Wuhu decoction combined with azithromycin for treatment of Mycoplasma pneumoniae pneumonia in Asian children: a systematic review and meta analysis of randomized controlled trials.

Objective: This study constitutes a pioneering systematic review and meta analysis delving into the clinical efficacy and safety of the combined therapy involving Wuhu Decoction and azithromycin for treating Mycoplasma pneumoniae pneumonia in pediatric patients. Methods: This study conducted a comprehensive computerized search, covering 6 Chinese databases and 6 English databases, to collect randomized controlled trials related to the combined use of Wuhu Decoction and azithromycin for treating Mycoplasma pneumoniae pneumonia in pediatric patients. The search was extended until August 2023. Two independent researchers were involved in literature screening, data extraction, and bias risk assessment. Meta-analysis was performed using Stata 14.0 and RevMan 5.4 software. Additionally, meta-regression analysis and subgroup analysis were carried out on primary outcomes to identify potential sources of heterogeneity and confounding factors. Results: A total of 22 randomized controlled trials involving 2,026 patients were included in this study. The combined therapy of Wuhu Decoction and azithromycin demonstrated superior efficacy compared to azithromycin alone (RR = 1.17, 95% CI [1.13, 1.21], p < 0.00001; low certainty of evidence). Additionally, patients receiving the combination therapy experienced significantly reduced the disappearance time of fever (MD = -1.42, 95% CI [-1.84, -1.00], p < 0.00001; very low certainty of evidence), disappearance time of cough (MD = -2.08, 95% CI [-2.44, -1.71], p < 0.00001; very low certainty of evidence), disappearance of pulmonary rales (MD = -1.97, 95% CI [-2.31, -1.63], p < 0.00001; very low certainty of evidence), and disappearance time of wheezing (MD = -1.47, 95% CI [-1.72, -1.22], p < 0.00001; very low certainty of evidence). Meta-regression analysis suggested that course of disease, sample size, and age might be sources of heterogeneity. Subgroup and sensitivity analyses reaffirmed the stability of these results. Furthermore, analyses of secondary outcomes such as T lymphocytes, serum inflammatory factors, and the incidence rate of adverse reactions consistently favored the combination therapy of WHD and azithromycin over azithromycin alone, with statistically significant differences. Conclusion: Based on our meta-analysis findings, the combined therapy of Wuhu Decoction and azithromycin for treating pediatric Mycoplasma pneumoniae pneumonia exhibited superior overall efficacy in comparison to azithromycin monotherapy. However, in the included 22 studies, the majority of evaluated factors showed unclear bias risks, and a persistent bias risk was consistently present within one category. Moreover, due to the low quality of evidence, interpreting these results should be approached with caution. Hence, we emphasize the necessity for future high-quality, multicenter, and large-sample clinical randomized controlled trials. These trials are essential to provide more robust data for evidence-based research and to establish higher-quality evidence support. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023465606.

Visualization of the Ferroptosis in Atherosclerotic Plaques with Nanoprobe Engineered by Macrophage Cell Membranes.

Atherosclerosis (AS) is the root cause of cardiovascular diseases. Ferroptosis is characterized by highly iron-dependent lipid peroxidation and has been reported to play an important role in the pathogenesis of AS. Visualization of the ferroptosis process in atherosclerotic plaques is of great importance for diagnosing and treating AS. In this work, the rationally designed fluorescent probe FAS1 exhibited excellent advantages including large Stokes shift, sensitivity to environmental viscosity, good photostability, and improved water solubility. It also could co-locate with commercial lipid droplets (LDs) probes (BODIPY 493/503) well in RAW264.7 cells treated by the ferroptosis inducer. After self-assembly into nanoparticles and then encapsulation with macrophage membranes, the engineered FAS1@MM NPs could successfully target the atherosclerotic plaques in Western diet-induced apolipoprotein E knockout (ApoE-/-) mice and reveal the association of ferroptosis with AS through fluorescence imaging in vivo. This study may provide additional insights into the roles of ferroptosis in the diagnosis and treatment of AS.

Near-Infrared Light-Driven Nanoparticles for Cancer Photoimmunotherapy by Synergizing Immune Cell Death and Epigenetic Regulation.

Histone deacetylases (HDACs) are a class of epigenetic enzymes that are closely related to tumorigenesis and suppress the expression of tumor suppressor genes. Whereas the HDACs inhibitors can release DNA into the cytoplasm and trigger innate immunity. However, the high density of chromatin limits DNA damage and release. In this study, suitable nanosized CycNHOH NPs (150 nm) and CypNHOH NPs (85 nm) efficiently accumulate at the tumor site due to the enhanced permeability and retention (EPR) effect. In addition, robust single-linear oxygen generation and good photothermal conversion efficiency under NIR laser irradiation accelerated the DNA damage process. By effectively initiating immune cell death, CypNHOH NPs activated both innate and adaptive immunity by maturing dendritic cells, infiltrating tumors with natural killer cells, and activating cytotoxic T lymphocytes, which offer a fresh perspective for the development of photo-immunotherapy.

