A dual-rule encoding DNA storage system using chaotic mapping to control GC content.

MOTIVATION: DNA as a novel storage medium is considered an effective solution to the world's growing demand for information due to its high density and long-lasting reliability. However, early coding schemes ignored the biologically constrained nature of DNA sequences in pursuit of high density, leading to DNA synthesis and sequencing difficulties. This article proposes a novel DNA storage coding scheme. The system encodes half of the binary data using each of the two GC-content complementary encoding rules to obtain a DNA sequence. RESULTS: After simulating the encoding of representative document and image file formats, a DNA sequence strictly conforming to biological constraints was obtained, reaching a coding potential of 1.66 bit/nt. In the decoding process, a mechanism to prevent error propagation was introduced. The simulation results demonstrate that by adding Reed-Solomon code, 90% of the data can still be recovered after introducing a 2% error, proving that the proposed DNA storage scheme has high robustness and reliability. Availability and implementation: The source code for the codec scheme of this paper is available at https://github.com/Mooreniah/DNA-dual-rule-rotary-encoding-storage-system-DRRC.

CYP2E1 deficit mediates cholic acid-induced malignant growth in hepatocellular carcinoma cells.

BACKGROUND: Increased level of serum cholic acid (CA) is often accompanied with decreased CYP2E1 expression in hepatocellular carcinoma (HCC) patients. However, the roles of CA and CYP2E1 in hepatocarcinogenesis have not been elucidated. This study aimed to investigate the roles and the underlying mechanisms of CYP2E1 and CA in HCC cell growth. METHODS: The proteomic analysis of liver tumors from DEN-induced male SD rats with CA administration was used to reveal the changes of protein expression in the CA treated group. The growth of CA-treated HCC cells was examined by colony formation assays. Autophagic flux was assessed with immunofluorescence and confocal microscopy. Western blot analysis was used to examine the expression of CYP2E1, mTOR, AKT, p62, and LC3II/I. A xenograft tumor model in nude mice was used to examine the role of CYP2E1 in CA-induced hepatocellular carcinogenesis. The samples from HCC patients were used to evaluate the clinical value of CYP2E1 expression. RESULTS: CA treatment significantly increased the growth of HCC cells and promoted xenograft tumors accompanied by a decrease of CYP2E1 expression. Further studies revealed that both in vitro and in vivo, upregulated CYP2E1 expression inhibited the growth of HCC cells, blocked autophagic flux, decreased AKT phosphorylation, and increased mTOR phosphorylation. CYP2E1 was involved in CA-activated autophagy through the AKT/mTOR signaling. Finally, decreased CYP2E1 expression was observed in the tumor tissues of HCC patients and its expression level in tumors was negatively correlated with the serum level of total bile acids (TBA) and gamma-glutamyltransferase (GGT). CONCLUSIONS: CYP2E1 downregulation contributes to CA-induced HCC development presumably through autophagy regulation. Thus, CYP2E1 may serve as a potential target for HCC drug development.

Cortical activation for adolescent-onset minor depression and major depressive disorder: an fNIRS study.

BACKGROUND: While depression is increasing worldwide, some patients are diagnosed as having Major Depressive Disorder (MDD), but others are diagnosed with minor depression, however, the potential neuro mechanism is unknown. METHODS: Sixty-two patients with minor depression, 44 adolescents with MDD and 54 healthy adolescents participated in this study. Functional near-infrared spectroscopy (fNIRS), both HAMD and HAMA data were collected from all of the participants. RESULTS: The result indicates the pervasively decreased activation of BA, 11, 21, 45 and 46 were observed in the MDD group and reduced activation of BA 45 was observed in the minor depression group. However, cortical activation was not observed between the minor depression or MDD groups. Cortical activation was also not correlated with the depressive/anxious score in the minor and MDD groups separately. CONCLUSIONS: Cortical activation was pervasively decreased in the MDD group and slightly reduced in the minor depression group, which may be a potential neural mechanism. As reduced cortical activation in minor depression, interventions in the early stages of minor depression may help slow or even modify the development of the illness.

