The aging of mesenchymal stromal cells (MSCs) is characterized by impaired osteogenic differentiation and enhanced adipogenic differentiation. Studies have identified stanniocalcin‑1 (STC1) as a core component of the senescence‑associated secretory phenotype and a regulator of osteoblast maturation; however, its role in MSC biology remains poorly understood. In the present study, bone marrow‑derived MSCs were used and in vitro functional assays together with molecular and omics‑based analyses were performed to investigate the role of STC1. It was observed that STC1 expression was upregulated in aged MSCs and during both osteogenic and adipogenic differentiation. Small interfering RNA‑mediated depletion of STC1 reduced cellular senescence and notably impaired osteogenic differentiation, whereas adipogenic and chondrogenic differentiation were not significantly affected. RNA sequencing revealed that STC1 knockdown led to the downregulation of osteogenesis‑related genes and the concomitant upregulation of inflammatory factors. Genes associated with closing differentially accessible regions (DARs) were enriched in osteogenic pathways, whereas those associated with opening DARs were predominantly involved in inflammatory responses. Mechanistically, STC1 knockdown led to the activation of NF‑κB signaling. Pharmacological inhibition assays using NF‑κB inhibitors were performed to validate pathway involvement. Pharmacological inhibition of NF‑κB signaling significantly mitigated the impairment in osteogenic differentiation and attenuated the inflammatory response induced by STC1 depletion. Collectively, these findings suggest that STC1 is involved in the regulation of osteogenic differentiation and inflammatory signaling through the modulation of NF‑κB activity in MSCs. Furthermore, targeting STC1 while inhibiting NF‑κB signaling may represent a promising therapeutic strategy for alleviating MSC dysfunction and age‑related bone loss.

Oral submucous fibrosis (OSF) is a chronic, progressive, premalignant disorder with expanding epidemiology, rising annual incidence, and increasing malignant transformation rates. Therefore, elucidating its pathogenesis and establishing early intervention strategies remain urgent priorities. In this study, we evaluated the interplay between USP10 and IL-6 and its potential influence on the development of oral submucous fibrosis. Immunohistochemistry and immunofluorescence were used to examine the correlation among IL-6, USP10, and pathological angiogenesis in OSF clinical samples and mouse models, revealing high IL-6 expression in the inflammatory microvasculature alongside downregulated USP10. Functional experiments on human umbilical vein endothelial cells (HUVECs) in vitro, including administration of recombinant human IL-6, demonstrated that USP10 inhibited angiogenesis, cell migration, and cell proliferation, and that targeting USP10 reversed IL-6-mediated pathological angiogenesis. RNA sequencing further identified differentially expressed genes in HUVECs, while mass spectrometry, western blotting, and co-immunoprecipitation uncovered that USP10 interacts with vascular endothelial growth factor receptor 1 (VEGFR1) and inhibits its ubiquitination, thereby suppressing angiogenesis. Collectively, these findings indicate that IL-6 promotes pathological angiogenesis by suppressing USP10 and its interaction with VEGFR1, thus accelerating OSF progression, and suggest that targeting USP10 may represent a promising mechanism for further investigation in OSF therapy.

Cisplatin-based chemotherapy responses are highly heterogeneous across cancers, with the mechanisms governing drug sensitivity remaining incompletely understood. Using genome-wide CRISPR-Cas9 knockout screening, we systematically characterized regulators of cisplatin response and uncovered a counterintuitive finding: mTOR inhibition promotes cisplatin tolerance, contradicting the canonical view that PI3K-AKT-mTOR activation confers chemoresistance. Mechanistically, both mTOR suppression and cisplatin treatment converge to activate cytoprotective autophagy, which enhances cancer cell survival under therapeutic stress. The amino acid transporter SLC7A5 was identified and validated as a key integrator of the mTOR-autophagy axis that modulates cisplatin sensitivity. SLC7A5 expression positively correlates with cisplatin sensitivity across cancer cell lines, and its downregulation is associated with cisplatin resistance in multiple cancer types, supporting its potential as a mechanistically grounded predictive biomarker. Translationally, leucine supplementation sensitizes cancer cells to cisplatin in an SLC7A5-mTOR-autophagy-dependent manner. Collectively, our study defines a novel mTOR-autophagy adaptive loop governing cisplatin tolerance, positions SLC7A5 as a central regulatory node with both biomarker and therapeutic target value, and proposes leucine supplementation as a simple, translatable strategy to improve cisplatin efficacy in SLC7A5-expressing tumors.

