Photobacterium pectinilyticum sp. nov., a novel bacterium isolated from surface seawater of Qingdao offshore.

A Gram-staining-negative, facultative aerobic, motile strain, designated strain ZSDE20T, was isolated from the surface seawater of Qingdao offshore. Phylogenetic analysis of the 16S rRNA gene of strain ZSDE20T, affiliated it to the genus Photobacterium. It was closely related to Photobacterium lutimaris DF-42 T (98.92% 16S rRNA gene sequence similarity). Growth occurred at 4-28ºC (optimum 28ºC), pH 1.0-7.0 (optimum 7.0) and in the presence of 1-7% (w/v) NaCl (optimum 3%). The dominant fatty acids were summed feature 3 (C16:1 ω7c or/and C16:1 ω6c, 34.23%), summed feature 8 (C18:1 ω7c and C18:1 ω6c, 10.36%) and C16:0 (20.05%). The polar lipids of strain ZSDE20T comprised phosphatidylethanolamine, phosphatidylcholine, lyso-phosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol dimannoside, phosphatidylinositol mannosides and two unknown lipids. The major respiratory quinone was ubiquinone-8 (Q-8). The DNA G + C content of strain ZSDE20T was 45.6 mol%. Average nucleotide identity (ANI) values between ZSDE20T and its reference species were lower than the threshold for species delineation (95-96%); in silico DNA-DNA hybridization further showed that strain ZSDE20T had less than 70% similarity to its relatives. Based on the polyphasic evidences, strain ZSDE20T is proposed as representing a novel species of the genus Photobacterium, for which the name Photobacterium pectinilyticum sp. nov. is proposed. The type strain is ZSDE20T (= MCCC 1K06283T = KCTC 82885 T).

Safety and effectiveness of tunneled peripherally inserted central catheters versus conventional PICC in adult cancer patients.

OBJECTIVES: This study aimed to compare the safety and effectiveness of tunneled peripherally inserted central catheters (T-PICC) vs. conventional PICCs (C-PICC) in adult cancer patients. METHODS: A multicentre randomized controlled trial was conducted between April 2021 and January 2022 in seven hospitals in China. 564 participants were randomly assigned to T-PICC or C-PICC. These data were collected and compared: the baseline characteristics and catheterization-related characteristics, periprocedural complications, and long-term complications. RESULTS: Five-hundred fifty-three participants (aged, 52.6 ± 12.3 years; female, 39.1%) were ultimately analyzed. No significant differences in periprocedural complications were found between the T-PICC and C-PICC groups (all p > 0.05). Compared with C-PICC, T-PICC significantly reduced the incidence of long-term complications (26.4% vs. 39.9%, p < 0.001). Specifically, reduced complications were found in central line-associated bloodstream infection (1.8% vs. 5.1%, p = 0.04), thrombosis (1.1% vs. 4.0%, p = 0.03), catheter dislodgement (4.7% vs. 10.1%, p = 0.01), non-infectious oozing (17.3% vs. 28.6%, p = 0.002), local infection (3.6% vs. 7.6%, p = 0.04), skin irritation (6.1% vs. 10.9%, p = 0.046), and reduced unplanned catheter removal (2.2% vs. 7.2%, p = 0.005). No significant differences were found between T-PICC and C-PICC regarding catheter occlusion (6.5% vs. 5.8%, p = 0.73) or skin damage (2.2% vs. 2.9%, p = 0.58). CONCLUSION: T-PICC is safe and effectively reduces long-term complications. CLINICAL RELEVANCE STATEMENT: The tunneled technique is effective in reducing PICC-related long-term complications. Thus, it is recommended for cancer patients at high risk of PICC-related complications. TRIAL REGISTRATION: The registration number on https://www.chictr.org.cn/ is ChiCTR2100044632. The name of the trial registry is "A multicenter randomized controlled study of clinical use of tunneled vs. non-tunneled PICC". KEY POINTS: Cather-related complications are associated with the technique of catheterization. Compared with conventional PICC, tunneled PICC reduced catheter-related long-term complications. Tunneled PICC placement provides an alternative catheterization method for cancer patients.

