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The necrotrophic fungus Rhizoctonia cerealis is the causal agent of devastating diseases of cereal crops including wheat (Triticum aestivum). We present a high-quality genome assembly of R. cerealis Rc207, a virulent strain causing wheat sharp eyespot. The assembly (56.36 Mb) is composed of 17.87% repeat sequences and 14,433 predicted protein-encoding genes. The Rc207 genome encodes a large and diverse set of genes involved in pathogenicity, especially rich in those encoding secreted proteins, carbohydrate-active enzymes (CAZymes), peptidases, nucleases, cytochrome P450, and secondary metabolism-associated enzymes. Most secretory protein-encoding genes, including CAZymes, peroxygenases, dehydrogenases, and cytochrome P450, were up-regulated during fungal infection of wheat. We identified 831 candidate secretory effectors and validated the functions of 10 up-regulated candidate effector proteins. Of them, nine were confirmed as necrotrophic pathogen’s effectors promoting fungal infection. Abundant potential mobile or plastic genomic regions rich in repeat sequences suggest their roles in fungal adaption and virulence-associated genomic evolution. This study provides valuable resources for further comparative and functional genomics on important fungal pathogens, and provides essential tools for development of effective disease control strategies.

In this study, univariate and Box-Behnken response surface experiments were used to optimize the polyphenol extraction process of Rhodiola rosea. Then, a α-glucosidase inhibition system was constructed in vitro to study the inhibition activity of Rhodiola rosea polyphenols. At the same time, the type of inhibition was judged by enzyme inhibition kinetics. The univariate and response surface results showed that the optimal extraction process conditions were: Ethanol concentration of 71%, feed-to-liquid ratio 1:40, ultrasonic power 320 W, ultrasonic temperature 55 °C. Under this condition, the yield of Rhodiola rosea polyphenol extraction could reach 11.45%. Rhodiola rosea polyphenols had certain inhibitory activities on α-glucosidase, and the inhibition ability was quantitatively effective. Half inhibition concentration (IC50) was 2.83 mg/mL, lower than the positive control acarbose (3.36 mg/mL of IC50). When Rhodiola rosea polyphenol concentration was 50 mg/mL, the inhibition rate could reach 97.86%. Enzyme inhibitory kinetic studies showed that Rhodiola rosea polyphenols were reversible hybrid inhibitory types of α-glucosidase. As the concentration of the inhibitor increased, the maximum reaction rate Vmax decreased and the Michael's constant Km increased, which belonged to the competitive and non-competitive mixed types. This optimization test was effective and feasible, and the extracted Rhodiola rosea polyphenols had good inhibitory activity against α-glucosidase in vitro.

Peroxisomes are single-membrane-bound organelles that play critical roles in eukaryotic cellular functions. Peroxisome quantity is a key factor influencing the homeostasis and pathogenic processes of pathogenic fungi. The aim of the present study was to investigate the underlying mechanisms of the reduction in number of peroxisomes in Fusarium graminearum consequent to FgPex4 and FgPex22-like deletion. The number of peroxisomes decreased by 40.55% and 39.70% when FgPex4 and FgPex22-like, respectively, were absent. Peroxisome biogenesis-related proteins, as well as inheritance- and division-related dynamin-like proteins were reduced at the transcriptional level in the mutant strains. In addition, the degree of pexophagy was intensified and the accumulation of ubiquitinated FgPex5 was also increased in F. graminearum when FgPex4 or FgPex22-like was absent. The findings suggest that FgPex4 and FgPex22-like influence the number of peroxisomes by influencing peroxisome biogenesis and pexophagy.

