Experimental and Theoretical Study of Phosphine-Catalyzed Reaction Modes in the Reaction of α-Substituted Allenes with Aryl Imines.

A new phosphine-catalyzed reaction of α-substituted allenes with aryl imines, in stark contrast to classic cycloaddition reactions, has been developed. This reaction delivers valuable highly functionalized itaconimides with excellent stereoselectivities by a new «un-cyclizing¼ reaction mode involving ß'-carbon of α-substituted allenes. Moreover, the present «un-cyclizing¼ reaction can also be carried out in a one-pot fashion and scaled up to the gram scale by using aryl aldehydes, without the need to isolate the aryl imines. Mechanistic studies and control experiments reveal the crucial role of H2 CO3 for the present reaction mode. In addition, density functional theory (DFT) calculations were performed to understand the possible mechanism.

Tetrazine-Induced Bioorthogonal Activation of Vitamin E-Modified siRNA for Gene Silencing.

The temporal activation of siRNA provides a valuable strategy for the regulation of siRNA activity and conditional gene silencing. The bioorthogonal bond-cleavage reaction of benzonorbonadiene and tetrazine is a promising trigger in siRNA temporal activation. Here, we developed a new method for the bio-orthogonal chemical activation of siRNA based on the tetrazine-induced bond-cleavage reaction. Small-molecule activatable caged siRNAs were developed with the 5'-vitamin E-benzonobonadiene-modified antisense strand targeting the green fluorescent protein (GFP) gene and the mitotic kinesin-5 (Eg5) gene. The addition of tetrazine triggered the reaction with benzonobonadiene linker and induced the linker cleavage to release the active siRNA. Additionally, the conditional gene silencing of both exogenous GFP and endogenous Eg5 genes was successfully achieved with 5'-vitamin E-benzonobonadiene-caged siRNAs, which provides a new uncaging strategy with small molecules.

Triton X-100-Modified Adenosine Triphosphate-Responsive siRNA Delivery Agent for Antitumor Therapy.

Modified polyethyleneimine (PEI) has been widely used as siRNA delivery agents. Here, a new Triton X-100-modified low-molecular-weight PEI siRNA delivery agent is developed together with the coupling of 4-carboxyphenylboronic acid (PBA) and dopamine grafted vitamin E (VEDA). Triton X-100, a nonionic detergent, greatly improves the cellular uptake of siRNA as well as the siRNA escape from endosome/lysosome because of its high transmembrane ability. In addition, the boronate bond between PBA and VEDA of the transfection agent can be triggered to release its entrapped siRNA because of the high level of adenosine triphosphate (ATP) in cancer cells. The transfection agent is successfully applied to deliver siRNAs targeting endogenous genes of epidermal growth factor receptor (EGFR) and kinesin-5 (Eg5) to cancer cells, showing good results on Eg5 and EGFR silencing ability and inhibition of cancer cell migration. Further in vivo study indicates that the Triton X-100-modified transfection agent is also efficient to deliver siRNA to cancer cells and shows significant tumor growth inhibition on mice tumor models. These results indicate that the Triton X-100-modified ATP-responsive transfection agent is a promising gene delivery vector for target gene silencing in vitro and in vivo.

Distribution of endotoxins in full scale pharmaceutical wastewater treatment plants and its relationship with microbial community structure.

Endotoxins are potential toxics impacting human health through respiration derived in wastewater treatment plants (WWTPs), yet the formation of endotoxins during wastewater treatment processes is still lacking research. In our study, the distribution of endotoxins and bacterial community structure in the wastewater of three full scale pharmaceutical WWTPs were explored using the limulus amebocyte lysate (LAL) test and MiSeq technique. Results showed that higher endotoxin activities in the influent of Plant A and Plant C (560 and 1140 EU/mL), stemming from the fermentation process, were found compared to that of Plant B (135 EU/mL), coming from the process of chemical synthesis. During the anaerobic treatment and the cyclic activated sludge system (CASS) in the three WWTPs, the endotoxin activity increased, while it declined in the aerobic treatment system. In all bioreactors, the relative abundance of Gram-negative bacteria accounted for 50.0-94.6%. Bacteria with high lipopolysaccharide (LPS) in LAL assay were found at the genus level of Bacteroides, Enterococcus, Desulfovibrio, and Megasphaera.

