CG001, a C3b-targeted complement inhibitor blocks three complement pathways: development and preclinical evaluation.

Excessively activated or dysregulated complement activation may contribute to the pathogenesis of a wide range of human diseases, thus leading to a surge in complement inhibitors. Herein, we developed a human-derived and antibody-like C3b-targeted fusion protein (CRIg-FH-Fc) *2, termed CG001, that could potently block all three complement pathways. CRIg and FH bind to distinct sites in C3b and synergistically inhibit complement activation. CRIg occupancy in C3b prevents the recruitment of C3 and C5 substrates, while FH occupancy in C3b accelerates the decay of C3/C5 convertases and promotes the Factor I-mediated degradation and inactivation of C3b. CG001 also showed therapeutic effects in AP-induced hemolytic mouse and CP-induced MsPGN rat models. In the pharmacological/toxicological evaluation in rats and cynomolgus monkeys, CG001 displayed an antibody-like pharmacokinetic profile, a convincing complement inhibitory effect, and no observable toxic effects. Therefore, CG001 holds substantial potential for human clinical studies.

Enhancing prognostic insights: myometrial invasion patterns in endometrial carcinoma, with emphasis on MELF pattern-a comprehensive review and meta-analysis.

PURPOSE: The microcystic, elongated, and fragmented (MELF) pattern, characterized by myxoid and inflamed stroma, is readily identifiable as a form of myometrial infiltration. This meta-analysis endeavors to assess the prognostic significance of MELF infiltration patterns in patients diagnosed with endometrial cancer. METHODS: A comprehensive literature search, spanning until 11 October 2023, across PubMed, Embase, Cochrane, and Web of Science databases, identified 23 relevant studies involving 5199 patients. Data analysis was performed using Stata 16.0. RESULTS: Analysis indicates that MELF infiltration predicts a higher risk of lymph node metastasis in endometrial cancer patients [hazard ratios (HR) = 5.05; 95% confidence interval (CI), 3.62-7.05; P < 0.05]. Notably, this association remains consistent across various patient demographics, analytical approaches, study designs, and treatment modalities. However, MELF infiltration does not significantly correlate with recurrence (HR = 1.05; 95% CI, 0.73-1.52; P > 0.05), overall survival (HR = 1.24; 95% CI, 0.91-1.68; P > 0.05), or disease-free survival (HR = 1.40; 95% CI, 0.85-2.28; P > 0.05). CONCLUSION: While MELF infiltration heightens the risk of lymph node metastasis in endometrial cancer, its impact on recurrence, overall survival, and disease-free survival remains statistically insignificant.

Reactive oxygen species mediated extracellular polymeric substances production assisting the recovery of Thalassiosira pseudonana from polystyrene micro and nanoplastics exposure.

As emerging pollutants in the aquatic environments, micro- and nano-plastics (MNPs) aroused widespread environmental concerns for their potential threats to the ecological health. Previous research has proved that microalgae growth could recover from the MNPs toxicities, in which the extracellular polymeric substances (EPS) might play the key role. In order to comprehensively investigate the recovery process of microalgae from MNPs stress and the effecting mechanisms of EPS therein, this study conducted a series of experiments by employing two sizes (0.1 and 1 µm) of polystyrene (PS) MNPs and the marine model diatom Thalassiosira pseudonana during 14 days. The results indicated: the pigments accumulations and photosynthetic recovery of T. pseudonana under MPs exposure showed in the early stage (4-5 days), while the elevation of reactive oxygen species (ROS) and EPS contents lasted longer time period (7-8 days). EPS was aggregated with MNPs particles and microalgal cells, corresponding to the increased settlement rates. More increase of soluble (SL)-EPS contents was found than bound (B)-EPS under MNPs exposure, in which the increase of the protein proportion and humic acid-like substances in SL-EPS was found, thus facilitating aggregates formation. ROS was the signaling molecule mediating the overproduction of EPS. The transcriptional results further proved the enhanced EPS biosynthesis on the molecular level. Therefore, this study elucidated the recovery pattern of microalgae from MNPs stress and linked "ROS-EPS production changes-aggregation formation" together during the growth recovery process, with important scientific and environmental significance.

