A review: Mechanisms and molecular pathways of signaling lymphocytic activation molecule family 3 (SLAMF3) in immune modulation and therapeutic prospects.

The signaling lymphocytic activation molecule (SLAM) family participates in the modulation of various innate and adaptive immune responses. SLAM family (SLAMF) receptors include nine transmembrane glycoproteins, of which SLAMF3 (also known as CD229 or Ly9) has important roles in the modulation of immune responses, from the fundamental activation and suppression of immune cells to the regulation of intricate immune networks. SLAMF3 is mainly expressed in immune cells, such as T, B, and natural killer cells. It has a unique molecular structure, including four immunoglobulin-like domains in the extracellular domain and two immunoreceptor tyrosine-based signaling motifs in the intracellular structural domains. These unique structures have important implications for protein functioning. SLAMF3 is involved in pathogenesis of various disease, particularly autoimmune diseases and cancer. However, despite its potential clinical significance, a comprehensive overview of the current paradigm of SLAMF3 research is lacking. This review summarizes the structure, functional mechanisms, and therapeutic implications of SLAMF3. Our findings highlight the significance of SLAMF3 in both physiological and pathological contexts, and underline its dual role in autoimmunity and malignancies, and including disease progression and prognosis. The review also proposes that future studies on SLAMF3 should explore its context-specific inhibitory and stimulatory effects, expand on its potential in disease mapping, investigate related signaling pathways, and explore its value as a drug target. Research in these areas related to SLAMF3 can provide more precise directions for future therapeutic strategies.

Coexistence of giant Goos-Hänchen shift and high reflectance in Dirac semimetal based multilayered structure.

Bulk Dirac semimetals (BDSs) possess Fermi energy dependent optical parameters, providing unprecedented opportunities for the study of the controllable Goos-Hänchen (GH) shift. However, the enhancement of GH shifts often comes at the cost of the reflectance in the previous BDS-based structures, which hinders their practical application. In this work, we theoretically present the investigation of the GH shift in a multilayered structure composed of one BDS film and a symmetric one-dimensional photonic crystal (1DPC) with a defect layer. We demonstrate that this well-designed structure supports a large GH shift at the specific working wavelength, whose magnitude can be enhanced up to 3883 times the incident wavelength. In particular, such an enhanced GH shift achieved in this structure is associated with high reflectance (0.94) and these remarkable features can be attributed to the sharp change in the reflective phase and the destructive interference that occurs between the simultaneously excited optical Tamm state (OTS) at the BDS/1DPC interface and the defect state at the 1D defected PC. In addition, we also explore the manipulation of the GH shift by adjusting the Fermi energy of the BDS as well as the geometrical parameter of the multilayered structure. Our results provide a new approach for realizing an enhanced and controllable GH shift in a BDS-based multilayered structure, which endows it with promising prospects for application in optical sensors, optical detectors and beam controllers.

SIRT1 activation ameliorates rhesus monkey liver fibrosis by inhibiting the TGF-ß/smad signaling pathway.

TGF-ß/Smad signaling pathway plays an important role in the pathogenesis and progression of liver fibrosis. Silent information regulator 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+) dependent enzyme and responsible for deacetylating the proteins. Increasing numbers of reports have shown that the molecular mechanism of SIRT1 as an effective therapeutic target for liver fibrosis but the transformation is not very clear. In the present study, liver fibrotic tissues were screened by staining with Masson, hematoxylin-eosin staining (H&E) and Immunohistochemistry (IHC) for histopathological observation from the liver biopsy of seventy-seven rhesus monkey, which fixed with 4% paraformaldehyde (PFA) after treatment with high-fat diet (HFD) for two years. And the liver function was further determined by serum biochemical tests. The mRNA levels and protein expression of rat hepatic stellate (HSC-T6) cells were determined after treatment with Resveratrol (RSV) and Nicotinamide (NAM), respectively. The results showed that with the increasing of hepatic fibrosis in rhesus monkeys, the liver function impaired, and the transforming growth factor-ß1 (TGF-ß1), p-Smad3 (p-Smad3) and alpha-smooth muscle actin (α-SMA) was up-regulated, while SIRT1 and Smad7 were down-regulated. Moreover, when stimulated the HSC-T6 with RSV to activate SIRT1 for 6, 12, and 24 h, the results showed that RSV promoted the expression of smad7, while the expression of TGF-ß1, p-Smad3 and α-SMA were inhibited. In contrast, when the cells stimulated with NAM to inhibit SIRT1 for 6, 12, and 24 h, the Smad7 expression was decreased, while TGF-ß1, p-Smad3, and α-SMA expressions were increased. These results indicate that SIRT1 acts as an important protective factor for liver fibrosis, which may be attributed to inhibiting the signaling pathway of TGF-ß/Smad in hepatic fibrosis of the rhesus monkey.

