CYTOSOLIC INVERTASE2 regulates flowering and reactive oxygen species-triggered programmed cell death in tomato.

Cytosolic invertase (CIN) in plants hydrolyzes sucrose into fructose and glucose, influencing flowering time and organ development. However, the underlying molecular mechanisms remain elusive. Through expressional, genetic, and histological analyses, we identified a substantially role of SlCIN2 (localized in mitochondria) in regulating flowering and pollen development in tomato (Solanum lycopersicum). The overexpression of SlCIN2 resulted in increased hexose accumulation and decreased sucrose and starch content. Our findings indicated that SlCIN2 interacts with Sucrose transporter2 (SlSUT2) to inhibit the sucrose transport activity of SlSUT2, thereby suppressing sucrose content in flower buds and delaying flowering. We found that higher levels of glucose in SlCIN2-overexpressing anthers result in the accumulation of abscisic acid (ABA) and reactive oxygen species (ROS), thereby disrupting programmed cell death (PCD) in anthers and delaying the end of tapetal degradation. Exogenous sucrose partially restored fertility in SlCIN2-overexpressing plants. This study revealed the mechanism by which SlCIN2 regulates pollen development and demonstrated a strategy for creating sugar-regulated gene male sterility lines for tomato hybrid seed production.

Major quantitative trait locus qLA3.1 is related to tomato leaf angle by regulating cell length at the petiole base.

KEY MESSAGE: qLA3.1, controlling leaf angle in tomato, was fine-mapped to an interval of 4.45 kb on chromosome A03, and one gene encoding auxin response factor was identified as a candidate gene. Leaf angle is a crucial trait in plant architecture that plays an important role in achieving optimal plant structure. However, there are limited reports on gene localization, cloning, and the function of plant architecture in horticultural crops, particularly regarding leaf angle. In this study, we selected 'Z3' with erect leaves and 'Heinz1706' with horizontal leaves as the phenotype and cytological observation. We combined bulked segregant analysis and fine genetic mapping to identify a candidate gene, known as, i.e., qLA3.1, which was related to tomato leaf angle. Through multiple analyses, we found that Solyc03g113410 was the most probably candidate for qLA3.1, which encoded the auxin response factor SlARF11 in tomato and was homologous to OsARF11 related to leaf angle in rice. We discovered that silencing SlARF11 resulted in upright leaves, while plants with over-expressed SlARF11 exhibited horizontal leaves. We also found that cultivars with erect leaves had a mutation from base G to base A. Moreover, quantitative analysis of plants treated with hormones indicated that SlARF11 might participate in cell elongation and the activation of genes related to auxin and brassinosteroid pathways. Transcriptome analysis further validated that SlARF11 may regulate leaf angle through hormone signaling pathways. These data support the idea that the auxin response factor SlARF11 may have an important function in tomato leaf petiole angles.

'There is always good fortune in misfortune to encourage us in coping with difficulties'-The lived experiences of family caregivers of people with dementia during the COVID-19 outbreak in China: A phenomenological study.

AIM: To describe the lived experiences of family caregivers of individuals with dementia during the coronavirus disease (COVID-19) outbreak in China. DESIGN: This study used a descriptive phenomenological research method. METHODS: Between May and September 2021, semi-structured interviews were conducted with 22 family caregivers of people with dementia. Colaizzi's method was used for manual analysis. RESULTS: Qualitative data revealed an overarching experience of finding 'There is always good fortune in misfortune to encourage us in coping with difficulties'. Three themes emerged: family reactions to the COVID-19 outbreak, feeling supported by multiple resources performing respective functions and resilient adaptation to new situations. CONCLUSION: During the COVID-19 outbreak, family caregivers of people living with dementia in China looked for positive aspects among difficulties and experienced corresponding reactions, social support resources and resilient adapted coping styles. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Nurses in China and other countries facing similar pandemic characteristics, cultures or economic development levels, can guide family caregivers to look at family hardships from a positive perspective, develop interventions to rapidly respond to families' reactions after a disaster and help them identify social support resources and form adapted coping styles. IMPACT: We identified the resilience and the positive experiences of Chinese family caregivers of individuals with dementia during the COVID-19 outbreak. The results can inform countries with similar cultures and economic levels, offering measures to support their adaptation to pandemics. REPORTING METHOD: This study followed the COREQ guidelines. PATIENT OR PUBLIC CONTRIBUTION: Family caregivers of people with dementia who met the inclusion criteria and who were interested in sharing their understanding of their experiences, participated in the study.

