Assessing the in vivo ameliorative effects of Lactobacillus acidophilus KLDS1.0901 for induced non-alcoholic fatty liver disease treatment

Reputed as a significant metabolic disorder, non-alcoholic fatty liver disease (NAFLD) is characterized by high-fat deposits in the liver and causes substantial economic challenges to any country's workforce. Previous studies have indicated that some lactic acid bacteria may effectively prevent or treat NAFLD. Overall, L. acidophilus KLDS1.0901 protected against HFD-induced NAFLD by improving liver characteristics and modulating microbiota composition, and thus could be a candidate for improving NAFLD. This study aimed to assess the protective effects of L. acidophilus KLDS1.0901 on a high-fat diet(HFD)-induced NAFLD. First, hepatic lipid profile and histological alterations were determined to study whether L. acidophilus KLDS1.0901 could ameliorate NAFLD. Then, the intestinal permeability and gut barrier were explored. Finally, gut microbiota was analyzed to elucidate the mechanism from the insights of the gut–liver axis. The results showed that Lactobacillus KLDS1.0901 administration significantly decreased body weight, Lee's index body, fat rate, and liver index. L. acidophilus KLDS1.0901 administration significantly improved lipid profiles by decreasing the hepatic levels of total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) and by increasing the high-density lipoprotein cholesterol (HDL-C) levels. A conspicuous decrease of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum was observed after L. acidophilus KLDS1.0901 administration. Meanwhile, the H&E and Oil Red O-stained staining showed that L. acidophilus KLDS1.0901 significantly reduced liver lipid accumulation of HFD-fed mice by decreasing the NAS score and lipid area per total area. Our results showed that L. acidophilus KLDS1.0901 administration decreased the interleukin-6 (IL-6), interleukin-1β (IL-1β), and tumor necrosis factor-alpha (TNF-α) concentrations accompanied by the increase of interleukin-10 (IL-10). L. acidophilus KLDS1.0901 administration could improve the intestinal barrier function by upregulating the mRNA levels of occludin, claudin-1, ZO-1, and Muc-2, which were coupled to the decreases of the concentration of LPS and D-lactic acid. Notably, L. acidophilus KLDS1.0901 administration modulated the gut microbiota to a near-normal pattern. Hence, our results suggested that L. acidophilus KLDS1.0901 can be used as a candidate to ameliorate NAFLD

Light Suppresses Bacterial Population through the Accumulation of Hydrogen Peroxide in Tobacco Leaves Infected with Pseudomonas syringae pv. tabaci

Pseudomonas syringae pv. tabaci (Pst) is a hemibiotrophic bacterial pathogen responsible for tobacco wildfire disease. Although considerable research has been conducted on the tobacco plant’s tolerance to Pst, the role of light in the responses of the photosystems to Pst infection is poorly understood. This study aimed to elucidate the underlying mechanisms of the reduced photosystem damage in tobacco leaves due to Pst infection under light conditions. Compared to dark conditions, Pst infection under light conditions resulted in less chlorophyll degradation and a smaller decline in photosynthetic function. Although the maximal quantum yield of photosystem II (PSII) and the activity of the photosystem I (PSI) complex decreased as Pst infection progressed, damage to PSI and PSII after infection was reduced under light conditions compared to dark conditions. Pst was 17-fold more abundant in tobacco leaves under dark compared to light conditions at 3 days post-inoculation (dpi). Additionally, hydrogen peroxide (H2O2) accumulated to a high level in tobacco leaves after Pst infection under light conditions; although to a lesser extent, H2O2 accumulation was also significant under dark conditions. Pretreatment with H2O2 alleviated chlorotic lesions and decreased Pst abundance in tobacco leaves at 3 dpi under dark conditions. Methyl viologen (MV) pretreatment had the same effects under light conditions, whereas 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU) pretreatment aggravated chlorotic lesions and increased the Pst population. These results indicate that chlorotic symptoms and the size of the bacterial population are each negatively correlated with H2O2 accumulation. In other words, light appears to suppress the Pst population in tobacco leaves through the accumulation of H2O2 during infection

Donor-derived cell-free DNA as a diagnostic marker for kidney-allograft rejection: A systematic review and meta-analysis

