A Molecular Dynamics Analysis of the Thickness and Adhesion Characteristics of the Quasi-Liquid Layer at the Asphalt-Ice Interface.

The quasi-liquid layer (QLL), a microstructure located between ice and an adhering substrate, is critical in generating capillary pressure, which in turn influences ice adhesion behavior. This study employed molecular dynamics (MD) methods to obtain QLL thickness and utilized these measurements to estimate the adhesive strength between ice and asphalt. The research involved constructing an ice-QLL-asphalt MD model, encompassing four asphalt types and five temperature ranges from 250 K to 270 K. The QLL thickness was determined for various asphalts and temperatures using the tetrahedral order parameter gradient. Additionally, capillary pressure was calculated based on the QLL thickness and other geometric parameters obtained from the MD analysis. These findings were then compared with ice adhesion strength data acquired from pull-off tests. The results indicate that QLL thickness varies with different asphalt types and increases with temperature. At a constant temperature, the QLL thickness decreases in the order of the basal plane, primary prism plane, and secondary prism plane. Furthermore, the adhesion strength of the QLL diminishes as the temperature rises, attributed to the disruption of hydrogen bonds at lower temperatures. The greater the polarity of the asphalt's interface molecules, the stronger the adhesion strength and binding free energy. The MD simulations of the asphalt-ice interface offer insights into the atomic-scale adhesive properties of this interface, contributing to the enhancement in QLL property prediction and calibration at larger scales.

Tunable electronic and optical properties of BAs/WTe2heterostructure for theoretical photoelectric device design.

The geometric structure of the BAs/WTe2heterojunction was scrutinized by employingab initiocalculations grounded on density functional theory. Multiple configurations are constructed to determine the equilibrium state of the heterojunction with optimal stability. The results show that the H1-type heterojunction with interlayer distance of 3.92 Å exhibits exceptional stability and showcases a conventional Type-II band alignment, accompanied by a direct band gap measuring 0.33 eV. By applying external electric field and introducing strain, one can efficaciously modulate both the band gap and the quantity of charge transfer in the heterojunction, accompanied by the transition of band alignment from Type-II to Type-I, which makes it expected to achieve broader applications in light-emitting diodes, laser detectors and other fields. Ultimately, the heterojunction undergoes a transformation from a semiconducting to a metallic state. Furthermore, the outstanding optical characteristics inherent to each of the two monolayers are preserved, the BAs/WTe2heterojunction also serves to enhance the absorption coefficient and spectral range of the material, particularly within the ultraviolet spectrum. It merits emphasis that the optical properties of the BAs/WTe2heterojunction are capable of modification through the imposition of external electric fields and mechanical strains, which will expand its applicability and potential for future progression within the domains of nanodevices and optoelectronic apparatus.

Targeting Cyclin-Dependent Kinase 1 Induces Apoptosis and Cell Cycle Arrest of Activated Hepatic Stellate Cells.

Liver fibrosis is the integral process of chronic liver diseases caused by multiple etiologies and characterized by excessive deposition of extracellular matrix (ECM). During liver fibrosis, hepatic stellate cells (HSCs) transform into a highly proliferative, activated state, producing various cytokines, chemokines, and ECM. However, the precise mechanisms that license HSCs into the highly proliferative state remain unclear. Cyclin-dependent kinase 1 (CDK1) is a requisite event for the transition of the G1/S and G2/M phases in eukaryotic cells. In this study, it is demonstrated that CDK1 and its activating partners, Cyclin A2 and Cyclin B1, are upregulated in both liver fibrosis/cirrhosis patient specimens and the murine hepatic fibrosis models, especially in activated HSCs. In vitro, CDK1 is upregulated in spontaneously activated HSCs, and inhibiting CDK1 with specific small-molecule inhibitors (CGP74514A, RO-3306, or Purvalanol A) orshort hairpin RNAs (shRNAs) resulted in HSC apoptosis and cell cycle arrest by regulating Survivin expression. Above all, it is illustrated that increased CDK1 expression licenses the HSCs into a highly proliferative state and can serve as a potential therapeutic target in liver fibrosis.

m 6 A-mediated gluconeogenic enzyme PCK1 upregulation protects against hepatic ischemia-reperfusion injury.