Comprehensive analysis of m6A regulators associated with immune infiltration in Hepatitis B virus-related hepatocellular carcinoma.

BACKGROUND: N6A methylation (m6A) is a significant epigenetic modification that critically impacts post-transcriptional regulation and tumor occurrence and development. While previous studies have identified a role for epigenetic regulation in hepatocellular carcinoma (HCC), the potential function of the m6A cluster in Hepatitis B virus (HBV)-related HCC remains unclear. METHODS: The related information was downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Based on the expression of 20 m6A regulators, we comprehensively evaluated the m6A clusters and systematically explored the correlation between these clusters and immune cell infiltration characteristics of the tumor microenvironment (TME). The patients were divided into low- and high-m6A score groups. Then, the immune cell infiltration, chemokines, and cytokines levels, and drug sensitivity were further explored between the two groups. RESULTS: The m6A cluster predicted a better prognosis that was accompanied by increased immune cell infiltration. Using these results, an m6A score was established that could predict overall survival, immune checkpoints, and clinical treatments for patients with HBV-related HCC. This study demonstrated that m6A modifications affected tumorigenesis, TME, and the prognosis of patients with HBV-related HCC. CONCLUSION: A comprehensive assessment of m6A patterns could improve the current understanding of immune cell infiltration patterns and inform the development of individualized cancer treatments.

A meta-analysis of the neural substrates of monetary reward anticipation and outcome in alcohol use disorder.

The capacity to anticipate and detect rewarding outcomes is fundamental for the development of adaptive decision-making and goal-oriented behavior. Delineating the neural correlates of different stages of reward processing is imperative for understanding the neurobiological mechanism underlying alcohol use disorder (AUD). To examine the neural correlates of monetary anticipation and outcome in AUD patients, we performed two separate voxel-wise meta-analyses of functional neuroimaging studies, including 12 studies investigating reward anticipation and 7 studies investigating reward outcome using the monetary incentive delay task. During the anticipation stage, AUD patients displayed decreased activation in response to monetary cues in mesocortical-limbic circuits and sensory areas, including the ventral striatum (VS), insula, hippocampus, inferior occipital gyrus, supramarginal gyrus, lingual gyrus and fusiform gyrus. During the outcome stage, AUD patients exhibited reduced activation in the dorsal striatum, VS and insula, and increased activation in the orbital frontal cortex and medial temporal area. Our findings suggest that different activation patterns are associated with nondrug rewards during different reward processing stages, potentially reflecting a changed sensitivity to monetary reward in AUD.

Identification of genes modified by N6-methyladenosine in patients with colorectal cancer recurrence.

Background: Recent studies demonstrate that N6-methyladenosine (m6A) methylation plays a crucial role in colorectal cancer (CRC). Therefore, we conducted a comprehensive analysis to assess the m6A modification patterns and identify m6A-modified genes in patients with CRC recurrence. Methods: The m6A modification patterns were comprehensively evaluated by the NMF algorithm based on the levels of 27 m6A regulators, and tumor microenvironment (TME) cell-infiltrating characteristics of these modification patterns were systematically assessed by ssGSEA and CIBERSORT algorithms. The principal component analysis algorithm based on the m6A scoring scheme was used to explore the m6A modification patterns of individual tumors with immune responses. The weighted correlation network analysis and univariable and multivariable Cox regression analyses were applied to identify m6A-modified gene signatures. The single-cell expression dataset of CRC samples was used to explore the tumor microenvironment affected by these signatures. Results: Three distinct m6A modification patterns with significant recurrence-free survival (RFS) were identified in 804 CRC patients. The TME characterization revealed that the m6A modification pattern with longer RFS exhibited robust immune responses. CRC patients were divided into high- and low-score subgroups according to the m6A score individually, which was obtained from the m6A-related signature genes. The patients with low m6A scores had both longer RFS and overall survival (OS) with altered immune cell infiltration. Notably, m6A-modified genes showed significant differences related to the prognosis of CRC patients in the meta-GEO cohort and TCGA cohort. Single-cell expression indicated that ALVRL1 was centrally distributed in endothelial tip cells and stromal cells. Conclusion: The m6A modification plays an indispensable role in the formation of TME diversity and complexity. Importantly, the signatures (TOP2A, LRRC58, HAUS6, SMC4, ACVRL1, and KPNB1) were identified as m6A-modified genes associated with CRC recurrence, thereby serving as a promising predictive biomarker or therapeutic target for patients with CRC recurrence.

