Isolation and Characterization of Paracoccus maritimus sp. nov., from Intertidal Sediment.

A novel Paracoccus-related strain, designated YLB-12T, was isolated from a sediment sample from the tidal zone of Shapowei Port, Xiamen, Fujian Province, PR China. The novel strain is a Gram-stain-negative, short, rod-shaped, nonmotile, catalase- and oxidase-positive strain that grows at 10-37 °C and pH 5.0-9.0 in the presence of 0-12.0% (w/v) NaCl. Phylogenetic analysis of the 16S rRNA gene sequences indicated that this strain belongs to the genus Paracoccus and that its highest sequence similarity was to Paracoccus homiensis DD-R11T (98.5%), followed by Paracoccus zeaxanthinifaciens ATCC 21588T (97.4%), Paracoccus rhizosphaerae LMG 26205T (97.2%), Paracoccus beibuensis CGMCC 1.7295T (97.1%) and Paracoccus halotolerans CFH 90064T (97.0%). The DNA‒DNA hybridization values between strain YLB-12T and the five closely related type strains ranged from 20.4 to 22.4%. The genomic G+C content of strain YLB-12T was 63.7%. In addition to diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine and phosphatidylglycerol, the polar lipids of the strain YLB-12T also consisted of an unidentified glycolipid and four unidentified polar lipids. The cells contained summed feature 8 (C18: 1ω6c /C18: 1ω7c, 62.7%) as the major cellular fatty acid and ubiquinone-10 as the predominant menaquinone. On the basis of its phenotypic and genotypic characteristics, strain YLB-12T represents a novel species within the genus Paracoccus, for which the name Paracoccus maritimus sp. nov. is proposed. The type strain was YLB-12T (= MCCC 1A17213T = KCTC 82197T).

Efficacy of Internet-Based Cognitive Behavioral Therapy for Subthreshold Depression Among Older Adults in Institutional Long-Term Care Settings: Pragmatic Randomized Controlled Trial.

BACKGROUND: Subthreshold depression (sD) is prevalent in older populations in long-term care (LTC) settings, but psychological therapy in LTC settings in China is not readily available. Thus, internet-based cognitive behavioral therapy (ICBT) may be suitable for this population, but research on the efficacy of ICBT for older adults with sD, especially those living in LTC settings, is limited. OBJECTIVE: This study aimed to evaluate the efficacy and acceptability of ICBT treatment for sD among LTC residents in China. We also examined whether ICBT is as effective as group-based cognitive behavioral therapy (CBT) for treating sD in this population. METHODS: We conducted a pragmatic randomized controlled trial, which included 18 LTC institutions. A total of 354 participants were randomized to ICBT, group-based CBT, or a waiting list and were followed up for 12 months. The primary outcome was self-reported depressive symptoms on the Center for Epidemiological Studies Depression Scale (CES-D). Secondary outcomes were the scores of the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7-Item (GAD-7), and Geriatric Depression Scale (GDS). A mixed-effects model was used to assess the efficacy of ICBT. RESULTS: The ICBT group showed a significant improvement in self-reported depressive symptoms, which was maintained at the 12-month follow-up (all P<.001). The ICBT group exhibited a significantly larger reduction in the scores of the CES-D (Cohen d=0.07, 95% CI 0.04-0.09; P=.01), PHQ-9 (d=0.30, 95% CI 0.28-0.33; P<.001), GDS (d=0.10, 95% CI 0.08-0.13; P<.001), and GAD-7 (d=0.19, 95% CI 0.17-0.22; P<.001) compared with a waiting list at postintervention. ICBT had significantly stronger effects than CBT on the PHQ-9 and GAD-7 at postintervention (d=0.15, 95% CI 0.13-0.17; P<.001 and d=0.21, 95% CI 0.19-0.23; P<.001, respectively), 6-month follow-up (d=0.18, 95% CI 0.16-0.21; P<.001 and d=0.18, 95% CI 0.15-0.21; P<.001, respectively), and 12-month follow-up (d=0.15, 95% CI 0.11-0.19; P<.001 and d=0.18, 95% CI 0.14-0.21; P<.001, respectively). CONCLUSIONS: ICBT is a relatively effective and acceptable intervention for reducing depressive symptoms among Chinese LTC residents with sD. These findings indicate the usefulness of ICBT application for sD in LTC settings. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2000030697; https://www.chictr.org.cn/showproj.aspx?proj=50781.

