Survival benefits of propofol-based versus inhalational anesthesia in non-metastatic breast cancer patients: a comprehensive meta-analysis.

Whether the anesthesia technique, inhalational general anesthesia (IGA) or propofol-based anesthesia (PBA), influences the long-term survival of non-metastatic breast cancer (eBC) remain unclear and controversial. We carried out a literature search on 16thJuly, 2022 for studies comparing IGA and PBA in eBC undergoing standard surgery, according to PRISMA 2020. The major endpoint in our study was overall survival (OS). Seventeen studies including four randomized clinical trials and thirteen retrospective cohort studies were included in the meta-analysis. Ten studies provided data for crude OS in unweighted eBC patients (imbalance in baseline characteristics). The summarized estimate HRs of the PBA group versus the IGA group (ten studies, N = 127,774, IGA group: 92,592, PBA group: 35,182.) was 0.83 (95%CI: 0.78-0.89). Compared with IGA, PBA was associated with both better 1-year OS (two studies, N = 104,083, IGA group: 84,074, PBA group: 20,009. Pooled HR = 0.80, 0.73-0.89) and 5-year OS (six studies, N = 121,580, IGA group: 89,472, PBA group: 32,108. HR = 0.80, 0.74-0.87). Ten studies applied PSM method to balance the baseline characteristics. In these weighted patients, PBA still showed a better OS (ten studies, N = 105,459, IGA group: 79,095, PBA group: 26,364. HR = 0.93, 0.87-1.00), a better 1-year OS (two studies, N = 83,007, IGA group: 67,609, PBA group: 15,398. HR = 0.88, 0.78-0.98) and a trend towards a better 5-year OS (nine studies, N = 121,580, IGA group: 76,797, PBA group: 24,066. HR = 0.95, 0.88-1.03). Loco-regional recurrence-free survival (LRRFS) was also better in PBA group (HR = 0.73, 0.61-0.86). The present study is the first comprehensive meta-analysis to demonstrate that propofol-based anesthesia could significantly improve OS and LRRFS in non-metastatic breast cancer patients, compared with inhalational anesthesia.

Physiologically-based pharmacokinetic modeling predicts the drug interaction potential of GLS4 in co-administered with ritonavir.

GLS4 is a first-in-class hepatitis B virus (HBV) capsid assembly modulator (class I) that is co-administered with ritonavir to maintain the anticipated concentration required for the effective antiviral activity of GLS4. In this study, the first physiologically-based pharmacokinetic (PBPK) model for GLS4/ritonavir was successfully developed. The predictive performance of the PBPK model was verified using data from 39 clinical studies, including single-dose, multiple-dose, food effects, and drug-drug interactions (DDI). The PBPK model accurately described the PK profiles of GLS4 and ritonavir, with predicted values closely aligning with observed data. Based on the verified GLS4/ritonavir model, it prospectively predicts the effect of hepatic impairment (HI) and DDI on its pharmacokinetics (PK). Notably, CYP3A4 inducers significantly influenced GLS4 exposure when co-administered with ritonavir; co-administered GLS4 and ritonavir significantly influenced the exposure of CYP3A4 substrates. Additionally, with the severity of HI increased, there was a corresponding increase in the exposure to GLS4 when co-administered with ritonavir. The GLS4/ritonavir PBPK model can potentially be used as an alternative to clinical studies or guide the design of clinical trial protocols.

Staring X-ray backscatter imaging based on ultra-high aspect ratio lobster eye lens: erratum.

An erratum to correct a mistake for the article titled "Staring X-ray backscatter imaging based on ultra-high aspect ratio lobster eye lens" published in Opt. Express32(7), 11600 (2024)10.1364/OE.514941. The corrections have no influence on the results and conclusions of the original paper.

Safety, tolerability, pharmacokinetics, and pharmacodynamics of a soluble guanylate cyclase stimulator, HEC95468, in healthy volunteers: a randomized, double-blinded, placebo-controlled phase 1 trial.

