The Effect of Gua Sha Therapy on Pain in Parkinson's Disease: a Randomized Controlled Trial.

Purpose: Pain is a common yet undertreated symptom of Parkinson's disease (PD). This study investigated the effect of Gua Sha therapy on pain in patients with PD. Patients and Methods: A total of 56 PD patients with pain were randomized into either the experimental group (n=28), receiving 12 sessions of Gua Sha therapy, or the control group (n=28) without additional treatment. Participants underwent assessment at baseline, after the twelfth invention, and at the 2-month follow-up timepoints. The primary outcome was KPPS and VAS. Secondary outcomes included UPDRS I-III, PDSS-2, HADS, PDQ-39, and blood biomarkers (5-HT, IL-8, IL-10). Results: The experimental group reported a significant improvement in pain severity, motor functions, affective disorder, and sleep quality (P < 0.05). Furthermore, increasing trends in both 5-HT and IL-10, as well as decreasing trends in IL-8 were observed. No serious adverse events occurred. Conclusion: The preliminary findings suggest that Gua Sha therapy may be effective and safe for alleviating pain and improving other disease-related symptoms in PD patients.

Augmented microglial endoplasmic reticulum-mitochondria contacts mediate depression-like behavior in mice induced by chronic social defeat stress.

Extracellular ATP (eATP) signaling through the P2X7 receptor pathway is widely believed to trigger NLRP3 inflammasome assembly in microglia, potentially contributing to depression. However, the cellular stress responses of microglia to both eATP and stress itself remain largely unexplored. Mitochondria-associated membranes (MAMs) is a platform facilitating calcium transport between the endoplasmic reticulum (ER) and mitochondria, regulating ER stress responses and mitochondrial homeostasis. This study aims to investigate how MAMs influence microglial reaction and their involvement in the development of depression-like symptoms in response to chronic social defeat stress (CSDS). CSDS induced ER stress, MAMs' modifications, mitochondrial damage, and the formation of the IP3R3-GRP75-VDAC1 complex at the ER-mitochondria interface in hippocampal microglia, all concomitant with depression-like behaviors. Additionally, exposing microglia to eATP to mimic CSDS conditions resulted in analogous outcomes. Furthermore, knocking down GRP75 in BV2 cells impeded ER-mitochondria contact, calcium transfer, ER stress, mitochondrial damage, mitochondrial superoxide production, and NLRP3 inflammasome aggregation induced by eATP. In addition, reduced GRP75 expression in microglia of Cx3cr1CreER/+Hspa9f/+ mice lead to reduce depressive behaviors, decreased NLRP3 inflammasome aggregation, and fewer ER-mitochondria contacts in hippocampal microglia during CSDS. Here, we show the role of MAMs, particularly the formation of a tripartite complex involving IP3R3, GRP75, and VDAC1 within MAMs, in facilitating communication between the ER and mitochondria in microglia, thereby contributing to the development of depression-like phenotypes in male mice.

Activation of CD14+ Monocytes via the IFN-γ Signaling Pathway Is Associated with Immune-Related Adverse Events in Hepatocellular Carcinoma Patients Receiving PD-1 Inhibition Combination Therapy.

(1) Background: Immune-related adverse events (irAEs) are a series of unique organ-specific inflammatory toxicities observed in patients with hepatocellular carcinoma (HCC) undergoing PD-1 inhibition combination therapy. The specific underlying mechanisms remain unclear. (2) Methods: We recruited 71 patients with HCC undergoing PD-1 inhibition combination therapy. These patients were then divided into two groups based on irAE occurrence: 34 had irAEs and 37 did not. Using Olink proteomics, we analyzed the aberrant inflammation-related proteins (IRPs) in these patient groups. For single-cell RNA sequencing (scRNA-seq) analysis, we collected peripheral blood mononuclear cells (PBMCs) from two representative patients at the pretreatment, irAE occurrence, and resolution stages. (3) Results: Our study revealed distinct plasma protein signatures in HCC patients experiencing irAEs after PD-1 inhibition combination therapy. We clarified the relationship between monocyte activation and irAEs, identified a strongly associated CD14-MC-CCL3 monocyte subset, and explored the role of the IFN-γ signaling pathway in monocyte activation during irAEs. (4) Conclusions: The activation of monocytes induced by the IFN-γ signaling pathway is an important mechanism underlying the occurrence of irAEs in HCC patients receiving PD-1 inhibition combination therapy.

