Nogo-B Silencing Expedites the Senescence of Platelet-Derived Growth Factor-BB-Induced Human Hepatic Stellate Cells Via Autophagy.

Liver fibrosis is a severe liver pathology in response to chronic or iterative liver injury. Senescence has emerged as a protective mechanism against liver fibrosis. Nogo-B has been well established as a significant contributor to liver fibrosis. Nonetheless, researches regarding the role of Nogo-B in cell senescence during liver fibrosis are few. In platelet-derived growth factor-BB (PDGF-BB)-treated human hepatic stellate cell line LX-2, cell proliferation was assayed by CCK-8 method. Western blotting estimated the expression of Nogo-B and fibrosis markers. After Nogo-B was silenced in LX-2 cells pretreated by an autophagy activator Rapamycin and PDGF-BB, CCK-8 method was used to assess cell proliferation. Fibrosis was measured by western blotting and immunofluorescence. Cell cycle was subjected to flow cytometry analysis and cell senescence was evaluated by SA-ß-gal staining. Immunofluorescence staining assessed autophagy. Nogo-B was elevated in PDGF-BB-exposed LX-2 cells. Nogo-B silencing suppressed the proliferation, fibrosis, and autophagy while induced cell cycle arrest and senescence of LX-2 cells. Additionally, pretreatment with Rapamycin partially restored the effects of Nogo-B knockdown on the autophagy, proliferation, fibrosis, cell cycle, and senescence of LX-2 cells upon exposure to PDGF-BB. Collectively, inactivation of autophagy mediated by Nogo-B deficiency might elicit protective activities against the development of liver fibrosis.

Efficient Solvent-Free Synthesis of Indolizines Using CuBr Catalyst from Pyridine, Acetophenone, and Electron-Deficient Alkenes.

Herein, we have developed a new approach for the synthesis of indolizine via Cu-catalyzed reaction of pyridine, acetophenone, and nitroolefin under mild conditions in high yields. This reaction involved the formation of C-N and C-C bonds and new indolizine compounds with high stereoselectivity and excellent functional group tolerance.

Phycosphere bacterial disturbance of Saccharina japonica caused by white rot disease relates to seawater nutrients.

In mid-November 2021, there were large areas of white rot disease on cultivated Saccharina japonica in Rongcheng City, China, and diseases were undetected on Sargassum horneri and Porphyra yezoensis. The disturbance direction of bacterial community in the phycosphere after disease outbreak and the relationship with seawater nutrients remain unclear. Here, in situ studies of bacterial community in the non-diseased and diseased areas (Shawo and Dongchu islands) and seawater nutrient levels were carried out. 16S rRNA sequencing showed that the bacterial richness of the studied seaweeds increased in the diseased area. Only in S. japonica, Algitalea outcompeted abundant primary bacteria with probiotic relationships to the host of the non-diseased area, and dominated in the diseased area (17.6% of the total abundance). Nitrogen and phosphorus levels in seawater were 57.8% and 19.6% higher in the non-diseased area than those in the diseased area, respectively, and were strongly correlated with the phycosphere bacteria at the family level of S. japonica. There was no difference in potential pathogenicity between the two areas, while positive signal communications decreased, and nitrogen cycle, chemoheterotrophy, and cellulolysis increased in the diseased area compared to the non-diseased area. Overall, white rot disease caused a structural disturbance in phycosphere bacterial community of S. japonica that related to seawater nutrient levels. Enriched degraders and altered bacterial community functions may exacerbate the disease. This evaluation will provide information for white rot disease management to prevent and mitigate the occurrence of S. japonica outbreaks.

Posttraumatic stress disorder and spousal relationships in natural disaster victims: a longitudinal study.

BACKGROUND: Posttraumatic stress disorder (PTSD) symptoms after natural disaster can have a detrimental effect on marital relationships, which may be through parenting-related factor. AIMS: The study aimed to examine the mechanism underlying the long-term effects of PTSD symptoms on marital satisfaction via coparenting, and its differences between men and women following the Super Typhoon Lekima. METHODS: Participants were 465 married victims with children. They reported their PTSD, coparenting, and marital satisfaction at three and fifteen months after the tropical cyclone. RESULTS: The results showed that for women, only higher negative cognitive and emotional alterations (NCEA) symptoms were associated with lower marital satisfaction through conflict coparenting. For men, higher intrusion, NCEA, and hyperarousal symptoms were associated with marital satisfaction through different coparenting. To be specific, for men, higher intrusion symptoms were associated with lower marital satisfaction via less reprimand coparenting; higher NCEA symptoms were associated with lower marital satisfaction via less integrity coparenting, and associated with higher marital satisfaction via less conflict coparenting; higher hyperarousal symptoms were associated with lower marital satisfaction via more conflict coparenting. CONCLUSIONS: These findings suggested that the long-term effect of PTSD symptoms on marital satisfaction via coparenting mainly showed for men.

