Differences between the intestinal microbial communities of healthy dogs from plateau and those of plateau dogs infected with Echinococcus.

OBJECTIVE: Cystic echinococcosis (CE) represents a profoundly perilous zoonotic disease. The advent of viral macrogenomics has facilitated the exploration of hitherto uncharted viral territories. In the scope of this investigation, our objective is to scrutinize disparities in the intestinal microbiotic ecosystems of canines dwelling in elevated terrains and those afflicted by Echinococcus infection, employing the tool of viral macrogenomics. METHODS: In this study, we collected a comprehensive total of 1,970 fecal samples from plateau dogs infected with Echinococcus, as well as healthy control plateau dogs from the Yushu and Guoluo regions in the highland terrain of China. These samples were subjected to viral macrogenomic analysis to investigate the viral community inhabiting the canine gastrointestinal tract. RESULTS: Our meticulous analysis led to the identification of 136 viral genomic sequences, encompassing eight distinct viral families. CONCLUSION: The outcomes of this study hold the potential to enhance our comprehension of the intricate interplay between hosts, parasites, and viral communities within the highland canine gut ecosystem. Through the examination of phage presence, it may aid in early detection or assessment of infection severity, providing valuable insights into Echinococcus infection and offering prospects for potential treatment strategies.

Exenatide and Metformin Improve Serum Indices and Intestinal Flora in patients with Type 2 Diabetes Mellitus and Non-Alcoholic Fatty Liver Disease.

The aim of the study was to investigate th e in flue nce of Exenatide comb ined with Met formin on fasti ng blood glucose, postpr andial glucose, triglycerides, total cholesterol, alanine aminotransferase, aspartate aminotransferase, and inte s tinal flora in typ e 2 diab etes mellitus cases with non-alcoholic fatty liver disease. A total of 128 type 2 diabetes mellitus patients with non-alcoholic fatty liver disease, diagnosed from Januar y 2019 to January 2022, were included and randomly assigned to either G roup A (n=64) or Gro up B (n =64). Group A received Metformin, while Group B received Exenatide injection and Metfor min. After 24 weeks of treat ment, blood glucose indices (fasting blood glucose and postprandial glucose), blood lipid indices (triglycerides and total cholesterol), liver func tion indices (alanine aminotransferase and aspar tate aminotransferase) were all lower in Group B than in Group A (p<0.001 for all). Counts o f Escherichia coli and Enterococcus faecalis were lower in Group B than in Group A (both p<0.05), counts of Bifidobacteria and Lactobacillus were highe r i n Group B than in Grou p A (both p<0.05). Combin ation of Exenati de and Metformi n may have synergistic effects in improving metabo lic an d hepatic pa rameters, a s well as re gulat ing intestinal flora, which cou ld provide a pro misin g therapeutic option for the management of these patients.

Current genetic strategies to investigate gene functions in Trichoderma reesei.

The filamentous fungus Trichoderma reesei (teleomorph Hypocrea jecorina, Ascomycota) is a well-known lignocellulolytic enzymes-producing strain in industry. To increase the fermentation titer of lignocellulolytic enzymes, random mutagenesis and rational genetic engineering in T. reesei were carried out since it was initially found in the Solomon Islands during the Second World War. Especially the continuous exploration of the underlying regulatory network during (hemi)cellulase gene expression in the post-genome era provided various strategies to develop an efficient fungal cell factory for these enzymes' production. Meanwhile, T. reesei emerges competitiveness potential as a filamentous fungal chassis to produce proteins from other species (e.g., human albumin and interferon α-2b, SARS-CoV-2 N antigen) in virtue of the excellent expression and secretion system acquired during the studies about (hemi)cellulase production. However, all the achievements in high yield of (hemi)cellulases are impossible to finish without high-efficiency genetic strategies to analyze the proper functions of those genes involved in (hemi)cellulase gene expression or secretion. Here, we in detail summarize the current strategies employed to investigate gene functions in T. reesei. These strategies are supposed to be beneficial for extending the potential of T. reesei in prospective strain engineering.

MiR-590-5p promotes cisplatin resistance via targeting hMSH2 in ovarian cancer.

