Sodium alginate-based coaxial fibers synergistically integrate moisture actuation, length tracing, humidity sensing, and electric heating.

The development of wearable electronics has driven the need for smart fibers with advanced multifunctional synergy. In this paper, we present a design of a multifunctional coaxial fiber that is composed of a biopolymer-derived core and an MXene/silver nanowire (AgNW) sheath by wet spinning. The fiber synergistically integrates moisture actuation, length tracing, humidity sensing, and electric heating, making it highly promising for portable devices and protective systems. The biopolymer-derived core provides deformation for moisture-sensitive actuation, while the MXene/AgNW sheath with good conductivity enables the fiber to perform electric heating, humidity sensing, and self-sensing actuation. The coaxial fiber can be programmed to rapidly desorb water molecules to shrink to its original length by using the MXene/AgNW sheath as an electrical heater. We demonstrate proof-of-concept applications based on the multifunctional fibers for thermal physiotherapy and wound healing/monitoring. The sodium alginate@MXene-based coaxial fiber presents a promising solution for the next-generation of smart wearable electronics.

Hepatotoxicity of oral exposure to 2-methyl-4-nitroaniline: toxicity prediction and in vivo evaluation.

2-Methyl-4-nitroaniline (MNA), an intermediate in the synthesis of azo dyes, is widely distributed in various environmental media and organisms. Although there is speculation regarding MNA's potential to be hepatotoxic, the underlying mechanisms of its hepatotoxicity and its definitive diagnostic process remain largely unexplored. In this research. In the present study, we initially predicted the toxicity and possible toxic effect pathways of MNA using ProTox-II, and found that MNA binds to the PPARγ receptor (binding energy －6.118 kcal/mol) with a potential PPARγ agonist effect. Subsequently, in vivo exposure evaluation was conducted on Wistar rats to assess the impact of MNA after a 90-day exposure period, by detecting serum biochemical indexes, hematological indexes, urinary indexes, inflammatory factors, liver histopathological observations and liver tissue PPARγ mRNA expression. The results showed that MNA causes liver function abnormalities, liver histopathological changes and inflammatory response, along with a pronounced increase in PPARγ mRNA levels. This study suggests that the hepatotoxic mechanism of MNA may be related to its possible upregulation of PPARγ expression, increased liver dysfunction and inflammatory responses. Based on these results, the benchmark dose lower limit (BMDL) of 1.503 mg/kg for male Wistar rats was also established, providing a vital benchmark for determining the safety threshold of MNA. Our data highlight the hepatotoxic mechanism of MNA and contribute to a better understanding of its potential etiological diagnosis.

Coiled Carbon Nanotube Fibers Sheathed by a Reinforced Liquid Crystal Elastomer for Strong and Programmable Artificial Muscles.

Fibers of liquid crystal elastomers (LCEs) as promising artificial muscle show ultralarge and reversible contractile strokes. However, the contractile force is limited by the poor mechanical properties of the LCE fibers. Herein, we report high-strength LCE fibers by introducing a secondary network into the single-network LCE. The double-network LCE (DNLCE) shows considerable improvements in tensile strength (313.9%) and maximum actuation stress (342.8%) compared to pristine LCE. To facilitate the controllability and application, a coiled artificial muscle fiber consisting of DNLCE-coated carbon nanotube (CNT) fiber is prepared. When electrothermally driven, the artificial muscle fiber outputs a high actuation performance and programmable actuation. Furthermore, by knitting the artificial muscle fibers into origami structures, an intelligent gripper and crawling inchworm robot have been demonstrated. These demonstrations provide promising application scenarios for advanced intelligent systems in the future.

Dasabuvir alleviates 5-fluorouracil-induced intestinal injury through anti-senescence and anti-inflammatory.

