Higher efficiency of vanadate iron in heterogeneous Fenton-like systems to pretreat sugarcane bagasse and its enzymatic saccharification.

Pretreatment is crucial for effective enzymatic saccharification of lignocellulose such as sugarcane bagasse (SCB). In the present study, SCB was pretreated with five kinds of heterogeneous Fenton-like systems (HFSs), respectively, in which α-FeOOH, α-Fe2O3, Fe3O4, and FeS2 worked as four traditional heterogeneous Fenton-like catalysts (HFCs), while FeVO4 worked as a novel HFC. The enzymatic reducing sugar conversion rate was then compared among SCB after different heterogeneous Fenton-like pretreatments (HFPs), and the optimal HFS and pretreatment conditions were determined. The mechanism underlying the difference in saccharification efficiency was elucidated by analyzing the composition and morphology of SCB. Moreover, the ion dissolution characteristics, variation of pH and Eh values, H2O2 and hydroxyl radical (·OH) concentration of FeVO4 and α-Fe2O3 HFSs were compared. The results revealed that the sugar conversion rate of SCB pretreated with FeVO4 HFS reached up to 58.25%, which was obviously higher than that under other HFPs. In addition, the surface morphology and composition of the pretreated SCB with FeVO4 HFS were more conducive to enzymatic saccharification. Compared with α-Fe2O3, FeVO4 could utilize H2O2 more efficiently, since the dissolved Fe3+ and V5+ can both react with H2O2 to produce more ·OH, resulting in a higher hemicellulose and lignin removal rate and a higher enzymatic sugar conversion rate. It can be concluded that FeVO4 HFP is a promising approach for lignocellulose pretreatment.

Tannic Acid-Modified Decellularized Tendon Scaffold with Antioxidant and Anti-Inflammatory Activities for Tendon Regeneration.

Tendon regeneration is greatly influenced by the oxidant and the inflammatory microenvironment. Persistent inflammation during the tendon repair can cause matrix degradation, tendon adhesion, and excessive accumulation of reactive oxygen species (ROS), while excessive ROS affect extracellular matrix remodeling and tendon integration. Herein, we used tannic acid (TA) to modify a decellularized tendon slice (DTS) to fabricate a functional scaffold (DTS-TA) with antioxidant and anti-inflammatory properties for tendon repair. The characterizations and cytocompatibility of the scaffolds were examined in vitro. The antioxidant and anti-inflammatory activities of the scaffold were evaluated in vitro and further studied in vivo using a subcutaneous implantation model. It was found that the modified DTS combined with TA via hydrogen bonds and covalent bonds, and the hydrophilicity, thermal stability, biodegradability, and mechanical characteristics of the scaffold were significantly improved. Afterward, the results demonstrated that DTS-TA could effectively reduce inflammation by increasing the M2/M1 macrophage ratio and interleukin-4 (IL-4) expression, decreasing the secretion of interleukin-6 (IL-6) and interleukin-1ß (IL-1ß), as well as scavenging excessive ROS in vitro and in vivo. In summary, DTS modified with TA provides a potential versatile scaffold for tendon regeneration.

Unraveling the Role of miR-200b-3p in Attention-Deficit/Hyperactivity Disorder (ADHD) and Its Therapeutic Potential in Spontaneously Hypertensive Rats (SHR).