OBJECTIVE: The mechanisms of ovarian cancer generate chemotherapy resistance are still unclear. This study aimed to explore the role of microRNA (miR)-590-5p in regulating hMSH2 expression and cisplatin resistance in ovarian cancer. METHODS: MiR-590-5p was identified as a regulator of hMSH2 with miRDB database and Target Scan database. Then cisplatin sensitive cell line (SKOV3) and resistant cell line (SKOV3-DDP) of ovarian cancer were cultured for cell functional assay and molecular biology assay. The expression levels of MiR-590-5p and hMSH2 were compared between the two cell lines. Dual luciferase reporter assay was used to verify the targeted regulatory relationship between miR-590-5p and hMSH2. CCK-8 assay and cell apoptosis assay were utilized to assess the role of MiR-590-5p and hMSH2 in cell viability under cisplatin. RESULTS: The expression of hMSH2 was significantly decreased, and miR-590-5p was significantly up-regulated in SKOV3-DDP. Up-regulation of hMSH2 weakened the viability of SKOV3 and SKOV3-DDP cell under cisplatin. Transfection with miR­590-5p mimics reduced the expression of hMSH2 and enhanced the viability of ovarian cancer cells under cisplatin, whereas inhibition of miR­590-5p increased the expression of hMSH2, and decreased ovarian cancer cells' viability under cisplatin. Furthermore, luciferase reporter assay showed that hMSH2 was a direct target of miR-590-5p. CONCLUSION: The present study demonstrates that miR­590-5p promotes cisplatin resistance of ovarian cancer via negatively regulating hMSH2 expression. Inhibition of miR­590-5p decreases ovarian cancer cells' viability under cisplatin. Thus miR­590-5p and hMSH2 may serve as therapeutic targets for cisplatin resistant ovarian cancer.

Phase-shift-mediated sensitive detection of propagating ultra-confined graphene plasmons.

The ultra-confined plasmon field supported by graphene provides an ideal platform for enhanced light-matter interactions and studies of fundamental physical phenomena. On the other hand, the intrinsic ultra-short plasmon wavelength obstructs in-plane detectability of plasmon behaviors, like wavelength variations induced by biomolecule or dragging current. The detection of plasmon wavefront and its spatial shift relies on scattering-type scanning near-field microscopy with a spatial resolution of 20 nm. Here we propose a configuration which can efficiently separate ultra-confined plasmon region from detection region, guaranteeing both field confinement and in-plane sensitive detection of wavelength variations. As an example, the application in detecting Fizeau drag effect is demonstrated. Our study can be applied for detecting strong light-matter interactions, including fundamental physical studies and biosensing applications.

Andrographolide Inhibits Biofilm and Virulence in Listeria monocytogenes as a Quorum-Sensing Inhibitor.

Listeria monocytogenes is a major foodborne pathogen that can cause listeriosis in humans and animals. Andrographolide is known as a natural antibiotic and exhibits good antibacterial activity. We aimed to investigate the effect of andrographolide on two quorum-sensing (QS) systems, LuxS/AI-2 and Agr/AIP of L. monocytogenes, as well as QS-controlled phenotypes in this study. Our results showed that neither luxS expression nor AI-2 production was affected by andrographolide. Nevertheless, andrographolide significantly reduced the expression levels of the agr genes and the activity of the agr promoter P2. Results from the crystal violet staining method, confocal laser scanning microscopy (CLSM), and field emission scanning electron microscopy (FE-SEM) demonstrated that andrographolide remarkably inhibited the biofilm-forming ability of L. monocytogenes 10403S. The preformed biofilms were eradicated when exposed to andrographolide, and reduced surviving cells were also observed in treated biofilms. L. monocytogenes treated with andrographolide exhibited decreased ability to secrete LLO and adhere to and invade Caco-2 cells. Therefore, andrographolide is a potential QS inhibitor by targeting the Agr QS system to reduce biofilm formation and virulence of L. monocytogenes.

One-Step Route to Fe2O3 and FeSe2 Nanoparticles Loaded on Carbon-Sheet for Lithium Storage.

