A cryptic homotypic interaction motif of insect STING is required for its antiviral signaling.

Stimulator of interferon genes (STING) mediates innate immune response upon binding to cyclic GMP-AMP (cGAMP). It recruits tank-binding kinase 1 (TBK1) and transcription factor interferon regulatory factor 3 (IRF3) through its C-terminal tail and facilitates TBK1-dependent phosphorylation of IRF3 via forming STING polymers in mammalian cells. However, the mechanism behind STING-mediated activation of NF-κB transcription factor, Relish, in insect cells is unknown. Our study revealed that insect STING formed oligomers and the cryptic RIP homotypic interaction motif (cRHIM) was required for its oligomerization and its anti-viral functions. Cells expressing cRHIM-deficient mutants exhibited lower levels of anti-viral molecules, higher viral load after viral infection and weak activation of Relish. Moreover, we observed that under cGAMP stimulation, insect STING interacted with IMD, and deletion of the cRHIM motif on either protein prevented this interaction. Finally, we demonstrated that cGAMP enhanced the amyloid-like property of insect STING aggregates by ThT staining. In summary, our research showed that insect STING employed a homotypic motif to form intermolecular interactions that are essential for its antiviral signaling.

Parabacteroides distasonis-Derived Outer Membrane Vesicles Enhance Antitumor Immunity Against Colon Tumors by Modulating CXCL10 and CD8+ T Cells.

Purpose: Given the potent immunostimulatory effects of bacterial outer membrane vesicles (OMVs) and the significant anti-colon tumor properties of Parabacteroides distasonis (Pd), this study aimed to elucidate the role and potential mechanisms of Pd-derived OMVs (Pd-OMVs) against colon cancer. Methods: This study isolated and purified Pd-OMVs from Pd cultures and assessed their characteristics. The effects of Pd-OMVs on CT26 cell uptake, proliferation, and invasion were investigated in vitro. In vivo, a CT26 colon tumor model was used to investigate the anti-colon tumor effects and underlying mechanisms of Pd-OMVs. Finally, we evaluated the biosafety of Pd-OMVs. Results: Purified Pd-OMVs had a uniform cup-shaped structure with an average size of 165.5 nm and a zeta potential of approximately -9.56 mV, and their proteins were associated with pathways related to immunity and apoptosis. In vitro experiments demonstrated that CT26 cells internalized the Pd-OMVs, resulting in a significant decrease in their proliferation and invasion abilities. Further in vivo studies confirmed the accumulation of Pd-OMVs in tumor tissues, which significantly inhibited the growth of colon tumors. Mechanistically, Pd-OMVs increased the expression of CXCL10, promoting infiltration of CD8+ T cells into tumor tissues and expression of pro-inflammatory factors TNF-α, IL-1ß, and IL-6. Notably, Pd-OMVs demonstrated a high level of biosafety. Conclusion: This paper elucidates that Pd-OMVs can exert significant anti-colon tumor effects by upregulating the expression of the chemokine CXCL10, thereby increasing the infiltration of CD8+ T cells into tumors and enhancing antitumor immune responses. This suggests that Pd-OMVs may be developed as a novel nanoscale potent immunostimulant with great potential for application in tumor immunotherapy. As well as developed as a novel nano-delivery carrier for combination with other antitumor drugs.

The effectiveness and safety of thermal ablation for thyroid carcinoma lymph node metastasis are affected by the diameter of metastatic lymph nodes: A meta-analysis.

BACKGROUND: To explore the diameter of lymph nodes with metastatic thyroid carcinoma and the effectiveness and safety of thermal ablation. METHODS: Several databases were searched for literature on the treatment of thyroid carcinoma metastatic lymph nodes by thermal ablation. A subgroup analysis was performed according to the diameter of the metastatic lymph nodes. The measures included pooled estimates of mean volume reduction, pooled proportions of total disappearance and recurrence, and the pooled proportions of overall complications. RESULTS: There were 20 studies with 372 patients and 620 metastatic lymph nodes included. Based on the average maximum diameter of the metastatic lymph nodes, they were divided into three groups: A (≤ 10 mm), B (10 < diameter ≤ 20 mm), and C (> 20 mm). The study results indicated a significant decrease in the average volume only in groups A and B. The ratio of tumor disappearance showed that group A had the highest percentage, followed by group B and then group C. The recurrence rates were comparable between groups A and B, but slightly lower than in group C. Moreover, the overall complication rates for the three groups were ranked as follows: group A > group C > group B. CONCLUSION: Overall, thermal ablation is an effective and safe treatment for thyroid cancer metastatic lymph nodes with diameters of 10-20mm.

