Bio-Polyethylene and Polyethylene Biocomposites: An Alternative toward a Sustainable Future.

Polyethylene (PE), a highly prevalent non-biodegradable polymer in the field of plastics, presents a waste management issue. To alleviate this issue, bio-based PE (bio-PE), derived from renewable resources like corn and sugarcane, offers an environmentally friendly alternative. This review discusses various production methods of bio-PE, including fermentation, gasification, and catalytic conversion of biomass. Interestingly, the bio-PE production volumes and market are expanding due to the growing environmental concerns and regulatory pressures. Additionally, the production of PE and bio-PE biocomposites using agricultural waste as filler materials, highlights the growing demand for sustainable alternatives to conventional plastics. According to previous studies, addition of ≈50% defibrillated corn and abaca fibers into bio-PE matrix and a compatibilizer, results in the highest Young's modulus of 4.61 and 5.81 GPa, respectively. These biocomposites have potential applications in automotive, building construction, and furniture industries. Moreover, the advancement made in abiotic and biotic degradation of PE and PE biocomposites is elucidated to address their environmental impacts. Finally, the paper concludes with insights into the opportunities, challenges, and future perspectives in the sustainable production and utilization of PE and bio-PE biocomposites. In summary, production of PE and bio-PE biocomposites can contribute to a cleaner and sustainable future.

Multi-step validation of a deep learning-based system with visual explanations for optical diagnosis of polyps with advanced features.

Artificial intelligence (AI) has been found to assist in optical differentiation of hyperplastic and adenomatous colorectal polyps. We investigated whether AI can improve the accuracy of endoscopists' optical diagnosis of polyps with advanced features. We introduced our AI system distinguishing polyps with advanced features with more than 0.870 of accuracy in the internal and external validation datasets. All 19 endoscopists with different levels showed significantly lower diagnostic accuracy (0.410-0.580) than the AI. Prospective randomized controlled study involving 120 endoscopists into optical diagnosis of polyps with advanced features with or without AI demonstration identified that AI improved endoscopists' proportion of polyps with advanced features correctly sent for histological examination (0.960 versus 0.840, p < 0.001), and the proportion of polyps without advanced features resected and discarded (0.490 versus 0.380, p = 0.007). We thus developed an AI technique that significantly increases the accuracy of colorectal polyps with advanced features.

Synergistic Combination of Sb2Si2Te6 Additives for Enhanced Average ZT and Single-Leg Device Efficiency of Bi0.4Sb1.6Te3-based Composites.

Thermoelectric materials are highly promising for waste heat harvesting. Although thermoelectric materials research has expanded over the years, bismuth telluride-based alloys are still the best for near-room-temperature applications. In this work, a ≈38% enhancement of the average ZT (300-473 K) to 1.21 is achieved by mixing Bi0.4Sb1.6Te3 with an emerging thermoelectric material Sb2Si2Te6, which is significantly higher than that of most BiySb2-yTe3-based composites. This enhancement is facilitated by the unique interface region between the Bi0.4Sb1.6Te3 matrix and Sb2Si2Te6-based precipitates with an orderly atomic arrangement, which promotes the transport of charge carriers with minimal scattering, overcoming a common factor that is limiting ZT enhancement in such composites. At the same time, high-density dislocations in the same region can effectively scatter the phonons, decoupling the electron-phonon transport. This results in a ≈56% enhancement of the thermoelectric quality factor at 373 K, from 0.41 for the pristine sample to 0.64 for the composite sample. A single-leg device is fabricated with a high efficiency of 5.4% at ΔT = 164 K further demonstrating the efficacy of the Sb2Si2Te6 compositing strategy and the importance of the precipitate-matrix interface microstructure in improving the performance of materials for relatively low-temperature applications.

Stable n-Type Perylene Derivative Ladder Polymer with Antiambipolarity for Electrically Reconfigurable Organic Logic Gates.

