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IntroductionNative endophytic microorganisms in tobacco seeds are closely related to their resistance to Ralstonia solanacearum (R. solanacearum) infections. However, the role of the native seed core microbiome in the suppression of bacterial wilt disease (BWD) remains underexplored.MethodsThe characteristics of endophytic bacterial communities in both resistant and susceptible tobacco varieties were characterized using high-throughput sequencing technology.ResultsThis study found Paenibacillus as a potential microbial antagonist against BWD based on its significantly greater presence in BWD-resistant tobacco varieties, with a relative abundance that was 83.10% greater in the seeds of resistant tobacco than in those of susceptible varieties. Furthermore, a Paenibacillus strain identified as Paenibacillus odorifer 6036-R2A-26 (P. odorifer 26) was isolated from the seeds of the resistant variety. Following irrigation treatment with P. odorifer 26, the BWD index was reduced by 51.08%. Additionally, this strain exhibited significant growth-promoting effects on tobacco. It significantly increased the fresh weight of the tobacco plants by 30.26% in terms of aboveground weight, 37.75% in terms of underground weight, and 33.97% in terms of aboveground dry weight. This study highlights the critical role of Paenibacillus in tobacco seeds in the suppression of BWD, which may result from its antagonistic and growth-promoting properties.DiscussionThe results of this study revealed differences in the structural characteristics of endophytic bacterial communities between resistant and susceptible tobacco varieties, with groups such as Paenibacillus potentially playing significant roles in resisting BWD. These findings highlight the superiority of seed endophytic microorganisms. In the context of declining plant disease resistance and the spread of bacterial wilt, core endophytic microorganisms in seeds may emerge as a viable option for enhancing the productivity of agricultural ecosystems.

The experiment was conducted for developing a sugar-free, low-fat and low-calorie angel cake with no-eggy flavour and palatability, so as to broaden the application of mulberry and satisfy the public's demand for novel baked foods. Using single-factors and response surface experiments for optimization of the processing technology, the experiment focused on the effect of main ingredients on the sensory quality and hardness of angel cake, i.e. the amount of mulberry juice, xylitol, egg white and low gluten flour, as well as the baking temperature and time. The texture properties of mulberry sugar-free angel cake and ordinary angel cake were measured under the same storage conditions. The results showed that the optimal processing parameters were: Low gluten flour 45 g, mulberry juice 33 g, xylitol 45 g, egg white 135 g, cream of tarta 3 g, lemon juice 2 g and milk 30 g. The best baking conditions was that the surface fire was 165 ℃ and the primer fire was 150 ℃ with 35 min. Under these conditions, the sensory score of mulberry angel cake was 91.8. The experiments of the texture characteristics of the cakes showed that the addition of mulberry juice could reduce the hardness and chewiness of the cakes with better water holding capacity and softer texture, simultaneously, it could improve the cohesiveness and adhesion, so that the cakes had concentrated stoma and compact structure.

In this paper, a dynamic simulation analysis model was established for CMGB (control moment gyroscope bearing) under the conditions of time-varying moment. The influences of the moment’s response time, axial preload, and working temperature on the dynamic characteristics and friction torque of CMGB were analyzed, and the relevant verification tests were conducted. The results show that the friction torque fluctuation of CMGB directly corresponds to the dynamic characteristics. The faster the response time of the time-varying moment, the larger the friction torque fluctuation of CMGB. The larger preload minimizes the difference in the ball’s loading state, which is the actual reason for reducing the friction torque fluctuation. Moreover, as the working temperature increases, the friction torque fluctuation of CMGB decreases.

A missense variant in the cytoplasmic domain of the insulin receptor (INSR) was identified by exome sequencing in affected members of a four-generation family with fatty liver disease (FLD). The variant (rs766457461, c.4063T>C, p.Y1355H) results in the substitution of histidine for a tyrosine that undergoes autophosphorylation in response to insulin stimulation in vitro. Because insulin promotes lipogenesis in hepatocytes, we hypothesized that the variant was causally linked to FLD in the family. To test this hypothesis, we used CRISPR/Cas9 technology to replace the corresponding tyrosine in mouse INSR with histidine (Y1345H). No significant differences were found in hepatic insulin signaling, as assessed by phosphorylation of INSR or AKT levels or in activation of the insulin-responsive transcription factor SREBP-1c. Glucose tolerance and hepatic triglyceride (TG) content in Insr1345H/H mice fed a chow diet or diets rich in fat, sucrose or fructose did not differ significantly from WT littermates. Thus, our studies in mice failed to support the notion that INSR (Y1355H) is causally related to FLD in the family or that phosphorylation of this residue alters hepatic TG metabolism.