A predictive model for patent ductus arteriosus seven days postpartum in preterm infants: an ultrasound-based assessment of ductus arteriosus intimal thickness within 24†h after birth.

Objectives: To develop a predictive model for patent ductus arteriosus (PDA) in preterm infants at seven days postpartum. The model employs ultrasound measurements of the ductus arteriosus (DA) intimal thickness (IT) obtained within 24 h after birth. Methods: One hundred and five preterm infants with gestational ages ranging from 27.0 to 36.7 weeks admitted within 24 h following birth were prospectively enrolled. Echocardiographic assessments were performed to measure DA IT within 24 h after birth, and DA status was evaluated through echocardiography on the seventh day postpartum. Potential predictors were considered, including traditional clinical risk factors, M-mode ultrasound parameters, lumen diameter of the DA (LD), and DA flow metrics. A final prediction model was formulated through bidirectional stepwise regression analysis and subsequently subjected to internal validation. The model's discriminative ability, calibration, and clinical applicability were also assessed. Results: The final predictive model included birth weight, application of mechanical ventilation, left ventricular end-diastolic diameter (LVEDd), LD, and the logarithm of IT (logIT). The receiver operating characteristic (ROC) curve for the model, predicated on logIT, exhibited excellent discriminative power with an area under the curve (AUC) of 0.985 (95% CI: 0.966-1.000), sensitivity of 1.000, and specificity of 0.909. Moreover, the model demonstrated robust calibration and goodness-of-fit (χ2 value = 0.560, p > 0.05), as well as strong reproducibility (accuracy: 0.935, Kappa: 0.773), as evidenced by 10-fold cross-validation. A decision curve analysis confirmed the model's broad clinical utility. Conclusions: Our study successfully establishes a predictive model for PDA in preterm infants at seven days postpartum, leveraging the measurement of DA IT. This model enables identifying, within the first 24 h of life, infants who are likely to benefit from timely DA closure, thereby informing treatment decisions.

Association of sugar-sweetened beverage consumption and sleep quality with anxiety symptoms: a cross-sectional study of Tibetan college students at high altitude.

Background: Research on the association between sugar-sweetened beverages (SSBs) consumption and sleep quality with anxiety symptoms has been highly emphasized. However, past studies have focused on college students in plains areas, while fewer research studies have been conducted on Tibetan college students at high altitudes. Whether this association changes due to ethnicity or altitude is unclear. The present study will contribute to the prevention and intervention of depressive symptoms among Tibetan college students at high altitude. Methods: A self-assessment questionnaire was administered to 3,026 university students (1,491 boys students, 49.27%) on SSBs consumption, sleep quality and anxiety symptoms status in the Tibetan Plateau, a high-altitude region of China. Logistic regression analysis and ordered logistic regression analysis in generalized linear model were used to analyze the association between SSBs consumption and sleep quality with anxiety symptoms. Results: The prevalence of anxiety symptoms among Tibetan college students at high altitude was 26.9%. SSBs consumption of ≤1 times/week, 2-5 times/week, and ≥ 6 times/week were 20.7, 28.1, and 45.7%, respectively, with statistically significant differences (χ2 value of 134.353, p < 0.001). Anxiety detection rates for Sleep quality of Good (PSQI ≤5), Moderate (PSQI 6-7), and Poor (PSQI >7) were 16.8, 19.8, and 32.0%, respectively, and the difference was also statistically significant (χ2 value was 73.761, p < 0.001). The ordered logistic regression analysis in the generalized linear model showed that, overall, the group of college students with SSBs ≤1 times/week and sleep quality of Good served as the reference group, and the group with SSBs ≥6 times/week and sleep quality of Poor (OR: 5.06, 95% CI: 3.75-6.83) had the highest risk of anxiety symptoms. Conclusion: SSBs consumption and sleep quality were associated with anxiety symptoms, and there was an interaction effect. Effective control of SSBs consumption and improvement of sleep quality may be important factors in preventing and reducing the occurrence of anxiety symptoms.