The Role and Therapeutic Potential of Macropinocytosis in Cancer.

Macropinocytosis, a unique endocytosis pathway characterized by nonspecific internalization, has a vital role in the uptake of extracellular substances and antigen presentation. It is known to have dual effects on cancer cells, depending on cancer type and certain microenvironmental conditions. It helps cancer cells survive in nutrient-deficient environments, enhances resistance to anticancer drugs, and promotes invasion and metastasis. Conversely, overexpression of the RAS gene alongside drug treatment can lead to methuosis, a novel mode of cell death. The survival and proliferation of cancer cells is closely related to macropinocytosis in the tumor microenvironment (TME), but identifying how these cells interface with the TME is crucial for creating drugs that can limit cancer progression and metastasis. Substantial progress has been made in recent years on designing anticancer therapies that utilize the effects of macropinocytosis. Both the induction and inhibition of macropinocytosis are useful strategies for combating cancer cells. This article systematically reviews the general mechanisms of macropinocytosis, its specific functions in tumor cells, its occurrence in nontumor cells in the TME, and its application in tumor therapies. The aim is to elucidate the role and therapeutic potential of macropinocytosis in cancer treatment.

Identification of circadian clock genes as regulators of immune infiltration in Hepatocellular Carcinoma.

Background: Multiple studies have reported that the immune system is under the control of a circadian clock, especially in cancers, but how circadian clock genes shape tumor immune cell infiltration in hepatocellular carcinoma (HCC) remains unclear. Methods: The rhythmicity of circadian clock genes was investigated using the GETx database. The expression and methylation level of circadian clock genes in HCC and paracancerous was evaluated using the GETx and TCGA databases. The differential expression of circadian clock genes in HCC was analyzed using the "limma" package of the R 4.0.4 software. The prognosis of each circadian clock gene was accessed by Kaplan-Meier survival analysis and Cox proportional hazards regression analysis. Quantitative real-time PCR and immunohistochemistry (IHC) was carried out to confirm the results. The relationship between circadian rhythm and immune infiltration in HCC was evaluated using the TIMER database and the CIBERSORT algorithm. Results: In addition to RORA, RORB, and ARNTL2, there was a rhythmic expression of other circadian clock genes in liver tissue. The correlation between the expression of circadian clock genes differed when comparing HCC and liver tissue. HCC patients who express low levels of PER-1and CRY2 had a poor overall survival (OS). In contrast, patients with higher expression of NPAS2 had a poor prognosis. In HCC, the expression of the PER-1, CRY2, and NPAS2 genes was closely related to immune infiltration. Conclusion: Our study indicated the disruption of the expression of circadian clock-regulated genes in HCC and identified PER-1, CRY2, and NPAS2 as independent predictors of survival. These genes may be applied as candidate molecular targets for diagnosis and therapy of HCC.

Identification of Genes Related to 5-Fluorouracil Based Chemotherapy for Colorectal Cancer.

