High fatigue resistance in a titanium alloy via near-void-free 3D printing.

The advantage of 3D printing-that is, additive manufacturing (AM) of structural materials-has been severely compromised by their disappointing fatigue properties1,2. Commonly, poor fatigue properties appear to result from the presence of microvoids induced by current printing process procedures3,4. Accordingly, the question that we pose is whether the elimination of such microvoids can provide a feasible solution for marked enhancement of the fatigue resistance of void-free AM (Net-AM) alloys. Here we successfully rebuild an approximate void-free AM microstructure in Ti-6Al-4V titanium alloy by development of a Net-AM processing technique through an understanding of the asynchronism of phase transformation and grain growth. We identify the fatigue resistance of such AM microstructures and show that they lead to a high fatigue limit of around 1 GPa, exceeding the fatigue resistance of all AM and forged titanium alloys as well as that of other metallic materials. We confirm the high fatigue resistance of Net-AM microstructures and the potential advantages of AM processing in the production of structural components with maximum fatigue strength, which is beneficial for further application of AM technologies in engineering fields.

CAFs-secreted exosomal cricN4BP2L2 promoted colorectal cancer stemness and chemoresistance by interacting with EIF4A3.

Cancer-associated fibroblasts secreted exosomes (CAFs-exo) are important for tumor carcinogenesis and chemoresistance, but its underlying mechanism in colorectal cancer (CRC) has not yet been clarified. In this study, we investigated the regulatory mechanism of CAFs-exo cricN4BP2L2 on the proliferation, apoptosis, stemness and chemoresistance of LoVo cells. We found that CAFs-exo promoted the oxaliplatin resistance and stemness of LoVo cells, while inhibited the LoVo cell apoptosis. Moreover, knockdown of cricN4BP2L2 in CAFs-exo inhibited the oxaliplatin resistance and stemness characteristics of LoVo cells. Mechanistically, cricN4BP2L2 regulated PI3K/AKT/mTOR axis by binding to EIF4A3. Rescue experiments proved that CAFs-derived exosomal cricN4BP2L2 promoted CRC cells stemness and oxaliplatin resistance by upregulating EIF4A3. Moreover, in vivo experiments showed that depletion of cricN4BP2L2 suppressed CRC tumorigenesis growth. In conclusion, CAFs-exo cricN4BP2L2 promoted the CRC cells stemness and oxaliplatin resistance through EIF4A3/PI3K/AKT/mTOR pathway.

Utilizing network pharmacological analysis to investigate the key targets and mechanisms of kaempferol against oxaliplatin-induced neurotoxicity.

This study investigated the pharmacological mechanism of kaempferol in the treatment of oxaliplatin-induced neuropathic pain by network pharmacological method and cells experiment. The kaempferol and disease target genes were obtained from several databases, including TCMSP, SwissTargetPrediction, GeneCards, and CTD. Then, the common target genes of drugs and diseases were obtained using Venny online tools. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analyses were carried out to obtain the enriched molecular pathways associated with the kaempferol and disease. Finally, we constructed a neuropathic pain cell experiment to confirm the findings. 138 intersection targets were identified between targets of kaempferol and oxaliplatin-induced neurotoxicity. Enrichment analyses revealed that the IL-17 signaling pathway was associated with the therapeutic effects of kaempferol. Kaempferol down-regulated the mRNA expression levels of TNF-α, IL-6, and CCL2 in oxaliplatin-treated astrocytes. Our findings showed that kaempferol alleviated oxaliplatin-induced neurotoxicity via regulation of inflammation-related genes.

S1P induces proliferation of pulmonary artery smooth muscle cells by promoting YAP-induced Notch3 expression and activation.

