CLCF1 inhibits energy expenditure via suppressing brown fat thermogenesis.

Brown adipose tissue (BAT) is the main site of nonshivering thermogenesis which plays an important role in thermogenesis and energy metabolism. However, the regulatory factors that inhibit BAT activity remain largely unknown. Here, cardiotrophin-like cytokine factor 1 (CLCF1) is identified as a negative regulator of thermogenesis in BAT. Adenovirus-mediated overexpression of CLCF1 in BAT greatly impairs the thermogenic capacity of BAT and reduces the metabolic rate. Consistently, BAT-specific ablation of CLCF1 enhances the BAT function and energy expenditure under both thermoneutral and cold conditions. Mechanistically, adenylate cyclase 3 (ADCY3) is identified as a downstream target of CLCF1 to mediate its role in regulating thermogenesis. Furthermore, CLCF1 is identified to negatively regulate the PERK-ATF4 signaling axis to modulate the transcriptional activity of ADCY3, which activates the PKA substrate phosphorylation. Moreover, CLCF1 deletion in BAT protects the mice against diet-induced obesity by promoting BAT activation and further attenuating impaired glucose and lipid metabolism. Therefore, our results reveal the essential role of CLCF1 in regulating BAT thermogenesis and suggest that inhibiting CLCF1 signaling might be a potential therapeutic strategy for improving obesity-related metabolic disorders.

Vibrio splendidus infection promotes circRNA-FGL1-regulated coelomocyte apoptosis via competitive binding to Myc with the deubiquitinase OTUB1 in Apostichopus japonicus.

Circular RNAs (circRNAs) are involved in various physiological and pathological processes in both vertebrates and invertebrates. However, most studies on circRNAs have focused on their roles as endogenous competitive RNAs. Here, we report a novel function of circRNA derived from the Fibrinogen-like protein 1 gene (circ-FGL1) that inhibits coelomocyte apoptosis via competing with the deubiquitinase AjOTUB1 to bind AjMyc in Apostichopus japonicus during Vibrio splendidus infection. The results showed that circ-FGL1 is significantly downregulated in coelomocytes of V. splendidus-induced A. japonicus and negatively regulates coelomocyte apoptosis through the AjBax-AjCyt c pathway. Mechanistically, the deubiquitinase AjOTUB1 and circ-FGL1 could interact with the transcription factor protein AjMyc in the same region with circ-FGL1/AjMyc having greater affinity. Under normal conditions, high levels of circ-FGL1 bind directly to AjMyc, inhibiting the deubiquitylation of AjMyc by AjOTUB1 and leading to the degradation of AjMyc. After V. splendidus infection, AjMyc disassociates from the depressed expression of circ-FGL1, promoting its deubiquitylation by binding to the induced deubiquitinase AjOTUB1 to inhibit its degradation. AjMyc is then transferred to nucleus and promotes the transcription of AjCyt c and AjBax to induce coelomocyte apoptosis. The new finding will expand our present outstanding on the functional role of circRNAs and suggests new therapeutic targets for the treatment of echinoderms during bacterial invasion.

A Prediction Rule for the Dystonic Spread of Blepharospasm: A 4-Year Prospective Cohort Study.

