Staphylococcus aureus (S. aureus), a prevalent foodborne pathogen, poses a serious threat to human health, highlighting the urgent need for reliable and sensitive detection methods. Given the limitations of single-mode sensors such as false positives/negatives, a colorimetric and fluorescent dual-mode biosensor based on quantum dot material was proposed for the evaluation of S. aureus in food. This sensor utilized CsPbBr3@SiO2 quantum dots as a stable fluorescent probe. The sensing mechanism relies on the inner filter effect, where gold nanoparticles effectively quench the fluorescence of CsPbBr3@SiO2, enabling rapid and highly sensitive biosensing. Under optimized conditions, the biosensor achieved a broad detection range of 1 to 106 colony-forming unit/mL (CFU/mL), with low detection limits of 103 CFU/mL for colorimetric mode and 0.54 CFU/mL for fluorescent mode. It also exhibited excellent selectivity and was successfully applied to analyze various food samples. This study demonstrates perovskite nanomaterials as a visual tool for detecting foodborne pathogens in complex matrices.

Single or combined ROS therapy will induce cancer resistance after long-term medication cure. Although currently concurrent H2/ROS therapy is a promising method, the mutual reaction between H2 and ROS dampens their efficiency. To address this issue, g-C3N4-based dual-heterojunctions, i.e., N-doped carbon nanoribbons (N-CNB)/g-C3N4 and core-shell-structured Au@Pd nanoparticles/g-C3N4, respectively, are constructed to decode alternate H2/ROS therapy. Therein, N-CNB/g-C3N4 heterojunctions enhance near-infrared (NIR) photoabsorption to unlock photocatalytic H2 evolution, and Au@Pd/g-C3N4 heterojunctions unlock the inherent and newly-emerging bioenzymes-like catalytic ROS birth. In this alternate H2/ROS therapy, photocatalytic H2 evolution and multienzymically-catalytic ROS birth are alternately decoded under NIR "on" and "off", respectively, because the photoirradiation-triggered structural shift insensitive to photothermal effects is reversible in response to NIR "on" and "off", displaying a temporal controllability. The alternate H2/ROS therapy expedites the infiltrations and intratumoral proliferation of anti-tumor immune cells including CTLs and Th17, hampers the infiltrations of exhausted CD8+ T cells and Tregs, and downregulates resistance-associated proteins (PARP, EpCAM, and CD133). These actions cooperatively activate robust immune responses, attenuate anti-tumor immunity confinements, and cancer resistance to suppress common and Sorafenib-induced resistant liver cancer. This work offers distinctive insights into cancer resistance removal.

(+)-Valencene is the characteristic volatile compound in 'Newhall' sweet orange, and CsTPS1 is the gene that codes for the (+)-valencene synthase. Here, four transcription factors, including CitUNE1, CitUNE3, CitSCL1, and CitSCL13, were screened as candidate proteins by yeast one-hybrid (Y1H) library screening with CsTPS1 promoter as the bait. Among them, CitUNE1 bound to the G-box on the promoter of CsTPS1 and suppressed CsTPS1 expression, confirmed by Y1H, dual-luciferase assay, point-mutation experiment and EMSA. The expression pattern of CitUNE1 showed a negative correlation with both the content of (+)-valencene and CsTPS1 transcripts level, both during fruit development and after ethylene treatment. Furthermore, the role of CitUNE1 in (+)-valencene synthesis was confirmed using the transient over-expression and silencing in 'Newhall' sweet orange. Transient over-expression of CitUNE1 inhibited CsTPS1 expression and reduced the accumulation of (+)-valencene, while silencing of CitUNE1 induced CsTPS1 expression and triggered (+)-valencene synthesis in 'Newhall' sweet orange.

