Generation and Application of Mouse-Rat Allodiploid Embryonic Stem Cells.

Mammalian interspecific hybrids provide unique advantages for mechanistic studies of speciation, gene expression regulation, and X chromosome inactivation (XCI) but are constrained by their limited natural resources. Previous artificially generated mammalian interspecific hybrid cells are usually tetraploids with unstable genomes and limited developmental abilities. Here, we report the generation of mouse-rat allodiploid embryonic stem cells (AdESCs) by fusing haploid ESCs of the two species. The AdESCs have a stable allodiploid genome and are capable of differentiating into all three germ layers and early-stage germ cells. Both the mouse and rat alleles have comparable contributions to the expression of most genes. We have proven AdESCs as a powerful tool to study the mechanisms regulating X chromosome inactivation and to identify X inactivation-escaping genes, as well as to efficiently identify genes regulating phenotypic differences between species. A similar method could be used to create hybrid AdESCs of other distantly related species.

PEBP4 deficiency aggravates LPS-induced acute lung injury and alveolar fluid clearance impairment via modulating PI3K/AKT signaling pathway.

Acute lung injury (ALI) is a common clinical syndrome, which often results in pulmonary edema and respiratory distress. It has been recently reported that phosphatidylethanolamine binding protein 4 (PEBP4), a basic cytoplasmic protein, has anti-inflammatory and hepatoprotective effects, but its relationship with ALI remains undefined so far. In this study, we generated PEBP4 knockout (KO) mice to investigate the potential function of PEBP4, as well as to evaluate the capacity of alveolar fluid clearance (AFC) and the activity of phosphatidylinositide 3-kinases (PI3K)/serine-theronine protein kinase B (PKB, also known as AKT) signaling pathway in lipopolysaccharide (LPS)-induced ALI mice models. We found that PEBP4 deficiency exacerbated lung pathological damage and edema, and increased the wet/dry weight ratio and total protein concentration of bronchoalveolar lavage fluid (BALF) in LPS-treated mice. Meanwhile, PEBP4 KO promoted an LPS-induced rise in the pulmonary myeloperoxidase (MPO) activity, serum interleuin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α levels, and pulmonary cyclooxygenase-2 (COX-2) expression. Mechanically, PEBP4 deletion further reduced the protein expression of Na+ transport markers, including epithelial sodium channel (ENaC)-α, ENaC-γ, Na,K-ATPase α1, and Na,K-ATPase ß1, and strengthened the inhibition of PI3K/AKT signaling in LPS-challenged mice. Furthermore, we demonstrated that selective activation of PI3K/AKT with 740YP or SC79 partially reversed all of the above effects caused by PEBP4 KO in LPS-treated mice. Altogether, our results indicated the PEBP4 deletion has a deterioration effect on LPS-induced ALI by impairing the capacity of AFC, which may be achieved through modulating the PI3K/AKT pathway.

Highly Sensitive and Selective Detection of Pharmaceuticals on Au/MIL-101(Cr) by SERS.

The detection of pharmaceuticals has been a matter of concern among scientists and health researchers in the past few decades. However, it is still difficult to realize the sensitivity and selectivity detection of pharmaceuticals with similar structures. Herein, the pharmaceutical molecules of 2-mercaptobenzimidazole (MBI) and 2-mercaptobenzothiazole (MBT) with so similar structures can be selectively detected by surface-enhanced Raman spectroscopy (SERS) taking advantage of the fingerprint identification on Au/MIL-101(Cr), with sensitive detection limits of 0.5 ng·mL-1 for MBI and 1 ng·mL-1 for MBT. MBI is selectively enriched by Au/MIL-101(Cr) from the mixture solution and detected by SERS below 30 ng·mL-1. MBI can also be selectively detected in the serum samples with a detection limit of 10 ng·mL-1. Density functional theory calculations combined with the SERS experiments explained that the high sensitivity and selectivity are caused by the intrinsic differences in Raman intensity and different adsorption energies from the pharmaceutical molecules adsorbed on Au/MIL-101(Cr), respectively. This study provides an effective way to enrich and detect pharmaceutical molecules with similar structures.

