Protective effects of bioactive components targeting ß2-adrenergic receptors and muscarinic-3 acetylcholine receptor in Zhisou San on ovalbumin-induced allergic asthma.

One promising approach to overcome drug resistance in asthma treatments involves dual-target therapy, specifically targeting the ß2 adrenergic receptor (ß2-AR) and muscarinic-3 acetylcholine receptor (M3R). This study investigated the anti-asthma effects and dual-target mechanisms of glycyrrhizic acid, hesperidin, and platycodin D (GHP) from Zhisou San. GHP administration effectively attenuated OVA-induced inflammatory infiltration and overproduction of mucus in asthmatic mice. Additionally, GHP treatment significantly suppressed M3R and promoted ß2-AR activation, resulting in the relaxation of tracheal smooth muscle. These findings concluded that GHP mitigated asthma by targeting ß2-AR and M3R to ameliorate airway inflammation and modulate airway smooth muscle relaxation.

Self-assembly of a unique triangle-like tungstovanadate containing pentagonal {(WO7)W3(SnR)2} cluster.

In aqueous solution, a novel triangle-like tungstovanadate estertin derivative K10H10.5[(W4O15(H2O)2){(SnCH2CH2COO)2(V0.75W10.75/V0.25O39)}{{(SnCH2CH2COO)2(µ-OH)}2(SnCH2CH2COO)(VW10O37)}2]·31H2O ((SnR)8-V3W35, R = CH2CH2COO) was assembled by a conventional synthetic method. (SnR)8-V3W35 is composed of one [VW11O39]7- ({VW11}) and two [VW10O37]9- ({VW10}) units connected by eight [Sn(CH2)2COO]2+ groups and a {W4O19} cluster. Interestingly, there exists a pentagonal bipyramid WO7 polyhedral center surrounded by two SnCO5 and three WO6 octahedra, forming a pentagonal {(WO7)W3(SnR)2} cluster in this polyoxometalate (POM), which is also the first example of a pentagonal structure formed by transition metals (TMs) and main group organometals in the POM family. Furthermore, the structure of this organic-inorganic hybrid POM also exhibits the largest number of organotin groups introduced into the POM system. It was characterized with various physico-chemical and spectroscopic methods, including X-ray single crystal and powder diffraction analysis, 119Sn and 51V NMR, IR, thermal gravimetric analysis (TGA), etc. In addition, the catalytic activity of (SnR)8-V3W35 as a mimic of peroxidase was evaluated using o-phenylenediamine (OPD) as a peroxidase substrate. The major factors influencing the oxidation reaction such as pH, the dosage of (SnR)8-V3W35, and concentrations of OPD and H2O2 were mainly studied. (SnR)8-V3W35 exhibits good peroxidase-like catalytic activity. From another perspective, the successful acquisition of (SnR)8-V3W35 further proves the instability and easy reassembly characteristics of TM-sandwich-type tungstovanadates, which also provides a new assembly strategy for synthesizing POM-estertin derivatives.

[Study on mechanism of inhibiting proliferation of head and neck cancer cells by citral, active ingredient of lemon essential oil].