Organic electrochemical transistors (OECTs) are one of the promising building blocks to realize next-generation bioelectronics. To date, however, the performance and signal processing capabilities of these devices remain limited by their stability and speed. Herein, the authors demonstrate stable and fast n-type organic electrochemical transistors based on a side-chain-free ladder polymer, poly(benzimidazoanthradiisoquinolinedione). The device demonstrated fast normalized transient speed of 0.56 ± 0.17 ms um-2 and excellent long-term stability in aqueous electrolytes, with no significant drop in its doping current after 50 000 successive doping/dedoping cycles and 2-month storage at ambient conditions. These unique characteristics make this polymer especially suitable for bioelectronics, such as being used as a pull-down channel in a complementary inverter for long-term stable detection of electrophysiological signals. Moreover, the developed device shows a reversible anti-ambipolar behavior, enabling reconfigurable electronics to be realized using a single material. These results go beyond the conventional OECT and demonstrate the potential of OECTs to exhibit dynamically configurable functionalities for next-generation reconfigurable electronics.

Bioinspired Solar-Driven Osmosis for Stable High Flux Desalination.

The growing global water crisis necessitates sustainable desalination solutions. Conventional desalination technologies predominantly confront environmental issues such as high emissions from fossil-fuel-driven processes and challenges in managing brine disposal during the operational stages, emphasizing the need for renewable and environmentally friendly alternatives. This study introduces and assesses a bioinspired, solar-driven osmosis desalination device emulating the natural processes of mangroves with effective contaminant rejection and notable productivity. The bioinspired solar-driven osmosis (BISO) device, integrating osmosis membranes, microporous absorbent paper, and nanoporous ceramic membranes, was evaluated under different conditions. We conducted experiments in both controlled and outdoor settings, simulating seawater with a 3.5 wt % NaCl solution. With a water yield of 1.51 kg m-2 h-1 under standard solar conditions (one sun), the BISO system maintained excellent salt removal and accumulation resistance after up to 8 h of experiments and demonstrated great cavitation resistance even at 58.14 °C. The outdoor test recorded a peak rate of 1.22 kg m-2 h-1 and collected 16.5 mL in 8 h, showing its practical application potential. These results highlight the BISO device's capability to address water scarcity using a sustainable approach, combining bioinspired design with solar power, presenting a viable pathway in renewable-energy-driven desalination technology.

Engineering High Voltage Aqueous Aluminum-Ion Batteries.

The energy transition to renewables necessitates innovative storage solutions beyond the capacities of lithium-ion batteries. Aluminum-ion batteries (AIBs), particularly their aqueous variants (AAIBs), have emerged as potential successors due to their abundant resources, electrochemical advantages, and eco-friendliness. However, they grapple with achieving their theoretical voltage potential, often yielding less than expected. This perspective article provides a comprehensive examination of the voltage challenges faced by AAIBs, attributing gaps to factors such as the aluminum reduction potential, hydrogen evolution reaction, and aluminum's inherent passivation. Through a critical exploration of methodologies, strategies, such as underpotential deposition, alloying, interface enhancements, tailored electrolyte compositions, and advanced cathode design, are proposed. This piece seeks to guide researchers in harnessing the full potential of AAIBs in the global energy storage landscape.

Artemisinin-naphthoquine plus lower-dose primaquine to treat and prevent recurrence of Plasmodium vivax malaria: an open-label randomized and non-inferiority trial.

BACKGROUND: Plasmodium vivax malaria, with the widest geographic distribution, can cause severe disease and death. Primaquine is the main licensed antimalarial drug that can kill hypnozoites. The dose-dependent acute haemolysis in individuals with glucose-6-phospate dehydrogenase (G6PD) deficiency is the main safety concern when using primaquine. The recommended treatment regimen for P. vivax malaria is chloroquine plus primaquine for 14 days (CQPQ14) in Myanmar. The study aimed to evaluate the therapeutic efficacy, safety and adherence for the regimen of artemisinin-naphthoquine plus primaquine for 3 days (ANPQ3) in patients with P. vivax infections compared to those with CQPQ14. METHODS: The patients in the ANPQ3 group were given fixed-dose artemisinin-naphthoquine (a total 24.5 mg/kg bodyweight) plus a lower total primaquine dose (0.9 mg/kg bodyweight) for 3 days. The patients in the CQPQ14 group were given a total chloroquine dose of 30 mg/kg body weight for 3 days plus a total primaquine dose of 4.2 mg/kg bodyweight for 14 days. All patients were followed up for 365 days. RESULTS: A total of 288 patients completed follow-up, 172 in the ANPQ3 group and 116 in the CQPQ14 group. The first recurrence patients were detected by day 58 in both groups. By day 182, 16 recurrences had been recorded: 12 (7.0%) patients in the ANPQ3 group and 4 (3.4%) in the CQPQ14 group. The difference in recurrence-free patients was 3.5 (-8.6 to 1.5) percentage points between ANPQ3 and CQPQ14 group (P = 0.2946). By day 365, the percentage of recurrence-free patients was not significant between the two groups (P = 0.2257). Mean fever and parasite clearance time of ANPQ3 group were shorter than those in CQPQ14 group (P ≤ 0.001). No severe adverse effect was observed in ANPQ3 group, but five (3.9%) patients had acute haemolysis in CQPQ14 group (P = 0.013). Medication percentage of ANPQ3 group was significantly higher than that of CQPQ14 group (P < 0.0001). CONCLUSIONS: Both ANPQ3 and CQPQ14 promised clinical cure efficacy, and the radical cure efficacy was similar between the ANPQ3 and CQPQ14 group. ANPQ3 clears fever and parasites faster than CQPQ14. ANPQ3 is safer and shows better patient adherence to the regimen for treatment of P. vivax malaria along the China-Myanmar border. TRIAL REGISTRATION: ChiCTR-INR-17012523. Registered 31 August 2017, https://www.chictr.org.cn/showproj.html?proj=21352.