Heart failure is the most costly cardiovascular disorder. New treatments are urgently needed. This study aims to evaluate the safety, pharmacokinetics, and pharmacodynamic profile of HEC95468, a soluble guanylate cyclase (sGC) stimulator, in healthy volunteers. Sixty-two, eighteen, and forty-eight participants were enrolled in the single ascending dose (SAD) study, the food effect (FE) study, and the multiple ascending dose (MAD) study, respectively. The study conforms to good clinical practice and the Declaration of Helsinki. Overall, HEC95468 was safe and tolerable; a higher proportion of HEC95468-treated participants reported mild headaches, dizziness, decreased blood pressure, increased heart rate, and gastrointestinal-related treatment-emergent adverse events (TEAEs), similar to the sGC stimulators riociguat and vericiguat. In terms of pharmacokinetic parameters, the maximum observed plasma concentration (Cmax) and the area under the concentration-time curve (AUC0-t) were dose-proportional over the dose range. Moderate accumulation was observed after multiple administrations of HEC95468. Systolic blood pressure (SBP) and diastolic blood pressure decreased, while 3',5'-cyclic guanosine monophosphate (cGMP) concentration in plasma increased and heart rate was induced. Vasoactive hormones (renin, angiotensin II, and norepinephrine) in plasma were compensatorily elevated after oral administration. These data supported further clinical trials of HEC95468 in the treatment of heart failure and pulmonary arterial hypertension. Systematic Review Registration: http://www.chinadrugtrials.org.cn, identifier CTR20210064.

Identification of Key Hypolipidemic Components and Exploration of the Potential Mechanism of Total Flavonoids from Rosa sterilis Based on Network Pharmacology, Molecular Docking, and Zebrafish Experiment.

Hyperlipidemia is a prevalent chronic metabolic disease that severely affects human health. Currently, commonly used clinical therapeutic drugs are prone to drug dependence and toxic side effects. Dietary intervention for treating chronic metabolic diseases has received widespread attention. Rosa sterilis is a characteristic fruit tree in China whose fruits are rich in flavonoids, which have been shown to have a therapeutic effect on hyperlipidemia; however, their exact molecular mechanism of action remains unclear. Therefore, this study aimed to investigate the therapeutic effects of R. sterilis total flavonoid extract (RS) on hyperlipidemia and its possible mechanisms. A hyperlipidemic zebrafish model was established using egg yolk powder and then treated with RS to observe changes in the integral optical density in the tail vessels. Network pharmacology and molecular docking were used to investigate the potential mechanism of action of RS for the treatment of hyperlipidemia. The results showed that RS exhibited favorable hypolipidemic effects on zebrafish in the concentration range of 3.0-30.0 µg/mL in a dose-dependent manner. Topological and molecular docking analyses identified HSP90AA1, PPARA, and MMP9 as key targets for hypolipidemic effects, which were exerted mainly through lipolytic regulation of adipocytes and lipids; pathway analysis revealed enrichment in atherosclerosis, chemical carcinogenic-receptor activation pathways in cancers, and proteoglycans in prostate cancer and other cancers. Mover, chinensinaphthol possessed higher content and better target binding ability, which suggested that chinensinaphthol might be an important component of RS with hypolipidemic active function. These findings provide a direction for further research on RS interventions for the treatment of hyperlipidemia.

Synergistic activities of Panobinostat and doxorubicin in soft tissue sarcomas.

BACKGROUND: Soft tissue sarcomas (STS) are rare diseases typically arising from connective tissues in children and adults. However, chemotherapies involved in the treatment of STS may cause toxic side effects and multi-drug chemoresistance, making the treatment even more challenging. Histone deacetylase inhibitors (HDACi) are epigenetic agents which have shown anti-tumor effects as single agent as well as combination use with other drugs. Our project intends to prove the same effects in STS. METHODS: Panobinostat (LBH589) plus doxorubicin was selected for investigations based on our previous research. Tumor xenografts were tried in an epithelioid sarcoma model to validate good synergy effects in vivo and a leiomyosarcoma model was used as a negative comparison group. Gene profile changes were studied afterwards. The possible pathway changes caused by HDACi were explored and validated by several assays. RESULTS: Synergy effect of LBH589 plus doxorubicin was successfully validated in STS cell lines and an epithelioid sarcoma mice model. We tried to reduce the dose of doxorubicin to a lower level and found the drug combination can still inhibit tumor size in mice. Furthermore, gene profile changes caused by LBH589 was studied by RNA-Sequencing analysis. Results showed LBH589 can exert effects on a group of target genes which can regulate potential biological functions especially in the cell cycle pathway.

