Exploring the role of ITGB6: fibrosis, cancer, and other diseases.

Integrin ß6 (ITGB6), a member of the integrin family of proteins, is only present in epithelial tissues and frequently associates with integrin subunit αv to form transmembrane heterodimers named integrin αvß6. Importantly, ITGB6 determines αvß6 expression and availability. In addition to being engaged in organ fibrosis, ITGB6 is also directly linked to the emergence of cancer, periodontitis, and several potential genetic diseases. Therefore, it is of great significance to study the molecular-biological mechanism of ITGB6, which could provide novel insights for future clinical diagnosis and therapy. This review introduces the structure, distribution, and biological function of ITGB6. This review also expounds on ITGB6-related diseases, detailing the known biological effects of ITGB6.

Hemoadsorption in acute respiratory distress syndrome patients requiring venovenous extracorporeal membrane oxygenation: a systematic review.

BACKGROUND: Venovenous extracorporeal membrane oxygenation (VV ECMO) has been widely used for severe acute respiratory distress syndrome (ARDS) in recent years. However, the role of hemoadsorption in ARDS patients requiring VV ECMO is unclear. METHODS: Therefore, we conducted a systematic review to describe the effect of hemoadsorption on outcomes of ARDS patients requiring VV ECMO and elucidate the risk factors for adverse outcomes. We conducted and reported a systematic literature review based on the principles derived from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The systematic review searched Embase, CINHAL, and Pubmed databases for studies on ARDS patients receiving hemoadsorption and VV ECMO. The demographic data, clinical data and biological data of the patients were collected. RESULTS: We ultimately included a total of 8 articles including 189 patients. We characterized the population both clinically and biologically. Our review showed most studies described reductions in inflammatory markers and fluid resuscitation drug dosage in ARDS patients with Coronavirus disease 2019 (COVID-19) or sepsis after hemoadsorption. CONCLUSION: Because most of the studies have the characteristics of high heterogeneity, we could only draw very cautious conclusions that hemoadsorption therapy may enhance hemodynamic stability in ARDS patients with COVID-19 or sepsis receiving VV ECMO support. However, our results do not allow us to draw conclusions that hemoadsorption could reduce inflammation and mortality. Prospective randomized controlled studies with a larger sample size are needed in the future to verify the role of hemoadsorption in ARDS patients requiring VV ECMO.

A Cu/MnOx Composite with Copper-Doping-Induced Oxygen Vacancies as a Cathode for Aqueous Zinc-Ion Batteries.

Aqueous zinc-ion batteries are anticipated to be the next generation of important energy storage devices to replace lithium-ion batteries due to the ongoing use of lithium resources and the safety hazards associated with organic electrolytes in lithium-ion batteries. Manganese-based compounds, including MnOx materials, have prominent places among the many zinc-ion battery cathode materials. Additionally, Cu doping can cause the creation of an oxygen vacancy, which increases the material's internal electric field and enhances cycle stability. MnOx also has great cyclic stability and promotes ion transport. At a current density of 0.2 A g-1, the Cu/MnOx nanocomposite obtained a high specific capacitance of 304.4 mAh g-1. In addition, Cu/MnOx nanocomposites showed A high specific capacity of 198.9 mAh g-1 after 1000 cycles at a current density of 0.5 A g-1. Therefore, Cu/MnOx nanocomposites are expected to be a strong contender for the next generation of zinc-ion battery cathode materials in high energy density storage systems.

Dynamic Changes in Ion Channels during Myocardial Infarction and Therapeutic Challenges.

In different areas of the heart, action potential waveforms differ due to differences in the expressions of sodium, calcium, and potassium channels. One of the characteristics of myocardial infarction (MI) is an imbalance in oxygen supply and demand, leading to ion imbalance. After MI, the regulation and expression levels of K+, Ca2+, and Na+ ion channels in cardiomyocytes are altered, which affects the regularity of cardiac rhythm and leads to myocardial injury. Myocardial fibroblasts are the main effector cells in the process of MI repair. The ion channels of myocardial fibroblasts play an important role in the process of MI. At the same time, a large number of ion channels are expressed in immune cells, which play an important role by regulating the in- and outflow of ions to complete intracellular signal transduction. Ion channels are widely distributed in a variety of cells and are attractive targets for drug development. This article reviews the changes in different ion channels after MI and the therapeutic drugs for these channels. We analyze the complex molecular mechanisms behind myocardial ion channel regulation and the challenges in ion channel drug therapy.

