Establishment of pseudorabies virus latency and reactivation model in mice dorsal root ganglia culture.

Pseudorabies virus (PRV) belongs to the alpha herpesvirus family and is responsible for Aujeszky's disease in pigs. Similar to other alpha herpesviruses, PRV establishes a lifelong latent infection in trigeminal ganglion. These latently infected pigs serve as a reservoir for recurrent infections when reactivation is triggered, making the eradication of PRV a challenging task. However, the molecular mechanism underlying PRV latency and reactivation in neurons is still poorly understood due to limitations in the in vitro model. To establish a pseudorabies virus latency and reactivation model in primary neuron cultures, we isolated dorsal root ganglion (DRG) from newborn Kunming mice using a method named epineurium-pulling for DRG collection (EPDC) and cultured primary neurons in vitro. A dual-colour recombinant PRV BAC mRuby-VP16 was constructed and 0.5 multiplicity of infection (MOI) was found as an appropriate dose in the presence of aciclovir to establish latency. Reactivation was induced using UV-inactivated herpesviruses or a series of chemical inhibitors. Interestingly, we found that not only UV-PRV, but also UV-HSV-1 and UV-BHoV-5 were able to induce rapid PRV reactivation. The efficiency of reactivation for LY294002, forskolin, etoposide, dexamethasone, and acetylcholine was found to be dependent on their concentration. In conclusion, we developed a valuable model of PRV latency and reactivation, which provides a basis for future mechanism research.

Gait performance and non-motor symptoms burden during dual-task condition in Parkinson's disease.

INTRODUCTION: Impaired gait is observed in patients with Parkinson's disease (PD) in both single-task (ST) and dual-task (DT) conditions. Non-motor symptoms (NMSs), another vital symptom future experienced along the PD disease trajectory, contribute to gait performance in PD. However, whether DT gait performance is indicative of NMS burden (NMSB) remains unknown. This study investigated correlation between NMS and DT gait performance and whether NMSB is reflected in the DT effects (DTEs) of gait parameters in PD. METHODS: Thirty-three idiopathic PD participants were enrolled in this study; the median H-Y staging was 2.5. NMSB was assessed by Non-motor Symptoms Scale (NMSS). Spatiotemporal gait parameters under ST and DT conditions were evaluated by wearable sensors. Gait parameters under ST and DT conditions and DTEs of gait parameters were compared across NMSB groups. The associations between NMS and DTEs of gait parameters were analyzed by correlation analysis and linear regression models. RESULTS: Compared to PD patients with mild-moderate NMSB, the severe-very severe NMSB group showed slower gait speed and shorter stride length under both ST and DT conditions (p < 0.05). DT had significantly negative effect on gait parameters in PD patients, including gait speed, stride length, and gait cycle duration (p < 0.05). PD patients with mild-moderate NMSB showed larger DTEs of cadence and bilateral gait cycle duration (p < 0.05). DTEs of bilateral gait cycle duration and swing phase on the more affected (MA) side were significantly correlated with NMSS scores (∣rSp∣ ≥ 0.3, p < 0.05). Gait cycle duration on the less affected (LA) side explained 43% of the variance in NMSS scores, when accounting for demographic and clinical confounders (ß = - 1.095 95% CI - 4.061 ~ - 0.058, p = 0.044; adjusted R2 = 0.434). CONCLUSION: DT gait performance could reflect NMSB in PD patients at early stage, and gait cycle duration is a valuable gait parameter to further investigate and to provide more evidence for PD management.

Diagnostic values of MRI indexes for polycystic ovary syndrome.

