Metabolic plasticity sustains the robustness of Caenorhabditis elegans embryogenesis.

Embryogenesis is highly dependent on maternally loaded materials, particularly those used for energy production. Different environmental conditions and genetic backgrounds shape embryogenesis. The robustness of embryogenesis in response to extrinsic and intrinsic changes remains incompletely understood. By analyzing the levels of two major nutrients, glycogen and neutral lipids, we discovered stage-dependent usage of these two nutrients along with mitochondrial morphology changes during Caenorhabditis elegans embryogenesis. ATGL, the rate-limiting lipase in cellular lipolysis, is expressed and required in the hypodermis to regulate mitochondrial function and support embryogenesis. The embryonic lethality of atgl-1 mutants can be suppressed by reducing sinh-1/age-1-akt signaling, likely through modulating glucose metabolism to maintain sustainable glucose consumption. The embryonic lethality of atgl-1(xd314) is also affected by parental nutrition. Parental glucose and oleic acid supplements promote glycogen storage in atgl-1(xd314) embryos to compensate for the impaired lipolysis. The rescue by parental vitamin B12 supplement is likely through enhancing mitochondrial function in atgl-1 mutants. These findings reveal that metabolic plasticity contributes to the robustness of C. elegans embryogenesis.

Prognostic value of oxidative stress-related genes in colorectal cancer and its correlation with tumor immunity.

Oxidative stress (OS) plays an essential role in chronic diseases such as colorectal cancer (CRC). In this study, we aimed to explore the relation between oxidative stress-related genes and CRC prognosis and their involvement in the immune microenvironment. Totally 101 OS-related genes were selected from the MsigDB database. Then, univariate Cox regression was used to explore the prognostic value of the selected genes correlated with the CRC patient survival in the TCGA database. A total of 9 prognostic OS-related genes in CRC were identified. Based on consensus clustering, CRC patients were then categorized into two molecular subtypes. A prognostic risk model containing 8 genes was established using Lasso regression, and CRC patients were divided into high or low-risk groups based on the median risk scores. The predictive value of the 8 genes in CRC prognosis was validated using ROC curves, which indicate that CTNNB1, STK25, RNF112, SFPQ, MMP3, and NOL3 were promising prognostic biomarkers in CRC. Furthermore, the immune cell infiltration levels in different risk groups or CRC subtypes were analyzed. We found that the high-risk or C1 subtype had immunosuppressive microenvironment, which might explain the unfavorable prognosis in the two groups of CRC patients. Additionally, functional experiments were conducted to investigate the effects of OS-related genes on CRC cell proliferation, stemness, and apoptosis. We found that CTNNB1, HSPB1, MMP3, and NOL3 were upregulated in CRC tissues and cells. Knockdown of CTNNB1, HSPB1, MMP3, and NOL3 significantly suppressed CRC cell proliferation, stemness and facilitated CRC cell apoptosis. In conclusion, we established prognostic CRC subtypes and an eight-gene risk model, which may provide novel prognostic indicators and benefit the design of individualized therapeutic strategies for CRC patients.

Association of disease activity with depression and anxiety in systemic lupus erythematosus: A comparison of SLEDAI-2K and SLE-DAS.

OBJECTIVE: To explore the association of disease activity, as evaluated by both the Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) and the Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K), with depression and anxiety in patients with systemic lupus erythematosus (SLE). METHODS: A cross-sectional study was conducted among 85 Chinese patients with SLE. Disease activity was measured using SLEDAI-2K and SLE-DAS scoring systems. Depression and anxiety were assessed using Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder Scale-7 (GAD-7), respectively. Multivariate logistic regression analysis was performed to evaluate the association of disease activity scores, as well as specific clinical and laboratory items, with depression and anxiety. RESULTS: There was a robust correlation between SLEDAI-2K and SLE-DAS scores in overall patients (Spearman's r = 0.764, 95% confidence interval (CI) 0.655-0.842; p< 0.001) and those with moderate-to-high disease activity (Spearman's r = 0.792, 95%CI 0.616-0.892; p< 0.0001). However, the correlation weakened for patients with mild disease activity or remission (Spearman's r = 0.450, 95%CI 0.188-0.652; p= 0.001). Multivariate logistic regression analysis did not show a significant correlation between SLEDAI-2K and SLE-DAS scores and depression/anxiety. The presence of mucosal ulcer/serositis significantly increased the risk of depression (OR = 4.472, 95%CI 1.035-19.328, p= 0.045) and anxiety (OR = 3.978, 95%CI 1.051-15.049, p= 0.042). CONCLUSION: The SLE-DAS scoring system demonstrated a comparable ability to assess disease activity in SLE compared with SLEDAI-2K. Though neither scoring system showed significant associations with depression and anxiety, the presence of mucosal ulcer/serositis markedly heightened the risk of both among SLE patients.

