Review of the Real-Time Monitoring Technologies for Lithium Dendrites in Lithium-Ion Batteries.

Lithium-ion batteries (LIBs) have the advantage of high energy density, which has attracted the wide attention of researchers. Nevertheless, the growth of lithium dendrites on the anode surface causes short life and poor safety, which limits their application. Therefore, it is necessary to deeply understand the growth mechanism of lithium dendrites. Here, the growth mechanism of lithium dendrites is briefly summarized, and the real-time monitoring technologies of lithium dendrite growth in recent years are reviewed. The real-time monitoring technologies summarized here include in situ X-ray, in situ Raman, in situ resonance, in situ microscopy, in situ neutrons, and sensors, and their representative studies are summarized. This paper is expected to provide some guidance for the research of lithium dendrites, so as to promote the development of LIBs.

A Hydrogel Dressing Comprised of Silk Fibroin, Ag Nanoparticles, and Reduced Graphene Oxide for NIR Photothermal-Enhanced Antibacterial Efficiency and Skin Regeneration.

Bacterial infection, inflammation, and excessive oxidative stress are the primary factors that contribute to delayed healing of skin wounds. In this study, a multifunctional wound dressing (SF/Ag@rGO hydrogel) is developed to promote the healing of infected skin wounds by combining the inherent antibacterial activity of Ag nanoparticles (NPs) with near-infrared (NIR)-assisted antibacterial therapy. Initially, L-ascorbic acid is used as a reducing agent and PVP-K17 as a stabilizer and dispersant, this facilitates the synthesis of reduced graphene oxide loaded with Ag NPs (Ag@rGO). Ag@rGO is then blended with a silk fibroin (SF) solution to form an instantly gelling SF/Ag@rGO hydrogel that exhibits rapid self-healing, injectability, shape adaptability, NIR responsiveness, antioxidant, high tissue adhesion, and robust mechanical properties. In vitro and in vivo experiments show that the SF/Ag@rGO hydrogel demonstrates strong antioxidant and photothermal antibacterial capabilities, promoting wound healing through angiogenesis, stimulating collagen generation, alleviating inflammation, antioxidant, and promoting cell proliferation, indicating that the SF/Ag@rGO hydrogel dressing is an ideal candidate for clinical treatment of full-thickness bacterial-stained wounds.

(±)-hypermonanones A-G, seven pairs of monoterpenoid polyprenylated acylphloroglucinol enantiomers from Hypericum monanthemum.

Seven pairs of undescribed monoterpenoid polyprenylated acylphloroglucinol enantiomers [(±)-hypermonanones A-G (1-7)], together with three known analogues, were identified from the whole plant of Hypericum monanthemum Hook. The structures of these compounds were determined by analyses of their UV, HRESIMS, 1D/2D NMR spectroscopic data, and NMR calculations. The absolute configurations of these compounds were assigned by ECD calculations after chiral HPLC separation. Diverse monoterpene moieties were fused at C-3/C-4 of the dearomatized acylphloroglucinol core, which led to 3,4-dihydro-2H-pyran-integrated angular or linear type 6/6/6 tricyclic skeletons in 1-7. Compounds (-)-2 and (+)-2 exhibited significant NO inhibitory activity against LPS induced RAW264.7 cells with the IC50 values of 7.07 ± 1.02 µM and 11.39 ± 0.24 µM, respectively.

Plasma ctDNA enhances the tissue-based detection of oncodriver mutations in colorectal cancer.

PURPOSE: The advent of circulating tumor DNA (ctDNA) technology has provided a convenient and noninvasive means to continuously monitor cancer genomic data, facilitating personalized cancer treatment. This study aimed to evaluate the supplementary benefits of plasma ctDNA alongside traditional tissue-based next-generation sequencing (NGS) in identifying targetable mutations and tumor mutational burden (TMB) in colorectal cancers (CRC). METHODS: Our study involved 76 CRC patients, collecting both tissue and plasma samples for NGS. We assessed the concordance of gene mutational status between ctDNA and tissue, focusing on actionable genes such as KRAS, NRAS, PIK3CA, BRAF, and ERBB2. Logistic regression analysis was used to explore variables associated with discordance and positive mutation rates. RESULTS: In total, 26 cancer-related genes were identified. The most common variants in tumor tissues and plasma samples were in APC (57.9% vs 19.7%), TP53 (55.3% vs 22.4%) and KRAS (47.4% vs 43.4%). Tissue and ctDNA showed an overall concordance of 73.53% in detecting actionable gene mutations. Notably, plasma ctDNA improved detection for certain genes and gene pools. Variables significantly associated with discordance included gender and peritoneal metastases. TMB analysis revealed a higher detection rate in tissues compared to plasma, but combining both increased detection. CONCLUSIONS: Our study highlights the importance of analyzing both tissue and plasma for detecting actionable mutations in CRC, with plasma ctDNA offering added value. Discordance is associated with gender and peritoneal metastases, and TMB analysis can benefit from a combination of tissue and plasma data. This approach provides valuable insights for personalized CRC treatment.