Donor-derived cell-free DNA (dd-cfDNA) has emerged as a promising biomarker for detecting graft rejection. This study aimed to evaluate the diagnostic accuracy and clinical value of applying it to kidney transplant rejection. Relevant literature on dd-cfDNA diagnostics in kidney transplant rejection was reviewed from PubMed, Embase, Cochrane Library, and Web of Science databases up to 2023. Data and study characteristics were extracted independently by two researchers, and disagreements were resolved through discussion. Diagnostic accuracy data for any rejection (AR) and antibody-mediated rejection (ABMR) were analyzed separately. Potential heterogeneity was analyzed by subgroup analysis or meta-regression. Funnel plots were used to clarify the presence or absence of publication bias. Nine publications provided data on dd-cfDNA accuracy in diagnosing patients with AR. The pooled sensitivity, specificity, and the area under the receiver operating characteristic (AUROC) curve with 95% confidence intervals (CI) were 0.59 (95% CI, 0.48-0.69), 0.83 (95% CI, 0.76-0.88), and 0.80 (95% CI, 0.76-0.83), respectively. Additionally, 12 studies focused on the diagnostic accuracy of dd-cfDNA for ABMR, showing pooled sensitivity, specificity, and the AUROC curve with 95% CI of 0.81 (95% CI, 0.72–0.88), 0.80 (95% CI, 0.73–0.86), and 0.87 (95% CI, 0.84-0.90), respectively. Study type, age group, and sample size contributed to heterogeneity. In summary, our findings indicate that while plasma dd-cfDNA accuracy in diagnosing patients with AR is limited by significant heterogeneity, it is a valuable biomarker for diagnosing ABMR

Proteomics identifies neddylation as a potential therapy target in small intestinal neuroendocrine tumors.

Patients with small intestinal neuroendocrine tumors (SI-NETs) frequently develop spread disease; however, the underlying molecular mechanisms of disease progression are not known and effective preventive treatment strategies are lacking. Here, protein expression profiling was performed by HiRIEF-LC-MS in 14 primary SI-NETs from patients with and without liver metastases detected at the time of surgery and initial treatment. Among differentially expressed proteins, overexpression of the ubiquitin-like protein NEDD8 was identified in samples from patients with liver metastasis. Further, NEDD8 correlation analysis indicated co-expression with RBX1, a key component in cullin-RING ubiquitin ligases (CRLs). In vitro inhibition of neddylation with the therapeutic agent pevonedistat (MLN4924) resulted in a dramatic decrease of proliferation in SI-NET cell lines. Subsequent mass spectrometry-based proteomics analysis of pevonedistat effects and effects of the proteasome inhibitor bortezomib revealed stabilization of multiple targets of CRLs including p27, an established tumor suppressor in SI-NET. Silencing of NEDD8 and RBX1 using siRNA resulted in a stabilization of p27, suggesting that the cellular levels of NEDD8 and RBX1 affect CRL activity. Inhibition of CRL activity, by either NEDD8/RBX1 silencing or pevonedistat treatment of cells resulted in induction of apoptosis that could be partially rescued by siRNA-based silencing of p27. Differential expression of both p27 and NEDD8 was confirmed in a second cohort of SI-NET using immunohistochemistry. Collectively, these findings suggest a role for CRLs and the ubiquitin proteasome system in suppression of p27 in SI-NET, and inhibition of neddylation as a putative therapeutic strategy in SI-NET

Genomic Analyses Reveal Mutational Signatures and Frequently Altered Genes in Esophageal Squamous Cell Carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the most common cancers worldwide and the fourth most lethal cancer in China. However, although genomic studies have identified some mutations associated with ESCC, we know little of the mutational processes responsible. To identify genome-wide mutational signatures, we performed either whole-genome sequencing (WGS) or whole-exome sequencing (WES) on 104 ESCC individuals and combined our data with those of 88 previously reported samples. An APOBEC-mediated mutational signature in 47% of 192 tumors suggests that APOBEC-catalyzed deamination provides a source of DNA damage in ESCC. Moreover, PIK3CA hotspot mutations (c.1624G>A [p.Glu542Lys] and c.1633G>A [p.Glu545Lys]) were enriched in APOBEC-signature tumors, and no smoking-associated signature was observed in ESCC. In the samples analyzed by WGS, we identified focal (<100 kb) amplifications of CBX4 and CBX8. In our combined cohort, we identified frequent inactivating mutations in AJUBA, ZNF750, and PTCH1 and the chromatin-remodeling genes CREBBP and BAP1, in addition to known mutations. Functional analyses suggest roles for several genes (CBX4, CBX8, AJUBA, and ZNF750) in ESCC. Notably, high activity of hedgehog signaling and the PI3K pathway in approximately 60% of 104 ESCC tumors indicates that therapies targeting these pathways might be particularly promising strategies for ESCC. Collectively, our data provide comprehensive insights into the mutational signatures of ESCC and identify markers for early diagnosis and potential therapeutic targets

Chemical Stability between NiCr2O4 Material and Molten Calcium-Magnesium-Alumino-Silicate (CMAS) at High Temperature

NiCr2O4 as a potential protection for thermal barrier coatings (TBCs) against the attack of molten calcium-magnesium-alumino-silicate (CMAS) was studied by a CMAS-contacting experiment. Atmospheric plasma sprayed coatings and sintered bulk materials were fabricated, covered with CMAS deposits, and exposed to 1200 °C for 24 h. Nano-sized CMAS-NiCr2O4 mixed powder was manufactured by ball milling and then conducted heat treatment under the same condition. The results show that no reacting product was found at the border between molten CMAS and NiCr2O4 and no element transportation occurred. It can be inferred that NiCr2O4 has outstanding chemical stability with the molten CMAS

