Serum GSDMD for Early Diagnosis of Bloodstream Infection and Differentiating Bacterial from Fungal Infections.

BACKGROUND: The role of Gasdermin D (GSDMD) in bloodstream infection (BSI) diagnosis is unknown. METHODS: Serum GSDMD levels were measured in BSI patients. Endothelial cells and PBMCs were isolated, infected with bacteria/fungi, and intracellular/extracellular GSDMD concentrations were measured. An animal model was established to investigate the association between serum GSDMD levels and BSI incidence/progression. RESULTS: ROC curve analysis indicated that GSDMD could be a potential early diagnostic biomarker for BSI (AUC = 0.9885). Combining GSDMD with procalcitonin (PCT) improved the differential diagnosis of Gram-positive and Gram-negative bacteria (AUC = 0.6699, 66.15% specificity), and early diagnosis of Gram-positive bacteria (98.46% sensitivity), while PCT was not significantly elevated. The combined GSDMD and G-test had higher sensitivity (AUC = 0.7174) for differential diagnosis of bacterial and fungal infections, and early detection of fungal infections (98.44% sensitivity). In vitro and in vivo experiments confirmed that GSDMD levels increased significantly within 2 hours, peaked at 16 hours, and exhibited a time-dependent upward trend. CONCLUSIONS: Serum GSDMD, alone or combined with other biomarkers, has potential for early diagnosis and differential diagnosis of BSI caused by various pathogens. This finding offers a new strategy for early detection and treatment of BSI.

TFAP2A downregulation mediates tumor-suppressive effect of miR-8072 in triple-negative breast cancer via inhibiting SNAI1 transcription.

BACKGROUND: Triple-negative breast cancer (TNBC) represents a highly aggressive subset of breast malignancies characterized by its challenging clinical management and unfavorable prognosis. While TFAP2A, a member of the AP-2 transcription factor family, has been implicated in maintaining the basal phenotype of breast cancer, its precise regulatory role in TNBC remains undefined. METHODS: In vitro assessments of TNBC cell growth and migratory potential were conducted using MTS, colony formation, and EdU assays. Quantitative PCR was employed to analyze mRNA expression levels, while Western blot was utilized to evaluate protein expression and phosphorylation status of AKT and ERK. The post-transcriptional regulation of TFAP2A by miR-8072 and the transcriptional activation of SNAI1 by TFAP2A were investigated through luciferase reporter assays. A xenograft mouse model was employed to assess the in vivo growth capacity of TNBC cells. RESULTS: Selective silencing of TFAP2A significantly impeded the proliferation and migration of TNBC cells, with elevated TFAP2A expression observed in breast cancer tissues. Notably, TNBC patients exhibiting heightened TFAP2A levels experienced abbreviated overall survival. Mechanistically, TFAP2A was identified as a transcriptional activator of SNAI1, a crucial regulator of epithelial-mesenchymal transition (EMT) and cellular proliferation, thereby augmenting the oncogenic properties of TFAP2A in TNBC. Moreover, miR-8072 was unveiled as a negative regulator of TFAP2A, exerting potent inhibitory effects on TNBC cell growth and migration. Importantly, the tumor-suppressive actions mediated by the miR-8072/TFAP2A axis were intricately associated with the attenuation of AKT/ERK signaling cascades and the blockade of EMT processes. CONCLUSIONS: Our findings unravel the role and underlying molecular mechanism of TFAP2A in driving tumorigenesis of TNBC. Targeting the TFAP2A/SNAI1 pathway and utilizing miR-8072 as a suppressor represent promising therapeutic strategies for treating TNBC.

Genetic predisposition to porto-sinusoidal vascular disorder: A functional genomic-based, multigenerational family study.