OBJECTIVE: Blepharospasm (BSP), focal dystonia with the highest risk of spread, lacks clear understanding of early spreading risk factors and objective prognostic indicators. We aimed to identify these risk factors through clinical and electrophysiological assessments, and to establish a predictive model for dystonic spread in BSP. METHODS: We prospectively followed BSP patients for 4 years, collecting data on dystonic spread, and conducting electrophysiological evaluations. The blink reflex, masseter inhibitory reflex, and trigeminal somatosensory evoked potential were assessed. Univariable and multivariable Cox proportional hazard regression models were used to assess clinical characteristics associated with BSP dystonic spread. A predictive model was constructed using a nomogram, and performance of the model was evaluated using the area under the receiver operating characteristic curve. RESULTS: A total of 136 enrolled participants (mean age 56.34 years) completed a 4-year follow-up. Among them, 62 patients (45.6%) showed spread to other body regions. Multivariable Cox regression analysis showed that a high Hamilton Anxiety Scale score (hazard ratio 1.19, 95% confidence interval 1.13-1.25, p < 0.001), prolonged trigeminal somatosensory evoked potential mandibular branch P1-N2 peak interval (hazard ratio 1.11, 95% confidence interval 1.02-1.21, p = 0.017), and elevated trigeminal somatosensory evoked potential mandibular branch P1-N2 peak amplitude (hazard ratio 1.26, 95% confidence interval 1.12-1.41, p < 0.001) were independent risk factors for BSP dystonic spread within 4 years. Combining these factors, the predictive models demonstrated excellent discriminative ability, with the receiver operating characteristic curve score being 0.797, 0.790, 0.847, and 0.820 at 1, 2, 3 and 4 years after enrollment, respectively. INTERPRETATION: We established a predictive model with significant value for anticipating dystonic spread in BSP, offering crucial evidence. These findings contribute essential insights into the early clinical identification of the development and evolution of BSP diseases. ANN NEUROL 2024.

SIRT5 exacerbates eosinophilic chronic rhinosinusitis by promoting polarization of M2 macrophage.

BACKGROUND: Previous studies implied that local M2 polarization of macrophage promoted mucosal edema and exacerbated TH2 type inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). However, the specific pathogenic role of M2 macrophages and the intrinsic regulators in the development of CRS remains elusive. OBJECTIVE: We sought to investigate the regulatory role of SIRT5 in the polarization of M2 macrophages and its potential contribution to the development of CRSwNP. METHODS: Real-time reverse transcription-quantitative PCR and Western blot analyses were performed to examine the expression levels of SIRT5 and markers of M2 macrophages in sinonasal mucosa samples obtained from both CRS and control groups. Wild-type and Sirt5-knockout mice were used to establish a nasal polyp model with TH2 inflammation and to investigate the effects of SIRT5 in macrophage on disease development. Furthermore, in vitro experiments were conducted to elucidate the regulatory role of SIRT5 in polarization of M2 macrophages. RESULTS: Clinical investigations showed that SIRT5 was highly expressed and positively correlated with M2 macrophage markers in eosinophilic polyps. The expression of SIRT5 in M2 macrophages was found to contribute to the development of the disease, which was impaired in Sirt5-deficient mice. Mechanistically, SIRT5 was shown to enhance the alternative polarization of macrophages by promoting glutaminolysis. CONCLUSIONS: SIRT5 plays a crucial role in promoting the development of CRSwNP by supporting alternative polarization of macrophages, thus providing a potential target for CRSwNP interventions.

Cross-phase modulation in two-dimensional spectroscopy.

Developing from transient absorption (TA) spectroscopy, two-dimensional (2D) spectroscopy with pump-probe geometry has emerged as a versatile approach for alleviating the difficulty in implementing 2D spectroscopy with other geometries. However, the presence of cross-phase modulation (XPM) in TA spectroscopy introduces significant spectral distortions, particularly when the pump and probe pulses overlap. We demonstrate that this phenomenon is extended to the 2D spectroscopy with pump-probe geometry and the XPM is induced by the interference of the two pump pulses. We present the oscillatory behavior of XPM in the 2D spectrum and its displacement with respect to the waiting time delay through both experimental measurements and numerical simulations. Additionally, we explore the influence of probe pulse chirp on XPM and discover that by compressing the chirp, the impact of XPM on the desired signal can be reduced.

KARS Mutations Impair Brain Myelination by Inducing Oligodendrocyte Deficiency: One Potential Mechanism and Improvement by Melatonin.

