Revealing cell-cell communication pathways with their spatially coupled gene programs.

Inference of cell-cell communication (CCC) provides valuable information in understanding the mechanisms of many important life processes. With the rise of spatial transcriptomics in recent years, many methods have emerged to predict CCCs using spatial information of cells. However, most existing methods only describe CCCs based on ligand-receptor interactions, but lack the exploration of their upstream/downstream pathways. In this paper, we proposed a new method to infer CCCs, called Intercellular Gene Association Network (IGAN). Specifically, it is for the first time that we can estimate the gene associations/network between two specific single spatially adjacent cells. By using the IGAN method, we can not only infer CCCs in an accurate manner, but also explore the upstream/downstream pathways of ligands/receptors from the network perspective, which are actually exhibited as a new panoramic cell-interaction-pathway graph, and thus provide extensive information for the regulatory mechanisms behind CCCs. In addition, IGAN can measure the CCC activity at single cell/spot resolution, and help to discover the CCC spatial heterogeneity. Interestingly, we found that CCC patterns from IGAN are highly consistent with the spatial microenvironment patterns for each cell type, which further indicated the accuracy of our method. Analyses on several public datasets validated the advantages of IGAN.

Protecting effects of 4-octyl itaconate on neonatal hypoxic-ischemic encephalopathy via Nrf2 pathway in astrocytes.

BACKGROUND: Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the most common neurological problems occurring in the perinatal period. However, there still is not a promising approach to reduce long-term neurodevelopmental outcomes of HIE. Recently, itaconate has been found to exhibit anti-oxidative and anti-inflammatory effects. However, the therapeutic efficacy of itaconate in HIE remains inconclusive. Therefore, this study attempts to explore the pathophysiological mechanisms of oxidative stress and inflammatory responses in HIE as well as the potential therapeutic role of a derivative of itaconate, 4-octyl itaconate (4OI). METHODS: We used 7-day-old mice to induce hypoxic-ischemic (HI) model by right common carotid artery ligation followed by 1 h of hypoxia. Behavioral experiments including the Y-maze and novel object recognition test were performed on HI mice at P60 to evaluate long-term neurodevelopmental outcomes. We employed an approach combining non-targeted metabolomics with transcriptomics to screen alterations in metabolic profiles and gene expression in the hippocampal tissue of the mice at 8 h after hypoxia. Immunofluorescence staining and RT-PCR were used to evaluate the pathological changes in brain tissue cells and the expression of mRNA and proteins. 4OI was intraperitoneally injected into HI model mice to assess its anti-inflammatory and antioxidant effects. BV2 and C8D1A cells were cultured in vitro to study the effect of 4OI on the expression and nuclear translocation of Nrf2. We also used Nrf2-siRNA to further validate 4OI-induced Nrf2 pathway in astrocytes. RESULTS: We found that in the acute phase of HI, there was an accumulation of pyruvate and lactate in the hippocampal tissue, accompanied by oxidative stress and pro-inflammatory, as well as increased expression of antioxidative stress and anti-inflammatory genes. Treatment of 4OI could inhibit activation and proliferation of microglial cells and astrocytes, reduce neuronal death and relieve cognitive dysfunction in HI mice. Furthermore, 4OI enhanced nuclear factor erythroid-2-related factor (Nfe2l2; Nrf2) expression and nuclear translocation in astrocytes, reduced pro-inflammatory cytokine production, and increased antioxidant enzyme expression. CONCLUSION: Our study demonstrates that 4OI has a potential therapeutic effect on neuronal damage and cognitive deficits in HIE, potentially through the modulation of inflammation and oxidative stress pathways by Nrf2 in astrocytes.

Effect of Acupoint Therapies on Postoperative Sleep Quality: A Narrative Review.

