SiSGC: A Drug Repositioning Prediction Model Based on Heterogeneous Simplifying Graph Convolution.

Drug repositioning plays a key role in disease treatment. With the large-scale chemical data increasing, many computational methods are utilized for drug-disease association prediction. However, most of the existing models neglect the positive influence of non-Euclidean data and multisource information, and there is still a critical issue for graph neural networks regarding how to set the feature diffuse distance. To solve the problems, we proposed SiSGC, which makes full use of the biological knowledge information as initial features and learns the structure information from the constructed heterogeneous graph with the adaptive selection of the information diffuse distance. Then, the structural features are fused with the denoised similarity information and fed to the advanced classifier of CatBoost to make predictions. Three different data sets are used to confirm the robustness and generalization of SiSGC under two splitting strategies. Experiment results demonstrate that the proposed model achieves superior performance compared with the six leading methods and four variants. Our case study on breast neoplasms further indicates that SiSGC is trustworthy and robust yet simple. We also present four drugs for breast cancer treatment with high confidence and further give an explanation for demonstrating the rationality. There is no doubt that SiSGC can be used as a beneficial supplement for drug repositioning.

tRF3-IleAAT reduced extracellular matrix synthesis in diabetic kidney disease mice by targeting ZNF281 and inhibiting ferroptosis.

It is well established that the synthesis of extracellular matrix (ECM) in mesangial cells is a major determinant of diabetic kidney disease (DKD). Elucidating the major players in ECM synthesis may be helpful to provide promising candidates for protecting against DKD progression. tRF3-IleAAT is a tRNA-derived fragment (tRF) produced by nucleases at tRNA-specific sites, which is differentially expressed in the sera of patients with diabetes mellitus and DKD. In this study we investigated the potential roles of tRFs in DKD. Db/db mice at 12 weeks were adapted as a DKD model. The mice displayed marked renal dysfunction accompanied by significantly reduced expression of tRF3-IleAAT and increased ferroptosis and ECM synthesis in the kidney tissues. The reduced expression of tRF3-IleAAT was also observed in high glucose-treated mouse glomerular mesangial cells. We administered ferrostatin-1 (1 mg/kg, once every two days, i.p.) to the mice from the age of 12 weeks for 8 weeks, and found that inhibition of the onset of ferroptosis significantly improved renal function, attenuated renal fibrosis and reduced collagen deposition. Overexpression of tRF3-IleAAT by a single injection of AAV carrying tRF3-IleAAT via caudal vein significantly inhibited ferroptosis and ECM synthesis in DKD model mice. Furthermore, we found that the expression of zinc finger protein 281 (ZNF281), a downstream target gene of tRF3-IleAAT, was significantly elevated in DKD models but negatively regulated by tRF3-IleAAT. In high glucose-treated mesangial cells, knockdown of ZNF281 exerted an inhibitory effect on ferroptosis and ECM synthesis. We demonstrated the targeted binding of tRF3-IleAAT to the 3'UTR of ZNF281. In conclusion, tRF3-IleAAT inhibits ferroptosis by targeting ZNF281, resulting in the mitigation of ECM synthesis in DKD models, suggesting that tRF3-IleAAT may be an attractive therapeutic target for DKD.

Optical Imaging of Ultrafast Phonon-Polariton Propagation through an Excitonic Sensor.

Hexagonal boron nitride (hBN) hosts phonon polaritons (PhP), hybrid light-matter states that facilitate electromagnetic field confinement and exhibit long-range ballistic transport. Extracting the spatiotemporal dynamics of PhPs usually requires "tour de force" experimental methods such as ultrafast near-field infrared microscopy. Here, we leverage the remarkable environmental sensitivity of excitons in two-dimensional transition metal dichalcogenides to image PhP propagation in adjacent hBN slabs. Using ultrafast optical microscopy on monolayer WSe2/hBN heterostructures, we image propagating PhPs from 3.5 K to room temperature with subpicosecond and few-nanometer precision. Excitons in WSe2 act as transducers between visible light pulses and infrared PhPs, enabling visible-light imaging of PhP transport with far-field microscopy. We also report evidence of excitons in WSe2 copropagating with hBN PhPs over several micrometers. Our results provide new avenues for imaging polar excitations over a large frequency range with extreme spatiotemporal precision and new mechanisms to realize ballistic exciton transport at room temperature.