Blahut-Arimoto Algorithms for Inner and Outer Bounds on Capacity Regions of Broadcast Channels.

The celebrated Blahut-Arimoto algorithm computes the capacity of a discrete memoryless point-to-point channel by alternately maximizing the objective function of a maximization problem. This algorithm has been applied to degraded broadcast channels, in which the supporting hyperplanes of the capacity region are again cast as maximization problems. In this work, we consider general broadcast channels and extend this algorithm to compute inner and outer bounds on the capacity regions. Our main contributions are as follows: first, we show that the optimization problems are max-min problems and that the exchange of minimum and maximum holds; second, we design Blahut-Arimoto algorithms for the maximization part and gradient descent algorithms for the minimization part; third, we provide convergence analysis for both parts. Numerical experiments validate the effectiveness of our algorithms.

The complexity of p53-mediated metabolic regulation in tumor suppression.

Although the classic activities of p53 including induction of cell-cycle arrest, senescence, and apoptosis are well accepted as critical barriers to cancer development, accumulating evidence suggests that loss of these classic activities is not sufficient to abrogate the tumor suppression activity of p53. Numerous studies suggest that metabolic regulation contributes to tumor suppression, but the mechanisms by which it does so are not completely understood. Cancer cells rewire cellular metabolism to meet the energetic and substrate demands of tumor development. It is well established that p53 suppresses glycolysis and promotes mitochondrial oxidative phosphorylation through a number of downstream targets against the Warburg effect. The role of p53-mediated metabolic regulation in tumor suppression is complexed by its function to promote both cell survival and cell death under different physiological settings. Indeed, p53 can regulate both pro-oxidant and antioxidant target genes for complete opposite effects. In this review, we will summarize the roles of p53 in the regulation of glucose, lipid, amino acid, nucleotide, iron metabolism, and ROS production. We will highlight the mechanisms underlying p53-mediated ferroptosis, AKT/mTOR signaling as well as autophagy and discuss the complexity of p53-metabolic regulation in tumor development.

PTBP1 drives c-Myc-dependent gastric cancer progression and stemness.

BACKGROUND: Gastric cancer (GC) tumorigenesis and treatment failure are caused by cancer stem cells. Polypyrimidine tract binding protein 1 (PTBP1) was shown to be involved in the development of embryonic stem cells and is now being considered as a therapeutic target for tumour progression and stem-cell characteristics. METHODS: PTBP1 expression in GC samples was detected using tissue microarrays. Proliferation, colony formation, spheroid formation and stem-cell analysis were used to examine PTBP1's role in tumorigenesis and stem-cell maintenance. In AGS and HGC-27 cells with or without PTBP1 deficiency, ubiquitin-related protein expression and co-precipitation assays were performed. RESULTS: We identified that PTBP1 was aberrantly highly expressed and represented a novel prognostic factor in GC patients. PTBP1 maintained the tumorigenic activity and stem-cell characteristics of GC in vitro and in vivo. PTBP1 directly interacts with c-Myc and stabilises its protein levels by preventing its proteasomal degradation. This is mediated by upregulating the ubiquitin-specific proteases USP28 and limiting FBW7-mediated ubiquitination of c-Myc. Moreover, the depletion of PTBP1-caused tumour regression was significantly compromised by exogenous c-Myc expression. CONCLUSIONS: By preserving the stability of c-Myc through the ubiquitin-proteasome pathway, the oncogene PTBP1 supports stem-cell-like phenotypes of GC and is involved in GC progression.

A LncRNA gene polymorphism (rs1814343) is associated with the risk of coronary artery lesions in southern Chinese Kawasaki disease patients.

