Membrane vesicles derived from Enterococcus faecalis promote the co-transfer of important antibiotic resistance genes located on both plasmids and chromosomes.

BACKGROUND: Bacterial membrane vesicles (BMVs) are novel vehicles of antibiotic resistance gene (ARG) transfer in Gram-negative bacteria, but their role in the spread of ARGs in Gram-positive bacteria has not been defined. The purpose of this study was to evaluate the role of MVs in the transmission of antimicrobial resistance in Gram-positive bacteria. METHODS: A linezolid-resistant Enterococcus faecalis CQ20 of swine origin was selected as the donor strain. Linezolid-susceptible E. faecalis SC032 of human origin, Enterococcus faecium BM4105 and Escherichia coli were selected as recipient strains. The presence of plasmids (pCQ20-1 and pCQ20-2) and an optrA-carrying transposon Tn6674 in CQ20, MVs and vesiculants was verified by WGS or PCR. MVs were isolated with density gradient centrifugation, and MV-mediated transformation was performed to assess the horizontal transferability of MVs. The MICs for CQ20 and its vesiculants were determined by the broth microdilution method. RESULTS: CQ20-derived MVs (CQ20-MV) were isolated, and PCR identified the presence of two plasmids and the optrA gene in the CQ20-MVs. MV-mediated transformation to E. faecalis SC032 and E. faecium BM4105 was successfully performed, and the WGS data also showed that both plasmids pCQ20-1 and pCQ20-2 and optrA-carrying transposon Tn6674 were transferred to E. faecalis SC032 and E. faecium BM4105, but failed for E. coli. Additionally, vesiculants that had acquired ARGs still had the ability to spread these genes via MVs. CONCLUSIONS: To our knowledge, this is the first report of MV-mediated co-transfer of ARG-carrying plasmids and transposons in the Gram-positive bacterium E. faecium.

Endobronchial ultrasound-based support vector machine model for differentiating between benign and malignant mediastinal and hilar lymph nodes.

INTRODUCTION: To establish an ultrasonographic radiomics machine learning model based on endobronchial ultrasound (EBUS) to assist in diagnosing benign and malignant mediastinal and hilar lymph nodes (LNs). METHODS: The clinical and ultrasonographic image data of 197 patients were retrospectively analyzed. The radiomics features extracted by EBUS-based radiomics were analyzed by the least absolute shrinkage and selection operator (LASSO). Then, we used a support vector machine (SVM) algorithm to establish an EBUS-based radiomics model. A total of 205 lesions were randomly divided into training (n=143) and validation (n=62) groups. The diagnostic efficiency was evaluated by receiver operating characteristic (ROC) curve analysis. RESULTS: A total of 13 stable radiomics features with non-zero coefficients were selected. The SVM model exhibited promising performance in both groups. In the training group, the SVM model achieved a ROC area under the curve (AUC) of 0.892 (95% CI: 0.885-0.899), with an accuracy of 85.3%, sensitivity of 93.2%, and specificity of 79.8%. In the validation group, the SVM model had an ROC AUC of 0.906 (95% CI: 0.890-0.923), an accuracy of 74.2%, a sensitivity of 70.3%, and a specificity of 74.1%. CONCLUSION: The EBUS-based radiomics model can be used to differentiate mediastinal and hilar benign and malignant LNs. The SVM model demonstrated excellent potential as a diagnostic tool in clinical practice.

JA-induced FtBPM3 accumulation promotes FtERF-EAR3 degradation and rutin biosynthesis in Tartary buckwheat.

Buckwheat accumulates abundant flavonoids, which exhibit excellent health-promoting value. Flavonoids biosynthesis is mediated by a variety of phytohormones, among which jasmonates (JAs) induce numerous transcription factors, taking part in regulation of flavonoids biosynthesis genes. However, some transcriptional repressors appeared also induced by JAs. How these transcriptional repressors coordinately participate in JA signaling remains unclear. Here, we found that the disruption of the GCC-box in FtF3H promoter was associated with flavonoids accumulation in Tartary buckwheat. Further, our study illustrated that the nucleus-localized FtERF-EAR3 could inhibit FtF3H expression and flavonoids biosynthesis through binding the GCC-box in the promoter of FtF3H. The JA induced FtERF-EAR3 gene expression while facilitating FtERF-EAR3 protein degradation via the FtBPM3-dependent 26S proteasome pathway. Overall, these results illustrate a precise modulation mechanism of JA-responsive transcription suppressor participating in flavonoid biosynthesis, and will further help to improve the efficiency of flavonoids biosynthesis in Tartary buckwheat.