Investigation the mechanism of iron overload-induced colonic inflammation following ferric citrate exposure.

Iron overload occurs due to excessive iron intake compared to the body's demand, leading to iron deposition and impairment of multiple organ functions. Our previous study demonstrated that chronic oral administration of ferric citrate (FC) caused colonic inflammatory injury. However, the precise mechanism underlying this inflammatory response remains unclear. The current study aims to investigate the mechanism by which iron overload induced by FC exposure leads to colonic inflammation. To accomplish this, mice were orally exposed to three different concentrations of FC (71 mg/kg/bw (L), 143 mg/kg/bw (M) and 286 mg/kg/bw (H)) for continuous 16 weeks, with the control group receiving ultrapure water (C). Exposure to FC caused disturbances in the excretory system, altered colonic flora alpha diversity, and enriched pathogenic bacteria, such as Mucispirillum, Helicobacter, Desulfovibrio, and Shigella. These changes led to structural disorders of the colonic flora and an inflammatory response phenotype characterized by inflammatory cells infiltration, atrophy of intestinal glands, and irregular thickening of the intestinal wall. Mechanistic studies revealed that FC-exposure activated the NF-κB signaling pathway by up-regulating TLR4, MyD88, and NF-κB mRNA levels and protein expression. This activation resulted in increased production of pro-inflammatory cytokines, further contributing to the colonic inflammation. Additionally, in vitro experiments in SW480 cells confirmed the activation of NF-κB signaling pathway by FC exposure, consistent with the in vivo findings. The significance of this study lies in its elucidation of the mechanism by which iron overload caused by FC exposure leads to colonic inflammation. By identifying the role of pathogenic bacteria and the NF-κB signaling pathway, this study could potentially offer a crucial theoretical foundation for the research on iron overload, as well as provide valuable insights for clinical iron supplementation.

Hybrid surgery for the treatment of lumbar spine surgery complicated with iliac artery pseudoaneurysm, arteriovenous fistula, and lower limb artery embolism: A rare case report.

INTRODUCTION AND IMPORTANCE: Vascular injuries during lumbar surgery are rare, but complications such as false aneurysm of the iliac artery, arteriovenous fistula, and lower limb artery embolism are even rarer. These complications can easily be misdiagnosed and result in the inability to choose an appropriate surgical approach, leading to serious consequences. CASE PRESENTATION: A 36-year-old male patient experienced swelling in both lower limbs, along with numbness, coldness, and dysfunction in his right lower limb, after undergoing a "posterior lumbar discectomy" surgery. On the 20th day post-surgery, a clear diagnosis was established through CTV: 1) Right common iliac artery injury with pseudoaneurysm formation; 2) Right iliac arteriovenous fistula; 3) Right popliteal artery embolism. The patient underwent hybrid surgery to address multiple complications simultaneously and made a good recovery after the procedure. CLINICAL DISCUSSION: Rarely, lumbar spine surgery can concurrently lead to conditions such as pseudoaneurysm, arteriovenous fistula, and lower limb artery embolism. Due to atypical symptoms and signs, it is often misdiagnosed. Hybrid surgery involves incising the femoral artery, using a thrombectomy catheter to remove clots from the iliac artery above and the popliteal artery below, and then re-implanting a covered stent to treat pseudoaneurysm and arteriovenous fistula. CONCLUSION: With a solid clinical knowledge, one can make a timely diagnosis and choose an appropriate surgical method to intervene, thereby improving the prognosis. Hybrid surgery combines the minimally invasive and safe effects of endovascular techniques with the precise effects of open surgery, and it also allows for the simultaneous treatment of multiple comorbidities.