CT-based radiomics research for discriminating the risk stratification of pheochromocytoma using different machine learning models: a multi-center study.

OBJECTIVES: The purpose of this study was to explore and verify the value of various machine learning models in preoperative risk stratification of pheochromocytoma. METHODS: A total of 155 patients diagnosed with pheochromocytoma through surgical pathology were included in this research (training cohort: n = 105; test cohort: n = 50); the risk stratification scoring system classified a PASS score of < 4 as low risk and a PASS score of ≥ 4 as high risk. From CT images captured during the non-enhanced, arterial, and portal venous phase, radiomic features were extracted. After reducing dimensions and selecting features, Logistic Regression (LR), Extra Trees, and K-Nearest Neighbor (KNN) were utilized to construct the radiomics models. By adopting ROC curve analysis, the optimal radiomics model was selected. Univariate and multivariate logistic regression analyses of clinical radiological features were used to determine the variables and establish a clinical model. The integration of radiomics and clinical features resulted in the creation of a combined model. ROC curve analysis was used to evaluate the performance of the model, while decision curve analysis (DCA) was employed to assess its clinical value. RESULTS: 3591 radiomics features were extracted from the region of interest in unenhanced and dual-phase (arterial and portal venous phase) CT images. 13 radiomics features were deemed to be valuable. The LR model demonstrated the highest prediction efficiency and robustness among the tested radiomics models, with an AUC of 0.877 in the training cohort and 0.857 in the test cohort. Ultimately, the composite of clinical features was utilized to formulate the clinical model. The combined model demonstrated the best discriminative ability (AUC, training cohort: 0.887; test cohort: 0.874). The DCA of the combined model showed the best clinical efficacy. CONCLUSION: The combined model integrating radiomics and clinical features had an outstanding performance in differentiating the risk of pheochromocytoma and could offer a non-intrusive and effective approach for making clinical decisions.

Lactobacillus acidophilus and its metabolite ursodeoxycholic acid ameliorate ulcerative colitis by promoting Treg differentiation and inhibiting M1 macrophage polarization.

Lactobacillus acidophilus (LA) is a common clinical probiotic that improves ulcerative colitis (UC) by restoring intestinal immune balance. However, the interaction of LA with the gut microbiota and its metabolites in the treatment of UC remains unknown. Therefore, this study seeks to elucidate whether the gut microbiota and its metabolites act as pivotal effectors in LA's therapeutic mechanisms and how precisely they modulate intestinal immunity. In this study, we verified that LA can obviously ameliorate the disease severity, and regulate intestinal immune disorders in UC mice. Subsequently, antibiotic (ABX)-mediated depletion of the gut microflora demonstrated that the therapeutic efficiency of LA was closely associated with gut microbiota. In addition, the results of metabolomics revealed that ursodeoxycholic acid (UDCA), a metabolite of intestinal flora, may be a potential effector molecule mediating therapeutic effects of LA. Indeed, we found that UDCA can improve the macro pathological characteristics of UC mice, and through a comprehensive set of in vivo and in vitro experiments, we discovered that UDCA exerts dual effects on immune regulation. Firstly, it promotes the differentiation of Treg cells, resulting in increased secretion of anti-inflammatory cytokines. Secondly, UDCA inhibits the polarization of M1 macrophages, effectively reducing the secretion of pro-inflammatory cytokines. Moreover, we found that UDCA regulation of immune response is directly related to the RapGap/PI3K-AKT/NF-κB signaling pathway. In conclusion, LA and its metabolite, UDCA, may treat UC by activating the RapGap/PI3K-AKT/NF-κB signaling pathway and modulating Treg cells and M1 macrophages. All in all, our findings highlight the potential of microbial metabolites in enhancing probiotic for UC treatment.

