The effect of coronary stent policies on the risk of percutaneous coronary intervention among acute coronary syndrome patients in Shanghai: Real-world evidence.

OBJECTIVE: This study aimed to analyze the effect of coronary stent policies implemented in Shanghai on the risk of percutaneous coronary intervention (PCI) in acute coronary syndrome (ACS) inpatients based on real-world data. METHODS: Two retrospective cohorts of inpatients with a first diagnosis of ACS who had undergone PCI for the first time in the previous year in Shanghai hospitals were examined (one for the postpolicy period and the other for the prepolicy period). χ2 tests were used to compare categorical variables between the two cohorts. Single- and multivariate Cox proportional hazards models were used to compare the risk of major adverse cardiovascular events (MACEs) between the two cohorts. RESULTS: A total of 31,760 ACS patients were included in this study. The proportion of ACS inpatients who had at least one bid-winning stent and 3 or more coronary stents implanted for first-time PCI in the postpolicy cohort was higher than that in the prepolicy cohort (86.52% vs. 55.67% and 6.27% vs. 4.39%, respectively; all p values < 0.0001). The single- and multivariate Cox proportional hazards models revealed that the unadjusted and adjusted hazard ratios for MACEs at 1 year after PCI for the postpolicy cohort relative to the prepolicy cohort were 0.869 (P<0.0001) and 0.814 (P = 0.0007), respectively. CONCLUSIONS: The implementation of coronary stent policies changed coronary stent utilization but had no significant adverse effects on the risk of PCI among ACS patients in Shanghai in the short term. However, the reasons for changes in the number of coronary stents implanted should be analyzed and addressed in the future.

Bulk Trapping Organic Semiconductor with Amino-Additive Enabling Ultrasensitive NO2 Sensors.

Organic semiconductor (OSC) gas sensors have garnered considerable attention due to their promising selectivity and inherent flexibility. Introducing a functional group or modification layer is an important route to modulate the doping/trapping state of the active layer and the gas absorption/desorption process. However, the majority of the functionalization lies in the surface/interface assembling process, which is difficult to control the functional group density. This in turn brings challenges for precise modulation of the charge transport and the doping/trapping density, which will affect the repeatability and reproducibility of sensing performance. Herein, we propose a facile bulk trapping strategy incorporating amino-terminated additive molecules via the vacuum deposition process, achieving ultrahigh sensitivity of ∼2000%/ppm at room temperature to NO2 gas and approaching ∼3000%/ppm at 50 °C. Additionally, the device exhibits commendable reproducibility, stability, and low concentration detection ability, reaching down to several ppb, indicating promising potential for future applications. Comprehensive analysis of electrical properties and density functional theory calculations reveals that these exceptional properties arise from the favorable electrical characteristics of the bulk trapping structure, the high mobility of C8-BTBT, and the elevated adsorption energy of NO2. This approach enables the construction of stable and reproducible sensitive sensors and helps to understand the sensing mechanism in OSC gas sensors.

Identification of Mycobacterium tuberculosis Resistance to Common Antibiotics: An Overview of Current Methods and Techniques.

Multidrug-resistant tuberculosis (MDR-TB) is an essential cause of tuberculosis treatment failure and death of tuberculosis patients. The rapid and reliable profiling of Mycobacterium tuberculosis (MTB) drug resistance in the early stage is a critical research area for public health. Then, most traditional approaches for detecting MTB are time-consuming and costly, leading to the inappropriate therapeutic schedule resting on the ambiguous information of MTB drug resistance, increasing patient economic burden, morbidity, and mortality. Therefore, novel diagnosis methods are frequently required to meet the emerging challenges of MTB drug resistance distinguish. Considering the difficulty in treating MDR-TB, it is urgently required for the development of rapid and accurate methods in the identification of drug resistance profiles of MTB in clinical diagnosis. This review discussed recent advances in MTB drug resistance detection, focusing on developing emerging approaches and their applications in tangled clinical situations. In particular, a brief overview of antibiotic resistance to MTB was present, referred to as intrinsic bacterial resistance, consisting of cell wall barriers and efflux pumping action and acquired resistance caused by genetic mutations. Then, different drug susceptibility test (DST) methods were described, including phenotype DST, genotype DST and novel DST methods. The phenotype DST includes nitrate reductase assay, RocheTM solid ratio method, and liquid culture method and genotype DST includes fluorescent PCR, GeneXpert, PCR reverse dot hybridization, ddPCR, next-generation sequencing and gene chips. Then, novel DST methods were described, including metabolism testing, cell-free DNA probe, CRISPR assay, and spectral analysis technique. The limitations, challenges, and perspectives of different techniques for drug resistance are also discussed. These methods significantly improve the detection sensitivity and accuracy of multidrug-resistant tuberculosis (MRT) and can effectively curb the incidence of drug-resistant tuberculosis and accelerate the process of tuberculosis eradication.

