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IntroductionMycobacterium tuberculosis (Mtb), the main cause of tuberculosis (TB), has brought a great burden to the world's public health. With the widespread use of Mtb drug-resistant strains, the pressure on anti-TB treatment is increasing. Anti-TB drugs with novel structures and targets are urgently needed. Previous studies have revealed a series of CYPs with important roles in the survival and metabolism of Mtb. However, there is little research on the structure and function of CYP138.MethodsIn our study, to discover the function and targetability of CYP138, a cyp138-knockout strain was built, and the function of CYP138 was speculated by the comparison between cyp138-knockout and wild-type strains through growth curves, growth status under different carbon sources, infection curves, SEM, MIC tests, quantitative proteomics, and lipidomics.Results and discussionThe knockout of cyp138 was proven to affect the Mtb's macrophage infection, antibiotics susceptibility, and the levels of fatty acid metabolism, membrane-related proteins, and lipids such as triacylglycerol. We proposed that CYP138 plays an important role in the synthesis and decomposition of lipids related to the cell membrane structure as a new potential anti-tuberculosis drug target.

Abstract Snowmelt floods are highly hazardous meteorological disasters that can potentially threaten human lives and property. Hence, snowmelt susceptibility mapping (SSM) plays an important role in flood prevention systems and aids emergency responders and flood risk managers. In this paper, a method of identifying snowmelt flood hazards is proposed, and a large‐scale snowmelt flood hazard zonation scheme based on historical recordings and multisource remote sensing data is established. To assess the quality of our approach, the proposed model was tested in the cold and arid region of Xinjiang, China. Overall, 140 historical snowmelt flood events and 27 explanatory factors were selected to construct a geospatial dataset for SSM of the contemporary period. GridSearchCV was used to comprehensively search the candidate parameters from the grid of given parameters obtained with the random forest (RF) algorithm. Then, the geospatial dataset was divided into two subsets: 70% for training and 30% for testing. Next, SSM results were obtained with the RF algorithm using optimized parameters. The results indicate that our optimized RF classifier performs well for the task of SSM, with a high AUC value (0.975) for the test dataset. The validation and analysis suggest that the proposed method can efficiently identify snowmelt flood hazards in undersampled arid areas at a regional scale.

In space-based gravitational wave detection, gravitational wave signals are detected by measuring the Doppler frequency shift of laser exchange between three satellites. Although the laser is pre-stabilized, the laser phase noise is significantly higher than the gravitational wave signal, approximately 7–8 orders of magnitude higher. To reduce the otherwise-overwhelming laser phase noise, the time delay interferometry (TDI) technique is employed by properly time-shifting and linearly combining raw data. Different TDI combinations have various abilities in suppressing laser phase noise, and the response function of gravitational wave signal as well as the power spectral density of noise floor (including test mass acceleration noise and optical path noise) are also different. In this work, we present a unique class of TDI combinations, denoted as [ZX]116,[ZX]216,[ZX]316,[ZX]416, and [ZX]516, which exhibit a distinct geometric space–time diagrams composed of Michelson interferometers as the fundamental constituents. Specifically, when the detector arm lengths are assumed to be equal, these combinations yield response functions and noise power spectral densities of zero. To evaluate the detection performance of these combinations, we investigate their response functions and noise power spectral densities when the detector arm lengths are unequal, and furthermore, derive the analytical expressions for their sensitivity functions. Through our analysis, we have discovered some intriguing results. When the detector arm lengths are unequal, both the response functions and noise spectral densities of these combinations are correlated with the difference in arm lengths L3−L2. However, the sensitivity functions of these TDI combinations remain unaffected by the specific values of the arm length difference, and are consistent with the sensitivity functions of widely-used TDI combinations. For instance, the sensitivity function of [ZX]116 combination is the same as that of the Michelson combination, while the sensitivity functions of [ZX]216 and [ZX]416 combinations match with that of the Sagnac combination. Furthermore, the [ZX]316 and [ZX]516 combinations share the same sensitivity function as the fully symmetric Sagnac combination, enabling the identification of instrument noise and stochastic gravitational wave backgrounds. The discovery of this class of combinations provides support for the diversity of data processing.

