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Supplementary Figure 1-6

Immunosuppression is common in head and neck squamous cell carcinoma (HNSCC). In previous studies, the TIGIT/CD155 pathway was identified as an immune-checkpoint signaling pathway that contributes to the “exhaustion” state of infiltrating T cells. Here, we sought to explore the clinical significance of TIGIT/CD155 signaling in HNSCC and identify the therapeutic effect of the TIGIT/CD155 pathway in a transgenic mouse model. TIGIT was overexpressed on tumor-infiltrating CD8+ and CD4+ T cells in both HNSCC patients and mouse models, and was correlated with immune-checkpoint molecules (PD-1, TIM-3, and LAG-3). TIGIT was also expressed on murine regulatory T cells (Treg) and correlated with immune suppression. Using a human HNSCC tissue microarray, we found that CD155 was expressed in tumor and tumor-infiltrating stromal cells, and also indicated poor overall survival. Multispectral IHC indicated that CD155 was coexpressed with CD11b or CD11c in tumor-infiltrating stromal cells. Anti-TIGIT treatment significantly delayed tumor growth in transgenic HNSCC mouse models and enhanced antitumor immune responses by activating CD8+ T-cell effector function and reducing the population of Tregs. In vitro coculture studies showed that anti-TIGIT treatment significantly abrogated the immunosuppressive capacity of myeloid-derived suppressor cells (MDSC), by decreasing Arg1 transcripts, and Tregs, by reducing TGFβ1 secretion. In vivo depletion studies showed that the therapeutic efficacy by anti-TIGIT mainly relies on CD8+ T cells and Tregs. Blocking PD-1/PD-L1 signaling increased the expression of TIGIT on Tregs. These results present a translatable method to improve antitumor immune responses by targeting TIGIT/CD155 signaling in HNSCC.

Supplementary Figure Legends

Pearson's correlation coefficients (r) of CMTM6 with immune checkpoints correlation analysis

CMTM6, a regulator of PD-L1 expression, also modulates tumor immunity. Little is known about the function of CMTM6 and its mechanism of action in head and neck squamous cell carcinoma (HNSCC). In this study, we found by IHC analysis that CMTM6 overexpression predicted a poor prognosis for patients with HNSCC. We discovered that CMTM6 expression was correlated with increased activity through the Wnt/β-catenin signaling pathway, which is essential for tumorigenesis, maintenance of cancer stem cells (CSC), and the epithelial-to-mesenchymal transition (EMT) characteristic of multiple cancers. We used short hairpin RNA to eliminate expression of CMTM6, which led, in HNSCC cells, to reduced expression of nuclear β-catenin as well as inhibition of stem cell–like properties, TGFβ-induced EMT, and cell proliferation. Consistent with these results, we identified a significant positive correlation between expression of CMTM6 and EMT- and CSC-related genes in The Cancer Genome Atlas (TCGA). We found positive correlations for both RNA and protein between expression of CMTM6 and immune checkpoint components. CMTM6 silencing–induced PD-L1 downregulation delayed SCC7 tumor growth and increased CD8+ and CD4+ T-cell infiltration. The proportions of PD-1+, TIM-3+, VISTA+, LAG-3+, and B7-H3+ exhausted T cells were decreased significantly in the CMTM6 knockdown group. CMTM6 thus regulates stemness, EMT, and T-cell dysfunction and may be a promising therapeutic target in the treatment of HNSCC.

Supplementary Figures

Association of CMTM6 expression and clinicopathologic parameters in HNSCC

Supplementary Figure Legends

The clustered regularly interspaced short palindromic repeats (CRISPR) system is inarguably the most valuable gene editing tool ever discovered. Currently, three classes of CRISPR-based genome editing systems have been developed for gene editing, including CRISPR/CRISPR associate system (Cas) nucleases, base editors, and prime editors. Ever-evolving CRISPR technology plays an important role in medicine; however, the biggest obstacle to its use in clinical practice is the induction of off-target effects (OTEs) during targeted editing. Therefore, continuous improvement and optimization of the CRISPR system for reduction of OTEs is a major focus in the field of CRISPR research. This review aims to provide a comprehensive guide for optimization of the CRISPR-based genome editing system.