Comprehensive assessment of the effects of concurrent strength and endurance training on lipid profile, glycemic control, and insulin resistance in type 2 diabetes: A meta-analysis.

BACKGROUND: To investigate the effect of concurrent strength combined with endurance training on the lipid and glucose profile of type 2 diabetes mellitus (T2DM) using Meta-analysis. METHODS: The literature was searched from PubMed, Web of Science, EBSCO, and China National Knowledge Infrastructure(CNKI) databases for relevant randomized controlled trials with dates from the date of establishment to June 2023, and the included studies were individually assessed according to the Cochrane Risk of Bias tool in the Cochrane Systematic Assessor's Handbook, and the data were analyzed using RevMan 5.4 analysis software to analyze and process the data. RESULTS: A total of 9 articles were included, including 589 subjects, including 308 in the experimental group and 281 in the control group. The results of Meta analysis showed that concurrent strength combined with endurance training improved TC (SMD = -1.12, 95% CI = [-1.81, -0.44], P < 0.01), TG (SMD = -0.46, 95% CI = [-0.85, -0.07], P < 0.05), LDL-C (SMD = -1.3, 95% CI = [-2.09, -0.50], P < 0.01), HDL-C (SMD = 0.61, 95% CI = [0.05, 1.17], P < 0.05), FBG (SMD = -0.65, 95% CI = [-1.27, -0.04], P < 0.05), HOMA-IR (SMD = -1.23, 95% CI = [-2.40, -0.06], P < 0.05). CONCLUSION: Concurrent strength combined with endurance training has a positive effect on the improvement of lipid and glucose profile in patients with type 2 diabetes.

Boosting physical performance in SD rats through brain-targeted delivery of caffeine-loaded transferrin liposomes.

This study aimed to explore the impact of caffeine (CAF) encapsulated in transferrin-modified, sterically-stabilized liposomes (Tf-SSL) on the physical performance of rats, specifically forelimb grip strength, running, and swimming. The brain-targeted drug delivery system, Tf-SSL, was used for the administration of caffeine. 168 male Sprague-Dawley (SD) rats were randomly assigned to different groups, including swimming, running, running wheel, and strength groups. Each group was further subdivided into high, medium, and low dose free caffeine (HCAF, MCAF, LCAF) and Tf-SSL CAF groups, along with a control group (CON). The strength, swimming, and running groups underwent training for four weeks, three times per week. The running wheel group was placed in rearing cages for a one-week adaptation period. After the final training session, the resistance, swimming, running, and running wheel exercise capacities of the rats were tested. The rats were administered treatment via tail vein injection, while the blank CON group received 0.9 % saline solution without treatment throughout the entire process. The results demonstrated a Tf-SSL CAF group encapsulation rate of 70.58 ± 5.14 %. Increasing the concentration of supplemented caffeine led to enhanced forelimb grip strength in rats, with significant differences observed in HCAF alone group, medium-dose Tf-SSL CAF (MTf-SSL CAF), and high-dose Tf-SSL CAF (HTf-SSL CAF) groups compared to the CON group. In the running and swimming experiments, higher caffeine supplementation concentrations correlated with increased running and swimming time to exhaustion, and the MTf-SSL CAF group showed longer running and swimming time compared to the HCAF alone group. The results of rat striatal dopamine levels indicated that increased caffeine supplementation concentrations led to higher dopamine secretion, with significantly different striatal concentrations in the HCAF group, MTf-SSL CAF group, and HTf-SSL CAF group compared to the CON group. The running wheel experiment revealed that rats in the medium- and high-dose Tf-SSL CAF groups exhibited greater 6-h running distances than the HCAF group and CON group. In conclusion, caffeine supplementation improved the physical performance of rats, with the high concentration CAF group outperforming the low and medium concentration groups. Furthermore, Tf-SSL CAF demonstrated superior physical enhancement compared to caffeine supplementation alone.