Identification of four biotypes in temporal lobe epilepsy via machine learning on brain images.

Artificial intelligence provides an opportunity to try to redefine disease subtypes based on similar pathobiology. Using a machine-learning algorithm (Subtype and Stage Inference) with cross-sectional MRI from 296 individuals with focal epilepsy originating from the temporal lobe (TLE) and 91 healthy controls, we show phenotypic heterogeneity in the pathophysiological progression of TLE. This study was registered in the Chinese Clinical Trials Registry (number: ChiCTR2200062562). We identify two hippocampus-predominant phenotypes, characterized by atrophy beginning in the left or right hippocampus; a third cortex-predominant phenotype, characterized by hippocampus atrophy after the neocortex; and a fourth phenotype without atrophy but amygdala enlargement. These four subtypes are replicated in the independent validation cohort (109 individuals). These subtypes show differences in neuroanatomical signature, disease progression and epilepsy characteristics. Five-year follow-up observations of these individuals reveal differential seizure outcomes among subtypes, indicating that specific subtypes may benefit from temporal surgery or pharmacological treatment. These findings suggest a diverse pathobiological basis underlying focal epilepsy that potentially yields to stratification and prognostication - a necessary step for precise medicine.

Planar Cation Passivation on Colloidal Quantum Dots Enables High-Performance 0.35-1.8 µm Broadband TFT Imager.

Solution-processed colloidal quantum dots (CQDs) are promising candidates for broadband photodetectors from visible light to shortwave infrared (SWIR). However, large-size PbS CQDs sensitive to longer SWIR are mainly exposed with nonpolar (100) facets on the surface, which lack robust passivation strategies. Herein, an innovative passivation strategy that employs planar cation, is introduced to enable face-to-face coupling on (100) facets and strengthen halide passivation on (111) facets. The defect density of CQDs film (Eg ≈ 0.74 eV) is reduced from 2.74 × 1015 to 1.04  × 1015 cm-3, coupled with 0.1 eV reduction in the activation energy of defects. The resultant CQDs photodiodes exhibit a low dark current density of 14 nA cm-2 with a high external quantum efficiency (EQE) of 62%, achieving a linear dynamic range of 98 dB, a -3dB bandwidth of 103 kHz and a detectivity of 4.7 × 1011 Jones. The comprehensive performance of the CQDs photodiodes outperforms previously reported CQDs photodiodes operating at >1.6 µm. By monolithically integrated with thin-film transistor (TFT) readout circuit, the broadband CQDs imager covering 0.35-1.8 µm realizes the functions including silicon wafer perspectivity and material discrimination, showing its potential for wide range of applications.

Insight into the High Mobility and Stability of In2 O3 :H Film.

Wide bandgap semiconductors, particularly In2 O3 :Sn (ITO), are widely used as transparent conductive electrodes in optoelectronic devices. Nevertheless, due to the strohave beenng scattering probability of high-concentration oxygen vacancy (VO ) defects, the mobility of ITO is always lower than 40 cm2  V-1  s-1 . Recently, hydrogen-doped In2 O3 (In2 O3 :H) films have been proven to have high mobility (>100 cm2  V-1  s-1 ), but the origin of this high mobility is still unclear. Herein, a high-resolution electron microscope and theoretical calculations are employed to investigate the atomic-scale mechanisms behind the high carrier mobility in In2 O3 :H films. It is found that VO can cause strong lattice distortion and large carrier scattering probability, resulting in low carrier mobility. Furthermore, hydrogen doping can simultaneously reduce the concentration of VO , which accounts for high carrier mobility. The thermal stability and acid-base corrosion mechanism of the In2 O3 :H film are investigated and found that hydrogen overflows from the film at high temperatures (>250 °C), while acidic or alkaline environments can cause damage to the In2 O3 grains themselves. Overall, this work provides insights into the essential reasons for high carrier mobility in In2 O3 :H and presents a new research approach to the doping and stability mechanisms of transparent conductive oxides.