Hsa_circ_0092355 Accelerates Papillary Thyroid Cancer Progression by Regulating the miR-543/PDE5A Pathway.

CircRNAs have been found to participate in the progression of various tumors. In the present study, we aimed to clarify the role of hsa_circ_0092355 in papillary thyroid cancer (PTC) cell development. RT-qPCR was used to determine the expression of hsa_circ_0092355, miR-543, and PDE5A. PTC cell proliferation was ascertained via a cell colony formation assay and the CCK-8 test. Western blotting was performed to examine the expression levels of PDE5A and apoptosis-associated proteins (Bcl-2 and Bax) in PTC cells. A scratch wound assay was performed to measure the migration of PTC cells. A mouse xenograft test was performed to assess the effects of hsa_circ_0092355 in vivo. RIP and dual-luciferase reporter assays confirmed the association between miR-543 and hsa_circ_0092355 or PDE5A. Associations between miR-543, hsa_circ_0092355, and PDE5A were evaluated using Pearson's correlation coefficient. Upregulation of hsa_circ_0092355 was observed in PTC tissues. The hsa_circ_0092355 knockdown blocked the proliferation and migration of PTC cells and induced apoptosis. Moreover, hsa_circ_0092355 knockdown blocked PTC xenograft tumor growth in vivo. The miR-543 inhibitor could reverse the changes induced by hsa_circ_0092355 knockdown by hsa_circ_0092355 targeting miR-543. Furthermore, miR-543 suppresses PTC progression by downregulating PDE5A expression. Our findings suggest that the PTC tumor promoter hsa_circ_0092355 may promote carcinogenesis by controlling the miR-543/PDE5A pathway.

Pengzhenrongella frigida sp. nov., isolated from a glacier.

A Gram-stain-positive, rod-shaped bacterium, designated as HLT2-17T, was isolated from soil sample taken from the Hailuogou glacier in Sichuan province, PR China. Strain HLT2-17T was capable of growing at 4-25°C and in NaCl concentrations ranging from 0 to 2% (w/v). The highest level of 16S rRNA gene sequence similarity was observed with Pengzhenrongella phosphoraccumulans M0-14T (98.3 %) and Pengzhenrongella sicca LRZ-2T (98.2 %). The average nucleotide identity and digital DNA-DNA hybridization values between strain HLT2-17T and its closest relatives, P. phosphoraccumulans M0-14T and P. sicca LRZ-2T, were 80.0-84.0 % and 23.3-27.7 %, respectively. Phylogenomic analysis indicated that strain HLT2-17T clustered together with strains P. phosphoraccumulans M0-14T and P. sicca LRZ-2T. Strain HLT2-17T contained C16 : 0 and anteiso-C15 : 0 as the major fatty acids, and MK-9(H4) as the menaquinone. Therefore, based on a polyphasic approach, we propose that strain HLT2-17T (=CGMCC 1.11116T= NBRC 110443T) represents a novel species of the genus Pengzhenrongella and suggest the name Pengzhenrongella frigida sp. nov.

Complications and adverse events of high-intensity focused ultrasound in its application to gynecological field - a systematic review and meta-analysis.