Several studies have reported that sleep quality often decreases in patients after surgery, especially in elderly patients, which seriously affects postoperative prognosis and outcomes, inducing diseases such as postoperative delirium, long-term chronic pain, and potentially fatal cardiovascular events. With the popularization of comfortable medicine, medical workers pay more attention to the postoperative sleep quality of patients. The causes underlying the decrease in postoperative sleep quality may include postoperative pain, the severity of surgical trauma and stress, perioperative anxiety and depression, and postoperative complications. Patients with insomnia often use acupoint therapies as a safe and effective alternative to drugs. Acupoint therapies are among the oldest medical therapies of Traditional Chinese Medicine and are gradually gaining recognition among medical workers worldwide. Various types of acupoint stimulation methods such as transcutaneous electrical acupoint simulation (TEAS), acupressure, acupuncture, and electroacupuncture can change the brain's local electrical activity, inhibit the central nervous system, and achieve deep sedation through stimulating the related acupoints, which provides a novel idea and basis for improvement in factors affecting postoperative sleep quality. This review explores the mechanism of acupoint therapies from several aspects of affecting the sleep quality of patients after surgery and its clinical results. We found that acupoint therapies effectively improve sleep quality and alleviate the postoperative complications of patients, and we emphasize the importance of acupoint therapies to guide future research and clinical practice. Large-scale, multicenter studies are needed to determine the optimal duration, frequency, and timing of acupoint stimulation for improving postoperative sleep quality.

Necessity and Importance of Developing AI in Anesthesia from the Perspective of Clinical Safety and Information Security.

The rapid development of artificial intelligence (AI) technology is due to the significant progress in big data, databases, algorithms, and computing power, and medical research is a vital application direction of AI. The integrated development of AI and medicine has improved medical technology, and the efficiency of medical services and equipment has enabled doctors to better serve patients. The tasks and characteristics of the anesthesia discipline also make AI necessary for its development, and AI has also been initially applied in different fields of anesthesia. Our review aims to clarify the current situation and challenges of AI application in anesthesiology to provide clinical references and guide the future development of AI in anesthesiology. This review summarizes progress in the application of AI in perioperative risk assessment and prediction, deep monitoring and regulation of anesthesia, essential anesthesia skills operation, automatic drug administration systems, and teaching and training in anesthesia. Also discussed herein are the accompanying risks and challenges of applying AI in anesthesia: patient privacy and information security, data sources, and ethical issues, lack of capital and talent, and the "black box" phenomenon.

Cerebellar malfunction and postoperative sleep disturbances after general anesthesia: a narrative review.

The cerebellum is widely regarded as a brain region involved in motor processing, non-motor processing, and even sleep-wake cycles. Cerebellar dysfunction may cause changes in the sleep-wake cycle, leading to sleep disturbances. At present, there is limited research on its effect on postoperative sleep after general anesthesia, despite the suspicion of its implication in postoperative sleep disturbances. With this review, we aim to provide a clear and comprehensive review of the cerebellar activity during the normal sleep-wake cycle, the correlation between cerebellar dysfunction and postoperative sleep disturbances, and the effects of general anesthesia on cerebellar dysfunction. Future large-scale multicenter trials are needed to objectively support the present results, identify the initial cerebellar dysfunction to prevent postoperative sleep disturbances, and develop new therapeutic measures targeting sleep disturbances with possible far-reaching implications for neurodegenerative diseases in general.

Study on the Construction of a Time-Space Four-Dimensional Combined Imaging Model and Moving Target Location Prediction Model.

Time-space four-dimensional motion target localization is a fundamental and challenging task in the field of intelligent driving, and an important part of achieving the upgrade in existing target localization technologies. In order to solve the problem of the lack of localization of moving targets in a spatio-temporal four-dimensional environment in the existing spatio-temporal data model, this paper proposes an optical imaging model in the four-dimensional time-space system and a mathematical model of the object-image point mapping relationship in the four-dimensional time-space system based on the central perspective projection model, combined with the one-dimensional "time" and three-dimensional "space". After adding the temporal dimension, the imaging system parameters are extended. In order to solve the nonlinear mapping problem of complex systems, this paper proposes to construct a time-space four-dimensional object-image mapping relationship model based on a BP artificial neural network and demonstrates the feasibility of the joint time-space four-dimensional imaging model theory. In addition, indoor time-space four-dimensional localization prediction experiments verify the performance of the model in this paper. The maximum relative error rates of the predicted motion depth values, time values, and velocity values of this localization method compared with the real values do not exceed 0.23%, 2.03%, and 1.51%, respectively.

The efficacy of acupuncture in postoperative sleep quality: a literature review.