Identification of three potential novel biomarkers for early diagnosis of acute ischemic stroke via plasma lipidomics.

INTRODUCTION: Acute ischemic stroke (AIS) accounts for the majority of all stroke, globally the second leading cause of death. Due to its rapid development after onset, its early diagnosis is crucial. OBJECTIVES: We aim to identify potential highly reliable blood-based biomarkers for early diagnosis of AIS using quantitative plasma lipid profiling via a machine learning approach. METHODS: Lipidomics was used for quantitative plasma lipid profiling, based on ultra-performance liquid chromatography tandem mass spectrometry. Our samples were divided into a discovery and a validation set, each containing 30 AIS patients and 30 health controls (HC). Differentially expressed lipid metabolites were screened based on the criteria VIP > 1, p < 0.05, and fold change > 1.5 or < 0.67. The least absolute shrinkage and selection operator (LASSO) and random forest algorithms in machine learning were used to select differential lipid metabolites as potential biomarkers. RESULTS: Three key differential lipid metabolites, CarnitineC10:1, CarnitineC10:1-OH and Cer(d18:0/16:0), were identified as potential biomarkers for early diagnosis of AIS. The former two, associated with thermogenesis, were down-regulated, whereas the latter, associated with necroptosis and sphingolipd metabolism, was upregulated. Univariate and multivariate logistic regressions showed that these three lipid metabolites and the resulting diagnostic model exhibited a strong ability in discriminating between AIS patients and HCs in both the discovery and validation sets, with an area under the curve above 0.9. CONCLUSIONS: Our work provides valuable information on the pathophysiology of AIS and constitutes an important step toward clinical application of blood-based biomarkers for diagnosing AIS.

Paenibacillus rhizolycopersici sp. nov., an oligotrophic bacterium isolated from a tomato plant in China.

A Gram-positive, rod-shaped, motile, endospore-forming strain, DXFW5T, was isolated from the rhizosphere soil of tomato. Strain DXFW5T grew at 20-50 °C (optimum, 25-37 °C), pH 5-8 (optimum, pH 7) and in the presence of 3 % NaCl. It was positive for catalase and oxidase. Phylogenetic analysis using 16S rRNA gene sequences showed this strain was most closely related to Paenibacillus timonensis DSM 16943T (98.0 %) and Paenibacillus barengoltzii DSM 22255T (97.4 %). The DNA G+C content was 52.9 mol%. The digital DNA-DNA hybridization values between strain DXFW5T and P. timonensis DSM 16943T, P. barengoltzii DSM 22255T and P. macerans DSM 24T were 33.1, 24.9 and 21.2 %, respectively. The average nucleotide identity values between strain DXFW5T and P. timonensis DSM 16943T , P. barengoltzii DSM 22255T and P. macerans DSM 24T were 86.93, 81.77 and 75.98 %, respectively. The major fatty acids were anteiso-C15 : 0 (55.1 %), iso-C16 : 0 (13.2 %) and C16 : 0 (10 %). The polar lipids of strain DXFW5T consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine two unidentified phospholipids and three unidentified lipids. MK-7 was the major isoprenoid quinone. Based on these results, it was concluded that the isolate represents a novel species of the genus Paenibacillus, for which the name Paenibacillus rhizolycopersici sp. nov. is proposed, with DXFW5T (=ACCC 61751T=JCM 34488T) as the type strain.

Dark-Exciton Driven Energy Funneling into Dielectric Inhomogeneities in Two-Dimensional Semiconductors.