BACKGROUND: Magnetic resonance imaging (MRI) is a useful non-invasive modality for observation of ovarian morphologic characteristics. Few studies have focused on the value of MRI-derived indexes in reproductive-aged women with polycystic ovary syndrome (PCOS). PURPOSE: To assess the diagnostic value of MRI in women with PCOS. MATERIAL AND METHODS: This prospective case-control study included 85 women with PCOS and 50 controls who underwent pelvic MRI during 2017-2019. Ovarian volume (OV), follicle count (FC; counts of follicles sizing 2-3, 4-6, 7-9, 2-9 mm, respectively), follicular peripheral distribution, absence of a dominant follicle and stromal to total area ratio (S:A) were determined with MRI. The diagnostic value (sensitivity, specificity, area under the receiver operating characteristic curve [AUC]) of OV, FC2-9, and follicular peripheral distribution for PCOS were assessed. RESULTS: The AUCs were 0.94 for OV, 0.96 for FC2-9, and 0.78 for follicular peripheral distribution. The optimal threshold to detect PCOS was 8.5 mL for OV (sensitivity 78%; specificity 96%) and 26 for FC2-9 (sensitivity 85%; specificity 98%). Sensitivity and specificity were 73% and 82% for follicular peripheral distribution, respectively. Reproducibility was perfect for OV (ICC = 0.96) and absence of a dominant follicle (k = 0.85), substantial for FC2-9 (ICC = 0.79) and S:A (ICC = 0.69), and moderate for follicular peripheral distribution (k = 0.56). CONCLUSION: Detected by MRI, OV >8.5 mL or FC2-9 >26 are accurate for diagnosing PCOS.

Single-Cell RNA-Seq Reveals Changes in Cell Subsets in the Cortical Microenvironment during Acute Phase of Ischemic Stroke Rats.

BACKGROUND: Ischemic stroke, the most common stroke type, has threatened human life and health. Currently, intravenous thrombolysis and endovascular thrombectomy are the mainstream treatment methods, but they may cause cerebral ischemia-reperfusion injury (CIRI), which aggravates brain injury. Consequently, it is worthwhile to start with a study of CIRI mechanism to identify better prevention and treatment methods. Applying single-cell RNA sequencing (scRNA-seq) technology to further understand the biological functions of various cell types in CIRI will facilitate the intervention of CIRI. METHODS: This study aimed to establish a rat middle cerebral artery occlusion (MCAO) model to simulate cerebral ischemia-reperfusion, perform enzymatic hydrolysis, and suspend cerebral cortex tissue edema. Single-cell transcriptome sequencing was used, combined with cluster analysis, t-distributed stochastic neighbor embedding (t-SNE) visualization, and other bioinformatics methods to distinguish cell subgroups while using gene ontology (GO) function enrichment and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment to reveal the biological function of each cell subgroup. RESULTS: We identified 21 brain clusters with cell type-specific gene expression patterns and cell subpopulations, as well as 42 marker genes representing different cell subpopulations. The number of cells in clusters 0-3 increased significantly in MCAO group compared to that in the sham group, and nine-cell subpopulations exhibited remarkable differences in the number of genes. Subsequently, GO and KEGG analyses were performed on the top 40 differentially expressed genes (DEGs) in the six cell subpopulations with significant differences. These results indicate that biological processes and signaling pathways are involved in different cell subpopulations. CONCLUSIONS: ScRNA-seq revealed the diversity of cell differentiation and the unique information of cell subpopulations in the cortex of rats with acute ischemic stroke, providing novel insight into the pathological process and drug discovery in stroke.

[Research progress on oxaliplatin-induced neurotoxicity in traditional Chinese medicine (TCM) and western medical cognition and prevention and treatment by TCM].

Chemotherapy is one of the main options in clinical tumor treatment. Although chemotherapy drugs have a good therapeutic effect, they can also cause a series of adverse reactions, such as neurotoxicity. Chemotherapy-induced neurotoxicity is a dose-limi-ting adverse reaction that significantly affects patients' long-term treatment and quality of life. This article reviewed literature from 2000 to the present on chemotherapy-induced neurotoxicity and found that oxaliplatin was the most frequently used chemotherapy drug. Based on the clinical characteristics of oxaliplatin-induced neurotoxicity, this article summarized the understanding of its pathogenesis from both traditional Chinese medicine(TCM) and western medicine perspectives, discussed the role and mechanism of TCM compounds and monomeric components, and explored the research direction of using cutting-edge biotechnology to reveal the mechanism of oxaliplatin-induced neurotoxicity from a temporal-spatial perspective of intercellular communication and the application prospects of an interdisciplinary model combining TCM pathogenesis, western medicine manifestations, and artificial intelligence in precise intervention decision-making for TCM, aiming to provide research ideas for the prevention and treatment of oxaliplatin-induced neurotoxicity and the development of new drugs.