Complement C1q/C3-CR3 signaling pathway mediates abnormal microglial phagocytosis of synapses in a mouse model of depression.

BACKGROUND: Both functional brain imaging studies and autopsy reports have indicated the presence of synaptic loss in the brains of depressed patients. The activated microglia may dysfunctionally engulf neuronal synapses, leading to synaptic loss and behavioral impairments in depression. However, the mechanisms of microglial-synaptic interaction under depressive conditions remain unclear. METHODS: We utilized lipopolysaccharide (LPS) to induce a mouse model of depression, examining the effects of LPS on behaviors, synapses, microglia, microglial phagocytosis of synapses, and the C1q/C3-CR3 complement signaling pathway. Additionally, a C1q neutralizing antibody was employed to inhibit the C1q/C3-CR3 signaling pathway and assess its impact on microglial phagocytosis of synapses and behaviors in the mice. RESULTS: LPS administration resulted in depressive and anxiety-like behaviors, synaptic loss, and abnormal microglial phagocytosis of synapses in the hippocampal dentate gyrus (DG) of mice. We found that the C1q/C3-CR3 signaling pathway plays a crucial role in this abnormal microglial activity. Treatment with the C1q neutralizing antibody moderated the C1q/C3-CR3 pathway, leading to a decrease in abnormal microglial phagocytosis, reduced synaptic loss, and improved behavioral impairments in the mice. CONCLUSIONS: The study suggests that the C1q/C3-CR3 complement signaling pathway, which mediates abnormal microglial phagocytosis of synapses, presents a novel potential therapeutic target for depression treatment.

Comparison of six Z-score formulas based on echocardiography for coronary artery lesions in Kawasaki disease.

GOAL: Kawasaki disease (KD) patients are at risk of developing the serious complication of coronary artery dilation (CAD). To diagnose CAD caused by KD, various Z-Score formulas are used worldwide. This paper aims to evaluate the differences and inclusiveness among the six most commonly used Z-Score formulas in diagnosing CAD in Suzhou, China. Additionally, the study seeks to compare the differences in CAD diagnosis among different high-risk factor groups. By doing so, this research provides a valuable reference for accurately diagnosing CAD in KD patients. METHOD: This paper presents a retrospective analysis of 1509 patients diagnosed with KD at the Children's Hospital of Soochow University between January 2018 and December 2020. We collected the patients' clinical and echocardiographic data and used six Z-Score formulas (Kobayashi et al., de Zorzi et al., Kurotobi et al., McCrindle et al., Olivieri et al., and Dallaire et al.) to diagnose the degree of CAD in different segments. We then compared the diagnostic differences and inclusiveness of these formulas, especially the diagnostic differences in medium to giant CAA. To achieve this, we divided the patients into groups based on their age (≤12 months, 13-30 months, and > 30 months) and fever duration (≤5 days, 6-7 days, 8-9 days, and ≥ 10 days). Using the McNemar test and the Kappa test, we compared the differences and the consistencies of CDA diagnosis among the six Z-Score formulas. Moreover, we used the Friedman test and Chi-square segmentation formula to compare the differences in age and number of fever duration between groups and to compare each Z-Score formula pair within the group. RESULTS: Except for the LMCA segment, where there were no statistically significant differences between de Zorzi formula and McCrindle formula, the Z-score formulas showed statistically significant differences in the degree of CAD diagnosis across all other segments. Inclusiveness assessment revealed that Kobayashi formula and Dallaire formula showed significantly higher rates of dilatation (6.58% and 5.32%), or of small aneurysms (6.52% and 4.52%) compared to other formulas (1.0%-1.73%). Medium aneurysms were also more likely to be identified with Kobayashi and Dallaire formulas (0.8% and 0.8%) compared to the remaining formulas (0.13-0.40%). There are significant differences in the diagnoses of medium to giant CAA made by these six formulas in LAD and RCA. The longer the duration of fever and the younger the age, the higher the diagnosis rates of CAD and CAA. There were no statistically significant differences between de Zorzi formula and McCrindle formula, de Zorzi formula and Oliveri formula, and Kurotobi formula and Dallaire formula within the four groups based on the duration of fever. Similarly, there were no statistically significant differences between Kobayashi formula and Dallaire formula, and between de Zorzi formula and Oliveri formula in the age groups of ≤12 months and 13-30 months. CONCLUSION: There are diagnostic differences among these six Z-score formulas, considering the aforementioned statistics. Kobayashi formula and Dallaire formula are more inclusive, and less likely to under-diagnose significant CAD. They perform evenly for dilatation only, for small aneurysms and the median size aneurysms, and that is for segments of LMCA, LAD and RCA. In addition, McCrindle formula joins the "inclusive" pack for LAD and RCA in the matter of CAD. The younger the age of the patients and the longer the duration of fever, the higher the diagnosis rates of CAD and CAA. Furthermore, the younger the age of the patients and the shorter the duration of fever, the greater the differences between the various formulas.