Vasoprotective Effects of Hyperoside against Cerebral Ischemia/Reperfusion Injury in Rats: Activation of Large-Conductance Ca2+-Activated K+ Channels.

Hyperoside (Hyp), a kind of Chinese herbal medicine, exerts multiple therapeutic effects on many diseases. However, the role and mechanisms of Hyp in vascular pathophysiology in ischemic stroke need to be further established. The study aimed to investigate the role of (large-conductance Ca2+-activated K+) BK channels on the vasoprotection of Hyp against cerebral ischemia and reperfusion (I/R) injury in rats. The concentration gradient of Hyp was pretreated in both the middle cerebral artery occlusion and reperfusion model and oxygen-glucose deprivation/reoxygenation (OGD/R) model of primary vascular smooth muscle cells (VSMCs) in rats. A series of indicators were detected, including neurological deficit score, infarct volume, malondialdehyde (MDA), superoxide dismutase (SOD), cerebral blood flow (CBF), cell viability, membrane potential, and BK channels α- and ß1-subunits expression. The results showed that Hyp significantly reduced infarct volume and ameliorated neurological dysfunction in I/R-injured rats. Besides, the effects of I/R-induced reduction of BK channels α- and ß1-subunits expression were significantly reversed by Hyp in endothelial-denudated cerebral basilar arteries. Furthermore, the protective effect against I/R-induced increases of MDA and reduction of SOD as well as CBF induced by Hyp was significantly reversed by iberiotoxin (IbTX). In OGD/R-injured VSMCs, downregulated cellular viability and BK channels ß1-subunits expression were remarkably reversed by Hyp. However, neither OGD/R nor Hyp affected BK channels α-subunits expression, and Hyp failed to induced hyperpolarization of VSMCs. Moreover, the protective effect against OGD/R-induced reduction of cell viability and SOD level and increases of MDA production induced by Hyp was significantly reversed by IbTX in VSMCs. The study indicates that Hyp has the therapeutic potential to improve vascular outcomes, and the mechanism is associated with suppressing oxidative stress and improving CBF through upregulating BK channels.

Expression of Pinellia pedatisecta Agglutinin PPA Gene in Transgenic Sugarcane Led to Stomata Patterning Change and Resistance to Sugarcane Woolly Aphid, Ceratovacuna lanigera Zehntner.

The sugarcane woolly aphid is one of the main pests of sugarcane worldwide. The Pinellia pedatisecta agglutinin (PPA) gene has been demonstrated to function towards aphid resistance in other crops. In our study, in order to investigate the PPA function towards aphid control in sugarcane and its underlying mechanism, the PPA gene was overexpressed in a sugarcane Zhongzhe 1 (ZZ1) cultivar in independent transgenic sugarcane lines. It was confirmed in this study that PPA transgenic sugarcane can resist aphids via detecting the aphids' development and tracing the survival number on PPA-transgenic sugarcane lines as well as PPA negative control lines. The mechanism of PPA lectin-associated defense against aphids was preliminarily explored. Stomatal patterning differences of sugarcane leaves between PPA-transgenic sugarcane lines and negative control lines were found. PPA overexpression led to an increase in stomata number and a decrease in stomata size that might have changed the transpiration status, which is critical for aphids' passive feeding. Moreover, the antioxidant enzyme, sugar, tannin and chlorophyll content in sugarcane leaves before and after aphid infestation was determined. The results indicated that PPA overexpression in sugarcane resulted in an increase in antioxidant enzyme activity and tannin content, as well as a reduction in the decline of certain sugars. These together may improve sugarcane resistance against the sugarcane woolly aphid.

Highly Efficient Near-Infrared Thermally Activated Delayed Fluorescent Emitters in Non-Doped Electroluminescent Devices.

