Molecular Mimicry of Transposable Elements in Plants.

Transposable elements (TEs) are mobile DNA elements that are particularly abundant in the plant genomes. They have long been considered as junk DNA; however, a growing body of evidence suggests that TE insertions promote genetic diversity that is essential for the adaptive evolution of a species. Thus far, studies have mainly investigated the cis-acting regulatory roles of TEs generated by their insertions nearby or within the host genes. However, the trans-acting effects of TE-derived RNA and DNA remained obscure to date. TEs contain various regulatory elements within their sequences that can accommodate the binding of specific RNAs and proteins. Recently, it was suggested that some of these cellular regulators are shared between TEs and the host genes, and the competition for the common host factors underlies the fine-tuned developmental reprogramming. In this review, we will highlight and discuss the latest discoveries on the biological functions of plant TEs, with a particular focus on their competitive binding with specific developmental regulators.

Multitask deep learning for prediction of microvascular invasion and recurrence-free survival in hepatocellular carcinoma based on MRI images.

BACKGROUND AND AIMS: Accurate preoperative prediction of microvascular invasion (MVI) and recurrence-free survival (RFS) is vital for personalised hepatocellular carcinoma (HCC) management. We developed a multitask deep learning model to predict MVI and RFS using preoperative MRI scans. METHODS: Utilising a retrospective dataset of 725 HCC patients from seven institutions, we developed and validated a multitask deep learning model focused on predicting MVI and RFS. The model employs a transformer architecture to extract critical features from preoperative MRI scans. It was trained on a set of 234 patients and internally validated on a set of 58 patients. External validation was performed using three independent sets (n = 212, 111, 110). RESULTS: The multitask deep learning model yielded high MVI prediction accuracy, with AUC values of 0.918 for the training set and 0.800 for the internal test set. In external test sets, AUC values were 0.837, 0.815 and 0.800. Radiologists' sensitivity and inter-rater agreement for MVI prediction improved significantly when integrated with the model. For RFS, the model achieved C-index values of 0.763 in the training set and ranged between 0.628 and 0.728 in external test sets. Notably, PA-TACE improved RFS only in patients predicted to have high MVI risk and low survival scores (p < .001). CONCLUSIONS: Our deep learning model allows accurate MVI and survival prediction in HCC patients. Prospective studies are warranted to assess the clinical utility of this model in guiding personalised treatment in conjunction with clinical criteria.

Application of contrast-enhanced ultrasound in the diagnosis of tuberous vas deferens tuberculosis.

BACKGROUND: To assess the value of contrast-enhanced ultrasound (CEUS) in the diagnosis of tuberous vas deferens tuberculosis (VD TB) and improve the positive diagnostic rate of VD TB. METHODS: CEUS and routine ultrasound (US) images of 17 patients with tuberous VD TB confirmed by surgery, pathology, or laboratory semen examination were retrospectively analyzed and summarized, and the positive rates of both imaging techniques were compared. RESULTS: The 19 VD lesions of the 17 patients were divided into two types according to the CEUS findings: Type I and Type II, and type II was divided into Types IIa, IIb, and IIc. Of the nodules with transverse diameters > 1 cm, 100% presented as type II. Of the nodules with transverse diameters < 1 cm, 37.5% (3/8) presented as type I and 62.5% (5/8) presented as type II. The sonographic manifestations of tuberous VD TB were hypoechoic and mixed echoic. The positive diagnostic rate was 89.5% for CEUS and 68.4% for US, but the difference was not significant (χ2 = 2.533; P = 0.111). CONCLUSIONS: CEUS was able to show the blood supply characteristics of tuberous VD TB, the internal necrosis of nodules was more easily observed by CEUS than by routine US, which is helpful for the diagnosis of tuberous VD TB.

Application of ultrasound multimodal imaging in the prediction of cervical tuberculous lymphadenitis rupture.

