The risk of endocrine immune-related adverse events induced by PD-1 inhibitors in cancer patients: a systematic review and meta-analysis.

Objective: Endocrinopathies are the most common immune-related adverse events (irAEs) observed during therapy with PD-1 inhibitors. In this study, we conducted a comprehensive systematic review and meta-analysis to evaluate the risk of immune-related endocrinopathies in patients treated with PD-1 inhibitors. Methods: We performed a systematic search in the PubMed, Embase, and Cochrane Library databases to retrieve all randomized controlled trials (RCTs) involving PD-1 inhibitors, spanning from their inception to November 24, 2023. The comparative analysis encompassed patients undergoing chemotherapy, targeted therapy, or receiving placebo as control treatments. This study protocol has been registered with PROSPERO (CRD42023488303). Results: A total of 48 clinical trials comprising 24,514 patients were included. Compared with control groups, patients treated with PD-1 inhibitors showed an increased risk of immune-related adverse events, including hypothyroidism, hyperthyroidism, hypophysitis, thyroiditis, diabetes mellitus, and adrenal insufficiency. Pembrolizumab was associated with an increased risk of all aforementioned endocrinopathies (hypothyroidism: RR=4.76, 95%CI: 3.55-6.39; hyperthyroidism: RR=9.69, 95%CI: 6.95-13.52; hypophysitis: RR=5.47, 95%CI: 2.73-10.97; thyroiditis: RR=5.95, 95%CI: 3.02-11.72; diabetes mellitus: RR=3.60, 95%CI: 1.65-7.88; adrenal insufficiency: RR=4.80, 95%CI: 2.60-8.88). Nivolumab was associated with an increased risk of hypothyroidism (RR=7.67, 95%CI: 5.00-11.75) and hyperthyroidism (RR=9.22, 95%CI: 4.71-18.04). Tislelizumab and sintilimab were associated with an increased risk of hypothyroidism (RR=19.07, 95%CI: 5.46-66.69 for tislelizumab and RR=18.36, 95%CI: 3.58-94.21 for sintilimab). For different tumor types, both hypothyroidism and hyperthyroidism were at high risks. Besides, patients with non-small cell lung cancer were at a higher risk of thyroiditis and adrenal insufficiency. Patients with melanoma were at a higher risk of hypophysitis and diabetes mellitus. Both low- and high-dose group increased risks of hypothyroidism and hyperthyroidism. Conclusion: Risk of endocrine irAEs may vary in different PD-1 inhibitors and different tumor types. Increased awareness and understanding of the risk features of endocrine irAEs associated with PD-1 inhibitors is critical for clinicians. Systematic review registration: crd.york.ac.uk/prospero, identifier PROSPERO (CRD42023488303).

Incidence, clinical features, and risk factors of hemocoagulase-induced hypofibrinogenemia: A retrospective real-world study.

The objective of this study was to explore the real-world incidence, severity, clinical features, and potential risk factors associated with hypofibrinogenemia induced by hemocoagulase. Based on Chinese Hospital Pharmacovigilance System, a retrospective case-control study was conducted, enrolling hospitalized patients who received hemocoagulase for the treatment or prevention of hemorrhage in Weifang People's Hospital in China from January 2021 to May 2022. Univariate and multivariate logistic regression was performed to analyze the potential risk factors. Out of 10,397 hospitalized patients who received hemocoagulase, 341 patients showed positive triggers, with 235 patients ultimately conformed as hemocoagulase-associated hypofibrinogenemia. The system positive alarm rate was 68.91%, and the overall incidence of hemocoagulase-induced hypofibrinogenemia was 2.26%, predominantly characterized by mild to moderate severity levels. The incidence varied among the 4 types of hemocoagulase, with the highest incidence observed in hemocoagulase Agkistrodon Halys Pallas at 4.59%. The incidence of hemocoagulase from Deinagkistrodon acutus, Bothrops Atrox and Adder were 0.97%, 0.44% and 0.12%, respectively. Multivariate logistic regression analysis revealed that age (odds ratios [OR] = 177.328, P < .001), source of snake venom (OR = 5.641, P < .05), albumin (OR = 2.487, P < .001), and cumulative dosage (OR = 1.106, P < .001) were independent risk factors. Increased risk of hemocoagulase-related hypofibrinogenemia may be associated with children, elderly patients, low albumin levels, high cumulative doses and hemocoagulase from Agkistrodon Halys Pallas. Early recognition and close drug monitoring for these high-risk patients are vital in clinical practice.

