Pre-coating cRGD-modified bovine serum albumin enhanced the anti-tumor angiogenesis of siVEGF-loaded chitosan-based nanoparticles by manipulating the protein corona composition.

Chitosan-based nanoparticles inevitably adsorb numerous proteins in the bloodstream, forming a protein corona that significantly influences their functionality. This study employed a pre-coated protein corona using cyclic Arg-Gly-Asp peptide (cRGD)-modified bovine serum albumin (BcR) to confer tumor-targeting capabilities on siVEGF-loaded chitosan-based nanoparticles (CsR/siVEGF NPs) and actively manipulated the serum protein corona composition to enhance their anti-tumor angiogenesis. Consequently, BcR effectively binds to the nanoparticles' surface, generating nanocarriers of appropriate size and stability that enhance the inhibition of endothelial cell proliferation, migration, invasion, and tube formation, as well as suppress tumor proliferation and angiogenesis in tumor-bearing nude mice. Proteomic analysis indicated a significant enrichment of serotransferrin, albumin, and proteasome subunit alpha type-1 in the protein corona of BcR-precoated NPs formed in the serum of tumor-bearing nude mice. Additionally, there was a decrease in proteins associated with complement activation, immunoglobulins, blood coagulation, and acute-phase responses. This modification resulted in an enhanced impact on anti-tumor angiogenesis, along with a reduction in opsonization and inflammatory responses. Therefore, pre-coating of nanoparticles with a functionalized albumin corona to manipulate the composition of serum protein corona emerges as an innovative approach to improve the delivery effectiveness of chitosan-based carriers for siVEGF, targeting the inhibition of tumor angiogenesis.

Apoptotic vesicles are required to repair DNA damage and suppress premature cellular senescence.

It is well known that DNA damage can cause apoptosis. However, whether apoptosis and its metabolites contribute to DNA repair is largely unknown. In this study, we found that apoptosis-deficient Fasmut and Bim- /- mice show significantly elevated DNA damage and premature cellular senescence, along with a significantly reduced number of 16,000 g apoptotic vesicles (apoVs). Intravenous infusion of mesenchymal stromal cell (MSC)-derived 16,000 g apoVs rescued the DNA damage and premature senescence in Fasmut and Bim-/- mice. Moreover, a sublethal dose of radiation exposure caused more severe DNA damage, reduced survival rate, and loss of body weight in Fasmut mice than in wild-type mice, which can be recovered by the infusion of MSC-apoVs. Mechanistically, we showed that apoptosis can assemble multiple nuclear DNA repair enzymes, such as the full-length PARP1, into 16,000 g apoVs. These DNA repair components are directly transferred by 16,000 g apoVs to recipient cells, leading to the rescue of DNA damage and elimination of senescent cells. Finally, we showed that embryonic stem cell-derived 16,000 g apoVs have superior DNA repair capacity due to containing a high level of nuclear DNA repair enzymes to rescue lethal dose-irradiated mice. This study uncovers a previously unknown role of 16,000 g apoVs in safeguarding tissues from DNA damage and demonstrates a strategy for using stem cell-derived apoVs to ameliorate irradiation-induced DNA damage.

Hepatic progenitor cell-originated ductular reaction facilitates liver fibrosis through activation of hedgehog signaling.

