Five new glycosides from the culms of Phyllostachys nigra var. henonis.

Five new glycosides, namely methyl 3-methoxybenzoate-4,5-di-O-ß-D-glucopyranoside (1), (1aS,3aS,3R)-3-(4'-O-ß-D-glucopyranosyl-3'-methoxyphenyl)-5,6-dioxa-bicyclo[3.3.0]octane-1-one (2), quinolin-4(1H)-one-3-O-ß-D-glucopyranoside (3), 3-methoxy-propiophenone 4-O-(6'-ß-D-xylopyranosyl)-ß-D-glucopyranoside (4), methyl 3-methoxybenzoate 4-O-(6'-ß-D-xylopyranosyl)-ß-D-glucopyranoside (5), and one known compound, bambulignan B (6) were isolated from the culms of Phyllostachys nigra var. henonis. Their structures were determined using spectroscopic analysis. All compounds were evaluated for their DPPH radical scavenging activity. Compound 6 exhibited antioxidant activity with IC50 value of 59.5 µM (positive control, L-ascorbic acid, IC50 = 12.4 µM; 2,6-ditertbutyl-4-methyl phenol, IC50 = 11.8 µM).

A Chromosome-level Genome Assembly Provides Insights into the Local Adaptation of Tamarix austromongolica in the Yellow River Basin, China.

Tamarix austromongolica is endemic to the Yellow River Basin and has adapted to diverse ecological settings in the region, including the arid areas of northwestern China and the saline soil regions of the Yellow River Delta. However, the genetic basis of its local adaptation remains unclear. We report a chromosome-level assembly of the T. austromongolica genome based on PacBio high-fidelity sequencing and Hi-C technology. The 12 pseudochromosomes cover 98.44% of the 1.32 Gb assembly, with a contig N50 of 52.57 Mb and a BUSCO score of 98.2%. The genome comprises 913.6 Mb (68.83%) of repetitive sequences and 22,374 protein-coding genes. Genome evolution analyses suggest that genes under positive selection and significantly expanded gene families have facilitated T. austromongolica's adaptability to diverse environmental factors and high resistance to diseases. Using genotyping-by-sequencing, we conducted population structure and selection analyses of 114 samples from 15 sites. Two genetic groups were identified, and 114 and 289 candidate genes were assigned to the populations of the northwestern and eastern parts of the Yellow River, respectively. Furthermore, we discovered numerous candidate genes associated with high-altitude adaptability and salt tolerance. This research provides valuable genomic resources for the evolutionary study and genetic breeding of tamarisk.

PEX3 promotes regenerative repair after myocardial injury in mice through facilitating plasma membrane localization of ITGB3.

The peroxisome is a versatile organelle that performs diverse metabolic functions. PEX3, a critical regulator of the peroxisome, participates in various biological processes associated with the peroxisome. Whether PEX3 is involved in peroxisome-related redox homeostasis and myocardial regenerative repair remains elusive. We investigate that cardiomyocyte-specific PEX3 knockout (Pex3-KO) results in an imbalance of redox homeostasis and disrupts the endogenous proliferation/development at different times and spatial locations. Using Pex3-KO mice and myocardium-targeted intervention approaches, the effects of PEX3 on myocardial regenerative repair during both physiological and pathological stages are explored. Mechanistically, lipid metabolomics reveals that PEX3 promotes myocardial regenerative repair by affecting plasmalogen metabolism. Further, we find that PEX3-regulated plasmalogen activates the AKT/GSK3ß signaling pathway via the plasma membrane localization of ITGB3. Our study indicates that PEX3 may represent a novel therapeutic target for myocardial regenerative repair following injury.

Ameliorating and refining islet organoids to illuminate treatment and pathogenesis of diabetes mellitus.