BACKGROUND: Kawasaki disease (KD) is a multisystemic angiitis, and its most disastrous complication is coronary artery lesions (CALs). Recently, the role of long non-coding RNAs (lncRNAs) in KD has been reported. rs1814343 is a lncRNA, but the relationship between the lncRNA rs1814343 polymorphism and KD risk remains elusive. METHODS: We enrolled 1625 Kawasaki disease patients (583 patients with CAL and 1042 without CAL) and 1000 healthy controls from a southern Chinese population. We genotyped the rs1814343 C > T polymorphism in KD and control patients using the TaqMan method. The odds ratio (OR) and 95% confidence interval (CI) were used to estimate the strength of the association. RESULTS: There was no significant association between the lncRNA rs1814343 C > T polymorphism and KD susceptibility. However, we stratified patients in this study by CAL and sex. First, compared with the control groups, we found that the rs1814343 genotype increased risk for KD patients with CAL (TT vs. CC + CT: OR = 1.36, 95% CI = 1.08-1.71, p = 0.009). Moreover, when KD patients were stratified by CAL, the TT genotypes of this lncRNA polymorphism contributed to a relatively higher occurrence of KD with CAL than that was found in the CC/CT genotype patients (TT vs. CC + CT: OR = 1.35, 95% CI = 1.07-1.69, p = 0.011). In addition, our research suggested that the TT variant genotype in the lncRNA rs1814343 had an obvious risk of KD with CAL susceptibility in male children. CONCLUSION: The lncRNA rs1814343 C > T polymorphism was related to higher susceptibility of KD with CAL.

PTBP1 plays an important role in the development of gastric cancer.

BACKGROUND: Polypyrimidine tract binding protein 1 (PTBP1) has been found to play an important role in the occurrence and development of various tumors. At present, the role of PTBP1 in gastric cancer (GC) is still unknown and worthy of further investigation. METHODS: We used bioinformatics to analyze the expression of PTBP1 in patients with GC. Cell proliferation related experiments were used to detect cell proliferation after PTBP1 knockdown. Skeleton staining, scanning electron microscopy and transmission electron microscopy were used to observe the changes of actin skeleton. Proliferation and actin skeleton remodeling signaling pathways were detected by Western Blots. The relationship between PTBP1 and proliferation of gastric cancer cells was further detected by subcutaneous tumor transplantation. Finally, tissue microarray data from clinical samples were used to further explore the expression of PTBP1 in patients with gastric cancer and its correlation with prognosis. RESULTS: Through bioinformatics studies, we found that PTBP1 was highly expressed in GC patients and correlated with poor prognosis. Cell proliferation and cycle analysis showed that PTBP1 down-regulation could significantly inhibit cell proliferation. The results of cell proliferation detection related experiments showed that PTBP1 down-regulation could inhibit the division and proliferation of GC cells. Furthermore, changes in the morphology of the actin skeleton of cells showed that PTBP1 down-regulation inhibited actin skeletal remodeling in GC cells. Western Blots showed that PTBP1 could regulate proliferation and actin skeleton remodeling signaling pathways. In addition, we constructed PTBP1 Cas9-KO mouse model and performed xenograft assays to further confirm that down-regulation of PTBP1 could inhibit the proliferation of GC cells. Finally, tissue microarray was used to further verify the close correlation between PTBP1 and poor prognosis in patients with GC. CONCLUSIONS: Our study demonstrates for the first time that PTBP1 may affect the proliferation of GC cells by regulating actin skeleton remodeling. In addition, PTBP1 is closely related to actin skeleton remodeling and proliferation signaling pathways. We suppose that PTBP1 might be a potential target for the treatment of GC.

Establishment and identification of an animal model of Hirschsprung disease in suckling mice.

BACKGROUND: Hirschsprung disease (HSCR) is a congenital intestinal malformation. Previous HSCR animal model needs invasive operation on adult animal. The aim of this study is to establish an early-onset animal model which is consistent with the clinical manifestation of HSCR patients. METHODS: The neonatal mice were randomly divided into the benzalkonium chloride (BAC) group, treated with BAC via enema, and the control group, treated with saline. Weight changes, excretion time of carmine, CT scan, hematoxylin-eosin staining and immunofluorescence staining were used to evaluate the effect of the model. Differentially expressed genes (DEGs) in the HSCR mice were analyzed by using DAVID 6.8 database and compared with DEGs from HSCR patients. RESULTS: The weight of mice was lower and the excretion time of carmine was longer in the BAC group. Moreover, distal colon stenosis and proximal colon enlargement appeared in the BAC group. Neurons in the distal colon decreased significantly after 4 weeks of BAC treatment and almost disappeared completely after 12 weeks. Transcriptome profiling of the mouse model and HSCR patients is similar in terms of altered gene expression. CONCLUSIONS: An economical and reliable HSCR animal model which has similar clinical characteristics to HSCR patients was successfully established. IMPACT: The animal model of Hirschsprung disease was first established in BALB/c mice. This model is an animal model of early-onset HSCR that is easy to operate and consistent with clinical manifestations. Transcriptome profiling of the mouse model and HSCR patients is similar in terms of altered gene expression.

