Enhancing harmonic brightness near the cutoff region by using laser pulses with a small positive chirp.

Efficient enhancement of harmonic brightness near the cutoff region is achieved by employing laser pulses with a small positive chirp in theory, where the laser intensity and frequency near the peak of the laser pulse are almost unchanged relative to the chirp-free field. The improvement of harmonic brightness is achieved under the condition that the ionization probability is almost unchanged. Through the analysis of the harmonics contributed by the rising and falling parts of the laser pulse, we have uncovered a "frequency compensation" mechanism that leads to an enhanced harmonic brightness near the cutoff region. Under appropriate chirp parameters, the harmonics contributed by the rising and falling parts can be constructively interfered in a smaller frequency range with greater intensity, thereby obtaining harmonics with good monochromaticity and high brightness. This study explains the mechanism of harmonic brightness enhancement from a new perspective, and provides a new idea for harmonic regulation without changing the ionization.

The efficient method to get better raw brain signal on rat anesthetics experiment.

This paper introduces an efficient methodology for conducting rat anesthesia experiments, aimed at enhancing the quality of raw brain signals obtained. The proposed approach enables the acquisition of animal brain signals during experiments without the confounding influence of muscle noise. Initially, the use of alpha-chloralose (a-c) in conjunction with Isoflurane is introduced to induce anesthesia in rats. Subsequently, Dexdomitor is administered to prevent muscular movements during the collection of brain signals, further refining the signal quality. Experimental outcomes conclusively demonstrate that our anesthesia method produces cleaner raw signals and exhibits improved robustness during data acquisition, outperforming existing methods that rely solely on Isoflurane or the Ketamine-Xylazine combination. Notably, this improved performance is achieved with minimal alterations to vital physiological parameters, including body temperature, respiration, and heart rates. Moreover, the efficacy of a-c in maintaining anesthesia for up to 7 h stands in contrast to the shorter durations achievable with continuous Isoflurane administration or the 30-min window offered by Ketamine-Xylazine, highlighting the practical advantages of our proposed method. Finally, post-experiment observations confirmed that the animals gradually returned to normal behavior without any signs of distress or adverse effects, indicating that our method was both effective and safe.

Effect of a comprehensive geriatric assessment nursing intervention model on older patients with diabetes and hypertension.

BACKGROUND: The Comprehensive Geriatric Assessment (CGA) was introduced late in China and is primarily used for investigating and evaluating health problems in older adults in outpatient and community settings. However, there are few reports on its application in hospitalized patients, especially older patients with diabetes and hypertension. AIM: To explore the nursing effect of CGA in hospitalized older patients with diabetes and hypertension. METHODS: We performed a retrospective single-center analysis of patients with comorbid diabetes mellitus and hypertension who were hospitalized and treated in the Jiangyin Hospital of Traditional Chinese Medicine between September 2020 and June 2022. Among the 80 patients included, 40 received CGA nursing interventions (study group), while the remaining 40 received routine nursing care (control group). The study group's comprehensive approach included creating personalized CGA profiles, multidisciplinary assessments, and targeted interventions in areas, such as nutrition, medication adherence, exercise, and mental health. However, the control group received standard nursing care, including general and medical history collection, fall prevention measures, and regular patient monitoring. After 6 months of nursing care implementation, we evaluated the effectiveness of the interventions, including assessments of blood glucose levels fasting blood glucose, 2-h postprandial blood glucose, and glycated hemoglobin, type A1c (HbA1c); blood pressure indicators such as diastolic blood pressure (DBP) and systolic blood pressure (SBP); quality of life as measured by the 36-item Short Form Survey (SF-36) questionnaire; and treatment adherence. RESULTS: After 6 months, the nursing outcomes indicated that patients who underwent CGA nursing interventions experienced a significant decrease in blood glucose indicators, such as fasting blood glucose, 2-h postprandial blood glucose, and HbA1c, as well as blood pressure indicators, including DBP and SBP, compared with the control group (P < 0.05). Quality of life assessments, including physical health, emotion, physical function, overall health, and mental health, showed marked improvements compared to the control group (P < 0.05). In the study group, 38 patients adhered to the clinical treatment requirements, whereas only 32 in the control group adhered to the clinical treatment requirements. The probability of treatment adherence among patients receiving CGA nursing interventions was higher than that among patients receiving standard care (95% vs 80%, P < 0.05). CONCLUSION: The CGA nursing intervention significantly improved glycemic control, blood pressure management, and quality of life in hospitalized older patients with diabetes and hypertension, compared to routine care.