[Clinical characteristics of fetal cardiac disease in patients with anti-SSA antibody positive].

OBJECTIVE: To investigate the clinical manifestations and laboratory indicators of anti-Sjögren's-syndrome-related antigen A (SSA) antibody associated fetal cardiac disease. METHODS: Pregnant women hospitalized at Peking University People's Hospital from January 2013 to July 2023 were included. Eleven patients with anti-SSA antibody positive were eventually diagnosed with fetal cardiac di-sease. And patients with anti-SSA antibody positive without fetal cardiac disease were selected as controls. Clinical manifestations, laboratory indications and drug usage were compared between the two groups. RESULTS: Among these 11 patients, congenital heart block was confirmed in seven, which was the most common manifestations of fetal cardiac malformation. The proportion of the patients diagnosed with autoimmune disease before pregnancy in fetal cardiac malformation group was significantly lower than that in the control group (P=0.032), while most of the patients in the fetal cardiac malformation group received immune-related examinations for the first time because of this time's fetal cardiac diagnosis. While most of the patients in the control group received routine examinations because of autoimmune diseases diagnosed before pregnancy. During pregnancy, the white blood cell level [(9.29±2.58)×109/L vs. (7.10±1.90×109/L, t=3.052, P=0.004], erythrocyte sedimentation rate [(49.50 (48.00, 51.00) mm/h vs. 23.00 (15.00, 30.25) mm/h, Z=-2.251, P=0.024], IgA level [3.46 (2.30, 5.06) g/L vs. 2.13 (1.77, 2.77) g/L, Z=-2.181, P=0.029], and antinuclear antibody (ANA) titers [1∶320 (1∶160, 1∶320) vs. 1∶80 (1∶40, 1∶160), Z=-3.022, P=0.003] were significantly higher in fetal cardiac malformation group than in the control group. The proportion of positive anti-SSB antibody during pregnancy did not show a statistically significant difference between the two groups (37.5% vs. 7.7%, P=0.053). There was no significant difference in hydroxychloroquine dosage and initiation time between the two groups. The dosage of prednisone in the second and third trimesters was significantly higher in the cardiac malformation group than that in the control group, but there was no significant difference in the first trimester. CONCLUSION: Fetal cardiac disease is rare in pregnant women with anti-SSA antibody. White blood cell, erythrocyte sedimentation rate, IgA, the titer of ANA positivity were higher in the fetal heart disease group during pregnancy. Since congenital heart block is difficult to reverse, its prevention and monitoring are more important than remedial treatment.

Rat embryonic stem cells produce fertile offspring through tetraploid complementation.

Pluripotency of embryonic stem cells (ESCs) can be functionally assessed according to the developmental potency. Tetraploid complementation, through which an entire organism is produced from the pluripotent donor cells, is taken as the most stringent test for pluripotency. It remains unclear whether ESCs of other species besides mice can pass this test. Here we show that the rat ESCs derived under 2i (two small molecule inhibitors) conditions at very early passages are able to produce fertile offspring by tetraploid complementation. However, they lose this capacity rapidly during culture due to a nearly complete loss of genomic imprinting. Our findings support that the naïve ground state pluripotency can be captured in rat ESCs but also point to the species-specific differences in its regulation and maintenance, which have implications for the derivation and application of naïve pluripotent stem cells in other species including human.

Preferred Experience of Modifications to Emergency Surgical Treatment for Total Scalp Avulsion With Halo-Vest Head Ring and Quick Hair Removing.