16S rRNA and Metagenomics Combined with UPLC-Q/TOF-MS Metabolomics Analysis Reveals the Potential Mechanism of Radix Astragali Against Hyperuricemia in Mice.

Purpose: This study aimed to investigate the underlying treatment mechanism of Radix Astragali (RA) in hyperuricemia from the perspective of microbiota and metabolomics. Methods: We used potassium oxyazinate (PO) to induce hyperuricemia mice, and we determined serum alanine aminotransferase/aspartate aminotransferase (ALT/AST), xanthine oxidase (XOD), creatinine (CRE), uric acid (UA), blood urea nitrogen (BUN) levels, liver XOD levels and assessed the kidney tissue histopathology. The therapeutic mechanism of RA in hyperuricemic mice was studied by 16S rRNA, metagenomic sequencing and metabolomics. Results: Our research showed that RA has therapeutic effect in hyperuricemia mice, such as slow the weight loss, repair kidney damage, and downregulate serum UA, XOD, CRE, ALT/AST, BUN, and liver XOD levels. RA restored the disturbance structure of the microbiota in hyperuricemia mice by increasing the relative abundances of beneficial bacteria (Lactobacillaceae and Lactobacillus murine) but decreasing the relative abundances of pathogenic bacteria (Prevotellaceae, Rikenellaceae and Bacteroidaceae). Meanwhile, we found that RA directly regulated the metabolic pathway (such as linoleic acid metabolism and glycerophospholipid metabolism) and indirectly regulated bile acid metabolism by mediating microbiota to ameliorate metabolic disorders. Subsequently, there was a robust correlation between specific microbiota, metabolites and the disease index. Conclusion: The ability of RA to protect mice against hyperuricemia is strongly linked to the microbiome-metabolite axis, which would provide evidence for RA as a medicine to prevent or treat hyperuricemia.

PIN2/3/4 auxin carriers mediate root growth inhibition under conditions of boron deprivation in Arabidopsis.

The mechanistic basis by which boron (B) deprivation inhibits root growth via the mediation of root apical auxin transport and distribution remains elusive. This study showed that B deprivation repressed root growth of wild-type Arabidopsis seedlings, which was related to higher auxin accumulation (observed with DII-VENUS and DR5-GFP lines) in B-deprived roots. Boron deprivation elevated the auxin content in the root apex, coinciding with upregulation of the expression levels of auxin biosynthesis-related genes (TAA1, YUC3, YUC9, and NIT1) in shoots, but not in root apices. Phenotyping experiments using auxin transport-related mutants revealed that the PIN2/3/4 carriers are involved in root growth inhibition caused by B deprivation. B deprivation not only upregulated the transcriptional levels of PIN2/3/4, but also restrained the endocytosis of PIN2/3/4 carriers (observed with PIN-Dendra2 lines), resulting in elevated protein levels of PIN2/3/4 in the plasma membrane. Overall, these results suggest that B deprivation not only enhances auxin biosynthesis in shoots by elevating the expression levels of auxin biosynthesis-related genes but also promotes the polar auxin transport from shoots to roots by upregulating the gene expression levels of PIN2/3/4, as well as restraining the endocytosis of PIN2/3/4 carriers, ultimately resulting in auxin accumulation in root apices and root growth inhibition.

Pogostemon cablin (Blanco) Benth granule revealed a positive effect on improving intestinal barrier function and fecal microbiota in mice with irinotecan-induced intestinal mucositis.

Pogostemon cablin (Blanco) Benth (PCB), a medicinal and edible homologous Chinese herb, has a protective effect on the structure and function of intestine. In this study, we aimed to investigate the effect of PCB granule (PCBG) on the improvement of irinotecan-induced intestinal mucositis and the regulation of intestinal microorganisms in mice. Our results demonstrated that PCBG supplementation significantly improved diarrhea symptoms caused by irinotecan, as evidenced by inhibiting weight loss, reversing intestinal atrophy, protecting against splenomegaly and balancing oxidative stress. Furthermore, compared with the model group, PCBG restored the intestinal morphology and improved intestinal barrier dysfunction by promoting the expression of tight junction proteins and mucin. Moreover, high-throughput sequencing analysis revealed that PCBG improved the flora disorder caused by irinotecan and regulated microbial community structure, such as decreasing the relative abundance of Bacteroides as well as increasing the relative abundance of Lactobacillus. Meanwhile, the disordered microbial functions in intestinal mucositis mice were recovered more closely to the controls by PCBG. Finally, we found that a robust correlation between the specific microbiota and intestinal mucositis-related index. In summary, these findings revealed the beneficial effects of PCBG on the intestinal barrier and gut microbiota of irinotecan-induced intestinal mucositis, which may be one of the potential strategies to reduce the clinical side effects of irinotecan.