The optoelectronic and transport properties of two-dimensional transition metal dichalcogenide semiconductors (2D TMDs) are highly susceptible to external perturbation, enabling precise tailoring of material function through postsynthetic modifications. Here, we show that nanoscale inhomogeneities known as nanobubbles can be used for both strain and, less invasively, dielectric tuning of exciton transport in bilayer tungsten diselenide (WSe2). We use ultrasensitive spatiotemporally resolved optical scattering microscopy to directly image exciton transport, revealing that dielectric nanobubbles are surprisingly efficient at funneling and trapping excitons at room temperature, even though the energies of the bright excitons are negligibly affected. Our observations suggest that exciton funneling in dielectric inhomogeneities is driven by momentum-indirect (dark) excitons whose energies are more sensitive to dielectric perturbations than bright excitons. These results reveal a new pathway to control exciton transport in 2D semiconductors with exceptional spatial and energetic precision using dielectric engineering of dark state energetic landscapes.

Relationship between sarcopenic obesity and cognitive function in patients with mild to moderate Alzheimer's disease.

BACKGROUND: Previous research has linked sarcopenic obesity (SO) to cognitive function; however, the relationship between cognitive performance and SO Alzheimer's disease (AD) patients remains unclear. This study aimed to investigate their relationship in AD patients. METHODS: One hundred and twenty mild to moderate AD patients and 56 normal controls were recruited. According to sarcopenia or obesity status, AD patients were classified into subgroups: normal, obesity, sarcopenia, and SO. Body composition, demographics, and sarcopenia parameters were assessed. Cognitive performance was evaluated using neuropsychological scales. RESULTS: Among the 176 participants, the prevalence of SO in the moderate AD group was higher than in the normal control group. The moderate AD group had the lowest appendicular skeletal muscle mass index (ASMI) and the highest percentage of body fat (PBF). Hypertension and diabetes were more prevalent in the SO group than in the normal group among the subgroups. The sarcopenia and SO groups exhibited worse global cognitive function compared to the normal and obesity groups. Partial correlation analysis revealed that ASMI, PBF, and visceral fat area were associated with multiple cognitive domains scores. In logistic regression analysis, after adjusting for confounders, obesity was not found to be associated with AD. However, sarcopenia (odds ratio (OR) = 5.35, 95% CI: 1.27-22.46) and SO (OR = 5.84, 95% CI: 1.26-27.11) were identified as independent risk factors for AD. CONCLUSIONS: SO was associated with cognitive dysfunction in AD patients. Moreover, the impact of SO on cognitive decline was greater than that of sarcopenia. Early identification and intervention for SO may have a positive effect on the occurrence and progression of AD.

[Clinical efficacy of Manlyman Spray combined with biofeedback therapy on premature ejaculation].

Objective： To observe the clinical effect of Manlyman Spray combined with biofeedback therapy in the treatment of premature ejaculation (PE)．Methods： A total of 60 primary premature ejaculation patients with stable sexual partners and regular sexual activity (≥１ times per week) from April 2021 to October 2022 were involved in the clinical observation, The patients' age is (34.3 ± 4.9) years old, and the course of the disease is (112.5 ± 65.5) months, and Manlyman Spray combined with biofeedback therapy was used to treat patients for 8 weeks. Manlyman Spray was sprayed 3 times on the surface of the penisqd for 4 weeks, and Biofeedback therapy is treated twice a week according to the AI setting module, for a total of 8 weeks. Before and 8 weeks after medication and at 4 weeks after drug withdrawal, the Intravaginal Ejaculation Latency Time (IELT), Premature Ejaculation Diagnostic Tool (PEDT) scores and Clinical Global Impression of Change (CGIC) scores were Obtained and compared. Results： After 8 weeks of treatment, the IELT of the patients was significantly prolonged (ï¼»351.4 ± 76.7ï¼½ vs ï¼»87 ± 16.8ï¼½,P<0.05) and at 4 weeks after drug withdrawal, the therapeutic effect still existed (ï¼»345.9 ± 80.3ï¼½ vs ï¼»87 ± 16.8ï¼½,P<0.05), the PEDT scores were significantly improved after treatment (ï¼»18.2 ± 1.1ï¼½ vs ï¼»9.0 ± 1.4ï¼½,P<0.05)and at 4 weeks after drug withdrawal(ï¼»18.0 ± 1.2ï¼½ vs ï¼»9.0 ± 1.4ï¼½,P<0.05), and so were the CGIC scores (ï¼»13.4 ± 1.3ï¼½ vs ï¼»3.3 ± 1.4ï¼½,P<0.05, and ï¼»12.6 ± 1.6ï¼½ vs ï¼»3.3 ± 1.4ï¼½,P<0.05). Conclusion： The combination of Manlyman Spray and biofeedback therapy can effectively treat primary premature ejaculation, with a long duration of treatment and good safety, and the specific mechanism needs further study.