Color restoration based on digital pathology image.

OBJECTIVE: Protective color restoration of faded digital pathology images based on color transfer algorithm. METHODS: Twenty fresh tissue samples of invasive breast cancer from the pathology department of Qingdao Central Hospital in 2021 were screened. After HE staining, HE stained sections were irradiated with sunlight to simulate natural fading, and every 7 days was a fading cycle, and a total of 8 cycles were experienced. At the end of each cycle, the sections were digitally scanned to retain clear images, and the color changes of the sections during the fading process were recorded. The color transfer algorithm was applied to restore the color of the faded images; Adobe Lightroom Classic software presented the histogram of the image color distribution; UNet++ cell recognition segmentation model was used to identify the color restored images; Natural Image Quality Evaluator (NIQE), Information Entropy (Entropy), and Average Gradient (AG) were applied to evaluate the quality of the restored images. RESULTS: The restored image color met the diagnostic needs of pathologists. Compared with the faded images, the NIQE value decreased (P<0.05), Entropy value increased (P<0.01), and AG value increased (P<0.01). The cell recognition rate of the restored image was significantly improved. CONCLUSION: The color transfer algorithm can effectively repair faded pathology images, restore the color contrast between nucleus and cytoplasm, improve the image quality, meet the diagnostic needs and improve the cell recognition rate of the deep learning model.

Phototheranostic Agents Based on Nonionic Heptamethine Cyanine for Realizing Synergistic Cancer Phototherapy.

Asymmetrical heptamethine cyanine with near-infrared (NIR) absorption is used for photothermal therapy (PTT) of cancer. Aiming to overcome the drawbacks caused by the high temperature of PTT, the development of asymmetrical heptamethine cyanine with photothermal and photodynamic properties is still an attractive strategy. Different from the traditional method of the heavy atom effect, in this work, the carboxyl or sulfonic groups are introduced into the indole ring or branch chain of asymmetrical heptamethine cyanine to afford a series of new phototherapy agents. After being encapsulated by DSPE-PEG2000 , BSS-Et NPs exhibit robust photostability, efficient reactive oxygen species generation (49%), and excellent photothermal conversion efficiency of about 37.6% under 808 nm laser irradiation. BSS-Et NPs possess passive tumor-targeting properties in vivo to not only visualize the tumor by NIR fluorescence imaging but also eliminate the tumor without any recurrence by photodynamic therapy and PTT synergistic therapy under laser irradiation. In addition, benefitting from the characteristics of organic small molecules, they can be metabolized quickly through the liver without inducing toxicity in the whole body. In general, this study provides a new direction for the development of multifunctional phototherapy agents for cancer treatment.

Multifaceted Elevation of ROS Generation for Effective Cancer Suppression.

The in situ lactate oxidase (LOx) catalysis is highly efficient in reducing oxygen to H2O2 due to the abundant lactate substrate in the hypoxia tumor microenvironment. Dynamic therapy, including chemodynamic therapy (CDT), photodynamic therapy (PDT), and enzyme dynamic therapy (EDT), could generate reactive oxygen species (ROS) including ·OH and 1O2 through the disproportionate or cascade biocatalytic reaction of H2O2 in the tumor region. Here, we demonstrate a ROS-based tumor therapy by integrating LOx and the antiglycolytic drug Mito-LND into Fe3O4/g-C3N4 nanoparticles coated with CaCO3 (denoted as FGLMC). The LOx can catalyze endogenous lactate to produce H2O2, which decomposes cascades into ·OH and 1O2 through Fenton reaction-induced CDT and photo-triggered PDT. Meanwhile, the released Mito-LND contributes to metabolic therapy by cutting off the source of lactate and increasing ROS generation in mitochondria for further improvement in CDT and PDT. The results showed that the FGLMC nanoplatform can multifacetedly elevate ROS generation and cause fatal damage to cancer cells, leading to effective cancer suppression. This multidirectional ROS regulation strategy has therapeutic potential for different types of tumors.

A novel ratiometric fluorescent probe for the detection and imaging of cysteine in living cells.

