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Celangulin V is a natural

The preparation of degradable polymeric nanomaterials with a high solid content and multiple morphologies is highly desirable but still challenging. Here, the RAFT dispersion polymerization of styrene and 5,6-benzo-2-methylene-1,3-dioxepane was demonstrated to achieve various morphologies, including spheres, vesicles, worms, and large compound vesicles, with a high solid content through polymerization-induced self-assembly, which opens up a new avenue for the preparation of degradable polymeric nanomaterials.

The discovery of new highly active molecules from natural products is a common method to create new pesticides. Celangulin V targeting Mythimna separate (M. separate) midgut V-ATPase H subunit, has received considerable attention for its excellent insecticidal activity and unique mechanism of action. Therefore, combined with our preliminary work, thirty-seven sulfonamide derivatives bearing propargyloxy or pyridine groups were systematically synthesized to search for insecticidal candidate compounds with low cost and high efficiency on the H subunit of V-ATPase. Bioactive results showed that compounds A2-A4 and A6-A7 exhibited a better bioactivity with median effective concentration (LC50) values (2.78, 3.11, 3.34, 3.54 and 2.48 mg/mL, respectively) against third-instar larvae of M. separate than Celangulin V (LC50 = 18.1 mg/mL). Additionally, molecular docking experiments indicated that these molecules may act on the H subunit of V-ATPase. Based on the above results, these compounds provide new ideas for the discovery of insecticides.

Gut microbial disturbance has been established as potential pathogenesis of mental disorders. However, the signatures and differences regarding patients with schizophrenia (SCH) or bipolar disorder (BD) in emerging adulthood as well as their subtypes have been poorly addressed.In the present study, stool samples obtained from 63 emerging adult patients with schizophrenia (SCH), 50 with bipolar disorder (BD), and 40 healthy controls (HC) were analyzed by 16 S rRNA gene sequencing; psychiatric symptoms and psychological, social, and professional functioning were also assessed.We found that gut microbiota composition was remarkably changed in the patients with SCH and BD. Moreover, the distinct gut microbiome signatures and their potential function in bipolar depression (BP-D) and SCH with predominantly negative symptoms (SCH-N) as well as bipolar mania (BP-M) and SCH with predominantly positive symptoms (SCH-P) were also observed. Furthermore, we identified diagnostic potential biomarkers that can distinguish BD from HC (38 genera, AUC = 0.961), SCH from HC (32 genera, AUC = 0.962), and BD from Scheme (13 genera, AUC = 0.823). Potential diagnostic biomarkers that can distinguish BD-D from SCH-N (16 genera, AUC = 0.969) and BD-M from SCH-P (31 genera, AUC = 0.938) were also identified.This study provides further understanding of abnormal gut microbiome in emerging adulthood patients with SCH and BD and lay the potential foundation for the development of microbe-based clinical diagnosis for BD and SCH.

Patients with NTG or POAG with more than one outpatient or discharge diagnosis from the ophthalmology department were included in the study. These data were merged with the PM2.5 data from the Air Quality Monitoring Network for analysis. This was a case–control study, with 1006 participants in the NTG group and 2533 in the POAG group. To investigate fine particulate matter (PM2.5) exposure levels in patients with normal-tension glaucoma (NTG) and primary open-angle glaucoma (POAG), patient data were obtained from Taiwan’s Longitudinal Health Insurance Database 2000 for the 2008 to 2013 period. We used a multivariate logic regression model to assess the risk for each participant. The PM2.5 exposure levels were divided into four groups: 75th percentile (Q4), >2113 μg/mm3. The results are expressed in terms of odds ratio (OR) and 95% CI. A multiple logistic regression was used to compare the results of the NTG group with those of the POAG group. Compared with the PM2.5 Q1 level, the OR of the PM2.5 Q2 level was 1.009 (95% CI 0.812–1.254), the PM2.5 Q3 level was 1.241 (95% CI 1.241–1.537, p < 0.05), and the PM2.5 Q4 level was 1.246 (95% CI 1.008–1.539, p < 0.05). Our research reveals that compared with POAG, the risk of developing NTG is more closely related with PM2.5 exposure, and PM2.5 has a concentration–dose effect. It is hoped that in the future, in the clinical judgment of NTG and POAG, the level of PM2.5 in the environment can be taken as a risk factor.