Constructing organic near-infrared (NIR) luminescent materials to confront the formidable barrier of "energy gap law" remains challenging. Herein, two NIR thermally activated delayed fluorescence (TADF) molecules named T-ß-IQD and TIQD were developed by connecting N,N-diphenylnaphthalen-2-amine and triphenylamine with a novel electron withdrawing unit 6-(4-(tert-butyl)phenyl)-6H-indolo[2,3-b]quinoxaline-2,3-dicarbonitrile. It is confirmed NIR-TADF emitters concurrent with aggregation-induced emission effect, J-aggregate with intra- and intermolecular CN⋅⋅⋅H-C and C-H⋅⋅⋅π interactions, and large center-to-center distance in solid states can boost the emissive efficiencies both in thin films and non-doped organic light-emitting diodes (OLEDs). Consequently, the T-ß-IQD-based non-doped NIR-OLED achieved the maximum external quantum efficiency (EQEmax ) of 9.44 % with emission peak at 711 nm, which is one of the highest efficiencies reported to date for non-doped NIR-OLEDs.

Efficacy of antepartum administration of hepatitis B immunoglobulin in preventing mother-to-child transmission of hepatitis B virus.

The aim of this study was to investigate the efficacy of antepartum administration of three doses of hepatitis B immunoglobulin (HBIG) in interrupting mother-to-child transmission (MTCT) of hepatitis B virus (HBV). In this trial, a total of 728 HBeAg-positive pregnant women with chronic HBV infection who had an HBV DNA level higher than 6log10  copies/mL were enrolled. They were divided into three groups based on individual preference. Subjects in group A and group B received 200 IU (unit) HBIG and 400 IU (unit) HBIG intramuscularly once a month at the third, second and first month before delivery, respectively. Subjects in the control group (C) received no special treatment. All the infants received passive-active immunoprophylaxis. The HBsAg-positive rate of all infants at 7-12 months of age was 5.1% (37/728). Specifically, the HBsAg-positive rate of infants was comparable in all three groups (5.3% vs 5.1% vs 5%, P = 0.988). No significant difference was found in anti-HBs levels between the infants aged 7-12 months in the three groups (P = 0.469). HBV DNA levels of the umbilical cord blood in the HBV-infected group were higher than those in the uninfected group (5.2 vs 3.4log10  copies/mL, P < 0.001), and these with family history of HBV infection were also higher (45.9% vs 28.5%, P = 0.034). To conclude, administration of passive-active immunoprophylaxis to infants contributed to effective prevention of the MTCT of HBV; extra antepartum administration of HBIG during pregnancy could not decrease the rate of MTCT or increase the anti-HBs levels of infants born to HBsAg-positive mothers with HBV DNA higher than 6log10  copies/mL.

Development of a 10-litre pilot scale micro-nano bubble (MNB)-enhanced photocatalytic system for wastewater treatment.

A 10-litre pilot scale micro-nano bubble (MNB)-enhanced photocatalytic degradation system was developed using ZnO as the photocatalyst and salicylic acid (SA) as the model pollutant. The effectiveness of the MNB/ZnO/UV system was systematically compared with those of MNB, UV, MNB/UV, MNB/ZnO and ZnO/UV degradation systems. The effects of process parameters, including catalyst dosage, pollutant concentration, air-intake rate, pH and salt content on the degradation of SA, were comprehensively investigated. Optimum performance was obtained at neutral conditions with a catalyst dosage of 0.3 g/L and an air-intake rate of 0.1 L/min. For the degradation of SA, a kinetic constant of 0.04126/min was achieved in the MNB/ZnO/UV system, which is 4.5 times greater than that obtained in the conventional ZnO/UV system. The substantial increase in the degradation rate can be attributed to that the air MNB not only enhanced the gas-liquid mass transfer efficiency but also elevated the concentration of dissolved oxygen. A 10-litre pilot scale MNB/ZnO/UV system was successfully applied to the purification of lake water and river water, demonstrating great application potential for wastewater treatment.

PARP inhibitor plus radiotherapy reshape the immune suppressive microenvironment and potentiate the efficacy of immune checkpoint inhibitors in tumors with IDH1 mutation.

Isocitrate dehydrogenase 1 mutant (IDH1mut) tumors respond poorly to immunotherapy, but are more sensitive to chemoradiotherapy and poly (ADP-ribose) polymerase inhibition (PARPi). Accordingly, some efforts have aimed to capitalize on the IDH1 mutation rather than reverse it. Moreover, radiotherapy (RT) and PARPi can stimulate antitumor immunity, raising the possibility of reversing the immunosuppression caused by IDH1 mutation while killing the tumor. To assess this possibility, we treated IDH1mut tumors and cells with RT + PARPi. RT + PARPi showed enhanced efficacy over either modality alone both in vitro and in vivo. RT + PARPi induced more DNA damage and activated the cGAS-STING pathway more. IFNß, CXCL10, and CCL5 were also more highly expressed at both the mRNA and protein levels. In two different tumor models, RT + PARPi increased infiltration and cytolytic function of CD8+ T cells, with one model also showing increased CD8+T cell proliferation. RT+PARPi also increased PD-L1 expression and enhanced checkpoint inhibition. Knocking out cGAS reversed the increased CD8+ T cell infiltration and the antitumor effect of RT+PARPi. We conclude that RT + PARPi reshapes the IDH1mut tumor immunosuppressive microenvironment, thereby augmenting checkpoint inhibition.