Identification and pathogenicity of hepatitis E Virus from laboratory Bama miniature pigs.

BACKGROUND: Hepatitis E virus (HEV) genotypes 3 and 4 are zoonotic. In this study, HEV infection in laboratory Bama miniature pigs in Sichuan Province of China was investigated. Firstly, one hundred rectal swabs were collected for HEV RNA testing, and chose positive samples for sequence analysis. Concurrently, for pathogenicity study, six healthy Bama miniature pigs were randomly divided into two groups of 3 pigs each. A total of 500 µL of HEV stock (positive fecal samples identified in this study) was inoculated intravenously into each pig in the experimental group, and the three pigs in the other group served as negative controls. Serum and fecal samples were collected at 1 to 10 weeks post-inoculation (wpi) for alanine aminotransferase (ALT) levels, anti-HEV antibodies and HEV RNA detection, respectively. During necropsies, liver lesions and HEV antigen in liver were observed at 10 wpi. RESULTS: The rate of fecal sample HEV RNA-positivity was 12% (12/100). Sequence comparisons indicated that partial ORF1 and ORF2 gene sequences of this isolate shared highest identities with corresponding sequences of genotype 4a HEV isolates (81.4%-96.1% and 89.9%-97.1%, respectively). Phylogenetic tree analysis further demonstrated that sequences of this isolate clustered together with sub-genotype 4a HEV isolate sequences. Experimentally, the pathogenicity of Bama miniature pigs infected with this isolate exhibited viremia, fecal virus shedding, seroconversion, ALT level increasing, liver lesions and HEV antigen in liver. CONCLUSIONS: This is the first study to confirm that HEV is currently circulating in laboratory Bama miniature pigs in China and this isolate can successfully infect Bama miniature pigs experimentally. More importantly, this study suggested HEV screening of laboratory pigs should be conducted to prevent research personnel from acquiring zoonotic HEV infections.

Lower serum triglyceride levels linked to more severe motor performance in Parkinson's disease.

INTRODUCTION: Emerging evidence has suggested that lipid metabolism is correlated with Parkinson's disease (PD) onset and progression. However, the effect of lipid metabolism on motor performance in PD patients is still unknown. This study estimated the association between lipid profiles and the severity of motor performance in PD. METHODS: This cross-sectional study enrolled 279 idiopathic PD patients from the Department of Neurology of Beijing Tiantan Hospital from May 2016 to August 2018. Serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (Apo-A1), and apolipoprotein B (Apo-B) levels were detected in fast serum samples. Motor performance was assessed by Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III (MDS-UPDRS III) total scores and subscores in these patients. The associations of lipid profiles with motor performance were analyzed using multivariable linear regression models. RESULTS: Compared to males, females with PD exhibited significantly higher serum TC, LDL-C, HDL-C, Apo-A1, and Apo-B levels. When accounting for covariates, lower serum TG levels were significantly associated with higher MDS-UPDRS III total scores and gait/postural instability subscores. Additionally, the univariate linear regression model showed that in males with PD, serum HDL-C or Apo-A1 levels were significantly associated with tremor subscores. CONCLUSION: Lower serum TG levels were associated with more severe motor performance in patients with PD and TG may be a potential predictive biomarker for motor performance in PD patients.

Circ003429 Regulates Unsaturated Fatty Acid Synthesis in the Dairy Goat Mammary Gland by Interacting with miR-199a-3p, Targeting the YAP1 Gene.

