Solute transport characteristics at the lakebed sediment-water interface due to multiple influences of dual seasonal lakes.

Multiple coexisting seasonal lakes are observed in the Poyang Lake basin. The interaction between surface water and groundwater, along with solute transport at the sediment-water interface (SWI), plays a crucial role in material cycling within the Poyang Lake ecosystem. However, the mechanisms governing how the relative positions of these lakes influence solute transport at the SWI remain unclear. This study employs indoor experiments and simulations based on real topography to investigate how the separation distance and elevation differences between two seasonal lakes, termed "lake A" (situated farther from the main lake) and "lake B" (closer to the main lake), affect solute transport. Findings highlight a distinct recharge pattern from lake A to lake B and the main lake during periodic water level fluctuations. A reduced distance between dual seasonal lakes results in a diminished water level drop in lake B during dry seasons. Proximity allows lake A to contribute more solutes to the main lake while promoting solute transport from lake B to the main lake, increasing the pore water recharge flux to overlying water in lake B. In cases where the separation distance has insufficient impact on water levels, the speed of pore water flow in this area inversely correlates with the distance between dual lakes. Reducing the distance intensifies solute transport into the bottom of lake A. Lower the elevation of lake B increases the water level difference between dual seasonal lakes, curtailing pollution within the lakebed. Elevating lake B forms hydrological isolation and more severe pollution of the lakebed. Solutes predominantly transport between lake B and the main lake, with pollution spreading to the lakebed of lake A and transitioning to downward diffusion over time. This research provides valuable insights for the hydraulic regulation of seasonal lakes and holds significance for the ecological restoration of Poyang Lake.

LSD1 in drug discovery: From biological function to clinical application.

Lysine-specific demethylase 1 (LSD1) is a flavin adenine dinucleotide (FAD) dependent monoamine oxidase (MAO) that erases the mono-, and dimethylation of histone 3 lysine 4 (H3K4), resulting in the suppression of target gene transcriptions. Besides, it can also demethylate some nonhistone substrates to regulate their biological functions. As reported, LSD1 is widely upregulated and plays a key role in several kinds of cancers, pharmacological or genetic ablation of LSD1 in cancer cells suppresses cell aggressiveness by several distinct mechanisms. Therefore, numerous LSD1 inhibitors, including covalent and noncovalent, have been developed and several of them have entered clinical trials. Herein, we systemically reviewed and discussed the biological function of LSD1 in tumors, lymphocytes as well as LSD1-targeting inhibitors in clinical trials, hoping to benefit the field of LSD1 and its inhibitors.

The Mediation Role of Sleep Disturbances between Vitamin D and Depressive Symptoms: A Cross-Sectional Study.

Depression and sleep disturbances are highly prevalent health problems that have been suggested to be associated with vitamin D deficiency. This study investigated whether sleep disturbances affect the association between vitamin D and depressive symptoms. A total of 425 patients with depression were included in this study. Spearman correlation coefficients were chosen to assess the relation between vitamin D concentrations and depressive symptomatology (according to the PHQ-9 and HAMD-17 scores). The GLM Mediation Model in the Medmod module for data analysis in Jamovi 2.2.5 was used to analyze the mediation models for sleep disturbances. Vitamin D concentrations were significantly correlated with PHQ-9 and HAMD-17 scale scores. In addition, item 3 was suggested to have a mediating effect between vitamin D and depressive symptoms in the mediating model of PHQ-9, and item 4 was suggested to have a mediating effect between vitamin D and depressive symptoms in the mediating model of HAMD-17. Sleep disturbances (especially difficulty falling asleep) are mediators between vitamin D and depressive symptoms, suggesting that increasing vitamin D levels at the right time to regulate sleep disturbances may improve depression symptoms, yet further research is necessary.

Novel acridine-based LSD1 inhibitors enhance immune response in gastric cancer.