[Clinical study on the treatment of premature ejaculation with Nailifu Spray].

OBJECTIVE: To observe the effect of Nailifu Spray on the treatment of premature ejaculation. METHODS: A total of 90 patients were included in this study from January 1, 2022 to January 1, 2023. Nailifu spray was used to spray the surface of penile skin once a day, 2 sprays per session for 4 weeks.And the patients' premature ejaculation diagnostic tool (PEDT) scores, intravaginal ejaculation latency time (IELT), and international index of erectile function-5 (IIEF-5) scores were collected before and after treatment, respectively. RESUTS: The median (P25,P75) PEDT scores was 16.0(15.0,18.0) scores before treatment and 10.0(10.0,10.0) scores after treatment. The median (P25,P75) of IELT was 20.0 (10.0,30.0) s before treatment and 240.0 (180.0,300.0) s after treatment. The median (P25,P75) of IIEF-5 scores was 21.0 (21.0,22.0) scores before treatment and 21.0 (21.0,21.0) scores after treatment. Compared with baseline levels, IELT was significantly longer and PEDT scores were significantly lower, with statistically significant differences. No significant changes in IIEF-5 scores were seen. CONCLUSION: Nailifu spray treatment of premature ejaculation is accurate and effective, worthy of clinical promotion.

Role of the hydrogen sulfide-releasing donor ADT-OH in the regulation of mammal neural precursor cells.

Neural precursor cells (NPCs) generate new neurons to supplement neuronal loss as well as to repair damaged neural circuits. Therefore, NPCs have potential applications in a variety of neurological diseases, such as spinal cord injury, traumatic brain injury, and glaucoma. Specifically, improving NPCs proliferation and manipulating their differentiated cell types can be a beneficial therapy for a variety of these diseases. ADT-OH is a slow-releasing organic H2 S donor that produces a slow and continuous release of H2 S to maintain normal brain functions. In this study, we aimed to explore the effect of ADT-OH on NPCs. Our results demonstrated that ADT-OH promotes self-renewal and antiapoptosis ability of cultured NPCs. Additionally, it facilitates more NPCs to differentiate into neurons and oligodendrocytes, while inhibiting their differentiation into astrocytes. Furthermore, it enhances axonal growth. Moreover, we discovered that the mRNA and protein expression of ß-catenin, TCF7L2, c-Myc, Ngn1, and Ngn2, which are key genes that regulate NPCs self-renewal and differentiation, were increased in the presence of ADT-OH. Altogether, these results indicate that ADT-OH may be a promising drug to regulate the neurogenesis of NPCs, and needs to be studied in the future for clinical application potential.

Chitinophaga hostae sp. nov., isolated from the rhizosphere soil of Hosta plantaginea.

