Age and Density of Mated Females Affect Dispersal Strategies in Spider Mite Tetranychus ludeni Zacher.

The dispersal strategies of a species can affect its invasion success. Investigations into the dispersal strategies of invasive species in relation to different factors help improve our understanding of invasion mechanisms and provide knowledge for population management and invasion evaluation. Tetranychus ludeni Zacher (Acari: Tetranychidae) is an invasive species which is native to Europe but is now cosmopolitan. Here, we examined the effects of age and density on dispersal in mated females. Our results show that older females that are capable of producing more eggs within 24 h were more likely to disperse and moved longer distances than younger ones with fewer eggs. Older females spread most of their eggs out of their natal habitats and over longer distances, which reduced competition and increased offspring fitness. Females exhibited significantly increased dispersal probability and distances with an increase in population density to avoid crowding. The synchronization of dispersal and reproduction, along with the positive density-dependent dispersal strategy, may facilitate the habitat colonization and invasion speed of T. ludeni.

Parasitoid-host interaction behaviors in relation to host stages in the Tamarixia triozae (Hymenoptera: Eulophidae)-Bactericera cockerelli (Hemiptera: Triozidae) system.

Females of host-feeding parasitic wasps often partition hosts of different stages for feeding and parasitization, but the underlying behavioral mechanisms are largely unknown, making it difficult to evaluate parasitoid-host interactions and their effects on biological control success. Tamarixia triozae (Burks) is an ectoparasitoid of tomato-potato psyllid Bactericera cockerelli (Sulc), which utilizes nymphs and kills them both by parasitization and host feeding. In this study, we exposed female wasps to 1st- to 5th-instar psyllid nymphs simultaneously and made 13-h continuous video recording of parasitoid-host interactions. We then quantified host stage-dependent handling time for feeding and oviposition and behaviors of parasitoid attacks and host defenses from encountering to successful feeding and oviposition. Female wasps were more likely to encounter and evaluate older hosts. However, the encounter and evaluation did not necessarily result in the success of feeding and oviposition. Our findings suggest that (i) T. triozae continues to assess the host using its ovipositor after the evaluation phase, (ii) females prefer the mid-aged hosts for feeding piercing and feeding and the later instars for oviposition probing and oviposition, (iii) the combination of stage-specific host nutrition value, integument thickness and defense behavior determines the success of feeding attacks, and (iv) the optimal host resource for parasitoid offspring fitness defines host stage selection for oviposition. This study contributes to our understanding of parasitoid-host interactions and mechanisms behind host stage selections.

Dual-monomer solvatochromic probe system (DSPS) for effectively differentiating lipid raft cholesterol and active membrane cholesterol in the inner-leaflet plasma membrane.

Monitoring active membrane cholesterol and lipid raft cholesterol in the inner leaflet of the plasma membrane is significant for understanding the membrane function and cellular physiopathological processes. Limited by existing methods, it is difficult to differentiate active membrane cholesterol and lipid raft cholesterol. A novel dual-monomer solvatochromic probe system (DSPS) that targets two types of cholesterol was developed. Acrylodan-BG/SNAP-D4 composed of SNAP-D4 cholesterol-recognizing monomers and solvatochromic acrylodan-BG-sensing monomers exhibits excellent cholesterol detecting properties in terms of selectivity, accuracy, convenience and economic benefits. Cell imaging revealed that lipid raft cholesterol emitted blue fluorescence, whereas active membrane cholesterol (which partially bobbed in aqueous cytosol) displayed green fluorescence; both the fluorescence emissions increased or decreased in a cholesterol-dependent manner. This system provides a new technology for the determination of two types of cholesterol, which is beneficial for the further study of membrane function, intracellular cholesterol trafficking, and cell signaling.

Vegetation-fire feedbacks increase subtropical wildfire risk in scrubland and reduce it in forests.

Climate dictates wildfire activity around the world. But East and Southeast Asia are an apparent exception as fire-activity variation there is unrelated to climatic variables. In subtropical China, fire activity decreased by 80% between 2003 and 2020 amid increased fire risks globally. Here, we assessed the fire regime, vegetation structure, fuel flammability and their interactions across subtropical Hubei, China. We show that tree basal area (TBA) and fuel flammability explained 60% of fire-frequency variance. Fire frequency and fuel flammability, in turn, explained 90% of TBA variance. These results reveal a novel system of scrubland-forest stabilized by vegetation-fire feedbacks. Frequent fires promote the persistence of derelict scrubland through positive vegetation-fire feedbacks; in forest, vegetation-fire feedbacks are negative and suppress fire. Thus, we attribute the decrease in wildfire activity to reforestation programs that concurrently increase forest coverage and foster negative vegetation-fire feedbacks that suppress wildfire.