Objective: Multiple programmed cell death (PCD) pathways have been individually reported to be triggered by cisplatin, but whether and how they are co-regulated remains unclear. In this study, we comprehensively investigate the spectrum of cisplatin-induced PCD. Methods: We employed integrated in vitro and in vivo models, including human cancer cell lines, a Cal27 xenograft mouse model, and paired clinical specimens from an oral squamous cell carcinoma patient receiving neoadjuvant cisplatin-based chemotherapy. A comprehensive methodological suite-encompassing cell death assays, Western blotting, Hematoxylin and eosin staining, immunofluorescence, Cyclic multiplexed tissue staining, and pathway-specific pharmacological inhibitors was utilized to dissect the activation of apoptosis, necroptosis, pyroptosis, and ferroptosis. Results: Cisplatin simultaneously upregulates markers of PCD pathways (including apoptosis, necroptosis, pyroptosis, and ferroptosis) in a dose- or time-dependent manner. Pharmacological inhibition or genetic knockdown of key genes in each pathway significantly reduced cytotoxicity, confirming their functional roles. Notably, indicators of key pro-inflammatory death modalities, pyroptosis and ferroptosis, were prominently co-upregulated in both xenograft tumors and clinical patient samples, suggesting that these two forms of PCD may represent the predominant death forms in cisplatin-induced tumor cell death. Conclusion: Cisplatin induces the coordinated activation of multiple cell death programs within a unified framework. Prominent engagement of immunogenic cell death pathways, particularly pyroptosis and ferroptosis, provides a mechanistic basis for the clinically observed synergy between cisplatin and immune checkpoint blockade therapy.

Early intervention of precancers is significant for improving cancer outcome. EZH2-mediated epigenetic modification was responsible for the immune escape of cancers; besides, tumor immune evasion is correlated with the impaired MHC-I antigen presentation machinery (APM). Oral potentially malignant disorders (OPMDs), represented by oral leukoplakia (OLK), usually precede head and neck squamous cell carcinoma (HNSCC). EZH2 is correlated with malignant transformation (MT) of OPMDs including OLK, while it remains undetermined that whether EZH2 mediates the initiation of HNSCC by repressing APM. Herein, EZH2 was first reported to negatively correlate with MHC-I and CD8+ GZMB+ T subsets which promote antitumor immunity in OPMDs. In vitro study uncovered that EZH2 triggers H3K27me3 on the promoters of MHC-I associated genes such as HLA-A/B/C, B2M and TAP1. Next, we constructed one hydrogel loaded with GSK126, a specific EZH2 inhibitor, denoted as PPT@GSK126 which is well-tolerated and highly adhesive to mucosa. Preclinical trials demonstrated that topical PPT@GSK126 could significantly prevent the MT of OPMDs and induce robust specific immune killing of dysplastic cells; while individual local αPD-1 therapy was unavailable, PPT@GSK126 synergized with topical αPD-1 therapy to significantly repress the cancerization of OPMDs. As EZH2 is highly expressed in numerous precancers, PPT@GSK126 has broad application prospects for reducing these tumor burdens.

BACKGROUND:Serum response factor (SRF) and myocardial-associated transcription factor-A (MRTF-A) had different regulatory effects on the tumorigenesis and development in different cancers. However, the role of MRTF-A/SRF in oral squamous cell carcinoma (OSCC) remains to be determined. METHODS:CCK-8 assay, cell scratch experiment, and transwell invasion assay were conducted to investigate the effects of MRTF-A/SRF on biological behavior of OSCC cells. The expression pattern and prognostic value of MRTF-A/SRF in OSCC were analyzed based on cBioPortal website and TCGA database. Protein-protein interaction network was visualized to identify protein functions. Go and KEGG pathway analyses were performed to investigate related pathways. The effect of MRTF-A/SRF on epithelial-mesenchymal transformation (EMT) of OSCC cells was explored by western blot assay. RESULTS:Overexpression of MRTF-A/SRF inhibited the proliferation, migration, and invasion of OSCC cells in vitro. High expression of SRF was related to better prognosis of OSCC patients on hard palate, alveolar ridge, and oral tongue. Besides, overexpression of MRTF-A/SRF inhibited the EMT of OSCC cells. CONCLUSION:SRF was closely related to the prognosis of OSCC. High expression of SRF and its co-activator MRTF-A inhibited proliferation, migration, and invasion of OSCC cells in vitro, possibly via EMT suppression.