Chemical Constituents with Anti-Proliferative Activity on Pulmonary Arterial Smooth Muscle Cells from the Roots of Anthriscus sylvestris (L.) Hoffm.

A chemical investigation of Anthriscus sylvestris roots led to the isolation and characterization of two new nitrogen-containing phenylpropanoids (1-2) and two new phenol glycosides (8-9), along with fifteen known analogues. Structure elucidation was based on HRESIMS, 1D and 2D NMR spectroscopy, and electronic circular dichroism (ECD). In addition, compounds 3, 6, 9-10, 12, and 17 exhibited inhibitory effects against the abnormal proliferation of pulmonary arterial smooth muscle cells with IC50 values ranging from 10.7 ± 0.6 to 57.1 ± 1.1 µM.

Psychological characteristics and emotional difficulties underlying school refusal in adolescents using functional near-infrared spectroscopy.

BACKGROUND: This study aims to explore the psychological characteristics, related emotional problems and potential NIR brain function mechanism of adolescents who refuse to attend school. METHODS: The study included 38 adolescents (12-18 years old) who were not attending school and 35 healthy controls (12-18 years old) who are attending school regularly. Participants completed (1) general demographics, (2) Eysenck Personality Questionnaire (EPQ), (3) Zung Self-Rating Depression Scale (SDS), (4) Zung Self-Rating Anxiety Scale (SAS), and (5) Symptom Checklist-90 (SCL-90). In addition to the clinical tests, participants completed functional near-infrared spectroscopy (fNIRS). Mental health, personality, and emotional state were evaluated in both groups to explore the differences and to understand the underlying mechanisms of school refusal during adolescence. RESULTS: Adolescents who did not attend school had higher neuroticism scores on the Eysenck Personality Questionnaire than healthy controls (p(FDR) < 0.001), introversion and concealment scores were lower than those of healthy controls (p(FDR) < 0.001), there was no significant difference in psychoticism scores between groups. SDS, SAS, SCL-90 scores and factor scores were higher than those of healthy control group (p(FDR) < 0.001), NIR functional brain imaging was different from healthy control group in the 12 and 27 channels (p(FDR) = 0.030, p(FDR) = 0.018), and no difference was found in the remaining channels (p(FDR) > 0.05). There were statistically significant differences in age and gender between the adolescents who refused school and the control group (p(FDR) < 0.001). CONCLUSION: School refusal adolescents are relatively introverted and sensitive and need more attention in daily life. Although the adolescents' emotional problems did not reach the diagnostic criteria of depressive disorder and anxiety disorder, their scores were still higher than those of the control group, suggesting that we should pay more attention to their emotional problems in order to better help them return to school. Using fNIRS, it was found that abnormalities in frontal lobe regions in adolescents with school refusal behaviors, which would contribute to early diagnosis and timely intervention of school refusal behaviors.

AGS3-dependent trans-Golgi network membrane trafficking is essential for compaction in mouse embryos.

Activator of G-protein signaling 3 (AGS3, also known as GPSM1) regulates the trans-Golgi network. The AGS3 GoLoco motif binds to Gαi and thereby regulates the transport of proteins to the plasma membrane. Compaction of early embryos is based on the accumulation of E-cadherin (Cdh1) at cell-contacted membranes. However, how AGS3 regulates the transport of Cdh1 to the plasma membrane remains undetermined. To investigate this, AGS3 was knocked out using the Cas9-sgRNA system. Both trans-Golgi network protein 46 (TGN46, also known as TGOLN2) and transmembrane p24-trafficking protein 7 (TMED7) were tracked in early mouse embryos by tagging these proteins with a fluorescent protein label. We observed that the majority of the AGS3-edited embryos were developmentally arrested and were fragmented after the four-cell stage, exhibiting decreased accumulation of Cdh1 at the membrane. The trans-Golgi network and TMED7-positive vesicles were also dispersed and were not polarized near the membrane. Additionally, increased Gαi1 (encoded by GNAI1) expression could rescue AGS3-overexpressed embryos. In conclusion, AGS3 reinforces the dynamics of the trans-Golgi network and the transport of TMED7-positive cargo containing Cdh1 to the cell-contact surface during early mouse embryo development.