Par6α encoded by PARD6A is a member of the PAR6 family and is reported to promote cancer initiation and progression. PARD6A is frequently upregulated in different types of cancers, but its regulatory role in lung cancer progression is yet to be established. In this study, we analyzed the PARD6A expression in biopsies from lung adenocarcinoma (LUAD) patients, and the survival probability using LUAD tissue microarray (TMA) and online datasets from TCGA and GEO. We conducted in vitro and in vivo assays to assess the role of PARD6A in regulating lung cancer progression, including proliferation, wound healing, transwell, RNA-seq, and subcutaneous tumor mice models. Our findings revealed that PARD6A is highly expressed in cancer tissues from LUAD patients and is associated with poor prognosis in LUAD patients. In vitro assays showed that PARD6A promoted cell proliferation, migration, and invasion. The transcriptome sequencing identified Serpina3 as one of the key downstream molecules of PARD6A. Ectopic expression of Serpina3 rescued impaired proliferation, migration, and invasion in PARD6A-knocking down H1299 cells, whereas silencing Serpina3 impeded enhanced proliferation, migration, and invasion in PARD6A-overexpressing H1975 cells. Our findings suggest that PARD6A promotes lung cancer progression by inducing Serpina3, which may be a promising therapeutic target.

Currently, the construction of novel biomimetic reduced graphene oxide (RGO)-based nanocomposites to induce neurite sprouting and repair the injured neurons represents a promising strategy in promoting neuronal development or treatment of cerebral anoxia or ischemia. Here, we present an effective method for constructing palladium-reduced graphene oxide (Pd-RGO) nanocomposites by covalently bonding Pd onto RGO surfaces to enhance neurite sprouting of cultured neurons. As described, the Pd-RGO nanocomposites exhibit the required physicochemical features for better biocompatibility without impacting cell viability. Primary neurons cultured on Pd-RGO nanocomposites had significantly increased number and length of neuronal processes, including both axons and dendrites, compared with the control. Western blotting showed that Pd-RGO nanocomposites improved the expression levels of growth associate protein-43 (GAP-43), as well as β-III tubulin, Tau-1, microtubule-associated protein-2 (MAP2), four proteins that are involved in regulating neurite sprouting and outgrowth. Importantly, Pd-RGO significantly promoted neurite length and complexity under oxygen-glucose deprivation/re-oxygenation (OGD/R) conditions, an in vitro cellular model of ischemic brain damage, that closely relates to neuronal GAP-43 expression. Furthermore, using the middle cerebral artery occlusion (MCAO) model in rats, we found Pd-RGO effectively reduced the infarct area, decreased neuronal apoptosis in the brain, and improved the rats’ behavioral outcomes after MCAO. Together, these results indicate the great potential of Pd-RGO nanocomposites as a novel excellent biomimetic material for neural interfacing that shed light on its applications in brain injuries.

Epilepsy is a complex disease in the brain. Complete control of seizure has always been a challenge in epilepsy treatment. Currently, clinical management primarily involves pharmacological and surgical interventions, with the former being the preferred approach. However, antiepileptic drugs often exhibit low bioavailability due to inherent limitations such as poor water solubility and difficulty penetrating the blood-brain barrier (BBB). These issues significantly reduce the drugs' effectiveness and limit their clinical application in epilepsy treatment. Additionally, the diagnostic accuracy of current imaging techniques and electroencephalography (EEG) for epilepsy is suboptimal, often failing to precisely localize epileptogenic tissues. Accurate diagnosis is critical for the surgical management of epilepsy. Thus, there is a pressing need to enhance both the therapeutic outcomes of epilepsy medications and the diagnostic precision of the condition. In recent years, the advancement of nanotechnology in the biomedical sector has led to the development of nanomaterials as drug carriers. These materials are designed to improve drug bioavailability and targeting by leveraging their large specific surface area, facile surface modification, ability to cross the BBB, and high biocompatibility. Furthermore, nanomaterials have been utilized as contrast agents in imaging and as materials for EEG electrodes, enhancing the accuracy of epilepsy diagnoses. This review provides a comprehensive examination of current research on nanomaterials in the treatment and diagnosis of epilepsy, offering new strategies and directions for future investigation.

