Dehydrozaluzanin C- derivative protects septic mice by alleviating over-activated inflammatory response and promoting the phagocytosis of macrophages.

Host-directed therapy (HDT) is a new adjuvant strategy that interfere with host cell factors that are required by a pathogen for replication or persistence. In this study, we assessed the effect of dehydrozaluzanin C-derivative (DHZD), a modified compound from dehydrozaluzanin C (DHZC), as a potential HDT agent for severe infection. LPS-induced septic mouse model and Carbapenem resistant Klebsiella pneumoniae (CRKP) infection mouse model was used for testing in vivo. RAW264.7 cells, mouse primary macrophages, and DCs were used for in vitro experiments. Dexamethasone (DXM) was used as a positive control agent. DHZD ameliorated tissue damage (lung, kidney, and liver) and excessive inflammatory response induced by LPS or CRKP infection in mice. Also, DHZD improved the hypothermic symptoms of acute peritonitis induced by CRKP, inhibited heat-killed CRKP (HK-CRKP)-induced inflammatory response in macrophages, and upregulated the proportions of phagocytic cell types in lungs. In vitro data suggested that DHZD decreases LPS-stimulated expression of IL-6, TNF-α and MCP-1 via PI3K/Akt/p70S6K signaling pathway in macrophages. Interestingly, the combined treatment group of DXM and DHZD had a higher survival rate and lower level of IL-6 than those of the DXM-treated group; the combination of DHZD and DXM played a synergistic role in decreasing IL-6 secretion in sera. Moreover, the phagocytic receptor CD36 was increased by DHZD in macrophages, which was accompanied by increased bacterial phagocytosis in a clathrin- and actin-dependent manner. This data suggests that DHZD may be a potential drug candidate for treating bacterial infections.

Multi-frequency steady-state visual evoked potential dataset.

The Steady-State Visual Evoked Potential (SSVEP) is a widely used modality in Brain-Computer Interfaces (BCIs). Existing research has demonstrated the capabilities of SSVEP that use single frequencies for each target in various applications with relatively small numbers of commands required in the BCI. Multi-frequency SSVEP has been developed to extend the capability of single-frequency SSVEP to tasks that involve large numbers of commands. However, the development on multi-frequency SSVEP methodologies is falling behind compared to the number of studies with single-frequency SSVEP. This dataset was constructed to promote research in multi-frequency SSVEP by making SSVEP signals collected with different frequency stimulation settings publicly available. In this dataset, SSVEPs were collected from 35 participants using single-, dual-, and tri-frequency stimulation and with three different multi-frequency stimulation variants.

Chronic exposure to parabens promotes non-alcoholic fatty liver disease in association with the changes of the gut microbiota and lipid metabolism.

Non-alcoholic fatty liver disease (NAFLD) has become a serious public health issue due to changing dietary patterns and composition. However, the relationship between NAFLD occurrence and food additives, such as preservatives, remains unknown. This study aimed to evaluate the toxicity of parabens, namely methylparaben (MeP) and ethylparaben (EtP), in relation to NAFLD occurrence in mice under different dietary conditions. Exposure to MeP and EtP exacerbated high-fat diet (HFD)-induced obesity, glucose intolerance, higher serum lipid concentrations, and fat accumulation by upregulating genes involved in lipid metabolism. Untargeted metabolomics revealed that arachidonic acid (AA) metabolism was the top enriched pathway upon MeP and EtP exposure in the presence of HFD. 11,12-Epoxyeicosatrienoic acid (11,12-EET) was the most abundant AA metabolite and was significantly reduced upon exposure to MeP or EtP. Moreover, an integrative analysis of differential fecal taxa at the genus level and serum AA metabolites revealed significant associations. In addition, MeP and EtP enhanced lipid accumulation in AML12 cells and HepG2 cells cultured with oleic acid. 11,12-EET supplementation could significantly alleviate lipid accumulation by suppressing the expression of lipid metabolism-related genes and proteins. The present study suggests that chronic exposure to MeP and EtP promoted NAFLD via gut microbiota-dependent AA metabolism. These results highlight the need for reducing oral exposure to synthetic preservatives to improve metabolic disturbance under HFD conditions.