From DNMT1 degrader to ferroptosis promoter: Drug repositioning of 6-Thioguanine as a ferroptosis inducer in gastric cancer.

Though various therapeutic strategies have been developed to overcome gastric cancer, the overall prognosis and therapeutic effect are still not optimistic. As a novel identified type of cell death, ferroptosis has been considered as a promising tumor suppression mechanism with therapeutic potential against gastric cancer. In this work, we screened a collection of 4890 bioactivity compounds and committed to find novel agents that can induce apoptosis in gastric cancer. Among these compounds, 6-TG was identified as a potential ferroptosis inducer in gastric cancer cells for the first time. It could inactivate system xc-, block the generation of GSH, down-regulate the expression of GPX4, increase the level of lipid ROS, and finally trigger the Fe2+-mediated ferroptosis in MGC-803 and AGS cell lines. The date in vivo also suggested that compound 6-TG performed anti-tumor activity via inducing ferroptosis. These findings gave a support for 6-TG may play as a novel leading compound for gastric cancer treatment as a ferroptosis inducer.

Evaluate Short-Term Outcomes of abciximab in ST-Segment Elevation Myocardial Infarction Patients Undergoing Percutaneous Coronary Intervention: A Meta-Analysis of Randomized Clinical Trials.

Objectives: This meta-analysis was to verify the short-time efficacy and safety of abciximab in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). Background: Abciximab has long-term efficacy in patients with STEMI undergoing PCI, but the short-term efficacy is still controversial. Methods: We conducted a systematic review and meta-analysis compared with or without abciximab in patients with STEMI undergoing PCI. The relevant randomized controlled trials were included by searching PubMed, EMBASE, Cochrane Library, and Web of Science databases and other sources. The relative risk (RR) and 95% confidence intervals (CI) of outcomes were calculated by the fixed-effects model. Results: Ten randomized controlled trials with 5008 patients met inclusion criteria. There were no significant differences in risk of all-cause death at 30-day (RR 0.79, CI 0.55-1.12, P=0.18), major bleeding (1.37, 0.93-2.03, P=0.11), and transfusion (1.23, 0.94-1.61, P=0.13) between the two groups. However, there were significant differences in risk of all-cause death at 6 months (0.57, 0.36-0.90, P=0.02), recurrent myocardial infarction (0.55, 0.33-0.92, P=0.02), repeat revascularization (0.58, 0.43-0.78, P=0.0004), final TIMI flow <3 (0.77, 0.62-0.96, P=0.02), minor bleeding (1.29, 1.02-1.63, P=0.04), and thrombocytopenia (2.04, 1.40-2.97, P=0.0002). Conclusions: The application of abciximab can lead to a lower risk of reinfarction, revascularization, and all-cause death at 6 months, but a higher risk of minor bleeding, and thrombocytopenia.

Comparison of Ticagrelor With Clopidogrel in East Asian Patients With Acute Coronary Syndrome: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