Most of the malignant melanomas are already in the middle and advanced stages when they are diagnosed, which is often accompanied by the metastasis and spread of other organs.Besides, the prognosis of patients is bleak. The characteristics of the local immune microenvironment in metastatic melanoma have important implications for both tumor progression and tumor treatment. In this study, data on patients with metastatic melanoma from the TCGA and GEO datasets were selected for immune, stromal, and estimate scores, and overlapping differentially expressed genes (DEGs) were screened. A nine-IRGs prognostic model (ALOX5AP, ARHGAP15, CCL8, FCER1G, GBP4, HCK, MMP9, RARRES2 and TRIM22) was established by univariate COX regression, LASSO and multivariate COX regression. Receiver operating characteristic (ROC) curves were used to test the predictive accuracy of the model. Immune infiltration was analyzed by using CIBERSORT, Xcell and ssGSEA in high-risk and low-risk groups. The immune infiltration of the high-risk group was significantly lower than that of the low-risk group. Immune checkpoint analysis revealed that the expression of PDCD1, CTLA4, TIGIT, CD274, HAVR2 and LAG3 were significantly different in groups with different levels of risk scores. WGCNA analysis found that the yellow-green module contained seven genes (ALOX5AP, FCER1G, GBP4, HCK, MMP9, RARRES2 and TRIM22) from the nine-IRG prognostic model, of which the yellow-green module had the highest correlation with risk scores. The results of GO and KEGG suggested that the genes in the yellow-green module were mainly enriched in immune-related biological processes. Finally, we analyzed the prognostic ability and expression characteristics of ALOX5AP, ARHGAP15, CCL8, FCER1G, GBP4, HCK, MMP9, RARRES2 and TRIM22 in metastatic melanoma. Overall, a prognostic model for metastatic melanoma based on the characteristics of the tumor immune microenvironment was established, which was helpful for further studies.It could function well in helping people to understand the characteristics of the immune microenvironment in metastatic melanoma and to find possible therapeutic targets.

Ecosystem services are the bridge between ecosystem functions and human welfare. Climate regulation service (CRS) has an extremely important role in ecosystem services. It is important to conduct a comprehensive assessment based on the whole process of CRS occurrence for scientific assessment of ecosystem services. With Fuzhou City as a case, we carried out the assessment of CRS at the local and municipal scales, and analyzed the spatial and temporal variations of CRS at the administrative unit and land use and land cover scales. The results showed that the aggregated physical capacity of CRS in Fuzhou City was 4.01×10生态系统服务是衔接生态系统功能和人类福利的桥梁,气候调节服务在生态系统服务中占有极其重要的地位。对气候调节服务发生的全过程进行评估,对科学开展生态系统服务评估具有重要意义。本研究以福州市为案例,开展地市尺度气候调节服务评估,分析气候调节服务在行政单元、地类尺度上的时空变化特征。结果表明: 2015、2018年,福州市气候调节服务总实物量分别为4.01×10

Exploring the spatio-temporal variation characteristics of carbon source and carbon sink under different disposal methods of crop straw is of great significance for optimizing the utilization policy of crop straw resources in China and realizing the goal of maximizing carbon emission reduction and carbon neutralization. Based on data from National Statistical Yearbook, we examined the changing trends of both the amount and value of carbon emission, carbon emission reduction, carbon sink enhancement under different crop straw disposal methods in 31 provinces of Chinese mainland. The results showed that the mean annual carbon emissions of straw burning in China from 2008 to 2019 were 8.74 million tons of CO探明农作物秸秆在不同处置方式下的碳源汇时空变化特征,对优化我国秸秆资源利用政策、实现碳减排最大化、实现碳中和目标具有重要意义。本研究以国家统计年鉴数据为基础,对我国31个省农作物秸秆不同处置下的碳排放、碳减排、碳增汇及其价值量的变化趋势进行研究。结果表明: 2008—2019年间,我国秸秆焚烧年均碳排放量为874万t CO

We report the first systematic evaluation of the reaction of trifluoromethyl diazomethane (2,2,2-trifluorodiazoethane, CF3CHN2) with drug-like molecules. We found our previous copper-catalyzed transformation of carboxylic acids to the corresponding N-trifluoro­ethylimides with CF3CHN2 and acetonitrile is well-suited for the late-stage modification of drug and drug-like acids. A procedure that enables the use of solid nitriles and nitriles with high boiling points as viable substrates is also disclosed.