ABSTRACT Sudapyridine (WX-081) is a structural analog of bedaquiline (BDQ), which shows anti-tuberculosis and non-tuberculous mycobacteria (NTM) activities but, unlike BDQ, did not prolong QT interval in animal model studies. This study evaluated the antibacterial activity of this novel compound against Mycobacterium avium, Mycobacterium abscessus, and Mycobacterium chelonae in vitro and in vivo. The minimum inhibitory concentration (MIC) of WX-081 against three kinds of non-tuberculous mycobacteria (NTM) clinical strains was determined using microplate-based alamarBlue assay (MABA), and the antibacterial activity of WX-081 against NTM in J774A.1 cells and mice was evaluated. MIC ranges of WX-081 against clinical strains of M. avium and M. abscessus were 0.05–0.94 μg/mL, 0.88–7.22 μg/mL (M. abscessus subsp. abscessus), and 0.22–8.67 μg/mL (M. abscessus subsp. massiliense), respectively, which were slightly higher than those of BDQ. For M. avium, M. abscessus, and M. chelonae, WX-081 can reduce the intracellular bacterial load by 0.13–1.18, 0.18–1.50, and 0.17–1.03 log10 colony forming units (CFU)/mL, respectively, in a concentration-dependent manner. WX-081 has bactericidal activity against three NTM species in mice. WX-081 exhibited anti-NTM activity to the same extent as BDQ both in vivo and in vitro. WX-081 is a promising clinical candidate and should be studied further in clinical trials.IMPORTANCEDue to the rapidly increased cases globally, non-tuberculous mycobacteria (NTM) disease has become a significant public health problem. NTM accounted for 11.57% of all mycobacterial isolates in China, with a high detection rate of Mycobacterium abscessus, Mycobacterium avium, and Mycobacterium chelonae during 2000–2019. Treatment of NTM infection is often challenging, as natural resistance to most antibiotics is quite common among different NTM species. Hence, identifying highly active anti-NTM agents is a priority for potent regimen establishment. The pursuit of new drugs to treat multidrug-resistant tuberculosis may also identify some agents with strong activity against NTM. Sudapyridine (WX-081) is a structural analog of bedaquiline (BDQ), which was developed to retain the anti-tuberculosis efficacy but eliminates the severe side effects of BDQ. This study initially evaluated the antimicrobial activity of this novel compound against M. avium, M. abscessus, and M. chelonae in vitro, in macrophages and mice, respectively.

This study explored solid-state additive friction stir deposition (AFSD) as a modular manufacturing technology, with the aim of enabling a more rapid and streamlined on-site fabrication process for large meter-scale nuclear structural components with fully dense parts. Austenitic 316 stainless steel (SS) is an excellent candidate to demonstrate AFSD, as it is a commonly-used structural material for nuclear applications. The microstructural evolution and concomitant changes in mechanical properties after 5 MeV Fe++ ion irradiation were studied comprehensively via transmission electron microscopy and nanoindentation. AFSD-processed 316 SS led to a fine-grained and ultrafine-grained microstructure that resulted in a simultaneous increase in strength, ductility, toughness, irradiation resistance, and corrosion resistance. The AFSD samples did not exhibit voids even at 100 dpa dose at 600 °C. The enhanced radiation tolerance as compared to conventional SS was reasoned to be due to the high density of grain boundaries that act as irradiation-induced defect sinks.

