Anti-virulence and bactericidal activities of Stattic against Shigella sonnei.

IMPORTANCE: Shigella sonnei is a major human enteric pathogen that causes bacillary dysentery. The increasing spread of drug-resistant S. sonnei strains has caused an emergent need for the development of new antimicrobial agents against this pathogenic bacterium. In this study, we demonstrate that Stattic employs two antibacterial mechanisms against S. sonnei. It exerted both anti-virulence activity and bactericidal activity against S. sonnei, suggesting that it shows advantages over traditional antibiotics. Moreover, Stattic showed excellent synergistic effects with kanamycin, ampicillin, chloramphenicol, and gentamicin against S. sonnei. Our findings suggest that Stattic has promising potential for development as a new antibiotic or as an adjuvant to antibiotics for infections caused by S. sonnei.

Total synthesis of chondroitin sulfate E oligosaccharides and biological study.

A total synthesis approach of CS-E oligosaccharides was established and a series of derivatives were synthesized. These oligosaccharides were evaluated for a glycosaminoglycan (GAG)-binding protein interaction against cytokines, midkine, and pleiotrophin, by surface-plasmon resonance (SPR) assay. The binding epitopes of oligosaccharides to midkine were mapped using a saturation transfer difference (STD) NMR technique. The groups on the reducing end contributed to binding affinity, and should not be ignored in biological assays. These findings contribute to the structure and activity relationship research and a foundation of understanding that will underpin potential future optimization of this class of oligosaccharides as pharmaceutical agents.

Discrimination between Different DNA Lesions by Monitoring Single-Molecule Polymerase Stalling Kinetics during Nanopore Sequencing.

O6-Carboxymethylguanosine (O6-CMG), O6-methylguanosine (O6-MeG), and abasic site (AP site) are DNA lesions induced by alkylating agents. Identification of these lesions in DNA may aid in understanding their relevance to carcinogenesis and may be used for diagnosis. Nanopore sequencing (NPS) may directly report nucleotide modifications solely from the nanopore readout. However, the conventional NPS strategy still suffers from interferences from neighboring sequences. Instead, by observation of the enzymatic stalling kinetics caused by the O6-CMG, O6-MeG, or AP site, discrimination between different DNA lesions is directly achieved. This strategy is not interfered with by the sequence context around the lesion. The lesion, which retards the movement of the DNA through the pore, efficiently prohibits misreading of the DNA lesion. These results suggest a new strategy in the identification of DNA lesions or DNA modifications. It also provides a high-resolution biophysical tool to investigate enzymatic kinetics caused by DNA lesions and the corresponding enzymes.

Fiber coupling efficiency of a Bessel-Gaussian beam received by a Cassegrain antenna under atmospheric turbulence.

A coupling efficiency calculation method for a Bessel-Gaussian (BG) beam in a free space optical communication system received by a parabolic Cassegrain antenna and coupled into a few-mode fiber is proposed. The system of the antenna and the coupling lens is approximate to a ring-shaped lens. The effect of the antenna in the coupling system is analyzed, and maximum coupling efficiency is increased by 76.25% on average by applying the antenna. With the application of the antenna, the configurations to generate the maximum point of coupling efficiency among BG beams of different topological charges are restricted to being almost the same, which is useful for the simultaneous propagation of multiple BG beams. The effects of radial displacement and atmospheric turbulence on coupling efficiency are researched as well. Coupling efficiency becomes more sensitive to radial displacement, while the influence of turbulence on coupling efficiency remains almost the same after applying the antenna. Our calculation method has an average absolute error of only 0.6625% while increasing the calculation speed greatly, which is practical for further studies of vortex beams.

Single Molecule Ratcheting Motion of Peptides in a Mycobacterium smegmatis Porin A (MspA) Nanopore.