Reducing Nogo-B Improves Hepatic Fibrosis by Inhibiting BACe1-Mediated Autophagy.

BACKGROUND: Hepatic fibrosis (HF) is a histopathological change in the process of long-term liver injury caused by cytokine secretion and internal environment disturbance, resulting in excessive liver repair and fiber scar. Nogo-B protein is widely distributed in peripheral tissues and organs and can regulate the migration of endothelial cells by activating TGF-ß1 in vascular remodeling after injury. Nogo-B has been shown to promote organ fibrosis. This study was to determine the role of Nogo-B in HF. METHODS: An HF model was built by intraperitoneal injections with 20% carbon tetrachloride. Localization of Nogo-B was detected by FISH. The interaction between Nogo-B and BACE1 was confirmed by Co-IP. Autophagy flux was analyzed using tandem mRFP-GFP-LC3 fluorescence microscopy, electron microscopy, and western blotting. Detection of serum AST and ALT and H&E staining were utilized to detect the degree of liver injury. The HF was evaluated by Masson trichromatic staining. RT-qPCR, western blotting, and immunofluorescence were employed to detect relevant indicators. RESULTS: Reducing Nogo-B suppressed AST and ALT levels, the accumulation of collagen I and α-SMA, and expressions of pro-fibrotic genes in mouse liver. BACE1 was a potential downstream target of Nogo-B. Nogo-B was upregulated in TGF-ß1-activated hepatic stellate cells (HSCs). Knocking down Nogo-B caused the downregulation of pro-fibrotic genes and inhibited viability of HSCs. Nogo-B knockdown prevented CCL4-induced fibrosis, accompanied by downregulation of extracellular matrix. Nogo-B inhibited HSC autophagy and increased lipid accumulation. BACE1 knockdown inhibited HSC autophagy and activation in LX-2 cells. CONCLUSION: Nogo-B knockdown prevents HF by directly inhibiting BACe1-mediated autophagy.

Blockade of the deubiquitinating enzyme USP48 degrades oncogenic HMGA2 and inhibits colorectal cancer invasion and metastasis.

HMGA2, a pivotal transcription factor, functions as a versatile regulator implicated in the progression of diverse aggressive malignancies. In this study, mass spectrometry was employed to identify ubiquitin-specific proteases that potentially interact with HMGA2, and USP48 was identified as a deubiquitinating enzyme of HMGA2. The enforced expression of USP48 significantly increased HMGA2 protein levels by inhibiting its degradation, while the deprivation of USP48 promoted HMGA2 degradation, thereby suppressing tumor invasion and metastasis. We discovered that USP48 undergoes SUMOylation at lysine 258, which enhances its binding affinity to HMGA2. Through subsequent phenotypic screening of small molecules, we identified DUB-IN-2 as a remarkably potent pharmacological inhibitor of USP48. Interestingly, the small-molecule inhibitor targeting USP48 induces destabilization of HMGA2. Clinically, upregulation of USP48 or HMGA2 in cancerous tissues is indicative of poor prognosis for patients with colorectal cancer (CRC). Collectively, our study not only elucidates the regulatory mechanism of DUBs involved in HMGA2 stability and validates USP48 as a potential therapeutic target for CRC, but also identifies DUB-IN-2 as a potent inhibitor of USP48 and a promising candidate for CRC treatment.

Childhood maltreatment patterns and suicidal ideation: mediating roles of depression, hope, and expressive suppression.

Childhood maltreatment has long-term negative effects on individuals' physical and mental well-being, and may increase the risk for suicidal ideation. However, how different patterns of childhood maltreatment affect subsequent suicidal ideation and the underlying mediating mechanisms remain unclear, particularly among Chinese adolescents. This study used latent profile analysis to identify patterns of childhood maltreatment among adolescents and explored how these patterns predicted subsequent suicidal ideation via depression, hope, and expressive suppression. This study used a two-wave, 1-year longitudinal design and included 2156 adolescents (Mage = 13.97 years, SDage = 1.61 years; 49.6% females). We identified three patterns of childhood maltreatment: low maltreatment, high psychological neglect, and high maltreatment. Compared with the low maltreatment group, the high maltreatment group indirectly predicted subsequent suicidal ideation 1 year later via depression through hope and expressive suppression, whereas the direct effect on suicidal ideation was not significant. Compared with the low maltreatment group, the high psychological neglect group had a significant direct effect on subsequent suicidal ideation and indirectly predicted suicidal ideation through depression or hope. Identifying patterns of childhood maltreatment among adolescents will assist mental health workers in developing targeted interventions to effectively alleviate suicidal ideation.