PURPOSE: General anesthesia may affect the quality of postoperative sleep, especially after surgery on elderly patients. The decline of postoperative sleep quality may produce harmful effects on the postoperative recovery of patients. In this review, we summarized the efficacy and potential mechanism of acupuncture on postoperative sleep quality. METHODS: We review the effect of general anesthesia on circadian sleep rhythm. In addition, to provide evidence about the impairment of decreased postoperative sleep quality, we also emphasize the mechanism of acupuncture alleviates factors that affect sleep quality after general anesthesia. RESULTS: The application of acupuncture technology has been helpful to improve sleep quality and alleviate postoperative complications affecting postoperative sleep quality after general anesthesia. CONCLUSION: Acupuncture at different acupoints could effectively improve body's neurotransmitter levels and regulate biological clock genes through various mechanisms, and then improve postoperative sleep quality. Large-scale multi-center trials are needed to verify these findings.

[Application of preputial endoscopy in the treatment of phimosis].

OBJECTIVE: To explore the application value of preputial endoscopy in the treatment of phimosis. METHODS: The clinical data were obtained on 58 cases of phimosis with an obvious narrow ring at the prepuce mouth and unable to reveal the glans penis when pushed up, which were treated in hour department from October 2018 to May 2020. The patients underwent preputial endoscopic examination followed by circumcision (group A, n = 30) or simple circumcision (group B, n = 28). A ureteroscope was used for preputial endoscopy, and the foreign matter removed with forceps to prepare for later circumcision. Under surface anesthesia, the ureteroscope was entered into the preputial cavity to observe the intactness and smoothness of the right, left and anterior walls and the frenulum side, as well as possible bleeding, tumor or hypospadias. RESULTS: Preputial endoscopy was successfully performed in all the 30 cases, which revealed 1 case of adhesive integration of the inner preputial lamina to the glans, 1 case of hypospadias, 2 cases of preputial adhesion and 2 cases of glans hemorrhage. Pathological biopsy confirmed penile cancer in 1 of the 6 cases. Lateral wall hemorrhage was found in 4 cases, preputial stones in 3, which was removed with foreign matter forceps, and preputial infection in 5 cases, which was treated by intrapreputial irrigation and antibiotic anti-inflammation therapy. The preputial endoscopic examinations lasted (6.52 ± 2.03) min. The operation time was significantly shorter in group A than in B (ï¼»37.81 ± 4.09ï¼½ vs ï¼»48.04 ± 5.48ï¼½ min, P < 0.01), and so were the postoperative pain duration (ï¼»110.74 ± 22.09ï¼½ vs ï¼»121.43 ± 26.80ï¼½ min, P < 0.01) and postoperative recovery time (ï¼»7.96 ± 1.83ï¼½ vs ï¼»12.04 ± 3.28ï¼½ d, P < 0.01). CONCLUSIONS: Preputial endoscopy is a safe and efficient method for the diagnosis and treatment of phimosis, with the advantages of simple operation, short examination time and less intraoperative pain, making essential preparations for subsequent circumcision.

Algorithm Design for Edge Detection of High-Speed Moving Target Image under Noisy Environment.

For some measurement and detection applications based on video (sequence images), if the exposure time of camera is not suitable with the motion speed of the photographed target, fuzzy edges will be produced in the image, and some poor lighting condition will aggravate this edge blur phenomena. Especially, the existence of noise in industrial field environment makes the extraction of fuzzy edges become a more difficult problem when analyzing the posture of a high-speed moving target. Because noise and edge are always both the kind of high-frequency information, it is difficult to make trade-offs only by frequency bands. In this paper, a noise-tolerant edge detection method based on the correlation relationship between layers of wavelet transform coefficients is proposed. The goal of the paper is not to recover a clean image from a noisy observation, but to make a trade-off judgment for noise and edge signal directly according to the characteristics of wavelet transform coefficients, to realize the extraction of edge information from a noisy image directly. According to the wavelet coefficients tree and the Lipschitz exponent property of noise, the idea of neural network activation function is adopted to design the activation judgment method of wavelet coefficients. Then the significant wavelet coefficients can be retained. At the same time, the non-significant coefficients were removed according to the method of judgment of isolated coefficients. On the other hand, based on the design of Daubechies orthogonal compactly-supported wavelet filter, rational coefficients wavelet filters can be designed by increasing free variables. By reducing the vanishing moments of wavelet filters, more high-frequency information can be retained in the wavelet transform fields, which is benefit to the application of edge detection. For a noisy image of high-speed moving targets with fuzzy edges, by using the length 8-4 rational coefficients biorthogonal wavelet filters and the algorithm proposed in this paper, edge information could be detected clearly. Results of multiple groups of comparative experiments have shown that the edge detection effect of the proposed algorithm in this paper has the obvious superiority.

