The potential role of iron-carbon micro-electrolysis materials in curtailing lag-phase stimulates kitchen waste anaerobic digestion at different solid contents: Performance, synergistic effect and microbial response.

High-solid anaerobic digestion (HSAD) of kitchen waste was generally faced to the common problems such as systemic acidification, prolonged lag-phase time and low methane production. Iron-carbon micro-electrolysis (ICME) materials exhibited advantages that porous structure, large specific surface area and excellent conductivity. It was beneficial for organic compounds to hydrolysis. Moreover, ICME materials could establish direct interspecies electron transfer (DIET) pathway between bacteria and methanogens. ICME materials were commonly used to enhance the AD of wastewater, but they were rarely applied to HSAD of kitchen waste. In this study, ICME materials were utilized to enhance HSAD of kitchen waste at different solid content conditions. The results showed that the highest cumulative biogas yield (705.23 mL/g VS) was obtained in the experimental group (TS = 10%), which was 94.15% higher than that of the control group. At the same time, the addiction of ICME could shorten lag-phase time. Electrochemical characteristics and XPS analysis showed that ICME materials promoted the release of Fe2+ in the AD system and acceleration of direct interspecies electron transfer between microorganisms. Microbial community analysis showed that ICME materials enriched electroactive bacteria (Proteiniphilum), Methanosarcina, Methanobrevibacter and Methanofollis. Functional gene prediction revealed that ICME materials increased the relative abundance of carbohydrate transport and metabolism and coenzyme transport and metabolism. It provided a potential measure to treat kitchen waste.

DNA damage-mediated FTO downregulation promotes CRPC progression by inhibiting FOXO3a via an m6A-dependent mechanism.

Polyadenosine diphosphate-ribose polymerase inhibitors (PARPi) represent a promising novel treatment for castration-resistant prostate cancer (CRPC) with encouraging results. However, the combination targets in CRPC remain largely unexplored. N6-methyladenosine (m6A) has been shown to play a crucial role in cancer progression and DNA damage response. Here, we observed a higher overall level of m6A and a downregulation of Fat mass and obesity-associated protein (FTO), which correlated with unfavorable clinicopathological parameters in prostate cancer (PCa). Functionally, reduced FTO promotes PCa growth, while overexpression of FTO has the opposite effect. Mechanistically, FOXO3a was identified as the downstream target of FTO in PCa. FTO downregulates the expression of FOXO3a in an m6A-dependent manner, leading to the degradation of its mRNA. Importantly, DNA damage can degrade FTO through the ubiquitination pathway. Finally, we found that overexpression of FTO can enhance the effect of PARPi on PCa. Therefore, our findings may provide insight into novel therapeutic approaches for CRPC.

APC/C-regulated CPT1C promotes tumor progression by upregulating the energy supply and accelerating the G1/S transition.

BACKGROUND: In addition to functioning as a precise monitoring mechanism in cell cycle, the anaphase-promoting complex/cyclosome (APC/C) is reported to be involved in regulating multiple metabolic processes by facilitating the ubiquitin-mediated degradation of key enzymes. Fatty acid oxidation is a metabolic pathway utilized by tumor cells that is crucial for malignant progression; however, its association with APC/C remains to be explored. METHODS: Cell cycle synchronization, immunoblotting, and propidium iodide staining were performed to investigate the carnitine palmitoyltransferase 1 C (CPT1C) expression manner. Proximity ligation assay and co-immunoprecipitation were performed to detect interactions between CPT1C and APC/C. Flow cytometry, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H-tetrazolium, inner salt (MTS) assays, cell-scratch assays, and transwell assays and xenograft transplantation assays were performed to investigate the role of CPT1C in tumor progression in vitro and in vivo. Immunohistochemistry was performed on tumor tissue microarray to evaluate the expression levels of CPT1C and explore its potential clinical value. RESULTS: We identified CPT1C as a novel APC/C substrate. CPT1C protein levels exhibited cell cycle-dependent fluctuations, peaking at the G1/S boundary. Elevated CPT1C accelerated the G1/S transition, facilitating tumor cell proliferation in vitro and in vivo. Furthermore, CPT1C enhanced fatty acid utilization, upregulated ATP levels, and decreased reactive oxygen species levels, thereby favoring cell survival in a harsh metabolic environment. Clinically, high CPT1C expression correlated with poor survival in patients with esophageal squamous cell carcinoma. CONCLUSIONS: Overall, our results revealed a novel interplay between fatty acid utilization and cell cycle machinery in tumor cells. Additionally, CPT1C promoted tumor cell proliferation and survival by augmenting cellular ATP levels and preserving redox homeostasis, particularly under metabolic stress. Therefore, CPT1C could be an independent prognostic indicator in esophageal squamous cell carcinoma.

Effect of alkali pretreatment time on kitchen waste anaerobic digestion performance enhanced by alkali pretreatment combined with bentonite: performance enhancement, microbial community structure, and functional gene analysis.

