Pig-to-human kidney xenotransplants using genetically modified minipigs.

This study develops an observational model to assess kidney function recovery and xenogeneic immune responses in kidney xenotransplants, focusing on gene editing and immunosuppression. Two brain-dead patients undergo single kidney xenotransplantation, with kidneys donated by minipigs genetically modified to include triple-gene knockouts (GGTA1, ß4GalNT2, CMAH) and human gene transfers (hCD55 or hCD55/hTBM). Renal xenograft functions are fully restored; however, immunosuppression without CD40-CD154 pathway blockade is ineffective in preventing acute rejection by day 12. This rejection manifests as both T cell-mediated rejection and antibody-mediated rejection (AMR), confirmed by natural killer (NK) cell and macrophage infiltration in sequential xenograft biopsies. Despite donor pigs being pathogen free before transplantation, xenografts and recipient organs test positive for porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV) by the end of the observation period, indicating reactivation and contributing to significant immunopathological changes. This study underscores the critical need for extended clinical observation and comprehensive evaluation using deceased human models to advance xenograft success.

Long-term expanded hepatic progenitor cells ameliorate D-GalN/LPS-induced acute liver failure through repolarizing M1 macrophage to M2-Like phenotype via activation of the IL-10/JAK2/STAT3 signaling pathway.

Acute liver failure (ALF) is a devastating liver disease characterized by the rapid deterioration of hepatocytes, which causes a series of clinical complications, including hepatic dysfunction, coagulopathy, encephalopathy, and multiorgan failure. Cell-based therapy is a promising alternative as it can bridge patients until their livers regenerate, releasing immunomodulatory molecules to suppress inflammation. This study reports an iPSCs-derived long-term expanded hepatic progenitor cell (LTHepPCs), which can differentiate into hepatocyte-like cells (HLCs) in vivo. When introduced into drug-induced ALF models, LTHepPCs mitigate liver damage by modulating the local immune microenvironment. This is achieved by shifting macrophages/Kupffer cells towards an anti-inflammatory state, resulting in a decrease in the expression of inflammatory cytokines such as TNF-a, IL-1ß, and IL-8, and an increase in the expression of anti-inflammatory cytokines such as IL-10 and ARG-1. In vitro co-culturing of THP-1 or mBMDMs with LTHepPCs suggested that LTHepPCs could activate the anti-inflammatory state of macrophages/Kupffer cells via the IL-10/JAK2/STAT3 signaling pathway. Therefore, LTHepPC transplantation is a promising therapy for ALF patients.

Analysis of the predictive value of microRNA-199b-5p combined with nitric oxide for venous thrombosis in patients undergoing total knee arthroplasty.

BACKGROUND: Deep vein thrombosis (DVT) of lower extremity is a common complications after total knee arthroplasty (TKA). The purpose of this study was to evaluate the risk factors for DVT after TKA and analyze the expression of miR-199b-5p and nitric oxide (NO) before and after TKA, as well as their predictive value for DVT. METHODS: Basic clinical information of 121 patients with TKA was analyzed retrospectively. RT-qPCR was used to detect the relative expression level of miR-199b-5p in patients before and after TKA treatment. Based on the occurrence of DVT, patients were divided into DVT and non-DVT groups. Logistic regression analysis evaluated the risk factors of DVT. The receiver operating characteristic (ROC) curve assessed the predictive value of postoperative miR-199b-5p level, preoperative NO level, and their combination in DVT. The target genes of miR-199b-5p and their functions were predicted and annotated using bioinformatics analysis. RESULTS: The level of miR-199b-5p after TKA was upregulated compared with that before TKA (P < 0.001). DVT occurred in 20 of 121 patients after TKA, with an incidence of 16.53%. Multivariate analysis showed that age, family history of DVT, decrease of NO and increase of miR-199b-5p were risk factors for DVT after TKA (P < 0.05). The ROC curve showed that both miR-199b-5p and NO had certain diagnostic value for DVT, but the combination of miR-199b-5p and NO had the highest diagnostic accuracy (P < 0.001). CONCLUSION: This study showed that the expression of miR-199b-5p was up-regulated after TKA, and miR-199b-5p levels were higher in DVT patients than in non-DVT patients. miR-199b-5p combined with NO is of great value in the diagnosis of DVT after TKA.

HSPA8 inhibitors augment cancer chemotherapeutic effectiveness via potentiating necroptosis.