Diabetes mellitus, a significant global public health challenge, severely impacts human health worldwide. The organoid, an innovative in vitro three-dimensional (3D) culture model, closely mimics tissues or organs in vivo. Insulin-secreting islet organoid, derived from stem cells induced in vitro with 3D structures, has emerged as a potential alternative for islet transplantation and as a possible disease model that mirrors the human body's in vivo environment, eliminating species difference. This technology has gained considerable attention for its potential in diabetes treatment. Despite advances, the process of stem cell differentiation into islet organoid and its cultivation demonstrates deficiencies, prompting ongoing efforts to develop more efficient differentiation protocols and 3D biomimetic materials. At present, the constructed islet organoid exhibit limitations in their composition, structure, and functionality when compared to natural islets. Consequently, further research is imperative to achieve a multi-tissue system composition and improved insulin secretion functionality in islet organoid, while addressing transplantation-related safety concerns, such as tumorigenicity, immune rejection, infection, and thrombosis. This review delves into the methodologies and strategies for constructing the islet organoid, its application in diabetes treatment, and the pivotal scientific challenges within organoid research, offering fresh perspectives for a deeper understanding of diabetes pathogenesis and the development of therapeutic interventions.

Tumor microenvironment responsive nano-herb and CRISPR delivery system for synergistic chemotherapy and immunotherapy.

Chemoresistance remains a significant challenge for effective breast cancer treatment which leads to cancer recurrence. CRISPR-directed gene editing becomes a powerful tool to reduce chemoresistance by reprogramming the tumor microenvironment. Previous research has revealed that Chinese herbal extracts have significant potential to overcome tumor chemoresistance. However, the therapeutic efficacy is often limited due to their poor tumor targeting and in vivo durability. Here we have developed a tumor microenvironment responsive nanoplatform (H-MnO2(ISL + DOX)-PTPN2@HA, M(I + D)PH) for nano-herb and CRISPR codelivery to reduce chemoresistance. Synergistic tumor inhibitory effects were achieved by the treatment of isoliquiritigenin (ISL) with doxorubicin (DOX), which were enhanced by CRISPR-based gene editing to target protein tyrosine phosphatase non-receptor type 2 (PTPN2) to initiate long-term immunotherapy. Efficient PTPN2 depletion was observed after treatment with M(I + D)PH nanoparticles, which resulted in the recruitment of intratumoral infiltrating lymphocytes and an increase of proinflammatory cytokines in the tumor tissue. Overall, our nanoparticle platform provides a diverse technique for accomplishing synergistic chemotherapy and immunotherapy, which offers an effective treatment alternative for malignant neoplasms.

Efficacy and Safety of DPP-4 Inhibitors and Metformin Combinations in Type 2 Diabetes: A Systematic Literature Review and Network Meta-Analysis.

Objective: Several oral antidiabetic regimens are available for treating type 2 diabetes mellitus (T2DM), dipeptidyl peptidase-4 inhibitors (DPP4i) being one of them. We conducted a network meta-analysis (NMA) comparing DPP4i plus metformin (Met) combination with other Met-based oral antidiabetic drug (OAD) combinations used in treating patients with T2DM. Methods: We searched PubMed and Embase from inception until 19th April, 2022 for phase II and phase III trials in patients with T2DM on Met-based traditional OADs. The primary outcome was assessed by change in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), and 2-hour post-prandial blood glucose (2h-PPG). The secondary safety outcomes assessed were hypoglycemic events, serious adverse events (SAEs), cardiovascular (CV) events, and gastrointestinal (GI) events. Results: Sixty-two trials were included in the analysis. The combination of DPP4i + Met revealed a comparable mean reduction in HbA1c levels to the glinides (Gli) + Met combination (mean difference [MD]: -0.03%, 95% CI: 0.69, -0.65), although the difference was not statistically significant. The mean HbA1c reduction with DPP4i + Met was greater than with sulfonylureas (SU) + Met (MD: -0.05, 95% CI: -0.29, 0.39), thiazolidinedione (TZD) + Met (MD: -0.69, 95% CI: -1.39, -0.02), and SU + TZD (MD: 0.21; 95% CI: -1.30, 1.71), with no statistical significance. DPP4i + Met demonstrated a non-significant lower incidence of CV events in comparison to TZD + Met (RR: 1.01, 95% CI: 0.46, 2.45) and SU + Met (RR: 1.06, 95% CI: 0.61, 2.06). Conclusion: DPP4i in combination with Met was efficacious and had a well-tolerated safety profile compared with other traditional OADs. This combination can be considered as a suitable treatment option for patients with T2DM.