Membrane Protein Amuc_1100 Derived from Akkermansia muciniphila Facilitates Lipolysis and Browning via Activating the AC3/PKA/HSL Pathway.

Obesity, defined as a disorder of lipid metabolism caused by white fat accumulation, is closely related to the gut microbiota. Akkermansia muciniphila (Akk), one of the most common gut commensals, can reduce fat storage and promote the browning of white adipocytes, alleviating disorders of lipid metabolism. However, which components of Akk produce the effect remain unclear, limiting the application of Akk in the treatment of obesity. Here, we found that the membrane protein Amuc_1100 of Akk decreased formation of lipid droplets and fat accumulation during the differentiation process and stimulated browning in vivo and in vitro. Transcriptomics revealed that Amuc_1100 accelerated lipolysis through upregulation of the AC3/PKA/HSL pathway in 3T3-L1 preadipocytes. Quantitative PCR (qPCR) and Western blotting showed that Amuc_1100 intervention promotes steatolysis and browning of preadipocytes by increasing lipolysis-related genes (AC3/PKA/HSL) and brown adipocyte marker genes (PPARγ, UCP1, and PGC1α) at both the mRNA and protein levels. These findings introduce new insight into the effects of beneficial bacteria and provide new avenues for the treatment of obesity. IMPORTANCE An important intestinal bacterial strain Akkermansia muciniphila contributes to improving carbohydrate and lipid metabolism, thus alleviating obesity symptoms. Here, we find that the Akk membrane protein Amuc_1100 regulates lipid metabolism in 3T3-L1 preadipocytes. Amuc_1100 inhibits lipid adipogenesis and accumulation during the differentiation process of preadipocytes, upregulates the browning-related genes of preadipocytes, and promotes thermogenesis through activation of uncoupling protein-1 (UCP-1), including Acox1 involved in lipid oxidation. Amuc_1100 accelerates lipolysis via the AC3/PKA/HSL pathway, phosphorylating HSL at Ser 660. The experiments illustrated here identify the specific molecules and functional mechanisms of Akk. Therapeutic approaches with Amuc_1100 derived from Akk may help alleviate obesity and metabolic disorders.

Transcranial Alternating Current Stimulation Improves Memory Function in Alzheimer's Mice by Ameliorating Abnormal Gamma Oscillation.

Transcranial alternating current stimulation (tACS) is considered to have a positive effect on the rehabilitation of Alzheimer's disease (AD) as an intervention method that matches stimulation frequency to neurogenesis frequency. However, when tACS intervention is delivered to a single target, the current received by brain regions outside the target may be insufficient to trigger neural activity, compromising the effectiveness of stimulation. Therefore, it is worth studying how single-target tACS restores gamma-band activity in the whole hippocampal-prefrontal circuit during rehabilitation. We used Sim4Life software to conduct finite element methods (FEM) on the stimulation parameters to ensure that tACS intervened only in the right hippocampus (rHPC) and did not activate the left hippocampus (lHPC) or prefrontal cortex (PFC). We stimulated the rHPC by tACS for 21 days to improve the memory function of AD mice. We simultaneously recorded local field potentials (LFPs) in the rHP, lHPC and PFC and evaluated the neural rehabilitative effect of tACS stimulation with power spectral density (PSD), cross-frequency coupling (CFC) and Granger causality. Compared to the untreated group, the tACS group exhibited an increase in the Granger causality connection and CFC between the rHPC and PFC, a decrease in those between the lHPC and PFC, and enhanced performance on the Y-maze test. These results suggest that tACS may serve as a noninvasive method for Alzheimer's disease rehabilitation by ameliorating abnormal gamma oscillation in the hippocampal-prefrontal circuit.

A prediction model for COVID-19 liver dysfunction in patients with normal hepatic biochemical parameters.

Coronavirus disease 2019 (COVID-19) patients with liver dysfunction (LD) have a higher chance of developing severe and critical disease. The routine hepatic biochemical parameters ALT, AST, GGT, and TBIL have limitations in reflecting COVID-19-related LD. In this study, we performed proteomic analysis on 397 serum samples from 98 COVID-19 patients to identify new biomarkers for LD. We then established 19 simple machine learning models using proteomic measurements and clinical variables to predict LD in a development cohort of 74 COVID-19 patients with normal hepatic biochemical parameters. The model based on the biomarker ANGL3 and sex (AS) exhibited the best discrimination (time-dependent AUCs: 0.60-0.80), calibration, and net benefit in the development cohort, and the accuracy of this model was 69.0-73.8% in an independent cohort. The AS model exhibits great potential in supporting optimization of therapeutic strategies for COVID-19 patients with a high risk of LD. This model is publicly available at https://xixihospital-liufang.shinyapps.io/DynNomapp/.