Major-effect quantitative trait locus qLKR4.1 encodes a phospholipase Dδ protein associated with low-K+ stress tolerance by promoting root length.

KEY MESSAGE: qLKR4.1, controlling low K+ resistance in tomato, was fine-mapped to an interval of 67.5 kb on chromosome A04, and one gene encoding phospholipase Dδ was identified as a candidate gene. In plants, changes in root length are an important morphological response to low K+ (LK) stress; however, the underlying genetics in tomato remain unclear. Here, we combined bulked segregant analysis-based whole-genome sequencing, single-nucleotide polymorphism haplotyping, and fine genetic mapping to identify a candidate gene as a major-effect quantitative trait loci (QTL), i.e., qLKR4.1, which was associated with LK tolerance due to increased root elongation in the tomato line JZ34. Through multiple analyses, we found that Solyc04g082000 is the most likely candidate for qLKR4.1, which encodes phospholipase Dδ (PLDδ). Increased root elongation under LK in JZ34 may be attributed to a non-synonymous single-nucleotide polymorphism in the Ca2+-binding domain region of this gene. Solyc04g082000 increases root length through its PLDδ activity. Silencing of Solyc04g082000Arg in JZ34 led to a significant decrease in root length compared with silencing of Solyc04g082000His allele in JZ18 under LK conditions. Mutation of a Solyc04g082000 homologue in Arabidopsis, pldδ, resulted in decreased primary root lengths under LK conditions, compared to the wild type. Transgenic tomato expressing the qLKR4.1Arg allele from JZ34 exhibited a significant increase in root length compared with the wild type expressing the allele from JZ18 under LK conditions. Taken together, our results confirm that the PLDδ gene Solyc04g082000 exerts important functions in increasing tomato root length and LK tolerance.

Abbreviated Versus Full-Protocol MRI for Breast Cancer Neoadjuvant Chemotherapy Response Assessment: Diagnostic Performance by General and Breast Radiologists.

BACKGROUND. Abbreviated protocols could allow wider adoption of MRI in patients undergoing breast cancer neoadjuvant chemotherapy (NAC). However, abbreviated MRI has been explored primarily in screening settings. OBJECTIVE. The purpose of this article was to compare diagnostic performance of abbreviated MRI and full-protocol MRI for evaluation of breast cancer NAC response, stratifying by radiologists' breast imaging expertise. METHODS. This retrospective study included 203 patients with breast cancer (mean age, 52.1 ± 11.2 [SD] years) from two hospitals who underwent MRI before NAC initiation and after NAC completion before surgical resection from March 2017 to April 2021. Abbreviated MRI was extracted from full-protocol MRI and included the axial T2-weighted sequence and precontrast and single early postcontrast T1-weighted sequences. Three general radiologists and three breast radiologists independently interpreted abbreviated and full-protocol MRI in separate sessions, identifying enhancing lesions to indicate residual tumor and measuring lesion size. The reference standard was presence and size of residual tumor on pathologic assessment of post-NAC surgical specimens. RESULTS. A total of 50 of 203 patients had pathologic complete response (pCR). Intraobserver and interobserver agreement for abbreviated and full-protocol MRI for general and breast radiologists ranged from substantial to nearly perfect (κ = 0.70-0.81). Abbreviated MRI compared with full-protocol MRI showed no significant difference for general radiologists in sensitivity (54.7% vs 57.3%, p > .99), specificity (92.8% vs 95.6%, p = .29), or accuracy (83.4% vs 86.2%, p = .30), nor for breast radiologists in sensitivity (60.0% vs 61.3%, p > .99), specificity (94.6% vs 97.4%, p = .22), or accuracy (86.0% vs 88.5%, p = .30). Sensitivity, specificity, and accuracy were not significantly different between protocols for any reader individually (p > .05). Mean difference in residual tumor size on MRI relative to pathology for abbreviated protocol ranged for general radiologists from -0.19 to 0.03 mm and for breast radiologists from -0.15 to -0.05 mm, and for full protocol ranged for general radiologists from 0.57 to 0.65 mm and for breast radiologists from 0.66 to 0.79 mm. CONCLUSION. Abbreviated compared with full-protocol MRI showed similar intraobserver and interobserver agreement and no significant difference in diagnostic performance. Full-protocol MRI but not abbreviated MRI slightly overestimated pathologic tumor sizes. CLINICAL IMPACT. Abbreviated protocols may facilitate use of MRI for post-NAC response assessment by general and breast radiologists.