Curcumin-dependent phenotypic transformation of microglia mediates resistance to pseudorabies-induced encephalitis.

Pseudorabies virus (PRV) causes viral encephalitis, a devastating disease with high mortality worldwide. Curcumin (CUR) can reduce inflammatory damage by altering the phenotype of microglia; however, whether and how these changes mediate resistance to PRV-induced encephalitis is still unclear. In this study, BV2 cells were infected with/without PRV for 24 h and further treated with/without CUR for 24 h. The results indicated that CUR promoted the polarization of PRV-infected BV2 cells from the M1 phenotype to the M2 phenotype and reversed PRV-induced mitochondrial dysfunction. Furthermore, M1 BV2 cell secretions induced signalling pathways leading to apoptosis in PC-12 neuronal cells, and this effect was abrogated by the secretions of M2 BV2 cells. RNA sequencing and bioinformatics analysis predicted that this phenotypic shift may be due to changes in energy metabolism. Furthermore, Western blot analysis showed that CUR inhibited the increase in AMP-activated protein kinase (AMPK) phosphorylation, glycolysis, and triacylglycerol synthesis and the reduction in oxidative phosphorylation induced by PRV infection. Moreover, the ATP levels in M2 BV2 cells were higher than those in M1 cells. Furthermore, CUR prevented the increase in mortality, elevated body temperature, slowed growth, nervous system excitation, brain tissue congestion, vascular cuffing, and other symptoms of PRV-induced encephalitis in vivo. Thus, this study demonstrated that CUR protected against PRV-induced viral encephalitis by switching the phenotype of BV2 cells, thereby protecting neurons from inflammatory injury, and this effect was mediated by improving mitochondrial function and the AMPK/NF-κB p65-energy metabolism-related pathway.

Leaf Spot of Sanhua Plum caused by Botryosphaeria wangensis in China.

Sanhua plum (Prunus salicina L.) is planted widely in Babu district of Hezhou, Guangxi with a planting history of more than 70 years (Zhou et al., 2021). In August 2021, leaf spot disease was observed with approximately 50% incidence on Sanhua plum leaves in Babu district in Hezhou, Guangxi (N23°49'-24°48', E111°12'-112°03'). The symptoms initially appeared as small, round, and chlorotic spots. As the disease progressed, the lesions enlarged and margins became dark brown. To isolate the pathogen, small pieces (5 × 5 mm) of the infected tissue margins were sterilized by exposure to 75% ethanol for 10 sec, 2% sodium hypochlorite for 1 min and rinsed three times in sterile water. Pieces were incubated on potato dextrose agar (PDA) at 28℃. In total, 75 isolates were obtained from leaves which were collected from three trees. Fifty of them were morphologically identical with a 67% average isolation frequency. Three representative isolates (HZ13-1, HZ26-3 and HZ47-1) were selected for further study. The cultures on PDA were initially white, fluffy with uneven margins and turned smoky gray to olivaceous at the surface. The reverse sides were olivaceous gray to iron gray after seven days. The growth rate of mycelium was 2.5 cm/day. Conidia were produced after two weeks by exposure to near-fluorescent light for 10 hours per day. Conidia were fusiform, hyaline, thin-walled, smooth with granular contents unicellular, and 19.7 ± 0.13 × 5.8 ± 0.06 µm (n=90), 19.8 ± 0.09 × 6.5 ± 0.23 µm (n=90), and 20.6 ± 0.20 × 6.7 ± 0.12 µm (n=90) for HZ13-1, HZ26-3 and HZ47-1, respectively. These characteristics were consistent with the descriptions of the Botryosphaeria wangensis (Hattori et al. 2021). The DNA was extracted from mycelia, and the internal transcribed spacer (ITS), elongation factor 1-alpha gene (EF1-α) and ß-tubulin (TUB2) were amplified using the primer pairs ITS1/ITS4, EF1-728F/EF1-986R and T1/BT2b (White et al. 1990, Carbone et al. 1999, Yu et al. 2021), respectively. The sequences were compared with GenBank and they all showed over 99% identity to the type strain of B. wangensis CERC 2298 (Li et al. 2020). Sequences of the three isolates were deposited in GenBank (Accession Nos.: ITS, OP804110-OP804112; EF1-α, OP821748-OP821750; TUB2, OP821745-OP821747). The three isolates were identified as B. wangensis based on the maximum likelihood phylogenetic tree of concatenated sequences of ITS, EF1-α, and TUB2 with RAxML version 2.0. Pathogenicity tests were performed on healthy leaves of 2-year-old Sanhua plum, which were wounded by a sterilized needle in a greenhouse. A 5-mm-diam hyphal plug was placed on the wound. Each isolate was used to inoculate three plants, with 20 leaves per plant. Control plants were inoculated with sterile PDA plugs. All the plants were sprayed with distilled water and covered with plastic bags. After four days of incubation at 28℃ with constant light, lesion began to develop in the inoculated leaves. After ten days, the average diameter of lesions was up to 1.5 cm but controls remained symptom-free. The fungi were reisolated from inoculated symptomatic leaves and were identical to the inoculated isolates, thus completing Koch's postulates. To our knowledge, this is the first report of B. wangensis associated with leaf spot of Sanhua plum in China. The results will contribute to accelerating the development of future epidemiological studies of B. wangensis on Sanhua plum.