Exogenous melatonin improves germination rate in buckwheat under high temperature stress by regulating seed physiological and biochemical characteristics.

The germinations of three common buckwheat (Fagopyrum esculentum) varieties and two Tartary buckwheat (Fagopyrum tataricum) varieties seeds are known to be affected by high temperature. However, little is known about the physiological mechanism affecting germination and the effect of melatonin (MT) on buckwheat seed germination under high temperature. This work studied the effects of exogenous MT on buckwheat seed germination under high temperature. MT was sprayed. The parameters, including growth, and physiological factors, were examined. The results showed that exogenous MT significantly increased the germination rate (GR), germination potential (GP), radicle length (RL), and fresh weight (FW) of these buckwheat seeds under high-temperature stress and enhanced the content of osmotic adjustment substances and enzyme activity. Comprehensive analysis revealed that under high-temperature stress during germination, antioxidant enzymes play a predominant role, while osmotic adjustment substances work synergistically to reduce the extent of damage to the membrane structure, serving as the primary key indicators for studying high-temperature resistance. Consequently, our results showed that MT had a positive protective effect on buckwheat seeds exposed to high temperature stress, providing a theoretical basis for improving the ability to adapt to high temperature environments.

Principal Components and Cluster Analysis of Trace Elements in Buckwheat Flour.

Essential trace elements are required at very low quantities in the human body but are essential for various physiological functions. Each trace element has a specific role and a lack of these elements can easily cause a threat to health and can be potentially fatal. In this study, inductively coupled plasma mass spectrometry (ICP-MS) and inductively coupled plasma atomic emission spectrometry (ICP-AES) were used to determine the content of trace metal elements Ca, Fe, Cu, Mg, Zn, Se, Mo, Mn, and Cd in buckwheat flour. The content and distribution characteristics of trace metal elements were investigated using principal component and cluster analysis. The principal component analysis yielded a four-factor model that explained 73.64% of the test data; the cumulative contribution of the variance of the 1st and 2nd principal factors amounted to 44.41% and showed that Cu, Mg, Mo, and Cd are the characteristic elements of buckwheat flour. The cluster analysis divided the 28 buckwheat samples into two groups, to some extent, reflecting the genuineness of buckwheat flour. Buckwheat flour is rich in essential trace metal elements and can be used as a source of dietary nutrients for Mg and Mo.

Genome-wide analysis of NBS-LRR genes revealed contribution of disease resistance from Saccharum spontaneum to modern sugarcane cultivar.

Introduction: During plant evolution, nucleotide-binding sites (NBS) and leucine-rich repeat (LRR) genes have made significant contributions to plant disease resistance. With many high-quality plant genomes sequenced, identification and comprehensive analyses of NBS-LRR genes at whole genome level are of great importance to understand and utilize them. Methods: In this study, we identified the NBS-LRR genes of 23 representative species at whole genome level, and researches on NBS-LRR genes of four monocotyledonous grass species, Saccharum spontaneum, Saccharum officinarum, Sorghum bicolor and Miscanthus sinensis, were focused. Results and discussion: We found that whole genome duplication, gene expansion, and allele loss could be factors affecting the number of NBS-LRR genes in the species, and whole genome duplication is likely to be the main cause of the number of NBS-LRR genes in sugarcane. Meanwhile, we also found a progressive trend of positive selection on NBS-LRR genes. These studies further elucidated the evolutionary pattern of NBS-LRR genes in plants. Transcriptome data from multiple sugarcane diseases revealed that more differentially expressed NBS-LRR genes were derived from S. spontaneum than from S. officinarum in modern sugarcane cultivars, and the proportion was significantly higher than the expected. This finding reveals that S. spontaneum has a greater contribution to disease resistance for modern sugarcane cultivars. In addition, we observed allelespecific expression of seven NBS-LRR genes under leaf scald, and 125 NBS-LRR genes responding to multiple diseases were identified. Finally, we built a plant NBS-LRR gene database to facilitate subsequent analysis and use of NBSLRR genes obtained here. In conclusion, this study complemented and completed the research of plant NBS-LRR genes, and discussed how NBS-LRR genes responding to sugarcane diseases, which provided a guide and genetic resources for further research and utilization of NBS-LRR genes.