Our recent work has uncovered a novel function of HSPA8 as an amyloidase, capable of dismantling the RHIM-containing protein fibrils to suppress necroptosis. However, the impact of HSPA8 inhibitors on cancer regression via necroptosis remains unexplored. In this study, we conducted a comprehensive investigation to assess the potential of HSPA8 inhibitors in enhancing necroptosis both in vitro and in vivo. Our findings indicate that pharmacologic inhibition of HSPA8, achieved either through VER (VER-155008) targeting the nucleotide binding domain or pifithrin-µ targeting the substrate binding domain of HSPA8, significantly potentiates necroptosis induced by diverse treatments in cellular assays. These inhibitors effectively disrupt the binding of HSPA8 to the RHIM protein, impeding its regulatory function on RHIM amyloid formation. Importantly, HSPA8 inhibitors significantly enhanced cancer cell sensitivity to microtubule-targeting agents (MTAs) in vitro, while reversing chemoresistance and facilitating tumor regression by augmenting necroptosis in vivo. Our findings suggest a promising therapeutic approach to cancer through necroptosis modulation via HSPA8 targeting, particularly in combination with MTA drugs for enhanced treatment efficacy.

Aggregation promotes charge separation in fullerene-indacenodithiophene dyad.

Fast photoinduced charge separation (CS) and long-lived charge-separated state (CSS) in small-molecules facilitate light-energy conversion, while simultaneous attainment of both remains challenging. Here we accomplish this through aggregation based on fullerene-indacenodithiophene dyads. Transient absorption spectroscopy reveals that, compared to solution, the CS time in aggregates is accelerated from 41.5 ps to 0.4 ps, and the CSS lifetime is prolonged from 311.4 ps to 40 µs, indicating that aggregation concomitantly promotes fast CS and long-lived CSS. Fast CS arises from the hot charge-transfer states dissociation, opening up additional resonant channels to free carriers (FCs); subsequently, charge recombination into intramolecular triplet CSS becomes favorable mediated by spin-uncorrelated FCs. Different from fullerene/indacenodithiophene blends, the unique CS mechanism in dyad aggregates reduces the long-lived CSS dependence on molecular order, resulting in a CSS lifetime 200 times longer than blends. This endows the dyad aggregates to exhibit both photoelectronic switch properties and superior photocatalytic capabilities.

Constructing Slip Stacking Diversity in Van der Waals Homobilayers.

The van der Waals (vdW) interface provides two important degrees of freedom-twist and slip-to tune interlayer structures and inspire unique physics. However, constructing diversified high-quality slip stackings (i.e., lattice orientations between layers are parallel with only interlayer sliding) is more challenging than twisted stackings due to angstrom-scale structural discrepancies between different slip stackings, sparsity of thermodynamically stable candidates and insufficient mechanism understanding. Here, using transition metal dichalcogenide (TMD) homobilayers as a model system, this work theoretically elucidates that vdW materials with low lattice symmetry and weak interlayer coupling allow the creation of multifarious thermodynamically advantageous slip stackings, and experimentally achieves 13 and 9 slip stackings in 1T″-ReS2 and 1T″-ReSe2 bilayers via direct growth, which are systematically revealed by atomic-resolution scanning transmission electron microscopy (STEM), angle-resolved polarization Raman spectroscopy, and second harmonic generation (SHG) measurements. This work also develops modulation strategies to switch the stacking via grain boundaries (GBs) and to expand the slip stacking library from thermodynamic to kinetically favored structures via in situ thermal treatment. Finally, density functional theory (DFT) calculations suggest a prominent dependence of the pressure-induced electronic band structure transition on stacking configurations. These studies unveil a unique vdW epitaxy and offer a viable means for manipulating interlayer atomic registries.

Polyprodrug nanomedicine for chemiexcitation-triggered self-augmented cancer chemotherapy and gas therapy.

Carbon monoxide (CO) has emerged as a potential antitumor agent by inducing the dysfunction of mitochondria and the apoptosis of cancer cells. However, it remains challenging to deliver appropriate amount of CO into tumor to ensure efficient tumor growth suppression with minimum side effects. Herein we developed a CO prodrug-loaded nanomedicine based on the self-assembly of camptothecin (CPT) polyprodrug amphiphiles. The polyprodrug nanoparticles readily dissociate upon exposure to endogenous H2O2 in the tumor, resulting in rapid release of CPT and generation of high-energy intermediate dioxetanedione. The latter can transfer the energy to neighboring CO prodrugs to activate CO production by chemiexcitation, while CPT promotes the generation of H2O2 in tumors, which in turn facilitates cascade CPT and CO release. As a result, the polyprodrug nanoparticles display remarkable tumor suppression in both subcutaneous and orthotopic breast tumor-bearing mice owing to the self-augmented CPT release and CO generation. In addition, no obvious systemic toxicity was observed in mice treated with the metal-free CO prodrug-loaded nanomedicine, suggesting the good biocompatibility of the polyprodrug nanoparticles. Our work provides new insights into the design and construction of polyprodrug nanomedicines for synergistic chemo/gas therapy.