Background: It is poorly understood what cellular types participate in ductular reaction (DR) and whether DR facilitates recovery from injury or accelerates hepatic fibrosis. The aim of this study is to gain insights into the role of hepatic progenitor cell (HPC)-originated DR during fibrotic progression. Methods: DR in liver specimens of PBC, chronic HBV infection (CHB) or NAFLD, and four rodent fibrotic models by different pathogenic processes was evaluated. Gli1 expression was inhibited in rodent models or cell culture and organoid models by AAV-shGli1 or treating with GANT61. Results: Severity of liver fibrosis was positively correlated with DR extent in patients with PBC, CHB or NAFLD. HPCs were activated, expanded, differentiated into reactive cholangiocytes and constituted "HPC-originated DR", accompanying with exacerbated fibrosis in rodent models of HPC activation & proliferation (CCl4/2-AAF-treated), Μdr2-/- spontaneous PSC, BDL-cholestatic fibrosis or WD-fed/CCl4-treated NASH-fibrosis. Gli1 expression was significantly increased in enriched pathways in vivo and in vitro. Enhanced Gli1 expression was identified in KRT19+-reactive cholangiocytes. Suppressing Gli1 expression by administration of AAV-shGli1 or GANT61 ameliorated HPC-originated DR and fibrotic extent. KRT19 expression was reduced after GANT61 treatment in sodium butyrate-stimulated WB-F344 cells or organoids or in cells transduced with Gli1 knockdown lentiviral vectors. In contrast, KRT19 expression was elevated after transducing Gli1 overexpression lentiviral vectors in these cells. Conclusions: During various modes of chronic injury, Gli1 acted as an important mediator of HPC activation, expansion, differentiation into reactive cholangiocytes that formed DR, and subsequently provoked hepatic fibrogenesis.

Is There an Optimal Time Window of Placement of Intracranial Pressure (ICP) Monitor for Elderly Patients With Severe Traumatic Brain Injury? An 11-Year Institutional Cohort Study With Restricted Cubic Spline Analysis.

Severe traumatic brain injury (sTBI) is a prominent contributor to both morbidity and mortality in the elderly population. The monitoring of intracranial pressure (ICP) is crucial in the management of sTBI patients. Nevertheless, the appropriate timing for the placement of ICP monitor in elderly sTBI patients remains uncertain. To determine the optimal timing for the placement of ICP monitor in elderly sTBI patients, in this retrospective cohort study, we collected data from elderly patients (> 65 years) who suffered sTBI and received ICP monitors at Tangdu Hospital, The Fourth Military Medical University, between January 2011 and December 2021. To examine the relationship between the time of ICP monitor placement and in-hospital mortality, we conducted a multi-variate-adjusted restricted cubic spline (RCS) analysis. Additionally, logistic regression analysis was applied to further analyze the influencing factors contributing to early or late ICP monitor placements. A total of 283 eligible elderly TBI patients were included in the current analysis. The in-hospital mortality rate was 73 out of 283 (26%). The RCS analysis demonstrated an inverted U-shaped curve in the relationship between the timing of ICP monitor placement and in-hospital mortality. For the elderly sTBI patient cohort, 6 h was identified as the crucial moment for the treatment strategy. In addition, the protective time window for ICP placement was less than 4.92 h for the GCS 3-5 group, and less than 8.26 h for the GCS 6-8 group. However, the clinical benefit of ICP placement decreased gradually over time. The relationship between ICP placement and in-hospital mortality was non-linear, exhibiting an inverted U-shaped curve in elderly patients with sTBI. For elderly patients with sTBI, early (≤ 6 h) ICP placement was associated with reduced in-hospital mortality. The clinical benefit of ICP placement decreased beyond the optimal time window.

A dual network cross-linked hydrogel with multifunctional Bletilla striata polysaccharide/gelatin/tea polyphenol for wound healing promotion.

Wound healing is a dynamic and complex biological process, and traditional biological excipients cannot meet the needs of the wound healing process, and there is an urgent need for a biological dressing with multifunctionality and the ability to participate in all stages of wound healing. This study developed tea polyphenol (TP) incorporated multifunctional hydrogel based on oxidized Bletilla striata polysaccharide (OBSP) and adipic acid dihydrazide modified gelatin (Gel-ADH) with antimicrobial, antioxidant hemostatic, and anti-inflammatory properties to promote wound healing. The composite OBSP, Gel-ADH, TP (OBGTP) hydrogels prepared by double crosslinking between OBSP, TP and Gel-ADH via Schiff base bonding and hydrogen bonding had good rheological and swelling properties. The introduction of TP provided the composite hydrogel with excellent antioxidant antibacterial activities against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coil). In the rat liver hemorrhage model and skin injury model, the OBGTP composite hydrogel had significant (p < 0.001) hemostatic ability, and had the ability to accelerate collagen deposition, reduce the expression of inflammatory factors, and promote rapid wound healing. In addition, OBGTP hydrogels had adhesive properties and good biocompatibility. In conclusion, OBGTP multifunctional composite hydrogels have great potential for wound healing applications.