IgA is the predominant antibody isotype at intestinal mucosae, where it plays a critical role in homeostasis and provides a first line of immune protection. Dysregulation of IgA production, however, can contribute to immunopathology, particularly in kidneys in which IgA deposition can cause nephropathy. Class-switch DNA recombination (CSR) to IgA is directed by TGF-β signaling, which activates Smad2 and Smad3. Activated Smad2/Smad3 dimers are recruited together with Smad4 to the IgH α locus Iα promoter to activate germline Iα-Cα transcription, the first step in the unfolding of CSR to IgA. Epigenetic factors, such as non-coding RNAs, particularly microRNAs, have been shown to regulate T cells, dendritic cells and other immune elements, as well as modulate the antibody response, including CSR, in a B cell-intrinsic fashion. Here we showed that the most abundant miRNA in resting B cells, miR-146a targets Smad2, Smad3 and Smad4 mRNA 3’UTRs and keeps CSR to IgA in check in resting B cells. Indeed, enforced miR-146a expression in B cells aborted induction of IgA CSR by decreasing Smad levels. By contrast, upon induction of CSR to IgA, as directed by TGF-β, B cells downregulated miR-146a, thereby reversing the silencing of Smad2, Smad3 and Smad4, which, once expressed, led to recruitment of Smad2, Smad3 and Smad4 to the Iα promoter for activation of germline Iα-Cα transcription. Deletion of miR-146a in miR-146a–/– mice significantly increased circulating levels of steady state total IgA, but not IgM, IgG or IgE, and heightened the specific IgA antibody response to OVA. In miR-146a–/– mice, the elevated systemic IgA levels were associated with increased IgA+ B cells in intestinal mucosae, increased amounts of fecal free and bacteria-bound IgA as well as kidney IgA deposition, a hallmark of IgA nephropathy. Increased germline Iα-Cα transcription and CSR to IgA in miR-146a–/– B cells in vitro proved that miR-146a-induced Smad2, Smad3 and Smad4 repression is B cell intrinsic. The B cell-intrinsic role of miR-146a in the modulation of CSR to IgA was formally confirmed in vivo by construction and OVA immunization of mixed bone marrow μMT/miR-146a–/– chimeric mice. Thus, by inhibiting Smad2, Smad3 and Smad4 expression, miR-146a plays an important and B cell intrinsic role in modulation of CSR to IgA and the IgA antibody response.

In rhizospheres, chemical barrier-forming natural compounds play a key role in preventing pathogenic bacteria from infecting plant roots. Here, we sought to identify specific phenolic exudates in tobacco (Nicotiana tobaccum) plants infected by the soil-borne pathogen Ralstonia solanacearum that may exhibit antibacterial activity and promote plant resistance against pathogens. Among detected phenolic acids, only caffeic acid was significantly induced in infected plants by R. solanacearum relative to healthy plants, and the concentration of caffeic acid reached 1.95 μg/mL. In vivo, caffeic acid at 200 μg/mL was highly active against R. solanacearum and obviously damaged the membrane structure of the R. solanacearum cells, resulting in the thinning of the cell membrane and irregular cavities in cells. Moreover, caffeic acid significantly inhibited biofilm formation by repressing the expression of the lecM and epsE genes. In vitro, caffeic acid could effectively activate phenylalanine ammonia-lyase (PAL) and peroxidase (POD) and promote the accumulation of lignin and hydroxyproline. In pot and field experiments, exogenous applications of caffeic acid significantly reduced and delayed the incidence of tobacco bacterial wilt. Taken together, all these results suggest that caffeic acid played a crucial role in defending against R. solanacearum infection and was a potential and effective antibacterial agent for controlling bacterial wilt.

Ralstonia solanacearum (R. solanacearum) is one of the most devastating plant bacterial pathogens and leads to serious economic losses in crops worldwide. In this study, the antibacterial mechanism of 7-methoxycoumarin, a new coumarin antibiotic, was preliminarily investigated by the observation of symptoms and physical and biochemical analyses. The results showed that 7-methoxycoumarin significantly suppressed bacterial growth of R. solanacearum, with the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) values of 75 and 175 mg/L, respectively. Electron microscopy observations showed that the bacterial cell membrane was destroyed after 7-methoxycoumarin treatment. Biofilm formation of R. solanacearum was significantly suppressed by 7-methoxycoumarin at concentrations ranging from 25 to 100 mg/L. Furthermore, virulence-associated genes epsE, hrpG, and popA of R. solanacearum were significantly inhibited by 7-methoxycoumarin. The application of 7-methoxycoumarin effectively suppressed tobacco bacterial wilt progress in pot experiments, with relative control efficiencies of 83.61, 68.78, and 58.11% at 6, 8, and 10 days post inoculation, respectively.