BACKGROUND AND AIMS: Porto-sinusoidal vascular disorder (PSVD) is a group of liver vascular diseases featuring lesions encompassing the portal venules and sinusoids unaccompanied by cirrhosis, irrespective of the presence/absence of portal hypertension. It can occur secondary to coagulation disorders or insult by toxic agents. However, the cause of PSVD remains unknown in most cases. Hereditary cases of PSVD are exceptionally rare, but they are of particular interest and may unveil genetic alterations and molecular mechanisms associated with the disease. APPROACH AND RESULTS: We performed genome sequencing of four patients and two healthy individuals of a large multigenerational Lebanese family with PSVD and identified a heterozygous deleterious variant (c.547C>T, p.R183W) of FCH and double SH3 domains 1 ( FCHSD1 ), an uncharacterized gene, in patients. This variant segregated with the disease, and its pattern of inheritance was suggestive of autosomal dominant with variable expressivity. RNA structural modelling of human FCHSD1 suggests that the C-to-T substitution at position 547, corresponding to FCHSD1R183W , may increase both messenger RNA (mRNA) and protein stability and its interaction with MTOR-associated protein, LST8 homolog, a key protein of the mechanistic target of rapamycin (mTOR pathway). These predictions were substantiated by biochemical analyses, which showed that FCHSD1R183W induced high FCHSD1 mRNA stability, overexpression of FCHSD1 protein, and an increase in mTORC1 activation. This human FCHSD1 variant was introduced into mice through CRISPR/Cas9 genome editing. Nine out of the 15 mice carrying the human FCHSD1R183W variant mimicked the phenotype of human PSVD, including splenomegaly and enlarged portal vein. CONCLUSIONS: Aberrant FCHSD1 structure and function leads to mTOR pathway overactivation and may cause PSVD.

Statistical properties for an optically injected chaotic semiconductor laser with a high-pass filter.

Chaotic waveforms with Gaussian distributions are significant for laser-chaos-based applications such as random number generation. By exploring the injection parameter space of the optical injection semiconductor lasers, we numerically investigate the associated probability density functions of the generated chaotic waveforms when different high-pass filters with different cutoff frequencies are used. Our results demonstrate that the chaotic waveforms with Gaussian probability density functions can be obtained once the cutoff frequency of the high-pass filter is larger than the laser relaxation resonance frequency. Especially, we find that the Gaussian probability density function can reach a superhigh coefficient of determination R2 ≥ 99.5% and an ultralow skewness |S|<0.1 in a large parameter space by jointly controlling the injection parameter and cutoff frequency.

Direct chemical-vapor-deposition growth of alloyed perovskite microcrystals for tunable emissions.

Tunable composition of perovskite micro/nanostructures are perfect candidate for the designing of multifunctional optoelectronic circuits. Especially, integrated polychromatic luminescence based on the perovskite materials along a single substrate or chip is essential to the integrated photonic devices and multicolor displays. Here, we reported a synthesis of composition tunable CsPbI3(1-x)Br3x(X = 0.65-0.9) perovskite microstructures on a single substrate via a magnetic-pulling CVD method. The PL emissions can be changed gradually from green (558 nm, 2.23 eV) to red (610 nm, 2.03 eV) under a focused 375 nm laser illumination. Furthermore, these composition-graded alloyed perovskite microcrystals show stable emissions after six months in air, which may find applications in multicolor display and broad band light sources in the future.

Retrospective analysis of the clinical significance of Ro52/TRIM21 antibody and specific antinuclear antibody patterns by indirect immunofluorescence.