Recently, histone lysine specific demethylase 1 (LSD1) has become an emerging and promising target for cancer immunotherapy. Herein, based on our previously reported LSD1 inhibitor DXJ-1 (also called 6x), a series of novel acridine-based LSD1 inhibitors were identified via structure optimizations. Among them, compound 5ac demonstrated significantly enhanced inhibitory activity against LSD1 with an IC50 value of 13 nM, about 4.6-fold more potent than DXJ-1 (IC50 = 73 nM). Molecular docking studies revealed that compound 5ac could dock well into the active site of LSD1. Further mechanism studies showed that compound 5ac inhibited the stemness and migration of gastric cancer cells, and reduced the expression of PD-L1 in BGC-823 and MFC cells. More importantly, BGC-823 cells were more sensitive to T cell killing when treated with compound 5ac. Besides, the tumor growth was also suppressed by compound 5ac in mice. Together, 5ac could serve as a promising candidate to enhance immune response in gastric cancer.

Recent advances in lithium-rich manganese-based cathodes for high energy density lithium-ion batteries.

The development of society challenges the limit of lithium-ion batteries (LIBs) in terms of energy density and safety. Lithium-rich manganese oxide (LRMO) is regarded as one of the most promising cathode materials owing to its advantages of high voltage and specific capacity (more than 250 mA h g-1) as well as low cost. However, the problems of fast voltage/capacity fading, poor rate performance and the low initial Coulombic efficiency severely hinder its practical application. In this paper, we review the latest research advances of LRMO cathode materials, including crystal structure, electrochemical reaction mechanism, existing problems and modification strategies. In this review, we pay more attention to recent progress in modification methods, including surface modification, doping, morphology and structure design, binder and electrolyte additives, and integration strategies. It not only includes widely studied strategies such as composition and process optimization, coating, defect engineering, and surface treatment, but also introduces many relatively novel modification methods, such as novel coatings, grain boundary coating, gradient design, single crystal, ion exchange method, solid-state batteries and entropy stabilization strategy. Finally, we summarize the existing problems in the development of LRMO and put forward some perspectives on the further research.

Discovery of acridine-based LSD1 inhibitors as immune activators targeting LSD1 in gastric cancer.

LSD1 is overexpressed in various cancers and promotes tumor cell proliferation, tumor expansion, and suppresses immune cells infiltration and is closely associated with immune checkpoint inhibitors therapy. Therefore, the inhibition of LSD1 has been recognized as a promising strategy for cancer therapy. In this study, we screened an in-house small-molecule library targeting LSD1, an FDA-approved drug amsacrine for acute leukemia and malignant lymphomas was found to exhibit moderate anti-LSD1 inhibitory activity (IC50 = 0.88 µM). Through further medicinal chemistry efforts, the most active compound 6x increased anti-LSD1 activity significantly (IC50 = 0.073 µM). Further mechanistic studies demonstrated that compound 6x inhibited the stemness and migration of gastric cancer cell, and decreased the expression of PD-L1 (programmed cell death-ligand 1) in BGC-823 and MFC cells. More importantly, BGC-823 cells are more susceptible to T-cell killing when treated with compound 6x. Moreover, tumor growth was also suppressed by compound 6x in mice. Altogether, our findings demonstrated that acridine-based novel LSD1 inhibitor 6x may be a lead compound for the development of activating T cell immune response in gastric cancer cells.

Gastroscopy sedation: clinical trial comparing propofol and sufentanil with or without remimazolam.