Mechanisms of vemurafenib-induced anti-tumor effects in ATC FRO cells.

Background: Anaplastic Thyroid Carcinoma (ATC) is a rare and deadly malignant tumor in humans. It is prone to developing resistance to radiotherapy and chemotherapy. Molecular targeted therapy offers a novel way to treat ATC. The BRAF mutation is closely associated with many cancers, including thyroid carcinoma. Vemurafenib, a small-molecule inhibitor, is specifically designed to target the mutant serine/threonine kinase BRAF. The objective of this study is to elucidate the regulatory mechanisms underlying the effects of vemurafenib on human anaplastic thyroid carcinoma cell line FRO and to assess its potential therapeutic role. Methods: The effects of vemurafenib on the proliferation of FRO cells were assessed by the CCK-8 method and Colony-forming assay. Transwell chambers and scratch tests were employed to examine the impact of vemurafenib on the invasion and migration of FRO cells. Apoptosis and cycle distribution of FRO cells were analyzed by tunel assay and flow cytometry. The effects of vemurafenib on the expression of BRAF-activated non-protein coding RNA (BANCR), Bax, Bcl2, and E-cadherin were evaluated by qRT-PCR. Furthermore, the effects of vemurafenib on the expression of phosphoinositol-3-kinase (PI3K)/phosphoinositol-3-kinase (AKT) pathway-related proteins, BRAF, CyclinD1, Bcl-2, Bax, and E-cadherin proteins in FRO cells were investigated through the western-blot method. All experiments were conducted in three replicates. Results: Vemurafenib was observed to inhibit proliferation and induce apoptosis in a dose- and time-dependent manner (P < 0.05). The formation of FRO cell colonies, as well as migration and invasion, all showed a dose-dependent reduction (P < 0.05). Flow cytometric analysis indicated G0/G1 cell cycle arrest (P < 0.05). QRT-PCR revealed that vemurafenib could suppress the expression of BANCR and Bcl2 while increasing the expression of Bax and E-cadherin in a dose-dependent manner (P < 0.05). The protein expression levels of Bax and E-cadherin were up-regulated significantly, and the expression levels of BRAF, CyclinD1, Bcl-2, p-PI3K, p-AKT, and p-mTOR were markedly down-regulated with increasing concentrations of vemurafenib (P < 0.05). Conclusions: The proliferation and metastasis of FRO cells can be suppressed by vemurafenib through the silencing of BRAF and BANCR expression, inhibition of PI3K/AKT signaling pathway activation, induction of apoptosis, and cell cycle arrest.

Electronically Manipulated Molecular Strategy Enabling Highly Efficient Tin Perovskite Photovoltaics.

Buried interface modification can effectively improve the compatibility between interfaces. Given the distinct interface selections in perovskite solar cells (PSCs), the applicability of a singular modification material remains limited. Consequently, in response to this challenge, we devised a tailored molecular strategy based on the electronic effects of specific functional groups. Therefore, we prepared three distinct silane coupling agents, and due to the varying inductive effects of these functional groups, the electronic distribution and molecular dipole moments of the coupling agents are correspondingly altered. Among them, trimethoxy (3,3,3-trifluoropropyl)-silane (F3 -TMOS), which possesses electron-withdrawing groups, generates a molecular dipole moment directed toward the hole transport layer (HTL). This approach changes the work function of the HTL, optimizes the energy level alignment, reduces the open-circuit voltage loss, and facilitates carrier transport. Furthermore, through the buffering effect of the coupling agent, the interface strain and lattice distortion caused by annealing the perovskite are reduced, enhancing the stability of the tin-based perovskite. Encouragingly, tin PSCs treated with F3 -TMOS achieved a champion efficiency of 14.67 %. This strategy provides an expedient avenue for the design of buried interface modification materials, enabling precise molecular adjustments in accordance with distinct interfacial contexts to ameliorate mismatched energetics and enhance carrier dynamics.

Fecal fermentation and high-fat diet-induced obesity mouse model confirmed exopolysaccharide from Weissella cibaria PFY06 can ameliorate obesity by regulating the gut microbiota.