Lymph node tuberculosis is particularly common in regions with a high tuberculosis burden, and it has a great risk of rupture. This study aims to investigate the utility of ultrasound multimodal imaging in predicting the rupture of cervical tuberculous lymphadenitis (CTL). 128 patients with unruptured CTL confirmed by pathology or laboratory tests were included. Various ultrasonic image features, including long-to-short-axis ratio (L/S), margin, internal echotexture, coarse calcification, Color Doppler Flow Imaging (CDFI), perinodal echogenicity, elastography score, and non-enhanced area proportion in contrast-enhanced ultrasound (CEUS), were analyzed to determine their predictive value for CTL rupture within a one-year follow-up period. As a result, L/S (P < 0.001), margin (P < 0.001), internal echotexture (P < 0.001), coarse calcification (P < 0.001), perinodal echogenicity (P < 0.001), and the area of non-enhancement in CEUS (P < 0.001) were identified as significant imaging features for predicting CTL rupture. The prognostic prediction showed a sensitivity of 89.29%, specificity of 100%, accuracy of 95.31%, respectively. Imaging findings such as L/S < 2, unclear margin, heterogeneous internal echotexture, perinodal echogenicity changed, and non-enhancement area in CEUS > 1/2, are indicative of CTL rupture, while coarse calcification in the lymph nodes is associated with a favorable prognosis.

Anti-EGFR ScFv functionalized exosomes delivering LPCAT1 specific siRNAs for inhibition of lung cancer brain metastases.

Brain metastasis (BM) is one of the leading causes of cancer-related deaths in patients with advanced non-small cell lung cancer (NSCLC). However, limited treatments are available due to the presence of the blood-brain barrier (BBB). Upregulation of lysophosphatidylcholine acyltransferase 1 (LPCAT1) in NSCLC has been found to promote BM. Conversely, downregulating LPCAT1 significantly suppresses the proliferation and metastasis of lung cancer cells. In this study, we firstly confirmed significant upregulation of LPCAT1 in BM sites compared to primary lung cancer by analyzing scRNA dataset. We then designed a delivery system based on a single-chain variable fragment (scFv) targeting the epidermal growth factor receptor (EGFR) and exosomes derived from HEK293T cells to enhance cell-targeting capabilities and increase permeability. Next, we loaded LPCAT1 siRNA (siLPCAT1) into these engineered exosomes (exoscFv). This novel scFv-mounted exosome successfully crossed the BBB in an animal model and delivered siLPCAT1 to the BM site. Silencing LPCAT1 efficiently arrested tumor growth and inhibited malignant progression of BM in vivo without detectable toxicity. Overall, we provided a potential platform based on exosomes for RNA interference (RNAi) therapy in lung cancer BM.

The combined effect of air pollution and non-optimal temperature on mortality in Shandong Province, China: establishment of air health index.

PURPOSE: The air health index (AHI) captures the combined effects of air pollution and non-optimal temperatures and helps assess the atmospheric environment's overall health risk. Shandong Province is a crucial industrial base in China, and the health effects of air pollution and non-optimal temperature cannot be ignored. To construct an AHI for Shandong Province and assess the district-level mortality burden due to AHI in the study area. METHODS: Daily district-specific mortality, meteorological, and air pollution data over 2013-2018 were collected in Shandong Province, China. The AHI construction eventually incorporated PM2.5 and NO2, O3, and non-optimal temperatures. Attributable fraction (AF) and attributable number (AN) were used to estimate the district-specific mortality burden attributable to AHI. RESULTS: The average AHI value observed in Shandong Province was 6. Our research revealed a positive association between the total AHI and total mortality, with an overall trend of a slow increase followed by a rapid increase. The exposure-response curves, when stratified by gender, age, and cause of death, were approximately consistent with the overall trend. The provincial attributable fraction (AF) was 5.31% (95% CI 4.58%, 5.91%), and the attributable number (AN) was 188,246 (95% CI 162,396, 209,533). Overall, higher ANs mainly appeared in the southwestern area, while higher values of AF were observed in the central-eastern and central-northern areas. CONCLUSIONS: The air health index performs well in predicting death burden and can convey health risks related to exposure to the ambient environment to the public.

Impacts of heatwaves on type 2 diabetes mortality in China: a comparative analysis between coastal and inland cities.