Effect of physical exercise on young anesthesiologists with on-call-related fatigue.

To explore whether exercise can effectively relieve the fatigue state of overnight shift anesthesiologists with chronic fatigue. 78 anesthesiologists between 30 and 40 years of age at four hospitals in China were analyzed in the investigation. The Profile of Mood States (POMS) and Chalder Fatigue Scale (CFS) were used to assess psychological symptoms and fatigue respectively, and data regarding demographics, health, exercise and work-related variables were also collected. The total and physical fatigue score were highest among those who seldom do exercise compared to those who always do exercise (p < .05, respectively). Moreover, anesthesiologists who exercised 30-60 min everyday had the lowest total and physical fatigue score. When exercise for more than 60 min, the total and physical fatigue scores then increased. After completing a night shift, the post-on-call total Profile of Mood States scores of those who seldom do exercise was significantly increased (t = -4.9, p < .001). These study findings suggested that regular exercise 30-60 min everyday could effectively reduce anesthesiologists' physical fatigue and decrease their negative psychological state, and anesthesiologists should positively adjust working and exercise time.

Enantioselective amination of nitroolefins under base-free and water-rich conditions using chiral bifunctional phase-transfer catalysts.

The direct enantioselective amination of nitroolefins has been performed with l-tert-leucine-derived squaramide-scaffold bifunctional phase-transfer catalysts under base-free and water-rich conditions with low catalyst loading (0.5-1 mol%) to provide 2-aminonitroalkanes in good yields (up to 96%) and enantioselectivities (up to 93% ee).

[Effect of Transcutaneous Acupoint Electrical Stimulation on Propofol Usage in Closed-loop Anes- thesia Delivery System in Pediatric Cardiac Surgery].

Objective To evaluate the effect of transcutaneous acupoint electrical stimulation (TEAS) on propofol usage in closed-loop anesthesia delivery system and pediatric hemodynamics. Methods Sixty children patients undergoing selective tonsillectomy and adenoidectomy surgeries were randomly allocated to the TEAS group (T) and the control group (C) , 30 in each group. Anesthesia maintenance in both groups was performed by propofol closed-loop anesthesia infusion system after induction of anesthesia. Patients in group T were treated with continuous TEAS (2/100 Hz sparsedense wave, 8 - 12 mA) at unilateral Hegu (L14) and Shenmen till the end of surgery. No TEAS was performed to patients in group C. Mean arterial pressure (MAP) and heart rate (HR) were recorded before anesthesia (TO), immediately after intubation ( T1) , 5 min after intubation (T2) , 10 min after intubation (T3) , 15 min after intubation (T4) , the time for intubation (T5) , respectively. The total dose of propofol, times for propofol dose adjustment, average target concentration, cases of patients with extra Fentanyl were recorded during anesthesia maintenance. Bispectral index (BIS) was recorded. Pediatric Anesthesia Emergence Delirium (PAED) scale and Modified Children's Hospital of Eastern Ontario Pain Scale (MCHEOPS) were assessed at T5, 5 min after extubation (T6) , 10 min after extubation (T7) , 15 min after extubation (T8), 30 min after extubation (T9) , respectively. Epinephrine (NE) was measured at TO, T1, T5, and T9, concentrations of IL-1 and IL-6 were measured at TO, T5, 24 h after surgery ( T10) , 48 h after surgery (T11), respectively. Results Compared with group C, MAP at T4 and T5 and HR at T1-T5 all de- creased, PAED scale and MCHEOPS decreased at T5-T9, NE concentrations were significantly reduced at T5 and T9, concentrations of IL-1 and IL-6 decreased at T5, T10, T1 1 in group T (P <0. 05, P <0. 01). Compared with group C, the total dose of propofol, times for propofol dose adjustment, average target concentration were reduced in group T during surgery (P <0. 05, P <0. 01). Twenty cases (67%) used propofol in group C and 9 cases (30% ) used propofol in group T during surgery, with statistical difference (P <0. 01). Changes of BIS was not statistically different between the two groups (P >0. 05). Conclusion TEAS could inhibit stress response and inflammatory response of children patients, stabilize their hemo- dynamics during surgery, thereby reducing propofol dose in closed-loop anesthesia delivery system.