Reactivating PTEN to impair glioma stem cells by inhibiting cytosolic iron-sulfur assembly.

Glioblastoma, the most lethal primary brain tumor, harbors glioma stem cells (GSCs) that not only initiate and maintain malignant phenotypes but also enhance therapeutic resistance. Although frequently mutated in glioblastomas, the function and regulation of PTEN in PTEN-intact GSCs are unknown. Here, we found that PTEN directly interacted with MMS19 and competitively disrupted MMS19-based cytosolic iron-sulfur (Fe-S) cluster assembly (CIA) machinery in differentiated glioma cells. PTEN was specifically succinated at cysteine (C) 211 in GSCs compared with matched differentiated glioma cells. Isotope tracing coupled with mass spectrometry analysis confirmed that fumarate, generated by adenylosuccinate lyase (ADSL) in the de novo purine synthesis pathway that is highly activated in GSCs, promoted PTEN C211 succination. This modification abrogated the interaction between PTEN and MMS19, reactivating the CIA machinery pathway in GSCs. Functionally, inhibiting PTEN C211 succination by reexpressing a PTEN C211S mutant, depleting ADSL by shRNAs, or consuming fumarate by the US Food and Drug Administration-approved prescription drug N-acetylcysteine (NAC) impaired GSC maintenance. Reexpressing PTEN C211S or treating with NAC sensitized GSC-derived brain tumors to temozolomide and irradiation, the standard-of-care treatments for patients with glioblastoma, by slowing CIA machinery-mediated DNA damage repair. These findings reveal an immediately practicable strategy to target GSCs to treat glioblastoma by combination therapy with repurposed NAC.

Selective recovery of metals in spent batteries by electrochemical precipitation to cathode material for sodium-ion batteries.

The recycling of key components in waste lithium-ion batteries (LIBs) is an important route to make up for the shortage of battery materials. Metal separation and purification is an important step. It is of great significance to propose an efficient and green separation technology. In this paper, an electrochemical precipitation method was applied to metal separation from spent LiNi0.5Mn1.5O4 cathode material. The Li and metal elements were effective separated and the precipitates were then used as precursor to synthesize high-performance R-O3-NaNFM cathode material for sodium-ion batteries. The R-O3-NaNFM exhibits excellent electrochemical cycling stability. The capacity retains 71.3 mAh g-1 after a long-term cycling of 200 times at 1 C. This method offers a referable strategy of the recycling for the waste cathode material in spent LIBs.

PGC-1α-Coordinated Hypothalamic Antioxidant Defense Is Linked to SP1-LanCL1 Axis during High-Fat-Diet-Induced Obesity in Male Mice.

High-fat-diet (HFD)-induced obesity parallels hypothalamic inflammation and oxidative stress, but the correlations between them are not well-defined. Here, with mouse models targeting the antioxidant gene LanCL1 in the hypothalamus, we demonstrate that impaired hypothalamic antioxidant defense aggravates HFD-induced hypothalamic inflammation and obesity progress, and these could be improved in mice with elevated hypothalamic antioxidant defense. We also show that peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a critical transcriptional coactivator, is implicated in regulating hypothalamic LanCL1 transcription, in collaboration with SP1 through a direct interaction, in response to HFD-induced palmitic acid (PA) accumulation. According to our results, when exposed to HFD, mice undergo a process of overwhelming hypothalamic antioxidant defense; short-time HFD exposure induces ROS production to activate PGC-1α and elevate LanCL1-mediated antioxidant defense, while long-time exposure promotes ubiquitin-mediated PGC-1α degradation and suppresses LanCL1 expression. Our findings show the critical importance of the hypothalamic PGC-1α-SP1-LanCL1 axis in regulating HFD-induced obesity, and provide new insights describing the correlations of hypothalamic inflammation and oxidative stress during this process.

Current Status of Novel Multifunctional Targeted Pt(IV) Compounds and Their Reductive Release Properties.