BACKGROUND: Propofol-sufentanil is often used in clinical anesthesia for patients undergoing sedative gastroscopy, but there are still adverse events such as longer recovery time, respiratory depression and higher doses of propofol etc. This study was to evaluate the sedative effect of remimazolam-propofol-sufentanil in sedative gastroscopy. METHODS: Patients who were going to have gastroscopy examination were randomly divided into two groups: group RM (remimazolam-propofol-sufentanil group) and group PR (propofol-sufentanil group). Patients of each group were anesthetized according to the corresponding anesthesia procedure, and all observation indices were recorded. RESULTS: In the RM group, there were only small and unsignificant changes in the values of SBP, HR, RR and SpO2 after anesthesia (P>0.05), while the values of SBP, HR, RR and SpO2 in the PR group at each time point after anesthesia were significantly lower than those at T0, and the values of SBP and RR at T2, T3 and T4 were also significantly lower than those at T1 (P<0.05). The dosage of propofol (38±9 mg) in the RM group was significantly less than that (115±15 mg) in the PR group, meanwhile the anesthesia time (8.4±1.6 min), awakening time (2.9±0.8 min), discharge time (6.7±3.1 min) of the RM group were also significantly shorter than those of the PR group (14.5±3.3, 8.7±1.9, 12.4±3.6 min) (P<0.05), but there was no statistical significance between the two groups in other indices (P>0.05). CONCLUSIONS: In clinical practice, remimazolam-propofol-sufentanil sedative scheme has more advantages than propofol-sufentanil sedative scheme.

Ultrasound-guided parasternal intercostal nerve block for postoperative analgesia in mediastinal mass resection by median sternotomy: a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Ultrasound-guided parasternal intercostal nerve block is rarely used for postoperative analgesia, and its value remains unclear. This study aimed to evaluate the effectiveness of ultrasound-guided parasternal intercostal nerve block for postoperative analgesia in patients undergoing median sternotomy for mediastinal mass resection. METHODS: This randomized, double-blind, placebo-controlled trial performed in Renmin Hospital, Wuhan University, enrolled 41 participants aged 18-65 years. The patients scheduled for mediastinal mass resection by median sternotomy were randomly assigned were randomized into 2 groups, and preoperatively administered 2 injections of ropivacaine (PSI) and saline (control) groups, respectively, in the 3rd and 5th parasternal intercostal spaces with ultrasound-guided (USG) bilateral parasternal intercostal nerve block. Sufentanil via patient-controlled intravenous analgesia (PCIA) was administered to all participants postoperatively. Pain score, total sufentanil consumption, and postoperative adverse events were recorded within the first 24 h. RESULTS: There were 20 and 21 patients in the PSI and control group, respectively. The PSI group required 20% less PCIA-sufentanil compared with the control group (54.05 ± 11.14 µg vs. 67.67 ± 8.92 µg, P < 0.001). In addition, pain numerical rating scale (NRS) scores were significantly lower in the PSI group compared with control patients, both at rest and upon coughing within 24 postoperative hours. Postoperative adverse events were generally reduced in the PSI group compared with controls. CONCLUSIONS: USG bilateral parasternal intercostal nerve block effectively reduces postoperative pain and adjuvant analgesic requirement, with good patient satisfaction, therefore constituting a good option for mediastinal mass resection by median sternotomy.

Corrigendum to "Interleukin-9 Deletion Relieves Vascular Dysfunction and Decreases Blood Pressure via the STAT3 Pathway in Angiotensin II-Treated Mice".

[This corrects the article DOI: 10.1155/2020/5741047.].

Interleukin-9 Deletion Relieves Vascular Dysfunction and Decreases Blood Pressure via the STAT3 Pathway in Angiotensin II-Treated Mice.