It is very crucial to investigate key molecules that are involved in myelination to gain an understanding of brain development and injury. We have reported for the first time that pathogenic variants p.R477H and p.P505S in KARS, which encodes lysyl-tRNA synthetase (LysRS), cause leukoencephalopathy with progressive cognitive impairment in humans. The role and action mechanisms of KARS in brain myelination during development are unknown. Here, we first generated Kars knock-in mouse models through the CRISPR-Cas9 system. Kars knock-in mice displayed significant cognitive deficits. These mice also showed significantly reduced myelin density and content, as well as significantly decreased myelin thickness during development. In addition, Kars mutations significantly induced oligodendrocyte differentiation arrest and reduction in the brain white matter of mice. Mechanically, oligodendrocytes' significantly imbalanced expression of differentiation regulators and increased capase-3-mediated apoptosis were observed in the brain white matter of Kars knock-in mice. Furthermore, Kars mutations significantly reduced the aminoacylation and steady-state level of mitochondrial tRNALys and decreased the protein expression of subunits of oxidative phosphorylation complexes in the brain white matter. Kars knock-in mice showed decreased activity of complex IV and significantly reduced ATP production and increased reactive oxygen species in the brain white matter. Significantly increased percentages of abnormal mitochondria and mitochondrion area were observed in the oligodendrocytes of Kars knock-in mouse brain. Finally, melatonin (a mitochondrion protectant) significantly attenuated mitochondrion and oligodendrocyte deficiency in the brain white matter of KarsR504H/P532S mice. The mice treated with melatonin also showed significantly restored myelination and cognitive function. Our study first establishes Kars knock-in mammal models of leukoencephalopathy and cognitive impairment and indicates important roles of KARS in the regulation of mitochondria, oligodendrocyte differentiation and survival, and myelination during brain development and application prospects of melatonin in KARS (or even aaRS)-related diseases.

The nuclear receptor coactivator 4 regulates ferritinophagy induced by vibrio splendidus in coelomocytes of Apostichopus japonicus.

Iron homeostasis is vital for the host's defense against pathogenic invasion and the ferritinophagy is a crucial mechanism in maintaining intracellular iron homeostasis by facilitating the degradation and recycling of stored iron. The nuclear receptor coactivator 4 (NCOA4) serves as a ferritinophagy receptor, facilitating the binding and delivery of ferritin to the autophagosome and lysosome. However, NCOA4 of the sea cucumber Apostichopus japonicus (AjNCOA4) has not been reported until now. In this study, we identified and characterized AjNCOA4 in A. japonicus. This gene encodes a polypeptide containing 597 amino acids with an open reading frame of 1794 bp. The inferred amino acid sequence of AjNCOA4 comprises an ARA70 domain. Furthermore, a multiple sequence alignment demonstrated varying degrees of sequence homology between AjNCOA4 from A. japonicus and other NCOA4 orthologs. The phylogenetic tree of NCOA4 correlates with the established timeline of metazoan evolution. Expression analysis revealed that AjNCOA4 is expressed in all tested tissues, including the body wall, muscle, intestine, respiratory tree, and coelomocytes. Following challenge with Vibrio splendidus, the coelomocytes exhibited a significant increase in AjNCOA4 mRNA levels, peaking at 24 h. We successfully obtained recombinant AjNCOA4 protein through prokaryotic expression and prepared a specific polyclonal antibody. Immunofluorescence and co-immunoprecipitation experiments demonstrated an interaction between AjNCOA4 and AjFerritin in coelomocytes. RNA interference-mediated knockdown of AjNCOA4 expression resulted in elevated iron ion levels in coelomocytes. Bacterial stimulation enhanced ferritinophagy in coelomocytes, while knockdown of AjNCOA4 reduced the occurrence of ferritinophagy. These findings suggest that AjNCOA4 modulates ferritinophagy induced by V. splendidus in coelomocytes of A. japonicus.

Genome-wide identification and expression analysis of C-type lectins in discus fish (Symphysodon aequifasciatus) during parental care.

