 10% with a reduced sugar yield of 9.81 mg gTS-1. The addition of hydrolysate could enhance methane production by 21.6-50.4% from the anaerobic digestion of pig manure than that without the hydrolysate addition. After HT, the hygienic quality, including fecal coliform number and ascaris egg mortality, was improved in the residual digestate. Antibiotics such as sulfamonomethoxine, oxytetracycline, doxycycline and sulfaclodazine in the pig manure digestate were decomposed during HT and decreased environmental risk. These findings indicated that the hydrothermal process might be an effective technique to recover energy from the digestate of livestock and poultry manure and to improve the residual digestate for subsequent utilization.

Evaluation and Optimization of Cultural Perception of Coastal Greenway Landscape Based on Structural Equation Model.

The island-type greenway should emphasize the role of maintaining and promoting the island cultural landscape as it serves the function of a general greenway green infrastructure while also having a unique landscape appearance. The northern greenway of Pingtan is used as an example in the paper to illustrate how regional culture is perceived. The first part of the analysis looks at how demographic factors affect the quality of cultural perception. The study reveals that: from a gender perspective, women are more likely than men to perceive regional culture; from an age perspective, people between the ages of 18 and 40 are more likely to perceive regional culture; older people and children are less likely to perceive regional culture; and from a level of education perspective, the higher the education, the stronger the perception. The relationship between tourists' perceived quality, cognitive image, perceived value, satisfaction, and loyalty to the cultural expression of the greenway landscape is then analyzed by building a structural equation model. According to the findings, visitors' perceptions of the island's cultural quality have a positive impact on their cognitive images and perceptions of value, while their satisfaction with the cultural expressions along the coastal greenway has a positive impact on their loyalty.

Genetic compensation response could exist in colorectal cancer: UPF3A upregulates the oncogenic homologue gene SRSF3 expression corresponding to SRSF6 to promote colorectal cancer metastasis.

BACKGROUND: Genetic compensation response (GCR) is a mechanism that maintains the robustness of functional genes, which has been recently identified. Whether GCR exists in tumors and its effects on tumor progression remains unknown. METHODS: Whole exome sequencing was performed to identify premature termination codon (PTC) gene mutations in colorectal cancer (CRC) tissues. RNA sequencing, Cancer Cell Line Encyclopedia database analysis, and high-throughput output of homologous genes using the Ensemble genome database were performed to further identify homologous genes of target PTC gene mutations. RESULTS: Serine and arginine-rich splicing factor 3 (SRSF3) increased the invasion ability in CRC cells and could be the target gene of up-frameshift 3A (UPF3A). The deletion of the 660th base A in the coding sequence region of SRSF6 caused a frameshift mutation of serine at position 220 (s220fs), which contributed to a PTC UAA termination of translation in HCT116 cells. We further found that SRSF3 was the only homologue of SRSF6 with a frameshift mutation. The transfection of s220fs of SRSF6 into HCT116 cells led to upregulation of its corresponding oncogenic homologue gene SRSF3 expression to promote CRC metastasis. SRSF3 was highly expressed in CRC liver metastases and was positively correlated with UPF3A expression and contributed to poor prognosis. CONCLUSION: GCR may exist in CRC and exert effects on the progression of CRC. Targeted inhibition of UPF3A could reduce the GCR effects and suppress the expression of oncogenic homologue genes corresponding to PTC mutations, indicating a novel therapeutic strategy for treatment of CRC metastasis.

Development of Sequence-Controlled, Degradable, and Cytocompatible Oligomers with Explicit Fragmentation Pathways.

Sequence-defined and degradable polymers can mimic biopolymers, such as peptides and DNA, to undertake life-supporting functions in a chemical way. The design and development of well-structured oligomers/polymers is the most concern for the public, even to further uncover their degradation process illustrating the degraded products and their properties. However, seldom investigation has been reported on the aforementioned aspects. In this work, the alternating photo-reversible addition-fragmentation chain-transfer (photo-RAFT) single unit monomer insertion (SUMI) of different N-substituted maleimides and thermal radical ring-opening SUMI of a cyclic ketene acetal monomer (i.e., 5,6-benzo-2-methylene-1,3-dioxepane (BMDO)) is adopted, to produce two degradable pentamers owing to the conversion of the exo-methylene group of BMDO into ester bonds along the main chains of the prepared products. Moreover, the possible degraded approach of pentamers is studied by combining high-resolution mass spectrometry (HRMS) and liquid chromatography-mass spectrometry (LC-MS) for the first time. This work also sheds light on the precise structures and cytotoxicity of SUMI products and their degraded compounds, proposing a detailed and credible outlook for biomedical applications.