BACKGROUND AND AIMS: Ischemia-reperfusion (I/R) injury frequently occurs during liver surgery, representing a major reason for liver failure and graft dysfunction after operation. The metabolic shift from oxidative phosphorylation to glycolysis during ischemia increased glucose consumption and accelerated lactate production. We speculate that donor livers will initiate gluconeogenesis, the reverse process of glycolysis in theory, to convert noncarbohydrate carbon substrates (including lactate) to glucose to reduce the loss of hepatocellular energy and foster glycogen storage for use in the early postoperative period, thus improving post-transplant graft function. APPROACH AND RESULTS: By analyzing human liver specimens before and after hepatic I/R injury, we found that the rate-limiting enzyme of gluconeogenesis, PCK1, was significantly induced during liver I/R injury. Mouse models with liver I/R operation and hepatocytes treated with hypoxia/reoxygenation confirmed upregulation of PCK1 during I/R stimulation. Notably, high PCK1 level in human post-I/R liver specimens was closely correlated with better outcomes of liver transplantation. However, blocking gluconeogenesis with PCK1 inhibitor aggravated hepatic I/R injury by decreasing glucose level and deepening lactate accumulation, while overexpressing PCK1 did the opposite. Further mechanistic study showed that methyltransferase 3-mediated RNA N6-methyladinosine modification contributes to PCK1 upregulation during hepatic I/R injury, and hepatic-specific knockout of methyltransferase 3 deteriorates liver I/R injury through reducing the N6-methyladinosine deposition on PCK1 transcript and decreasing PCK1 mRNA export and expression level. CONCLUSIONS: Our study found that activation of the methyltransferase 3/N6-methyladinosine-PCK1-gluconeogenesis axis is required to protect against hepatic I/R injury, providing potential intervention approaches for alleviating hepatic I/R injury during liver surgery.

Photocatalytic water splitting properties of GeC/InS van der Waals heterostructure: first-principles calculations.

Based on first-principles, we conducted an in-depth study of the GeC/InS van der Waals heterostructure formed by GeC and InS and discussed its structure, electronic properties and optical properties. First, we observe that this heterostructure has negative binding energy, indicating that the interlayer interactions are mainly affected by van der Waals forces. Through band structure and density of state analysis, we confirmed its type-II band alignment characteristics, which means that photogenerated carriers have the ability to automatically separate in space. Moreover, the average charge density difference and Bader charge analysis show that there is a built-in electric field in the heterostructure, and further proves that GeC/InS forms a Z-scheme charge transfer mechanism. Interestingly, the band edge position spans the water redox potential and can fully induce the redox reaction of water splitting, indicating that it is a potential photocatalyst. The high light absorption coefficient shown in the absorption spectrum also further confirms its excellent photocatalytic activity. The most striking thing is that the solar hydrogen production efficiency of GeC/InS heterostructure is as high as 44.39%. Our research demonstrates the theoretical basis for GeC/InS heterostructure as a photocatalyst.

Recent Progress of Natural and Recombinant Phycobiliproteins as Fluorescent Probes.

Phycobiliproteins (PBPs) are natural water-soluble pigment proteins, which constitute light-collecting antennae, and function in algae photosynthesis, existing in cyanobacteria, red algae, and cryptomonads. They are special pigment-protein complexes in algae with a unique structure and function. According to their spectral properties, PBPs can be mainly divided into three types: allophycocyanin, phycocyanin, and PE. At present, there are two main sources of PBPs: one is natural PBPs extracted from algae and the other way is recombinant PBPs which are produced in engineered microorganisms. The covalent connection between PBP and streptavidin was realized by gene fusion. The bridge cascade reaction not only improved the sensitivity of PBP as a fluorescent probe but also saved the preparation time of the probe, which expands the application range of PBPs as fluorescent probes. In addition to its function as a light-collecting antenna in photosynthesis, PBPs also have the functions of biological detection, ion detection, and fluorescence imaging. Notably, increasing studies have designed novel PBP-based far-red fluorescent proteins, which enable the tracking of gene expression and cell fate.