The impacts of extreme temperatures on diabetes have been explored in previous studies. However, it is unknown whether the impacts of heatwaves appear variations between inland and coastal regions. This study aims to quantify the associations between heat exposure and type 2 diabetes mellitus (T2DM) deaths in two cities with different climate features in Shandong Province, China. We used a case-crossover design by quasi-Poisson generalized additive regression with a distributed lag model with lag 2 weeks, controlling for relative humidity, the concentration of air pollution particles with a diameter of 2.5 µm or less (PM2.5), and seasonality. The wet- bulb temperature (Tw) was used to measure the heat stress of the heatwaves. A significant association between heatwaves and T2DM deaths was only found in the coastal city (Qingdao) at the lag of 2 weeks at the lowest Tw = 14℃ (relative risk (RR) = 1.49, 95% confidence interval (CI): 1.11-2.02; women: RR = 1.51, 95% CI: 1.02-2.24; elderly: RR = 1.50, 95% CI: 1.08-2.09). The lag-specific effects were significant associated with Tw at lag of 1 week at the lowest Tw = 14℃ (RR = 1.14, 95% CI: 1.03-1.26; women: RR = 1.15, 95% CI: 1.01-1.31; elderly: RR = 1.15, 95% CI: 1.03-1.28). However, no significant association was found in Jian city. The research suggested that Tw was significantly associated with T2DM mortality in the coastal city during heatwaves on T2DM mortality. Future strategies should be implemented with considering socio-environmental contexts in regions.

Long non-coding RNA BBOX1-AS1 exacerbates esophageal squamous cell carcinoma development by regulating HOXB7/ß-catenin axis.

Mounting evidence suggests that long non-coding RNAs play a critical role in the occurrence and development of human malignancies. Nonetheless, it remains unknown whether Gamma-Butyrobetaine Hydroxylase 1-Antisense RNA 1 (BBOX1-AS1) participates in the regulation of esophageal squamous cell carcinoma (ESCC) carcinogenesis. Herein, we validated that BBOX1-AS1 was notably overexpressed in ESCC tissues compared to the adjacent non-tumor tissues and significantly correlated with tumor sizes. BBOX1-AS1 enhanced the malignant behavior of ESCC cells in vitro, such as cell proliferation, migration, and invasion. In addition, knockdown of BBOX1-AS1 augmented the proportion of apoptotic cells in ESCC cells. Mechanistically, BBOX1-AS1 regulated HOXB7 expression, and rescue experiments indicated that silencing of HOXB7 could abolish the malignant phenotypes mediated by BBOX1-AS1 to a certain extent. Moreover, HOXB7 participated in the activation of the Wnt/ß-catenin signaling pathway. In summary, our findings substantiated that BBOX1-AS1 could activate the Wnt/ß-catenin pathway by upregulating HOXB7 expression to promote ESCC progression, providing a rationale to develop novel therapeutic approaches.

The Role of Cellular Defense Systems of Ferroptosis in Parkinson's Disease and Alzheimer's Disease.

Parkinson's disease (PD) and Alzheimer's disease (AD) are the most common rapidly developing neurodegenerative diseases that lead to serious health and socio-economic consequences. Ferroptosis is a non-apoptotic form of cell death; there is growing evidence to support the notion that ferroptosis is involved in a variety of pathophysiological contexts, and there is increasing interest in the role of ferroptosis in PD and AD. Simultaneously, cells may have evolved four defense systems to counteract the toxic effects of ferroptosis occasioned by lipid peroxidation. This review, which focuses on the analysis of ferroptosis in the PD and AD context, outlines four cellular defense systems against ferroptosis and how each of them is involved in PD and AD.

Dysfunction of CYC2g is responsible for the evolutionary shift from radiate to disciform flowerheads in the Chrysanthemum group (Asteraceae: Anthemideae).