Sphingosine-1-phosphate (S1P), a natural multifunctional phospholipid, is highly increased in plasma from patients with pulmonary arterial hypertension and mediates proliferation of pulmonary artery smooth muscle cells (PASMCs) by activating the Notch3 signaling pathway. However, the mechanisms underpinning S1P-mediated induction of PASMCs proliferation remain unclear. In this study, using biochemical and molecular biology approaches, RNA interference and gene expression analyses, 5'-ethynyl-2'-deoxyuridine incorporation assay, and 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay, we demonstrated that S1P promoted the activation of signal transducers and activators of transcription 3 (STAT3) through sphingosine-1-phosphate receptor 2 (S1PR2), and subsequently upregulated the expression of the microRNA miR-135b, which further reduced the expression of E3 ubiquitin ligase ß-transduction repeat-containing protein and led to a reduction in yes-associated protein (YAP) ubiquitinated degradation in PASMCs. YAP is the core effector of the Hippo pathway and mediates the expression of particular genes. The accumulation of YAP further increased the expression and activation of Notch3 and ultimately promoted the proliferation of PASMCs. In addition, we showed that preblocking S1PR2, prior silencing of STAT3, miR-135b, or YAP, and prior inhibition of Notch3 all attenuated S1P-induced PASMCs proliferation. Taken together, our study indicates that S1P stimulates PASMCs proliferation by activation of the S1PR2/STAT3/miR-135b/ß-transduction repeat-containing protein/YAP/Notch3 pathway, and our data suggest that targeting this cascade might have potential value in ameliorating PASMCs hyperproliferation and benefit pulmonary arterial hypertension.

Substance P modulates BMSCs migration for tissue repair through NK-1R/CXCR4/p-Akt signal activation.

BACKGROUND: The migration of bone marrow-derived mesenchymal stem cells (BMSCs) to the wound site played an important role in tissue repair. Substance P (SP) has been studied and reported to be involved in tissue repair by promoting the growth of endothelial cells and the migration of BMSCs. However, the complicated process and the molecular mechanisms were not fully understood. Thus, we aimed to investigate the effect of SP-induced BMSCs migration on tissue repair and its possible mechanism. METHODS AND RESULTS: Western blot and q-PCR assay revealed that SP could induce the BMSCs migration through overexpression of CXCR4 and upregulation of Akt phosphorylation. And the upregulation was related to the activation of neurokinin-1 receptor (NK-1R). Besides, we found that the increased phosphorylation Akt caused by SP could be canceled by the inhibition of CXCR4 both in vitro and in vivo. Furthermore, a skin-injury animal model was established and used to observe the tissue repair process. Results showed that SP could accelerate wound closure, gain more granulation tissue accumulation, and more collagen deposition through the promotion of angiogenesis and induction of the BMSCs migration to the wound site. And these effects could be impaired by inhibition of CXCR4 and p-Akt. CONCLUSIONS: Our results suggested that SP promoted tissue repair through BMSCs migration via upregulation of CXCR4 and p-Akt. The expression of CXCR4 and p-Akt were regulated by NK-1R activation. These findings add more evidence in understanding the mechanisms of SP-induced BMSCs migration and highlight the potential for clinical implementation of SP in tissue repair.

Effectiveness of eHealth Self-management Interventions in Patients With Heart Failure: Systematic Review and Meta-analysis.

BACKGROUND: Heart failure (HF) is a common clinical syndrome associated with substantial morbidity, a heavy economic burden, and high risk of readmission. eHealth self-management interventions may be an effective way to improve HF clinical outcomes. OBJECTIVE: The aim of this study was to systematically review the evidence for the effectiveness of eHealth self-management in patients with HF. METHODS: This study included only randomized controlled trials (RCTs) that compared the effects of eHealth interventions with usual care in adult patients with HF using searches of the EMBASE, PubMed, CENTRAL (Cochrane Central Register of Controlled Trials), and CINAHL databases from January 1, 2011, to July 12, 2022. The Cochrane Risk of Bias tool (RoB 2) was used to assess the risk of bias for each study. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria were used to rate the certainty of the evidence for each outcome of interest. Meta-analyses were performed using Review Manager (RevMan v.5.4) and R (v.4.1.0 x64) software. RESULTS: In total, 24 RCTs with 9634 participants met the inclusion criteria. Compared with the usual-care group, eHealth self-management interventions could significantly reduce all-cause mortality (odds ratio [OR] 0.83, 95% CI 0.71-0.98, P=.03; GRADE: low quality) and cardiovascular mortality (OR 0.74, 95% CI 0.59-0.92, P=.008; GRADE: moderate quality), as well as all-cause readmissions (OR 0.82, 95% CI 0.73-0.93, P=.002; GRADE: low quality) and HF-related readmissions (OR 0.77, 95% CI 0.66-0.90, P<.001; GRADE: moderate quality). The meta-analyses also showed that eHealth interventions could increase patients' knowledge of HF and improve their quality of life, but there were no statistically significant effects. However, eHealth interventions could significantly increase medication adherence (OR 1.82, 95% CI 1.42-2.34, P<.001; GRADE: low quality) and improve self-care behaviors (standardized mean difference -1.34, 95% CI -2.46 to -0.22, P=.02; GRADE: very low quality). A subgroup analysis of primary outcomes regarding the enrolled population setting found that eHealth interventions were more effective in patients with HF after discharge compared with those in the ambulatory clinic setting. CONCLUSIONS: eHealth self-management interventions could benefit the health of patients with HF in various ways. However, the clinical effects of eHealth interventions in patients with HF are affected by multiple aspects, and more high-quality studies are needed to demonstrate effectiveness.