ABSTRACT: The risk of bleeding is high in East Asians, whether East Asian patients with acute coronary syndrome choose ticagrelor or clopidogrel is still controversial. In this study, PubMed, EMBASE, Cochrane Library database, and other sources were systematically searched. The primary efficacy outcome was all-cause death, the primary safety outcomes were any bleeding, PLATO major bleeding, and fatal bleeding. The secondary outcomes included vascular-cause death, myocardial infarction, stent thrombosis, stroke, and dyspnea. A total of 8 randomized controlled trials with 3597 patients met inclusion criteria. Compared with clopidogrel, ticagrelor had significantly higher incidence of any bleeding [risk ratio (RR), 1.63; 1.33-1.99; P < 0.00001], PLATO major bleeding (RR 1.56; 1.15-2.12; P = 0.004), and dyspnea (RR 2.60; 1.68-4.00; P < 0.00001). However, ticagrelor was associated with a significantly reduced risk of stent thrombosis (RR 0.42; 0.19-0.92; P = 0.03). There was no significant difference in the risk of all-cause death (RR 0.87; 0.64-1.24; P = 0.44), fatal bleeding (RR 2.49; 0.79-7.86; P = 0.12), vascular-cause death (RR 0.88; 1.60-0.30; P = 0.52), myocardial infarction (RR 0.89; 0.65-1.23; P = 0.49), and stroke (RR 0.84; 0.47-1.50; P = 0.56) between the 2 groups. The present findings demonstrated that ticagrelor was associated with a higher risk of any bleeding, PLATO major bleeding, and dyspnea compared with clopidogrel in East Asian patients with acute coronary syndrome. However, it significantly reduced the risk of stent thrombosis. (Registered by PROSPERO, CRD42021255215).

Efficacy and Safety of Proton Pump Inhibitors in Patients With Coronary Artery Diseases Receiving Oral Antiplatelet Agents and/or Anticoagulants: A Systematic Review and Meta-Analysis.

ABSTRACT: The purpose of this meta-analysis was to evaluate the efficacy and safety of proton pump inhibitors (PPIs) plus antithrombotic strategy in patients with coronary artery diseases compared with antithrombotic strategy alone. We searched PubMed, EMBASE, Cochrane Library, and Chinese Biomedical Medical Literature databases to retrieve randomized controlled trials investigating PPIs combined with antithrombotic strategy in coronary artery diseases. The primary efficacy outcome was major adverse cardiovascular and cerebrovascular events (MACCE). The primary safety outcome was gastrointestinal events. Secondary outcomes included all-cause death, cardiovascular death, myocardial infarction, stent thrombosis, significant bleeding from gastroduodenal lesions, and gastroduodenal ulcer. Overall, 43,943 patients were enrolled from 19 trials. The incidence of MACCE [relative risk (RR) 1.05; 95% confidence interval (CI) 0.96-1.15], all-cause death (RR 0.84; 95% CI 0.69-1.01), cardiovascular death (RR 0.88; 95% CI 0.69-1.12), myocardial infarction (RR 0.98; 95% CI 0.88-1.09), stent thrombosis (RR 1.01; 95% CI 0.76-1.34), and gastroduodenal ulcer (RR 0.40; 95% CI 0.13-1.29) did not increase significantly in patients receiving PPIs compared with patients without those. There were significant differences in the risk of gastrointestinal events (RR 0.34; 95% CI 0.21-0.54) and significant bleeding from gastroduodenal lesions (RR 0.09; 95% CI 0.03-0.28) between the 2 groups. In patients with coronary artery diseases, PPIs plus antithrombotic strategy could reduce the risk of gastrointestinal events and significant bleeding from gastroduodenal lesions but may not affect the incidence of MACCE, all-cause death, cardiovascular death, myocardial infarction, stent thrombosis, and gastroduodenal ulcer (PROSPERO: CRD42021277899, date of registration October 10, 2021).

Efficacy and Safety of De-escalation of Antiplatelet Therapy After Percutaneous Coronary Intervention in Patients With Acute Coronary Syndrome: A Meta-Analysis of Randomized Clinical Trials.

