Differentiation of Polygonatum Cyrtonema Hua from Different Geographical Origins by near-Infrared Spectroscopy with Chemometrics.

BACKGROUND: The identification of the geographical origin of Polygonatum cyrtonema Hua is of particular importance because the quality and market value of Polygonatum cyrtonema Hua from different production areas are highly variable due to differences in the growing environment and climatic conditions. OBJECTIVE: This study utilized near-infrared spectra (NIR) of Polygonatum cyrtonema Hua (n = 400) to develop qualitative models for effective differentiation of Polygonatum cyrtonema Hua from various regions. METHODS: The models were produced under different conditions to distinguish the origins distinctly. Ten pre-processing methods have been used to pre-process the original spectra (OS) and to select the most optimal spectral pre-processing method. Principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and orthogonal partial least squares discriminant analysis (OPLS-DA) were employed to determine appropriate models. For simplicity, the pretreated full spectrum was calculated by different wavelength selection methods, and the four most significant variables were selected as discriminant indicator variables. RESULTS: The results show that Polygonatum cyrtonema Hua from different regions can be effectively distinguished using spectra from a series of samples analyzed by OPLS-DA. The accuracy of the OPLS-DA model is also satisfactory, with a good differentiation rate. CONCLUSION: The study findings indicate the feasibility of using spectroscopy in combination with multivariate analysis to identify the geographical origins of Polygonatum cyrtonema Hua. HIGHLIGHTS: The utilization of near-infrared spectroscopy combined with chemometrics exhibits high efficacy in discerning the provenance of herbal medicines and foods, thereby facilitating quality assurance measures.

Development of gene panel for predicting recurrence in early-stage cervical cancer patients.

Cervical cancer (CC) is a common malignancy affecting women worldwide. Our objective was to develop a consensus-based gene panel using multi-omics data that could effectively predict recurrence in early-stage cervical cancer patients. We utilized the "Multi-Omics Consensus Integration Analysis (MOVICS)" package for consensus clustering design to integrate multiple omics datasets and improve the molecular classification landscape of early-stage CC. We identified the "resting and naive" tumor microenvironment (TME) as cancer subtype (CS) 2. Leveraging the feature genes from the CS classifier, we employed machine learning algorithms to identify a gene panel, including ALDH1A1, CLDN10, MUC13, and C10orf99, which could generate a consensus machine learning-driven score (CMLS) for each patient. Stratifying patients into high and low CMLS groups resulted in Kaplan-Meier curves demonstrating a significant difference in recurrence rates between the two groups. This difference remained significant even after adjusting for clinical features in multivariate Cox regression analysis, with the risk ratio of CMLS surpassing that of clinical characteristics. Furthermore, the TME exhibited notable differences between the different CMLS groups, suggesting that patients with low CMLS may exhibit a better response to immunotherapy. This study highlights the potential of the CMLS approach in predicting recurrence in early-stage cervical cancer patients and provides a screening model for selecting patients suitable for immunotherapy.

Macrophage activation markers are associated with infection and mortality in patients with acute liver failure.

BACKGROUND AND AIMS: Acute liver failure is a multisystem disorder with a high mortality and frequent need for emergency liver transplantation. Following massive innate immune system activation, soluble markers of macrophage activation are released during liver damage and their association with disease severity and prognosis requires exploration. METHODS: Patients ALF from the United States Acute Liver Failure Study Group (USALFSG, n = 224) and King's College Hospital (n = 40) together with healthy controls (HC, n = 50) were recruited. Serum from early (Days 1-3) and late (>Day 3) time points were analysed for MAMs by enzyme-linked immunosorbent assay correlated to markers of illness severity and 21-day spontaneous survival. Surface expression phenotyping was performed via Flow Cytometry on CD14+ monocytes. RESULTS: All MAMs serum concentrations were significantly higher in ALF compared to controls (p < .0001). sCD206 concentration was higher in early and late stages of the disease in patients with bacteraemia (p = .002) and infection in general (p = .006). In MELD-adjusted multivariate modelling, sCD206 and sCD163 were independently associated with mortality. CD14+ monocyte expression of CD206 (p < .001) was higher in patients with ALF compared with controls and correlated with SOFA score (p = .018). sCD206 was independently validated as a predictor of infection in an external cohort. CONCLUSIONS: sCD206 is increased in serum of ALF patients with infections and poor outcome and is upregulated on CD14+ monocytes. Later measurements of sCD163 and sCD206 during the evolution of ALF have potential as mechanistic predictors of mortality. sCD206 should be explored as a biomarker of sepsis and mortality in ALF.