Tire–road characteristics are a critical focus of research in the automotive and transportation industries. On the one hand, the research can help optimize tires’ structural design; on the other hand, it can analyze the mechanical response of the pavement structure under the vehicle load. In addition, the non-uniformity distribution of the tire ground stress will also have a direct impact on the skid resistance, which determines the driving safety. Due to the limitation of testing technology, the measurement of tire ground pressure was mainly carried out on a flat test platform, ignoring the roughness of the actual pavement surface texture. The tire–road contact characteristics research on the macro-texture and micro-texture of asphalt pavement needs to be broken through. A high-precision pressure-sensitive film measurement system is utilized to examine the actual contact characteristics between two types of automobile tires and three types of asphalt pavement in this paper. The influence law of pavement texture and patterned tires on the contact area and stress was explored, and the concentration effect of tire–road contact stress was evaluated. The results indicate that the contact area of grounding tires exhibits a nearly linear relationship with tire inflation pressure and load. Notably, the change in load has a more significant influence on the contact area than tire inflation pressure. On asphalt pavement, the contact reduction rate decreases by approximately 5–10% for block pattern tires and 10–15% for longitudinal pattern tires. Furthermore, as the texture depth of the pavement increases, the contact area between tires and the pavement texture decreases. The actual tire–road interface experiences significant stress concentration due to the embedding and meshing effects between the tire and road surface. Even on a flat steel surface, the peak stress at the edge of the tread block exceeds the 0.7 MPa design load, which is about 2.5–3 times higher than the design uniform load. The peak stress between the tire and asphalt pavement reaches 4–10 times the design uniform load, with a rising trend as the pavement texture depth increases. This study can provide relevant experimental technical support for tire design and functional design of asphalt pavement.

Acrylamide exposure through environment pollution and diet is very common in daily life. With the deepening of the study on the toxicity of acrylamide, it has attracted widespread attention for the effects of acrylamide on multiple organs through affecting a variety of programmed cell death. Multiple studies have shown that acrylamide could exert its toxic effect by inducing programmed cell death, but its specific molecular mechanism is still unclear. In this review, the research on the main forms of programmed cell death (apoptosis, autophagy, and programmed necrosis) induced by acrylamide and their possible mechanisms are reviewed. This review may provide basic data for further research of acrylamide and prevention of its toxicity.

Members of the human epidermal growth factor receptor (HER) family, which includes HER1 (also known as EGFR), HER2, HER3 and HER4, have played a central role in regulating cell proliferation, survival, differentiation and migration. The overexpression of the HER family has been recognized as one of the most common cellular dysregulation associated with a wide variety of tumor types. Antibody-drug conjugates (ADCs) represent a new and promising class of anticancer therapeutics that combine the cancer specificity of antibodies with cytotoxicity of chemotherapeutic drugs. Two HER2-directed ADCs, trastuzumane-emtansine (T-DM1) and trastuzumab-deruxtecan (DS-8201a), have been approved for HER2-positive metastatic breast cancer by the U.S. Food and Drug Administration (FDA) in 2013 and 2019, respectively. A third HER2-directed ADC, disitamab vedotin (RC48), has been approved for locally advanced or metastatic gastric or gastroesophageal junction cancer by the NMPA (National Medical Products Administration) of China in 2021. A total of 11 ADCs that target HER family receptors (EGFR, HER2 or HER3) are currently under clinical trials. In this review article, we summarize the three approved ADCs (T-DM1, DS-8201a and RC48), together with the investigational EGFR-directed ADCs (ABT-414, MRG003 and M1231), HER2-directed ADCs (SYD985, ARX-788, A166, MRG002, ALT-P7, GQ1001 and SBT6050) and HER3-directed ADC (U3-1402). Lastly, we discuss the major challenges associated with the development of ADCs, and highlight the possible future directions to tackle these challenges.

Trichoderma atroviride, a soil fungus, has important applications in the biocontrol of plant diseases. Glycosyltransferases enhance the root colonization ability of Trichoderma spp. This study aimed to functionally characterize glycosyltransferase Taugt17b1 in T. atroviride. We investigated the effect of Taugt17b1 overexpression in T. atroviride H18-1-1 on its biocontrol properties, especially its ability to colonize roots. Our results demonstrated that the overexpression of the Taugt17b1 increases the T. atroviride colony growth rate, improves its root colonization ability, promotes the growth and activity of the defensive enzymatic system of plants, and prevents plant diseases. This study put forth a new role of T. atroviride glycosyltransferase and furthered the understanding of the mechanisms by which fungal biocontrol agents exert their effect.

