Explore the vast range of titles available.

Multidrug-resistant (MDR) bacteria cause severe clinical infections and a high mortality rate of over 40% in patients with immunodeficiencies. Therefore, more effective, broad-spectrum, and accurate treatment for severe cases of infection is urgently needed. Here, we present an adoptive transfer of macrophages loaded with a near-infrared photosensitizer ( Lyso700D ) in lysosomes to boost innate immunity and capture and eliminate bacteria through a photodynamic effect. In this design, the macrophages can track and capture bacteria into the lysosomes through innate immunity, thereby delivering the photosensitizer to the bacteria within a single lysosome, maximizing the photodynamic effect and minimizing the side effects. Our results demonstrate that this therapeutic strategy eliminated MDR Staphylococcus aureus (MRSA) and Acinetobacter baumannii (AB) efficiently and cured infected mice in both two models with 100% survival compared to 10% in the control groups. Promisingly, in a rat model of central nervous system bacterial infection, we performed the therapy using bone marrow-divided macrophages and implanted glass fiber to conduct light irradiation through the lumbar cistern. 100% of infected rats survived while none of the control group survived. Our work proposes an efaficient and safe strategy to cure MDR bacterial infections, which may benefit the future clinical treatment of infection. There is increased demand for effective, broad-spectrum treatment options against severe, multi-drug resistant bacterial infections. Here, Wang et al describe an effective photodynamic therapy based on the adoptive transfer of macrophages loaded with a lysosomal photosensitiser.

In engineering practices such as backfill mining, the existence and characteristics of the rock-backfill interface significantly influence the propagation of explosive stress waves and the dynamic response of the rock mass. This study aims to reveal how, among these characteristics, different backfill media and their wave impedance differences with the rock specifically affect these processes. To this end, physical experiments were combined with numerical simulations, utilizing Digital Image Correlation (DIC) technology to capture strain field evolution under blasting, and LS-DYNA was employed for numerical analysis. The research indicates that the wave impedance difference between the rock and the backfill medium is key to controlling stress wave propagation and energy distribution. When the wave impedances are similar, stress wave transmission is dominant, leading to higher peak strain values at various points and a more uniform action of the stress wave on the rock mass, resulting in relatively uniform final failure. When the wave impedance difference is large, interface reflection is enhanced, forming a significant “blocking effect”; in this case, although the initial peak strain may be lower, the continuous action of the interface can lead to greater final strain and plastic deformation in the rock mass. Numerical simulations further show that the greater the wave impedance difference, the more pronounced the “guiding” and “blocking” effects of the backfill on crack propagation. This leads to intensified damage and crack accumulation in the rock mass adjacent to the backfill due to energy concentration, which also results in a higher fractal dimension of the cracks. Therefore, the type of backfill medium directly determines the strain response characteristics and final damage patterns of the rock mass by modulating the reflection and transmission behavior of waves at the interface. These findings have practical guiding significance for optimizing backfill material selection and blasting parameter design in backfill mining.

Antibodies targeting costimulatory receptors of T cells have been developed for the activation of T cell immunity in cancer immunotherapy. However, costimulatory molecule expression is often lacking in tumor-infiltrating immune cells, which can impede antibody-mediated immunotherapy. Here, we hypothesize that delivery of costimulatory receptor mRNA to tumor-infiltrating T cells will enhance the antitumor effects of antibodies. We first design a library of biomimetic nanoparticles and find that phospholipid nanoparticles (PL1) effectively deliver costimulatory receptor mRNA (CD137 or OX40) to T cells. Then, we demonstrate that the combination of PL1-OX40 mRNA and anti-OX40 antibody exhibits significantly improved antitumor activity compared to anti-OX40 antibody alone in multiple tumor models. This treatment regimen results in a 60% complete response rate in the A20 tumor model, with these mice being resistant to rechallenge by A20 tumor cells. Additionally, the combination of PL1-OX40 mRNA and anti-OX40 antibody significantly boosts the antitumor immune response to anti-PD-1 + anti-CTLA-4 antibodies in the B16F10 tumor model. This study supports the concept of delivering mRNA encoding costimulatory receptors in combination with the corresponding agonistic antibody as a strategy to enhance cancer immunotherapy. Antibodies targeting OX40 or CD137, two T cell costimulatory receptors, have been shown to improve antitumor immunity. Here the authors design a phospholipid-derived nanoparticle to deliver OX40 or CD137 mRNA to T cells in vivo, improving efficacy of anti-OX40 and anti-CD137 antibody therapy in preclinical tumor models.

The 2-oxoglutarate-dependent dioxygenase (2-OGD) superfamily is one of the largest protein families in plants. The main oxidation reactions they catalyze in plants are hydroxylation, desaturation, demethylation, epimerization, and halogenation. Four members of the 2-OGD superfamily, i.e., flavonone 3β-hydroxylase (F3H), flavones synthase I (FNS I), flavonol synthase (FLS), and anthocyanidin synthase (ANS)/leucoanthocyanidin dioxygenase (LDOX), are present in the flavonoid pathway, catalyzing hydroxylation and desaturation reactions. In this review, we summarize the recent research progress on these proteins, from the discovery of their enzymatic activity, to their functional verification, to the analysis of the response they mediate in plants towards adversity. Substrate diversity analysis indicated that F3H, FNS Ⅰ, ANS/LDOX, and FLS perform their respective dominant functions in the flavonoid pathway, despite the presence of functional redundancy among them. The phylogenetic tree classified two types of FNS Ⅰ, one mainly performing FNS activity, and the other, a new type of FNS present in angiosperms, mainly involved in C-5 hydroxylation of SA. Additionally, a new class of LDOXs is highlighted, which can catalyze the conversion of (+)-catechin to cyanidin, further influencing the starter and extension unit composition of proanthocyanidins (PAs). The systematical description of the functional diversity and evolutionary relationship among these enzymes can facilitate the understanding of their impacts on plant metabolism. On the other hand, it provides molecular genetic evidence of the chemical evolution of flavonoids from lower to higher plants, promoting plant adaptation to harsh environments.

PpCAD2 was originally isolated from the ‘Wangkumbae’ pear (Pyrus pyrifolia Nakai), and it encodes for cinnamyl alcohol dehydrogenase (CAD), which is a key enzyme in the lignin biosynthesis pathway. In order to verify the function of PpCAD2, transgenic tomato (Solanum lycopersicum) ‘Micro-Tom’ plants were generated using over-expression constructs via the agrobacterium-mediated transformation method. The results showed that the PpCAD2 over-expression transgenic tomato plant had a strong growth vigor. Furthermore, these PpCAD2 over-expression transgenic tomato plants contained a higher lignin content and CAD enzymatic activity in the stem, leaf and fruit pericarp tissues, and formed a greater number of vessel elements in the stem and leaf vein, compared to wild type tomato plants. This study clearly indicated that overexpressing PpCAD2 increased the lignin deposition of transgenic tomato plants, and thus validated the function of PpCAD2 in lignin biosynthesis.

A disorder in pears that is known as ‘hard-end’ fruit affects the appearance, edible quality, and market value of pear fruit. RNA-Seq was carried out on the calyx end of ‘Whangkeumbae’ pear fruit with and without the hard-end symptom to explore the mechanism underlying the formation of hard-end. The results indicated that the genes in the phenylpropanoid pathway affecting lignification were up-regulated in hard-end fruit. An analysis of differentially expressed genes (DEGs) identified three NAC transcription factors, and RT-qPCR analysis of PpNAC138, PpNAC186, and PpNAC187 confirmed that PpNAC187 gene expression was correlated with the hard-end disorder in pear fruit. A transient increase in PpNAC187 was observed in the calyx end of ‘Whangkeumbae’ fruit when they began to exhibit hard-end symptom. Concomitantly, the higher level of PpCCR and PpCOMT transcripts was observed, which are the key genes in lignin biosynthesis. Notably, lignin content in the stem and leaf tissues of transgenic tobacco overexpressing PpNAC187 was significantly higher than in the control plants that were transformed with an empty vector. Furthermore, transgenic tobacco overexpressing PpNAC187 had a larger number of xylem vessel elements. The results of this study confirmed that PpNAC187 functions in inducing lignification in pear fruit during the development of the hard-end disorder.