Advanced Gastric Cancer: CT Radiomics Prediction of Lymph Modes Metastasis After Neoadjuvant Chemotherapy.

This study aims to create and assess machine learning models for predicting lymph node metastases following neoadjuvant treatment in advanced gastric cancer (AGC) using baseline and restaging computed tomography (CT). We evaluated CT images and pathological data from 158 patients with resected stomach cancer from two institutions in this retrospective analysis. Patients were eligible for inclusion if they had histologically proven gastric cancer. They had received neoadjuvant chemotherapy, with at least 15 lymph nodes removed. All patients received baseline and preoperative abdominal CT and had complete clinicopathological reports. They were divided into two cohorts: (a) the primary cohort (n = 125) for model creation and (b) the testing cohort (n = 33) for evaluating models' capacity to predict the existence of lymph node metastases. The diagnostic ability of the radiomics-model for lymph node metastasis was compared to traditional CT morphological diagnosis by radiologist. The radiomics model based on the baseline and preoperative CT images produced encouraging results in the training group (AUC 0.846) and testing cohort (AUC 0.843). In the training cohort, the sensitivity and specificity were 81.3% and 77.8%, respectively, whereas in the testing cohort, they were 84% and 75%. The diagnostic sensitivity and specificity of the radiologist were 70% and 42.2% (using baseline CT) and 46.3% and 62.2% (using preoperative CT). In particular, the specificity of radiomics model was higher than that of conventional CT in diagnosing N0 cases (no lymph node metastasis). The CT-based radiomics model could assess lymph node metastasis more accurately than traditional CT imaging in AGC patients following neoadjuvant chemotherapy.

Effect of Wearing Noise-Canceling Headphones on Delivery Process in Natural Childbirth Puerperae: A Single-Center Study.

OBJECTIVE: To investigate the effect of incorporating noise-canceling headphones into the delivery process for natural childbirth puerperae. METHODS: We conducted a retrospective analysis of clinical data encompassing natural childbirth puerperae in the People's Hospital of Suzhou New District from January 2021 to February 2023. The implementation of routine noise reduction management was done from January 2021 to January 2022. During this interval, 69 natural childbirth puerperae were selected as subjects, with 7 excluded, resulting in 62 participants constituting the reference group. Subsequently, noise-canceling headphones were distributed to natural childbirth puerperae from February 2022 to February 2023. In this phase, 66 subjects were selected, and 6 were excluded, resulting in 60 participants forming the observation group. Following admission, both groups underwent corresponding nursing management. Emotional states, pain levels, and various indicators were systematically collected and meticulously compared. RESULTS: The observation group exhibited significantly lower Hamilton Anxiety Rating Scale scores than the reference group before delivery and during the first stage of labor (P < 0.05). The observation group demonstrated significantly lower visual analog scale scores and substance P, nitric oxide, and prostaglandin E2 levels than the reference group during the first stage of labor (P < 0.001). During the second stage of labor, the visual analog) scale scores were significantly lower in the observation group than in the reference group (P < 0.05). The durations of first and second labor stages were significantly shorter in the observation group than in the reference group (P < 0.05). No significant difference existed in Apgar scores between the two groups (P > 0.05). CONCLUSION: The utilization of noise-canceling headphones emerges as an effective intervention, alleviating anxiety, reducing pain during T1, and abbreviating total labor time in natural childbirth puerperae, suggesting its substantial clinical application value and potential as a beneficial addition to maternity care practices.

Checkpoint Kinase 1 Stimulates Endogenous Cardiomyocyte Renewal and Cardiac Repair by Binding to Pyruvate Kinase Isoform M2 C-Domain and Activating Cardiac Metabolic Reprogramming in a Porcine Model of Myocardial Ischemia/Reperfusion Injury.