Pargyline-phosphine copper(I) clusters with tunable emission for light-emitting devices.

Three pargyline-phosphine copper(I) clusters, [Cu4(CC-C9H12N)3(PPh3)4](PF6) (1) and [Cu6(CC-C9H12N)4(dppy)4](X)2 (dppy = diphenyl-2-pyridylphosphine; X = PF6 for 2 and X = ClO4 for 3), were synthesized. Their structures were fully characterized using various spectroscopic methods and X-ray crystallography, which showed that the stoichiometry and nature of pargyline and phosphine ligands play an important role in tuning the structure and photophysical features of Cu(I) clusters. Interestingly, clusters 1, 2 and 3 exhibited red, orange and yellow phosphorescence with high quantum yields of 88.5%, 22.0% and 40.2%, respectively, at room temperature. Moreover, clusters 1-3 show distinct temperature-dependent emissions. The excellent luminescence performance of 1 and 3 was designed and employed for the construction of monochrome and white light-emitting devices (LEDs).

Chromosome structure modeling tools and their evaluation in bacteria.

The three-dimensional (3D) structure of bacterial chromosomes is crucial for understanding chromosome function. With the growing availability of high-throughput chromosome conformation capture (3C/Hi-C) data, the 3D structure reconstruction algorithms have become powerful tools to study bacterial chromosome structure and function. It is highly desired to have a recommendation on the chromosome structure reconstruction tools to facilitate the prokaryotic 3D genomics. In this work, we review existing chromosome 3D structure reconstruction algorithms and classify them based on their underlying computational models into two categories: constraint-based modeling and thermodynamics-based modeling. We briefly compare these algorithms utilizing 3C/Hi-C datasets and fluorescence microscopy data obtained from Escherichia coli and Caulobacter crescentus, as well as simulated datasets. We discuss current challenges in the 3D reconstruction algorithms for bacterial chromosomes, primarily focusing on software usability. Finally, we briefly prospect future research directions for bacterial chromosome structure reconstruction algorithms.

Role of automated functional imaging and myocardial work in assessment of cardiac function in children with obstructive sleep apnea.

BACKGROUND: Early identification of abnormal left ventricular function in children with obstructive sleep apnea (OSA) is difficult using conventional echocardiographic indices and commonly used clinical markers of myocardial damage. We sought to investigate the value of automatic function imaging and myocardial work parameters in predicting early cardiac impairment in children having OSA with preserved left heart function and thereby identifying an optimal index for assessment. PATIENTS AND METHODS: Fifty-two children who presented with symptoms of nocturnal sleep snoring and open-mouth breathing and 34 healthy controls were enrolled in this study. Clinical characteristics and conventional echocardiographic data were collected, and image analysis was performed using two-dimensional speckle-tracking echocardiography to obtain left ventricular global longitudinal strain (GLS), post-systolic index, peak strain dispersion, global work index (GWI), global constructive work (GCW), global wasted work, and global work efficiency. RESULTS: Children with OSA had significantly lower GLS, GWI, and GCW than those without (P < 0.05). Additionally, GWI (ß = -32.87, 95% CI: -53.47 to -12.27), and GCW (ß = -35.09, 95% CI: -55.35 to -14.84) were found to correlate with the disease severity in the multiple linear regression mode, with worsening values observed as the severity of the disease increased. ROC curve analysis revealed that GCW was the best predictor of myocardial dysfunction, with an AUC of 0.809 (P < 0.001), and the best cutoff point for diagnosing myocardial damage in children with OSA was 1965.5 mmHg%, with a sensitivity of 92.5% and a specificity of 58.7%. CONCLUSIONS: GLS, GWI, and GCW were identified as predictors of myocardial dysfunction in children with OSA, with GCW being the best predictor.