Clinical characteristics and risk factors of IgA vasculitis with intussusception and intestinal perforation.

AIM: Intussusception is the most common surgical complication of IgA vasculitis (IgAV), and intestinal perforation is usually associated with intussusception. If they are not recognised and treated in a timely manner, serious consequences may occur. The objective is to summarise the clinical features of IgAV complicated by intussusception and intestinal perforation and explore its risk factors. METHODS: The clinical data of 32 patients with IgAV complicated by surgical complications (25 cases of intussusception and 7 cases of intestinal perforation) were retrospectively analysed. A total of 160 IgAV children with gastrointestinal (GI) involvement but without surgical complications were randomly selected as a control group. Binary logistic regression analysis was performed to explore the risk factors for IgAV with intussusception and intestinal perforation. RESULTS: Compared with the intussusception group, the intestinal perforation group had a significantly higher number of patients with GI symptoms prior to skin purpura and GI bleeding, a significantly higher number of days of abdominal pain, a significantly higher Wong-Baker score, and a significantly higher white blood cell count. Multivariate logistic regression analysis indicated that age ≤7 years, GI symptoms prior to skin purpura, abdominal pain intensity (Wong-Baker scale) and timing of glucocorticoid treatment were independent risk factors of IgAV with intussusception and intestinal perforation. CONCLUSION: Age less than 7 years, severe abdominal pain, and GI symptoms prior to skin purpura were risk factors for IgAV with intussusception and intestinal perforation. Early use of glucocorticoids may prevent intussusception and intestinal perforation.

Pycard deficiency inhibits microRNA maturation and prevents neointima formation by promoting chaperone-mediated autophagic degradation of AGO2/argonaute 2 in adipose tissue.

PYCARD (PYD and CARD domain containing), a pivotal adaptor protein in inflammasome assembly and activation, contributes to innate immunity, and plays an essential role in the pathogenesis of atherosclerosis and restenosis. However, its roles in microRNA biogenesis remain unknown. Therefore, this study aimed to investigate the roles of PYCARD in miRNA biogenesis and neointima formation using pycard knockout (pycard-/-) mice. Deficiency of Pycard reduced circulating miRNA profile and inhibited Mir17 seed family maturation. The systemic pycard knockout also selectively reduced the expression of AGO2 (argonaute RISC catalytic subunit 2), an important enzyme in regulating miRNA biogenesis, by promoting chaperone-mediated autophagy (CMA)-mediated degradation of AGO2, specifically in adipose tissue. Mechanistically, pycard knockout increased PRMT8 (protein arginine N-methyltransferase 8) expression in adipose tissue, which enhanced AGO2 methylation, and subsequently promoted its binding to HSPA8 (heat shock protein family A (Hsp70) member 8) that targeted AGO2 for lysosome degradation through chaperone-mediated autophagy. Finally, the reduction of AGO2 and Mir17 family expression prevented vascular injury-induced neointima formation in Pycard-deficient conditions. Overexpression of AGO2 or administration of mimic of Mir106b (a major member of the Mir17 family) prevented Pycard deficiency-mediated inhibition of neointima formation in response to vascular injury. These data demonstrate that PYCARD inhibits CMA-mediated degradation of AGO2, which promotes microRNA maturation, thereby playing a critical role in regulating neointima formation in response to vascular injury independently of inflammasome activity and suggest that modulating PYCARD expression and function may represent a powerful therapeutic strategy for neointima formation.Abbreviations: 6-AN: 6-aminonicotinamide; ACTB: actin, beta; aDMA: asymmetric dimethylarginine; AGO2: argonaute RISC catalytic subunit 2; CAL: carotid artery ligation; CALCOCO2: calcium binding and coiled-coil domain 2; CMA: chaperone-mediated autophagy; CTSB: cathepsin B; CTSD: cathepsin D; DGCR8: DGCR8 microprocessor complex subunit; DOCK2: dedicator of cyto-kinesis 2; EpiAdi: epididymal adipose tissue; HSPA8: heat shock protein family A (Hsp70) member 8; IHC: immunohistochemical; ISR: in-stent restenosis; KO: knockout; LAMP2: lysosomal-associated membrane protein 2; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; miRNA: microRNA; NLRP3: NLR family pyrin domain containing 3; N/L: ammonium chloride combined with leupeptin; PRMT: protein arginine methyltransferase; PVAT: peri-vascular adipose tissues; PYCARD: PYD and CARD domain containing; sDMA: symmetric dimethylarginine; ULK1: unc-51 like kinase 1; VSMCs: vascular smooth muscle cells; WT: wild-type.