OBJECTIVE: To analyze and summarize the types, incidence rates and relevant influencing factors of adverse events (AEs) after high-intensity focused ultrasound ablation of gynecological diseases and provide reference and basis for handling such events in clinical practice. METHOD: We searched PubMed, Cochrane Library, Web of Science and Embase databases to retrieve all literature since its establishment until February 2024. We evaluated the quality of included literature and publication bias and conducted a meta-analysis of single group rates for various AEs using Stata 17.0. RESULTS: This systematic review finally included 41 articles. We summarized 34 kinds of AEs in 7 aspects and conducted a single group rate meta-analysis and sub-group analysis of 16 kinds of AEs. Among the common AEs of High-Intensity Focused Ultrasound (HIFU), the incidence of lower abdominal pain/pelvic pain is 36.1% (95% CI: 24.3%∼48.8%), vaginal bleeding is 20.6% (95% CI: 13.9%∼28.0%), vaginal discharge is 14.0% (95% CI: 9.6%∼19.1%), myoma discharge is 24% (95% CI: 14.6%∼34.8%), buttock pain is 10.8% (95% CI: 6.0%∼16.5%) and sacral pain is 10% (95% CI: 8.8%∼11.2%). Serious complications include uterine rupture, necrotic tissue obstruction requiring surgical intervention, third degree skin burns and persistent lower limb pain or movement disorders. CONCLUSION: The common AEs after HIFU surgery are mostly mild and controllable, and the incidence of serious complications is extremely low. By reasonable prevention and active intervention, these events can be further reduced, making it a safe and effective treatment method. It is a good choice for patients who crave noninvasive treatment or have other surgical contraindications.

Analysis of related factors influencing postoperative recurrence of adenomyosis treated with HIFU.

OBJECTIVE: To analyze the efficacy of high-intensity focused ultrasound (HIFU) for adenomyosis and postoperative recurrence and its influencing factors. METHODS: Clinical and follow-up data of 308 patients with adenomyosis who were treated with HIFU in Haifu Center, Affiliated Hospital of Chengdu University of Traditional Chinese Medicine from September 2017 to January 2022 were retrospectively analyzed. The recurrence of adenomyosis and the efficacy of HIFU at 6 months after surgery were followed up. To explore factors influencing postoperative prognosis and recurrence, the following variables were analyzed: patients' age, course of disease, gravidity and parity, size of the uterus, duration of HIFU, duration of irradiation, treatment intensity, dysmenorrhea score, time of follow-up, combined treatment of traditional Chinese medicine (TCM), western medicine adjuvant treatment, lesion location and type, and menorrhagia. RESULTS: Among the 308 patients, 238 (77%) were followed up from 6 to 36 months, with an average follow-up time of 15.24 ± 9.97 months. The other 70 (23%) were lost to follow-up. At 6-month after surgery, efficacy rates of dysmenorrhea and menorrhagia management were 86.7% and 89.3%, respectively. Postoperative recurrence rates were 4.8% (1-12 months), 9.0% (12-24 months), and 17.0% (24-36 months) for dysmenorrhea; and 6.3% (1-12 months), 2.4% (12-24 months), and 12.2% (24-36 months) for menorrhagia. Multivariate logistic regression analyses showed that parity (P = 0.043, OR = 1.773, 95% CI 1.018-3.087), uterine size (P = 0.019, OR = 1.004, 95% CI 1.001-1.007), combined treatment of TCM (P = 0.047, OR = 1.846, 95% CI 1.008-3.381), diffuse lesion type (P = 0.013, OR = 0.464, 95% CI 0.254-0.848) and ablation rate (P = 0.015, OR = 0.481, 95%CI 0.267-0.868) were prognostic factors (P < 0.05). Age, course of disease, gravidity, duration of HIFU, duration of irradiation, treatment intensity, preoperative dysmenorrhea score, time of follow-up, western medicine adjuvant therapy, lesion location, and preoperative menstrual volume had no effect on prognosis (P > 0.05). CONCLUSION: HIFU can effectively relieve dysmenorrhea and reduce menstrual volume in patients with adenomyosis. Parity, uterine size, lesion type (diffuse), and ablation rate are risk factors for symptom recurrence after HIFU, while the combination of TCM therapy is a protective factor for relapse. We, therefore, recommend TCM in the adjuvant setting after HIFU according to patient condition.

