Icaritin Derivative IC2 Induces Cytoprotective Autophagy of Breast Cancer Cells via SCD1 Inhibition.

Breast cancer is one of the most prevalent malignancies and the leading cause of cancer-associated mortality in China. Icaritin (ICT), a prenyl flavonoid derived from the Epimedium Genus, has been proven to inhibit the proliferation and stemness of breast cancer cells. Our previous study demonstrated that IC2, a derivative of ICT, could induce breast cancer cell apoptosis by Stearoyl-CoA desaturase 1 (SCD1) inhibition. The present study further investigated the mechanism of the inhibitory effects of IC2 on breast cancer cells in vitro and in vivo. Our results proved that IC2 could stimulate autophagy in breast cancer cells with the activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling and mitogen-activated protein kinase (MAPK) signaling. Combination treatment of the AMPK inhibitor decreased IC2-induced autophagy while it markedly enhanced IC2-induced apoptosis. In common with IC2-induced apoptosis, SCD1 overexpression or the addition of exogenous oleic acid (OA) could also alleviate IC2-induced autophagy. In vivo assays additionally demonstrated that IC2 treatment markedly inhibited tumor growth in a mouse breast cancer xenograft model. Overall, our study was the first to demonstrate that IC2 induced cytoprotective autophagy by SCD1 inhibition in breast cancer cells and that the autophagy inhibitor markedly enhanced the anticancer activity of IC2. Therefore, IC2 was a potential candidate compound in combination therapy for breast cancer.

Targeted Mitochondrial Epigenetics: A New Direction in Alzheimer's Disease Treatment.

Mitochondrial epigenetic alterations are closely related to Alzheimer's disease (AD), which is described in this review. Reports of the alteration of mitochondrial DNA (mtDNA) methylation in AD demonstrate that the disruption of the dynamic balance of mtDNA methylation and demethylation leads to damage to the mitochondrial electron transport chain and the obstruction of mitochondrial biogenesis, which is the most studied mitochondrial epigenetic change. Mitochondrial noncoding RNA modifications and the post-translational modification of mitochondrial nucleoproteins have been observed in neurodegenerative diseases and related diseases that increase the risk of AD. Although there are still relatively few mitochondrial noncoding RNA modifications and mitochondrial nuclear protein post-translational modifications reported in AD, we have reason to believe that these mitochondrial epigenetic modifications also play an important role in the AD process. This review provides a new research direction for the AD mechanism, starting from mitochondrial epigenetics. Further, this review summarizes therapeutic approaches to targeted mitochondrial epigenetics, which is the first systematic summary of therapeutic approaches in the field, including folic acid supplementation, mitochondrial-targeting antioxidants, and targeted ubiquitin-specific proteases, providing a reference for therapeutic targets for AD.

Electroacupuncture alleviates sciatic nerve injury and inhibits autophagy in rats.

BACKGROUND: Sciatic nerve injury is a common form of peripheral nerve injury (PNI). It has been suggested that electroacupuncture (EA) stimulation at GB30 and ST36 can improve nerve dysfunction post-PNI. Autophagy is an important factor in the regeneration of sciatic nerves and recovery of motor function. Therefore, we investigated the biological effects of EA and examined whether these were mediated by autophagy in sciatic nerve injury. METHODS: Mechanical clamping of the sciatic nerve in Sprague-Dawley rats was performed to establish an experimental model of sciatic nerve injury. EA stimulation was administered once daily for 15 min for seven consecutive days beginning 1 week after successful modeling. The recovery of sciatic nerve function was examined via the sciatic functional index (SFI) test. Morphometric analysis was conducted by staining nerve samples with toluidine blue. Autophagy-associated protein levels were measured via Western blotting. RESULTS: EA stimulation at GB30 and ST36 significantly increased the number of myelinated fibers, axonal and fiber diameters, and the thickness of the myelin sheath in our rat model of sciatic nerve injury. In addition, EA stimulation greatly facilitated nerve regeneration following sciatic nerve injury. Moreover, sciatic nerve injury-induced autophagy was inhibited by EA stimulation. CONCLUSION: EA facilitates recovery of injured sciatic nerves and inhibits autophagy in a rat model.