Background: Colorectal cancer (CRC) is one of the most common malignancies and its incidence and mortality are increasing yearly. 5-Fluorouracil (5-FU) has long been used as a standard first-line treatment for CRC patients. Although 5-FU-based chemotherapy is effective for advanced CRC, the consequent resistance remains a key problem and causes the poor prognosis of CRC patients. Thus, there is an urgent need to identify new biomarkers to predict the response to 5-FU-based chemotherapy. Methods: CRC samples were retrieved from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA). The immune-related genes were retrieved from the ImmPort database. Single-cell sequencing results from colorectal cancer were obtained by the ArrayExpress database. 5-FU resistance-related genes were filtered and validated by R packages. ESTIMATE algorithms were used to assess the tumor microenvironment (TME). KEGG and GO analysis were performed to explore the biological signaling pathway for resistant-response patients and sensitive-response patients in the tumor microenvironment. pRRophetic algorithms were used to predict 5-FU sensitivity. GSEA and GSVA analysis was performed to excavate the biological signaling pathway of the RBP7 gene. Results: Nine immune-related genes were identified to be associated with 5-FU resistance and poor disease-free survival (DFS) of CRC patients and the signature of these genes was developed in a DFS-prognostic model. Four immune-related genes were determined to be associated with 5-FU resistance and overall survival (OS) of CRC patients. The signature of these genes was developed an OS-prognostic model. ESTIMATE scores showed a significant difference between 5-FU resistant and 5-FU sensitive CRC patients. Resistant-response patients and sensitive-response patients to 5-FU based chemotherapy showed different GO and KEGG enrichment on the tumor microenvironment. RBP7, as a tumor immune microenvironment (TIME) related gene, was found to have the potential of predicting chemotherapy resistance and poor prognosis of CRC patients. GSEA analysis showed multiple signaling differences between the high and low expression of RBP7 in CRC patients. Hypoxia and TNFα signaling via NFκB gene sets were significantly different between chemotherapy resistant (RBP7High) and chemotherapy sensitive (RBP7Low) patients. Single-cell RNA-seq suggested RBP7 was centrally distributed in endothelial stalk cells, endothelial tip cells, and myeloid cells. Conclusions: Immune-related genes will hopefully be potential prognostic biomarkers to predict chemotherapy resistance for CRC. RBP7 may function as a tumor microenvironment regulator to induce 5-FU resistance, thereby affecting the prognosis of CRC patients.

Emerging Technologies for the Detection of Cancer Micrometastasis.

The most efficient way to treat tumors is through surgery. However, many cancer patients have a poor prognosis even when they undergo radical excision at an early stage. Micrometastasis is one of the most critical factors that induced this situation. Undetected micrometastasis can lead to the failure of initial treatment. Therefore, preoperative and intraoperative detection of micrometastasis could have a significant clinical influence on the prognosis and optimal therapy for cancer patients. Additionally, to achieve this goal, researchers have aimed to create more effective detection technologies. Herein, we classify the currently reported micrometastasis detection technologies, introduce some representative samples for each technology, including the limitations, and provide future directions to overcome the limitations.

A Novel Diagnostic and Therapeutic Strategy for Cancer Patients by Integrating Chinese Medicine Syndrome Differentiation and Precision Medicine.

Applying Chinese medicine (CM) is an important strategy for malignant tumor treatment in China. One of the significant characteristics of CM is to treat diseases based on syndrome differentiation. For Western medicine, it is of important clinical significance to formulate guidelines for the diagnosis and treatment of cancer patients based on the characteristics of disease differentiation. In Chinese clinical practice, the combination of disease differentiation and syndrome differentiation is an important feature for cancer treatment in the past. Currently, molecular profiling and genomic analysis-based precision medicine optimizes the anticancer drug design and holds the greatest success in treating cancer patients. Therefore, we want to know which populations of cancer patients can benefit more from CM treatment if the theory of precision medicine is applied to CM clinical practice. So, we developed a novel diagnostic and therapeutic strategy "disease-syndrome differentiation-genomic profiling-prescriptions" for cancer patients by CM syndrome differentiation and precision medicine. As a result, this strategy has greatly enhanced the anti-tumor efficacy of CM and improved clinical outcomes for cancer patients with some gene mutations. Our idea will hopefully establish a novel approach for the inheritance and innovation of CM.

Exploring the Effect of Polyphyllin I on Hepatitis B Virus-related Liver Cancer through Network Pharmacology and in vitro Experiments.