Nanomaterials (NMs) have emerged as promising tools for disease diagnosis and therapy due to their unique physicochemical properties. To maximize the effectiveness and design of NMs-based medical applications, it is essential to comprehend the complex mechanisms of cellular uptake, subcellular localization, and cellular retention. This review illuminates the various pathways that NMs take to get from the extracellular environment to certain intracellular compartments by investigating the various mechanisms that underlie their interaction with cells. The cellular uptake of NMs involves complex interactions with cell membranes, encompassing endocytosis, phagocytosis, and other active transport mechanisms. Unique uptake patterns across cell types highlight the necessity for customized NMs designs. After internalization, NMs move through a variety of intracellular routes that affect where they are located subcellularly. Understanding these pathways is pivotal for enhancing the targeted delivery of therapeutic agents and imaging probes. Furthermore, the cellular retention of NMs plays a critical role in sustained therapeutic efficacy and long-term imaging capabilities. Factors influencing cellular retention include nanoparticle size, surface chemistry, and the cellular microenvironment. Strategies for prolonging cellular retention are discussed, including surface modifications and encapsulation techniques. In conclusion, a comprehensive understanding of the mechanisms governing cellular uptake, subcellular localization, and cellular retention of NMs is essential for advancing their application in disease diagnosis and therapy. This review provides insights into the intricate interplay between NMs and biological systems, offering a foundation for the rational design of next-generation nanomedicines.

Osteoarthritis (OA) is a prevalent chronic condition that primarily impacts the articular cartilage and surrounding bone tissue, resulting in joint inflammation and structural deterioration. The etiology of OA is multifaceted and intricately linked to the oxidative stress response of joint tissue. Oxidative stress (OS) in OA leads to the creation of reactive oxygen species (ROS) and other oxidizing agents, resulting in detrimental effects on chondrocytes. This oxidative damage diminishes the flexibility and robustness of cartilage, thereby expediting the progression of joint deterioration. Therefore, the antioxidant effect is crucial in the treatment of OA. Currently, a considerable number of components found in traditional Chinese medicine (TCM) have been scientifically demonstrated to exhibit remarkable antioxidant and anti-inflammatory properties. Nevertheless, the utilization of this program is considerably constrained as a result of intrinsic deficiencies, notably stability concerns. The successful amalgamation of TCM components with nanotechnology has properly tackled these concerns and enhanced the efficacy of therapeutic results. The objective of this study is to delineate the antioxidant characteristics of nano-TCM and assess the current inventory of literature pertaining to the application of nano-TCM in the treatment of OA. In conclusion, this paper will now turn to the constraints and potential avenues for the advancement of nano-TCM within the realm of OA therapy.

Cellular senescence is characterized by the permanent arrest of cell proliferation and is a response to endogenous and exogenous stress. The continuous accumulation of senescent cells (SnCs) in the body leads to the development of aging and age-related diseases (such as neurodegenerative diseases, cancer, metabolic diseases, cardiovascular diseases, and osteoarthritis). In the face of the growing challenge of aging and age-related diseases, several compounds have received widespread attention for their potential to target SnCs. As a result, senolytics (compounds that selectively eliminate SnCs) and senomorphics (compounds that alter intercellular communication and modulate the behavior of SnCs) have become hot research topics in the field of anti-aging. In addition, strategies such as combination therapies and immune-based approaches have also made significant progress in the field of antiaging therapy. In this article, we discuss the latest research on anti-aging targeting SnCs and gain a deeper understanding of the mechanism of action and impact of different anti-aging strategies on aging and age-related diseases, with the aim of providing more effective references and therapeutic ideas for clinical anti-aging treatment in the face of the ever-grave challenges of aging and age-related diseases.

BackgroundCoronavirus disease 2019 (COVID-19) has a clinical manifestation of hypoxic respiratory failure and acute respiratory distress syndrome. However, COVID-19 still lacks of effective clinical treatments so far. As a promising potential treatment against COVID-19, stem cell therapy raised recently and had attracted much attention. Here we review the mechanisms of mesenchymal stem cell-based treatments against COVID-19, and provide potential cues for the effective control of COVID-19 in the future.MethodsLiterature is obtained from databases PubMed and Web of Science. Key words were chosen for COVID- 19, acute respiratory syndrome coronavirus 2, mesenchymal stem cells, stem cell therapy, and therapeutic mechanism. Then we summarize and critically analyze the relevant articles retrieved.Results Mesenchymal stem cell therapy is a potential effective treatment against COVID-19. Its therapeutic efficacy is mainly reflected in reducing severe pulmonary inflammation, reducing lung injury, improving pulmonary function, protecting and repairing lung tissue of the patients. Possible therapeutic mechanisms might include immunoregulation, anti-inflammatory effect, tissue regeneration, anti-apoptosis effect, antiviral, and antibacterial effect, MSC - EVs, and so on.ConclusionMesenchymal stem cells can effectively treat COVID-19 through immunoregulation, anti-inflammatory, tissue regeneration, anti-apoptosis, anti-virus and antibacterial, MSC - EVs, and other ways. Systematically elucidating the mechanisms of mesenchymal stem cell-based treatments for COVID-19 will provide novel insights into the follow-up research and development of new therapeutic strategies in next step.