5-Fluorouracil (5-Fu) is a basic drug that is used to treat colorectal cancer. Patients who receive 5-Fu chemotherapy often experience side effects that affect the digestive system, such as intestinal injury and diarrhoea, which significantly affect patient compliance with anticancer treatment and quality of life. Therefore, identifying approaches to treat or prevent these side effects is urgent. Dasabuvir (DSV) is a hepatitis C virus inhibitor, but its impact on 5-Fu-induced intestinal injury remains unknown. Our study investigated the effects of DSV on 5-Fu-induced intestinal injury in HUVECs, HIECs and male BALB/c mice. We found that 5-Fu caused intestinal damage by inducing senescence, increasing inflammatory factor expression, and generating oxidative stress. Compared with 5-Fu treatment alone, DSV inhibited senescence by reducing senescence-ß-galactosidase (SA-ß-gal) activity, the senescence-associated secretory phenotype (SASP, including IL-1, IL-6, and TNF-α) and senescence marker expression levels (p16, p21, and p53). Moreover, the anti-senescence effect of DSV was achieved by inhibiting the mTOR signaling pathway. DSV increased antioxidant enzyme levels and alleviated intestinal tissue injury in mice. In addition, DSV suppressed the 5-Fu-induced increase the diarrhoea scores and ameliorated the weight loss, food intake and water intake of the mice. Overall, this study indicated that DSV could be used to treat chemotherapy-induced intestinal damage.

Detection of Ascorbic Acid by Two-Dimensional Conductive Metal-Organic Framework-Based Electrochemical Sensors.

The realization of efficient and accurate detection of biomolecules has become a key scientific issue in the field of life sciences. With the rapid development of nanotechnology, electrochemical sensors constructed from the superior physical and chemical properties of nanomaterials show faster and more accurate detection. Among nanomaterials, two-dimensional conductive MOF (2D cMOF) is considered to be a star material in electrochemical sensors due to its remarkable conductivity, high porosity, and stability. In this paper, a Cu3(HHTP)2/SPE electrochemical sensor for the detection of ascorbic acid (AA) was constructed by modifying 2D cMOF (Cu3(HHTP)2) on the surface of the screen-printed electrode (SPE). The sensor exhibited excellent catalytic activity in the detection of AA, with a lower detection limit of 2.4 µmol/L (S/N = 3) and a wide linear range of 25-1645 µmol/L. This high catalytic activity can be attributed to the abundant catalytic sites in Cu3(HHTP)2 and the rapid electron transfer between Cu+ and Cu2+, which accelerates the oxidation of AA. This work lays a foundation for the subsequent development of MOFs with special electrochemical catalytic properties and the integration of 2D cMOF into intelligent electrical analysis devices.

Zincophilic Nanospheres Assembled as Solid-Electrolyte Interphase on Zn Metal Anodes for Reversible High-rate Zn-Ion Storage.

Aqueous Zn-ion batteries (ZIBs) are considered to be one of the most promising energy storage devices in the post-lithium-ion era with fast ionic conductivity, safety, and low cost. However, excessive accumulation of zinc dendrites will fracture and produce dead zinc, resulting in the unsatisfied utilization rate of Zn anodes, which greatly restricts the lifespan of the battery and reduces the reversibility. In this paper, by constructing a protective layer of ZnSnO3 hollow nanospheres in situ growth on the surface of the Zn anode, more zincophilic sites are established on the electrode surface. It demonstrates that uniform deposition of Zn ions by deepening the binding energy with Zn ion and its unique hollow structure shortens the diffusion distance of Zn ions and enhances the reaction kinetics. The assembled Zn-ion hybrid supercapacitor (ZHSC) of ZnSnO3@Zn//AC achieved a long-term lifespan with 4000 cycles at a current density of 10 mA cm-2 with a Coulombic efficiency of 99.31% and capacity retention of 79.6%. This work offers a new path for advanced Zn anodes interphase supporting the long cycle life with large capacities and improving electrochemical reversibility.

Temporal-spatial variability of grazing behaviors of yaks and the drivers of their intake on the eastern Qinghai-Tibetan Plateau.