BACKGROUND: Total scalp avulsion is a fairly rear but severe soft tissue injury. Even with microsurgical replantation, the survival rate is still low. In this study, the authors incorporated 2 main modifications (Halo-Vest head ring and quick hair removing) and assessed the surgical outcomes versus those of traditional replantation. METHODS:: Eighteen patients were included in the study who suffered from total scalp avulsion. After consideration of the outcomes from the first 7 patients, the authors modified our surgical procedures and introduced the use of Halo-Vest head ring and quick hair removing in the treatments for the rest 11 patients. The surgical outcomes with both approaches were observed and compared, including the operation time and incidence of scalp necrosis. RESULTS:: The mean debridement time was 3.5 hours in traditional treatment versus 1.68 hours in modified treatment. The mean operative time was 11.14 hours in traditional treatment versus 8.05 hours in modified treatment. After the replantation, in those 7 patients without modifications, there was 1 total scalp necrosis and 6 partial scalp necrosis. In those 11 patients with modifications, there was 1 total scalp necrosis and 1 suffered a partial scalp necrosis, while the scalp survived well in other 9 patients. Classical cases with modified or traditional methods were reported respectively. CONCLUSION: The application of Halo-Vest head ring and quick hair removing provides a reliable method to treat total scalp avulsion. It is safe, technically easy and worth being widely used in the clinical application.

Long Noncoding RNA CIR Promotes Chondrocyte Extracellular Matrix Degradation in Osteoarthritis by Acting as a Sponge For Mir-27b.

BACKGROUND/AIMS: Osteoarthritis (OA) is a degenerative joint disease characterized by articular cartilage degradation. The degradation of the extracellular matrix (ECM) of chondrocyte is closely associated with the destruction of joints in OA patients. lncRNAs are non-coding segments of RNA that possess important regulatory functions at the cellular level and in a variety of pathophysiological processes. The present study was conducted to investigate whether lncRNA-CIR regulated the expression of MMP13 as a sponge of miR-27 in OA. METHODS: Primary cultured chondrocytes were challenged by IL-1ß and TNF-α to simulate OA conditions. qRT-PCR was performed to detect the miR-27, lncRNA-CIR, MMP13 mRNA expression levels. Western blot was applied to detect MMP13 protein expression. Soluble sGAG secretion/ formation was analysed by the dimethylmethylene blue (DMMB) assay. lncRNA-CIR overexpression or inhibition was performed using overexpression plasmid and small interfering RNAs (siRNAs), respectively. RESULTS: lncRNA-CIR significantly up-regulated in OA patients, concomitantly down-regulated miR-27 and up-regulated MMP13. Bioinformatics analysis predicted miR-27 was the target of both lncRNA-CIR and MMP13. Overexpression of lncRNA-CIR significantly increased the expression of MMP13, while miR-27 remarkably suppressed the expression of MMP13, Accompanying with the increases of mRNA level, protein level and relative luciferase activity. CONCLUSION: The present findings indicated that lncRNA-CIR/miR-27/MMP13 axis involved in the degradation of the ECM of chondrocyte in OA.

(-)-Epigallocatechin-3-Gallate Inhibits Arsenic-Induced Inflammation and Apoptosis through Suppression of Oxidative Stress in Mice.

BACKGROUND/AIMS: Exposure to arsenic in individuals has been found to be associated with various health-related problems including skin lesions, cancer, and cardiovascular and immunological disorders. (-)-Epigallocatechin-3-gallate (EGCG), the main and active polyphenolic catechin present in green tea, has shown potent antioxidant, anti-apoptotic and anti-inflammatory activity in vivo and in vitro. Thus, the present study was conducted to investigate the protective effects of EGCG against arsenic-induced inflammation and immunotoxicity in mice. METHODS: Serum IL-1ß, IL-6 and TNF-α were determined by ELISA, tissue catalase (CAT), malonyldialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), nitric oxide and caspase 3 by commercial kits, mitochondrial membrane potential with Rh 123, mitochondrial ROS with 2',7'-dichlorofluorescin diacetate (DCFH-DA), apoptotic and necrotic cells and T-cell phenotyping with Flow cytometry analysis. RESULTS: The results showed that arsenic treatment significantly increased oxidative stress levels (as indicated by catalase, malonyldialdehyde, superoxide dismutase, glutathione and reactive oxygen species), increased levels of inflammatory cytokines and promoted apoptosis. Arsenic exposure increased the relative frequency of the CD8+(Tc) cell subpopulation (from 2.8 to 18.9%) and decreased the frequency of CD4+(Th) cells (from 5.2 to 2.7%). Arsenic exposure also significantly decreased the frequency of T(CD3) (from 32.5% to 19.2%) and B(CD19) cells (from 55.1 to 32.5%). All of these effects induced by NaAsO2 were attenuated by EGCG. CONCLUSIONS: The present in vitro findings indicate that EGCG attenuates not only NaAsO2-induced immunosuppression but also inflammation and apoptosis.