Bacterial Leaf Spot of Plum Caused by Sphingomonas spermidinifaciens in Guangxi, China.

Plum (Prunus salicina L.) is a traditional fruit in Southern China and is ubiquitous throughout the world. In August 2021, leaves of plum trees showed water-soaking spots and light yellow-green halos with incidence exceeding 50% in Babu district in Hezhou, Guangxi (N23°49'-24°48', E111°12'-112°03'). To isolate the causal agent, three diseased leaves collected from three different trees growing in different orchards were cut into 5 mm × 5 mm pieces, disinfected with 75% ethanol for 10 sec, 2% sodium hypochlorite for 1 min and rinsed three times in sterile water. The diseased pieces were ground in sterile water and then kept static for about 10 min. Ten-fold serial dilutions in water were prepared and 100 µL of each dilution from 10-1 to 10-6 were plated on Luria-Bertani (LB) Agar. After incubation at 28℃ for 48 h, the proportion of isolates with similar morphology was 73%. Three representative isolates (GY11-1, GY12-1 and GY15-1) were selected for further study. The colonies were non-spore-forming, yellow, round, opaque, rod shaped, convex with smooth and bright neat edges. Biochemical test results showed that the colonies were strictly aerobic and gram-negative. The isolates were able to grow on LB agar containing 0-2% (w/v) NaCl and could utilize glucose, lactose, galactose, mannose, sucrose, maltose and rhamnose as a carbon source. They displayed a positive reaction for H2S production, oxidase, catalase and gelatin, but negative for starch. Genomic DNA of the three isolates was extracted for amplification of the 16S rDNA with primers 27F and 1492R. The resulting amplicons were sequenced. Additionally, five housekeeping genes atpD, dnaK, gap, recA, and rpoB of the three isolates were amplified using the corresponding primer pairs and sequenced. The sequences were deposited in GenBank (16S rDNA, OP861004-OP861006; atpD, OQ703328-OQ703330; dnaK, OQ703331-OQ703333; gap, OQ703334-OQ703336; recA, OQ703337-OQ703339; and rpoB, OQ703340-OQ703342). The isolates were identified as Sphingomonas spermidinifaciens based on the phylogenetic tree inferred by maximum-likelihood using MegaX 7.0 of the concatenated six sequences (multilocus sequence analysis, MLSA) compared with sequences from different Sphingomonas type strains . Pathogenicity of the isolates was tested on healthy leaves of the two-year-old plum plants in a greenhouse. The leaves were wounded by a sterilized needle and sprayed with bacterial suspensions prepared in PBS (Phosphate buffer saline) at OD600=0.5. PBS buffer solution was used as negative control. Each isolate was used to inoculate on 20 leaves per plum tree. The plants were covered with plastic bags to maintain high humidity. Dark brown-to-black lesions were observed on leaves 3 days post incubation at 28℃ with constant light. The average diameter of lesions was 1 cm after seven days, but the negative controls were symptomless. Bacteria reisolated from the diseased leaves were the same as the ones used for inoculation on the basis of morphological and molecular identification, fulfilling Koch's postulates. Plant disease caused by a Sphingomonas species has been reported on mango, pomeand Spanish melon. However, this is the first report of S. spermidinifaciens causing leaf spot disease of plum in China. This report will help to develop effective disease control strategies in the future.