Investigation of core symptoms and symptom clusters in maintenance hemodialysis patients: A network analysis.

PURPOSE: To construct a symptom network of maintenance hemodialysis patients and identify the core symptoms and core symptom clusters. Finally, this study provides a reference for accurate symptom management. DESIGN AND METHOD: A correlational cross-sectional design. A total of 368 patients who underwent maintenance hemodialysis were enrolled from two hemodialysis centers in Chengdu, Sichuan Province, China. A symptom network was constructed with the R coding language to analyze the centrality index. Symptom clusters were extracted by exploratory factor analysis, and core symptom clusters were preliminarily determined according to the centrality index of the symptom network. FINDINGS: The most common symptoms in maintenance hemodialysis patients were fatigue, dry skin, and pruritus. In the symptom network, headache had the highest mediation centrality (rB = 2.789) and closeness centrality (rC = 2.218) and the greatest intensity of numbness or tingling in the feet (rS = 1.952). A total of six symptom clusters were extracted, including pain and discomfort symptom clusters, emotional symptom clusters, gastrointestinal symptom clusters, sleep disorder symptom clusters, dry symptom clusters, and sexual dysfunction symptom clusters. The cumulative variance contribution rate was 69.269%. CONCLUSIONS: Fatigue, dry skin, and pruritus are the sentinel symptoms of maintenance hemodialysis patients, headache is the core symptom and bridge symptom, and pain symptom clusters are the core symptom clusters of MHD patients. Nurses can develop interventions based on core symptoms and symptom clusters to improve the effectiveness of symptom management in maintenance hemodialysis patients. CLINICAL RELEVANCE: Understanding the core symptoms and symptom groups that plague maintenance hemodialysis patients is critical to providing accurate symptom management. To ensure that maintenance hemodialysis patients receive effective support during treatment, reduce the adverse effects of symptoms, and improve the quality of life of patients.

Novel Alkaloids from Aspergillus fumigatus VDL36, an Endophytic Fungus Associated with Vaccinium dunalianum.

Eleven alkaloids (1-11) including seven new ones, 1-7, were isolated from the solid fermentation of Aspergillus fumigatus VDL36, an endophytic fungus isolated from the leaves of Vaccinium dunalianum Wight (Ericaceae), a perennial evergreen shrub distributed across the Southwest regions of China, Myanmar, and Vietnam. Their structures were elucidated on the basis of extensive spectroscopic methods. The isolates were evaluated for in vitro antifungal activities against five phytopathogenic fungi (Fusarium oxysporum, Coriolus versicolor, Fusarium solani, Botrytis cinerea, Fusarium graminearum). As a result, the new compounds fumigaclavine I (1), 13-ethoxycyclotryprostatin A (5), 13-dehydroxycyclotryprostatin A (6), and 12ß-hydroxy-13-oxofumitremorgin C (7) exhibited antifungal activities with MIC values of 7.8-62.5 µg/mL which were comparable to the two positive controls ketoconazole (MIC = 7.8-31.25 µg/mL) and carbendazim (MIC = 1.95-7.8 µg/mL). Furthermore, compounds 1 and 5 demonstrated potent protective and curative effects against the tomato gray mold in vivo. Preliminary structure-activity relationships of the tested indole diketopiperazine alkaloids indicate that the introduction of a substituent group at position C-13 enhances their biological activities.

Retracted: MD-1 Deficiency Accelerates Myocardial Inflammation and Apoptosis in Doxorubicin-Induced Cardiotoxicity by Activating the TLR4/MAPKs/Nuclear Factor kappa B (NF-κB) Signaling Pathway.