Diverse functions of proteins, including synthesis, catalysis, and signaling, result from their highly variable amino acid sequences. The technology allowing for direct analysis of protein sequences, however, is still unsatisfactory. Recent developments of nanopore sequencing of DNA or RNA have motivated attempts to realize nanopore sequencing of peptides in a similar manner. The core challenge has been to achieve a controlled ratcheting motion of the target peptide, which is currently restricted to a limited choice of compatible enzymes. By constructing peptide-oligonucleotide conjugates (POCs) and measurements with nanopore-induced phase-shift sequencing (NIPSS), direct observation of the ratcheting motion of peptides has been successfully achieved. The generated events show a clear sequence dependence on the peptide that is being tested. The method is compatible with peptides with either a conjugated N- or C-terminus. The demonstrated results suggest a proof of concept of nanopore sequencing of peptide and can be useful for peptide fingerprinting.

[Unsupervised deep learning for identifying the O 6-carboxymethyl guanine by nanopore sequencing].

O 6-carboxymethyl guanine(O 6-CMG) is a highly mutagenic alkylation product of DNA that causes gastrointestinal cancer in organisms. Existing studies used mutant Mycobacterium smegmatis porin A (MspA) nanopore assisted by Phi29 DNA polymerase to localize it. Recently, machine learning technology has been widely used in the analysis of nanopore sequencing data. But the machine learning always need a large number of data labels that have brought extra work burden to researchers, which greatly affects its practicability. Accordingly, this paper proposes a nano-Unsupervised-Deep-Learning method (nano-UDL) based on an unsupervised clustering algorithm to identify methylation events in nanopore data automatically. Specially, nano-UDL first uses the deep AutoEncoder to extract features from the nanopore dataset and then applies the MeanShift clustering algorithm to classify data. Besides, nano-UDL can extract the optimal features for clustering by joint optimizing the clustering loss and reconstruction loss. Experimental results demonstrate that nano-UDL has relatively accurate recognition accuracy on the O 6-CMG dataset and can accurately identify all sequence segments containing O 6-CMG. In order to further verify the robustness of nano-UDL, hyperparameter sensitivity verification and ablation experiments were carried out in this paper. Using machine learning to analyze nanopore data can effectively reduce the additional cost of manual data analysis, which is significant for many biological studies, including genome sequencing.

A Single-Molecule Observation of Dichloroaurate(I) Binding to an Engineered Mycobacterium smegmatis porin A (MspA) Nanopore.

Gold(I) compounds are known to bind sulfur-containing proteins, forming the basis in the design of gold(I)-based drugs. However, the intrinsic molecular mechanism of the chemical reaction is easily hidden when monitored in ensemble. We have previously demonstrated that Mycobacterium smegmatis porin A (MspA) can be engineered (MspA-M) to contain a specialized nanoreactor to probe chemical reactions involving tetrachloroaurate(III). Here, we provide further investigations of coordination interactions between dichloroaurate(I) and MspA-M. Gold compounds of different coordination geometry and valence states are as well probed and evaluated, demonstrating the generality of MspA-M. With single-molecule evidence, MspA-M demonstrates a preference for dichloroaurate(I) than tetrachloroaurate(III), an observation in a single molecule that has never been reported. By counting the maximum number of simultaneous ion bindings, the narrowly confined pore restriction also efficiently distinguishes dichloroaurate(I) and tetrachloroaurate(III) according to their differences in geometry or size. The above demonstration complemented a previous study by demonstrating other possible gold-based single-molecule chemical reactions observable by MspA. These observations bring insights in the understanding of gold-based coordination chemistry in a nanoscale.

Growth characteristics of the novel goose parvovirus SD15 strain in vitro.