Complement C1s as a diagnostic marker and therapeutic target: Progress and propective.

The molecules of the complement system connect the effectors of innate and adaptive immunity and play critical roles in maintaining homeostasis. Among them, the C1 complex, composed of C1q, C1r, and C1s (C1qr2s2), is the initiator of the classical complement activation pathway. While deficiency of C1s is associated with early-onset systemic lupus erythematosus and increased susceptibility to bacteria infections, the gain-of- function variants of C1r and C1s may lead to periodontal Ehlers Danlos syndrome. As C1s is activated under various pathological conditions and associated with inflammation, autoimmunity, and cancer development, it is becoming an informative biomarker for the diagnosis and treatment of a variety of diseases. Thus, more sensitive and convenient methods for assessing the level as well as activity of C1s in clinic samples are highly desirable. Meanwhile, a number of small molecules, peptides, and monoclonal antibodies targeting C1s have been developed. Some of them are being evaluated in clinical trials and one of the antibodies has been approved by US FDA for the treatment of cold agglutinin disease, an autoimmune hemolytic anemia. In this review, we will summarize the biological properties of C1s, its association with development and diagnosis of diseases, and recent progress in developing drugs targeting C1s. These progress illustrate that the C1s molecule is an effective biomarker and promising drug target.

Sesame allergy: mechanisms, prevalence, allergens, residue detection, effects of processing and cross-reactivity.

Sesame allergy is a serious public health problem and is mainly induced by IgE-mediated reactions, whose prevalence is distributed all over the world. Sesame has been included on the priority allergic food list in many countries. This review summarizes the mechanism and prevalence of sesame allergy. The characteristics, structures and epitopes of sesame allergens (Ses i 1 to Ses i 7) are included. Moreover, the detection methods for sesame allergens are evaluated, including nucleic-acid, immunoassays, mass spectrometry, and biosensors. Various processing techniques for reducing sesame allergenicity are discussed. Additionally, the potential cross-reactivity of sesame with other plant foods is assessed. It is found that the allergenicity of sesame is related to the structures and epitopes of sesame allergens. Immunoassays and mass spectrometry are the major analytical tools for detecting and quantifying sesame allergens in food. Limited technologies have been successfully used to reduce the antigenicity of sesame, involving microwave heating, high hydrostatic pressure, salt and pH treatment. More technologies for reducing the allergenicity of sesame should be widely investigated in future studies. The reduction of allergenicity in processed sesames should be ultimately confirmed by clinical studies. What's more, sesame may exhibit cross-reactivity with peanut and tree nuts.

Research progress of anti-environmental factor stress mechanism and anti-stress tolerance way of Saccharomyces cerevisiae during the brewing process.

Saccharomyces cerevisiae plays a decisive role in the brewing of alcohol products, and the ideal growth and fermentation characteristics can give the pure flavor of alcohol products. However, S. cerevisiae can be affected profoundly by environmental factors during the brewing process, which have negative effects on the growth and fermentation characteristics of S. cerevisiae, and seriously hindered the development of brewing industry. Therefore, we summarized the environmental stress factors (ethanol, organic acids, temperature and osmotic pressure) that affect S. cerevisiae during the brewing process. Their impact mechanisms and the metabolic adaption of S. cerevisiae in response to these stress factors. Of note, S. cerevisiae can increase the ability to resist stress factors by changing the cell membrane components, expressing transcriptional regulatory factors, activating the anti-stress metabolic pathway and enhancing ROS scavenging ability. Meantime, the strategies and methods to improve the stress- tolerant ability of S. cerevisiae during the brewing process were also introduced. Compared with the addition of exogenous anti-stress substances, mutation breeding and protoplast fusion, it appears that adaptive evolution and genetic engineering are able to generate ideal environmental stress tolerance strains of S. cerevisiae and are more in line with the needs of the current brewing industry.