Mangroves colonize the intertidal area of estuaries (e.g., Pichavaram, Payardia, and Mai Po) with remarkable cadmium (Cd) pollution. A study on the mechanism of mangrove plant response to Cd pollution can help to understand the adaptive characteristics of plants under Cd stress. This study explored the roles of peroxidase (PRX), pectate lyase (PL), and phytosulfokine (PSK) genes in cadmium tolerance of mangrove Avicennia marina. Full-length sequences of four genes (i.e., AmPRX1, AmPRX2, AmPL, and AmPSK) associated with metal tolerance were identified with suppression subtractive hybridization and rapid amplification of cDNA ends. These genes showed the characteristic features of the respective protein family, indicating functions similar to other plant proteins. Real-time quantitative PCR analysis demonstrated that cadmium exposure resulted in differences in expression patterns among the tissues. Our findings emphasize the complex regulatory mechanism of these four genes in response to trace metal pollution and reveal their functions in metabolic signaling during the stress response.

Peroxisomes are essential organelles that play important roles in a variety of biological processes in eukaryotic cells. To understand the synthesis of peroxisomes comprehensively, we identified the gene FgPEX22-like, encoding FgPEX22-like, a peroxin, in Fusarium graminearum. Our results showed that although FgPEX22-like was notably different from other peroxins (PEX) in Saccharomyces cerevisiae, it contained a predicted PEX4-binding site and interacted with FgPEX4 as a rivet protein of FgPEX4. To functionally characterize the roles of FgPEX22-like in F. graminearum, we performed homologous recombination to construct a deletion mutant (ΔPEX22-like). Analysis of the mutant showed that FgPEX22-like was essential for sexual and asexual reproduction, fatty acid utilization, pathogenicity, and production of the mycotoxin deoxynivalenol. Deletion of FgPEX22-like also led to increased production of lipid droplets and decreased elimination of reactive oxygen species. In addition, FgPEX22-like was required for the biogenesis of Woronin bodies. Taken together, our data demonstrate that FgPEX22-like is a peroxin in F. graminearum that interacts with PEX4 by anchoring PEX4 at the peroxisomal membrane and contributes to the peroxisome function in F. graminearum.

The soil-borne fungi Fusarium pseudograminearum and Rhizoctonia cerealis are the major pathogens for the economically important diseases Fusarium crown rot (FCR) and sharp eyespot of common wheat (Triticum aestivum), respectively. However, there has been no report on the broad resistance of wheat genes against both F. pseudograminearum and R. cerealis. In the current study, we identified TaWAK-6D, a wall-associated kinase (WAK) which is an encoding gene located on chromosome 6D, and demonstrated its broad resistance role in the wheat responses to both F. pseudograminearum and R. cerealis infection. TaWAK-6D transcript induction by F. pseudograminearum and R. cerealis was related to the resistance degree of wheat and the gene expression was significantly induced by exogenous pectin treatment. Silencing of TaWAK-6D compromised wheat resistance to F. pseudograminearum and R. cerealis, and repressed the expression of a serial of wheat defense-related genes. Ectopic expression of TaWAK-6D in Nicotiana benthamiana positively modulated the expression of several defense-related genes. TaWAK-6D protein was determined to localize to the plasma membrane in wheat and N. benthamiana. Collectively, the TaWAK-6D at the plasma membrane mediated the broad resistance responses to both F. pseudograminearum and R. cerealis in wheat at the seedling stage. This study, therefore, concludes that TaWAK-6D is a promising gene for improving wheat broad resistance to FCR and sharp eyespot.