Attention-deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder in children with unknown etiology. Impaired learning ability was commonly reported in ADHD patients and has been associated with dopamine uptake in the striatum of an animal model. Another evidence also indicated that micro-RNA (miR)-200b-3p is associated with learning ability in various animal models. However, the association between miR-200b-3p and ADHD-related symptoms remains unclear. Therefore, the current study investigated the role of miR-200b-3p in ADHD-related symptoms such as inattention and striatal inflammatory cytokines. To verify the influence of miR-200b-3p in ADHD-related symptoms, striatal stereotaxic injection of miR-200b-3p antagomir (AT) was performed on spontaneously hypertensive rats (SHR). The antioxidant activity and expressions of miR-200b-3p, slit guidance ligand 2 (Slit2), and inflammatory cytokines in the striatum of SHR were measured using quantitative real-time polymerase chain reaction (RT-qPCR), immunohistochemistry (IHC), immunoblotting, and enzyme-linked immunosorbent assay (ELISA). The spontaneous alternation of SHR was tested using a three-arm Y-shaped maze. The administration of miR-200b-3p AT or taurine significantly decreased striatal tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 in SHR, along with increased super-oxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities and significantly higher spontaneous alternation. In this paper, we show that miR-200b-3p AT and taurine alleviates ADHD-related symptoms in SHR. These findings provide insights into ADHD's molecular basis and suggest miR-200b-3p as a potential therapeutic target. Concurrently, this study also suggests broad implications for treating neurodevelopmental disorders affecting learning activity such as ADHD.

Improved capacitive performances and electrocatalytic reduction activity by regulating the bonding interaction between Zn-bistriazole-pyrazine/pyridine units and diverse Anderson-type polyoxometalates.

Electrochemical performances can be effectively improved by introducing metal-organic units (MOUs) into polyoxometalates (POMs). However, regulating the bonding strength between POMs and MOUs at the molecular level to improve the electrochemical performance is a challenging task. Three new POM-based metal-organic complexes (MOCs), namely H{Zn2(Hpytty)2(H2O)8[CrMo6(OH)6O18]}·2H2O (1), H{Zn2(Hpyttz)2(H2O)6[CrMo6(OH)6O18]}·8H2O (2), and {(µ2-OH)2Zn6(pyttz)2(H2O)10[TeMo6O24]}·2H2O (3) (H2pytty = 3-(pyrazin-2-yl)-5-(1H-1,2,4-triazol-3-yl)-1,2,4-triazolyl, H2pyttz = 3-(pyrid-2-yl)-5-(1H-1,2,4-triazol-3-yl)-1,2,4-triazolyl), were obtained. Single-crystal X-ray diffraction shows that the bonding strength (from the hydrogen bond to the coordination bond) between Zn-bistriazole-pyrazine/pyridine units and diverse Anderson-type POMs gradually increases from complexes 1 to 3. Glassy carbon electrodes modified with complex 3 (3-GCE) has the highest specific capacitance, which is 930 F g-1 at 1 A g-1. Moreover, carbon paste electrodes (1-3-CPEs) modified with complexes 1-3 are used as electrochemical sensors for detecting Cr(VI) ions, with limits of detection well below the World Health Organization (WHO) maximum level in drinking water.

Influence paradigms of soil moisture on land surface energy partitioning under different climatic conditions.

Soil moisture (SM) directly controls the land surface energy partition which plays an important role in the formation of extreme weather events. However, its dependence on specific climatic conditions is not thoroughly understood due to the complexity of soil moisture effects. Here, we examine the relationship between SM and surface energy partitioning under different climate conditions, and identify the influence paradigms of soil moisture on surface energy partition. We find that temperature changes can explicitly determine the impact paradigm of different physical processes, i.e. evapotranspiration, soil freezing and thawing, and such influence paradigms are also affected by atmospheric aridity (VPD). Globally, there are five paradigms that effects on surface energy partitioning, including the warm-wet paradigm (WW), transitional paradigm (TP), warm-dry paradigm (WD), cool-wet paradigm (CW) and cold paradigm (CP). Since 1981, the global area proportion for TP is observed to increase pronouncedly. We also find that the critical SM threshold exhibits regional variations and the global average is 0.45 m3/m3. The identified paradigms and their long-term change trends provide new insights into the global intensification of land-atmosphere interaction, which has important implications for global warming and the formation of heatwaves.

Quantitative comparison of three thyroidectomy approaches in neck muscles, voice, and swallowing functions.