Evolutionary shifts among radiate, disciform and discoid flowerheads have occurred repeatedly in a number of major lineages across the Asteraceae phylogeny; such transitions may also appear within evolutionarily young groups. Although several studies have demonstrated that CYC2 genes partake in regulating floral morphogenesis in Asteraceae, the evolution of capitulum forms within a recently diverging lineage has remained poorly understood. Here, we study the molecular regulation of the shift from a radiate to a disciform capitulum within the Chrysanthemum group. This is a recently radiating group mainly comprising two genera, Chrysanthemum and Ajania, that are phylogenetically intermingled but distinct in flowerhead morphology: Chrysanthemum spp. with radiate capitula and Ajania spp. with disciform capitula. We found that the morphogenesis of zygomorphy in the marginal floret in Ajania was disrupted soon after floral primordium emergence; CYC2g, one of the CYC2 copies that was expressed prominently in the ray floret of Chrysanthemum was not expressed in flowerheads of Ajania. Weakening the expression of ClCYC2g in Chrysanthemum lavandulifolium led to the gradual transition of a ray flower toward the disc-like form. Molecular evolutionary analyses indicated that the disciform capitulum might have evolved only once, approximately 8 Mya, arising from dysfunction of the CYC2g orthologs. A 20-nt deletion, including a putative TATA-box of the Ajania-type CYC2g promoter, appeared to inhibit the expression of the gene. Considering the divergent habitats of Chrysanthemum and Ajania, we propose that the shift from radiate to disciform capitulum must have been related to changes in pollination strategies under selective pressure.

Co-option of a carotenoid cleavage dioxygenase gene (CCD4a) into the floral symmetry gene regulatory network contributes to the polymorphic floral shape-color combinations in Chrysanthemum sensu lato.

Morphological novelties, including formation of trait combinations, may result from de novo gene origination and/or co-option of existing genes into other developmental contexts. A variety of shape-color combinations of capitular florets occur in Chrysanthemum and its allies. We hypothesized that co-option of a carotenoid cleavage dioxygenase gene into the floral symmetry gene network would generate a white zygomorphic ray floret. We tested this hypothesis in an evolutionary context using species in Chrysanthemum sensu lato, a monophyletic group with diverse floral shape-color combinations, based on morphological investigation, interspecific crossing, molecular interaction and transgenic experiments. Our results showed that white color was significantly associated with floret zygomorphy. Specific expression of the carotenoid cleavage dioxygenase gene CCD4a in marginal florets resulted in white color. Crossing experiments between Chrysanthemum lavandulifolium and Ajania pacifica indicated that expression of CCD4a is trans-regulated. The floral symmetry regulator CYC2g can activate expression of CCD4a with a dependence on TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING (TCP) binding element 8 on the CCD4a promoter. Based on all experimental findings, we propose that gene co-option of carotenoid degradation into floral symmetry regulation, and the subsequent dysfunction or loss of either CYC2g or CCD4a, may have led to evolution of capitular shape-color patterning in Chrysanthemum sensu lato.

Clinical characteristics and postoperative outcomes of systemic artery-to-pulmonary vessel fistula in hemoptysis patients.

OBJECTIVES: To investigate the clinical characteristics and outcomes on the success of bronchial arterial embolization (BAE) in patients with and without systemic artery-to-pulmonary vessel fistula (SA-PF) and to evaluate the feasibility of CTA in the assessment of SA-PF. METHODS: We retrospectively enrolled 420 consecutive patients that underwent BAE for hemoptysis control in our hospital from September 2011 to May 2019. The clinical characteristics, preprocedural CTA findings, BAE procedural findings, and follow-up outcomes were collected. Patients were divided into two groups according to DSA findings: patients with SA-PF and those without. RESULTS: A total of 184 (43.7%) patients presented with SA-PF. Pneumonia was less likely to be the concomitant condition in patients with SA-PF (p < 0.001). The mean number of culprit arteries per patient was significantly higher in patients with SA-PF compared to that in patients without SA-PF (p = 0.017). The SA-PF patients saw a greater probability of recurrence (HR: 2.782, 95% CI: 1.617-4.784, p < 0.001). SA-pulmonary venous fistula (SA-PVF) favored lower hemoptysis recurrence rate (HR: 0.199, 95%CI: 0.052-0.765, p = 0.019). SA-pulmonary artery fistula (SA-PAF) can be detected by optimized CTA protocol with a detection rate of 65.3% (49/75). CONCLUSIONS: The presence of SA-PF is an independent risk factor predicting early recurrence of hemoptysis after BAE. SA-PVF seems to be a protective factor for longer hemoptysis control compared to SA-PAF. Optimized preprocedural CTA is a reliable examination to identify SA-PAF. KEY POINTS: • The appearance of SA-PF is associated with a greater probability of early recurrent hemoptysis after bronchial artery embolization. • The presence of SA-PVF seems to be a protective factor for longer hemoptysis control after BAE compared to SA-PAF. • Optimized CTA protocol seems to be a promising auxiliary examination to detect SA-PAF.