Background Adaptive drug resistance is an unfavourable prognostic factor in cancer therapy. Pemetrexed-resistant lung cancer cells possess high-metastatic ability via ERK–ZEB1 pathway-activated epithelial–mesenchymal transition. GMI is a fungal immunomodulatory protein that suppresses the survival of several cancer cells. Methods Cell viability was analysed by MTT, clonogenic, tumour spheroid, and cancer stem cell sphere assays. Western blot assay was performed to detect the protein expression. Chemical inhibitors and ATG5 shRNA were used to inhibit autophagy. Tumour growth was investigated using xenograft mouse model. Results GMI decreased the viability with short- and long-term effects and induced autophagy but not apoptosis in A549/A400 cells. GMI downregulated the expression levels of CD133, CD44, NANOG and OCT4. GMI induces the protein degradation of CD133 via autophagy. CD133 silencing decreased the survival and proliferation of A549/A400 cells. GMI suppressed the growth and CD133 expression of A549/A400 xenograft tumour. Conclusions This study is the first to reveal the novel function of GMI in eliciting cytotoxic effect and inhibiting CD133 expression in pemetrexed-resistant lung cancer cells via autophagy. Our finding provides evidence that CD133 is a potential target for cancer therapy.

Depression is a common mental disorder that affects more than 264 million people worldwide. Anxiety, diabetes, Alzheimer’s disease, myocardial infarction, and cancer, among other disorders, are known to increase the risk of depression. Exposure to ultraviolet B (UVB) can cause human serotonin levels to increase. The vitamin D pathway is one mechanism through which ultraviolet light absorbed through the skin can affect mood; however, UVB exposure is known to increase the risk of cancer. In this study, we explored the effects of prolonged exposure to UVB on depression. Data were retrieved from the Taiwan National Health Insurance Research Database for 2008 to 2013. Each patient with depression was matched 1:4 with a comparison patient by sex and age (±5 years); thus, the study included 23,579 patients with depression and 94,316 healthy controls for comparison. The patients had been exposed to UVB for at least 1 year to observe the cumulative effect of UVB exposure. Based on the World Health Organization UV index, we divided the observation period data into five UV levels: low, moderate, high, very high, and extreme. A multivariate Poisson regression model was used to assess the risk of depression according to UVB exposure level, adjusting for sex, age, income, urbanization level, month, and comorbidities. The results revealed that the incidence rate ratio (IRR) for patients with depression was 0.889 for moderate levels (95% CI 0.835–0.947), 1.134 for high levels (95% CI: 1.022–1.260), 1.711 for very high levels (95% CI: 1.505–1.945), and 2.785 for extreme levels (95% CI: 2.439–3.180) when compared to low levels. Moderate levels of UVB lowered the risk of depression, while high levels of UVB gradually increased the risk. We propose that UVB at normal concentrations can effectively improve depression. However, exposure to high concentrations of UVB damage DNA results in physical diseases such as skin cancer, which increase the risk of depression.

Annual production of textile fibers is continuing to rise and the substantial discharge of undegradable waste polyester fibers can cause serious environmental and even health problems. Thus, the recycling and reuse of recycled poly(ethylene terephthalate) from waste textiles (rPET-F) is highly desirable but still challenging. Here, five chain extenders with a different number of epoxy groups per molecules were used to blend with discarded PET fibers and improve its viscosity and quality loss in the recycling process. The molecule weight, thermal properties, rheological properties and macromolecular architecture of modified r-PET were investigated. It was found that all modified rPET-F samples show higher viscosities and better thermal properties. rPET-F modified by difunctional EXOP molecules show linear structure and improved rheological properties. rPET-F modified by polyfunctional commercial ADR and synthesized copolymers exhibit a long chain branched structure and better crystallization. This study reveals a deeper understanding of the chain extension and opens an avenue for the recycling of PET textiles.

A series of 4-(propargyloxy) benzenesulfonamide derivatives with different substituents on the benzene ring were synthesized and evaluated for their insecticidal activity. Some of the compounds showed good insecticidal activity against Mythimna separata, and the LC50 value of the most active compound B2.5 was 0.235 mg/ml. Ultrastructural changes in the midgut epithelial cells of Mythimna separata were observed using transmission electron microscopy, and severe structural damage was found in microvilli, mitochondria and rough endoplasmic reticulum. It indicates that the possible site of action of these benzenesulfonamides is the cytoplasmic membrane and endomembrane system of the midgut epithelial cells. The above provides a basis for the development of novel insecticidal active compounds with a novel mechanism of action.