Background The clinical value and molecular characteristics of tumor differentiation in oral squamous cell carcinoma (OSCC) remain unclear. There is a lack of a related molecular classification prediction system based on pathological images for precision medicine. Methods Integration of epidemiology, genomics, experiments, and deep learning to clarify the clinical value and molecular characteristics, and develop a novel OSCC molecular classification prediction system. Results Large-scale epidemiology data ( n = 118,817) demonstrated OSCC differentiation was a significant prognosis indicator ( p < 0.001), and well-differentiated OSCC was more chemo-resistant than poorly differentiated OSCC. These results were confirmed in the TCGA database and in vitro. Furthermore, we found chemo-resistant related pathways and cell cycle-related pathways were up-regulated in well- and poorly differentiated OSCC, respectively. Based on the characteristics of OSCC differentiation, a molecular grade of OSCC was obtained and combined with pathological images to establish a novel prediction system through deep learning, named ShuffleNetV2-based Molecular Grade of OSCC (SMGO). Importantly, our independent multi-center cohort of OSCC ( n = 340) confirmed the high accuracy of SMGO. Conclusions OSCC differentiation was a significant indicator of prognosis and chemotherapy selection. Importantly, SMGO could be an indispensable reference for OSCC differentiation and assist the decision-making of chemotherapy.

Catechins are a group of natural polyphenols extracted from green tea. Notably, they have been proven to have excellent anti-HPV and anti-tumour properties and to be effective against some HPV-related diseases, showing great potential in the treatment of HPV-associated oral squamous cell carcinoma (HPV+ OSCC). However, the poor bioavailability, short half-lives, and stability issues of catechins hamper their clinical application. To overcome these shortcomings of catechins, we innovatively synthesised an injectable supramolecular hydrogel, namely catechin-phenylenebisboronic acid-isoguanosine (CPBisoG), with catechin (one of the simplest catechins) and isoguanosine (isoG), another natural product with self-assembly ability, via dynamic phenylborate diester bonds. The biodegradation and sustained-release time of the CPBisoG hydrogel in mice lasted up to 72 h. This supramolecular hydrogel not only functioned as a good local drug delivery platform with good stability, injectability, self-healing properties, biocompatibility, biodegradability, but also exhibited therapeutic effects toward HPV+ OSCC in vitro and in vivo. And interestingly, it also showed selective inhibition against HPV+ OSCC cells. In all, these results demonstrate that this catechin-based hydrogel could sustainedly and highly effectively treat HPV+ OSCC topically, which could also provide a promising strategy for the management of other HPV-associated diseases in the future.

In this project, we propose a highly effective photosensitizer that breaks through drug-resistant bacterial infections with zinc-doped carbon dots. By passing through the membrane of drug-resistant bacteria, the photosensitizers produce ROS in bacteria under the action of blue light to directly kill bacteria, so as to realize the antibacterial local treatment of drug-resistant bacteria. The experiment firstly uses an efficient one-step hydrothermal method to prepare zinc-doped red-light CDs as photosensitizers, in which zinc metal was doped to improve the optical properties of the CDs. Then we try first to use EDTA as a second-step attenuator for preparing CDs to obtain photosensitizers with high-efficiency and low toxicity. In vitro cytotoxicity tests, bacterial effect tests, and in vivo animal experiments have also demonstrated that this antibacterial method has great potential for clinical translation, with a bactericidal efficiency of up to 90%. More notably, we used this antibacterial regimen seven times repeatedly to simulate the bacterial resistance process, with a bactericidal efficiency of up to 90% every time. The result indicated that S. aureus did not develop resistance to our method, showing that our method has the potential to break through drug-resistant bacterial infections as an alternative to antibiotic candidates.

As a nano-material, carbon dots have been extensively studied and applied in many ways.