ABSTRACT: Considering that there is no definite conclusion on the efficacy and safety of switching from potent P2Y 12 inhibitors to clopidogrel, we conducted a systematic review and meta-analysis of patients with acute coronary syndromes undergoing percutaneous coronary intervention and compared the efficacy and safety of de-escalation or not of antiplatelet therapy. The relevant randomized controlled trials were included by searching several databases. Net adverse clinical events were identified as the composite end point, which was defined as a composite of cardiovascular death, myocardial infarction, revascularization, stroke, and bleeding at 12 months after acute coronary syndromes. The efficacy end points were cardiovascular death, myocardial infarction, revascularization, stroke, all-cause death, and stent thrombosis. Bleeding was designed as the safety end point. The risk ratio and 95% confidence intervals of end point events were calculated by the fixed-effects model. Six randomized controlled trials with 7627 patients met inclusion criteria. There were significant differences in the risk of net adverse clinical events (RR, 0.67, CI, 0.58-0.78, P < 0.00001) and bleeding end point (0.61, 0.52-0.71, P < 0.00001) between the 2 groups. However, there were no significant differences in the risk of all efficacy end points. In general, the strategy of de-escalation from prasugrel or ticagrelor to clopidogrel can reduce the incidence of net adverse clinical events and bleeding events in patients with ACS undergoing percutaneous coronary intervention.

Dual Antiplatelet Therapy After Drug-Eluting Stents Implantation in East Asians: A Network Meta-Analysis of Randomized Controlled Trials.

ABSTRACT: Dual antiplatelet therapy (DAPT) is essential to prevent the risk of ischemia events, but it is difficult to avoid concurrent bleeding events. East Asians are associated with a higher tendency of bleeding than Caucasians, which may affect the DAPT duration. Therefore, this network meta-analysis to explore optimum DAPT duration for East Asians. The related randomized controlled trials that compared the different DAPT duration in East Asian patients were included by searching PubMed, EMBASE, and Cochrane Library database. The outcomes included myocardial infarction, stent thrombosis, all-cause death, stroke, and major bleeding. In addition, net adverse cardiac and cardiovascular events was defined as a composite outcome in this study. We calculated the odds ratio (OR) and 95% confidence intervals for end point events by the fixed effects model in the Bayesian's network frame. We included a total of 12 randomized controlled trials with 30,640 patients. Compared with 12-month DAPT, 1- to 3-month DAPT is effective in myocardial infarction (OR 0.72, 0.46-1.08), stents thrombosis (OR 1.27, 0.59-2.84), all-cause death (OR 0.91, 0.65-1.28), and stroke (OR 0.89, 0.57-1.39). The 1- to 3-month DAPT was associated with a lower risk of major bleeding compared with 12-month DAPT (OR 0.55, 0.4-0.76), 6-month DAPT (OR 0.54, 0.31-0.94), and >12-month DAPT (OR 0.43, 0.28-0.65). In addition, more than 12 months of DAPT did not reduce the incidence of myocardial infarction (OR 0.75, 0.51-1.11) and increased the risk of major bleeding (OR 1.28, 0.88-1.87) compared with 12-month DAPT. The 1- to 3-month DAPT was more secure and effective than the other 3 DAPT strategies. Although East Asians have a higher risk of bleeding, more than 12 months of DAPT does not increase this incidence of major bleeding.

Efficacy of intravascular imaging-guided drug-eluting stent implantation: a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Traditional angiography only displays two-dimensional images of the coronary arteries during stent implantation. However, intravascular imaging can show the structure of the vascular wall, plaque characteristics. This article aims to evaluate the efficacy of intravascular imaging-guided drug-eluting stent (DES) implantation. METHOD: We conducted a systematic review and meta-analysis of randomized controlled trials of intravascular imaging-guided, including patients with DES implantation guided by intravascular ultrasound or optical coherence tomography and traditional angiography. The databases of PubMed, EMBASE, web of science, and Cochrane Library were searched. The primary outcome was target lesion revascularization (TLR). The secondary outcomes included the target vessel revascularization (TVR), myocardial infarction (MI), stent thrombosis (ST), cardiac death, all-cause death, and the major adverse cardiac events (MACE) during the 6-24 months follow-up. The fixed-effects model was used to calculate the relative risk (RR) and 95% confidence interval of the outcome event. Meanwhile, the trial sequence analysis was employed to evaluate the results. RESULT: This meta-analysis included fourteen randomized controlled trials with 7307 patients. Compared with angiography-guided, intravascular imaging-guided DES implantation can significantly reduce the risk of TLR (RR 0.63, 0.49-0.82, P = 0.0004), TVR (RR 0.66, 0.52-0.85, P = 0.001), cardiac death (RR 0.58; 0.38-0.89; P = 0.01), MACE (RR 0.67, 0.57-0.79; P < 0.00001) and ST (RR 0.43, 0.24-0.78; P = 0.005). While there was no significant difference regarding MI (RR 0.77, 0.57-1.05, P = 0.10) and all-cause death (RR 0.87, 0.58-1.30, P = 0.50). CONCLUSIONS: Compared with angiography, intravascular imaging-guided DES implantation is associated with better clinical outcomes in patients with coronary artery disease, especially complex lesions (Registered by PROSPERO, CRD 42021289205).