Expression of Acid-Sensing Ion Channels in Renal Tubular Epithelial Cells and Their Role in Patients with Henoch-Schönlein Purpura Nephritis.

BACKGROUND Acid-sensing ion channels (ASICs) are ligand-gated cation channels activated by extracellular protons. However, the role of ASICs in kidney diseases remains uncertain. This study investigated ASICs expression in kidney tissues and their role in the development of Henoch-Schönlein purpura nephritis (HSPN). MATERIAL AND METHODS The expression of ASIC subunits was examined by immunochemical techniques in the kidney tissue from HSPN patients. Acid-induced ASICs expression in cultured renal tubular epithelial cells was determined by quantitative RT-PCR analysis. The expression of K7 and K18 protein in renal tubular epithelial cells was used to evaluate acid-induced cell injury. In addition, we observed the effect of blocking ASICs on acid-induced cell injury to assess the role of ASICs in renal tubular epithelial cell injury. RESULTS The results showed that ASIC1, ASIC2, and ASIC3 proteins were obviously expressed in renal tubular cells from HSPN patients. ASIC1 expression and 24-h urine protein level were higher in the pathological grade ISKD III group than in the ISKD II group. ASIC1, ASIC2, and ASIC3 mRNA, and K7 and K18 protein expression in cultured renal tubular epithelial cells were increased when exposed to pH 6.5. K7 and K18 protein expression was closely related to ASIC1 expression, and ASICs blockers reduced K7 and K18 protein expression in tubular epithelial cells. CONCLUSIONS These findings suggest ASICs are most highly expressed in renal tubular cells of HSPN patients, which is closely related to renal tubular injury. ASICs might be involved in the development of HSPN.

Acupuncture and related acupoint therapies for smoking cessation: An umbrella review and updated meta-analysis.

INTRODUCTION: Acupuncture and related acupoint therapies have been widely used for smoking cessation. Some relevant systematic reviews (SRs) have been published. There is a need to summarize and update the evidence to inform practice and decision-making. METHODS: Eight databases were searched from their inception to December 2023. SRs, any randomized controlled trials (RCTs) comparing acupuncture therapies with sham acupuncture, pharmacotherapy, behavioral therapy, or no treatment, were included. The primary outcome was the abstinence rate. AMSTAR-2 was employed to assess the quality of SRs. An updated meta-analysis was conducted based on SRs and RCTs. Data were synthesized using risk ratios (RR) with 95% confidence intervals (CIs). The GRADE approach was employed to assess the certainty of the updated evidence. RESULTS: Thirteen SRs and 20 RCTs outside of the SRs were identified. The SRs were of low or very low quality by AMSTAR-2. Sixteen (80%) RCTs were at high risk of performance bias. Eight acupuncture and related acupoint therapies were involved. The short-term (≤6 months) abstinence rate outcome was summarized as follows. Most SRs suggested that filiform needle acupuncture or acupressure had a better effect than sham acupuncture, but the findings were inconsistent. The updated meta-analysis also suggested that filiform needle acupuncture was more effective than sham acupuncture (RR=1.44; 95% CI: 1.02-2.02; I2 = 66%; low certainty; 9 RCTs, n=1358). Filiform needle acupuncture combined with acupressure was comparable to nicotine patches (RR=0.99; 95% CI: 0.74-1.32; low certainty; 6 RCTs, n= 524). Acupressure was superior to counseling (RR=1.46; 95% CI: 1.14-1.87; I2=5%; low certainty; 8 RCTs, n=595). No serious adverse events were reported in these SRs or RCTs. CONCLUSIONS: Low certainty evidence suggests that filiform needle acupuncture and auricular acupressure appear to be safe and effective in achieving short-term smoking cessation. However, long-term follow-up data are needed.