Triptonodiol, a Diterpenoid Extracted from Tripterygium wilfordii, Inhibits the Migration and Invasion of Non-Small-Cell Lung Cancer.

Lung cancer is the most prevalent oncological disease worldwide, with non-small-cell lung cancer accounting for approximately 85% of lung cancer cases. Tripterygium wilfordii is a traditional Chinese herb that is widely used to treat rheumatism, pain, inflammation, tumors, and other diseases. In this study, we found that Triptonodiol extracted from Tripterygium wilfordii inhibited the migration and invasion of non-small-cell lung cancer and inhibited cytoskeletal remodeling, which has not been previously reported. Triptonodiol significantly inhibited the motility activity of NSCLC at low toxic concentrations and suppressed the migration and invasion of NSCLC. These results can be confirmed by wound healing, cell trajectory tracking, and Transwell assays. We found that cytoskeletal remodeling was inhibited in Triptonodiol-treated NSCLC, as evidenced by the reduced aggregation of actin and altered pseudopod morphology. Additionally, this study found that Triptonodiol induced an increase in complete autophagic flux in NSCLC. This study suggests that Triptonodiol reduces the aggressive phenotype of NSCLC by inhibiting cytoskeletal remodeling and is a promising anti-tumor compound.

Prediction model for labour dystocia occurring in the active phase.

To establish and verify a model for labour dystocia occurring in the active phase, this study retrospectively analysed the clinical data of primiparas with singleton cephalic full-term foetuses, who had delivered after a trial of labour. The Chi-square test, t-test, Mann-Whitney U test and multivariate logistic regression analysis were used for statistical analysis. Based on the model a nomogram was established using the R programming language. Multivariate logistic regression analysis showed that the foetal abdominal circumference, premature rupture of membranes (PROM), prolonged latent phase, foetal station and foetal position at the early stage of the active phase were independent factors influencing labour dystocia occurring in the active phase. The established model could effectively and accurately support clinicians in the early identification of labour dystocia to improve maternal and infant outcomes.Impact statementWhat is already known on this subject? Labour dystocia occurring during the active phase of the first stage, is the most commonly diagnosed as labour aberration. Previous studies have suggested that maternal age, body mass index, macrosomia and abnormal foetal position are the independent risk factors for labour dystocia. However, only the risk factors were reported, and few prediction models were established.What do the results of this study add? This study uses data in the real world to establish a prediction model of full-term singleton primipara with labour dystocia occurring in the active phase by logistic regression analysis. Foetal abdomen circumference, PROM, prolonged latent phase, the foetal station and foetal position at the early stage of the active phase are independent factors influencing labour dystocia that occurs in the active phase. In addition, a nomogram is established as a visual graph to predict the probability of it.What are the implications of these findings for clinical practice and/or further research? The nomogram based on the predictive model discarded complicated calculations and presented an easy visual graph-based method to predict the probability of labour dystocia occurring in the active phase. It helps to introduce interventions that could reduce the CS rate and occurrence of adverse maternal and foetal outcomes to ensure the safety of mothers and infants.

Study on influencing parameters and long-term operation of electrocoagulation phosphorus removal from small rural domestic sewage.

Excessive discharge of phosphorus can produce eutrophication in aquatic environments, damaging public health, the living environment, and the economy. The conventional mechanical-biological phosphorus removal methods are not suitable for small rural domestic sewage due to the features of small scale, scattered distribution, intermittent emission, and large fluctuation. This work evaluated electrocoagulation (EC) with industrial steel as electrodes on small rural domestic sewage. Results showed that the best performance was achieved at a current density of 1 mA/cm2, electrode distance of 2 cm, electrode number of 2, pH of 7, and Hydraulic Retention Time of 30 min, respectively. Under optimum conditions, the EC process removed 93.91% phosphorus while consuming around 0.25 kWh/m3 of electricity. In addition, the electrode passivation of EC was further investigated; the long-term research found that the phosphorus removal efficiency only decreased by 4.34% after 10 days of continuous flow operation, and the operational energy consumption was 0.07 kWh/m3 at a Cl- concentration of 500 mg/L.

Development and validation of a prediction model for tuberculous pleural effusion: a large cohort study and external validation.