Fatty acid composition is a key factor affecting the flavor and quality of goat milk. CircRNAs are now recognized as important regulators of transcription, and they play an important role in the control of fatty acid synthesis. Thus, understanding the regulatory mechanisms controlling this process in ruminant mammary glands is of great significance. In the present study, mammary tissue from dairy goats during early lactation and the dry period (nonlactating) were collected and used for high-throughput sequencing. Compared to levels during the dry period, the expression level of circ003429 during early lactation was lower (12.68-fold downregulated). In isolated goat mammary epithelial cells, circ003429 inhibited the synthesis of triglycerides (TAG) and decreased the content of unsaturated fatty acids (C16:1, C18:1, and C18:2), indicating that this circRNA plays an important role in regulating lipid synthesis. A binding site for miR-199a-3p in the circ003429 sequence was detected, and a dual-luciferase reporter system revealed that circ003429 targets miR-199a-3p. Overexpression of circ003429 (pcDNA-circ003429) downregulated the abundance of miR-199a-3p. In contrast, overexpression of miR-199a-3p increased TAG content and decreased mRNA abundance of Yes-associated protein 1 (YAP1) (a target gene of miR-199a-3p), and TAG content was decreased and mRNA abundance was increased in response to overexpression of circ003429. These results indicate that circ003429 alleviates the inhibitory effect of miR-199a-3p on the mRNA abundance of YAP1 by binding miR-199a-3p, resulting in subsequent regulation of the synthesis of TAG and unsaturated fatty acids.

Telomeric epigenetic response mediated by Gadd45a regulates stem cell aging and lifespan.

Progressive attrition of telomeres triggers DNA damage response (DDR) and limits the regenerative capacity of adult stem cells during mammalian aging. Intriguingly, telomere integrity is not only determined by telomere length but also by the epigenetic status of telomeric/sub-telomeric regions. However, the functional interplay between DDR induced by telomere shortening and epigenetic modifications in aging remains unclear. Here, we show that deletion of Gadd45a improves the maintenance and function of intestinal stem cells (ISCs) and prolongs lifespan of telomerase-deficient mice (G3Terc-/-). Mechanistically, Gadd45a facilitates the generation of a permissive chromatin state for DDR signaling by inducing base excision repair-dependent demethylation of CpG islands specifically at sub-telomeric regions of short telomeres. Deletion of Gadd45a promotes chromatin compaction in sub-telomeric regions and attenuates DDR initiation at short telomeres of G3Terc-/- ISCs. Treatment with a small molecule inhibitor of base excision repair reduces DDR and improves the maintenance and function of G3Terc-/- ISCs. Taken together, our study proposes a therapeutic approach to enhance stem cell function and prolong lifespan by targeting epigenetic modifiers.

Effect of small vessel disease burden and lacunes on gait/posture impairment in Parkinson's disease.

INTRODUCTION: The comorbidity of cerebral small vessel disease (CSVD) may worsen gait impairment of Parkinson's disease (PD). However, the evidence remains scarce and controversial, and the mechanism of their potential interaction remains largely unknown. The present study aimed to investigate the overall impact of quantity and location of CSVD on gait/posture function in PD. METHODS: This cross-sectional study included 315 consecutive eligible patients with PD from Beijing Tiantan Hospital from May 2016 to August 2018. Associations of gait/posture subscores with the burden score of CSVD and four CSVD imaging markers were assessed using multivariate linear regression models. RESULTS: Burden of CSVD was significantly associated with more severe gait/posture impairment in PD in the unadjusted model (ß = 0.521, P = 0.011, 95% CI 0.118-0.923) and in the model adjusted for age, hypertension, ischemic stroke, low-density lipoprotein level, cholesterol level, and cognitive statues (ß = 0.448, P = 0.047, 95% CI 0.006-0.891). The presence of lacunes, but not other CSVD markers, was significantly associated with higher gait/posture subscores after the adjustment (ß = 0.492, P = 0.041, 95% CI 0.021-0.964), and the number of lacunes in the basal ganglia significantly correlated with the gait/posture subscores in patients with PD (P = 0.012, Spearman r = 0.161). CONCLUSIONS: CSVD and lacunes in the basal ganglia may independently contribute to gait/posture dysfunction in PD. Promoting neurovascular health may preserve some gait/posture function of PD.

Risk thresholds of levodopa dose for dyskinesia in Chinese patients with Parkinson's disease: a pilot study.