A Gram-negative, rod-shaped aerobic bacterium designated as strain 2R12T was isolated from the rhizosphere soil of Hosta plantaginea. Phylogenetic analyses based on the 16S rRNA gene revealed that strain 2R12T should be assigned to the genus Chitinophaga with the highest sequence similarity to Chitinophaga arvensicola DSM 3695T (99.1 %) and Chitinophaga ginsengisegetis DSM 18108T (98.6 %). The major fatty acids of strain 2R12T (>10 %) were iso-C15 : 0, C16 :1 ω5c and iso-C17 : 0 3-OH. The major polar lipids were phosphatidylethanolamine, two unidentified aminolipids and five unidentified lipids. The predominant respiratory quinone was MK-7. The genomic DNA G+C content was 46.1 mol%. The average nucleotide identity values of strain 2R12T with C. arvensicola DSM 3695T and C. ginsengisegetis DSM 18108T were 77.9 and 78.8 %, respectively, while in silico DNA-DNA hybridization values for strain 2R12T with these strains were 22.8 and 23.3 %, respectively. Based on comparative analysis of phylogenetic, phylogenomic, phenotypic and chemotaxonomic characteristics, strain 2R12T represents a novel species in the genus Chitinophaga, for which the name Chitinophaga hostae sp. nov. is proposed. The type strain is 2R12T (=ACCC 61757T=JCM 34719T).

Transcriptional regulator CTR9 promotes hepatocellular carcinoma progression and metastasis via increasing PEG10 transcriptional activity.

Cln Three Requiring 9 (CTR9), a scaffold protein of the polymerase-associated factor-1 (PAF1) complex (PAF1c), is primarily localized in the nucleus of cells. Recent studies show that CTR9 plays essential roles in the development of various human cancers and their occurrence; however, its regulatory roles and precise mechanisms in hepatocellular carcinoma (HCC) remain unclear. In this study, we investigated the roles of CTR9 using in vitro assays and a xenograft mouse model. We found that CTR9 protein is upregulated in tumor tissues from HCC patients. Knockdown of CTR9 substantially reduced HCC cell proliferation, invasion, and migration, whereas its overexpression promoted these activities. In addition, in vitro results revealed that CTR9 silencing dramatically increased cell cycle regulators, p21 and p27, but markedly decreased matrix metalloproteinases, MMP2 and MMP9, with these outcomes reversed upon CTR9 overexpression. Furthermore, the underlying molecular mechanism suggests that CTR9 promoted the oncogene paternally expressed gene 10 (PEG10) transcription via its promoter region. Finally, the oncogenic roles of CTR9 were confirmed in a xenograft mouse model. This study confirms that CTR9, an oncoprotein that promotes HCC cell proliferation, invasion, and migration, increases tumor growth in a xenograft mouse model. CTR9 could be a novel therapeutic target. Further investigation is warranted to verify CTR9 potential in novel therapies for HCC.

Metabacillus rhizolycopersici sp. nov., Isolated from the Rhizosphere Soil of Tomato Plants.

A Gram-positive, endospore-forming, rod-shaped and aerobic bacterium, with swarming and swimming motility, designated strain DBTR6T, was isolated from the rhizosphere soil of tomato plants. Strain DBTR6T grew at 20-45 â„ƒ (optimum 30-37℃), pH 4-9 (optimum 7-8) and at salinities from 0 to 5% (optimum 1%). Phylogenetic analysis using 16S rRNA gene sequences showed this strain belonged to the genus Metabacillus and was most closely related to Metabacillus litoralis DSM 16303 T (98.3%) and Metabacillus sediminilitoris MCCC 1K03777T (98.3%). The DNA G + C content of the genomic DNA was 36.4%. The digital DNA-DNA hybridization value between strain DBTR6T and reference strains M. sediminilitoris MCCC 1K03777T and "M. bambusae" BG109T were less than 70% (26.7% and 26.0%), and the average nucleotide identity score were less than 95% (78.55% and 78.38%), and the Amino Acid Identity values calculated were less than 96% (79.99% and 80.18%), respectively, suggesting that strain DBTR6T represented a novel species in the genus Metabacillus. Chemotaxonomic analysis showed that strain DBTR6T contained MK-7 as the major respiratory quinone. The predominant fatty acids (> 10.0%) were iso-C15:0, anteiso-C15:0 and C16:0. The major polar lipids were diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), glycolipids (GL) and three unidentified lipids (L). Based on the differential physiological properties, biochemical characteristics and genotypic data, strain DBTR6T represents a novel species of the genus Metabacillus, for which the name Metabacillus rhizolycopersici sp. nov. is proposed. The type strain is DBTR6T (= ACCC 61900 T = JCM 35080 T).