Cannabinoid type 2 receptors play a crucial role in social defeat-induced depression.

BACKGROUND: The endocannabinoid system plays a crucial role in regulating mood, but the specific involvement of cannabinoid receptor type 2 (CB2R) in depression remains poorly understood. Similarly, the mechanisms by which electroacupuncture (EA) provides therapeutic benefits for depression are not clearly defined. This research aims to explore the function of CB2R in depression and examine if the therapeutic effects of EA are associated with the hippocampal CB2R system. METHODS: Mice experiencing social defeat stress (SDS) were used to model depression and anxiety behaviors. We quantified hippocampal CB2R and N-arachidonoylethanolamide (AEA) levels. The efficacy of a CB2R agonist, JWH133, in mitigating SDS-induced behaviors was evaluated. Additionally, EA's impact on CB2R and AEA was assessed, along with the influence of CB2R antagonist AM630 on EA's antidepressant effects. RESULTS: SDS led to depressive and anxiety-like behaviors, with corresponding decreases in hippocampal CB2R and AEA. Treatment with JWH133 ameliorated these behaviors. EA treatment resulted in increased CB2R and AEA levels, while AM630 blocked these antidepressant effects. LIMITATIONS: The study mainly focused on the SDS model, which may not entirely reflect other depression models. Besides, further investigation is needed to understand the precise mechanisms by which CB2R and AEA contribute to EA's effects. CONCLUSIONS: The study suggests hippocampal downregulation of CB2R and AEA contributes to depression. Upregulation of CB2R and AEA in response to EA suggests their involvement in EA's antidepressant effects. These findings provide insights into the role of the hippocampal CB2R system in depression and the potential mechanisms underlying EA's therapeutic effects.

Myocardial Work for Dynamic Monitoring of Myocardial Injury in Neonatal Asphyxia.

To assess the value of parameters of myocardial work for dynamic monitoring of myocardial injury after neonatal asphyxia. Fifty-three neonates with asphyxia admitted within 24 h after delivery were divided into a mild asphyxia group (n = 40) and severe asphyxia group (n = 13). Echocardiography was performed within 24 h post-birth, within 72 h post-birth (48 h after first echo), and during recovery. The left ventricular ejection fraction on M-mode echocardiography and by Simpson's biplane method (LVEF and Bi-EF, respectively), stroke volume (SV), cardiac output (CO), cardiac index (CI), global longitudinal strain (GLS), global work index (GWI), global constructive work (GCW), and other parameters were measured. Echocardiographic indicators were compared between groups and over time. GWI was significantly increased at 72 h in the mild asphyxia group (P < 0.05) but showed no significant change over time in the severe asphyxia group (P > 0.05). While GCW increased significantly over time in both groups (P < 0.05), it increased earlier in the mild asphyxia group. Time and grouping factors had independent effects on GWI and GCW (P > 0.05). The characteristics of differences in GWI and GCW between the two groups were different from those for LVEF, Bi-EF, SV, CO, CI, and GLS and their change characteristics with improvement from treatment. GWI and GCW changed significantly during recovery from neonatal asphyxia, and their change characteristics differed between mild and severe asphyxia cases. Myocardial work parameters can be used as valuable supplements to traditional indicators of left ventricular function to dynamically monitor the recovery from myocardial injury after neonatal asphyxia.

Ionic Liquids-Driven Cluster-to-Cluster Conversion of Polyhydrido Copper(I) Clusters Cu7H5 to Cu8H6 and Cu12H9.