Evaluation of the Effects of Anti-PD-1 Therapy on Triple-Negative Breast Cancer in Mice by Diffusion Kurtosis Imaging and Dynamic Contrast-Enhanced Imaging.

BACKGROUND: The monitoring of immunotherapies is still based on changes in the tumor size in imaging, with a long evaluation period and low sensitivity. PURPOSE: To investigate the effectiveness of diffusion kurtosis imaging (DKI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing the therapeutic efficacy of anti-programmed death-1 (PD-1) therapy in a mouse triple negative breast cancer (TNBC) model. STUDY TYPE: Prospective. ANIMAL MODEL: A total of 54 BALB/c mouse subcutaneous 4 T1 transplantation models of TNBC. FIELD STRENGTH/SEQUENCE: A 3.0-T; turbo spin echo (TSE) T2-weighted imaging, DKI with seven b values (0, 500, 1000, 1500, 2000, 2500, and 3000 sec/mm2 ) and T1-twist DCE acquisition series. ASSESSMENT: DKI and DCE-MRI parameters were evaluated by two radiologists independently. Regions of interest (ROIs) were drawn manually on the maximum cross-sectional area of the lesion; care was taken to avoid necrotic areas. The tumor cell density, the CD45 and CD31 levels were analyzed by two pathologists. STATISTICAL TESTS: The two-tailed unpaired t-test, Mann-Whitney U test, Fisher's exact test and Pearson correlation coefficient were performed. A P < 0.05 was considered statistically significant. RESULTS: The apparent diffusion coefficient (ADC), mean diffusivity (MD), Ktrans and Kep values were significantly different between the two groups at each time point after treatment. There were significant differences in the mean kurtosis (MK) and Ve values between the two groups at 5 and 10 days after treatment but no significant differences at 15 days (P = 0.317 and 0.183, respectively). The ADC and MD values were significantly correlated with tumor cell density (ADC, r = -0.833; MD, r = 0.890) and the CD45 level (ADC, r = 0.720; MD, r = 0.718). The Ktrans and Kep values were significantly correlated with the CD31 level (Ktrans , r = 0.820; Kep , r = 0.683). DATA CONCLUSION: DKI and DCE-MRI could reflect the changes in tumor microstructure and tumor tissue vasculature after anti-PD-1 therapy, respectively. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: Stage 4.

Deep Neural Networks Offer Morphologic Classification and Diagnosis of Bacterial Vaginosis.