To explore the active substances exerting anti-tumour effect in lemon essential oil and the molecular mechanism inhibiting the proliferation of head and neck cancer cells SCC15 and CAL33, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay(MTT) was utilized to identify the active component inhibiting the proliferation of head and neck cancer cells, namely citral. The IC_(50) of citral inhibiting the proliferation of head and neck cancer cells and normal cells were also determined. In addition, a 5-ethynyl-2'-deoxyuridine(EdU) staining assay was used to detect the effect of citral on the proliferation rate of head and neck cancer cells, and a colony formation assay was used to detect the effect of citral on tumor sphere formation of head and neck cancer cells in vitro. The cell cycle arrest and apoptosis induction of head and neck cancer cells by citral were evaluated by flow cytometry, and Western blot was used to detect the effect of citral on the expression levels of cell cycle-and apoptosis-related proteins in head and neck cancer cells. The findings indicated that citral could effectively inhibit the proliferation and growth of head and neck cancer cells, with anti-tumor activity, and its half inhibitory concentrations for CAL33 and SCC15 were 54.78 and 25.23 µg·mL~(-1), respectively. Furthermore, citral arrested cell cycle at G_2/M phase by down-regulating cell cycle-related proteins such as S-phase kinase associated protein 2(SKP2), C-MYC, cyclin dependent kinase 1(CDK1), and cyclin B. Moreover, citral increased the cysteinyl aspartate-specific proteinase-3(caspase-3), cysteinyl aspartate-specific proteinase-9(caspase-9), and cleaved poly ADP-ribose polymerase(PARP). It up-regulated the level of autophagy-related proteins including microtubule associated protein 1 light chain 3B(LC3B), sequestosome 1(P62/SQSTM1), autophagy effector protein Beclin1(Beclin1), and lysosome-associate membrane protein 1(LAMP1), suggesting that citral could effectively trigger cell apoptosis and cell autophagy in head and neck cancer cells. Furthermore, the dual-tagged plasmid system mCherry-GFP-LC3 was used, and it was found that citral impeded the fusion of autophagosomes and lysosomes, leading to autophagic flux blockage. Collectively, our findings reveal that the main active anti-proliferation component of lemon essential oil is citral, and this component has a significant inhibitory effect on head and neck cancer cells. Its underlying molecular mechanism is that citral induces apoptosis and autophagy by cell cycle arrest and ultimately inhibits cell proliferation.

A Versatile Strategy for the Generation of Air-stable Radical-functionalized Materials.

The exploration of a facile approach to create structurally versatile substances carrying air-stable radicals is highly desired, but still a huge challenge in chemistry and materials science. Herein, a non-contact method to generate air-stable radicals by exposing pyridine/imidazole ring-bearing substances to volatile cyanuric chloride vapor, harnessed as a chemical fuel is reported. This remarkable feat is accomplished through a nucleophilic substitution reaction, wherein an intrinsic electron transfer event transpires spontaneously, originating from the chloride anion (Cl- ) to the cationic nitrogen (N+ ) atom, ultimately giving rise to pyridinium/imidazolium radicals. Impressively, the generated radicals exhibit noteworthy stability in the air over one month owing to the delocalization of the unpaired electron through the extended and highly fused π-conjugated pyridinium/imidazolium-triazine unit. Such an approach is universal to diverse substances, including organic molecules, metal-organic complexes, hydrogels, polymers, and organic cage materials. Capitalizing on this versatile technique, surface radical functionalization can be readily achieved across diverse substrates. Moreover, the generated radical species showcase a myriad of high-performance applications, including mimicking natural peroxidase to accelerate oxidation reactions and achieving high-efficiency near-infrared photothermal conversion and photothermal bacterial inhibition.

Hyperlactatemia in patients undergoing pulmonary endarterectomy with deep hypothermic circulatory arrest: Risk factors and its effects on the outcome.

INTRODUCTION: To determine the risk factors of hyperlactatemia in pulmonary endarterectomy (PEA) surgery and assess whether elevated blood lactate levels are associated with adverse outcomes. METHODS: In this retrospective observational study, a total of 111 consecutive patients who underwent PEA for chronic thromboembolic pulmonary hypertension at the XXX Hospital between December 2016 and January 2022 were included. We retrospectively evaluated arterial blood samples analyzed intraoperatively. The pre- and intraoperative risk factors for hyperlactatemia and the postoperative outcomes were recorded. RESULTS: Lactate levels gradually increased during surgery. The optimal cut-off lactate level for major postoperative complications, calculated using receiver operating characteristic analysis, was 7.0 mmol/L. Deep hypothermic circulatory arrest (DHCA) duration, nadir hematocrit, and preoperative pulmonary vascular resistance were risk factors for lactate levels >7 mmol/L. Moreover, the intraoperative peak lactate level during PEA under DHCA was found to be a statistically significant predictor of major complications being associated with longer mechanical ventilation time (r = 0.294; p = .003) and intensive care unit length of stay (r = 0.327; p = .001). CONCLUSIONS: Deep hypothermic circulatory arrest duration, nadir hematocrit, and preoperative pulmonary vascular resistance were associated with hyperlactatemia. Increased lactate levels were independent predictors of longer mechanical ventilation time, intensive care unit length of stay, and major complications.