Osteoarthritis (OA) progresses due to the excessive generation of reactive oxygen and nitrogen species (ROS/RNS) and abnormal ATP energy metabolism related to the oxidative phosphorylation pathway in the mitochondria. Highly active single-atom nanozymes (SAzymes) can help regulate the redox balance and have shown their potential in the treatment of inflammatory diseases. In this study, we innovatively utilised ligand-mediated strategies to chelate Pt4+ with modified g-C3N4 by π–π interaction to prepare g–C3N4–loaded Pt single-atom (Pt SA/C3N4) nanozymes that serve as superoxide dismutase (SOD)/catalase (CAT) mimics to scavenge ROS/RNS and regulate mitochondrial ATP production, ultimately delaying the progression of OA. Pt SA/C3N4 exhibited a high loading of Pt single atoms (2.45 wt%), with an excellent photothermal conversion efficiency (54.71%), resulting in tunable catalytic activities under near-infrared light (NIR) irradiation. Interestingly, the Pt–N6 active centres in Pt SA/C3N4 formed electron capture sites for electron holes, in which g-C3N4 regulated the d-band centre of Pt, and the N-rich sites transferred electrons to Pt, leading to the enhanced adsorption of free radicals and thus higher SOD- and CAT-like activities compared with pure g-C3N4 and g–C3N4–loaded Pt nanoparticles (Pt NPs/C3N4). Based on the use of H2O2-induced chondrocytes to simulate ROS-injured cartilage in vitro and an OA joint model in vivo, the results showed that Pt SA/C3N4 could reduce oxidative stress-induced damage, protect mitochondrial function, inhibit inflammation progression, and rebuild the OA microenvironment, thereby delaying the progression of OA. In particular, under NIR light irradiation, Pt SA/C3N4 could help reverse the oxidative stress-induced joint cartilage damage, bringing it closer to the state of the normal cartilage. Mechanistically, Pt SA/C3N4 regulated the expression of mitochondrial respiratory chain complexes, mainly NDUFV2 of complex 1 and MT-ATP6 of ATP synthase, to reduce ROS/RNS and promote ATP production. This study provides novel insights into the design of artificial nanozymes for treating oxidative stress-induced inflammatory diseases.

生物化学与分子生物学是医学专业的核心基础课,知识点相对微观和复杂.小规模限制性在线课程(small private on-line course,SPOC)是近十年来发展起来一种教学模式.SPOC结合了慕课的丰富资源和小规模特色教学的两大优势.为了提升生物化学与分子生物学课堂的教学效果和激发学生的学习主动性,文章以医科大学医科类专业为研究对象,采用异步SPOC在线课堂的方式进行教学实践,并通过统计分析三个学期异步SPOC课程实践的教学数据,发现异步SPOC在线课堂能够提高学生学习的主导性和主动性.