Nonlinear relationship between body mass index and clinical outcomes after kidney transplantation: A dose-response meta-analysis of 50 observational studies.

BACKGROUND: Exact dose-response relationship between body mass index at transplantation and clinical outcomes after kidney transplantation remained unclear, and no specific body mass index threshold and pretransplant weight loss aim were recommended for kidney transplantation candidates among transplant centers. METHODS: PubMed, Embase, Web of Science, and Cochrane Library were searched for literature published up to December 31, 2019. The two-stage, random effect meta-analysis was performed to estimate the dose-response relationship between body mass index and clinical outcomes after kidney transplantation. RESULTS: Ninety-four studies were included for qualitative assessment and 50 for dose-response meta-analyses. There was a U-shaped relationship between graft loss, patient death, and body mass index. Body mass index with the lowest risk of graft loss was 25.2 kg/m2, and preferred body mass index range was 22-28 kg/m2. Referring to a body mass index of 22 kg/m2, the risk of graft loss was 1.088, 0.981, 1.003, and 1.685 for a body mass index of 18, 24, 28, and 40 kg/m2, respectively. Body mass index with the lowest risk of patient death was 24.7 kg/m2, and preferred body mass index range was 22-27 kg/m2. Referring to a body mass index of 22 kg/m2, the patient death risk was 1.115, 0.981, 1.032, and 2.634 for a body mass index of 18, 24, 28, and 40 kg/m2, respectively. J-shaped relationships were observed between body mass index and acute rejection, delayed graft function, primary graft nonfunction, and de novo diabetes. Pair-wise comparisons showed that higher body mass index was also a risk factor for cardiovascular diseases, hypertension, infection, longer length of hospital stay, and lower estimated glomerular filtration rate level. CONCLUSION: Underweight and severe obesity at transplantation are associated with a significantly increased risk of graft loss and patient death. A target body mass index at kidney transplantation is 22-27 kg/m2.

Long-term gamma transcranial alternating current stimulation improves the memory function of mice with Alzheimer's disease.

Background: The main manifestation of Alzheimer's disease (AD) in patients and animal models is impaired memory function, characterized by amyloid-beta (Aß) deposition and impairment of gamma oscillations that play an important role in perception and cognitive function. The therapeutic effect of gamma band stimulation in AD mouse models has been reported recently. Transcranial alternating current stimulation (tACS) is an emerging non-invasive intervention method, but at present, researchers have not completely understood the intervention effect of tACS. Thus, the intervention mechanism of tACS has not been fully elucidated, and the course of treatment in clinical selection also lacks theoretical support. Based on this issue, we investigated the effect of gamma frequency (40 Hz) tACS at different durations in a mouse model of AD. Materials and methods: We placed stimulating electrodes on the skull surface of APP/PS1 and wild-type control mice (n = 30 and n = 5, respectively). Among them, 20 APP/PS1 mice were divided into 4 groups to receive 20 min 40 Hz tACS every day for 1-4 weeks. The other 10 APP/PS1 mice were equally divided into two groups to receive sham treatment and no treatment. No intervention was performed in the wild-type control mice. The short-term memory function of the mice was examined by the Y maze. Aß levels and microglia in the hippocampus were measured by immunofluorescence. Spontaneous electroencephalogram gamma power was calculated by the average period method, and brain connectivity was examined by cross-frequency coupling. Results: We found that the long-term treatment groups (21 and 28 days) had decreased hippocampal Aß levels, increased electroencephalogram spontaneous gamma power, and ultimately improved short-term memory function. The treatment effect of the short-term treatment group (7 days) was not significant. Moreover, the treatment effect of the 14-day treatment group was weaker than that of the 21-day treatment group. Conclusion: These results suggest that long-term gamma-frequency tACS is more effective in treating AD by reducing Aß load and improving gamma oscillation than short-term gamma-frequency tACS.

Improving the Effect of Transcranial Alternating Current Stimulation (tACS): A Systematic Review.