This study proposes a miniature and highly sensitive Fabry-Perot interferometer (FPI) based on aluminum - polyimide diaphragm integrated with a mass block for acceleration sensing. The composite diaphragms with a radius and thickness of 3.5 mm and 630 nm are manufactured by Micro-ElectroMechanical System (MEMS) technology. To increase the adhesion of the polyimide diaphragm to silicon wafer and improve the quality of deflectable diaphragm, a 30-nm-thick aluminum diaphragm is first coated on the silicon wafer by magnetron sputtering; a silicon wafer in the intermediate diaphragm is reserved as a mass block to form an integrated structure. Air cavity of the FPI formed by this composite diaphragm is modulated via external vibration signals, leading to a variation in the length of the cavity. Three fiber optic Fabry-Perot accelerometers (FOFPAs) are fabricated with a measured average sensitivity and acceleration resolution of 2.6 V/g (100 Hz-3.2 kHz) and 4.12 μg/Hz1/2 respectively, which show high consistency and manufacturing reproducibility. Good heat resistance performance of the sensor below 280° can also be observed obviously. Thus, this proposed sensor is anticipated to have wide application prospects in micro vibration monitoring in high temperature.

Lipogenesis in liver is highest in the postprandial state; insulin activates SREBP-1c, which transcriptionally activates genes involved in FA synthesis, whereas glucose activates carbohydrate-responsive element-binding protein (ChREBP), which activates both glycolysis and FA synthesis. Whether SREBP-1c and ChREBP act independently of one another is unknown. Here, we characterized mice with liver-specific deletion of ChREBP (L-Chrebp−/− mice). Hepatic ChREBP deficiency resulted in reduced mRNA levels of glycolytic and lipogenic enzymes, particularly in response to sucrose refeeding following fasting, a dietary regimen that elicits maximal lipogenesis. mRNA and protein levels of SREBP-1c, a master transcriptional regulator of lipogenesis, were also reduced in L-Chrebp−/− livers. Adeno-associated virus-mediated restoration of nuclear SREBP-1c in L-Chrebp−/− mice normalized expression of a subset of lipogenic genes, while not affecting glycolytic genes. Conversely, ChREBP overexpression alone failed to support expression of lipogenic genes in the livers of mice lacking active SREBPs as a result of Scap deficiency. Together, these data show that SREBP-1c and ChREBP are both required for coordinated induction of glycolytic and lipogenic mRNAs. Whereas SREBP-1c mediates insulin's induction of lipogenic genes, ChREBP mediates glucose's induction of both glycolytic and lipogenic genes. These overlapping, but distinct, actions ensure that the liver synthesizes FAs only when insulin and carbohydrates are both present.

Abstract We demonstrate a new scheme for realizing the Optical Bistability (OB) inside an all-fiber ring cavity with an external control field. In the absence of the external control field, the pump power is fixed below the threshold value of laser, and there is no laser in the cavity. However, when the control signal of 1505 nm to 1520 nm is injected into the cavity, laser begins to oscillate and OB appears. We found that the wavelength and power of the control signal can affect the OB behavior dramatically, which can be used to manipulate efficiently the threshold intensity and the hysteresis loop. We also give an explanation of the bistability phenomenon based on numerical simulations, which are agreed very well with our experimental results. Our scheme may provide some new possibilities for technological applications in optical power limiters, switches or memories.

Ralstonia solanacearum is one of the most devastating phytopathogens and causes bacterial wilt, which leads to severe economic loss due to its worldwide distribution and broad host range. Certain plant-derived compounds (PDCs) can impair bacterial virulence by suppressing pathogenic factors of R. solanacearum. However, the inhibitory mechanisms of PDCs in bacterial virulence remain largely unknown. In this study, we screened a library of coumarins and derivatives, natural PDCs with fused benzene and α-pyrone rings, for their effects on expression of the type III secretion system (T3SS) of R. solanacearum. Here, we show that umbelliferone (UM), a 7-hydroxycoumarin, suppressed T3SS regulator gene expression through HrpG–HrpB and PrhG–HrpB pathways. UM decreased gene expression of six type III effectors (RipX, RipD, RipP1, RipR, RipTAL, and RipW) of 10 representative effector genes but did not alter T2SS expression. In addition, biofilm formation of R. solanacearum was significantly reduced by UM, though swimming activity was not affected. We then observed that UM suppressed the wilting disease process by reducing colonization and proliferation in tobacco roots and stems. In summary, the findings reveal that UM may serve as a plant-derived inhibitor to manipulate R. solanacearum T3SS and biofilm formation, providing proof of concept that these key virulence factors are potential targets for the integrated control of bacterial wilt.