Balanced medial-lateral wall vs selective 3-wall orbital decompression for sight-threatening Graves's orbitopathy: a clinical retrospective cohort study from 2016 to 2022.

PURPOSE: Although urgent orbital decompression surgery for sight-threatening Graves' orbitopathy unresponsive to available medical treatments continues to evolve, post-operative new-onset or worsened pre-operative strabismus or diplopia remains a significant complication. At present, the optimal surgical technique remains debatable. Here, we sought to compare long-term outcomes after balanced medial-lateral wall versus selective 3-wall decompression as an urgent treatment for unresponsive sight-threatening GO. METHODS: This retrospective study examined the post-operative outcome of 102 eyes (57 patients) that underwent urgent orbital decompression for sight-threatening GO. Treatment effectiveness was measured by visual acuity, proptosis, perimetry, and strabismus/diplopia, while fundus findings were detected by fundus color photography and optical coherence tomography and followed up for more than 12 months. RESULTS: Fifty-seven patients (102 orbits) with an average age of 52.7 ± 10.2 years were evaluated. Balanced medial-lateral wall (BMLW-OD) or selective 3-wall decompression(S3W-OD) were performed in 54 and 48 eyes, respectively. Twelve months after orbital decompression, all parameters significantly improved in both groups, including best-corrected visual acuity (BCVA), mean defect of visual field (VF-MD), pattern standard deviation of visual field (VF-PSD), and proptosis (all P < 0.01). However, new-onset esotropia occurred in 25.8% and 3.8% of patients who underwent BMLW-OD surgery or S3W-OD, respectively. Moreover, 6.5% and 38.5% of patients improved after decompression in the medial-lateral wall decompression group and the selective 3-wall decompression group, respectively. CONCLUSIONS: We demonstrated that S3W-OD provides a lower rate of new-onset strabismus/diplopia as compared with BMLW-OD surgery, while still allowing for satisfactory visual outcomes. TRIAL REGISTRATION NUMBER:  : NCT05627401. Date of registration: November 25, 2022.

HOXA9 gene inhibits proliferation and differentiation and promotes apoptosis of bovine preadipocytes.

BACKGROUND: Hox gene family is an important transcription factor that regulates cell process, and plays a role in the process of adipocytes differentiation and fat deposition. Previous transcriptome sequencing studies have indicated that the Homeobox A9 gene (HOXA9) is a candidate gene for regulating the process of bovine lipid metabolism, but the function and specific mechanism of action remain unclear. Therefore, this study aims to explore the role of HOXA9 in the proliferation, differentiation and apoptosis of bovine preadipocytes through gain-of-function and lose-of-function. RESULT: It found HOXA9 highly expressed in bovine adipose tissue, and its expression level changed significantly during adipocytes differentiation process. It gave a hint that HOXA9 may be involved in the process of bovine lipid metabolism. The results of HOXA9 gain-of-function experiments indicated that HOXA9 appeared to act as a negative regulator not only in the differentiation but also in the proliferation of bovine preadipocytes, which is mainly reflected that overexpression of HOXA9 down-regulate the mRNA and protein expression level of PPARγ, CEBPα and FABP4 (P < 0.05). The mRNA expression level of CDK1, CDK2, PCNA, CCNA2, CCNB1, CCND1 and CCNE2, as well as the protein expression of CDK2 also significantly decreased. The decrease of lipid droplets content was the main characteristic of the phenotype (P < 0.01), which further supported the evidence that HOXA9 was a negative regulator of preadipocytes differentiation. The decrease of cell proliferation rate and EdU positive rate, as well as the limitation of transition of preadipocytes from G0/G1 phase to S phase also provided evidence for the inhibition of proliferation. Apart from this above, we noted an interesting phenomenon that overexpression of HOXA9 showed in a significant upregulation of both mRNA and protein level of apoptosis markers, accompanied by a significant increase in cell apoptosis rate. These data led us not to refute the fact that HOXA9 played an active regulatory role in apoptosis. HOXA9 loss-of-function experiments, however, yielded the opposite results. Considering that HOXA9 acts as a transcription factor, we predicted its target genes. Dual luciferase reporter assay system indicated that overexpression of HOXA9 inhibits activity of PCNA promoter. CONCLUSION: Taken together, we demonstrated for the first time that HOXA9 played a role as a negative regulatory factor in the differentiation and proliferation of preadipocytes, but played a positive regulatory role in apoptosis, and it may play a regulatory role by targeting PCNA. This study provides basic data for further exploring the regulatory network of intramuscular fat deposition in bovine.