Objectives: To determine the clinical significance of Ro52 protein/tripartite motif-containing 21 antibody and specific antinuclear antibody patterns using indirect immunofluorescence technique. METHODS: The retrospective study was conducted at the clinical laboratory of the First Affiliated Hospital of Chongqing Medical University, China, and comprised data from January 2017 to December 2021 of patients who underwent antinuclear antibody and anti-extractable nuclear antigen antibody detection. Inpatients with Ro52 antibody-positive status were taken as the cases, while anti-Ro52 negative patients with clear clinical diagnosis were taken as the controls. Data was analysed using SPSS 19. RESULTS: There were 1802 cases and 1211 controls. Positive Ro52 showed significantly greater frequency in patients with primary Sjogren's syndrome, systemic lupus erythematosus, inflammatory myositis, dry eyes and interstitial lung disease (p<0.05). Ro52 antibody showed high positive predictive value for primary Sjogren's syndrome 25(96.15%), systemic lupus erythematosus 259(91.20%), connective tissue disease-associated interstitial lung disease 45(86.67%) and inflammatory myositis 60(86.67%). Antinuclear antibody indirect immunofluorescence patterns most frequently detected were nuclear speckled 128(40.89%) and cytoplasmic speckled 126(40.26%) (p<0.05). Interstitial lung disease was associated with the presence of cytoplasmic speckled antinuclear antibody indirect immunofluorescence pattern 24(19.2%), while tumours 47(36.5%) and hepatitis B 26(20.3%) seemed to be more frequent with nuclear speckled pattern (p<0.05). The simultaneous reactivity extractable nuclear antigen antibodies most frequently detected were antinuclear antibody+Ro52+anti-Sjogren's syndrome A+ 558(33.96%). CONCLUSIONS: Ro52 antibody positivity was found to be associated with Sjogren's syndrome, systemic lupus erythematosus, inflammatory myositis, dry eye and interstitial lung disease. The antinuclear antibody immunofluorescence pattern of Ro52 positive was single and primarily granular cytoplasm type. Antinuclear antibody negative and Ro52 positive in the serum of patients also had certain significance in auxiliary disease diagnosis.

Identification of FCN1 as a novel macrophage infiltration-associated biomarker for diagnosis of pediatric inflammatory bowel diseases.

BACKGROUND: The incidence of pediatric inflammatory bowel disease (PIBD) has been steadily increasing globally. Delayed diagnosis of PIBD increases the risk of complications and contributes to growth retardation. To improve long-term outcomes, there is a pressing need to identify novel markers for early diagnosis of PIBD. METHODS: The candidate biomarkers for PIBD were identified from the GSE117993 dataset by two machine learning algorithms, namely LASSO and mSVM-RFE, and externally validated in the GSE126124 dataset and our PIBD cohort. The role of ficolin-1 (FCN1) in PIBD and its association with macrophage infiltration was investigated using the CIBERSORT method and enrichment analysis of the single-cell dataset GSE121380, and further validated using immunoblotting, qRT-PCR, and immunostaining in colon biopsies from PIBD patients, a juvenile murine DSS-induced colitis model, and THP-1-derived macrophages. RESULTS: FCN1 showed great diagnostic performance for PIBD in an independent clinical cohort with the AUC of 0.986. FCN1 expression was upregulated in both colorectal biopsies and blood samples from PIBD patients. Functionally, FCN1 was associated with immune-related processes in the colonic mucosa of PIBD patients, and correlated with increased proinflammatory M1 macrophage infiltration. Furthermore, single-cell transcriptome analysis and immunostaining revealed that FCN1 was almost exclusively expressed in macrophages infiltrating the colonic mucosa of PIBD patients, and these FCN1+ macrophages were related to hyper-inflammation. Notably, proinflammatory M1 macrophages derived from THP-1 expressed high levels of FCN1 and IL-1ß, and FCN1 overexpression in THP-1-derived macrophages strongly promoted LPS-induced activation of the proinflammatory cytokine IL-1ß via the NLRP3-caspase-1 axis. CONCLUSIONS: FCN1 is a novel and promising diagnostic biomarker for PIBD. FCN1+ macrophages enriched in the colonic mucosa of PIBD exhibit proinflammatory phenotypes, and FCN1 promotes IL-1ß maturation in macrophages via the NLRP3-caspase-1 axis.

Leader-laggard synchronization of polarization chaos in mutually coupled free-running VCSELs.