AIM AND OBJECTIVE: To investigate the effect of Polyphyllin I (PPI) on HBV-related liver cancer through network pharmacology and in vitro experiments, and to explore its mechanism of action. MATERIALS AND METHODS: Use bioinformatics software to predict the active ingredient target of PPI and the disease target of liver cancer, and perform active ingredient-disease target analysis. The results of network pharmacology through molecular docking and in vitro experiments can be further verified. The HepG2 receptor cells (HepG2. 2. 15) were transfected with HBV plasmid for observation, with the human liver cancer HepG2 being used as the control. RESULTS: Bioinformatics analysis found that PPI had a total of 161 protein targets, and the predicted target and liver cancer targets were combined to obtain 13 intersection targets. The results of molecular docking demonstrated that PPI had a good affinity with STAT3, PTP1B, IL2, and BCL2L1. The results of the in vitro experiments indicated that the PPI inhibited cell proliferation and metastasis in a concentration-dependent manner (P<0.01). Compared with the vehicle group, the PPI group of 1.5, 3, and 6 µmol/L can promote the apoptosis of liver cancer to different degrees (P<0.01). CONCLUSION: The present study revealed the mechanism of PPI against liver cancer through network pharmacology and in vitro experiments. Its mechanism of action is related to the inhibition of PPI on the proliferation of HBV-related liver cancer through promoting the apoptosis of liver cancer cells. Additionally, in vitro experiments have also verified that PPI can promote the apoptosis of HepG2 and HepG2.2.15 cells.

Neurobiological correlates of cue-reactivity in alcohol-use disorders: A voxel-wise meta-analysis of fMRI studies.

Altered brain responses to alcohol-associated stimuli are a neural hallmark of alcohol-use disorder (AUD) and a promising target for pharmacotherapy. However, findings in cue-reactivity based functional MRI (fMRI) studies are inconclusive. To investigate the neural substrates of cue-reactivity and their relevance to treatment outcomes, alcohol craving and relapse in AUD patients, we performed five meta-analyses using signed differential mapping software. Our meta-analysis revealed that alcohol cues evoke greater cue-reactivity than neutral cues in the mesocorticolimbic circuit and lower reactivity in the parietal and temporal regions in AUD patients. Compared to controls, AUD individuals displayed hyperactivations in the medial prefrontal cortex and anterior/middle part of the cingulate cortex. After receiving AUD treatment, AUD patients exhibited greater activations in the precentral gyrus but reduced activations in the bilateral caudate nucleus, insula, right DLPFC, and left superior frontal gyrus. No significant results were found in cue-reactivity correlates of alcohol craving and relapse. Our results implicate cue-induced abnormalities in corticostriatal-limbic circuits may underline the pathophysiology of AUD, and have translational value for treatment development.

Exploring the effect of Gupi Xiaoji Prescription on hepatitis B virus-related liver cancer through network pharmacology and in vitro experiments.