Fusarium crown rot (FCR) of wheat, an important soil-borne disease, presents a worsening trend year by year, posing a significant threat to wheat production. Fusarium pseudograminearum cv. b was reported to be the dominant pathogen of FCR in China. Peroxisomes are single-membrane organelles in eukaryotes that are involved in many important biochemical metabolic processes, including fatty acid β-oxidation. PEX11 is important proteins in peroxisome proliferation, while less is known in the fungus F. pseudograminearum. The functions of FpPEX11a, FpPEX11b, and FpPEX11c in F. pseudograminearum were studied using reverse genetics, and the results showed that FpPEX11a and FpPEX11b are involved in the regulation of vegetative growth and asexual reproduction. After deleting FpPEX11a and FpPEX11b, cell wall integrity was impaired, cellular metabolism processes including active oxygen metabolism and fatty acid β-oxidation were significantly blocked, and the production ability of deoxynivalenol (DON) decreased. In addition, the deletion of genes of FpPEX11a and FpPEX11b revealed a strongly decreased expression level of peroxisome-proliferation-associated genes and DON-synthesis-related genes. However, deletion of FpPEX11c did not significantly affect these metabolic processes. Deletion of the three protein-coding genes resulted in reduced pathogenicity of F. pseudograminearum. In summary, FpPEX11a and FpPEX11b play crucial roles in the growth and development, asexual reproduction, pathogenicity, active oxygen accumulation, and fatty acid utilization in F. pseudograminearum.

Fusarium head blight (FHB) caused by Fusarium graminearum is a significant disease among cereal crops. In F. graminearum, biosynthesis of leucine, which is a branched chain amino acid, is achieved by converting α-isopropylmalate to β-isopropylmalate catalyzed by isopropylmalate isomerase encoded by LEU1. Considering the potential for targeting this pathway by fungicides, we characterized the gene FgLEU1 (FGSG-09589) in the Fusarium graminearum genome using bioinformatics methods. For functional characterization, we constructed a deletion mutant of FgLEU1 (ΔLEU1) through homologous recombination. Compared with the wild-type strain PH-1, ΔLEU1 showed slower colony growth and fewer aerial mycelia. Leucine addition was needed to ensure proper mutant growth. Further, ΔLEU1 showed decreased conidial production and germination rates, and could not produce ascospores. Moreover, ΔLEU1 showed complete loss of pathogenicity and reduced ability to produce deoxynivalenol (DON) and aurofusarin. Upstream and downstream genes of FgLEU1 were significantly upregulated in ΔLEU1. Contrary to previous reports, the deletion mutant was more resistant to osmotic stress and cell wall-damaging agents than the wild-type. Taken together, FgLEU1 plays a crucial role in leucine synthesis, aerial mycelial growth, sexual and asexual reproduction, pathogenicity, virulence, and pigmentation in Fusarium graminearum, indicating its potential as a target for novel antifungal agents.

Mitochondrial porin, the voltage-dependent anion-selective channel (VDAC), is the most abundant protein in the outer membrane, and is critical for the exchange of metabolites and phospholipids in yeast and mammals. However, the functions of porin in phytopathogenic fungi are not known. In this study, we characterized a yeast porin orthologue, Fgporin, in Fusarium graminearum. The deletion of Fgporin resulted in defects in hyphal growth, conidiation, and perithecia development. The Fgporin deletion mutant showed reduced virulence, deoxynivalenol production, and lipid droplet accumulation. In addition, the Fgporin deletion mutant exhibited morphological changes and the dysfunction of mitochondria, and also displayed impaired autophagy in the non-nitrogen medium compared to the wild type. Yeast two-hybrid and bimolecular fluorescence complementation assays indicated that Fgporin interacted with FgUps1/2, but not with FgMdm35. Taken together, these results suggest that Fgporin is involved in hyphal growth, asexual and sexual reproduction, virulence, and autophagy in F. graminearum.