Fatty acid esters of hydroxy fatty acids: A potential treatment for obesity-related diseases.

Obesity, a burgeoning worldwide health system challenge, is associated with multiple chronic diseases, including diabetes and chronic inflammation. Fatty acid esters of hydroxy fatty acids (FAHFAs) are newly identified lipids with mitigating and anti-inflammatory effects in diabetes. Increasing work has shown that FAHFAs exert antioxidant activity and enhance autophagy in neuronal cells and cardiomyocytes. We systematically summarized the biological activities of FAHFAs, including their regulatory effects on diabetes and inflammation, antioxidant activity, and autophagy augmentation. Notably, the structure-activity relationships and potential biosynthesis of FAHFAs are thoroughly discussed. FAHFAs also showed potential roles as diagnostic biomarkers. FAHFAs are a class of resources with promising applications in the biomedical field that require in-depth research and hotspot development, as their structure has not been fully resolved and their biological activity has not been fully revealed.

Phosphorylation-dependent deubiquitinase OTUD3 regulates YY1 stability and promotes colorectal cancer progression.

Yin Yang 1 (YY1) is a key transcription factor that has been implicated in the development of several malignancies. The stability of YY1 is regulated by the ubiquitin-proteasome system. The role of deubiquitinases (DUBs) and their impact on YY1 remain to be fully elucidated. In this study, we screened for ubiquitin-specific proteases that interact with YY1, and identified OTUD3 as a DUB for YY1. Over-expressed OTUD3 inhibited YY1 degradation, thereby increasing YY1 protein levels, whereas OTUD3 knockdown or knockout promoted YY1 degradation, thereby decreasing the proliferation of colorectal cancer (CRC). Furthermore, PLK1 mediates OTUD3 S326 phosphorylation, which further enhances OTUD3 binding and deubiquitination of YY1. In CRC tissues, elevated the expression level of OTUD3 and YY1 were significantly associated with poor prognostic outcomes. These findings suggest that the OTUD3-YY1 pathway has therapeutic potential in CRC, and OTUD3 plays a critical role in regulating YY1.

Inhibition of Pard3 promotes breast cancer metastasis via the USP28 mediated deubiquitination of Snail1.

Pard3 is a core component of the Par complex and is a critical regulator of cell polarity. However, the biological role of Pard3 in breast cancer (BC) remains unclear. In this study we found that Pard3 levels were down-regulated in BC cells and tissues. Pard3 down-regulation was associated with the TNM stage of BC. Further, Pard3 knockdown enhanced colony formation and metastasis in vitro and in vivo. Interestingly, Pard3 knockdown also enhanced Snail1 deubiquitination and promoted BC invasion and migration via Snail1. Moreover, Pard3 silencing led to activation of the NFκB pathway, promoting the expression of USP28. Subsequently, USP28 interacted with and deubiquitinated Snail1; these effects were dependent on GSK-3ß-mediated phosphorylation. Together, the findings indicated that Pard3 knockdown facilitated the migration and invasion of BC cells by enhancing USP28-mediated Snail1 deubiquitination. Collectively, targeting the Pard3/NFκB/USP28/Snail1 signaling pathway might be a promising treatment option for breast cancer.

Performance of the mid-infrared Q-switched LD side-pumped Er:YSGG MOPA laser.

We report on a laser-diode (LD)-pumped master-oscillator power amplifier (MOPA) mid-infrared laser system based on an LD side-pumped Er:YSGG seed laser that can operate in both free-running and Q-switched regimes. In the free-running mode of the seed laser, the maximum amplified single-pulse energy was 83.4 mJ. In Q-switched mode of the seed laser, a maximum single-pulse energy of 7.8 mJ was achieved at 100 Hz repetition rate with the pulse width of 90 ns, corresponding to the peak power of 86.7 kW and the single-pass amplification factor of 1.66. The results indicate that the LD side-pumped MOPA structure is an effective way to realize a nanosecond ∼3µm mid-infrared laser with high repetition rate and high pulse energy.