A fully integrated wearable ultrasound system to monitor deep tissues in moving subjects.

Recent advances in wearable ultrasound technologies have demonstrated the potential for hands-free data acquisition, but technical barriers remain as these probes require wire connections, can lose track of moving targets and create data-interpretation challenges. Here we report a fully integrated autonomous wearable ultrasonic-system-on-patch (USoP). A miniaturized flexible control circuit is designed to interface with an ultrasound transducer array for signal pre-conditioning and wireless data communication. Machine learning is used to track moving tissue targets and assist the data interpretation. We demonstrate that the USoP allows continuous tracking of physiological signals from tissues as deep as 164 mm. On mobile subjects, the USoP can continuously monitor physiological signals, including central blood pressure, heart rate and cardiac output, for as long as 12 h. This result enables continuous autonomous surveillance of deep tissue signals toward the internet-of-medical-things.

Predictive Shared Control of Robotic Arms Using Simulated Brain-Computer Interface Inputs.

Low decoding accuracy makes brain-computer interface (BCI) control of a robotic arm difficult. Shared control (SC) can overcome limitations of a BCI by leveraging external sensor data and generating commands to assist the user. Our study explored whether reaching targets with a robot end-effector was easier using SC rather than direct control (DC). We simulated a motor imagery BCI using a joystick with noise introduced to explicitly control interface accuracy to be 65% or 79%. Compared to DC, our prediction-based implementation of SC led to a significant reduction in the trajectory length of successful reaches for 4 (3) out of 5 targets using the 65% (79%) accurate interface, with failure rates being equivalent to DC for 2 (1) out of 5 targets. Therefore, this implementation of SC is likely to improve reaching efficiency but at the cost of more failures. Additionally, the NASA Task Load Index results suggest SC reduced user workload.Clinical relevance-Shared control can minimise the impact of BCI decoder errors on robot motion, making robotic arm control using noninvasive BCIs more viable.

Experimental validation on dual-frequency outperforms single-frequency SSVEP with large numbers of targets within a given frequency range.

Multi-frequency steady-state visual evoked potential (SSVEP) aims to increase the number of targets in SSVEP-based brain-computer interfaces. However, the effectiveness of multi-frequency SSVEP when there is a large number of targets compared to traditional single-frequency SSVEP has not been demonstrated to date. It is also unclear the degree to which multi-frequency SSVEP outperforms single-frequency SSVEP as the number of targets increases. This study directly compares single-frequency and dual-frequency SSVEPs for different numbers of targets within a fixed (5 Hz) frequency range. Our results demonstrate that dual-frequency SSVEP maintains its performance at a high level of accuracy in the range while single-frequency SSVEP performance falls as the number of targets becomes very high within the given frequency range. In this particular study, dual-frequency SSVEP has a clear advantage when there are more than 120 targets in a 5 Hz frequency range.

Effect of alpha range activity on SSVEP decoding in brain-computer interfaces.