Comprehensive analysis of stearoyl-coenzyme A desaturase in prostate adenocarcinoma: insights into gene expression, immune microenvironment and tumor progression.

Prostate adenocarcinoma (PRAD) is a prevalent global malignancy which depends more on lipid metabolism for tumor progression compared to other cancer types. Although Stearoyl-coenzyme A desaturase (SCD) is documented to regulate lipid metabolism in multiple cancers, landscape analysis of its implications in PRAD are still missing at present. Here, we conducted an analysis of diverse cancer datasets revealing elevated SCD expression in the PRAD cohort at both mRNA and protein levels. Interestingly, the elevated expression was associated with SCD promoter hypermethylation and genetic alterations, notably the L134V mutation. Integration of comprehensive tumor immunological and genomic data revealed a robust positive correlation between SCD expression levels and the abundance of CD8+ T cells and macrophages. Further analyses identified significant associations between SCD expression and various immune markers in tumor microenvironment. Single-cell transcriptomic profiling unveiled differential SCD expression patterns across distinct cell types within the prostate tumor microenvironment. The Gene Ontology and Kyoto Encyclopedia of Genes and Genome analyses showed that SCD enriched pathways were primarily related to lipid biosynthesis, cholesterol biosynthesis, endoplasmic reticulum membrane functions, and various metabolic pathways. Gene Set Enrichment Analysis highlighted the involvement of elevated SCD expression in crucial cellular processes, including the cell cycle and biosynthesis of cofactors pathways. In functional studies, SCD overexpression promoted the proliferation, metastasis and invasion of prostate cancer cells, whereas downregulation inhibits these processes. This study provides comprehensive insights into the multifaceted roles of SCD in PRAD pathogenesis, underscoring its potential as both a therapeutic target and prognostic biomarker.

Formation and detection of biocoronas in the food industry and their fate in the human body.

The rapid advancement of nanotechnology has opened up new avenues for applications in all stages of the food industry. Over the past decade, extensive research has emphasized that when nanoparticles (NPs) enter organisms, they spontaneously adsorbed biomolecules, leading to the formation of biocorona. This paper provided a detailed review of the process of biocorona formation in the food industry, including their classification and influencing factors. Additionally, various characterization methods to investigated the morphology and structure of biocoronas were introduced. As a real state of food industry nanoparticles in biological environments, the biocorona causes structural transformations of biomolecules bound to NPs, thus affecting their fate in the body. It can either promote or inhibit enzyme activity in the human environment, and may also positively or negatively affect the cellular uptake and toxicity of NPs. Since NPs present in the food industry will inevitably enter the human body, further investigations on biocoronas will offer valuable insights and perspectives on the safety of incorporating more NPs into the food industry.

Inhibitory mechanism of carboxymethyl chitosan-lotus seedpod oligomeric procyanidin nanoparticles on dietary advanced glycation end products released from glycated casein during digestion.

Lotus seedpod oligomeric procyanidins (LSOPC) are potent inhibitors of advanced glycation end products (AGEs), whose gastrointestinal susceptibility to degradation limits their use in vivo. In this study, carboxymethyl chitosan-lotus seedpod oligomeric procyanidin nanoparticles (CMC-LSOPC NPs) were constructed with a binding ratio of 1:6.51. CMC-LSOPC NPs significantly inhibited the release of AGEs from glycated casein (G-CS) during digestion, increasing the inhibition rate by 25.76% in the gastric phase and by 14.33% in the intestinal phase compared with LSOPC alone. To further investigate the inhibition mechanism, fluorescence microscopy, scanning electron microscopy and FTIR were used to find that CMC-LSOPC NPs could form cohesions to encapsulate G-CS in the gastric phase and hinder G-CS hydrolysis. In the intestinal phase, LSOPC was targeted for release and bound to trypsin through hydrophobic interactions and hydrogen bonding, resulting in protein peptide chain rearrangement, changes in secondary structure and significant reduction in trypsin activity. In addition, CMC-LSOPC NPs increased the antioxidant capacity of digestive fluid and could reduce the oxidative stress in the gastrointestinal tract caused by the release of AGEs. It's the first time that CMC-LSOPC NPs were constructed to enhance the stability of LSOPC during digestion and explain the mechanism by which CMC-LSOPC NPs inhibit the release of AGEs from G-CS in both stomach and intestine. This finding will present a novel approach for reducing AGEs during gastrointestinal digestion.