Many traditional Chinese medicines (TCMs) have been confirmed to have antibacterial activities. However, very few substances have been found to be active against Gram-negative bacteria. This study aimed to identify antimicrobial activity substances against Gram-negative bacteria from fourteen TCMs. Fourteen TCMs with antibacterial potential were chosen for quantitative extraction and antibacterial activity assay, and the plant with the highest activity against Escherichia coli was selected to construct the component-target network. The following virtual screening and enzyme inhibition experiments were performed to analyse the antibacterial mechanisms of the compounds from Galla chinensis. The chemical constituents of Galla chinensis were identified by chemical fingerprinting. 1, 2, 3, 4, 6-Penta-O-galloyl-β-D-glucose (PGG) from Galla chinensis exhibited significant inhibition activity against adenylyl transferase (ATase) of E. coli and antibacterial activity against E. coli. Meanwhile, PGG was identified in the Galla chinensis ethanol extract as the abundant ingredient with a high content of 1.95% (w/w). PGG enriched in Galla chinensis is a promising natural antibiotic with the mode of action inhibiting ATase activity. To our knowledge, this is the first study attributing the antibacterial activity of PGG to its affinity with ATase.

Background and aimMild hypothermia in hepatic ischemia-reperfusion injury is increasingly being studied. This study aimed to conduct a systematic evaluation of the effectiveness of mild hypothermia in improving hepatic ischemia-reperfusion injury.MethodsWe systematically searched CNKI, WanFang Data, PubMed, Embase, and Web of Science for original studies that used animal experiments to determine how mild hypothermia(32-34°C) pretreatment improves hepatic ischemia-reperfusion injury(in situ 70% liver IR model). The search period ranged from the inception of the databases to May 5, 2023. Two researchers independently filtered the literature, extracted the data, and assessed the risk of bias incorporated into the study. The meta-analysis was performed using RevMan 5.4.1 and Stata 15 software.ResultsEight randomized controlled trials (RCTs) involving a total of 117 rats/mice were included. The results showed that the ALT levels in the mild hypothermia pretreatment group were significantly lower than those in the normothermic control group [Standardized Mean Difference (SMD) = -5.94, 95% CI(-8.09, -3.78), PConclusionMild hypothermia can attenuate hepatic ischemia-reperfusion injury, effectively reduce oxidative stress and inflammatory response, prevent hepatocyte apoptosis, and protect liver function.

A large number of red cultural sites preserved in the Chinese countryside, as well as the red spirit are combined with cultural tourism, and the red cultural tourism industry comes into being. This paper takes the service personnel of the rural red cultural tourism industry in County M as the research object, designs the relevant questionnaire, conducts the reliability test, and then obtains the relevant data of rural revitalization and rural red cultural tourism industry chain through the questionnaire survey method. Then, using the industrial environment and policies of the rural red cultural tourism industry chain as the independent variables and rural revitalization as the dependent variable, a round-off multiple regression analysis was carried out to explore the interrelationship between the two. The results show that rural revitalization = 1.374+0.086*tourism projects + 0.147*infrastructure + 0.169*tourism market + 0.177*tourist distribution = 1.074+0.246*history and culture + 0.259*red culture + 0.214*government policies + 0.268*funding inputs. This paper assists Chinese villages in improving the red cultural tourism industry chain and promoting rural revitalization by developing the red cultural tourism industry chain.

"Flow experience" is a term used to describe the state of being fully immersed in what you are doing. The Flow State Scale (FSS-2) was developed to assess how people feel when they are in the flow state while participating in certain sports activities. The goal of this study was to obtain a short adapted version of the FSS-2 for the Brazilian-Portuguese language and for general activities (FSS-BR-S). To do this, we translated it both ways (forwards and backwards) and verified that the translation was accurate. Methods: After getting answers from 396 Brazilian participants, we performed (1) the construct validity of the FSS-BR-S and (2) the psychometric item quality analysis. The confirmatory factorial analysis shows that a FSS-BR-S factorial model is the best fit for the data (χ2 = 44.36, p = .023, df = 27, χ2/df = 1.64, CFI = 0.99, TLI = 0.98, and RMSEA = 0.04). Reliability tests done in this structure show that the FSS-BR-S (which only has nine items) has good internal consistency. The item quality analysis reveals that its difficulty and differentiating parameters are good for estimating the overall flow state. The test information curve for the short version demonstrates that it is very useful for estimating the flow states of each disposition. Discussion and Conclusions: Based on these findings, we can conclude that the FSS-BR-S has demonstrated sufficient validity to be used with Brazilians.