Identification of Flavobacterium algoritolerans sp. nov. and Flavobacterium yafengii sp. nov., two novel members of the genus Flavobacterium.

Six psychrotolerant, Gram-stain-negative, aerobic bacterial strains, designated as LB1P51T, LB2P87T, LB2P84, LB3P48, LB3R18 and XS2P67, were isolated from glaciers on the Tibetan Plateau, PR China. The results of 16S rRNA gene analysis confirmed their classification within the genus Flavobacterium. Strain LB2P87T displayed the highest sequence similarity to Flavobacterium sinopsychrotolerans 0533T (98.18 %), while strain LB1P51T exhibited the highest sequence similarity to Flavobacterium glaciei CGMCC 1.5380T (98.15 %). Strains LB2P87T and LB1P51T had genome sizes of 3.8 and 3.9 Mb, respectively, with DNA G+C contents of 34.2 and 34.1 %, respectively. Pairwise average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) calculations revealed that these strains represented two distinct species within the genus Flavobacterium. The results of phylogenomic analysis using 606 core genes indicated that the six strains formed a distinct clade and were most closely related to F. glaciei CGMCC 1.5380T. The ANI and dDDH values between the two species and other members of the genus Flavobacterium were below 90.3 and 40.1 %, respectively. Genome relatedness, the results of phylogenomic analysis and phenotypic characteristics collectively support the proposal of two novel species of the genus Flavobacterium: Flavobacterium algoritolerans sp. nov. (LB1P51T = CGMCC 1.11237T = NBRC 114813T) and Flavobacterium yafengii sp. nov. (LB2P87T = CGMCC 1.11249T = NBRC 114814T).

Flavobacterium frigoritolerans sp. nov. and Flavobacterium shii sp. nov., isolated from glaciers on the Tibetan Plateau.

The genus Flavobacterium belongs to the family Flavobacteriaceae and its members are widely distributed in the environment. Taxonomic descriptions of strains LS1R47T and LS1R49T isolated from the Laigu glacier on the Tibetan Plateau, China, are presented in this study. Both strains were psychrotolerant, Gram-stain-negative, aerobic and rod-shaped. The comparative analysis of 16S rRNA gene sequences showed that strain LS1R47T was closest to Flavobacterium bizetiae CIP 105534T (98.90 %) and strain LS1R49T was closest to Flavobacterium collinsii 983-08T (98.73 %). The 16S rRNA gene sequence similarity, average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between the two novel isolates were 99.4, 86.0 and 30.9 %, respectively. The ANI and dDDH values between strains LS1R47T and LS1R49T and their closely relatives were below 87.6 and 33.3 %, respectively. Phylogenomic analysis showed that the two strains cluster together with Flavobacterium hydatis ATCC 29551T. Both strains contained MK-6 as sole quinone, phosphatidylethanolamine as the principal polar lipid, and summed feature 3 (iso-C15 : 0 2-OH and/or C16 : 1 ω7c), iso-C15 : 0 3-OH, C15 : 0 3-OH and iso-C17 : 0 3-OH as the main fatty acids. These results indicated that strains LS1R47T and LS1R49T represented two novel species within the genus Flavobacterium. Therefore, we propose two novel species, Flavobacterium frigoritolerans sp. nov. (LS1R47T=CGMCC 1.11577T=NBRC 113654T) and Flavobacterium shii sp. nov. (LS1R49T=CGMCC 1.11581T=NBRC 113652T).

Association of anti-Ro52 antibody with depression and anxiety in patients with connective tissue diseases: an observational, single-centre, cross-sectional study.