The main purpose of influence maximization is to find a subset of key nodes that could maximize the spread of information under a certain diffusion model. In recent years, many studies have focused on the problem of influence maximization. However, these studies usually ignore the role of community structure which captures a significant effect on the process of influence propagation. To address above problem, we propose a novel hybrid algorithm PHG, which is a three-phase algorithm for influence maximization based on community structure. In our algorithm the influence propagation process is divided into three phases: 1) partition phase; 2) heuristic phase; and 3) greedy phase. Specifically, we first design an efficient algorithm CCSC that finds key nodes in each community to construct a candidate set by detecting community structure. Second, we find the most potential influence nodes from a candidate set by combing the influence weight of nodes and the community influence of nodes through the analysis of the community structure of the impact on nodes. Finally, we greedily select the nodes with maximization marginal gain from remaining a candidate set. The extensive experimental results on artificial and real-world social networks show that our algorithm obtains a better influence spread as well as an acceptable running time.

Iris localization is the most crucial part of the iris processing because its accuracy can directly affect the accuracy of biometric identification in subsequent steps. Yet, the quality of iris images may be sharply degraded due to interference from eyelashes and reflections during image acquisition, which can affect the localization accuracy adversely. To solve the problem, an iris localization algorithm based on effective area is proposed. First, YOLOv4 is used to crop the image to obtain the effective iris area, which is beneficial in improving the accuracy of subsequent localization. Furthermore, a method to remove reflective noise is proposed, which can effectively avoid the problem of noise interference in the process of inner boundary determination. Finally, aiming at the edge deviation caused by eyelashes, an outer boundary adjustment method is proposed. The experimental results show that the proposed method achieves good performance in the localization of iris images of both good quality and noise interference and outperforms other state-of-the-art methods.

The fungus F. pseudograminearum can cause the destructive disease Fusarium crown rot (FCR) of wheat, an important staple crop. Functional roles of FCR resistance genes in wheat are largely unknown. In the current research, we characterized the antifungal activity and positive-regulatory function of the cysteine-rich repeat receptor-like kinase TaCRK-7A in the defense against F. pseudograminearum in wheat. Antifungal assays showed that the purified TaCRK-7A protein inhibited the growth of F. pseudograminearum. TaCRK-7A transcript abundance was elevated after F. pseudograminearum attack and was positively related to FCR-resistance levels of wheat cultivars. Intriguingly, knocking down of TaCRK-7A transcript increased susceptibility of wheat to FCR and decreased transcript levels of defense-marker genes in wheat. Furthermore, the transcript abundances of TaCRK-7A and its modulated-defense genes were responsive to exogenous jasmonate treatment. Taken together, these results suggest that TaCRK-7A can directly inhibit F. pseudograminearum growth and mediates FCR-resistance by promoting the expression of wheat defense genes in the jasmonate pathway. Thus, TaCRK-7A is a potential gene resource in FCR-resistant wheat breeding program.

Fusarium graminearum is one of the causal agents of Fusarium head blight and produces the trichothecene mycotoxin, deoxynivalenol (DON). Thioredoxin reductases (TRRs) play critical roles in the recycling of oxidized thioredoxin. However, their functions are not well known in plant pathogenic fungi. In this study, we characterized a TRR orthologue FgTRR in F. graminearum. The FgTRR-GFP fusion protein localized to the cytoplasm. FgTRR gene deletion demonstrated that FgTRR is involved in hyphal growth, conidiation, sexual reproduction, DON production, and virulence. The ΔTRR mutants also exhibited a defect in pigmentation, the expression level of aurofusarin biosynthesis-related genes was significantly decreased in the FgTRR mutant. Furthermore, the ΔTRR mutants were more sensitive to oxidative stress and aggravated apoptosis-like cell death compared with the wild type strain. Taken together, these results indicate that FgTRR is important in development and pathogenicity in F. graminearum.

