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AbstractContext Current chemotherapeutic drugs cannot meet the treatment needs of patients with nasopharyngeal carcinoma (NPC), so urgent action is needed to discover novel chemotherapeutic agents. Our previous study revealed that garcinone E (GE) inhibited the proliferation and metastasis of NPC, suggesting that the compound might display promising anticancer activity.Objective To examine the mechanism underlying the anti-NPC activity of GE for the first time.Materials and methods For MTS assay, NPC cells were treated with 2.5-20 μmol/L GE or dimethyl sulfoxide for 24, 48, and 72 h. Colony formation capacity, cell cycle distribution, and in vivo xenograft experiment of GE were assessed. MDC staining, StubRFP-sensGFP-LC3 observation, LysoBrite Blue staining, and immunofluorescence examined the autophagy of NPC cells after GE exposure. Western blotting, RNA-sequencing, and RT-qPCR measured protein and mRNA levels.Results GE suppressed cell viability with an IC50 of 7.64, 8.83 and 4.65 μmol/L for HK1, HONE1 and S18 cells. GE inhibited colony formation and cell cycle, increased autophagosome number, and inhibited the autophagic flux partially by blocking lysosome-autophagosome fusion, and repressed S18 xenograft growth. GE dysregulated the expression of autophagy- and cell cycle-related proteins such as Beclin-1, SQSTM1/p62, LC3, CDKs, and Cyclins. Bioinformatics GO and KEGG pathway enrichment analysis of RNA-seq showed that autophagy was enriched in differentially expressed genes upon GE treatment.Discussion and conclusion GE acts as an autophagic flux inhibitor, which may have potential chemotherapeutic use for NPC treatment and may have an application in basic research to explore the mechanisms of autophagy.

A. baumannii is a common clinical pathogen that often causes pneumonia and bloodstream infections in ICU patients. Sequence types (ST) are used to investigate the distribution and spread of A. baumannii. Biological characteristics such as virulence and resistance may play a role in A. baumannii becoming a specific dominant ST(DST,ST191, ST195 and ST208) strain. To characterize the biological, genetic, and transcriptomic differences between the DST and non-dominant ST(NST,ST462 and ST547,etc.) strains in A. baumannii, we performed several biological experiments and genetic, and transcriptomic analyses. The DST group displayed more resistance ability to desiccation, oxidation, multiple antibiotics, and complement killing than the NST group. However, the latter had higher biofilm formation ability than the former. The genomic analysis showed the DST group exhibited more capsule-related and aminoglycoside-resistant genes. Besides, GO analysis indicated that functions involved in lipid biosynthetic, transport, and the metabolic process were up-regulated in the DST group, while KEGG analysis manifested that the two-component system related to potassium ion transport and pili were down-regulated. In short, resistance to desiccation, oxidation, multiple antibiotics, and serum complement killing are important reasons for the formation of DST. Genes related to capsule synthesis and lipid biosynthesis and metabolism play an important role at the molecular level in the formation of DST.