[Whole-cell catalytic production of pseudouridine by recombinant Escherichia coli].

Pseudouridine is the most abundant modified nucleoside found in non-coding RNA and is widely used in biological and pharmaceutical fields. However, current methods for pseudouridine production suffer from drawbacks such as complex procedures, low efficiency and high costs. This study presents a novel enzymatic cascade reaction route in Escherichia coli, enabling the whole-cell catalytic synthesis of pseudouridine from uridine. Initially, a metabolic pathway was established through plasmid-mediated overexpression of endogenous pseudouridine-5-phosphase glycosidase, ribokinase, and ribonucleoside hydrolase, resulting in the accumulation of pseudouridine. Subsequently, highly active endogenous ribonucleoside hydrolase was screened to enhance uridine hydrolysis and provide more precursors for pseudouridine synthesis. Furthermore, modifications were made to the substrates and products transport pathways to increase the pseudouridine yield while avoiding the accumulation of by-product uridine. The resulting recombinant strain Ψ-7 catalyzed the conversion of 30 g/L uridine into 27.24 g/L pseudouridine in 24 h, achieving a conversion rate of 90.8% and a production efficiency of 1.135 g/(L·h). These values represent the highest reported yield and production efficiency achieved by enzymatic catalysis methods to date.

The exonuclease TREX1 constitutes an innate immune checkpoint limiting cGAS/STING-mediated antitumor immunity.

The DNA exonuclease TREX1 (Three-prime repair exonuclease 1) is critical for preventing autoimmunity in mice and humans by degrading endogenous cytosolic DNA, which otherwise triggers activation of the innate cGAS/STING pathway leading to the production of type I IFNs. Since tumor cells are prone to aberrant cytosolic DNA accumulation, we hypothesized that they are critically dependent on TREX1 activity to limit their immunogenicity. Here we show, that in tumor cells TREX1 indeed restricts the spontaneous activation of the cGAS/STING pathway and the subsequent induction of a type I IFN response. As a result, TREX1 deficiency compromised in vivo tumor growth in mice. This delay depended on a functional immune system, systemic type I IFN signaling, and tumor-intrinsic cGAS expression. Mechanistically, we show that tumor TREX1 loss drove activation of CD8 T cells and NK cells, prevented CD8 T cell exhaustion, and remodeled an immunosuppressive myeloid compartment. Consequently, TREX1 deficiency synergized with T cell-directed immune checkpoint blockade. Collectively, we conclude that TREX1 is essential to limit tumor immunogenicity, and that targeting this innate immune checkpoint remodels the tumor microenvironment and enhances anti-tumor immunity by itself and in combination with T cell-targeted therapies.

Flooding Length Mediates Fencing and Grazing Effects on Soil Respiration in Meadow Steppe.