Kidney tea ameliorates hyperuricemia in mice via altering gut microbiota and restoring metabolic profile.

Clerodendranthus spicatus (Thunb.) C. Y. Wu, also known as kidney tea (KT), has been widely employed in kidney protection in Chinese Medicine. It has been reported that KT can lower uric acid (UA) and mitigate gout, while the mechanism remains to be elucidated. Given the close relationship between hyperuricemia (HUA), intestinal flora and host metabolism, this study aimed to explore the mechanism by which KT lowers UA from the perspective of the fecal microbiome and metabolome. Initially, mice were intraperitoneally injected with potassium oxonate to induce the HUA model. The results showed that KT markedly reduced the serum level of UA and impaired renal damage in HUA mice. Subsequently, the result of 16S rRNA gene sequencing analysis indicated that KT administration appeared a significant improvement in the structure of the intestinal flora, especially increased the abundances of Roseburia and Enterorhabdus, while decreased the abundances of Ileibacterium and UBA1819. Moreover, the levels of differential metabolites (including twenty-five in feces and eight in serum) identified by untargeted metabolomics returned to normal after KT intervention. Taken together, the mechanism of KT in alleviating HUA is related to the regulation of the intestinal flora and the remodeling of metabolic disorders, which will lay a theoretical foundation for KT as a UA-lowering drug.

Boron supply restores aluminum-blocked auxin transport by the modulation of PIN2 trafficking in the root apical transition zone.

The supply of boron (B) alleviates the toxic effects of aluminum (Al) on root growth; however, the mechanistic basis of this process remains elusive. This study filled this knowledge gap, demonstrating that boron modifies auxin distribution and transport in Al-exposed Arabidopsis roots. In B-deprived roots, treatment with Al induced an increase in auxin content in the root apical meristem zone (MZ) and transition zone (TZ), whereas in the elongation zone (EZ) the auxin content was decreased beyond the level required for adequate growth. These distribution patterns are explained by the fact that basipetal auxin transport from the TZ to the EZ was disrupted by Al-inhibited PIN-FORMED 2 (PIN2) endocytosis. Experiments involving the modulation of protein biosynthesis by cycloheximide (CHX) and transcriptional regulation by cordycepin (COR) demonstrated that the Al-induced increase of PIN2 membrane proteins was dependent upon the inhibition of PIN2 endocytosis, rather than on the transcriptional regulation of the PIN2 gene. Experiments reporting on the profiling of Al3+ and PIN2 proteins revealed that the inhibition of endocytosis of PIN2 proteins was the result of Al-induced limitation of the fluidity of the plasma membrane. The supply of B mediated the turnover of PIN2 endosomes conjugated with indole-3-acetic acid (IAA), and thus restored the Al-induced inhibition of IAA transport through the TZ to the EZ. Overall, the reported results demonstrate that boron supply mediates PIN2 endosome-based auxin transport to alleviate Al toxicity in plant roots.

BmCaspase-8-like regulates autophagy by suppressing BmDREDD-mediated cleavage of BmATG6.

Autophagy plays an important role in tissue remodeling during insect development. The interplay between autophagy-related (ATG) proteins and caspases regulates the autophagic activity of ATGs, thereby modulating the process of autophagy. Our previous study characterized BmCaspase-8-like (BmCasp8L) as a caspase suppressor that inhibits apoptosis and immune signaling by suppressing the activation of death-related ced-3/Nedd2-like caspase (DREDD), a caspase-8 homolog in silkworm. In this study, we explored the regulatory role of BmCasp8L in autophagy. We found that the expression of Bmcasp8l increased from the late spinning stage to the pupa stage in the posterior silk gland (PSG), correlating with the expression patterns of Bmatg8 and Bmatg6. RNA interference-mediated downregulation of BmCasp8L expression significantly decreased starvation-induced autophagic influx as determined by the levels of BmATG8-phosphatidylethanolamine and the percentage of cells displaying punctate enhanced green fluorescent protein-BmATG8. Conversely, the overexpression of BmCasp8L significantly increased autophagic influx. We also found that BmCasp8L underwent autophagic degradation induced by starvation and that it was colocalized with BmATG8. Lastly, we demonstrated that BmDREDD attenuated autophagy and BmCasp8L suppressed BmDREDD-mediated cleavage of BmATG6. Taken together, our results demonstrated that BmCasp8L is a novel proautophagic molecule which suppresses BmDREDD-mediated cleavage of BmATG6 and is a target for autophagy.