Individualised prediction of progression of solitary sub-solid pulmonary nodules based on CT semantic and clinical features: a 3-year follow-up study.

AIM: To develop and validate a progressive prediction model for estimating the time to progression (TTP) of sub-solid pulmonary nodules (SSNs). MATERIALS AND METHODS: A total of 126 cases who met inclusion and exclusion criteria were included in the study. The primary endpoint of the study was TTP of SSNs. Baseline characteristics were assessed in terms of clinical and CT semantic features. Kaplan-Meier analysis and Cox regression analysis were performed to determine the relationship between SSNs TTP and factors from the entire data set. The nomogram was constructed based on the result of multivariate analysis and internal validation was performed using the bootstrapping. The nomogram's performance was assessed with the C-index, calibration curves, and decision curve analysis. RESULTS: The median follow-up time of the population was 42.5 (21.5) months. On Kaplan-Meier analysis, patients with higher or positive values of the indices had higher cumulative progression rates (p<0.05). Multivariate Cox regression models identified diameter, consolidation tumour ratio (CTR), morphology, and vasodilation sign (VDS) as independent risk factors of TTP. These predictors were included in the final model to estimate individual probabilities of progression in the 3 years, which performed well in the discrimination (the C-index was 0.901 [95%CI: 0.830-0.981] and 0.875 [95%CI: 0.805-0.942] in the training and internally validation sets). CONCLUSION: The radiological semantic features nomogram is a promising and favourable prognostic biomarker for predicting progression and may aid in clinical risk stratification and decision-making for SSNs.

Sudomotor dysfunction is associated with impaired left ventricular diastolic function in persons with type 2 diabetes: a cross-sectional study.

BACKGROUND: The incidence of preserved ejection fraction heart failure has significantly increased in persons with type 2 diabetes mellitus (T2DM). Left ventricular (LV) diastolic dysfunction is an early and important manifestation of preserved ejection fraction heart failure. The onset of heart failure in persons with diabetes is associated with diabetic neuropathy. However, the relationship among sudomotor function, which is an early manifestation of small fiber neuropathy, and LV diastolic function remains unclear. This study aimed to explore the association between sudomotor function and LV diastolic function in persons with T2DM. METHODS: In total, 699 persons with T2DM were enrolled and divided into three groups according to electrochemical skin conductance (ESC) assessed using the SUDOSCAN device: "no dysfunction" group (NSF), "moderate dysfunction" group (MDF), and "severe dysfunction" group (SDF). LV diastolic function was assessed using Doppler echocardiography. To evaluate the relationship between ESC and echocardiographic parameters, Pearson's correlation analysis was performed. Additionally, logistic regression analysis was used to determine the association between LV diastolic function and ESC. A receiver operating characteristic (ROC) curve was constructed to evaluate the performance of sudomotor function indicators in detecting impaired cardiac diastolic function. RESULTS: There were 301 persons (43.06%) in the NSF group, 232 (33.19%) in the MDF group, and 166 (23.75%) in the SDF group. Compared to the NSF group, the MDF and SDF groups had higher A and E/e' and lower e' values (all p < 0.05). Pearson's correlation analysis showed that A and E/e' were negatively associated with foot ESC (FESC) and hand ESC (HESC), whereas e' was positively associated with FESC and HESC (all p < 0.05). After adjusting for confounding factors, binary logistic regression analysis showed that ESC was independently associated with impaired LV diastolic function (p = 0.003). The area under the ROC curve values for FESC and HESC were 0.621 and 0.635, respectively (both p < 0.05). CONCLUSIONS: Deteriorating sudomotor function was associated with reduced diastolic function indicators. ESC can be used as a biomarker for detecting LV diastolic impairment.

[Treatment of intrauterine adhesions in rats with hypoxia-cultured BMSC-derived exosomes].