Iron-based anode materials, such as Fe2O3 and FeSe2 have attracted widespread attention for lithium-ion batteries due to their high capacities. However, the capacity decays seriously because of poor conductivity and severe volume expansion. Designing nanostructures combined with carbon are effective means to improve cycling stability. In this work, ultra-small Fe2O3 nanoparticles loaded on a carbon framework were synthesized through a one-step thermal decomposition of the commercial C15H21FeO6 [Iron (III) acetylacetonate], which could be served as the source of Fe, O, and C. As an anode material, the Fe2O3@C anode delivers a specific capacity of 747.8 mAh g-1 after 200 cycles at 200 mA g-1 and 577.8 mAh g-1 after 365 cycles at 500 mA g-1. When selenium powder was introduced into the reaction system, the FeSe2 nano-rods encapsulated in the carbon shell were obtained, which also displayed a relatively good performance in lithium storage capacity (852 mAh g-1 after 150 cycles under the current density of 100 mA·g-1). This study may provide an alternative way to prepare other carbon-composited metal compounds, such as FeNx@C, FePx@C, and FeSx@C, and found their applications in the field of electrochemistry.

The SALT-Readout ASIC for Silicon Strip Sensors of Upstream Tracker in the Upgraded LHCb Experiment.

SALT, a new dedicated readout Application Specific Integrated Circuit (ASIC) for the Upstream Tracker, a new silicon detector in the Large Hadron Collider beauty (LHCb) experiment, has been designed and developed. It is a 128-channel chip using an innovative architecture comprising a low-power analogue front-end with fast pulse shaping and a 40 MSps 6-bit Analog-to-Digital Converter (ADC) in each channel, followed by a Digital Signal Processing (DSP) block performing pedestal and Mean Common Mode (MCM) subtraction and zero suppression. The prototypes of SALT were fabricated and tested, confirming the full chip functionality and fulfilling the specifications. A signal-to-noise ratio of about 20 is achieved for a silicon sensor with a 12 pF input capacitance. In this paper, the SALT architecture and measurements of the chip performance are presented.

Butyrate improves cardiac function and sympathetic neural remodeling following myocardial infarction in rats.

Increased inflammation is found in cardiac sympathetic neural remodeling with malignant ventricular arrhythmia (VA) following myocardial infarction (MI). Butyrate, as a microbiota-derived short-chain fatty acid, can inhibit inflammation and myocardial hypertrophy. However, the role of butyrate in sympathetic neural remodeling after MI is unknown. This study aimed to investigate whether butyrate could improve cardiac dysfunction and VA following MI by regulating inflammation and sympathetic neural remodeling. MI rats were randomized to administrate the butyrate or vehicle through intraperitoneal injection to undergo the study. Our data demonstrated that butyrate treatment preserved the partial cardiac function at 7 days post-MI. Butyrate downregulated the expression of essential for inflammatory response in the infarct border zone at 3 days post-MI. Particularly, butyrate promoted expression of M2 macrophage markers. Increased expressions of nerve growth factor and norephinephrine at 7 days after MI were inhibited in butyrate-treated rats. Furthermore, butyrate significantly decreased the density of nerve fibers for growth-associated protein-43 and tyrosine hydroxylase and resulted in fewer episodes of inducible VA. In conclusion, butyrate administration ameliorated cardiac function and VA after MI possibly through promoting M2 macrophage polarization to suppress inflammatory responses and inhibit sympathetic neural remodeling and may present an effective pharmacological strategy for the prevention of MI-related remodeling.

Experimental observed plasmon near-field response in isolated suspended graphene resonators.

Because of extreme three-dimensional field confinement and easy electrically tunability, plasmons in graphene nanostructures are promising candidates for many applications, such as biosensing, photodetectors and modulators. However, up to now, graphene plasmons have been explored mostly on substrates. Scatterers, corrugations and dopants induced by substrates not only add damping to plasmons but also obscure the intrinsic electronic properties of graphene. In this work, the near-field response of surface plasmons of suspended graphene circular resonators is studied with the scattering-type scanning near-field optical microscopy under different excitation wavelengths, λ = 10.653 and 10.22 µm, respectively. Fundamental and higher order breathing plasmon modes are revealed in real-space with the Fermi energy of graphene of only 0.132 eV. Moreover, the direct experimental evidence on near-field electric tuning in suspended graphene resonators is demonstrated by using back-gate tuning. Our work not only provides a foundation to truly understand the properties of electrons inside pure graphene, but shines light on the applications in optoelectronic devices with suspended two-dimensional materials.