Discus fish (Symphysodon aequifasciatus) exhibit a unique parental care behavior: adult discus produces secretion through their skin, on which the larvae live after birth. The immune components in the skin mucus of parental discus would change during different parental care. C-type lectins (CTLs) could identify and eliminate pathogenic microorganisms and play important roles in innate immunity. Studies on CTLs of discus fish especially during parental care, however, are scarce. Here, we identified 186 CTL genes that distributed in 27 linkage groups based on discus genome. Phylogenetic analysis showed that S. aequifasciatus CTL (SaCTL) members were grouped into 14 subfamilies. A total of 80 gene replication events occurred, of which 15 pairs were subjected to segmental duplication and 65 pairs underwent tandem duplication. Ka/Ks ranged from 0.11 (SaCTL25/SaCTL158) to 0.68 (SaCTL36/SaCTL69), all undergoing purifying selection. RNA-seq analysis revealed that SaCTL members, including duplicated genes, in the skin of parental discus show distinct expression patterns in different care stages and between male and female parents. The SaCTL11 was differentially expressed in most care stages and reached the maximum after eggs spawned, but the expression of its paired SaCTL14 was low in each stage. The SaCTL39 increased first and then decreased, reaching a peak in eggs spawned, while paired SaCTL48 first decreased and then increased, reaching a peak in hatched eggs. The SaCTL50 was differentially expressed only in female fish during care, but not in male fish. These results provide new insights into the evolution and potential functional differentiation of CTLs in discus fish during parental care.

Chlorogenic acid can improve spermatogenic dysfunction in rats with varicocele by regulating mitochondrial homeostasis and inhibiting the activation of NLRP3 inflammasomes by oxidative mitochondrial DNA and cGAS/STING pathway.

In recent years, Varicocele (VC) has been recognized as a common cause of male infertility that can be treated by surgery or drugs. How to reduce the damage of VC to testicular spermatogenic function has attracted extensive attention in recent years. Among them, overexpressed ROS and high levels of inflammation may play a key role in VC-induced testicular damage. As the key mediated innate immune pathways, cGAS-STING shaft under pathological conditions, such as in cell and tissue damage stress can be cytoplasmic DNA activation, induce the activation of NLRP3 inflammatory corpuscle, triggering downstream of the inflammatory cascade reaction. Chlorogenic acid (CGA), as a natural compound from a wide range of sources, has strong anti-inflammatory and antioxidant activities, and is a potential effective drug for the treatment of varicocele infertility. The aim of this study is to investigate the role of CGA in the spermatogenic dysfunction of the rat testis induced by VC and the potential mechanisms. The results of this study have shown that CGA gavage treatment ameliorated the pathological damage of seminiferous tubules, increased the number of sperm in the lumen, and increased the expression levels of Occludin and ZO-1, which indicated the therapeutic effect of CGA on spermatogenic dysfunction in the testis of VC rats. Meanwhile, the damage of mitochondrial structure was alleviated and the expression levels of ROS, NLRP3 and pro-inflammatory cytokines (IL-1ß, IL-6, IL-18) were significantly reduced in the testicular tissues of model rats after CGA treatment. In addition, we demonstrated for the first time the high expression status of cGAS and STING in testicular tissues of VC model rats, and this was ameliorated to varying degrees after CGA treatment. In conclusion, this study suggests that CGA can improve the spermatogenic function of the testis by reducing mitochondrial damage and inhibiting the activation of the cGAS-STING axis, inhibiting the activation of the NLRP3 inflammasome, and improving the inflammatory damage of the testis, highlighting the potential of CGA as a therapeutic agent for varicocele infertility.

Transhiatal bilateral cervical approach for mediastinoscopy-assisted esophagectomy: A retrospective cohort study.