BACKGROUND: The regenerative capacity of the adult mammalian hearts is limited. Numerous studies have explored mechanisms of adult cardiomyocyte cell-cycle withdrawal. This translational study evaluated the effects and underlying mechanism of rhCHK1 (recombinant human checkpoint kinase 1) on the survival and proliferation of cardiomyocyte and myocardial repair after ischemia/reperfusion injury in swine. METHODS AND RESULTS: Intramyocardial injection of rhCHK1 protein (1 mg/kg) encapsulated in hydrogel stimulated cardiomyocyte proliferation and reduced cardiac inflammation response at 3 days after ischemia/reperfusion injury, improved cardiac function and attenuated ventricular remodeling, and reduced the infarct area at 28 days after ischemia/reperfusion injury. Mechanistically, multiomics sequencing analysis demonstrated enrichment of glycolysis and mTOR (mammalian target of rapamycin) pathways after rhCHK1 treatment. Co-Immunoprecipitation (Co-IP) experiments and protein docking prediction showed that CHK1 (checkpoint kinase 1) directly bound to and activated the Serine 37 (S37) and Tyrosine 105 (Y105) sites of PKM2 (pyruvate kinase isoform M2) to promote metabolic reprogramming. We further constructed plasmids that knocked out different CHK1 and PKM2 amino acid domains and transfected them into Human Embryonic Kidney 293T (HEK293T) cells for CO-IP experiments. Results showed that the 1-265 domain of CHK1 directly binds to the 157-400 amino acids of PKM2. Furthermore, hiPSC-CM (human iPS cell-derived cardiomyocyte) in vitro and in vivo experiments both demonstrated that CHK1 stimulated cardiomyocytes renewal and cardiac repair by activating PKM2 C-domain-mediated cardiac metabolic reprogramming. CONCLUSIONS: This study demonstrates that the 1-265 amino acid domain of CHK1 binds to the 157-400 domain of PKM2 and activates PKM2-mediated metabolic reprogramming to promote cardiomyocyte proliferation and myocardial repair after ischemia/reperfusion injury in adult pigs.

Semirecumbent Positioning During Anesthesia Recovery and Postoperative Hypoxemia: A Randomized Clinical Trial.

Importance: The efficacy of a semirecumbent position (SRP) in reducing postoperative hypoxemia during anesthesia emergence is unclear despite its widespread use. Objective: To determine the differences in postoperative hypoxemia between patients in an SRP and a supine position. Design, Setting, and Participants: This randomized clinical trial was performed at a tertiary hospital in China between March 20, 2021, and May 10, 2022. Patients scheduled to undergo laparoscopic upper abdominal surgery under general anesthesia were enrolled. Study recruitment and follow-up are complete. Interventions: Patients were randomized to 1 of the following positions at the end of the operation until leaving the postanesthesia care unit: supine (group S), 15° SRP (group F), or 30° SRP (group T). Main Outcomes and Measures: The primary outcome was the incidence of postoperative hypoxemia in the postanesthesia care unit. Severe hypoxemia was also evaluated. Results: Out of 700 patients (364 men [52.0%]; mean [SD] age, 47.8 [11.3] years), 233 were randomized to group S (126 men [54.1%]; mean [SD] age, 48.2 [10.9] years), 233 to group F (122 men [52.4%]; mean [SD] age, 48.1 [10.9] years), and 234 to group T (118 women [50.4%]; mean [SD] age, 47.2 [12.1] years). Postoperative hypoxemia differed significantly among the 3 groups (group S, 109 of 233 [46.8%]; group F, 105 of 233 [45.1%]; group T, 76 of 234 [32.5%]; P = .002). This difference was statistically significant for groups T vs S (risk ratio [RR], 0.69 [95% CI, 0.55-0.87]; P = .002) and groups T vs F (RR, 0.72 [95% CI, 0.57-0.91]; P = .007), but not for groups F vs S (RR, 0.96 [95% CI, 0.79-1.17]; P = .78). Severe hypoxemia also differed among the 3 groups (group S, 61 of 233 [26.2%]; group F, 53 of 233 [22.7%]; group T, 36 of 234 [15.4%]; P = .01). This difference was statistically significant for groups T vs S (RR, 0.59 [95% CI, 0.41-0.85]; P = .005). Conclusions and Relevance: In this randomized clinical trial of SRP during anesthesia recovery in patients undergoing laparoscopic upper abdominal surgery, postoperative hypoxemia was significantly reduced in group T compared with group F or group S. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2100045087.