Introduction: Cognitive decline is the core schizophrenia symptom, which is now well accepted. Holding a role in various aspects of cognition, lentiform nucleus (putamen and globus pallidus) dysfunction contributes to the psychopathology of this disease. However, the effects of lentiform nucleus function on cognitive impairments in schizophrenia are yet to be investigated.Objectives: We aim to detect the fractional amplitude of low-frequency fluctuation (fALFF) alterations in patients with schizophrenia, and examine how their behavior correlates in relation to the cognitive impairments of the patients.Methods: All participants underwent magnetic resonance imaging (MRI) and cognitive assessment (digit span and digit symbol coding tests). Screening of brain regions with significant changes in fALFF values was based on analysis of the whole brain. The data were analyzed between Jun 2020 and Mar 2021. There were no interventions beyond the routine therapy determined by their clinicians on the basis of standard clinical practice.Results: There were 136 patients (75 men and 61 women, 24.1 ± 7.4 years old) and 146 healthy controls (82 men and 64 women, 24.2 ± 5.2 years old) involved in the experiments seriatim. Patients with schizophrenia exhibited decreased raw scores in cognitive tests (p < 0.001) and increased fALFF in the bilateral lentiform nuclei (left: 67 voxels; x = −24, y = −6, z = 3; peak t-value = 6.90; right: 16 voxels; x = 18, y = 0, z = 3; peak t-value = 6.36). The fALFF values in the bilateral lentiform nuclei were positively correlated with digit span-backward test scores (left: r = 0.193, p = 0.027; right: r = 0.190, p = 0.030), and the right lentiform nucleus was positively correlated with digit symbol coding scores (r = 0.209, p = 0.016).Conclusion: This study demonstrates that cognitive impairments in schizophrenia are associated with lentiform nucleus function as revealed by MRI, involving working memory and processing speed.

ObjectivesWe aimed to determine predictors of mortality within 90 days and develop a simple score for patients with mechanical thrombectomy (MT).DesignAnalysis of a multicentre prospective registry.SettingIn six participating centres, patients who had an acute ischaemic stroke (AIS) treated by MT between March 2017 and May 2018 were documented prospectively.Participants224 patients with AIS were treated by MT.ResultsOf 224 patients, 49 (21.9%) patients died, and 87 (38.8%) were independent. Variables associated with 90-day mortality were age, previous stroke, admission National Institutes of Health Stroke Scale (NIHSS), fasting blood glucose and occlusion site. Logistic regression identified four variables independently associated with 90-day mortality: age ≥80 years (OR 3.26, 95% CI 1.45 to 7.33), previous stroke (OR 2.33, 95% CI 1.04 to 5.21), admission NIHSS ≥18 (OR 2.37, 95% CI 1.13 to 4.99) and internal carotid artery or basilar artery occlusion (OR 2.92, 95% CI 1.34 to 6.40). Using these data, we developed predicting 90-day mortality of AIS with MT (PRACTICE) score ranging from 0 to 6 points. The receiver operator curve analysis found that PRACTICE score (area under the curve (AUC)=0.744, 95% CI 0.669 to 0.820) was numerically better than iScore (AUC=0.661, 95% CI 0.577 to 0.745) and Predicting Early Mortality of Ischemic Stroke score (AUC=0.638, 95% CI 0.551 to 0.725) for predicting 90-day mortality.ConclusionsWe developed a simple score to estimate the 90-day mortality of patients who had an AIS treated with MT. But the score needs to be prospectively validated.Trial registration numberChinese Clinical Trial Registry (ChiCTR-OOC-17013052).