In this work, a specific monoclonal antibody against tyramine was produced based on a new hapten design. Then, we developed a high-resolution multicolor colorimetric immunoassay for tyramine based on this antibody by integrating enzyme-induced multicolor generation with smartphone-assistant signal readout. The multicolor generation is due to the shift of the local surface plasmon resonance band of gold nanostructure controlled by alkaline phosphatase-induced the growth of gold nanostars. Quantitative detection of tyramine was achieved via analyzing the red/blue channel values of assay solution's image taken by a smartphone with the support of a color recognizer application. The limit of detection of this immunoassay for tyramine detection in beef, pork and yoghurt was 19.7 mg/kg or L. The average recoveries were between 83 % and 103 %., and the results were validated by high performance liquid chromatography to be reliable. Overall, this developed immunoassay provides a promising platform for on-site detection of tyramine.

Puerarin has potential therapeutic effects on diabetic nephropathy (DN), but the effectiveness as a treatment for DN and the underlying mechanism remain to be elucidated. The DN-like model induced by high glucose in vitro and the DN model induced by streptozotocin in vivo were used to observe the effect of puerarin. The results showed that puerarin can enhance the activity of HBZY-1 cells and reduce apoptosis. in vivo enzymelinked immunosorbent assay and biochemical assay showed that puerarin can improve DN symptoms. Using hematoxylin and eosin staining to stain kidney tissues confirmed that puerarin has a protective effect on DN. Furthermore, puerarin can reduce the content of collagen type IV, laminin LN, tumor necrosis factor, p38, CREB, Fos, Jun, and MMP9 in HBZY-1 cells and DN rats. In conclusion, puerarin can effectively prevent apoptosis in vitro and improve DN-like symptoms by inhibiting the p38/MAPK signaling pathway in vivo. Therefore, puerarin has the potential to treat DN.

Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger (P-Rex) proteins control many fundamental cellular functions including cell migration, actin cytoskeletal rearrangement and adhesion in many cancers. However, P-Rex1 expression and its prognostic effect and possible clinical value are not clearly elucidated in human oral squamous cell carcinoma (OSCC). Here, OSCC tissue microarrays were used to verify the expression levels of P-Rex1, coinhibitory immune checkpoints and tumor associated macrophage (TAM) markers, and to analyze the relationship between PREX1 expression levels and clinicopathological characteristics in OSCC. The study found that P-Rex1 expression was elevated in OSCC compared to dysplasia and normal mucosa (P

Our study investigated the expression of malic enzyme 2 (ME2) in human oral squamous cell carcinoma (OSCC) and associated pathological and clinical pattern. We demonstrated that human OSCC tissues expressed a high level of ME2, and the overexpression of ME2 is closely connected to a high pathological grade, lymphatic metastasis, large tumor size and human papillomavirus (HPV) (P < 0.001). Similarly, high levels of ME2 expression in OSCC tissue were shown to be correlated with poor prognosis (P < 0.05). The expression of ME2 was correlated with Slug, SOX2, and aldehyde dehydrogenase-1 (ALDH1) immunoreactivity.ME2 was shown to be overexpressed in OSCC tissue and indicated a poor prognosis for OSCC. ME2 may be correlated with several immune markers.