Ralstonia solanacearum, an agent of bacterial wilt, is a highly variable species with a broad host range and wide geographic distribution. As a species complex, it has extensive genetic diversity and its living environment is polymorphic like the lowland and the highland area, so more genomes are needed for studying population evolution and environment adaptation. In this paper, we reported the genome sequencing of R. solanacearum strain CQPS-1 isolated from wilted tobacco in Pengshui, Chongqing, China, a highland area with severely acidified soil and continuous cropping of tobacco more than 20 years. The comparative genomic analysis among different R. solanacearum strains was also performed. The completed genome size of CQPS-1 was 5.89 Mb and contained the chromosome (3.83 Mb) and the megaplasmid (2.06 Mb). A total of 5229 coding sequences were predicted (the chromosome and megaplasmid encoded 3573 and 1656 genes, respectively). A comparative analysis with eight strains from four phylotypes showed that there was some variation among the species, e.g., a large set of specific genes in CQPS-1. Type III secretion system gene cluster (hrp gene cluster) was conserved in CQPS-1 compared with the reference strain GMI1000. In addition, most genes coding core type III effectors were also conserved with GMI1000, but significant gene variation was found in the gene ripAA: the identity compared with strain GMI1000 was 75% and the hrpII box promoter in the upstream had significantly mutated. This study provided a potential resource for further understanding of the relationship between variation of pathogenicity factors and adaptation to the host environment.

Soil acidification is a major problem in modern agricultural systems and is an important factor affecting the soil microbial community and soil health. However, little is known about the effect of soil acidification on soil-borne plant diseases. We performed a 4-year investigation in South China to evaluate the correlation between soil acidification and the occurrence of bacterial wilt. The results showed that the average soil pH in fields infected by bacterial wilt disease was much lower than that in non-disease fields. Moreover, the proportion of infected soils with pH lower than 5.5 was much higher than that of non-infected soils, and this phenomenon became more obvious as the area of bacterial wilt disease increased at soil pH lower than 5.5 from 2011 to 2014. Then, in a field pot experiment, bacterial wilt disease developed more quickly and severely in acidic conditions of pH 4.5, 5.0, and 5.5. These results indicate that soil acidification can cause the outbreak of bacterial wilt disease. Further experiments showed that acidic conditions (pH 4.5–5.5) favored the growth of the pathogen Ralstonia solanacearum but suppressed the growth and antagonistic activity of antagonistic bacteria of Pseudomonas fluorescens and Bacillus cereus. Moreover, acidic conditions of pH 5.5 were conducive to the expression of the virulence genes PopA, PrhA, and SolR but restrained resistance gene expression in tobacco. Finally, application of wood ash and lime as soil pH amendments improved soil pH and reduced the occurrence of bacterial wilt. Together, these findings improve our understanding of the correlation between soil acidification and soil-borne plant diseases and also suggest that regulation of soil acidification is the precondition and foundation of controlling bacterial wilt.

An increasing number of investigations have been performed on the phytotoxicity of carbon-based nanomaterials duo to their extensive use in various fields. In the present study, we investigated the phytotoxicity of unfunctionalized graphene oxide (GO) and amine-functionalized graphene oxide (G-NH2) on wheat (Triticum aestivum) in the concentration range from 125 to 2000 μg/mL after 9 days of hydroponic culture. Our results found that the incubation with both nanomaterials did not affect the final seed germination rate, despite some influence in the initial stage. Transmission electron microscopy (TEM) observations indicated that exposure to GO at a high concentration (above 1000 μg/mL) resulted in a severe loss of morphology of seedlings, and a decrease in root length, shoot length and relative biomass, along with obvious damage to plant tissue structures (root, stem and leaf) when compared with the control. GO induced increased damage to root cells, which were determined by electrolyte leakage. Conversely, the plant growth was enhanced under G-NH2 exposure, and the root and stem lengths were increased by 19.27% and 19.61% at 2000 μg/mL, respectively. The plant tissue structures were not affected, and neither GO nor G-NH2 were observed to accumulate in the wheat plant root cells. The present investigations provide important information for evaluation of the environmental safety of GO and better understanding plant-nanoparticle interactions.

Bacterial wilt is a destructive disease caused by the phytopathogen Ralstonia solanacearum (R. solanacearum), which is widely found in various tobacco-growing areas all over the world. Botanical bactericidal substances have gradually emerged as a hot topic in modern pesticide research. In this study, the antibacterial activities of two phytochemicals (resveratrol and coumarin) against R. solanacearum and their in vivo and in vitro efficacy for controlling tobacco bacterial wilt were evaluated. We rule out significant biological effects of both phytochemicals using transmission electron microscope (TEM) and fluorescence microscope, which suppressed the growth of R. solanacearum. Furthermore, we demonstrated that the toxicity mechanisms mainly involved damaging bacterial cell membrane and preventing swarming motility and biofilm formation. A further pot experiment demonstrated that coumarin and resveratrol significantly inhibited early adhesion and colonization of R. solanacearum in tobacco plants and the corresponding control efficacies were 68% and 85% after incubation for 13 days, respectively. The findings of this study suggest that both resveratrol and coumarin have potential as non-toxic antimicrobial strategies for controlling tobacco bacterial wilt disease.