Ubiquitin-specific protease 22 ameliorates chronic alcohol-associated liver disease by regulating BRD4.

Alcohol-associated liver disease (ALD) is a liver system disease caused by alcohol abuse, and it involves complex processes ranging from steatosis to fibrosis, cirrhosis and hepatocellular carcinoma. Steatosis and inflammation are the main phenomena involved in ALD. Ubiquitin-specific protease 22 (USP22) plays an important role in liver steatosis; however, its functional contribution to ALD remains unclear. USP22-silenced mice were fed a Lieber-DeCarli liquid diet. AML-12 and HEK293T cells were used to detect the interaction between USP22 and BRD4. Here, we report that hepatic USP22 expression was dramatically upregulated in mice with ALD. Inflammation and steatosis were significantly ameliorated following USP22 silencing in vivo, as indicated by decreased IL-6 and IL-1ß levels. We further showed that the overexpression of USP22 increased inflammation, while knocking down BRD4 suppressed the inflammatory response in AML-12 cells. Notably, USP22 functioned as a BRD4 deubiquitinase to facilitate BRD4 inflammatory functions. More importantly, the expression levels of USP22 and BRD4 in patients with ALD were significantly increased. In conclusion, USP22 acts a key pathogenic factor in ALD by deubiquitinating BRD4, which facilitates the inflammatory response and aggravates ALD.

The efficacy and safety of Serenoa repens extract for the treatment of patients with chronic prostatitis/chronic pelvic pain syndrome: a multicenter, randomized, double-blind, placebo-controlled trial.

PURPOSE: To perform a placebo-controlled trial to evaluate the efficacy and safety of Serenoa repens extract (SRE) for the treatment of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). METHODS: We conducted a double-blind, randomized, placebo-controlled, multicenter, clinical phase 4 study of 221 patients with CP/CPPS across 11 centers. Participants were randomly assigned in a 2:1 ratio to receive SRE or placebo for 12 weeks. The primary efficacy endpoint was the change in total score on the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI). Secondary efficacy endpoints included improvements within each domain of NIH-CPSI, clinical response rate, and International Index of Erectile Function 5 items (IIEF-5). RESULTS: In total, 226 patients were enrolled and randomized between January 2017 and June 2018. Of these 221 patients were included in the intent-to-treat analysis: 148 in the SRE group and 73 patients in the placebo group. Compared to the placebo, SRE led to statistically significant improvements in the NIH-CPSI total score and sub-scores. The significant improvements of NIH-CPSI scores were established after 2 weeks from the first dose, and continued to the end of the treatment. Furthermore, a significantly higher rate of patients achieved a clinical response in the SRE group compared with that in the placebo group (73.0% vs 32.9%, P < 0.0001). Only minor adverse events were observed across the entire study population. CONCLUSIONS: SRE was effective, safe, and clinically superior to placebo for the treatment of CP/CPPS. ChiCTR-IPR-16010196, December 21, 2016 retrospectively registered.

Rhizobium rhizolycopersici sp. nov., Isolated from the Rhizosphere Soil of Tomato Plants in China.