Compound 275# Induces Mitochondria-Mediated Apoptosis and Autophagy Initiation in Colorectal Cancer Cells through an Accumulation of Intracellular ROS.

Colorectal cancer (CRC) is the most common intestinal malignancy, and nearly 70% of patients with this cancer develop metastatic disease. In the present study, we synthesized a novel compound, termed N-(3-(5,7-dimethylbenzo [d]oxazol-2-yl)phenyl)-5-nitrofuran-2-carboxamide (compound 275#), and found that it exhibits antiproliferative capability in suppressing the proliferation and growth of CRC cell lines. Furthermore, compound 275# triggered caspase 3-mediated intrinsic apoptosis of mitochondria and autophagy initiation. An investigation of the molecular mechanisms demonstrated that compound 275# induced intrinsic apoptosis, and autophagy initiation was largely mediated by increasing the levels of the intracellular accumulation of reactive oxygen species (ROS) in CRC cells. Taken together, these data suggest that ROS accumulation after treatment with compound 275# leads to mitochondria-mediated apoptosis and autophagy activation, highlighting the potential of compound 275# as a novel therapeutic agent for the treatment of CRC.

Pyrrolyldihydropyrazino[1,2-a]indoletrione Analogue Microtubule Inhibitor Induces Cell-Cycle Arrest and Apoptosis in Colorectal Cancer Cells.

In this study, 2-benzyl-10a-(1H-pyrrol-2-yl)-2,3-dihydropyrazino[1,2-a]indole-1,4,10(10aH)-trione (DHPITO), a previously identified inhibitor against hepatocellular carcinoma cells, is shown to exert its cytotoxic effects by suppressing the proliferation and growth of CRC cells. An investigation of its molecular mechanism confirmed that the cytotoxic activity of DHPITO is mediated through the targeting of microtubules with the promotion of subsequent microtubule polymerisation. With its microtubule-stabilising ability, DHPITO also consistently arrested the cell cycle of the CRC cells at the G2/M phase by promoting the phosphorylation of histone 3 and the accumulation of EB1 at the cell equator, reduced the levels of CRC cell migration and invasion, and induced cellular apoptosis. Furthermore, the compound could suppress both tumour size and tumour weight in a CRC xenograft model without any obvious side effects. Taken together, the findings of the present study reveal the antiproliferative and antitumour mechanisms through which DHPITO exerts its activity, indicating its potential as a putative chemotherapeutic agent and lead compound with a novel structure.

Air-Stable Radical Organic Cages as Cascade Nanozymes for Enhanced Catalysis.

The pursuit of single-assembled molecular cage reactors for complex tandem reactions is a long-standing target in biomimetic catalysis but still a grand challenge. Herein, nanozyme-like organic cages are reported by engineering air-stable radicals into the skeleton upon photoinduced electron transfer. The generation of radicals is accompanied by single-crystal structural transformation and exhibits superior stability over six months in air. Impressively, the radicals throughout the cage skeleton can mimic the peroxidase of natural enzymes to decompose H2 O2 into OH· and facilitate oxidation reactions. Furthermore, an integrated catalyst by encapsulating Au clusters (glucose oxidase mimics) into the cage has been developed, in which the dual active sites (Au cluster and radical) are spatially isolated and can work as cascade nanozymes to prominently promote the enzyme-like tandem reaction via a substrate channeling effect.

Photosynthetic mechanism of maize yield under fluctuating light environments in the field.