Bacterial vaginosis (BV) is caused by the excessive and imbalanced growth of bacteria in vagina, affecting 30 to 50% of women. Gram staining followed by Nugent scoring based on bacterial morphotypes under the microscope is considered the gold standard for BV diagnosis; this method is often labor-intensive and time-consuming, and results vary from person to person. We developed and optimized a convolutional neural network (CNN) model and evaluated its ability to automatically identify and classify three categories of Nugent scores from microscope images. The CNN model was first established with a panel of microscopic images with Nugent scores determined by experts. The model was trained by minimizing the cross-entropy loss function and optimized by using a momentum optimizer. The separate test sets of images collected from three hospitals were evaluated by the CNN model. The CNN model consisted of 25 convolutional layers, 2 pooling layers, and a fully connected layer. The model obtained 82.4% sensitivity and 96.6% specificity with the 5,815 validation images when altered vaginal flora and BV were considered the positive samples, which was better than the rates achieved by top-level technologists and obstetricians in China. The capability of our model for generalization was so strong that it exhibited 75.1% accuracy in three categories of Nugent scores on the independent test set of 1,082 images, which was 6.6% higher than the average of three technologists, who are hold bachelor's degrees in medicine and are qualified to make diagnostic decisions. When three technologists ran one specimen in triplicate, the precision of three categories of Nugent scores was 54.0%. One hundred three samples diagnosed by two technologists on different days showed a repeatability of 90.3%. The CNN model outperformed human health care practitioners in terms of accuracy and stability for three categories of Nugent score diagnosis. The deep learning model may offer translational applications in automating diagnosis of bacterial vaginosis with proper supporting hardware.

Portable Pulsed Coherent Lidar for Noncooperation Targets at the Few-Photon Level.

The decoherence in coherent lidar becomes serious with the increase in distance. A small laser spot can suppress the decoherence of the echo light from noncooperation targets. However, it is very difficult to keep a small light spot over a long distance. In this paper, a pulsed coherent lidar with high sensitivity at the few-photon level was demonstrated. A phase plate was used to modulate the wavefront of the laser to achieve 100 m focusing which reduced the decoherence effect. Based on coherent detection and time-of-flight (TOF) measurements, long-distance laser ranging and imaging on all days was realized. A signal classification and superposition method was used to extract the echo signal submerged in noise. The system was experimentally demonstrated by ranging different noncooperation targets within 105.0 m. The measurement rate was 10 k/s, and the measurement uncertainty was 1.48 cm. In addition, laser imaging was realized at ~50.0 m. The system was simple and portable as well as eye safe, and it may offer new application possibilities in automated vehicle lidar.

[Clinical and genetic analysis of a neonate with Cornelia de Lange syndrome 5 caused by HDAC8 gene mutation].

OBJECTIVE: To explore the genetic cause of a neonate with congenital dysplasia, growth retardation through clinical evaluation, laboratory tests and next generation sequencing (NGS). METHODS: Peripheral blood samples were obtained from the child and his parents. Whole genomic DNA was extracted and subjected to NGS. Suspected mutation was predicted by bioinformatic tools and validated by Sanger sequencing. RESULTS: The child was found to carry a c.556G>A (p.E186K) mutation of the HDAC8 gene on the X chromosome, which was predicted to be pathogenic by Bioinformatic analysis. CONCLUSION: The patient was diagnosed as Cornelia de Lange syndrome 5 caused by the c.556G>A mutation of the HDAC8 gene.

Engineering Corynebacterium glutamicum for methanol-dependent growth and glutamate production.

Methanol is a promising feedstock for bioproduction of fuels and chemicals, thus massive efforts have been devoted to engineering non-native methylotrophic platform microorganisms to utilize methanol. Herein, we rationally designed and experimentally engineered the industrial workhorse Corynebacterium glutamicum to serve as a methanol-dependent synthetic methylotroph. The cell growth of the methanol-dependent strain relies on co-utilization of methanol and xylose, and most notably methanol is an indispensable carbon source. Due to the methanol-dependent characteristic, adaptive laboratory evolution was successfully applied to improving methanol utilization. The evolved mutant showed a 20-fold increase in cell growth on methanol-xylose minimal medium and utilized methanol and xylose with a high mole ratio of 3.83:1. 13C-labeling experiments demonstrated that the carbon derived from methanol was assimilated into intracellular building blocks, high-energy carriers, cofactors, and biomass (up to 63% 13C-labeling). By inhibiting cell wall biosynthesis, methanol-dependent glutamate production was also achieved, demonstrating the potential application in bioconversion of methanol into useful chemicals. Genetic mutations detected in the evolved strains indicate the importance of intracellular NAD+/NADH ratio, substrate uptake, and methanol tolerance on methanol utilization. This study reports significant improvement in the area of developing fully synthetic methylotrophs.