The gross economic-ecological product (GEEP) accounting is crucial to promote the construction of ecological civilization, and practice the ideas of "lucid waters and lush mountains are invaluable assets". GEEP accounting had been conducted at national and provincial scales, but not at urban scale. According to the economic and ecological development, the GEEP accounting framework was built in Fuzhou City. The GEEP value of Fuzhou City in 2015 and 2018 was calculated and the spatiotemporal variation was analyzed. The results showed that the GEEP value of Fuzhou City was 1208.568 billion yuan in 2015. Among which, the value of GDP and ecological regulation, and the cost of environmental degradation and ecological damage were 577.742, 636.420, 3.095 and 2.500 billion yuan, respectively. Minqing County had the highest GEEP, with a value of 170.022 billion yuan, which accounted for 14.1% of that in Fuzhou City. The lowered values were found in Fuqing City, Minhou County and Yongtai County, accounting for 12.2%, 12.1% and 10.4%, respectively. In 2018, the GEEP of Fuzhou City increased to 1445.399 billion yuan, with an increase rate of 19.6%, mainly due to the GDP increase (up by 47.4% from 2015). The highest proportions of GEEP were observed in Minqing County and Gulou District (12.0%), followed by Fuqing and Minhou counties (11.0%). Compared with 2015, the increase trends were observed for the total value of GEEP, unit area and per capita of GEEP values in Fuzhou City. The cost of environmental and ecological degradation in Fuzhou decreased by 7.2% and 12.4%, respectively, indicating that the overall ecological environment of Fuzhou was improving. The accounting of GEEP in Fuzhou could effectively make up for the shortage of GDP assessment at the urban scale in China. It could provide an instrument for Fuzhou government to formulate rational ecological civilization assessment system and promote regional sustainable development.经济生态生产总值(GEEP)核算是推进生态文明建设、践行“绿水青山就是金山银山”理论的重要实践。目前已有研究开展了全国和省级尺度的GEEP核算,但关于城市尺度的GEEP核算尚鲜见。本研究根据福州市经济和生态发展情况,构建了适于福州市的GEEP核算框架体系,对2015和2018年福州市GEEP进行核算,探讨了福州市GEEP时空变化特征。结果表明: 2015年,福州市GEEP为12085.68亿元,其中,国民生产总值(GDP)为5777.42亿元,生态调节价值为6364.20亿元,环境退化成本和生态破坏成本分别为30.95和25.00亿元;其中,闽清县GEEP值最大,为1700.22亿元,占全市GEEP的14.1%,其次为福清市、闽侯县和永泰县,占比分别为12.2%、12.1%和10.4%。2018年,福州市GEEP有所增加,达14453.99亿元,较2015年上升19.6%,主要源于GDP的增长(较2015年增长了47.4%),闽清县和鼓楼区GEEP占比较大(12.0%),其次为福清市和闽侯县(11.0%)。与2015年相比,2018年福州市GEEP、单位面积和人均GEEP均有所升高,环境退化和生态破坏成本有所下降(降幅分别为7.2%和12.4%),表明福州市生态环境整体向好。本研究对福州市GEEP的核算可有效弥补目前我国唯GDP论考核的不足,同时也可为福州市政府合理制定生态文明考核体系建设、促进区域可持续发展奠定科学基础。.

Wetland plays an important role in ecological protection and social development. Scientific and rational evaluation of the values of wetland ecosystem service is the basis of protection and sustainable utilization of wetland resources. How to scientifically and effectively assess the wetland ecosystem gross ecosystem product (GEP) and make it into the national GDP accounting system are the focus of the scientific community and government departments. In this study, the accounting framework of wetland ecosystem GEP was constructed. Based on multi-source data and from the aspects of function and value, the accounting of wetland GEP in Fuzhou City was carried out. The results showed that the GEP of wetland ecosystem in Fuzhou City was 239.23 billion yuan in 2015. Such value mainly came from the ecological regulation service value (157.869 billion yuan), which accounted for 66.0% of the total and was about 2.2 and 15.6 times of the product supply service value and cultural service value. Among the ecological regulation services of wetlands, hydrodynamic regulation service and climate regulation service were the highest. Together, they accounted for 82.9% of the ecological regulation service value. The ecological regulation value per unit area of wetland in Fuzhou City was 1347.8 thousand yuan·hm湿地在生态保护和社会发展中占据重要地位,科学合理评估湿地生态系统价值,是湿地保护与合理开发、确保湿地资源可持续性利用的基础。如何科学有效、标准化地评估湿地生态系统生产总值(GEP)并使之纳入国民经济体系核算是科学界和政府部门关注的焦点。本研究构建了湿地生态系统生产总值核算框架体系,并以福州市为研究案例,以多源数据为基础,从功能量与价值量层面,开展了福州市湿地GEP核算研究。结果表明: 2015年,福州市湿地生态系统GEP为2392.33亿元,主要源于湿地的生态调节服务价值(1578.69亿元,占总价值的66.0%),约是产品供给服务价值和精神文化服务价值的2.2和15.6倍。湿地生态调节服务中,以水流动调节服务价值和气候调节服务价值最高,两者占生态调节服务价值的82.9%。福州市湿地单位面积生态调节价值为134.78万元·hm