A high concentrate diet inhibits forkhead box protein A2 expression, and induces oxidative stress, mitochondrial dysfunction and mitochondrial unfolded protein response in the liver of dairy cows.

High-concentrate diet induce subacute ruminal acidosis (SARA) and cause liver damage in ruminants. It has been reported that forkhead box protein A2 (FOXA2) can enhance mitochondrial membrane potential but its function in mitochondrial dysfunction induced by high concentrate diets is still unknown. Therefore, the aim of this study was to elucidate the effect of high-concentrate (HC) diet on hepatic FOXA2 expression, mitochondrial unfolded protein response (UPRmt), mitochondrial dysfunction and oxidative stress. A total of 12 healthy mid-lactation Holstein cows were selected and randomized into 2 groups: the low concentrate (LC) diet group (concentrate:forage = 4:6) and HC diet group (concentrate:forage = 6:4). The trial lasted 21 d. The rumen fluid, blood and liver tissue were collected at the end of the experiment. The results showed that the rumen fluid pH level was reduced in the HC group and the pH was lower than 5.6 for more than 4 h/d, indicating that feeding HC diets successfully induced SARA in dairy cows. Both FOXA2 mRNA and protein abundance were significantly reduced in the liver of the HC group compared with the LC group. The activity of antioxidant enzymes (CAT, G6PDH, T-SOD, Cu/Zn SOD, Mn SOD) and mtDNA copy number in the liver tissue of the HC group decreased, while the level of H2O2 significantly increased, this increase was accompanied by a decrease in oxidative phosphorylation (OXPHOS). The balance of mitochondrial division and fusion was disrupted in the HC group, as evidenced by the decreased mRNA level of OPA1, MFN1, and MFN2 and increased mRNA level of Drp1, Fis1, and MFF. At the same time, HC diet downregulated the expression level of SIRT1, SIRT3, PGC-1α, TFAM, and Nrf 1 to inhibit mitochondrial biogenesis. The HC group induced UPRmt in liver tissue by upregulating the mRNA and protein levels of CLPP, LONP1, CHOP, Hsp10, and Hsp60. In addition, HC diet could increase the protein abundance of Bax, CytoC, Caspase 3 and Cleaved-Caspase 3, while decrease the protein abundance of Bcl-2 and the Bcl-2/Bax ratio. Overall, our study suggests that the decreased expression of FOXA2 may be related to UPRmt, mitochondrial dysfunction, oxidative stress, and apoptosis in the liver of dairy cows fed a high concentrate diet.

Erratum: Author correction to "Cascade two-stage tumor re-oxygenation and immune re-sensitization mediated by self-assembled albumin-sorafenib nanoparticles for enhanced photodynamic immunotherapy" [Acta Pharm Sin B (2022) 4204-4223].

[This corrects the article DOI: 10.1016/j.apsb.2022.07.023.].

Metabolome profiling and transcriptome analysis filling the early crucial missing steps of piperine biosynthesis in Piper nigrum L.

Black pepper (Piper nigrum L.), the world renown as the King of Spices, is not only a flavorsome spice but also a traditional herb. Piperine, a species-specific piper amide, is responsible for the major bioactivity and pungent flavor of black pepper. However, several key steps for the biosynthesis of piperoyl-CoA (acyl-donor) and piperidine (acyl-acceptor), two direct precursors for piperine, remain unknown. In this study, we used guilt-by-association analysis of the combined metabolome and transcriptome, to identify two feruloyldiketide-CoA synthases responsible for the production of the C5 side chain scaffold feruloyldiketide-CoA intermediate, which is considered the first and important step to branch metabolic fluxes from phenylpropanoid pathway to piperine biosynthesis. In addition, we also identified the first two key enzymes for piperidine biosynthesis derived from lysine in P. nigrum, namely a lysine decarboxylase and a copper amine oxidase. These enzymes catalyze the production of cadaverine and 1-piperideine, the precursors of piperidine. In vivo and in vitro experiments verified the catalytic capability of them. In conclusion, our findings revealed enigmatic key steps of piperine biosynthetic pathway and thus provide a powerful reference for dissecting the biosynthetic logic of other piper amides.