Trajectories of parental posttraumatic stress disorder and children's mental health following Super Typhoon Lekima: The mediating role of feeling of safety.

INTRODUCTION: Several studies have examined the impact of parents' posttraumatic stress disorder (PTSD) on their children's mental health, but few have evaluated the role of parents' specific PTSD trajectories. The aim of this study was to assess the mechanisms underlying distinct trajectories of parental PTSD that affect children's PTSD and depression through the feeling of safety. METHODS: The final sample comprised 242 dyads of parents and their children who experienced Super Typhoon Lekima in 2019. All participants were surveyed at three time points after the typhoon: 3 months (T1), 15 months (T2), and 27 months (T3). Parental PTSD symptoms at three time points and children's PTSD, depression, and feeling of safety at T3 were analyzed. RESULTS: Four parental PTSD trajectories were identified: recovery, resilience, delayed, and coping. Compared with the resilient group, children of parents with delayed PTSD trajectories reported higher levels of depression at T3, while children of parents in the coping group were more likely to experience severe PTSD at T3. Children of parents in the recovery group, with a reduced feeling of safety, exhibited more severe depression and PTSD at T3, whereas children of parents in the delayed group were at an increased risk of PTSD at T3. CONCLUSIONS: These findings highlight the heterogeneity of parental PTSD trajectories following natural disasters and their distinct effects on children's PTSD and depression. Furthermore, feeling of safety emerges as a crucial mechanism in this process.

Bullying Victimization and Comorbid Patterns of PTSD and Depressive Symptoms in Adolescents: Random Intercept Latent Transition Analysis.

Many studies have examined post-traumatic stress disorder (PTSD) or depressive symptoms in adolescents under the background of school bullying, but not their comorbidities and changes over time. This study used random intercept latent transition analysis (RI-LTA) to examine the transitions in comorbid patterns of PTSD and depressive symptoms among 815 adolescents (45.0% boys; Mage-baseline = 13.69, SD = 1.60), who reported their symptoms in a 3-year longitudinal study. Three comorbid patterns were found: low symptoms, predominantly PTSD symptoms, and symptoms of comorbidity. Among these patterns, five trends were found through 3 years: stable low symptoms, stable PTSD symptoms, improving symptoms, worsening symptoms, and an inverted-U pattern. Age, time that parents spend with their child, being an only child, family income and experiencing relational bullying were predictors of these transitions. These suggest that patterns of PTSD and depressive symptoms are heterogeneous and may change over time since trauma events. Developing targeted interventions based on underlying factors through distinct patterns and transitions may help us better optimize and utilize intervention resources to alleviate symptoms from bullying victims.

Effects of instantaneous changes in temperature, light, and salinity on the dynamics of dissolved organic carbon release by Sargassum thunbergii.

Although macroalgae are regarded as the emerging fourth category of "blue carbon", few studies are available on the dynamics of dissolved organic carbon (DOC) release. Sargassum thunbergii is a typical intertidal macroalgae; and tidal action usually triggers instantaneous changes in temperature, light and salinity. Therefore, we investigated the mechanism of short-term changes in temperature, light and salinity on DOC release by S. thunbergii. As well as these factors coupled with desiccation, the combined effect of DOC release was revealed. The results showed the DOC release rate of S. thunbergii was from 0.028 to 0.037 mg C g -1(FW) h-1 under different photosynthetically active radiation (PAR, 0-1500 µmol photons m-2 s-1). The DOC release rate of S. thunbergii was from 0.008 to 0.208 mg C g -1(FW) h-1 under different salinity (5-40). The DOC release rate of S. thunbergii was from 0.031 to 0.034 mg C g -1(FW) h-1 under different temperature (10-30 °C). Either the increase in intracellular organic matter concentration due to increased photosynthesis (change in PAR and temperature, active), cell dehydration due to dry-out process (passive) or the decrease in extracellular salt concentration (passive) would lead to an increase in the difference in osmotic pressure and promote DOC release.

Robust fusion for skin lesion segmentation of dermoscopic images.