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The development of human erythroid cells has been mostly examined in models of adult hematopoiesis, while their early derivation during embryonic and fetal stages is largely unknown. We observed the development and maturation of erythroblasts derived from human pluripotent stem cells (hPSCs) by an efficient co-culture system. These hPSC-derived early erythroblasts initially showed definitive characteristics with a glycophorin A+ (GPA+) CD34lowCD36− phenotype and were distinct from adult CD34+ cell-derived ones. After losing CD34 expression, early GPA+CD36− erythroblasts matured into GPA+CD36low/+ stage as the latter expressed higher levels of β-globin along with a gradual loss of mesodermal and endothelial properties, and terminally suppressed CD36. We establish a unique in vitro model to trace the early development of hPSC-derived erythroblasts by serial expression of CD34, GPA, and CD36. Our findings may provide insight into the understanding of human early erythropoiesis and, ultimately, therapeutic potential.

The domain of unknown function 26 (DUF26), harboring a conserved cysteine-rich motif (C-X8-C-X2-C), is unique to land plants. Several cysteine-rich repeat proteins (CRRs), belonging to DUF26-containing proteins, have been implicated in the defense against fungal pathogens in ginkgo, cotton, and maize. However, little is known about the functional roles of CRRs in the important staple crop wheat (Triticum aestivum). In this study, we identified a wheat CRR-encoding gene TaCRR1 through transcriptomic analysis, and dissected the defense role of TaCRR1 against the soil-borne fungi Rhizoctonia cerealis and Bipolaris sorokiniana, causal pathogens of destructive wheat diseases. TaCRR1 transcription was up-regulated in wheat towards B. Sorokiniana or R. cerealis infection. The deduced TaCRR1 protein contained a signal peptide and two DUF26 domains. Heterologously-expressed TaCRR1 protein markedly inhibited the mycelia growth of B. sorokiniana and R. cerealis. Furthermore, the silencing of TaCRR1 both impaired host resistance to B. sorokiniana and R. cerealis and repressed the expression of several pathogenesis-related genes in wheat. These results suggest that the TaCRR1 positively participated in wheat defense against both B. sorokiniana and R. cerealis through its antifungal activity and modulating expression of pathogenesis-related genes. Thus, TaCRR1 is a candidate gene for improving wheat resistance to B. sorokiniana and R. cerealis.

Rhizoctonia cerealis is the causal pathogen of the devastating disease, sharp eyespot, of the important crop wheat (Triticum aestivum L.). In phytopathogenic fungi, several M36 metalloproteases have been implicated in virulence, but pathogenesis roles of M35 family metalloproteases are largely unknown. Here, we identified four M35 family metalloproteases from R. cerealis genome, designated RcMEP2–RcMEP5, measured their transcriptional profiles, and investigated RcMEP2 function. RcMEP2-RcMEP5 are predicted as secreted metalloproteases since each protein sequence contains a signal peptide and an M35 domain that includes two characteristic motifs HEXXE and GTXDXXYG. Transcription levels of RcMEP2-RcMEP5 markedly elevated during the fungus infection to wheat, among which RcMEP2 expressed with the highest level. Functional dissection indicated that RcMEP2 and its M35 domain could trigger H2O2 rapidly-excessive accumulation, induce cell death, and inhibit expression of host chitinases. This consequently enhanced the susceptibility of wheat to R. cerealis and the predicated signal peptide of RcMEP2 functions required for secretion and cell death-induction. These results demonstrate that RcMEP2 is a virulence factor and that its M35 domain and signal peptide are necessary for the virulence role of RcMEP2. This study facilitates a better understanding of the pathogenesis mechanism of metalloproteases in phytopathogens including R. cerealis.