The photosynthetic mechanism of crop yields in fluctuating light environments in the field remains controversial. To further elucidate this mechanism, we conducted field and simulation experiments using maize (Zea mays) plants. Increased planting density enhanced the light fluctuation frequency and reduced the duration of daily high light, as well as the light-saturated photosynthetic rate, biomass, and yield per plant. Further analysis confirmed a highly significant positive correlation between biomass and yield per plant and the duration of photosynthesis related to daily high light. The simulation experiment indicated that the light-saturated photosynthetic rate of maize leaves decreased gradually and considerably when shortening the daily duration of high light. Under an identical duration of high light exposure, increasing the fluctuation frequency decreased the light-saturated photosynthetic rate slightly. Proteomic data also demonstrated that photosynthesis was mainly affected by the duration of high light and not by the light fluctuation frequency. Consequently, the current study proposes that an appropriate duration of daily high light under fluctuating light environments is the key factor for greatly improving photosynthesis. This is a promising mechanism by which the photosynthetic productivity and yield of maize can be enhanced under complex light environments in the field.

Conjugated Poly(ionic liquid)-Based Nanoporous Membrane for Rapid Moisture Response.

Stimuli-responsive nanoporous materials represent a newly emerging category of functional materials, for which instant and significant response behavior is strongly demanded but still challenging. Herein, a new kind of conjugated poly(ionic liquid)s (PILs) synthesized via a simple one-pot spontaneous nucleophilic substitution and polymerization between 4,4'-vinylenedipyridine and propargyl bromide is reported. A nanoporous membrane actuator is further developed via ionic complexation between the current PIL and trimesic acid. The actuator carries a gradient density in the hydrophobicity content along the membrane cross-section, which results in a fast response to moisture.

Comprehensive analysis of treatment-related adverse events of immunotherapy in advanced gastric or gastroesophageal junction cancer: A meta-analysis of randomized controlled trials.

AIMS: Immune checkpoint inhibitors (ICIs) have been recognized as an effective treatment for advanced gastric or gastroesophageal junction cancer (AG/GEJC). However, the safety of ICIs in patients has not been established. We aimed to systematically assess the risk of all common treatment-related adverse events (TRAEs) in immunotherapy of AG/GEJC. METHODS: A systematic search of randomized controlled trials (RCTs) published until May 2022 was performed using PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials. And a meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: A total of nine RCTs, including 2918 patients, met the eligibility criteria. The pooled overall incidences of all grade TRAEs, grade 3 or higher TRAEs and treatment-related death were 54.5% (95% confidence interval [CI]: 48.7%-60.2%, I2=75.55%), 12.8% (95% CI: 10.2%-15.7%, I2=51.61%) and 0.11% (95% CI: 0.00%-0.51%, I2=1.63%). Subgroup analyses showed that CTLA-4 inhibitors had a higher risk of any type of TRAEs, when compared with PD-1 and PD-L1 inhibitors. Meta-regression showed significant correlation between all grade TRAEs and proportion of female. Fatigue and diarrhoea were involved in common TRAEs. CONCLUSIONS: Our study provides a comprehensive overview of ICIs-associated AEs in AG/GEJC. Immunotherapy did not have a significantly increased risk experiencing any type of TRAEs, and ICIs had a more manageable safety profile than chemotherapy. These findings provide important guidance to clinicians in counseling and management of patients with AG/GEJC.

Discovery of fused benzimidazole-imidazole autophagic flux inhibitors for treatment of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) with the absence of estrogen receptor (ER), progesterone receptor (PR) and HER2 ptotein, is the highly aggressive subtype of breast cancer that exhibits poor prognosis and high tumor recurrence. It is vital to develop effective agents regulating the core molecular pathway of TNBC. Through a medium throughput screening and iterative medicinal chemistry optimization, we identified compound 7h as an autophagic flux inhibitor, which showed potent activities against human TNBC (MDA-MB-231 and MDA-MB-468) cell lines with IC50 values of 8.3 µM, and 6.0 µM, respectively, which are comparable to the potency of 5-FU and Cisplatin, the first line therapies for TNBC. Extensive investigation of mechanisms of action indicated that 7h inhibits autophagic flux and sequential accumulation of p62, leading to DNA damage and disrepair in TNBC cells. Importantly, nuclear p62 accumulation induced by compound 7h results in the inhibition of RNF168-mediated chromatin ubiquitination and the degradation of HR-related proteins in regulating the DNA damage response (DDR) process. In in vivo studies, compound 7h completely suppressed tumor growth in the MDA-MB-231 xenograft model at a dose of 15 mg/kg/q.d. Our findings indicate that compound 7h is an autophagic flux inhibitor and induced the degradation of HR-related proteins. Compound 7h could be potentially developed as an anti-cancer therapeutics for TNBC.