Safety and efficacy of anti-inflammatory therapy in patients with coronary artery disease: a systematic review and meta-analysis.

BACKGROUND: The inflammation hypothesis of atherosclerosis has been put forward for more than 20 years. Although many animal experiments have suggested that anti-inflammatory therapy can inhibit the atherosclerotic process, the efficacy of anti-inflammatory therapy for patients with coronary artery disease (CAD) is still controversial. Therefore, this study aims to evaluate the safety and efficacy of anti-inflammatory drugs in patients with CAD. METHOD: We conducted this systematic review and meta-analysis of randomized controlled trials by searching PubMed, EMBASE, web of science, and Cochrane Library database. The primary outcome was a composite outcome of cardiovascular death, myocardial infarction (MI), or stroke. The secondary outcomes included individual MI, coronary revascularization, cardiovascular death, all-cause death, and stroke. The relative risk (RR) and 95% confidence intervals (CI) for outcome events were calculated by the fixed effects model, and trial sequential analysis was applied to assess the results. RESULT: A total of ten randomized controlled trials and 60,782 patients with CAD was included. Compared with patients receiving placebo, anti-inflammatory therapy significantly reduced the incidence of the primary outcome in patients with CAD (RR 0.93, 0.89-0.98, P = 0.007). In addition, the anti-inflammatory therapy can also reduce the risk of MI (RR 0.90, 0.84-0.96, P = 0.002) and coronary revascularization (RR 0.74, 0.66-0.84, P < 0.00001) remarkably. However, there was no significant difference in the incidence of cardiovascular death (RR 0.94, 0.86-1.02, P = 0.14), all-cause death (RR 1.00, 0.94-1.07, P = 0.98) and stroke (RR 0.96, 0.85-1.09, P = 0.51) between two groups. CONCLUSIONS: Anti-inflammatory therapy can reduce the incidence of the primary outcome in patients with CAD, especially the risk of MI and coronary revascularization. However, anti-inflammatory therapy increases the risk of infection. (Registered by PROSPERO, CRD 420212291032).

Expression and role of anti-oxidative damage factors in the placenta of preterm infants with premature rupture of membranes. / æŠ—æ°§åŒ–æŸä¼¤å› å­åœ¨èƒŽè†œæ—©ç ´æœªè¶³æœˆå„¿èƒŽç›˜ä¸­çš„è¡¨è¾¾åŠä½œç”¨.