Background: Non-T2 asthma and hypothyroidism share several inflammatory mechanisms in common. However, large-scale, real-world studies evaluating the association between asthma and hypothyroidism are lacking. The objective of this study was to evaluate the risk for asthma patients of developing hypothyroidism. Methods: In the retrospective cohort study, people with asthma were recruited from the Longitudinal Health Insurance Database in Taiwan. After excluding ineligible patients with a previous history of hypothyroidism, 1:1 propensity matching was conducted to select a non-asthma control group. Based on the multivariate Cox regression model, the adjusted hazard ratio of asthma patients developing hypothyroidism was calculated. Results: In total, 95,321 asthma patients were selected as the asthma group and the same amount of people without asthma were selected as the control group. The incidence levels of new-onset hypothyroidism in asthma and non-asthma groups were 8.13 and 6.83 per 100,000 people per year, respectively. Compared with the non-asthma group, the adjusted hazard ratio of the asthma group developing hypothyroidism was 1.217 (95% confidence interval, 1.091–1.357). Conclusions: We found having asthma to be associated with an increased risk of hypothyroidism. Clinicians should be concerned regarding the endocrinological and inflammatory interaction between the two diseases while caring for people with asthma.

To investigate the safety and efficacy of intensive statin in the acute phase of ischemic stroke after intravenous thrombolysis therapy. A total of 310 stroke patients treated with rt-PA were randomly scheduled into the intensive statin group (rosuvastatin 20 mg daily × 14 days) and the control group (rosuvastatin 5 mg daily × 14 days). The primary clinical endpoint was excellent functional outcome (mRS ≤ 1) at 3 months, and the primary safety endpoint was symptomatic intracranial hemorrhage (sICH) in 90 days. The intensive statin users did not achieve a favorable outcome in excellent functional outcome (mRS ≤ 1) at 3 months compared with controls (70.3% vs. 66.5%, p = 0.464). Intensive statin also not significantly improved the overall distribution of scores on the modified Rankin scale, as compared with controls (p = 0.82 by the Cochran–Mantel–Haenszel test). The incidence of primary safety endpoint events (sICH) in 90 days did not significantly differ between the intensive statin group and control group (0.6% vs. 1.3%, p > 0.999). The INSPIRE study indicated that intensive statin therapy may not improve clinical outcomes compared with the low dose of statin therapy in AIS patients undergoing intravenous thrombolysis, and the two groups had similar safety profile. URL: http://www.chictr.org . Unique identifier: ChiCTR-IPR-16008642

Objectives: This study aims to explore in detail, the mechanism of the carbon monoxide releasing molecule-3 (CORM-3) in regulating the activity of microglia (MG) in the treatment of radiation brain injury (RBI). Methods: The brain injury models of BV2 cells and Balb/C mice were established and randomly divided into three groups: the normal control group (CON), the single radiation group (RAD), and the radiation plus CORM-3 intervention group (RAD+CORM). Immunofluorescence was used to observe the effects on activation of the MG. The expressions of inflammatory factors, such as intercellular adhesion molecule-1 (ICAM-1) and inducible nitric oxide synthase (iNOS), were detected by Western blot. Neuron apoptosis and regeneration in the radiation brain injury (RBI) model were detected by neuronal nuclear antigen (NeuN)+TUNEL and NeuN+BrdU double staining. A Morris water maze was used to assess the spatial learning and memory of the mice. Results: Within 48 h after radiation, CORM-3 inhibited activation of the MG, blocked the phosphorylation of P38, and increased the expression of ICAM-1 and iNOS. Therefore, CORM-3 might alleviate MG-mediated neuronal apoptosis and promote neural regeneration in the subgranular zone (SGZ) of the dentate gyrus of the hippocampus. CORM-3 could increase the swimming distance and platform-stay time of the mice in the target platform quadrant after radiation. Conclusion: CORM-3 could effectively improve the inflammatory response induced by activation of the MG, reduce neuronal apoptosis, promote neural regeneration, and improve the learning and memory performance of mice after radiation.

Saracatinib is an oral Src-kinase inhibitor and has been studied in preclinical models and clinical trials of cancer therapy. GMI, a fungal immunomodulatory protein from Ganoderma microsporum, possesses antitumor capacity. The aim of this study is to evaluate the cytotoxic effect of combination treatment with saracatinib and GMI on parental and pemetrexed-resistant lung cancer cells. Cotreatment with saracatinib and GMI induced synergistic and additive cytotoxic effect in A549 and A400 cells by annexin V/propidium iodide assay and combination index. Using western blot assay, saracatinib, and GMI combined treatment synergistically induced caspase-7 activation in A549 cells. Different from A549 cells, saracatinib and GMI cotreatment markedly increased LC3B-II in A400 cells. ATG5 silencing abolished the caspase-7 activation and reduced cell death in A549 cells after cotreatment. This is the first study to provide a novel strategy of treating lung cancer with or without drug resistance via combination treatment with GMI and saracatinib.