[Sleep-improving mechanism of Chaiqin Ningshen Granules in insomnia rats: based on hippocampal metabonomics].

With the ultra high performance liquid chromatography-quadruple-electrostatic field orbitrap high resolution mass spectrometry(UHPLC-Q Exactive Orbitrap-MS)-based metabonomics technology, this study aims to analyze the effect of Chaiqin Ningshen Granules(CNG) on endogenous metabolites in insomnia rats of liver depression syndrome and explore the sleep-improving mechanism of this prescription. Parachlorophenylalanine(PCPA, ip) and chronic stimulation were combined to induce insomnia of liver depression pattern in rats, and the effect of CNG on the macroscopic signs, hemorheology, and neurotransmitters in the hippocampus of insomnia rats of liver depression syndrome was observed. After the administration, rat hippocampus was collected for liquid chromatography-mass spectrometry(LC-MS) analysis of the metabolomics. Principal component analysis(PCA), partial least squares discriminant analysis(PLS-DA), and orthogonal partial least squares discriminant analysis(OPLS-DA) were employed for analyzing the metabolites in rat hippocampus and screening potential biomarkers. MetPA was used to yield the related metabolic pathways and metabolic networks. The results show that the drugs can significantly improve the mental state, liver depression, and blood stasis of rats, significantly increase the content of 5-hydroxytryptamine(5-HT) and gamma aminobutyric acid(GABA) in hippocampus(except low-dose CNG), and significantly reduce the content of glucose(Glu)(except low-dose CNG). Among them, estazolam and high-dose CNG had better effect than others. Metabolomics analysis yielded 27 potential biomarkers related to insomnia. MetPA analysis showed 4 metabolic pathways of estazolam in intervening insomnia and 3 metabolic pathways of high-dose CNG in intervening insomnia, involving purine metabolism, glycerophospholipid metabolism, histidine metabolism, and caffeine metabolism. CNG can alleviate insomnia by regulating endogenous differential metabolites and further related metabolic pathways. The result lays a basis for further elucidating the mechanism of CNG in improving sleep.

Isoflurane Attenuates Cerebral Ischaemia-Reperfusion Injury via the TLR4-NLRP3 Signalling Pathway in Diabetic Mice.

Ischaemic stroke is a severe disease worldwide. Restoration of blood flow after ischaemic stroke leads to cerebral ischaemia-reperfusion injury (CIRI). Various operations, such as cardiac surgery with deep hypothermic circulatory arrest, predictably cause cerebral ischaemia. Diabetes is related to the occurrence of perioperative stroke and exacerbates neurological impairment after stroke. Therefore, the choice of anaesthetic drugs has certain clinical significance for patients with diabetes. Isoflurane (ISO) exerts neuroprotective and anti-neuroinflammatory effects in patients without diabetes. However, the role of ISO in cerebral ischaemia in the context of diabetes is still unknown. Toll-like receptor 4 (TLR4) and NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome activation play important roles in microglia-mediated neuroinflammatory injury. In this study, we treated a diabetic middle cerebral artery occlusion mouse model with ISO. We found that diabetes exacerbated cerebral ischaemia damage and that ISO exerted neuroprotective effects in diabetic mice. Then, we found that ISO decreased TLR4-NLRP3 inflammasome activation in microglia and the excessive autophagy induced by CIRI in diabetic mice. The TLR4-specific agonist CRX-527 reversed the neuroprotective effects of ISO. In summary, our study indicated that ISO exerts neuroprotective effects against the neuroinflammation and autophagy observed during diabetic stroke via the TLR4-NLRP3 signalling pathway.