AIM AND OBJECTIVE: To study the effect of Gupi Xiaoji Prescription (GXP) on hepatitis B virus(HBV)-related liver cancer through network pharmacology coupled with in vitro experiments and explore their related mechanisms. MATERIALS AND METHODS: Gupi Xiaoji Prescription's chemical constituents and the action targets of its six medicinal components were identified using several databases. These included the Traditional Chinese Medicine Systems Pharmacology Database （TCMSP), the Bioinformatics Analysis Tool for Molecular mechANism of TCM (BATMAN-TCM), and the Traditional Chinese Medicine Integrated Database (TCMID), while GeneCards and OMIM were used to compile relevant liver cancer disease targets. Pathway enrichment of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), analysis of potential targets, and analysis of the enriched pathways in literature were executed in R. The Hepatocellular carcinoma (HCC)-derived HepG2.2.15 cell line stably expresses and replicates HBV. In vitro experiments with HepG2.2.15 were used to verify GXP's effects on HBV-related liver cancer, while the human liver cancer cell line HepG2 was used as the control. RESULTS: 171 active ingredients and 259 potential drug targets were screened from GXP, involving 181 pathways in vitro. These assays identified Polyphyllin I as an effective GXP component. Notably, GXP inhibited cell proliferation and metastasis in a concentration-dependent manner (P < 0.01). In comparison with the vehicle group, the fluorescence intensity of each drug group was significantly weakened (P < 0.01), while the drug group Mitofusins 1(MFN1) and protein expression level of Mitofusins 2 (MFN2) increased significantly. The protein expression level of Mitochondrial fission protein 1 (FIS1) and Optic Atrophy 1 (OPA1) also showed significant decreases (P < 0.01). Molecular docking revealed Fructus saponins I's high affinity with FIS1, MFN1, MFN2, and OPA1. CONCLUSION: The network pharmacology results indicate that Gupi Xiaoji Prescription may treat liver cancer by regulating mitochondrial division and fusion of key genes to disrupt liver cancer cells' energy metabolism. In vitro experiments also verified that GXP could inhibit the proliferation and migration of HepG2.2.15 cells by up-regulating MFN1 and MFN2, down-regulating the expression of FIS1 and OPA1 in addition to damaging mitochondria. Consistent with network pharmacology and molecular docking results, Polyphyllin I may be the most active compound of the formula's components. It also shows that Traditional Chinese medicine (TCM) plays a significant, targeted role in the treatment of HBV-related liver cancer.

Community characteristics and ecological roles of bacterial biofilms associated with various algal settlements on coastal reefs.

Bacterial biofilms, which are a group of bacteria attaching to and ultimately forming communities on reefs, perform essential ecological functions in coastal ecosystems. Particularly, they may attract or repulse the settling down of opportunistic algae. However, this phenomenon and the interaction mechanism are not fully understood. This study investigated reefs from the Changdao coastal zone to determine the structures and functions of bacterial biofilms symbiosing with various algae using high-throughput sequencing analysis. The Shannon diversity index of microbiota with algal symbiosis reached 5.34, which was higher than that of microbiota wherein algae were absent (4.80). The beta diversity results for 11 samples revealed that there existed a separation between bacterial communities on reefs with and without attached algae, while communities with similar algae clustered together. The taxa mostly associated with algae-symbiotic microbiota are the Actinobacteria phylum, and the Flavobacteriia and Gammaproteobacteria classes. The Cyanobacteria phylum was not associated with algae-symbiotic microbiota. As revealed by functional analysis, the bacteria mostly involved in the metabolism of sulfur were represented by brown and red algae in the biofilm symbiosis. Bacteria related to the metabolism of certain trace elements were observed only in specific groups. Moreover, phototrophy-related bacteria were less abundant in samples coexisting with algae. This study established the link between bacterial biofilms and algal settlements on costal reefs, and revealed the possible holobiont relationship between them. This may provide new technical directions toward realizing algal cultivation and management during the construction of artificial reef ecosystems.

microRNA-378 promotes autophagy and inhibits apoptosis in skeletal muscle.

The metabolic regulation of cell death is sophisticated. A growing body of evidence suggests the existence of multiple metabolic checkpoints that dictate cell fate in response to metabolic fluctuations. However, whether microRNAs (miRNAs) are able to respond to metabolic stress, reset the threshold of cell death, and attempt to reestablish homeostasis is largely unknown. Here, we show that miR-378/378* KO mice cannot maintain normal muscle weight and have poor running performance, which is accompanied by impaired autophagy, accumulation of abnormal mitochondria, and excessive apoptosis in skeletal muscle, whereas miR-378 overexpression is able to enhance autophagy and repress apoptosis in skeletal muscle of mice. Our in vitro data show that metabolic stress-responsive miR-378 promotes autophagy and inhibits apoptosis in a cell-autonomous manner. Mechanistically, miR-378 promotes autophagy initiation through the mammalian target of rapamycin (mTOR)/unc-51-like autophagy activating kinase 1 (ULK1) pathway and sustains autophagy via Forkhead box class O (FoxO)-mediated transcriptional reinforcement by targeting phosphoinositide-dependent protein kinase 1 (PDK1). Meanwhile, miR-378 suppresses intrinsic apoptosis initiation directly through targeting an initiator caspase-Caspase 9. Thus, we propose that miR-378 is a critical component of metabolic checkpoints, which integrates metabolic information into an adaptive response to reduce the propensity of myocytes to undergo apoptosis by enhancing the autophagic process and blocking apoptotic initiation. Lastly, our data suggest that inflammation-induced down-regulation of miR-378 might contribute to the pathogenesis of muscle dystrophy.