Additive Neuroprotection of a 20-HETE Inhibitor with Delayed Therapeutic Hypothermia after Hypoxia-Ischemia in Neonatal Piglets.

The severity of perinatal hypoxia-ischemia and the delay in initiating therapeutic hypothermia limit the efficacy of hypothermia. After hypoxia-ischemia in neonatal piglets, the arachidonic acid metabolite 20-hydroxyeicosatetraenoic acid (20-HETE) has been found to contribute to oxidative stress at 3 h of reoxygenation and to eventual neurodegeneration. We tested whether early administration of a 20-HETE synthesis inhibitor after reoxygenation augments neuroprotection with 3-hour delayed hypothermia. In two hypothermic groups, whole body cooling from 38.5 to 34°C was initiated 3 h after hypoxia-ischemia. Rewarming occurred from 20 to 24 h; then anesthesia was discontinued. One hypothermic group received a 20-HETE inhibitor at 5 min after reoxygenation. A sham-operated group and another hypoxia-ischemia group remained normothermic. At 10 days of recovery, resuscitated piglets with delayed hypothermia alone had significantly greater viable neuronal density in the putamen, caudate nucleus, sensorimotor cortex, CA3 hippocampus, and thalamus than did piglets with normothermic recovery, but the values remained less than those in the sham-operated group. In piglets administered the 20-HETE inhibitor before hypothermia, the density of viable neurons in the putamen, cortex and thalamus was significantly greater than in the group with hypothermia alone. Cytochrome P450 4A, which can synthesize 20-HETE, was expressed in piglet neurons in these regions. We conclude that early treatment with a 20-HETE inhibitor enhances the therapeutic benefit of delayed hypothermia in protecting neurons in brain regions known to be particularly vulnerable to hypoxia-ischemia in term newborns.

Enantiomeric analysis of γ(δ)-lactones by reversed phase high performance liquid chromatography using amylose tris(5-chloro-2-methylphenylcarbamate) as stationary phase.

A Chiralpak AY-3R column was investigated for analytical enantiomeric separation of twelve racemic γ(δ)-lactones using reversed phase high performance liquid chromatography. Main influence factors, including organic modifier, flow rate and column temperature, were optimized. Five kinds of γ(δ)-lactones were successfully enantioseparated using the established method: γ-nonanolactone, δ-decalactone, δ-undecalactone, δ-dodecalactone and δ-tetradecalactone. Under optimized conditions, enantiomeric peak resolution (Rs) for the five γ(δ)-lactones reached more than 1.09, 1.08, 1.54, 1.43, and 1.11, respectively. Their chromatographic elution behavior was investigated using Van't Hoff equation and Van Deemter equation. It was found that an exothermic process occurred during enantiomeric separation of γ(δ)-lactones using this chromatographic column, and it showed a typical Van Deemter curve. Finally, this method was applied in enantiomeric ratio analysis of γ(δ)-lactones contents for purchased butter samples, and results confirmed the predominant content of the (R)-configuration of δ-dodecalactone in natural animal butter, while in margarine, an equal proportion of (R/S)-configuration of δ-dodecalactone was detected.

Investigating Novel Therapeutic Approaches for Idiopathic Short Stature: Targeting siRNA and Growth Hormone Delivery to the Growth Plate Using Exosome Nanoparticles.

Idiopathic short stature (ISS) is a common childhood condition with largely unknown underlying causes. Recent research highlights the role of circulating exosomes in the pathogenesis of various disorders, but their connection to ISS remains unexplored. In the experiments, human chondrocytes are cocultured with plasma exosomes from ISS patients, leading to impaired chondrocyte growth and bone formation. Elevated levels of a specific long non-coding RNA (lncRNA), ISSRL, are identified as a distinguishing factor in ISS, boasting high specificity and sensitivity. Silencing ISSRL in ISS plasma exosomes reverses the inhibition of chondrocyte proliferation and bone formation. Conversely, overexpression of ISSRL in chondrocytes impedes their growth and bone formation, revealing its mechanism of action through the miR-877-3p/GZMB axis. Subsequently, exosomes (CT-Exo-siISSRL-oeGH) with precise cartilage-targeting abilities are engineered, loaded with customized siRNA for ISSRL and growth hormone. This innovative approach offers a therapeutic strategy to address ISS by rectifying abnormal non-coding RNA expression in growth plate cartilage and delivering growth hormone with precision to promote bone growth. This research provides valuable insights into ISS diagnosis and treatment, highlighting the potential of engineered exosomes.