Thermoelectric nanowires for dense 3D printed architectures.

The large-scale employment of 3D printed inorganic thermoelectrics is primarily constrained because of their lower efficiencies as compared to those fabricated from conventional methods such as spark plasma sintering and hot-pressing. This originates from the significant challenge in the densification of printed parts, particularly through the direct-ink-writing fabrication process, which demands a high binder content for printability. To achieve high-density printed thermoelectrics, the ink formulation process often involves the addition of substantial filler content and sintering aids, coupled with prolonged sintering periods. Here, we propose a strategy to resolve the low densification issue of 3D printed thermoelectrics through a binder-less and sintering aid-free thermoelectric nanowire ink system that can achieve dense thermoelectric structures (up to 82.5% theoretical density). The increase in density and corresponding enhancement of thermoelectric material efficiency are attained in a more tunable and controlled manner without compromising the material composition. A high filler-derived density index (FDI) of 2.51 is also achieved, implying the potential to obtain high-density parts with minimal filler content, thus unlocking a cascade of profound impacts. Crucially, this advancement enables the possibilities of anisotropic engineering in thermoelectric materials, thereby shattering the limitations that have hindered the widespread adoption of 3D printed inorganic thermoelectrics.

Synthesis and bioevaluation of Scutellarein-Tertramethylpyrazine hybrid molecules for the treatment of ischemic stroke.

Ischemic stroke caused by insufficient blood supply to the brain may produce a sequence of cascade reactions, leading to oxidative stress and ultimately inducing nerve cell damage. Therefore, hybrid molecules with multiple therapeutic effects have irreplaceable advantages for the treatment of ischemic stroke. Based on the previous works, two types of Scutellarein and Tertramethylpyrazine hybrid molecules were designed and synthesized according to the PepT 1-based design. After systematic research, all synthesized hybrid molecules exhibited more excellent neuroprotective effect and antiplatelet activity compared to the original drugs. Among them, the selected compound 1e with superior neuroprotective and antiplatelet effects could significantly enhance the permeability on the Caco-2 monolayer membrane and inhibit the Gly-Sar uptake on Caco-2 cells. Meanwhile, the result of intestinal perfusion has also confirmed that the absorption of the selected compound 1e is indeed increased. Further, the selected compound 1e significantly reduce the cerebral infarction volume of middle cerebral artery occlusion/reperfusion rats. Especially, the cerebral infarction volume of the high-dose 1e group reduced to one fourth of the model group. Meanwhile, results of hematoxylin-eosin staining also indicated that the damage in the hippocampus CA1 region was significantly alleviated after treatment with the compound 1e. Accordingly, molecular hybridization strategy is one of the simple and feasible ways to improve the therapeutic effect of single targeted drug.

Ultra-rapid lispro improved postprandial glucose control compared to insulin lispro in predominantly Chinese patients with type 1 diabetes: A prospective, randomized, double-blind phase 3 study.