Minimally invasive valve surgery including patients of combined simultaneous surgery: a retrospective study.

OBJECTIVE: This study investigated the perioperative safety and advantages of performing a minimally invasive valve surgery (MIVS) and conducting a preliminary examination of the combined simultaneous surgery (CSS). METHODS: A total of 29 patients (16 men and 13 women; mean age, 58.41 ± 13.08 years) who underwent MIVS at our center from July 2021 to March 2022 were selected. Among them, 16 patients underwent aortic valve surgery (AVS), 13 patients underwent mitral valve surgery (MVS), and four patients additionally underwent CSS. RESULTS: The MIVS time ranged from 165 to 420 min, with a mean of 230.54 ± 54.61 min; the cardiopulmonary bypass (CPB) time ranged from 54 to 164 min, with a mean of 120.24 ± 25.98 min; the aortic cross-clamp (ACC) time ranged from 36 to 118 min, with a mean of 78.66 ± 21.01 min and an automatic heart resuscitating rate was 89.66%; the mean tracheal intubation time was 6.30 ± 3.87 h, and the median total postoperative drainage was 317.5 (35, 1470) ml. No difference was observed between preoperative and postoperative left ventricular ejection fraction (LVEF) (61.90% ± 6.28% vs. 60.21% ± 5.52%, P = 0.281). The difference in postoperative drainage (419.20 ml ± 377.20 ml vs. 588.75 ml ± 673.63 ml, P = .461), tracheal intubation time (6.66 h ± 4.27 h vs. 4.63 h ± 1.11 h, P = .359), intensive care unit (ICU) stay (3.96 ± 8.62 days vs. 2.00 ± 0.816 days, P = .658), and postoperative hospital stay (9.96 ± 8.45 days vs. 8.25 ± 1.26 days, P = .694) between MIVS and CSS was not significant. CONCLUSION: MIVS in our center may be safe and effective. Additionally, CSS may be a feasible option that could be performed after a thorough preoperative evaluation and multidisciplinary discussion.

Combined inhibition of surface CD51 and γ-secretase-mediated CD51 cleavage improves therapeutic efficacy in experimental metastatic hepatocellular carcinoma.

BACKGROUND & AIMS: Integrin αv (ITGAV, CD51) is regarded as a key component in multiple stages of tumor progression. However, the clinical failure of cilengitide, a specific inhibitor targeting surface CD51, suggests the importance of yet-unknown mechanisms by which CD51 promotes tumor progression. METHODS: In this study, we used several hepatocellular carcinoma (HCC) cell lines and murine hepatoma cell lines. To investigate the role of CD51 on HCC progression, we used a 3D invasion assay and in vivo bioluminescence imaging. We used periostin-knockout transgenic mice to uncover the role of the tumor microenvironment on CD51 cleavage. Moreover, we used several clinically relevant HCC models, including patient-derived organoids and patient-derived xenografts, to evaluate the therapeutic efficacy of cilengitide in combination with the γ-secretase inhibitor LY3039478. RESULTS: We found that CD51 could undergo transmembrane cleavage by γ-secretase to produce a functional intracellular domain (CD51-ICD). The cleaved CD51-ICD facilitated HCC invasion and metastasis by promoting the transcription of oxidative phosphorylation-related genes. Furthermore, we identified cancer-associated fibroblast-derived periostin as the major driver of CD51 cleavage. Lastly, we showed that cilengitide-based therapy led to a dramatic therapeutic effect when supplemented with LY3039478 in both patient-derived organoid and xenograft models. CONCLUSIONS: In summary, we revealed previously unrecognized mechanisms by which CD51 is involved in HCC progression and uncovered the underlying cause of cilengitide treatment failure, as well as providing evidence supporting the translational prospects of combined CD51-targeted therapy in the clinic. IMPACT AND IMPLICATIONS: Integrin αv (CD51) is a widely recognized pro-tumoral molecule that plays a crucial role in various stages of tumor progression, making it a promising therapeutic target. However, despite early promising results, cilengitide, a specific antagonist of CD51, failed in a phase III clinical trial. This prompted further investigation into the underlying mechanisms of CD51's effects. This study reveals that the γ-secretase complex directly cleaves CD51 to produce an intracellular domain (CD51-ICD), which functions as a pro-tumoral transcriptional regulator and can bypass the inhibitory effects of cilengitide by entering the nucleus. Furthermore, the localization of CD51 in the nucleus is significantly associated with the prognosis of patients with HCC. These findings provide a theoretical basis for re-evaluating cilengitide in clinical settings and highlight the importance of identifying a more precise patient subpopulation for future clinical trials targeting CD51.