Crosstalk among Oxidative Stress, Autophagy, and Apoptosis in the Protective Effects of Ginsenoside Rb1 on Brain Microvascular Endothelial Cells: A Mixed Computational and Experimental Study.

OBJECTIVE: Brain microvascular endothelial cells (BMECs) were found to shift from their usually inactive state to an active state in ischemic stroke (IS) and cause neuronal damage. Ginsenoside Rb1 (GRb1), a component derived from medicinal plants, is known for its pharmacological benefits in IS, but its protective effects on BMECs have yet to be explored. This study aimed to investigate the potential protective effects of GRb1 on BMECs. METHODS: An in vitro oxygen-glucose deprivation/reperfusion (OGD/R) model was established to mimic ischemia-reperfusion (I/R) injury. Bulk RNA-sequencing data were analyzed by using the Human Autophagy Database and various bioinformatic tools, including gene set enrichment analysis (GSEA), Gene Ontology (GO) classification and enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein-protein interaction network analysis, and molecular docking. Experimental validation was also performed to ensure the reliability of our findings. RESULTS: Rb1 had a protective effect on BMECs subjected to OGD/R injury. Specifically, GRb1 was found to modulate the interplay between oxidative stress, apoptosis, and autophagy in BMECs. Key targets such as sequestosome 1 (SQSTM1/p62), autophagy related 5 (ATG5), and hypoxia-inducible factor 1-alpha (HIF-1α) were identified, highlighting their potential roles in mediating the protective effects of GRb1 against IS-induced damage. CONCLUSION: GRbl protects BMECs against OGD/R injury by influencing oxidative stress, apoptosis, and autophagy. The identification of SQSTM1/p62, ATG5, and HIF-1α as promising targets further supports the potential of GRb1 as a therapeutic agent for IS, providing a foundation for future research into its mechanisms and applications in IS treatment.

Isolation and identification of three new phenylpropanoids from the culms of phyllostachys nigra var. henonis (mitford) Rendle.

Three new phenylpropanoids, namely (7'R,8'R) guaiacylglycerol 4'-O-ß-D-[6″-O-(4-O-ß-D-glucopyranosyl)-p-hydroxyl-benzoyl]-glucopyranoside (1), (7 R,8R) guaiacylglycerol 8-O-1'-(2',6'-dimethoxy-4'-O-ß-D-glucopyranosyl)-benzene (2), (7'R,8'R) guaiacylglycerol 4'-O-ß-D-[6″-O-3,5-dimethoxy-4-hydroxylbenzoyl]-gluco-pyranoside (3), along with one known phenylpropanoid (4) were isolated from the ethanol extract of Phyllostachys nigra var. henonis fresh culm. The structures of all compounds were determined by analysis of UV, 1D NMR, 2D NMR, HR-ESI-MS and CD data. All compounds were evaluated for their DPPH radical scavenging activity. Compound 2 (IC50 54.9 µM) and 3 (IC50 77.2 µM) exhibited moderate antioxidant activity compared with two positive control compounds L-ascorbic acid (IC50 15.5 µM) and 2,6-ditertbutyl-4-methyl phenol (IC50 19.1 µM).

Regulation of Fuzheng Huayu capsule on inhibiting the fibrosis-associated hepatocellular carcinogenesis.