Brain-computer interfaces (BCIs) facilitate direct communication between the brain and external devices. For BCI technology to be commercialized for wide scale applications, BCIs should be accurate, efficient, and exhibit consistency in performance for a wide variety of users. A core challenge is the physiological and anatomical differences amongst people, which causes a high variability amongst participants in BCI studies. Hence, it becomes necessary to analyze the mechanisms causing this variability and address them by improving the decoding algorithms. In this paper, a publicly available steady-state visual evoked potential (SSVEP) dataset is analyzed to study the effect of SSVEP flicker on the endogenous alpha power and the subsequent overall effect on the classification accuracy of the participants. It was observed that the participants with classification accuracy below 95% showed increased alpha power in their brain activities. Incorrect prediction in the decoding algorithm was observed a maximum number of times when the predicted frequency was in the range 9-12 Hz. We conclude that frequencies between 9-12 Hz may result in below par performance in some participants when canonical correlation analysis is used for classification.Clinical relevance-If alpha-band frequencies are used for SSVEP stimulation, alpha power interference in EEG may alter BCI accuracy for some users.

Association between psoriasis and serum apolipoprotein A1 and B: A systematic review and meta-analysis.

Background: Psoriasis has been linked to dyslipidemia. However, the magnitude of the association between psoriasis and serum apolipoproteins A1 and B remains unclear. Methods: We systematically searched PubMed, Embase, and Cochrane Library databases for eligible studies published before August 10, 2023. Data were pooled using Stata software. We adopted a random-effects model for the meta-analysis. Additionally, we conducted subgroup analyses of the studies according to the psoriasis type and matched body mass index (BMI). Results: Seventeen studies involving 2467 participants were included. Psoriasis was associated with decreased serum apolipoprotein A1 (weighted mean difference [WMD] = -9.05, P < 0.001) and increased serum apolipoprotein B (WMD = 11.68, P < 0.001). In subgroup analysis after matching BMI, the findings showing an association of psoriasis with serum apolipoprotein A1 (WMD = -14.07, P < 0.001) and serum apolipoprotein B (WMD = 13.07, P < 0.001) were consistent with the overall results. The subgroup analysis for the presence or absence of psoriatic arthritis showed that serum apolipoprotein A1 was significantly decreased in psoriasis with (WMD = -11.29, P < 0.001) and without arthritis (WMD = -8.69, P = 0.039); whereas serum apolipoprotein B was significantly increased in psoriasis with (WMD = 13.57, P < 0.001) and without arthritis (WMD = 9.21, P < 0.001). Conclusions: Our study revealed that psoriasis is associated with decreased serum apolipoprotein A1 and increased serum apolipoprotein B levels compared with healthy controls.

Low-k SiOx/AlOx Nanolaminate Dielectric on Dielectric Achieved by Hybrid Pulsed Chemical Vapor Deposition.

Selective and smooth low-k SiOx/AlOx nanolaminate dielectric on dielectric (DOD) was achieved by a hybrid water-free pulsed CVD process consisting of 50 pulses of ATSB (tris(2-butoxy)aluminum) at 330 °C and a 60 s TBS (tris(tert-butoxy)silanol) exposure at 200 °C. Aniline selective passivation was demonstrated on W surfaces in preference to Si3N4 and SiO2 at 300 °C. At 200 °C, TBS pulsed CVD exhibited no growth on W or SiO2, but its growth was catalyzed by AlOx. Using a two-temperature pulsed CVD process, ∼2.7 nm selective SiOx/AlOx nanolaminate was deposited on Si3N4 in preference to aniline passivated W. Nanoselectivity was confirmed and demonstrated on nanoscale W/SiO2 patterned samples by TEM analysis. For a 1:1 Si:Al ratio, a dielectric constant (k) value of 3.3 was measured. For a 2:1 Si:Al ratio, a dielectric constant (k) value of 2.5 was measured. The k value well below that of Al2O3 and SiO2 is consistent with the formation of a low-density, low-k SiO2/Al2O3 nanolaminate in a purely thermal process. This is the first report of a further thermal CVD process for deposition of a low-k dielectric and the first report for a selective low-k process on the nanoscale.

Practical study on the application of full-cycle fast track surgical nursing model in patients with replantation of severed fingers: A retrospective analysis.