Chinese medicine Phragmites communis (Lu Gen) for acute respiratory tract infections: a systematic review and meta-analysis of randomized controlled trials.

Background: Acute respiratory tract infections (ARTIs) are the most common cause of morbidity and mortality worldwide, with most people experiencing at least one episode per year. Current treatment options are mainly symptomatic therapy. Antivirals, antibiotics, and glucocorticoids are of limited benefit for most infections. Traditional Chinese medicine has shown potential benefits in the treatment of ARTIs. Objective: The objective of this study was to determine the efficacy, effectiveness, and safety of Phragmites communis Trin. (P. communis, a synonym of Phragmites australis (Cav.) Trin. ex Steud) as monotherapy or as part of an herb mixture for ARTIs. Method: Eight databases and two clinical trial registries were searched from inception to 8 February 2023 for randomized controlled trials (RCTs) evaluating any preparation involving P. communis without language restrictions. The Risk of Bias Tool 2.0 was used to assess the risk of bias of the included trials. RevMan 5.3 software was used for data analyses with effects estimated as risk ratios (RRs), mean differences (MDs), or standardized mean differences (SMDs) with 95% confidence intervals (CIs). The online GRADEpro tool was used to assess the certainty of the evidence, if available. Results: Forty-two RCTs involving 6,879 patients with ARTIs were included, with all trials investigating P. communis as part of an herbal mixture. Of the included trials, the majority (38/42) were considered high risk. Compared to the placebo, P. communis preparations improved the cure rate [RR = 1.60, 95% CI (1.13, 2.26)] and fever clearance time [MD = -2.73 h, 95% CI (-4.85, -0.61)]. Compared to usual care alone, P. communis preparations also significantly improved the cure rate [RR = 1.57, 95% CI (1.36, 1.81)] and fever clearance time [SMD = -1.24, 95% CI (-2.37, -0.11)]. P. communis preparations plus usual care compared to usual care alone increased the cure rate [RR = 1.55, 95% CI (1.35, 1.78)], shortened the fever clearance time [MD = -19.31 h, 95% CI (-33.35, -5.27)], and improved FEV1 [ MD = 0.19 L, 95% CI (0.13, 0.26)] and FVC [ MD = 0.16 L, 95% CI (0.03, 0.28)]. Conclusion: Low- or very low-certainty evidence suggests that P. communis preparations may improve the cure rate of ARTIs, shorten the fever clearance time in febrile patients, and improve the pulmonary function of patients with acute exacerbation of chronic obstructive pulmonary disease or chronic bronchitis. However, these findings are inconclusive and need to be confirmed in rigorously designed trials. Systematic review registration: PROSPERO, identifier CRD42021239936.

Chinese herbal medicine Shufeng Jiedu capsule for mild to moderate COVID-19: a multicenter, randomized, double-blind, placebo-controlled phase II trial.

Background: The COVID-19 pandemic has had a profound global impact, although the majority of recently infected cases have presented with mild to moderate symptoms. Previous clinical studies have demonstrated that Shufeng Jiedu (SFJD) capsule, a Chinese herbal patent medicine, effectively alleviates symptoms associated with the common cold, H1N1 influenza, and COVID-19. This study aimed to assess the efficacy and safety of SFJD capsules in managing symptoms of mild to moderate COVID-19 infection. Methods: A randomized, double-blind, placebo-controlled trial was conducted from May to December 2022 at two hospitals in China. Mild and moderate COVID-19-infected patients presenting respiratory symptoms within 3 days from onset were randomly assigned to either the SFJD or placebo groups in a 1:1 ratio. Individuals received SFJD capsules or a placebo three times daily for five consecutive days. Participants were followed up for more than 14 days after their RT-PCR nucleoid acid test for SARS-CoV-2 turned negative. The primary outcome measure was time to alleviate COVID-19 symptoms from baseline until the end of follow-up. Results: A total of 478 participants were screened; ultimately, 407 completed the trial after randomization (SFJD, n = 203; placebo, n = 204). No statistically significant difference in baseline parameters was observed between the two groups. The median time to alleviate all symptoms was 7 days in the SFJD group compared to 8 days in the placebo group (p = 0.037). Notably, the SFJD group significantly attenuated fever/chills (p = 0.04) and headache (p = 0.016) compared to the placebo group. Furthermore, the median time taken to reach normal body temperature within 24 h was reduced by 7 hours in the SFJD group compared to the placebo group (p = 0.033). No deaths or instances of serious or critical conditions occurred during this trial period; moreover, no serious adverse events were reported. Conclusion: The trial was conducted in a unique controlled hospital setting, and the 5-day treatment with SFJD capsules resulted in a 1-day reduction in overall symptoms, particularly headache and fever/chills, among COVID-19-infected participants with mild or moderate symptoms. Compared to placebo, SFJD capsules were found to be safe with fewer side effects. SFJD capsules could potentially serve as an effective treatment for alleviating mild to moderate symptoms of COVID-19. Clinical Trial Registration: https://www.isrctn.com/, identifier ISRCTN14236594.

