Banana
wilt, which is caused by
f.sp.
Tropical Race 4 (FOC TR4), is one of the most serious fungal diseases in the banana-producing regions in east Asia.
Gxun-2 could significantly inhibit the growth ...of FOC TR4. Strain Gxun-2 strongly inhibited the mycelial growth of FOC TR4 on dual culture plates and caused hyphal wrinkles, ruptures, and deformities on in vitro cultures. Banana seedlings under pot experiment treatment with Gxun-2 in a greenhouse resulted in an 84.21% reduction in the disease. Comparative transcriptome analysis was applied to reveal the response and resistance of FOC TR4 to Gxun-2 stress. The RNA-seq analysis of FOC TR4 during dual-culture with
Gxun-2 revealed 3075 differentially expressed genes (DEGs) compared with the control. Among the genes, 1158 genes were up-regulated, and 1917 genes were down-regulated. Further analysis of gene function and the pathway of DEGs revealed that genes related to the cell membrane, cell wall formation, peroxidase, ABC transporter, and autophagy were up-regulated, while down-regulated DEGs were enriched in the sphingolipid metabolism and chitinase. These results indicated that FOC TR4 upregulates a large number of genes in order to maintain cell functions. The results of qRT-PCR conducted on a subset of 13 genes were consistent with the results of RNA-seq data. Thus, this study serves as a valuable resource regarding the mechanisms of fungal pathogen resistance to biocontrol agents.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Community-acquired pneumonia (CAP) is a common and serious condition that can be caused by a variety of pathogens. However, much remains unknown about how these pathogens interact with the lower ...respiratory commensals, and whether any correlation exists between the dysbiosis of the lower respiratory microbiota and disease severity and prognosis.
We conducted a retrospective cohort study to investigate the composition and dynamics of sputum microbiota in patients diagnosed with CAP. In total, 917 sputum specimens were collected consecutively from 350 CAP inpatients enrolled in six hospitals following admission. The V3-V4 region of the 16 S rRNA gene was then sequenced.
The sputum microbiota in 71% of the samples were predominately composed of respiratory commensals. Conversely, 15% of the samples demonstrated dominance by five opportunistic pathogens. Additionally, 5% of the samples exhibited sterility, resembling the composition of negative controls. Compared to non-severe CAP patients, severe cases exhibited a more disrupted sputum microbiota, characterized by the highly dominant presence of potential pathogens, greater deviation from a healthy state, more significant alterations during hospitalization, and sparser bacterial interactions. The sputum microbiota on admission demonstrated a moderate prediction of disease severity (AUC = 0.74). Furthermore, different pathogenic infections were associated with specific microbiota alterations. Acinetobacter and Pseudomonas were more abundant in influenza A infections, with Acinetobacter was also enriched in Klebsiella pneumoniae infections.
Collectively, our study demonstrated that pneumonia may not consistently correlate with severe dysbiosis of the respiratory microbiota. Instead, the degree of microbiota dysbiosis was correlated with disease severity in CAP patients.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Community-acquired pneumonia (CAP) is a major public health challenge worldwide. However, the aetiological and disease severity-related pathogens associated with CAP in adults in China are not well ...established based on the detection of both viral and bacterial agents.
A multicentre, prospective study was conducted involving 10 hospitals located in nine geographical regions in China from 2014 to 2019. Sputum or bronchoalveolar lavage fluid (BALF) samples were collected from each recruited CAP patient. Multiplex real-time PCR and bacteria culture methods were used to detect respiratory pathogens. The association between detected pathogens and CAP severity was evaluated.