To explore the effect of full-cycle fast track surgical (FTS) nursing in patients with replantation of severed fingers, and observe its effect on functional recovery of replanted fingers and quality of life of patients. From January 2021 to December 2022, 86 patients with replantation of severed fingers were selected from Rizhao People's Hospital, 41 patients were given routine perioperative care, 45 patients were given full-cycle rapid rehabilitation surgical care. Compare the relevant indexes of the 2 groups of patients during hospitalization. Three months after discharge, the finger function recovery of the 2 groups were compared, and the quality of life of the patients was scored with the QL-Index scale, and the satisfaction was evaluated at the same time. The first time of getting out of bed and the time of hospitalization in the full-cycle FTS nursing group were significantly shorter than those in the conventional nursing group, and the incidence of postoperative nausea, vomiting, constipation and venous thromboembolism were significantly lower than those in the conventional nursing group. The anxiety score was significantly lower than that in the conventional nursing group, the difference was statistically significant (P < .05). There was no significant difference in the incidence of arteriovenous crisis between the 2 groups (P > .05). Three months after discharge, the scores of finger sensation and movement, quality of life and satisfaction of patients in the FTS nursing group were higher than those in the conventional nursing group, and the difference was statistically significant (P < .05). Full-cycle fast track surgical nursing model can improve the in-patient experience, reduce the incidence of complications, promote rapid rehabilitation, improve the quality of life of patients, and improve satisfaction.

Proteomic Analysis of Two Different Methods to Induce Skin Melanin Deposition Models in Guinea Pigs.

Objective: In this study, we analyzed the differential expression and key signaling pathways of proteins in the skin of guinea pigs with melanin deposition caused by two different modeling methods by utilizing proteomics techniques. Methods: Guinea pig skin melanin deposition models were: (1) induced by ultraviolet (UV) irradiation alone (U group), (2) induced by UV combined with progesterone injection (P group), and guinea pigs treated without any treatment were used as blank group (B group). H&E staining and Masson staining were used to observe the extent of skin damage and melanin deposition in guinea pigs. The differentially expressed proteins (DEPs) in the skin tissues of melanin-deposited guinea pigs were screened by proteomic techniques, the functions of DEPs were analyzed, and a protein-protein interaction network (PPI) was constructed. Results: There was a significant difference in grayscale between the U and P groups of guinea pig skin before and after modeling (P < 0.01). H&E and Masson staining showed that the U and P groups both exhibited incomplete keratinization of the stratum corneum, increased proliferation of epidermal cells with large nuclei and disordered arrangement, neovascularization of the dermis, and increased the number of melanin particles in the epidermis of the U and P groups of guinea pigs compared with the B group. Proteomics analysis showed that there were 171 DEPs between the U and P groups. These DEPs focused on biological processes such as fibrillar collagen trimer, extracellular matrix containing collagen proteins, metalloproteinase activity, and peroxidase activity. Conclusion: The melanin pigmentation model induced solely by UV radiation negatively regulates biological processes such as extracellular matrix and collagen synthesis, while inducing significant skin photoaging. The combination of progesterone injections and UV radiation-induced melanin pigmentation model can cause abnormal protein expression in fatty acid and phospholipid metabolism, possibly being closer to the environment of melasma formation.

Flexible and fast estimation method of far-field patterns for digital-coding metasurfaces.

We propose a flexible and fast estimation method to calculate the far-field patterns of digital-coding metasurfaces (DCMs) by performing chirp Z-transform (CZT), called the DCM-CZT method. Because of the expression form of convolution, CZT can be accelerated by fast Fourier transform. Compared with the traditional discrete Fourier transform (DFT) method, the DCM-CZT method can accurately estimate the far-field patterns with arbitrary element periods. More importantly, the DCM-CZT method can calculate partial far-field patterns for some specific orientations, instead of the global far-field patterns like DFT does. We show that the DCM-CZT method can efficiently improve the partial space-resolution to avoid the calculation error caused by the fence effect under acceptable computing time. We present six representative examples to demonstrate the capabilities of the proposed method. Results show that the far-field patterns calculated by the DCM-CZT method have good agreements with full-wave simulations and experimental measurements. However, the results of main-lobes calculated by the DFT method have obvious deviations when the element period is about 0.2 wavelengths. We believe that the DCM-CZT method has potential applications in wireless communications and radar detections.