Obesity associated with diet and intestinal dysbiosis is a worldwide public health crisis, and exopolysaccharides (EPS) produced by lactic acid bacteria (LAB) have prebiotic potential to ameliorate obesity. Therefore, the present study obtained LAB with the ability to produce high EPS, examined the structure of EPS, and explained its mechanism of alleviating obesity by in vivo and in vitro models. The results showed that Weissella cibaria PFY06 with a high EPS yield was isolated from strawberry juice, and pure polysaccharide (PFY06-EPS) was purified by Sephadex G-100. The structural characteristics of PFY06-EPS showed that the molecular weight was 8.08 × 106 Da and composed of α-(1,6)-D glucosyl residues. An in vitro simulated human colon fermentation test demonstrated that PFY06-EPS increased the abundance of Prevotella and Bacteroides. Cell tests confirmed that PFY06-EPS after fecal fermentation inhibited fat accumulation by promoting the secretion of endogenous gastrointestinal hormones and insulin and inhibiting the secretion of inflammatory factors. Notably, PFY06-EPS reduced weight gain, fat accumulation, inflammatory reactions and insulin resistance in a high-fat diet-induced obesity mouse model and improved glucolipid metabolism. PFY06-EPS intervention reversed obesity-induced microflora disorders, such as reducing the Firmicutes/Bacteroides ratio and increasing butyrate-producing bacteria (Roseburia and Oscillibacter), and reduced endotoxemia to maintain intestinal barrier integrity. Therefore, in vivo and in vitro models showed that PFY06-EPS had potential as a prebiotic that may play an anti-obesity role by improving the function of the gut microbiota.

Rapid Prediction of Multidrug-Resistant Klebsiella pneumoniae through Deep Learning Analysis of SERS Spectra.

Klebsiella pneumoniae is listed by the WHO as a priority pathogen of extreme importance that can cause serious consequences in clinical settings. Due to its increasing multidrug resistance all over the world, K. pneumoniae has the potential to cause extremely difficult-to-treat infections. Therefore, rapid and accurate identification of multidrug-resistant K. pneumoniae in clinical diagnosis is important for its prevention and infection control. However, the limitations of conventional and molecular methods significantly hindered the timely diagnosis of the pathogen. As a label-free, noninvasive, and low-cost method, surface-enhanced Raman scattering (SERS) spectroscopy has been extensively studied for its application potentials in the diagnosis of microbial pathogens. In this study, we isolated and cultured 121 K. pneumoniae strains from clinical samples with different drug resistance profiles, which included polymyxin-resistant K. pneumoniae (PRKP; n = 21), carbapenem-resistant K. pneumoniae, (CRKP; n = 50), and carbapenem-sensitive K. pneumoniae (CSKP; n = 50). For each strain, a total of 64 SERS spectra were generated for the enhancement of data reproducibility, which were then computationally analyzed via the convolutional neural network (CNN). According to the results, the deep learning model CNN plus attention mechanism could achieve a prediction accuracy as high as 99.46%, with robustness score of 5-fold cross-validation at 98.87%. Taken together, our results confirmed the accuracy and robustness of SERS spectroscopy in the prediction of drug resistance of K. pneumoniae strains with the assistance of deep learning algorithms, which successfully discriminated and predicted PRKP, CRKP, and CSKP strains. IMPORTANCE This study focuses on the simultaneous discrimination and prediction of Klebsiella pneumoniae strains with carbapenem-sensitive, carbapenem-resistant, and polymyxin-resistant phenotypes. The implementation of CNN plus an attention mechanism makes the highest prediction accuracy at 99.46%, which confirms the diagnostic potential of the combination of SERS spectroscopy with the deep learning algorithm for antibacterial susceptibility testing in clinical settings.

Antisense transcription and its roles in adaption to environmental stress in E. coli.