BackgroundPrevious studies have reported that sodium bicarbonate ingestion may enhance high-intensity exercise performance and cause severe gastrointestinal distress. However, enteric-coated sodium bicarbonate may reduce gastrointestinal symptoms of sodium bicarbonate after oral administration. This remains to be confirmed. This study aimed to verify the effects of serial and acute enteric-coated sodium bicarbonate supplementation on anaerobic performance, physiological profile, and metabolomics in healthy young men.MethodsHealthy young males (n = 12) ingested 0.2 g/kg body mass of enteric-coated sodium bicarbonate (ES) in serial enteric-coated sodium bicarbonate (SES, continuous ES supplementation for 5 days) and acute enteric-coated sodium bicarbonate (AES, acute ES supplementation before exercise) or a placebo (PL) in a randomized crossover design. After each supplement protocol, the participants completed four Wingate anaerobic tests (WAT). The first three Wingate tests (testing anaerobic capacity) were performed with a 5-min passive recovery between each. After the third Wingate test, participants were required to complete a 50-min recovery followed by a fourth WAT test (testing the recovery of anaerobic capacity after 50-min intervals). Blood lactate (BLA), heart rate (HR), and ratings of perceived exertion (RPE) were measured in all conditions during the test, as was the subjective gastrointestinal–symptoms assessment questionnaire (GSAQ). Mean power (MP) and peak power (PP) were recorded after four WATs. Urine samples were collected before the test and 50 min after the 3rd WAT.ResultsSerial enteric-coated sodium bicarbonate supplementation improved anaerobic capacity in the third bout of WATs, as observed based on an increase in mean power (SES vs. PL (613 ± 57 vs. 542 ± 64 W), P = 0.024) and peak power (SES vs. PL (1,071 ± 149 vs. 905 ± 150 W), P = 0.016). Acute ES supplementation did not affect anaerobic capacity. The occurrence of gastrointestinal symptoms after enteric-coated sodium bicarbonate supplementation was minimal and no difference compared to placebo in the current study. In particular, serial enteric-coated sodium bicarbonate supplementation had no gastrointestinal side effects before the test. The AES and SES groups had a trivial effect on blood lactate compared to the PLA group. There was no significant difference in HR and RPE among the three groups. Based on targeted metabolomics analysis, the 50 min after the third WAT, the levels of lactate (P < 0.001), L-Malic acid (P < 0.05), and oxaloacetate (P < 0.05) were significantly higher in the SES group than in the PL group. Compared with the AES group, the levels of lactate and fumarate in the SES group were significantly increased (P < 0.05).ConclusionsOur study indicates that serial enteric-coated sodium bicarbonate supplementation positively improves anaerobic performance among healthy young men. However, acute ingestion of enteric-coated sodium bicarbonate did not improve anaerobic exercise performance. Either with serial or acute supplementation doses, enteric-coated sodium bicarbonate produced fewer gastrointestinal symptoms and no difference compared to placebo, especially with no gastrointestinal side effects after serial supplementation. Serial and acute supplementation of enteric-coated sodium bicarbonate might tend to promote lactate clearance. Furthermore, serial enteric-coated sodium bicarbonate ingestion may cause changes in the metabolism of lactate, L-Malic acid, oxaloacetate, and fumarate 50 min after exercise, which presumably may promote the tricarboxylic acid cycle and lactate clearance.

BackgroundCarbapenem-resistant Acinetobacter baumannii (CRAB) is a common cause of ventilator-associated pneumonia (VAP) in intensive care unit (ICU) patients, but its infection and colonization state are difficult to distinguish. If the judgment is wrong, it may aggravate the abuse of antibiotics and further accelerate the evolution of drug resistance. We sought to provide new clues for the diagnosis, pathogenesis and treatment of CRAB VAP based on lower respiratory tract (LRT) microbiota.MethodsA prospective study was conducted on patients with mechanical ventilation from July 2018 to December 2019 in a tertiary hospital. Multi-genomics studies (16S rRNA amplicon, metagenomics, and whole-genome sequencing [WGS]) of endotracheal deep aspirate (ETA) were performed.ResultsFifty-two ICU patients were enrolled, including 24 with CRAB VAP (CRAB-I), 22 with CRAB colonization (CRAB-C), and six CRAB-negative patients (infection-free) (CRAB-N). Diversity of pulmonary microbiota was significantly lower in CRAB-I than in CRAB-C or CRAB-N (mean Shannon index, 1.79 vs. 2.73 vs. 4.81, P < 0.05). Abundances of 11 key genera differed between the groups. Acinetobacter was most abundant in CRAB-I (76.19%), moderately abundant in CRAB-C (59.14%), and least abundant in CRAB-N (11.25%), but its interactions with other genera increased in turn. Metagenomics and WGS analysis showed that virulence genes were more abundant in CRAB-I than in CRAB-C. Multi-locus sequence typing (MLST) of 46 CRAB isolates revealed that the main types were ST208 (30.43%) and ST938 (15.22%), with no difference between CRAB-I and CRAB-C.ConclusionLower respiratory tract microbiota dysbiosis including elevated relative abundance of Acinetobacter and reduced bacterial interactions, and virulence enrichment may lead to CRAB VAP.