Introduction: Grassland-livestock balance is an important principle of sustainable development of grassland livestock production and grassland ecosystem health. Grassland degradation becomes more serious at global scales and especially at the area that is sensitive to climate change and human activities. Decreases in pasture biomass and shifts in plant community composition in degraded grasslands can largely affect grazing behaviors of livestock. Up to date, however, it is unclear that whether livestock behaviors change across spatial and temporal scales and what key factors are to shape observed behavioral patterns of livestock. Methods: Here, yak behaviors including grazing, rumination and walking on the eastern Qinghai-Tibetan Plateau (QTP) were monitored by a continuous visual observation, to investigate temporal and spatial variations of grazing behavior of yaks (Bos grunniens); based on the data from public database in the past 18 years, a meta-analysis was conducted to examine the main factors that affect grazing behaviors and intake of yaks. Results: We showed that grazing behaviors of yaks differed significantly within hours, among hours of each day and among days as well as across different observation sites. Intake rate of yaks was higher in the morning than in the afternoon, but walking speed showed an inverse trend compared with intake rate. Resting, altitude, the mean annual precipitation (MAP), the mean annual temperature (MAT), forage ash, yak age and season were the main predictors for yak intake, and forage and yak individual characteristics had direct effects on grazing behaviors and intake of yaks. Discussion: The findings confirm that grazing behaviors of yaks can vary even at small temporal scales and regional scales, which is closely related to the shift in forage quality and biomass caused by environmental changes. The study suggests that multiple factors can be responsible for the variation in livestock behaviors and shifts in behavioral patterns may consequently lead to positive or negative feedback to grassland ecosystems through plant-animal interactions.

A novel surgical scheme for hepatectomy in hepatocellular carcinoma patients with clinically significant portal hypertension.

OBJECTIVE: Clinically significant portal hypertension (CSPH) seriously affects the feasibility and safety of surgical treatment for hepatocellular carcinoma (HCC) patients. The aim of this study was to establish a new surgical scheme defining risk classification of post-hepatectomy liver failure (PHLF) to facilitate the surgical decision-making and identify suitable candidates for individual hepatectomy among HCC patients with CSPH. BACKGROUNDS: Hepatectomy is the preferred treatment for HCC. Surgeons must maintain a balance between the expected oncological outcomes of HCC removal and short-term risks of severe PHLF and morbidity. CSPH aggravates liver decompensation and increases the risk of severe PHLF thus complicating hepatectomy for HCC. METHODS: Multivariate logistic regression and stochastic forest algorithm were performed, then the independent risk factors of severe PHLF were included in a nomogram to determine the risk of severe PHLF. Further, a conditional inference tree (CTREE) through recursive partitioning analysis validated supplement the misdiagnostic threshold of the nomogram. RESULTS: This study included 924 patients, of whom 137 patients (14.8%) suffered from mild-CSPH and 66 patients suffered from (7.1%) with severe-CSPH confirmed preoperatively. Our data showed that preoperative prolonged prothrombin time, total bilirubin, indocyanine green retention rate at 15 min, CSPH grade, and standard future liver remnant volume were independent predictors of severe PHLF. By incorporating these factors, the nomogram achieved good prediction performance in assessing severe PHLF risk, and its concordance statistic was 0.891, 0.850 and 0.872 in the training cohort, internal validation cohort and external validation cohort, respectively, and good calibration curves were obtained. Moreover, the calculations of total points of diagnostic errors with 95% CI were concentrated in 110.5 (range 76.9-178.5). It showed a low risk of severe PHLF (2.3%), indicating hepatectomy is feasible when the points fall below 76.9, while the risk of severe PHLF is extremely high (93.8%) and hepatectomy should be rigorously restricted at scores over 178.5. Patients with points within the misdiagnosis threshold were further examined using CTREE according to a hierarchic order of factors represented by the presence of CSPH grade, ICG-R15, and sFLR. CONCLUSION: This new surgical scheme established in our study is practical to stratify risk classification in assessing severe PHLF, thereby facilitating surgical decision-making and identifying suitable candidates for individual hepatectomy.

Natural Variation in the Promoter of GmSPL9d Affects Branch Number in Soybean.