Comprehensive optimization of the metabolomic methodology for metabolite profiling of Corynebacterium glutamicum.

Metabolomics has been a potential tool for strain improvement through analyzing metabolite changes in the context of different conditions. However, the availability of a universal metabolite profiling analysis is still a big challenge. In this study, we presented an optimized liquid chromatography-tandem mass spectrometry-based metabolomics methodology for Corynebacterium glutamicum, an important industrial workhorse. It was found that quenching the cellular metabolism with 5-fold volume of - 20 °C 40% methanol was highly recommended due to its lower cell damage rate and higher intracellular metabolite recovery rate. For extracting intracellular metabolites, ethanol/water (3:1, v/v) at 100 °C combined with acidic acetonitrile/water (1:1, v/v, with 0.1% formic acid) at - 20 °C achieved the unbiased metabolite profiling of C. glutamicum. The established methodology was then applied to investigate the intracellular metabolite differences between C. glutamicum ATCC 13032 and an mscCG-deleted mutant under biotin limitation condition. It was observed that in the presence of the functional L-glutamate exporter MscCG, biotin limitation led to accumulation of intracellular 2-oxoglutarate but not L-glutamate. Deletion of mscCG severely inhibited L-glutamate excretion and resulted in a dramatical increase of intracellular L-glutamate, which in turn affected the metabolite profile. The optimized metabolomics methodology holds promise for promoting studies on metabolic mechanism of C. glutamicum.

Förster Energy Transport in Metal-Organic Frameworks Is Beyond Step-by-Step Hopping.

Metal-organic frameworks (MOFs) with light-harvesting building blocks designed to mimic photosynthetic chromophore arrays in green plants provide an excellent platform to study exciton transport in networks with well-defined structures. A step-by-step exciton random hopping model made of the elementary steps of energy transfer between only the nearest neighbors is usually used to describe the transport dynamics. Although such a nearest neighbor approximation is valid in describing the energy transfer of triplet states via the Dexter mechanism, we found it inadequate in evaluating singlet exciton migration that occurs through the Förster mechanism, which involves one-step jumping over longer distance. We measured migration rates of singlet excitons on two MOFs constructed from truxene-derived ligands and zinc nodes, by monitoring energy transfer from the MOF skeleton to a coumarin probe in the MOF cavity. The diffusivities of the excitons on the frameworks were determined to be 1.8 × 10(-2) cm(2)/s and 2.3 × 10(-2) cm(2)/s, corresponding to migration distances of 43 and 48 nm within their lifetimes, respectively. "Through space" energy-jumping beyond nearest neighbor accounts for up to 67% of the energy transfer rates. This finding presents a new perspective in the design and understanding of highly efficient energy transport networks for singlet excited states.

Dual targeting of TIGIT and PD-1 with a novel small molecule for cancer immunotherapy.

Immune checkpoint inhibitors have unveiled promising clinical prospects in cancer treatment. Nonetheless, their effectiveness remains restricted, marked by consistently low response rates and affecting only a subset of patients. The co-blockade of TIGIT with PD-1 has exhibited substantial anti-tumor effects. Notably, there is a dearth of reports on small-molecule inhibitors concurrently targeting both TIGIT and PD-1. In this study, we employed Microscale Thermophoresis (MST) to screen our laboratory's existing repository of small molecules. Our findings illuminated Gln(TrT) 's affinity for both TIGIT and PD-1, affirming its potential to effectively inhibit TIGIT/PVR and PD-1/PD-L1 pathways. In vitro co-culture experiments substantiated Gln(TrT)'s proficiency in restoring Jurkat T-cell functionality by blocking both TIGIT/PVR and PD-1/PD-L1 interactions. In the MC38 murine tumor model, Gln(TrT) emerges as a pivotal modulator, promoting the intratumoral infiltration and functional competence of CD8+ T cells. Furthermore, whether used as a monotherapy or in conjunction with radiotherapy, Gln(TrT) substantially impedes MC38 tumor progression, significantly extending the survival of murine subjects.