BACKGROUND: Distinguishing tuberculous pleural effusion (TPE) from non-tuberculosis (TB) benign pleural effusion (BPE) remains to be a challenge in clinical practice. The aim of the present study was to develop and validate a novel nomogram for diagnosing TPE. METHODS: In this retrospective analysis, a total of 909 consecutive patients with TPE and non-TB BPE from Ningbo First Hospital were divided into the training set and the internal validation set at a ratio of 7:3, respectively. The clinical and laboratory features were collected and analyzed by logistic regression analysis. A diagnostic model incorporating selected variables was developed and was externally validated in a cohort of 110 patients from another hospital. RESULTS: Six variables including age, effusion lymphocyte, effusion adenosine deaminase (ADA), effusion lactatedehy drogenase (LDH), effusion LDH/effusion ADA, and serum white blood cell (WBC) were identified as valuable parameters used for developing a nomogram. The nomogram showed a good diagnostic performance in the training set. A novel scoring system was then established based on the nomogram to distinguish TPE from non-TB BPE. The scoring system showed good diagnostic performance in the training set [area under the curve (AUC) (95% confidence interval (CI)), 0.937 (0.917-0.957); sensitivity, 89.0%, and specificity, 89.5%], the internal validation set [AUC (95%CI), 0.934 (0.902-0.966); sensitivity, 88.7%, and specificity, 90.3%], and the external validation set [(AUC (95%CI), 0.941 (0.891-0.991); sensitivity, 93.6%, and specificity, 87.5%)], respectively. CONCLUSIONS: The study developed and validated a novel scoring system based on a nomogram originated from six clinical parameters. The novel scoring system showed a good diagnostic performance in distinguishing TPE from non-TB BPE and can be conveniently used in clinical settings.

Radical Acylalkylation of 1,3-Enynes To Access Allenic Ketones via N-Heterocyclic Carbene Organocatalysis.

An N-heterocyclic carbene organocatalytic 1,4-difunctionalization of 1,3-enynes was developed. This organocatalytic strategy was suitable for a broad spectrum of substrates to efficiently synthesize allenic ketones bearing diverse substituents. Preliminary mechanistic studies suggest a radical reaction pathway for this organocatalytic acylalkylation process.

Asymmetric organocatalysis: an enabling technology for medicinal chemistry.

The efficacy and synthetic versatility of asymmetric organocatalysis have contributed enormously to the field of organic synthesis since the early 2000s. As asymmetric organocatalytic methods mature, they have extended beyond the academia and undergone scale-up for the production of chiral drugs, natural products, and enantiomerically enriched bioactive molecules. This review provides a comprehensive overview of the applications of asymmetric organocatalysis in medicinal chemistry. A general picture of asymmetric organocatalytic strategies in medicinal chemistry is firstly presented, and the specific applications of these strategies in pharmaceutical synthesis are systematically described, with a focus on the preparation of antiviral, anticancer, neuroprotective, cardiovascular, antibacterial, and antiparasitic agents, as well as several miscellaneous bioactive agents. The review concludes with a discussion of the challenges, limitations and future prospects for organocatalytic asymmetric synthesis of medicinally valuable compounds.

Oxygen-Glucose Deprivation Promoted Fibroblast Senescence and Collagen Expression via IL11.

Cell senescence is one of the most important forms of injury induced by cardiovascular and other ischemic diseases. Fibroblasts are important participants in tissue repair after ischemic injury and the main source of IL11 secretion. However, the roles of oxygen-glucose deprivation (OGD) and IL11 in promoting fibroblast senescence and their regulatory mechanisms remain unclear. This study selected the NIH3T3 and L929 fibroblast cell lines as research objects. We found that OGD could induce the expression of p53, P16, p21, and collagen in fibroblasts. In the condition of OGD, when IL11 intervened, fibroblasts' senescence and collagen expression were changed. Some studies have found that changes in kynurenine (KYN) metabolism are related to aging diseases, and indoleamine 2,3-dioxygenase 1 (IDO1) is a key rate-limiting enzyme in the KYN metabolic pathway. We found that KYN secretion decreased after OGD increased fibroblast senescence, and inhibition of IL11 promoted IDO1 and increased KYN secretion. These results suggest that OGD may promote fibroblast senescence and collagen expression via IL11 inhibition of the IDO1/KYN metabolic pathway. Therefore, the revealed mechanism of OGD-promoted fibroblast senescence could provide an effective theoretical basis for the clinical treatment of aging-related ischemic diseases.