Ecological degradation accounting is a critical content of building green GDP and gross economic-ecological product (GEEP) accounting systems. With ecosystems in Fuzhou City as a research object, we built an accounting framework for the cost of ecological degradation according to the unreasonable human activity. Following the accounting framework, we calculated the ecological degradation cost in Fuzhou City of 2015 and 2018. The results showed that the ecological degradation cost in Fuzhou City of 2015 was 9.08 billion yuan, accounting for 1.6% of local GDP. For different ecosystem types, marine ecological degradation cost was the largest, about 6.311 billion yuan, accounting for 69.5% of the total loss, followed by wetland ecosystem, accounting for 28.7%, and then arable land, contributing only 1.8%. In term of functions, the cost of provisioning degradation was the largest, about 6.313 billion yuan, accounting for 69.5% of the total loss, followed by regulation loss, accounting for 27.5%, mainly from the loss of climate regulation and hydrological regulation. In the regional distribution, the ecological degradation cost was mainly concentrated in Lianjiang County, Luoyuan County, Fuqing City, and Minqing County, up to 8.092 billion yuan in total, accounting for 89.7% of total loss. Compared with 2015, the ecological degradation cost in 2018 decreased by 2.608 billion yuan, showing an obvious downward trend, with a decrease rate of 28.7%. The reductions were major in Lianjiang County (86.4%), Luoyuan County (14.8%), Fuqing City (19.9%), and Minqing County (12.6%), and mainly concentrated in marine and wetland ecosystems. Such a result indicated that people's awareness of ecological protection in Fuzhou City was increasing, and that the ecological damage due to human activity in marine and wetland system was obviously decreased. This study provided data support for promoting regional sustainable development and ecological civilization construction.生态系统破坏损失核算是构建绿色国民经济和经济生态生产总值核算体系的关键内容。本研究以福州市生态系统为研究对象,根据其人类不合理利用生态情况,构建了符合福州市的生态系统破坏损失核算框架体系,对2015和2018年福州市生态系统破坏损失进行核算。结果表明: 福州市2015年生态破坏损失成本为90.81亿元,占GDP比重的1.6%。在系统类型上,海洋的生态破坏损失最大,为63.11亿元,占总生态破坏损失的69.5%,其次为湿地生态系统,占比28.7%,农田生态破坏损失最小,占比仅为1.8%;在功能组成上,产品供给功能损失最大,为63.13亿元,占总生态破坏损失的69.5%,其次为调节功能损失,占比27.5%,主要源于水流动调节功能和气候调节功能损失;在区域分布上,生态破坏损失成本主要集中在罗源县、连江县、福清市和闽清县,累计高达80.92亿元,占总生态破坏损失的89.7%。与2015年相比,2018年福州市生态系统破坏损失成本减少26.08亿元,呈明显降低趋势,降幅达28.7%,主要源于连江县、罗源县、福清市和闽清县生态破坏损失成本的降低,降幅分别为86.4%、14.8%、19.9%和12.6%,主要源于海洋和湿地生态系统类型人为破坏率的降低,表明福州市人民生态保护意识不断增强,海洋与湿地系统人为生态破坏现象明显好转。本研究对生态系统生态破坏损失的定价为促进区域可持续发展和生态文明建设提供了数据支撑。.