This publication has been retracted by the Editor due to the identification of non-original figure images and manuscript content that raise concerns regarding the credibility and originality of the study and the manuscript. Reference: Ying-Jun Zhang, He Huang, Yu Liu, Bin Kong, Guangji Wang. MD-1 Deficiency Accelerates Myocardial Inflammation and Apoptosis in Doxorubicin-Induced Cardiotoxicity by Activating the TLR4/MAPKs/Nuclear Factor kappa B (NF-kappaB) Signaling Pathway. Med Sci Monit, 2019; 25: 7898-7907. DOI: 10.12659/MSM.919861.

Undescribed Cyclohexene and Benzofuran Alkenyl Derivatives from Choerospondias axillaris, a Potential Hypoglycemic Fruit.

The fruit of Choerospondias axillaris (Anacardiaceae), known as south wild jujube in China, has been consumed widely in several regions of the world to produce fruit pastille and leathers, juice, jam, and candy. A comprehensive chemical study on the fresh fruits led to the isolation and identification of 18 compounds, including 7 new (1-7) and 11 known (8-18) comprised of 5 alkenyl (cyclohexenols and cyclohexenones) derivatives (1-5), 3 benzofuran derivatives (6-8), 6 flavonoids (9-14) and 4 lignans (15-18). Their structures were elucidated by extensive spectroscopic analysis. The known lignans 15-18 were isolated from the genus Choerospondias for the first time. Most of the isolates exhibited significant inhibitory activity on α-glucosidase with IC50 values from 2.26 ± 0.06 to 43.9 ± 0.96 µM. Molecular docking experiments strongly supported the potent α-glucosidase inhibitory activity. The results indicated that C. axillaris fruits could be an excellent source of functional foods that acquire potential hypoglycemic bioactive components.

Pacidusin B isolated from Phyllanthus acidus triggers ferroptotic cell death in HT1080 cells.

Cancer cells generally exhibit 'iron addiction' phenotypes, which contribute to their vulnerability to ferroptosis inducers. Ferroptosis is a newly discovered form of programmed cell death caused by iron-dependent lipid peroxidation. In the present study, pacidusin B, a dichapetalin-type triterpenoid from Phyllanthus acidus (L.) Skeels (Euphorbiaceae), induces ferroptosis in the HT1080 human fibrosarcoma cell line. Cells treated with pacidusin B exhibited the morphological characteristic 'ballooning' phenotype of ferroptosis. The biochemical hallmarks of ferroptosis were also observed in pacidusin B-treated cells. Both oxidative stress and ER stress play significant roles in pacidusin B-induced ferroptosis. The activation of the PERK-Nrf2-HO-1 signaling pathway led to iron overload, while inhibition of GPX4 further sensitized cancer cells to ferroptosis. Furthermore, the molecular docking study showed that pacidusin B docked in the same pocket in xCT as the ferroptosis inducer erastin. These results revealed that pacidusin B exerts anticancer effects via inducing ER-mediated ferroptotic cell death.

Phenolic constituents with potent α-glucosidase inhibitory and cytotoxic activities from Rumex nepalensis var. remotiflorus.

Quantitative analysis of Rumex nepalensis var. remotiflorus revealed that its roots contain rich anthraquinones, which has emodin, chrysophanol, and physcion contents of up to 0.30, 0.67, and 0.98 mg/g, respectively. Further phytochemical study led to the isolation and purification of seven undescribed phenolic constituents, including one flavan derivative with a 13-membered ring, polygorumin A (1), two dianthrone glucosides, polygonumnolides F and G (2, 3), two diphenylmethanones, rumepalens A and B (4, 5), and a pair of epimeric oxanthrone C-glucosides, rumejaposides K and L (6a, 6b) from the roots of R. nepalensis var. remotiflorus. Furthermore, 1 undescribed natural product, 1-ß-D-glucoside-6'-[(2E)-3-(4-hydroxy-3-methoxyphenyl)-2-propenoate]-3-hydroxy-5-methylphenyl (19), and 21 known phenolic compounds were obtained from the aforementioned plant for the first time. Their structures were elucidated through extensive spectroscopic data analysis. Notably, compounds 1, 4-5, and 7-9 exhibited inhibitory activity on α-glucosidase with IC50 values ranging from 1.61 ± 0.17 to 32.41 ± 0.87 µM. In addition, the isolated dianthrone, chrysophanol bianthrone (14), showed obvious cytotoxicity against four human cancer cell lines (HL-60, SMMC-7721, A-549, and MDA-MB-231) with IC50 values ranging from 3.81 ± 0.17 to 35.15 ± 2.24 µM. In silico target prediction and molecular docking studies demonstrated that the mechanism of the anticancer activity of 14 may be related to the interaction with protein kinase CK2.