Grassland management affects soil respiration (Rs, consists of heterotrophic respiration and autotrophic respiration) through soil micro-ecological processes, such as hydrothermal, plant root, organic carbon decomposition and microbial activity. Flooding, an irregular phenomenon in grasslands, may strongly regulate the response of soil respiration and its components to grassland management, but the regulatory mechanism remains unclear. We conducted a 3-year experiment by grassland management (fencing and grazing) and flooding conditions (no flooding (NF), short-term flooding (STF) and long-term flooding (LTF)) to study their effects on Rs and its components in a meadow steppe in the Hui River basin of Hulunbuir. We found differences in the patterns of Rs and its components under grassland management and flooding conditions. In 2021-2023, the temporal trends of Rs, heterotrophic respiration (Rh) and autotrophic respiration (Ra) were generally consistent, with peaks occurring on days 190-220, and the peaks of grazing were higher than that of fencing. In NF, Rs of grazed grassland was significantly higher than that of fenced grassland in 2021-2022 (p < 0.05). In STF and LTF, there was no significant difference in Rs between fenced and grazed grassland (p > 0.05). The dependence of Rs on soil temperature (ST) decreased with increasing flooding duration, and the dependence of Rs on ST of grazed grassland was higher than fenced grassland under NF and STF, but there was no difference between fenced grassland and grazed grassland under LTF. In addition, Rh was more sensitive to ST than Ra. This may be due to the different pathways of ST effects on Rs under grazing in different flooding conditions. Our study indicates that the effect of flooding on Rs is the key to the rational use of grassland under future climate change. To reduce regional carbon emissions, we recommend grazing on flooding grassland and fencing on no-flooding grassland.

Restoring long-lasting midface volume in the Asian face with a hyaluronic acid filler: A randomized controlled multicenter study.

BACKGROUND: Hyaluronic acid (HA) filler treatment is a minimally-invasive alternative to surgery to volumize the cheeks. HAVOL (Restylane® Volyme) is a flexible HA filler suited to contouring and volumizing the midface. METHODS: This randomized, evaluator-blinded, no-treatment controlled study evaluated effectiveness and safety of HAVOL for correction of midface volume deficit and midface contour deficiency in Chinese subjects. In total 111 subjects were randomized to HAVOL and 37 to no treatment (control). The primary endpoint was response, on the blinded evaluator-assessed Medicis Midface Volume Scale (MMVS), at 6 months after last injection for the treatment group and 6 months after randomization for controls, where response was defined as ≥1-point improvement from baseline on both sides of the face. RESULTS: HAVOL was superior to no treatment at 6 months, meeting the primary objective: 76% versus 8% MMVS responders, a difference of 68% (CI: 55.7%-79.4%, p < 0.0001). These effects were sustained in 51% at 12 months after last injection. A majority (≥96%) had improved aesthetic appearance of midface fullness at Month 1 (using the Global Aesthetic Improvement Scale [GAIS]), effects which remained in ≥80% up to 12 months. Volume change captured by 3D photography increased after 1 month to 3.6 mL (close to the total injected volume of 3.4 mL), and remained stable through 12 months. Over 97% reported satisfaction with results after treatment with HAVOL . Additionally, HAVOL was well tolerated, with no unanticipated related adverse events. CONCLUSIONS: This study showed that HAVOL is effective and well tolerated for midface treatment in a Chinese population.

Identify CTBP1-DT as an immunological biomarker that promotes lipid synthesis and apoptosis resistance in KIRC.

Recently, mounting evidence has highlighted the essential function of the C-terminal binding protein-1 divergent transcript (CTBP1-DT) in malignancies. However, its role in kidney renal clear cell carcinoma (KIRC) remains largely unknown. Our study aimed to identify the potential function of CTBP1-DT in KIRC. RT-qPCR, Kaplan-Meier survival analysis, Cox regression analysis, and nomogram analysis were utilized to determine the expression and effects of CTBP1-DT on survival. The subcellular localization of CTBP1-DT was determined using RNA fluorescence in situ hybridization (FISH). To investigate the functions of CTBP1-DT in regulating KIRC cell proliferation, migration, invasion, lipid synthesis, and apoptosis, we conducted CCK8, EdU, Transwell, and Oil Red O staining and cell apoptosis staining assays. The relationships between CTBP1-DT and the tumor microenvironment were investigated with multiple bioinformatics analysis algorithms and databases, including CYBERSORT, TIMER2, Spearman correlation test, tumor mutation burden (TMB), microsatellite instability (MSI), and immunophenoscore (IPS). According to our results, CTBP1-DT is a lncRNA located in the nucleus that is significantly upregulated in KIRC and is correlated with better clinical outcomes. Downregulating CTBP1-DT inhibited cell viability, migration, invasion, and lipid synthesis but triggered cell apoptosis. Additionally, we explored the potential effect of CTBP1-DT in regulating immune cell infiltration in KIRC and other malignancies. Furthermore, CTBP1-DT could be used to predict the effectiveness of targeted drugs and immune checkpoint inhibitors. In conclusion, we identified CTBP1-DT as a potential immunological biomarker and discovered the potential role of CTBP1-DT in regulating lipid synthesis and apoptosis resistance.