目的:构建钯负载氧化石墨(GO@Pd)纳米酶,探究其类酶活性对脑胶质细胞凋亡的影响.方法:通过原位生长法合成GO@Pd纳米酶并进行表征;体外检测GO@Pd的类超氧化物歧化酶(SOD)活性、类过氧化物酶(POD)活性和消耗谷胱甘肽(GSH)的能力;并利用亚甲基蓝检测其羟基自由基(·OH-)的生成;通过细胞增殖试剂盒评价GO@Pd的体外生物安全性;分别将Pd、GO和GO@Pd与人脑星形胶质母细胞瘤(U-118MG)细胞共同孵育,利用DCFH-DA荧光探针检测各组细胞内活性氧(ROS)水平;通过线粒体膜电位染色检测各组细胞内线粒体膜电位变化.结果:经一系列材料表征表明成功制备了大小均一、分散性良好的GO@Pd纳米酶;类酶活性检测结果显示,GO@Pd同时拥有类SOD和类POD双重类酶活性,并且可以催化H2O2生成·OH-和消耗GSH;当GO@Pd浓度在0～100μg/mL之间,C8-D1A细胞的活率保持在90％以上;与空白对照组相比,GO@Pd组的U-118MG细胞内ROS水平显著升高(P<0.001),并且其线粒体膜电位染色结果红色/绿色荧光强度比值显著降低(P<0.0001).结论:成功制备了具有双重酶样活性的GO@Pd纳米酶,且其可以通过促进胶质瘤细胞内ROS生成,诱导线粒体损伤,从而引发胶质瘤细胞凋亡.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading rapidly across the world, posing a major health concern with the coronavirus disease 2019 (COVID-19). Patients with rheumatoid arthritis (RA) may be at higher risk of infection and disease progression due to impaired autoimmune systems, immunosuppressants, and comorbidities. Therefore, we review the possible immune mechanisms and pathological interactions between COVID-19 and RA, as the uncontrolled immune activation and cytokine response in COVID-19 resemble the immune inflammation of RA. We also discuss the potential mechanisms that may lead to cardiovascular complications as well as the challenges of treating RA patients with COVID-19. While several therapeutic agents are being developed to cure COVID-19, antirheumatic drugs could also be potential options due to the similar proinflammatory cytokines induced in both diseases. Additionally, we discuss the safety and effectiveness of SARS-CoV-2 vaccines and novel therapeutic approaches against RA based on the shared mechanisms between COVID-19 and RA.

OBJECTIVE:The pandemic of Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues, and SARS-CoV-2 variants continue to emerge. In addition to typical fever and respiratory symptoms, many patients with COVID-19 experience a variety of neurological complications. In this review, we analyzed and reviewed the current status and possible mechanisms between COVID-19 and several typical neurodegenerative diseases, particularly Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, hoping to propose the potential direction of further research and concern.MATERIALS AND METHODS:Electronic literature search of the databases (Medline/PubMed, Web of Science, and Google Scholar). The keywords used were COVID-19, SARS-CoV-2, neurodegenerative disease, Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. The retrieved relevant articles were reviewed and critically analyzed.RESULTS:SARS-CoV-2 is a highly neuroinvasive neurotropic virus that invades cells through angiotensin-converting enzyme 2 (ACE2) receptor-driven pathway. SARS-CoV-2 neuroinvasion, neuroinflammation, and blood-brain barrier (BBB) dysfunction may contribute to the pathogenesis of neurodegenerative diseases.CONCLUSIONS:Some patients with neurodegenerative diseases have already shown more susceptibility to SARS-CoV-2 infection and significantly higher mortality due to the elderly population with underlying diseases. Moreover, SARS-CoV-2 could cause damage to the central nervous system (CNS) that may substantially increase the incidence of neurodegenerative diseases and accelerate the progression of them.

The ability to recognize mRNA with high efficiency in cells would greatly facilitate the elucidation of mRNA-mediated cellular cascades and their disease associations. However, most traditional electrochemical strategies targeting nucleotides are always confronted with cumbersome interface operation and washing procedures, as well as the high cost of labeling and the strict reaction conditions of tool enzymes, limiting their potential applications. To address these issues, herein we reported, for the first time, a simple label-free, isothermal, non enzymatic, and ultrasensitive homogeneous electrochemical biosensor based on autonomous proximity dependent surface hybridization chain reaction (HCR), for sensitive signal amplification and highly specific detection of target survivin mRNA with a detection limit of 3 fM. The target triggers hybridization chain reaction and mRNA-fueled surface hybridization of ferrocene-tagged metastable DNA hairpin probes on proximity dependent surface hybridization, resulting in the formation of multiple long-range duplex DNA chains which are immobilized onto the gold electrodes with a substantially stable ferrocene-mediated redox current. Thus, a significant electrochemical signal increase is observed dependent on the concentration of the target RNA, with a very low detection limit. Mo-reover, this molecular biosensor also exhibits excellent specificity to distinguish even single base mismatched, with strong reliability. The developed biosensor provides a novel promising tool for ultra-sensitive and selective detection, and it has great potential to be applied in mRNA-related biochemical research and clinical cancer diagnostics in more detail.