Prognostic effects of previous cancer history on patients with major salivary gland cancer.

OBJECTIVES: To explore the prognostic effects of previous cancer history on patients with major salivary gland cancer (SGC). SUBJECTS AND METHODS: SGC patients with (sec-SGC) and without (one-SGC) a previous cancer from the SEER database were identified. Cox proportional hazards regression (CoxPH) models were used to compare the prognosis between sec-SGC and one-SGC patients. Subgroup analyses for sec-SGC patients by gender, previous cancer types, previous cancer histology, and cancer diagnosis interval (CDI) were performed. Two CoxPH models were constructed to distinguish sec-SGC patients with different prognostic risks. RESULTS: 9098 SGC patients were enrolled. Overall, sec-SGC patients (adjusted HR [aHR] = 1.26, p < 0.001), especially those with a CDI ≤ 5 years (aHR = 1.47, p < 0.001), had worse overall survival (OS) than one-SGC patients. In subgroup analysis, only sec-SGC patients with a previous head and neck cancer who were female (aHR = 2.38, p = 0.005), with a CDI ≤ 5 years (aHR = 1.65, p = 0.007) or with a previous squamous cell carcinoma (aHR = 6.52, p < 0.001) had worse OS. Our models successfully differentiated all sec-SGC patients into high-, intermediate- and low-risk groups with different prognosis. CONCLUSIONS: Sec-SGC patients with different previous cancer types, gender, CDI and previous cancer histology had varied prognosis. The models we constructed could help differentiate the prognosis of sec-SGC patients with different risks.

Discrepant assembly processes of prokaryotic communities between the abyssal and hadal sediments in Yap Trench.

Abyssal and hadal sediments represent two of the most type ecosystems on Earth and have the potential interactions with geochemistry. However, little is known about the prokaryotic community assembly and the response of prokaryotic communities to metal(loid)s in trench sediments due to the lack of adequate and appropriate samples. In this study, a systematic investigation combined the assembly mechanisms and co-occurrence patterns of prokaryotic communities between the hadal and abyssal sediments across the Yap Trench. The results revealed that the hadal prokaryotes had less species diversity, but more abundant function than the abyssal prokaryotes. The prokaryotic communities in the abyssal sediments had more core taxa than the hadal sediments. Twenty-one biomarkers mostly affiliated with Nitrosopumilaceae were detected using Random-Forests machine learning algorithm. Furthermore, stochasticity was dominant in the prokaryotic community assembly processes of the Yap Trench sediments. Meanwhile, homogeneous selection (32.6%-52.9%) belonging to deterministic processes governed the prokaryotic community assembly in hadal sediments with increasing of sediment depth. In addition to total nitrogen and total organic carbon, more metal(loid)s were significantly correlated with the prokaryotic community in the hadal sediments than that in the abyssal sediments. The hadal prokaryotic communities was most positively related to bismuth (r = 0.31, p < 0.01), followed by calcium, chromium, cerium, potassium, plumbum, scandium, titanium, and vanadium. Finally, co-occurrence networks revealed two potential dominant prokaryotic modules in Yap Trench sediments covaried across oceanographic zonation. By contrast, the hadal network had relatively more complexity, more bacterial taxa, and more associations among prokaryotic taxa, relative to the abyssal network. This study reveals potentially metal variables and community assembly mechanisms of the prokaryotic community in abyssal and hadal sediments and provides a better understanding on the prokaryotic diversity and ecology in trench sediment ecosystems.

Low Bone Mineral Density and the Risk of Benign Paroxysmal Positional Vertigo.