Trichoderma and its role in biological control of plant fungal and nematode disease.

Trichoderma is mainly used to control soil-borne diseases as well as some leaf and panicle diseases of various plants. Trichoderma can not only prevent diseases but also promotes plant growth, improves nutrient utilization efficiency, enhances plant resistance, and improves agrochemical pollution environment. Trichoderma spp. also behaves as a safe, low-cost, effective, eco-friendly biocontrol agent for different crop species. In this study, we introduced the biological control mechanism of Trichoderma in plant fungal and nematode disease, including competition, antibiosis, antagonism, and mycoparasitism, as well as the mechanism of promoting plant growth and inducing plant systemic resistance between Trichoderma and plants, and expounded on the application and control effects of Trichoderma in the control of various plant fungal and nematode diseases. From an applicative point of view, establishing a diversified application technology for Trichoderma is an important development direction for its role in the sustainable development of agriculture.

The distribution variation of pathogens and virulence factors in different geographical populations of giant pandas.

Intestinal diseases caused by opportunistic pathogens seriously threaten the health and survival of giant pandas. However, our understanding of gut pathogens in different populations of giant pandas, especially in the wild populations, is still limited. Here, we conducted a study based on 52 giant panda metagenomes to investigate the composition and distribution of gut pathogens and virulence factors (VFs) in five geographic populations (captive: GPCD and GPYA; wild: GPQIN, GPQIO, and GPXXL). The results of the beta-diversity analyzes revealed a close relationship and high similarity in pathogen and VF compositions within the two captive groups. Among all groups, Proteobacteria, Firmicutes, and Bacteroidetes emerged as the top three abundant phyla. By using the linear discriminant analysis effect size method, we identified pathogenic bacteria unique to different populations, such as Klebsiella in GPCD, Salmonella in GPYA, Hafnia in GPQIO, Pedobacter in GPXXL, and Lactococcus in GPQIN. In addition, we identified 12 VFs that play a role in the intestinal diseases of giant pandas, including flagella, CsrA, enterobactin, type IV pili, alginate, AcrAB, capsule, T6SS, urease, type 1 fimbriae, polar flagella, allantoin utilization, and ClpP. These VFs influence pathogen motility, adhesion, iron uptake, acid resistance, and protein regulation, thereby contributing to pathogen infection and pathogenicity. Notably, we also found a difference in virulence of Pseudomonas aeruginosa between GPQIN and non-GPQIN wild populations, in which the relative abundance of VFs (0.42%) of P. aeruginosa was the lowest in GPQIN and the highest in non-GPQIN wild populations (GPXXL: 23.55% and GPQIO: 10.47%). In addition to enhancing our understanding of gut pathogens and VFs in different geographic populations of giant pandas, the results of this study provide a specific theoretical basis and data support for the development of effective conservation measures for giant pandas.

Pan-cancer survey of lncRNA rewiring and functional alternation in tumor-infiltrating T cell by scLNC.

Long non-coding RNAs (lncRNAs) have been reported to involve in diverse biological processes, including tumor immunity. Since lncRNAs are expressed with high cell-type specificity, investigation of lncRNAs at the single-cell level will unveil the cell-type-specific functions of lncRNAs. However, at the single-cell level, a systematic pan-cancer analysis of lncRNA functions in tumor immune microenvironments (TIMEs) remains lacking. Here, we performed pan-cancer single-cell profiling of lncRNA functions in TIMEs and developed a tool, scLNC, tailored for lncRNA functional characterization at the single-cell level. scLNC enabled the comparison of lncRNA function from the levels of lncRNA-mRNA pairs, lncRNA regulatory unit activity and unit function in a cell-type-specific manner. Applying scLNC, our analysis depicted the cross-tumor and tumor-specific lncRNA regulatory profiles in the T cell subtypes and revealed the new regulatory units that lncRNAs established in tumor-infiltrating T cells, particularly in the tumor-enriched T cells. We further characterized the activity and functional alternations of lncRNAs through their regulatory units. Overall, our findings suggested that lncRNAs played an important role in the regulation of cytokine production, cell activation and migration in tumor-enriched T cells and further in immunotherapy.