Kitchen waste was mainly composed of carbohydrates, lipids, and proteins. Anaerobic digestion (AD) of kitchen waste usually occurred acidification and further deteriorated. In our previous study, alkali pretreatment combined with bentonite (AP/Be) treatment was proved to enhance high solid AD of kitchen waste. However, effects of AP time on AP/Be were not yet studied. This study investigated the effects of AP time on AP/Be treatment on enhancing high solid AD. The results showed that compared with the control group, the cumulative methane production rate could be increased by 3.30 times (149.7 mL CH4/g VS) and the volatile solids (VS) reduction rate increased by 63.36%. Microbial community analysis showed that the relative abundance of Methanosarcina and Methanosaeta were increased from 6.49 and 7.83% to 47.14 and 16.39% respectively. Predictive functional analysis showed that AP/Be treatment increased the abundance of energy production and conversion, coenzyme transport, and metabolism. This study revealed the potential mechanism of AP/Be enhanced kitchen waste AD performance and AP/Be was a potential strategy to strengthen AD.

Aberrant expression of PELI1 caused by Jagged1 accelerates the malignant phenotype of pancreatic cancer.

Pancreatic cancer is one of the most aggressive cancers. PELI1 has been reported to promote cell survival and proliferation in multiple cancers. As of now, the role of PELI1 in pancreatic cancer is largely unknown. Here, we found that the PELI1 mRNA was higher expressed in pancreatic tumor tissues than in adjacent normal tissues, and the high PELI1 level in pancreatic cancer patients had a short survival time compared with the low level. Moreover, the results showed that PELI1 promoted cell proliferation, migration, and invasion, and inhibited apoptosis in vitro. Xenograft tumor experiments were used to determine the biological function of PELI1, and the results showed that PELI1 promoted tumor growth in vivo. Additionally, we found that Jagged1 activated PELI1 transcription in pancreatic cancer cells. To sum up, our results show that PELI1 affects the malignant phenotype of pancreatic cancer.

Microbial response behavior to powdered activated carbon in high-solids anaerobic digestion of kitchen waste: Metabolism and functional prediction analysis.

Anaerobic digestion (AD) can not only treat organic waste, but also recycle energy. However, high-solids AD of kitchen waste usually failed due to excessive acidification. In this study, the effect of activated carbon (AC) on kitchen waste AD performance was investigated under high-solids conditions (total solids contents = 15%). The results showed that efficiencies of acidogenesis and methanogenesis were promoted in presence of moderate concentration (50 g/L > AC >5 g/L), but high concentration (AC >70 g/L) weakened AD performance. Moreover, AC addition enhanced the methane production rate from 66.0 mL/g VS to 231.50 mL/g VS, i.e., up to 250.7%. High-throughput sequencing results demonstrated that the abundance of electroactive DMER64 increased from less than 1%-29.7% (20 g/L AC). As AC gradually increased，aceticlastic methanogenesis changed to hydrogenotrophic pathway. Predicted functional analysis indicated that AC can enhance abundances of energy and inorganic ion metabolism, resulting in high methane production.

Enhanced anaerobic digestion of kitchen waste at different solids content by alkali pretreatment and bentonite addition: Methane production enhancement and microbial mechanism.

High solid anaerobic digestion (AD) has been considered as a promising and sustainable technology for treating kitchen waste. To enhance AD of kitchen waste, alkali pretreatment and bentonite addition treatment (AP/Be) was performed on kitchen waste, and microbial community was investigated at different total solids (TS) content (10%, 13%, 19%, 22% and 25%). The results indicated that after AP/Be treatment, methane yield was as high as 198 mL CH4/g volatile solid (VS), which increased by 236% as the control. Moreover, microbial community analysis revealed that AP/Be treatment enriched bacterial microbial diversity. At TS of 10%, AP/Be treatment enhanced the hydrogenotrophic methanogens (Methanobacterium) significantly. In addition, the dominant methanogenic pathways changed at different TS content. These results demonstrated AP/Be treatment had a positive effect on methanogenesis during kitchen waste anaerobic digestion process. This study threw new insights towards enhancing kitchen waste anaerobic digestion, as well as the microbial mechanism.

[Panax notoginseng: a review on chemical components, chromatographic analysis, P. notoginseng extracts, and pharmacology in recent five years].

As a famous and precious Chinese medicinal material, Panax notoginseng(PN) has been commonly used for a long history in China. As reported, PN exhibits significant pharmacological actions in protecting cardiocerebral vascular system and nervous system and suppressing tumors. In recent years, with the innovation in ideas, as well as the development of methods and equipment, PN has been extensively investigated, and notable progress has been made. This paper reviewed the advancements of PN in recent five years from chemical components, chromatographic analysis, P. notoginseng extracts, and pharmacology, in which the application of PN extracts in quality control was first summarized. The present study aims to provide a theoretical basis for quality control, product development, and rational medication of PN.

Long non-coding RNA SMASR inhibits the EMT by negatively regulating TGF-ß/Smad signaling pathway in lung cancer.