The branch number is a crucial factor that influences density tolerance and is closely associated with the yield of soybean. However, its molecular regulation mechanisms remain poorly understood. This study cloned a candidate gene GmSPL9d for regulating the soybean branch number based on the rice OsSPL14 homologous gene. Meanwhile, the genetic diversity of the GmSPL9d was analyzed using 3599 resequencing data and identified 55 SNP/InDel variations, which were categorized into seven haplotypes. Evolutionary analysis classified these haplotypes into two groups: GmSPL9d H-I and GmSPL9d H-II. Soybean varieties carrying the GmSPL9d H-II haplotype exhibited a significantly lower branch number compared with those carrying the GmSPL9d H-I haplotype. Association analysis between the variation sites and branch number phenotypes revealed a significant correlation between the promoter variations and the branch number. Promoter activity assays demonstrated that the GmSPL9d H-II promoter displayed significantly higher activity than the GmSPL9d H-I promoter. Transgenic experiments confirmed that the plants that carried the GmSPL9d H-II promoter exhibited a significantly lower branch number compared with those that carried the GmSPL9d H-I promoter. These findings indicate that the variation in the GmSPL9d promoter affected its transcription level, leading to differences in the soybean branch number. This study provides valuable molecular targets for improving the soybean plant structure.

Research progress of circular RNAs in myocardial ischemia.

Circular RNAs (circRNAs) are a type of single-stranded RNA that forms a covalently closed continuous loop. Its structure, stability, properties, and cell- and tissue-specificity have gained considerable recognition in the research and clinical sectors, as its role has been observed in different diseases, such as cardiovascular diseases, cancers, and central nervous system diseases, etc. Cardiovascular disease is still named as the number one cause of death globally, with myocardial ischemia (MI) accounting for 15 % of mortality annually. A number of circRNAs have been identified and are being studied for their ability to reduce MI by inhibiting the molecular mechanisms associated with myocardial ischemia reperfusion injury, such as inflammation, oxidative stress, autophagy, apoptosis, and so on. CircRNAs play a significant role as crucial regulatory elements at transcriptional levels, regulating different proteins, and at posttranscriptional levels, having interactions with RNA-binding proteins, ribosomal proteins, micro-RNAS, and long non-coding RNAS, making it possible to exert their effects through the circRNA-miRNA-mRNA axis. CircRNAs are a potential novel biomarker and therapeutic target for myocardial ischemia and cardiovascular diseases in general. The purpose of this review is to summarize the relationship, function, and mechanism observed between circRNAs and MI injury, as well as to provide directions for future research and clinical trials.

Salidroside modulates repolarization through stimulating Kv2.1 in rats.

BACKGROUND: Voltage-gated potassium (Kv) channel growth is strongly associated with the development of arrhythmia. Salidroside (Sal), an active component from Rhodiola crenulata, has been shown to exert protective effects against heart disease. The present study was conducted to investigate the effects of Sal on Kv2.1 channel, and to explore the ionic mechanism of anti-arrhythmic. METHODS: In this study, we utilized cisapride (Cis., A stimulant that prolongs the QT interval and causes cardiac arrhythmias) by intravenous injection to establish an arrhythmia model, and detected the effects of Sal on electrocardiography (ECG) and pressure volume loop (P-V loop) in SD rats. The effect of Sal on ECG of citalopram (Cit., a Kv2 channel inhibition)-evoked arrhythmia rat models was further evaluated by monitoring the dynamic changes of multiple indicators of ECG. Then, we detected the effect of Sal on the viability of hypoxic H9c2 cells using CCK-8 assay. After that, the effect of Sal on Kv channel currents (IKv) and Kv2.1 channel currents (IKv2.1) in H9c2 cells under normal and hypoxic conditions was examined using whole-cell patch clamp technique. In addition, the effect of Sal on IKv and IKv2.1 in H9c2 cells was determined under the inhibition of Kv and Kv2.1 channels. HEK293 cells stably transfected with Kv2.1 plasmids were also used to investigate the IKv2.1 changes under Sal pre-treated and co-incubated conditions. In addition, potential interactions of Sal with Kv2.1 protein were predicted and tested by molecular docking, molecular dynamics simulation (MDS), localized surface plasmon resonance (LSPR), and cellular thermal shift assay (CETSA) techniques, respectively. Furthermore, gene and protein levels of Kv2.1 in Sal-treated H9c2 cell were estimated by qRT-PCR, Western blot (WB) and immunofluorescence (IF) analysis. RESULTS: Sal shortened the prolongated QT interval and ameliorated the cardiac impairment associated with arrhythmia in SD rats caused by Cis., as reflected in the ECG and P-V loop data. And Sal was also protective against arrhythmia in rats caused by Kv2 channel inhibition. At the cellular level, Sal increased cell viability after CoCl2-induced hypoxic injury in H9c2 cells. Whole-cell patch clamp assay confirmed that Sal inhibited both IKv and IKv2.1 in normal H9c2 cells, while enhanced IKv and IKv2.1 in cardiomyocytes after hypoxic injury. And Sal enhanced IKv inhibited by 1.5 mM 4-AP and upregulated all inhibition of Kv2 channels induced by 20 mM 4-AP administration, antagonized the IKv2.1 inhibitory effect of Cit. Moreover, Sal pre-administration for 24 h and immediate administration increased IKv2.1 in HEK293 cells stably transfected with Kv2.1 plasmids. Molecular docking demonstrated the potential binding of Sal to the Kv2.1 protein, with calculated binding energy of -5.4 kcal/mol. MDS test illustrated that the average hydrogen bonding of the Sal-Kv2.1 complexes was 30.89%. LSPR results verified the potential binding of Sal to Kv2.1 protein with an affinity value of 9.95 × 10-4 M. CETSA assay confirmed Sal can enhance the expression of Kv2.1 protein in H9c2 cells treated with heat, which suggests that Sal may bind to Kv2.1 protein. The results of WB, qRT-PCR, and IF further argued that Sal pre-administration for 24 h enhanced the levels of the Kv2.1 gene and protein (with no effects on the Kv2.1 gene and protein for H9c2 cells co-incubated with Sal for 6 h and 12 h). CONCLUSION: Overall, our findings indicate that Sal can resist drug-induced arrhythmias in SD rats, partially by modulating repolarization through stimulating Kv2.1.