It has been reported that a highly varying proportion (1% ∼ 93%) of genes in various prokaryotes have antisense RNA (asRNA) transcription. However, the extent of the pervasiveness of asRNA transcription in the well-studied E. coli K12 strain has thus far been an issue of debate. Furthermore, very little is known about the expression patterns and functions of asRNAs under various conditions. To fill these gaps, we determined the transcriptomes and proteomes of E. coli K12 at multiple time points in five culture conditions using strand-specific RNA-seq, differential RNA-seq, and quantitative mass spectrometry methods. To reduce artifacts of possible transcriptional noise, we identified asRNA using stringent criteria with biological replicate verification and transcription start sites (TSSs) information included. We identified a total of 660 asRNAs, which were generally short and largely condition-dependently transcribed. We found that the proportions of the genes which had asRNA transcription highly depended on the culture conditions and time points. We classified the transcriptional activities of the genes in six transcriptional modes according to their relative levels of asRNA to mRNA. Many genes changed their transcriptional modes at different time points of the culture conditions, and such transitions can be described in a well-defined manner. Intriguingly, the protein levels and mRNA levels of genes in the sense-only/sense-dominant mode were moderately correlated, but the same was not true for genes in the balanced/antisense-dominant mode, in which asRNAs were at a comparable or higher level to mRNAs. These observations were further validated by western blot on candidate genes, where an increase in asRNA transcription diminished gene expression in one case and enhanced it in another. These results suggest that asRNAs may directly or indirectly regulate translation by forming duplexes with cognate mRNAs. Thus, asRNAs may play an important role in the bacterium's responses to environmental changes during growth and adaption to different environments. IMPORTANCE: The cis -antisense RNA (asRNA) is a type of understudied RNA molecules in prokaryotes, which is believed to be important in regulating gene expression. Our current understanding of asRNA is constrained by inconsistent reports about its identification and properties. These discrepancies are partially caused by a lack of sufficient samples, biological replicates, and culture conditions. This study aimed to overcome these disadvantages and identified 660 putative asRNAs using integrated information from strand-specific RNA-seq, differential RNA-seq, and mass spectrometry methods. In addition, we explored the relative expression between asRNAs and sense RNAs and investigated asRNA regulated transcriptional activity changes over different culture conditions and time points. Our work strongly suggests that asRNAs may play a crucial role in bacterium's responses to environmental changes during growth and adaption to different environments.

Long noncoding RNA CR46040 is essential for injury-stimulated regeneration of intestinal stem cells in Drosophila.

Long noncoding RNAs (lncRNAs) play important regulatory roles in stem cell self-renewal, pluripotency maintenance, and differentiation. Till now, there is very limited knowledge about how lncRNAs regulate intestinal stem cells (ISCs), and lncRNAs mediating ISC regeneration in Drosophila have yet been characterized. Here, we identify a lncRNA, CR46040, that is essential for the injury-induced ISC regeneration in Drosophila. Loss of CR46040 greatly impairs ISC proliferation in response to tissue damage caused by dextran sulfate sodium (DSS) treatment. We demonstrate that CR46040 is a genuine lncRNA that has two isoforms transcribed from the same transcription start site and works in trans to regulate intestinal stem cells. Mechanistically, CR46040 knock-out flies failed to fully activate JNK, JAK/STAT, and HIPPO signaling pathways after tissue damage, which are required for ISC proliferation after intestinal injury. Moreover, CR46040 knock-out flies are highly susceptible to DSS treatment and enteropathogenic bacteria Erwinia carotovora ssp. carotovora 15 (Ecc15) infection. Our findings characterize, for the first time, a lncRNA that mediates damage-induced ISC proliferation in Drosophila and provide new insights into the functional links among the long noncoding RNAs, ISC proliferation, and tissue homeostasis.

Evaluation of antioxidation, regulation of glycolipid metabolism and potential as food additives of exopolysaccharide from Sporidiobolus pararoseus PFY-Z1.

At present, there are relatively few studies on the production of exopolysaccharide (EPS) by yeasts. Therefore, exploring the properties of EPS produced by yeast can not only enrich the source of EPS, but also play an important role in its future application in the food field. The aim of this study was to explore the biological activities of EPS (named SPZ) from Sporidiobolus pararoseus PFY-Z1, as well as the dynamic changes in physical and chemical properties that occur during simulated gastrointestinal digestion, and the effects of SPZ on microbial metabolites during fecal fermentation in vitro. The results revealed that SPZ had good water solubility index, water-holding capacity, emulsifying ability, coagulated skim milk, antioxidant properties, hypoglycemic activities, and bile acid-binding abilities. Furthermore, the content of reducing sugars increased from 1.20 ± 0.03 to 3.34 ± 0.11 mg/mL after gastrointestinal digestion, and had little effect on antioxidant activities. Moreover, SPZ could promote the production of short-chain fatty acids during fermentation for 48 h, in particular, propionic acid and n-butyric acid increased to 1.89 ± 0.08 and 0.82 ± 0.04 mmol/L, respectively. Besides this, SPZ could inhibit LPS production. In general, this study can help us to better understand the potential bioactivities, and the changes in bio-activities of compounds after digestion of SPZ.