Histone acetyltransferase GCN5-mediated lysine acetylation modulates salt stress aadaption of Trichoderma.

Trichoderma viride has a wide range of applications in plant growth promotion, biological control, cellulase production, and biomass utilization. Salinity is a major limitation to Trichoderma strains in the natural environment and fermentation environment, and to improve the adaptability of Trichoderma to salt stress is of great significance to its applications in industry and agriculture. Histone acetylation plays important roles in the regulation of physiological and biochemical processes including various stress responses. GCN5 is the most representative histone acetylase, which plays vital roles in chromatin remodeling of promoters to facilitate the transcription activation. In this paper, we identified a GCN5-encoding gene TvGCN5 in T. viride Tv-1511, and characterized the function and regulating mechanism of TvGCN5-mediated acetylation of histone H3 in the salt adoption of Tv-1511, by constructions of the deletion mutants (Tv-1511-△GCN5) and overexpression mutants (Tv-1511-GCN5-OE) of TvGCN5. Results showed that compared with wild-type Tv-1511, the over-expression of TvGCN5 resulted in the longer mycelia diameter and more biomass under salt stress. Furthermore, Tv-1511-△GCN5 strains obtained the improved sodium (Na+) compartmentation and antioxidant capacity by upregulating the transcriptional levels of genes encoding PM H+-ATPase, vacuolar H+-ATPase, and antioxidant enzymes. Notably, the changes in the transcriptional expressions of these genes are tightly modulated by the TvGCN5-mediated acetylated level of histone H3 in their promoter regions. In all, these results reveal that TvGCN5 plays an important role in stress tolerance of T. viride Tv-1511, and provides potential insight to facilitate the application of epigenetic modulation in the expanding utilization of Trichoderma. KEY POINTS: • Overexpresison of TvGCN5 improves the adoption of T. viride Tv-1511 to salt stress by increasing acetylation level of histone H3 on the promoter regions of sodium-transport and antioxidant-related genes, at H3K9ac, H3K14ac, H3K23ac, and H3K27ac. • Overexprsison of TvGCN5 enhances the ion transport and compartmentation capacity by upregulating the expressions and activities of PM and vacuolar H+-ATPase to tolerate salt stress. • Overexprsison of TvGCN5 promotes the antioxidant capacity by increasing the expressions and activities of antioxidant enzymes in response to salt stress.

METTL3 restrains papillary thyroid cancer progression via m6A/c-Rel/IL-8-mediated neutrophil infiltration.

Growing evidence indicates that N6-methyladenosine (m6A) is the most pervasive RNA modification in eukaryotic cells. However, the specific role of METTL3 in papillary thyroid carcinoma (PTC) initiation and development remains elusive. Here we found that downregulation of METTL3 was correlated with malignant progression and poor prognosis in PTC. A variety of gain- and loss-of-function studies clarified the effect of METTL3 on regulation of growth and metastasis of PTC cells in vitro and in vivo. By combining RNA sequencing (RNA-seq) and methylated RNA immunoprecipitation sequencing (meRIP-seq), our mechanistic studies pinpointed c-Rel and RelA as downstream m6A targets of METTL3. Disruption of METTL3 elicited secretion of interleukin-8 (IL-8), and elevated concentrations of IL-8 promoted recruitment of tumor-associated neutrophils (TANs) in chemotaxis assays and mouse models. Administration of the IL-8 antagonist SB225002 substantially retarded tumor growth and abolished TAN accumulation in immunodeficient mice. Our findings revealed that METTL3 played a pivotal tumor-suppressor role in PTC carcinogenesis through c-Rel and RelA inactivation of the nuclear factor κB (NF-κB) pathway by cooperating with YTHDF2 and altered TAN infiltration to regulate tumor growth, which extends our understanding of the relationship between m6A modification and plasticity of the tumor microenvironment.

SNHG9/miR-214-5p/SOX4 feedback loop regulates osteosarcoma progression.