The dual effects of dexmedetomidine on intestinal barrier and intestinal motility during sepsis.

BACKGROUND: Sepsis, characterized by dysregulated host responses to infection, remains a critical global health concern, with high morbidity and mortality rates. The gastrointestinal tract assumes a pivotal role in sepsis due to its dual functionality as a protective barrier against injurious agents and as a regulator of motility. Dexmedetomidine, an α2-adrenergic agonist commonly employed in critical care settings, exhibits promise in influencing the maintenance of intestinal barrier integrity during sepsis. However, its impact on intestinal motility, a crucial component of intestinal function, remains incompletely understood. METHODS: In this study, we investigated dexmedetomidine's multifaceted effects on intestinal barrier function and motility during sepsis using both in vitro and in vivo models. Sepsis was induced in Sprague-Dawley rats via cecal ligation and puncture. Rats were treated with dexmedetomidine post-cecal ligation and puncture, and various parameters were assessed to elucidate dexmedetomidine's impact. RESULTS: Our findings revealed a dichotomous influence of dexmedetomidine on intestinal physiology. In septic rats, dexmedetomidine administration resulted in improved intestinal barrier integrity, as evidenced by reduced mucosal hyper-permeability and morphological alterations. However, a contrasting effect was observed on intestinal motility, as dexmedetomidine treatment inhibited both the frequency and amplitude of contractions in isolated intestinal strips and decreased the distance of ink migration in vivo. Additionally, dexmedetomidine suppressed the secretion of pro-motility hormones while having no influence on hormones that inhibit intestinal peristalsis. CONCLUSION: The study revealed that during sepsis, dexmedetomidine exhibited protective effects on barrier integrity, although concurrently it hindered intestinal motility, partly attributed to its modulation of pro-motility hormone secretion. These findings underscore the necessity of a comprehensive understanding of dexmedetomidine's impact on multiple facets of gastrointestinal physiology in sepsis management, offering potential implications for therapeutic strategies and patient care.

Synthesis and Application of 1,8-Naphthalimide Derivatives Fluorescent Probe for Sequential Recognition of Cu2+ and H2PO4.

A naphthalimide Schiff base fluorescent probe (BSS) was designed and synthesized from 4-bromo-1,8-naphthalic anhydride, and its structure was characterized by 1HNMR, 13CNMR, FTIR, and MS. Fluorescence emission spectra showed that probe BSS could realize the "turn-off" detection of Cu2+ in acetonitrile solution, detection process with strong specificity and excellent anti-interference of other metal ions. In the fluorescence titration experiments, fluorescence intensity of BSS showed a good linear relationship with the Cu2+ concentration (0-10 µmol/L), and the detection limit was up to 7.0 × 10- 8 mol/L. Meanwhile, BSS and Cu2+ could form a 1:1 complex (BSS-Cu2+) during the reaction process. Under the same detection conditions, complex BSS-Cu2+ had specific fluorescence recovery properties for H2PO4- and the whole process was not only fast (6 s) but also free of interference from other anions, with a detection limit was as low as 5.7 × 10- 8 mol/L. In addition, complex BSS-Cu2+ could be successfully applied to the detection of H2PO4- in actual water samples, which with excellent application prospects.

Conserved methylation signatures associate with the tumor immune microenvironment and immunotherapy response.