Stepwise extraction of Fe, Al, Ca, and Zn: A green route to recycle raw electroplating sludge.

Electroplating sludge is a hazardous waste produced in large quantities in the electroplating industry during production. It is rich in heavy metal resources and can be recovered as value-added heavy metal products. To recover Zn in electroplating sludge, Fe/Al/Ca impurities were effectively removed as hematite, boehmite, and calcium sulfate, respectively, via a facile hydrothermal method with reduction of nitric acid by addition of glucose. After the sludge was dissolved in nitric acid, the generated solution contained 6.1 g/L of Zn, 2.2 g/L of Fe, 2.5 g/L of Al, and 2.9 g/L of Ca. First, approximately 100% Fe was extracted as hematite nanoparticles containing 94.6 wt% Fe2O3 after the solution was treated at 190 °C for 6 h. Second, when the temperature was elevated to 270 °C, nearly 99% Al was isolated as boehmite particles containing 95.2 wt% Al2O3. Third, more than 98% Ca was removed as anhydrite, which contained 95.9 wt% CaSO4, by adding sulfuric acid. During the steps, the total loss of Zn was less than 3%, and 5.75 g/L of residual Zn was recovered as zincite containing 92.2 wt% ZnO by adjusting the pH to 8. The dissolved Fe, Al, and Ca impurities were successfully removed as purified hematite, boehmite, and anhydrite, respectively, through the stepwise separation method by adjusting reaction temperatures and pH. The high content of Zn in the electroplating sludge was finally purified as zincite.

Effective recycling of Co and Sr from Co/Sr-bearing wastewater via an integrated Fe coagulation and hematite precipitation approach.

Flocculant overdose has been considered an inefficient technique for precipitating heavy metals from wastewater at low levels due to the high yield of hazardous waste sludge that should be treated properly before it can be disposed of safely in landfills. This problem was effectively solved in this study via a novel method that recycles sludge separately into high-purity hematite and heavy metal-bearing products. The wastewater, which contained 10.3 mg/L of Co and 4.8 mg/L of Sr, was coagulated by adding ferric salt to generate Co/Sr-bearing sludge. The sludge was dissolved in HNO3, followed by hydrothermal treatment with the addition of organic matter (e.g. methanol or isopropanol). Without the addition of organic matter, only 56.5% of total Fe was removed as irregular hematite particles, whilst Co/Sr remained unchanged in the acid. Over 99.5% of total Fe was eliminated as hematite nanoparticles with 97.7% Fe2O3 content, but more than 98% Co/Sr remained in the acid when methanol with a molar ratio (Mmethanol/MFe) of 5 was added. Nearly 100% Co was precipitated by adjusting the pH of the acid to 8 to generate Co hydroxide with 83.9% purity. Meanwhile, the residual Sr was further precipitated by adding Na2CO3 to generate SrCO3 with 96.8% purity. Isopropanol achieved total Fe removal similar to that of methanol. The optimal molar ratio (MIsopropanol/MFe) was 1, which corresponded to the removal of 98.7% total Fe. Methanol and isopropanol can react with NO3- in acid to reduce NO2- concentration and improve acid pH, promoting hydrolysis followed by the crystallisation of ferric Fe with hematite as the final product. This paper is the first report on an environment-friendly method for enriching Co/Sr without generating any waste.