Many cereals accumulate hydroxamic acids involved in defense of plant against various fungi, bacteria, and insects. 2,4-dihydroxy-7-methoxy-1,4-benzoxazine-3-one, commonly known as DIMBOA, is one of the principal cyclic hydroxamic acids in aqueous extracts of maize. The aim of this study was to evaluate the antibacterial activity of the isolated DIMBOA and its derivatives 2-benzoxazolinone (BOA), 6-chloro-2-benzoxazolinone (CDHB), and 2-mercaptobenzothiazole (MBT) against Ralstonia solanacearum. MBT showed the strongest antibacterial activity, followed by CDHB and DIMBOA, with minimum inhibitory concentrations (MICs) of 50, 100 and 200 mg/L, respectively, better than the BOA with 300 mg/L. These compounds also significantly affect bacterial growth, reduce biofilm formation, and inhibit swarming motility within 24 h. This paper is the first to report the anti-R. solanacearum activity of DIMBOA from Z. mays. The bioassay and pot experiment results suggested that DIMBOA and its derivatives exhibit potential as a new matrix structure of designing target bactericide or elicitor for controlling tobacco bacterial wilt. Further studies must evaluate the efficacy of DIMBOA and its derivatives in controlling bacterial wilt under natural field conditions where low inoculum concentrations exist.

Protocatechualdehyde (PCA) is an important plant-derived natural product that has been associated with a wide variety of biological activities and has been widely used in medicine as an antioxidant, anti-aging and an anti-inflammatory agent. However, fewer reports concerning its antibacterial effects on plant-pathogenic bacteria exist. Therefore, in this study, protocatechualdehyde was evaluated for its antibacterial activity against plant pathogens along with the mechanism of its antibacterial action. PCA at 40 μg/mL was highly active against R. solanacearum and significantly inhibited its growth. The minimum bactericidal concentration and minimum inhibitory concentration values for PCA were 40 μg/mL and 20 μg/mL, respectively. Further investigation of the mechanism of action of PCA via transmission electron microscopy and biological assays indicated that the destruction of the cell structure, the shapes and the inhibition of biofilm formation were important. In addition, the application of PCA effectively reduced the incidence of bacterial wilt on tobacco under greenhouse conditions, and the control efficiency was as high as 92.01% at nine days after inoculation. Taken together, these findings suggest that PCA exhibits strong antibacterial activity against R. solanacearum and has the potential to be applied as an effective antibacterial agent for controlling bacterial wilt caused by R. solanacearum.

Coumarins are important plant-derived natural products with wide-ranging bioactivities and extensive applications. In this study, we evaluated for the first time the antibacterial activity and mechanisms of action of coumarins against the phytopathogen Ralstonia solanacearum, and investigated the effect of functional group substitution. We first tested the antibacterial activity of 18 plant-derived coumarins with different substitution patterns, and found that daphnetin, esculetin, xanthotol, and umbelliferone significantly inhibited the growth of R. solanacearum. Daphnetin showed the strongest antibacterial activity, followed by esculetin and umbelliferone, with MICs of 64, 192, and 256 mg/L, respectively, better than the archetypal coumarin with 384 mg/L. We further demonstrated that the hydroxylation of coumarins at the C-6, C-7 or C-8 position significantly enhanced the antibacterial activity against R. solanacearum. Transmission electron microscope (TEM) and fluorescence microscopy images showed that hydroxycoumarins may interact with the pathogen by mechanically destroying the cell membrane and inhibiting biofilm formation. The antibiofilm effect of hydroxycoumarins may relate to the repression of flagellar genes fliA and flhC. These physiological changes in R. solanacearum caused by hydroxycoumarins can provide information for integral pathogen control. The present findings demonstrated that hydroxycoumarins have superior antibacterial activity against the phytopathogen R. solanacearum, and thus have the potential to be applied for controlling plant bacterial wilt.