Although ionic liquids (ILs) are of prime interest for the synthesis of various nanomaterials, they are scarcely utilized for the polyhydrido copper(I) [Cu(I)H] clusters. Herein, two air-stable Cu(I)H clusters, [Cu8H6(dppy)6](NTf2)2 (Cu8H6) and {Cu12H9(dppy)6[N(CN)2]3} (Cu12H9), are synthesized in high yields for the first time from the ILs-driven conversion of an unprecedented cluster [Cu7H5(dppy)6](ClO4)2 (Cu7H5) by a facile three-layers diffusion crystal (TLDC) method, strategically introducing IL-NTf2 and IL-N(CN)2 as two types of unusual interfacial crystallized templates, respectively. Their structures are fully characterized by various spectroscopic methods and X-ray crystallography, which shows that the anion of IL plays an important role as an anion template and an anion ligand in controlling the structural conversion of Cu(I)H clusters. Their photophysical properties are also investigated, and it is found that all reported clusters exhibit red luminescence with λem ranging from 600 to 690 nm.

Independent Component Analysis Reveals the Transcriptional Regulatory Modules in Bradyrhizobium diazoefficiens USDA110.

The dynamic adaptation of bacteria to environmental changes is achieved through the coordinated expression of many genes, which constitutes a transcriptional regulatory network (TRN). Bradyrhizobium diazoefficiens USDA110 is an important model strain for the study of symbiotic nitrogen fixation (SNF), and its SNF ability largely depends on the TRN. In this study, independent component analysis was applied to 226 high-quality gene expression profiles of B. diazoefficiens USDA110 microarray datasets, from which 64 iModulons were identified. Using these iModulons and their condition-specific activity levels, we (1) provided new insights into the connection between the FixLJ-FixK2-FixK1 regulatory cascade and quorum sensing, (2) discovered the independence of the FixLJ-FixK2-FixK1 and NifA/RpoN regulatory cascades in response to oxygen, (3) identified the FixLJ-FixK2 cascade as a mediator connecting the FixK2-2 iModulon and the Phenylalanine iModulon, (4) described the differential activation of iModulons in B. diazoefficiens USDA110 under different environmental conditions, and (5) proposed a notion of active-TRN based on the changes in iModulon activity to better illustrate the relationship between gene regulation and environmental condition. In sum, this research offered an iModulon-based TRN for B. diazoefficiens USDA110, which formed a foundation for comprehensively understanding the intricate transcriptional regulation during SNF.

Study on the Fingerprint Spectrum and the Spectrum-Effect Relationship of Analgesic and Anti-Inflammatory Effects of the Aqueous Extract from Dalbergia hancai Benth.

Dalbergia hancai Benth. (D. hancai) is one of the most frequently utilized traditional Chinese medicine in Zhuang medicine. Simultaneously, it has been included in the "Quality Standard of Zhuang medicine in Guangxi Zhuang Autonomous Region (Vol. 2)" and possessed outstanding pharmacological effects. However, the pharmacodynamic material basis of D. hancai still remains unclear. In this study, the high-performance liquid chromatography (HPLC) method had been employed to establish the fingerprint of 10 batches of aqueous extract of D. hancai originated from different parts of China. At the same time, similarity evaluation, cluster analysis, and principal component analysis (PCA) had also been conducted to evaluate the common peaks. The acetic acid-induced writhing in mice had been employed as an analgesic model, and the carrageenan-induced toe swelling in mice was utilized as an anti-inflammatory model for pharmacodynamic experiments. The gray relational analysis (GRA) and partial least squares regression (PLSR) were applied to correlate the fingerprint and pharmacodynamic data to thoroughly examine its spectrum-effect relationship, whereby its analgesic and anti-inflammatory material basis had been comprehensively explored. The results revealed that the HPLC fingerprint of the aqueous extract of D. hancai had successfully identified 12 common peaks whereby two of which were further identified as protocatechuic acid and vitexin. Subsequently, through the analysis of GRA and PLSR, the chromatographic peaks that possess a critical correlation degree with the analgesic and anti-inflammatory effects of D. hancai had also been successfully discovered. Ultimately, the analgesic and anti-inflammatory effects of the 10 batches of D. hancai aqueous extract had been conclusively proved, and it was evidently indicated that these effects were attributable to the synergistic interactions between various components. Therefore, this study aims to serve as an effective analytical method for screening and predicting the effective substances of traditional Chinese medicine on the basis of the spectrum-effect relationship.