Effect of Cobalt on Lifetime of Sb4O5Cl2-Graphene Anode in Chloride-Ion Batteries.

Anode materials based on metal oxychlorides hold promise in addressing electrode dissolution challenges in aqueous-based chloride ion batteries (CIBs). However, their structural instability following chloride ion deintercalation can lead to rapid degradation and capacity fading. This paper investigates a cobalt-doped Sb4O5Cl2-graphene (Co-Sb4O5Cl2@GO) composite anode for aqueous-based CIBs. It exhibits significantly enhanced discharge capacity of 82.3 mAh g-1 after 200 cycles at 0.3 A g-1; while, the undoped comparison is only 23.5 mAh g-1 in the same condition. It also demonstrated with a long-term capacity retention of 72.8 % after 1000 cycles (65.5 mAh g-1) and a favorable rate performance of 25 mAh g-1 at a high current density of 2 A g-1. Undertaken comprehensive studies via in-situ experiments and DFT calculations, the cobalt (Co) dopant is demonstrated as the crucial role to enhance the lifetime of Sb4O5Cl2-based anodes. It is found that, the Co dopant improves electronic conductivity and the diffusion of chloride ions beside increases the structural stability of Sb4O5Cl2 crystal. Thus, this element doping strategy holds promise for advancing the field of Sb4O5Cl2-based anodes for aqueous-based CIBs, and insights gain from this study also offer valuable knowledge to develop high-performance electrode materials for electrochemical deionization.

Study of the growth mechanism of a self-assembled and ordered multi-dimensional heterojunction at atomic resolution.

Multi-dimensional heterojunction materials have attracted much attention due to their intriguing properties, such as high efficiency, wide band gap regulation, low dimensional limitation, versatility and scalability. To further improve the performance of materials, researchers have combined materials with various dimensions using a wide variety of techniques. However, research on growth mechanism of such composite materials is still lacking. In this paper, the growth mechanism of multi-dimensional heterojunction composite material is studied using quasi-two-dimensional (quasi-2D) antimonene and quasi-one-dimensional (quasi-1D) antimony sulfide as examples. These are synthesized by a simple thermal injection method. It is observed that the consequent nanorods are oriented along six-fold symmetric directions on the nanoplate, forming ordered quasi-1D/quasi-2D heterostructures. Comprehensive transmission electron microscopy (TEM) characterizations confirm the chemical information and reveal orientational relationship between Sb2S3 nanorods and the Sb nanoplate as substrate. Further density functional theory calculations indicate that interfacial binding energy is the primary deciding factor for the self-assembly of ordered structures. These details may fill the gaps in the research on multi-dimensional composite materials with ordered structures, and promote their future versatile applications.

Efficacy and safety of trastuzumab deruxtecan in the treatment of HER2-low/positive advanced breast cancer: a single-arm meta-analysis.