PDGF-AA activates AKT and ERK signaling for testicular interstitial Leydig cell growth via primary cilia.

Testes control the development of male reproductive system. The testicular interstitial Leydig cells (Leydig cells) synthesize testosterone for promoting spermatogenesis and secondary sexual characteristics. Type A platelet-derived growth factor (PDGF-AA) is one of the most important growth factors in regulating Leydig cell growth and function. Knockout of PDGF-AA or its congenital receptor PDGFR-α leads to poor testicular development caused by reducing Leydig cell numbers, supporting PDGF-AA/PDGFR-α signaling regulates Leydig cell development. Primary cilium is a cellular antenna that functions as an integrative platform to transduce extracellular signaling for proper development and differentiation. Several receptors including PDGFR-α are observed on primary cilia for initiating signaling cascades in distinct cell types. Here we showed that PDGF-AA/PDGFR-α signaling promoted Leydig cells growth, migration, and invasion via primary cilia. Upon PDGF-AA treatment, AKT and ERK signaling were activated to regulate these cellular events. Interestingly, active AKT and ERK were detected around the base of primary cilia. Depletion of ciliary genes (IFT88 and CEP164) alleviated PDGF-AA-activated AKT and ERK, thus reducing Leydig cell growth, migration, and invasion. Thus, our study not only reveals the function of PDGF-AA/PDGFR-α signaling in maintaining testicular physiology but also uncovers the role of primary cilium and downstream signaling in regulating Leydig cell development.

[Comparison of Bacterial Community Structure in Soil Aggregates Between Natural Karst Wetland and Paddy Field].

Studying the impact of land-use changes in wetland systems on the community structure of bacteria in soil aggregates can provide a theoretical basis for elucidating the impact mechanisms of the stability of wetland soil aggregates. The soil samples (0-20 cm) were collected from a natural wetland and paddy field in the Huixian karst wetland. The bacterial community structure in soil aggregates (macroaggregates 0.25-2 mm, microaggregates 0.053-0.25 mm, and silt-clay<0.053 mm) were analyzed using high-throughput sequencing and ecological network analysis. The results showed that ① the proportion of microaggregates in the paddy field was 29.64%, which was significantly higher than that in the natural wetland (22.20%), and ② there were differences in the relative abundance of bacteria between the natural wetland and paddy field. The relative abundance of Chloroflexi in macroaggregates, microaggregates, and silt-clay in the paddy field were 7.97%, 8.56%, and 7.40%, respectively, which were significantly higher than those in the natural wetland (4.93%, 4.81%, and 3.76%). The relative abundance of Anaerolineales in macroaggregates, microaggregates, and silt-clay in the paddy field were 2.35%, 3.03%, and 2.65%, respectively, which were significantly higher than those in the natural wetland (0.92%, 0.91%, and 0.43%).③ Ecological network analysis showed that the number of nodes, edges, and the average numbers of neighbors in microaggregates and the silt-clay network in the paddy field were higher than those in the natural wetland, the average connectivity of the network was greater in the two components, and the characteristic path length was shorter. There was a longer characteristic path length, higher modularity, and lower average connectivity in the macroaggregate network of the paddy field. The above results indicated that the bacterial community structure in soil aggregates was altered after a natural wetland was used as a paddy field. The material circulation and information transmission efficiency of bacterial communities was higher in both microaggregates and silt-clay of the paddy field, whereas the bacterial community structure with low network tightness and high modularity in macroaggregates was more stable.

[Comparison of Bacterial Community Structure and Functional Groups of Paddy Soil Aggregates Between Karst and Non-karst Areas].