We systematically study the leader-laggard synchronization of polarization chaos in mutually coupled free-running vertical cavity surface emitting semiconductor lasers in two cases of parallel and orthogonal injection. Specifically, we quantitatively investigate the effect of critical external parameter mismatch such as the coupling intensity and frequency detuning on the leader-laggard relationship utilizing the cross-correlation function. When the difference between two main cross-correlation peak values exceeds 0.1, the leader-laggard relationship can be viewed to be stable. Our results demonstrate that compared with the coupling strength, the frequency detuning is the dominant factor in determining the stability of the leader-laggard relationship. The exchange of the leader-laggard role occurs within a frequency detuning region from -5 GHz to 5 GHz for both parallel and orthogonal injection. Once the leader-laggard relationship is stable, the difference between the two cross-correlation values can reach 0.242 for negative frequency detuning, but the corresponding value is only 0.146 under positive frequency detuning.

Forecasting the chaotic dynamics of external cavity semiconductor lasers.

Chaotic time series prediction has been paid intense attention in recent years due to its important applications. Herein, we present a single-node photonic reservoir computing approach to forecasting the chaotic behavior of external cavity semiconductor lasers using only observed data. In the reservoir, we employ a semiconductor laser with delay as the sole nonlinear physical node. By investigating the effect of the reservoir meta-parameters on the prediction performance, we numerically demonstrate that there exists an optimal meta-parameter space for forecasting optical-feedback-induced chaos. Simulation results demonstrate that using our method, the upcoming chaotic time series can be continuously predicted for a time period in excess of 2 ns with a normalized mean squared error lower than 0.1. This proposed method only utilizes simple nonlinear semiconductor lasers and thus offers a hardware-friendly approach for complex chaos prediction. In addition, this work may provide a roadmap for the meta-parameter selection of a delay-based photonic reservoir to obtain optimal prediction performance.

Integrative analysis of transcriptomic and metabolomic profiles reveals enhanced arginine metabolism in androgen-independent prostate cancer cells.

BACKGROUND: Prostate cancer is a common solid tumor that affects a significant number of men worldwide. Conventional androgen deprivation therapy (ADT) increases the risk of developing castration-resistant prostate cancer (CRPC). Effective clinical management of patients with CRPC is challenging due to the limited understanding. METHODS: In this study, transcriptomic and metabolomic profiles of androgen-dependent prostate cancer cell line LNCaP and the androgen-independent cells developed from LNCaP cells (LNCaP-ADR) were investigated using RNA-sequencing and LC-MS/MS, respectively. The differentially expressed genes and metabolites were analyzed, and integrative analysis of transcriptomic and metabolomic data was further conducted to obtain a comprehensive understanding of the metabolic characteristics in LNCaP-ADR cells. Quantitative real-time PCR (QPCR) was employed to ascertain the mRNA expression levels of the selected differentially expressed genes. RESULTS: The arginine and proline metabolism pathway was identified as a commonly altered pathway at both the transcriptional and metabolic levels. In the LNCaP-ADR cells, significant upregulation was observed for metabolites including 5-Aminopentanoic acid, L-Arginine, L-Glutamic acid, N-Acetyl-L-alanine, and Pyrrole-2-carboxylic acid at the metabolic level. At the transcriptional level, MAOA, ALDH3A2, ALDH2, ARG1, CKMT2, and CNDP1 were found to be significantly upregulated in the LNCaP-ADR cells. Gene set enrichment analysis (GSEA) identified various enriched gene sets in the LNCaP-ADR cells, encompassing inflammatory response, 9plus2 motile cilium, motile cilium, ciliary plasm, cilium or flagellum-dependent cell motility, cilium movement, cilium, response to endoplasmic reticulum stress, PTEN DN.V1 DN, SRC UP.V1 UP, IL15 UP.V1 DN, RB DN.V1 DN, AKT UP MTOR DN.V1 UP, VEGF A UP.V1 UP, and KRAS.LUNG.BREAST UP.V1 UP. CONCLUSIONS: These findings highlight the substantial association between the arginine and proline metabolism pathway and CRPC, emphasizing the need to prioritize strategies that target dysregulated metabolites and differentially expressed genes as essential interventions in the clinical management of CRPC.

Safety, tolerability, pharmacokinetics and immunogenicity of an antibody-drug conjugate (SHR-A1201) in patients with HER2-positive advanced breast cancer: an open, phase I dose-escalation study.