Objective: To perform intrauterine adhesion modeling, and to investigate the repair effect of hypoxic treated bone marrow mesenchymal stem cells (BMSC) and their derived exosomes (BMSC-exo) on endometrial injury. Methods: BMSC and their exosomes BMSC-exo extracted from rats' femur were cultured under conventional oxygen condition (21%O2) or hypoxia condition (1%O2). Intrauterine adhesion modeling was performed on 40 healthy female SD rats by intrauterine injection of bacterial lipopolysaccharide after curettage. On the 28th day of modeling, 40 rat models were randomly divided into five groups, and interventions were performed: (1) NC group: 0.2 ml phosphate buffered solution was injected into each uterine cavity; (2) BMSC group: 0.2 ml BMSC (1×106/ml) with conventional oxygen culture was injected intrauterine; (3) L-BMSC group: 0.2 ml of hypoxic cultured BMSC (1×106/ml) was injected intrauterine; (4) BMSC-exo group: 0.2 ml of BMSC-exo cultured with conventional oxygen at a concentration of 500 µg/ml was injected into the uterine cavity; (5) L-BMSC-exo group: 0.2 ml hypoxic cultured BMSC-exo (500 µg/ml) was injected intrauterine. On the 14th and 28th day of treatment, four rats in each group were sacrificed by cervical dislocation after anesthesia, and endometrial tissues were collected. Then HE and Masson staining were used to observe and calculate the number of glands and fibrosis area in the endometrium. The expressions of angiogenesis related cytokines [vascular endothelial growth factor A (VEGFA) and CD31], and fibrosis-related proteins [collagen-Ⅰ, collagen-Ⅲ, smooth muscle actin α (α-SMA), and transforming growth factor ß1 (TGF-ß1)] in endometrial tissues were detected by western blot. Results: (1) HE and Masson staining showed that the number of endometrial glands in L-BMSC group, BMSC-exo group and L-BMSC-exo group increased and the fibrosis area decreased compared with NC group on the 14th and 28th day of treatment (all P<0.05). Noteworthily, the changes of L-BMSC-exo group were more significant than those of BMSC-exo group (all P<0.05), and the changes of BMSC-exo group were greater than those of BMSC group (all P<0.05). (2) Western blot analysis showed that, compared with NC group, the expressions of collagen-Ⅲ and TGF-ß1 in BMSC group, L-BMSC group, BMSC-exo group and L-BMSC-exo group decreased on the 14th and 28th day of treatment (all P<0.05). As the treatment time went on, the expressions of fibrosis-related proteins were different. Compared with BMSC group, the expressions of collagen-Ⅲ, α-SMA and TGF-ß1 in the BMSC-exo group and L-BMSC group decreased on the 28th day (all P<0.05). Moreover, the expressions of collagen-Ⅲ and TGF-ß1 in L-BMSC-exo group were lower than those in BMSC-exo group on the 28th day (all P<0.05). And the expressions of collagen-Ⅰ, α-SMA and TGF-ß1 in L-BMSC-exo group were lower than those in L-BMSC group on the 28th day (all P<0.05). (3) The results of western blot analysis of VEGFA and CD31 showed that, the expressions of VEGFA and CD31 in BMSC group, L-BMSC group, BMSC-exo group and L-BMSC-exo group increased on the 14th and 28th day of treatment compared with NC group (all P<0.05). Treatment for 28 days, the expressions of VEGFA and CD31 in BMSC-exo group and CD31 in L-BMSC group were higher than those in BMSC group (all P<0.05). Moreover, the expressions of VEGFA and CD31 in L-BMSC-exo group were higher than those in BMSC-exo group and L-BMSC group on the 28th day (all P<0.05). Conclusions: Treatment of BMSC and their exosomes BMSC-exo with hypoxia could promote endometrial gland hyperplasia, inhibit tissue fibrosis, and further repair the damaged endometrium in rats with intrauterine adhesion. Importantly, hypoxic treatment of BMSC-exo is the most effective in intrauterine adhesion rats.

Associations of Body-Roundness Index and Sarcopenia with Cardiovascular Disease among Middle-Aged and Older Adults: Findings from CHARLS.