Cysteine is an essential amino acid for humans and can be generated from the conversion of methionine or the interconversions with cystine. The detection of cysteine in the living system is of great importance for the diagnosis of related diseases. Based on the classical cysteine response mechanism, the sulfhydryl group of cysteine undergoes Michael addition with the acrylate to rapidly respond to form a seven-membered ring that specifically recognizes cysteine. In the present work, we designed a novel ratiometric fluorescent probe N-1, which contained the benzo[cd]indol fluorophore and the response group acrylate. As the concentration of cysteine increased, the fluorescence of I485 was significantly enhanced while the fluorescence intensity at 635 nm was weakened. Moreover, probe N-1 showed excellent sensitivity and selectivity to Cys with the calculated LOD of 4.0 × 10-9 M. Probe N-1 was successfully used for imaging cysteine in the living Hela cells with low cytotoxicity, indicating that this ratiometric fluorescent probe would be a novel and useful tool to monitor cysteine in the physiological or pathological processes.

Genome-wide association analysis reveals a novel QTL CsPC1 for pericarp color in cucumber.

BACKGROUND: Cucumber is an important melon crop in the world, with different pericarp colors. However, the candidate genes and the underlying genetic mechanism for such an important trait in cucumber are unknown. In this study, a locus controlling pericarp color was found on chromosome 3 of cucumber genome. RESULTS: In this study, the light green inbred line G35 and the dark green inbred line Q51 were crossed to produce one F2 population. Consequently, we identified a major locus CsPC1 (Pericarp color 1). Next, we mapped the CsPC1 locus to a 94-kb region chromosome 3 which contains 15 genes. Among these genes, Csa3G912920, which encodes a GATA transcription factor, was expressed at a higher level in the pericarp of the NIL-1334 line (with light-green pericarp) than in that of the NIL-1325 line (with dark-green pericarp). This study provides a new allele for the improvement of cucumber pericarp color. CONCLUSION: A major QTL that controls pericarp color in cucumber, CsPC1, was identified in a 94-kb region that harbors the strong candidate gene CsGATA1.

Fine mapping of a novel QTL CsFSG1 for fruit skin gloss in cucumber (Cucumis sativus L.).

Cucumber (Cucumis sativus L.) is an important vegetable crop that is popular with many people. Peel gloss is a highly valued external quality trait that affects the market value of cucumbers, and it directly influences the purchasing psychology of consumers. Nonetheless, the candidate genes and underlying genetic mechanism for this important cucumber trait are not well understood. In this study, we successfully mapped a fruit skin gloss QTL interval to chromosome 3 (26.04-26.14 Mb) using BSA and GWAS methods. Among the eleven candidate genes in the interval, the cytochrome P450 family gene CsCYP86B1 was identified as the candidate for control of fruit skin gloss in cucumber. The expression of CsCYP86B1 in 0-day fruit skin was significantly lower in the low-gloss isogenic line NIL-1334 than in the high-gloss isogenic line NIL-1325. Our findings provide new insights for improving fruit skin gloss in cucumber breeding. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01291-y.

Identification of a major-effect QTL associated with pre-harvest sprouting in cucumber (Cucumis sativus L.) using the QTL-seq method.

BACKGROUND: Cucumber (Cucumis sativus L.) is cultivated worldwide, and it is essential to produce enough high-quality seeds to meet demand. Pre-harvest sprouting (PHS) in cucumber is a critical problem and causes serious damage to seed production and quality. Nevertheless, the genetic basis and molecular mechanisms underlying cucumber PHS remain unclear. QTL-seq is an efficient approach for rapid quantitative trait loci (QTL) identification that simultaneously takes advantage of bulked-segregant analysis (BSA) and whole-genome resequencing. In the present research, QTL-seq analysis was performed to identify QTLs associated with PHS in cucumber using an F2 segregating population. RESULTS: Two QTLs that spanned 7.3 Mb on Chromosome 4 and 0.15 Mb on Chromosome 5 were identified by QTL-seq and named qPHS4.1 and qPHS5.1, respectively. Subsequently, SNP and InDel markers selected from the candidate regions were used to refine the intervals using the extended F2 populations grown in the 2016 and 2017 seasons. Finally, qPHS4.1 was narrowed to 0.53 Mb on chromosome 4 flanked by the markers SNP-16 and SNP-24 and was found to explain 19-22% of the phenotypic variation in cucumber PHS. These results reveal that qPHS4.1 is a major-effect QTL associated with PHS in cucumber. Based on gene annotations and qRT-PCR expression analyses, Csa4G622760 and Csa4G622800 were proposed as the candidate genes. CONCLUSIONS: These results provide novel insights into the genetic mechanism controlling PHS in cucumber and highlight the potential for marker-assisted selection of PHS resistance breeding.