SHR-A1201 is an antibody-drug conjugate (ADC) that combines trastuzumab with DM1 (a chemotherapeutic agent) using a chemical connector. This phase I study investigated the safety, tolerability and pharmacokinetics of SHR-A1201 in patients with human epidermal growth factor receptor 2-positive advanced breast cancer. This phase I study enrolled patients in a traditional 3 + 3 dose-escalation design to receive a single dose of SHR-A1201 (1.2 mg/kg, 2.4 mg/kg, 3.6 mg/kg or 4.8 mg/kg). The observation period of dose-limiting toxicity (DLT) was 21 days. A total of 12 patients were enrolled and received SHR-A1201. Most treatment-emergent adverse events (TEAEs) were grade 1 or 2 in severity, with elevated aspartate aminotransferase (75%), thrombocytopenia (75%), and nausea (66.7%) being reported most frequently. The common grade 3 TEAEs were thrombocytopenia and decreased lymphocyte count, and there were no grade 4 or above TEAEs. There were no serious adverse events or drug-related deaths. One DLT occurred in one patient treated with SHR-A1201 4.8 mg/kg (asymptomatic grade 3 increased γ-glutamyltransferase). The maximum tolerated dose of SHR-A1201 was not lower than that of T-DM1 (3.6 mg/kg). A total of 8.3% (1/12) of patients had ADA-positive reactions 504 h after administration, but no differences were observed in the type, incidence, or severity of TEAEs between patients with and without ADA. SHR-A1201 exhibited the pharmacokinetics characteristics of typical ADCs. An encouraging antitumor effect was observed in the 4.8 mg/kg dose group. SHR-A1201 was well tolerated and safe in patients with advanced HER2-positive breast cancer. The pharmacokinetics parameters showed a linear trend, and the immunogenicity results met the clinical expectations.

Clinical application of single-layer annular vaginal flap in transvaginal repair for vesicovaginal fistula.

PURPOSE: To compare the first-time success rate and prognosis of repairing vesicovaginal fistula (VVF) by transvaginal and transvesical approaches, and to highlight a modified transvaginal repair technique which only require single layer closure of an annular vaginal flap. METHODS: Retrospective analysis of 57 consecutive patients who underwent VVF repair between 2007 and 2021. Fistula characteristics, operative factors, post-surgical complications and outcomes were analyzed. RESULTS: A total of 57 women with a median age of 50.4 (27-75) years were included. The history ranged from 7 days to 8 years, with an average of 20 months. 56 cases (98.2%) of VVFs were caused by pelvic surgery, and only one resulted from difficult labour. 11 cases (19.3%) had a history of surgical repair failure. All 57 cases of surgery were smoothly completed. Among them, 17 patients underwent transvaginal repair, whereas 40 (70.2%) women had transvesical repair. Transvaginal approach had a significantly shorter operative time, less intraoperative blood loss, reduced postoperative hospital stay, less hospitalization cost and lower minor complication rates than transvesical group (p < 0.05). No serious complications occurred in the two groups. No cystostomy was performed in the transvaginal group, but 12 cases (30%) in the transvesical group. The average follow-up time was 18.5 (3-48) months. The first-time success rates of transvaginal and transvesical techniques were 82.3 and 75%, respectively. CONCLUSION: VVF repair with single layer closure of an annular vaginal flap is a technically feasible, simple and successful approach with significantly better operative parameters and lower complications rates.

Effectiveness and degradation pathways of bisphenol A (BPA) initiated by hydroxyl radicals and sulfate radicals in water: Initial reaction sites based on DFT prediction.