Effects of slow-release nitrogen and urea combined application on soil physicochemical properties and fungal community under total straw returning condition.

Under the system of full straw returning, the relationship between soil fungal community diversity and soil physiochemical properties, and the combined application of slow-release nitrogen and urea is unclear. To evaluate its effect and provide an effective strategy for sustainable agricultural production, a 2-year field positioning trial was conducted using maize as the research object. The experiment was designed with two factors: straw treatment(S) and nitrogen fertilizer treatment(N),Six experimental treatments were set up,S1N0,S1N1,S1N2,S1N3,S1N4,S0N2,respectively.Analysis of 54 soil samples revealed 15 fungal phyla and 49 fungal classes. The composition of fungal communities in each treatment was basically the same, but there were significant differences in species abundance. Under total straw returning conditions, the combined application of slow-release nitrogen fertilizer and normal nitrogen fertilizer significantly increased the relative abundance of Ascomycota. During the jointing stage, tasseling stage and maturity stage, S1N4, S1N3 and S1N2 increased by 25.76%, 22.97%, 20.74%; 25.11%, 30.02%, 23.64% and 22.47%, 28.14%, 22.71% respectively compared with S0N2.The relative abundance of Basidiomycota was significantly reduced. Alpha diversity analysis showed that the straw returning mode significantly increased the Shannon index and decreased the Simpson index, which was obvious in the jointing stage and tasseling stage. The principal coordinate analysis analysis results showed that the fungal communities formed different clusters in the horizontal and vertical directions at the three growth stages of corn jointing, tasseling and maturity. At the jointing stage and tasseling stage, the communities of the straw return treatment and the straw removal treatment were separated, and the community distribution of each treatment was not significantly different in the mature stage. Total straw returning combined with slow-release fertilizer significantly (P＜0.05) increased the soil organic carbon, nitrate nitrogen and ammonia nitrogen content in each growth period, and increased the soil total nitrogen and hydrolyzable nitrogen content (P＞0.05).After the straw was returned to the field, the combined application of slow-release nitrogen fertilizer and common urea had a significant impact on soil urease, catalase, and sucrase activities. Among them, the three enzyme activities were the highest in the S1N3 treatment at the jointing stage and maturity stage, and the S1N4 treatment at the tasseling stage had the highest enzyme activity. Fungal community composition is closely related to environmental factors. Soil organic carbon, urease and catalase are positively correlated with Ascomycota and negatively correlated with Basidiomycota.

An aqueous alkaline zinc-sulfur flow battery.

We demonstrate a rechargeable aqueous alkaline zinc-sulfur flow battery that comprises environmental materials zinc and sulfur as negative and positive active species. Meanwhile, a nickel-based electrode is also obtained by a two-step process to decrease the polarization of the sulfur redox reaction, thus greatly improving the voltage efficiency of the system from 32% to 78% at 10 mA cm-2.

Analysis of clinical characteristics and imagological features of the aortic dissection patients with negative D-dimer results.

Background: D-dimer (DD) is a vital biomarker to rule out the diagnosis of aortic dissection (AD). However, the DD level in some patients with AD is not high in clinical practice, which often leads to missed diagnosis; therefore, understanding the characteristics of patients with AD and negative DD is of great clinical value. Methods: From May 2015 to October 2020, 286 patients with AD who visited the first medical contact (FMC) within 24 h of symptom onset and were hospitalized in the Xiamen Cardiovascular Hospital of Xiamen University were enrolled in this study. Clinical characteristics and outcomes of patients were assessed. Results: Among them, 13 cases (approximately 4.5%) had negative DD results. Compared to patients with positive DD results, patients with negative DD results had significantly higher platelet counts and lower aortic dissection detection risk scores (ADD-RS). The imagological analysis showed that patients with AD and negative DD had lower extension scores and milder damage to the mesenteric artery and three branches of the aortic arch. Furthermore, the results of the multivariable analysis showed that white blood cell count (WBC) [odds ratio (OR): 1.379, P = 0.028], FMC (OR: 0.904, P = 0.028), and extension score (OR: 1.623, P = 0.046) were associated with negative DD result. Conclusions: Patients with AD and negative DD results had longer FMC and lower WBC. Imaging showed a smaller tear extension range and less damage to the mesenteric artery and three branches of the aortic arch. A negative DD result could not completely rule out AD even if the ADD-RS was zero.