This research aims to describe and compare the effects of partial-body cryotherapy (PBC) and cold-water immersion (CWI) on the physiological responses of soccer players after cycling in a hot and humid environment. Sixteen elite soccer players participated in three experiments, and received CWI (13°C for 15 min), PBC (110°C−140°C for 3 min), and CON (room temperature: 21°C ± 2°C), respectively, after aerobic and anaerobic cycling in a hot and humid environment (temperature: 35°C–38°C; humidity: 60%–70%). Heart rate (HR), blood lactate (BLa-), perfusion index (PI), oxygen saturation (SaO 2 ), core temperature (Tc), skin temperature (Ts), and rating of perceived exertion (RPE) were assessed at baseline and through 20 min (5-min intervals). HR was lower in CWI than CON after 20 min ( p < .05). SaO 2 was higher in CWI than PBC and CON between 10 and 20 min ( p < .05). Tc was lower from CWI and PBC than CON between 10 and 20 min ( p < .05). Ts was lower in PBC than CWI between 15 and 20 min ( p < .05). RPE was lower in PBC than CON 20 min after the exercise ( p < .05). No main group differences for BLa- and PI were observed. The physiological effects of PBC are generally similar to CWI. Compared with CON, both CWI and PBC could promote the recovery of physiological indexes within 20 min of exercise in a hot and humid environment. However, PBC can lead to a decrease in SaO 2 due to excessive nitrogen inhalation.

The purpose of this study was to discuss the effect of voluntary wheel running on striatal dopamine levels and anxiety-like behavior in rats with global cerebral ischemia. The male Sprague-Dawley rats were signed on in this study and randomly divided into following 4 groups: Control group (C group), Sham group (S group), ischemia group (I group), and 3 weeks physical exercise before ischemia group (3RI group). The rats in the 3RI group were placed in a voluntary running wheel for three weeks to exercise. Then, the rats in I and 3RI groups received bilateral carotid artery ligation (2-VO) operation. The C and S group did not perform voluntary running exercise and the bilateral common carotid arteries of S group were exposed without ligation. In vivo microdialysis was used in conjunction with high performance liquid chromatography (HPLC) and electrochemical detection to ascertain the level of dopamine in the striatum. Elevated plus maze (EPM) and open field (OF) were used to test anxiety status at 24 hours and 7days after 2-VO cerebral ischemia. Meanwhile, gait and motor coordination evaluations were carried out to eliminate the influence of non-specific motor problems. The results indicated that cerebral ischemia instigate the increase of striatal dopamine in I group rats during acute cerebral ischemia. A 3-week voluntary wheel running significantly enhances the striatal dopamine before ischemia and obstructs a further increase of dopamine during acute cerebral ischemia in 3RI group rats. At 24 hours after ischemia, striatal dopamine returned to pre-ischemic levels in 3RI group. Striatal dopamine in I group were less than pre-ischemic levels at 7 days. Behavioral data indicated that 3-week voluntary wheel running promoted recovery of anxiety-like behavior and gait were not affected by 2-VO cerebral ischemia at 24 hours post-ischemia rats. Therefore, it can be concluded that 3-week physical exercise significantly increased the striatal dopamine and improved anxiety-like behavior by inhibiting the increase of dopamine during acute cerebral ischemia and suppressing the decrease of dopamine after 24 hours and 7 days cerebral ischemia.