The relationship between different bispectral index and the occurrence of dreams in elective surgery under general anesthesia: protocol for a randomized controlled clinical trial.

INTRODUCTION: Dreaming reported after anesthesia remains a poorly understood phenomenon. At present, there is a hypothesis that dreaming occurs intraoperatively and is related to light or inadequate anesthesia; thus, in order to further verify the hypothesis, we choose elective surgery under general anesthesia to observe whether the generation of dreams is related to the dose of general anesthetics maintenance. METHODS AND ANALYSIS: This randomized, double-blind controlled trial to observe whether the generation of dreams is related to the dose of general anesthetics maintenance in the elective surgery under general anesthesia. A total of 124 participants will be randomly allocated to a low bispectral index or high bispectral index group at a ratio of 1:1. The Hospital Anxiety and Depression Scale (HADS) is used to assess the anxiety and depression status of participants during the perioperative period. Ramsay score is used to assess patients' sedation level after surgery in the PACU. Modified Brice questionnaire and awareness classification are used to assess whether patients experienced dreaming during the surgery. ETHICS AND DISSEMINATION: This randomized, double-blind controlled trial received prospective ethics committee approval at the Human Research Ethical Committee of Shengjing Hospital, Shenyang, Liaoning Province, China (Institutional Review Board registration number 2021PS664K), and was compliant with the Declaration of Helsinki. Written informed consent was obtained from all subjects participating in the trial.

Effects of Preoperative Anxiety on Postoperative Outcomes and Sleep Quality in Patients Undergoing Laparoscopic Gynecological Surgery.

OBJECTIVE: Preoperative anxiety is a psychological state that commonly occurs before surgery and may have a negative impact on postoperative outcomes. This study aimed to investigate the effects of preoperative anxiety on postoperative sleep quality and recovery outcomes among patients undergoing laparoscopic gynecological surgery. METHODS: The study was conducted as a prospective cohort study. A total of 330 patients were enrolled and underwent laparoscopic gynecological surgery. After assessing the patient's preoperative anxiety score on the APAIS scale, 100 patients were classified into the preoperative anxiety (PA) group (preoperative anxiety score > 10) and 230 patients into the non-preoperative-anxiety (NPA) group (preoperative anxiety score ≤ 10). The Athens Insomnia Scale (AIS) was assessed on the night before surgery (Sleep Pre 1), the first night after surgery (Sleep POD 1), the second night after surgery (Sleep POD2), and the third night after surgery (Sleep POD 3). Postoperative pain was evaluated by the Visual Analog Scale (VAS), and the postoperative recovery outcomes and adverse effects were also recorded. RESULT: The AIS score in the PA group was higher than that of the NPA group at Sleep-pre 1, Sleep POD 1, Sleep POD 2, and Sleep POD 3 (p < 0.05). The VAS score was higher in the PA group than in the NPA group within 48 h postoperatively (p < 0.05). In the PA group, the total dosage of sufentanil was significantly higher, and more rescue analgesics were required. Patients with preoperative anxiety showed a higher incidence of nausea, vomiting, and dizziness than those without preoperative anxiety. However, there was no significant difference in the satisfaction rate between the two groups. CONCLUSION: The perioperative sleep quality of patients with preoperative anxiety is worse than that of patients without preoperative anxiety. Moreover, high preoperative anxiety is related to more severe postoperative pain and an increased requirement for analgesia.

Recent progress on chiral extractants for enantioselective liquid-liquid extraction.