Among the 3,403 recruited eligible patients, 462 (13.58%) had severe CAP, and the in-hospital mortality rate was 1.94% (66/3,403). At least one pathogen was detected in 2,054 (60.36%) patients, with two or more pathogens were co-detected in 725 patients. The ten major pathogens detected were Mycoplasma pneumoniae (11.05%), Haemophilus influenzae (10.67%), Klebsiella pneumoniae (10.43%), influenza A virus (9.49%), human rhinovirus (9.02%), Streptococcus pneumoniae (7.43%), Staphylococcus aureus (4.50%), adenovirus (2.94%), respiratory syncytial viruses (2.35%), and Legionella pneumophila (1.03%), which accounted for 76.06-92.52% of all positive detection results across sampling sites. Klebsiella pneumoniae (p < 0.001) and influenza viruses (p = 0.005) were more frequently detected in older patients, whereas Mycoplasma pneumoniae was more frequently detected in younger patients (p < 0.001). Infections with Klebsiella pneumoniae, Staphylococcus aureus, influenza viruses and respiratory syncytial viruses were risk factors for severe CAP.
The major respiratory pathogens causing CAP in adults in China were different from those in USA and European countries, which were consistent across different geographical regions over study years. Given the detection rate of pathogens and their association with severe CAP, we propose to include the ten major pathogens as priorities for clinical pathogen screening in China.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Non‐small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. MiRNAs are recognized as important molecules in cancer biology. The aim of the study was to identify ...a novel biomarker miR‐148b and its mechanism in the modulation of NSCLC progression.
Methods
The expressional level of miR‐148b was analyzed by RT‐PCR. The effect of miR‐4317 on proliferation was evaluated through 3‐(4,5‐Dimethyl‐2‐thiazolyl)‐2,5‐diphenyl‐2Htetrazolium bromide (MTT) assay. The effect of miR‐148b on the metastasis of NSCLC was detected through transwell assays. The verification of the target of miR‐148b was assessed by TargetScan and dual‐luciferase reporter assay. The related proteins in this study were analyzed by western blot.
Results
Our findings confirmed that miR‐148b was decreased in NSCLC and NSCLC patients with lower expression exhibited poorer overall survival (OS). Increasing miR‐148b significantly repressed proliferation, invasion and migration. More importantly, activated leukocyte cell adhesion molecule (ALCAM) was determined as the direct target of miR‐148b, and reintroduction of ALCAM attenuated miR‐148b effect on the progress of NSCLC. In addition, NF‐κB signaling pathway was modulated by miR‐148b/ALCAM axis.
Conclusions
Our results indicated that miR‐148b is able to suppress NSCLC growth and metastasis via targeting ALCAM through the NF‐κB pathway. These findings provided new evidence that miR‐148b serves as a potential biomarker and novel target for NSCLC treatment.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
This study aimed to conduct a comparative analysis of the survival rates after segmentectomy, wedge resection, or lobectomy in patients with cStage IA lung squamous cell carcinoma (SCC).
...Methods
We enrolled 4,316 patients who had cStage IA lung SCC from the Surveillance, Epidemiology, and End Results (SEER) database. The Cox proportional hazards model was conducted to recognize the potential risk factors for overall survival (OS) and lung cancer-specific survival (LCSS). To eliminate potential biases of included patients, the propensity score matching (PSM) method was used. OS and LCSS rates were compared among three groups stratified according to tumor size.
Results
Kaplan–Meier analyses revealed no statistical differences in the rates of OS and LCSS between wedge resection (WR) and segmentectomy (SG) groups for patients who had cStage IA cancers. In patients with tumors ≤ 1 cm, LCSS favored lobectomy (Lob) compared to segmentectomy (SG), but a similar survival rate was obtained for wedge resection (WR) and lobectomy (Lob). For patients with tumors sized 1.1 to 2 cm, lobectomy had improved OS and LCSS rates compared to the segmentectomy or wedge resection groups, with the exception of a similar OS rate for lobectomy and segmentectomy. For tumors sized 2.1 to 3 cm, lobectomy had a higher rate of OS or LCSS than wedge resection or segmentectomy, except that lobectomy conferred a similar LCSS rate compared to segmentectomy. Multivariable analyses showed that patients aged ≥75 and tumor sizes of >2 to ≤3 cm were potential risk factors for OS and LCSS, while lobectomy and first malignant primary indicator were considered protective factors. The Cox proportional analysis also confirmed that male patients aged ≥65 to <75 were independent prognostic factors that are indicative of a worse OS rate.