Effect of Bushen Chushi() decoction combined with platelet-rich plasma on regulating TGF-β1 and Smad-1 expression in serum of knee osteoarthritis patient / 中国骨伤

OBJECTIVE@#To investigate the effect of Bushen Chushi decoction combined with platelet-rich plasma(PRP) to treat knee osteoarthritis(KOA) in early and middle stage and its regulation on TGF-β1 and Smad-1 expression in serum.@*METHODS@#Total of 45 patients with KOA in early and middle stage from May 2020 to April 2022 were treated and divided into control group and observation group. In control group, there were 30 patients including 12 males and 18 females, aged from 43 to 69 years old with an average of(57.3±6.5) years old and disease duration ranged from 1.5 to 5.0 years with an average of(3.8±1.7) years, and there were 8 cases in gradeⅠ, 13 cases in gradeⅡ, and 9 cases in grade Ⅲ according to Kellgren-Lawrence Grade, PRP 5 ml was injected into knee joint on the first day of No1, 3 week together for 2 times. In the observation group, there were 15 cases including 7 males and 8 females, aged from 45 to 70 years old with an average of (56.7±6.2) years old and disease duration ranged from 1.8 to 5.7 years with an average of (4.0±1.8) years, there were 4 cases in gradeⅠ, 9 cases in gradeⅡand 4 cases in grade Ⅲ according to the Kellgren-Lawrence Grade, PRP 5 ml were injected into knee joints that the time and frequency were the same as those in the control group, and at the same time Bushen Chushi decoction orally were taken 1 dose per day with a total of 28 doses. All patients were treated for four weeks. Visual analogue scale(VAS) and Lequesne MG score before and after treatment were used to evaluate improvement of knee pain and joint function. The TGF-β1 and Smad-1 levels in serum were measured before and after treatment in two groups. The incidence of complications in two groups was observed.@*RESULTS@#All patients were followed up for 26 to 30 days with an average of (28.0±0.6) days. There was no significant difference in VAS and knee Lequesne MG scores between two groups before treatment(P>0.05). The scores of VAS and knee Lequesne MG on the first day after treatment in both groups were lower than those before treatment(P<0.05). The VAS and knee Lequesne MG scores in observation group were lower than those in control group(P<0.05) on the first day after treatment. The TGF-β1 level in serum after treatment were higher significantly than that before treatment in two groups(P<0.05). After treatment, TGF-β1 level in serum in observation group were lower than those in control group with statistically significant differences(P<0.05). The Smad-1 levels in serum after treatment in observation group were higher significantly than that in control group(P<0.05). The levels of Smad-1 were not statistically significant between before and after treatment(P>0.05). There was no significant difference in postopertaive complications between two groups (P>0.05).@*CONCLUSION@#The efficacy of Bushen Chushi decoction combined with PRP in treatment of early and middle KOA is better than that of PRP injection alone. The combined treatment could reduce TGF-β1 level and increase Smad-1 level in serum, which may be a mechanism to inhibit inflammation and alleviate cartilage degeneration to some extent.

Qualitative and quantitative study of flavonoids in Notoginseng Radix et Rhizoma based on UPLC-Q-TOF-MS and HPLC-DAD / 中国中药杂志

The flavonoids in Panax notoginseng were qualitatively analyzed by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UPLC-Q-TOF-MS), and the content of three main flavonoids in P. notoginseng of different specifications and grades collected from different habitats was determined by HPLC-DAD. Flavonoids and anthocyanins were analyzed by UPLC-Q-TOF-MS/MS in the positive and negative ion modes, respectively. Twelve flavonoid glycosides and one anthocyanin glycoside in P. notoginseng were identified, but no flavonoid aglycones were detected. Among them, 12 compounds were identified in the underground part of P. notoginseng for the first time and eight compounds were first reported in this plant. Moreover, six and four compounds were identified in the Panax genus and the Araliaceae family for the first time, respectively. A method for simultaneous determination of three flavonoids in P. notoginseng was established by HPLC-DAD. The content of flavonoids in 721 P. notoginseng samples of 124 specifications and grades collected from 20 different habitats was simultaneously determined. Among three flavonoids determined, the content of quercetin-3-O-(2″-β-D-xylosyl)-β-D-galactoside was the highest with the average content in the tested samples of 161.0 μg·g~(-1). The content of compounds quercetin-3-O-hexosyl-hexoside and kaempferol-3-O-pentosyl-hexoside was relatively low, with the average content of 18.5 μg·g~(-1)(calculated as quercetin-3-O-sophoroside) and 49.4 μg·g~(-1)(calculated as kaempferol-3-O-sangbu diglycoside). There were significant differences in flavonoids content of samples from different production area. The content of flavonoids in spring P. notoginseng was significantly lower than that in winter P. notoginseng when the other influencing factors such as production areas, germplasm resources, and cultivation conditions were fixed. As for P. notoginseng of different specifications, the flavonoid content in the part connecting the taproot and the aboveground stem was significantly higher than that in other parts. The results of large-scale data showed that the flavonoid content gradually increased with the increase in the number of heads. There were significant differences between the flavonoid content in most specifications and grades, especially the 20-head P. notoginseng and countless head P. notoginseng, whose content was significantly lower and significantly higher than that of other specifications and grades, respectively. This study provides a scientific basis for the study of the effective components and quality control of P. notoginseng from the perspective of flavonoids.