TGF-ß/Smad signaling pathway plays an important role in EMT during cancer progression. Long non-coding RNAs (lncRNAs) are involved in various behaviors of cancer cells, including EMT. Here, we report a novel lncRNA adjacent to Smad3, named Smad3-associated long non-coding RNA (SMASR). SMASR is downregulated by TGF-ß via Smad2/3 in lung cancer cells. Knockdown of SMASR induces EMT and increases the migration and invasion of lung cancer cells. Moreover, knockdown of SMASR promotes the phosphorylation of Smad2/3. Mechanistically, SMASR interacts with Smad2/3 and inhibits the expression of TGFBR1, the TGF-ß type I receptor responsible for phosphorylation of Smad2/3, thus leading to inactivation of TGF-ß/Smad signaling pathway. Clinically, SMASR is downregulated in lung cancer tissues. Collectively, our findings prove a critical role of SMASR in EMT of lung cancer by forming a negative feedback loop with TGF-ß/Smad signaling pathway.

Comorbidity of Pain and Depression in a Lumbar Disc Herniation Model: Biochemical Alterations and the Effects of Fluoxetine.

of Background Data: Depression is one of the most common comorbidities in patients with chronic low back pain. However, the mechanisms of depression in chronic low back pain patients and the effect of antidepressants on the comorbidity of pain and depression need to be further explored. The establishment of the appropriate animal models and of more effective therapies is critical for this comorbidity. Lumbar disc herniation (LDH) is the most common disease that causes low back pain. The current study examined whether an LDH model shows behavioral and biochemical alterations that are in accordance with the characteristics of the comorbidity of pain and depression and tested the effect of fluoxetine (FLX) on these measures. Objective: The current study examined whether an LDH model showed the behavioral and biochemical alterations that were in accordance with the characteristics of the comorbidity of pain and depression and tested the effect of FLX on these measures. Methods: The LDH animal model was generated by the implantation of the autologous nucleus pulposus on the left L5 nerve root just proximal to the dorsal root ganglion in Wistar rats. Pain intensity was evaluated by mechanical allodynia and thermal hyperalgesia, and changes in depressive behavior were examined by the taste preference and forced swim tests. Hippocampal serotonin (5-HT) levels were measured by liquid chromatography-mass spectrometry, and tumor necrosis factor-α (TNF-α) mRNA was quantified using real-time reverse transcriptase PCR. Results: LDH resulted in chronic pain, which further induced depressive behavior that persisted for 6 weeks after surgery. There were decreased 5-HT concentrations and upregulated TNF-α mRNA levels that were accompanied by behavioral changes. FLX treatment improved depressive behavior and moderately alleviated pain through increased 5-HT concentrations, and inhibited TNF-α mRNA expression. Conclusions: In summary, our studies provide initial evidence that the LDH chronic pain model might serve as a model of the comorbidity of low back pain and depression. The finding that FLX improved depressive behavior and pain through normalized 5-HT concentrations and TNF-α mRNA expression establishes the initial mechanism of the comorbidity of pain and depression.

Special AT-rich sequence-binding protein 2 acts as a negative regulator of stemness in colorectal cancer cells.

AIM: To find the mechanisms by which special AT-rich sequence-binding protein 2 (SATB2) influences colorectal cancer (CRC) metastasis. METHODS: Cell growth assay, colony-forming assay, cell adhesion assay and cell migration assay were used to evaluate the biological characteristics of CRC cells with gain or loss of SATB2. Sphere formation assay was used to detect the self-renewal ability of CRC cells. The mRNA expression of stem cell markers in CRC cells with upregulated or downregulated SATB2 expression was detected by quantitative real-time polymerase chain reaction. Chromatin immunoprecipitation (ChIP) was used to verify the binding loci of SATB2 on genomic sequences of stem cell markers. The Cancer Genome Atlas (TCGA) database and our clinical samples were analyzed to find the correlation between SATB2 and some key stem cell markers. RESULTS: Downregulation of SATB2 led to an aggressive phenotype in SW480 and DLD-1 cells, which was characterized by increased migration and invasion abilities. Overexpression of SATB2 suppressed the migration and invasion abilities in SW480 and SW620 cells. Using sequential sphere formation assay to detect the self-renewal abilities of CRC cells, we found more secondary sphere formation but not primary sphere formation in SW480 and DLD-1 cells after SATB2 expression was knocked down. Moreover, most markers for stem cells such as CD133, CD44, AXIN2, MEIS2 and NANOG were increased in cells with SATB2 knockdown and decreased in cells with SATB2 overexpression. ChIP assay showed that SATB2 bound to regulatory elements of CD133, CD44, MEIS2 and AXIN2 genes. Using TCGA database and our clinical samples, we found that SATB2 was correlated with some key stem cell markers including CD44 and CD24 in clinical tissues of CRC patients. CONCLUSION: SATB2 can directly bind to the regulatory elements in the genetic loci of several stem cell markers and consequently inhibit the progression of CRC by negatively regulating stemness of CRC cells.