Extracellular vesicles derived from bone marrow mesenchymal stem cells ameliorate chronic liver damage via microRNA-136-5p.

Chronic liver damage (CLD) encompasses a spectrum of conditions and poses a significant global health challenge, affecting millions of individuals. Currently, there is a deficiency of clinically validated therapeutics with minimal side effects. Emerging evidence underscores the significant potential of extracellular vesicles derived from bone marrow mesenchymal stem cells (BMSC-EVs) as a promising therapeutic method for CLD. This study aimed to evaluate the influence of BMSC-EVs containing microRNA-136-5p (BMSC-EVs-miR-136-5p) on macrophage polarization during chronic liver injury and elucidate the mechanisms associated with the GNAS/PI3K/ERK/STAT3 axis. Surface markers of BMSCs were detected via Immunofluorescent Staining. Subsequently, EVs were harvested from the BMSC culture medium. In vivo fluorescence imaging was employed to locate the BMSC-EVs. Additionally, fluorescence microscopy was used to visualize the uptake of DIR-labeled BMSC-EVs by RAW264.7 cells. Various methods were employed to assess the impact of BMSC-EVs on the expression levels of inflammatory factors (IL-1ß, IL-6, IL-10, and TNF-α), M1/M2 macrophage markers (iNOS and Arg-1), and members of inflammation-related signaling pathways (GNAS, PI3K, ERK, and STAT3) in RAW264.7 cells co-cultured with BMSC-EVs. Loss-of-function approaches targeting miR-136-5p in RAW264.7 cells were subsequently utilized to validate the role of BMSC-EVs-miR-136-5p. The Luciferase Reporter Assay indicates that GNAS was identified to be a target of miR-136-5p, and miR-136-5p demonstrating increased within BMSC-EVs compared to Raw264.7-EVs. BMSC-EVs-miR-136-5p mitigated CCl4-induced liver inflammation and improved liver function by Suppressing the GNAS/STAT3 Signaling. Notably, miR-136-5p suppressed lipopolysaccharide (LPS)-induced inflammation in RAW264.7 cells. BMSC-EVs-miR-136-5p alleviates CLD by activating M2 polarization through the GNAS-mediated PI3K/ERK/STAT3 axis. Accordingly, the members of this axis may serve as therapeutic targets.

The melanin pigment gene black mediates body pigmentation and courtship behaviour in the German cockroach Blattella germanica.

Genes involved in melanin production directly impact insect pigmentation and can affect diverse physiology and behaviours. The role these genes have on sex behaviour, however, is unclear. In the present study, the crucial melanin pigment gene black was functionally characterised in an urban pest, the German cockroach, Blattella germanica. RNAi knockdown of B. germanica black (Bgblack) had no effect on survival, but did result in black pigmentation of the thoraxes, abdomens, heads, wings, legs, antennae, and cerci due to cuticular accumulation of melanin. Sex-specific variation in the pigmentation pattern was apparent, with females exhibiting darker coloration on the abdomen and thorax than males. Bgblack knockdown also resulted in wing deformation and negatively impacted the contact sex pheromone-based courtship behaviour of males. This study provides evidence for black function in multiple aspects of B. germanica biology and opens new avenues of exploration for novel pest control strategies.

RNAi of yellow-y, required for normal cuticle pigmentation, impairs courtship behavior and oviposition in the German cockroach (Blattella germanica).

The insect cuticle plays a key role in maintaining the insect's physiological function and behavior. Herein, the yellow-y protein is required to produce black melanin, and is expressed in a pattern that correlates with the distribution of this pigment. However, yellow-y can also have other functions, for instance, in insect behavior, but not much is known. In this study, we have studied the yellow-y gene in one important model and pest species, namely the German cockroach (Blattella germanica), which is to our knowledge the first time reported. In essence, we identified the yellow-y gene (BgY-y) and characterized its function by using RNA interference (RNAi). Silencing of BgY-y gene led to different developmental abnormalities (body weight and wings) in both genders. Specifically, there was an abundant decrease in melanin, turning the body color in pale yellow and the cuticle softer and more transparent. Interestingly, we also observed that the knockdown of BgY-y impaired the male cockroaches to display a weaker response to female-emitted contact sex pheromones, and also that the oviposition ability was weakened in the RNAi females. This study comprehensively analyzed the biological functions of the yellow-y gene in German cockroaches from the perspectives of development, body color, courtship behavior and oviposition, and as a consequence, this may opens new avenues to explore it as a novel pest control gene.