Background: Clinical trials have shown that the use of trastuzumab deruxtecan (DS-8201) alone is expected to provide novel therapeutic options for HER2-low/positive patients. Nevertheless, there are some variations in the efficacy of trial results, with potential risks at the safety level. Most DS-8201 trials in HER2 advanced breast cancer (ABC) have been conducted in the form of small-sample nonrandomized controlled studies, resulting in a lack of validated indicators to evaluate the efficacy and safety of DS-8201. Thus, this meta-analysis aimed to pool the results of various trials of DS-8201 alone to explore the efficacy and safety of DS-8201 in patients with HER2-low/positive advanced breast cancer. Methods: Relevant studies were searched in seven databases, including Embase, PubMed, Web of Science, Cochrane Library, CNKI, VIP database and WanFang data, to collect single-arm studies on DS-8201 for HER2-low/positive ABC. MINORS was adopted for quality assessment and STATA 16.0 for data analysis. Results: Ten studies involving 1,108 patients were included in this meta-analysis. As for the tumor response rate, the pooled ORR and DCR of all studies reached 57% (95% CI: 47%-67%) and 92% (95% CI: 89%-96%) respectively, and the pooled ORRs of the HER2-low expression group and the HER2-positive expression group were 46% (95% CI: 35%-56%) and 64% (95% CI: 54%-74%). Only the low expression group achieved median survival time, with a pooled median PFS and median OS of 9.24 (95% CI: 7.54-10.94) months and 23.87 (95% CI: 21.56-26.17) months, respectively. The most common treatment-related adverse events from DS-8201 were nausea (all grades: 62%; ≥ grade III: 5%), fatigue (all grade: 44%; ≥ grade III: 6%), and alopecia (all grades: 38%; ≥ grade III: 0.5%). Drug-related interstitial lung disease or pneumonitis occurred in 13% of the 1,108 patients, with only a 1% incidence of AE ≥ grade III. Conclusion: The present study suggests that DS-8201 is effective and safe in the treatment of ABC with low or positive HER2 expression, providing additional relevant information for its clinical application. However, further strengthening of the pairs is needed, as well as more clinical studies to support individualized treatment. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023390316.

Increased α-HB links colorectal cancer and diabetes by potentiating NF-κB signaling.

Sufficient evidence has linked many different types of cancers and T2D through shared risk factors; however, the underlying mechanisms are not fully understood. α-Hydroxybutyrate (α-HB), a byproduct metabolite increased in diabetes and cancer, including colorectal cancer (CRC), triggers lactate dehydrogenase A (LDHA) nuclear translocation. Nuclear LDHA markedly extends NF-κB nuclear retention by interacting with phosphorylated p65, leading to an increase in TNF-α production, impaired insulin secretion and the exacerbation of azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CRC and high-fat diet (HFD)-induced type 2 diabetes. Furthermore, metformin interrupted this process by inhibiting the transcription of FOXM1 and c-MYC, the resultant downregulation of LDHA expression and α-HB-induced LDHA nuclear translocation. Thus, the results reveal the elevated α-HB level could be a novel shared risk factor of linking CRC, diabetes and the use of metformin treatment, as well as highlight the importance of preventing NF-κB activation for protecting against cancer and diabetes.

Clinical and electroencephalography characteristics of 45 patients with neonatal seizures.

OBJECTIVES: The aim of our study was to retrospectively research the semiology of neonatal seizures (NSs) based on the 2021 classification scheme of the International League Against Epilepsy, and the relationship between etiology and electroclinical features. METHODS: Patients admitted to Children's Hospital of Chongqing Medical University from May 1, 2020 to March 30, 2022 and diagnosed with NSs were included to retrospectively investigate the etiology, seizure characteristics, prognosis, and ictal and interictal video electroencephalography (EEG) characteristics. RESULTS: Of the 45 patients, 73.3% had definite etiology. Twenty-seven patients had electro-clinical seizures, of which two had both electro-clinical and electrographic-only seizures. Electrographic-only seizures were reported in 18 patients. The tonic, clonic, and electrographic-only seizures were associated with various etiologies. Both tonic and clonic seizures occurred in acute symptomatic seizures and were associated with neonatal epilepsy. 50% of tonic seizures were related to genetic factors. Among the clonic seizures, 50.0% occurred in acute symptomatic seizures. Epileptic spasms always indicated neonatal epilepsy. There were few patients who experienced automatisms and sequential seizures, and these two seizure types were associated with brain malformation and genetic factors, respectively. Patients with a normal interictal EEG had acute symptomatic seizures. whereas the interictal EEG of patients with neonatal epilepsy mainly showed burst-suppression or multifocal discharges. The ictal EEG recordings were related to seizure semiology. CONCLUSION: Seizure semiology and video EEG are suggestive of potential causes but do not provide a definite etiology.