Physical properties, antioxidant capacity, and starch digestibility of cookies enriched with steam-exploded wheat bran.

Wheat bran-based food is rich in bioactive compounds, and steam explosion enhances the nutritional properties of wheat bran. This study examined the potential utilization of steam-exploded wheat bran (SWB) in cookie formulation. The influence of steam explosion on the chemical compounds in wheat bran and the effects of SWB on the physical properties, antioxidant capacity, and starch digestibility of cookies were investigated. The results showed that steam explosion facilitated the release of reducing sugar, flavonoids, phenolic substances, and amino acid nitrogen in wheat bran, thereby improving its nutritional properties. The reduction of sugar, total flavonoids, total phenolics, and amino acid nitrogen contents of wheat bran after steam explosion increased by 34.22, 183.02, 284.09, and 93.39%, respectively, compared with those of native wheat bran. Substitution of SWB for wheat flour mainly induced higher water, sodium carbonate, and sucrose solvent retention capacities, which were positively related to the spread ratio and hardness of cookies. The cookies with more SWB substitution (30-50%) expressed a higher spread ratio and harder texture than the others. The substitution of SWB caused changes in the antioxidant properties of cookies, which were related to the phenolic content. The cookies with SWB showed a higher DPPH radical scavenging activity (16.30-30.93%) than that of the control (14.74%). SWB might form a matrix barrier to hinder starch digestion, thus reducing the digestibility of cookies. The cookies enriched with 30-50% of the SWB exhibited greater physical properties and antioxidant capacity but lower starch digestibility than those of other cookies. The results will contribute to expanding the application range and improving the quality of bran-rich flour products.

The role of APTX4870 peptide in reducing cellular inflammatory responses by inhibiting Mycobacterium tuberculosis-derived mycolic acid-induced cytotoxicity.

Tuberculosis is a serious zoonotic disease caused by Mycobacterium tuberculosis (M.tb) and the M.tb complex. Mycolic acid is an extracellular carbohydrate polymer produced, secreted, and accumulated outside the cells of various Mycobacterium tuberculosis strains. Mycolic acid produced by Mycobacterium plays an important role in infection. However, there have been few reports on drugs that inhibit mycolic acid-induced cytotoxicity. The purpose of this study was to investigate the role of the panned peptide in Mycobacterium-derived mycolic acid (M.tb-MA)-induced cell injury. The heptapeptide (APTX4870) was isolated from various phage libraries using phage display (Ph.D-7, Ph.D-12, and Ph.D-C7C). The efficacy of APTX4870 against mycolic acid was demonstrated by evaluating clinical samples and conducting in vitro and Vivo. APTX4870 inhibited apoptosis, increased autophagy to decrease inflammation, and reduced M.tb-MA-induced lung damage. These findings suggest that this heptapeptide, which selectively targets M.tb-MA, might be exploited as a potential novel M.tb therapeutic treatment.

Vitamin C inhibits apoptosis in THP­1 cells in response to incubation with Mycobacterium tuberculosis.

Tuberculosis (TB) is a chronic and fatal zoonotic infectious disease caused by Mycobacterium tuberculosis (M. tb) infection. The THP-1 cell line is a cell model for studying the function, mechanism and signaling pathways of macrophages; macrophages are the primary host cells of M. tb. Macrophages are important for the progression of tuberculosis, as they affect the release of various inflammatory cytokines, including IL-1ß, IL-6 and TNF-α. Vitamin C is a trace element for the human body. Its biological efficacy depends on its redox abilities and its role as a cofactor in several enzymatic reactions. However, whether vitamin C can protect THP-1 cells from M. tb infection has not yet been reported. The present study aimed to further investigate the effects of vitamin C on M. tb infection-induced THP-1 cell injury and its mechanism. In the present study, MTT assay, reverse transcription-quantitative PCR, EdU cell proliferation assay, western blotting, immunohistochemistry, flow cytometry and TUNEL staining assays were used to assess the cell viability, inflammation and apoptotic levels of THP-1 cells induced by M. tb following vitamin C treatment. The effect of vitamin C on M. tb infection was also assessed using Balb/c mice; pulmonary injury was assessed by H&E staining of the lung tissue. The results demonstrated that vitamin C markedly attenuated cellular damage caused by M. tb infection. The results demonstrated that vitamin C reduced the expression of M. tb-induced apoptosis-related proteins (Cleaved-caspase-9, Cleaved-caspase-3, Bcl-2, Cyt-c) and inflammatory factors (IL-1ß, IL-6, NLRP3, TNF-α, IL-8, NF-κB) in THP-1 cells and reduced apoptosis. Overall, these results suggested that vitamin C may reduce lung damage caused by M. tb infection.