CD24+LCN2+ liver progenitor cells in ductular reaction contributed to macrophage inflammatory responses in chronic liver injury.

BACKGROUND: CD24+CK19+/CD24+SOX9+ resident liver cells are activated and expanded after chronic liver injury in a ductular reaction. However, the sources and functions of these cells in liver damage remain disputed. RESULTS: The current study combined genetic lineage tracing with in vitro small-molecule-based reprogramming to define liver progenitor cells (LPCs) derived from hepatic parenchymal and non-parenchymal tissues. tdTom+ hepatocytes were isolated from ROSA26tdTomato mice following AAV8-Tbg-Cre-mediated recombination, EpCAM+ biliary epithelial cells (BECs) from wild-type intrahepatic bile ducts and ALB/GFP-EpCAM- cells were isolated from AlbCreERT/R26GFP mice. A cocktail of small molecules was used to convert the isolated cells into LPCs. These in vitro cultured LPCs with CD24 and SOX9 expression regained the ability to proliferate. Transcriptional profiling showed that the in-vitro cultured LPCs derived from the resident LPCs in non-parenchymal tissues expressed Lipocalin-2 (Lcn2) at high levels. Accordingly, endogenous Cd24a+Lcn2+ LPCs were identified by integration of sc-RNA-sequencing and pathological datasets of liver dysfunction which indicates that LPCs produced by ductular reactions might also originate from the resident LPCs. Transplantation of in-vitro cultured Cd24a+Lcn2+ LPCs into CCl4-induced fibrotic livers exacerbated liver damage and dysfunction, possibly due to LCN2-dependent macrophage inflammatory response. CONCLUSIONS: CD24+LCN2+ LPCs constituted the expanding ductular reaction and contributed to macrophage-mediated inflammation in chronic liver damage. The current findings highlight the roles of LPCs from distinct origins and expose the possibility of targeting LPCs in the treatment of chronic hepatic diseases.

Elucidation of the melitidin biosynthesis pathway in pummelo.

Specialized plant metabolism is a rich resource of compounds for drug discovery. The acylated flavonoid glycoside melitidin is being developed as an anti-cholesterol statin drug candidate, but its biosynthetic route in plants has not yet been fully characterized. Here, we describe the gene discovery and functional characterization of a new flavonoid gene cluster (UDP-glucuronosyltransferases (CgUGTs), 1,2 rhamnosyltransferase (Cg1,2RhaT), acyltransferases (CgATs)) that is responsible for melitidin biosynthesis in pummelo (Citrus grandis (L.) Osbeck). Population variation analysis indicated that the tailoring of acyltransferases, specific for bitter substrates, mainly determine the natural abundance of melitidin. Moreover, 3-hydroxy-3-methylglutaryl-CoA reductase enzyme inhibition assays showed that the product from this metabolic gene cluster, melitidin, may be an effective anti-cholesterol statin drug candidate. Co-expression of these clustered genes in Nicotiana benthamiana resulted in the formation of melitidin, demonstrating the potential for metabolic engineering of melitidin in a heterologous plant system. This study establishes a biosynthetic pathway for melitidin, which provides genetic resources for the breeding and genetic improvement of pummelo aimed at fortifying the content of biologically active metabolites.

Transparent dynamic infrared emissivity regulators.

Dynamic infrared emissivity regulators, which can efficiently modulate infrared radiation beyond vision, have emerged as an attractive technology in the energy and information fields. The realization of the independent modulation of visible and infrared spectra is a challenging and important task for the application of dynamic infrared emissivity regulators in the fields of smart thermal management and multispectral camouflage. Here, we demonstrate an electrically controlled infrared emissivity regulator that can achieve independent modulation of the infrared emissivity while maintaining a high visible transparency (84.7% at 400-760 nm). The regulators show high degree of emissivity regulation (0.51 at 3-5 µm, 0.41 at 7.5-13 µm), fast response ( < 600 ms), and long cycle life ( > 104 cycles). The infrared emissivity regulation is attributed to the modification of the carrier concentration in the surface depletion layer of aluminum-doped zinc oxide nanocrystals. This transparent infrared emissivity regulator provides opportunities for applications such as on-demand smart thermal management, multispectral displays, and adaptive camouflage.

Thyroid Hormone Reference Intervals among Healthy Individuals In Lanzhou, China.