OBJECTIVES: To explore the risk factors of anxiety and depression, especially their association with serum autoantibodies, in patients with connective tissue diseases (CTDs). METHODS: Three hundred and fifty-two inpatients with CTDs were recruited and their demographic, serological and imaging data were collected through the medical record system. Depression and anxiety were assessed by the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 Scale (GAD-7) respectively. Analysis of variance (ANOVA), rank sum test, chi-square test and logistic regression were performed to investigate risk factors for depression and anxiety. RESULTS: The prevalence of depression (PHQ-9 ≥ 5) and anxiety (GAD-7 ≥5) in CTD patients was significantly higher than that in the Chinese general population (depression: 44.3% vs. 32.2%, anxiety: 39.5% vs. 22.2%). Sleep time was a protective factor for both depression and anxiety (OR=0.734, 95% CI: 0.616~0.874, p<0.001 and OR=0.684, 95% CI: 0.559~0.835, P<0.001, respectively) while anti-Ro52 antibody was a risk factor for them (OR=5.466, 95% CI: 2.978~10.032, p<0.001 and OR=4.075, 95% CI: 2.073~8.010, p<0.001, respectively). Further analysis showed that anti-Ro52 antibody was a risk factor for depression and anxiety in all four subgroups, namely SLE, SS, RA, and other CTDs. CONCLUSIONS: Anti-Ro52 antibody is probably a risk factor for depression and anxiety in patients with connective tissue diseases. CTD patients with the presence of anti-Ro52 antibody are more prone to depression and anxiety than those without it.

Overexpression of LAG3, TIM3, and A2aR in adenoid cystic carcinoma and mucoepidermoid carcinoma.

OBJECTIVE: Adenoid cystic carcinoma (AdCC) and mucoepidermoid carcinoma (MEC) are the two most frequent malignancies of salivary glands. This study aims to explore the expression and migration of LAG3, TIM3, and A2aR in AdCC and MEC, and the potential relationship with oncogenic signaling molecules and immunosuppressive cytokines. MATERIALS AND METHODS: Custom made human salivary gland tissue microarrays included 81 AdCCs, 52 MECs, 76 normal salivary glands (NSG), and 14 pleomorphic adenoma (PMA) samples. Immunohistochemical analysis of lymphocyte activation gene 3 (LAG3), T-cell immunoglobulin and mucin domain-containing protein 3 (TIM3), adenosine 2a receptor (A2aR), oncogenic phosphorylated S6 kinase (p-S6) and ERK1/2 (p-ERK1/2 ), and TGF-ß1 was performed with salivary gland tissue microarrays of human samples. The correlation of the immunostaining was analyzed based on a digital pathological system, and data were evaluated by hierarchical cluster. Further in vitro studies of knockdown immune checkpoints LAG3, TIM3, and A2aR were carried out by siRNA transfection. RESULTS: The expression levels of LAG3, TIM3, and A2aR were remarkably increased in AdCC and MEC, compared with NSG and PMA samples, but were independent of pathology grade. They were closely correlated with TGF-ß1, slightly related to p-ERK1/2 and p-S6. After the knockdown of immune checkpoints LAG3, TIM3, and A2aR, the migration of SACC-LM cell line was significantly reduced. CONCLUSIONS: These results suggested that LAG3, TIM3, and A2aR are overexpressed in AdCC and MEC, may promote migration of SACC-LM cell and correlated with TGF-ß1 and oncogenic signaling pathways.

Efficacy of high-intensity focused ultrasound combined with LNG-IUS for adenomyosis: a systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of high-intensity focused ultrasound (HIFU) combined with the levonorgestrel intrauterine system (LNG-IUS) for adenomyosis. METHODS: We searched PubMed, Embase, Cochrane Library, Web of Science, CNKI, SinoMed, Wanfang, and VIP databases from their inception to Nov 20, 2021 for relevant articles that compared HIFU combined with LNG-IUS vs. HIFU alone in patients with adenomyosis. RevMan5.4 software was used for the data analysis. The primary outcome was changes in volume of the uterine. Secondary outcomes included visual analog scale (VAS) scores for dysmenorrhea, serum CA125 level, recurrence rate, changes in volume of the adenomyotic lesion, menstrual volume scores, and adverse reactions. Data synthesis was conducted using a random-effects model with significant heterogeneity (I2 > 50%), and using a fixed-effects model otherwise. This study is registered on the PROSPERO platform (CRD42021295214). RESULTS: The final analysis included 13 studies, with a total of 1861 patients. Results of analysis revealed that there was no significant difference in uterine volume reduction between the HIFU control group and the HIFU/LNG-IUS group at 3 months after procedure (MD:30.63). Compared with the HIFU control group, the HIFU/LNG-IUS group had more pronounced reduction in uterine volume at 6 (MD:29.04) and 12 months (MD:22.10) after procedure. The HIFU/LNG-IUS group has lower VAS scores for dysmenorrhea than the HIFU control group at 3 (MD:1.68), 6 (MD:1.69), and 12 months (MD:1.30) after procedure. Serum CA125 level in the HIFU/LNG-IUS group decreased more significantly than the HIFU control group at 6 (MD:18.34) and 12 months (MD:18.49) after procedure. The recurrence rate in the HIFU/LNG-IUS group was lower than that in the HIFU control group (RR:0.20). CONCLUSIONS: Compared to HIFU control group, HIFU/LNG-IUS group for the management of adenomyosis had more advantages in alleviating symptoms and decreasing the volumes of the uterine and adenomyotic lesions. However, since the number of the included studies was too small and some of them were not RCT, this conclusion needs to be referenced with caution.