Levodopa is widely used to treat Parkinson's disease (PD), and its long-term therapy may induce dyskinesia in a dose-dependent manner. However, the threshold dose with a relatively low risk for dyskinesia has not been determined. Demographic, clinical profiles and detailed information of dopaminergic drugs were recorded for 403 PD patients in treatment with levodopa. Variables were compared between dyskinesia and non-dyskinesia groups. Logistic regression analysis was used to assess the association between levodopa dose-related variables and dyskinesia. Receiver operating characteristic curve and decision tree classification model were used to investigate the cut-off value of levodopa dose to best separate the dyskinesia group from the non-dyskinesia group. Patients with dyskinesia tended to have a lower weight and age at onset, higher percentage of female and wearing-off, longer duration of disease and levodopa treatment, higher H-Y stage and MDS-UPDRS Part III score, and higher levodopa dose and levodopa equivalent dose than those without dyskinesia. After adjusted for demographical and clinical variables, levodopa dose-related factors (daily dose, cumulative dose, and weight-adjusted dose) were still associated with dyskinesia. Both the receiver operating characteristic and decision tree classification analysis indicated that patients who have taken levodopa dose ≤ 400 mg per day may be associated with a reduced risk for dyskinesia. In conclusion, we evaluated the thresholds of levodopa treatment with a relatively low risk for dyskinesia. These data should be considered for prevention and management of dyskinesia in patients with PD.

The role of sodA and sodB in Aeromonas hydrophila resisting oxidative damage to survive in fish macrophages and escape for further infection.

Several bacteria have been defined as extracellular pathogens; however, in recent years, it has been confirmed that they have the ability to survive and escape the attack of host phagocytes, thus causing further infection. Previous studies have shown that Aeromonas hydrophila could survive in fish macrophages; however, the mechanism remains unknown. In this study, sodA and sodB of the strain A. hydrophila B11 were stable silenced by shRNA. The survival rates of intracellular sodA-RNAi and sodB-RNAi decreased by 91.8% and 74.9% and the immune escape rates decreased by about 32% and 92% respectively. At the same time, reactive oxygen species (ROS) in fish macrophages that phagocytosed sodA-RNAi and sodB-RNAi increased by 40% and 32.6%, respectively, compared to those of macrophages that phagocytosed the wild-type strain. Compared to sodA, the expression of sodB predominates in A. hydrophila without oxidative stress; however, when exposed to oxidative stress, the magnitude of up-regulation of sodA expression is significantly higher than that of sodB. With increased of methyl viologen concentration, the survival rates of sodA-RNAi and sodB-RNAi were significantly decreased. The expressions of sodA and sodB did not affect the growth of A. hydrophila without oxidative stress, but the inhibition of sodA and sodB expression led to a slight decrease in bacterial growth under oxidative stress. These results indicated that (1) sodA and sodB play an important role in the process of bacterial resistance to ROS damage in host phagocytic cells, allowing them to survive or even escape fish macrophages; (2) the sodB expression was dominant in A. hydrophila without oxidative stress, the sodA expression was up-regulated more significantly under oxidative stress, and sodA and sodB contributed equally to the process of bacterial resistance to ROS; (3) sodA and sodB complement each other and cooperate in the process of intracellular survival of bacteria to protect against ROS damage.

The role and mechanism of icmF in Aeromonas hydrophila survival in fish macrophages.

Survival in host macrophages is an effective strategy for pathogenic bacteria to spread. Aeromonas hydrophila has been found to survive in fish macrophages, but the mechanisms remain unknown. In this paper, the roles and possible mechanisms of IcmF in bacterial survival in fish macrophages were investigated. First, a stable silencing strain icmF-RNAi was constructed by shRNA and RT-qPCR confirmed the expression of icmF was down-regulated by 94.42%. The expression of Hcp, DotU and VgrG was also decreased in icmF-RNAi. The intracellular survival rate of the wild-type strain was 92.3%, while the survival rate of icmF-RNAi was only 20.58%. The escape rate of the wild-type strain was 20%, while that of the icmF-RNAi was only 7.5%. Further studies indicated that the expression of icmF can significantly affect the adhesion, biofilm formation, motility and acid resistance of A. hydrophila, but has no significant effect on the growth of A. hydrophila even under the stress of H2 O2 . The results indicated that IcmF of A. hydrophila not only acts as a structural protein which participates in virulence-related characteristics such as bacterial motility, adhesion and biofilm formation, but also acts as a key functional protein which participates in the interaction between bacteria and host macrophages.