BACKGROUND: Short beak and dwarfism syndrome (SBDS) was caused by novel goose parvovirus (NGPV)--a variant of goose parvovirus (GPV). Ducks infected with NGPV shows clinical signs including growth retardation and protrusion of the tongue from an atrophied beak. SBDS outbreak was first reported at the northern coastal provinces of China during 2015 and it was again reported in Sichuan, an inland province of China in 2016. The disease caused a huge economic loss in Chinese duck feeding industry. RESULTS: The SD15 strain of NGPV was isolated from liver and intestinal tract tissue samples of infected ducks. Real-time quantitative PCR (qPCR) was used to estimate viral load in embryonated eggs and cells infected with adapted virus. The data showed that duck embryo fibroblasts (DEFs) were permissive to NGPV, while goose embryo fibroblasts (GEFs) cells were not, and the copy numbers of SD15 in the allantoic fluid of infected eggs remained at 105.0-106.5 copies/ml. The adaption procession of the virus was determined via qPCR, and viral proliferation was detected through indirect fluorescent antibody assay (IFA) in DEFs. It was further determined that viral copy numbers peaked at 96 h post-inoculation (hpi), which is the best time to harvest the virus in DEFs. Cytotoxic effects and cell death were observed at 72 hpi in SD15 infected DEFs, yet SD15 did not induce apoptosis. CONCLUSIONS: The growth characteristics of SD15 strain of NGPV determined would be beneficial for further molecular characterization of these viruses and develop potential vaccines if required.

A molecularly imprinted nanoprobe incorporating Cu2O@Ag nanoparticles with different morphologies for selective SERS based detection of chlorophenols.

In a new method for the determination of trace levels of chlorophenols in river waters, detection via surface-enhanced Raman scattering (SERS) is combined with recognition by a molecularly imprinted polymer (MIP). Nanoparticles of type Cu2O@Ag were synthesized by attaching silver particles to the surface of Cu2O nanoparticles. The Cu2O@Ag were then coated with a layer of a MIP that was obtained by atom transfer radical polymerization using from methacrylic acid as monomers and 2,6-dichlorophenol as the template. The morphology of Cu2O is found to be flower-like. The Cu2O@Ag-MIPs displays a strong SERS effect. Following removal of the template by rinsing with the mixture solution of methanol/acetic acid (9/1, v/v), the material was used to selectively bind 2,6-dichlorophenol, 2,4-dichlorophenol and 2,4-dichlorophenol. The SERS peak intensity at 1580 cm-1 increases linearly with the concentration of the various chlorophenols in the range from 10 nM to 1 mM, and the detection limit is 5.8 nM. The imprinting factor is 4.62. The method was applied to the analysis of (spiked) river water, with recoveries ranging from 91.8 to 115.4% and relative standard deviations of <4.5%. Graphical abstract.

A Framework for an Intelligent and Personalized Fire Evacuation Management System.

Many research studies have focused on fire evacuation planning. However, because of the uncertainties in fire development, there is no perfect solution. This research proposes a fire evacuation management framework which takes advantage of an information-rich building information modeling (BIM) model and a Bluetooth low energy (BLE)-based indoor real-time location system (RTLS) to dynamically push personalized evacuation route recommendations and turn-by-turn guidance to the smartphone of a building occupant. The risk score (RS) for each possible route is evaluated as a weighted summation of risk level index values of all risk factors for all segments along the route, and the route with the lowest RS is recommended to the evacuee. The system will automatically re-evaluate all routes every 2 s based on the most updated information, and the evacuee will be notified if a new and safer route becomes available. A case study with two testing scenarios was conducted for a commercial office building in Tianjin, China, in order to verify this framework.

Beneficial Metabolic Effects of 2',3',5'-Triacetyl-N6-(3-hydroxylaniline) adenosine in Multiple Biological Matrices and Intestinal Flora of Hyperlipidemic Hamsters.