With the continuous development of China's society and economy, the breadth and depth of cultivated land resources development and utilization have been continuously expanded, while the production efficiency and scale of cultivated land gradually have been improved. There were rapidly increases of carbon emission induced from cultivated land management, such as the agricultural inputs and energy consumptions. Taking carbon emission from cultivated land utilization in Northeast China as the research object, we determined the carbon emission accounting framework system according to the life cycle method. Based on estimation results of carbon emissions from 1979 to 2015 in Northeast China, the driver factor system affecting agricultural carbon emissions was constructed using logarithmic mean Divisia index model and the influence mechanism of cultivated land carbon emissions in Northeast China was deeply explored. The results showed that total carbon emission from cultivated land utilization in 2015 was 21.9% higher than that in 1979 and carbon emission intensity in 2015 was 1.54 t·hm随着我国社会经济的不断发展,耕地资源开发利用的广度和深度不断扩展,耕地的生产效率和生产规模逐步提高。与此同时,耕地管理活动中由农用品投入、能源消耗等产生的碳排放量也飞速增长。本研究以东北地区耕地利用碳排放为研究对象,采用生命周期法构建碳排放核算框架体系;基于东北地区1979—2015年碳排放量的估算结果,采用对数平均迪氏指数模型构建影响农业碳排放的驱动因素体系,深入探讨东北地区耕地碳排放的影响机制。结果表明: 与1979年相比,2015年耕地利用碳排放总量增长了21.9%,碳排放强度则降低了1.54 t·hm

The determination of regional ecological compensation quota and spatial selection are key issues in the study of horizontal transfer payment ecological compensation mechanism. Taking 12 districts of Fuzhou City as the basic research unit, we accounted the ecological function values of forest, grassland, wetland, agriculture, and marine ecosystems in 2015 and 2018. Combined with local economic development situation, we constructed an ecological compensation model. With this model, we determined the ecological compensation quota and spatial distribution of different ecosystems in various districts and counties of Fuzhou. The results showed that from 2015 to 2018, Gulou District had the largest ecological payment, with 36.384 billion yuan, followed by Mawei, Cangshan and Jin'an districts, with 7.809, 6.974 and 6.669 billion yuan, respectively. Luoyuan County and Taijiang District had lower payment, which were 2.942 and 1.903 billion yuan respectively. Among the areas requiring ecological compensation, Lianjiang County and Changle District had high compensation quotas, being 25.120 and 20.261 billion yuan, followed by Yongtai County (12.570 billion yuan). The compensation amounts in Minhou County, Fuqing City and Minqing County were less than 10 billion yuan. The distribution of ecological compensation differed across various ecosystems. In general, the main ecological compensation areas of forest, grassland, wetland and agriculture ecosystem were in Yongtai, Minqing, Minhou, Lianjiang and Luoyuan counties. The compensation amounts were 2.424-31.379 billion yuan in forest, 1.181-20.708 billion yuan in grassland, 1.015-45.493 billion yuan in wetland, and 5.780-23.954 billion yuan in cropland. The main regions that need compensation for marine ecosystem were Lianjiang County, Changle District, and Fuqing City, with the amount of compensation being 8.216-47.854 billion yuan. The results could properly reflect the coordinated development of regional ecological and economic conditions, which could provide a reference for the improvement of the ecological compensation mechanism in Fuzhou City.区域生态补偿额度的确定和空间选择是横向转移支付生态补偿机制研究的关键问题。本研究以福州市12区县为基本研究单元,通过核算2015和2018年福州市各区县森林、草地、湿地、农田和海洋五大生态系统的生态功能价值,结合当地经济发展状况,构建生态补偿模型,确定了福州市各区县不同生态系统的生态补偿额度及空间分布。结果表明: 2015—2018年间,生态支付额度最大的地区为鼓楼区(363.84亿元),其次为马尾区、仓山区和晋安区,分别为78.09、69.74和66.69亿元,罗源县和台江区的支付额度较小,分别为29.42和19.03亿元。需要生态补偿的区域中,连江县和长乐区的补偿额度较高,分别为251.20和202.61亿元,其次为永泰县(125.70亿元),再次为闽侯县、福清市和闽清县,补偿额度在100亿元以下。不同生态系统类型的生态补偿区域分布不同,其中,永泰县、闽清县、闽侯县、连江县和罗源县是森林、草地、湿地和农田生态系统的主要生态补偿区,森林、草地、湿地和农田的补偿额分别在24.24～313.79、11.81～207.08、10.15～454.93和57.80～239.54亿元;海洋生态系统的补偿区主要在连江县、长乐区和福清市,补偿额在82.16～478.54亿元。该结果较好地反映区域生态与经济协调发展状况,可为福州市生态补偿机制的完善提供参考。.