Effect of "needle sensation" and the real-time changes in autonomic nervous system activity during acupuncture analgesia.

Introduction: Acupuncture analgesia (AA) is widely used in clinical practice. The autonomic nervous system (ANS) may be an important pathway for acupuncture signal transduction. However, real-time changes in autonomic function during AA and the effect of "needle sensation" remain unclear. Methods: We established a human pain model in healthy adults and randomly assigned 128 participants to the model, sham acupuncture, and acupuncture groups in a 1:1:2 ratio. Heart rate variability (HRV), including total power (TP), low-frequency power (LF), high-frequency power (HF), ratio of LF to HF (LF/HF), standard deviation of the normal-normal intervals (SDNN), and root mean square of successive interval differences (RMSSD), were used to assess autonomic function. The visual analog scale (VAS) and efficiency were used to assess the analgesic effect of acupuncture. The Massachusetts General Hospital acupuncture sensation scale (MASS) was used to indicate the intensity of the needle sensation. Anxiety levels were also measured. Finally, the correlation of MASS with HRV, VAS, and anxiety levels was analyzed. Results: VAS decreased after 10 min of needling and 5 min after needle withdrawal in the acupuncture group compared with those in the model group (p = 0.038, p = 0.020). The efficacy rates were 82.0, 50.0, and 61.3% in the acupuncture, model, and sham groups, respectively. These represent significant differences between the acupuncture group and the model and sham acupuncture groups (p < 0.001 in each case). No differences were observed between the model and sham acupuncture groups. HF, TP, SDNN, and RMSSD were all increased in the acupuncture group compared with those in the model group (p = 0.045, p = 0.041, p = 0.002, p = 0.006, respectively). No differences were observed in the sham acupuncture group compared to the model group (p = 0.632, p = 0.542, p = 0.093, p = 0.222, respectively). The LF and LF/HF did not differ among all three groups. A positive correlation was observed between MASS and RMSSD2, LF2, RMSSD4, TP4, VAS5, and anxiety levels. Conclusion: AA was associated with enhanced vagal activity. The intensity of needle sensation was positively correlated with vagal and sympathetic nerve activities. Acupuncture is an effective means of regulating autonomic function, and needle sensation may be an important modulator.

Staring X-ray backscatter imaging based on ultra-high aspect ratio lobster eye lens.

In contrast to conventional X-ray imaging systems, the lobster eye lens, serving as a pivotal component for X-ray focusing, presents the potential for downsizing X-ray backscatter imaging systems. This study reports the successful implementation of a pioneering non-contact staring X-ray backscatter imaging experiment, with the target positioned 1.5 meters away from the system and employing a tube voltage of 60 kV for the X-ray light source. The system is built upon a novel high aspect ratio (500) meridian lobster eye lens, employing a laboratory low illuminance desktop light source and a commercial X-ray detector to achieve high-resolution focused imaging of hard X-rays. Point spread function testing and a series of imaging experiments were carried out to assess the resolution and optimal imaging photon energy of the proposed system. Furthermore, according to the characteristics of the point spread function of the cross image of the lobster eye lens, we proposed an image processing algorithm. The experimental results demonstrate that, after processing, the Structural Similarity (SSIM) Index of the backscatter image and the ground truth image can be improved from an average of 0.0526 to 0.5758. Our research significantly contributes to the advancement of a new generation of X-ray backscatter imaging systems.