Fixation of CO2 along with bromopyridines on a silver electrode.

Resulting from the drastic increase of atmospheric CO2 concentration day by day, global warming has become a serious environmental issue nowadays. The fixation of CO2 to obtain desirable, economically competitive chemicals has recently received considerable attention. This work investigates the fixation of CO2 along with three bromopyridines via a facile electrochemical method using a silver cathode to synthesize picolinic acids, which are important industrial and fine chemicals. Cyclic voltammetry is employed to investigate the cyclic voltammetric behaviour of bromopyridines. In addition, systematic study is conducted to study the relationships between the picolinic acids' yield and the electrolysis conditions and intrinsic parameters. The results show that the target picolinic acids' yields are strongly dependent on various conditions such as solvent, supporting electrolyte, current density, cathode material, charge passed, temperature and the nature of the substrates. Moreover, in the studied electrode materials such as Ag, Ni, Ti, Pt and GC, electrolysis and cyclic voltammetry show that Ag has a good electrocatalytic effect on the reduction and carboxylation of bromopyridine. This facile electrochemical route for fixation of CO2 provides an indispensable reference for the conversion and utilization of CO2 under mild conditions.

Metabolic benefits of inhibition of p38α in white adipose tissue in obesity.

p38 has long been known as a central mediator of protein kinase A (PKA) signaling in brown adipocytes, which positively regulate the transcription of uncoupling protein 1 (UCP-1). However, the physiological role of p38 in adipose tissues, especially the white adipose tissue (WAT), is largely unknown. Here, we show that mice lacking p38α in adipose tissues display a lean phenotype, improved metabolism, and resistance to diet-induced obesity. Surprisingly, ablation of p38α causes minimal effects on brown adipose tissue (BAT) in adult mice, as evident from undetectable changes in UCP-1 expression, mitochondrial function, body temperature (BT), and energy expenditure. In contrast, genetic ablation of p38α in adipose tissues not only markedly facilitates the browning in WAT upon cold stress but also prevents diet-induced obesity. Consistently, pharmaceutical inhibition of p38α remarkably enhances the browning of WAT and has metabolic benefits. Furthermore, our data suggest that p38α deficiency promotes white-to-beige adipocyte reprogramming in a cell-autonomous manner. Mechanistically, inhibition of p38α stimulates the UCP-1 transcription through PKA and its downstream cAMP-response element binding protein (CREB), which form a positive feedback loop that functions to reinforce the white-to-beige phenotypic switch during cold exposure. Together, our study reveals that inhibition of p38α is able to promote WAT browning and confer metabolic benefits. Our study also indicates that p38α in WAT represents an exciting pharmacological target to combat obesity and metabolic diseases.

Distribution of bacterial communities along the spatial and environmental gradients from Bohai Sea to northern Yellow Sea.

The eutrophic Bohai Sea receives large amount of suspended material, nutrients and contaminant from terrestrial runoff, and exchanges waters with the northern Yellow Sea through a narrow strait. This coastal region provides an ideal model system to study microbial biogeography. We performed high-throughput sequencing to investigate the distribution of bacterial taxa along spatial and environmental gradients. The results showed bacterial communities presented remarkable horizontal and vertical distribution under coastal gradients of spatial and environmental factors. Fourteen abundant taxa clustered the samples into three distinctive groups, reflecting typical habitats in shallow coastal water (seafloor depth ≤ 20 m), sunlit surface layer (at water surface with seafloor depth >20 m) and bottom water (at 2-3 m above sediment with seafloor depth >20 m). The most significant taxa of each cluster were determined by the least discriminant analysis effect size, and strongly correlated with spatial and environmental variables. Environmental factors (especially turbidity and nitrite) exhibited significant influences on bacterial beta-diversity in surface water (at 0 m sampling depth), while community similarity in bottom water (at 2-3 m above sediment) was mainly determined by depth. In both surface and bottom water, we found bacterial community similarity and the number of OTUs shared between every two sites decreased with increasing geographic distance. Bacterial dispersal was also affected by phosphate, which was possible due to the high ratios of IN/IP in this coastal sea area.