BACKGRUOUND: The common reference intervals (RIs) for thyroid hormones currently used in China are provided by equipment manufacturers. This study aimed to establish thyroid hormone RIs in the population of Lanzhou, a city in the subplateau region of northwest China, and compare them with previous reports and manufacturer-provided values. METHODS: In total, 3,123 individuals (1,680 men, 1,443 women) from Lanzhou, an iodine-adequate area of China, perceived as healthy were selected. The Abbott Architect analyzer was used to determine the serum concentration of thyroid hormones. The 95% RI was estimated using the 2.5th and 97.5th percentiles as the lower and upper reference limits, respectively. RESULTS: The serum levels of thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), antithyroglobulin (ATG) antibody, and antithyroid peroxidase (ATPO) antibody levels were significantly correlated with sex (P<0.05). TSH, total thyroxine (TT4), and ATPO levels were significantly correlated with age (P<0.05). The serum levels of TSH, ATG, and ATPO in men were significantly lower than in women; in contrast, the serum TT3 level was significantly higher in men than in women (P<0.05). Serum TSH, TT3, TT4, and ATG levels differed across age groups (P<0.05), but no such variation was observed for ATG levels (P>0.05). The established RIs of TSH, ATG, and ATPO in this study differed between sexes (P<0.05). The thyroid hormone RIs established herein were inconsistent with the manufacturer-provided values. CONCLUSION: The RIs of thyroid hormones in the healthy population of Lanzhou were inconsistent with those in the manufacturer's manual. Validated sex-specific values are required for diagnosing thyroid diseases.

Preoperative Prevalence and Risk Factors For Calf Muscular Vein Thrombosis in Elderly Patients with Hip Fracture.

OBJECTIVE: Increasing evidence has shown that calf muscular vein thrombosis (CMVT) can develop into proximal deep vein thrombosis, even causing pulmonary embolism. However, opinions about the prevalence and risk factors are still controversial. This study aimed to investigate the prevalence and risk factors for CMVT in elderly patients with hip fractures to facilitate their preoperative management. METHODS: We included 419 elderly patients with hip fracture who were treated in the orthopaedic department of our hospital from June 2017 to December 2020. The patients were divided into CMVT and non-CMVT groups based on color Doppler ultrasound screening of the venous system in the lower extremities. Clinical data, such as age, sex, body mass index, time from injury to admission, and laboratory data were collected. Univariate and multivariate logistic regression analyses were performed to determine independent risk factors for CMVT. A receiver operating characteristic curve was used to analyze the predictive effectiveness of the model. Finally, the clinical utility of the model was analyzed using decision curve analysis and clinical impact curves. RESULTS: The prevalence of preoperative CMVT was 30.5% (128/419). Independent predictors of preoperative CMVT identified by univariate and multivariate logistic regression analyses were sex, time from injury to admission, American Society of Anesthesiologists (ASA) classification, C-reactive protein (CRP) level, and D-dimer level (p < 0.05). The area under curve (AUC) was 0.750 (95% CI: 0.699-0.800, p < 0.001) and the sensitivity and specificity were 0.698 and 0.711, respectively, which meant the prediction model has a good efficacy in the prediction of CMVT risk. In addition, the fitting degree of the prediction model was also good (Hosmer-Lemeshow χ2 = 8.447, p > 0.05). The clinical utility of the model was verified using decision curve analysis and clinical impact curves. CONCLUSION: Sex, time from injury to admission, ASA classification, CRP level, and D-dimer levels are independent preoperative predictors of CMVT in elderly patients with hip fractures. Measures should be taken for patients with these risk factors to prevent the occurrence and deterioration of CMVT.

Intraindividual variance of lower limb rotation in patients with bilateral knee osteoarthritis.

Purpose: To determine the side-to-side difference in intraindividual rotation alignment of patients with bilateral varus-type knee osteoarthritis (OA) and compare it with control subjects. Methods: This retrospective study enrolled 60 patients with bilateral varus-type knee OA and 50 control subjects. All cases underwent bilateral lower limb CT angiography. Bilateral femoral and tibial rotation alignment were measured, and the overall lower limb rotation was calculated by two different methods. Method 1 was calculated by subtracting angle of the femoral torsion from the tibial torsion and method 2 was determined by relative rotation of the femoral neck angle to bimalleolar angle. The intraindividual variance and differences between the two groups were analyzed. Results: Both OA and control samples showed significant differences between right and left for all measurements. Femoral torsion for control group was 10.4 ± 5.5°, tibial torsion was -22.1 ± 6.1°, and overall leg rotation by method 1 was -15.6 ± 7.2° and method 2 was -11.7 ± 8.2°. Femoral torsion, tibial torsion, method 1, and method 2 in the patients with OA were 8.2 ± 6.3°, -18.6 ± 4.1°, -14.9 ± 7.9°, and -10.4 ± 7.6°, respectively. Patients with OA showed a more pronounced retroversion in the femur (p = 0.008) and more internal rotation in the tibia (p < 0.001). No statistical significance of both methods was found between the two groups. Patients with OA had a greater median side-to-side absolute difference in all measurements, though the differences of both two methods of overall lower limb rotation were not statistically significant. Conclusions: The discrepancy of side-to-side differences of bilateral lower limb rotation ought to be noticed with caution in diagnosing and treating rotational deformities of the lower limb, especially for patients with bilateral knee OA.