OBJECTIVES: To study the association of the anti-oxidative damage factors nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H:quinone oxidoreductase-1 (NQO1) with preterm premature rupture of membranes (PPROM). METHODS: A prospective study was conducted. The neonates who were hospitalized in Yanbian Hospital from 2019 to 2020 were enrolled as subjects, among whom there were 30 infants with PPROM, 32 infants with term premature rupture of membranes (TPROM), and 35 full-term infants without premature rupture of membranes (PROM). Hematoxylin and eosin staining was used to observe the inflammatory changes of placental tissue. Immunohistochemical staining was used to measure the expression of Nrf2, HO-1, and NQO1 in placental tissue. Western blot was used to measure the protein expression levels of Nrf2, HO-1, and NQO1 in placental tissue. RESULTS: Compared with the PPROM group, the TPROM group and the non-PROM full-term group had significantly higher positive expression rates and relative protein expression levels of Nrf2, HO-1, and NQO1 in placental tissue (P<0.05). There were no significant differences in the positive expression rates and relative protein expression levels of Nrf2, HO-1, and NQO1 in placental tissue between the TPROM and non-PROM full-term groups (P>0.05). CONCLUSIONS: The low expression levels of Nrf2, HO-1, and NQO1 in placental tissue may be associated with PPROM, suggesting that anti-oxidative damage is one of the directions to prevent PPROM.

Efficacy and Safety of Short-Term Dual Antiplatelet Therapy in East Asians: A Systematic Review and a Meta-Analysis of Randomized Clinical Trials.

ABSTRACT: The optimal duration of dual antiplatelet therapy (DAPT) for patients implanted with new-generation drug-eluting stents in East Asians is currently still controversial. The purpose of this meta-analysis was to investigate the efficacy and safety of short-term DAPT in patients with those. In this study, randomized controlled trials from PubMed, EMBASE, and Cochrane Library were searched to compare the efficacy and safety of short-term DAPT (6 months or less) with long-term DAPT (12 months or more) in patients implanted with new-generation drug-eluting stents in East Asian from inception to September 2020. The primary efficacy outcome was all-cause death, the primary safety outcome was major bleeding, and the secondary outcomes included cardiovascular death, myocardial infarction, definite or possible stent thrombosis, and stroke. A total of 6 randomized controlled trials with 15,688 patients met inclusion criteria; there were no significant differences in the incidence of all-cause death [risk ratio (RR), 1.03; 0.76-1.39; P = 0.856)], cardiovascular death (RR, 0.83; 0.55-1.24; P = 0.361), myocardial infarction (RR, 0.97; 0.72-1.31; P = 0.853), definite or possible stent thrombosis (RR, 1.52; 0.83-2.78; P = 0.170), and stroke (RR, 0.90; 0.61-1.31; P = 0.574) between short-term and long-term DAPTs. However, there was a significant difference in the risk of major bleeding (RR, 0.64; 0.49-0.85; P = 0.002) between the 2 groups. Compared with long-term DAPT, the short-term DAPT can reduce the risk of major bleeding without increasing the risk of death or ischemia for East Asians (Registered by PROSPERO, CRD42020213266).

Extended investigation of field-evolved resistance of the corn earworm Helicoverpa zea(Lepidoptera: Noctuidae) to Bacillus thuringiensis Cry1A.105 and Cry2Ab2 proteins in thesoutheastern United States.

Previous studies have reported that the corn earworm/bollworm, Helicoverpa zea (Boddie), has developed field resistance to pyramided Bacillus thuringiensis (Bt) Cry1A/Cry2A maize and cotton in certain areas of the southeastern United States. The objective of the current study was to determine the current status and distribution of the resistance to Cry1A.105 and Cry2Ab2 in H. zea. In the study, 31 H. zea populations were collected from major maize planting areas across seven southeastern states of the United States during 2018 and 2019 and assayed against the two Bt proteins. Diet over-lay bioassays showed that most of the populations collected during the two years were significantly resistant to the Cry1A.105 protein. Most of the populations collected during 2019 were also resistant to Cry2Ab2, while significant variances were observed in the susceptibility of the populations collected during 2018 to Cry2Ab2. The results showed that Cry1A.105 and Cry2Ab2 resistance in H. zea is widely distributed in the regions sampled. The resistance to Cry1A.105 appeared to have plateaued, while selection for Cry2Ab2 resistance is likely still occurring. Thus, effective measures for mitigating the Cry1A/Cry2A resistance need to be developed and implemented to ensure the sustainable use of Bt crop biotechnology.