Modification of whey protein isolate by ultrasound-assisted pH shift for complexation with carboxymethylcellulose: Structure and interfacial properties.

The application of whey protein isolate (WPI) is limited because of its compact spherical structure. In this study, ultrasound-assisted pH shift was employed to modify WPI for complexation with carboxymethylcellulose (CMC). The foaming and emulsifying properties of WPI/CMC complexes were investigated. The results demonstrate that the pretreatment of ultrasound-assisted pH 12 shift increased the content of free sulfhydryl groups from 16.5 µmol/g to 34.7 µmol/g and enhanced protein hydrophobicity from 311.4 to 370.6 (p < 0.05). Compared to the complexes formed by untreated WPI and CMC, the complexes pretreated with ultrasound-assisted pH 12 shift had a smaller size of 293.4 nm and a more uniform distribution. Furthermore, WPI/CMC complexes pretreated by ultrasound-assisted pH 12 shift exhibited higher emulsifying activity and emulsion stability index, which were increased by 8.9 % and 42.6 % respectively, in comparison with the control group (p < 0.05). A positive correlation was found between the surface hydrophobicity of WPI and emulsifying activity of WPI/CMC complexes. Ultrasound-assisted pH 2 shift improved the foaming capacity of complexes by 28.3 % over the control (p < 0.05). All the results indicate that the interfacial properties of WPI/CMC complexes can be improved significantly by the combination of pH shift and ultrasound.

Akkermansia muciniphila Protects Against Antibiotic-Associated Diarrhea in Mice.

Probiotics are used to prevent antibiotic-associated diarrhea (AAD) via the restoration of the gut microbiota. However, the precise effects of Akkermansia muciniphila (Akk), which is a promising probiotics, on AAD are unknown. Here, AAD models were established via the administration of lincomycin and ampicillin with or without pasteurized Akk or Amuc_1100 treatment. A diffusion test revealed that Akk was susceptible to the majority of the antibiotics, such as ampicillin. These effects were confirmed by the reduced Akk abundance in AAD model mice. Pasteurized Akk or Amuc_1100 significantly decreased the diarrhea status score and colon injury of AAD model mice. Additionally, these treatments significantly decreased the relative abundance of Citrobacter at genus level and reshaped the metabolic function of gut microbiota. Notably, pasteurized Akk or Amuc_1100 significantly changed the serum metabolome of AAD model mice. In addition, pasteurized Akk or Amuc_1100 suppressed intestinal inflammation by upregulating the expression of GPR109A and SLC5A8 and downregulating the expression of TNFα, IFNγ, IL1ß, and IL6. Furthermore, they enhanced water and electrolyte absorption by upregulating AQP4, SLC26A3, and NHE3. Pasteurized Akk or Amuc_1100 also restored intestinal barrier function by ameliorating the downregulation of ZO-1, OCLN, CLDN4, and Muc2 in AAD model mice. In summary, optimizing intestinal health with pasteurized Akk or Amuc_1100 may serve as an approach for preventing AAD.

Carbon dots-mediated synthesis of gold nanodendrites with extended absorption into NIR-II window for in vivo photothermal therapy.

BACKGROUND: Photothermal therapy (PTT) in the second near-infrared (NIR-II) window has attracted extensive attention due to the benefits in high maximum permissible exposure and penetration depth. Current photothermal agents generally show a broadband absorption accompanied by a gradual attenuation of absorption in the NIR-II window, leading to poor effect of PTT. It remains a great challenge to gain photothermal agents with strong and characteristic absorption in NIR-II regions. To overcome this problem, based on carbon dots (CDs)-mediated growth strategy, we proposed a simple and feasible approach to prepare plasmonic gold nanodendrites (AuNDs) with NIR-II absorption to enhance the therapeutic effect of PTT. RESULTS: By rationally regulating the size and branch length of AuNDs, the AuNDs exhibited a broadband absorption from 300 to 1350 nm, with two characteristic absorption peaks located at 1077 and 1265 nm. The AuNDs demonstrated desired optical photothermal conversion efficiency (38.0%), which was further applied in NIR-II photoacoustic imaging (PAI) and PTT in human colon cancer cells (HCT 116)-tumor-bearing mice model. The tumor cells could be effectively eliminated in vivo under 1064 nm laser irradiation by the guidance of PAI. CONCLUSIONS: We reported a simple but powerful synthetic method to obtain the unique AuNDs with strong and characteristic absorption peaks in the NIR-II window. This study provides a promising solution to tuning the growth of nanoparticles for bioimaging and phototherapy in the NIR-II window.