Alleviative Effect of Rutin on Zearalenone-Induced Reproductive Toxicity in Male Mice by Preventing Spermatogenic Cell Apoptosis and Modulating Gene Expression in the Hypothalamic-Pituitary-Gonadal Axis.

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin found in many agricultural products and can cause reproductive disorders, mainly affecting spermatogenesis in male animals. Rutin (RUT) is a natural flavonoid compound recognized for its significant antioxidant, anti-inflammatory and estrogenic properties. The present study aimed to determine the protective role of RUT against ZEN-induced reproductive toxicity in male mice. Twenty-four adult Kunming male mice were divided into four groups: control, RUT (500 mg/kg RUT), ZEN (10 mg/kg ZEN), ZEN + RUT (500 mg/kg RUT + 10 mg/kg ZEN), with six replicates per treatment. The results indicated that RUT mitigated ZEN-induced disruption in spermatogenic cell arrangement, decreased spermatozoa count, and increased sperm mortality in the testes. RUT significantly restored ZEN-induced reduction in T, FSH, LH, and E2 serum levels. Moreover, RUT mitigated ZEN-induced apoptosis by increasing the mRNA expression level of bcl-2, decreasing the mRNA expression level of kiss1-r, and decreasing the protein expression level of caspase 8 in reproductive tissues. These findings indicate the protective role of RUT against ZEN-induced reproductive toxicity in male mice by regulating gonadotropin and testosterone secretions to maintain normal spermatogenesis via the HPG axis, which may provide a new application direction for RUT as a therapeutic agent to mitigate ZEN-induced reproductive toxicity.

Correction: Deng et al. Therapeutic Potential of a Combination of Electroacupuncture and Human iPSC-Derived Small Extracellular Vesicles for Ischemic Stroke. Cells 2022, 11, 820.

The authors wish to make the following changes to their paper [...].

Development of LAG-3/FGL1 blocking peptide and combination with radiotherapy for cancer immunotherapy.

Aside from antibodies, peptides show great potential as immune checkpoint inhibitors (ICIs) due to several advantages, such as better tumor penetration and lower cost. Lymphocyte-activation gene 3 (LAG-3) is an immune checkpoint which can induce T cell dysfunction through interaction with its soluble ligand fibrinogen like protein-1 (FGL1). Here, we found that LAG-3 expression was higher than programmed cell death protein 1 (PD-1) in multiple human cancers by TCGA databases, and successfully identified a LAG-3 binding peptide LFP-6 by phage display bio-panning, which specifically blocks the interaction of LAG-3/FGL1 but not LAG-3/MHC-II. Subsequently, d-amino acids were introduced to substitute the N- and C-terminus of LFP-6 to obtain the proteolysis-resistant peptide LFP-D1, which restores T cell function in vitro and inhibits tumor growth in vivo. Further, a bispecific peptide LFOP targeting both PD-1/PD-L1 and LAG-3/FGL1 was designed by conjugating LFP-D1 with PD-1/PD-L1 blocking peptide OPBP-1(8-12), which activates T cell with enhanced proliferation and IFN-γ production. More importantly, LFOP combined with radiotherapy significantly improve the T cell infiltration in tumor and elevate systemic antitumor immune response. In conclusion, we developed a novel peptide blocking LAG-3/FGL1 which can restore T cell function, and the bispecific peptide synergizes with radiotherapy to further enhance the antitumor immune response.

Propofol decreases cisplatin resistance of non-small cell lung cancer by inducing GPX4-mediated ferroptosis through the miR-744-5p/miR-615-3p axis.