Classic citations in main plastic and reconstructive surgery journals.

BACKGROUND: The number of citations of an article in scientific journals reflects its impact on a biomedical specialty and its recognition in the scientific community. In this study, we identified and analyzed the 100 most highly cited articles published between 1971 and 2011 in journals pertaining to plastic and reconstructive surgery research. METHODS: We selected 6 high-impact journals for literature search in the database of the Science Citation Index (1971 to 2011). We identified the 100 most frequently cited articles published in these journals, and analyzed them. RESULTS: The most cited article received 1007 citations and the least cited article received 165 citations, with a mean of 274 citations per article. These citation classics were published in 5 high-impact journals, led by Plastic and Reconstructive Surgery (76 articles). The articles came from 17 countries, with the United States producing 57 articles. Sixty-two institutions produced these 100 top-cited articles, led by Royal Mountain Hospital, University of Melbourne (7 articles). Twenty-three authors published 2 or more of the top-cited articles, led by Taylor GI who authored 10 classic papers. CONCLUSIONS: This analysis of the top citation classics allows for the recognition of major advances and supplies a historic perspective on the progress of plastic and reconstructive surgery research.

The life history of Hayesiana triopus (Westwood, 1847), with taxonomic notes on both present and former species of the genus Hayesiana Fletcher, 1982 (Lepidoptera: Sphingidae).

The two species previously included in the genus Hayesiana Fletcher, 1982 were studied. The life history of the sole currently included species, Hayesiana triopus (Westwood, 1847) is illustrated in colour for the first time. Field records of Hayesiana triopus and Dahira farintaenia (Zhu & Wang, 1997) (previously Hayesiana farintaenia) are given, with the first description of the female genitalia of the latter. The diagnostic features and DNA barcoding data of Hayesiana triopus and Dahira farintaenia are also discussed.

Effect of Arsenic Exposure and Cigarette Smoking on Total and Cause-Specific Mortality: An Occupational Cohort With 27 Follow-up Years.

BACKGROUND: The relationship between arsenic exposure and all-cause mortality and the joint effects of arsenic exposure and smoking have been poorly described in previous studies. METHODS: After 27 years of follow-up, a total of 1738 miners were included in the analysis. Different statistical methods were used to explore the relationship between arsenic exposure and smoking and the risk of all-cause mortality and various causes of death. RESULTS: A total of 694 deaths occurred during the 36,199.79 person-years of follow-up. Cancer was the leading cause of death, and arsenic-exposed workers had significantly higher mortality rates for all-cause, cancer, and cerebrovascular disease. All-cause, cancer, cerebrovascular disease, and respiratory disease increased with cumulative arsenic exposure. CONCLUSIONS: We demonstrated the negative effects of smoking and arsenic exposure on all-cause mortality. More effective actions should be taken to reduce arsenic exposure in miners.

Protection of H9c2 Myocardial Cells from Oxidative Stress by Crocetin via PINK1/Parkin Pathway-Mediated Mitophagy.