Effects of a dammarane-type saponin, ginsenoside Rd, in nicotine-induced vascular endothelial injury.

BACKGROUND: Panax notoginseng (Burk.) F.H. Chen is a traditional medicinal plant widely used to prevent and treat cardiovascular diseases. Ginsenoside Rd (GRd) is a major bioactive component of P. notoginseng, but specific effects on cardiovascular disease-related pathogenic processes are rarely studied, especially vascular endothelial injury. PURPOSE: This study investigated the potential protective efficacy of GRd against nicotine-induced vascular endothelial cell injury, disruption of vascular nitric oxide (NO) signaling, aberrant endothelium-monocyte adhesion, platelet aggregation, and vasoconstriction. STUDY DESIGN/METHODS: Vascular endothelial injury and functional disruption were investigated in cultured human umbilical vein endothelial cells (HUVECs) by biochemical assays for nitric oxide (NO) and angiotensin II (Ang II), immunofluorescence (IF) and western blotting for expression analyses of apoptosis- related proteins, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), Ang II type receptor 1 (AGTR1), toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor-kappa B (NF-κB). In addition, vascular protection by GRd was examined in nicotine-administered Sprague-Dawley (SD) rats by serum NO and Ang II assays, and by hematoxylin-eosin (HE) and immunostaining of aorta. We also examined effects of GRd on monocyte (THP-1 cells) adhesion assays, adenosine diphosphate (ADP)-induced platelet aggregation, and phenylephrine (PE)-induced vasoconstriction of isolated rat aortic rings. RESULTS: In HUVECs, nicotine significantly suppressed NO production, enhanced Ang II production, downregulated eNOS expression, and upregulated expression levels of AGTR1, TLR4, MyD88, NF-κB, iNOS, Bax/Bcl-2 ratio, cleaved caspase-3, and cytochrome c (cyt c). All of these changes were significantly reversed by GRd. In rats, oral GRd reversed the reduction NO and enhanced Ang II production in serum induced by nicotine administration, and HE staining revealed protection of aortic endothelial cells. In addition, GRd reversed nicotine-mediated enhancement of HUVECs-monocyte adhesion, inhibited ADP-induced platelet aggregation and PE-induced vasoconstriction. CONCLUSION: GRd may prevent nicotine-induced cardiovascular diseases by preserving normal vascular endothelial NO signaling, suppressing platelet aggregation and vasoconstriction, and by preventing endothelial cell-monocyte adhesion.

An Improved Multi-Sensor Fusion Navigation Algorithm Based on the Factor Graph.

An integrated navigation system coupled with additional sensors can be used in the Micro Unmanned Aerial Vehicle (MUAV) applications because the multi-sensor information is redundant and complementary, which can markedly improve the system accuracy. How to deal with the information gathered from different sensors efficiently is an important problem. The fact that different sensors provide measurements asynchronously may complicate the processing of these measurements. In addition, the output signals of some sensors appear to have a non-linear character. In order to incorporate these measurements and calculate a navigation solution in real time, the multi-sensor fusion algorithm based on factor graph is proposed. The global optimum solution is factorized according to the chain structure of the factor graph, which allows for a more general form of the conditional probability density. It can convert the fusion matter into connecting factors defined by these measurements to the graph without considering the relationship between the sensor update frequency and the fusion period. An experimental MUAV system has been built and some experiments have been performed to prove the effectiveness of the proposed method.

The effect of biocontrol bacteria on rhizosphere bacterial communities analyzed by plating and PCR-DGGE.

Bacillus subtilis B579, which was isolated from rhizosphere of cucumber, exhibited an excellent biocontrol activity on soil-born pathogens under greenhouse conditions. It could colonize in rhizosphere of cucumber with large number of populations after inoculated in plant growth season. To reveal the effect of high level colonization of B. subtilis B579 on rhizobacteria community structure, cultivation-based analysis coupled with denaturing gradient gel electrophoresis (DGGE) analysis were used to profile the changes of rhizobacteria community structure sampling at 1 week interval. Cultivation-based and DGGE fingerprinting analysis showed significant plant-dependent and seasonal shifts in rhizobacteria populations. Only minimal and transient effects were observed at 4-9 weeks after sowing in samples of B579 treatment, without the pathogen inoculation and showed the best plant growth potential. Sequencing of dominant bands excised from the gel revealed that Streptomyces sp. was the dominate species in soils before and after sowing. Burkholderia sp. was the dominate species in bulk soil, while Bacillus sp. was dominated in rhizosphere within the growth season. Arthrobacter ramosus and Nocardioides sp. were identified as the specific species in samples treated by B579 at the maturity and flowering stages of cucumber.