Multivariate analysis of factors for failed continuous bladder irrigation in hemorrhagic cystitis patients after hematopoietic stem cell transplantation.

BACKGROUND: Continuous bladder irrigation (CBI) and proper adjustment of saline irrigation speed are important to avoid CBI failure in hemorrhagic cystitis (HC) patients after allogeneic hematopoietic stem cell transplantation (HSCT). Nevertheless, too fast irrigation speed could take away the patient's much heat, contribute to blood coagulopathy, and increase the nursing workload. Evaluation of risk for CBI failure remains an unmet clinical need. METHODS: The general information, clinical characteristics, and consultation records of HC patients in 1380 patients with hematopoietic stem cell transplantation in our center from 2017 to 2019 were analyzed retrospectively. The receiver operating characteristic (ROC) curve was used to calculate the cutoff point of the continuous variable, and multivariate logistic regression was used to analyze the risk factors affecting CBI failure in HC patients. RESULTS: The incidence of HC after HSCT was 23%. A total of 227 patients with HC above grade 2 were included. Univariate analysis showed that CRP, age, platelet counts, onset time after transplantation, albumin, and hemoglobin were associated with CBI failure in the short-term (P < 0.05). ROC curve and multivariate logistic regression analysis showed that CRP > 8.89 ng/ml (RR = 7.828, 95% CI 2.885-21.244), age < 14.5 years (RR = 9.940, 95% CI 3.219-30.697), and onset time of HC > 37d after transplantation (RR = 7.021, 95% CI 2.204-22.364), were independent risk factors for failure of CBI (P < 0.05). CONCLUSIONS: The study identified CRP > 8.89 ng/ml, age < 14.5 years, and onset time of HC after HSCT > 37d are independent factors for failure of CBI, which could be combined to allow stratification of HC after HSCT patients into low-, intermediate- and high-risk subgroups of CBI failure.

Clinical characteristics and predictors of permanent stoma in rectal cancer patients underwent anterior resections: the value of preoperative prognostic nutritional index.

OBJECTIVES: This study was aimed to investigate the correlation between preoperative prognostic nutritional index (PNI) and permanent stoma (PS) in patients with defunctioning stoma (DS) after anterior resections and, based on it, to reveal the clinical value of PNI on clinical strategies about the selection of stoma location. METHODS: A total of 281 consecutive rectal cancer patients who accepted anterior resection and DS in the National Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University from June 2008 to June 2018 were enrolled in this study. Receiver operating characteristic (ROC) curve for PNI was performed to discriminate PS. Univariate and multivariate analysis were conducted to identify the clinical characteristics and risk factors for PS. Specific reasons for patients with DS turned into PS were reviewed. RESULTS: ROC curve analysis defined PNI cutoff level of 45.85 corresponding to PS (area under the curve (AUC) = 0.71, 77% sensitivity, 56.9% specificity). Low PNI (OR = 3.23, P = 0.005), tumor crossing the peritoneal reflection (PR) (OR = 3.42, P = 0.003), postoperative distant metastasis (OR = 6.31, P < 0.001) were independently associated with PS. Besides, anastomotic complications (31.4%), poor oncological outcomes (35.3%), and personal preferences (33.3%) were the specific reasons for patients turning into PS. CONCLUSIONS: Preoperative PNI is an independent prognostic factor to predict PS in patients who underwent anterior resection and DS. Therefore, combined with other clinical characteristics and predictors, preoperative measurements of PNI could provide a significant support for clinical decision on patients prepared to accept anterior resection and DS.

Effective recycling of Cu from electroplating wastewater effluent via the combined Fenton oxidation and hydrometallurgy route.

Heavy metals, which commonly occur in complex forms, are difficult to remove in alkali electroplating wastewater effluent, and their resource recycling is rarely reported. Here, a Cu-bearing alkali wastewater effluent was effectively treated through Fenton oxidation, and the generated Fenton sludge was recycled into highly pure tenorite and hematite particles. The effluent contained 1.51 mg/L Cu and was subjected to Fenton oxidation, pH adjustment and coagulation. Amongst the three methods, Fenton oxidation showed superior efficiency to Cu removal, and the residual Cu in the effluent was 0.06 mg/L, thereby meeting the discharge standard for electroplating wastewater. However, Cu removal achieved less than 20% after pH adjustment and coagulation. Cu-bearing sludge, which was generated through the Fenton process, was dissolved in a mixture of hydrochloric and nitric acids. The dissolved solution contained 1.92 g/L Cu and 73.6 g/L Fe impurity. Impure Fe (67.4%) was removed as hematite aggregates after the solution was directly treated via a hydrometallurgy route, whilst 99.2% Cu was kept. When 0.5 mL of methanol was introduced to the hydrometallurgy system, nearly 100% Fe was removed as hematite nanoparticles with 94.8% purity, whilst more than 98% Cu was kept. The residual Cu was 1.88 g/L and precipitated as a tenorite block with a CuO content of 91.1% by adjusting the treated solution to pH 9. This study presented an environment-friendly method for enriching Cu from electroplating wastewater effluent without generating any waste.

LncRNA HOTAIR is a Prognostic Biomarker for the Proliferation and Chemoresistance of Colorectal Cancer via MiR-203a-3p-Mediated Wnt/ß-Catenin Signaling Pathway.

BACKGROUND/AIMS: HOX transcript antisense RNA (HOTAIR) plays a vital role in carcinogenesis. However, its functional and regulatory roles remain unclear. In this study, we aimed to investigate its biological function and clinical significance in human colorectal cancer (CRC). METHODS: We examined the expression levels of lncRNA HOTAIR and miR-203a-3p in CRC tissues and CRC cell lines by qRT-PCR. Gain and loss-of-function assays were performed to examine the effects of HOTAIR and miR-203a-3p on the proliferation and chemoresistance of CRC cells. The possible mechanisms of HOTAIR were also explored by fluorescence reporter assay and Western blot. RESULTS: The expressions of HOTAIR were upregulated in CRC tissue tissues compared to adjacent control tissues. We also found HOTAIR was downregulated by miR-203a-3p in CRC cell lines. Both HOTAIR knockdown and miR-203a-3p overexpression in CRC cell lines led to inhibited cell proliferation and reduced chemoresistance. We also determined that ß-catenin and GRG5 were inhibitory targets of miR-203a-3p, and that Wnt/ß-catenin signaling was inhibited by both HOTAIR knockdown and miR-203a-3p overexpression. Significantly, we found that increased expression of miR-203a-3p is essential for cell proliferation repression, chemoresistance reduction, and Wnt/ß-catenin signaling inhibition induced by HOTAIR knockdown. CONCLUSIONS: Our study demonstrated that the lncRNA HOTAIR could regulate the progression and chemoresistance of CRC via modulating the expression levels of miR-203a-3p and the activity of Wnt/ß-catenin signaling pathway.

Resveratrol enhances anticancer effects of paclitaxel in HepG2 human liver cancer cells.

BACKGROUND: The aim of this in vitro study was to measure the enhanced anticancer effects of Res (resveratrol) on PA (paclitaxel) in HepG2 human liver cancer cells. METHODS: The MTT (thiazolyl blue tetrazolium bromide, 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide), flow cytometry, qPCR (real-time quantitative polymerase chain reaction) and western blot assay were used for cells growth inhibitory effects, cells apoptosis (DNA content of sub-G1), mRNA and protein expressions, respectively. RESULTS: The 10 µg/mL of Res had no growth inhibitory effect on Nthy-ori 3-1 normal cells or HepG2 cancer cells meanwhile the 5 or 10 µg/mL of PA also had no growth inhibitory effect on Nthy-ori 3-1 normal cells. Where as PA-L (5 µg/mL) and PA-H (10 µg/mL) had the growth inhibitory effects in HepG2 cancer cells, and Res increase these growth inhibitory effects. By flow cytometry experiment, after Res (5 µg/mL) + PA-H (10 µg/mL) treatment, the HepG2 cells showed the most apoptosis in cells as compared to other treatments groups, and after additionally treated with Res, both the apoptosis cells of two concentrations PA were raised. As PA raised it also raised the mRNA and protein expressions of caspase-3, caspase-8, caspase-9, Bax (Bcl-2 assaciated X protein), p53, p21, IκB-α (inhibitor of NF-κB alpha), Fas (factor associated suicide), FasL (factor associated suicide ligand), TIMP-1 (tissue inhibitor of metalloproteinases 1), TIMP-2 (tissue inhibitor of metalloproteinases 2) and decrease Bcl-2 (B cell leukemia 2), Bcl-xL (B cell leukemia extra large), HIAP-1 (cIAP-1, cellular inhibitor of apoptosis 1), HIAP-2 (cIAP-2, cellular inhibitor of apoptosis 2), NF-κB (nuclear factor kappa B), COX-2 (cyclooxygenase 2), iNOS (inducible nitric oxide synthase), MMP-2 (metalloproteinase 2), MMP-9 (metalloproteinase 9), EGF (epidermal growth factor), EGFR (epidermal growth factor receptor), VEGF (vascular endothelial growth factor), Fit-1 (VEGFR-1, vascular endothelial growth factor receptor 1). Meanwhile, the 5 µg/mL of Res could enhance these mRNA expressions changes as compared to the control cells. CONCLUSION: From these results, we can conclude that Res could raise the anticancer effects of PA in HepG2 cells, Res could be used as a good sensitizing agent for PA.

Autophagy prevention sensitizes AKTi-1/2-induced anti-hepatocellular carcinoma cell activity in vitro and in vivo.

Molecule-targeted therapy has become the research focus for hepatocellular carcinoma (HCC). Persistent PI3K-AKT activation is often detected in HCC, representing a valuable oncotarget for treatment. Here, we tested the anti-HCC activity by a potent AKT inhibitor: AKT inhibitor 1/2 (AKTi-1/2). In both established (HepG2 and Huh-7) and primary human HCC cells, treatment with AKTi-1/2 inhibited cell survival and proliferation, but induced cell apoptosis. AKTi-1/2 blocked AKT-mTOR activation, yet simultaneously provoked cytoprotective autophagy in HCC cells. The latter was evidenced by ATG-5 and Beclin-1 upregulation, p62 downregulation as well as LC3B-GFP puncta formation. Autophagy inhibition, via pharmacological inhibitors (3-methyladenine, ammonium chloride, and bafilomycin A1) or Beclin-1 siRNA knockdown, significantly potentiated AKTi-1/2-induced HepG2 cell death and apoptosis. In nude mice, AKTi-1/2 intraperitoneal injection inhibited HepG2 tumor growth. Significantly, its anti-tumor activity in vivo was further sensitized when combined with Beclin-1 shRNA knockdown in HepG2 tumors. Together, these results demonstrate that autophagy activation serves as a main resistance factor of AKTi-1/2 in HCC cells. Autophagy prevention therefore sensitizes AKTi-1/2-induced anti-HCC activity in vitro and in vivo.

Efficacy of e-health interventions for smoking cessation management in smokers: a systematic review and meta-analysis.

Background: Smoking is one of the major risk factors for shortened lifespan and disability, while smoking cessation is currently the only guaranteed method to reduce the harm caused by smoking. E-health is a field that utilizes information and communication technology to support the health status of its users. The emergence of this digital health approach has provided a new way of smoking cessation support for smokers seeking help, and an increasing number of researchers are attempting to use e-health for a wide range of effective smoking cessation interventions. We conducted a systematic review and meta-analysis of studies that used e-health as a smoking cessation support tool. Methods: This systematic review and meta-analysis searched the PubMed, Embase, and Cochrane Library databases until December 2022. The included studies were randomized controlled trials (RCTs) comparing the use of e-health interventions and traditional offline smoking cessation care interventions. The primary outcome of the studies was the point smoking cessation rate (7-day and 30-day), and the secondary outcome was sustained smoking cessation rates. Studies were excluded if there was no clear e-health intervention described or if standard-compliant cessation outcomes were not clearly reported. Fixed-effects meta-analysis and meta-regression analyses were performed on the included study data to evaluate the effectiveness of the interventions. The meta-analysis outcome was the risk ratio (RR) and a 95% confidence interval. The study was registered with PROSPERO, CRD42023388667. Findings: We collectively screened 2408 articles, and ultimately included 39 articles with a total of 17,351 eligible participants, of which 44 studies were included in the meta-analysis. The meta-analysis revealed that compared to traditional smoking cessation interventions, e-health interventions can increase point quit rates (RR 1.86, 95% CI 1.69-2.04) as well as sustained quit rates in the long-term (RR 1.79, 95% CI 1.60-2.00) among smokers. Subgroup analysis showed that text and telephone interventions in e-health significantly improved short-term quit rates for up to 7 days (RR 2.10, 95% CI 1.77-2.48). Website and app interventions also had a positive impact on improving short-term quit rates for up to 7 days (RR 1.74, 95% CI 1.56-1.94). The heterogeneity of the study results was low, demonstrating the significant smoking cessation advantages of e-health interventions. Interpretation: We have found that personalized e-health interventions can effectively help smokers quit smoking. The diverse remote intervention methods of e-health can provide more convenient options for further customization. Additionally, further follow-up research is needed to evaluate the sustained effectiveness of interventions on smokers' continuous abstinence over a longer period (greater than one year). In the future, e-health can further optimize smoking cessation strategies. Funding: No funding.

Molecular Engineering of Electrosprayed Hydrogel Microspheres to Achieve Synergistic Anti-Tumor Chemo-Immunotherapy with ACEA Cargo.

Molecular engineering of drug delivering platforms to provide collaborative biological effects with loaded drugs is of great medical significance. Herein, cannabinoid receptor 1 (CB1)- and reactive oxygen species (ROS)-targeting electrosprayed microspheres (MSs) are fabricated by loading with the CB1 agonist arachidonoyl 2'-chloroethylamide (ACEA) and producing ROS in a photoresponsive manner. The synergistic anti-tumor effects of ACEA and ROS released from the MSs are assessed. ACEA inhibits epidermal growth factor receptor signaling and altered tumor microenvironment (TME) by activating CB1 to induce tumor cell death. The MSs are composed of glycidyl methacrylate-conjugated xanthan gum (XGMA) and Fe3+, which form dual molecular networks based on a Fe3+-(COO-)3 network and a C═C addition reaction network. Interestingly, the Fe3+-(COO-)3 network can be disassembled instantly under the conditions of lactate sodium and ultraviolet exposure, and the disassembly is accompanied by massive ROS production, which directly injures tumor cells. Meanwhile, the transition of dual networks to a single network boosts the ACEA release. Together, the activities of the ACEA and MSs promote immunogenic tumor cell death and create a tumor-suppressive TME by increasing M1-like tumor-associated macrophages and CD8+ T cells. In summation, this study demonstrates strong prospects of improving anti-tumor effects of drug delivering platforms through molecular design.

A 2D carbon nitride-based electrochemical aptasensor with reverse amplification for highly sensitive detection of okadaic acid in shellfish.

Okadaic acid (OA) is one of the main virulence factors of diarrheal shellfish toxins (DSP). It is of great significance to detect OA with an accurate, specific and cost-effective technique in the fields of seafood safety and water quality control. In this work, an electrochemical aptasensor with reverse amplification was developed for the sensitive detection of OA. A two-dimensional graphite-phase nanomaterial (carbon nitride) modified with an anti-OA aptamer and thionine (Th) was immobilized onto the surface of the electrochemical electrode as the sensitive element to capture target OA molecules. ssDNA-modified carbon nitride was used as the reverse amplification element by hybridizing with non-OA linked aptamers. The preparation of the electrochemical aptasensor was well characterized by Scanning Electron Microscopy (SEM), zeta potential detection, UV-Vis absorption, Brunner-Emmet-Teller (BET) measurements, and electrochemical measurements. The quantitative assessment of OA was achieved by differential pulse voltammetry (DPV). Experimental results indicated that this aptasensor showed a concentration-dependent response to OA with a good detection performance including in terms of selectivity, repeatability, reproducibility, and stability. It exhibited 100-fold selectivity between OA and other toxins including dinophysistoxins (DTX), pectenotoxins (PTX), and yessotoxins (YTX). In addition, it showed a much wider quantification range, which is 10-13 M-10-10 M (0.080-80.50 pg mL-1). The detection limit was as low as 10-13 M (0.080 pg mL-1). The aptasensor also successfully achieved significant practicality on real shellfish samples contaminated by OA. All these results demonstrated that the reverse amplification strategy for marine toxin detection may provide a label-free and rapid detection approach for portable applications in the fields of environmental monitoring and food security.