TACE combined Lenvatinib plus Camrelizumab versus TACE alone in efficacy and safety for unresectable hepatocellular carcinoma: a propensity score-matching study.

BACKGROUNDS: To compare the efficacy and safety of transcatheter arterial chemoembolization (TACE) combined Lenvatinib plus Camrelizumab (TLC) in unresectable hepatocellular carcinoma (uHCC) with those of TACE alone . METHODS: A retrospective analysis was performed on 222 patients with uHCC who were treated between September 2013 and Jun 2023. One group received TACE + lenvatinib + camrelizumab (TLC) (n = 97) and another group received TACE alone (n = 151). Efficacy and safety were compared after propensity score matching between the TLC and TACE groups. RESULTS: After propensity matching, the TLC group had higher objective response rate (ORR) (88.6% vs. 28.6%, P < 0.001), disease control rate (DCR) (94.3%% vs. 72.9%, P < 0.001), and conversion rates before and after propensity matching were 44.1% and 41.4%, respectively, compared with the TACE group. The median progression free survival (PFS) was longer in the TLC group than in the TACE group (12.7 vs. 6.1 months, P = 0.005). The median overall survival (OS) was longer in the TLC group than in the TACE group (19.4 vs. 13.0 months, P = 0.023). Cox multivariate analysis with different modes of adjustment showed that treatment was an independent influencing factor of PFS and OS. The interaction analysis showed that cirrhosis and Child-Pugh stage an interactive role in the PFS of different treatment. Decreased AFP after treatment portends higher ORR and DCR. CONCLUSION: TACE combined Lenvatinib plus Camrelizumab regimen was safe and superior to TACE alone in improving PFS, OS, and tumor response rates for unresectable recurrent HCC patients.

Exploring the Mechanism of Zhishi-Xiebai-Guizhi Decoction for the Treatment of Hypoxic Pulmonary Hypertension Based on Network Pharmacology and Experimental Analyses.