Risk factors for hemorrhage in patients with long-term aspirin therapy undergoing emergency external ventricular drainage/intracranial pressure probe placement.

Background: Studies have been inconclusive on the risk for hemorrhage in patients with a history of aspirin use who underwent emergency external ventricular drainage (EVD)/intracranial pressure (ICP) probe placement. The aim of this study was to explore hemorrhage-related risk factors in order to reduce the risk for hemorrhage in these patients. Methods: Between July 2014 and July 2020, patients were retrospectively divided into EVD/ICP-related hemorrhage and non-hemorrhage groups. The collected data included age, gender, major diagnosis, medical history, imaging examinations, conventional coagulation test data, thromboelastography with platelet mapping (TEG-PM), surgical procedures and discharge conditions. Results: In total 94 patients, 21 in the hemorrhage group (15 males, 6 females) and 73 in the non-hemorrhage group (52 males, 21 females) were included. The majority of hemorrhages were recorded in EVD patients (19/21; 90.5%). Platelet AA pathway inhibition rate of ≥75% (sensitivity: 79.45% specificity: 52.38%) (P = 0.014) and SBP ≥125 mmHg (P = 0.006) were significantly related to hemorrhage. When the platelet AA pathway inhibition rate was ≥75% and the during-procedure SBP was ≥125 mmHg, the hemorrhage rate was significantly higher (83.3%) than with SBP <125 mmHg (6.7%) (P < 0.001). When the inhibition rate was <75%, there were no significant differences in the hemorrhage rates between the during-procedure SBP ≥125 mmHg group (17.2%) and the SBP <125 mmHg group (13.2%) (P > 0.05). Multivariate logistic regression analysis revealed that a platelet AA pathway inhibition rate ≥75% (OR = 5.183, 95% CI: 1.683-15.960) and during-procedure SBP ≥125 mmHg (OR = 4.609, 95% CI: 1.466-14.484) were independent risk factors for EVD/ICP-related hemorrhage. Conclusion: Patients with long-term aspirin therapy, a platelet AA pathway inhibition rate ≥75% and during-procedure SBP ≥125 mmHg had a significantly higher risk of hemorrhage, which could be reduced by adjusting the SBP to <125 mmHg.

A Photo-induced Cross-Linking Enhanced A and B Combined Multi-Functional Spray Hydrogel Instantly Protects and Promotes of Irregular Dynamic Wound Healing.

Wounds in harsh environments can face long-term inflammation and persistent infection, which can slow healing. Wound spray is a product that can be rapidly applied to large and irregularly dynamic wounds, and can quickly form a protective film in situ to inhibit external environmental infection. In this study, a biodegradable A and B combined multi-functional spray hydrogel is developed with methacrylate-modified chitosan (CSMA1st ) and ferulic acid (FA) as type A raw materials and oxidized Bletilla striata polysaccharide (OBSP) as type B raw materials. The precursor CSMA1st -FA/OBSP (CSOB-FA1st ) hydrogel is formed by the self-cross-linking of dynamic Schiff base bonds, the CSMA-FA/OBSP (CSOB-FA) hydrogel is formed quickly after UV-vis light, so that the hydrogel fits with the wound. Rapid spraying and curing provide sufficient flexibility and rapidity for wounds and the hydrogel has good injectability, adhesive, and mechanical strength. In rats and miniature pigs, the A and B combined spray hydrogel can shrink wounds and promote healing of infected wounds, and promote the enrichment of fibrocyte populations. Therefore, the multifunctional spray hydrogel combined with A and B can protect irregular dynamic wounds, prevent wound infection and secondary injury, and be used for safe and effective wound treatment, which has a good prospect for development.