Conclusions
The tumor size can influence the surgical procedure recommended for individuals with cStage IA lung SCC. For patients with tumors ≤1 cm, lobectomy is the recommended approach, and wedge resection or segmentectomy might be an alternative for those who cannot tolerate lobectomy if adequate surgical margin is achievable and enough nodes are sampled. For tumors >1 to ≤3 cm, lobectomy showed better survival outcomes than sublobar resection. Our findings require further validation by randomized controlled trial (RCT) or other evidence.
Bartter syndrome is a rare inherited disease caused by CLCNKB mutation, which results in inactivation of the chloride channel Kb protein. Bartter syndrome is characterized by extreme hypokalemia, ...hypochloremia, metabolic alkalosis, hyperrenin-induced angiotensinemia, hyperaldosteronemia, and normal blood pressure. We herein report a case of Bartter syndrome that manifested as vomiting, hypokalemia, metabolic alkalosis, normal blood pressure, and significant hyperrenin-induced angiotensinemia. The patient, a 5-month-old girl, carried two known heterozygous pathogenic mutations: c.88C > T (p.Arg30*), which she had inherited from her father, and c.1313G > A (p.Arg438His), which she had inherited from her mother. Treatment with indomethacin, a nonsteroidal anti-inflammatory drug, led to rapid improvement of the hypokalemia, and treatment was continued for 14 years. The indomethacin also induced a sustainable reduction in the hypokalemia and metabolic alkalosis.
Klebsiella pneumoniae is a leading cause of highly drug-resistant infections in hospitals worldwide. Strain-level bacterial identification on the genetic determinants of multidrug resistance and high ...pathogenicity is critical for the surveillance and treatment of this clinically relevant pathogen. In this study, metagenomic next-generation sequencing was performed for specimens collected from August 2020 to May 2021 in Ruijin Hospital, Ningbo Women and Children's Hospital, and the Second Affiliated Hospital of Harbin Medical University. Genome biology of K. pneumoniae prevalent in China was characterized based on metagenomic data. Thirty K. pneumoniae strains derived from 14 sequence types were identified by multilocus sequence typing. The hypervirulent ST11 K. pneumoniae strains carrying the KL64 capsular locus were the most prevalent in the hospital population. The phylogenomic analyses revealed that the metagenome-reconstructed strains and public isolate genomes belonging to the same STs were closely related in the phylogenetic tree. Furthermore, the pangenome structure of the detected K. pneumoniae strains was analyzed, particularly focusing on the distribution of antimicrobial resistance genes and virulence genes across the strains. The genes encoding carbapenemases and extended-spectrum beta-lactamases were frequently detected in the strains of ST11 and ST15. The highest numbers of virulence genes were identified in the well-known hypervirulent strains affiliated to ST23 bearing the K1 capsule. In comparison to traditional cultivation and identification, strain-level metagenomics is advantageous to understand the mechanisms underlying resistance and virulence of K. pneumoniae directly from clinical specimens. Our findings should provide novel clues for future research into culture-independent metagenomic surveillance for bacterial pathogens.
Routine culture and PCR-based molecular testing in the clinical microbiology laboratory are unable to recognize pathogens at the strain level and to detect strain-specific genetic determinants involved in virulence and resistance. To address this issue, we explored the strain-level profiling of K. pneumoniae prevalent in China based on metagenome-sequenced patient materials. Genome biology of the targeted bacterium can be well characterized through decoding sequence signatures and functional gene profiles at the single-strain resolution. The in-depth metagenomic analysis on strain profiling presented here shall provide a promising perspective for culture-free pathogen surveillance and molecular epidemiology of nosocomial infections.