As the demand for enantiopure compounds increases, chiral separation has become increasingly important in many fields. Enantioselective liquid-liquid extraction is an up-and-coming technology for enantiomeric separation because it is highly efficient and easy to be scaled up. The key factor for enantioselective liquid-liquid extraction is the development of novel chiral extractants with high enantiorecognition performance. With successful studies on catalytically active metal complexes as chiral extractants, novel chiral extractants can be screened and designed from the field of asymmetric catalysis. Chiral ionic liquids, sulfobutylether-ß-cyclodextrins bonded magnetic nanoparticles and 2,2',3,3'-tetrahydro-1,1'-spirobi[indene]-7,7'-diol (SPINOL) based phosphoric acid host show unique potential ability in enantioselective liquid-liquid extraction and they deserve further study. Brief principles, extraction equipment and solvent systems in enantioselective liquid-liquid extraction are presented in the present paper, and recent progress in development of new chiral extractants in the past decade is mainly reviewed, including metal complexes, cyclodextrins, ionic liquids, tartrate acids and crown ethers.

Enantioseparation of two antifungal azole drugs by analytical countercurrent chromatography using sulfobutyl ether-ß-cyclodextrin as chiral selector.

This study reports a successful enantioseparation of two antifungal drugs, Ketoconazole and Voriconazole, using countercurrent chromatography (CCC) with synthesized sulfobutyl ether-ß-cyclodextrin (SBE-ß-CD) as chiral selector. Two biphasic solvent systems composed of dichloromethane: 0.1 mol L-1 of phosphate buffer solution (pH 3.0) (1:1, v/v) and n-hexane: ethyl acetate: 0.1 mol L-1 phosphate buffer solution (pH 3.0) (1.5:0.5:2, v/v/v) were selected. Influence factors were investigated, including degree of substitution of SBE-ß-CD, concentration of SBE-ß-CD, equilibrium temperature, and pH of aqueous phase. Under optimized separation conditions, a large enantioseparation factor of α ≥ 3.26 and a high peak resolution Rs= 1.82, was achieved for enantioseparation of Voriconazole by countercurrent chromatography, and purity of two azole stereoisomers collected from CCC separation reached 98.5%, as determined by HPLC. Molecular docking was employed to investigate the formation of inclusion complex.

Exploring the immune microenvironment of osteosarcoma through T cell exhaustion-associated gene expression: a study on prognosis prediction.

Background: Osteosarcoma is a highly aggressive type of bone cancer with a poor prognosis. In the tumor immune microenvironment, T-cell exhaustion can occur due to various factors, leading to reduced tumor-killing ability. The purpose of this study was to construct a prognostic model based on T-cell exhaustion-associated genes in osteosarcoma. Methods: Patient data for osteosarcoma were retrieved from the TARGET and GEO databases. Consensus clustering was employed to identify two novel molecular subgroups. The dissimilarities in the tumor immune microenvironment between these subgroups were evaluated using the "xCell" algorithm. GO and KEGG analyses were conducted to elucidate the underlying mechanisms of gene expression. Predictive risk models were constructed using the least absolute shrinkage and selection operator algorithm and Cox regression analysis. To validate the prognostic significance of the risk gene expression model at the protein level, immunohistochemistry assays were performed on osteosarcoma patient samples. Subsequently, functional analysis of the key risk gene was carried out through in vitro experimentation. Results: Four gene expression signatures (PLEKHO2, GBP2, MPP1, and VSIG4) linked to osteosarcoma prognosis were identified within the TARGET-osteosarcoma cohort, categorizing patients into two subgroups. The resulting prognostic model showed strong predictive capability, with area under the receiver operating characteristic curve (AUC) values of 0.728/0.740, 0.781/0.658, and 0.788/0.642 for 1, 3, and 5-year survival in both training and validation datasets. Notably, patients in the low-risk group had significantly higher stromal, immune, and ESTIMATE scores compared to high-risk counterparts. Additionally, a nomogram was developed, exhibiting high accuracy in predicting the survival outcome of osteosarcoma patients. Immunohistochemistry, Kaplan-Meier, and time-dependent AUC analyses consistently supported the prognostic value of the risk model within our osteosarcoma patient cohort. In vitro experiments provided additional validation by demonstrating that the downregulation of GBP2 promoted the proliferation, migration, and invasion of osteosarcoma cells while inhibiting apoptosis. Conclusion: The current study established a prognostic signature associated with TEX-related genes and elucidated the impact of the pivotal gene GBP2 on osteosarcoma cells via in vitro experiments. Consequently, it introduces a fresh outlook for clinical prognosis prediction and sets the groundwork for targeted therapy investigations in osteosarcoma.