Alfalfa xeno-miR159a regulates bovine mammary epithelial cell proliferation and milk protein synthesis by targeting PTPRF.

Milk protein content is an important index to evaluate the quality and nutrition of milk. Accumulating evidence suggests that microRNAs (miRNAs) play important roles in bovine lactation, but little is known regarding the cross-kingdom regulatory roles of plant-derived exogenous miRNAs (xeno-miRNAs) in milk protein synthesis, particularly the underlying molecular mechanisms. The purpose of this study was to explore the regulatory mechanism of alfalfa-derived xeno-miRNAs on proliferation and milk protein synthesis in bovine mammary epithelial cells (BMECs). Our previous study showed that alfalfa miR159a (mtr-miR159a, xeno-miR159a) was highly expressed in alfalfa, and the abundance of mtr-miR159a was significantly lower in serum and whey from high-protein-milk dairy cows compared with low-protein-milk dairy cows. In this study, mRNA expression was detected by real-time quantitative PCR (qRT-PCR), and casein content was evaluated by enzyme-linked immunosorbent assay (ELISA). Cell proliferation and apoptosis were detected using the cell counting kit 8 (CCK-8) assay, 5-ethynyl-2'-deoxyuridine (EdU) staining, western blot, and flow cytometry. A dual-luciferase reporter assay was used to determine the regulation of Protein Tyrosine Phosphatase Receptor Type F (PTPRF) by xeno-miR159a. We found that xeno-miR159a overexpression inhibited proliferation of BMEC and promoted cell apoptosis. Besides, xeno-miR159a overexpression decreased ß-casein abundance, and increased α-casein and κ-casein abundance in BMECs. Dual-luciferase reporter assay result confirmed that PTPRF is a target gene of xeno-miR159a. These results provide new insights into the mechanism by which alfalfa-derived miRNAs regulate BMECs proliferation and milk protein synthesis.

Shenshuai Yingyang Jiaonang ameliorates chronic kidney disease-associated muscle atrophy in rats by inhibiting ferroptosis mediated by the HIF-1α/SLC7A11 pathway.

Objective: Shenshuai Yingyang Jiaonang (SSYYJN), a traditional Chinese medicine formula, can ameliorate muscle atrophy associated with chronic kidney disease (CKD). However, its mechanisms of action remain unclear. This study is to investigate the molecular mechanisms involved in the effects of SSYYJN in ameliorating muscle atrophy associated with CKD in rats. Methods: The chemical compounds of SSYYJN were identified by UPLC-Q-Orbitrap HRMS. Considering the dose-response relationship of the identified compounds, male SD rats were randomly divided into Sham, Model, SSYYJN, and α-Keto Acid (KA) groups. Subsequently, we assessed the therapeutic and anti-ferroptotic effects of SSYYJN. Network pharmacology studies were used to predict the molecular mechanism of SSYYJN on ferroptosis and were further verified for accuracy. Results: A total of 42 active compounds were identified from SSYYJN. SSYYJN alleviated muscle atrophy caused by CKD, as evidenced by changes in body weight, serum biochemical indices, mass and histopathology of the skeletal muscle, and the levels of MuRF1. SSYYJN reduced the levels of iron, MDA, and ROS, increased the levels of GSH, NAPDH, and Gpx4. Network pharmacology analysis indicated that SSYYJN exerted anti-ferroptotic effects that were closely related to the HIF-1α signaling pathway. Molecular protein and genetic test results showed that SSYYJN increased HIF-1α protein and increased SLC7A11. Conclusions: SSYYJN attenuates muscle atrophy in CKD by inhibiting ferroptosis through the activation of the HIF-1α/SLC7A11 pathway and might be a promising traditional Chinese medicine for muscle atrophy in CKD.

Analysis of blood biochemistry and non-targeted metabolomics of endometritis in dairy cows.