Aim. To investigate the specific expression profile, clinicopathological significance and mechanism of Zic family member 2 (ZIC2) in oral cancer were unclear. Patients and Methods. We explored the expression pattern and clinicopathological significance of ZIC2 in oral cancer through performing in-house tissue microarray and integrated analysis global RNA-seq and microarrays containing large samples. The molecular basis of ZIC2 in oral cancer was further investigated in the aspects of transcription network and immune correlations. We also performed in vitro experiments and calculated drug sensitivity of oral cancer with different ZIC2 expression levels in response to hundreds of compounds. Results. All data unanimously proved the significant overexpression of ZIC2 in oral cancer. The upregulation of ZIC2 was remarkably associated with the malignant clinical progression of oral cancer. ZIC2 was predicted to be targeted by miRNAs such as miR-3140, miR-4999, and miR-1322. The infiltration level of CD8+ T and central memory cells was positively related to the overexpression of ZIC2. Oral cancer patients with higher ZIC2 expression showed higher drug sensitivity to two compounds including AZD8186 and ERK_2240. Conclusions. We demonstrated the upregulation of ZIC2 in oral cancer and its promoting effect on the clinical advancement of oral cancer. The potential clinical value of ZIC2 in oral cancer deserves attention.

This paper aims to provide a communication service path without experience certificate for Yao costume patterns, and expounds on the relationship between the dissemination of intangible cultural heritage and the value of the cultural creative industry. Based on analyzing the classification of Yao costume patterns in Guangxi and the relationship between the spread of intangible cultural heritage and economic development, this paper uses the analytic hierarchy process and user research method to determine the first and second indexes of users' demand for Yao costume patterns in Guangxi and calculates the weights of each level of indexes. At the same time, it puts forward the closed-loop industrial measures for inheriting and promoting Yao traditional decoration and analyzes the game and value between traditional decoration intangible cultural heritage culture, and cultural creative industry. The following conclusions are drawn: a balance should be maintained between cultural inheritance and economic development; The government and all sectors of society should work together to protect and promote cultural diversity and cultural innovation, and at the same time give full play to the economic value of cultural industry to achieve a win-win situation between culture and economy. The construction of the value system of intangible cultural heritage should be emphasized so that it can play a more important role in the process of modernization.

With the continuous development of computer technology, the teaching of ancient Chinese has realized a quantitative and statistical research path for a large-scale corpus. In this paper, based on a multidimensional analysis model, six disciplines in the humanities domain (Chinese literature, history, philosophy) and social sciences domain (economics, sociology, law) of ancient Chinese were selected as dimensions, and 111 linguistic features of ancient Chinese in the corpus were factor analyzed. Multivariate ANOVA and post hoc tests were conducted on the discourse dimension scores of different disciplinary domains, and qualitative analyses were conducted in conjunction with the linguistic features in the specific corpus to further verify the linguistic domain coefficient of variation of ancient Chinese. The results of the study show that the results of the Levenes test for homogeneity of variance in the teaching of ancient Chinese in a single dimension are all p < 0.0001, while there are highly significant differences between the historical and philosophical domain features in the humanities (p = 0.001 ≤ 0.01), and extremely significant differences with the other four disciplines. The results of the multidimensional expression form of ancient Chinese teaching based on the multidimensional analysis method proposed in this paper effectively advance the advancement of ancient Chinese teaching and enable students to learn Chinese culture from other dimensions while learning ancient Chinese.