The Potential Role of Schistosome-Associated Factors as Therapeutic Modulators of the Immune System.

The parasites and eggs of helminths, including schistosomes, are associated with factors that can modulate the nature and outcomes of host immune responses, particularly enhancing type 2 immunity and impairing the effects of type 1 and type 17 immunity. The main species of schistosomes that cause infection in humans are capable of generating a microenvironment that allows survival of the parasite by evasion of the immune response. Schistosome infections are associated with beneficial effects on chronic immune disorders, including allergies, autoimmune diseases, and alloimmune responses. Recently, there has been increasing research interest in the role of schistosomes in immunoregulation during human infection, and the mechanisms underlying these roles continue to be investigated. Further studies may identify potential opportunities to develop new treatments for immune disease. In this review, we provide an update on the advances in our understanding of schistosome-associated modulation of the cells of the innate and adaptive immune systems as well as the potential role of schistosome-associated factors as therapeutic modulators of immune disorders, including allergies, autoimmune diseases, and transplant immunopathology. We also discuss potential opportunities for targeting schistosome-induced immunoregulation for future translation to the clinical setting.

PINK1 regulates mitochondrial morphology via promoting mitochondrial fission in porcine preimplantation embryos.

Phosphatase and tensin homolog-induced kinase 1 (PINK1) on the outer membranes of impaired mitochondria promotes mitophagy and regulates mitochondrial morphology. Mammalian oocytes and early embryos are mitochondria rich, but mitochondrial dynamics during preimplantation embryo development is not well-studied. To investigate whether PINK1 is required for mitochondrial dynamics in porcine preimplantation embryos, gene knockdown and inhibitors were used, and mitochondrial dynamics were observed by transmission electron microscopy. PINK1 knockdown significantly impaired blastocyst formation and quality, induced mitochondrial elongation and swelling, and reduced mitochondrial DNA copy number. PINK1 knockdown-induced mitochondrial elongation caused mitochondrial dysfunction, oxidative stress, and ATP deficiency, significantly increasing autophagy and apoptosis. Profission dynamin-related protein 1 overexpression prevented PINK1 knockdown-induced impairment of embryo development, mitochondrial elongation, and dysfunction. Thus, PINK1 promotes mitochondrial fission in porcine preimplantation embryos.-Niu, Y.-J., Nie, Z.-W., Shin, K.-T., Zhou, W., Cui, X.-S. PINK1 regulates mitochondrial morphology via promoting mitochondrial fission in porcine preimplantation embryos.

Melatonin enhances mitochondrial biogenesis and protects against rotenone-induced mitochondrial deficiency in early porcine embryos.

Melatonin, a major hormone of the pineal gland, exerts many beneficial effects on mitochondria. Several studies have shown that melatonin can protect against toxin-induced oocyte quality impairment during maturation. However, there is little information regarding the beneficial effects of melatonin on toxin-exposed early embryos, and the mechanisms underlying such effects have not been determined. Rotenone, a chemical widely used in agriculture, induces mitochondrial toxicity, therefore, damaging the reproductive system, impairing oocyte maturation, ovulation, and fertilization. We investigated whether melatonin attenuated rotenone exposure-induced impairment of embryo development by its mitochondrial protection effect. Activated oocytes were randomly assigned to four groups: the control, melatonin treatment, rotenone-exposed, and "rotenone + melatonin" groups. Treatment with melatonin abrogated rotenone-induced impairment of embryo development, mitochondrial dysfunction, and ATP deficiency, and significantly decreased oxidative stress and apoptosis. Melatonin also increased SIRT1 and PGC-1α expression, which promoted mitochondrial biogenesis. SIRT1 knockdown or pharmacological inhibition abolished melatonin's ability to revert rotenone-induced impairment. Thus, melatonin rescued rotenone-induced impairment of embryo development by reducing ROS production and promoting mitochondrial biogenesis. This study shows that melatonin rescues toxin-induced impairment of early porcine embryo development by promoting mitochondrial biogenesis.