Nuclear complement C3b promotes paclitaxel resistance by assembling the SIN3A/HDAC1/2 complex in non-small cell lung cancer.

In addition to the classical role as a serum effector system of innate immunity, accumulating evidence suggests that intracellular complement components have indispensable functions in immune defense, T cell homeostasis, and tumor cell proliferation and metastasis. Here, we revealed that complement component 3 (C3) is remarkably upregulated in paclitaxel (PTX)-resistant non-small cell lung cancer (NSCLC) cells and that knockdown of C3 promoted PTX-induced cell apoptosis, sensitizing resistant cells to PTX therapy. Ectopic C3 decreased PTX-induced apoptosis and induced resistance to PTX treatment in original NSCLC cells. Interestingly, C3b, the activated fragment of C3, was found to translocate into the nucleus and physically associate with the HDAC1/2-containing SIN3A complex to repress the expression of GADD45A, which plays an important role in cell growth inhibition and apoptosis induction. Importantly, C3 downregulated GADD45A by enhancing the binding of the SIN3A complex with the promoter of GADD45A, thus decreasing the H3Ac level to compress chromatin around the GADD45A locus. Subsequently, ectopic GADD45A promoted PTX-induced cell apoptosis, sensitizing resistant cells to PTX therapy, and insufficiency of GADD45A in original cancer cells induced resistance to PTX treatment. These findings identify a previously unknown nucleus location and oncogenic property for C3 in chemotherapy and provide a potential therapeutic opportunity to overcome PTX resistance.

UV-B radiation alleviated detrimental effects of polymethyl methacrylate microplastics on marine diatom Thalassiosira pseudonana.

Microplastics (MPs) in marine environments simultaneously affect microalgae with UV-B radiation, while their joint effecting mechanisms remain largely unknown. To fill this research gap, the joint effects of polymethyl methacrylate (PMMA) MPs and UV-B radiation (natural environments intensity) on the model marine diatom Thalassiosira pseudonana were investigated. Antagonism was found between the two factors with regards to population growth. Furthermore, we found more inhibited population growth and photosynthetic parameters when pre-treated with PMMA MPs compared to pre-treated with UV-B radiation before joint-treated by the two factors. Transcriptional analysis elucidated that UV-B radiation could alleviate the down-regulation of photosynthetic (PSII, cyt b6/f complex and photosynthetic electron transport) and chlorophyll biosynthesis genes caused by PMMA MPs. Besides, the genes encoding carbon fixation and metabolisms was up-regulated under UV-B radiation, which could provide extra energy for the enhanced anti-oxidative activities and DNA replication-repair processes. These consequences showed that the toxicity of PMMA MPs was comprehensively alleviated when T. pseudonana was jointed treated by UV-B radiation. Our results reveled the underlying molecular mechanisms of antagonistic effects between PMMA MPs and UV-B radiation. This study provides important information that environmental factors like UV-B radiation should be considered when accessing the ecological risks of MPs on marine organisms.

An Air-Rechargeable Zn Battery Enabled by Organic-Inorganic Hybrid Cathode.

Self-charging power systems collecting energy harvesting technology and batteries are attracting extensive attention. To solve the disadvantages of the traditional integrated system, such as highly dependent on energy supply and complex structure, an air-rechargeable Zn battery based on MoS2/PANI cathode is reported. Benefited from the excellent conductivity desolvation shield of PANI, the MoS2/PANI cathode exhibits ultra-high capacity (304.98 mAh g-1 in N2 and 351.25 mAh g-1 in air). In particular, this battery has the ability to collect, convert and store energy simultaneously by an air-rechargeable process of the spontaneous redox reaction between the discharged cathode and O2 from air. The air-rechargeable Zn batteries display a high open-circuit voltage (1.15 V), an unforgettable discharge capacity (316.09 mAh g-1 and the air-rechargeable depth is 89.99%) and good air-recharging stability (291.22 mAh g-1 after 50 air recharging/galvanostatic current discharge cycle). Most importantly, both our quasi-solid zinc ion batteries and batteries modules have excellent performance and practicability. This work will provide a promising research direction for the material design and device assembly of the next-generation self-powered system.