Cu-15%Co alloys have been synthesized by an induction furnace adopting electromagnetic stirring (EMS). The liquid-liquid separation behavior and the peritectic reaction under a forced melt flow were analyzed. The specimens were subjected to a conventional induction melting as well as enhanced melt stirring by a two-side electromagnetic stirrer. The stirred ingots showed a significant improvement in dispersivity and homogeneity of the Co-rich phase. Comparing the specimens subjected to different current intensities, we observed strong changes in the phase fraction, the degree of segregation, and the grain size. EMS had an effect of reducing the amount and size of Co-rich droplets and enhancing the amounts of small equiaxed dendrites and dendrite fragments, which led to a more dispersive distribution of α-Co phase and refined the grains of Cu-rich phase. We observed a considerable increase in the fraction of peritectic Cu-rich phase with increasing current intensity of EMS, indicating that the peritectic reaction was promoted by EMS. EMS also reduced the macrosegregation of Co-rich phase in both the vertical and radial direction of the ingot when the current intensity was appropriate.

Abstract Background SQ109 is a promising candidate drug for the treatment of patients with drug-resistant tuberculosis (DR-TB). The purpose of this study was to investigate the activity of SQ109 against clinical isolates of Mycobacterium tuberculosis (MTB) from patients with multidrug-resistant TB (MDR-TB) and pre-extensively drug-resistant TB (pre-XDR-TB), and to explore new drug-resistant mechanisms of SQ109. Methods We evaluated the in vitro activity of SQ109 against clinical isolates from patients with MDR-TB and pre-XDR-TB using minimal inhibitory concentration (MIC) assay. The drug-resistant gene, mmpL3 of SQ109-resistant strains was sequenced, and a quantitative real-time PCR assay was used to analyze 28 efflux pump genes in SQ109-resistant strains without mmpL3 mutations. The role of candidate efflux pumps mmpL5 and mmpL7 on the MIC of SQ109 was evaluated using recombinantly cloned MmpL5 and MmpL7 expressed in Mycobacterium smegmatis. Results The MIC90, MIC95 and MIC99 values of SQ109 for 225 clinical isolates of MTB were 0.25 mg/L, 0.5 mg/L and 1.0 mg/L, respectively. Among the pre-XDR strains, six showed resistance to SQ109 despite the absence of gene mutations in mmpL3. In six resistant pre-XDR strains, the MIC of SQ109 decreased with the use of an efflux pump inhibitor, and there was significant upregulation of mmpL5 and mmpL7 in two strains after exposure to SQ109. The presence of MmpL7 in Mycobacterium smegmatis resulted in decreased susceptibility to SQ109, with the MIC increasing from 16 mg/L to 32 mg/L. Conclusions Our data demonstrated that SQ109 exhibited excellent levels of in vitro activity against MTB. MmpL7 may be a potential gene for MTB resistance to SQ109, providing a useful target for detecting SQ109 resistance in MTB.

Abstract As robots are increasingly participating in our daily lives, the quests to mimic human abilities have driven the advancements of robotic multimodal senses. However, current perceptual technologies still unsatisfied robotic needs for home tasks/environments, particularly facing great challenges in multisensory integration and fusion, rapid response capability, and highly sensitive perception. Here, we report a flexible tactile sensor utilizing thin-film thermistors to implement multimodal perceptions of pressure, temperature, matter thermal property, texture, and slippage. Notably, the tactile sensor is endowed with an ultrasensitive (0.05 mm/s) and ultrafast (4 ms) slip sensing that is indispensable for dexterous and reliable grasping control to avoid crushing fragile objects or dropping slippery objects. We further propose and develop a robotic tactile-visual fusion architecture that seamlessly encompasses multimodal sensations from the bottom level to robotic decision-making at the top level. A series of intelligent grasping strategies with rapid slip feedback control and a tactile-visual fusion recognition strategy ensure dexterous robotic grasping and accurate recognition of daily objects, handling various challenging tasks, for instance grabbing a paper cup containing liquid. Furthermore, we showcase a robotic desktop-cleaning task, the robot autonomously accomplishes multi-item sorting and cleaning desktop, demonstrating its promising potential for smart housekeeping.