Platinum-based drugs are widely used in chemotherapy for various types of cancer and are considered crucial. Tetravalent platinum (Pt(IV)) compounds have gained significant attention and have been extensively researched among these drugs. Traditionally, Pt(IV) compounds are reduced to divalent platinum (Pt(II)) after entering cells, causing DNA lesions and exhibiting their anti-tumor effect. However, the available evidence indicates that some Pt(IV) derivatives may differ from the traditional mechanism and exert their anti-tumor effect through their overall structure. This review primarily focuses on the existing literature regarding targeted Pt(II) and Pt(IV) compounds, with a specific emphasis on their in vivo mode of action and the properties of reduction release in multifunctional Pt(IV) compounds. This review provides a comprehensive summary of the design and synthesis strategies employed for Pt(II) derivatives that selectively target various enzymes (glucose receptor, folate, telomerase, etc.) or substances (mitochondria, oleic acid, etc.). Furthermore, it thoroughly examines and summarizes the rational design, anti-tumor mechanism of action, and reductive release capacity of novel multifunctional Pt(IV) compounds, such as those targeting p53-MDM2, COX-2, lipid metabolism, dual drugs, and drug delivery systems. Finally, this review aims to provide theoretical support for the rational design and development of new targeted Pt(IV) compounds.

Suppression of neutrophil extracellular traps is responsible for the amelioration of chemotherapeutic intestinal injury by the natural compound PEITC.

Intestinal injury is one of the most debilitating side effects of many chemotherapeutic agents, such as irinotecan hydrochloride (CPT-11). Accumulating evidence indicates that neutrophil extracellular traps (NETs) play a critical role in the symptoms of ischemia and inflammation related to chemotherapy. The present study investigated the effects and possible mechanisms of phenethyl isothiocyanate (PEITC) in inhibiting NETs and alleviating chemotherapeutic intestinal injury. CPT-11 induced robust neutrophil activation, as evidenced by increased NETs release, intestinal ischemia, and mRNA expression of inflammatory factors. PEITC prolonged the clotting time of chemotherapeutic mice, improved the intestinal microcirculation, inhibited the expression of inflammatory factors, and protected the tight junctions of the intestinal epithelium. Both in vivo and in vitro experiments revealed that PEITC directly suppresses CPT-11-induced NETs damage to intestinal cells, resulting in significant attenuation of epithelial injury. These results suggest that PEITC may be a novel agent to relieve chemotherapeutic intestinal injury via inhibition of NETs.

An open-cage bis[60]fulleroid as an electron transport material for tin halide perovskite solar cells.

An open-cage bis[60]fulleroid (OC) was applied as an electron transport material (ETM) in tin (Sn) halide perovskite solar cells (PSCs). Due to the reduced offset between the energy levels of Sn-based perovskites and ETMs, the power conversion efficiency (PCE) of Sn-based PSCs with OC reached 9.6% with an open-circuit voltage (VOC) of 0.72 V. Additionally, OC exhibited superior thermal stability and provided 75% of the material without decomposition after vacuum deposition. The PSC using vacuum-deposited OC as the ETM could afford a PCE of 7.6%, which is a big leap forward compared with previous results using vacuum-deposited fullerene derivatives as ETMs.

B cell development and antibody responses in human immune system mice: current status and future perspective.

Humanized immune system (HIS) mice have been developed and used as a small surrogate model to study human immune function under normal or disease conditions. Although variations are found between models, most HIS mice show robust human T cell responses. However, there has been unsuccessful in constructing HIS mice that produce high-affinity human antibodies, primarily due to defects in terminal B cell differentiation, antibody affinity maturation, and development of primary follicles and germinal centers. In this review, we elaborate on the current knowledge about and previous attempts to improve human B cell development in HIS mice, and propose a potential strategy for constructing HIS mice with improved humoral immunity by transplantation of human follicular dendritic cells (FDCs) to facilitate the development of secondary follicles.

Exploration of the prognostic effect of costimulatory genes in bladder cancer.