Insig-1 and Insig-2 are endoplasmic reticulum (ER) proteins that inhibit lipid synthesis by blocking transport of sterol regulatory element-binding proteins (SREBP-1 and SREBP-2) from ER to Golgi. In the Golgi, SREBPs are processed proteolytically to release their transcription-activating domains, which enhance the synthesis of fatty acids, triglycerides, and cholesterol. Heretofore, the two Insigs have redundant functions, and there is no rationale for two isoforms. The current data identify a specific function for Insig-2. We show that eicosapentaenoic acid (EPA), a polyunsaturated fatty acid, inhibits fatty acid synthesis in human fibroblasts and rat hepatocytes by activating adenylate cyclase, which induces protein kinase A (PKA) to phosphorylate serine-106 in Insig-2. Phosphorylated Insig-2 inhibits the proteolytic processing of SREBP-1, thereby blocking fatty acid synthesis. Phosphorylated Insig-2 does not block the processing of SREBP-2, which activates cholesterol synthesis. Insig-1 lacks serine-106 and is not phosphorylated at this site. EPA inhibition of SREBP-1 processing was reduced by the replacement of serine-106 in Insig-2 with alanine or by treatment with KT5720, a PKA inhibitor. Inhibition did not occur in mutant human fibroblasts that possess Insig-1 but lack Insig-2. These data provide an Insig-2- specific mechanism for the long-known inhibition of fatty acid synthesis by polyunsaturated fatty acids. [ABSTRACT FROM AUTHOR]

The differential absorption lidar (DIAL) has been proposed as an effective method for detecting ozone in the atmosphere. An important factor affecting its detecting precision is the asynchronous offset between backscattered signals at different wavelengths. Recently, a DIAL was built by our group, and the impact of the asynchronous offset was tested and studied. The simulation results show that the measurement error caused by the offset is negatively correlated with the altitude. Meanwhile, the offset has an additional effect in areas with sharp ozone concentration changes. Comparative experiments were carried out by our DIAL system and an airborne atmospheric monitoring system in the Nanjing test site. The results show that a 15 m offset in DIAL led to serious errors in retrieval results. These errors are inversely related to the detection altitude and reach up to 13 ppb, which is consistent with the results from simulations. After controlling the relative position of the backscattered signal to minimize the asynchronous offset, the maximum error was reduced to 2 ppb. Then the optimized DIAL was used for 48-hour continuous observation with a proven ozone analyzer. It shows that the optimized DIAL has high detecting accuracy and stability as point-fixed instruments. [ABSTRACT FROM AUTHOR]

Lipid synthesis is regulated by the actions of Scap, a polytopic membrane protein that binds cholesterol in membranes of the endoplasmic reticulum (ER). When ER cholesterol levels are low, Scap activates SREBPs, transcription factors that upregulate genes for synthesis of cholesterol, fatty acids, and triglycerides. When ER cholesterol levels rise, the sterol binds to Scap, triggering conformational changes that prevent activation of SREBPs and halting synthesis of lipids. To achieve a molecular understanding of how cholesterol regulates the Scap/SREBP machine and to identify therapeutics for dysregulated lipid metabolism, cholesterol-mimetic compounds that specifically bind and inhibit Scap are needed. To accomplish this goal, we focused on Anthrolysin O (ALO), a pore-forming bacterial toxin that binds cholesterol with a specificity and sensitivity that is uncannily similar to Scap. We reasoned that a small molecule that would bind and inhibit ALO might also inhibit Scap. High-throughput screening of a ~300,000-compound library for ALO-binding unearthed one molecule, termed UT-59, which binds to Scap's cholesterol-binding site. Upon binding, UT-59 triggers the same conformation changes in Scap as those induced by cholesterol and blocks activation of SREBPs and lipogenesis in cultured cells. UT-59 also inhibits SREBP activation in the mouse liver. Unlike five previously reported inhibitors of SREBP activation, UT-59 is the only one that acts specifically by binding to Scap's cholesterol-binding site. Our approach to identify specific Scap inhibitors such as UT-59 holds great promise in developing therapeutic leads for human diseases stemming from elevated SREBP activation, such as fatty liver and certain cancers. [ABSTRACT FROM AUTHOR]

Myostatin is a member of the TGF-β superfamily and functions as a negative regulator for skeletal muscle development and growth. It has become the most targeted gene in aquaculture that used for selective breeding. Previous studies involved in genome editing in several fish species confirmed that CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats) system was highly efficient with lower off-target effect, however, no reports were raised in Culter alburnus. In this study, we employed CRISPR/Cas9 gene editing system to successfully disrupt mstn gene by co-injection with Cas9 protein and the targeted sgRNA in C. alburnus. Various Indel mutations were obtained with 82% knockout efficiency in the F0 generation by PCR sequencing. In addition, mutations in mstn that induced by CRISPR/Cas9 were detected in the F1 generation by individually mating the wild-type female with the F0 generation of mstn-KO male at sexual maturity. More importantly, the body weight and length were significantly elevated in mstn ± group when compared to those of the control. As expected in mstn ± group, the expression level of mstn was sharply reduced, whereas a slight increase was observed in two growth-related genes (myod and myog). Moreover, higher numbers of muscle fibers were observed in mstn ± group, meaning that growth performance in mstn ± individuals might be represented by increasing the number of muscle fibers. Taken together, our current study successfully obtained a site-specific modification of mstn using CRISPR/Cas9 technology, and these results provided a new insight for facilitating topmouth culter genetic studies and breeding.