During characterization of rhizobacteria, strain DBTS2T was isolated from the rhizosphere soil samples of healthy tomato plants and characterized using a polyphasic taxonomic approach. Phylogenetic analysis using 16S rRNA gene sequences showed this strain belonged to the genus Rhizobium and was most closely related to Rhizobium subbaraonis JC85T (99.1%) and Rhizobium daejeonense CCBAU 10050T (97%). Cells of strain DBTS2T were Gram-negative, short rod, aerobic and non-motile. This novel strain was found to grow at 20-45 °C (optimum 25-37 °C), pH 5-9 (optimum 8) and in the presence of 4% NaCl. It was positive for catalase and oxidase. The predominant cellular fatty acids were Summed Feature 8 (52.7%) and C19:0 cyclo ω8c (23.3%). The polar lipids of strain DBTS2T consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, unidentified aminophospholipid, unidentified aminolipid, four unidentified phospholipids, unidentified lipid, phosphatidylcholine, unknown glycolipid and unknown aminophosphoglycolipids. Q-10 was the major quinone. The DNA-DNA hybridization similarity values between the strain DBTS2T and R. subbaraonis JC85T, R. daejeonense CCBAU 10050T and Rhizobium azooxidifex DSM100211T were 46.4%, 20.7% and 25.5%, respectively. The ANI value was 91.96% between strain DBTS2T and R. subbaraonis JC85T and 75.18% between strain DBTS2T and R. daejeonense CCBAU 10050T. The DNA G+C content of the genomic DNA was 63.1 mol%. Based on these results, it was concluded that the isolate represents a novel species of the genus Rhizobium, for which the name Rhizobium rhizolycopersici sp. nov. is proposed, with DBTS2T (= CICC 24887T = ACCC61707 = JCM 34245) as the type strain.

Conditioned Media of Adipose-Derived Stem Cells Suppresses Sidestream Cigarette Smoke Extract Induced Cell Death and Epithelial-Mesenchymal Transition in Lung Epithelial Cells.

The role of the epithelial-mesenchymal transition (EMT) in lung epithelial cells is increasingly being recognized as a key stage in the development of COPD, fibrosis, and lung cancers, which are all highly associated with cigarette smoking and with exposure to second-hand smoke. Using the exposure of human lung cancer epithelial A549 cells and non-cancerous Beas-2B cells to sidestream cigarette smoke extract (CSE) as a model, we studied the protective effects of adipose-derived stem cell-conditioned medium (ADSC-CM) against CSE-induced cell death and EMT. CSE dose-dependently induced cell death, decreased epithelial markers, and increased the expression of mesenchymal markers. Upstream regulator analysis of differentially expressed genes after CSE exposure revealed similar pathways as those observed in typical EMT induced by TGF-ß1. CSE-induced cell death was clearly attenuated by ADSC-CM but not by other control media, such as a pass-through fraction of ADSC-CM or A549-CM. ADSC-CM effectively inhibited CSE-induced EMT and was able to reverse the gradual loss of epithelial marker expression associated with TGF-ß1 treatment. CSE or TGF-ß1 enhanced the speed of A549 migration by 2- to 3-fold, and ADSC-CM was effective in blocking the cell migration induced by either agent. Future work will build on the results of this in vitro study by defining the molecular mechanisms through which ADSC-CM protects lung epithelial cells from EMT induced by toxicants in second-hand smoke.

Salvianic acid A alleviates chronic alcoholic liver disease by inhibiting HMGB1 translocation via down-regulating BRD4.