Acoustic Characterization and Enhanced Ultrasound Imaging of Long-Circulating Lipid-Coated Microbubbles.

OBJECTIVES: A long-circulating lipid-coated ultrasound (US) contrast agent was fabricated to achieve a longer wash-out time and gain more resistance against higher-mechanical index sonication. Systemic physical, acoustic, and in vivo imaging experiments were performed to better understand the underlying mechanism enabling the improvement of contrast agent performance by adjusting the physical and acoustic properties of contrast agent microbubbles. METHODS: By simply altering the gas core, a kind of US contrast agent microbubble was synthesized with a similar lipid-coating shell as SonoVue microbubbles (Bracco SpA, Milan, Italy) to achieve a longer wash-out time and higher inertial cavitation threshold. To bridge the structure-performance relationship of the synthesized microbubbles, the imaging performance of the microbubbles was assessed in vivo with SonoVue as a control group. The size distribution and inertial cavitation threshold of the synthesized microbubbles were characterized, and the shell parameters of the microbubbles were determined by acoustic attenuation measurements. All of the measurements were compared with SonoVue microbubbles. RESULTS: The synthesized microbubbles had a spherical shape, a smooth, consistent membrane, and a uniform distribution, with an average diameter of 1.484 µm. According to the measured attenuation curve, the synthesized microbubbles resonated at around 2.8 MHz. Although the bubble's shell elasticity (0.2 ± 0.09 N/m) was comparable with SonoVue, it had relatively greater viscosity and inertial cavitation because of the different gas core. Imaging studies showed that the synthesized microbubbles had a longer circulation time and a better chance of fighting against rapid collapse than SonoVue. CONCLUSIONS: Nano/micrometer long-circulating lipid-coated microbubbles could be fabricated by simply altering the core composition of SonoVue microbubbles with a higher-molecular weight gas. The smaller diameter and higher inertial cavitation threshold of the synthesized microbubbles might make it easier to access deep-seated organs and give prolonged imaging enhancement in the liver.

Consecutive Sonogashira Coupling and Hydroamination Cyclization for the Synthesis of Isoindolo[1,2-b]quinazolin-10(12H)-ones Catalyzed by CuI/l-Proline.

A consecutive Sonogashira coupling reaction, acetylene hydroamination cyclization of 2-(2-bromophenyl)quinazolin-4(3H)-ones and terminal alkynes, is described catalyzed by CuI/l-proline in the presence of Cs2CO3. This procedure provided a facile method for the synthesis of isoindolo[1,2-b]quinazolin-10(12H)-one derivatives in good yields.

Gadd45a regulates hematopoietic stem cell stress responses in mice.

Gadd45a has been involved in DNA damage response and in many malignancies, including leukemia. However, the function of Gadd45a in hematopoietic stem cells (HSCs) remains unknown. Here, we reported that Gadd45a-deficient (Gadd45a(-/-)) mice showed a normal hematologic phenotype under homeostatic conditions. However, following 5-fluorouracil treatment, Gadd45a(-/-) HSCs exhibited a faster recovery, associated with an increase in the proliferation rate. Interestingly, young Gadd45a(-/-) HSCs showed enhanced reconstitution ability in serial transplantation. Following ionizing radiation (IR), young Gadd45a(-/-) HSCs exhibited an increased resistance to IR-induced DNA damage, associated with a decrease in the apoptosis rate and delayed DNA repair. The significantly higher level of DNA damage in Gadd45a(-/-) HSCs ultimately promoted B-cell leukemia in further transplanted recipient mice. In old mice, Gadd45a(-/-) HSCs were functionally equal to wild-type HSCs but exhibited more DNA damage accumulation and increased sensitivity to IR than wild-type HSCs. In conclusion, Gadd45a plays a significant role in HSC stress responses. Gadd45a deficiency leads to DNA damage accumulation and impairment in apoptosis after exposure to IR, which increases the susceptibility of leukemogenesis.

A new method for noninvasive venous blood oxygen detection.