AIMS: To investigate the efficacy and safety of ultra-rapid lispro (URLi) versus insulin lispro in predominantly Chinese patients with type 1 diabetes (T1D) in a prospective, randomized, double-blind, treat-to-target, phase 3 study. MATERIALS AND METHODS: Following a lead-in period, during which insulin glargine U-100 or insulin degludec U-100 was optimized, patients were randomly assigned (1:1) to URLi (n = 176) or insulin lispro (n = 178). The primary objective was to test the noninferiority of URLi to insulin lispro in glycaemic control (noninferiority margin = 0.4% for glycated haemoglobin [HbA1c] change from baseline to week 26), with testing for the superiority of URLi to insulin lispro with regard to 1- and 2-hour postprandial glucose (PPG) excursions during a mixed-meal tolerance test and HbA1c change at week 26 as the multiplicity-adjusted objectives. RESULTS: From baseline to week 26, HbA1c decreased by 0.21% and 0.28% with URLi and insulin lispro, respectively, with a least squares mean treatment difference of 0.07% (95% confidence interval -0.11 to 0.24; P = 0.467). URLi demonstrated smaller 1- and 2-hour PPG excursions at week 26 with least squares mean treatment differences of -1.0 mmol/L (-17.8 mg/dL) and -1.4 mmol/L (-25.5 mg/dL), respectively (p < 0.005 for both) versus insulin lispro. The safety profiles of URLi and insulin lispro were similar. CONCLUSIONS: In this study, URLi administered in a basal-bolus regimen demonstrated superiority to insulin lispro in controlling PPG excursions, with noninferiority of HbA1c control in predominantly Chinese patients with T1D.

Deep learning predicts cervical lymph node metastasis in clinically node-negative papillary thyroid carcinoma.

OBJECTIVES: Precise determination of cervical lymph node metastasis (CLNM) involvement in patients with early-stage thyroid cancer is fairly significant for identifying appropriate cervical treatment options. However, it is almost impossible to directly judge lymph node metastasis based on the imaging information of early-stage thyroid cancer patients with clinically negative lymph nodes. METHODS: Preoperative US images (BMUS and CDFI) of 1031 clinically node negative PTC patients definitively diagnosed on pathology from two independent hospitals were divided into training set, validation set, internal test set, and external test set. An ensemble deep learning model based on ResNet-50 was built integrating clinical variables, BMUS, and CDFI images using a bagging classifier to predict metastasis of CLN. The final ensemble model performance was compared with expert interpretation. RESULTS: The ensemble deep convolutional neural network (DCNN) achieved high performance in predicting CLNM in the test sets examined, with area under the curve values of 0.86 (95% CI 0.78-0.94) for the internal test set and 0.77 (95% CI 0.68-0.87) for the external test set. Compared to all radiologists averaged, the ensemble DCNN model also exhibited improved performance in making predictions. For the external validation set, accuracy was 0.72 versus 0.59 (p = 0.074), sensitivity was 0.75 versus 0.58 (p = 0.039), and specificity was 0.69 versus 0.60 (p = 0.078). CONCLUSIONS: Deep learning can non-invasive predict CLNM for clinically node-negative PTC using conventional US imaging of thyroid cancer nodules and clinical variables in a multi-institutional dataset with superior accuracy, sensitivity, and specificity comparable to experts. CRITICAL RELEVANCE STATEMENT: Deep learning efficiently predicts CLNM for clinically node-negative PTC based on US images and clinical variables in an advantageous manner. KEY POINTS: • A deep learning-based ensemble algorithm for predicting CLNM in PTC was developed. • Ultrasound AI analysis combined with clinical data has advantages in predicting CLNM. • Compared to all experts averaged, the DCNN model achieved higher test performance.

Targeting GDP-Dissociation Inhibitor Beta (GDI2) with a Benzo[a]quinolizidine Library to Induce Paraptosis for Cancer Therapy.