In the current study, bioinformatics analysis of the hepatocellular carcinoma (HCC) dataset was conducted with the hepatoprotective effect of the Fuzheng Huayu (FZHY) capsule against the diethylnitrosamine-induced HCC progression analyzed. Eight cell clusters were defined and tanshinone IIA, arachidonic acid, and quercetin, compounds of the FZHY capsule, inhibit HCC progression-related fibrosis by regulating the expression of PLAU and IGFBP3. Combined with the ameliorative effect of the FZHY capsule against liver dysfunctions and expression of PLAU and IGFBP3, our study confirmed the effect of the FZHY capsule on inhibiting the fibrosis-associated HCC progression via regulating the expression of PLAU and IGFBP3.

The beneficial effects of neutrophil elastase inhibitor on gastrointestinal dysfunction in sepsis.

To investigate the effects of neutrophil elastase inhibitor (sivelestat sodium) on gastrointestinal function in sepsis. A reanalysis of the data from previous clinical trials conducted at our center was performed. Septic patients were divided into either the sivelestat group or the non-sivelestat group. The gastrointestinal dysfunction score (GIDS), feeding intolerance (FI) incidence, serum levels of intestinal barrier function and inflammatory biomarkers were recorded. The clinical severity and outcome variables were also documented. A total of 163 septic patients were included. The proportion of patients with GIDS ≥2 in the sivelestat group was reduced relative to that in the non-sivelestat group (9.6% vs. 22.5%, p = 0.047) on the 7th day of intensive care unit (ICU) admission. The FI incidence was also remarkably reduced in the sivelestat group in contrast to that in the non-sivelestat group (21.2% vs. 37.8%, p = 0.034). Furthermore, the sivelestat group had fewer days of FI [4 (3, 4) vs. 5 (4-6), p = 0.008]. The serum levels of d-lactate (p = 0.033), intestinal fatty acid-binding protein (p = 0.005), interleukin-6 (p = 0.001), white blood cells (p = 0.007), C-reactive protein (p = 0.001), and procalcitonin (p < 0.001) of the sivelestat group were lower than those of the non-sivelestat group. The sivelestat group also demonstrated longer ICU-free days [18 (0-22) vs. 13 (0-17), p = 0.004] and ventilator-free days [22 (1-24) vs. 16 (1-19), p = 0.002] compared with the non-sivelestat group. In conclusion, sivelestat sodium administration appears to improve gastrointestinal dysfunction, mitigate dysregulated inflammation, and reduce disease severity in septic patients.

Salvianolic acid B protects against UVB-induced skin aging via activation of NRF2.

BACKGROUND: Prolonged exposure to sun radiation may result in harmful skin photoaging. Therefore, discovering novel anti-photoaging treatment modalities is critical. An active component isolated from Salvia miltiorrhiza (SM), Salvianolic acid B (Sal-B), is a robust antioxidant and anti-inflammatory agent. This investigation aimed to discover the therapeutic impact and pathways of salvianolic acid B for UVB-induced skin photoaging, an area that remains unexplored. METHODS: We conducted in vitro experiments on human dermal fibroblasts (HDFs) exposed to UVB radiation, assessing cellular senescence, superoxide dismutase (SOD) activity, cell viability, proliferation, migration, levels of reactive oxygen species (ROS), and mitochondrial health. The potential mechanism of Sal-B was analyzed using RNA sequencing, with further validation through Western blotting, PCR, and nuclear factor erythroid 2-related factor 2 (NRF2) silencing methods. In vivo, a model of skin photoaging induced by UVB in nude mice was employed. The collagen fiber levels were assessed utilizing hematoxylin and eosin (H&E), Masson, and Sirus red staining. Additionally, NRF2 and related gene and protein expression levels were identified utilizing PCR and Western blotting. RESULTS: Sal-B was found to significantly counteract photoaging in UVB-exposed skin fibroblasts, reducing aging-related decline in fibroblast proliferation and an increase in apoptosis. It was observed that Sal-B aids in protecting mitochondria from excessive ROS production by promoting NRF2 nuclear translocation. NRF2 knockdown experiments established its necessity for Sal-B's anti-photoaging effects. The in vivo studies also verified Sal-B's anti-photoaging efficacy, surpassing that of tretinoin (Retino-A). These outcomes offer novel insights into the contribution of Sal-B in developing clinical treatment modalities for UVB-induced photodamage in skin fibroblasts. CONCLUSION: In this investigation, we identified the Sal-B protective impact on the senescence of dermal fibroblasts and skin photoaging induced by radiation of UVB. The outcomes suggest Sal-B as a potential modulator of the NRF2 signaling pathway.