The energy-intensive industrial sector (EIIS) occupies a majority of global CO2 emissions, but spatially monitoring the spatiotemporal dynamics of these emissions remains challenging. In this study, we used the Chinese province with the largest carbon emissions, Shandong Province, as an example to investigate the capacity of remotely sensed thermal anomaly products to identify annual industrial heat source (IHS) patterns at a 1 km resolution and estimated the carbon emissions of these sources using auxiliary datasets and the boosting regression tree (BRT) model. The IHS identification accuracy was evaluated based on two IHS references and further attributed according to corporate inventory data. We followed a bottom-up approach to estimate carbon emissions for each IHS object and conducted model fitting using the explanatory strength of the annual population density, nighttime light (NTL), and relevant thermal characteristic information derived from the Visible Infrared Imaging Radiometer Suite (VIIRS). We generated a time series of IHS distributions from 2012 to 2020 containing a total of over 3700 IHS pixels exhibiting better alignment with the reference data than that obtained in previous work. The results indicated that the identified IHSs mostly belonged to the EIIS, such as energy-related industries (e.g., thermal power plants) and heavy manufacturing industries (e.g., chemistry and cement plants), that primarily use coal and coke as fuel sources. The BRT model exhibited a good performance, explaining 61.9% of the variance in the inventory-based carbon emissions and possessing an index of agreement (IOA) of 0.83, suggesting a feasible goodness of fit of the model when simulating carbon emissions. Explanatory variables such as the population density, thermal power radiation, NTL, and remotely sensed thermal anomaly durations were found to be important factors for improving carbon emissions modeling. The method proposed in this study is useful to aid management agencies and policymakers in tracking the carbon footprint of the EIIS and regulating high-emission corporations to achieve carbon neutrality.

Background: The purpose of this study is threefold: (1) compare differences in countermovement jump (CMJ) variables and squat jump (SJ) variables in male track and field athletes; (2) explore the correlation of Fast Twitch Fibers (FT), Effect of Pre-stretch (EP) and other variables during the CMJ in male track and field athletes; (3) explore the correlation of SJ variables in male track and field athletes. Methods: 96 male university athletes (21.25 ± 1.04 years; 71.96 ± 8.58 kg; 180.05 ± 5.66 cm) in track and field volunteered to participate in this study. They are from Capital University of Physical Education and Sports, and all athletes are above the national standard at the second level. Subjects sequentially completed 3 CMJs and 3 SJs on the force plate. Throughout the entire range of motion, the CMJ and SJ were performed with both hands on the hips. In a laboratory, all of the individuals were assessed at the same time. SPSS 25.0 (Chicago, IL, USA) was used to run independent samples t-test and Pearson correlation analysis. Results: The vertical jump displacement (VJD) (p < 0.01), squat displacement (SD) (p < 0.01), peak velocity (PV) (p < 0.01), peak power (PP) (p < 0.05), average power (AP) (p < 0.01) were significantly higher during the CMJ than during the SJ. The peak force (PF) (p < 0.01) was significantly smaller during the CMJ than during the SJ. The FT and EP during the CMJ were associated with low test-retest reliability (coefficient of variation (CV): 9.73–8.86%). VJD, SD, PF, PP, and AP produced high test-retest reliability (CV: 2.29–4.48%) during both the CMJ and SJ movements. The correlation results were as follows, the VJD during the CMJ was significantly related to SD, PF, PP, AP (r = 0.21, r = 0.42, r = 0.8, r = 0.69, respectively). The PF during the CMJ was significantly related to PP and AP (r = 0.87, r = 0.72, respectively). The PV during the CMJ was significantly related to PP and AP (r = 0.63, r = 0.79, respectively). During the CMJ, there were significant connections between PP and AP (r = 0.94). Except for SD showed no significant relationships and the results for the correlation of other variables were the same as CMJ during the SJ. Furthermore, the Fast Twitch Fibers (FT) during the CMJ was significantly related to PP and AP (r = 0.49, r = 0.46, respectively). The Effect of Pre-stretch (EP) during the CMJ was significantly related to PV, PP, AP and FT (r = 0.36, r = 0.24, r = 0.27, r = 0.22, respectively). Conclusions: Our results indicate that both FT and EP were highly significantly correlated with PP in CMJ, and both FT and EP were significantly correlated with AP in CMJ. In addition, FT and EP data have good reliability. It means that FT and EP may be important indicators of lower limb strength in male track and field athletes under certain conditions. This will inform the training of male track and field athletes.