BACKGROUND: Hypoxic Pulmonary Hypertension (HPH), a prevalent disease in highland areas, is a crucial factor in various complex highland diseases with high mortality rates. Zhishi-Xiebai-Guizhi Decoction (ZXGD), traditional Chinese medicine with a long history of use in treating heart and lung diseases, lacks a clear understanding of its pharmacological mechanism. OBJECTIVE: This study aimed to investigate the pharmacological effects and mechanisms of ZXGD on HPH. METHODS: We conducted a network pharmacological prediction analysis and molecular docking to predict the effects, which were verified through in vivo experiments. RESULTS: Network pharmacological analysis revealed 51 active compounds of ZXGD and 701 corresponding target genes. Additionally, there are 2,116 target genes for HPH, 311 drug-disease co-target genes, and 17 core target genes. GO functional annotation analysis revealed that the core target genes primarily participate in biological processes such as apoptosis and cellular response to hypoxia. Furthermore, KEGG pathway enrichment analysis demonstrated that the core targets are involved in several pathways, including the phosphatidylinositol- 3 kinase/protein kinase B (PI3K/Akt) signaling pathway and Hypoxia Inducible Factor 1 (HIF1) signaling pathway. In vivo experiments, the continuous administration of ZXGD demonstrated a significant improvement in pulmonary artery pressure, right heart function, pulmonary vascular remodeling, and pulmonary vascular fibrosis in HPH rats. Furthermore, ZXGD was found to inhibit the expression of PI3K, Akt, and HIF1α proteins in rat lung tissue. CONCLUSION: In summary, this study confirmed the beneficial effects and mechanism of ZXGD on HPH through a combination of network pharmacology and in vivo experiments. These findings provided a new insight for further research on HPH in the field of traditional Chinese medicine.

Soil fungal community structure and function response to rhizoma perennial peanut cultivars.

BACKGROUND: Crop-associated microorganisms play a crucial role in soil nutrient cycling, and crop growth, and health. Fine-scale patterns in soil microbial community diversity and composition are commonly regulated by plant species or genotype. Despite extensive reports in different crop or its cultivar effects on the microbial community, it is uncertain how rhizoma peanut (RP, Arachis glabrata Benth.), a perennial warm-season legume forage that is well-adapted in the southern USA, affects soil microbial community across different cultivars. RESULTS: This study explored the influence of seven different RP cultivars on the taxonomic composition, diversity, and functional groups of soil fungal communities through a field trial in Marianna, Florida, Southern USA, using next-generation sequencing technique. Our results showed that the taxonomic diversity and composition of the fungal community differed significantly across RP cultivars. Alpha diversity (Shannon, Simpson, and Pielou's evenness) was significantly higher in Ecoturf but lower in UF_Peace and Florigraze compared to other cultivars (p < 0.001). Phylogenetic diversity (Faith's PD) was lowest in Latitude compared to other cultivars (p < 0.0001). The dominant phyla were Ascomycota (13.34%), Mortierellomycota (3.82%), and Basidiomycota (2.99%), which were significantly greater in Florigraze, UF_Peace, and Ecoturf, respectively. The relative abundance of Neocosmospora was markedly high (21.45%) in UF_Tito and showed large variations across cultivars. The relative abundance of the dominant genera was significantly greater in Arbrook than in other cultivars. There were also significant differences in the co-occurrence network, showing different keystone taxa and more positive correlations than the negative correlations across cultivars. FUNGuild analysis showed that the relative abundance of functional guilds including pathogenic, saprotrophic, endophytic, mycorrhizal and parasitic fungi significantly differed among cultivars. Ecoturf had the greatest relative abundance of mycorrhizal fungal group (5.10 ± 0.44), whereas UF_Peace had the greatest relative abundance of endophytic (4.52 ± 0.56) and parasitic fungi (1.67 ± 0.30) compared to other cultivars. CONCLUSIONS: Our findings provide evidence of crop cultivar's effect in shaping fine-scale fungal community patterns in legume-based forage systems.

Exploring the therapeutic mechanisms of Coptidis Rhizoma in gastric precancerous lesions: a network pharmacology approach.