The incidence of bovine endometritis, which has a negative impact on the reproduction of dairy cows, has been recently increasing. In this study, the differential markers and metabolites of healthy cows and cows with endometritis were analyzed by measuring blood biochemical indicators and immune factors using biochemical and enzyme-linked immunosorbent assay kits combined with nontargeted metabolomics. The LC-QTOF platform was used to evaluate the serum metabolomics of healthy cows and cows with endometritis after 21-27 days of calving. The results showed that glucose, free fatty acid, calcium, sodium, albumin, and alanine aminotransferase levels were significantly lower in the serum of cows with endometritis than in healthy cows (P < 0.05). However, the serum potassium, interleukin-1, interleukin-6, and tumor necrosis factor levels were significantly higher in cows with endometritis (P < 0.05). In addition, the serum metabolome data analysis of the two groups showed that the expression of 468 metabolites was significantly different (P < 0.05), of which 291 were upregulated and 177 were downregulated. These metabolites were involved in 78 metabolic pathways, including amino acid, nucleotide, carbohydrate, lipid, and vitamin metabolism pathways; signal transduction pathways, and other biological pathways. Taken together, negative energy balance and immune activation, which are related to local abnormalities in amino acid, lipid, and carbohydrate metabolism, were the important causes of endometritis in dairy cows. Metabolites such as glucose, carnosine, dehydroascorbic acid, L-malic acid, tetrahydrofolic acid, and UDP-glucose may be used as key indicators in the hematological diagnosis and treatment of endometritis in dairy cows.

Artemyriantholides A-K, guaiane-type sesquiterpenoid dimers from Artemisia myriantha var. pleiocephala and their antihepatoma activity.

Artemyriantholides A-K (1-11) as well as 14 known compounds (12-25) were isolated from Artemisia myriantha var. pleiocephala (Asteraceae). The structures and absolute configuration of compounds 2 and 8-9 were confirmed by the single crystal X-ray diffraction analyses, and the others were elucidated by MS, NMR spectral data and electronic circular dichroism calculations. All compounds were chemically characterized as guaiane-type sesquiterpenoid dimers (GSDs). Compound 1 was the first example of the GSD fused via C-3/C-11' and C-5/C-13' linkages, and compounds 2 and 5 were rare GSDs containing chlorine atoms. Eleven compounds showed obvious inhibitory activity in HepG2, Huh7 and SK-Hep-1 cell lines by antihepatoma assay to provide the IC50 values ranging from 7.9 to 67.1 µM. Importantly, compounds 5 and 8 exhibited the best inhibitory activity with IC50 values of 14.2 and 18.8 (HepG2), 9.0 and 11.5 (Huh7), and 8.8 and 11.3 µM (SK-Hep-1), respectively. The target of compound 5 was predicted to be MAP2K2 by a computational prediction model. The interaction between compound 5 and MAP2K2 was conducted to give docking score of -9.0 kcal/mol by molecular docking and provide KD value of 43.7 µM by Surface Plasmon Resonance assay.

Simultaneously enhancing organic phosphorescence quantum yields and lifetimes for triphenylphosphine salt doped polymer films.

Simultaneously enhancing the quantum yields and luminescence lifetimes of organic persistent room temperature phosphorescence (RTP) molecules is a priority in the organic photonic area, but it remains a formidable challenge. Here, an effective strategy was proposed to improve both quantum efficiencies and emission decay times for phosphorescent triphenylphosphine salts. This approach involves integrating an electron donor unit into a triphenylphosphine salt via an alkyl chain. This structure facilitates an intermediate through-space charge transfer excited state, which enhances the intersystem crossing process to boost RTP performance. Moreover, the electron donor moiety contributes additional triplet excitons to the triphenylphosphine salts through triplet-to-triplet energy transfer, substantially increasing the population of triplet excitons. Specifically, compared to butyl(naphthalen-1-yl) diphenylphosphonium bromide (Φphos. = 4.9% and τ = 255.79 ms), (2-(9H-carbazol-9-yl)ethyl)(naphthalen-1-yl)diphenylphosphonium bromide demonstrates a higher phosphorescence quantum yield of 19.6% and an extended emission lifetime of 800.59 ms. This advancement lays the groundwork for developing high-performance organic RTP materials, unlocking new possibilities for advanced photonic applications.

Leprosy: treatment, prevention, immune response and gene function.