A Bi-Co Corridor Construction Effectively Improving the Selectivity of Electrocatalytic Nitrate Reduction toward Ammonia by Nearly 100.

Improving the selective ammonia production capacity of electrocatalytic nitrate reduction reaction (NO3 RR) at ambient conditions is critical to the future development and industrial application of electrosynthesis of ammonia. However, the reaction involves multi-proton and electron transfer as well as the desorption and underutilization of intermediates, posing a challenge to the selectivity of NO3 RR. Here the electrodeposition site of Co is modulated by depositing Bi at the bottom of the catalyst, thus obtaining the Co+Bi@Cu NW catalyst with a Bi-Co corridor structure. In 50 mm NO3 - , Co+Bi@Cu NW exhibits a highest Faraday efficiency of ≈100% (99.51%), an ammonia yield rate of 1858.2 µg h-1  cm-2 and high repeatability at -0.6 V versus the reversible hydrogen electrode. Moreover, the change of NO2 - concentration on the catalyst surface observed by in situ reflection absorption imaging and the intermediates of the NO3 RR process detected by electrochemical in situ Raman spectroscopy together verify the NO2 - trapping effect of the Bi-Co corridor structure. It is believed that the measure of modulating the deposition site of Co by loading Bi element is an easy-to-implement general method for improving the selectivity of NH3 production as well as the corresponding scientific research and applications.

Metal-organic frameworks modified melamine foam in pipette-tip for rapid solid-phase extraction of organophosphorus pesticides in fruits and vegetables.

In this work, metal-organic frameworks (MOFs) including Fe-MIL-101 and Ti-MIL-125 were prepared and fixed on the melamine foam (MF) by polyvinylidene fluoride (PVDF) to prepare MF/PVDF/MOFs, which was used as adsorbents in pipette-tip solid-phase extraction (PT-SPE) for rapid extraction of organophosphorus pesticides (OPPs). Then, a gas chromatograph-flame thermionic detector (GC-FTD) was used for simultaneous analysis of Dimethoate (DMT), Iprobenfos (IBF), Parathion-methyl (PAM), and Chlorpyrifos (CPF). The morphology, crystal structure, and functional groups of MF/PVDF/MOFs were characterized, indicating that Ti-MIL-125 and Fe-MIL-101 were successfully synthesized and distributed on MF. The Fe-MIL-101 and Ti-MIL-125 showed good extraction ability for OPPs, which was mainly due to the π-π interaction and the multiple porous structures. Under the optimal conditions, the limit of detection (LODs) of four OPPs was 0.03-0.14 µg L-1 and the RSDs were less than 9.9%. The developed PT-SPE method showed a short extraction time (<3 min). The recoveries in fruits and vegetables (Celery, cabbages, and oranges) ranged from 75.3%-118.8% (RSDs<9.6%). The prepared MF/PVDF/MOFs demonstrated the efficient extraction performance of OPPs, contributing to the rapid pretreatment of OPPs from food and the environment.

Optimizing the Spatial Density of Single Co Sites via Molecular Spacing for Facilitating Sustainable Water Oxidation.