Robust skin lesion segmentation of dermoscopic images is still very difficult. Recent methods often take the combinations of CNN and Transformer for feature abstraction and multi-scale features for further classification. Both types of combination in general rely on some forms of feature fusion. This paper considers these fusions from two novel points of view. For abstraction, Transformer is viewed as the affinity exploration of different patch tokens and can be applied to attend CNN features in multiple scales. Consequently, a new fusion module, the Attention-based Transformer-And-CNN fusion module (ATAC), is proposed. ATAC augments the CNN features with more global contexts. For further classification, adaptively combining the information from multiple scales according to their contributions to object recognition is expected. Accordingly, a new fusion module, the GAting-based Multi-Scale fusion module (GAMS), is also introduced, which adaptively weights the information from multiple scales by the light-weighted gating mechanism. Combining ATAC and GAMS leads to a new encoder-decoder-based framework. In this method, ATAC acts as an encoder block to progressively abstract strong CNN features with rich global contexts attended by long-range relations, while GAMS works as an enhancement of the decoder to generate the discriminative features through adaptive fusion of multi-scale ones. This framework is especially good at lesions of varying sizes and shapes and of low contrasts and its performances are demonstrated with extensive experiments on public skin lesion segmentation datasets.

The entertainment videos pushed by WeChat promote the mental health of undergraduate students.

The present study addressed whether watching entertainment videos in succession could have a positive effect on the mental health of undergraduate students. Two experiments were designed. One hundred and sixteen university students participated in experiment 1. It aimed to explore whether watching motivational videos pushed by WeChat in continuous four weeks could affect mental health at the individual level, including mental health level and achievement goal orientation level. Experiment 2 enrolled 108 undergraduate students. It aimed to explore whether watching motivational and comedy videos pushed by WeChat in continuous four weeks could affect the mental health of undergraduate students at the social adaptation level, including interpersonal relationships and class atmosphere level. Results showed that entertainment videos pushed by WeChat in succession have significant positive effects on the university students' mental health and positive psychological quality.

Golgi fucosyltransferase 1 reveals its important role in α-1,4-fucose modification of N-glycan in CRISPR/Cas9 diatom Phaeodactylum tricornutum.

Phaeodactylum tricornutum (Pt) is a critical microbial cell factory to produce a wide spectrum of marketable products including recombinant biopharmaceutical N-glycoproteins. N-glycosylation modification of proteins is important for their activity, stability, and half-life, especially some special modifications, such as fucose-modification by fucosyltransferase (FucT). Three PtFucTs were annotated in the genome of P. tricornutum, PtFucT1 was located on the medial/trans-Golgi apparatus and PtFucT2-3 in the plastid stroma. Algal growth, biomass and photosynthesis efficiency were significantly inhibited in a knockout mutant of PtFucT1 (PtFucT1-KO). PtFucT1 played a role in non-core fucose modification of N-glycans. The knockout of PtFucT1 might affect the activity of PtGnTI in the complex and change the complex N-glycan to mannose type N-glycan. The study provided critical information for understanding the mechanism of protein N-glycosylation modification and using microalgae as an alternative ecofriendly cell factory to produce biopharmaceuticals.

Cadmium-containing windmill-like heteropolyoxoniobate macrocycle with high yield for catalyzing Knoevenagel condensation.

A rare cadmium-containing windmill-like heteropolyoxoniobate macrocycle has been successfully synthesized with stable 1-D cyclic cluster aggregates. The compound exhibited promising basic catalytic ability for Knoevenagel condensation with a high yield under mild reaction conditions and high cycling stability. The theoretical calculation showed that the promising basic catalytic ability is due to the dense and stronger basic sites of the surface terminal O atoms.

The Inhibitory Effect of Phycocyanin Peptide on Pulmonary Fibrosis In Vitro.

Phycocyanin is an excellent antioxidant with anti-inflammatory effects on which recent studies are growing; however, its specific target remains unclear. Linear tetrapyrrole compounds such as bilirubin have been shown to lead to the induction of heme oxygenase 1 expression in vivo, thus achieving antioxidant and anti-inflammatory effects. Phycocyanin is bound internally with linear tetrapyrrole phycocyanobilin in a similar structure to bilirubin. We speculate that there is probably a way of inducing the expression of heme oxygenase 1, with which tissue oxidative stress and inflammation can be inhibited, thus inhibiting pulmonary fibrosis caused by oxidative damage and inflammation of lung. By optimizing the enzymatic hydrolysis process, phycocyanobilin-bound phycocyanin peptide were obtained, and its in vitro antioxidant, anti-inflammatory, and anti-pulmonary fibrosis activities were investigated. The results show that the phycocyanobilin peptide was able to alleviate oxidative and inflammatory damage in cells through the Keap1-Nrf2-HO-1 pathway, which in turn relieved pulmonary fibrosis symptoms.