Maximizing Electron Channels Enabled by MXene Aerogel for High-Performance Self-Healable Flexible Electronic Skin.

Among the increasingly popular miniature and flexible smart electronics, two-dimensional materials show great potential in the development of flexible electronics owing to their layered structures and outstanding electrical properties. MXenes have attracted much attention in flexible electronics owing to their excellent hydrophilicity and metallic conductivity. However, their limited interlayer spacing and tendency for self-stacking lead to limited changes in electron channels under external pressure, making it difficult to exploit their excellent surface metal conductivity. We propose a strategy for rapid gas foaming to construct interlayer tunable MXene aerogels. MXene aerogels with rich interlayer network structures generate maximized electron channels under pressure, facilitating the effective utilization of the surface metal properties of MXene; this forms a self-healable flexible pressure sensor with excellent sensing properties such as high sensitivity (1,799.5 kPa-1), fast response time (11 ms), and good cycling stability (>25,000 cycles). This pressure sensor has applications in human body detection, human-computer interaction, self-healing, remote monitoring, and pressure distribution identification. The maximized electron channel design provides a simple, efficient, and scalable method to effectively exploit the excellent surface metal conduction of 2D materials.

The adsorption and absorption kinetics of BDE-47 by Chlorella sp. and the role of extracellular polymer substances influenced by environmental factors.

Microalgae act as the entrance of polybrominated diphenyl ethers (PBDEs) from abiotic to biotic environments, which controlled the environmental fate of PBDEs in aquatic environments. Combing with typical coastal environmental characteristics including extracellular polymer substances (EPS) enrichment, light limitation and nitrogen starvation, the changes of adsorption and absorption kinetics of BDE-47 by Chlorella sp. and the role of EPS therein were investigated. The results quantified the adsorption and absorption kinetics of BDE-47 by Chlorella sp. cells and fitted it by the Lagergren pseudo first order model. Furthermore, we found the adsorption and absorption kinetics could be changed by the above mentioned environmental factors. To be specific, the total BDE-47 adsorption amounts per microalgal cell were increased as the increase of ambient EPS (proteins or carbohydrates), attributing to the increase of soluble (SL)-EPS contents; increased total BDE-47 adsorption amounts but decreased absorption rates were found under light limitation and nitrogen starvation, which were attributed to increased bound (B)-EPS contents and protein/carbohydrates (P/C) ratios therein, respectively. Therefore, our study elucidated the adsorption and absorption kinetics of PBDEs by microalgae could be influenced by ambient environmental changes, clarified the roles of SL-EPS, B-EPS contents and P/C ratios, providing a solid basis for evaluating the environmental fate of PBDEs in the marine environments.

Maximizing the ion accessibility and high mechanical strength in nanoscale ion channel MXene electrodes for high-capacity zinc-ion energy storage.

Two-dimensional transition-metal carbides (MXenes) have superhydrophilic surfaces and superior metal conductivity, making them competitive in the field of electrochemical energy storage. However, MXenes with layered structures are easily stackable, which reduces the ion accessibility and transport paths, thus limiting their electrochemical performance. To fully exploit the advantages of MXenes in electrochemical energy storage, this study reports the etching of large-sized MXene into nanosheets with nanoscale ion channels via a chemical oxidation method. While the resulting ion-channel MXene electrodes retain the excellent mechanical strength and electrical conductivity of large-sized MXene nanosheets, they can effectively shorten the ion transport distance and improve the overall electrochemical activity. The fabricated self-healing MXene-based zinc-ion microcapacitor exhibits a high areal specific capacitance (532.8 mF cm-2) at the current density of 2 mA cm-2, a low self-discharge rate (4.4 mV h-1), and high energy density of 145.1 µWh cm-2 at the power density of 2800 µW cm-2. The proposed nanoscale ion channel structure provides an alternative strategy for constructing high-performance electrochemical energy storage electrodes, and has great application prospects in the fields of electrochemical energy storage and flexible electronics.