Tracking the extensive three-dimensional motion of single ions by an engineered point-spread function.

Three-dimensional (3D) imaging of individual atoms is a critical tool for discovering new physical phenomena and developing new technologies in microscopic systems. However, the current single-atom-resolved 3D imaging methods are limited to static circumstances or a shallow detection range. Here, we demonstrate a generic dynamic 3D imaging method to track the extensive motion of single ions by exploiting the engineered point-spread function (PSF). We show that the image of a single ion can be engineered into a helical PSF, thus enabling single-snapshot acquisition of the position information of the ion in the trap. A preliminary application of this technique is demonstrated by recording the 3D motion trajectory of a single trapped ion and reconstructing the 3D dynamical configuration transition between the zig and zag structures of a 5-ion crystal. This work opens the path for studies on single-atom-resolved dynamics in both trapped-ion and neutral-atom systems.

Comparative effects of high-intensity interval training and moderate-intensity continuous training on weight and metabolic health in college students with obesity.

The purpose of this study was to compare the effects of High-Intensity Interval Training (HIIT) and Moderate-Intensity Continuous Training (MICT) on weight, body composition, blood lipid indicators, and metabolic status in college students living with obesity. The study focused on a sample of 40 college students living with obesity, including 20 males and 20 females, aged between 18 and 25. Participants were randomly assigned to either the HIIT group or the MICT group. Both groups underwent an 8-week intervention, consisting of three sessions per week with alternate-day training. The MICT group's training consisted of continuous aerobic exercise for 35 min at 60-70% of maximum heart rate. The HIIT group engaged in 28 min of alternating high-intensity and low-intensity exercise, where the high-intensity phase was at 85-90% of maximum heart rate for 4 min, followed by a 3-min recovery period at 50-60% of maximum heart rate, repeated four times. Both groups underwent heart rate monitoring before and after the training sessions to ensure the accuracy of the training intensity. Within each group, further distinctions were made based on gender, resulting in the following subgroups: Male HIIT group (n = 10), Female HIIT group (n = 10), Male MICT group (n = 10), and Female MICT group (n = 10). Differences in anthropometric and biochemical indicators among the groups were analyzed, and the different effects of the two intervention strategies on the obese college student population were comprehensively evaluated. Compared to the baseline assessment, the HIIT group showed a more favorable declining trend than the MICT group in terms of body morphology and body composition, particularly in the aspect of body fat percentage (BF%). The male HIIT group, female HIIT group, male MICT group, and female MICT group respectively reduced by - 23.71%, - 26.76%, - 9.81%, - 7.16%. Male and female HIIT group experienced a more pronounced decrease compared to the MICT group, with the female HIIT group reducing an additional 3.75% more than the male HIIT group. Regarding intergroup differences, BF% significant differences were shown between male MICT group and the HIIT group (P < 0.05), and female MICT group and the HIIT group (P < 0.01). In terms of biochemical indicators, the HIIT group also presented a more favorable declining trend compared to the MICT group, with male HIIT participants showing more reduction than female HIIT participants, especially in total cholesterol (TC) (10.64%), low-density lipoprotein cholesterol (LDL-C) (11.73%), alanine aminotransferase (ALT) (11.99%), and uric acid (UA) (11.76%). Regarding triglycerides (TG), significant intergroup differences were observed between male MICT and HIIT groups (P < 0.01) and female MICT and HIIT groups (P < 0.01). Concerning ALT, a significant difference was shown between female MICT and HIIT groups (P < 0.01), while no significant difference was observed among male participants. Overall, for college students living with obesity, both HIIT and MICT have shown positive effects. Among these, HIIT demonstrates greater effectiveness compared to MICT in BF% and biochemical markers.