Alcoholic liver disease (ALD) is the major cause of chronic liver disease and a global health concern. ALD pathogenesis is initiated with liver steatosis, and ALD can progress to steatohepatitis, fibrosis, cirrhosis and even hepatocellular carcinoma. Salvianic acid A (SAA) is a phenolic acid component of Danshen, a Chinese herbal medicine with possible hepatoprotective properties. The purpose of this study was to investigate the effect of SAA on chronic alcoholic liver injury and its molecular mechanism. We found that SAA significantly inhibited alcohol-induced liver injury and ameliorated ethanol-induced hepatic inflammation. These protective effects of SAA were likely carried out through its suppression of the BRD4/HMGB1 signalling pathway, because SAA treatment largely diminished alcohol-induced BRD4 expression and HMGB1 nuclear translocation and release. Importantly, BRD4 knockdown prevented ethanol-induced HMGB1 release and inflammatory cytokine production in AML-12 cells. Similarly, alcohol-induced pro-inflammatory cytokines were blocked by HMGB1 siRNA. Collectively, our results reveal that activation of the BRD4/HMGB1 pathway is involved in ALD pathogenesis. Therefore, manipulation of the BRD4/HMGB1 pathway through strategies such as SAA treatment holds great therapeutic potential for chronic alcoholic liver disease therapy.

KIAA1429 regulates cell proliferation by targeting c-Jun messenger RNA directly in gastric cancer.

N6-methyladenosine (m6A) modification regulatory proteins are involved in the development of many types of cancer. KIAA1429 serves as a scaffold in bridging the catalytic core components of the m6A methyltransferase complex. The role of KIAA1429 in gastric cancer and its related mechanism has not been reported upon. The expression of KIAA1429 was detected in human gastric cancer tissues and cell lines by quantitative real-time polymerase chain reaction and western blot. The effects of KIAA1429 on gastric cancer proliferation were evaluated by cell counting kit assays, colony formation assays, flow cytometry assay, and in vivo experiments with nude mice. And messenger RNA (mRNA) high-throughput sequencing, RNA immunoprecipitation assay (RIP), luciferase assay, and a rescue experiment were used to identify the relationship between KIAA1429 and its specific targeted gene, c-Jun. We found that KIAA1429 was upregulated in gastric cancer tissues, and expressed lower in adjacent tissues. The upregulated KIAA1429 promoted proliferation and downregulated KIAA1429 was proved to inhibit proliferation of gastric cancer in vitro and in vivo. Then, we identified the potential KIAA1429 regulating gene as c-Jun by mRNAs high-throughput sequencing and RIP assay. By luciferase assay, we verified that KIAA1429 regulated the expression of c-Jun in an m6A-independent manner. Finally, the overexpression of c-Jun rescued the inhibition of proliferation caused by KIAA1429 knockdown in gastric cancer cells. KIAA1429 could act as an oncogene in gastric cancer by stabilizing c-Jun mRNA in an m6A-independent manner. This highlights the functional role for KIAA1429 as a potential prognostic biomarker and therapeutic target in gastric cancer.

RNA-Seq revealed that infection with white tip nematodes could downregulate rice photosynthetic genes.

White-tip nematode, Aphelenchoides besseyi is a kind of widely distributed migratory parasitic nematode that can infect plant shoots. Transcriptome sequencing of plant parasitic nematodes and their host plants is helpful for understanding their interaction relationship. This study first reported expression patterns of defense-related genes in rice, and rice transcriptomes at different periods after infection with A. besseyi. The result showed that the defense response pathways of rice changed obviously in the early stage of A. besseyi infection, including upregulated salicylic acid and jasmonate pathways and a downregulated ethylene pathway. Transcriptome analysis results suggested that A. besseyi infection was associated with the downregulation of multiple genes related to photosynthesis with possible suppression of the photosynthetic activity. It suggested that the photosynthesis system of rice could be suppressed by infections of migratory nematodes, including A. besseyi and Hirschmanniella oryzae, but was stimulated by that of a sedentary nematode, Meloidogyne graminicola, by comparing our study with the reported transcriptome. OS09G0417800 (OsWRKY62) might play an important role in the interaction of migratory nematodes and rice. It also indicated that the infection strategy of both A. besseyi and the reported migratory nematode H. oryzae was similar to that of the fungal pathogen Magnaporthe grisea. These results provided an interesting starting point to elucidate the mechanism of the interaction between rice and A. besseyi, as well as the host and migratory plant nematodes.