Advances in single-atom (-site) catalysts (SACs) provide a new solution of atomic economy and accuracy for designing efficient electrocatalysts. In addition to a precise local coordination environment, controllable spatial active structure and tolerance under harsh operating conditions remain great challenges in the development of SACs. Here, we show a series of molecule-spaced SACs (msSACs) using different acid anhydrides to regulate the spatial density of discrete metal phthalocyanines with single Co sites, which significantly improve the effective active-site numbers and mass transfer, enabling one of the msSACs connected by pyromellitic dianhydride to exhibit an outstanding mass activity of (1.63 ± 0.01) × 105 A·g-1 and TOFbulk of 27.66 ± 1.59 s-1 at 1.58 V (vs RHE) and long-term durability at an ultrahigh current density of 2.0 A·cm-2 under industrial conditions for oxygen evolution reaction. This study demonstrates that the accessible spatial density of single atom sites can be another important parameter to enhance the overall performance of catalysts.

Deleterious synonymous mutation identification based on selective ensemble strategy.

Although previous studies have revealed that synonymous mutations contribute to various human diseases, distinguishing deleterious synonymous mutations from benign ones is still a challenge in medical genomics. Recently, computational tools have been introduced to predict the harmfulness of synonymous mutations. However, most of these computational tools rely on balanced training sets without considering abundant negative samples that could result in deficient performance. In this study, we propose a computational model that uses a selective ensemble to predict deleterious synonymous mutations (seDSM). We construct several candidate base classifiers for the ensemble using balanced training subsets randomly sampled from the imbalanced benchmark training sets. The diversity measures of the base classifiers are calculated by the pairwise diversity metrics, and the classifiers with the highest diversities are selected for integration using soft voting for synonymous mutation prediction. We also design two strategies for filling in missing values in the imbalanced dataset and constructing models using different pairwise diversity metrics. The experimental results show that a selective ensemble based on double fault with the ensemble strategy EKNNI for filling in missing values is the most effective scheme. Finally, using 40-dimensional biology features, we propose a novel model based on a selective ensemble for predicting deleterious synonymous mutations (seDSM). seDSM outperformed other state-of-the-art methods on the independent test sets according to multiple evaluation indicators, indicating that it has an outstanding predictive performance for deleterious synonymous mutations. We hope that seDSM will be useful for studying deleterious synonymous mutations and advancing our understanding of synonymous mutations. The source code of seDSM is freely accessible at https://github.com/xialab-ahu/seDSM.git.

Synthesis and in vitro anticancer evaluation of novel flavonoid-based amide derivatives as regulators of the PI3K/AKT signal pathway for TNBC treatment.

Aberrant activation of the PI3K/AKT pathway is considered in many malignant tumors and plays a crucial role in mediating malignancy progression, metastasis, and chemoresistance. Consequently, development of PI3K/AKT pathway targeted drugs is currently an attractive research field for tumor treatment. In this study, twenty-six flavonoid-based amide derivatives were synthesized and evaluated for their antiproliferation effects against seven cancer cell lines, including MDA-MB-231, MCF-7, HCC1937, A549, HepG2, GTL-16 and HeLa. Among them, compound 7t possessed the best specific cytotoxicity against triple negative breast cancer MDA-MB-231 cells with an IC50 value of 1.76 ± 0.91 µM and also presented inhibitory ability on clonal-formation, migration and invasion of MDA-MB-231 cells. Further cell-based mechanistic studies demonstrated that compound 7t caused cell cycle arrest of MDA-MB-231 cells at the G0/G1 phase and induced apoptosis. Meanwhile, the western blot assay revealed that compound 7t could down-regulate the expression of p-PI3K, p-AKT, and Bcl-2 and up-regulate the production of PTEN, Bax, and caspase-3. Molecular docking also showed a possible binding mode of 7t with PI3Kα. Together, compound 7t was eligible as a potential TNBC therapeutic candidate for further development.

Green Total Factor Productivity and Its Saving Effect on the Green Factor in China's Strategic Minerals Industry from 1998-2017.