BACKGROUND: The McKeown minimally invasive esophagectomy (McMIE) procedure has various limitations, including surgical contraindications and a high rate of postoperative pulmonary complications. A novel mediastinoscopic esophagectomy procedure was described in this study by using esophageal invagination and a transhiatal and bilateral cervical approach (EITHBC). METHODS: According to the mode of operation, a total of 259 patients were divided into two groups, among which 106 underwent EITHBC and 153 underwent McMIE. The number of lymph nodes dissected, intraoperative outcomes, and postoperative outcomes were compared between the two groups of patients. RESULTS: The results revealed that the average number of resected lymph node in the EITHBC group was significantly higher in the recL106 and TbL106 stations (recL106: 1.75 vs. 1.51, p = 0.016, TbL106: 1.53 vs. 1.19, p = 0.016) and significantly lower in the 107 stations (1. 74 vs. 2. 07, p < 0.001) than in the McMIE group. The intraoperative blood loss in the EITHBC group was significantly lower than that in the McMIE group (63.30 vs. 80.45 mL, p < 0.001). The incidence of postoperative pulmonary complications in the EITHBC group was lower than that in the McMIE group (14.15% vs. 27.45%, p = 0.008). The incidence of recurrent laryngeal nerve paralysis in the EITHBC group was significantly higher than that in the McMIE group (26.41% vs. 10.46%, p = 0.003). CONCLUSION: Compared with the McMIE procedure, the EITHBC procedure has advantages in terms of removing the upper mediastinal lymph nodes and reducing postoperative pulmonary complications.

Presurgical computed tomography-guided localization of lung ground glass nodules: comparing hook-wire and indocyanine green.

BACKGROUND: Presurgical computed tomography (CT)-guided localization is frequently employed to reduce the thoracotomy conversion rate, while increasing the rate of successful sublobar resection of ground glass nodules (GGNs) via video-assisted thoracoscopic surgery (VATS). In this study, we compared the clinical efficacies of presurgical CT-guided hook-wire and indocyanine green (IG)-based localization of GGNs. METHODS: Between January 2018 and December 2021, we recruited 86 patients who underwent CT-guided hook-wire or IG-based GGN localization before VATS resection in our hospital, and compared the clinical efficiency and safety of both techniques. RESULTS: A total of 38 patients with 39 GGNs were included in the hook-wire group, whereas 48 patients with 50 GGNs were included in the IG group. There were no significant disparities in the baseline data between the two groups of patients. According to our investigation, the technical success rates of CT-based hook-wire- and IG-based localization procedures were 97.4% and 100%, respectively (P = 1.000). Moreover, the significantly longer localization duration (15.3 ± 6.3 min vs. 11.2 ± 5.3 min, P = 0.002) and higher visual analog scale (4.5 ± 0.6 vs. 3.0 ± 0.5, P = 0.001) were observed in the hook-wire patients, than in the IG patients. Occurrence of pneumothorax was significantly higher in hook-wire patients (27.3% vs. 6.3%, P = 0.048). Lung hemorrhage seemed higher in hook-wire patients (28.9% vs. 12.5%, P = 0.057) but did not reach statistical significance. Lastly, the technical success rates of VATS sublobar resection were 97.4% and 100% in hook-wire and IG patients, respectively (P = 1.000). CONCLUSIONS: Both hook-wire- and IG-based localization methods can effectively identified GGNs before VATS resection. Furthermore, IG-based localization resulted in fewer complications, lower pain scores, and a shorter duration of localization.

A randomized trial of Bacteroides fragilis 839 on preventing chemotherapy-induced myelosuppression and gastrointestinal adverse effects in breast cancer patients.