OBJECTIVES: Sarcopenia and obesity may contribute to chronic disease. However, little is known about the association between sarcopenia, body roundness index (BRI), and cardiovascular disease (CVD). The aim of this study was to investigate the association of sarcopenia and BRI with CVD in middle-aged and older Chinese population. DESIGN: Cohort study with an 8-year follow-up. SETTING AND PARTICIPANTS: Data were derived from 4 waves of the China Health and Retirement Longitudinal Study, and 6152 participants aged 45 or above were included in the study. METHODS: Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019 criteria. CVD was defined as the presence of physician-diagnosed heart disease, diabetes and/or stroke. The associations of BRI and sarcopenia with CVD risk were explored using Cox proportional hazards regression models. RESULTS: The mean age of the participants was 58.3 (8.9) years, and 2936 (47.7%) were males. During the 8 years follow-up, 2385 cases (38.8%) with incident CVD were identified. Longitudinal results demonstrated that compared to neither sarcopenia or high BRI, both sarcopenia and high BRI (HR: 1.49, 95%CI: 1.08, 2.07) were associated with higher risk of CVD. In the subgroup analysis, individuals with both sarcopenia and high BRI were more likely to have new onset stroke (HR: 1.93, 95%CI: 1.12, 3.32) and increased risk of multimorbidity (HR: 2.15, 95% CI: 1.14, 4.04). CONCLUSIONS: Coexistence of sarcopenia and high BRI was associated with higher risk of CVD. Early identification and intervention for sarcopenia and BRI not only allows the implementation of therapeutic strategies, but also provides an opportunity to mitigate the risk of developing CVD.

Effect of emodin combined with cisplatin on the invasion and migration of HepG2 hepatoma cells.

Cisplatin is the leading chemotherapy agent for advanced liver cancer. However, the resistance to cisplatin in liver cancer reduces its efficacy. A potential strategy to increase its effectiveness and reduce toxicity is to combine cisplatin with 1,3,8-trihydroxy-6-methylanthraquinone (emodin). In this study, we examined the effects of emodin combined with cisplatin on the invasion and migration of HepG2 cells and analyzed the role of emodin. The effects of cisplatin, emodin and their combination were assessed in HepG2 cells. Proliferation, invasion and migration of HepG2 cells were examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT), scar and Transwell assays. The gelatinase spectrum and an ELISA detected the expression of matrix metallopeptidase 2 (MMP-2) and matrix metallopeptidase 9 (MMP-9). The expression of E-cadherin and vimentin was detected by immunofluorescence and Western blots. Emodin inhibited cell invasion and migration in HepG2 hepatoma cells, increased E-cadherin expression, decreased vimentin, MMP-2, and MMP-9 expression. The combination of emodin and cisplatin-induced a more significant effect in a dose-dependent manner. In this study, we found that emodin inhibited hepatocellular carcinoma (HCC) metastasis. Compared with either cisplatin or emodin alone, the combination of both showed a more significant synergistic effect. Emodin can enhance the sensitivity of HepG2 HCC cells to cisplatin by inhibiting epithelial-mesenchymal transition, and thus, play a role in preventing recurrence and metastasis in HCC.

Serum SIRT6 Levels Are Associated with Frailty in Older Adults.

OBJECTIVES: Frailty is one of the major health problems facing aging societies worldwide. We investigated the association between serum SIRT6 and frailty in older adults. DESIGN: Cross-sectional analysis of associations of serum SIRT6 and frailty in older people. SETTING: Enrolled community-dwelling and hospital outpatient clinic adults older than 65 years old in Wuhan City, Hubei Province, China. PARTICIPANTS: A total of 540 community-dwelling older adults (age ≥ 65 years) in Wuhan were included in the study. MEASURES: We used Frailty Phenotype criteria for classifying participants based on their frailty status. Serum SIRT6 was measured using an ELISA kit. RESULTS: A total of 540 older adults were included in this cross-sectional study. Serum SIRT6 was lower in the slowness group (7.23±1.81 vs 5.89±1.74, p<0.001), weakness group (6.87±1.88 vs 5.68±1.64, p<0.001), and exhaustion group (6.73±1.90 vs 5.88±1.74, p<0.001) compare with the normal group. ROC curves were used to assess the efficiency of SIRT6 in predicting frailty in older adults. The AUC for SIRT6 was 0.792 (95% CI: 0.7514 to 0.8325), with the highest sensitivity of 68.0% and the specificity of 91.9%, and the optimal critical value of 4.65ng/ml according to Youden's index. Multivariate logistic regression analysis showed that serum SIRT6 level was independently associated with frailty in older people. CONCLUSION: In conclusion, serum SIRT6 was decreased in frailty compared with robust older adults. A decreased serum SIRT6 was independently associated with an increased risk of frailty. SIRT6 may be a potential target for the treatment of patients with frailty.