Correlation of microbiomes in "plant-insect-soil" ecosystem.

Introduction: Traditional chemical control methods pose a damaging effect on farmland ecology, and their long-term use has led to the development of pest resistance. Methods: Here, we analyzed the correlations and differences in the microbiome present in the plant and soil of sugarcane cultivars exhibiting different insect resistance to investigate the role played by microbiome in crop insect resistance. We evaluated the microbiome of stems, topsoil, rhizosphere soil, and striped borers obtained from infested stems, as well as soil chemical parameters. Results and Discussion: Results showed that microbiome diversity was higher in stems of insect-resistant plants, and contrast, lower in the soil of resistant plants, with fungi being more pronounced than bacteria. The microbiome in plant stems was almost entirely derived from the soil. The microbiome of insect-susceptible plants and surrounding soil tended to change towards that of insect-resistant plants after insect damage. Insects' microbiome was mainly derived from plant stems and partly from the soil. Available potassium showed an extremely significant correlation with soil microbiome. This study validated the role played by the microbiome ecology of plant-soil-insect system in insect resistance and provided a pre-theoretical basis for crop resistance control.

Feeding regimens affecting carcass and quality attributes of sheep and goat meat - A comprehensive review.

Sheep and goats can efficiently convert low quality forage into high-quality meat which contains specific nutrients and quality traits. Carcass traits and quality attributes of sheep and goat meat depend upon several factors and one of most effective strategies amongst these is feeding regimens. In this review, the major aspects of feeding regimens affecting growth rate, carcass traits and quality attributes of sheep and goat meat are thoroughly discussed, with a particular focus on physical-chemical composition, flavor profile, and fatty acid (FA) profile. Grazing lambs and kids receiving concentrate or under stall-feeding systems had greater average daily gain and carcass yield compared with animals reared on pasture only. However, growth rate was higher in lambs/kids grazing on pastures of improved quality. Moreover, the meat of grazing lambs receiving concentrate had more intense flavor, intramuscular fat (IMF) content, and unhealthy FA composition, but comparable color, tenderness, juiciness, and protein content compared to that of lambs grazed on grass only. In contrast, meat of concentrate-fed lambs had more intense color, greater tenderness and juiciness, IMF and protein contents, and lower flavor linked to meat. Additionally, the meat of kids grazed on concentrate supplementation had higher color coordinates, tenderness, IMF content and unhealthy FA composition, whereas juiciness and flavor protein content were similar. In contrast, kids with concentrate supplementation had superior color coordinates, juiciness, IMF content and unhealthy FA composition, but lower tenderness and flavor intensity compared to pasture-grazed kids. Thus, indoor-finished or supplemented grazing sheep/goats had higher growth rate and carcass quality, higher IMF content and unhealthy FA composition compared to animals grazed on grass only. Finally, supplementation with concentrate increased flavor intensity in lamb meat, and improved color and tenderness in kid meat, whereas indoor-fed sheep/goats had improved color and juiciness as well as reduced flavor compared to pasture-grazed animals.

Virtual Reality Visual Perceptual Plastic Training Promotes Retinal Structure and Macular Function Recovery in Glaucoma Patients.

Twenty-seven glaucoma patients (54 eyes in total) with well-controlled intraocular pressure were trained with binocular virtual reality visual software for 3 months to investigate whether virtual reality visual perceptual plastic training promotes macular retinal structure and macular function recovery in glaucoma patients. The thickness of peripapillary retinal nerve fiber layer (pRNFL), macular ganglion cell layer-inner plexiform layer (mGCIPL), and mean macular sensitivity (mMS) were evaluated 3 months after training. The mean value of pRNFL thickness in glaucoma patients did not change significantly (Z = 0.642, p = 0.521), nor did the mean value (t = 1.916, p = 0.061) and minimum value (Z = 1.428, p = 0.153) of mGCIPL after 3 months. However, the significant increases were found in superior temporal mGCIPL thickness (t = 2.430, p = 0.019) as well as superior mGCIPL thickness (t = 2.262, p = 0.028). Additionally, the mMS was increased (Z = 2.259, p < 0.05), with the inferior square to be a more pronounced mMS increase (Z = 2.070, p = 0.038). In conclusion, virtual reality visual perceptual plastic training can increase the thickness of retinal ganglion cells complexes in the macular area of glaucoma patients and improve the macular function of the corresponding area. Clinical Trial registration number: ChiCTR1900027909.