OBJECTIVE: This study compares endoscopic thyroidectomy by gasless unilateral axillary approach (ETGUA) and sternocleidomastoid leading-edge approach (SLEA) with conventional open thyroidectomy (COT) in hemithyroidectomy. The main focus is on the protection of neck muscles (sternocleidomastoid, omohyoid, sternothyroid) and the postoperative function of voice and swallowing yielded through these common approaches. METHODS: A total of 302 patients who underwent hemithyroidectomy were enrolled and divided into three groups: ETGUA (n = 101), SLEA (n = 100), and COT (n = 101). Ultrasound was used to measure the thickness of bilateral neck muscles, including the sternocleidomastoid, omohyoid, and sternothyroid. The changes in thickness on the surgical side compared to the non-surgical side. Analyzed factors included muscle thickness changes, Swallowing Impairment Score (SIS), Voice Handicap Index (VHI), Scar Cosmesis Assessment and Rating (SCAR), Neck Injury Index (NII), surgery duration, drainage volume, hospitalization, and number of lymph nodes. RESULTS: The clinical characteristics among the three groups were consistent except for differences in sex, age, and BMI. Metrics such as sternocleidomastoid muscle, NII, hypocalcemia, postoperative PTH, transient hoarseness, and number of lymph nodes showed no significant differences among the three groups. However, significant differences were found in the duration of surgery, drainage volume, hospitalization period omohyoid muscle, Sternohyoid muscle, VHI, SIS, and SCAR (all p < 0.001). CONCLUSION: In comparison to COT, ETGUA and SLEA demonstrate superiority in protecting neck muscles and preserving voice and swallowing function without compromising surgical safety or radicality.

Facilely Prepared Thirsty Granules Arouse Tough Wet Adhesion on Overmoist Wounds for Hemostasis and Tissue Repair.

Bioadhesives have been widely used in hemostasis and tissue repair, but the overmoist and wet nature of wound surface (due to the presence of blood and/or wound exudate) has led to poor wet adhesion of bioadhesives, which interrupts the continuous care of wounds. Here, a thirsty polyphenolic silk granule (Tan@SF-pwd-hydro), which absorbs blood and exudate to self-convert to robust bioadhesives (Tan@SF-gel-hydro) in situ, was facilely developed in this study for enhanced wet adhesion toward hemostasis and tissue repair. Tan@SF-pwd-hydro could shield wounds' wetness and immediately convert itself to Tan@SF-gel-hydro to seal wounds for hemorrhage control and wound healing. The maximum adhesiveness of Tan@SF-gel-hydro over wet pigskin was as high as 59.8 ± 2.1 kPa. Tan@SF-pwd-hydro is a promising transformative dressing for hemostasis and tissue repair since its hemostatic time was approximately half of that of the commercial hemostatic product, CeloxTM, and its healing period was much shorter than that of the commercial bioadhesive product, TegadermTM. This pioneering study utilized adverse wetness over wounds to arouse robust adhesiveness by converting thirsty granules to bioadhesives in situ, creatively turning adversity into opportunities. The facile fabrication approach also offers new perspectives for manufacturing sustainability of biomaterials.

Chitosan/silk fibroin nanofibers-based hierarchical sponges accelerate infected diabetic wound healing via a HClO self-producing cascade catalytic reaction.