BACKGROUND: Multiple interleukin (IL) family members were reported to be closely related to hypertension. We aimed to investigate whether IL-9 affects angiotensin II- (Ang II-) induced hypertension in mice. METHODS: Mice were treated with Ang II, and IL-9 expression was determined. In addition, effects of IL-9 knockout (KO) on blood pressure were observed in Ang II-infused mice. To determine whether the effects of IL-9 on blood pressure was mediated by the signal transducer and activator of the transcription 3 (STAT3) pathway, Ang II-treated mice were given S31-201. Furthermore, circulating IL-9 levels in patients with hypertension were measured. RESULTS: Ang II treatment increased serum and aortic IL-9 expression in a dose-dependent manner; IL-9 levels were the highest in the second week and continued to remain high into the fourth week after the treatment. IL-9 KO downregulated proinflammatory cytokine expression, whereas it upregulated anti-inflammatory cytokine levels, relieved vascular dysfunction, and decreased blood pressure in Ang II-infused mice. IL-9 also reduced smooth muscle 22α (SM22α (SM22. CONCLUSIONS: IL-9 KO alleviates inflammatory response, prevents phenotypic transformation of smooth muscle, reduces vascular dysfunction, and lowers blood pressure via the STAT3 pathway in Ang II-infused mice. IL-9 might be a novel target for the treatment and prevention of clinical hypertension.

Hypothalamic gastrin-releasing peptide receptor mediates an antidepressant-like effect in a mouse model of stress.

Evidence has shown that gastrin-releasing peptide receptor (GRPR) is involved in responses to stress and anxiety. The primary role of GRPR is to stimulate corticotrophin-releasing hormone (CRH) or adrenocorticotropic hormone (ACTH) secretion. Thus, the mechanisms of GRPR signaling should be elucidated to discover novel therapeutic targets for treating depression. This study aimed to investigate GRPR alterations in the C57 mouse hypothalamus after the animals were subjected to stress and fluoxetine treatments. Specifically, we subjected the mice to isolation and chronic unpredictable mild stress (CUMS) for three weeks to establish an experimental model of depression. These mice were subsequently treated with fluoxetine for three weeks. Then, we performed the sucrose preference test and the open field test and measured food intake and body weight to explore the effects of stress and fluoxetine on activity and anhedonia. After fluoxetine treatment, we also assessed changes in the levels of GRPR expression in the hypothalamus using immunohistochemistry, western blotting, and real-time quantitative PCR (RT-PCR). We found that stressed mice showed significant reductions in locomotion, food intake/body weight, and sucrose preference; these reduced parameters indicated a state of anhedonia. Marked increases in mRNA and protein expression of GRPR in the hypothalamus of CUMS-exposed mice were also observed, although treatment with fluoxetine reversed these stress-induced changes. Our results also demonstrated the feasibility and effectiveness of the C57 mouse model of depression established by CUMS and isolation. After fluoxetine treatment was administered, the animals' depression symptoms were alleviated, and these behavioral alterations were accompanied by specific changes in mRNA and protein expression of GRPR in the hypothalamus. These results suggest that GRPR may be implicated in depression; therefore, new therapeutic targets of depression focused on GRPR signaling should be explored.

[Protection of Transcutaneous Acupoint Electrical Stimulation for Brain Injury Undergoing Intervention: a Clinical Observation].

OBJECTIVE: To observe the effect of transcutaneous acupoint electrical stimulation (TAES) combined dexmedetomidine on hemodynamic of intracranial aneurysmal subarachnoid hemorrhage patients undergoing intervention, and their protection for brain Injury. METHODS: Totally 108 intracranial aneurysmal subarachnoid hemorrhage patients undergoing intervention were randomly assigned to the electroacupuncture (EA) group and the control group according to random digit table, 54 in each group. All patients were anesthetized with dexmedetomidine. Patients in the EA group were needled at bilateral Neiguan (PC6), Lieque (LU7), and Yunmen (LU2). Parameter setting was as follows: The dilatational wave at 1. 5 Hz, strength 2 - 4 mA, 30 min. Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR) were compared between the two groups immediately after entry into the room (T0), after administration (T1), intubating (T2), resuscitation (T3), extubation (T4), and leaving the operating room (T5). Levels of S100ß protein (S100ß) and neuron specific enolase (NSE) were compared between the two groups at T0, immediately after surgery (T6), 6 h after operation (T7), 12 h after operation (T8), and 24 h after operation (T9). RESULTS: Compared with the same group at T0, SBP, DBP, MAP, and HR were significantly reduced in the two groups at T1-T5(P <0. 05), serum levels of S100ß and NSE in the two groups were significantly increased at T6-T9 (P<0. 05). Compared with the control group at T1 - T5, SBP, DBP, MAP, and HR decreased in the EA group (P <0. 05). Compared with the control group at T6-T9, serum levels of S100ß and NSE decreased in the EA group (P <0. 05). CONCLUSION: TAES combined dexmedetomidine could effectively maintain stable hemodynamics of intracranial aneurysmal subarachnoid hemorrhage patients undergoing intervention, and regulate their serum levels of S100ß and NSE.