BACKGROUND: A prognostic model of bladder cancer was constructed based on costimulatory molecules, and its stability and accuracy were verified in different datasets. METHOD: The expression profile of bladder cancer RNA and the corresponding clinical data in The Cancer Genome Atlas (TCGA) database were analyzed employing computational biology, and a prognostic model was constructed for costimulating molecule-related genes. The model was applied in GSE160693, GSE176307, Xiangya_Cohort, GSE13507, GSE19423, GSE31684, GSE32894, GSE48075, GSE69795 and GSE70691 in TCGA dataset and Gene Expression Omnibus database. The role of costimulating molecules in bladder cancer tumor subtypes was also explored. By consistent cluster analysis, bladder cancer in the TCGA dataset was categorized into two subtypes: C1 and C2. The C1 subtype exhibited a poor prognosis, high levels of immune cell infiltration and significant enrichment of natural killer cells, T cells and dendritic cells in the C1 subtype. In addition, the ImmuneScore calculated by the ESTIMATE algorithm differed greatly between the two subtypes, and the ImmuneScore of the C1 subtype was greater than the C2 subtype in a significant manner. RESULTS: This study also assessed the relationship between costimulating molecules and immunotherapy response. The high-risk group responded poorly to immunotherapy, with significant differences in the amount of most immune cells between the two groups. Further, three indices of the ESTIMATE algorithm and 22 immune cells of the CIBERSORT algorithm were significantly correlated with risk values. These findings suggest the potential value of costimulating molecules in predicting immunotherapy response. CONCLUSION: A costimulatory molecule-based prognostic model for bladder cancer was established and validated across multiple datasets. This model introduces a novel mode for tailoring treatments to each individual with bladder cancer, and offers valuable insights for informed clinical choices. Simultaneously, this research also delved into the significance of costimulating molecules within distinct bladder cancer subtypes, shedding novel insights into improving immunotherapy strategies for the treatment of bladder cancer.

Anchoring and catalytic insights into bilayer C4N3 material for lithium-selenium batteries: a first-principles study.

In the present work, a theoretical design for the viability of bilayer C4N3 (bi-C4N3) as a promising host material for Li-Se battery was conducted utilizing first-principles calculations. The AA- and AB-stacking configurations of bilayer C4N3 can effectively inhibit the shuttling of high-order polyselenides through the synergistic effect of physical confinement and strong Li-N bonds. Compared to conventional electrolytes, the AA- and AB-stacking bilayer C4N3 demonstrate enhanced adsorption capabilities for the polyselenides. The anchored structures of Se8 or Li2Sen (n = 1, 2, 4, 6, 8) molecules within the bilayer C4N3 exhibit high electrical conductivities, which are beneficial for enhancing the electrochemical performance. The catalytic effects of AA- and AB-stacking bilayer C4N3 were investigated by the reduction of Se8 and the energy barrier associated with the decomposition of Li2Se. The AA- and AB-stacking bilayer C4N3 can significantly decrease the activation barrier and promote the decomposition of Li2Se. The mean square displacement (MSD) curves reveal the pronounceably sluggish Li-ions diffusions in polyselenides within the AA- and AB-stacking bilayer C4N3, which in turn demonstrates the notable prospects in mitigating the shuttle effect.

Scaffold-based non-viral CRISPR delivery platform for efficient and prolonged gene activation to accelerate tissue regeneration.

Clustered regularly interspaced short palindromic repeat activation (CRISPRa) technology has emerged as a precise genome editing tool for activating endogenous transgene expression. While it holds promise for precise cell modification, its translation into tissue engineering has been hampered by biosafety concerns and suboptimal delivery methods. To address these challenges, we have developed a CRISPRa non-viral gene delivery platform by immobilizing non-viral CRISPRa complexes into a biocompatible hydrogel/nanofiber (Gel/NF) composite scaffold. The Gel/NF scaffold facilitates the controlled and sustained release of CRISPRa complexes and also promotes cell recruitment to the scaffold for efficient and localized transfection. As a proof of concept, we employed this CRISPRa delivery platform to activate the vascular endothelial growth factor (VEGF) gene in a rat model with full-thickness skin defects. Our results demonstrate sustained upregulation of VEGF expression even at 21 days post-implantation, resulting in enhanced angiogenesis and improved skin regeneration. These findings underscore the potential of the Gel/NF scaffold-based CRISPRa delivery platform as an efficient and durable strategy for gene activation, offering promising prospects for tissue regeneration. STATEMENT OF SIGNIFICANCE: Translation of clustered regularly interspaced short palindromic repeat activation (CRISPRa) therapy to tissue engineering is limited by biosafety concerns and unsatisfactory delivery strategy. To solve this issue, we have developed a CRISPRa non-viral gene delivery platform by immobilizing non-viral CRISPRa complexes into a biocompatible hydrogel/nanofiber (Gel/NF) composite scaffold. This scaffold enables controlled and sustained release of CRISPRa and can induce cell recruitment for localized transfection. As a proof of concept, we activated vascular endothelial growth factor (VEGF) in a rat model with full-thickness skin defects, leading to sustained upregulation of VEGF expression, enhanced angiogenesis and improved skin regeneration in vivo. These findings demonstrate the potential of this platform for gene activation, thereby offering promising prospects for tissue regeneration.