BackgroundCigarette smoking and particulate matter (PM) with aerodynamic diameter Q3, corresponding to PM2.5 ≤ 27.137, 27.137 38.205 μg/m3.ResultsThe prevalence of MS was significantly different according to PM2.5 exposure (p-value = 0.0280) and cigarette smoking (p-value 38.205 μg/m3, respectively. The risk of MS was significantly higher among former and current smokers with OR; 95% CI = 1.062; 1.008–1.118 and 1.531; 1.450–1.616, respectively, and a dose-dependent p-value 38.205 μg/m3, respectively. According to PM2.5 quartiles, current smokers had a higher risk of MS, regardless of PM2.5 levels (OR); 95% CI = 1.605; 1.444–1.785, 1.561; 1.409–1.728, 1.359; 1.211–1.524, and 1.585; 1.418–1.772 for PM2.5 ≤ 27.137, 27.137 38.205 μg/m3, respectively. After combining both exposures, the group, current smokers; PM2.5 > 38.205 μg/m3 had the highest odds (1.801; 95% CI =1.625–1.995).ConclusionPM2.5 and cigarette smoking were independently and jointly associated with a higher risk of MS. Stratified analyses revealed that cigarette smoking might have a much higher effect on MS than PM2.5. Nonetheless, exposure to both PM2.5 and cigarette smoking could compound the risk of MS.

Phthalates (PEs) are widely used plasticizers in polymer products, and humans are increasingly exposed to them. This study was designed to investigate the alleviative effect of phytochemicals quercetin (Que) against male reproductive toxicity caused by the mixture of three commonly used PEs (MPEs), and further to explore the underlying mechanism. Forty-eight male SD rats were randomly and evenly divided into control group, Que group, MPEs group and MPEs+Que group (n = 12); The oral exposure doses of MPEs and Que were 450 mg/kg/d and 50 mg/kg/d, respectively. After 91 days of continuous intervention, compared with control group, the testes weight, epididymis weight, serum sex hormones, and anogenital distance were significantly decreased in MPEs group (P

Background: Inflammatory bowel diseases (IBD), such as severe colitis, are associated with the development of lung inflammation and tissue damage. Pueraria lobata (P. lobata) plays an essential role in controlling cytokines. However, the exact mechanism of the inflammation response is still unknown. Purpose: To investigate the effects of the P. lobata-derived exosomes-like nanovesicles (PLDENs) on colitis and their role in the lung inflammatory response. Methods: In this study, we investigated the effects of PLDENs on the dextran sulfate sodium (DSS)-induced colitis and explored the mechanisms by forming the gut-lung axis. PLDENs were characterized by mass spectrometry-based proteomic analysis. Results: The results showed that PLDENs had significant preventive effects in DSS-induced colitis and pathological changes in colons in a dose-dependent manner. Simultaneously, the treatment of PLDENs could effectively reduce inflammatory changes in the lung. PLDENs could selectively regulate the composition of gut microbiota. Conclusion: These data suggested that the treatment of PLDENs could ‘attenuate DSS-induced colitis and lung inflammation, providing an efficacious supplement for reducing co-morbidities in IBD patients.

A multifunctional terahertz (THz) device with frequency tunability, amplitude modulation and spectral filtering abilities, and substrate flexibility is highly desired for various applications, such as THz communication, sensing, wearable optoelectronics. Therefore, this study proposed a 3D artificial material based on a flexible polyethylene terephthalate (PET) woven-wire mesh with conductive coating surfaces. This material was conceptually demonstrated in experiments as a dual-functional THz device. In addition, the transmission properties of this artificial material were experimentally and numerically explored with reasonable agreement. Then, the underlying mechanism of the spectral characteristics was qualitatively elucidated. The amplitudes and frequencies of the spectral characteristics were successfully validated to be passively manipulated by tailoring the structural parameters of a unit cell and changing the surface conductivities of a device. This process opened the application feasibility of a frequency tunable bandpass filter and a power switch at the THz regime. For the bandpass filter application, the tri-frequency modulation capability was experimentally demonstrated, and a frequency tuning bandwidth of 0.249 THz was achieved by varying the conductivity of the device’s surface-coating layer from 0.44 to 77 MS/m. For the power switch application, the largest modulation depth between the on and off states of a device was successfully demonstrated at approximately 21.3 dB at 0.271 THz. This dual-function THz device has the advantages of compactness, low cost, and easy fabrication, thus providing an alternative strategy to develop tunable, flexible, and versatile THz devices for broad applications.