The circ_0002538/miR-138-5p/plasmolipin axis regulates Schwann cell migration and myelination in diabetic peripheral neuropathy.

Circular RNAs (circRNAs) play a vital role in diabetic peripheral neuropathy. However, their expression and function in Schwann cells in individuals with diabetic peripheral neuropathy remain poorly understood. Here, we performed protein profiling and circRNA sequencing of sural nerves in patients with diabetic peripheral neuropathy and controls. Protein profiling revealed 265 differentially expressed proteins in the diabetic peripheral neuropathy group. Gene Ontology indicated that differentially expressed proteins were mainly enriched in myelination and mitochondrial oxidative phosphorylation. A real-time polymerase chain reaction assay performed to validate the circRNA sequencing results yielded 11 differentially expressed circRNAs. circ_0002538 was markedly downregulated in patients with diabetic peripheral neuropathy. Further in vitro experiments showed that overexpression of circ_0002538 promoted the migration of Schwann cells by upregulating plasmolipin (PLLP) expression. Moreover, overexpression of circ_0002538 in the sciatic nerve in a streptozotocin-induced mouse model of diabetic peripheral neuropathy alleviated demyelination and improved sciatic nerve function. The results of a mechanistic experiment showed that circ_0002538 promotes PLLP expression by sponging miR-138-5p, while a lack of circ_0002538 led to a PLLP deficiency that further suppressed Schwann cell migration. These findings suggest that the circ_0002538/miR-138-5p/PLLP axis can promote the migration of Schwann cells in diabetic peripheral neuropathy patients, improving myelin sheath structure and nerve function. Thus, this axis is a potential target for therapeutic treatment of diabetic peripheral neuropathy.

Application and Properties of Microporous Carbons Activated by ZnCl2: Adsorption Behavior and Activation Mechanism.

Herein, polypyrrole-based porous carbon (PPC) was prepared by ZnCl2 activation for toluene adsorption from paraffin liquid. The structure properties were adjusted by a dosage of activating agents and carbonization temperature. The result with a 3:1 mass ratio of ZnCl2/PPy at 600 °C showed the highest micropore area and percentage of micropore volume of 1105 m2/g and 86.26%, respectively. In addition, the PPC surface was rich in functional groups and obtained a high N-doped content from 7.00 to 8.82%. The toluene adsorption behavior onto the PPC was comprehensively investigated including isotherms, kinetics, and thermodynamics. The adsorption isotherm accorded with the Freundlich model well, and the kinetic model was fitted more closely to the pseudo-second-order chemisorption. The thermodynamic research uncovered that the adsorption was spontaneous and an endothermic process in essence. The ZnCl2 activation mechanism is discussed based on TG/TGA curves and pore structure analysis at last. The devised way of synthesized microporous carbon is green and simple, which is suited to mass production for the adsorption of toluene from paraffin liquid and reducing environmental pollution.

Efficient Toluene Adsorption on Metal Salt-Activated Porous Carbons Derived from Low-Cost Biomass: A Discussion of Mechanism.