The Impact of Praise on Cooperative Behavior in Three-Player Public Goods Games and Its Gender Differences.

Previous research has primarily focused on static factors influencing cooperative behavior in social dilemmas, with less attention given to dynamic factors within group social interactions, such as positive feedback received during interactions, i.e., praise. This study, through a between-subjects online experiment with a single-factor, two-level design (praise: public praise/no praise), investigates the impact of praise on cooperative behavior changes across two rounds of a three-player public goods problem. Results revealed the following: (1) A positive correlation between individuals' contributions across two rounds and a negative correlation with the number of correct answers in rule comprehension questions were evident; for men, a correlation between rule comprehension and first-round contributions was observed. (2) Multilevel model results showed that praise, role, and rule comprehension significantly positively affected contribution changes across two rounds; gender did not significantly affect contribution changes. Specifically, under public-praise conditions, contribution changes were greater. Publicly praised individuals showed positive or negative behavior changes, while those not praised in the same group showed positive changes. Men contributed significantly more in the first round than women, with no gender difference found in contribution changes. Rule comprehension positively predicted contribution changes, indicating that more correct answers led to greater positive changes in contributions. These results not only support the inferential social learning perspective, suggesting that through praise, individuals can infer external world perceptions and self-evaluations, affecting both the praised (positively or negatively) and positively influencing non-praised individuals in the same group, but also provide a theoretical basis and intervention strategies for team and organizational management in groups.

Enhancing Polyvinyl Alcohol Nanocomposites with Carboxy-Functionalized Graphene: An In-Depth Analysis of Mechanical, Barrier, Electrical, Antibacterial, and Chemical Properties.

To enhance the various properties of polyvinyl alcohol (PVA), varying concentrations of carboxy-functionalized graphene (CFG) were employed in the preparation of CFG/PVA nanocomposite films. FTIR and XRD analyses revealed that CFG, in contrast to graphene, not only possesses carboxylic acid group but also exhibits higher crystallinity. Mechanical testing indicated a notable superiority of CFG addition over graphene, with optimal mechanical properties such as tensile and yield strengths being achieved at a 3% CFG concentration. Relative to pure PVA, the tensile strength and yield strength of the composite increased by 2.07 and 2.01 times, respectively. XRD analysis showed distinct changes in the crystalline structure of PVA with the addition of CFG, highlighting the influence of CFG on the composite structure. FTIR and XPS analyses confirmed the formation of ester bonds between CFG and PVA, enhancing the overall performance of the material. TGA results also demonstrated that the presence of CFG enhanced the thermal stability of CFG/PVA nanocomposite films. However, analyses using scanning electron microscopy and transmission electron microscopy revealed that a 3% concentration of CFG was uniformly dispersed, whereas a 6% concentration of CFG caused aggregation of the nanofiller, leading to a decrease in performance. The incorporation of CFG significantly enhanced the water vapor and oxygen barrier properties of PVA, with the best performance observed at a 3% CFG concentration. Beyond this concentration, barrier properties were diminished owing to CFG aggregation. The study further demonstrated an increase in electrical conductivity and hydrophobicity of the nanocomposites with the addition of CFG. Antibacterial tests against E. coli showed that CFG/PVA nanocomposites exhibited excellent antibacterial properties, especially at higher CFG concentrations. These findings indicate that CFG/PVA nanocomposites, with an optimized CFG concentration, have significant potential for applications requiring enhanced mechanical strength, barrier properties, and antibacterial capabilities.

Defoliation, trampling and nutrient return differentially influence grassland productivity by modulating trait-dependent plant community composition: insights from a simulated grazing experiment.