Salmonella enterica is a zoonotic bacterium that not only causes serious economic losses to the livestock and poultry industries but also seriously endangers human health. Long-term indiscriminate use of antibiotics has led to drug resistance in Salmonella, and thus the identification of alternatives to antibiotics is crucial. In this study, the effects of puerarin on the S. enterica-infected chickens were investigated. A total of 360 chicks were randomly assigned as the control group (CON), the S. enterica group (S), and puerarin-treatment group (P). Chicks in the P group were fed the basal diet supplemented with 50 (P50), 100 (P100), 200 (P200), and 400 (P400) mg/kg puerarin, respectively. It was found that puerarin treatment markedly altered the serum activities of aspartate aminotransferase (AST), alanine transaminase (ALT), and superoxide dismutase (SOD), together with the malondialdehyde (MDA) and total antioxidant capacity (T-AOC) contents in the serum. The mRNA expression of IL-6, IL-1β, TNF-α, Bcl-2, and caspase-8 in the livers of S. enterica-infected chicks was increased after infection but significantly reduced after treatment with puerarin. Histologic analysis showed that puerarin effectively mitigated morphological damage in the liver caused by S. enterica. Proteomic analysis revealed that S. enterica infection led to metabolic disorders in the liver, resulting in oxidative stress, increased inflammation, and significantly elevated levels of hepatocellular carcinoma biomarkers. The findings of the filtered sequencing were verified by using quantitative PCR (qPCR). Treatment with 100 mg/mL puerarin thus effectively alleviated disordered liver metabolism, reduced inflammation and oxidative damage and significantly reduced the levels of hepatocellular carcinoma biomarkers in the liver. The results suggest that puerarin has the potential to replace antibiotics to control Salmonella infection in poultry and thus improve food safety.

The last decades of neuroimaging research has revealed atypical development of intrinsic functional connectivity within and between large-scale cortical networks in autism spectrum disorder, but much remains unknown about cortico-subcortical developmental connectivity atypicalities. This study examined cortico-striatal developmental intrinsic functional connectivity changes in autism spectrum disorder and explored how those changes may be correlated with autistic traits. We studied 49 individuals with autism spectrum disorder and 52 age-, sex-, and head motion-matched typically developing individuals (5-30 years old (14.0 ± 5.6)) using resting-state functional magnetic resonance imaging. Age-related differences in striatal intrinsic functional connectivity were compared between the two groups by adopting functional network--based parcellations of the striatum as seeds. Relative to typically developing individuals, autism spectrum disorder individuals showed atypical developmental changes in intrinsic functional connectivities between almost all striatal networks and sensorimotor network/default network, with connectivity increasing with age in the autism spectrum disorder group and decreasing or constant in typically developing individuals. Age-related degree centrality and voxel-mirrored homotopic connectivity atypicalities in sensorimotor network/default network and voxel-mirrored homotopic connectivity disruptions in striatal regions were also observed in autism spectrum disorder. Significant correlations were found between cortico-striatal intrinsic functional connectivities and Autism Diagnostic Observation Schedule communication/repetitive and restricted-behavior subscores in autism spectrum disorder. Our results indicated that developmental atypicalities of cortico-striatal intrinsic functional connectivities might contribute to the neuropathology of autism spectrum disorder.