目的 分析优化手术流程在深低温保存钴-60灭菌自体颅骨修补颅骨缺损手术降低近期(1个月)并发症发生率的方法、优点及意义.方法 回顾性分析我院2018年10月～2020年10月收治的46例颅骨缺损病人的临床资料,全部采用深低温保存自体颅骨修补颅骨缺损.根据术前颅骨处理方式不同分为两组,实验组24例,采用80℃无菌生理盐水1000 ml+地塞米松20 mg复温30分钟;对照组22例,采用传统处理方式.结果 实验组皮下积液1例;对照组硬膜外血肿2例,皮下积液11例,其中严重皮下积液1例,颅骨感染1例(再手术).通过80℃无菌生理盐水+地塞米松20 mg复温30分钟,大大减少手术近期并发症,提升手术效果及病人舒适度.随访证实无骨瓣塌陷、无骨髓炎、无皮下积液.结论 改进颅骨处理方式能大大降低深低温保存自体颅骨修补颅骨缺损近期并发症.对于有条件开展自体颅骨修补的单位值得推荐,是一种简便、经济、安全、可行的方法.

以超高效液相色谱建立参芪复方浸膏的指纹图谱,对其浸膏的质量控制进行研究.采用Opalshell C18(100 mm×4.6 mm,2.6μm)为色谱柱,含有0.1％甲酸的乙腈为流动相A,0.1％甲酸为流动相B,采用梯度洗脱分离并在波长254 nm处进行检测,获得参芪复方浸膏指纹图谱;采用LC-MS-MS法对色谱峰进行检测并分析裂解途径,获得20个共有峰的组分与结构信息;基于超高效液相指纹图谱对11个批次不同产地的参芪复方药材质量进行相似度分析、聚类分析和主成分分析.所测各批次样品指纹图谱与对照图谱的相似度较高,具有良好的相关性,表明不同批次间成分含量变化小,成品质量稳定.该方法重复性、精密度和稳定性良好,测得的指纹图谱可较好地反映出参芪复方浸膏中组分的分布,是评价本品及其药材质量的较好方法.

DNA computation is considered a fascinating alternative to silicon-based computers; it has evoked substantial attention and made rapid advances. Besides realizing versatile functions, implementing spatiotemporal control of logic operations, especially at the cellular level, is also of great significance to the development of DNA computation. However, developing simple and efficient methods to restrict DNA logic gates performing in live cells is still a challenge. In this work, a series of DNA logic gates was designed by taking full advantage of the diversity and programmability of the G-quadruplex (G4) structure. More importantly, by further using the high affinity and specific endocytosis of cells to aptamer G4, an INHIBIT logic gate has been realized whose operational site is precisely restricted to specific live cells. The design strategy might have great potential in the field of molecular computation and smart bio-applications.

Carbon dots (CDS) have been proved to be a type of ideal biological imaging probe. They have the advantages of spontaneous fluorescence, anti-photobleaching, good biocompatibility and easy surface decoration, and are receiving special attention from researchers. The early imaging diagnosis of tumors has always been a practical means of clinical diagnosis. Finding an efficient and low-toxicity tumor probe is the continuous goal of tumor clinical diagnosis and treatment. Therefore, this article uses the modifiable properties of the surface structure of carbon dots, and at the same time, uses the characteristics of tumors with high expression of folate receptors (FR) that can specifically take up folic acid (FA) to construct folic acid carbon dot conjugates (FA–CDs) to achieve targeted tumor uptake. Firstly, CCK8 toxicity tests proved that FA–DCCDs had good biocompatibility and were almost non-toxic. Further, confocal cell imaging experiments, microplate quantitative experiments and flow cytometry experiments proved that FA–CDs were selective and more easily absorbed by tumor cells with high expression of folate receptors, and bare carbon dots could be absorbed into cells without selectivity. Through in vivo experiments, the law of injection of bare CDs into the body was explored, which proved that they had no obvious accumulation and had high distribution in the liver and kidneys. FA–CDs was applied to the targeted imaging of a mouse tumor model in vivo for the first time, which proved again that the carbon point coupled with folic acid had selectivity for tumor cells with high expression of FR receptors, which provided a basis for tumor drug research and early clinical diagnosis of tumors.

针对肿瘤血管抑制剂DX1002的含量测定,构建一种基于新型纳米碳点材料(CDs)的特异性荧光定量方法.以柠檬酸和尿素为原料,热解法制得碳点(CACCDs),经TEM、IR、UV/Vis、Flu等方法对其进行结构表征.内滤光效应下碳点荧光可被DX1002特异性定量猝灭,CACCDs浓度为250?μg/mL时,于λex/λem=400/530处测定猝灭前后的荧光差值(ΔF).结果表明,DX1002浓度在2.5～75?μg/mL范围内与ΔF具良好线性关系(r2=0.9988),检出限为1.16?μg/mL,平均加标回收率为101.7％(RSD=2.08％),常见细胞阳离子、微量金属离子、糖类、氨基酸等潜在共存物质及有关物质对测定无干扰,DX1002含量测定的结果(101.3％±1.33％)与HPLC法测定结果(99.4％±1.19％)基本吻合(P>0.05),但较HPLC分析时间快约75倍.该方法快速、灵敏、特异性强,可为建立DX1002高通量特异性体内分析方法提供体外定量的依据.

