► Bioflocculant from Solibacillus silvestris flocculates Nannochloropsis oceanica. ► No metal ion was required by the bioflocculant to flocculate N. oceanica. ► Flocculation induced by the ...bioflocculant is insensitive to temperature. ► The bioflocculant can be recycled and reused.
Microalgae are widely studied for biofuel production, however, current technologies to harvest microalgae for this purpose are not well developed. In this work, a bacterial strain W01 was isolated from activated sludge and identified as Solibacillus silvestris. Bioflocculant in the culture broth of W01 showed 90% flocculating efficiency on marine microalga Nannochloropsis oceanica, and no metal ion was required for the flocculation process. Chemical analysis of the purified bioflocculant indicated that it is a proteoglycan composed of 75.1% carbohydrate and 24.9% protein (w/w). The bioflocculant exhibits no effect on the growth of microalgal cells and can be reused to for economical harvesting of N. oceanica. This is the first report that strain of S. silvestris can produce bioflocculant for microalgae harvest. The novel bioflocculant produced by W01 has the potential to harvest marine microalgae for cost-effective production of microalgal bioproducts.
Retinitis pigmentosa (RP) is the most common inherited retinal degenerative disease yet with no effective treatment available. The sigma-1 receptor (S1R), a ligand-regulated chaperone, emerges as a ...potential retina-protective therapeutic target. In particular, pharmacological activation of S1R was recently shown to rescue cones in the rd10 mouse, a rod Pde6b mutant that recapitulates the RP pathology of autonomous rod degeneration followed by secondary death of cones. The mechanisms underlying the S1R protection for cones are not understood in detail.
By rearing rd10/S1R
and rd10/S1R
mice in dim light to decelerate rapid rod/cone degeneration, we were able to compare their retinal biochemistry, histology and functions throughout postnatal 3-6 weeks (3 W-6 W).
The receptor-interacting protein kinases (RIP1/RIP3) and their interaction (proximity ligation) dramatically up-regulated after 5 W in rd10/S1R
(versus rd10/S1R
) retinas, indicative of intensified necroptosis activation, which was accompanied by exacerbated loss of cones. Greater rod loss in rd10/S1R
versus rd10/S1R
retinas was evidenced by more cleaved Caspase3 (4 W) and lower rod electro-retinographic a-waves (4 W-6 W), concomitant with reduced LC3-II and CHOP (4 W-6 W), markers of autophagy and endoplasmic reticulum stress response, respectively. However, the opposite occurred at 3 W.
This study reveals previously uncharacterized S1R-associated mechanisms during rd10 photoreceptor degeneration, including S1R's influences on necroptosis and autophagy as well as its biphasic role in rod degeneration upstream of cone death.
Drug-eluting stents are the most commonly employed method to control post-angioplasty restenosis. Unfortunately, they exacerbate life-threatening stent thrombosis because of endothelium damage caused ...by both drug and stenting. To solve this major medical problem, an endothelium-protective and stent-free anti-restenotic method is highly desirable. Here we have generated a biomimetic intravenous delivery system using dendritic polymer-based nanoclusters, which were coated with platelet membranes for targeting to the injured arterial wall where restenosis occurs. These nanoclusters were loaded with an endothelium-protective epigenetic inhibitor (JQ1) or an endothelium-toxic status quo drug (rapamycin), and compared for their ability to mitigate restenosis without hindering the process of re-endothelialization. Fluorescence imaging of Cy5-tagged biomimetic nanoclusters indicated their robust homing to injured, but not uninjured arteries. Two weeks after angioplasty, compared to no-drug control, both rapamycin- and JQ1-loaded biomimetic nanoclusters substantially reduced (by >60%) neointimal hyperplasia, the primary cause of restenosis. However, whereas the rapamycin formulation impaired the endothelial re-coverage of the denuded inner arterial wall, the JQ1 formulation preserved endothelial recovery. In summary, we have created an endothelium-protective anti-restenotic system with biomimetic nanoclusters containing an epigenetic inhibitor. This system warrants further development for a non-thrombogenic and stent-free method for clinical applications.
The biogenesis of mammalian autophagosomes remains to be fully defined. Here, we used cellular and in vitro membrane fusion analyses to show that autophagosomes are formed from a hitherto ...unappreciated hybrid membrane compartment. The autophagic precursors emerge through fusion of FIP200 vesicles, derived from the cis-Golgi, with endosomally derived ATG16L1 membranes to generate a hybrid pre-autophagosomal structure, HyPAS. A previously unrecognized apparatus defined here controls HyPAS biogenesis and mammalian autophagosomal precursor membranes. HyPAS can be modulated by pharmacological agents whereas its formation is inhibited upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection or by expression of SARS-CoV-2 nsp6. These findings reveal the origin of mammalian autophagosomal membranes, which emerge via convergence of secretory and endosomal pathways, and show that this process is targeted by microbial factors such as coronaviral membrane-modulating proteins.