Insights into the Phylogeny and Evolution of Cold Shock Proteins: From Enteropathogenic Yersinia and Escherichia coli to Eubacteria.

Psychrotrophic foodborne pathogens, such as enteropathogenic Yersinia, which are able to survive and multiply at low temperatures, require cold shock proteins (Csps). The Csp superfamily consists of a diverse group of homologous proteins, which have been found throughout the eubacteria. They are related to cold shock tolerance and other cellular processes. Csps are mainly named following the convention of those in Escherichia coli. However, the nomenclature of certain Csps reflects neither their sequences nor functions, which can be confusing. Here, we performed phylogenetic analyses on Csp sequences in psychrotrophic enteropathogenic Yersinia and E. coli. We found that representative Csps in enteropathogenic Yersinia and E. coli can be clustered into six phylogenetic groups. When we extended the analysis to cover Enterobacteriales, the same major groups formed. Moreover, we investigated the evolutionary and structural relationships and the origin time of Csp superfamily members in eubacteria using nucleotide-level comparisons. Csps in eubacteria were classified into five clades and 12 subclades. The most recent common ancestor of Csp genes was estimated to have existed 3585 million years ago, indicating that Csps have been important since the beginning of evolution and have enabled bacterial growth in unfavorable conditions.

Laser direct writing of graphene nanostructures beyond the diffraction limit by graphene oxidation.

The fabrication ability of graphene nanostructures is the cornerstone of graphene-based devices, which are of particular interest because of their broad optical response and gate-tunable properties. Here, via laser-induced redox reaction of graphene and silica, we fabricate nano-scale graphene structures by femtosecond laser direct writing. The resolution of destructed graphene lines is far beyond the diffraction limit up to 100 nm with a precision as small as ± 7 nm. Consequently, graphene nanostructures are fabricated precisely and excellent plasmon responses are detected. This novel fabrication method of graphene nanostructures has the advantages of low costs, high efficiency, maskless and especially high precision, which would pave the way for practical application of graphene-based optical and electronic devices.

Near-field imaging of graphene triangles patterned by helium ion lithography.

Plasmon nanoresonators in graphene have many applications in biosensing, photodetectors and modulators. As a result, an efficient and precise patterning technique for graphene is required. Helium ion lithography (HIL) emerges as a promising tool for direct writing fabrication because it owns improved fabrication precision compared to electron beam lithography and conventional gallium focused ion beam technique. In this paper, utilizing HIL, a set of graphene triangles are patterned and excellent plasmon response is detected. Particularly, the evolution of breathing mode in these structures is unveiled by scattering-type scanning near-field optical microscopy. Besides, the plasmon response of graphene structures can be efficiently tuned by adjusting the irradiated ion dose during the etching process, which can be explained by the phenomenal simulation model. Our work demonstrates that HIL is a feasible way for precise plasmonic nanostructure fabrication, and can be applied to graphene plasmon control at the nanoscale as well.

cIAP2 promotes gallbladder cancer invasion and lymphangiogenesis by activating the NF-κB pathway.

Several studies have produced contradictory findings about the prognostic implications for inhibitor of apoptosis proteins (IAP) in different types of cancer. Cellular inhibitor of apoptosis 2 (cIAP2/BIRC) is one of the most extensively characterized human IAP. To date, no studies have focused on the expression level of cIAP2 in human gallbladder cancer (GBC), and the mechanism of cIAP2 in GBC invasion and lymphangiogenesis remains unclear. Therefore, in the present study, cIAP2 expression in GBC was detected using quantitative real-time polymerase chain reaction and immunohistochemistry, and the relationship between cIAP2 levels in cancer tissues and the clinicopathological characteristics of patients was analyzed. The biological effect of cIAP2 in GBC cells was tested using the Cell Counting Kit-8 Assay, Transwell assays and the ability of human dermal lymphatic endothelial cells (HDLEC) to undergo tube formation. The role of cIAP2 in activating the NF-κB pathway was determined using a dual-luciferase reporter assay, immunofluorescence staining, western blotting and ELISA. Finally, an animal model was used to further confirm the role of cIAP2 in lymphangiogenesis. We showed that cIAP2 expression was elevated in human GBC tissues and correlated with a negative prognosis for patients. Moreover, cIAP2 was identified as a lymphangiogenic factor of GBC cells and, thus, promoted lymph node metastasis in GBC cells. Our study is the first to suggest that cIAP2 can promote GBC invasion and lymphangiogenesis by activating the NF-κB pathway.