阿尔茨海默病(Alzheimer's disease,AD)是一种老年人群中高发的进行性神经退行性疾病.β-淀粉样蛋白(β-amyloid,Aβ)假说是目前科学界广泛支持的AD发病机制.清除Aβ、阻止Aβ聚集和解聚Aβ纤维的策略有望给AD的治疗提供有效途径.然而,目前已报道的抗Aβ治疗AD的药物存在的诸多缺点,限制了其临床应用.随着纳米技术的飞速发展,二维纳米材料在医学上的应用逐渐受到研究人员的关注.二维纳米材料不仅理化特性优异,而且生物相容性良好,还易于穿越细胞膜及血脑屏障.近年来研究发现,多种二维纳米材料能通过分子间相互作用力、近红外光热效应、光催化氧化、Cu2+螯合以及药物负载等机制来抑制Aβ聚集,或使Aβ纤维解聚,在治疗AD方面有着很大的潜力.本文将围绕石墨烯和类石墨烯二雏纳米材料,例如二硫化钼、石墨相氮化碳、黑磷等用于抗Aβ治疗AD方面的研究进行综述.

阐述国内外便携式智能可穿戴健康监测设备应用现状及优缺点,分析国内外便携式智能监测设备之间区别以及存在的问题,提出相关建议,包括统一标准,规范数据采集;增加中医学健康监测指标;提升设备续航能力.

阿尔茨海默病( AD)在老年人群中已成为继心脑血管、肿瘤、外伤之后,位居第四位的死亡病因,截止2018年,AD在世界范围内已造成高达6. 8 万亿元人民币(1万亿美元)的经济损失,严重阻碍了社会经济发展,因此它已成为一个全球性的重大健康问题,在人口与健康领域和科学研究工作中也日益被高度关注〔1,2〕.然而,目前尚无有效的治疗手段可以阻止AD的进展或延迟其发作.当前AD治疗所面临的两个主要挑战是:一, AD发病机制尚不清楚,虽然科学家已经提出不少AD发病机制的假说,例如β淀粉样蛋白( Aβ)级联假说、tau 蛋白假说、胆碱能假说、氧化应激假说、金属假说等〔3〕,但目前还没有一个假说能很好地解释AD的病因;二,血脑屏障( BBB)的存在显著地阻碍了药物通过外周循环进入脑内,使其无法到达AD的病变区域发挥有效作用,与此同时外周脏器却承担了药物的超负荷效应.随着纳米技术的迅速发展,科学家们发现许多有机纳米材料自身可以有效穿过BBB,基于有机纳米材料具备半衰期长、负载率高、生物相容性好、毒性低等优点,既可通过掩盖、包封、嵌入等方式装载上亲水或疏水性药物从而促进药物分子有效跨越BBB,又因有机纳米材料的分子组成易于修饰、接枝,可实现安全靶向及可控释放,以发挥积极作用〔4〕.

光声成像是一种新兴的非侵入式的生物成像方式,具有极高的空间分辨率和良好的成像对比度,已逐步应用于肿瘤成像诊断基础研究.光声成像主要依赖于光声信号转换,而光声信号转换能力主要取决于造影剂的选择.近年来,随着无机纳米材料在生物医学成像领域的研究逐渐深入,越来越多的二维无机纳米材料也应用于光声成像造影剂,尤其是新型类石墨烯二维纳米材料,其优异的近红外吸收率类似于石墨烯,光热转换效率高,生物相容性良好,而且部分材料还具备带隙可调特性以及良好的生物降解性,因此有望成为肿瘤光声成像理想的造影剂.其中,二维过渡金属硫化物、二维过渡金属碳/氮化物以及二维单元素材料已被多次报道应用于肿瘤光声成像造影剂的研发.该文将综述上述几类二维纳米材料在肿瘤光声成像诊断中的应用进展.