Case Report: MR-LINAC-guided adaptive radiotherapy for gastric cancer.

Background: The stomach is one of the most deformable organs. Its shape can be easily affected by breathing movements, and daily diet, and it also varies when the body position is different. The susceptibility of stomach has made it challenging to treat gastric cancer using the conventional image-guided radiotherapy, i.e., the techniques based on kilovoltage X-ray imaging. The magnetic resonance imaging guided radiotherapy (MRgRT) is usually implemented using a hybrid system MR-LINAC. It is feasible to implement adaptive radiotherapy using MR-LINAC for deformable organs such as stomach. In this case report, we present our clinical experience to treat a gastric cancer patient using MR-LINAC. Case description: The patient is a 58-year-old male who started having black stools with no apparent cause a year ago. Gastroscopy result showed pancreatic cancer, pathology: adenocarcinoma on gastric cancer biopsy, adenocarcinoma on gastric body minor curvature biopsy. The patient was diagnosed with gastric cancer (adenocarcinoma, cTxN+M1, stage IV, HER-2 positive). The patient was treated in 25 fractions with radiotherapy using MR-LINAC with online adaptive treatment plans daily. The target area in daily MR images varied considerably when compared with the target area on the CT simulation images. During the course of treatment, there have even been instances where the planned target area where the patient received radiotherapy did not cover the lesion of the day. Conclusion: Online adaptive MRgRT can be a meaningful innovation for treating malignancies in the upper abdomen. The results in the current study are promising and are indicative for further optimizing online adaptive MRgRT in patients with inoperable tumors of the upper abdomen.

Pesticin-Like Effector VgrG3cp Targeting Peptidoglycan Delivered by the Type VI Secretion System Contributes to Vibrio cholerae Interbacterial Competition.

Vibrio cholerae can utilize a type VI secretion system (T6SS) to increase its intra- and interspecies competition. However, much still remains to be understood about the underlying mechanism of this intraspecies competition. In this study, we isolated an environmental V. cholerae strain E1 that lacked the typical virulence factors toxin-coregulated pilus and cholera toxin and that encoded a functional T6SS. We identified an evolved VgrG3 variant with a predicted C-terminal pesticin-like domain in V. cholerae E1, designated VgrG3cp. Using heterologous expression, protein secretion, and peptidoglycan-degrading assays, we demonstrated that VgrG3cp is a T6SS-dependent effector harboring cell wall muramidase activity and that its toxicity can be neutralized by cognate immunity protein TsiV3cp. Site-directed mutagenesis proved that the aspartic acid residue at position 867 is crucial for VgrG3cp-mediated antibacterial activity. Bioinformatic analysis showed that genes encoding VgrG3cp-like homologs are distributed in Vibrio species, are linked with T6SS structural genes and auxiliary genes, and the vgrG3cp-tsiV3cp gene pair of V. cholerae probably evolved from Vibrio anguillarum and Vibrio fluvialis via homologous recombination. Through a time-lapse microscopy assay, we directly determined that cells accumulating VgrG3cp disrupted bacterial division, while the cells continued to increase in size until the loss of membrane potential and cell wall breakage and finally burst. The results of the competitive killing assay showed that VgrG3cp contributes to V. cholerae interspecies competition. Collectively, our study revealed a novel T6SS E-I pair representing a new T6SS toxin family which allows V. cholerae to gain dominance within polymicrobial communities by T6SS. IMPORTANCE The type VI secretion system used by a broad range of Gram-negative bacteria delivers toxic proteins to target adjacent eukaryotic and prokaryotic cells. Diversification of effector proteins determines the complex bacterium-bacterium interactions and impacts the health of hosts and environmental ecosystems in which bacteria reside. This work uncovered an evolved valine-glycine repeat protein G3, carrying a C-terminal pesticin-like domain (VgrG3cp), which has been suggested to harbor cell wall hydrolase activity and is able to affect cell division and the integrity of cell wall structure. Pesticin-like homologs constitute a family of T6SS-associated effectors targeting bacterial peptidoglycan which are distributed in Vibrio species, and genetic loci of them are linked with T6SS structural genes and auxiliary genes. T6SS-delivered VgrG3cp mediated broad-spectrum antibacterial activity for several microorganisms tested, indicating that VgrG3cp-mediated antimicrobial activity is capable of conferring bacteria a competitive advantage over competitors in the same niches.