The diabetic chronic wound healing is extremely restricted by issues such as hyperglycemia, excessive exudate and reactive oxygen species (ROS), and bacterial infection, causing significant disability and fatality rate. Herein, the chitosan/silk fibroin nanofibers-based hierarchical 3D sponge (CSSF-P/AuGCs) with effective exudate transfer and wound microenvironment modulation are produced by integrating cascade reactor (AuGC) into sponge substrates with parallel-arranged microchannels. When applied to diabetic wounds, the uniformly parallel-arranged microchannels endow CSSF-P/AuGCs with exceptional exudate absorption capacity, keeping the wound clean and moist; additionally, AuGCs efficiently depletes glucose in wounds to generate H2O2, which is then converted into HClO via cascade catalytic reaction to eliminate bacterial infection and reduce inflammation. Experiments in vitro demonstrated that the antibacterial activity of CSSF-P/AuGCs against S. aureus and E. coli was 92.7 and 94.27 %, respectively. Experiments on animals indicated that CSSF-P/AuGC could cure wounds in 11 days, displaying superior wound-healing abilities when compared to the commercial medication Tegaderm™. This versatile CSSF-P/AuGCs dressing may be an attractive choice for expediting diabetic wound healing with little cytotoxicity, providing a novel therapeutic method for establishing a favorable pathological microenvironment for tissue repair.

Impact of cerebral collateral flow on stroke outcomes after carotid stenting.

OBJECTIVE: Internal carotid artery stenosis is a main contributor to recurrent ischemic stroke. This study aimed to evaluate associations between recurrent stroke and changes in prestenting flow direction in the primary collaterals or both primary and secondary collaterals, and the potential interaction between extra- and intracranial arteries. METHODS: This longitudinal study recruited stroke patients without intracranial stenosis who underwent right-side carotid stenting between 2011 and 2019. The main study outcome was recurrent stroke. Predictive factors were anterior circulation flow direction change (ACFDC), posterior circulation flow direction change, and reversal of ophthalmic artery/leptomeningeal anastomosis (ROALA) detected by transcranial color-coded duplex (TCCD) before carotid stenting. Patient follow-up was 9 years. Risk factors for recurrent stroke were identified by Kaplan-Meier plot and Cox regression analyses. RESULTS: A total of 234 patients (mean age 70.88 ± 10.3 years, 86.32% male) were included, and 115 had recurrent stroke. Kaplan-Meier plot showed that patients with left ACFDC and ROALA had worse outcomes than those with ACFDC only, while patients with left ACFDC had worse outcome than those with right ACFDC (both p < 0.001). Cox regression analysis showed that recurrent stoke was associated with ACFDC at right (hazard ratio [95% CI]: 20.988 [2.549-172.790], p < 0.01), left (151.441 [20.100-1140.993], p < 0.001), and both sides (144.889 [19.089-1099.710], p < 0.001). INTERPRETATION: Anterior circulation flow direction change is significantly associated with recurrent stroke in patients with unilateral carotid stenosis. Patients with ACFDC and ROALA together have worse outcomes compared to those with ACFDC only. Prestenting TCCD images help provide definitive information to predict outcomes after carotid stenting.

In situ generation of bioadhesives using dry tannic silk particles: a wet-adhesion strategy relying on removal of hydraulic layer over wet tissues for wound care.

Tissue adhesives have been widely used in biomedical applications. However, the presence of a hydrated layer on the surface of wet tissue severely hinders their adhesion capacities, resulting in ineffective wound treatment. To address this issue, a dry particle dressing (plas@SF/tann-hydro-pwd) capable of removing the hydrated layer and converting in situ to bioadhesives (plas@SF/tann-hydro-gel) was fabricated via simple physical mixing based on the hydrophobic-hydrogen bonding synergistic effect and Schiff-base reaction. It was found that the plas@SF/tann-hydro-gel bioadhesive, which was changed from plas@SF/tann-hydro-pwd dressing by adsorption of water, exhibited good wet adhesion to diverse biological tissues. In addition, the wet adhesion qualities of the plas@SF/tann-hydro-gel adhesive was studied under a variety of demanding conditions, including a wide range of temperatures, varying pH levels, highly concentrated salt solutions, and simulated fluids. Experiments on animals had showed that the adhesive plas@SF/tann-hydro-gel has superior wet adhesion qualities and superior wound healing properties compared to the commercial product Tegaderm™. This study develops a new wet-adhesion technique employing dry particle dressing to eliminate the hydrated layer over wet tissues for the in situ creation of gel bioadhesives for wound healing.