[Discrimination of anti-tumor and cardioprotective effect quality markers from Aidi Injection based on "spider web" mode].

Chinese medicinal preparations play an equally important role in reducing toxicity and treating tumors. Few studies discriminate the quality markers(Q-markers) conferring different therapeutic effects of traditional Chinese medicine preparations. Therefore, we take Aidi Injection(AD) as an example to comprehensively identify the Q-markers of anti-tumor and cardioprotective effects based on the "spider web" mode. Firstly, based on the principle of measurability, the chemical components in the prescription were qualitatively analyzed, and then the components with high content and capable to be measured were quantitatively analyzed as measurable evaluation indexes. Based on the principle of stability, the effects of light and temperature on the content of each component of AD were investigated as indicators of stability. Based on the principle of compatibility, the compounds were classified according to the law of compatibility of sovereign, minister, assistant, and guide medicinal materials in the prescription. Based on the principle of efficacy, the anti-tumor and antiangiogenic activities of the Q-markers were evaluated, and their synergistic effects with doxorubicin(DOX) in inhibiting tumorigenesis and angiogenesis and lowering cardiotoxicity were evaluated as the evaluation indexes of effectiveness. The seven-dimensional spider web of "compatibility-content-stability-antitumor activity-synergistic anti-tumor activity with DOX-antiangiogenic activity-synergistic anti-angiogenic activity with DOX" and the four-dimensional spider web of "compatibility-content-stability-protective effects against DOX-induced myocardial toxicity" were established, on the basis of which the Q-markers of anti-tumor and cardioprotective effects of AD were comprehensively analyzed. The results showed that 12 components were selected as the Q-markers of AD, among which cantharidin, ginsenoside Re, ginsenoside Rb_1, astragaloside Ⅱ, cryptochlorogenic acid, and ginsenoside Rg_2 were the anti-tumor Q-markers of AD. Ginsenoside Rd, isofraxidin, syringin, eleutheroside E, calycosin-7-O-ß-D-glucoside, and azelaic acid were the cardioprotective Q-markers of AD. Taking into account both the anti-tumor and cardioprotective effects, these Q-markers could cover the four herbs constituting the prescription. The findings provides a scientific basis for the quality control of AD and an effective method for identifying comprehensive and reasonable Q-markers for the two effects of Chinese medicinal preparations.

Automatic breast ultrasound (ABUS) tumor segmentation based on global and local feature fusion.

Accurate segmentation of tumor regions in automated breast ultrasound (ABUS) images is of paramount importance in computer-aided diagnosis system. However, the inherent diversity of tumors and the imaging interference pose great challenges to ABUS tumor segmentation. In this paper, we propose a global and local feature interaction model combined with graph fusion (GLGM), for 3D ABUS tumor segmentation. In GLGM, we construct a dual branch encoder-decoder, where both local and global features can be extracted. Besides, a global and local feature fusion module is designed, which employs the deepest semantic interaction to facilitate information exchange between local and global features. Additionally, to improve the segmentation performance for small tumors, a graph convolution-based shallow feature fusion module is designed. It exploits the shallow feature to enhance the feature expression of small tumors in both local and global domains. The proposed method is evaluated on a private ABUS dataset and a public ABUS dataset. For the private ABUS dataset, the small tumors (volume smaller than 1 cm3) account for over 50% of the entire dataset. Experimental results show that the proposed GLGM model outperforms several state-of-the-art segmentation models in 3D ABUS tumor segmentation, particularly in segmenting small tumors.

Per- and polyfluoroalkyl substances and human health outcomes: An umbrella review of systematic reviews with meta-analyses of observational studies.