The mineralization process below the surface of the seafloor in a hydrothermal field has an important influence on the distribution and enrichment of elements. The Duanqiao hydrothermal field (DHF) is located on the new axial volcanic ridge of the ultraslow-spreading Southwest Indian Ridge. Owing to the limited surface sulfide samples, the metallogenic processes occurring below the seafloor surface such as the element enrichment mechanism and the temporal evolution of the sulfide deposits remain unclear. In this study, we conducted mineral texture, geochemical, 230Th/U dating, and laser ablation inductively coupled plasma mass spectrometer analyses of a drill core containing shallow sulfide deposits to study their evolution process. The results revealed that pyrite is enriched in Mn, Co, As, Mo, Ag, Cd, Sb, Tl, and Pb, chalcopyrite is characterized by high concentrations of Se, Sn, In, As, Ag and Pb, and sphalerite is enriched in Co, Ga, Ge, As, Ag, Cd, Sb, and Pb. The 230Th/U dating data suggested five different mineralization periods during 4,552–2,297 years. Apart from the top and bottom, the core exhibited obvious characteristics of gradual accumulation of mineralization. Results revealed that the variations in the elemental contents of different layers and different types of pyrite were controlled by the interaction of seawater and hydrothermal fluids within the sulfide mound over five different mineralization periods. Compared with other hydrothermal fields on other mid-ocean ridges, DHF pyrite is generally enriched in Zn, Pb, As, Ag, Cd, Mo, and Sb, which might reflect shallow subsurface mixing during different periods of hydrothermal activity.

The topmouth culter (Culter alburnus) is at the top of the food chain and plays an important role in the maintenance of freshwater ecosystem stability. It is also a commercially important aquaculture fish species in China. To establish conservation strategies and breeding programs, a total of 16 polymorphic microsatellite loci were isolated from transcriptome-derived sequences of C. alburnus. Characterization of these loci was assessed against 1 wild and 3 cultured populations in Huzhou, China. The number of alleles per locus ranged from 3 to 10 with an average of 5.25. A bottleneck effect was observed in all 4 populations; The ChangXing population showed moderate genetic differentiation when compared with other populations (FST values, 0.0695–0.0788). The microsatellite loci would be useful for further studies on population genetic diversity, genetic structure, and assessments of the artificial propagation release effect of C. alburnus.

Abstract An integration of 3D chromatin structure and gene expression at single-cell resolution has yet been demonstrated. Here, we develop a computational method, a multiomic data integration (MUDI) algorithm, which integrates scHi-C and scRNA-seq data to precisely define the 3D-regulated and biological-context dependent cell subpopulations or topologically integrated subpopulations (TISPs). We demonstrate its algorithmic utility on the publicly available and newly generated scHi-C and scRNA-seq data. We then test and apply MUDI in a breast cancer cell model system to demonstrate its biological-context dependent utility. We find the newly defined topologically conserved associating domain (CAD) is the characteristic single-cell 3D chromatin structure and better characterizes chromatin domains in single-cell resolution. We further identify 20 TISPs uniquely characterizing 3D-regulated breast cancer cellular states. We reveal two of TISPs are remarkably resemble to high cycling breast cancer persister cells and chromatin modifying enzymes might be functional regulators to drive the alteration of the 3D chromatin structures. Our comprehensive integration of scHi-C and scRNA-seq data in cancer cells at single-cell resolution provides mechanistic insights into 3D-regulated heterogeneity of developing drug-tolerant cancer cells.