Chemerin promotes the pathogenesis of preeclampsia by activating CMKLR1/p-Akt/CEBPɑ axis and inducing M1 macrophage polarization.

A higher ratio of M1/M2 macrophages and an elevated chemerin level are both related to increased risk of preeclampsia. However, the crosstalk between these two events and their collective contribution to preeclampsia are not well understood. In this study, we assessed the impacts of chemerin chemokine-like receptor 1 (CMKLR1)/p-Akt/CEBPα axis in regulating macrophage polarization and mediating the pathogenic effects of chemerin on preeclampsia. We showed that chemerin, in a dose- and time-dependent manner, stimulated M1 macrophage polarization, inhibited macrophage-induced trophoblast invasion and migration, and suppressed macrophage-mediated angiogenesis. All these chemerin-induced phenotypes are essentially mediated by sequentially CMKLR1, Akt activation, and CEBPα. Mechanistically, CEBPα acted as a transcriptional activator for both IRF8 and chemerin. In vivo, chemerin aggravated preeclampsia, while α-NETA, an inhibitor for CMKLR1, significantly suppressed M1 macrophage polarization and alleviated preeclampsia. In summary, chemerin, by activating CMKLR1/Akt/CEBPα axis, forms a positive feedback loop, promotes M1 macrophage polarization, suppresses trophoblast migration/invasion and angiogenesis, and contributes to preeclampsia. Therefore, targeting chemerin signaling may benefit the prevention and/or treatment of preeclampsia.

The complete mitochondrial genome of Taiwan slug-eating snake (Pareas formosensis) and phylogenetic analysis.

We report the complete mitochondrial genome (mtDNA) of Pareas formosensis (Squamata: Colubridae). This circular mtDNA is 17,703 bp in size and consists of 13 protein-coding genes, 22 transfer RNAs, 2 ribosomal RNAs, and 2 non-coding sequence (D-loop). The total of mtDNA was composition of 57.26% A + T and 42.74% G + C (T: 25.21%, C: 28.84%, A: 32.05%, G: 13.90%). The phylogenetic analysis revealed that P. formosensis formed a clade with other species of Pareas. This mtDNA sequence of P. formosensis provides useful data for studying the population genetics and phylogeography of Colubridae.

Low-to-Moderate-Intensity Resistance Exercise Effectively Improves Arterial Stiffness in Adults: Evidence From Systematic Review, Meta-Analysis, and Meta-Regression Analysis.

Background/Purpose: Resistance exercise (RE) is known to improve cardiovascular health, but the role of RE variables on arterial stiffness is inconclusive. In this systematic review and meta-analysis, we investigated the influence of RE and its intensities on arterial stiffness measured as pulse wave velocity (PWV) in young and middle-aged adults. Methods: Web of Science, PubMed/MEDLINE, Scopus, EMBASE, Cochrane Library, ScienceDirect, CINAHL, Wiley Online Library, and Google Scholar were searched for relevant studies. RE trials that reported PWV data, and compared with respective controls were included. The Cochrane Collaboration tool was used to assess the risk of bias. Results: Data were synthesized from a total of 20 studies, involving 981 participants from control (n = 462) and exercise (n = 519) trials. The test for overall effect (pooled outcome) showed RE intervention had no effect on arterial stiffness (SMD = -0.09; 95% CI: -0.32, 0.13; P = 0.42), but risk of heterogeneity (I 2) was 64%. Meta-regression results revealed a significant correlation (P = 0.042) between RE intensity and PWV changes. Consequently, the trials were subgrouped into high-intensity and low-to-moderate-intensity to identify the effective RE intensity. Subgroup analysis showed that low-to-moderate-intensity significantly decreased PWV (SMD = -0.34; 95% CI: -0.51, -0.17; P < 0.0001), while high-intensity had no effect (SMD = 0.24; 95% CI: -0.18, 0.67; P = 0.26). When trials separated into young and middle-aged, low-to-moderate-intensity notably decreased PWV in young (SMD = -0.41; 95% CI: -0.77, -0.04; P = 0.03) and middle-aged adults (SMD = -0.32; 95% CI: -0.51, -0.14; P = 0.0007), whereas high-intensity had no effect in both age groups. Conclusions: Our findings demonstrated that RE intensity is the key variable in improving arterial stiffness. Low-to-moderate-intensity can prescribe as an effective non-pharmacological strategy to treat cardiovascular complications in young and middle-aged adults.