Genomes shed light on the evolution of Begonia, a mega-diverse genus.

Clarifying the evolutionary processes underlying species diversification and adaptation is a key focus of evolutionary biology. Begonia (Begoniaceae) is one of the most species-rich angiosperm genera with c. 2000 species, most of which are shade-adapted. Here, we present chromosome-scale genome assemblies for four species of Begonia (B. loranthoides, B. masoniana, B. darthvaderiana and B. peltatifolia), and whole genome shotgun data for an additional 74 Begonia representatives to investigate lineage evolution and shade adaptation of the genus. The four genome assemblies range in size from 331.75 Mb (B. peltatifolia) to 799.83 Mb (B. masoniana), and harbor 22 059-23 444 protein-coding genes. Synteny analysis revealed a lineage-specific whole-genome duplication (WGD) that occurred just before the diversification of Begonia. Functional enrichment of gene families retained after WGD highlights the significance of modified carbohydrate metabolism and photosynthesis possibly linked to shade adaptation in the genus, which is further supported by expansions of gene families involved in light perception and harvesting. Phylogenomic reconstructions and genomics studies indicate that genomic introgression has also played a role in the evolution of Begonia. Overall, this study provides valuable genomic resources for Begonia and suggests potential drivers underlying the diversity and adaptive evolution of this mega-diverse clade.

Molecular characterization and antimicrobial resistance profile of pathogenic Escherichia coli from goats with respiratory disease in eastern China.

Pathogenic Escherichia coli (E. coli) can cause a variety of intestinal and extra-intestinal infections in humans and animals. Similar with the intestinal disease, respiratory disease is also a major threat to the breeding industry of goats. But the reports on respiratory disease associated E. coli are very limited. In this study, E. coli and other pathogens were examined for the 77 submitted respiratory cases. The serotypes, virulence genes, phylogenetic group and antimicrobial resistance characteristics of the E. coli isolates were identified. The results showed that 34 cases (44.16%) were associated with E. coli and 22 cases showed mixed infections of E. coli with Mycoplasma ovipneumoniae, Mannheimia haemolytica or Pasteurella . Among the 49 E. coli isolates, O8 (32.65%), O9 (20.41%) and O89 (10.20%) were the predominant serotypes (31/49, 63.27%). 22 virulence genes were detected and the most prevalent genes were fimH (100%), yijp (100%), mat (97.96%), ompA (95.92%) ibeB (91.84%) and fyuA (77.55%). In addition, ibeA was detected in 6.12% (3/49) of the strains. Markers of extra-intestinal pathogenic E. coli (ExPEC) were also identified and 14 strains were classified as ExPECs. 14 (28.57%), 25 (51.02%), 3 (6.12%) and 7 (14.29%) strains belonged to phylogenetic group A, B1, B2 and D, respectively, and group A and B1 were the predominant ones. The E. coli strains showed high resistant (48.98%-100%) to the 14 selected antimicrobials and all of them were defined as multiple drug resistant (MDR) strains. This is the first systemically study on E. coli of goats respiratory diseases origin in eastern China. The results suggest that E. coli infection may play an important role in goat respiratory diseases and that goats are reservoir hosts of ExPECs, which needs continuous monitoring in the future.