Temporal and spatial contamination of polybrominated diphenyl ethers (PBDEs) in wastewater treatment plants in Hong Kong.

Polybrominated diphenyl ethers (PBDEs) are widely used as flame retardants which cause adverse effects to human health and environments. Wastewater treatment plants (WWTPs) receive PBDEs from various discharges but also release them back to the environment via treated effluent and sludge, depending on the removal efficiency of WWTPs. This study investigated the contamination of PBDEs in primary influent, final effluent and dewatered sludge in four WWTPs in Hong Kong from October 2011 to January 2013. Results showed that the concentrations and composition profiles of eight PBDE congeners (BDE-28, －47, －99, －100, －153, －154,－183 and －209) differed among WWTPs and fluctuated during the study period. Higher concentrations of PBDEs were detected in the influent and dewatered sludge from the two WWTPs receiving both domestic and industrial wastewaters than the two serve mainly residential and commercial districts. However, the PBDE concentrations in the effluent were comparable among WWTPs. The concentrations of Σ8PBDEs (total of eight congeners) in the influent of all WWTPs ranged from 1 to 254 ng L(-1) but decreased to 12-27 ng L(-1) in effluent, with removal efficiency ranged from 20 to 53%. High concentrations of PBDEs, ranging from 9 to 307 ng g(-1) dry weights, were detected in dewatered sludge. The predominated congeners in influent were BDE-47 and -209 but shifted to BDE-47 and －99 in effluent and BDE-209 in dewatered sludge. Every day, it is estimated 0.66-73 g PBDEs entered the four WWTPs, while 0.38-38 g and 0.17-17 g PBDEs were discharged to the surrounding waters via effluent and disposed to landfill sites in sludge form, respectively. These results indicated that the four WWTPs in Hong Kong were not designed for effectively removal of PBDEs, 52-80% of the incoming PBDEs were still remained in effluent and 21-45% was precipitated in sludge, both outputs became significant contamination sources.

Continuous right thoracic paravertebral block following bolus initiation reduced postoperative pain after right-lobe hepatectomy: a randomized, double-blind, placebo-controlled trial.

BACKGROUND AND OBJECTIVES: We hypothesized that continuous right thoracic paravertebral block, following bolus initiation, decreases opioid consumption after right-lobe hepatectomy in patients receiving patient-controlled intravenous analgesia with sufentanil. METHODS: Patients undergoing right-lobe hepatectomy with a right thoracic paravertebral catheter placed at T7 30 minutes before surgery were randomly assigned to receive through this catheter either a 10-mL bolus of 0.2% ropivacaine before emergence, followed by a continuous infusion of 6 mL/h for 24 hours (PVB group), or saline at the same scheme of administration (control group). All patients were started on patient-controlled intravenous analgesia with sufentanil in the postanesthesia care unit. The primary outcome measure was total sufentanil consumption during the first 24 postoperative hours. P = 0.05 was considered as significant. For the multiple comparisons of data at 5 different time points, the P value for the 0.05 level of significance was adjusted to 0.01. RESULTS: Sixty-six patients were assessed for eligibility, and a PVB catheter was successfully placed for 48 patients. Data were analyzed on 22 patients in group PVB and 22 patients in the control group. The cumulative sufentanil consumption in the PVB group (54.3 ± 12.1 µg) at 24 postoperative hours was more than 20% less than that of the control group (68.1 ± 9.9 µg) (P < 0.001). There was also a significant difference in pain scores (numerical rating scale) between groups, where the PVB group had lower scores than did the control group at rest and with coughing for the first 24 hours (P < 0.001). CONCLUSIONS: Continuous right thoracic paravertebral block, following bolus initiation, has an opioid-sparing effect on sufentanil patient-controlled intravenous analgesia for right-lobe hepatectomy patients and reduces numerical rating scale pain scores at rest and with coughing in the first 24 postoperative hours.