Since the leprosy cases have fallen dramatically, the incidence of leprosy has remained stable over the past years, indicating that multidrug therapy seems unable to eradicate leprosy. More seriously, the emergence of rifampicin-resistant strains also affects the effectiveness of treatment. Immunoprophylaxis was mainly carried out through vaccination with the BCG but also included vaccines such as LepVax and MiP. Meanwhile, it is well known that the infection and pathogenesis largely depend on the host's genetic background and immunity, with the onset of the disease being genetically regulated. The immune process heavily influences the clinical course of the disease. However, the impact of immune processes and genetic regulation of leprosy on pathogenesis and immunological levels is largely unknown. Therefore, we summarize the latest research progress in leprosy treatment, prevention, immunity and gene function. The comprehensive research in these areas will help elucidate the pathogenesis of leprosy and provide a basis for developing leprosy elimination strategies.

Synthesis and antihepatoma activity of guaianolide dimers derived from lavandiolide I.

Guaianolide dimers represent a unique class of natural products with anticancer activities, but their low content in plants has limited in-depth pharmacological studies. Lavandiolide I is a guaianolide dimer isolated from Artemisia species, and had been synthesized on a ten-gram scale in four steps with 60 % overall yield, which showed potent antihepatoma activity on the HepG2, Huh7, and SK-Hep-1 cell lines with IC50 values of 12.1, 18.4, and 17.6 µM, respectively. To explore more active dimers, 33 lavandiolide I derivatives were designed, synthesized, and evaluated for their inhibitory activity on human hepatoma cell lines. Among them, 10 derivatives were more active than lavandiolide I and sorafenib on the three cell lines. The primary structure-activity relationship concluded that the introduction of aldehyde, ester, azide, amide, carbamate and urea functional groups at C-14' of the guaianolide dimer significantly enhanced the antihepatoma activity. Among these compounds, derivatives 25, 27, and 33 enhanced antihepatoma activity more than 1.2-5.8 folds than that of lavandiolide I, and demonstrated low toxicity to the human liver cell lines (THLE-2) and good safety profiles with selective index ranging from 1.3 to 3.4, while lavandiolide I was more toxic to THLE-2 cells. This work provides new insights into enhancing the antihepatoma efficacy and reducing the toxicity of sesquiterpenoid dimers.

Photoactivated Circularly Polarized Luminescent Organic Radicals in Doped Amorphous Polymer.

Luminescent organic radicals, especially those with photoactivated circularly polarized luminescence (CPL) features, hold great significance for cutting-edge optoelectronic applications, but their development still remains a challenge. In this study, we propose a novel strategy to achieve photoactivated CPL radicals by bonding two phosphine centers within an axial chiral system, yielding a compound of R/S-5,5-bis(diphenylphosphino)-4,4'-bibenzo[d][1,3]dioxole (R/S-BDP). The photoactivated R/S-BDP molecules in polymer matrix display a robust quantum yield of 19.8 % and a dissymmetry factor (glum) of 1.2×10-4, marking this work as the first example of photoactivated CPL radicals. Furthermore, the glum is improved to 1.0×10-2 by using a liquid crystal as host. Experimental and theoretical analyses reveal that R/S-BDP molecules, endowed with double phosphine cores in axial chirality, offer a direct way for intramolecular electron transfer upon photoirradiation. This leads to the generation of radical ionic pairs, which subsequently trigger the donor-acceptor arrangement through intermolecular electron transfer, thereby resulting in stable radical emission. The extended photoactivated BDP-F exhibits a remarkably high quantum efficiency of 57.8%. Ultimately, the distinctive photo-responsive CPL radical luminescence has been successfully used for information displays and anti-counterfeiting.

Nanoparticle-delivered RNAi-based pesticide target screening for the rice pest white-backed planthopper and risk assessment for a natural predator.