Preparation of nano-sized multi-vesicular vesicles (MVVs) and its application in co-delivery of doxorubicin and curcumin.

Multi-vesicular vesicles (MVVs) offer structural advantages in terms of drug encapsulation and physiological stability. In this study, we address the challenge of preparing small-sized MVVs for drug delivery. The nano-sized MVVs (∼120 nm) loaded with doxorubicin (DOX) and curcumin (CUR) (DOX/CUR@MVVs) were successfully prepared using a glass bead combined with a thin film dispersion method. Transmission electron microscopy (TEM) and dynamic light scattering (DLS) analysis confirmed the independent non-homocentric vesicle structures of DOX/CUR@MVVs with homogeneous particle sizes. The experimental results showed high encapsulation rates of DOX and CUR in DOX/CUR@MVVs, reaching 82.5 ± 0.75 % and 85.9 ± 0.69 %, respectively. Moreover, the MVVs exhibited good biosafety and sustained release properties. Notably, the bioavailability of DOX and CUR in DOX/CUR@MVVs was enhanced compared to free DOX and CUR, with increases of 4.2 and 2.1 times, respectively. And the half-life of DOX and CUR was extended by 10 times in DOX/CUR@MVVs. In vivo antitumor experiments demonstrated that nano-sized DOX/CUR@MVVs significantly improved the antitumor activity while reducing the toxic side effects of DOX. Overall, the successful preparation of nano-sized DOX/CUR@MVVs and their potent and low-toxic antitumor effects provide a critical experimental reference for the combined antitumor therapy of MVVs and liposomes.

Effectiveness of renin-angiotensin-aldosterone system blockers in patients with Alport syndrome: a systematic review and meta-analysis.

BACKGROUND: Although renin-angiotensin-aldosterone system (RAAS) blockers have been considered the primary treatment for patients with Alport syndrome (AS) for a decade, there is no comprehensive review with evidence-based analysis evaluating the effectiveness of RAAS blockers in AS. METHODS: A systematic review and meta-analysis was performed of published studies that compared outcomes related to disease progression between patients with AS receiving RAAS blockers with those taking non-RAAS treatment. Outcomes were meta-analyzed using the random effects models. Cochrane risk-of-bias, Newcastle-Ottawa Scale and Grading of Recommendations Assessment, Development and Evaluation methodology (GRADE) assessment determined the certainty of evidence. RESULTS: A total of eight studies (1182 patients) were included in the analysis. Overall, the risk of bias was low to moderate. Compared with non-RAAS treatment, RAAS blockers could reduce the rate of progression to end-stage kidney disease (ESKD) [four studies; hazard ratio (HR) 0.33, 95% confidence interval (CI) 0.24-0.45; moderate certainty evidence]. After stratified by genetic types, a similar benefit was detected: male X-linked AS (XLAS) (HR 0.32, 95% CI 0.22-0.48), autosomal recessive AS (HR 0.25, 95% CI 0.10-0.62), female XLAS and autosomal dominant AS (HR 0.40, 95% CI 0.21-0.75). In addition, RAAS blockers showed a clear gradient of benefit depending on the stage of disease at the initiation of treatment. CONCLUSION: This meta-analysis suggested that RAAS blockers could be considered as a specific therapy to delay of ESKD for AS with any genetic type, especially at the early stage of the disease, and every further more-effective therapy would be advised to be applied on top of this standard of care.

Level II lateral neck dissection for papillary thyroid carcinoma: A retrospective cohort study.