BACKGROUND AND OBJECTIVES: To evaluate the potential benefits of Bacteroides fragilis 839 (BF839), a next-generation probiotics, in reducing myelosuppression and gastrointestinal toxicity associated with chemotherapy in breast cancer patient. METHODS AND STUDY DESIGN: 40 women with early breast cancer were randomly assigned to the BF839 (n=20) or placebo (n=20) during the administration of adjuvant chemotherapy (4 cycles of epirubicin 100mg/m2 and cyclophosphamide 600mg/m2). Myelosuppression and gastrointestinal adverse effects were monitored in both groups. RESULTS: Throughout the four treatment cycles, the percentage of patients experiencing myelosuppression was 42.5% in the BF839 group, significantly lower than the 66.3% observed in the control group (p=0.003). Two patients in the BF839 group and three patients in the placebo group received recombinant human granulocyte colony-stimulating factor (rhG-CSF) due to leuko-penia/neutropenia. When considering an ITT analysis, which included all patients regardless of rhG-CSF treatment, the BF839 group exhibited less reduction from baseline in white blood cells (-0.31±1.19 vs -1.15±0.77, p=0.012) and neutrophils (0.06±1.00 vs -0.84±0.85, p=0.004) compared to the placebo group. The difference became even more significant when excluding the patients who received rhG-CSF injections. Throughout the four treatment cycles, compared to the placebo group, the BF839 group had significantly lower rates of 3-4 grade nausea (35.0% vs 71.3%, p=0.001), vomiting (20.0% vs 45.0%, p=0.001), and diarrhea (15.0% vs 30.0%, p=0.023). CONCLUSIONS: These findings suggest that BF839 has the potential to effectively mitigate myelosuppression and gastrointestinal toxicity associated with chemotherapy in breast cancer patients.

Progress of studies on natural products for glioblastoma therapy.

Glioblastoma (GBM) is the most common, malignant, and lethal primary brain tumor in adults. Up to now, the chemotherapy approaches for GBM are limited. Therefore, more studies on identifying and exploring new chemotherapy drugs or strategies overcome the GBM are essential. Natural products are an important source of drugs against various human diseases including cancers. With the better understanding of the molecular etiology of GBM, the development of new anti-GBM drugs has been increasing. Here, we summarized recent researches of natural products for the GBM therapy and their potential mechanisms in details, which will provide new ideas for the research on natural products and promote developing drugs from nature products for GBM therapy.

Lewis-Acid-Catalyzed (3+2) Annulation of 2-Indolylmethanols with Propargylic Alcohols to Access Cyclopenta[b]indoles.

Herein, a Sc(OTf)3-catalyzed (3+2) annulation of 2-indolylmethanols with propargylic alcohols is reported. The reaction proceeds via a Friedel-Crafts-type allenylation/5-exo-annulation cascade. In the reaction, 2-indolylmethanol is used as a three-carbon synthon, and propargyl alcohol is used as a two-carbon synthon. This method provides a direct and high-yield pathway for synthetically useful cyclopenta[b]indoles. In general, the method features easily accessible substrates with broad scope and generality, the formation of multiple bonds with high efficiency, and easy scale-up.

Short-term associations between ambient PM1, PM2.5, and PM10 and hospital admissions, length of hospital stays, and hospital expenses for patients with cardiovascular diseases in rural areas of Fuyang, East China.

Evidence on the impacts of PM1, PM2.5, and PM10 on the hospital admissions, length of hospital stays (LOS), and hospital expenses among patients with cardiovascular disease (CVD) is still limited in China, especially in rural areas. This study was performed in eight counties of Fuyang from 1 January 2015 to 30 June 2017. We use a three-stage time-series analysis to explore the effects of short-term exposure to PM1, PM2.5, and PM10 on hospital admissions, LOS, and hospital expenses for CVDs. An increment of 10 ug/m3 in PM1, PM2.5, and PM10 corresponded to an increment of 1.82% (95% CI: 1.34, 2.30), 0.96% (95% CI: 0.44, 1.48), and 0.79% (95% CI: 0.63%, 0.95%) in CVD hospital admissions, respectively. We observed that daily concentrations of PMs were associated with an increase in hospital admissions, LOS, and expenses for CVDs. Sustained endeavors are required to reduce air pollution so as to attenuate disease burdens from CVDs.

Investigation on vehicle occupant dummy applicability for under-foot impact loading conditions.