The efficacy of neoadjuvant chemotherapy is different for type 4 and large type 3 gastric cancer.

BACKGROUND: In the JCOG0501 study, neoadjuvant chemotherapy (NAC) failed to demonstrate survival benefits for type 4 and large type 3 gastric cancer (GC). The prognosis of these patients is still poor. We conducted this study to explore the value of NAC with non-SP regimens for type 4 and large type 3 â€‹GC in the Chinese population. METHODS: We retrospectively collected data from our electronic medical record system. Patients with large type 3 or type 4 â€‹GC who underwent D2 gastrectomy and AC were included. Patients were divided into two groups based on whether they received NAC: the CSC (NAC â€‹+ â€‹surgery â€‹+ â€‹AC) and SC (surgery â€‹+ â€‹AC) groups. The survival and perioperative outcomes for large type 3 or type 4 â€‹GC were analyzed between the CSC and SC groups, separately. RESULTS: Between May 2009 and December 2018, 189 patients were reviewed. Among large type 3 â€‹GC, the 5-year overall survival (OS) rates for patients in the CSC and SC groups were 54.4 â€‹% and 28.0 â€‹%, respectively (P â€‹= â€‹0.0008). Among type 4 â€‹GC, the 5-year OS rates for patients in the CSC and SC groups were 15.8 â€‹% and 24.8 â€‹%, respectively (P â€‹> â€‹0.05). CONCLUSIONS: This study showed NAC can improve the prognosis of large type 3 â€‹GC. However, NAC did not demonstrate significant survival advantages for type 4 â€‹GC.

The safety and effectiveness of laparoscopic off-clamp tumor evacuation versus traditional nephron-sparing surgery for large (>4 cm) sporadic renal angiomyolipomas.

BACKGROUND: Off-clamp nephron-sparing surgery (NSS) have been selectively performed in renal tumors in which the majority are T1a (<4 cm) renal caners. Less is known, however, whether off-clamp is a safe and effective option for treatment of Sporadic Renal Angiomyolipomas (RAML), especially in those >4 cm. The objective of our study was to compare the perioperative and renal function outcomes of a novel off-clamp tumor evacuation technique versus conventional laparoscopic NSS for the treatment of large sporadic RAMLs (>4 cm). METHODS: From January 2021 to June 2022, 42 patients diagnosed with RAML were prospectively randomized to receive laparoscopic standard NSS (Group 1) and off-clamp tumor evacuation (Group 2). The surgical and postoperative outcomes of both groups were compared. RESULTS: Baseline characteristics demonstrated no discernible variation between Group 1 and Group 2. Compared to Group 1, Group 2 was associated shorter operative time (92.5 vs 82.3 min, p < 0.001), elimination of warm ischemic time (22.9 vs 0 min, p < 0.001), more blood loss (92.6 vs 161.9 ml, p = 0.02), and lower short-term renal function reduction of the operated kidney (17.2% vs 9%; p < 0.001). Neither major complication nor recurrence occurred. CONCLUSION: It seems that transperitoneal laparoscopic off-clamp tumor evacuation is a feasible and safe option for the treatment of RAML, with the added benefit of preserving renal function to a greater extent than the traditional methods.

ERNet: Edge Regularization Network for Cerebral Vessel Segmentation in Digital Subtraction Angiography Images.