Deficiency of p38α in macrophage ameliorates d-galactosamine/TNF-α-induced acute liver injury in mice.

Growing evidence suggests that hepatic macrophages play an important role in tissue repair after liver injury by coordinating the induction and resolution of inflammation, removing apoptotic cells, and promoting hepatocyte proliferation. Understanding the role of macrophages in the pathogenesis of liver injury will help pave the way to future therapeutics. Here, we investigated whether macrophage p38α plays a regulatory role in the tissue repair following d-galactosamine (GalN)/tumor necrosis factor-α (TNF-α)-induced acute liver injury. We found that macrophage p38α-deficient mice displayed decreased mortality and relieved liver injury as evident from less apoptosis, accelerated regeneration, decreased granulocytes recruitment, monocytes infiltration, and cytokine production after GalN/TNF-α treatment. Mechanistically, we found that p38 signaling was activated by lipopolysaccharide/interferon-γ treatment but not by inteleukin-4 stimulation, while pharmaceutical inhibition of p38α induced a shift in polarization from M1 macrophages to M2 macrophages. Together, our results indicated that macrophage p38α signaling is involved in the pathogenesis of liver injury induced by GalN/TNF-α, and inhibition of p38α signaling in macrophage could ameliorate liver injury and accelerate regeneration, probably by promoting the polarization of macrophages from the M1 phenotype to the M2 phenotype.

Ligand-dependent corepressor (LCoR) represses the transcription factor C/EBPß during early adipocyte differentiation.

Nuclear receptors (NRs) regulate gene transcription by recruiting coregulators, involved in chromatin remodeling and assembly of the basal transcription machinery. The NR-associated protein ligand-dependent corepressor (LCoR) has previously been shown to suppress hepatic lipogenesis by decreasing the binding of steroid receptor coactivators to thyroid hormone receptor. However, the role of LCoR in adipogenesis has not been established. Here, we show that LCoR expression is reduced in the early stage of adipogenesis in vitro LCoR overexpression inhibited 3T3-L1 adipocyte differentiation, whereas LCoR knockdown promoted it. Using an unbiased affinity purification approach, we identified CCAAT/enhancer-binding protein ß (C/EBPß), a key transcriptional regulator in early adipogenesis, and corepressor C-terminal binding proteins as potential components of an LCoR-containing complex in 3T3-L1 adipocytes. We found that LCoR directly interacts with C/EBPß through its C-terminal helix-turn-helix domain, required for LCoR's inhibitory effects on adipogenesis. LCoR overexpression also inhibited C/EBPß transcriptional activity, leading to inhibition of mitotic clonal expansion and transcriptional repression of C/EBPα and peroxisome proliferator-activated receptor γ2 (PPARγ2). However, LCoR overexpression did not affect the recruitment of C/EBPß to the promoters of C/EBPα and PPARγ2 in 3T3-L1 adipocytes. Of note, restoration of PPARγ2 or C/EBPα expression attenuated the inhibitory effect of LCoR on adipogenesis. Mechanistically, LCoR suppressed C/EBPß-mediated transcription by recruiting C-terminal binding proteins to the C/EBPα and PPARγ2 promoters and by modulating histone modifications. Taken together, our results indicate that LCoR negatively regulates early adipogenesis by repressing C/EBPß transcriptional activity and add LCoR to the growing list of transcriptional corepressors of adipogenesis.