Demethylzeylasteral (T-96) initiates extrinsic apoptosis against prostate cancer cells by inducing ROS-mediated ER stress and suppressing autophagic flux.

BACKGROUND: Demethylzeylasteral (T-96) is a pharmacologically active triterpenoid monomer extracted from Tripterygium wilfordii Hook F (TWHF) that has been reported to exhibit anti-neoplastic effects against several types of cancer cells. However, the potential anti-tumour effects of T-96 against human Prostate cancer (CaP) cells and the possible underlying mechanisms have not been well studied. RESULTS: In the current study, T-96 exerted significant cytotoxicity to CaP cells in vitro and induced cell cycle arrest at S-phase in a dose-dependent manner. Mechanistically, T-96 promoted the initiation of autophagy but inhibited autophagic flux by inducing ROS-mediated endoplasmic reticulum (ER) stress which subsequently activated the extrinsic apoptosis pathway in CaP cells. These findings implied that T-96-induced ER stress activated the caspase-dependent apoptosis pathway to inhibit proliferation of CaP cells. Moreover, we observed that T-96 enhances the sensitivity of CaP cells to the chemotherapeutic drug, cisplatin. CONCLUSIONS: Taken together, our data demonstrated that T-96 is a novel modulator of ER stress and autophagy, and has potential therapeutic applications against CaP in the clinic.

Low-to-Moderate-Intensity Resistance Exercise Is More Effective than High-Intensity at Improving Endothelial Function in Adults: A Systematic Review and Meta-Analysis.

Aerobic exercise has been confirmed to improve endothelial function (EF). However, the effect of resistance exercise (RE) on EF remains controversial. We conducted this systematic review and meta-analysis on randomized controlled trials (RCTs) to determine the effect of RE and its intensities on EF. We searched Web of Science, PubMed/MEDLINE, Scopus, and Wiley Online Library, and included 15 articles (17 trials) for the synthesis. Overall, RE intervention significantly improved flow-mediated dilatation (FMD) in brachial artery (SMD = 0.76; 95% CI: 0.47, 1.05; p < 0.00001), which represents improved EF. Meta-regression showed that the RE intensity was correlated with changes in FMD (Coef. = -0.274, T = -2.18, p = 0.045). We found both intensities of RE improved FMD, but the effect size for the low- to moderate-intensity (30-70%1RM) was bigger (SMD = 1.02; 95% CI: 0.60, 1.43; p < 0.0001) than for the high-intensity (≥70%1RM; SMD = 0.48; 95% CI: 0.21, 0.74; p = 0.005). We further noticed that RE had a beneficial effect (SMD = 0.61; 95% CI: 0.13, 1.09; p = 0.01) on the brachial artery baseline diameter at rest (BADrest), and the age variable was correlated with the changes in BADrest after RE (Coef. = -0.032, T = -2.33, p = 0.038). Young individuals (<40 years) presented with a bigger effect size for BADrest (SMD = 1.23; 95% CI: 0.30, 2.15; p = 0.009), while middle-aged to elderly (≥40 years) were not responsive to RE (SMD = 0.07; 95% CI: -0.28, 0.42; p = 0.70). Based on our findings, we conclude that RE intervention can improve the EF, and low- to moderate-intensity is more effective than high-intensity.