Non-small cell lung cancer (NSCLC) is associated with high morbidity and mortality. Propofol functions as a tumor-inhibitor drug by regulating microRNAs (miRNAs). The primary objective of this study is to explore the functional mechanism of propofol in cisplatin (Cis) resistance of NSCLC cells by regulating the miR-744-5p/miR-615-3p axis. Cis-resistant NSCLC cell lines were cultured and chemotherapy-resistance (CR) to Cis of NSCLC cells to Cis was confirmed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method, flow cytometry, and colony formation assay. Ferroptosis was evaluated by measurement of iron content, ferroptosis-related proteins (GPX4/ ACSL4/SLC7A11) and lipid peroxidation (SOD/GSH/MDA) through Western blot analysis and assay kits. After the dual-luciferase reporter assay to testify gene interactions, the functional rescue experiments and nude mouse tumor formation assay were performed. Based on results, propofol reduced IC50 value and CR of NSCLC cells to Cis and induced ferroptosis. Propofol upregulated miR-744-5p/miR-615-3p to inhibit GPX4 transcription. Upregulation of GPX4 or downregulation of miR-744-5p/miR-615-3p attenuated the inhibitory effect of propofol on CR to Cis. In vivo, propofol inhibited tumor growth and CR to Cis by upregulating miR-744-5p/miR-615-3p and inhibiting GPX4 to induce ferroptosis. In summary, propofol inhibited GPX4-mediated ferroptosis and reduces CR of NSCLC cells to Cis through the miR-744-5p/miR-615-3p axis. SIGNIFICANCE: To study the effect of propofol on chemoresistance of non-small cell lung cancer (NSCLC), and to provide a new theoretical basis for the treatment of NSCLC.

Electroacupuncture and human iPSC-derived small extracellular vesicles regulate the gut microbiota in ischemic stroke via the brain-gut axis.

Electroacupuncture (EA) and induced pluripotent stem cell (iPSC)-derived small extracellular vesicles (iPSC-EVs) have substantial beneficial effects on ischemic stroke. However, the detailed mechanisms remain unclear. Here, we explored the mechanisms underlying the regulation of EA and iPSC-EVs in the microbiome-gut-brain axis (MGBA) after ischemic stroke. Ischemic stroke mice (C57BL/6) were subjected to middle cerebral artery occlusion (MCAO) or Sham surgery. EA and iPSC-EVs treatments significantly improved neurological function and neuronal and intestinal tract injury, downregulated the levels of IL-17 expression and upregulated IL-10 levels in brain and colon tissue after cerebral ischemia-reperfusion. EA and iPSC-EVs treatments also modulated the microbiota composition and diversity as well as the differential distribution of species in the intestines of the mice after cerebral ischemia-reperfusion. Our results demonstrated that EA and iPSC-EVs treatments regulated intestinal immunity through MGBA regulation of intestinal microbes, reducing brain and colon damage following cerebral ischemia and positively impacting the outcomes of ischemic stroke. Our findings provide new insights into the application of EA combined with iPSC-EVs as a treatment for ischemic stroke.

Characteristics and potential diagnostic ability of vaginal microflora in patients with aerobic vaginitis using 16S Ribosomal RNA sequencing.

PURPOSE: We aimed to explore the possible function of guiding dominant microflora for aerobic vaginitis (AV) women patients in China to know its diagnostic ability for the further clinical application. METHOD: The characteristics and community compositions of AV vaginal microbiota was evaluated by high-throughput 16S ribosomal RNA (16S rRNA) sequencing after the vaginal microecology evaluations. RESULTS: The increased colonization of Streptococcus agalactiae and Streptococcus anginosus and the absence of Lactobacillus are typical manifestations of AV patients. In addition, Lactobacillus were the major correlated bacteria with control groups of Modified Donders' Score under 3. Most of the significant KEGG pathways were classified into metabolism pathway, where the two bacteria behaved their own metabolism characteristics. CONCLUSION: The increased colonizations of Streptococcus agalactiae and Streptococcus anginosus and the absences of Lactobacillus are the typical manifestations of AV.