Abstract Background China has made remarkable achievements in tuberculosis (TB) prevention and control, but it still takes long way to achieve the End TB goal especially in underdeveloped Southwest China. TB healthcare workers (HCWs) are core forces in TB prevention and control but often face job burnout. This study aimed to explore the burden and associated factors of job burnout among TB HCWs in Southwest China. Methods This cross-sectional study used both survey questionnaires and semi-structured interviews, to assess job burnout among TB HCWs based on Malasch Model and explore the associated factors based on Herzberg’s two-factor theory (different hygiene and motivation factors). Quantitative data analysis adopts multiple linear regression to in SPSS 22.0, and qualitative data were analyzed through a framework approach. Results A total of 1140 TB HCWs were included in questionnaire surveys. The overall job burnout rates of TB HCWs in Centers for Disease Control and Prevention (CDC), designated hospitals and Primary Health Care (PHC) sectors were 55%, 70.1% and 67.5%, respectively. TB HCWs in CDC who scored lower in interpersonal factors had a higher risk of depersonalization (DP) [B(95%CI): -0.89 (-1.71 to -0.80)]. TB HCWs in designated hospitals who scored lower in doctor-patient relationship factors [B (95%CI): 6.63 (-12.06 to -1.20)] were more likely to have emotional exhaustion (EE). TB HCWs who were less satisfied with training, supervision and assessment in PHC sectors [B(95%CI): 0.65 (0.03 to 1.26)] had less personal accomplishment (PA). Interviews with nine TB HCWs showed that poor environment could lead to high infection and heavy workload could lead to work pressure among TB HCWs in Chongqing. It is also found that performance assessment and management of TB HCWs, communication and cooperation and so on are related to job burnout. Conclusions TB HCWs had different levels of job burnout in CDC, designated hospitals, and PHC sectors of Chongqing, which were affected by different hygiene and motivation factors. Governments, organizations and individuals should take cooperative measures such as strengthening communication to deal with job burnout among TB HCWs.

Abstract Background Tuberculosis (TB) is a major cause of death worldwide, and Chinese TB burden ranked the second globally. Chinese primary healthcare (PHC) sectors implement the TB Control Program (TCP) to improve active case finding, referral, treatment adherence, and health education. This study aimed to identify barriers and enablers of TCP implementation in high TB burden regions of West China. Methods We conducted a representative study using mixed-methods in 28 counties or districts in Chongqing Municipality and Guizhou Province of West China from October 2021 to May 2022. Questionnaire surveys and semi-structured in-depth interviews were conducted with 2720 TB healthcare workers (HCWs) and 20 interviewees in PHC sectors. Descriptive statistical analysis was used to investigate TB HCWs’ characteristics, and path analysis model was utilized to analyze the impact of associated factors on TCP implementation. Thematic framework analysis was developed with the guide of the adapted Consolidated Framework for Implementation Research (CFIR) on factors of TCP implementation. Results This study found that 84.6% and 94.1% of community and village HCWs had low professional titles. Based on the results of multiple regression analysis and correlation analysis, lower TB core knowledge scores (-0.09) were identified as barriers for TCP implementation in community PHC sectors, and low working satisfaction (-0.17) and low working willingness (-0.10) are barriers for TPC implementation in village PHC sectors. The results of in-depth interviews reported barriers in all domains and enablers in four domains of CFIR. There were identified 19 CFIR constructs associated with TCP implementation, including 22 barriers such as HCWs’ heavy workload, and 12 enablers such as HCWs’ passion towards TCP planning. Conclusions With the guide of the CFIR framework, complex factors (barriers and enablers) of TCP implementation in PHC sectors of West China were explored, which provided important evidences to promote TB program in high TB burden regions. Further implementation studies to translate those factors into implementation strategies are urgent needed. Graphical Abstract

Abstract Background Conflicts, natural disasters, and complex emergencies present substantial health challenges to United Nations (UN) peacekeepers deployed in mission areas. This scoping review aims at summarizing previous research on the health of UN peacekeepers and identifies issues for further investigation. Methods Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for Scoping Reviews, we systematically searched Web of Science, PubMed, EMBASE, Scopus and China National Knowledge Infrastructure (CNKI) for English and Chinese literature published from April 1997 to November 2023. A data charting form was developed by two reviewers to extract relevant themes and provided narrative descriptions. Results We screened 1079 de-duplicated records and included 143 studies in this scoping review. There were 112 studies on the health status of UN peacekeepers, with more than half on mental health problems such as stress and anxiety. Many studies explored the health status of UN peacekeepers in African countries deployed from mainly U.S., Canada, U.K., China, Australia and Norway. There were 39 studies on the health risk factors of UN peacekeepers, including natural environmental, social environmental, psychological, behavioral lifestyle, biological factors and health service factors. There were 62 articles on the health protection of UN peacekeepers, mainly based on previous deployment experience, with a lack of theoretical guidance from global health perspectives. This scoping review found that health problems of UN peacekeepers are complicated, and whose impacts are cross-border. Social environmental factors were explored the most among health risk factors. Disease prevention measures, medical and health measures, and psychosocial measures were the main health protection for UN peacekeepers. Conclusions This scoping review highlighted that health problems of UN peacekeepers were typical global health issues with complicated and cross-border health risk factors. Therefore, comprehensive strategies could be taken from global health perspectives, including multi-phases (before-deployment, during-deployment, and post-deployment), multi-disciplines (public health, medicine, politics, health diplomacy, and others), and multi-levels (the UN, host countries, troop-contributing countries, the UN peacekeeping team, and UN peacekeepers).