Bisphenol A (BPA), one of the widely known endocrine-disrupting chemicals, can be effectively degraded by advanced oxidation processes in water because of the powerful reactive oxygen species. In this study, Fenton, UV/Fenton, and metal ion/peroxymonosulfate (PMS) processes were compared to investigate BPA degradation efficiency and pathways initiated by hydroxyl radicals and sulfate radicals. In contrast to the Fenton system, which only degraded 60% of BPA within 15 min, the UV/Fenton system could degrade greater than 80% of BPA, because more hydroxyl radicals (•OH) were generated under the reduction of Fe3+ to Fe2+. The optimized parameters of the UV/Fenton system were as follows: 8 µmol/L of Fe2+, 80 µmol/L of H2O2, and a pH value of 3.0. As for the metal ion/PMS system, the BPA degradation efficiency was closely associated with the applied metal ions, and the order was as follows: Co2+/PMS (∼100%) > Fe2+/PMS (∼80%) > Cu2+/PMS (∼79%). The degradation pathways of BPA were theoretically interpreted through density functional theory prediction and degradation products during various processes. Two major initial reaction sites (4C and 6C) for •OH initiated using the UV/Fenton system and one initial reaction site (4C) for sulfate radicals (SO4•-) using the metal ion/PMS system were recognized for BPA degradation processes. The degradation products by •OH showed a larger average molecular weight than those by SO4•-. These studies are instructive for the application of different advanced oxidation systems in the treatment process of BPA in wastewater.

Using deep learning to track time × frequency whistle contours of toothed whales without human-annotated training data.

Many odontocetes produce whistles that feature characteristic contour shapes in spectrogram representations of their calls. Automatically extracting the time × frequency tracks of whistle contours has numerous subsequent applications, including species classification, identification, and density estimation. Deep-learning-based methods, which train models using analyst-annotated whistles, offer a promising way to reliably extract whistle contours. However, the application of such methods can be limited by the significant amount of time and labor required for analyst annotation. To overcome this challenge, a technique that learns from automatically generated pseudo-labels has been developed. These annotations are less accurate than those generated by human analysts but more cost-effective to generate. It is shown that standard training methods do not learn effective models from these pseudo-labels. An improved loss function designed to compensate for pseudo-label error that significantly increases whistle extraction performance is introduced. The experiments show that the developed technique performs well when trained with pseudo-labels generated by two different algorithms. Models trained with the generated pseudo-labels can extract whistles with an F1-score (the harmonic mean of precision and recall) of 86.31% and 87.2% for the two sets of pseudo-labels that are considered. This performance is competitive with a model trained with 12 539 expert-annotated whistles (F1-score of 87.47%).

The Synergistic Antimicrobial Effect and Mechanism of Nisin and Oxacillin against Methicillin-Resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for skin and soft tissue infections with multi-resistance to many antibiotics. It is thus imperative to explore alternative antimicrobial treatments to ensure future treatment options. Nisin (NIS), an antibacterial peptide produced by Lactococcus lactis, was selected to combine with Oxacillin (OX), to evaluate the antimicrobial effect and potential mechanism against MRSA. The synergistic antimicrobial effect of OX and NIS was verified by Minimal Inhibitory Concentration (MIC) assays, checkerboard analysis, time-kill curve, biofilm producing ability, and mice skin infection model in vivo. For the potential synergistic antimicrobial mechanism, the microstructure and integrity change of MRSA cells were determined by Scanning and Transmission Electron Microscope (SEM and TEM), intracellular alkaline phosphatase activity and propidium iodide staining were assayed; And transcription of mecA, main gene of MRSA resistant to OX, were detected by qRT-PCR. The results showed NIS could restore the sensitivity of MRSA to OX and inhibit biofilm production; OX + NIS can make MRSA cell deform; NIS may recover OX sensitivity by inhibiting the transcription of mecA. In vivo, mice skin infection models indicate that OX + NIS can substantially alleviate MRSA infections. As a safe commercially available biological compound, NIS and the combination of antibiotics are worth developing as new anti-MRSA biomaterials.

A Photoelectrochemical Sensor Based on DNA Bio-Dots-Induced Aggregation of AuNPs for Methionine Detection.