With the development of electrical stimulation technology, traditional transcranial alternating current stimulation (tACS) technology has been found to have the drawback of not targeting a specific area accurately. Studies have shown that optimizing the number and position of electrodes during electrical stimulation has a very good effect on enhancing brain stimulation accuracy. At present, an increasing number of laboratories have begun to optimize tACS. However, there has been no study summarizing the optimization methods of tACS. Determining whether different optimization methods are effective and the optimization approach could provide information that could guide future tACS research. We describe the results of recent research on tACS optimization and integrate the optimization approaches of tACS in recent research. Optimization approaches can be classified into two groups: high-definition electrical stimulation and interference modulation electrical stimulation. The optimization methods can be divided into five categories: high-definition tACS, phase-shifted tACS, amplitude-modulated tACS, the temporally interfering (TI) method, and the intersectional short pulse (ISP) method. Finally, we summarize the latest research on hardware useful for tACS improvement and outline future directions.

Enhanced liver targeting of 5-fluorouracil using galactosylated human serum albumin as a carrier molecule.

The objective of this study was to develop a liver-specific antihepatocarcinoma agent. The galactosylated human serum albumin 5-fluorouracil conjugate (GHSA-5-FU) was prepared and tested for its chemical characteristic, biodistribution and primary cytotoxicity. The matrix assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) was applied to determined the molar ratio (moles of 5-FU/mole of G-HSA and moles of galactose/mole of HSA) of the conjugate. The liver targeting ability of GHSA-5-FU labeled by (131)I was evaluated by measuring the total radioactivity in organs after i.v. administration in mice and rabbits, and the cytotoxicity of the conjugate was assayed by MTT method. The results showed that the molar ratio of galactose to HSA was 50, and the 5-FU to GHSA was 15. Liver uptake in rabbits and mice peaked within 5-20 min after injection. The radioactivity (counts/g tissue) of the conjugate in the liver was several times higher than those in the other organs. The conjugate showed strong cytotoxicity, but no significant cytotoxicity difference was found between GHSA-5-FU and free 5-FU.

Effects of acupuncture on the expression of glial cell line-derived neurotrophic factor (GDNF) and basic fibroblast growth factor (FGF-2/bFGF) in the left sixth lumbar dorsal root ganglion following removal of adjacent dorsal root ganglia.

This investigation studied the temporal changes in the expression of GDNF and FGF-2 in the left sixth lumbar (L6) dorsal root ganglion (DRG) after acupuncture in adult cats subjected to unilateral removal of adjacent DRG. The cats were divided into three groups. Group I were normal control animals. Group II cats were subjected to removal of DRG associated with the left L1-L5 and L7-S2 spinal nerves, sparing the L6 DRG. Group III cats received similar treatment as Group II ones, but in addition were subjected to acupuncture on the left side at acupuncture points (xuewei) the day after the operation. Both Groups II and III animals were perfused under anesthesia at 7 and 14 days post-operation (dpo) and their left DRG were processed for the immunohistochemical demonstration of GDNF and FGF-2. Following removal of adjacent DRG, the average number of all GDNF stained neurons in L6 DRG was decreased at 7 dpo and more so at 14 dpo. Acupuncture reversed this trend, as demonstrated in the increased average number of immunopositive small-to-medium sized neurons. FGF-2 expression was also less marked at 7 dpo but returned to normal at 14 dpo. Acupuncture significantly increased the average number of FGF-2 positive neurons compared with that in operated animals. This increase was observed in both large and small-to-medium sized neurons. In conclusion, our results demonstrated that the average number of GDNF and FGF-2 neurons in L6 DRG was decreased after unilateral removal of adjacent DRG but acupuncture could reverse some of the changes.

[Partial dorsal root rhizotomy increases the anterograde transportation of neunotrophic factors in primary sensory neuron].