This study aimed to explore the oxidative stress-protective effect of crocetin on H2O2-mediated H9c2 myocardial cells through in vitro experiments, and further explore whether its mechanism is related to the impact of mitophagy. This study also aimed to demonstrate the therapeutic effect of safflower acid on oxidative stress in cardiomyocytes and explore whether its mechanism is related to the effect of mitophagy. Here, an H2O2-based oxidative stress model was constructed and assessed the degree of oxidative stress injury of cardiomyocytes by detecting the levels of lactate dehydrogenase (LDH), creatine kinase (CK), malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH Px). Reactive oxygen species (ROS)-detecting fluorescent dye DCFH-DA, JC-1 dye, and TUNEL dye were employed to assess mitochondrial damage and apoptosis. Autophagic flux was measured by transfecting Ad-mCherry-GFP-LC3B adenovirus. Mitophagy-related proteins were then detected via western blotting and immunofluorescence. However, crocetin (0.1-10 µM) could significantly improve cell viability and reduce apoptosis and oxidative stress damage caused by H2O2. In cells with excessive autophagic activation, crocetin could also reduce autophagy flow and the expression of mitophagy-related proteins PINK1 and Parkin, and reverse the transfer of Parkin to mitochondria. Crocetin could reduce H2O2-mediated oxidative stress damage and the apoptosis of H9c2 cells, and its mechanism was closely related to mitophagy.

Effectively removing gaseous polycyclic aromatic hydrocarbons (PAHs) by willow catkins: Do you still dislike the catkins floating?

The floating catkins generated by willow and poplar trees have been criticized for spreading germ and causing fire for decades. It has been found that catkins are with a hollow tubular structure, which made us wonder if the floating catkins can adsorb atmospheric pollutions. Thus, we conducted a project in Harbin, China to investigate whether and how willow catkins could adsorb atmospheric polycyclic aromatic hydrocarbons (PAHs). The results suggest that both the catkins floating in the air and on the ground preferred to adsorb gaseous PAHs rather than particulate PAHs. Moreover, 3- and 4-ring PAHs were the dominating compositions adsorbed by catkins, which significantly increased with exposure time. The gas/catkins partition (KCG) was defined, which explained why 3-ring PAHs are more easily adsorbed by catkins than by airborne particles when their subcooled liquid vapor pressure is high (log PL > -1.73). The removal loading of atmospheric PAHs by catkins were estimated as 1.03 kg/year in the center city of Harbin, which may well explain the phenomenon that levels of gaseous and total (particle + gas) PAHs are relatively low in the months with catkins floating reported in peer-reviewed papers.

Assessing attentive monitoring levels in dynamic environments through visual neuro-assisted approach.

Objective: This work aims to establish a framework in measuring the various attentional levels of the human operator in a real-time animated environment through a visual neuro-assisted approach. Background: With the increasing trend of automation and remote operations, understanding human-machine interaction in dynamic environments can greatly aid to improve performance, promote operational efficiency and safety. Method: Two independent 1-hour experiments were conducted on twenty participants where eye-tracking metrics and neuro activities from electroencephalogram (EEG) were recorded. The experiments required participants to exhibit attentive behaviour in one set and inattentive in the other. Two segments ("increasing flight numbers" and "relatively constant flight numbers") were also extracted to study the participants' visual behavioral differences in relation to aircraft numbers. Results: For the two experimental studies, those in the attentive behavioral study show incidences of higher fixation count, fixation duration, number of aircraft spotted, and landing fixations whereas those in inattentive behavior study reveal higher zero-fixation frame count. In experiments involving 'increasing flight numbers', a higher percentage of aircraft were spotted as compared to those with 'constant flight numbers' in both the groups. Three parameters (number of aircraft spotted, and landing fixations and zero-fixation frame count) are newly established. As radar monitoring is a brain engagement activity, positive EEG data were registered in all the participants. A newly Task Engagement Index (TEI) was also formulated to predict different attentional levels. Conclusion: Results provide a refined quantifiable tool to differentiate between attentive and inattentive monitoring behavior in a real-time dynamic environment, which can be applied across various sectors. Recommendation: With the quantitative TEI established, this paves the way for future studies into attentional levels by regions, time based, as well as eye signature studies in relation to visual task engagement and management and determining expertise levels to be explored. Factors relating to fatigue could also be investigated using the TEI approach proposed.