Improving green total factor productivity (GTFP) is a fundamental solution to help the strategic mineral industry to achieve green and sustainable development. This study incorporates the dual negative externalities of resource depletion and environmental pollution into the GTFP measurement to capture the 'green' elements. By employing a truncated third-order (TTO) translog cost function and the feasible generalized least squares (FGLS) approach, we evaluate the GTFP growth performance and its components in China's strategic minerals industry from 1998 to 2017. Moreover, we explore the bias of technological progress toward the resource and environmental factors to grasp the green factor saving effects. The results show that: (1) during the sample period, the average GTFP growth rate of China's strategic minerals industry was 0.46%, but there were variances between mineral sectors. Nevertheless, after 2012, the GTFP of all mineral sectors experienced different degrees of decrease. (2) The main driver of adjustments in GTFP growth shifted from technological progress to changes in scale efficiency, with technological progress contributing less to GTFP growth. This is particularly evident in the metal and energy minerals sectors. (3) Green technological progress is biased toward saving environmental factor input but enhancing resource extraction. Therefore, the current development of China's strategic minerals industry falls into a non-sustainable mode of being environmentally friendly but not resource-saving.

Construction of Stomach Cancer Lesion Detection Combined with Drug Therapy Based on Artificial Intelligence.

The number of stomach cancer (SC) patients is increasing sharply every year, and gastroscope is a common method to check stomach-related diseases. A bulging lesion in the stomach is encountered during a gastroscopy. Due to the change in eating habits, the enhancement of health awareness, and the wide application of gastroscopy, the detection rate and cure rate of tumors have been significantly improved. This has certain clinical value for the early diagnosis and treatment of early SC. In this paper, based on the background of artificial intelligence, image segmentation technology is used to analyze and process the detection results of SC, so as to judge the effect of drug treatment. A total of 1408 gastric bulge lesions were investigated in 11023 patients during the one-year period 2019-2020. It also analyzed the age, lesion location, size, pathological type, and tumor detection results of 1408 patients. The experiment showed that among the 289 cases of submucosal bulging lesions, the detection rates of the young group, middle-aged group, and elderly group were 14.9% (43/289), 67.5% (195/289), and 17.6% (51/289), respectively. Among them, middle-aged people aged 41-65 have the highest detection rate. The incidence of gastric polyps was similar between different age groups. But with age, the rate of fundic gland polyps increases. The incidence of SC is not related to the age of the patient, but to its pathological type. The incidence of SC in middle-aged and elderly people is significantly higher than that in young people. SC is more common in the cardia, and gastrointestinal stromal tumors are most common with submucosal protrusion.

Chromosome-Scale Assembly of the Dendrobium nobile Genome Provides Insights Into the Molecular Mechanism of the Biosynthesis of the Medicinal Active Ingredient of Dendrobium.

Orchids constitute approximately 10% of flowering plant species. However, only about 10 orchid genomes have been published. Metabolites are the main way through which orchids respond to their environment. Dendrobium nobile, belonging to Dendrobium, the second largest genus in Orchidaceae, has high ornamental, medicinal, and ecological value. D. nobile is the source of many popular horticultural varieties. Among the Dendrobium species, D. nobile has the highest amount of dendrobine, which is regarded as one of the criteria for evaluating medicinal quality. Due to lack of data and analysis at the genomic level, the biosynthesis pathways of dendrobine and other related medicinal ingredients in D. nobile are unknown. In this paper, we report a chromosome-scale reference genome of D. nobile to facilitate the investigation of its genomic characteristics for comparison with other Dendrobium species. The assembled genome size of D. nobile was 1.19 Gb. Of the sequences, 99.45% were anchored to 19 chromosomes. Furthermore, we identified differences in gene number and gene expression patterns compared with two other Dendrobium species by integrating whole-genome sequencing and transcriptomic analysis [e.g., genes in the polysaccharide biosynthesis pathway and upstream of the alkaloid (dendrobine) biosynthesis pathway]. Differences in the TPS and CYP450 gene families were also found among orchid species. All the above differences might contribute to the species-specific medicinal ingredient biosynthesis pathways. The metabolic pathway-related analysis will provide further insight into orchid responses to the environment. Additionally, the reference genome will provide important insights for further molecular elucidation of the medicinal active ingredients of Dendrobium and enhance the understanding of orchid evolution.

Commutation Torque Ripple Reduction Strategy of Brushless DC Motor Drives Based on Boosting Voltage of DC-Link Small Capacitor.