The present study aimed to assess the efficacy of Near-infrared spectroscopy (NIRS) real-time neurofeedback (NF) vs. atomoxetine (AT) in children with attention deficit hyperactivity disorder (ADHD). A parallel-group study was conducted to enroll children with ADHD between 8 and 12 years of age. Participants were assigned into the NIRS group and AT group as their wish. Subjects in the NIRS group received 12 sessions of NF training within 6 weeks, and subjects in the AT group were given oral medication. Changes in Swanson, Nolan, and Pelham-V rating scales (SNAP-IV), and performance of Go/No-Go and N-back working memory tasks at week 3, 6 and 8 were evaluated. Forty-nine patients completed the study, including 18 ADHD in the NIRS group and 31 in the AT group. Total scores of SNAP-IV significantly decreased from baseline to week 3, week 6, and week 8 in both groups. Patients in the NIRS group showed significant lower scores on the inattention subscale of SNAP-IV at week 3 and week 6, compared to the AT group. NIRS group had a shorter reaction time during the Go/No-Go task at week 6 and fewer errors during 2-back than the AT group at week 3. The findings revealed that NIRS real-time NF is more efficacious relative to AT in improving behavioral performance, highlighting its potential role and advantages in treating patients with ADHD.

Klippel-Trénaunay syndrome (KTS) is a rare angio-osteo-hypertrophic syndrome characterized by vascular malformations, soft tissue and/or bone hypertrophy, and varicose veins. For the purpose of describing the imaging findings and elucidating the role of medical imaging in the diagnosis and assessment of patient with KTS, we have reviewed the imaging data of 14 KTS patients. The imaging features on different imaging modalities were analyzed. Unilateral lower limb involvement was evident in 71% of cases (n=10) and bilateral but asymmetric lower limb involvement in the remaining 29% of cases (n=4). The most commonly depicted imaging features were varicosities in 93% (n=13), muscle hypertrophy in 79% (n=11) and venous anomalies in 64% (n=9). Other less common imaging findings included lymphedema in 29% (n=4), arterial malformations 29% (n=4), soft tissue hemangiomas 21% (n=3), pelvic and thigh phleboliths 21% (n=3), venous aneurysms 21% (n=3), bone abnormalities 14% (n=2) and lymphadenopathy 14% (n=2). A severe unilateral lower limb deformity resulting in contractures and muscle atrophy of the whole limb was depicted in 1 case. The pathognomonic marginal vein of Servelle was identified in 2 cases. AV shunt was highly suspected in 4 cases and was confirmed by DSA in 1 case, making Klippel-Trénaunay-Weber syndrome a more apt diagnosis. Associated ipsilateral duplicated renal artery was found in 1 case. We have concluded that medical imaging is the cornerstone in the diagnosis and assessment of severity and complications, follow-up and differentiation of KTS from other similar conditions. Different imaging modalities play complementary roles in the evaluation of KTS patients.

To improve the clinical outcome of tumor chemotherapy, more effective combination treatments against tumor metastasis and recurrence are required. Licochalcone A (LicA) is the root of Glycyrrhiza inflata and has been reported to possess anti-inflammatory, antimicrobial, and antitumor effects. Sorafenib (Sor), a multikinase inhibitor, is used to treat patients with solid tumors such as advanced hepatocellular carcinoma (HCC). However, the synergistic effects of LicA and Sor on the metastasis of human HCC cells have not been reported. We found that LicA and Sor did not have cytotoxic effects or arrest growth in human SK-Hep-1 and Huh-7 cells. In addition, treatment with LicA or Sor alone inhibited migration and invasion in human SK-Hep-1 and Huh-7 HCC cells. Furthermore, cotreatment with LicA and Sor synergistically inhibited the migration and invasion of HCC cells and significantly inhibited uPA protein expression. Notably, cotreatment of LicA and Sor synergistically and significantly downregulated MKK4-JNK expression. Through tail vein injection in nude mice, the aforementioned cotreatment synergistically suppressed SK-Hep-1 cell-mediated lung metastasis. These findings first revealed the synergistic effects of LicA and Sor cotreatment against human HCC cells, further suggesting that beneficial effects on tumor regression could be confirmed through prospective clinical trials.