Administration of AG490 decreases the senescence of umbilical cord-mesenchymal stem cells and promotes the cytotherapeutic effect in liver fibrosis.

The therapeutic potential of umbilical cord-mesenchymal stem cell (UC-MSC) transplantation in liver fibrosis has been highlighted. However, the fate of transplanted MSCs in the fibrotic microenvironment remains unclear. In this study, we aim to uncover the fate of transplanted MSCs and develop targeting strategies that could enhance the therapeutic efficacy of MSC therapy in liver fibrosis. We used human UC-MSCs as the study object. For in vitro experiments, we stimulated UC-MSCs with several fibrotic-related factors (Liver fibrotic Factors, LF), including TGFß, TNFα and IFNγ for downstream investigations. We co-cultured LF-treated UC-MSCs with hepatic stellate cell line LX-2 to assess the anti-fibrotic effect. We showed that upon LF stimulation, UC-MSCs exhibited reduced anti-fibrotic activity and underwent rapid senescence. Pathway analysis showed that JAK/STAT3 signaling was highly activated upon LF stimulation, which significantly elevated senescence-associated secretory phenotype (SASP) and senescence in UC-MSCs and could be reversed by a specific JAK inhibitor AG490. Moreover, using both carbon tetrachloride (CCl4) and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-induce fibrosis models, we demonstrated that AG490 pretreatment promoted UC-MSCs survival within the fibrotic liver microenvironment and exhibited enhance therapeutic efficacy. Overall, we showed that targeting MSC senescence in vivo through AG490 pretreatment could enhance the anti-fibrotic activities of UC-MSCs.

Long Noncoding RNA RP11-89K21.1 Interacts with miR-146a/b-5p to Promote Proliferation and Gefitinib Resistance Through Regulating RHPN2 and RhoA/ROCK Pathway in Lung Adenocarcinoma.

Background: Long noncoding RNAs (lncRNAs) have major roles in lung adenocarcinoma (LUAD). lncRNA RP11-89K21.1 was reported to be abnormally expressed in LUAD, yet its biological functions in LUAD progression remain unclear. Materials and Methods: Forty LUAD tissues and pair-matched adjacent normal tissues were enrolled in this study. Quantitative real-time polymerase chain reaction was performed to detect the expression of lncRNA, miRNA, and mRNA in LUAD samples and cell lines. Loss-of-function assays were used to evaluate the effects of RP11-89K21.1 on LUAD cell proliferation and gefitinib resistance. Bioinformatics analysis, luciferase reporter assay, and Western blot were employed to explore the regulatory relationships among RP11-89K21.1, miR-146a/b-5p, and RHPN2. Results: RP11-89K21.1 was identified as being highly expressed in LUAD tissues and cell lines. Moreover, upregulated RP11-89K21.1 was strongly associated with unfavorable overall survival of patients with LUAD. Knockdown of RP11-89K21.1 significantly suppressed proliferation and sensitized cell to gefitinib. Mechanistically, RP11-89K21.1 could directly bind miR-146a-5p and miR-146b-5p and decrease their expression to upregulate RHPN2, and subsequently activated RhoA/ROCK pathway. More importantly, overexpression of RHPN2 reversed regulatory effects of RP11-89K21.1 knockdown on cell proliferation and gefitinib resistance. Conclusions: These observations provide new insights into the role of RP11-89K21.1 in regulating LUAD tumorigenesis, suggesting that RP11-89K21.1 is a potential therapeutic target for LUAD treatment.