Based on the brushless DC motor system with DC-link small capacitance powered by a single-phase AC power source, a boosting DC-link voltage strategy to reduce the commutation torque ripple of brushless DC motors is proposed in this paper. The control strategy utilizes the special topology of the motor system to boost the DC-link capacitor voltage in a specific zone during the non-commutation period. During the commutation period, the high voltage of the DC-link capacitor is released to meet the voltage requirement of the brushless DC motor during commutation. In order to reduce the commutation torque ripple and ensure the normal operation of the brushless DC motor, each rectifier cycle is divided into three zones according to the characteristics of the periodic change of the rectifier output voltage. Different operation modes are proposed for different zones. In DC-link capacitor boost voltage mode, the DC-link capacitor boosts the voltage to meet the voltage of the motor demand during the commutation period for achieving the purpose of reducing the commutation torque ripple. In this paper, the controller of the brushless DC motor system is designed and the experimental platform is built. The experimental results verified the correctness of the theoretical analysis and the feasibility of the proposed method.

Complete genome sequencing and comparative genome analysis of the extremely halophilic archaea, Haloterrigena daqingensis.

In the present study, we report the complete genome sequencing of Haloterrigena daqingensis species. The genome of H. daqingensis JX313T consisted of a circular chromosome with three plasmids. The genome size and G+C content were estimated to be 3835796 bp and 61.7%, respectively. A total of 4158 genes were predicted with six rRNAs and 45 tRNAs. Metabolic pathway analysis suggests that H. daqingensis JX313T codes for all the necessary genes responsible to sustain its life at saline environment. The pan-genome analysis suggests that the number of singleton-gene between H. daqingensis and other Haloterrigena species varied. The study not only helps us understand H. daqingensis strategy for dealing with high stress, but it also provides an overview of its genomic makeup.

Development and validation of a nomogram for steroid-resistance prediction in immune thrombocytopenia patients.

OBJECTIVES: Corticosteroid is first-line therapy in immune thrombocytopenia. However, nearly 30% of patients appear in steroid-resistance. Our research analyses the relevant indicators of patients and develops a risk prediction model to predict the poor response to steroid-therapy in ITP patients. METHODS: We collected data from 111 ITP patients admitted to Xiamen University Zhongshan Hospital from 2013 to 2019 as the training cohort and 65 ITP patients during 2019-2020 as the external validation cohort. Screening significant factors(P < 0.05) in univariate analysis, and further identified to be independent variables in multivariable logistic regression analysis. Incorporated the significant risk factors in and presented them with a nomogram based on independent risk predictors. The nomogram was assessed by receiver operating characteristics curves and decision curve analysis. RESULTS: We constructed a steroid-resistance prediction model based on the potential predictors including age, serum ferritin and expression of HBsAg. As a result, based on the area under the ROC curves, the training cohort (AUC: 0.718, 95% CI: 0.615-0.821) and the external validation cohort (AUC:0.799,95%CI:0.692-0.905), which displayed good discrimination. The decision curve showed that predicting the steroid-refractory risk in ITP patients using this nomogram with a range of the threshold probability between >16% and <70%. The nomogram appears good performance in predicting steroid-refractory ITP patients. CONCLUSION: Prediction model shows that elder patients with a high level of ferritin and positive expression of HBsAg may appear a high possibility of steroid-resistance. For these patients, TPO-RAs can be considered to help patients to get better treatment effects and develop a better health-related quality of life.

Curcumin in Combination With Omacetaxine Suppress Lymphoma Cell Growth, Migration, Invasion, and Angiogenesis via Inhibition of VEGF/Akt Signaling Pathway.