Continuous cropping and soilborne diseases affect soil properties and soil microbial diversity and structure, which are the main factors posing obstacles to the continuous cropping of ginseng. This ...study explored the response of the physicochemical properties, enzyme activity, and microbial community of ginseng rhizosphere soil to continuous cropping and soilborne disease (root rot of ginseng). We used woodland soil without ginseng planting as a control to study these changes. The results showed that continuous cropping and soilborne disease significantly affected soil physicochemical properties, enzyme activities, and microbial communities. The levels of total nitrogen, hydrolyzable nitrogen, organic matter, and soil pH decreased significantly, while available phosphorus, available potassium, total phosphorus, and total potassium showed significant accumulation after continuous cropping. The activities of urease, catalase, sucrase, acid phosphatase, alkaline phosphatase, and polyphenol oxidase decreased significantly after continuous cropping. Using MiSeq high-throughput sequencing, we found that the alpha diversity and the number of bacterial and fungal communities significantly changed after continuous cropping and soilborne disease. A redundancy analysis suggests that soil physicochemical properties and enzyme activities also affect soil microbial communities. In summary, this study revealed the effects of continuous cropping and soilborne disease on soil and provides a theoretical basis for alleviating soilborne disease in ginseng.
Gastric cancer can be a fatal tumor and therefore represents one of the primary challenges in modern oncology. Survivin and X-linked inhibitor of apoptosis protein (XIAP) are members of the IAP ...family, which exerts a strong inhibitory effect on cellular apoptosis. In previous studies, the expression levels of survivin and XIAP have been demonstrated to influence the prognosis of patients with gastric cancer; therefore, the present study investigated the effect of silencing survivin and XIAP on the biological activity of the gastric cancer HGC-27 cell line. It was demonstrated that the expression levels of survivin and XIAP were significantly increased in gastric cancer tissues, compared with the adjacent non-tumor tissues. Furthermore, it was observed that the expression levels of survivin and XIAP were similarly elevated in gastric cancer HGC-27 cells, compared with normal gastric epithelial GES-1cells. Furthermore, small interfering RNA-mediated surviving- or XIAP-knockdown, in addition to the dual knockdown of survivin and XIAP, inhibited the proliferation and promoted the apoptosis of HGC-27 cells. Simultaneous inhibition of XIAP and survivin expression was more effective, compared with inhibition of XIAP or survivin alone. These results indicated that the dual knockdown of survivin and XIAP may be an effective strategy for treating gastric cancer in the future.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The outbreaks of 2019 novel coronavirus disease (COVID-19) caused by SARS-CoV-2 infection have posed a severe threat to global public health. It is unclear how the human immune system responds to ...this infection. Here, we used metatranscriptomic sequencing to profile immune signatures in the bronchoalveolar lavage fluid of eight COVID-19 cases. The expression of proinflammatory genes, especially chemokines, was markedly elevated in COVID-19 cases compared to community-acquired pneumonia patients and healthy controls, suggesting that SARS-CoV-2 infection causes hypercytokinemia. Compared to SARS-CoV, which is thought to induce inadequate interferon (IFN) responses, SARS-CoV-2 robustly triggered expression of numerous IFN-stimulated genes (ISGs). These ISGs exhibit immunopathogenic potential, with overrepresentation of genes involved in inflammation. The transcriptome data was also used to estimate immune cell populations, revealing increases in activated dendritic cells and neutrophils. Collectively, these host responses to SARS-CoV-2 infection could further our understanding of disease pathogenesis and point toward antiviral strategies.
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•BALF cell transcriptome indicates robust innate immune responses in COVID-19 patients•COVID-19 patients exhibit chemokine-dominant hypercytokinemia•ISGs are highly expressed in COVID-19 patients and exhibit pathogenic potential
Zhou et al. use metatranscriptomic sequencing to profile immune signatures in the bronchoalveolar lavage fluid of COVID-19 patients. COVID-19 patients exhibit robust innate immune responses with notable hypercytokinemia and increased expression of IFN-stimulated genes. This analysis provides timely information for understanding SARS-CoV-2-host interactions and COVID-19 pathogenesis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP