An eco-friendly porous hydrogel adsorbent based on dextran/phosphate/amino for efficient removal of Be(II) from aqueous solution.

A novel environmentally-friendly porous hydrogel adsorbent (GHPN) is firstly designed and prepared using dextran, phosphate, and calcium hydroxide for the adsorption of Be(II). GHPN shows good adsorption selectivity for Be(II) (Kd = 1.53 × 104 mL/g). According the adsorption kinetics and thermodynamics, the theoretical adsorption capacity of GHPN to Be(II) is 43.75 mg/g (35 °C, pH = 6.5), indicating a spontaneous exothermic reaction. After being reused for 5 cycles, the adsorption and desorption efficiencies of Be(II) with GHPN are obtained to be more than 80 %, showing acceptable recycling performance. Both of the characterizations and theoretical calculations indicate that the phosphate group, hydroxyl group, and amino group own the affinity to form stable complexes with Be(II). Benefiting from the introduction of phosphate and amino, the adsorption effect of the hydrogel adsorbent on Be(II) can be greatly improved, and surface precipitation, complexation, and ligand exchange are the dominant mechanisms of beryllium adsorption. The results suggest that GHPN has great potential to be utilized as an eco-friendly and useful adsorbent of Be(II) from aqueous solution.

The Influence of Drug-Eluting Beads Transarterial Chemoembolization on Serum Levels of Soluble Programmed Cell Death Protein-1 in Advanced Hepatocellular Carcinoma Patients.

Aim: This study aims to explore the role of soluble programmed cell death protein 1 (sPD-1) in individuals with hepatocellular carcinoma (HCC) undergoing treatment with drug-eluting beads transarterial chemoembolization (D-TACE). Additionally, we aim to assess the potential utility of sPD-1 for determining the optimal timing for combining D-TACE with immune checkpoint inhibitors (ICIs). Materials and Methods: A total of 44 HCC patients eligible for D-TACE and 55 healthy volunteers were enrolled in this study. Three milliliters of peripheral venous blood from the patients were collected on the day before D-TACE and 3, 7, and 30 days after D-TACE, respectively, for the assay of sPD-1. The relationships between sPD-1 levels, clinical features, outcomes, and the fluctuation of sPD-1 during treatment were analyzed. Results: The initial sPD-1 levels in patients were found to be significantly higher than those in the control group. Although the initial sPD-1 levels displayed a decreasing trend with an increase in BCLC stage, no significant differences were observed among patients at different BCLC stages. The sPD-1 level on day 3 after D-TACE was similar to that on day 7 after D-TACE and significantly lower than the initial level. The sPD-1 level on day 30 after D-TACE was significantly higher than that on day 3 and day 7 after D-TACE and nearly returned to the initial level before D-TACE. Conclusion: The level of sPD-1 was found to be significantly elevated in patients with HCC. However, further research is deemed necessary to fully understand the role of sPD-1 as a potential biomarker in the initiation, progression, and prognosis of HCC. The decrease in sPD-1 following D-TACE suggests that immune effector cells might potentially be reduced, as well as immune function weakened, highlighting the need to avoid the prompt administration of ICIs after D-TACE.

Rigid tape dynamic fixation in conservative treatment of acute anterior talofibular ligament tear: A retrospective cohort study.

Objectives: This study aims to compare results of rigid tape (RT) dynamic fixation and static fixation in conservative treatment of acute anterior talofibular ligament (ATFL) tear. Patients and methods: Between September 2021 and December 2021, a total of 91 patients (41 males, 50 females, mean age: 28.5±6.5 years, range, 18 to 40 years) who were diagnosed with ATFL tear and underwent rigid tape (RT) or cast/brace rehabilitation protocol were retrospectively analyzed. The patients were divided into two groups as the RT group (n=36) and the control group (n=55). Follow-up (FU) was performed at six months. Outcomes included pain (Numerical Rating Scale [NRS]), ankle function (American Orthopaedic Foot & Ankle Society [AOFAS] hindfoot score), deviation of center of gravity (DCG), and symptoms after returning to sports. Results: The difference at each time point of pain, AOFAS, DCG and SRS between the two groups was statistically significant (p<0.05 for all). Only one patient at Week 12 in the RT group had pain in the lateral side of the ankle, while 36 patients at Week 12 and 21 patients (18 in the medial side) at FU had pain in the control group. Conclusion: Our study results suggest that RT dynamic fixation can accurately lock the ATFL function and may prevent pseudo-stability, so as to quickly repair injury, restore function, and return to sports earlier.

Porous durian shell biochar modified by KMnO4 (Mn-DSB) as a highly selective adsorbent for Be(II).

The mining of uranium-beryllium ores has resulted in substantial beryllium (Be) contamination. In this study, agricultural waste durian shells were utilized as raw materials to prepare biochar, which was further modified to enhance its adsorption capacity (Mn-DSB). The results effectively demonstrated Mn loading onto the DSB surface. Batch experiments were conducted to identify the optimal adsorption conditions of Mn-DSB for beryllium. At a temperature of 35 °C and pH 6, beryllium's maximum adsorption capacity (Qe) was 42.08 mg·g-1. The materials' internal structure was analyzed before and after adsorption via multiple techniques. Mn-DSB manifested potent selectivity towards beryllium in multicomponent mixed solutions, binary systems, and uranium-beryllium wastewater, as the beryllium removal rate exceeded 90%. The study investigated the recyclability of Mn-DSB and found that after five reuse cycles, the adsorption and desorption efficiencies were 90% and 85%, respectively. The strong ligand complexation (N-H, CO32-, -OH) and ion exchange mechanisms (with Mn7+ ions) of Mn-DSB explained its high adsorption capacity. Therefore, this study demonstrates the potential of Mn-DSB for treating uranium-beryllium tailing wastewater.

In Vivo Osteo-organoid Approach for Harvesting Therapeutic Hematopoietic Stem/Progenitor Cells.

Hematopoietic stem cell transplantation (HSCT) requires a sufficient number of therapeutic hematopoietic stem/progenitor cells (HSPCs). To identify an adequate source of HSPCs, we developed an in vivo osteo-organoid by implanting scaffolds loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) into an internal muscle pouch near the femur in mice. After 12 weeks of implantation, we retrieved the in vivo osteo-organoids and conducted flow cytometry analysis on HPSCs, revealing a significant presence of HSPC subsets within the in vivo osteo-organoids. We then established a sublethal model of hematopoietic/immune system injury in mice through radiation and performed hematopoietic stem cell transplantation (HSCT) by injecting the extracted osteo-organoid-derived cells into the peripheral blood of radiated mice. The effect of hematopoietic recovery was evaluated through hematological, peripheral blood chimerism, and solid organ chimerism analyses. The results confirmed that in vivo osteo-organoid-derived cells can rapidly and efficiently reconstruct damaged peripheral and solid immune organs in irradiated mice. This approach holds potential as an alternative source of HSPCs for HSCT, offering benefits to a larger number of patients.

Factors Affecting Selection of TraineE for Neurointervention (FASTEN).

BACKGROUND AND IMPORTANCE: Neurointervention is a very competitive specialty in the United States due to the limited number of training spots and the larger pool of applicants. The training standards are continuously updated to ensure solid training experiences. Factors affecting candidate(s) selection have not been fully established yet. Our study aims to investigate the factors influencing the selection process. METHODS: A 52-question survey was distributed to 93 program directors (PDs). The survey consisted of six categories: (a) Program characteristics, (b) Candidate demographics, (c) Educational credentials, (d) Personal traits, (e) Research and extracurricular activities, and (f) Overall final set of characteristics. The response rate was 59.1%. As per the programs' characteristics, neurosurgery was the most involved specialty in running the training programs (69%). Regarding demographics, the need for visa sponsorship held the greatest prominence with a mean score of 5.9 [standard deviation (SD) 2.9]. For the educational credentials, being a graduate from a neurosurgical residency and the institution where the candidate's residency training is/was scored the highest [5.4 (SD = 2.9), 5.4 (SD = 2.5), respectively]. Regarding the personal traits, assessment by faculty members achieved the highest score [8.9 (SD = 1)]. In terms of research/extracurricular activities, fluency in English had the highest score [7.2 (SD = 1.9)] followed by peer-reviewed/PubMed-indexed publications [6.4 (SD = 2.2)]. CONCLUSION: Our survey investigated the factors influencing the final decision when choosing the future neurointerventional trainee, including demographic, educational, research, and extracurricular activities, which might serve as valuable guidance for both applicants and programs to refine the selection process.

Polyvinyl alcohol/phytic acid/phosphorylated chitosan hydrogel electrode highly efficient electroadsorption of low concentration uranium from uranium tailings leachate.

In order to improve the removal rate of uranium and reduce the harm of radioactive pollution, a physically crosslinked polyvinyl alcohol/phosphorylated chitosan (PPP) hydrogel electrode was designed by freezing thawing method. The results show that PPP hydrogel has a good adsorption effect on uranium, and 200 mL of uranium tailings leachate is absorbed, and the treatment efficiency reaches 100 % within 15 min. PPP hydrogel can adapt to a wide range of pH conditions and exhibit excellent adsorption efficiency in the range of 3-9. At the same time, PPP hydrogel maintains an adsorption efficiency of over 85 % for 950 mg/L uranium solution. This lays the foundation for the practical application of PPP hydrogel. In addition, PPP hydrogel also exhibits good repeatability, after 7 cycles, the material still retains 95 % of its initial performance. The synergistic effect of various functional groups such as phosphate, hydroxyl, and ammonium in the material is the main mechanism of PPP's adsorption capacity for uranium. Furthermore, electrochemical adsorption method significantly enhances the adsorption performance of PPP hydrogel.

Preparation of novel polyvinyl alcohol-carbon nanotubes containing imidazolyl ionic liquid/chitosan hydrogel for highly efficient uranium extraction from seawater.

A novel polyvinyl alcohol-carbon nanotube containing an imidazolyl ionic liquid/chitosan composite hydrogel (termed CBCS) was prepared for highly selective uranium adsorption from seawater. The results show that CBCS has good adsorption properties for uranium within the pH range of 5.0-8.0. Kinetics and thermodynamics experiments show that the theoretical maximum adsorption capacity of CBCS to U(VI) is 496.049 mg/g (288 K, pH = 6.0), indicating a spontaneous exothermic reaction. Mechanism analysis shows that the hydroxyl group, amino group, and CN bond on the surface of CBCS directly participate in uranium adsorption and that the dense pores on the surface of CBCS play an important role in uranium adsorption. The competitive adsorption experiment shows that CBCS has excellent uranium adsorption selectivity. In addition, CBCS exhibits good reusability. After five adsorption-desorption cycles, the uranium adsorption rate of CBCS can still reach >98 %. Hence, CBCS has excellent potential for uranium extraction from seawater.

New prediction equations for knee isokinetic strength in young and middle-aged non-athletes.

BACKGROUND: This study aimed to develop alternative prediction equations to predict isokinetic muscle strength at 60°/s based on anthropometric characteristics, including body mass, height, age, and sex for young and middle-aged non-athlete populations. METHODS: Three hundred and thirty-two healthy non-athletic participants (174 females, 158 males) between 20 and 59 years underwent a 60°/s isokinetic knee joint concentric contraction test. Forty people were randomly selected for retesting to assess the reliability of the isokinetic instrument. Multivariate linear regression was used to establish extension peak torque (EPT) and flexion peak torque (FPT) prediction equations. Sixty extra participants were used individually to validate the prediction equations, and Bland Altman plots were constructed to assess the agreement of predicted values with actual measurements. RESULTS: The result demonstrated that the instrument we used has excellent reliability. The multivariable linear regression model showed that body mass, age, and sex were significant predictors of PT (EPT: Adjusted R2 = 0.804, p < 0.001; FPT: Adjusted R2 = 0.705, p < 0.001). Furthermore, the equations we established had higher prediction accuracy than those of Gross et al. and Harbo et al. CONCLUSION: The equations developed in this study provided relatively low bias, thus providing a more suitable reference value for the knee isokinetic strength of young and middle-aged non-athletes.

Selective, rapid extraction of uranium from aqueous solution by porous chitosan-phosphorylated chitosan-amidoxime macroporous resin composite and differential charge calculation.

Herein, a new porous chitosan-phosphorylated chitosan-amidoxime macroporous resin composite (PCAR) was designed and synthesized for the rapid and selective extraction of uranium resources from aqueous solution. This study showed that PCAR exhibited excellent adsorption toward uranium in a pH range of 5-9. The dynamic adsorption process aligned with the quasi-second-order kinetic model and corresponded to the chemical adsorption process. The maximum adsorption capacity was 561.28 mg·g-1 at pH 6 and 308 K. Mechanism analysis showed that the synergistic effect of the amidoxime group (-(NH2)C=N-OH), PO, and -NH2 on the PCAR surface improved the uranium adsorption performance. The differential charge density indicated that the amidoxime and phosphate groups provide lone-pair electrons for the adsorption of UO22+ and their synergistic effect improves the UO22+ adsorption performance of PCAR. The uranium distribution coefficients of PCAR and CAR are 4.6 and 2.4 times those of vanadium, respectively. These results indicate that phosphorylation can ameliorate the disadvantage of competitive vanadium adsorption of the amidoxime adsorbent. In addition, PCAR exhibits good reusability and stable adsorption capacity after five adsorption-desorption cycles. Hence, PCAR has excellent potential for uranium extraction from aqueous solution.

Smoking relapse reasons among current smokers with previous cessation experience in Shanghai: A cross-sectional study.

INTRODUCTION: Quitting smoking can lead to substantial health gains, even later in life. Many smokers who attempt to quit experience several relapses before achieving sustainable cessation. This study aims to ascertain the differences between quitters with short and long abstinence time and to explore relapse reasons among smokers with cessation experience in Shanghai. METHODS: From January to December 2022, 1745 current smokers were recruited in Minhang, Jiading, Qingpu and Songjiang districts of Shanghai. We used an electronic questionnaire to collect data. We implemented logistic regression for odds ratio (OR) and 95% confidence interval (CI) calculation to explore factors associated with long cessation time among smokers with cessation experience of ≥3 months, ≥6 months, and ≥12 months. RESULTS: Of the 1745 smokers included, 1452 (83.2%) were males, with an average age of 44.2 years, and 48.0% (838/1745) had cessation experience but relapsed. Logistic regression indicated that smokers aged ≥45 years had a longer cessation duration (adjusted odds ratio, AOR=3.10; 95% CI: 1.97-4.88). Moreover, longer cessation duration among smokers was positively associated with low education level of junior high or lower (AOR=2.30; 95% CI: 1.42-3.72) and senior high (AOR=2.19; 95% CI: 1.53-3.15), older age at first tobacco smoking (AOR=1.62; 95% CI: 1.1.16-2.25), but was negatively associated with longer smoking duration (AOR=0.67; 95% CI: 0.43-0.00) and higher smoking burden (AOR=0.44; 95% CI: 0.28-0.72). The main reasons for cessation relapse were social interaction needs (34.5%) and discomfort due to abstinence (29.1%). CONCLUSIONS: The relapse rate was high among smokers even after 12 months of abstinence. Smokers with older age, lower education level, shorter smoking duration and lower tobacco burden had longer cessation duration. Social interaction needs and withdrawal symptoms were the main relapse reasons. It is highly recommended that health bureaux consistently conduct tobacco control initiatives to spread awareness about the detrimental effects of tobacco smoke and the advantages of quitting smoking, even after achieving cessation.

Selective adsorption of uranium (VI) from wastewater using a UiO-66/calcium alginate/hydrothermal carbon composite material.

Uranium mining, smelting, and nuclear industries generate a considerable amount of wastewater containing uranium. To treat this wastewater effectively and inexpensively, a novel hydrogel material (cUiO-66/CA) was developed by co-immobilizing UiO-66 with calcium alginate and hydrothermal carbon. Batch tests were conducted to determine the optimal adsorption conditions for uranium using cUiO-66/CA, and the adsorption behavior was spontaneous and endothermic, confirming the quasi-second-order dynamics model and the Langmuir model. At a temperature of 308.15 K and pH = 4, the maximum adsorption capacity of uranium was 337.77 mg g-1. The surface appearance and interior structure of the material were analyzed using SEM, FTIR, XPS, BET, and XRD techniques. The results indicated two possible uranium adsorption processes of cUiO-66/CA: (1) Ca2+ and UO22+ ion exchange process and (2) coordination of uranyl ions with hydroxyl and carboxyl ions to form complexes. cUiO-66/CA exhibited strong selectivity for U (VI) in a multicomponent mixed solution and uranium-containing wastewater, with uranium removal rates of 99.03 % and 81.45 %, respectively. The hydrogel material demonstrated excellent acid resistance, and the uranium adsorption rate exceeded 98 % in the pH range of 3-8. Therefore, this study suggests that cUiO-66/CA has the potential to treat uranium-containing wastewater in a broad pH range.

Effect of mechanical-chemical modification on adsorption of beryllium by calcite.

The treatment of beryllium wastewater has become a major problem in industry. In this paper, CaCO3 is creatively proposed to treat beryllium-containing wastewater. Calcite was modified by an omnidirectional planetary ball mill by a mechanical-chemical method. The results show that the maximum adsorption capacity of CaCO3 for beryllium is up to 45 mg/g. The optimum treatment conditions were pH = 7 and the amount of adsorbent was 1 g/L, and the best removal rate was 99%. The concentration of beryllium in the CaCO3-treated solution is less than 5 µg/L, which meets the international emission standard. The results show that the surface co-precipitation reaction between CaCO3 and Be (II) mainly occurs. Two different precipitates are generated on the used-CaCO3 surface; one is the tightly connected Be (OH)2 precipitation, and the other is the loose Be2(OH)2CO3 precipitation. When the pH of the solution exceeds 5.5, Be2+ in the solution is first precipitated by Be (OH)2. After CaCO3 is added, CO32- will further react with Be3(OH)33+ to form Be2(OH)2CO3 precipitation. CaCO3 can be considered as an adsorbent with great potential to remove beryllium from industrial wastewater.

Meta-analysis of the efficacy and adverse drug reactions of adrenergic alpha-antagonists in treating children with ureteral calculi.

This meta-analysis investigated the efficacy and adverse drug reactions (ADRs) of three different adrenergic alpha-antagonists during the treatment of pediatric ureteral stones. Studies were retrieved from MEDLINE, EMBASE, and the Cochrane Controlled Trial Registry until January 2022. We identified 7 articles, including six RCTs and one cohort study. 610 children received either adrenergic alpha-antagonists or placebo. The results confirmed that the three different adrenergic alpha-antagonists could significantly increase the ureteral calculi expulsive rate and shorten the ureteral calculi expulsive time, regardless of the size of the stone "<5 mm" or "5-10 mm". Subgroup analysis suggested that all three adrenergic alpha-antagonists increased the ureteral calculi expulsive rate. Tamsulosin and silodosin also have the effect of shortening ureteral calculi expulsive time, while doxazosin has an insignificant effect on ureteral calculi expulsive time. Besides, tamsulosin and silodosin obviously reduced the number of pain episodes caused by ureteral calculi in children. We analyzed the treatment-emergent adverse events (TEAEs) caused by the treatment of three different adrenergic alpha-antagonists to explore their ADRs. The probability of ADRs was increased after treatment with adrenergic alpha-antagonists. Further subgroup analysis revealed the application of tamsulosin was positively correlated with ADRs in children with ureteral calculi, while the application of doxazosin and silodosin had no statistically significant effect on the probability of TEAEs. In a conclusion, this article systematically analyzed the efficacy and ADRs of three different adrenergic alpha-antagonists, and provided reference and guidance for the application of adrenergic alpha-antagonists to treat children ureteral calculi.

Phosphorylation improved the competitive U/V adsorption on chitosan-based adsorbent containing amidoxime for rapid uranium extraction from seawater.

A novel chitosan-based porous composite adsorbent with multifunctional groups, such as phosphoric acid, amidoxime, and quaternary ammonium groups, was prepared to improve the adsorption rate and competitive uranium­vanadium adsorption of amidoxime group adsorbents. The maximum uranium adsorption capacity of PACNC was 962.226 mg g-1 at 308 K and pH = 7. The maximum adsorption rate constant of PACNC for uranium was 2.83E-2 g mg-1 min-1, which is 2.38 times that of ACNC (1.19E-2 g mg-1 min-1). Moreover, the adsorption equilibrium time was shortened from 300 (ACNC) to 50 (PACNC) min. In simulated and real seawater, the Kd and adsorption capacity of PACNC for uranium were approximately 8 and 6.62 times those for vanadium, respectively. These results suggest that phosphorylation significantly improved the competitive adsorption of uranium­vanadium and uranium adsorption rate. PACNC also exhibited good recycling performance and maintained stable adsorption capacity after five cycles. DFT calculations were used to analyze and calculate the possible co-complex structure of PACNC and uranium. The binding structure of phosphate and amidoxime is the most stable, and its synergistic effect effectively improves the competitive adsorption of uranium-vanadium of amidoxime. All the results demonstrated that PACNC has substantial application potential for uranium extraction from seawater.

Low expression of SLC34A1 is associated with poor prognosis in clear cell renal cell carcinoma.

OBJECTIVE: Clear cell renal cell carcinoma (ccRCC) is a malignant renal tumor that is highly prone to metastasis and recurrence. The exact pathogenesis of this cancer is still not well understood. This study aimed to identify novel hub genes in renal clear cell carcinoma and determine their diagnostic and prognostic value. METHODS: Intersection genes were obtained from multiple databases, and protein-protein interaction analysis and functional enrichment analysis were performed to identify key pathways related to the intersection genes. Hub genes were identified using the cytoHubba plugin in Cytoscape. GEPIA and UALCAN were utilized to observe differences in mRNA and protein expression of hub genes between KIRC and adjacent normal tissues. The Wilcoxon rank sum test was used to analyze hub gene levels between paired KIRC and matched non-cancer samples. IHC results were obtained from the HPA online database, and according to the median gene expression level, they were divided into a high-expression group and a low-expression group. The correlation of these groups with the prognosis of KIRC patients was analyzed. Logistic regression and the Wilcoxon rank sum test were used to test the relationship between SLC34A1 level and clinicopathological features. The diagnostic value of SLC34A1 was evaluated by drawing the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). Cox regression analysis was used to analyze the relationship between clinicopathological features, SLC34A1 expression, and KIRC survival rate. LinkedOmics was used to obtain the genes most related to SLC34A1 and their functional enrichment. Genetic mutations and methylation levels of SLC34A1 in KIRC were obtained from the cBioPortal website and the MethSurv website, respectively. RESULTS: Fifty-eight ccRCC differential genes were identified from six datasets, and they were mainly enriched in 10 functional items and 4 pathways. A total of 5 hub genes were identified. According to the GEPIA database analysis, low expression of SLC34A1, CASR, and ALDOB in tumors led to poor prognosis. Low expression of SLC34A1 mRNA was found to be related to clinicopathological features of patients. SLC34A1 expression in normal tissues could accurately identify tumors (AUC 0.776). SLC34A1 was also found to be an independent predictor of ccRCC in univariate and multivariate Cox analyses. The mutation rate of the SLC34A1 gene was 13%. Eight of the 10 DNA methylated CpG sites were associated with the prognosis of ccRCC. SLC34A1 expression in ccRCC was positively correlated with B cells, eosinophils, neutrophils, T cells, TFH, and Th17 cells, and negatively correlated with Tem, Tgd, and Th2 cells. CONCLUSION: The expression level of SLC34A1 in KIRC samples was found to be decreased, which predicted a decreased survival rate of KIRC. SLC34A1 may serve as a molecular prognostic marker and therapeutic target for KIRC patients.

Lysyl hydroxylase LH1 promotes confined migration and metastasis of cancer cells by stabilizing Septin2 to enhance actin network.

BACKGROUND: Excessive extracellular matrix deposition and increased stiffness are typical features of solid tumors such as hepatocellular carcinoma (HCC) and pancreatic ductal adenocarcinoma (PDAC). These conditions create confined spaces for tumor cell migration and metastasis. The regulatory mechanism of confined migration remains unclear. METHODS: LC-MS was applied to determine the differentially expressed proteins between HCC tissues and corresponding adjacent tissue. Collective migration and single cell migration microfluidic devices with 6 µm-high confined channels were designed and fabricated to mimic the in vivo confined space. 3D invasion assay was created by Matrigel and Collagen I mixture treat to adherent cells. 3D spheroid formation under various stiffness environment was developed by different substitution percentage GelMA. Immunoprecipitation was performed to pull down the LH1-binding proteins, which were identified by LC-MS. Immunofluorescent staining, FRET, RT-PCR, Western blotting, FRAP, CCK-8, transwell cell migration, wound healing, orthotopic liver injection mouse model and in vivo imaging were used to evaluate the target expression and cellular phenotype. RESULTS: Lysyl hydroxylase 1 (LH1) promoted the confined migration of cancer cells at both collective and single cell levels. In addition, LH1 enhanced cell invasion in a 3D biomimetic model and spheroid formation in stiffer environments. High LH1 expression correlated with poor prognosis of both HCC and PDAC patients, while it also promoted in vivo metastasis. Mechanistically, LH1 bound and stabilized Septin2 (SEPT2) to enhance actin polymerization, depending on the hydroxylase domain. Finally, the subpopulation with high expression of both LH1 and SEPT2 had the poorest prognosis. CONCLUSIONS: LH1 promotes the confined migration and metastasis of cancer cells by stabilizing SEPT2 and thus facilitating actin polymerization.

Electrospun fibrous membrane reinforced hydrogels with preferable mechanical and tribological performance as cartilage substitutes.

Hydrogels have attracted much attention as cartilage substitutes due to their human tissue-like characteristics. However, developing cartilage substitutes require the combination of high mechanical strength and low friction. Despite great success in tough hydrogels, this combination was hardly realized. Inspired by the natural cartilage, electrospun fibrous membrane reinforced hydrogels with superior mechanical properties and low friction coefficient were designed using electrospinning, freeze-thawing, and annealing techniques. An ordered fibrous membrane was first constructed by electrospinning, in which the tensile strength and modulus have been improved successfully. Then the PVA/PAA/GO hydrogel was modified layer-by-layer by the multilayer ordered electrospun membrane of PVA/PAA/GO. The ordered fibrous membrane significantly enhanced the mechanical strength and friction properties in a manner that mimicked the collagen fibrils in the cartilage. When the number of the membranes was 4, the mechanical properties of the fibrous membrane reinforced hydrogel is maximized, which can be compared to natural cartilage, which can achieve a tensile strength of 13.7 ± 1.5 MPa, tensile modulus of 27.5 ± 3.2 MPa, compressive strength of 12.32 ± 1.35 MPa, compressive modulus of 20.35 ± 2.50 MPa. The ordered fibrous membrane endows the hydrogel with a higher tearing energy of 39.16 ± 4.05 KJ m-2, which is the 5 times that of pure hydrogel (7.74 ± 0.86 KJ m-2). In addition, the friction coefficient of the fibrous membrane reinforced hydrogel is as low as 0.039, 2 times smaller than that of the hydrogel without addition of the fibrous membrane. Therefore, such hydrogels had excellent mechanical properties and tribological properties, which could be widely used in tissue engineering such as in cartilage replacement.

Spatially resolved transcriptomics revealed local invasion-related genes in colorectal cancer.

Objective: Local invasion is the first step of metastasis, the main cause of colorectal cancer (CRC)-related death. Recent studies have revealed extensive intertumoral and intratumoral heterogeneity. Here, we focused on revealing local invasion-related genes in CRC. Methods: We used spatial transcriptomic techniques to study the process of local invasion in four CRC tissues. First, we compared the pre-cancerous, cancer center, and invasive margin in one section (S115) and used pseudo-time analysis to reveal the differentiation trajectories from cancer center to invasive margin. Next, we performed immunohistochemical staining for RPL5, STC1, AKR1B1, CD47, and HLA-A on CRC samples. Moreover, we knocked down AKR1B1 in CRC cell lines and performed CCK-8, wound healing, and transwell assays to assess cell proliferation, migration, and invasion. Results: We demonstrated that 13 genes were overexpressed in invasive clusters, among which the expression of CSTB and TM4SF1 was correlated with poor PFS in CRC patients. The ribosome pathway was increased, while the antigen processing and presentation pathway was decreased along CRC progression. RPL5 was upregulated, while HLA-A was downregulated along cancer invasion in CRC samples. Pseudo-time analysis revealed that STC1, AKR1B1, SIRPA, C4orf3, EDNRA, CES1, PRRX1, EMP1, PPIB, PLTP, SULF2, and EGFL6 were unpregulated along the trajectories. Immunohistochemic3al staining showed the expression of STC1, AKR1B1, and CD47 was increased along cancer invasion in CRC samples. Knockdown of AKR1B1 inhibited CRC cells' proliferation, migration, and invasion. Conclusions: We revealed the spatial heterogeneity within CRC tissues and uncovered some novel genes that were associated with CRC invasion.

Transcriptional regulation of NDUFA4L2 by NFIB induces sorafenib resistance by decreasing reactive oxygen species in hepatocellular carcinoma.

Sorafenib is one a first-line therapeutic drugs for advanced hepatocellular carcinoma (HCC). However, only 30% of patients benefit from sorafenib due to drug resistance. We and other groups have revealed that nuclear factor I B (NFIB) regulates liver regeneration and carcinogenesis, but its role in drug resistance is poorly known. We found that NFIB was more upregulated in sorafenib-resistant SMMC-7721 cells compared to parental cells. NFIB knockdown not only sensitized drug-resistant cells to sorafenib but also inhibited the proliferation and invasion of these cells. Meanwhile, NFIB promoted the proliferation and invasion of HCC cells in vitro and facilitated tumor growth and metastasis in vivo. Knocking down NFIB synergetically inhibited tumor growth with sorafenib. Mechanically, gene expression profiling and subsequent verification experiments proved that NFIB could bind with the promoter region of a complex I inhibitor NDUFA4L2 and promote its transcription. Transcriptional upregulation of NDUFA4L2 by NFIB could thus inhibit the sorafenib-induced reactive oxygen species accumulation. Finally, we found that NFIB was highly expressed in HCC tissues, and high NFIB expression level was associated with macrovascular invasion, advanced tumor stage, and poor prognosis of HCC patients (n = 156). In summary, we demonstrated that NFIB could transcriptionally upregulate NDUFA4L2 to enhance both intrinsic and acquired sorafenib resistance of HCC cells by reducing reactive oxygen species induction.