The Chinese medicine babaodan suppresses LPS-induced sepsis by inhibiting NLRP3-mediated inflammasome activation.

ETHNOPHARMACOLOGICAL RELEVANCE: BBD is a well-known traditional Chinese medicine widely used in clinic to treat viral hepatitis, cholecystitis, angiocholitis and urinary tract infection. According to traditional medicinal theory, BBD exerts the effects of "clearing and humid heat, activating blood and removing toxicity, curing jaundice and relieving pain", the signs of which are recognized as common symptoms of inflammation during infectious diseases in modern medicine. AIM OF THE STUDY: To determine the therapeutic effect of BBD on bacterial endotoxin lipopolysaccharide (LPS) induced sepsis and to investigate the relevant pharmacological and molecular mechanisms of action whereby BBD mitigates inflammation. MATERIALS AND METHODS: In vivo, a mouse sepsis model was induced by intraperitoneally injection of LPS; the BBD were formulated as drug suspension for intragastric administration. The survival rate, secretion of pro-inflammatory cytokines of IL-1ß and TNF-α, and multiple organ injury of lung, liver and spleen were examined. In vitro, peritoneal macrophages (PMs) were stimulated with LPS plus ATP for NLRP3 inflammasome activation; polar gradient extractions of BBD from ultrapure water (sample 1) followed by 70% ethanol (sample 2) were added as interventions. In addition to detect the secretion of IL-1ß and TNF-α, the activation of NF-κB, ASC-speck formation and ASC oligomerization were examined by western blotting and immunofluorescent stainning. Eventually, the extractions of BBD were applied for UPLC-QTOF-MS analyses; refer to the identified chemicals, the bioactive compounds in BBD with anti-NLRP3 inflammasome activities were discussed. RESULTS: BBD improved the survival of sepsis mice accomplished with diminished inflammatory cytokines production and multiple organ injury. Mechanistically, BBD inhibited both the NF-κB pathway and the assembly of NLRP3 complex in PMs. There were 29 chemical compounds identified from sample 1 and 20 from sample 2. Both samples contained bile acids and saponins and sample 2 contained 2 extra chemicals in the category of bile acids. CONCLUSIONS: BBD presents therapeutic role of endotoxin induced sepsis by inhibiting NLRP3-medaited inflammasome activation, which supports its traditional use for the treatment of infectious diseases. The bile acids and saponins are most likely related to the anti-NLRP3 inflammasome activation effect of BBD.

Pharmacological regulation of tissue fibrosis by targeting the mechanical contraction of myofibroblasts.

Fibrosis can occur in almost all tissues and organs and affects normal physiological function, which may have serious consequences, such as organ failure. However, there are currently no effective, broad-spectrum drugs suitable for clinical application. Revealing the process of fibrosis is an important prerequisite for the development of new therapeutic targets and drugs. Studies have shown that the limiting of myofibroblast activation or the promoting of their elimination can ameliorate fibrosis. However, it has not been reported whether a direct decrease in cell contraction can inhibit fibrosis in vivo. Here, we have shown that (-)-blebbistatin (Ble), a non-muscle myosin Ⅱ inhibitor, displayed significant inhibition of liver fibrosis in different chronic injury mouse models in vivo. We found that Ble reduced the stiffness of fibrotic tissues from the early stage, which reduced the extent of myofibroblast activation induced by a stiffer extracellular matrix (ECM). Moreover, Ble also reduced the activation of myofibroblasts induced by TGF-ß1, which is the most potent pro-fibrotic cytokine. Mechanistically, Ble reduced mechanical contraction, which inhibited the assembly of stress fibers, decreased the F/G-actin ratio, and led to the exnucleation of YAP1 and MRTF-A. Finally, we verified its broad-spectrum antifibrotic effect in multiple models of organ fibrosis. Our results highlighted the important role of mechanical contraction in myofibroblast activation and maintenance, rather than just a characteristic of activation, suggesting that it may be a potential target to explore broad-spectrum drugs for the treatment of fibrotic diseases.