Abstract Background A long-term follow-up of close contacts to monitor their infection status is essential to formulate a promising screening strategy. The study aimed to assess the dynamics of tuberculosis (TB) infection using Interferon-γ release assay (IGRA) and determine risk factors associated with TB infection. Methods Definite TB patients were interviewed and their household contacts were screened for TB infection by IGRA during 12-month longitudinal investigation. Results We included in our analyses 184 household contacts of 92 index TB patients. 87 individuals (47.3%) in contact group progressed to TB infection, of whom 86 developed into IGRA positive within 24 weeks. Close contacts with a higher age and comorbidities are easier to exhibit TB infection. Analysis showed that risk factors for becoming IGRA-positive individuals included residence, older age, comorbidities, BCG scar and high bacterial load. Contacts with BCG scar had a lower IGRA-positive rate. Conclusion IGRA conversion generally occurs within 24 weeks after exposure. The TB transmission happens since subclinical TB stage and the presence of BCG scar is an independent protective factor reducing risk of TB infection among close contacts. Repeated IGRA tests are sensible to conducted among close contacts at 24 weeks after exposure to identify the IGRA-positive individuals.

Depression is a psychological disorder associated with prolonged stress, which involves abnormal activation of the hypothalamic-pituitary-adrenal (HPA) axis, leading to elevated levels of glucocorticoids (GC). Excessive GC can cause damage to the structure and function of the hippocampus, thereby triggering depressive symptoms. Studies suggest that the bile acid receptor farnesoid X receptor (FXR) may play a role in adrenal GC synthesis. This study aimed to explore the potential therapeutic effects of dried bear bile (DBB) on depression and its mechanism. We used the chronic unpredictable mild stress (CUMS) mouse model and FXR agonist GW4064 stimulated mice, as well as H295R human adrenal cortical carcinoma cells, employing behavioral tests, biochemical analysis, and gene expression analysis to assess the effects of DBB treatment on depressive behavior, serum corticosterone (CORT) levels, and adrenal FXR and steroid biosynthesis-related gene expression. The results showed that in both CUMS and GW4064-stimulated mice, DBB treatment significantly improved depressive-like behaviors and reversed serum CORT levels. Additionally, DBB suppressed the expression of steroidogenic regulatory genes in the adrenal glands of CUMS mice. In H295R cells, DBB treatment effectively reduced cortisol secretion induced by Forskolin, inhibited the expression of steroid biosynthesis-related genes, and suppressed cortisol production and HSD3B2 expression under conditions of FXR overexpression and FXR activation. Our findings suggest that DBB regulates adrenal FXR to modulate glucocorticoid synthesis and exerts antidepressant effects. DBB may serve as a potential therapeutic agent for depression by regulating GC levels and steroidogenesis pathway. Further research is underway to test the antidepressant effects of each DBB component to understand their specific contribution.

Pedestrian safety evacuation in aircraft cabins has been a challenging problem because of the aircraft's unique characteristics, such as the diversity of passengers and the restricted evacuation environment. It is difficult to reproduce evacuation activities in aircraft cabin due to safety concerns and cost constraints. To fill this gap, an improved cellular automaton model of crowd evacuation for aircraft cabin is established by incorporating the characteristics of cabin space structures and passenger attributes. Passengers are divided into healthy individual passengers and disabled-healthy group passengers, whose movement mechanisms are quantified. Based on the constructed model, simulation experiments are conducted using the configuration cabin layout of B737-800 as an example. The results show that the evacuation time is prolonged with increased passenger density and the number of disabled passengers. Moreover, the overall evacuation time is insignificantly affected by whether disabled-healthy group passengers' seats are close to the aisle or window, and the evacuation efficiency is best when their seats are evenly distributed in the cabin. The evacuation time is the shortest when all cabin doors are open, and pedestrians are evacuated the slowest when the central emergency doors are closed. This study provides valuable insights into effective strategies for pedestrian evacuation and crowd emergency management of civil aircraft.