[Immune effects of three different programs for revaccination among adults of non- and hypo-responders to hepatitis B vaccine].

OBJECTIVE: To investigate the immune effects of three different programs for revaccination among adults of non- and hypo-responders to recombinant Hepatitis B vaccine. METHODS: Those who were once immunized with recombinant Hepatitis B vaccine more than one standard schedule (0, 1, and 6 months) in two years and negative for Hepatitis B markers were randomly given three-different projects for revaccination. 34 adults of A group were given GM-CSF 300 microg by subcutaneous injection for the first day, then 10 microg each time by intramuscular route for routine immune method. 33 adults of B group were given Hepatitis B vaccine 20 microg each time. 33 adults of C group were given Hepatitis B vaccine 10 microg each time. The blood samples were collected before the first injection and in 1, 2 and 8 months following the first injection to test Anti-HBs. RESULTS: At T1, the anti-HBs positive conversion rate of group A, B and C was 26.47%, 48.48% and 18.18% respectively (chi-2 = 7.20, P = 0.027). At T8, the anti-HBs positive conversion rate of group A (64.71%) and group B (75.76%) were higher than group C (39.39%), and there was significant difference (chi-2 = 9.07, P = 0.011). At T1, the anti-HBs level of group B (417.00 +/- 69.36) was higher than that of group A (203.74 +/- 79.56). At T2, the anti-HBs level of group B (458.17 +/- 64.09) was higher than that of group C (257.86 +/- 76.60). At T8, the anti-HBs level of group A (501.48 +/- 70.00) and group B (532.73 +/- 68.82) were higher than those of group C (256.12 +/- 75.39) (t =4.27, P = 0.0173). CONCLUSION: Schemes of augmentation doses of Hepatitis B vaccine and being combined with GM-CSF should be in effect for non- and hypo-responders to Hepatitis B vaccine.

[Study on rhGM-CSF as adjuvant in revaccination among adults of non-and hyporesponders to hepatitis B vaccine].

OBJECTIVE: To investigate the effect of recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF) as adjuvant on immune response in adults of non-and hyporesponders to hepatitis B vaccine. METHODS: Those who were once immunized with recombined yeast gene hepatitis B vaccine more than one standard scheme in two years and negative for hepatitis B markers were randomly sorted as group A and group B. 33 adults of group A were given hepatitis B vaccine 10 microg each time. The immune procedure was 0, 1 and 6 month. 34 adults of group B were given rhGM-CSF 300 microg for the first day, then 10 microg each time for routine immune. The blood samples were collected before the first injection and in 1, 2 and 8 months (T1, T2, T8) following the first injection to test Anti-HBs. RESULTS: Anti-HBs positive conversion rates of group A and B at T8 was 39.39% and 64.71% respectively (P = 0.038). Anti-HBs levels of group B at T1, T2, T8 were (113.85 +/- 198.56) mIU/ml, (312.40 +/- 349.44) mIU/ml, (427.74 +/- 411.58) mIU/ml (P = 0.001). There was significant difference between group A and B in T8 Anti-HBs levels (P = 0.010). CONCLUSION: Better immune response was found in the group of rhGM-CSF with hepatitis B vaccine. So rhGM-CSF can induce the immune respond to hepatitis B vaccine.