Vacuolar-type (H+)-ATPase (vATPase) is a conserved multi-subunit eukaryotic enzyme composed of 14 subunits that form a functional complex consisting of an ATP-hydrolytic domain (V1) and a proton-translocation domain (V0). ATP hydrolysis and subsequent H+ translocation rely heavily on a fully assembled V1/V0 complex. Since vATPase is crucial for insect survival, it is a viable molecular target for pest control. However, detailed functional analyses of the 14 subunits and their suitability for pest control have not been fully explored in a single insect species. In this study, we identified 22 vATPase subunit transcripts that correspond to 13 subunits (A1, A2, B, C, D, E, F, G, H, a1, a2, c and d) in the white-backed planthopper (WBPH), Sogatella furcifera, a major hemipteran pest of rice. RNAi screens using microinjection and spray-based methods revealed that the SfVHA-F, SfVHA-a2 and SfVHA-c2 subunits are critical. Furthermore, star polymer (SPc) nanoparticles were utilized to conduct spray-induced and nanoparticle-delivered gene silencing (SI-NDGS) to evaluate the pest control efficacy of RNAi targeting the SfVHA-F, SfVHA-a2 and SfVHA-c2 transcripts. Target mRNA levels and vATPase enzymatic activity were both reduced. Honeydew excreta was likewise reduced in WBPH treated with dsRNAs targeting SfVHA-F, SfVHA-a2 and SfVHA-c2. To assess the environmental safety of the nanoparticle-wrapped dsRNAs, Cyrtorhinus lividipennis Reuter, a major natural enemy of planthoppers, was also sprayed with dsRNAs targeting SfVHA-F, SfVHA-a2 and SfVHA-c2. Post-spray effects of dsSfVHA-a2 and dsSfVHA-c2 on C. lividipennis were innocuous. This study identifies SfVHA-a2 and SfVHA-c2 as promising targets for biorational control of WBPH and lays the foundation for developing environment-friendly RNAi biopesticides.

High-precision ground simulator for laser tracking of gravity satellite.

Inter-satellite laser ranging is a key technology to improve the measurement precision of gravity satellites in future missions. However, it requires a stable laser link between satellites, which would be affected by external disturbances in space and internal couplings of satellite components. This paper presents a dynamic model to describe the tracking error and proposes a high-precision satellite simulator for the validation of inter-satellite laser tracking. Then, the noises of the sensors and actuators are tested to give the theoretical tracking performance of the simulator. Finally, the laser tracking performance is validated through two experiments: fixed-position tracking and motion tracking. The experimental results show that the measured tracking error of the satellite platform is better than 10 mrad/Hz in the fixed-position tracking and 50 mrad/Hz in the motion tracking. Furthermore, the optical platform can reduce the measured tracking error to 80 µrad/Hz in both two experiments. This work provides a theoretical foundation for optimizing laser tracking performance in space missions, and the proposed simulator has demonstrated a potential for mission simulation with laser tracking.

Artesunate-Nanoliposome-TPP, a Novel Drug Delivery System That Targets the Mitochondria, Attenuates Cisplatin-Induced Acute Kidney Injury by Suppressing Oxidative Stress and Inflammatory Effects.

Background: Acute kidney injury (AKI) is a syndrome, posing a substantial healthcare burden. The pathological basis of AKI is associated with inflammation and oxidative stress which cause additional damage to mitochondria. Artesunate (ATS) is a derivative of artemisinin isolated from Artemisia annua L. that is an effective treatment for malaria and favored for the prevention and treatment of kidney diseases. However, there are still challenges related to its efficacy, including poor water solubility, limited oral bioavailability and short half-life. Liposome-based nanoparticles are used for drug delivery due to their ideal biocompatibility and their ability to improve the bioavailability of specific drugs and enhance drug efficacy. Methods: In this study, a novel TPP-based natural ATS-nanoliposome, namely T-A-Ls, was applied for the treatment of AKI. ATS was encapsulated with or without triphenylphosphonium (TPP)-modified nanoliposomes. AKI was induced by cisplatin in C57BL/6J mice and a cisplatin-induced injury model was generated in HK-2 cells in vitro. Blood urea nitrogen (BUN), serum creatinine (Scr) measurements and section staining were utilized to assess renal protective effect of T-A-Ls. Inflammatory-related factors and proteins were quantified via Elisa, Immunofluorescence and Western Blot (WB). The anti-mitochondrial oxidative stress effect of T-A-Ls was determined by ROS, JC-1 and oxygen consumption rate (OCR) kits. Immunohistochemistry and WB were conducted to measure associated protein expressions. In vivo biodistribution and the concentration of T-A-Ls in kidney were also explored. Results: T-A-Ls exhibited good oxidative resistance, preferential renal uptake, mitochondrial targeting, and it ameliorated kidney injury in cisplatin-induced AKI mice. Mitochondrial dysfunction, ATP production and respiratory capacity were improved in damaged HK-2 cells; ROS content decreased while mitochondrial membrane potential recovered. T-A-Ls exerted renal protection by inhibiting inflammation and reducing oxidative stress; these effects were mediated by a downregulation in the expression of RAGE and iNOS and an upregulation in both Nrf2 and HO-1. Conclusion: T-A-Ls could improve the delivery of ATS to the kidney, offering a promising avenue to treat AKI.