Chemical Constituents from the Heartwood of Solanum Verbascifolium L. And Their Anti-Inflammatory Activities Combined Network Pharmacology.

Phytochemical studies on 95 % ethanol extract of the heartwood of Solanum verbascifolium L. resulted in the isolation of one new amide derivative (1), and 21 known phenylpropanoids compounds. The structures were characterized by spectral analysis and high-resolution mass spectrometric analysis. The anti-inflammatory activity of amide compounds 1-4 and 6-9 by investigating their impact on the release of nitric oxide (NO) in MH-S cells. Our findings unveiled significant inhibitory effects on NO secretion. Compound 1 exhibited robust dose-dependent suppression, with pronounced inhibition observed at both 20 µM (P<0.01) and 40 µM (P<0.01). Furthermore, compound 9 demonstrated noteworthy inhibitory effects at 40 µM (P<0.01). Similarly, compounds 3 and 4 displayed substantial inhibition of NO secretion at the same concentration, although the significance level was slightly lower (P<0.05). It is expected that there is a substantial association between the anti-inflammatory activities of amides and their targets, specifically PTGS2, by combining network pharmacology and molecular docking techniques. This discovery emphasizes amides' potential as an interesting subject for additional study in the realm of anti-inflammatory medications.

STAMENLESS1 activates SUPERWOMAN 1 and FLORAL ORGAN NUMBER 1 to control floral organ identities and meristem fate in rice.

Floral patterns are unique to rice and contribute significantly to its reproductive success. SL1 encodes a C2H2 transcription factor that plays a critical role in flower development in rice, but the molecular mechanism regulated by it remains poorly understood. Here, we describe interactions of the SL1 with floral homeotic genes, SPW1, and DL in specifying floral organ identities and floral meristem fate. First, the sl1 spw1 double mutant exhibited a stamen-to-pistil transition similar to that of sl1, spw1, suggesting that SL1 and SPW1 may located in the same pathway regulating stamen development. Expression analysis revealed that SL1 is located upstream of SPW1 to maintain its high level of expression and that SPW1, in turn, activates the B-class genes OsMADS2 and OsMADS4 to suppress DL expression indirectly. Secondly, sl1 dl displayed a severe loss of floral meristem determinacy and produced amorphous tissues in the third/fourth whorl. Expression analysis revealed that the meristem identity gene OSH1 was ectopically expressed in sl1 dl in the fourth whorl, suggesting that SL1 and DL synergistically terminate the floral meristem fate. Another meristem identity gene, FON1, was significantly decreased in expression in sl1 background mutants, suggesting that SL1 may directly activate its expression to regulate floral meristem fate. Finally, molecular evidence supported the direct genomic binding of SL1 to SPW1 and FON1 and the subsequent activation of their expression. In conclusion, we present a model to illustrate the roles of SL1, SPW1, and DL in floral organ specification and regulation of floral meristem fate in rice.

Considerations and anesthetic management of a patient with giant right atrial myxoma: A case report and literature review.

BACKGROUND: Myxoma is a common type of primary cardiac tumor. However, there are few researches to illustrate challenge of safely inducing anesthesia in a patient with a giant right atrial myxoma at moderate altitude. PATIENT CONCERNS AND DIAGNOSES: A 54-year-old female patient lived in a city with an average altitude of 1932 m with scheduled surgical treatment for giant right atrial myxoma, prompting discussions on appropriate anesthesia modalities given her prolonged residence at moderate altitude. METHODS AND RESULTS: Considering the potential impact of moderate altitude on perioperative management, this study emphasizes the necessity of adequate volume preload therapy and the utility of transthoracic echocardiography or transesophageal echocardiography to prevent hemodynamic compromise. Furthermore, it highlights the unique consideration that, post-tumor removal, hypotension may not necessarily lead to decreased oxygen saturation in these patients. CONCLUSION: This case underscores the importance of avoiding hypotension, as pre-tumor resection blood pressure maintenance primarily determines blood oxygen concentration. Additionally, it sheds light on the intriguing observation that post-tumor removal hypotension may not result in decreased oxygen saturation. These findings have significant implications for the perioperative care of patients with giant right atrial myxoma at moderate altitudes.

Temperature, pH, and oxygen availability contributed to the functional differentiation of ancient Nitrososphaeria.

Ammonia-oxidizing Nitrososphaeria are among the most abundant archaea on Earth and have profound impacts on the biogeochemical cycles of carbon and nitrogen. In contrast to these well-studied ammonia-oxidizing archaea (AOA), deep-branching non-AOA within this class remain poorly characterized because of a low number of genome representatives. Here, we reconstructed 128 Nitrososphaeria metagenome-assembled genomes from acid mine drainage and hot spring sediment metagenomes. Comparative genomics revealed that extant non-AOA are functionally diverse, with capacity for carbon fixation, carbon monoxide oxidation, methanogenesis, and respiratory pathways including oxygen, nitrate, sulfur, or sulfate, as potential terminal electron acceptors. Despite their diverse anaerobic pathways, evolutionary history inference suggested that the common ancestor of Nitrososphaeria was likely an aerobic thermophile. We further surmise that the functional differentiation of Nitrososphaeria was primarily shaped by oxygen, pH, and temperature, with the acquisition of pathways for carbon, nitrogen, and sulfur metabolism. Our study provides a more holistic and less biased understanding of the diversity, ecology, and deep evolution of the globally abundant Nitrososphaeria.

Trans-Defect Underlay Watertight Duraplasty for Traumatic Anterior Skull Base Dural Defect: Technical Report.

BACKGROUND: Watertight duraplasty is essential for surgical management of traumatic anterior skull base (ASB) dural defect but challenging in the deep and narrow operative corridor. Here, the authors report a trans-defect underlay watertight duraplasty (TDUWD) technique for traumatic ASB dural defect. METHODS: TDUWD was performed by inserting a free pericranium graft under the dural defect. The diameter of the pericranium graft was larger than the dural defect. The pericranium graft was sutured to the dural defect watertightly in an "inside-to-outside" direction, with the needle not penetrating the inner layer of pericranium graft. The pedicled pericranium flap was used as a second layer of reconstruction. The characteristics, complications, and outcomes of patients who received TDUWD are reported. RESULTS: A total of 29 patients received TDUWD. Immediate postoperative cessation of cerebrospinal fluid (CSF) leak occurred in 28 patients. One patient recovered after lumber drainage. No patient needed a second operation or reported delayed recurrence of CSF leak. No complication related to the surgical technique was observed. CONCLUSIONS: Use of TDUWD for traumatic ASB dural defect results in an immediate, 1-stage, and definitive correction of CSF leak and seems to be simple, safe, and reliable for large and deeply located dural defects.

Coloration differences in three Camellia reticulata Lindl. cultivars: 'Tongzimian', 'Shizitou' and 'Damanao'.