Hyperlipidemia is one of the main causes of obesity, type 2 diabetes mellitus (T2DM), and atherosclerosis. The adenosine derivative, 2',3',5'-triacetyl-N6-(3-hydroxylaniline) adenosine (IMM-H007) is an effective lipid-lowering compound that has important implications for the development of lipid-lowering drugs. Metabolomic analysis based on 1H NMR was used to monitor dynamic changes in diverse biological media including serum, liver, urine, and feces in response to high-fat diet (HFD) and IMM-H007 treatments. Ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and gas chromatography (GC) analyses were performed to quantify the bile acids and fatty acids in the liver and feces. Fecal microbiome profiling was performed using Illumina sequencing of the 16S rRNA ( 16S rRNA) gene. IMM-H007 improved the metabolism of carbohydrate, ketone bodies, fatty acids, amino acids, and bile acids in hyperlipidemic hamsters. The correlation between metabolite changes was explored in different biological media. Significant changes in gut microbiota were observed in the HFD and IMM-H007 treatment groups. In the HFD group at the phylum level, we found high levels of the Firmicutes genus and low levels of Bacteroidetes. In contrast, the administration of IMM-H007 reversed the levels of Firmicutes and Bacteroidetes. This reversal suggested that IMM-H007 may have the ability to regulate the composition of the gut flora. We also analyzed the correlation between the gut flora and the metabolites. Our results indicate that IMM-H007 treatment improves the hyperlipidemic metabolism and the structure of the gut microbiota in hyperlipidemic hamsters.

Duck stimulator of interferon genes plays an important role in host anti-duck plague virus infection through an IFN-dependent signalling pathway.

The human stimulator of interferon gene (STING) is an important molecule in innate immunity that stimulates type I interferon (IFN) production. However, the role of duck STING (duSTING) in innate immunity has yet to be explained. In this study, the full length of the duSTING cDNA sequence (1149bp), which encodes 382 amino acid (aa) residues, was reported and showed the highest sequence similarity with chicken STINGs. The phylogenetic analysis based on STING aa showed that duSTING was grouped onto the birds clade. According to the tissue distribution spectrum analysis, duSTING was highly present in the bursa of Fabricius, glandular stomach, liver, pancreas, and small intestine of ducklings, as well as in the blood and pancreas of the adult duck. DuSTING mainly colocalized with the endoplasmic reticulum (ER) and mitochondria in transfected Baby Hamster Syrian Kidney (BHK21) and duck embryo fibroblasts (DEF) cells by an indirect immunofluorescence assay. The transfection of the DEFs with duSTING activated NF-κB, which induced the transcription of IFN-ß, and the activated IFN induced the interferon-stimulated response element (ISRE). Furthermore, the overexpression of duSTING significantly upregulated the mRNA level of duck IFN-ß and IFN-stimulated genes (ISGs), such as duMx and duOASL and inhibited the replication of the double-stranded DNA duck plague virus (DPV) in vitro. In addition, the knockdown of endogenous duSTING by shRNA significantly reduced the poly (I:C) (pIC), poly (dA:dT), and Tembusu virus (TMUV), induced IFN-ß production and significantly promoted DPV replication in vitro. In general, these data demonstrate that duSTING is vital for duck type I interferon induction and plays an important role in the host defence of DPV infection.

Spatial spillover effects of manufacturing agglomeration on China's total factor carbon productivity: evidence from the regulatory role of fiscal decentralization.

Based on the theory of new economic geography, this paper used panel data from 284 cities in China from 2006 to 2019 to determine the effects of spatial spillover and heterogeneity of manufacturing agglomeration (MA) on urban total factor carbon productivity (TFCP) and the regulatory effect of fiscal decentralization on the outcome. The results showed that (1) MA shifted from the eastern region of China to the central and western regions, with the center of gravity moving towards the south. The spatial pattern of urban TFCP displayed the solidifying characteristics of "low-level agglomeration and high-level dispersion," with technological progress being the primary driver. (2) The MA had a significant U-shaped effect on the TFCP of local and nearby cities, promoting the improvement of urban TFCP through Jacobs' and Porter's externalities but not MAR externalities. (3) Regarding regional differences, MA had a significant U-shaped impact on urban TFCP in the eastern and central regions. At different levels of manufacturing development, there was an inverted U-shaped relationship in both manufacturing and non-manufacturing metropolitan areas. For varying degrees of manufacturing industry agglomeration, increasing the level of MA improved urban TFCP in low agglomeration areas, but inhibited it in high agglomeration areas. (4) The implementation of fiscal decentralization nationwide and in the eastern and central regions significantly weakened the impact of MA on TFCP. Furthermore, fiscal decentralization significantly enhanced the influence of MA on TFCP in cities exhibiting high levels of economic development, advanced industrial structure and strict environmental regulations. Therefore, based on the unique developmental characteristics of the manufacturing industry in various cities, fiscal policies ought to be tailored to local circumstances to support key areas. This strategy should facilitate the high-quality development of manufacturing industry and low-carbon development of cities.