Production, characterization and antioxidant activity of exopolysaccharide from Sporidiobolus pararoseus PFY-Z1.

At present, the study on exopolysaccharid is mainly focused on lactic acid bacteria, and the research on exopolysaccharide produced by yeast, especially Sporidiobolus pararoseus, is relatively few. Therefore, the aim of this study was to explore the characterization and antioxidant activities of a novel neutral exopolysaccharide SPZ, which was isolated and purified from S. pararoseus PFY-Z1. The results showed that SPZ was mainly composed of mannose, followed by glucose, with a molecular weight was 24.98 kDa, had O-glycosidic bonds, no crystalline, and no triple helix structure. Based on fourier transform-infrared, high-performance liquid chromatography and nuclear magnetic resonance analyses, SPZ was identified to be a exopolysaccharide with some side chains, presence of α-, ß-pyranose ring and nine sugar residues. Furthermore, the morphology features of SPZ have performed a relatively rough and uneven surface, covered with small pores and fissures. Moreover, SPZ had higher antioxidant activities and the maximum scavenging abilities of ⋅OH, NO2- and reducing power were 28.05 ± 0.73%, 92.76 ± 1.86% and 0.345 ± 0.024, respectively. Hence, SPZ could be used as a potential antioxidant application in the food and pharmaceutical industries.

Machine learning analysis of SERS fingerprinting for the rapid determination of Mycobacterium tuberculosis infection and drug resistance.

Over the past decades, conventional methods and molecular assays have been developed for the detection of tuberculosis (TB). However, these techniques suffer limitations in the identification of Mycobacterium tuberculosis (Mtb), such as long turnaround time and low detection sensitivity, etc., not even mentioning the difficulty in discriminating antibiotics-resistant Mtb strains that cause great challenges in TB treatment and prevention. Thus, techniques with easy implementation for rapid diagnosis of Mtb infection are in high demand for routine TB diagnosis. Due to the label-free, low-cost and non-invasive features, surface enhanced Raman spectroscopy (SERS) has been extensively investigated for its potential in bacterial pathogen identification. However, at current stage, few studies have recruited handheld Raman spectrometer to discriminate sputum samples with or without Mtb, separate pulmonary Mtb strains from extra-pulmonary Mtb strains, or profile Mtb strains with different antibiotic resistance characteristics. In this study, we recruited a set of supervised machine learning algorithms to dissect different SERS spectra generated via a handheld Raman spectrometer with a focus on deep learning algorithms, through which sputum samples with or without Mtb strains were successfully differentiated (5-fold cross-validation accuracy = 94.32%). Meanwhile, Mtb strains isolated from pulmonary and extra-pulmonary samples were effectively separated (5-fold cross-validation accuracy = 99.86%). Moreover, Mtb strains with different drug-resistant profiles were also competently distinguished (5-fold cross-validation accuracy = 99.59%). Taken together, we concluded that, with the assistance of deep learning algorithms, handheld Raman spectrometer has a high application potential for rapid point-of-care diagnosis of Mtb infections in future.

Autophagy inhibition restores CD200 expression under IL-1ß microenvironment in placental mesenchymal stem cells of fetal origin and improves its pulmonary fibrosis therapeutic potential.