OBJECTIVE: This study aimed to comprehensively analyze the relationship between low bone mineral density (BMD) and the risk of benign paroxysmal positional vertigo (BPPV) based on the large prospective population-based UK Biobank (UKB) cohort. STUDY DESIGN: Prospective population-based cohort study. SETTING: The UKB. METHODS: This prospective cohort study included UKB participants recruited between 2006 and 2010 who had information on BMD and did not have BPPV before being diagnosed with low BMD. Univariable and multivariable logistic regression models were constructed to assess the association between low BMD (overall low BMD, osteopenia, and osteoporosis) and BPPV. We further conducted sex and age subgroup analysis, respectively. Finally, the effects of antiosteoporosis and female sex hormone medications on BPPV in participants with osteoporosis were evaluated. RESULTS: In total, 484,303 participants were included in the final analysis, and 985 developed BPPV after a maximum follow-up period of 15 years. Osteoporosis was associated with a higher risk of BPPV (odds ratio [OR] = 1.37, P = .0094), whereas osteopenia was not. Subgroup analyses suggested that the association between osteoporosis and BPPV was significant only in elderly females (≥60 years, OR = 1.51, P = .0007). However, no association was observed between antiosteoporosis or female sex hormone medications and BPPV in the participants with osteoporosis. CONCLUSION: Osteoporosis was associated with a higher risk of developing general BPPV, especially in females aged ≥ 60 years old, whereas osteopenia was not associated with BPPV.

Sinkhole Attack Defense Strategy Integrating SPA and Jaya Algorithms in Wireless Sensor Networks.

A sinkhole attack is characterized by low difficulty to launch, high destructive power, and difficulty to detect and defend. It is a common attack mode for wireless sensor networks. This paper proposes a sinkhole attack detection and defense strategy integrating SPA and Jaya algorithms in wireless sensor networks (WSNs). Then, combined with the SPA trust model, the trust values of suspicious nodes were calculated, and the attack nodes were detected. The Jaya algorithm was adopted to avoid the attacked area so that nodes can find the route to communicate with the real Sink, and attack nodes are isolated in the network to improve the capabilities of network directional defense. The simulation results show that the improved detection algorithm can effectively detect malicious nodes in the network, and the defense strategy implemented in the attacked area can improve the packet delivery rate, reduce network delay and energy consumption, and improve the security and reliability of wireless sensor networks.

Vibrio intestinalis sp. nov., isolated from intestine of seahorse.

A novel Gram-stain-negative, catalase- and oxidase-positive, facultatively anaerobic, and rod-shaped motile bacterial strain, designated as YLB-11T, was isolated from seahorse intestine. The 16S rRNA gene sequencing analysis showed that YLB-11T was most closely related Vibrio mytili LMG 19157T (98.9 % nucleotide sequence identity). Phylogenetic analysis placed strain YLB-11T within the genus Vibrio. The major cellular fatty acids were summed feature 3 (C16: 1 ω6c/C16 : 1 ω7c, 36.4 %), C16 : 0 (19.1 %) and summed feature 8 (C18:1 ω6c/C18:1 ω7c, 12.3 %). The DNA G+C content of YLB-11T was 44.7 mol %. The in silico DNA-DNA hybridization and average nucleotide identity values for whole-genome sequence comparisons between YLB-11T and related species were clearly below the thresholds used for the delineation of a novel species. Therefore, YLB-11T is considered to represent novel species of the genus Vibrio, for which the name Vibrio intestinalis sp. nov. is proposed. The type strain is YLB-11T (=MCCC 1A17441T=KCTC 72604T).

Application of CECT, CEMRI, and contrast-enhanced ultrasonography in the evaluation of renal cystic lesions: a systematic review and meta-analysis of retrospective studies.

The purpose of this meta-analysis was to investigate the role and effect of CECT, CEMRI and CEUS in the detection of renal cystic lesions, and to provide evidence-based basis for clinical examination and treatment. The Cochrane Library, EMBASE, and PUBMED databases were searched from January 2012 to December 2022 for article retrieval. The articles on the treatment of cystic renal disease were searched. According to the inclusion criteria, the included articles were evaluated with the Jad scale and Cochrane manual version 5.1, and the included articles was analyzed by Review Manager 5.4.1. A total of ten relevant articles were included in this meta-analysis. The results of this meta-analysis indicated that CEUS had high sensitivity and specificity in diagnosing renal cystic lesions, which was statistically significant.

Efficacy of an internet-based cognitive behavioral therapy for subthreshold depression among Chinese adults: a randomized controlled trial.