Role and mechanism of the zinc finger protein ZNF580 in foam-cell formation.

Coronary atherosclerotic heart disease poses a significant threat to human health. The pathological basis is atherosclerosis and foam-cell formation is the key factor in the initiation of atherosclerosis. In the present study, foam cell models were established using 50 ng/ml oxidized low-density lipoprotein to stimulate in vitro cultures of THP-1 cells for 72 h. The expression of zinc finger protein 580 (ZNF580), a Cys2-His2 zinc finger protein containing 172 amino acids that was originally cloned by screening a human aortic cDNA library, was measured in foam cells and its interaction with various regulatory factors during foam-cell formation was investigated. Oil red O staining was used to observe cell morphology and intracellular lipid levels. Lentivirus transfection was employed to either overexpress or silence ZNF580 in THP-1 cells, and an inverted fluorescence microscope was used to observe the distribution of ZNF580 immunofluorescence to determine the transfection rate. RNA and total protein were extracted and the expression levels of ZNF580, CD36, peroxisome proliferator-activated receptor-γ (PPAR-γ), ATP-binding cassette transporter A1 (ABCA1) and apolipoprotein E (ApoE) were measured by reverse transcription-quantitative PCR. The protein levels were examined by western blot analysis to evaluate the interaction between ZNF580 and associated regulatory factors. ZNF580 was able to significantly increase the expression levels of ApoE and ABCA1 and significantly decrease the expression levels of CD36 and PPAR-γ, suggesting that ZNF580-mediated inhibition of foam-cell formation is associated with the PPAR-γ-CD36 signalling pathway. Based on these findings, ZNF580 may be a potential therapeutic candidate for the treatment of coronary atherosclerotic heart disease.

The m6A methyltransferase Mettl3 deficiency attenuates hepatic stellate cell activation and liver fibrosis.

Activation of hepatic stellate cells (HSCs) is a central driver of liver fibrosis. Previous investigations have identified various altered epigenetic landscapes during the cellular progression of HSC activation. N6-methyladenosine (m6A) is the most abundant internal RNA modification in eukaryotic cells and is dynamically regulated under various physiological and pathophysiological conditions. However, the functional role of Mettl3-mediated m6A in liver fibrosis remains elusive. Here, we found that the HSC-specific knockout of m6A methyltransferase Mettl3 suppressed HSC activation and significantly alleviated liver fibrosis. Multi-omics analysis of HSCs showed that Mettl3 depletion reduced m6A deposition on mRNA transcripts of Lats2 (a central player of the Hippo/YAP signaling pathway) and slowed down their degradation. Elevated Lats2 increased phosphorylation of the downstream transcription factor YAP, suppressed YAP nuclear translocation, and decreased pro-fibrotic gene expression. Overexpressing YAP mutant resistant to phosphorylation by Lats2 partially rescued the activation and pro-fibrotic gene expression of Mettl3-deficient HSCs. Our study revealed that disruption of Mettl3 in HSCs mitigated liver fibrosis by controlling the Hippo/YAP signaling pathway, providing potential therapeutic strategies to alleviate liver fibrosis by targeting epitranscriptomic machinery.

Predicting Dynamic Properties of Asphalt Mastic Considering Asphalt-Filler Interaction Based on 2S2P1D Model.