Objective A retrospective analysis was conducted to evaluate the application of the intraoperative fluoroscopic positioning and anatomical landmark positioning methods in medial patellofemoral ligament (MPFL) reconstruction for recurrent patellar dislocation. The aim was to summarize the positioning accuracy and clinical efficacy of each method, to serve as a reference for femoral positioning. Method We conducted a retrospective analysis of a cohort comprising 75 patients who underwent treatment for recurrent patellar dislocation at our institution between January 2014 and September 2020.Based on the different positioning methodologies utilized for identifying the MPFL femoral footprint, the included patients were systematically allocated to either the fluoroscopy group or the palpation group.Preoperative evaluations and assessments at the latest follow-up encompassed the International Knee Documentation Committee (IKDC) score, Lysholm score, and Kujala score for both groups.We utilized immediate postoperative CT scans for our evaluations. A total of 48 knee 3D-CT scans were acquired using Mimics Medical 21.0 for both groups. From these scans, we constructed a standard lateral Schottle point on a 3D-CT image. To assess the relative positions between the actual and standard location points in both groups, we established a coordinate system based on a simplified, constructed standard point baseline (as illustrated in Chart e). Subsequently, the relative positions of the actual points were evaluated. Result All 75 patients were followed up for a period ranging from 36 to 96 months( mean: 62.27 ± 21.36 months). Significant improvements were observed in the IKDC score, Lysholm score, and Kujala score from preoperative to the latest follow-up ( p  < 0.05) (Table 2), indicating statistical significance.Furthermore, the latest follow-up revealed no significant differences in knee function scores between the two groups ( P  > 0.05) (Table 3). Similarly, the latest evaluation showed no significant differences in knee function scores between patients undergoing MPFLR and MPFLR + TTO In their respective groups ( P  > 0.05) (Table 4).CT-3D reconstruction was conducted on 48 postoperative patients (24 in the fluoroscopy group and 24 in the palpation group). Evaluation of the positioning revealed that most cases in the palpation group were located in quadrants 1 and 3, whereas those in the fluoroscopy group were primarily distributed across quadrants 1, 3, and 4 ( p  < 0.05), indicating statistical significance.In the palpation group, the isometric distance was 3.90 ± 2.17 mm, with an isometric rate of 75%. In the fluoroscopy group, the isometric distance was 7.55 ± 3.94 mm, with an isometric rate of 29.2%.The femoral tunnel isometric rate was significantly higher in the palpation group, at 75%, compared to 29.2% in the fluoroscopy group. among the two positioning methods, there was no statistical difference in the positioning of the femoral footprint at the anterior and posterior ends of the standard point, but there was a statistical difference at the proximal and distal ends ( P  < 0.05). Conclusion Clinical outcomes significantly improved and were similar in both groups. Nevertheless, the palpation of femoral anatomical landmarks exhibited superior convenience and efficiency for experienced sports medicine practitioners, and additionally, it frequently achieved a more isometric femoral footprint than fluoroscopic positioning in certain scenarios.

Background The homeodomain-leucine zipper ( HD-Zip ) transcription factors play crucial roles in plant growth and development or in response to various abiotic stresses. Results In our research, fifty-eight HD-Zip genes were identified in tea plant, namely CsHDZ01 - 58 and divided into four subfamilies, I-IV. All the CsHDZ proteins of four subfamilies harbored HD and LZ domains. Subfamily II CsHDZs contained two additional motifs, EAR and CPSCE. Two extra characteristic domains, START and SAD, were included in subfamily III and IV CsHDZs. While MEKHLA domain was distinctive in subfamily III members. All the subfamily III CsHDZ s were predicted to be targets of csn-miR166. A total of 24 duplicated CsHDZ gene pairs were identified and generated by segmental duplication in tea plant. The expression analysis indicated that most subfamily IV CsHDZ genes were expressed at high level in apical bud, and most subfamily III CsHDZs were high-expressed in stem. CsHDZ family genes exibited diverse expression profiles under cold, drought and salt stresses respectively. It implied that CsHDZ gene family may participate in regulating the response to various abiotic stresses in tea plant. Conclusion These results will provide an important foundation for further exploring the function and molecular mechanism of HD-Zip genes in response to various abiotic stresses in tea plant.