Studying the similarities and differences in microbial community structure and functional groups in soil aggregates between karst areas (KA) and non-karst areas (NKA) can provide a theoretical basis for revealing the interaction mechanism between soil organic microorganisms and soil aggregate structure stability in KA. The surface soils (0-20 mm) were collected from paddy fields both in KA and NKA. The aggregates were divided into macro-aggregates (Mac, 0.25-2 mm), micro-aggregates (Mic, 0.053-0.25 mm), and silt-clay fractions (SC,<0.053 mm) using the wet sieving method. The microbial community structure of soil aggregates was analyzed using high-throughput sequencing. The keystone taxa were analyzed by the co-occurrence network, and their functions were predicted by FAPROTAX. The results showed that:① the proportion of Mac, mean weight diameter, and geometric mean diameter of aggregates in KA were 30.94%, 0.41 mm, and 0.15 mm, respectively. These three factors in KA were significantly higher than those in NKA, indicating that the environment in the KA was conducive to the formation of aggregates. ② The relative abundances of Acidobacteria, Proteobacteria, Acidobacteria(Gp3, Gp4, and Gp6), and Sphingomonas in three particle size aggregates in KA were higher than those in NKA. The relative abundance of Chloroflexi (6.13%) in Mic in KA was significantly higher than that in SC (2.79%). ③ Co-occurrence network analysis showed that Proteobacteria and Acidobacteria were keystone taxa in three particle size aggregates. The positive correlation edge (65.5%) of bacteria in KA was the highest, and most of the correlation was synergistic. ④ Chemoheterotrophy (15.52%, 15.30%, and 16.89%) and aerobic chemoheterotrophy (14.62%, 14.38%, and 15.97%) were the most dominant functional groups in the three particle size aggregates in KA, and their relative abundance was significantly higher than those in NKA. The relative abundance of chitinolysis in Mac in KA (0.46%) was significantly higher than that in SC (0.39%). The results showed that the soil environment in KA can improve the stability of the aggregates, and the bacterial community structure, key groups, and functional groups in the three particle size aggregates in KA were significantly different from those in NKA.

Thermal ablation for cervical lymph node metastasis from papillary thyroid carcinoma: A meta-analysis.

BACKGROUND: Traditionally, surgery has been the standard treatment for cervical lymph node metastasis in patients with papillary thyroid carcinoma (PTC). However, thermal ablation is currently recommended by several guidelines. This study aimed to evaluate the efficacy and safety of thermal ablation for lymph node metastasis in patients with PTC. METHODS: We searched PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases until March 2022 to collect studies on thermal ablation (including radiofrequency, microwave, and laser ablations) for cervical lymph node metastasis from PTC. RESULTS: A total of 190 patients were included, ranging from 5 to 39 in each study, with a sex ratio (male/female) ranging from 1/4 to 17/20, an average age ranging from 15.6 ±â€…3.0 to 62.3 ±â€…13.2 (yr), and a total of 270 cervical lymph nodes, ranging from 8 to 98. The follow-up results showed that thermal ablation significantly reduced the maximum diameter and volume of metastatic lymph nodes in PTC (P < .01). The pooled complete disappearance rate was 86% (95% confidence interval 79% to 93%). Thyroglobulin levels were significantly lower after surgery (P < .01). No major complications occurred, and the combined voice change rate was as low as 1% [CI 0% to 3%]. CONCLUSION: Our meta-analysis showed that thermal ablation is an effective and safe method for the treatment of cervical lymph node metastases from PTC. Considering the limitations of this study, more prospective, multicenter, large-sample studies are needed in the future.

[Investigation of Soil Fungal Communities and Functionalities within Karst Paddy Fields].