The relationship between the various phases of asphalt materials, from asphalt binder to mastic and mixture, has received great attention over the years, with efforts being made to establish linkages among these phases. Many methods for predicting the rheology properties of asphalt mastics from those of asphalt and filler volume fractions exist. However, most prediction methods are based on an empirical formula and on the micromechanical model. Very few research studies focus on the constitutive model. In addition, relatively little research has explored the influence of asphalt-filler interaction on mastic's rheology properties, which is believed to be an important factor. In this study, the 2S2P1D (two springs, two parabolic elements, and one dashpot) model was applied to link the behavior of asphalt binder, filler volume fraction, asphalt-filler interaction and asphalt mastic. First, the interaction between asphalt and filler was evaluated, and the interaction parameter C of the Palierne model was used as an assessment indicator to calculate the effective filler volume fraction of asphalt mastic. Then, the relation between the 2S2P1D model parameters of asphalt mastic and those of asphalt binder and the effective filler volume fraction was analyzed. Finally, a simple relationship associating the 2S2P1D model parameters h, log(τ0) of mastic and that of asphalt binder and the effective filler volume fraction was developed. The proposed expression was validated, and the result showed that it was an efficient model for the shear complex modulus prediction of virgin asphalt mastic.

Phycobiliproteins-A Family of Algae-Derived Biliproteins: Productions, Characterization and Pharmaceutical Potentials.

Phycobiliproteins (PBPs) are colored and water-soluble biliproteins found in cyanobacteria, rhodophytes, cryptomonads and cyanelles. They are divided into three main types: allophycocyanin, phycocyanin and phycoerythrin, according to their spectral properties. There are two methods for PBPs preparation. One is the extraction and purification of native PBPs from Cyanobacteria, Cryptophyta and Rhodophyta, and the other way is the production of recombinant PBPs by heterologous hosts. Apart from their function as light-harvesting antenna in photosynthesis, PBPs can be used as food colorants, nutraceuticals and fluorescent probes in immunofluorescence analysis. An increasing number of reports have revealed their pharmaceutical potentials such as antioxidant, anti-tumor, anti-inflammatory and antidiabetic effects. The advances in PBP biogenesis make it feasible to construct novel PBPs with various activities and produce recombinant PBPs by heterologous hosts at low cost. In this review, we present a critical overview on the productions, characterization and pharmaceutical potentials of PBPs, and discuss the key issues and future perspectives on the exploration of these valuable proteins.

Deletion of Mettl3 at the Pro-B Stage Marginally Affects B Cell Development and Profibrogenic Activity of B Cells in Liver Fibrosis.

N6-methyladenosine (m6A) modification plays a pivotal role in cell fate determination. Previous studies show that eliminating m6A using Mb1-Cre dramatically impairs B cell development. However, whether disturbing m6A modification at later stages affects B cell development and function remains elusive. Here, we deleted m6A methyltransferase Mettl3 from the pro-B stage on using Cd19-Cre (Mettl3 cKO) and found that the frequency of total B cells in peripheral blood, peritoneal cavity, and liver is comparable between Mettl3 cKO mice and wild-type (WT) littermates, while the percentage of whole splenic B cells slightly increases in Mettl3 cKO individuals. The proportion of pre-pro-B, pro-B, pre-B, immature, and mature B cells in the bone marrow were minimally affected. Loss of Mettl3 resulted in increased apoptosis but barely affected B cells' proliferation and IgG production upon LPS, CD40L, anti-IgM, or TNF-α stimulation. Different stimuli had different effects on B cell activation. In addition, B cell-specific Mettl3 knockout had no influence on the pro-fibrogenic activity of B cells in liver fibrosis, evidenced by comparable fibrosis in carbon tetrachloride- (CCl4-) treated Mettl3 cKO mice and WT controls. In summary, our study demonstrated that deletion of Mettl3 from the pro-B stage on has minimal effects on B cell development and function, as well as profibrogenic activity of B cells in liver fibrosis, revealing a stage-specific dependence on Mettl3-mediated m6A of B cell development.

Characterization of multiple soluble immune checkpoints in individuals with different Mycobacterium tuberculosis infection status and dynamic changes during anti-tuberculosis treatment.