Disease resistance conferred by components of essential chrysanthemum oil and the epigenetic regulation of OsTPS1.

The sesquiterpene alpha-bisabolol is the predominant active ingredient in essential oils that are highly valued in the cosmetics industry due to its wound healing, anti-inflammatory, and skin-soothing properties. Alpha-bisabolol was thought to be restricted to Compositae plants. Here we reveal that alpha-bisabolol is also synthesized in rice, a non-Compositae plant, where it acts as a novel sesquiterpene phytoalexin. Overexpressing the gene responsible for the biosynthesis of alpha-bisabolol, OsTPS1, conferred bacterial blight resistance in rice. Phylogenomic analyses revealed that alpha-bisabolol-synthesizing enzymes in rice and Compositae evolved independently. Further experiments demonstrated that the natural variation in the disease resistance level was associated with differential transcription of OsTPS1 due to polymorphisms in its promoter. We demonstrated that OsTPS1 was regulated at the epigenetic level by JMJ705 through the methyl jasmonate pathway. These data reveal the cross-family accumulation and regulatory mechanisms of alpha-bisabolol production.

Cascade two-stage tumor re-oxygenation and immune re-sensitization mediated by self-assembled albumin-sorafenib nanoparticles for enhanced photodynamic immunotherapy.

As a promising modality for cancer therapy, photodynamic therapy (PDT) still acquired limited success in clinical nowadays due to the extremely serious hypoxia and immunosuppression tumor microenvironment. To ameliorate such a situation, we rationally designed and prepared cascade two-stage re-oxygenation and immune re-sensitization BSA-MHI148@SRF nanoparticles via hydrophilic and hydrophobic self-assembly strategy by using near-infrared photodynamic dye MHI148 chemically modified bovine serum albumin (BSA-MHI148) and multi-kinase inhibitor Sorafenib (SRF) as a novel tumor oxygen and immune microenvironment regulation drug. Benefiting from the accumulation of SRF in tumors, BSA-MHI148@SRF nanoparticles dramatically enhanced the PDT efficacy by promoting cascade two-stage tumor re-oxygenation mechanisms: (i) SRF decreased tumor oxygen consumption via inhibiting mitochondria respiratory. (ii) SRF increased the oxygen supply via inducing tumor vessel normalization. Meanwhile, the immunosuppression micro-environment was also obviously reversed by two-stage immune re-sensitization as follows: (i) Enhanced immunogenic cell death (ICD) production amplified by BSA-MHI148@SRF induced reactive oxygen species (ROS) generation enhanced T cell infiltration and improve its tumor cell killing ability. (ii) BSA-MHI148@SRF amplified tumor vessel normalization by VEGF inhibition also obviously reversed the tumor immune-suppression microenvironment. Finally, the growth of solid tumors was significantly depressed by such well-designed BSA-MHI148@SRF nanoparticles, which could be potential for clinical cancer therapy.

Multiprocessing Quantum Computing through Hyperfine Couplings in Endohedral Fullerene Derivatives.

Magnetic molecules have shown great potential in quantum information processing due to the chemical tunablity of their quantum behaviors. Chemical derivatives of endohedral nitrogen fullerenes with long coherence time and rich energy levels were synthesized and studied to demonstrate the ability of multiprocessing in quantum information using electron magnetic resonance. After initialization of the 12-levelled spin system, subgroups of spin energy levels coursed by the hyperfine couplings can be selectively manipulated. The cooperatively combining of the parallel calculations enabled quantum error correction, increasing the correct rate by up to 17.82 %. Also, different subgroups of transitions divided by hyperfine coupling can be treated as independent qubits, and multi-task quantum computing were realized by performing Z-gate and X-gate simultaneously, which accelerates the overall gating speed.