Ungulate grazing involves multiple components, including defoliation, dung and urine return, and trampling, which supply offsetting or synergistic effects on plant community composition and productivity (ANPP), but these effects have not been fully studied. Plant functional traits may reflect the response of plants to disturbance and their impact on ecosystem functions. Species turnover and intraspecific trait variation (ITV) are important drivers of community trait composition. We conducted a simulated grazing experiment in a steppe grassland in northern China to examine the effects of defoliation, dung and urine return, and trampling on community-weighted mean (CWM), functional diversity (FD) and ANPP, and to disentangle the roles of species turnover and ITV in driving these changes. We found that defoliation had a dominant effect on CWMs and FDs of all four traits through species turnover and ITV, respectively, resulting in a convergence of traits towards as more resource-acquisitive strategy. Dung-urine return resulted in more resource-acquisitive community traits mainly through ITV, whereas there were no significant effects on FDs except for leaf C/N. Trampling increased CWM of leaf dry matter content primarily driven by ITV, and had no significant effect on FDs. Furthermore, our simulated grazing positively affected ANPP, primarily due to nutrient additions from dung and urine, and ITV largely explained the variation in ANPP. These findings highlight the multifaceted effects of grazing components on community structure and ANPP, and the significance of ITV in shaping grassland plant communities and productivity.

Robust autofocus method based on patterned active illumination and image cross-correlation analysis.

For the effectiveness of a computer-aided diagnosis system, the quality of whole-slide image (WSI) is the foundation, and a useful autofocus method is an important part of ensuring the quality of WSI. The existing autofocus methods need to balance focusing speed and focusing accuracy, and need to be optimized separately for different samples or scenes. In this paper, a robust autofocus method based on fiber bundle illumination and image normalization analysis is proposed. For various application scenes, it meets the requirements of autofocusing through active illumination, such as bright field imaging and fluorescence imaging. For different structures on samples, it ensures the autofocusing accuracy through image analysis. The experimental results imply that the autofocusing method in this paper can effectively track the change of the distance from the sample to the focal plane and significantly improve the WSI quality.

Current treatment strategies targeting histone deacetylase inhibitors in acute lymphocytic leukemia: a systematic review.

Acute lymphocytic leukemia is a hematological malignancy that primarily affects children. Long-term chemotherapy is effective, but always causes different toxic side effects. With the application of a chemotherapy-free treatment strategy, we intend to demonstrate the most recent results of using one type of epigenetic drug, histone deacetylase inhibitors, in ALL and to provide preclinical evidence for further clinical trials. In this review, we found that panobinostat (LBH589) showed positive outcomes as a monotherapy, whereas vorinostat (SAHA) was a better choice for combinatorial use. Preclinical research has identified chidamide as a potential agent for investigation in more clinical trials in the future. In conclusion, histone deacetylase inhibitors play a significant role in the chemotherapy-free landscape in cancer treatment, particularly in acute lymphocytic leukemia.

Hypolipidemic and Antithrombotic Effect of 6'-O-Caffeoylarbutin from Vaccinium dunalianum Based on Zebrafish Model, Network Pharmacology, and Molecular Docking.

Vaccinium dunalianum leaf buds make one of the most commonly used herbal teas of the Yi people in China, which is used to treat articular rheumatism, relax tendons, and stimulates blood circulation in the body. In addition, 6'-O-caffeoylarbutin (CA) is a standardized extract of V. dunalianum, which has been found in dried leaf buds, reaching levels of up to 31.76%. Because of the uncommon phenomenon, it is suggested that CA may have a potential therapeutic role in hyperlipidemia and thrombosis. This study was designed to study the efficacy of CA on treating hyperlipidemia and thrombosis and the possible mechanisms behind these effects. Hyperlipidemia and thrombosis zebrafish models were treated with CA to observe variations of the integrated optical density within the vessels and the intensity of erythrocyte staining within the hearts. The possible mechanisms were explored using network pharmacology and molecular docking. The results demonstrate that CA exhibits an excellent hypolipidemic effect on zebrafish at concentrations ranging from 3.0 to 30.0 µg/mL and shows thrombosis inhibitory activity in zebrafish at a concentration of 30.0 µg/mL, with an inhibition rate of 44%. Moreover, network pharmacological research shows that MMP9, RELA, MMP2, PRKCA, HSP90AA1, and APP are major targets of CA for therapy of hyperlipidemia and thrombosis, and may relate to pathways in cancer, chemical carcinogenesis-receptor activation, estrogen signaling pathway, and the AGE-RAGE signaling pathway in diabetic complications.