BACKGROUND: For N1b papillary thyroid carcinoma (PTC) patients, lateral neck dissection encompassing levels Ⅱ-Ⅴ is generally recommended. However, routine level Ⅱ dissection is controversial given the low incidence of metastasis, and potential complications such as increased shoulder syndrome. METHODS: Retrospective analysis of consecutive patients with papillary thyroid carcinoma who underwent lateral neck dissection at a single institution from January 2019 to April 2021 was performed. Clinicopathological features such as age, gender, tumor location, tumor size, TgAb and TPOAb levels, capsular invasion, multifocality and lymph node metastases were examined to evaluate the occurrence of metastatic Level Ⅱ lymph nodes. RESULTS: Overall and occult level Ⅱ metastases were observed in 51.83% and 34.84% of cN1b PTC patients. Multivariant analysis showed that primary tumor, location of primary tumor and positive level Ⅴ can serve as independent risk factors of metastasis in level Ⅱ. For cN1b PTC patients not suspected of level Ⅱ lymph nodes preoperatively, independent risk factors for predicting occult level Ⅱ metastases may include the location of primary tumor, positive level Ⅲ and positive level Ⅴ. CONCLUSION: A significant number of patients with PTC and lateral neck disease experienced Level Ⅱ metastasis, with the location of primary tumor and multilevel lymph node involvement being the independent risk factors. If the tumor is less than 1 cm and located at lower 2/3 lobe, there is minimal possibility of level Ⅱ lymph node metastasis.

Dissecting the effect of ethylene in the transcriptional regulation of chilling treatment in grapevine leaves.

Ethylene (ETH) plays important roles in various development programs and stress responses in plants. In grapevines, ETH increased dramatically under chilling stress and is known to positively regulate cold tolerance. However, the role of ETH in transcriptional regulation during chilling stress of grapevine leaves is still not clear. To address this gap, targeted hormone profiling and transcriptomic analysis were performed on leaves of Vitis amurensis under chilling stress with and without aminoethoxyvinylglycine (AVG, a inhibitor of ETH synthesis) treatment. APETALA2/ETHYLENE RESPONSIVE FACTOR (AP2/ERF) and WRKY transcription factors (TF) were only the two highly enriched TF families that were consistently up-regulated during chilling stress but inhibited by AVG. The comparison of leaf transcriptomes between chilling treatment and chilling with AVG allowed the identification of potential ETH-regulated genes. Potential genes that are positively regulated by ETH are enriched in solute transport, protein biosynthesis, phytohormone action, antioxidant and carbohydrate metabolism. Conversely, genes related to the synthesis and signaling of ETH, indole-3-acetic acid (IAA), abscisic acid (ABA) were up-regulated by chilling treatment but inhibited by AVG. The contents of ETH, ABA and IAA also paralleled with the transcriptome data, which suggests that the response of ABA and IAA during chilling stress may regulate by ETH signaling, and together may belong to an integrated network of hormonal signaling pathways underpinning chilling stress response in grapevine leaves. Together, these findings provide new clues for further studying the complex regulatory mechanism of ETH under low-temperature stress in plants more generally and new opportunities for breeding cold-resilient grapevines.

Discovery of Highly Potent and Selective Thyroid Hormone Receptor ß Agonists for the Treatment of Nonalcoholic Steatohepatitis.

Nonalcoholic steatohepatitis (NASH) is a progressive stage of nonalcoholic fatty liver disease (NAFLD) and is characterized by steatosis, inflammation, hepatocyte ballooning, and fibrosis. While there are currently no approved therapies for NASH, the thyroid hormone receptor ß (THR-ß), primarily expressed in the liver, is emerging as an effective molecular target for the treatment of NASH. However, the adverse cardiac and bone effects mediated by thyroid hormone receptor α (THR-α) need to be minimized. Herein, we reported the discovery of a series of novel THR-ß agonists featuring pyrrolo[3,2-b]pyridin-5-one skeletons based on structure-based drug design. Further optimization led to compound 15, which exhibited higher potency and selectivity for THR-ß over THR-α compared to clinical drug MGL-3196. More significantly, an excellent liver-to-serum ratio of 93:1 was observed for compound 15. We believe that the high hepatic concentration of compound 15 may result in no cardiotoxicity.