BACKGROUND: Immune checkpoints are crucial for the maintenance of subtle balance between self-tolerance and effector immune responses, but the role of soluble immune checkpoints (sICs) in Mycobacterium tuberculosis (M. tb) infection remains unknown. We assessed the levels of multiple sICs in individuals with distinct M. tb infection status, and their dynamic changes during anti-tuberculosis treatment. METHODS: We enrolled 24 patients with pulmonary tuberculosis, among which 10 patients were diagnosed with tuberculous pleurisy (TBP), 10 individuals with latent tuberculosis infection (LTBI), and 10 healthy volunteers from Wuxi Fifth People's Hospital and Huashan Hospital between February 2019 and May 2021. Plasma concentrations of thirteen sICs were measured at enrollment and during anti-tuberculosis treatment using luminex-based multiplex assay. sICs levels in tuberculous pleural effusion (TPE) and their relations to laboratory test markers of TPE were also assessed in TBP patients. RESULTS: The circulating levels of sPD-1, sPD-L1, sCTLA-4, sBTLA, sGITR, sIDO, sCD28, sCD27 and s4-1BB were upregulated in tuberculosis patients than in healthy controls. A lower sPD-L1 level was found in LTBI individuals than in tuberculosis patients. In TBP patients, the levels of sPD-1, sPD-L2, sCD28, sCD80, sCD27, sTIM-3, sLAG-3, sBTLA, s4-1BB and sIDO increased significantly in TPE than in plasma. In TPE, sBTLA and sLAG-3 correlated positively with the adenosine deaminase level. sIDO and sCD80 correlated positively with the lactate dehydrogenase level and the percentage of lymphocytes in TPE, respectively. Meanwhile, sCD27 correlated negatively with the specific gravity and protein level in TPE. In tuberculosis patients, the circulating levels of sBTLA and sPD-L1 gradually declined during anti-tuberculosis treatment. CONCLUSIONS: We characterized the changing balance of sICs in M. tb infection. And our results revealed the relations of sICs to laboratory test markers and treatment responses in tuberculosis patients, indicating that certain sICs may serve as potential biomarkers for disease surveillance and prognosis of tuberculosis.

Butorphanol reduces the neuronal inflammatory response and apoptosis via inhibition of p38/JNK/ATF2/p53 signaling.

Neuronal cell apoptosis is a complex pathophysiological change that occurs following spinal cord injury (SCI) and affects self-repair. Therefore, preventing neuronal cell apoptosis can promote the recovery of nerve function. The present study aimed to investigate the effects of butorphanol on neuronal inflammatory response and apoptosis. The effects of butorphanol on cell viability and pathway-related protein expression were first assessed using the CCK8 and western blot assays, respectively. Lipopolysaccharide (LPS) was used to establish models. The influences of additional anisomycin, an agonist of MAPK pathway, on cell viability, pathway-related protein expression and lactate dehydrogenase level were determined using the CCK8 assay, western blotting and assay kits, respectively. In addition, the roles of butorphanol and anisomycin in inflammatory factor levels and cell apoptosis were determined using reverse transcription-quantitative PCR, TUNEL and western blot assays. Butorphanol was found to protect PC12 cells from the action of LPS on viability and effectively upregulated the p38/JNK/activation of transcription factor 2 (ATF2)/p53 protein expression levels. In addition, anisomycin could break the protective role of butorphanol in cell viability and the inhibitory roles in inflammatory response and apoptosis. To sum up, butorphanol reduces neuronal inflammatory response and apoptosis via inhibiting p38/JNK/ATF2/p53 signaling. The present findings may provide a new direction for the treatment for SCI.

Human Wharton's jelly-derived mesenchymal stem cells alleviate concanavalin A-induced fulminant hepatitis by repressing NF-κB signaling and glycolysis.