Inducing paraptosis, a nonapoptotic form of cell death, has great therapeutic potential in cancer therapy, especially for drug-resistant tumors. However, the specific molecular target(s) that trigger paraptosis have not yet been deciphered yet. Herein, by using activity-based protein profiling, we identified the GDP-dissociation inhibitor beta (GDI2) as a manipulable target for inducing paraptosis and uncovered benzo[a]quinolizidine BQZ-485 as a potent inhibitor of GDI2 through the interaction with Tyr245. Comprehensive target validation revealed that BQZ-485 disrupts the intrinsic GDI2-Rab1A interaction, thereby abolishing vesicular transport from the endoplasmic reticulum (ER) to the Golgi apparatus and initiating subsequent paraptosis events including ER dilation and fusion, ER stress, the unfolded protein response, and cytoplasmic vacuolization. Based on the structure of BQZ-485, we created a small benzo[a]quinolizidine library by click chemistry and discovered more potent GDI2 inhibitors using a NanoLuc-based screening platform. Leveraging the engagement of BQZ-485 with GDI2, we developed a selective GDI2 degrader. The optimized inhibitor (+)-37 and degrader 21 described in this study exhibited excellent in vivo antitumor activity in two GDI2-overexpressing pancreatic xenograft models, including an AsPc-1 solid tumor model and a transplanted human PDAC tumor model. Altogether, our findings provide a promising strategy for targeting GDI2 for paraptosis in the treatment of pancreatic cancers, and these lead compounds could be further optimized to be effective chemotherapeutics.

N-Type Thermoelectric AgBiPbS3 with Nanoprecipitates and Low Thermal Conductivity.

Thermoelectric sulfide materials are of particular interest due to the earth-abundant and cost-effective nature of sulfur. Here, we report a new n-type degenerate semiconductor sulfide, AgBiPbS3, which adopts a Fm3̅m structure with a narrow band gap of ∼0.32 eV. Despite the homogeneous distribution of elements at the scale of micrometer, Ag2S nanoprecipitates with dimensions of several nanometers were detected throughout the matrix. AgBiPbS3 exhibits a low room-temperature lattice thermal conductivity of 0.88 W m-1 K-1, owing to the intrinsic low lattice thermal conductivity of Ag2S and the effective scattering of phonons at nanoprecipitate boundaries. Moreover, compared to AgBiS2, AgBiPbS3 demonstrates a significantly improved weighted mobility of >16 cm2 V-1 s-1 at 300 K, leading to an enhanced PF of 1.6 µW cm-1 K-2 at 300 K. The superior electrical transport in AgBiPbS3 can be attributed to the high valley degeneracy of the L point (the conduction band minimum), which is contributed by the Pb s and Pb p orbitals. Further, Ga doping is found to be effective in modulating the Fermi levels of AgBiPbS3, leading to further enhancement of PF with a PFave of 2.7 µW cm-1 K-2 in the temperature range of 300-823 K. Consequently, a relatively high ZTave of 0.22 and a peak ZT of ∼0.4 at 823 K have been achieved in 3% Ga-doped AgBiPbS3, highlighting the potential of AgBiPbS3 as an n-type thermoelectric sulfide.

Dihydroartemisinin-piperaquine efficacy in Plasmodium falciparum treatment and prevalence of drug-resistant molecular markers along China-Myanmar border in 2014-2023.

OBJECTIVES: The study aims to monitor dihydroartemisinin-piperaquine (DHA-PPQ) efficacy in Plasmodium falciparum and detect molecular markers associated with its resistance. METHODS: The World Health Organization's standard protocol for therapeutic efficacy studies (TES) was performed from 2014 to 2018; integrated drug efficacy surveillance (iDES) was performed from from 2019 to July 2023. Molecular markers were detected by polymerase chain reaction. The association between gene mutations and delayed parasite clearance was analysed by multivariate logistic regression analysis. RESULTS: A total of 226 P. falciparum patients were enrolled in the TES from 2014 to 2018, and 26 patients with P. falciparum from Africa were recruited in the iDES from 2019 to July 2023. The PCR-adjusted clinical and parasitological cure rate was 93.7% (95% CI: 92.6-99.5%) in the TES and 96.2% (95% CI: 80.4-99.9%) in the iDEs. Twelve mutants and an overall 55.0% prevalence of pfK13 mutations were detected. Of them, G533S, C447R, C447S, N458Y, C469Y, and A676D were first detected out along the China-Myanmar border. Referred to the wild strain, adjusted odds ratios of treatment failure for G533S, N458Y, and P574L by 42 days were 7.54 (95% CI: 1.605-45.86), 13.68 (95% CI: 1.95-130.72), and 89.00 (95% CI: 1.98-2482.1), respectively. CONCLUSION: The efficacy of DHA-PPQ from 2014 to 2018 declined in comparison with 2003 to 2013, but it is still effective for treatment of P. falciparum malaria. Results of the iDES indicate a risk of artemisinin resistance in Africa. G533S, N458Y, and P574L are associated with delayed parasite clearance and treatment failure.