Background The tea plant ( Camellia sinensis (L.) O. Kuntze) is one of the most economically important woody crops. Plastic greenhouse covering cultivation has been widely used in tea areas of northern China. Chlorophyll is not only the crucial pigment for green tea, but also plays an important role in the growth and development of tea plants. Currently, little is known about the effect of plastic greenhouse covering cultivation on chlorophyll in tea leaves. Results To investigate the effect of plastic greenhouse covering cultivation on chlorophyll in tea leaves, color difference values, chlorophyll contents, gene expression, enzyme activities and photosynthetic parameters were analyzed in our study. Sensory evaluation showed the color of appearance, liquor and infused leaves of greenhouse tea was greener than field tea. Color difference analysis for tea liquor revealed that the value of ∆L, ∆b and b/a of greenhouse tea was significantly higher than field tea. Significant increase in chlorophyll content, intracellular CO 2 , stomatal conductance, transpiration rate, and net photosynthetic rate was observed in greenhouse tea leaves. The gene expression and activities of chlorophyll-metabolism-related enzymes in tea leaves were also activated by greenhouse covering. Conclusion The higher contents of chlorophyll a, chlorophyll b and total chlorophyll in greenhouse tea samples were primarily due to higher gene expression and activities of chlorophyll-metabolism-related enzymes especially, chlorophyll a synthetase (chlG), pheophorbide a oxygenase (PAO) and chlorophyllide a oxygenase (CAO) in tea leaves covered by greenhouse. In general, our results revealed the molecular basis of chlorophyll metabolism in tea leaves caused by plastic greenhouse covering cultivation, which had great significance in production of greenhouse tea.

Shandong matcha has the quality characteristics of bright green color, seaweed-like aroma and strong, fresh and brisk taste. In order to identify the characteristic aroma components and clarify the contribution of the grinding process to the aroma of Shandong matcha. Three grades of Shandong matcha and corresponding tencha material were firstly tested with sensory evaluation, and the volatile components were extracted with headspace solid-phase microextraction (HS-SPME) and solvent-assisted flavor evaporation (SAFE) and analyzed using GC–MS. The sensory evaluation results showed that high-grade matcha (M-GS) had prominent seaweed-like, fresh and roasted notes, whereas medium and low-grade matcha (M-G1, M-G2) were gradually coupled with grassy, fatty and high-fired aromas. GC–MS results showed that in the HS-SPME method, heterocyclic compounds (45.84–65.35%) were the highest in Shandong matcha, followed by terpenoids (7.44–16.92%) and esters (6.91–15.27%), while in the safe method, esters were the highest (12.96–24.99%), followed by terpenoids (10.76–25.09%) and heterocyclic compounds (12.12–17.07%). As a whole, the composition of volatile components between M-G1 and M-G2 is relatively close, and there are more differences in volatile components between them and M-GS. The volatile components unique to M-GS were screened using the odor activity value (OAV) evaluation method, with components such as 3-methyl-2-butene-1-thiol, 3-ethyl-Phenol, 2-thiophenemethanethiol, 2,4-undecadienal, (E,E)-2,6-nonadienal, (E,Z)- being evaluated. There were other differentially volatile components, that is, volatile components that coexist in the three grades of matcha, but with different concentrations and proportions. M-G1 and M-G2 contained more volatile substances with high-fired aroma, such as 2-ethyl-3-methyl-pyrazine, coumarin and 5,6,7,8-tetrahydroquinoxaline. The grinding process not only changes the appearance of tencha, but also increases the content of volatile components of matcha as a whole, enhancing the aroma and flavor characteristics of matcha. In this study, the contents of 24 volatile components in matcha were mainly increased, such as benzene, (2,2-dimethoxyethyl)-, cis-7-decen-1-al, safranal and fenchyl acetate. The dual factors of material tencha and matcha grinding technology are indispensable in forming the differences in aroma and flavor of Shandong matcha at different levels.