Association between ambient air pollution exposure and insomnia among adults in Taipei City.

Ambient air pollution was known to cause central nervous system diseases and depressive symptoms. In this study, we examined the associations between air pollution exposure and the prevalence of insomnia in Taipei City of Taiwan. We applied the health information system of electrical medical records of Taipei City Hospital to collect a total of 5108 study subjects (insomniacs N = 912 and non-insomniacs N = 4196) over 18 years old from the family medicine and internal medicine outpatients of six branches of Taipei City Hospital. These patients were grouped into insomniacs and non-insomniacs following the primary insomnia diagnosis (ICD9:780.52, 780.54, 307.41, 307.42, ICD10: G47.00, G47.01, G47.09, F51.01, F51.09) and the prescription times of anxiolytics and hypnotics. We estimated one-year average concentrations of PM2.5, ozone, and NOx before the first date of insomnia diagnosis and the last date of outpatient visit for insomniacs and non-insomniacs, respectively, by using the data of nearest air quality monitoring stations relative to study subjects' residential addresses. Logistic regression analysis was employed to examine the independent effects of air pollution concentrations on the risk of insomnia. One-year average PM2.5, ozone, and NOx levels for insomniacs was significantly higher than those of non-insomniacs. After adjusting for confounding factors, increase each 1(µg/m3) in one-year average PM2.5 showed a statistically significant association with insomnia (the odds ratio 1.610, 95% CI [1.562,1.660]). As to multi pollutants, one-year average PM2.5 (1.624, [1.570, 1.681] and ozone (1.198, [1.094, 1.311]) exposure showed a significant association with insomnia. Subgroup analysis revealed that the influence of PM2.5 and ozone on insomnia have significant risks in people with major chronic disease. This study demonstrated a positive association between PM2.5 and ozone exposure and the prevalence of hypnotic-treated insomnia. Especially, the people with major chronic diseases were with obvious effect of PM2.5 and ozone on risk of insomnia.

An Acid-Sensitive Nanofiber Conjugate Based on a Short Aromatic Peptide for Targeted Delivery of Doxorubicin in Liver Cancer.

Purpose: This study aimed to construct a DOX conjugate with liver tumor targeting and acid sensitivity based on a short aromatic peptide FFYEE, which could amplify the tumor inhibition efficacy of DOX and alleviate tissue toxicity. Methods: A novel DOX-peptide conjugate, D-gal-FFYEE-hyd-DOX, was constructed by linking DOX to the side chain of FFYEE with acid-sensitive hydrazone bond and by modifying the C-terminal of peptide with α-D-galactosamine (D-gal) as targeting ligand. The structure of D-gal-FFYEE-hyd-DOX was characterized by mass spectrometry, infrared spectroscopy (IR), and UV-Vis spectroscopy (UV-Vis). The assembly characteristics of pentapeptide FFYEE and D-gal-FFYEE-hyd-DOX were observed by transmission electron microscope (TEM). In vitro drug release, cytotoxicity, endocytosis, in vivo antitumor experiment and histopathology analysis were investigated. Results: Peptide FFYEE endowed the D-gal-FFYEE-hyd-DOX with self-assembly performance and improved biocompatibility. D-gal-FFYEE-hyd-DOX can self-assemble into nanofibers with a diameter of ~ 40 nm in neutral aqueous solution and significantly reduced the cytotoxicity of free DOX to L02 cells. In vitro drug release results showed that D-gal-FFYEE-hyd-DOX had acid sensitivity and controlled release characteristics. The cytotoxicity and endocytosis investigations confirmed that D-gal-FFYEE-hyd-DOX enhanced the cellular uptake of DOX and inhibition effect on HepG2 cells. In vivo antitumor experiment indicated that D-gal-FFYEE-hyd-DOX could significantly inhibit the growth of liver tumor in mice and reduce the side effects of DOX. Conclusion: The conjugate D-gal-FFYEE-hyd-DOX with liver tumor targeting and acid sensitivity has the characteristics of strong tumor inhibition and low toxicity, hinting the great clinical application potential for targeted delivery of DOX in cancer treatment.