Porous carbons (PCS) derived from sodium lignin sulfonate were activated by four common metal salts. The samples exhibit distinct characteristics of irregular, sunflower-like, interconnected sheet, and tine block morphologies under the impact of NaCl, CaCl2, ZnCl2, and FeCl3, respectively (PCS-MCl x ). Surprisingly, the maximum and minimum specific surface areas are 1524 and 44 m2/g corresponding to PCS-ZnCl2 and PCS-NaCl. All of the samples have plentiful functional groups; herein, PCS-NaCl and PCS-FeCl3 are detected with the highest O and S contents (11.85, 1.08%), respectively, which signifies sufficient active sites for adsorption. These porous materials were applied in toluene adsorption from paraffin liquid and matched the Langmuir isotherm models well. Thus, the activation mechanism was discussed in detail. PCS-MCl x has a completely different pyrolysis behavior according to thermogravimetry/derivative thermogravimetry (TG/DTG) analysis. It is speculated that H[ZnCl2(OH)] would have an etching effect on the carbon structure of PCS-ZnCl2, and HCl or H2SO4, resulting from FeCl3 hydrolysis and a reduction reaction, would be corrosive to the sodium lignin sulfonate (SLS) surface. Each metal salt plays a different role in activation. The devised method for the synthesis of porous carbons is green and economical, which is suited to mass production.

Draft genome sequence of ramie, Boehmeria nivea (L.) Gaudich.

Ramie, Boehmeria nivea (L.) Gaudich, family Urticaceae, is a plant native to eastern Asia, and one of the world's oldest fibre crops. It is also used as animal feed and for the phytoremediation of heavy metal-contaminated farmlands. Thus, the genome sequence of ramie was determined to explore the molecular basis of its fibre quality, protein content and phytoremediation. For further understanding ramie genome, different paired-end and mate-pair libraries were combined to generate 134.31 Gb of raw DNA sequences using the Illumina whole-genome shotgun sequencing approach. The highly heterozygous B. nivea genome was assembled using the Platanus Genome Assembler, which is an effective tool for the assembly of highly heterozygous genome sequences. The final length of the draft genome of this species was approximately 341.9 Mb (contig N50 = 22.62 kb, scaffold N50 = 1,126.36 kb). Based on ramie genome annotations, 30,237 protein-coding genes were predicted, and the repetitive element content was 46.3%. The completeness of the final assembly was evaluated by benchmarking universal single-copy orthologous genes (BUSCO); 90.5% of the 1,440 expected embryophytic genes were identified as complete, and 4.9% were identified as fragmented. Phylogenetic analysis based on single-copy gene families and one-to-one orthologous genes placed ramie with mulberry and cannabis, within the clade of urticalean rosids. Genome information of ramie will be a valuable resource for the conservation of endangered Boehmeria species and for future studies on the biogeography and characteristic evolution of members of Urticaceae.

An analysis of the current status of hospital emergency preparedness for infectious disease outbreaks in Beijing, China.

BACKGROUND: In the event of a large-scale infectious disease outbreak, hospitals will play a critical role. The objective of our study is to understand the current status of hospitals preparedness for infectious disease outbreaks in Beijing and to provide basic information for infectious disease prevention and control in hospitals. METHODS: One hundred fifty-two secondary and tertiary care hospitals in Beijing were surveyed by a standardized questionnaire. Data related to hospital demographic information and their emergency plans, laboratory diagnosis capacity, medical treatment procedures for infectious diseases, stockpiles of drugs and personal protective equipment, and staff training were collected. RESULTS: Responses were received from 134 (88.2%) of the 152 hospitals surveyed. Overall, hospitals reported that the number of physicians and nurses in infectious disease accounted for only 1.8% of the total physicians and 2.5% of the total nurses, and surgery beds accounted for 8.5% of all the fixed beds. Approximately 93.3% of the hospitals surveyed reported that they had an emergency plan, and none of those reported that their laboratories were able to isolate and identify all 8 kinds of common pathogens of infectious diseases: 22.4% of the hospitals had medical treatment procedures for all these infectious diseases, 23.1% had stored specific drugs for treatment, 2.2% had all personal protective equipment, and 30.6% reported that their health care staff had been trained in hospital emergency preparedness for infectious diseases. In general, emergency preparedness for infectious diseases in tertiary care hospitals was better than that in secondary care hospitals; the preparedness at general hospitals was better than that at specialized hospitals; and that at teaching hospitals was better than that at nonteaching hospitals. CONCLUSION: Emergency preparedness for infectious disease at hospitals in Beijing was in an early stage of development during this survey. Comprehensive measures should be developed and implemented to enhance their capacity for infectious disease emergency.