BACKGROUND: Aberrant DNA methylation is a major characteristic of cancer genomes. It remains unclear which biological processes determine epigenetic reprogramming and how these processes influence the variants in the cancer methylome, which can further impact cancer phenotypes. METHODS: We performed pairwise permutations of 381,900 loci in 569 paired DNA methylation profiles of cancer tissue and matched normal tissue from The Cancer Genome Atlas (TCGA) and defined conserved differentially methylated positions (DMPs) based on the resulting null distribution. Then, we derived independent methylation signatures from 2,465 cancer-only methylation profiles from the TCGA and 241 cell line-based methylation profiles from the Genomics of Drug Sensitivity in Cancer (GDSC) cohort using nonnegative matrix factorization (NMF). We correlated DNA methylation signatures with various clinical and biological features, including age, survival, cancer stage, tumor immune microenvironment factors, and immunotherapy response. We inferred the determinant genes of these methylation signatures by integrating genomic and transcriptomic data and evaluated the impact of these signatures on cancer phenotypes in independent bulk and single-cell RNA/methylome cohorts. RESULTS: We identified 7,364 differentially methylated positions (2,969 Hyper-DMPs and 4,395 Hypo-DMPs) in nine cancer types from the TCGA. We subsequently retrieved three highly conserved, independent methylation signatures (Hyper-MS1, Hypo-MS1, and Hypo-MS4) from cancer tissues and cell lines based on these Hyper and Hypo-DMPs. Our data suggested that Hypo-MS4 activity predicts poor survival and is associated with immunotherapy response and distant tumor metastasis, and Hypo-MS4 activity is related to TP53 mutation and FOXA1 binding specificity. In addition, we demonstrated a correlation between the activities of Hypo-MS4 in cancer cells and the fractions of regulatory CD4 + T cells with the expression levels of immunological genes in the tumor immune microenvironment. CONCLUSIONS: Our findings demonstrated that the methylation signatures of distinct biological processes are associated with immune activity in the cancer microenvironment and predict immunotherapy response.

Clinical efficacy and pathological outcomes of transanal endoscopic intersphincteric resection for low rectal cancer.

BACKGROUND: Transanal endoscopic intersphincteric resection (ISR) surgery currently lacks sufficient clinical research and reporting. AIM: To investigate the clinical effectiveness of transanal endoscopic ISR, in order to promote the clinical application and development of this technique. METHODS: This study utilized a retrospective case series design. Clinical and pathological data of patients with lower rectal cancer who underwent transanal endoscopic ISR at the First Affiliated Hospital of Xiamen University between May 2018 and May 2023 were included. All patients underwent transanal endoscopic ISR as the surgical approach. We conducted this study to determine the perioperative recovery status, postoperative complications, and pathological specimen characteristics of this group of patients. RESULTS: This study included 45 eligible patients, with no perioperative mortalities. The overall incidence of early complications was 22.22%, with a rate of 4.44% for Clavien-Dindo grade ≥ III events. Two patients (4.4%) developed anastomotic leakage after surgery, including one case of grade A and one case of grade B. Postoperative pathological examination confirmed negative circumferential resection margins and distal resection margins in all patients. The mean distance between the tumor lower margin and distal resection margin was found to be 2.30 ± 0.62 cm. The transanal endoscopic ISR procedure consistently yielded high quality pathological specimens. CONCLUSION: Transanal endoscopic ISR is safe, feasible, and provides a clear anatomical view. It is associated with a low incidence of postoperative complications and favorable pathological outcomes, making it worth further research and application.

Antibacterial Micelles-Loaded Carboxymethyl Chitosan/Oxidized Konjac Glucomannan Composite Hydrogels for Enhanced Wound Repairing.

Antibacterial hydrogels have emerged as a promising approach for effective wound treatment. However, despite extensive research on the fabrication of antibacterial hydrogels, it remains challenging to develop injectable, biocompatible, transparent, and mass-producible hydrogels with antibacterial properties. In this study, we successfully fabricated an antibacterial drug-loaded composite hydrogel, named CC45/OKG40/HS, through a Schiff base reaction between carboxymethyl chitosan (CC) and oxidized konjac glucomannan (OKG), followed by the encapsulation of stevioside-stabilized honokiol (HS) micelles. The CC45/OKG40/HS hydrogel exhibited several favorable properties, including a short gel time (<10 min), high water content (>92%), injectability, good adhesiveness, self-healing ability, and high transparency. In vitro experiments confirmed its excellent antibacterial properties, antioxidant activities, and high biocompatibility (no cytotoxicity, hemolysis ratio <5%). Furthermore, in vivo evaluation demonstrated that the CC45/OKG40/HS0.5 hydrogel accelerated wound healing by relieving inflammatory responses and enhancing re-epithelization. Given its feasibility for mass production, the findings showed that the CC45/OKG40/HS hydrogel has the potential as an advanced antibacterial wound dressing for commercial use.