Based on DNA bio-dots-induced aggregation of gold nanoparticles (AuNPs), a methionine (Met) photoelectrochemical (PEC) sensor with CS-GSH-CuNCs/TiO2 NPs as the photoelectric conversion element and AuNPs as the specific recognition element was constructed. First, a TiO2 NPs/ITO electrode and CS-GSH-CuNCs were prepared, and then the CS-GSH-CuNCs/TiO2 NPs/ITO photosensitive electrode was obtained by self-assembly. Next, DNA bio-dots were modified to the upper surface of the electrode using a coupling reaction to assemble the DNA bio-dots/CS-GSH-CuNCs/TiO2 NPs electrode. Amino-rich DNA bio-dots were used to induce the aggregation of AuNPs on the electrode surface via Au-N interactions and prepare the AuNPs/DNA bio-dots/CS-GSH-CuNCs/TiO2 NPs electrode. Due to the fluorescence resonance energy transfer (FRET) between CS-GSH-CuNCs and AuNPs, the complexation chance of electron-hole (e--h+) pair in CS-GSH-CuNCs increased, which, in turn, led to a decrease in photocurrent intensity. When Met was present, AuNPs aggregated on the electrode surface were shed and bound to Met since the Au-S interaction is stronger than the Au-N interaction, resulting in the recovery of the photocurrent signal. Under optimal conditions, the photocurrent intensity of the PEC sensor showed good linearity with the logarithm of Met concentration in the range of 25.0 nmol/L-10.0 µmol/L with the limit of detection (LOD) of 5.1 nmol/L (S/N = 3, n = 10).

A novel prognostic index of stomach adenocarcinoma based on immunogenomic landscape analysis and immunotherapy options.

Stomach adenocarcinoma (STAD) is one of the most common malignant tumors worldwide. In this study, we attempted to construct a valid immune-associated gene prognostic index risk model that can predict the survival of patients with STAD and the efficacy of immune checkpoint inhibitors (ICIs) treatment. Transcriptome, clinical, and gene mutational data were obtained from the TCGA database. Immune-related genes were downloaded from the ImmPort and InnateDB databases. A total of 493 immune-related genes were identified to be enriched in functions associated with immune response, as well as in immune and tumor-related pathways. Further, 36 candidate genes related to the overall survival (OS) of STAD were obtained by weighted gene co-expression network analysis (WGCNA). Next, based on a Cox regression analysis, we constructed an immune-associated gene prognostic index (IAGPI) risk model based on eight genes, which was verified using the GEO STAD cohort. The patients were divided into two subsets according to their risk score. Patients in the low-risk group had better OS than those in the high-risk group. In the low-risk group, there were more CD8, activated memory CD4, and follicular helper T cells, and M1 macrophages, whereas monocytes, M2 macrophages, eosinophils, and neutrophils were more abundant in the high-risk group. The patients in the low-risk group were more sensitive to ICIs therapy. The IAGPI risk model can precisely predict the prognosis, reflect the tumor immune microenvironment, and predict the efficacy of ICIs therapy in patients with STAD.

On-wire bandgap engineering via a magnetic-pulled CVD approach and optoelectronic applications of one-dimensional nanostructures.

Since the emergence of one-dimensional nanostructures, in particular the bandgap-graded semiconductor nanowires/ribbons or heterostructures, lots of attentions have been devoted to unraveling their intriguing properties and finding applications for future developments in optical communications and integrated optoelectronic devices. In particular, the ability to modulate the bandgap along a single nanostructure greatly enhances their functionalities in optoelectronics, and hence these studies are essential to pave the way for future high-integrated devices and circuits. Herein, we focus on a brief review on recent advances about the synthesis through a magnetic-pulled chemical vapor deposition approach, crystal structure and the unique optical and electronic properties of on-nanostructures semiconductors, including axial nanowire heterostructures, asymmetrical/symmetric bandgap gradient nanowires, lateral heterostructure nanoribbons, lateral bandgap graded ribbons. Moreover, recent developments in applications using low-dimensional bandgap modulated structures, especially in bandgap-graded nanowires and heterostructures, are summarized, including multicolor lasers, waveguides, white-light sources, photodetectors, and spectrometers, where the main strategies and unique features are addressed. Finally, future outlook and perspectives for the current challenges and the future opportunities of one-dimensional nanostructures with bandgap engineering are discussed to provide a roadmap future development in the field.