Impact of low-carbon city pilot policies on urban green innovation from the perspective of spatial and temporal heterogeneity.

The low-carbon city pilot policy (LCPP) in China is an active response to climate change, with cities serving as the main agents of action. Enhancing green innovation at a city-wide level can effectively support the promotion of pilot cities' efforts towards sustainable growth. Using panel data from 204 prefectures collected from 2005 to 2019, we adopted the time-varying difference-in-differences (DID) model and the spatial Durbin model combined with time-varying DID (SDM-DID) to determine the impact of the LCPP on urban green innovation and its temporal and spatial heterogeneity. Empirical findings showed that (1) LCPP had a significant positive impact on urban green innovation, and green invention patents had a greater green innovation effect than green utility model patents. (2) Heterogeneity analysis revealed that in terms of geographical location, the pilot policy was more effective in promoting urban green innovation in the eastern and central regions in comparison to the western region. At the city level, the pilot policy had a greater impact on green innovation in first- and second-tier cities. With regard to city scale, large-scale cities showed a greater impact on green innovation than small- and medium-sized cities. (3) Mechanistic testing revealed that LCPPs stimulated urban green innovation by talent aggregation, increasing government support for innovation, and public participation; but the mechanism for alleviating financing constraints has yet to be effectively validated. (4) The LCPP showed a spatial spillover effect, whereby one city's low-carbon governance yielded institutional dividends for neighboring cities both geographically and economically, and the impact was more pronounced in those cities that were not resource-based. This study presents empirical evidence at the urban and spatial levels, supporting the comprehensive promotion of low-carbon city construction and development in China.

Qualitative and Quantitative Changes of Oligosaccharides in Human and Animal Milk over Lactation.

The aim of this study was to investigate the changes in human and animal milk oligosaccharides over lactation. In total, 89, 97, 115, and 71 oligosaccharides were identified in human, bovine, goat, and camel milk. The number of common oligosaccharides between camel and human milk was the highest (16 and 17 in transitional and mature milk). With respect to the absolute concentration of eight oligosaccharides (2'-FL, 3-FL, α3'-GL, LNT, LNnT, 3'-SL, 6'-SL, and DSL), 2'-FL, 3'-FL, LNT, and LNnT were much higher in human than three animal species. 3'-SL had a similar concentration in bovine colostrum (322.2 µg/mL) and human colostrum (321.0 µg/mL), followed by goat colostrum (105.1 µg/mL); however, it had the highest concentration in camel mature milk (304.5 µg/mL). The ratio of 6'-SL and 3'-SL (1.77) in goat colostrum was similar to that in human colostrum (1.68), followed by bovine colostrum (0.13). In terms of changes of eight oligosaccharides over lactation, they all decreased with the increase of lactation in bovine and goat milk; however, α3'-GL, 2'-FL, and 3-FL increased in camel species, and LNT increased first and then decreased over lactation in human milk. This study provides a better understanding of the variation of milk oligosaccharides related to lactation and species.

Evaluation of Behavior and Affective State of Different-Parity Sows with Strong/Weak Pupil Light Reflex.