BACKGROUND: Gastric precancerous lesions are a critical stage in the development of gastric cancer or gastric adenocarcinoma, and their outcome plays an important role in the malignant progression of gastric cancer. Coptidis Rhizoma has a good effect on Gastric precancerous lesions. However, the specific mechanisms of its action remain incompletely elucidated. METHODS: Network pharmacology and molecular docking techniques were used to explore the active ingredients and molecular mechanism of Coptidis Rhizoma in treating gastric precancerous lesions. The active compounds of Coptidis Rhizoma and their potential gastric precancerous lesions related targets were obtained from TCMSP, GeneCards, and OMIM databases. An interaction network based on protein-protein interactions (PPIs) was constructed to visualize the interactions between hub genes. Analysis of GO enrichment and KEGG pathway were conducted using the DAVID database. An investigation of interactions between active compounds and potential targets was carried out by molecular docking. Finally, animal experiments were conducted to verify the effect and mechanism of Coptidis Rhizoma in treating precancerous lesions of gastric cancer. RESULTS: A total of 11 active compounds and 95 anti-gastric precancerous lesions targets of Coptidis Rhizoma were screened for analysis. GO enrichment analysis showed that the mechanism of Coptidis Rhizoma acting on gastric precancerous lesions involves gene expression regulation and apoptosis regulation. KEGG pathway enrichment analysis showed that Coptidis Rhizoma against gastric precancerous lesions involving the AKT /HIF-1α/VEGF signalling pathway. Molecular docking simulations indicated potential interactions between these compounds and core targets involved in anti-gastric precancerous lesions activity. In addition, it was confirmed in vivo that Berberine and Coptidis Rhizoma may reverse atrophy and potential intestinal metaplasia by inhibiting the expression of p-AKT, HIFA, and VEGF. CONCLUSION: Bioactive compounds in Coptidis Rhizoma have the potential to prevent atrophy and intestinal metaplasia. These compounds function by regulating the proteins implicated in AKT /HIF-1α/VEGF signalling pathways that are crucial in gastric epithelial cell differentiation, proliferation and maturation.

Intra-Ocular Inflammation and Occlusive Retinal Vasculitis Following Intravitreal Injections of Faricimab: A Case Report.

PURPOSE: Faricimab is a bispecific antibody that inhibits angiopoietin-2 and vascular endothelial growth factor-A action and has been approved for the treatment of neovascular age-related macular degeneration and diabetic macular edema. Clinical trials have demonstrated its favorable safety profile. This report presents a case of intra-ocular inflammation and occlusive retinal vasculitis following a second intravitreal injection of faricimab. METHODS: A single case report was obtained from a tertiary referral center. RESULTS: A 73-year-old Asian man diagnosed with polypoidal choroidal vasculopathy presented with decreased vision in the left eye (OS) 2 weeks after the second faricimab administration. In the fourth week after the second faricimab injection, swept-source optical coherence tomography (OCT) revealed hyperreflective dots in the vitreous cavity, indicating vitreous cells. Color fundus photography showed new-onset perivenular hemorrhages and pallor of the inferonasal retina OS, of which OCT revealed retinal inner layer thickening, suggestive of retinal arteriolar occlusions. Retinal fluorescein angiography revealed delayed filling of the inferior temporal vein. The patient was diagnosed with intraocular inflammation and occlusive retinal vasculitis OS associated with repeated intravitreal faricimab administrations. Intravitreal dexamethasone implant was used instead of faricimab at this visit. CONCLUSIONS: The findings of this case hint towards the potential risk of retinal occlusive events associated with intravitreal faricimab injections.

Preclinical Evaluation of 131I/18F-Labeled Covalent Small-Molecule Inhibitors for STING Status Imaging.

The stimulator of interferon genes (STING) is a vital protein to the immune surveillance of the tumor microenvironment. In this study, we develop novel inhibitor-based radioligands and evaluate their feasibility for noninvasive visualization of STING expression in tumor-bearing mice. Analogous compounds to STING inhibitors C170 and C176 were synthesized and labeled with 131I and 18F to attain [131I]I-NFIP and [18F]F-NFEP, respectively. The radiosynthesis was achieved with high radiochemical purity (>95%) and molar activity (28.56-48.89 GBq/µmol). The affinity and specificity of tracers were assessed through cell uptake and docking experiments, demonstrating that [131I]I-NFIP exhibited high specificity for STING, with a cell-based IC50 value of 7.56 nM. Small-animal PET/SPECT imaging and biodistribution studies in tumor-bearing mice models were performed to verify the tracers' pharmacokinetics and tumor-targeting capabilities (n = 3/group). SPECT imaging demonstrated that [131I]I-NFIP rapidly accumulated in the Panc02 tumor quickly at 30 min post-injection, with a tumor-to-muscle (T/M) ratio of 2.03 ± 0.30. This ratio significantly decreased in the blocking group (1.10 ± 0.14, **P < 0.01, n = 3). Furthermore, tumor uptake and the T/M ratio of [131I]I-NFIP were positively associated with STING expression. In summary, [131I]I-NFIP is the first STING-specific inhibitor-based radioligand offering the potential for visualizing STING status in tumors.