Resource allocation strategies for survival and reproduction by an invasive pest in response to intermittent fasting.

Intermittent fasting (IF) is a type of dietary restriction that involves fasting periods in intervals, which has been used as a strategy to improve health and extend longevity. Regular fasting is common during the process of biological invasions in nature. Yet, it is not clear how invasive animals adjust their resource allocations to survival and reproduction when periodical starvation occurs. Here, we used Tetranychus ludeni, a haplodiploid spider mite and an important invasive pest of horticultural crops around the world, to investigate the effects of IF on its life history strategies. We show that IF increased the longevity in females but not in males probably because of differences in resource storage, metabolic rate, and mating cost between sexes. In response to IF, females traded off fecundity and egg size but not the number of daughters for longevity gain, suggesting that T. ludeni females can adjust their life history strategies for population survival and growth during invasion process. Eggs produced by fasted females realized the same hatch rate and resultant young had the same survival rate as those by unfasted ones. In addition, IF had transgenerational maternal effects which prolonged offspring development period. We suggest that the longer immature developmental period can increase the body size of resulting adults, compensating egg size loss for offspring fitness. Our findings provide insight into resource allocations as responses to fasting, knowledge of which can be used for evaluation of pest invasions and for management of animal survival and reproduction by dietary regulations.

Pest management of postharvest potatoes: lethal, sublethal and transgenerational effects of the ectoparasitic mite Pyemotes zhonghuajia on the potato worm Phthorimaea operculella.

BACKGROUND: Potato, Solanum tuberosum, is one of the most important food crops in the world, playing a significant role in global food security. However, many potato industries and farms may suffer losses of tuber yield and quality in storage due to lepidopteran pests. Here, we evaluated the effectiveness of an ectoparasitic idiobiont mite Pyemotes zhonghuajia in the biological control of the potato tuber moth (PTM) Phthorimaea operculella by determining the lethal, sublethal (nonconsumptive) and transgenerational effects of P. zhonghuajia of various population densities and exposure durations on PTM survival, development and reproduction. RESULTS: Pyemotes zhonghuajia females were capable of killing all instar stages of PTM, while resistance to mite parasitism increased with the development of PTM life stage. The mortality of mature larvae (i.e., fourth instar) and pupae increased with increasing mite density and exposure duration. P. zhonghuajia imposed significant negative sublethal impacts on PTM pupation rate, female fecundity and adult longevity but not on immature development. The sublethal stress was transgenerational, resulting in lower reproduction in the offspring generation. CONCLUSION: P. zhonghuajia induces lethal, sublethal and transgenerational effects and significantly decreases PTM survival and reproductive out, demonstrating its high efficiency in the biological control of PTM. Our study provides insight into the mechanisms underlying the nonconsumptive effects of parasitism in an ectoparasite-host system and delivers critical information for the design and implementation of augmentative releases of P. zhonghuajia in the biological control of PTM in potato storage. © 2023 Society of Chemical Industry.

Temperature but Not Photoperiod Can Predict Development and Survival of an Invasive Apple Pest.

The apple leaf-curling midge, Dasineura mali Kieffer (Diptera: Cecidomyiidae), is an invasive pest of apple, and can contaminate fresh fruit for export, causing biosecurity problems. To provide crucial information for its pest risk analysis, forecast, and management, we investigated the effects of temperatures (5, 10, 15, 20 and 25 °C) and daylengths (10, 11, 12, 13, 14 and 15 h) on its development and survival. The midge eggs failed to hatch at 5 °C and larvae could not complete development at 10 °C. Pupation and emergence rates were significantly higher at 20 °C than at 15 °C and 25 °C. Daylength had no effect on these parameters. The low temperature threshold and thermal requirement to complete development from eggs to adults were 3.7 °C and 627 degree-days, respectively. The midge had a significantly lower thermal requirement for the completion of its lifecycle at 20 °C (614.5 degree-days) than at 15 °C (650.1 degree-days) and 25 °C (634.8 degree-days). The thermal model developed in this study provided accurate predictions of the number of D. mali generations and adult emergence time in each generation in different regions of New Zealand. We suggest that the model could be used to predict population dynamics of this pest in other parts of the world.