The stall-housing system is commonly used in the modern swine industry in many countries; however, long-term space restrictions can cause affective and physiological abnormalities in sows. The pupil light reflex (PLR) can reflect the psychological and neurological changes in animals, and confined sows show higher pupillary rigidity. However, the PLR differs between same-parity sows, suggesting differences in behaviors and affective states between parity groups. We subjected confined Yorkshire × Landrace sows of parity 0, 2, and 5 to a PLR test and accordingly assigned them to the weak PLR (WR) group (n = 20) or the strong PLR (SR) group (n = 22). We then observed the sows' behaviors and performed a sucrose/quinine response test and novel object test (NOT) to assess the differences in their affective states. The standing and lateral lying behaviors of the sows were less frequent in WR than in SR (p < 0.05), whereas ventral lying and sitting behaviors was more frequent in WR than in SR (p < 0.05). No changes in chewing behaviors and sucrose/quinine responses were observed (p > 0.05); however, the numbers and duration of novel object contact were lower and the novel object response latency time was longer in WR than in SR (p < 0.05). Regarding parity, standing and lateral lying behaviors were less frequent and ventral lying and sitting behaviors were more frequent at parity 5 than at parity 0 (p < 0.05). Bar-biting, rooting, trough-biting, and sucrose response score were lower at parity 5 than at parity 0 (p < 0.05), and vacuum chewing behavior and quinine response score were higher in sows of parity 5 than in those of parity 0 (p < 0.05). NOT showed that the number of contacts and contact duration in sows decreased with increasing parity (p < 0.05), and the response latency time was longer in sows of parity 5 than in those of lower parity (p < 0.05). In conclusion, the behavioral expression and responses of confined sows to novel objects differed between PLRs. The evaluation of the affective state of sows also revealed marked differences with increasing parity. Thus, confined sows with WR and high parity apparently suffer from more severe psychological problems, and PLR may be a potent indicator for evaluating the affective state of confined sows.

Can reduced-input direct seeding improve resource use efficiencies and profitability of hybrid rice in China?

The mechanization of rice production in China has been accompanied by a rapid reduction in agricultural labor forces and increase in machinery purchase subsidies; however, the comprehensive performance of several major mechanized production modes regarding output, environmental protection, and profit remains uncertain to the Chinese government and farmers alike. Here, a five-year (2015-2019) field experiment was conducted to analyze the performance of farmers' mechanized seedling transplanting (FMST), farmers' mechanized direct seeding (FMDS), and reduced-input direct seeding (RIDS) concerning grain yield, energy use, greenhouse gas emissions, and economic benefits. RIDS used an unmanned aerial vehicle for sowing, fertilizing, and spraying, while adopting no-tillage, bed-furrow irrigation technology. The quantity and stability of RIDS-produced grain were similar to those of FMST and higher than those of FMDS. Furthermore, RIDS yields required significantly less machinery, human labor, fuel, and water, with 34.72% and 24.03% decreases in total energy input compared to that for FMST and FMDS, corresponding to 1.45- and 1.34-fold increases in energy productivity, respectively. The resulting CO2-eq emissions from agricultural inputs for RIDS were 71.26% and 71.32% of those for FMST and FMDS, while CH4 emissions were 32.60% and 29.24% of those for FMST and FMDS, respectively. Despite the high N2O emissions and decomposing trend of soil organic carbon in RIDS, the net global warming potential still decreased by 48.84-58.36%, and the carbon sustainability index and carbon efficiency ratio increased by 87.67-142.14% and 105.32-188.22%, respectively, compared with those of FMST and FMDS. RIDS had the lowest cost, its net return was USD 298.81 ha-1 higher than that of FMDS (similar to FMST), and its benefit-cost ratio was 10-36.19% higher than that of FMST and FMDS. Generally, RIDS offered a higher-yielding, cleaner, more sustainable rice production technology for meeting the needs of the Chinese government and farmers.

Identification of nucleoside monophosphates and their epigenetic modifications using an engineered nanopore.