BACKGROUND: Subthreshold depression (sD) negatively impacts well-being and psychosocial function and is more prevalent compared with major depressive disorder (MDD). However, as adults with sD are less likely to seek face-to-face intervention, internet-based cognitive-behavioral therapy (ICBT) may overcome barriers of accessibility to psychotherapy. Although several trials explored the efficacy of ICBT for sD, the results remain inconsistent. This study evaluated whether ICBT is effective in reducing depressive symptoms among Chinese adults with sD. METHODS: A randomized controlled trial was performed. The participants were randomly assigned to 5 weeks of ICBT, group-based face-to-face cognitive-behavioral therapy (CBT), or a waiting list (WL). Assessments were conducted at baseline, post-intervention and at a 6-month follow-up. The primary outcome measured depressive symptoms using the Center for Epidemiological Studies Depression Scale (CES-D). Outcomes were analyzed using a mixed-effects model to assess the effects of ICBT. RESULTS: ICBT participants reported greater reductions on all the outcomes compared to the WL group at post-intervention. The ICBT group showed larger improvement on the Patient Health Questionnaire-9 (PHQ-9) at post-intervention (d = 0.12) and at follow-up (d = 0.10), and with CES-D at post-intervention (d = 0.06), compared to the CBT group. CONCLUSIONS: ICBT is effective in reducing depressive symptoms among Chinese adults with sD, and improvements in outcomes were sustained at a 6-month follow-up. Considering the low rates of face-to-face psychotherapy, our findings highlight the considerable potential and implications for the Chinese government to promote the use of ICBT for sD in China.

Genomic analysis of Shewanella eurypsychrophilus YLB-09 reveals backgrounds related to its deep sea environment adaptation.

Shewanella eurypsychrophilus YLB-09 is a psychrophilic and piezotolerant bacterium that was isolated from 2699 m deep sea sediments of the Southwest Indian Ocean. The complete genome sequence of the strain Shewanella eurypsychrophilus YLB-09 was analyzed. The genome of Shewanella eurypsychrophilus YLB-09 contained one single circular chromosome 6,225,487 base pairs with a 43.6 mol% G + C content of 52 ribosomal RNA genes and 5124 protein-coding genes. YLB-09 has the largest number of genes related to energy production and conversion among 22 available complete genomes of Shewanella genus. Meanwhile， a large quantity of genes encoding flagellum/fimbrial-related proteins and two major secondary metabolic gene clusters were found in YLB-09. These data could provide insights into the mechanism of this strain in adapting to deep sea extreme environments.

Comparative Analysis of Proteomic of Curcumin Reversing Multidrug Resistance in HCT-8/VCR Cells.

To further explore the mechanisms of curcumin reversing multidrug resistance (MDR) in HCT8/VCR cells. Here, we employed comparative analysis of proteomic of essential proteins of human colon carcinoma HCT8/VCR cells with or without treatment of curcumin by separating and quantifying the essential protein posttranslational modification through radical-free two-dimensional polyacrylamide gel electrophoresis with strong reductant. The reverse impact of curcumin on multidrug resistance of HCT8/VCR and HCT8/VCR cells was evaluated using MTT assay. After adding curcumin 25 µM for 72 h, by 2-DE and mass spectrometry, twenty proteins were certified with changed expression levels. Three protein sites were upregulated and seventeen protein sites were downregulated in curcumin-treated HCT-8/VCR. Verification analyses were conducted using RT-PCR and Western blotting for downregulated proteins including GSTP1 and PRDX6. The proteins might have a direct or indirect contact with multidrug resistance. The finding of the research would provide novel sights for systematically comprehending the mechanisms of the reversal impacts of curcumin on MDR in HCT8/VCR cells and contribute to the recognition and application of new markers in clinical practice.

TM9SF4 is a novel regulator in lineage commitment of bone marrow mesenchymal stem cells to either osteoblasts or adipocytes.