Treatment-seeking behaviours of malaria patients versus non-malaria febrile patients along China-Myanmar border.

BACKGROUND: Appropriate malaria treatment-seeking behaviour (TSB) is critical for timely detecting malaria, prompt treatment, and prevention of onward transmission of the disease in a community. This study aimed to compare treatment-seeking behaviours between malaria patients and non-malaria febrile patients, and to analyse the factors associated with appropriate TSB along the China-Myanmar border. METHODS: A cross-sectional study was carried out to investigate the appropriate TSB of microscopy-confirmed malaria patients versus non-malaria febrile (NMF) patients. An unconditional logistic regression analysis (LRA) was used to identify factors associated with appropriate TSB. RESULTS: Among 223 malaria patients and 446 NMF patients, 129 (57.8%) of the malaria patients versus 163 (36.5%) of the NMF patients firstly sought treatment in health facilities without laboratory testing for malaria (P < 0.0001). A total of 85(38.1%) of the malaria patients versus 278 (62.3%) of the NMF patients had appropriate TSB, namely, seeking treatment in health facilities with laboratory testing for malaria within 48 h (P < 0.0001). Multivariate LRA identified that the malaria patients with Chinese nationality had less appropriate TSB compared to those with other nationalities (adjusted odds ratio [AOR]: 0.21, 95% confidence interval CI 0.07-0.68, P = 0.0097), and malaria patients residing in urban areas had more appropriate TSB compared to those living in rural areas (AOR: 2.16, 95%CI 1.06-4.39, P = 0.0337). CONCLUSIONS: TSB was not appropriate in malaria patients. Chinese citizenship and rural residence were two independent factors associated with inappropriate malaria TSB. It is urgently necessary to improve appropriate malaria TSB through effective campaigns of information, education, and communication for malaria control in Myanmar and preventing reestablishment of malaria transmission in Yunnan, China.

Three/Four-Dimensional Printed PLA Nano/Microstructures: Crystallization Principles and Practical Applications.

Compared to traditional methods, three/four-dimensional (3D/4D) printing technologies allow rapid prototyping and mass customization, which are ideal for preparing nano/microstructures of soft polymer materials. Poly (lactic acid) (PLA) is a biopolymer material widely used in additive manufacturing (AM) because of its biocompatibility and biodegradability. Unfortunately, owing to its intrinsically poor nucleation ability, a PLA product is usually in an amorphous state after industrial processing, leading to some undesirable properties such as a barrier property and low thermal resistance. Crystallization mediation offers a most practical way to improve the properties of PLA products. Herein, we summarize and discuss 3D/4D printing technologies in the processing of PLA nano/microstructures, focusing on crystallization principles and practical applications including bio-inspired structures, flexible electronics and biomedical engineering mainly reported in the last five years. Moreover, the challenges and prospects of 3D/4D printing technologies in the fabrication of high-performance PLA materials nano/microstructures will also be discussed.

UCA1 executes an oncogenic role in pancreatic cancer by regulating miR-582-5p/BRCC3.