Although several risk factors for metabolic syndrome (MetS) have been reported, there are few clinical scores that predict its incidence. Therefore, we created and validated a risk score for prediction of 3-year risk for MetS. Three-year follow-up data of 4395 initially MetS-free subjects, enrolled for an annual physical examination from Wenzhou Medical Center were analyzed. Subjects at enrollment were randomly divided into the training and the validation cohort. Univariate and multivariate logistic regression models were employed for model development. The selected variables were assigned an integer or half-integer risk score proportional to the estimated coefficient from the logistic model. Risk scores were tested in a validation cohort. The predictive performance of the model was tested by computing the area under the receiver operating characteristic curve (AUROC). Four independent predictors were chosen to construct the MetS risk score, including BMI (HR=1.906, 95% CI: 1.040–1.155), FPG (HR=1.507, 95% CI: 1.305–1.741), DBP (HR=1.061, 95% CI: 1.002–1.031), HDL-C (HR=0.539, 95% CI: 0.303–0.959). The model was created as –1.5 to 4 points, which demonstrated a considerable discrimination both in the training cohort (AUROC=0.674) and validation cohort (AUROC=0.690). Comparison of the observed with the estimated incidence of MetS revealed satisfactory precision. We developed and validated the MetS risk score with 4 risk factors to predict 3-year risk of MetS, useful for assessing the individual risk for MetS in medical practice.

β-catenin is important in development of lung cancer. In our previous study, GMI, a fungal immunomodulatory protein, inhibits lung cancer cell survival. The aim of this study is to evaluate the effect of GMI on β-catenin inhibition and apoptosis induction. GMI induced apoptosis in lung cancer cells bearing wild-type and mutated EGFR. GMI did not reduce the β-catenin mRNA expression but suppressed the protein expressions of β-catenin that resulted in the transcriptional downregulation of its target genes: survivin and cyclin-D1. The transcriptional activation activity of β-catenin was demonstrated by TOPFLASH/FOPFLASH luciferase reporter assay. Inhibition of GSK-3β and proteasome blocked the inhibiting effect of GMI on β-catenin and its target genes. β-catenin silencing increased activation of apoptosis in GMI-treated H1355 cells. This is the first study to reveal the novel function of GMI in inducing apoptosis via β-catenin inhibition. These results provide a new potential of GMI in against lung cancer.

To our knowledge, no study investigates the association of genetic variant distributions of WW domain-containing oxidoreductase (WWOX) gene with development of invasive cancer, clinicopathologic variables and patient survival in uterine cervical cancer for Taiwanese women. We therefore conducted this study to explore the clinical involvements of WWOX single nucleotide polymorphisms (SNPs) in cervical cancer. One hundred and thirty-one patients with cervical invasive cancer and 93 patients with precancerous lesions as well as 316 control women were consecutively enrolled. The genotypic frequencies of WWOX genetic variants rs73569323, rs383362, rs11545028, rs3764340 and rs12918952 were determined by real-time polymerase chain reaction. The results revealed that only WWOX SNP rs3764340 was associated between patients with cervical invasive cancer and normal controls among 5 WWOX genetic variants. Cervical cancer patients with genotypes GA/AA in WWOX SNP rs12918952 were associated with parametrium invasion and pelvic lymph node metastasis. Univariate analysis found that WWOX SNPs rs73569323 and rs11545028 were associated with patient survival, whereas multivariate analysis revealed CT/TT in rs11545028 was the only genetic variant, which could predict better overall survival, among 5 WWOX SNPs in Taiwan. In conclusion, Taiwanese women with CG/GG in WWOX SNP rs3764340 are susceptible to cervical invasive cancer. Cervical cancer patients with GA/AA in rs12918952 tend to have more risk to develop parametrium invasion and pelvic lymph node metastasis. Among 5 WWOX SNPs, rs11545028 is the only genetic variant associated with patient survival, in which CT/TT could predict better overall survival in Taiwanese women.