BACKGROUND: Osteoporosis is a common bone disease in elderly population caused by imbalanced bone formation and bone resorption. Mesenchymal stem cells (MSCs) are responsible for maintaining this bone homeostasis. The phenotype of transmembrane 9 superfamily 4 (TM9SF4) knockout mice suggests a relationship between TM9SF4 proteins and bone homeostasis. But the effect of TM9SF4 in osteology has never been reported. In the present study, we investigated the function of TM9SF4 in MSC differentiation commitment, as well as its role in osteoporosis. METHODS: Primary bone marrow MSCs, isolated from TM9SF4 wildtype (TM9SF4+/+) and knockout (TM9SF4-/-) mice, were induced to differentiate into osteoblasts or adipocytes, respectively. The osteogenesis was examined by qRT-PCR detection of osteogenic markers, ALP staining and Alizarin Red S staining. The adipogenesis was tested by qRT-PCR quantification of adipogenic markers and Oil Red O staining. The cytoskeletal organization of MSCs was observed under confocal microscope. The osteoporotic model was induced by ovariectomy in TM9SF4+/+ and TM9SF4-/- mice, followed by Toluidine blue and H&E staining to assess lipid accumulation in trabecular bones, as well as micro-computed tomography scanning and immunohistochemistry staining for bone mass density assessment. The experiments on signaling pathways were conducted using qRT-PCR, Western blot and Alizarin Red S staining. RESULTS: We determined the role of TM9SF4 in MSC differentiation and found that TM9SF4-/- MSCs had higher potential to differentiate into osteoblasts and lower capability into adipocytes, without affecting osteoclastogenesis in vitro. In ovariectomy-induced osteoporotic model, TM9SF4-/- mice retained higher bone mass and less lipid accumulation in trabecular bones, indicating an important role of TM9SF4 in the regulation of osteoporosis. Mechanistically, TM9SF4-depleted cells showed elongated actin fibers, which may act through mTORC2/Akt/ß-catenin pathway to promote their commitment into osteoblasts. Furthermore, TM9SF4-depleted cells showed higher activity of canonical Wnt pathway, suggesting the participation of Wnt/ß-catenin during TM9SF4-regulated osteogenesis. CONCLUSIONS: Our study demonstrates TM9SF4 as a novel regulator for MSC lineage commitment. Depletion of TM9SF4 preferentially drives MSCs into osteoblasts instead of adipocytes. Furthermore, TM9SF4-/- mice show delayed bone loss and reduced lipid accumulation during ovariectomy-induced osteoporosis. Our results indicate TM9SF4 as a promising target for the future clinical osteoporotic treatment.

Internet-based cognitive behavioral therapy for psychological distress in older adults without cognitive impairment living in nursing homes during the COVID-19 pandemic: A feasibility study.

BACKGROUND: The COVID-19 pandemic has had a detrimental effect on the mental health of older adults living in nursing homes. Very few studies have examined the effects of Internet-based Cognitive Behavioral Therapy (ICBT) on older adults living in nursing homes during the pandemic. We conducted a feasibility study using a single-group design, to explore the effectiveness of ICBT on psychological distress in 137 older adults (without cognitive impairment) from 8 nursing homes in 4 southeast cities in China, between January and March 2020. METHODS: Symptoms of depression, anxiety, general psychological distress, and functional disability were measured at baseline, post-treatment (5 weeks) and at a 1-month follow-up. Mixed-effects model was used to assess the effects of ICBT. RESULTS: Statistically significant changes with large effect sizes were observed from pre- to post-treatment on the PHQ-9 (p < .001, Cohen's d = 1.74), GAD-7 (p < .001, d = 1.71), GDS (p < .001, d = 1.30), K-10 (p < .001, d = 1.93), and SDS (p < .001, d = 2.03). Furthermore, improvements in treatment outcomes were sustained at 1-month follow-up, and high levels of adherence and satisfaction were indicated. CONCLUSION: ICBT was effective in reducing psychological distress in older adults without cognitive impairments living in nursing homes during the COVID-19 pandemic. Thus, it could be applied in improving the mental health of this vulnerable group during the pandemic.

Theoretical Study of a Two-Photon Fluorescent Probe Based on Nile Red Derivatives with Controllable Fluorescence Wavelength and Water Solubility.

Hypochloric acid (HOCl) plays a vital role in the natural defense system, but abnormal levels of it can cause cell damage, accelerated human aging, and various diseases. It is of great significance to develop new probes for detecting HOCl in biosystems nondestructively and noninvasively. The purpose of this work is to explore new chemical modification strategies of two-photon excitation fluorescence (TPEF) probes to improve the poor water solubility and low efficiency in imaging applications. Nil-OH-6 has a two-photon absorption cross-section value as high as 243 GM and attains a good quantum yield of 0.49. In addition, the modification of terminal groups with different azetidine-heterospirocycles or N,N-dialkyl fused amino groups to Nile Red can effectively improve the fluorescence efficiency as well as increase the solubility to some extent. This study provides some strategies to simultaneously improve the fluorescence performance and solubility of these two-photon probes and, hence, reliable guidance and a foundation for the subsequent synthesis of TPEF probes based on Nile Red.