BACKGROUND: Although evidence on the association between per- and polyfluoroalkyl substances (PFASs) and human health outcomes has grown exponentially, specific health outcomes and their potential associations with PFASs have not been conclusively evaluated. METHODS: We conducted a comprehensive search through the databases of PubMed, Embase, and Web of Science from inception to February 29, 2024, to identify systematic reviews with meta-analyses of observational studies examining the associations between the PFASs and multiple health outcomes. The quality of included studies was evaluated using the A Measurement Tool to Assess Systematic Reviews (AMSTAR) tool, and credibility of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) criteria. The protocol of this umbrella review (UR) had been registered in PROSPERO (CRD 42023480817). RESULTS: The UR identified 157 meta-analyses from 29 articles. Using the AMSTAR measurement tool, all articles were categorized as of moderate-to-high quality. Based on the GRADE assessment, significant associations between specific types of PFASs and low birth weight, tetanus vaccine response, and triglyceride levels showed high certainty of evidence. Moreover, moderate certainty of evidence with statistical significance was observed between PFASs and health outcomes including lower BMI z-score in infancy, poor sperm progressive motility, and decreased risk of preterm birth as well as preeclampsia. Fifty-two (33%) associations (e.g., PFASs and gestational hypertension, cardiovascular disease, etc) presented low certainty evidence. Additionally, eighty-five (55%) associations (e.g., PFASs with infertility, lipid metabolism, etc) presented very low certainty evidence. CONCLUSION: High certainty of evidence supported that certain PFASs were associated with the incidence of low birth weight, low efficiency of the tetanus vaccine, and low triglyceride levels.

CNOT7 regulates lipid deposition in nonalcoholic fatty liver disease.

BACKGROUND: In recent years, the incidence rate of nonalcoholic fatty liver disease (NAFLD) has ascended with the increasing number of metabolic diseases such as obesity and diabetes, which will bring great medical burden to society. At present, multiple scientific experiments have found that the CCR4-NOT complex can participate in regulating obesity and energy metabolism. This study is designed to explore the role and mechanism of CCR4-NOT transcription complex subunit 7 (CNOT7), a subunit of the CCR4-NOT complex in liver lipid deposition. METHODS: To establish the NAFLD cell model, palmitic acid (PA) was utilized to stimulate HepG2 cells and LO2 cells, promoting intracellular lipid deposition. CNOT7 was knockdown by siRNA and lentivirus to evaluate the effect of CNOT7 in NAFLD. RESULTS: Our results demonstrated that the expression of CNOT7 was increased in the NAFLD cell model. After knocking down CNOT7, the lipid deposition declined in HepG2 or LO2 cells treated by PA reduced. We found the lipid synthesis genes and the lipid uptake and transport factors in the CNOT7 knockdown group were significantly downregulated compared to the non-knockdown group. Furthermore, knockdown of CNOT7 might promote fatty acid oxidation. CONCLUSION: Knocking down CNOT7 can improve lipid deposition and CNOT7 may be a potential therapeutic target for NAFLD.

Giant ab-Plane Birefringence in Quasi-1D Fibrous Red Phosphorus.

Quasi-one-dimensional (quasi-1D) van der Waals crystal fibrous red phosphorus (RP) exhibits pronounced in-plane optical anisotropy, positioning it as a potential candidate for polarization-related micro-nano devices. Unfortunately, a comprehensive investigation into the complex refractive index of fibrous RP and the structure-activity relationship connecting the distinctive quasi-1D structure with optical anisotropy is currently deficient. Herein, we have collectively determined the complex refractive index of the fibrous RP flakes within the ab-plane through Kramers-Kronig (KK) analysis and theoretical calculation. Notably, the maximum birefringence of fibrous RP reaches 0.642@475 nm with an absolute extinction coefficient of only 0.08, superior to the reported traditional optical crystals and the emerging low-dimensional materials as well. The remarkable birefringence can be attributed to the synergistic influence of the large electronic dipole polarizability, anisotropic electron density distribution and the distortion of stereochemically active lone pair (SCALP). This work demonstrates the potential of fibrous RP for polarization-sensitive devices, illuminating possibilities to exploit novel giant birefringent crystals based on the structure-activity relationship.