Asymptomatic adult Wilms' tumor: A case report.

Wilms' tumor, also called nephroblastoma, is an extremely uncommon kidney tumor of adulthood. We reported a adult man with a left kidney mass diagnosed as Wilms' tumor. Case presentation: A 25-year-old man was hospitalized due to injury of the anterior cruciate ligament of the right knee. Preoperative imaging accidentally revealed a mass measuring 53 × 46 mm involving the middle and lower segments of the left kidney without evidence supporting the invasion of the surrounding structures or metastasis. The patient didn't show any symptom commonly occurred in Wilms' tumor, such as flank pain or hematuria. After nephrectomy, the diagnosis of adult Wilms' tumor was confirmed based on the tumor morphology and immunohistochemical findings. Conclusion: In adult patients without any clinical manifestations or favorable imaging findings for low-stage renal cell carcinoma, the diagnosis of Wilms' tumor should be taken into consideration.

Constructing a highly bioactive tendon-regenerative scaffold by surface modification of tissue-specific stem cell-derived extracellular matrix.

Developing highly bioactive scaffold materials to promote stem cell migration, proliferation and tissue-specific differentiation is a crucial requirement in current tissue engineering and regenerative medicine. Our previous work has demonstrated that the decellularized tendon slices (DTSs) are able to promote stem cell proliferation and tenogenic differentiation in vitro and show certain pro-regenerative capacity for rotator cuff tendon regeneration in vivo. In this study, we present a strategy to further improve the bioactivity of the DTSs for constructing a novel highly bioactive tendon-regenerative scaffold by surface modification of tendon-specific stem cell-derived extracellular matrix (tECM), which is expected to greatly enhance the capacity of scaffold material in regulating stem cell behavior, including migration, proliferation and tenogenic differentiation. We prove that the modification of tECM could change the highly aligned surface topographical cues of the DTSs, retain the surface stiffness of the DTSs and significantly increase the content of multiple ECM components in the tECM-DTSs. As a result, the tECM-DTSs dramatically enhance the migration, proliferation as well as tenogenic differentiation of rat bone marrow-derived stem cells compared with the DTSs. Collectively, this strategy would provide a new way for constructing ECM-based biomaterials with enhanced bioactivity for in situ tendon regeneration applications.

Biomechanically and biochemically functional scaffold for recruitment of endogenous stem cells to promote tendon regeneration.

Tendon regeneration highly relies on biomechanical and biochemical cues in the repair microenvironment. Herein, we combined the decellularized bovine tendon sheet (DBTS) with extracellular matrix (ECM) from tendon-derived stem cells (TDSCs) to fabricate a biomechanically and biochemically functional scaffold (tECM-DBTS), to provide a functional and stem cell ECM-based microenvironment for tendon regeneration. Our prior study showed that DBTS was biomechanically suitable to tendon repair. In this study, the biological function of tECM-DBTS was examined in vitro, and the efficiency of the scaffold for Achilles tendon repair was evaluated using immunofluorescence staining, histological staining, stem cell tracking, biomechanical and functional analyses. It was found that tECM-DBTS increased the content of bioactive factors and had a better performance for the proliferation, migration and tenogenic differentiation of bone marrow-derived stem cells (BMSCs) than DBTS. Furthermore, our results demonstrated that tECM-DBTS promoted tendon regeneration and improved the biomechanical properties of regenerated Achilles tendons in rats by recruiting endogenous stem cells and participating in the functionalization of these stem cells. As a whole, the results of this study demonstrated that the tECM-DBTS can provide a bionic microenvironment for recruiting endogenous stem cells and facilitating in situ regeneration of tendons.