PURPOSE: Under-foot impact loadings can cause serious lower limb injuries in many activities, such as automobile collisions and underbody explosions to military vehicles. The present study aims to compare the biomechanical responses of the mainstream vehicle occupant dummies with the human body lower limb model and analyze their robustness and applicability for assessing lower limb injury risk in under-foot impact loading environments. METHODS: The Hybrid III model, the test device for human occupant restraint (THOR) model, and a hybrid human body model with the human active lower limb model were adopted for under-foot impact analysis regarding different impact velocities and initial lower limb postures. RESULTS: The results show that the 2 dummy models have larger peak tibial axial force and higher sensitivity to the impact velocities and initial postures than the human lower limb model. In particular, the Hybrid III dummy model presented extremely larger peak tibial axial forces than the human lower limb model. In the case of minimal difference in tibial axial force, Hybrid III's tibial axial force (7.5 KN) is still 312.5% that of human active lower limb's (2.4 KN). Even with closer peak tibial axial force values, the biomechanical response curve shapes of the THOR model show significant differences from the human lower limb model. CONCLUSION: Based on the present results, the Hybrid III dummy cannot be used to evaluate the lower limb injury risk in under-foot loading environments. In contrast, potential improvement in ankle biofidelity and related soft tissues of the THOR dummy can be implemented in the future for better applicability.

[Sanshentongmai Mixture Improves Oxidative Damage in Rat Cardiomyocytes H9C2 via Upregulation of microRNA-146a]. / 三参通脉合剂通过上调microRNA-146aæ”¹å–„å¤§é¼ å¿ƒè‚Œç»†èƒžH9C2的氧化损伤.

Objective: To investigate the effect of Sanshentongmai (SSTM) mixture on the regulation of oxidative damage to rat cardiomyocytes (H9C2) through microRNA-146a and its mechanism. Methods: H9C2 were cultured in vitro, H2O2 was used as an oxidant to create an oxidative damage model in H9C2 cells. SSTM intervention was administered to the H9C2 cells. Then, the changes in H2O2-induced oxidative damage in H9C2 cells and the expression of microRNA-146a were observed to explore the protective effect of SSTM on H9C2 and its mechanism. H9C2 cells cultured i n vitro were divided into 3 groups, including a control group, a model group of H2O2-induced oxidative damage (referred to hereafter as the model group), and a group given H2O2 modeling plus SSTM intervention at 500 µg/L for 72 h (referred to hereafter as the treatment group). The cell viability was measured by CCK8 assay. In addition, the levels of N-terminal pro-brain natriuretic peptide (Nt-proBNP), nitric oxide (NO), high-sensitivity C-reactive protein (Hs-CRP), and angiotensin were determined by enzyme-linked immunosorbent assay (ELISA). The expression level of microRNA-146a was determined by real-time PCR (RT-PCR). Result: H9C2 cells were pretreated with SSTM at mass concentrations ranging from 200 to 1500 µg/L. Then, CCK8 assay was performed to measure cell viability and the findings showed that the improvement in cell proliferation reached its peak when the mass concentration of SSTM was 500 µg/L, which was subsequently used as the intervention concentration. ELISA was performed to measure the indicators related to heart failure, including Nt-proBNP, NO, Hs-CRP, and angiotensin Ⅱ. Compared with those of the control group, the expressions of Nt-proBNP and angiotensin Ⅱ in the treatment group were up-regulated (P<0.05), while the expression of NO was down-regulated (P<0.05). There was no significant difference in the expression of Hs-CRP between the treatment group and the control group. These findings indicate that SSTM could effectively ameliorate oxidative damage in H9C2 rat cardiomyocytes. Finally, according to the RT-PCR findings for the expression of microRNA-146a in each group, H2O2 treatment at 15 µmol/L could significantly reduce the expression of microRNA-146a, and the expression of microRNA-146a in the treatment group was nearly doubled compared with that in the model group. There was no significant difference between the treatment group and the control group. Conclusion: SSTM can significantly resist the H2O2-induced oxidative damage of H9C2 cells and may play a myocardial protective role by upregulating microRNA-146a.