Background: This study aimed to investigate the effects of cold water immersion (CWI) and contrast water therapy (CWT) on serum interleukin 6 and prostaglandin 2 levels in self-perceived exertion, and muscle soreness of elite race walkers over a 15-day high-intensity training period. Methods: Thirty elite male race walkers were randomly divided into three groups: control group (C, n = 10), cold-water immersion (CWI, n = 10) group, contrast water therapy (CWT, n = 10) group. After daily training, elite race walkers were exposed to either CWI (10 minutes at 10 °C) or CWT (4 cycles of 2.5 minutes, alternately at 12 °C and 38 °C). Elite race walkers in the control group only performed simple stretching without any additional treatment. The serum interleukin 6, prostaglandin 2, self-perceived exertion, and muscle soreness were tested at 6 training points at baseline (B), light load-1 (L1), heavy load-1 (H1), medium load (M), heavy load-2 (H2), light load-2 (L2), respectively. Results: When compared with the CWT group, the interleukin 6 level, prostaglandin 2 level, self-perceived exertion, and muscle soreness of the C group were not significantly different. When compared with the CWT group, the interleukin 6 level in the CWI group was significantly lower at the time point of L1 and H2. Similarly, CWI significantly reduced the prostaglandin 2 levels at M and L2, except for H2. Self-perceived exertion and muscle soreness were not significantly different in both groups. Conclusions: The results from this study demonstrate that CWI may be more effective than CWT for reducing inflammatory markers at certain points in a training cycle, but it does appear that this effect can be induced in a predictable fashion.

Background: Previous studies have demonstrated that pre-exercise suppresses anxiety-like behavior, but the effects of different exercise times on vascular dementia induced anxiety-like behavior have not been well investigated. Objective: The present study aims to investigate the underlying neurochemical mechanism of different pre-vascular-dementia exercise times on 5-HT and anxiety-like behavior in rats with vascular dementia. Methods: 32 Sprague-Dawley (SD) rats were randomly divided into 4 groups: sham group (S group, n = 8), vascular dementia group (VD group, n = 8), 1-week physical exercise and vascular dementia group (1WVD group, n = 8), and 4 weeks physical exercise and vascular dementia group (4WVD group, n = 8). 1 week and 4 weeks of voluntary wheel running were used as preexercise training. The vascular dementia model was established by bilateral common carotid arteries occlusion (BCCAo) for 1 week. But bilateral common carotid arteries were not ligated in the sham group. The level of hippocampal 5-HT was detected with in vivo microdialysis coupled with high-performance liquid chromatography (MD-HPLC). Elevated plus maze (EPM), open field (OF), and light/dark box test were used to test anxiety-like behavior. Results: Compared with the C group, the hippocampal 5-HT was significantly decreased in the VD group after 1 week of ligated operation. The hippocampal 5-HT levels in 1WVD and 4WVD groups were substantially higher than the level in the VD group. The hippocampal 5-HT level has no significant difference among C, 1WVD, and 4WVD. Behavioral data suggested that the rats in the VD group developed obvious anxiety-like behavior after 1 week of ligation surgery. Still, the rats in 1WVD and 4WVD groups did not show significant anxiety-like behavior. Conclusion: Both 1 week and 4 weeks of voluntary running wheel exercise can inhibit the anxiety-like behavior in rats with vascular dementia by upregulating 5-HT levels in the hippocampus in the VD model. [ABSTRACT FROM AUTHOR]