BACKGROUND: Blood oxygen saturation of vein (SvO2) is an important clinical parameter for patient monitoring. However, the existing clinical methods are invasive, expensive, which are also painful for patients. METHODS: Based on light-absorption, this study describes a new noninvasive SvO2 measurement method by using external stimulation signal to generate cyclical fluctuation signal in the vein, which overcomes the low signal-to-noise ratio problem in the measurement process. In this way, the value of SvO2 can be obtained continuously in real time. RESULTS: The experimental results demonstrate that the method can successfully measure venous oxygen saturation by artificial addition of stimulation. Under hypoxic conditions, the system can reflect the overall decline of venous oxygen saturation better. When the results measured by the new method are compared with those measured by the invasive method, the root mean square error of the difference is 5.31 and the correlation coefficient of the difference is 0.72. The new method can be used to measure SvO2 and evaluate body oxygen consumption, and its accuracy needs improvement. CONCLUSIONS: Real-time and continuous monitoring can be achieved by replacing invasive method with noninvasive method, which provides more comprehensive clinical information in a timely manner and better meet the needs of clinical treatment. However, the accuracy of the new noninvasive SvO2 measurement based on light-absorption has to be further improved.

[Anesthesia in the Signal Processing Methods].

Anesthesia plays an essential role in clinical operations. Guiding anesthesia by EEG signals is one of the most promising methods at present and it has obtained good results. The analysis and process of the EEG signals in anesthesia can provide clean signal for further research. This paper used variance threshold method to remove the mutation fast and large interfering signals; and used notch filter to remove frequency interference, smoothing filter to remove baseline drift and Butterworth low-pass filter to remove high frequency noise at the same time. In addition to this, the translation invariant wavelet method to remove interference noise on the signals which was after the classical filter and retained non-stationary characteristics was used to evaluate parameter calculation. By comparing the calculated parameters from treated signal using this paper's methods and untreated signal and standard signal, the standard deviation and correlation has been improved, particularly the major parameters BetaR, which provides better signal for integration of multi-parameter to evaluate depth of anesthesia index for the latter.

Halogenated metabolites isolated from Penicillium citreonigrum.

Three chromone analogs, 1-3, a chlorinated alkaloid sclerotioramine (4), together with two 11-noreremophilane-type sesquiterpenes with a conjugated enolic OH group and a brominated one, 5 and 6, respectively, were isolated from Penicillium citreonigrum (HQ738282). Compounds 1, 5, and 6 were new. Biological tests revealed that 4 exhibited a significant activity (IC50 7.32 µg/ml), and 6 showed a moderate activity (IC50 16.31 µg/ml) in vitro against HepG2 cell line, and 4 also displayed an activity comparable to that of acarbose against α-glucosidase.

Copper Sulfate Combined with Photodynamic Therapy Enhances Antifungal Effect by Downregulating AIF1.

Candida albicans is a clinically significant opportunistic fungus that is generally treated with antifungal drugs such as itraconazole and fluconazole. However, the recent emergence of fungal resistance has made treatment increasingly difficult. Therefore, novel antifungal treatment methods are urgently required. Hexanol ethosome photodynamic therapy (HE-PDT) is a method that uses photosensitizers (PS), such as hexanol ethosome, to exert antifungal effects, and can be used to treat resistant fungal strains. However, due to the high dose of PS required for antifungal treatment, excess photosensitizers may remain. Furthermore, once exposed to light, normal tissues or cells are damaged after photodynamic therapy, which limits the clinical application of HE-PDT. Therefore, improving the efficacy without increasing the dose is the key to this treatment. In this study, the antifungal effect of copper sulfate combined with HE-PDT was investigated, and its mechanism was explored. The results suggested that exogenous copper sulfate significantly increased the antifungal effect of HE-PDT by enhancing the rate of C. albicans inhibition, increasing reactive oxygen species (ROS) accumulation, increasing the rate of apoptosis, and altering the mitochondrial membrane potential (MMP) and ATP concentration, which is related to the downregulation of apoptosis-inducing factor (AIF1) expression. In conclusion, copper sulfate combined with photodynamic therapy significantly inhibited the activity of C. albicans by inducing apoptosis. The combined approach reported herein provides new insights for future antifungal therapy.