Osteosarcoma (OS) is a high-grade, aggressive bone sarcoma. LncRNAs play a key regulatory role in controlling biological and pathological processes. The expression of lncRNA SNHG9 varies among different cancer tissues, and the role of SNHG9 in OS progression is unclear. In this study, we found SNHG9 overexpression in OS tissues and cells. In addition, downregulated SNHG9 expression impaired the proliferation, migration, and invasion abilities of OS cells. SNHG9 expression was positively regulated by the transcription factor SOX4. SNHG9 interacted with miR-214-5p as a molecular sponge and SOX4 was identified as the target of miR-214-5p. The interaction affected the expression of SNHG9, miR-214-5p, and SOX4, and regulated OS cell proliferation, migration, and invasion. Therefore, the SNHG9/miR-214-5p/SOX4 feedback loop performs an important role in OS progression and might be used as a new potential therapeutic target for the treatment of OS.

Correlation between physical characteristics of biopsy specimen and disease of cervical lymph node after contrast-enhanced ultrasound.

BACKGROUND: To investigate the correlation between physical characteristics and disease of cervical lymph node biopsy specimens after contrast-enhanced ultrasound. METHODS: All patients were biopsied after CEUS, 235 patients were divided into three groups A, B and C according to the physical characteristics of specimens: 92 patients in group A were complete tissue specimens; 113 patients in group B were discontinuous tissue specimens. There were 30 patients in group C, including a small number of tissue and floc, purulent and bloody specimens. Pathological examination, pathogen culture examination and Gene X-Pert MIB examination were completed for all patients in the three groups, and statistical analysis was conducted on the integrity and traits of the specimens. RESULTS: Group A included 92 intact tissue specimens, 21 with reactive hyperplasia, 17 with lymphoma, 12 with metastatic carcinoma, 13 with lymphadenopathy, 15 with necrotizing lymphadenitis, and rare lymphadenopathy. In group B, 113 patients were treated with intermittent tissue specimens, including infected lymph nodes, lymphoma in 1 case, metastatic carcinoma in 3 cases and sarcoidosis in 1 case. There were 30 patients in group C, including a small amount of tissue and floc, purulent and bloody specimens, all of which were infected lymph nodes. The χ2 value of malignant and benign lymph nodes was 42.401, p = 0.000. CONCLUSION: The physical characteristics of cervical lymph node biopsy specimens after CEUS are correlated with the disease, which has guiding significance for postoperative specimen selection.

Structural Properties and Hydrolysability of Paulownia elongate: The Effects of Pretreatment Methods Based on Acetic Acid and Its Combination with Sodium Sulfite or Sodium Sulfite.

The effects of CH3COOH and Na2SO3 pretreatment on the structural properties and hydrolyzability of fast-growing Paulownia elongate were investigated. Acetic acid increased cellulose's crystallinity and hydrolyzability when combined with alkaline sodium sulfite and sodium hydroxide. The cellulose content increased by 21%, the lignin content decreased by 6%, and the product showed better enzymatic digestibility. With a cellulase dose of 30 FPU/g DM, after 72 h hydrolysis, the hydrolysis yields of glucose and xylose were 78% and 83%, respectively, which were 51% and 69% higher than those of untreated materials. When the enzyme dosage was 20 FPU/g DM, after 72 h hydrolysis, the hydrolysis yields of glucose and xylose were 74% and 79%, respectively. The high hydrolyzability, low enzyme loading, and high hydrolysis yield demonstrate the potential of the proposed system for producing platform sugars from fast-growing Paulownia elongate.

Protective effect of surfactin on copper sulfate-induced inflammation, oxidative stress, and hepatic injury in zebrafish.