Fungi are important drivers of soil biogeochemical cycles. However, the characteristics of fungal community structures and functional groups within karst area (KA) soils remain understudied. Top soil samples were collected from paddy fields within a KA and non-karst area (NKA) containing red soil, in the Maocun karst experimental site of Guilin. The fungal community structure was analyzed via high-throughput sequencing, and FUNGuild was used to predict the function of fungi. The average relative abundance of Mucormycota in KA was 4.87%, which was significantly lower than that in NKA (29.92%); The average relative abundance of Mortierellomycetes in KA was 3.36%, which was significantly lower than that in NKA (29.15%). However, in KA, the average relative abundances of Glomeromycetes, Chytridiomycetes, and Exobasidiomycetes were 0.91%, 0.98%, and 0.23%, respectively, significantly higher than those in NKA (0.47%, 0.28%, and 0.04%). In KA, the average relative abundances of Ramophialophora and Emericellopsis were 2.39% and 1.25%, respectively, significantly higher than those in NKA (0.05% and 0.09%). However, the average relative abundance of Mortierella was 3.04% in KA, which was lower than that in NKA (28.34%). KA contained 32 dominant OTUs, including OTU141, 99, and 192. There was more connectivity between OTU69 (Emericellopsis terricola) and OTU138 (Westerdykella globosa) with the cation exchange capacity (CEC), exchangeable Ca2+, and total phosphorus (TP) in the correlation network. In KA, the average abundances of symbiotroph and pathotroph-saprotroph fungi were 1.29% and 1.50%, respectively, significantly higher than those in NKA (0.08% and 0.09%). The average abundance of the saprotroph-symbiotroph fungi in KA was 10.81%, which was significantly lower than that in NKA (63.69%). In KA, dung saprotroph-wood saprotroph fungi were dominant, with an abundance of 9.73%, whereas in NKA, endophyte-litter saprotroph-soil saprotroph-undefined saprotroph fungi were dominant, with an abundance of 45.93%. The above results suggest that the soil factors of KA, such as CEC, exchangeable Ca2+, and TP, alter the structures and functions of fungi.

Longitudinal Chest CT Features in Severe/Critical COVID-19 Cases and the Predictive Value of the Initial CT for Mortality.

PURPOSE: To evaluate longitudinal computed tomography (CT) features and the predictive value of the initial CT and clinical characteristics for mortality in patients with severe/critical coronavirus disease 2019 (COVID-19) pneumonia. METHODS: A retrospective analysis was performed on patients with COVID-19 pneumonia confirmed by laboratory. By excluding mild and common patients, 155 severe/critical patients with definite outcome were finally enrolled. A total of 516 CTs of 147 patients were divided into four stages according to the time after onset (stage 1, 1-7 days; stage 2, 8-14 days; stage 3, 15-21 days, and stage 4, >21 days). The evolving imaging features between the survival and non-survival groups were compared by using Chi-square, Fisher's exact test, student's t-test or Mann-Whitney U-test, as appropriate. The predictive value of clinical and CT features at admission for mortality was analysed through logistic regression analysis. To avoid overfitting caused by CT scores, CT scores were divided into two parts, which were combined with clinical variables, respectively, to construct the models. RESULTS: Ground-glass opacities (GGO) patterns were predominant for stages 1 and 2 for both groups (both P>0.05). The numbers of consolidation lesions increased in stage 3 in both groups (P=0.857), whereas the linear opacity increased in the survival group but decreased in the non-survival group (P=0.0049). In stage 4, the survival group predominantly presented linear opacity patterns, whereas the non-survival group mainly showed consolidation patterns (P=0.007). Clinical and imaging characteristics correlated with mortality; multivariate analyses revealed age >71 years, neutrophil count >6.38 × 109/L, aspartate aminotransferase (AST) >58 IU/L, and CT score (total lesions score >17 in model 1, GGO score >14 and consolidation score >2 in model 2) as independent risk factors (all P<0.05). The areas under the curve of the six independent risk factors alone ranged from 0.65 to 0.75 and were 0.87 for model 2, 0.89 for model 1, and 0.92 for the six variables combined. Statistical differences were observed between Kaplan Meier curves of groups separated by cut-off values of these six variables (all P<0.01). CONCLUSION: Longitudinal imaging features demonstrated differences between the two groups, which may help determine the patient's prognosis. The initial CT score combined with age, AST, and neutrophil count is an excellent predictor for mortality in COVID-19 patients.

Genotoxic stress-activated DNA-PK-p53 cascade and autophagy cooperatively induce ciliogenesis to maintain the DNA damage response.