Combined effects of Rhodiola rosea and caffeine supplementation on aerobic endurance and muscle explosiveness: a synergistic approach.

This study examined the synergistic effects of combining Rhodiola rosea (RHO) and caffeine (CAF) supplementation on muscle endurance and explosiveness in SD rats and human subjects, encompassing individuals without prior exercise training experience and seasoned aerobic athletes. Male SD rats and healthy human volunteers were randomly divided into four groups: CAF, RHO, CAF + RHO, and a control group (CTR). Nutritional supplements were administered throughout the training period, and pre-and post-measurement data were collected. In both the rat model and human subjects, the RHO+CAF group demonstrated significantly greater effects compared to the use of RHO or CAF supplements individually. Rats in the RHO+CAF group demonstrated extended running and swimming times and an increase in erythropoietin (EPO) mRNA expression in comparison to the CTR. Blood parameters, such as serum EPO levels, were enhanced in the CAF + RHO group, while blood urea nitrogen (BUN) and lactate (LA) levels significantly decreased in both the RHO and CAF + RHO groups. Hepatic and muscle glycogen contents were also higher in these groups. The gene expression analysis in rats demonstrated an elevation in the mRNA levels of glucose transporter-4 (GLUT-4), peroxisome proliferator-activated receptor γ coactivator-1 alpha (PGC-1α), Monocarboxylate transporter 1 (MCT-1), and Heme Oxygenase-1 (HO-1) in both the RHO and RHO+CAF groups. For individuals without prior aerobic training experience, the RHO+CAF group showed significant improvements compared to the CTR group in maximal oxygen consumption (VO2max), 5 km run, countermovement jump (CMJ), standing long jump, and 30 m sprint. For individuals with years of aerobic training experience, the RHO+CAF group exhibited enhanced performance in the 5 km run, CMJ, and standing long jump compared to the CTR group. In conclusion, the continuous 30 days supplementation of RHO, combined with a single dose of CAF, demonstrated superior effects on muscle endurance and explosiveness in both animal and human studies when compared to the use of RHO or CAF individually.

Robust, Superhydrophobic Aluminum Fins with Excellent Mechanical Durability and Self-Cleaning Ability.

The self-cleaning ability of superhydrophobic metal surfaces has attracted extensive attention. The preparation of superhydrophobic material using the coating method is a common processing method. In this experiment, aluminum fins were processed by laser etching and perfluorinated two-step coating. The aluminum surface was modified using a femtosecond laser and 1H,1H,2H,2H- perfluorooctane triethoxysilane (PFOTES). A superhydrophobic aluminum surface with excellent mechanical stability and self-cleaning properties was obtained with the superhydrophobic contact angle (WCA) of 152.8° and the rolling angle (SA) of 0.6°. The results show that the superhydrophobic surface has an excellent cleaning effect compared with an ordinary surface in unit time. Then, a wear resistance test of the superhydrophobic surface was carried out by using the physical wear method. The results show that physical wear had a low influence on the hydrophobic property of the specimen surface. Finally, the Vickers hardness analysis found that the superhydrophobic surface hardness was significantly better than the ordinary surface hardness compared with the superhydrophobic surface hardness. Based on the excellent self-cleaning properties, wear resistance, and robustness of superhydrophobic materials, the laser-etched and perfluorinated superhydrophobic aluminum fins designed and manufactured in this study have broad application prospects in improving the heat transfer efficiency of finned heat exchangers.

Effects of different exercise modalities on lipid profile in the elderly population: A meta-analysis.