Background: As a fatal disease, the mechanism of pancreatic cancer is unclear. Urothelial carcinoma antigen 1(UCA1), a long noncoding RNA (lncRNA) that was first reported in bladder cancer, acts as an oncogene. However, the regulatory role and mechanism of UCA1 in pancreatic cancer remain unknown. This study aims to investigate the expression level and prognostic value of UCA1 in pancreatic cancer tissues, the effects and mechanism of UCA1 in regulating cell proliferation, apoptosis and metastasis. Methods: UCA1 expression levels in tissues were detected by in situ hybridization (ISH) and the prognostic value was evaluated by univariate and multivariate survival analysis. For in vitro experiments, proliferation was evaluated by a cell count kit assay, Edu experiments, and a clone formation assay. Apoptosis was evaluated by fluorescence-activated cell sorting flow-cytometry. Cell migration and invasion capacities were detected by wound healing and transwell assays. Western blots were performed to detect apoptotic associated molecules and epithelial-mesenchymal transition (EMT) markers. For the in vivo experiment, subcutaneous transplantation models of pancreatic cancer in nude mice were established to observe the tumor growth. The regulatory mechanism of UCA1 was explored by proteomics, bioinformatic analysis, luciferase reporter assays, and rescue experiments. Results: ISH staining revealed that UCA1 levels between cancer tissues (n=94) and tumor-adjacent tissues (n=73) did not show significant differences. Survival analysis indicated that high expression of UCA1 was an unfavorable prognosis factor for pancreatic cancer. Downregulation of UCA1 by siRNA significantly inhibited cell proliferation, decreased the capacities of cell migration and invasion, induced cell apoptosis, and inhibited EMT. Furthermore, we demonstrated that UCA1 positively regulated the expression of BRCC3 by inhibiting miR-582-5p. Rescue experiments indicated that either inhibiting the expression of miR-582-5p or enhancing expression of BRCC3 could partly attenuate the antitumor effects of downregulation of UCA1. Conclusion: UCA1 acted as an oncogene in pancreatic cancer by partly regulating miR-582-5p/BRCC3, which could be a new therapeutic target for pancreatic cancer.

Protective effect of water extracts of Veronicastrum latifolium (Hemsl.) Yamazaki on carbon tetrachloride-induced liver fibrosis in mice and its effect on intestinal flora.

Liver fibrosis refers to a reversible event of repair and reconstruction following injury due to various etiologies, and its continuous development will lead to cirrhosis and liver cancer. Abnormal alterations in intestinal microbiota can hasten the development of hepatic fibrosis and damage. Veronicastrum latifolium (Hemsl.) Yamazaki (VLY) is a classic drug applied extensively for managing acute and chronic hepatitis, liver cirrhosis and ascites in ethnic minority areas of Guizhou Province, China, which possesses broad-spectrum pharmacological activities. In view of the crucial role of intestinal microbiota in the development of liver fibrosis, the present study attempted to investigate the effects of VLY aqueous extract on ameliorating CCl4-elicited liver fibrosis in mice and on intestinal microbiota and to explore its possible mechanism. Phytochemical analysis showed that VLY water extract contained a variety of components, particularly rich in organic acids and their derivatives, flavonoids, phenolic acids, nucleotides and their derivatives, carbohydrates and other compounds. VLY water extract remarkably alleviated CCl4-induced liver damage and fibrosis in mice, improved liver histology, and improved liver function abnormalities. VLY water extract also inhibited the activation of hepatic stellate cells and invasion of intrahepatic inflammatory cells. Additionally, sequencing the 16 s rDNA gene revealed that VLY water extract changed the intestinal microbiota composition in liver fibrotic mice. It elevated the Firmicutes/Bacteroidota ratio and enriched the relative Lactobacillus richness, which is capable of mitigating fibrosis and inflammation in impaired liver. In summary, through modulation of inflammation and intestinal microbiota, VLY water extract can reduce the CCl4-elicited liver fibrosis.

Downregulating NHE-1 decreases the apoptosis of hippocampal cells in epileptic model rats based on the NHE-1/calpain1 pathway.

Seizure is associated with pathological changes of hippocampus, but the mechanism by which hippocampal neuronal apoptosis promotes epilepsy is unclear. Our previous study showed that the expression of NHE-1 was increased in epileptic model rats. Therefore, this study further explores the effect of NHE-1 on hippocampal cells apoptosis and seizure in lithium chloride-pilocarpine epileptic model rats. First, we established a lithium chloride-pilocarpine induced epileptic rat model and detected the expression of NHE-1, calpain1 and apoptosis in the hippocampus. Then, we further down-regulated NHE-1 to observe the expression of calpain1 and apoptosis in the hippocampus, as well as its effect on seizures in rats. We found that the expression of NHE-1 and calpain1 and apoptosis in the hippocampus was significant increased in the model group. After down-regulating NHE-1, the expression of calpain1 was decreased, and hippocampal cell apoptosis was alleviated. In addition, down-regulation of NHE-1 reduced the frequency and duration of seizures in epileptic rats. Therefore, hippocampal NHE-1 overexpression is closely related to the development of neuronal apoptosis in a rat model of epilepsy, and downregulating NHE-1 expression can reduce cell apoptosis. Moreover, the NHE-1/calpain1 signaling pathway may be an important mechanism leading to hippocampal cell apoptosis.