Spectrum-Effect Relationship between HPLC Fingerprint and Anti-Inflammatory and Analgesic Activities of Chloranthus fortunei (A. Gray) Solms-Laub.

The predominant objective of the research is to establish the anti-inflammatory and analgesic spectrum-effect relationship of Chloranthus fortunei (A. Gray) Solms-Laub (CF), to reveal the pharmacodynamic basis of the anti-inflammatory and analgesic effects of CF. The fingerprints of ten batches of CF from various origins were established by high-performance liquid chromatography (HPLC) and evaluated for similarity, hierarchical cluster analysis (HCA), and principal component analysis (PCA). The anti-inflammatory and analgesic effects of CF were evaluated with the xylene-induced ear swelling in mice and the acetic acid torsion test, while the anti-inflammatory and analgesic spectrum-effect relationship of CF was evaluated by gray relational analysis (GRA) and partial least squares regression analysis (PLSR) to effectively elucidate the anti-inflammatory and analgesic substance basis of CF. The ten batches of CF HPLC fingerprints established in this work successfully identified a total of 13 common peaks that refer to 4 components, with peak 1 being neochlorogenic acid, peak 3 being chlorogenic acid, peak 5 being cryptochlorogenic acid, and peak 10 being rosmarinic acid. The HCA results presented that the ten batches of CF samples were clustered into 3 categories, which was consistent with the PCA results. Simultaneously, the results of the spectrum-effect relationship also indicated that neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, and rosmarinic acid were the possible anti-inflammatory and analgesic substances of CF. In order to better understand the anti-inflammatory and analgesic substance basis of CF, this experiment established the anti-inflammatory and analgesic spectrum-effect relationship of CF, which can provide a scientific foundation for the quality evaluation and further research as well as the usage of CF herbs.

Schisandrin A ameliorates airway inflammation in model of asthma by attenuating Th2 response.

Asthma is a persistent respiratory ailment that displays periodicity and is linked to the equilibrium of T cells. Several compounds obtained from Chinese herbal medicines display beneficial impacts on T cell regulation and the attenuation of inflammatory mediator synthesis. Schisandrin A, an active lignan derived from the Schisandra fruit, exhibits anti-inflammatory characteristics. In the present study, the network analysis conducted revealed that the nuclear factor-kappaB (NF-κB) signaling pathway is likely a prominent contributor to the anti-asthmatic effects of schisandrin A. In addition, it has been established that the inhibition of cyclooxygenase 2 (COX-2/PTGS2) is likely a significant factor in this process. The results of in vitro experiments have substantiated that schisandrin A can effectively lower the expression of COX-2 and inducible nitric oxide synthase (iNOS) in 16 HBE cells and RAW264.7 cells in a manner that is dependent on the dosage administered. It was able to effectively reduce the activation of the NF-κB signaling pathway while simultaneously improving the injury to the epithelial barrier function. Furthermore, an investigation utilizing immune infiltration as a metric revealed an inequity in Th1/Th2 cells and a surge in Th2 cytokines in asthma patients. In the OVA-induced asthma mice model, it was observed that schisandrin A treatment effectively suppressed inflammatory cell infiltration, reduced the Th2 cell ratio, inhibited mucus secretion, and prevented airway remodeling. To summarize, the administration of schisandrin A has been found to effectively alleviate the symptoms of asthma by impeding the production of inflammation, which includes reducing the Th2 cell ratio and improving the integrity of the epithelial barrier function. These findings offer valuable insights into the potential therapeutic applications of schisandrin A for the treatment of asthma.

NLRP3 Inflammasome-Mediated Neuroinflammation and Related Mitochondrial Impairment in Parkinson's Disease.