BACKGROUND: Dyslipidemia, characterized by elevated total cholesterol (TC), triglycerides, and low-density lipoprotein cholesterol (LDL-C), as well as decreased high-density lipoprotein cholesterol (HDL-C), has long been recognized as a major risk factor for age-related diseases. Recent studies have shown that exercise can be effective in mitigating dyslipidemia in older adults. The aim of this study was to systematically evaluate the effects of different exercise modalities (aerobic exercise [AE], resistance exercise [RE], aerobic+resistance exercise [AE+RE], and high-intensity interval training) on lipid profile in the elderly population, in order to identify the most effective exercise modality for maintaining lipid profile health in older adults. METHODS: A comprehensive database search of PubMed, EBSCO, Web of Science, China National Knowledge Infrastructure, and Wanfang database. Eligible studies were individually assessed according to the Cochrane Risk of Bias Tool version 2, and the data were analyzed and processed using RevMan 5.4.1 analysis software. RESULTS: This study identified 20 randomized controlled trials with a total of 988 subjects, of which 541 were in the exercise group and 447 in the control group. Our analysis showed that AE significantly reduced TC (P < .05), triglycerides (P < .01), and LDL-C (P < .01), while increasing HDL-C (P < .01) in the elderly population. RE significantly reduced the elevation of TC (P < .01) and LDL-C (P < .05) indices in the elderly population, while AE+RE had a significant effect on decreasing TC (P < .01) and LDL-C (P < .01) indices. CONCLUSION: Our analysis indicates that AE is the most effective exercise modality for reducing dyslipidemia in older adults, compared to RE, AE+RE, and high-intensity interval training. These findings suggest that AE should be promoted as an important lifestyle intervention to improve lipid profile health in the elderly population. However, further research is needed to investigate the optimal duration, frequency, and intensity of AE required to achieve the most beneficial effects on lipid profile health in older adults.

Circular Antisense Oligonucleotides for Specific RNase-H-Mediated microRNA Inhibition with Reduced Off-Target Effects and Nonspecific Immunostimulation.

Antisense microRNA oligodeoxynucleotides (AMOs) are powerful tools to regulate microRNA functions. Unfortunately, severe off-target effects are sometimes observed. Due to the special topological and enzymatic properties of circular oligodeoxynucleotides (c-ODNs), we rationally designed and developed circular AMOs, which effectively inhibited microRNA functions with high target specificity and low off-target effects. Binding and enzymatic assays indicated that small circular AMOs could selectively bind to and further digest the target mature miR 21, which suggested that the topological properties of circular c-ODNs significantly decreased their off-target effects as microRNA inhibitors. Compared with their linear corresponding phosphorothioated AMOs, circular phosphorothioated AMOs could more effectively reduce the amount of carcinogenic miR 21 and miR 222 and upregulate the expression levels of downstream antitumor proteins of PTEN and PDCD4. In addition, c-PS-antimiRs induced much less nonspecific immunostimulatory effects compared with their linear partner PS-ODNs, further indicating the advantages of circular ODNs in nonspecific immunostimulation.

Catalyst-Free [3+2] Cycloaddition of Electron-Deficient Alkynes and o-Hydroxyaryl Azomethine Ylides in Water.

A catalyst-free [3 + 2] cycloaddition reaction of electron-deficient alkynes and o-hydroxyaryl azomethine ylides in water was developed, affording pyrroline derivatives in moderate to high yields (up to 90%).

Phosphine-Catalyzed Stereoselective Tandem Annulation Reaction for the Synthesis of Chromeno[4,3-b]pyrroles.

A phosphine-catalyzed tandem cyclization reaction has been developed to provide a series of chromeno[4,3-b]pyrrole derivatives, which contain three consecutive asymmetric centers. The reaction has a good yield, excellent stereoselectivity, and Z/E selectivity. The new method is simple, requires only mild conditions, and shows tolerance for various functional groups. Similarly, this reaction can be catalyzed by a chiral phosphine catalyst to achieve asymmetric synthesis.