Stereoselective synthesis of enamino ketones through an aza-Michael/hydrolysis cascade reaction.

We have developed a mild, convenient and efficient synthesis of highly functionalized (Z)-ß-enamino ketones from readily available 3,4-dihydroisoquinoline imines and ynones through an aza-Michael/hydrolysis cascade reaction. This method is also suitable for the preparation of (Z)-ß-enamino esters using alkynoates as starting materials. Complex fully substituted pyrroles can be constructed from the obtained (Z)-ß-enamino ketones. It is an attractive alternative approach for the preparation of highly functionalized enamino ketones, esters and pyrroles.

Catalyst-free synthesis of novel dimeric ß-carboline derivatives via an unexpected [2 + 2 + 2] annulation.

We report here an unexpected catalyst-free [2 + 2 + 2] annulation reaction which allows access to novel complex dimeric ß-carboline derivatives in a single step. Various substituted ynones could react with dihydro-ß-carboline imines to deliver interesting [2 + 2 + 2] annulation products in moderate to good yields. Alkynoates can also be tolerated in this system.

Cross-Phosphorylation between AgrC Histidine Kinase and the Noncognate Response Regulator Lmo1172 in Listeria monocytogenes under Benzalkonium Chloride Stress.

Benzalkonium chloride (BC) is widely used for disinfection in the food industry. However, Listeria monocytogenes strains with resistance to BC have been reported recently. In L. monocytogenes, the Agr communication system consists of a membrane-bound peptidase AgrB, a precursor peptide AgrD, a histidine kinase (HK) AgrC, and a response regulator (RR) AgrA. Our previous study showed that the agr genes are significantly upregulated by BC adaptation. This study aimed to investigate the role of the Agr system in BC resistance in L. monocytogenes. Our results showed that the Agr system was involved in BC resistance. However, a direct interaction between BC and AgrC was not observed, nor between BC and AgrA. These results indicated that BC could induce the Agr system via an indirect action. Both AgrBD and AgrC were required for growth under BC stress. Nevertheless, when exposed to BC, the gene deletion mutant ∆agrA strain exhibited better growth performance than its parental strain. The RR Lmo1172 played a role in BC resistance in the ∆agrA strain, suggesting that Lmo1172 may be an alternative to AgrA in the phosphotransfer pathway. Phosphorylation of Lmo1172 by AgrC was observed in vitro. The cognate HK Lmo1173 of Lmo1172 was not involved in BC stress, regardless of whether it was as the wild-type or the ∆agrA mutant strain. Our evidence suggests that the HK AgrC cross-phosphorylates its noncognate RR Lmo1172 to cope with BC stress when the cognate RR AgrA is absent. In vivo, further studies will be required to detect phosphotransfer of AgrC/AgrA and AgrC/Lmo1172.

Loop closure detection of visual SLAM based on variational autoencoder.

Loop closure detection is an important module for simultaneous localization and mapping (SLAM). Correct detection of loops can reduce the cumulative drift in positioning. Because traditional detection methods rely on handicraft features, false positive detections can occur when the environment changes, resulting in incorrect estimates and an inability to obtain accurate maps. In this research paper, a loop closure detection method based on a variational autoencoder (VAE) is proposed. It is intended to be used as a feature extractor to extract image features through neural networks to replace the handicraft features used in traditional methods. This method extracts a low-dimensional vector as the representation of the image. At the same time, the attention mechanism is added to the network and constraints are added to improve the loss function for better image representation. In the back-end feature matching process, geometric checking is used to filter out the wrong matching for the false positive problem. Finally, through numerical experiments, the proposed method is demonstrated to have a better precision-recall curve than the traditional method of the bag-of-words model and other deep learning methods and is highly robust to environmental changes. In addition, experiments on datasets from three different scenarios also demonstrate that the method can be applied in real-world scenarios and that it has a good performance.