Surfactin, an antibacterial peptide, produced by various Bacillus subtilis strains, have broad-spectrum antibacterial and immune-enhancing functions. In this study, we investigated the anti-inflammatory, antioxidant, and hepatoprotective effect of surfactin on zebrafish (Danio rerio) larvae following their exposure to copper sulfate (CuSO4 ). The mature AB wild-type and a transgenic line of zebrafish larvae that expressed enhanced GFP (EGFP) named Tg (Lyz:EGFP) were exposed to 0, 20, 40, and 60 µg/mL surfactin after incubation with 3.2 µg/mL CuSO4 for 2 h from 72 h postfertilization (hpf). Different endpoints, such as migration of GFP-labeled neutrophils, analysis of inflammatory cytokines and transaminases, markers of oxidation, expression of certain genes, and histological changes of liver, were studied to evaluate the function of surfactin. The protein expression levels of NF-κBp65, TNF-α, cyclooxygenase-2 (COX-2), and iNOS were determined in murine macrophage RAW 264.7 cells by western blotting. Our results show that surfactin reduced migration of neutrophils and relieved hepatic injury. In addition, surfactin reduced the index levels of inflammatory factors, oxidative stress response, and improved hepatic function. Surfactin also significantly inhibited the expression of IL-1ß, IL-8, TNF-α, nitric oxide, NF-κBp65, COX-2, and iNOS, and increased the expression of IL-10. Thus, our results demonstrate that surfactin has anti-inflammatory, antioxidant, and hepatoprotective activities. Surfactin has potential as a novel inflammation and immune adjustment.

Gasdermin E-derived caspase-3 inhibitors effectively protect mice from acute hepatic failure.

Programmed cell death (PCD), including apoptosis, apoptotic necrosis, and pyroptosis, is involved in various organ dysfunction syndromes. Recent studies have revealed that a substrate of caspase-3, gasdermin E (GSDME), functions as an effector for pyroptosis; however, few inhibitors have been reported to prevent pyroptosis mediated by GSDME. Here, we developed a class of GSDME-derived inhibitors containing the core structure of DMPD or DMLD. Ac-DMPD-CMK and Ac-DMLD-CMK could directly bind to the catalytic domains of caspase-3 and specifically inhibit caspase-3 activity, exhibiting a lower IC50 than that of Z-DEVD-FMK. Functionally, Ac-DMPD/DMLD-CMK substantially inhibited both GSDME and PARP cleavage by caspase-3, preventing apoptotic and pyroptotic events in hepatocytes and macrophages. Furthermore, in a mouse model of bile duct ligation that mimics intrahepatic cholestasis-related acute hepatic failure, Ac-DMPD/DMLD-CMK significantly alleviated liver injury. Together, this study not only identified two specific inhibitors of caspase-3 for investigating PCD but also, more importantly, shed light on novel lead compounds for treating liver failure and organ dysfunctions caused by PCD.

The value of multimodal ultrasonography in differential diagnosis of tuberculous and non-tuberculous superficial lymphadenitis.

BACKGROUND: To investigate the value of multimodal ultrasonography in differentiating tuberculosis from other lymphadenopathy. METHODS: Sixty consecutive patients with superficial lymphadenopathy treated at our hospital from January 2017 to December 2018 were categorized into four types based on the color Doppler ultrasound, five types based on contrast-enhanced ultrasound, and five types based on elastography. Sensitivity and specificity were calculated of all the three imaging, including color Doppler examination, contrast-enhanced ultrasound and one individual multimodal method, for detecting lymph nodes. RESULTS: A total of 60 patients were included in the final analysis. Of those, Mycobacterium tuberculosis was positive in 38 patients and negative in 22 patients. Among the 38 patients who were positive for Mycobacterium tuberculosis, of which 23 had a history of pulmonary tuberculosis, accounting for 60.53% of the positive cases, and the remaining patients did not combine lesions of other organs. Among the 60 superficial lymph nodes, 63.3% presented with tuberculous lymphadenitis. The sensitivity, specificity, and accuracy of the color Doppler examination were 73.68%, 68.18%, and 71.67%, respectively. The sensitivity, specificity and accuracy of contrast-enhanced ultrasound were 89.47%, 63.64% and 80.00%, respectively. The sensitivity, specificity and accuracy of the elastography were 63.16%, 63.64% and 63.33%, respectively. The sensitivity, specificity and accuracy of one individual multimodal method were 42.11%, 95.45% and 61.67%, respectively. The sensitivity, specificity and accuracy of all modes combined were 100.00%, 27.27% and 73.33%, respectively. CONCLUSION: Multimodal ultrasonography has high predictive value for the differential diagnosis of superficial tuberculous lymphadenitis.