CD36 regulates diurnal glucose metabolism and hepatic clock to maintain glucose homeostasis in mice.

The mammalian circadian clock and glucose metabolism are highly interconnected, and disruption of this coupling is associated with multiple negative health outcomes. Liver is the major source of endogenous glucose production and liver clock is one of the most vital peripheral clock systems. We demonstrate that fatty acid translocase (CD36) is expressed rhythmically in mouse liver and autonomously modulates the diurnal oscillations of liver clock and glucose homeostasis. CD36 knockout in hepatocytes inhibits the relay of insulin signaling and provokes FoxO1 nuclear shuttling, consequently increasing Per1 nuclear expression. Moreover, FoxO1 can activate the central clock gene Per1 at the transcriptional level. These changes lead to a disrupted clock oscillation and behavioral rhythm. Our study first reveal that CD36 is a key regulator of the circadian oscillator and its deficiency may cause liver clock disruption, which aggravates the imbalance of glucose homeostasis and contribute to augmentation and progression of metabolic disease.

SCAP contributes to embryonic angiogenesis by negatively regulating KISS-1 expression in mice.

Sterol regulatory element-binding protein (SREBP) cleavage-activating protein (SCAP) is indispensable in organ development because it maintains intracellular cholesterol homeostasis. The vessel is not widely conceived of as a cholesterol-sensitive tissue, so the specific role of SCAP in angiogenesis has not been paid attention to. As an important component of the vascular mesoderm, vascular smooth muscle cells (VSMCs) are widely involved in each step of angiogenesis. Here, we report for the first time that VSMC-specific ablation of SCAP inhibits VSMC proliferation and migration, interacting with endothelial cells (ECs), and finally causes defective embryonic angiogenesis in mice. Mechanistically, we demonstrated that SCAP ablation in VSMCs leads to the upregulation of KISS-1 protein, consequently resulting in suppressed activation of the MAPK/ERK signaling pathway and downregulation of matrix metalloproteinase 9 (MMP9) and vascular endothelial-derived growth factor (VEGF) expression to prevent angiogenesis. Importantly, we found that SCAP promotes the cleavage and nuclear translocation of SREBP2, which acts as a negative transcription regulator, regulating KISS-1 expression. Our findings suggest that SCAP contributes to embryonic angiogenesis by negatively regulating KISS-1 expression in mice and provide a new point of view for therapeutic targets of vascular development.

Hepatocyte CD36 modulates UBQLN1-mediated proteasomal degradation of autophagic SNARE proteins contributing to septic liver injury.

Macroautophagy/autophagy plays a protective role in sepsis-induced liver injury. As a member of class B scavenger receptors, CD36 plays important roles in various disorders, such as atherosclerosis and fatty liver disease. Here we found that the expression of CD36 in hepatocytes was increased in patients and a mouse model with sepsis, accompanied by impaired autophagy flux. Furthermore, hepatocyte cd36 knockout (cd36-HKO) markedly improved liver injury and the impairment of autophagosome-lysosome fusion in lipopolysaccharide (LPS)-induced septic mice. Ubqln1 (ubiquilin 1) overexpression (OE) in hepatocyte blocked the protective effect of cd36-HKO on LPS-induced liver injury in mice. Mechanistically, with LPS stimulation, CD36 on the plasma membrane was depalmitoylated and distributed to the lysosome, where CD36 acted as a bridge molecule linking UBQLN1 to soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins and hence promoting the proteasomal degradation of SNARE proteins, resulting in fusion impairment. Overall, our data reveal that CD36 is essential for modulating the proteasomal degradation of autophagic SNARE proteins in a UBQLN1-dependent manner. Targeting CD36 in hepatocytes is effective for improving autophagic flux in sepsis and therefore represents a promising therapeutic strategy for clinical treatment of septic liver injury.Abbreviations: AAV8: adeno-associated virus 8; AOSC: acute obstructive suppurative cholangitis; ATP1A1: ATPase, Na+/K+ transporting, alpha 1 polypeptide; CASP3: caspase 3; CASP8: caspase 8; CCL2: chemokine (C-C motif) ligand 2; cd36-HKO: hepatocyte-specific cd36 knockout; Co-IP: co-immunoprecipitation; CQ: chloroquine; Cys: cysteine; GOT1: glutamic-oxaloacetic transaminase 1, soluble; GPT: glutamic-pyruvic transaminase, soluble; IL1B: interleukin 1 beta; IL6: interleukin 6; KO: knockout; LAMP1: lysosomal associated membrane protein 1; LDH, lactate dehydrogenase; LPS: lipopolysaccharide; LYPLA1: lysophospholipase 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; OE: overexpression; qPCR: quantitative polymerase chain reaction; SNAP29: synaptosome associated protein 29; SNARE: soluble N-ethylmaleimide-sensitive factor attachment protein receptor; SQSTM1/p62: sequestosome 1; STX17: syntaxin 17; TNF: tumor necrosis factor; TRIM: tripartite motif-containing; UBA: ubiquitin-associated; UBL: ubiquitin-like; UBQLN: ubiquilin; VAMP8: vesicle associated membrane protein 8; WT: wild-type.