Inhibitory Effects of Phenazine Compounds and Volatile Organic Compounds Produced by Pseudomonas aurantiaca ST-TJ4 Against Phytophthora cinnamomi.

Phytophthora cinnamomi is an important plant pathogen that is widely distributed worldwide and has caused serious ecological damage and significant economic losses in forests and plantations in many countries. The use of plant growth-promoting rhizobacteria is an effective and environmentally friendly strategy for controlling diseases caused by P. cinnamomi. In this study, we investigated the antagonistic mechanism of Pseudomonas aurantiaca ST-TJ4 against P. cinnamomi through different antagonistic approaches, observations of mycelial morphology, study of mycelial metabolism, and identification of antagonistic substances. The results showed that Pseudomonas aurantiaca ST-TJ4 was able to significantly inhibit mycelial growth, causing mycelial deformation and disrupting internal cell structures. Additionally, pathogen cell membranes were damaged by ST-TJ4, and mycelial cell content synthesis was disrupted. Ultraperformance liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry analyses showed that phenazine compounds and 2-undecanone were the main antagonistic components. The ammonia produced by the ST-TJ4 strain also contributed to the inhibition of the growth of P. cinnamomi. In conclusion, our results confirm that Pseudomonas aurantiaca ST-TJ4 can inhibit P. cinnamomi through multiple mechanisms and can be used as a biological control agent for various plant diseases caused by P. cinnamomi.

Seasonal dynamics survey and association analysis of microbiota communities, antibiotic resistance genes distribution, and biotoxicities characterization in landfill-leachate.

OBJECTIVE: To reflect the potential and intrinsic association among microbiota structure, antibiotic resistance genes distribution and biological toxicity of landfill-leachate according to seasonal change, and accurately assess the potential threat of leachate to the surrounding environment. METHODS: On the basis of the leachate water quality monitoring data from January to December 2020, principal component analysis (PCA) was used to identify the main pollutants in the leachate; Vibrio fischeri luminescence inhibition test was used to detect the comprehensive biotoxicity of the leachate; 16S rDNA amplicon sequencing was used for leachate microbiota. q-PCR was used to detect the class 1 integron (intI1), and eight antibiotic resistance genes (sul1, sul2, tetA, tetB, tetM, tetQ, mefA, and mexF); Canonical correspondence (CCA) analysis was carried out for the association analysis. RESULT: The biotoxicity of leachate in the second quarter was the highest. The dominant phylum of leachate microbiota from 1st quarters to 4th quarters was Proteobacteria (94.97 %, 85.43 %, 88.20 %, and 84.11 %), and the dominant genera were Thiomonas (60.41 %, 26.83 %, 25.66 %, and 30.51 %), Pseudomonas (5.89 %, 1.86 %, 0.68 %, and 4.72 %), Desulfurella (8.52 %, 0.57 %, 3.81 %, and 8.25 %), and Acidithiobacillus (4.71 %, 0.69 %, 0.87 %, and 5.91 %); Nitrospirillum was negatively correlated with chemical oxygen demand (COD) (R=-0.561, P = 0.008) and five-day biochemical oxygen demand (BOD5) (R=-0.591, P = 0.005); Limnohabitans was positively correlated with pH (R=0.444, P = 0.044). Four AR genes (sul1, sul2，tetM, and tetQ) were detected in all the samples, while the second quarter had the highest concentration of sul1(6.31 ± 0.49 lg copies/ng DNA), tetM (3.01 ± 1.38 lg copies/ng DNA) and tetQ (3.64 ± 0.90 lg copies/ng DNA). CONCLUSION: As the mature landfill, the quality of this leachate met the pollution control standards for domestic waste landfills. Thiomycetes, Pseudomonas, Desulfurization, and Thiopterus acidophyllum constitute the dominant microbiota. However, leachate in the second quarter had more serious contamination, the higher biotoxicity, higher concentration of AR genes, together with higher microbiota richness and diversity, which deserved more attention for the potential threat to the surrounding environment.