In many plant species nonzygotic embryos can develop from diploid somatic cells grown in tissue culture. Extracellular glycoproteins have been identified that can rescue arrested somatic embryos. One of these glycoproteins may be part of a mechanism that controls the expansion of plant cells.

According to WADA guidelines, the presence of Higenamine (HG) in urine should not be ≥10 ng/mL. HG is widely found in materials used in Chinese herbal medicines as well as food and additives. This paper is the first method wherein a rat model has been used to evaluate the pharmacokinetics of orally administered HG by LC-MS/MS and would be helpful in doping control analysis. The method was found to be linear over a concentration range of 0.5(lower limit of quantification, LLOQ)-500 ng/mL for plasma and 0.5(LLOQ)-1000 ng/mL for urine. The values for intra- and inter-day accuracy and precision did not deviate by >12.25% for HG in plasma and 5.87% in urine. Extraction recoveries of HG were 70.30-86.71% from plasma and 74.93%-79.29% from urine. HG was stable in plasma and urine after the extraction process and when exposed to different storage conditions. The findings of this study could provide some reference value for the assessment of HG misuse and for the control of intake and external application of HG-related materials (foods and medicinal herbs). Our key findings are that high levels of external application or oral administration of HG-rich materials may lead to a positive urine test for HG in athletes.

The effects of radial diffusion and mobile phase heating on the column efficiency during chromatographic separation were investigated. Starting from the heat transfer equation, an equation of plate height for liquid chromatography was derived using the principle of chromatographic dynamics, with consideration of the mobile phase friction and electric heat generation:H=2γDm/u+2λdpu1/3/u1/3+ω(Dm/dp)1/3+2ku/(1+k)2(1+κ0)kd+θ(κ0+κ0k+k)2dp2u/30Dmκ0(1+κ0)2(1+k)2+κi(κ0+κ0k+k)2dp5/3u2/3/3κ0ΩDm2/3(1+κ0)2(1+k)2+r02(κ0+κ0k+k)u/4Dr(1+k)exp(-Kr02α)This equation summarized the relationship between plate heights for high performance liquid chromatography (HPLC), ultra performance liquid chromatography (UPLC), capillary electrochromatography (CEC), and eliminate stagnant fluid layer chromatography (ESFLC) and various factors. The last term in the equation represented the contribution of radial diffusion and column heating to the plate height. When the linear velocity of the mobile phase was low and the column diameter was fine, the contribution of the frictional heat generation of the mobile phase to the plate height approached zero, and the plate height equation reduced to the Horvath and Lin equation. When the linear velocity of the mobile phase was too high, friction heat was generated in the column system. The temperature difference between the axis and the edge of the column increased, resulting in a decrease in the column efficiency. The temperature difference between the axis and the edge of the column was proportional to the square of the velocity of the mobile phase. The authors clearly point out that the column efficiency in liquid chromatography is closely related to the inner diameter of the column. The use of a column with a small inner diameter is conducive to high analytical speed and high efficiency, a very high mobile phase line velocity would serious degrade the column efficiency.

Molecular computation, a rapidly developing multidisciplinary research field, has attracted increasing attention. A series of combinational logic circuits at the molecular level have been constructed, however, the development of sequential logic circuits is still in its infancy due to the lack of ideal design tools. Taking advantage of unique assembly behaviors of cyanine dyes, we constructed a two-bit molecular counter circuit that can implement fundamental sequential logic functions, including number cumulating and descending. Further introducing a guanine-rich DNA strand as the cycle index, the counter can be reused several times and eventually be scaled up to count up to 16 numbers. The supramolecular circuit shows high programmability, flexibility, and reversibility, and it is prospected that the strategy would be applied in designing other advanced molecular circuits.

G-quadruplex (G4) is a four-stranded DNA structure, viewed as an emerging therapeutic target in oncology. G4 coated magnetic screening system provides a feasible, easy-operating approach for anticancer drug discovery.