Characterization of two novel psychrophilic and piezotolerant strains, Shewanella psychropiezotolerans sp. nov. and Shewanella eurypsychrophilus sp. nov, adapted to an extreme deep-sea environment.

Three marine bacterial strains designated YLB-06T, YLB-08T and YLB-09 were isolated under high hydrostatic pressure from deep-sea sediment samples collected from the Southwest Indian Ocean. They were Gram-stain-negative, oxidase- and catalase-positive, facultative anaerobic and motile. In addition, the strains were capable of growing at 0-20 °C (optimum 4-10 °C) and 0.1-40 MPa (optimum 0.1 MPa), were psychrophiles and piezotolerant, and could use trimethylamine N-oxide (TMAO), DMSO, elemental sulfur and insoluble Fe (III) as terminal electron acceptors during anaerobic growth. Strain YLB-06T could also use nitrate, and strains YLB-08T and YLB-09 could use nitrite as a terminal electron acceptor. Phylogenetic tree analyses based on 16S rRNA gene sequences and 400 optimized universal marker sequences indicated that the strains belonged to the genus Shewanella. The 16S rRNA gene highest similarity, together with the estimated ANI and DDH values for these strains with their related type strains, were below the respective thresholds for species differentiation. The ANI and DDH values between YLB-08T and YLB-09 were 99.9% and 91.8%, respectively, implying that they should belong to the same genospecies. The YLB-06T genome had duplicated genes, and multiple movement modalities, attachment modalities, biofilm synthesis systems, intercellular interactions and a strong antioxidant system, which were all beneficial for survival in an extreme deep-sea environment. The G + C contents of strains YLB-06T, YLB-08T and YLB-09 were 45.1, 43.5 and 43.6 mol%, respectively. Based on polyphasic taxonomic properties, two novel psychropiezotolerant species are proposed, Shewanella psychropiezotolerans sp. nov. with YLB-06T (=MCCC 1A12715T = KCTC 62907T) and S. eurypsychrophilus sp. nov with YLB-08T (=MCCC 1A12718T = KCTC 62909T) as type strains.

Halomonas sedimenti sp. nov., a Halotolerant Bacterium Isolated from Deep-Sea Sediment of the Southwest Indian Ocean.

A Gram-staining-negative, aerobic, flagellated, motile, rod-shaped, halophilic bacterium QX-2T was isolated from the deep-sea sediment of the Southwest Indian Ocean at a depth of 2699 m. Growth of the QX-2T bacteria was observed at 4-50 °C (optimum 30 °C), pH 5.0-12.0 (optimum pH 6.0) and 0%-30% NaCl (w/v) [optimum 4% (w/v)]. 16S rRNA gene sequencing revealed that strain QX-2T has the closest relationship with Halomonas titanicae DSM 22872T (98.2%). Phylogeny analysis classified the strain QX-2T into the genus Halomonas. The average nucleotide identity and DNA-DNA hybridization values between strain QX-2T and related type strains were lower than the currently accepted new species definition standards. Principal fatty acids (> 10%) determined were C16:0 (12.41%), C12:0-3OH (25.15%), summed feature 3 (C16:1 ω7c and/or C16:1 ω6c, 11.55%) and summed feature 8 (C18:1 ω7c and/or C18:1 ω6c, 16.06%). Identified polar lipids in strain QX-2T were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, unidentified phospholipid, unidentified aminophospholipid and five unidentified lipids (L1-L5). The main respiratory quinone was Q-9. The content of DNA G+C was determined to be 54.34 mol%. The results of phylogenetic analysis, phenotypic analysis and chemotaxonomic studies showed that strain QX-2T represents a novel species within the genus Halomonas, for which the name Halomonas sedimenti sp. nov. is proposed, with the type strain QX-2T (MCCC 1A17876T = KCTC 82199T).

Blockage of AMPK-ULK1 pathway mediated autophagy promotes cell apoptosis to increase doxorubicin sensitivity in breast cancer (BC) cells: an in vitro study.