BACKGROUND: Both omacetaxine (HHT) and curcumin were shown to exhibit anti-proliferative effect on lymphoma cells. However, the role of combination of HHT with curcumin (HHT/curcumin combination) on lymphoma cells remains unclear. Thus, this study aimed to investigate the effect of HHT/curcumin combination on the proliferation, migration, and angiogenesis of lymphoma cells. METHODS: Cell counting kit-8 (CCK-8), Ki67 immunofluorescence and transwell assays were used to assess the viability, proliferation and migration of U937 and Raji cells respectively. In addition, tube formation assay was used to determine the effects of HHT/curcumin combination on angiogenesis in human umbilical vein endothelial cells (HUVECs). RESULTS: In this study, we found that HHT/curcumin combination significantly inhibited the proliferation, migration and invasion in U937 and Raji cells (all P < 0.01). In addition, combination treatment markedly inhibited the secreted levels of vascular endothelial growth factor (VEGF)-(A-D) (all P < 0.01) in Raji cells. Moreover, combination treatment exhibited anti-tumor effects in Raji cells, as shown by the decreased signals of phosphorylated VEGF receptor 2 (p-VEGFR2) and phosphorylated protein kinase B (p-Akt) (all P < 0.01). Meanwhile, combination treatment inhibited VEGFA levels (P < 0.01) in exosomes derived from Raji cells. Application of exosomes with downregulated VEGF to HUVECs notably inhibited proliferation, migration and tube formation of HUVECs, evidenced by the decreased signals of p-Akt, angiogenin-1, matrix metallopeptidase 2 (MMP2) and matrix metallopeptidase 9 (MMP9) (all P < 0.01). CONCLUSION: Our findings indicated that combination of HHT and curcumin could inhibit lymphoma cell growth and angiogenesis via inhibition of VEGF/Akt signaling pathway. These results suggested that HHT combined with curcumin might be regarded as a promising therapeutic approach for the treatment of lymphoma.

Integrated Design of Interlayer/Current-Collector: Heteronanowires Decorated Carbon Microtube Fabric for High-Loading and Lean-Electrolyte Lithium-Sulfur Batteries.

Low sulfur loading, high electrolyte/sulfur (E/S) ratio, and sluggish sulfur redox reaction are the main challenges that severely impede the practical application of lithium-sulfur batteries (LSBs). To address these problems, a self-standing hollow carbonized cotton cloth (CCC) decorated with TiO2 -TiN heteronanowires (CCC@TiO2 -TiN) is proposed to replace the traditional cathode. Concretely, one side of CCC@TiO2 -TiN serves as a current-collector to load sulfur (CCC@TiO2 -TiN/S), while the other side facing the separator acts as interlayer to inhibit shuttle effect. This advanced intergrated interlayer/current-collector cathode is endowed with excellent 3D electron/ion transportation, a strong confinement barrier, and vast sulfur loading sites. Moreover, the as-developed TiO2 -TiN heteronanowires work as in situ capture and catalysis sites for the reversible and accelerated sulfur redox reaction. Therefore, the intergrated cathode of CCC@TiO2 -TiN/S achieves an ultrahigh sulfur loading of 13 mg cm-2 and delivers a superb areal capacity of 9.09 mAh cm-2 under the ultralow E/S ratio of 4.6 µL mg-1 . This work provides a new model material to achieve high sulfur loading and lean-electrolyte toward the practical LSBs with high specific energy density.

Curcumin in combination with homoharringtonine suppresses lymphoma cell growth by inhibiting the TGF-ß/Smad3 signaling pathway.

Both homoharringtonine (HHT) and curcumin exhibit anti-proliferative effects on lymphoma cells, but the effects of combined HHT and curcumin treatment remain unclear. Here, we investigated the effects of HHT/curcumin combination on the proliferation, apoptosis, and invasion in lymphoma cells. CCK-8, flow cytometry, and transwell assays were used to assess proliferation, apoptosis, and invasion of U937 and Raji cells. p-Smad3, E-cadherin, and N-cadherin expression were also measured in Raji cells using Western blot assays. Combination of HHT and curcumin synergistically inhibited U937 and Raji cell proliferation and invasion. In addition, the combination treatment markedly increased apoptosis of Raji cells as evidenced by increased Bax, cleaved caspase 3, and cleaved caspase 9 expression. Meanwhile, the combination treatment promoted anti-tumor mechanisms in Raji cells as indicated by decreases in p-Smad3 and N-cadherin and increases in E-cadherin. In vivo experiments showed that the combination treatment suppressed tumor growth in a mouse Raji xenograft model. Our findings indicate that combination of HHT and curcumin inhibited lymphoma cell growth by downregulating the TGF-ß/Smad3 pathway. These results suggest that HHT combined with curcumin might be a promising therapeutic approach for the treatment of lymphoma.