Antidepressant-like effects of Cimicifuga dahurica (Turcz.) Maxim. via modulation of monoamine regulatory pathways.

Sheng-ma is recorded in the Compendium of Materia Medica and mainly originates from the rhizomes of Cimicifuga dahurica (Turcz.) Maxim. (CD), Cimicifuga heracleifolia Kom. and Cimicifuga foetida L. The alcoholic extract of Cimicifuga foetida L. (Brand name: Ximingting®) has been approved for the treatment of perimenopausal symptoms accompanying hot flash, depression and anxiety in China. However, there's no further study about the antidepressant-like effects of C. dahurica (CD). The aim of this study is to investigate the antidepressant-like effect of CD extracted by 75% ethanol and its possible mechanisms.The neuro-protective effects of CD on injured PC12 cells induced by corticosterone was measured firstly. Then, forced swim test (FST), tail suspension test (TST), reserpine-induced hypothermia, 5-hydroxytryptophan (5-HTP) induced head twitch response in mice and chronic unpredictable mild stress (CUMS) on sucrose preference tests were executed. Moreover, the potential mechanisms were explored by measuring levels of monoamine neurotransmitter in mice frontal cortex and hippocampus, testing monoamine oxidase enzyme A (MAO-A) activities in the brains of CUMS-exposed mice. Results showed that CD (60, 120 mg/kg) can significantly decreased the immobility period in FST and TST in mice without affecting locomotor activity. CD (30 mg/kg, 60 mg/kg, 120 mg/kg) could significantly counteracted reserpine-induced hypothermia and increased the number of head-twitches in 5-HTP induced head twitch response. It was also found that the monoamine neurotransmitter levels in the hippocampus and frontal cortex were significantly increased in 60 mg/kg and 120 mg/kg CD treated mice. In addition, CD (60 and 120 mg/kg) significantly inhibited MAO-A after 6-week CUMS exposure. CD can effectively produce an antidepressant-like effect, which involved with modulation of monoamine regulatory pathways.

A novel anoikis-related signature predicts prognosis risk and treatment responsiveness in diffuse large B-cell lymphoma.

BACKGROUND: Although anoikis plays a role in cancer metastasis and aggressiveness, it has rarely been reported in diffuse large B cell lymphoma (DLBCL). METHODS: We obtained RNA sequencing data and matched clinical data from the GEO database. An anoikis-related genes (ARGs)-based risk signature was developed in GSE10846 training cohort and validated in three other cohorts. Additionally, we predicted half-maximal inhibitory concentration (IC50) of drugs based on bioinformatics method and obtained the actual IC50 to some chemotherapy drugs via cytotoxicity assay. RESULTS: The high-risk group, as determined by our signature, was associated with worse prognosis and an immunosuppressive environment in DLBCL. Meanwhile, the nomogram based on eight variables had more accurate ability in forecasting the prognosis than the international prognostic index in DLBCL. The prediction of IC50 indicated that DLBCL patients in the high-risk group were more sensitive to doxorubicin, IPA-3, lenalidomide, gemcitabine, and CEP.701, while patients in the low-risk group were sensitive to cisplatin and dasatinib. Consistent with the prediction, cytotoxicity assay suggested the higher sensitivity to doxorubicin and gemcitabine and the lower sensitivity to dasatinib in the high-risk group in DLBCL. CONCLUSION: The ARG-based signature may provide a promising direction for prognosis prediction and treatment optimization for DLBCL patients.