[Soybean isoflavones alleviate cerebral ischemia/reperfusion injury in rats by inhibiting ferroptosis and inflammatory cascade reaction].

OBJECTIVE: To explore the mechanism that mediates the effect of soybean isoflavones (SI) against cerebral ischemia/reperfusion (I/R) injury in light of the regulation of regional cerebral blood flow (rCBF), ferroptosis, inflammatory response and blood-brain barrier (BBB) permeability. METHODS: A total of 120 male SD rats were equally randomized into sham-operated group (Sham group), cerebral I/R injury group and SI pretreatment group (SI group). Focal cerebral I/R injury was induced in the latter two groups using a modified monofilament occlusion technique, and the intraoperative changes of real-time cerebral cortex blood flow were monitored using a laser Doppler flowmeter (LDF). The postoperative changes of cerebral pathological morphology and the ultrastructure of the neurons and the BBB were observed with optical and transmission electron microscopy. The neurological deficits of the rats was assessed, and the severities of cerebral infarction, brain edema and BBB disruption were quantified. The contents of Fe2+, GSH, MDA and MPO in the ischemic penumbra were determined with spectrophotometric tests. Serum levels of TNF-α and IL-1ßwere analyzed using ELISA, and the expressions of GPX4, MMP-9 and occludin around the lesion were detected with Western blotting and immunohistochemistry. RESULTS: The rCBF was sharply reduced in the rats in I/R group and SI group after successful insertion of the monofilament. Compared with those in Sham group, the rats in I/R group showed significantly increased neurological deficit scores, cerebral infarction volume, brain water content and Evans blue permeability (P < 0.01), decreased Fe2+ level, increased MDA level, decreased GSH content and GPX4 expression (P < 0.01), increased MPO content and serum levels of TNF-α and IL-1ß (P < 0.01), increased MMP-9 expression and lowered occludin expression (P < 0.01). All these changes were significantly ameliorated in rats pretreated with IS prior to I/R injury (P < 0.05 or 0.01). CONCLUSION: SI preconditioning reduces cerebral I/R injury in rats possibly by improving rCBF, inhibiting ferroptosis and inflammatory response and protecting the BBB.

Loss of Splicing Factor SRSF3 Impairs Lipophagy Through Ubiquitination and Degradation of Syntaxin17 in Hepatocytes.

Lipid accumulation in hepatocytes is the distinctive characteristic of nonalcoholic fatty liver disease. Serine/arginine-rich splicing factor 3 (SRSF3) is highly expressed in the liver and expression decreases in high-fat conditions. However, the role of SRSF3 in hepatic lipid metabolism needs to be clarified. Here, we showed that loss of SRSF3 was associated with lipid accumulation. We determined that SRSF3 regulated lipophagy, the process of selective degradation of lipid droplets by autophagy. Mechanistically, loss of SRSF3 impaired the fusion of the autophagosome and lysosome by promoting the proteasomal degradation of syntaxin 17 (STX17), a key autophagosomal SNARE protein. We found that ubiquitination of STX17 was increased and upregulation of seven in absentia homolog 1 was responsible for the increased posttranslational modification of STX17. Taken together, our data primarily demonstrate that loss of SRSF3 weakens the clearance of fatty acids by impairing lipophagy in the progression of nonalcoholic fatty liver disease, indicating a novel potential therapeutic target for fatty liver disease treatment.