RNA modifications play critical roles in the regulation of various biological processes and are associated with many human diseases. Direct identification of RNA modifications by sequencing remains challenging, however. Nanopore sequencing is promising, but the current strategy is complicated by sequence decoding. Sequential nanopore identification of enzymatically cleaved nucleoside monophosphates may simultaneously provide accurate sequence and modification information. Here we show a phenylboronic acid-modified hetero-octameric Mycobacterium smegmatis porin A nanopore, with which direct distinguishing between monophosphates of canonical nucleosides, 5-methylcytidine, N6-methyladenosine, N7-methylguanosine, N1-methyladenosine, inosine, pseudouridine and dihydrouridine was achieved. A custom machine learning algorithm, which reports an accuracy of 0.996, was also applied to the quantitative analysis of modifications in microRNA and natural transfer RNA. It is generally suitable for sensing of a variety of other nucleoside or nucleotide derivatives and may bring new insights to epigenetic RNA sequencing.

Hydrogen sulfide alleviates the anxiety-like and depressive-like behaviors of type 1 diabetic mice via inhibiting inflammation and ferroptosis.

Studies reported that sodium hydrosulfide (NaHS) can remit the depressive-like and anxiety-like behaviors induced by type 1 diabetes mellitus (T1DM). However, the mechanism is still unclear. In this study, we aimed to investigate the mechanism of NaHS on T1DM. Mice were randomly divided into four groups, including the control group (CON group), DM group, DM + 5.6 mg/kg NaHS group, and CON + 5.6 mg/kg NaHS group. Data showed that NaHS did attenuate the depressive-like and anxiety-like behaviors by OFT, EPM test, FST, and TST. Results suggest that NaHS markedly alleviated the ferroptosis in the prefrontal cortex (PFC) of diabetic mice by reducing iron deposition and oxidative stress, increasing the expression of GPX4 and SLC7A11. Moreover, NaHS could dampen the activation of microglias and the release of pro-inflammatory cytokines, enhance the protein expression of sirtuin 6 (Sirt6) and the interaction between Sirt6 and the acetylation of histoneH3 lysine9 (H3K9ac), and decrease the protein expressions of the Notch1 receptor and H3K9ac. In vitro experiment, NaHS ameliorated the ferroptosis via increasing the protein expressions of SLC7A11, glutathione peroxidase 4 (GPX4), and cystathionine ß-synthase (CBS), reducing the pro-inflammatory cytokines, decreasing the levels of Fe2+, MDA, ROS, and lipid ROS. In conclusion, our results suggested that NaHS did alleviate anxiety-like and depressive-like behaviors. It can inhibit inflammation via modulating Sirt6 and was able to decrease the ferroptosis in the PFC of type 1 diabetic mice and the BV2 cells.

Hyperforin alleviates the psychiatric disorders of adult rats suffered from early maternal separation via activating autophagy.

Rodent animals exposed to early maternal separation (EMS) show abnormal behaviors. Our previous study reported that autophagy is inhibited in the hippocampus of EMS rats, and hyperforin (HYP) alleviates depressive-like and anxious-like behaviors induced by EMS. However, the underlying mechanism of HYP is still unclear. In this study, we tested whether HYP alleviates the psychiatric disorders of EMS rats via activating autophagy. Pups were randomly divided into the control (CON) group, the EMS group, the EMS +3 mg/kg/day HYP (EMS + HYP) group and the EMS + treatment with 3 mg/kg/day fluoxetine (EMS + FT) group. Pups were separated from their mothers for 6 h every day from postnatal day 1 (PD1) to PD21 except pups of the CON group. Besides, HYP and FT were administered from PD22 to PD35 in the EMS + HYP group and the EMS + FT group respectively. Data showed that HYP not only reduced the level of glutamate, decreased the expression of N-methyl-d-aspartate receptor subunit 2B and postsynaptic density-95, but also increased the expression of synaptophysin of EMS rats. Interestingly, the expression of beclin-1 and the ratio of LC3II/LC3I were up-regulated in the EMS + HYP group. Moreover, HYP reduced the expression of the Notch1 receptor and the acetylation of H3K9 of EMS rats. In conclusion, our findings demonstrated that HYP ameliorates the depressive-like and anxious-like behaviors via activating autophagy in the hippocampus of EMS rats.