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•Mammalian autophagosomes are formed via fusion of cis-Golgi and endosomal membranes•This forms a prophagophore termed hybrid pre-autophagosomal structure (HyPAS)•HyPAS depends on SNARE STX17 and its interactors E-SYT2, SIGMAR1, and SERCA2•SARS-CoV-2 inhibits prophagophore formation by nsp6 targeting HyPAS apparatus
Insights into the origin of mammalian autophagosomal membrane and its inhibition by SARS-CoV-2.
In the manufacturing sector, tool wear substantially affects product quality and production efficiency. While traditional sequential deep learning models can handle time-series tasks, their neglect ...of complex temporal relationships in time-series data often leads to errors accumulating in continuous predictions, which reduces their forecasting accuracy for tool wear. For addressing these limitations, the parallel convolutional and recurrent neural networks with attention-modulated residual learning (ParaCRN-AMResNet) model is introduced. Compared with conventional deep learning models, ParaCRN-AMResNet markedly enhances the efficiency and precision of feature extraction from time-series data through its innovative parallel architecture. The model adeptly combines dilated convolution neural network and bidirectional gated recurrent units, effectively addressing distance dependencies and enriching the quantity and dimensions of extracted features. The strength of ParaCRN-AMResNet lies in its refined ability to capture the complex dynamics of time-series data, significantly boosting the model’s accuracy and generalization capability. The model’s efficacy was validated through comprehensive milling experiments and vibration signal analyses, showcasing ParaCRN-AMResNet’s superior performance. In evaluation metrics, the model achieved a MAE of 2.6015, MSE of 15.1921, R2 of 0.9897, and MAPE of 2.7997%, conclusively proving its efficiency and accuracy in the precise prediction of tool wear.
Polycystic ovary syndrome (PCOS) is one of the most common female endocrine disorders and a leading cause of female subfertility. The mechanism underlying the pathophysiology of PCOS remains to be ...illustrated. Here, we identify two alternative splice variants (ASVs) of the androgen receptor (AR), insertion and deletion isoforms, in granulosa cells (GCs) in ∼62% of patients with PCOS. AR ASVs are strongly associated with remarkable hyperandrogenism and abnormalities in folliculogenesis, and are absent from all control subjects without PCOS. Alternative splicing dramatically alters genome-wide AR recruitment and androgen-induced expression of genes related to androgen metabolism and folliculogenesis in human GCs. These findings establish alternative splicing of AR in GCs as the major pathogenic mechanism for hyperandrogenism and abnormal folliculogenesis in PCOS.
Significance Excess androgens and abnormal follicle development, largely due to ovarian granulosa cell (GC) dysfunction, characterize polycystic ovary syndrome (PCOS), a common endocrinopathy of women predisposing to infertility. Thus, it is important to understand GC dysfunction. The androgen receptor (AR) is widely believed to be an essential regulator of GC biology. High expression of AR in GCs is primarily considered to associate with PCOS. However, we show that AR alternative splice variants in GCs disturb androgen metabolism and follicle growth, leading to PCOS because of impaired transcription factor function. These data considerably change our understanding of the role of AR in the etiology of PCOS, and inform the development of clinical diagnostic and classification tests as well as novel therapeutic interventions.
Gestational diabetes mellitus (GDM) is associated with an increased risk of metabolic disorders in offspring in later life. Although mounting evidence suggests that therapy for GDM could improve ...neonatal health, whether the therapy confers long-term metabolic benefits to offspring in their later adult lives is not known. Here, using a mouse model of diabetes in the latter half of pregnancy to mimic human GDM, we find that the efficient insulin therapy for GDM confers significant protection against glucose intolerance and obesity in offspring fed a normal chow diet. However, the therapy fails to protect offspring when challenged with a high-fat diet, especially for male offspring. Genome-wide DNA methylation profiling of pancreatic islets from male offspring identified hypermethylated regions in several genes that regulate insulin secretion, including
,
, and
that encode K
or Ca
channels, which are associated with reduced gene expression and impaired insulin secretion. This finding suggests a methylation-mediated epigenetic mechanism for GDM-induced intergenerational glucose intolerance. It highlights that even efficient insulin therapy for GDM is insufficient to fully protect adult offspring from diet-induced metabolic disorders.
Objective. This study aimed to analyze the clinical efficacy of the intervention of thumbtack needles (applicable to subcutaneous embedding) combined with Chinese medicine ironing therapy on ...postoperation nausea and vomiting (PONV). Methods. 106 patients who scheduled elective surgery were enrolled and randomized into control group and experimental group, with 53 cases in each group. The control group received modern medication, while the experimental group was given thumbtack needles combined with Chinese medicine ironing therapy based on the control group. The PONV score, incidence rate, gastrointestinal hormone level, Functional Living Index-Emesis (FLIE), and General Comfort Questionnaire (GCQ) of the two groups were compared. Results. After treatment, the incidence of PONV and GCQ in the experimental group was observed to be remarkably lower than that in the control group (P<0.05), while the levels of gastrointestinal hormones and the level in the FLIE of the experimental group were comparatively higher than those in the control group (P<0.05). Conclusion. Thumbtack needles combined with Chinese medicine ironing therapy can be utilized to reduce the incidence of PONV, to improve the level of gastrointestinal hormones, and to improve the comfort and quality of patients’ lives.
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