OBJECTIVE: To investigate whether partial dorsal root rhizotomy promotes the anterograde Five adult cats were transportation of BDNF, NT-3 and GDNF in the primary sensory neuron. METHODS: Subjected to unilateral spared root rhizotomy (the DRGs of L1-L5 and L7-S2 were removed, but L6 DRG was spared) and bilateral dorsal roots of L6 were ligated at the same time. Three days after operation, dorsal roots were taken out and made into frozen sections 20 microm in thickness. The sections were stained using specific BDNF, NT-3, GDNF antibody (1:1500) by ABC method. The immunoreactive density was observed in a site near DRG and a site near spinal cord. RESULTS: In the control group (with spared L6 DRG), there were no marked differences in NT-3 and GDNF immunoreactivity between the site near DRG and the site near spinal cord, while BDNF immunoreactivity was more intense in the site near DRG than that in the site near spinal cord. In the operation group, the immunoreactivity of each neurotrophin in the site near DRG was stronger than that in the site near spinal cord, and the immunoreactivities of BDNF, NT-3, GDNF in the site near DRG of the operation were stronger than those of the control group respectively. CONCLUSION: The increasing of immunoreactivities of neurotrophins near DRG following partial dorsal root rhizotomy suggests that partial dorsal root rhizotomy can promote their anterograde transportation from spared DRG to the spinal cord.

[The trkC expression in spared dorsal root ganglion following acupuncture].

OBJECTIVE: Investigating the TrkC expression in the spared dorsal root ganglion (DRG) after acupuncture stimulation of spared root. METHODS: Fifteen male adult cats were divided into three groups. Five cats were in the sham operation group; another five cats were subjected to unilateral root rhizotomy with (L1-L5, L7-S2 DRG sectioned, L6 DRG spared) and lived 7 days after operation; the last five cats were placed under electroneedle stimuli alternative at two groups of acupoints (including Tsusanli (St. 36) and Hsüanchung (G. B. 39), Fut'u (femur) (St. 32) and Sanyinchiao (Sp. 6) located in the distribution area of spinal nerve L6 on the operation side) 30 min a day for 7 days after unilateral root rhizotomy. On the 7th day, all animals were sacrificed. The L6 DRG from the experimental side of each animal was taken and made into frozen sections 20 microm in thickness. The sections were stained under the same condition using specific TrkC antibody (1:1000, Santa ) by immunohistochemistry ABC method. The number of TrkC immunoreaction (IR) neurons of DRG was observed and measured. RESULTS: In L6 DRG of sham operated group, TrkC-IR was found mainly distributed in the cell plasm of some large sized neurons and a few medium and small sized neurons. Following partial dorsal root rhizotomy, the number of trKC-IR large sized neurons apparently decreased, while the number of the small and medium sized neurons markedly increased (P < 0.05). The number and reaction level of TrkC-IR large sized neurons apparently increased after acupuncture (P < 0.05), but the number of TrkC-IR small and medium sized neurons were not significantly changed. CONCLUSION: This experimental study demonstrates that TrkC expression in L6 DRG neurons is upregulated after the acupuncture stimulation of spared root, suggesting that TrkC may be related to spinal plasticity.

[Synthesis of N1-(aryl)alkyloxyacyl-5-fluorouracil derivatives].

OBJECTIVE: To synthesize N1-(aryl)alkyloxyacyl-5-fluorouracil derivatives and investigate their antitumor activities. METHODS: Title compounds (I) were prepared by 5-fluorouracil which was trimethylsilylated by hexamethyl-di-silazane, and then acylated. Hydrogenization of compounds (I) brought on compounds (II), which were esterified to produce title compounds (III) afterwards. RESULTS: Twelve title compounds were synthesized. CONCLUSION: These compounds were designed products confirmed by 1H-NMR, IR and MS spectral data.

[Expression of NGF, BDNF and NT-3 in satellite cells of dorsal root ganglion].

OBJECTIVE: To investigate the distribution of NGF, BDNF, NT-3 and their mRNA in satellite cells of dorsal root ganglion (DRG) in adult cat. METHODS: Five male adult cats were used and their L6 DRGs unilateral side were taken and sectioned into frozen sections 20 microm in thickness respectively. The sections were stained by immunohistochemistry ABC method (NGF antibody 1:1000, Sigma; BDNF antibody 1:500, Santa Cruz; NT-3 antibody 1:1500, Santa Cruz), and in situ hybridization study(cRNA probe 1:100). RESULTS: NGF, BDNF, NT-3 and their mRNA were observed in some satellite cells. The positive signal of mRNA for NGF, BDNF and NT-3 was observed in cytoplasm. However, there was difference in the subcellular localization of protein for the three factors. BDNF immunoreactivity (BDNF-IR) was located in cytoplasm, while NGF-IR and NT-3-IR were located in nucleus. CONCLUSION: The results demonstrated that some satellite cells contain NGF, BDNF and NT-3 as well as their mRNA. The difference of subcellular localization for NGF, BDNF and NT-3 indicated that the functional mechanism of each factor in satellite cells in adult cats may be different.