Cinnamaldehyde Targets the LytTR DNA-Binding Domain of the Response Regulator AgrA to Attenuate Biofilm Formation of Listeria monocytogenes.

The Agr quorum sensing (QS) system is known to contribute to biofilm formation in Listeria monocytogenes. Cinnamaldehyde, a natural food preservative, is considered an inhibitor of Agr-mediated QS in L. monocytogenes. However, the exact mechanism by which cinnamaldehyde acts on Agr remains unclear. In this study, we assessed the effects of cinnamaldehyde on the histidine kinase AgrC and the response regulator AgrA in the Agr system. AgrC kinase activity was not influenced by cinnamaldehyde, and binding between AgrC and cinnamaldehyde was not observed when microscale thermophoresis (MST) was performed, indicating that AgrC was not the target of cinnamaldehyde. AgrA is specifically bound to the agr promoter (P2) to activate the transcription of the Agr system. However, AgrA-P2 binding was prevented by cinnamaldehyde. The interaction between cinnamaldehyde and AgrA was further confirmed with MST. Two conserved amino acids, Asn-178 and Arg-179, located in the LytTR DNA-binding domain of AgrA, were identified as the key sites for cinnamaldehyde-AgrA binding by alanine mutagenesis and MST. Coincidentally, Asn-178 was also involved in the AgrA-P2 interaction. Taken together, these results suggest that cinnamaldehyde acts as a competitive inhibitor of AgrA in AgrA-P2 binding, which leads to suppressed transcription of the Agr system and reduced biofilm formation in L. monocytogenes. IMPORTANCE Listeria monocytogenes can form biofilms on various food contact surfaces, posing a serious threat to food safety. Biofilm formation of L. monocytogenes is positively regulated by the Agr quorum sensing system. Thus, an alternative strategy for controlling L. monocytogenes biofilms is interfering with the Agr system. Cinnamaldehyde is considered an inhibitor of the L. monocytogenes Agr system; however, its exact mechanism of action is still unclear. Here, we found that AgrA (response regulator), rather than AgrC (histidine kinase), was the target of cinnamaldehyde. The conserved Asn-178 in the LytTR DNA-binding domain of AgrA was involved in cinnamaldehyde-AgrA and AgrA-P2 binding. Therefore, the occupation of Asn-178 by cinnamaldehyde suppressed transcription of the Agr system and reduced biofilm formation in L. monocytogenes. Our findings could provide a better understanding of the mechanism by which cinnamaldehyde inhibits L. monocytogenes biofilm formation.

Virome of high-altitude canine digestive tract and genetic characterization of novel viruses potentially threatening human health.

The majority of currently emerging infectious illnesses are zoonotic infections, which have caused serious public health and economic implications. The development of viral metagenomics has helped us to explore unknown viruses. We collected 1,970 canine feces from Yushu and Guoluo in the plateau region of China for this study to do a metagenomics analysis of the viral community of the canine digestive tract. Our analysis identified 203 novel viruses, classified into 11 known families and 2 unclassified groups. These viruses include the hepatitis E virus, first identified in dogs, and the astrovirus, coronavirus, polyomavirus, and others. The relationship between the newly identified canine viruses and known viruses was investigated through the use of phylogenetic analysis. Furthermore, we demonstrated the cross-species transmission of viruses and predicted new viruses that may cause diseases in both humans and animals, providing technical support for the prevention and control of diseases caused by environmental pollution viruses. IMPORTANCE Most emerging infectious diseases are due to zoonotic disease agents. Because of their effects on the security of human or animal life, agriculture production, and food safety, zoonotic illnesses and livestock diseases are of worldwide significance. Because dogs are closely related to humans and domestic animals, they serve as one of the important links in the transmission of zoonotic and livestock diseases. Canines can contaminate the environment in which humans live such as water and soil through secretions, potentially altering the human gut microbiota or causing diseases. Our study enriched the viral community in the digestive tract microbiome of dogs and found types of viruses that threaten human health, providing technical support for the prevention and control of early warning of diseases caused by environmental contaminant viruses.