Camellia reticulata Lindl., also known as Yunnan Camellia, is an important ornamental plant in China, especially for its large and stunning flowers. A comprehensive understanding of their coloration mechanisms can aid breeders in developing new cultivars and improving their ornamental value; however, it is still unclear in Yunnan Camellia, especially in mixed-color flowers. In this study, we conducted metabolic and transcriptomic comparison analyses to investigate the coloration differences in three Yunnan Camellia cultivars: C. reticulata 'Shizitou' (SZT), C. reticulata 'Damanao' (MN), and C. reticulata 'Tongzimian' (TZM). Our results revealed that the initial flowering stage may play a critical role in the color change of MN. Metabolome analysis demonstrated that cyanidin was the primary anthocyanin in SZT and MN's red region, while its content was low in TZM and MN's white region. According to the transcriptome analysis, the anthocyanins biosynthesis pathway was reconstructed in Yunnan Camellia, and the low expression of CHS was detected in TZM and MN's white region, while ANR maintained a high expression level, which may lead to the low content of cyanidin in them. Transcription factors MYBs, bHLH, and bZIP may play a key role in regulating anthocyanin-structural genes. The co-expression analysis showed that the meristem tissue may play a crucial role in the formation of the mixed white-red color in MN. Our study enriched the genetic basis of flower coloration differences in Yunnan Camellia which will be a valuable genomic resource to understanding the biology of coloration formation and for breeding the Camellia cultivars.

Astrocytes and Memory: Implications for the Treatment of Memory-related Disorders.

Memory refers to the imprint accumulated in the brain by life experiences and represents the basis for humans to engage in advanced psychological activities such as thinking and imagination. Previously, research activities focused on memory have always targeted neurons. However, in addition to neurons, astrocytes are also involved in the encoding, consolidation, and extinction of memory. In particular, astrocytes are known to affect the recruitment and function of neurons at the level of local synapses and brain networks. Moreover, the involvement of astrocytes in memory and memory-related disorders, especially in Alzheimer's disease (AD) and post-traumatic stress disorder (PTSD), has been investigated extensively. In this review, we describe the unique contributions of astrocytes to synaptic plasticity and neuronal networks and discuss the role of astrocytes in different types of memory processing. In addition, we also explore the roles of astrocytes in the pathogenesis of memory-related disorders, such as AD, brain aging, PTSD and addiction, thus suggesting that targeting astrocytes may represent a potential strategy to treat memory-related neurological diseases. In conclusion, this review emphasizes that thinking from the perspective of astrocytes will provide new ideas for the diagnosis and therapy of memory-related neurological disorders.

Mucoadhesive and thermosensitive Bletilla striata polysaccharide/chitosan hydrogel loaded nanoparticles for rectal drug delivery in ulcerative colitis.

Ulcerative colitis (UC) is a chronic disease with diffuse mucosal inflammation limited to the colon. A topical drug delivery system that could be facilely performed and efficiently retained at colon are attractive for clinical ulcerative colitis treatment. Herein, a novel platform for rectal administration of thermosensitive hydrogel co-loaded with nanoparticles to treat ulcerative colitis was developed. Thiolated-hyaluronic acid was synthesized, and prepared nanoparticles with zein and Puerarin. And the Bletilla striata polysaccharide with colonic mucosa repair effect was oxidized, and mixed with chitosan and ß-sodium glycerophosphate to prepare thermosensitive hydrogel. Thermosensitive hydrogels were combined with nanoparticles to investigate their mucosal adhesion, retention, and permeability, as well as their therapeutic effects on ulcerative colitis. Thiolated-hyaluronic acid nanoparticles had good stability, and could be quickly converted into hydrogel at body temperature when combined with thermosensitive hydrogel. The nanoparticles-loaded thermosensitive hydrogel also was excellent at mucosal penetration, enhancing the retention time of drugs in colon, and effectively controlling drug release. In vivo ulcerative colitis treatment revealed that the nanoparticles-loaded hydrogel significantly repaired the colonic mucosa and inhibit colonic inflammation. Therefore, the thermosensitive hydrogel co-loaded nanoparticles will have a promising application in effective treatment of ulcerative colitis by topical administration.