Isolation and Functional Characterization of the Promoters of Miltiradiene Synthase Genes, TwTPS27a and TwTPS27b, and Interaction Analysis with the Transcription Factor TwTGA1 from Tripterygium wilfordii

Miltiradiene synthase (MS) genes, TwTPS27a and TwTPS27b, are the key diterpene synthase genes in the biosynthesis of triptolide, which is an important medicinally active diterpenoid in Tripterygium wilfordii. However, the mechanism underlying the regulation of key genes TwTPS27a/b in triptolide biosynthesis remains unclear. In this study, the promoters of TwTPS27a (1496 bp) and TwTPS27b (1862 bp) were isolated and analyzed. Some hormone-/stress-responsive elements and transcription factor (TF) binding sites were predicted in both promoters, which might be responsible for the regulation mechanism of TwTPS27a/b. The β-glucuronidase (GUS) activity analysis in promoter deletion assays under normal and methyl jasmonate (MeJA) conditions showed that the sequence of −921 to −391 bp is the potential core region of the TwTPS27b promoter. And the TGACG-motif, a MeJA-responsive element found in this core region, might be responsible for MeJA-mediated stress induction of GUS activity. Moreover, the TGACG-motif is also known as the TGA TF-binding site. Yeast one-hybrid and GUS transactivation assays confirmed the interaction between the TwTPS27a/b promoters and the TwTGA1 TF (a MeJA-inducible TGA TF upregulating triptolide biosynthesis in T. wilfordii), indicating that TwTPS27a/b are two target genes regulated by TwTGA1. In conclusion, our results provide important information for elucidating the regulatory mechanism of MS genes, TwTPS27a and TwTPS27b, as two target genes of TwTGA1, in jasmonic acid (JA)-inducible triptolide biosynthesis

Association of sodium intake and major cardiovascular outcomes: a dose-response meta-analysis of prospective cohort studies

Abstract Background The association of sodium intake with the risk of cardiovascular morbidity and mortality is inconsistent. Thus, the present meta-analysis was conducted to summarize the strength of association between sodium intake and cardiovascular morbidity and mortality. Methods PubMed, Embase, and the Cochrane Library were searched systematically to identify the relevant studies up to October 2017. The effect estimates for 100 mmol/day increase in sodium intake were calculated using 95% confidence intervals (CIs) of cardiac death, total mortality, stroke, or stroke mortality for low ( 5 g/d) sodium intake, and minimal sodium intake comparison. Results A total of 16 prospective cohort studies reported data on 205,575 individuals. The results suggested that an increase in sodium intake by 100 mmol/d demonstrated little or no effect on the risk of cardiac death (P = 0.718) and total mortality (P = 0.720). However, the risk of stroke incidence (P = 0.029) and stroke mortality (P = 0.007) was increased significantly by 100 mmol/day increment of sodium intake. Furthermore, low sodium intake was associated with an increased risk of cardiac death (P = 0.003), while moderate (P < 0.001) or heavy (P = 0.001) sodium intake was associated with an increased risk of stroke mortality. Conclusions These findings suggested that sodium intake by 100 mmol/d increment was associated with an increased risk of stroke incidence and stroke mortality. Furthermore, low sodium intake was related to an increased cardiac death risk, while moderate or heavy sodium intake was related to an increased risk of stroke mortality

Nonsingular fast terminal sliding mode control for two-stage converters of AC island photovoltaic microgrid

Taking into account almost all kinds of variations and uncertainties to which AC island photovoltaic (PV) microgrid is often subjected, this paper proposes a new nonsingular fast terminal sliding mode control (NFTSMC) strategy for two-stage converters to enhance robustness against those disturbances and improve system dynamic performance. Firstly, to effectively decrease the adverse effect on the system from intermittent solar irradiation and uncertain environmental temperature, a NFTSMC cascaded with perturb and observe (P&amp;O) scheme is put forward for fore-stage DC/DC converter, and PV output voltage is controlled to track its reference and thus maximum power point tracking (MPPT) performance is improved. Then, to significantly decrease the adverse effect on the system from variations of load and LC filter parameters, by incorporating an extended state observer (ESO) into NFTSMC, an ESO-based NFTSMC scheme is proposed for post-stage DC/AC converter, and the load voltage is regulated to track its reference and thus system robustness is strengthened, in which ESO is designed to replace load current sensor and thus reduce hardware cost. By using global terminal attractor without discontinuous switching function, the proposed NFTSMC strategy can not only strengthen system robustness but also improve system dynamic performance. Lastly, on account of the variations of PV generation and load demand, a conventional double-loop PI scheme is put into use for bidirectional DC/DC converter and thus system power balance is ensured. Comprehensive MATLAB simulation and StarSim/Hardware experiment results show that the proposed NFTSMC strategy for two-stage converters can overcome negative effects caused by various internal and external disturbances, and thus enable island PV microgrid to operate reliably and supply high-quality AC power.<br/