Neuronal lipolysis participates in PUFA-mediated neural function and neurodegeneration.

Lipid droplets (LDs) are dynamic cytoplasmic organelles present in most eukaryotic cells. The appearance of LDs in neurons is not usually observed under physiological conditions, but is associated with neural diseases. It remains unclear how LD dynamics is regulated in neurons and how the appearance of LDs affects neuronal functions. We discovered that mutations of two key lipolysis genes atgl-1 and lid-1 lead to LD appearance in neurons of Caenorhabditis elegans. This neuronal lipid accumulation protects neurons from hyperactivation-triggered neurodegeneration, with a mild decrease in touch sensation. We also discovered that reduced biosynthesis of polyunsaturated fatty acids (PUFAs) causes similar effects and synergizes with decreased lipolysis. Furthermore, we demonstrated that these changes in lipolysis and PUFA biosynthesis increase PUFA partitioning toward triacylglycerol, and reduced incorporation of PUFAs into phospholipids increases neuronal protection. Together, these results suggest the crucial role of neuronal lipolysis in cell-autonomous regulation of neural functions and neurodegeneration.

Mucilaginibacter aurantiaciroseus sp. nov. and Mucilaginibacter flavidus sp. nov., isolated from Renlongba glacier on the Tibetan Plateau.

Strains RB4R14T and RT5R15T, two Gram-stain-negative, aerobic, rod-shaped, non-motile bacteria, were isolated from ice and cryoconite of Renlongba glacier, respectively, on the Tibetan Plateau, PR China. The results of phylogenetic analysis based on 16S rRNA genes indicated that strains RB4R14T and RT5R15T belonged to the genus Mucilaginibacter with the highest similarities to Mucilaginibacter rigui WPCB133T (98.78 %) and Mucilaginibacter xinganensis BJC16-A31T (97.64 %), respectively. The genomic DNA G+C contents of strains RB4R14T and RT5R15T were 42.8 and 43.1 mol%, respectively. The digital DNA-DNA hybridization values between strains RB4R14T, RT5R15T and their close relatives were below 31.9 and 17.4 %, respectively. The average nucleotide identity values between the two novel strains and their close relatives were 79.5-82.0 and 77.9-79.3 % respectively, indicating the novelty of the two isolates at a species level. The two novel strains contained MK-7 as the major menaquinone, and summed feature 3 (comprising C16 : 1 ω7c and/or C16 : 1 ω6c), iso-C15 : 0 and iso-C17 : 0-3OH as the major fatty acids. The major polar lipid of the two novel strains were phosphatidylethanolamine. Based on phenotypic, chemotaxonomic and phylogenetic results, we propose two novel species, Mucilaginibacter aurantiaciroseus sp. nov. (RB4R14T=CGMCC 1.11911T=NBRC 114020T) and Mucilaginibacter flavidus sp. nov. (RT5R15T=CGMCC 1.23117T=NBRC 113930T).

MiR-1-3p targets CENPF to repress tumor-relevant functions of gastric cancer cells.

Here we noted significantly downregulated miR-1-3p in gastric cancer (GC) tissue compared with adjacent normal tissue through qRT-PCR. Lowly expressed miR-1-3p correlated GC progression. Overexpressing miR-1-3p could restrain tumor-relevant cell behaviors in GC, while miR-1-3p inhibitor treatment triggered the opposite results. Moreover, dual-luciferase reporter gene detection identified specific binding sites of miR-1-3p in CENPF 3'untranslated region. Upregulating miR-1-3p constrained cell progression of GC via CENPF downregulation. Western blot, qRT-PCR and dual-luciferase detections manifested that miR-1-3p negatively mediated CENPF expression in GC cells. Thus, we demonstrated that miR-1-3p negatively mediated CENPF to hamper GC progression. CENPF may be an underlying target for GC therapy.

Three-Dimensional Covalent Organic Frameworks with Cross-Linked Pores for Efficient Cancer Immunotherapy.