Fenitrothion (FN) residue in food is a serious threat to public health. Consequently, a sensitive, cost-effective, and convenient immunoassay for FN urgently needs to be fabricated to safeguard human health. Herein, a nanobody-alkaline phosphatase fusion protein (Nb-ALP)-based fluorescent ELISA using red emissive carbon dots (r-CDs) anchored cobalt oxyhydroxide nanosheet (CoOOH NS) composite was developed for detecting FN. Briefly, a Nb-ALP was obtained by autoinduction expression and employed as a recognition, signal transduction, and amplification element. As the fluorescence signal source, r-CDs were assembled with CoOOH NS to yield the r-CDs@CoOOH NS composite, leading to the fluorescence quenching of r-CDs via Förster resonance energy transfer (FRET). After competitive immunoreaction, the Nb-ALP bounded to the immobilized antigen can mediate the production of ascorbic acid, which can reduce the CoOOH NS to Co

Expression of the family with sequence similarity 3 member C (FAM3C) is necessary for the epithelial-mesenchymal transition (EMT). However, the expression level and clinicopathological significance of FAM3C in oral squamous cell carcinoma (OSCC) has not been thoroughly elucidated to date. We performed immunohistochemical staining on human OSCC specimens with FAM3C, co-inhibitory immune checkpoints, EMT markers, and cancer stem cells (CSCs) markers to analyze the expression levels and clinicopathological features of FAM3C in OSCC. There were 210 primary OSCC specimens, 69 oral epithelial dysplasia and 42 normal oral mucosae in our human OSCC tissue microarrays cohort. We observed that FAM3C expression was upregulated in OSCC compared with normal mucosa and epithelial dysplasia (P 0.001). Moreover, patients with higher FAM3C expression levels had a worse prognosis than those with lower expression levels (P0.05). Also, FAM3C expression was positively correlated with the immune checkpoints PD-L1, VISTA, and B7-H4, the EMT marker Slug and the CSC markers SOX2 and ALDH1. In conclusion, these findings suggested that overexpression of FAM3C in human OSCC may predict a poor prognosis for OSCC patients.

Microvesicles (MVs), which are cell‐derived membrane vesicles present in body fluids, are closely associated with the development of malignant tumours. Saliva, one of the most versatile body fluids, is an important source of MVs. However, the association between salivary MVs (SMVs) and oral squamous cell carcinoma (OSCC), which is directly immersed in the salivary milieu, remains unclear. SMVs from 65 patients with OSCC, 21 patients with oral ulcer (OU), and 42 healthy donors were purified, quantified and analysed for their correlations with the clinicopathologic features and prognosis of OSCC patients. The results showed that the level of SMVs was significantly elevated in patients with OSCC compared to healthy donors and OU patients. Meanwhile, the level of SMVs showed close correlations with the lymph node status, and the clinical stage of OSCC patients. Additionally, the ratio of apoptotic to non‐apoptotic SMVs was significantly decreased in OSCC patients with higher pathological grade. Consistently, poorer overall survival was observed in patients with lower ratio of apoptotic to non‐apoptotic SMVs. In conclusion, the elevated level of SMVs is associated with clinicopathologic features and decreased survival in patients with OSCC, suggesting that SMVs are a potential biomarker and/or regulator of the malignant progression of OSCC.

Although anti-PD-1 immunotherapy is widely used to treat melanoma, its efficacy still has to be improved. In this work, we present a therapeutic method that combines immunotherapy and starvation therapy to achieve better antitumor efficacy. We designed the CMSN-GOx method, in which mesoporous silica nanoparticles (MSN) are loaded with glucose oxidase (GOx) and then encapsulate the surfaces of cancer cell membranes to realize starvation therapy. By functionalizing the MSN's biomimetic surfaces, we can synthesize nanoparticles that can escape the host immune system and homologous target. These attributes enable the nanoparticles to have improved cancer targeting ability and enrichment in tumor tissues. Our synthetic CMSN-GOx complex can ablate tumors and induce dendritic cell maturity to stimulate an antitumor immune response. We performed an in vivo analysis of these nanoparticles and determined that our combined therapy CMSN-GOx plus PD-1 exhibits a better antitumor therapeutic effect than therapies using CMSN-GOx or PD-1 alone. Additionally, we used the positron emission tomography imaging to measuring the level of glucose metabolism in tumor tissues, for which we investigate the effect with the cancer therapy in vivo.