BACKGROUND: Fulminant hepatitis is a severe life-threatening clinical condition with rapid progressive loss of liver function. It is characterized by massive activation and infiltration of immune cells into the liver and disturbance of inflammatory cytokine production. Mesenchymal stem cells (MSCs) showed potent immunomodulatory properties. Transplantation of MSCs is suggested as a promising therapeutic approach for a host of inflammatory conditions. METHODS: In the current study, a well-established concanavalin A (Con A)-induced fulminant hepatitis mouse model was used to investigate the effects of transplanting human umbilical cord Wharton's jelly-derived MSCs (hWJ-MSCs) on fulminant hepatitis. RESULTS: We showed that hWJ-MSCs effectively alleviate fulminant hepatitis in mouse models, primarily through inhibiting T cell immunity. RNA sequencing of liver tissues and human T cells co-cultured with hWJ-MSCs showed that NF-κB signaling and glycolysis are two main pathways mediating the protective role of hWJ-MSCs on both Con A-induced hepatitis in vivo and T cell activation in vitro. CONCLUSION: In summary, our data confirmed the potent therapeutic role of MSCs-derived from Wharton's jelly of human umbilical cord on Con A-induced fulminant hepatitis, and uncovered new mechanisms that glycolysis metabolic shift mediates suppression of T cell immunity by hWJ-MSCs.

Role of bronchoalveolar lavage fluid and serum interleukin-27 in the diagnosis of smear-negative pulmonary tuberculosis.

BACKGROUND: To evaluate the value of interleukin (IL)-27 measured in serum and bronchoalveolar lavage fluid (BALF) for the diagnosis of smear-negative pulmonary tuberculosis (TB). METHODS: This was a prospective study of patients planned to undergo bronchoscopy at Wuxi No.5 People's Hospital between January 2017 and September 2018. The patients were grouped as the TB and control groups. BALF and serum IL-27 were measured by ELISA. Receiver operating characteristic (ROC) curves were used to assess the diagnostic value and calculate the optimal cutoff values. RESULTS: There were 40 patients in the control group and 87 in the TB group. In the TB group, 20 had positive sputum smear results and 67 were negative. The area under the ROC curve (AUC) of BALF IL-27 for pulmonary TB was 0.897 (95% CI: 0.830-0.944) (P < .001). The AUC of serum IL-27 for pulmonary TB was 0.703 (95% CI: 0.616-0.781) (P < .001). In patients with negative sputum smear results, the AUCs of BALF IL-27 and serum IL-27 for pulmonary TB was 0.882 (95% confidence interval [CI]: 0.805-0.936) (P < .001) and 0.679 (95% CI: 0.601-0.782) (P < .001), respectively. CONCLUSIONS: BALF IL-27 can be used for the diagnosis of pulmonary TB, particularly in those with a negative sputum smear result. Serum IL-27 could be an auxiliary method for TB screening.

Controllable Synthesis of Enhanced Visible Light Responded Fe, N, Co Tri-TiO2@MCM-41 Nanocomposites and Its Photocatalytic Performance.

A novel method for in situ synthesis of Fe, N, Co tri-TiO2 (DT) loading on MCM-41 composite photocatalyst was proposed. Fe, N, Co tri-TiO2@MCM-41 (DTM) with adsorption-degradation synergy was prepared by adjusting tetrabutyl titanate (TBOT) concentrations, the alcohol-water ratio in the atmosphere of the reaction chamber. The influence of preparation parameters on the texture structure, catalytic activity, and the synergism of adsorption and degradation of the DTM was discussed, the optimal parameters were determined. The DTM was characterized by XRD, TEM, BET, FT-IR, and UV-Vis. Besides, the DTM exhibited obvious redshift and visible catalytic activity compared with undoped TiO2@MCM-41 (TM), which possessed excellent performance in the degradation of gaseous and liquid pollutants. The degradation rate of methylene blue (MB) and nitric oxide (NO) was 96.39% and 56.75%, respectively. Furthermore, DTM photocatalyst exhibited excellent reusability. The degradation efficiency of MB and NO after five cycles decreased by 4.54% and 5.89%, respectively.