Stroke is a leading cause of disability and fatality in the world, with ischemic stroke being the most common type. Digital Subtraction Angiography images, the gold standard in the operation process, can accurately show the contours and blood flow of cerebral vessels. The segmentation of cerebral vessels in DSA images can effectively help physicians assess the lesions. However, due to the disturbances in imaging parameters and changes in imaging scale, accurate cerebral vessel segmentation in DSA images is still a challenging task. In this paper, we propose a novel Edge Regularization Network (ERNet) to segment cerebral vessels in DSA images. Specifically, ERNet employs the erosion and dilation processes on the original binary vessel annotation to generate pseudo-ground truths of False Negative and False Positive, which serve as constraints to refine the coarse predictions based on their mapping relationship with the original vessels. In addition, we exploit a Hybrid Fusion Module based on convolution and transformers to extract local features and build long-range dependencies. Moreover, to support and advance the open research in the field of ischemic stroke, we introduce FPDSA, the first pixel-level semantic segmentation dataset for cerebral vessels. Extensive experiments on FPDSA illustrate the leading performance of our ERNet.

Physically cross-linked chitosan gel with tunable mechanics and biodegradability for tissue engineering scaffold.

Chitosan, a cationic polysaccharide, exhibits promising potential for tissue engineering applications. However, the poor mechanical properties and rapid biodegradation have been the major limitations for its applications. In this work, an effective strategy was proposed to optimize the mechanical performance and degradation rate of chitosan gel scaffolds by regulating the water content. Physical chitosan hydrogel (HG, with 93.57 % water) was prepared by temperature-controlled cross-linking, followed by dehydration to obtain xerogel (XG, with 2.84 % water) and rehydration to produce wet gel (WG, with 56.06 % water). During this process, changes of water content significantly influenced the water existence state, hydrogen bonding, and the chain entanglements of chitosan in the gel network. The mechanical compression results showed that the chitosan gel scaffolds exhibited tunable compressive strength (0.3128-139 MPa) and compressive modulus (0.2408-1094 MPa). XG could support weights exceeding 65,000 times its own mass while maintaining structural stability. Furthermore, in vitro and in vivo experiments demonstrated that XG and WG exhibited better biocompatibility and resistance to biodegradation compared with HG. Overall, this work contributes to the design and optimization of chitosan scaffolds without additional chemical crosslinkers, which has potential in tissue engineering and further clinical translation.

Oncological outcomes of conversion therapy in gastric cancer patients with peritoneal metastasis: a large-scale retrospective cohort study.

BACKGROUND: Data on the long-term oncological outcomes of patients who undergo conversion surgery (CS) in gastric cancer (GC) patients with peritoneal metastasis (PM) are limited. METHODS: GC patients with PM who received intraperitoneal (ip) and systemic chemotherapy between April 2015 and January 2021 were enrolled. Multivariate analysis was performed to identify risk factors associated with survival. Clinicopathological and survival outcomes were compared between those with CS and those without CS (NCS). The paclitaxel (PTX) plus tegafur-gimeracil-oteracil potassium capsules (S-1) (PS) + ip PTX and oxaliplatin plus S-1 (SOX) + ip PTX groups were matched in a 1:1 ratio using propensity score matching. Oncological and survival data were collected and analyzed. RESULTS: A total of 540 patients who received ip chemotherapy via subcutaneous port and systemic chemotherapy were analyzed and 268 patients were enrolled, including 113 who underwent CS and 155 who did not. Overall survival (OS) were 27.0 months and 11.8 months in the CS and NCS groups (P < 0.0001), respectively. R0 resection was an independent prognostic factor for patients who underwent CS. The OS of patients with or without ovariectomy was 21.3 or 12.0 months (P < 0.0001). No difference of clinicopathological and survival outcomes was found between the PS + ip PTX and SOX + ip PTX groups. CONCLUSION: Conversion therapy is safe and adverse events were manageable. CS improves the survival of GC patients with PM after ip and systemic chemotherapy. R0 is an important prognostic factor. Furthermore, outcomes are comparable between the PS + ip PTX and SOX + ip PTX groups.