Parkinson's disease (PD) is a common neurodegenerative disorder caused by the loss of dopamine neurons in the substantia nigra and the formation of Lewy bodies, which are mainly composed of alpha-synuclein fibrils. Alpha-synuclein plays a vital role in the neuroinflammation mediated by the nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing protein 3 (NLRP3) inflammasome in PD. A better understanding of the NLRP3 inflammasome-mediated neuroinflammation and the related mitochondrial impairment during PD progression may facilitate the development of promising therapies for PD. This review focuses on the molecular mechanisms underlying NLRP3 inflammasome activation, comprising priming and protein complex assembly, as well as the role of mitochondrial impairment and its subsequent inflammatory effects on the progression of neurodegeneration in PD. In addition, the therapeutic strategies targeting the NLRP3 inflammasome for PD treatment are discussed, including the inhibitors of NLRP3 inflammatory pathways, mitochondria-focused treatments, microRNAs, and other therapeutic compounds.

DHA inhibits invasion and metastasis in NSCLC cells by interfering with CCL18/STAT3 signaling pathway.

Omega-3 has been proposed as an antitumor substance that suppresses the growth and metastasis of multiple types of tumor cells, including lung cancer, but the specific mechanisms involved remain obscure. Our previous studies showed that the expression of chemokine ligand 18 was related to the migration and metastasis of non-small cell lung cancer. Here, we aim to explore whether omega-3 inhibits invasion and metastasis of NSCLC by regulating the expression of CCL18. The expression of CCL18, metastasis- and epithelial-mesenchymal transition (EMT)-related genes at mRNA and protein levels in NSCLC cell lines were detected by RT-qPCR and Western blot, respectively. The metastatic and invasive capability of NSCLC cells were evaluated by scratch wound healing and Transwell assays, respectively. Our results showed that the level of CCL18 is positively associated with metastatic ability of NSCLC cells. Docosahexaenoic acid, an important long-chain, polyunsaturated omega-3 (n-3) fatty acid, significantly inhibited invasion and metastasis of NSCLC cells, and concomitantly downregulated the expression of metastasis- and EMT-related genes and p-STAT3 signaling pathway. Additionally, we found that DHA inhibited CCL18 expression in lung cancer cells, while overexpression of CCL18 effectively reversed DHA-mediated downregulation in the expression of metastasis- and EMT-related genes and p-STAT3 signaling as well as DHA-mediated inhibitory effect on metastasis and invasion of NSCLC cells. DHA inhibits NSCLC cell invasion and metastasis possibly through targeted inhibition of CCL18/ STAT3 signaling pathway and EMT process.

HIV-1 Subtype Diversity and Factors Affecting Drug Resistance among Patients with Virologic Failure in Antiretroviral Therapy in Hainan Province, China, 2014-2020 / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to determine the HIV-1 subtype distribution and HIV drug resistance (HIVDR) in patients with ART failure from 2014 to 2020 in Hainan, China.@*METHODS@#A 7-year cross-sectional study was conducted among HIV/AIDS patients with ART failure in Hainan. We used online subtyping tools and the maximum likelihood phylogenetic tree to confirm the HIV subtypes with pol sequences. Drug resistance mutations (DRMs) were analyzed using the Stanford University HIV Drug Resistance Database.@*RESULTS@#A total of 307 HIV-infected patients with ART failure were included, and 241 available pol sequences were obtained. Among 241 patients, CRF01_AE accounted for 68.88%, followed by CRF07_BC (17.00%) and eight other subtypes (14.12%). The overall prevalence of HIVDR was 61.41%, and the HIVDR against non-nucleoside reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) were 59.75%, 45.64%, and 2.49%, respectively. Unemployed patients, hypoimmunity or opportunistic infections in individuals, and samples from 2017 to 2020 increased the odd ratios of HIVDR. Also, HIVDR was less likely to affect female patients. The common DRMs to NNRTIs were K103N (21.99%) and Y181C (20.33%), and M184V (28.21%) and K65R (19.09%) were the main DRMs against NRTIs.@*CONCLUSION@#The present study highlights the HIV-1 subtype diversity in Hainan and the importance of HIVDR surveillance over a long period.