3D Porous Structure in MXene/PANI Foam for a High-Performance Flexible Pressure Sensor.

The fields of electronic skin, man-machine interaction, and health monitoring require flexible pressure sensors with great sensitivity. However, most microstructure designs utilized to fabricate high-performance pressure sensors require complex preparation processes. Here, MXene/polyaniline (PANI) foam with 3D porous structure is achieved by using a steam-induced foaming method. Based on the structure, a flexible piezoresistive sensor is fabricated. It exhibits high sensitivity (690.91 kPa-1 ), rapid response, and recovery times (106/95 ms) and outstanding fatigue resistance properties (10 000 cycles). The MXene/PANI foam-based pressure sensor can swiftly detect minor pressure and be further used for human activity and health monitoring.

CD59-Regulated Ras Compartmentalization Orchestrates Antitumor T-cell Immunity.

T cell-mediated immunotherapy represents a promising strategy for cancer treatment; however, it has achieved satisfactory clinical responses in only a limited population. Thus, a broader view of the T-cell immune response is required. The Ras/MAPK pathway operates in many important signaling cascades and regulates multiple cellular activities, including T-cell development, proliferation, and function. Herein, we found that the typical membrane-bound complement regulatory protein CD59 is located intracellularly in T cells and that the intracellular form is increased in the T cells of patients with cancer. When intracellular CD59 is abundant, it facilitates Ras transport to the inner plasma membrane via direct interaction; in contrast, when CD59 is insufficient or deficient, Ras is arrested in the Golgi, thus enhancing Ras/MAPK signaling and T-cell activation, proliferation, and function. mCd59ab deficiency almost completely abolished tumor growth and metastasis in tumor-bearing mice, in which CD4+ and CD8+ T cells were significantly increased compared with their proportions in wild-type littermates, and their proportions were inversely correlated with tumor growth. Using bone marrow transplantation and CD4+ and CD8+ T-cell depletion assays, we further demonstrated the critical roles of these cells in the potent antitumor activity induced by mCd59ab deficiency. Reducing CD59 expression also enhanced MAPK signaling and T-cell activation in human T cells. Therefore, the subcellular compartmentalization of Ras regulated by intracellular CD59 provides spatial selectivity for T-cell activation and a potential T cell-mediated immunotherapeutic strategy.

Different effecting mechanisms of two sized polystyrene microplastics on microalgal oxidative stress and photosynthetic responses.

Increasing marine microplastics (MPs) pollution potentially threatens the stability of phytoplankton community structures in marine environments. MPs toxicities to microalgae are largely determined by particle size, while the size-dependent mechanisms are still not fully understood. In this study, two sizes (0.1 µm and 1 µm) of polystyrene (PS) MPs were used as experimental targets to systemically compare their different effecting mechanisms on the marine model diatom Thalassiosira pseudonana with respect to oxidative stress and photosynthesis. The results indicated the toxicity of 1 µm sized MPs was higher than 0.1 µm sized MPs regarding to population growth. In condition of similar microalgal population inhibition rates, we found more enhanced cellular oxidative stress and cell death happened in the 1 µm MPs treatments, which could be linked to higher zeta potential of 1 µm MPs and more severe cell surface damage; microalgal surface light shading and cellular pigments decline were more obvious in the 0.1 µm MPs treatment, which could be linked to high aggregation abilities of 0.1 µm MPs. Gene expressions supported the morphological and physiological findings on the transcriptional level. Environmental related MPs concentrations (5 µg L-1) also aroused gene expression changes of T. pseudonana while more changing genes were found under 0.1 µm MPs than 1 µm MPs. These results provide novel insights into the size-dependent mechanisms of MPs toxicity on marine microalgae, as well as their potential influence on the marine environment.