The DNA-PK maintains cell survival when DNA damage occurs. In addition, aberrant activation of the DNA-PK induces centrosome amplification, suggesting additional roles for this kinase. Here, we showed that the DNA-PK-p53 cascade induced primary cilia formation (ciliogenesis), thus maintaining the DNA damage response under genotoxic stress. Treatment with genotoxic drugs (etoposide, neocarzinostatin, hydroxyurea, or cisplatin) led to ciliogenesis in human retina (RPE1), trophoblast (HTR8), lung (A459), and mouse Leydig progenitor (TM3) cell lines. Upon genotoxic stress, several DNA damage signaling were activated, but only the DNA-PK-p53 cascade contributed to ciliogenesis, as pharmacological inhibition or genetic depletion of this pathway decreased genotoxic stress-induced ciliogenesis. Interestingly, in addition to localizing to the nucleus, activated DNA-PK localized to the base of the primary cilium (mother centriole) and daughter centriole. Genotoxic stress also induced autophagy. Inhibition of autophagy initiation or lysosomal degradation or depletion of ATG7 decreased genotoxic stress-induced ciliogenesis. Besides, inhibition of ciliogenesis by depletion of IFT88 or CEP164 attenuated the genotoxic stress-induced DNA damage response. Thus, our study uncovered the interplay among genotoxic stress, the primary cilium, and the DNA damage response.

Diagnostic performance of magnetic resonance imaging and ultrasonography on the detection of cesarean scar pregnancy: A meta-analysis.

BACKGROUND: : There is still a debate on which imaging method is the best to diagnose cesarean scar pregnancy (CSP). Accordingly, this study aimed to analyze the diagnostic performance of magnetic resonance imaging (MRI) and ultrasonography (US) on the detection of CSP based on current evidence in the literature. METHODS: PubMed, Embase, Cochrane, Chinese Biomedical Documentation Service System, WanFang, and China National Knowledge Infrastructure databases were searched up to June 2020. The included studies were all comparisons of MRI and US in the diagnosis of CSP that adopted postoperative histological examination as the reference standard. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and area under the summary receiver operating characteristic curve (AUC) were calculated for MRI and US. RESULTS: Thirteen studies were included, with a total sample size of 948 patients. The pooled sensitivity, specificity, PLR, NLR, and AUC of MRI in diagnosing CSP were 0.93 (95% CI, 0.91-0.95), 0.83 (95% CI, 0.75-0.89), 5.46 (95% CI, 3.70-8.05), 0.08 (95% CI, 0.06-0.11), and 0.96 (95% CI, 0.93-0.97), respectively; for US they were 0.84 (95% CI, 0.79-0.88), 0.73 (95% CI, 0.62-0.81), 3.06 (95% CI, 2.22-4.21), 0.23 (95% CI, 0.18-0.28), and 0.86 (95% CI, 0.83-0.89), respectively. CONCLUSION: We found that both MRI and US effectively diagnosed CSP; however, MRI had a higher diagnostic performance in detecting CSP than US.

[Formation of FADD amyloid fiber and its role in immune signaling in Drosophila melanogaster].

In this research, we studied the formation of Drosophila melanogaster FADD (Fas-associated death domain-containing protein) amyloid fiber and its influence on signal transduction in IMD (Immune deficiency) signaling pathway to better understand the regulation mechanism of Drosophila innate immune signaling pathway, which will provide reference for the immune regulation in other species. First, we purified dFADD protein expressed in Escherichia coli and performed Sulfur flavin T binding and transmission electron microscopy to identify the dFADD amyloid fibers formed in vitro. Then we investigated the formation of dFADD polymers in S2 cells using SDD-AGE and confocal microscope. We also constructed dFADD mutants to find out which domain is essential to fiber formation and its effect on IMD signal transduction. Our results revealed that dFADD could be polymerized to form amyloid fiber polymers in vitro and inside the cells. Formation of fibers relies on DED (Death-effector domain) domain of dFADD, since DED domain-deleted mutant existed as a monomer. Dual luciferase reporter assay showed that intact DED domain was required for the induction of downstream antimicrobial peptides, indicating that fiber formation was the key to IMD signal transduction. Our study revealed the role of dFADD in mediating the cascade between IMD and Dredd in the IMD signaling pathway by forming amyloid fibers, suggesting an evolutionarily conserved regulatory mechanism of innate immune signaling pathway.