BACKGROUND: Activation of autophagy flux contributed to resistance of breast cancer (BC) cells to current chemotherapeutic drugs, which seriously limited their therapeutic efficacy and facilitated BC recurrence in clinic. However, the detailed mechanisms are still not fully understood. In the present study, we identified that inactivation of AMPK-ULK1 signaling cascade mediated protective autophagy sensitized BC cells to doxorubicin in vitro. METHODS: Cell counting kit-8 (CCK-8) assay and colony formation assay were performed to evaluate cell proliferation abilities. Trypan blue staining assay was used to examine cell viability, and Annexin V-FITC/PI double staining method was conducted to determine cell apoptosis. The autophagosomes in BC cells were observed and photographed by electronic microscope (EM). Western Blot analysis was employed to examine genes expressions at protein levels. RESULTS: The parental doxorubicin-sensitive BC (DS-BC) cells were exposed to increasing concentrations of doxorubicin to establish doxorubicin-resistant BC (DR-BC) cells, and the DR-BC cells were much more resistant to high-dose doxorubicin treatment compared to the DS-BC cells. Interestingly, high-dose doxorubicin specifically increased LC3B-II/I ratio, promoted autophagosomes formation and decreased p62 expression levels to facilitate autophagy in DR-BC cells, instead of DS-BC cells, and the autophagy inhibitor 3-methyladenine (3-MA) enhanced the cytotoxic effects of high-dose doxorubicin on DR-BC cells. In addition, we proved that high-dose doxorubicin triggered protective autophagy in DR-BC cells by activating AMPK-ULK1 pathway. Functionally, high-dose doxorubicin increased the expression levels of phosphorylated AMPK (p-AMPK) and ULK1 (p-ULK1) to activate AMPK-ULK1 pathway in DR-BC cells, and the inhibitors for AMPK (compound C) and ULK1 (SBI-0206965) blocked autophagy to promote cell death and slow down cell growth in DR-BC cells treated with high-dose doxorubicin. CONCLUSIONS: Collectively, our in vitro data indicated that blockage of AMPK-ULK1 signaling cascade mediated protective autophagy might be a promising strategy to increase doxorubicin sensitivity for BC treatment.

Genomic analysis of Microbacterium sediminis YLB-01T reveals backgrounds related to its deep-sea environment adaptation.

Microbacterium sediminis YLB-01T, a piezotolerant and psychrotolerant actinomycete, was isolated from deep-sea sediment of the South-West Indian Ocean and could be a good model for understanding the adaptation of extremophiles to the benthic piezosphere. Here, we report the analysis of the complete genome sequence of strain YLB-01T. The genome sequence consists of a single circular chromosome comprising 2,792,195 bp and a linear plasmid comprising 127,669 bp with G + C content of 71.76 and 68.49 mol%, respectively. In this regard, strain YLB-01T possesses the smallest genome size but the highest G + C content among the genus Microbacterium sequenced to date. As the first complete genome sequence of the genus Microbacterium isolated from deep-sea environment, the strain YLB-01T genome is unique or enriched in genes involved in xenobiotics biodegradation and metabolism, compatible solutes, and transposases, some of which might be related to bacterial enhancement of ecological fitness in the deep sea.

Phylogenomic analysis reveals a two-stage process of the evolutionary transition of Shewanella from the upper ocean to the hadal zone.

Shewanella strains are characterized by versatile metabolic capabilities, resulting in their wide distribution in the ocean at different depths. Considering that particle sedimentation is an important dynamic process in the ocean, we hypothesized that hadal Shewanella species evolved from the upper ocean. In this study, we isolated three novel Shewanella strains from deep-sea sediments in the Southwest Indian Ocean. Genome sequencing indicated that strains YLB-06 and YLB-08 represent two novel species in the genus Shewanella. Through phylogenomic analysis, we showed that speciation and genomic changes in marine Shewanella strains are related to water depth. We further confirmed the aforementioned hypothesis and revealed a two-stage process of the evolutionary transition of Shewanella from the upper ocean to the hadal zone by comparative genomics and gene gain/loss analysis. Finally, the transcriptomic analysis demonstrated that recently obtained genes are strictly repressed and may thus play a minor role in the response to environmental changes.