We report the design and synthesis of a series of three-dimensional (3D) covalent organic frameworks (COFs) as immunogenic cell death (ICD) inducers for cancer immunotherapy. Three triple-topic amine building blocks, inactive to inducing ICD, were used to construct three COFs, COF-607, COF-608, and COF-609, with outstanding ICD eliciting efficiency. Mechanism studies revealed that after linking these ICD inert monomers into the COF backbone, the optical properties of these COFs could be systematically tuned to achieve excellent reactive oxygen species (ROS) production performance. This combined with 3D cross-linked pores, mimicking lung structure, favor the exchange and diffusion of oxygen and ROS, leading to excellent inducing ICD efficacy. One member, COF-609, is capable of triggering abscopal and long-lasting immune memory effects in a mouse model of breast cancer with >95% mice survival after being treated with COF-609+αCD47 for 110 days.

CircRASSF2 facilitates the proliferation and metastasis of colorectal cancer by mediating the activity of Wnt/ß-catenin signaling pathway by regulating the miR-195-5p/FZD4 axis.

Circular RNAs (circRNA) are a key regulator of cancer progression, including colorectal cancer (CRC). Nevertheless, the role of circRASSF2 in CRC remains unclear. Quantitative real-time PCR was used to measure the expression of circRASSF2 and miR-195-5p. Cell counting kit 8 assay, colony formation assay, flow cytometry and transwell assay were used to determine the proliferation, apoptosis, migration and invasion of cells, respectively. The levels of proliferation, metastasis and Wnt/ß-catenin signaling pathway-related proteins, as well as Frizzled 4 (FZD4) protein, were determined using western blot analysis. Furthermore, a dual-luciferase reporter assay, RNA immunoprecipitation assay and RNA pull-down assay were used to illumine the mechanism of circRASSF2. Animal experiments were used to determine the role of circRASSF2 in the tumor growth of CRC in vivo. Our study reported that circRASSF2 was upregulated in CRC tissues and cells, and its high expression was related to the poor prognosis of CRC patients. CircRASSF2 knockdown could inhibit proliferation, migration, invasion, and enhance apoptosis in CRC cells, and its overexpression had the opposite effect. Besides, our data revealed that circRASSF2 could sponge miR-195-5p, and miR-195-5p could target FZD4. The rescue experiments indicated that both miR-195-5p inhibitor and FZD4 overexpression could reverse the negative regulation of circRASSF2 silencing on CRC progression. Moreover, circRASSF2 could positively regulate the activity of Wnt/ß-catenin signaling pathway by the miR-195-5p/FZD4 axis. In addition, circRASSF2 knockdown restrained the tumor growth of CRC in vivo. Our findings suggested that circRASSF2 might function as a tumor promoter to accelerate the progression of CRC via regulating the miR-195-5p/FZD4/Wnt/ß-catenin pathway.

Flavobacterium franklandianum sp. nov. and Flavobacterium gawalongense sp. nov., isolated from glaciers on the Tibetan Plateau.

The genus Flavobacterium (family Flavobacteriaceae) can be found in diverse environments. In this study, seven novel strains were isolated from glaciers in PR China and subjected to taxonomic research. Phylogenetic analyses based on the 16S rRNA gene revealed that the strains belonged to the genus Flavobacterium. None of the seven strains grew at temperatures above 22 °C, indicating that they are psychrophilic. Furthermore, the average nucleotide identity (ANI) values of the seven strains were calculated and indicated that they represented two novel species in Flavobacterium. Strain LB3P56T was most closely related to Flavobacterium soyangense IMCC26223T (97.70 %) and strain GSP16T was most closely related to Flavobacterium sinopsychrotolerans 0533T (98.03 %). The ANI values between the two Flavobacterium strains and their closest relatives were less than 83.47 %, which was much lower than the threshold for species delineation of 95-96 %. Therefore, we propose two novel species, Flavobacterium franklandianum sp. nov. (LB3P56T=CGMCC 1.11934T=NBRC 113651T) and Flavobacterium gawalongense sp. nov. (GSP16T=CGMCC 1.24642T=NBRC 113664T).