BACKGROUND: Mesenchymal stem cells (MSCs) are promising remedies for various inflammatory disease including pulmonary fibrosis (PF). However, the properties of MSCs in PF pathological microenvironment remain unclear. In this study, the efficacy of autophagy in placental mesenchymal stem cells of fetal origin (fPMSCs) in either IL-1ß treatment or BLM induced pulmonary fibrosis mice model was examined. METHODS: The characteristic of fPMSCs was identified by morphological observation, flow cytometry and differentiation potential. In vitro experiments, fPMSCs were stimulated with IL-1ß, to mimic inflammatory microenvironment of pulmonary fibrosis. The immunosuppressive properties and autophagic function in fPMSCs treated with IL-1ß were evaluated by both macrophage cells THP-1 activation and the expression of CD200 situation, autophagy marker and MAPK signaling pathway. The in vivo anti-fibrotic activity of fPMSCs interfering autophagy was evaluated by using BLM induced pulmonary fibrosis mice model. RESULTS: fPMSCs belonged to CD73+CD90+CD105+/CD14- CD34-CD45-HLA-DR- cells, and capable differentiation to adipogenic, osteogenic and chondrogenic cells. In addition, immunoinhibitory activity of fPMSCs for macrophage was restrained by IL-1ß treatment in CD200 dependent manner. Suppression of autophagy by sh-Atg5 lentivirus increased the expression of CD200 and ratio of CD200 positive fPMSCs, and enhanced fPMSCs immunosuppression for THP-1 activation. Mechanistically, IL-1ß induced autophagy regulated by p38 signaling cascade. In vivo, autophagy inhibition induced by Atg5 knockdown in fPMSCs resulted in strengthening antifibrotic effects on PF mice model. CONCLUSIONS: Collectively, autophagy derived from inflammatory microenvironment hampered the immunoinhibitory properties of MSCs. Based on this, adjustment of autophagy may be a valid approach to facilitate their immunomodulatory and anti-fibrotic efficacy.

Improving Antioxidative and Antiproliferative Properties Through the Release of Bioactive Compounds From Eucommia ulmoides Oliver Bark by Steam Explosion.

Eucommia ulmoides Oliver bark is a potential medicinal plant-based feedstock for bioactive products and possesses the effective functions of antioxidant and antitumor. Network pharmacology was employed to reveal the oxidative and free radical damage and cancer-related potential compounds of Eucommia ulmoides Oliver in this study. The result showed that quercetin might be the key compound to resist these two types of diseases. Then, the effect of steam explosion on the release of bioactive compounds and the antioxidative and antiproliferative properties of the extract from Eucommia ulmoides Oliver bark were investigated. Results showed that steam explosion at 0.7 MPa for 30 min significantly enhanced the total phenolic, total flavonoids, and quercetin content of Eucommia ulmoides Oliver bark. Reducing power and 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) radical scavenging activity of the steam-exploded extracting solution were 1.72 and 2.76 times of native. The antiproliferative activity to CT26 and HepG2 of the extract from steam-exploded Eucommia ulmoides Oliver bark (SEU) was higher than those of native-exploded Eucommia ulmoides Oliver bark (NEU). All these results suggested that steam explosion could be applied to release the bioactive compounds, thus enhanced the antioxidative and antiproliferative activities of medicinal and edible plant-based sources.

[Thermal Environment Evolution and Response Mechanism of Urban Sprawl Based on Multi-source Data].

Improving the urban thermal environment and improving the quality of human settlements are important prerequisites for creating ecologically livable cities. The current research on the relationship between urban expansion and the thermal environment is mostly based on remote sensing data, and the application of multi-source data is weak. Here, we selected the Xi'an metropolitan core area, measured the urban expansion and temporal and spatial evolution of the thermal environment based on Landsat remote sensing images in 2010 and 2020, and used multi-source data, such as interest points and the Baidu thermal index, to study the response mechanism of the urban thermal environment through geoscience statistical analysis methods. The results showed that:① the construction land in the study area had expanded by 200.84 km2, and the area and intensity showed that "the center and the periphery are weaker, and the difference between the two" characteristics, and the expansion mode was mainly edge type and infill type. ② Between 2010 and 2020, the overall thermal environment in the study area deteriorated, and the area of the heat island area increased by 282.65 km2. The spread of the heat island area was in the same direction as the urban expansion, and the distribution pattern evolved from "southeast-northwest" to "northeast-southwest;" however, the average temperature in the central area of the city decreased 1.09℃. ③ Urban expansion was strongly positively correlated with the deterioration of the urban thermal environment. The expansion of urban space had a contribution rate of 60.40% to the deterioration of the thermal environment, and various socio-economic factors had a weaker effect, with an overall contribution rate of 39.60%. The vegetation water body had an obvious cooling effect; under the influence of multiple factors, the surface temperature increased by 0.241 units. In the process of urban expansion, changes in surface parameters and two-dimensional urban morphology were still the main factors for thermal environment changes, whereas three-dimensional morphology had a small effect on the warming of social and economic activities, and the contribution of water bodies and vegetation to cooling was prominent.