Construction of Highly Porous and Robust Hydrogen-Bonded Organic Framework for High-Capacity Clean Energy Gas Storage.

Development of highly porous and robust HOFs for high-pressure methane and hydrogen storage remains a grand challenge due to the fragile nature of hydrogen bonds. Herein, we report a strategy of constructing double-walled framework to target highly porous and robust HOF (ZJU-HOF-5a) for extraordinary CH4 and H2 storage. ZJU-HOF-5a features a minimized twofold interpenetration with double-walled structure, in which multiple supramolecular interactions are existed between the interpenetrated walls. This structural configuration can notably enhance the framework robustness while maintaining its high porosity, affording one of the highest gravimetric and volumetric surface areas of 3102 m2 g-1 and 1976 m2 cm-3 among the reported HOFs so far. ZJU-HOF-5a exhibits an extremely high volumetric H2 uptake of 43.6 g L-1 at 77 K/100 bar and working capacity of 41.3 g L-1 under combined swing conditions, and also impressive methane storage performance with a 5-100 bar working capacity of 187 (or 159) cm3 cm-3 at 270 K (or 296 K). SCXRD studies on CH4-loaded ZJU-HOF-5a reveal that abundant supramolecular binding sites combined with ultrahigh porosities account for its high CH4 storage capacities. Combined with high stability, super-hydrophobicity, and easy-recovery, ZJU-HOF-5a is placed among the most promising materials for H2 and CH4 storage applications.

Identification and Functional Analysis of an Epsilon Class Glutathione S-Transferase Gene Associated with α-Pinene Adaptation in Monochamus alternatus.

Alpha-pinene is one of the main defensive components in conifers. Monochamus alternatus (Coleoptera: Cerambycidae), a wood borer feeding on Pinaceae plants, relies on its detoxifying enzymes to resist the defensive terpenoids. Here, we assayed the peroxide level and GST activity of M. alternatus larvae treated with different concentrations of α-pinene. Meanwhile, a gst gene (MaGSTe3) was isolated and analyzed. We determined its expression level and verified its function. The results showed that α-pinene treatment led to membrane lipid peroxidation and thus increased the GST activity. Expression of MaGSTe3 was significantly upregulated in guts following exposure to α-pinene, which has a similar pattern with the malonaldehyde level. In vitro expression and disk diffusion assay showed that the MaGSTe3 protein had high antioxidant capacity. However, RNAi treatment of MaGSTe3 did not reduce the hydrogen peroxide and malonaldehyde levels, while GST activity was significantly reduced. These results suggested MaGSTe3 takes part in α-pinene adaptation, but it does not play a great role in the resistance of M. alternatus larvae to α-pinene.

[Comparison on anti-inflammatory activity of Gynostemma pentaphyllum processed with different methods].

The aim of this study is to investigate the effects of Gynostemma pentaphyllum dried with two different methods(air drying and heating) on inflammation in acute lung injury(ALI) mice in vivo and in vitro. Lipopolysaccharide(LPS) was sprayed into the airway of wild type C57BL/6J male mice to establish the model, and the drug was injected into the tail vein 24 h after modeling. Lung function, lung tissue wet/dry weight(W/D) ratio, the total protein concentration, interleukin 6(IL-6), IL-1ß, and tumor necrosis factor-α(TNF-α) in the bronchoalveolar lavage fluid(BALF), and pathological changes of the lung tissue were used to evaluate the effects of different gypenosides on ALI mice. The results showed that total gypenosides(YGGPs) and the gypenosides substituted with one or two glycosyl(GPs_(1-2)) in the air-dried sample improved the lung function, significantly lowered the levels of IL-1ß and TNF-α in BALF, and alleviated the lung inflammation of ALI mice. Moreover, GPs_(1-2) had a more significant effect on inhibiting NO release in RAW264.7 cells. This study showed that different drying methods affected the anti-inflammatory activity of G. pentaphyllum, and the rare saponins in the air-dried sample without heating had better anti-inflammatory activity.