Lipid safety of tenofovir alafenamide during 96-week treatment in treatment-naive chronic hepatitis B patients.

Background: This study was aimed at investigating the dynamics of lipids and the effect of TAF on the lipid profile of patients including fatty liver disease in CHB patients. Methods: The data of TC, LDL-c, HDL-c, TG, and TC/HDL ratio were collected at baseline, 24 weeks, 48 weeks, 72 weeks, and 96 weeks. CHB patients with fatty liver at baseline were further analyzed in a subgroup. Results: A total of 137 CHB patients treated with TAF were enrolled in this study. During 96 weeks of TAF treatment, there was no significant change in TC, LDL-c, HDL-c, and TG level (P > 0.05). The TC/HDL-c ratio was increased with no significant change (+0.24, P > 0.05). In CHB patients with fatty liver (n = 48), TC, LDL-c, and TC/HDL-c ratio increased gradually during TAF treatment, TG levels increased to 146.63 mg/dL at 48 weeks (P = 0.057) and then decreased, but there was still no significant change compared with the baseline level by 96 weeks (P > 0.05). Conclusion: TAF treatment had a low effect on the lipid profile of CHB patients over the course of 96 weeks, and it was safe even in patients with fatty liver. Clinical trial registration: [https://www.chictr.org.cn/showproj.html?proj=65123], identifier [ChiCTR2000041005].

Performance of Corvis ST Parameters Including Updated Stress-Strain Index in Differentiating Between Normal, Forme-Fruste, Subclinical, and Clinical Keratoconic Eyes.

PURPOSE: This study seeks to evaluate the ability of the updated stress strain index (SSIv2) and other Corvis ST biomechanical parameters in distinguishing between keratoconus at different disease stages and normal eyes. DESIGN: Diagnostic accuracy analysis to distinguish disease stages. METHODS: 1084 eyes were included and divided into groups of normal (199 eyes), forme fruste keratoconus (FFKC, 194 eyes), subclinical keratoconus (SKC, 113 eyes), mild clinical keratoconus (CKC-Ⅰ, 175 eyes), moderate clinical keratoconus (CKC-Ⅱ, 204 eyes), and severe clinical keratoconus (CKC-Ⅲ, 199 eyes). Each eye was subjected to a Corvis ST examination to determine the central corneal thickness (CCT), biomechanically corrected intraocular pressure (bIOP), SSIv2 (updated stress-strain index), and other 8 Corvis parameters including the stress-strain index (SSIv1), stiffness parameter at first applanation (SP-A1), first applanation time (A1T), Ambrósio relational thickness to the horizontal profile (ARTh), integrated inverse radius (IIR), maximum deformation amplitude (DAM), ratio between deformation amplitude at the apex and at 2 mm nasal and temporal (DARatio2), and Corvis biomechanical index (CBI). The sensitivity and specificity of these parameters in diagnosing keratoconus were analyzed through receiver operating characteristic curves. RESULTS: Before and after correction for CCT and bIOP, SSIv2 and ARTh were significantly higher and IIR and CBI were significantly lower in the normal group than in the FFKC group, SKC group and the 3 CKC groups (all P < .05). There were also significant correlations between the values of SSIv2, ARTh, IIR, CBI, and the CKC severity (all P < .05). AUC of SSIv2 was significantly higher than all other Corvis parameters in distinguishing normal eyes from FFKC, followed by IIR, ARTh and CBI. CONCLUSION: Corvis ST's updated stress-strain index, SSIv2, demonstrated superior performance in differentiating between normal and keratoconic corneas, and between corneas with different keratoconus stages. Similar, but less pronounced, performance was demonstrated by the IIR, ARTh and CBI.