Identification of a TuMV isolate (TuMV-ZR) from Pseudostellaria heterophylla and its development into a viral expression vector.

Pseudostellaria heterophylla (P. heterophylla) is a popular Chinese medicinal herb that is cultivated widely in China. Viral infection is commonly encountered during the production of P. heterophylla. To identify viruses causing P. heterophylla disease, sRNA and mRNA libraries were built for 2 sets of P. heterophylla plants, one set that was planted only once (FGP) and one that was planted three consecutive three times (TGP) in a field, using virus-free tuberous roots as reproductive materials. A comprehensive procedure, including assembling virus-derived sRNA (vsRNA), assessing and cloning the full-length viral genome, building an infectious cloning vector and constructing a virus-based expression vector, was performed to identify viruses infecting P. heterophylla. Ultimately, 48 contig-related viruses were mined from 6 sRNA and 6 mRNA P. heterophylla libraries. A 9762-bp fragment was predicted to be the complete genome of TuMV virus. This sequence was cloned from P. heterophylla, and its infectivity was evaluated using the virus-infection model plant Nicotiana benthamiana (N. benthamiana) and host plant P. heterophylla. The resulting 9839-bp viral genome was successfully obtained from P. heterophylla and identified as a new P. heterophylla TuMV-ZR isolate. Simultaneously, TuMV-ZR infectious clones were shown to effectively infect P. heterophylla. Furthermore, TuMV-ZR expression vectors were developed, and the ability of a TuMV-ZR-based vector to express foreign genes was determined by analysis with the reporter gene EGFP. TuMV-ZR-based vectors were found to continuously express foreign genes in different organs of P. heterophylla throughout the whole vegetative period. In addition, TuMV-ZR vectors carrying EGFP accumulated in the tuberous roots of P. heterophylla, confirming that tuberous roots are key targets for viral infection and transmission. This study revealed the core pathogenicity of P. heterophylla mosaic virus and developed a new TuMV-ZR-based expression tool that led to long-term protein expression in P. heterophylla, laying the foundation for the identification of the mechanisms of P. heterophylla infection with mosaic viruses and developing tools to express value proteins in the tuberous roots of the medicinal plant P. heterophylla.

Tuning the Organ Tropism of Polymersome for Spleen-Selective Nanovaccine Delivery to Boost Cancer Immunotherapy.

The past few decades have witnessed explosive development in drug delivery systems. However, in vivo delivery suffers from non-specific distribution in non-targeted organs or tissues, which may cause undesired side effects and even genotoxicity. Here, a general strategy that enables tuning the tropism of polymersomes for liver- and spleen-selective delivery is reported. By using a library screening approach, spleen-targeted polymersome PH9-Aln-8020 and liver-targeted polymersome PA9-ZP3-5050 are identified accordingly. Meanwhile, the second near-infrared (NIR-II) fluorescence imaging allows for in vivo dynamic evaluation of their spatial and temporal accumulation in specific tissues. O ur findings indicate that both polymer composition and protein corona on the surface are essential to determine the in vivo fate of polymersomes and tendency for specific organs. Importantly, PH9-Aln-8020 is employed as a systemic nanocarrier to co-deliver the antigen and adjuvant, which remarkably boost splenic immune responses in acute myeloid leukemia, melanoma, and melanoma lung metastasis mouse models. This study may open a new frontier for polymersomes in organ-selective delivery and other biomedical applications.