Enhancing Light Outcoupling Efficiency via Anisotropic Low Refractive Index Electron Transporting Materials for Efficient Perovskite Light-Emitting Diodes.

Thanks to the extensive efforts toward optimizing perovskite crystallization properties, high-quality perovskite films with near-unity photoluminescence quantum yield are successfully achieved. However, the light outcoupling efficiency of perovskite light-emitting diodes (PeLEDs) is impeded by insufficient light extraction, which poses a challenge to the further advancement of PeLEDs. Here, an anisotropic multifunctional electron transporting material, 9,10-bis(4-(2-phenyl-1H-benzo[d]imidazole-1-yl)phenyl) anthracene (BPBiPA), with a low extraordinary refractive index (ne ) and high electron mobility is developed for fabricating high-efficiency PeLEDs. The anisotropic molecular orientations of BPBiPA can result in a low ne of 1.59 along the z-axis direction. Optical simulations show that the low ne of BPBiPA can effectively mitigate the surface plasmon polariton loss and enhance the photon extraction efficiency in waveguide mode, thereby improving the light outcoupling efficiency of PeLEDs. In addition, the high electron mobility of BPBiPA can facilitate balanced carrier injection in PeLEDs. As a result, high-efficiency green PeLEDs with a record external quantum efficiency of 32.1% and a current efficiency of 111.7 cd A-1 are obtained, which provides new inspirations for the design of electron transporting materials for high-performance PeLEDs.

The fourth species of Leptobrachella (Anura, Megophryidae) found at Shiwandashan National Nature Reserve, Guangxi, China.

A new species of the genus Leptobrachella, L.guinanensissp. nov., is described in this study based on morphological, molecular, and bioacoustic data. The species was discovered in the Shiwandashan National Nature Reserve in Shangsi County, Guangxi, China. Phylogenetically, L.guinanensissp. nov. is closely related to L.ventripunctata. However, there are distinct morphological differences between L.guinanensissp. nov. and L.ventripunctata, as well as three other sympatric species (L.shangsiensis, L.shiwandashanensis, and L.sungi). These differences include body size (SVL 30.5-32.5 mm in males; 38.7-41.8 mm in females in the new species vs 25.5-28.0 mm in males, 31.5-35.0 mm in females in L.ventripunctata), the absence of brown spots on the ventral surface (vs chest and belly creamy white with many scattered brown spots in L.ventripunctata), 1/3 toe webbing and wide toe lateral fringes (vs no toe webbing and no lateral fringes in L.ventripunctata), and distinct dermal ridges under toes (vs absent in L.ventripunctata). Furthermore, the dominant vocal frequencies of the new species range from 7.3 to 8.3 kHz, which is unique compared to other Leptobrachella species and represents the highest dominant frequencies ever recorded. The Shiwandashan National Nature Reserve is now home to four known sympatric species of Leptobrachella.

Melatonin restores DNFB-induced dysbiosis of skin microbiota in a mouse model of atopic dermatitis.

BACKGROUND: The epidermic microbiota plays crucial roles in the pathogenesis of atopic dermatitis (AD), a common inflammatory skin disease. Melatonin (MLT) has been shown to ameliorate skin damage in AD patients, yet the underlying mechanism is unclear. METHODS: Using 2,4-dinitrofluorobenzene (DNFB) to induce an AD model, MLT intervention was applied for 14 days to observe its pharmaceutical effect. Skin lesions were observed using HE staining, toluidine blue staining and electron microscopy. Dermal proinflammatory factor (IL-4 and IL-13) and intestinal barrier indices (ZO1 and Occludin) were assessed by immunohistochemistry and RT-qPCR, respectively. The dysbiotic microbiota was analyzed using 16S rRNA sequencing. RESULTS: MLT significantly improved skin lesion size; inflammatory status (mast cells, IgE, IL-4, and IL-13); and the imbalance of the epidermal microbiota in AD mice. Notably, Staphylococcus aureus is the key bacterium associated with dysbiosis of the epidermal microbiota and may be involved in the fine modulation of mast cells, IL-4, IL-13 and IgE. Correlation analysis between AD and the gut revealed that intestinal dysbiosis occurred earlier than that of the pathological structure in the gut. CONCLUSION: Melatonin reverses DNFB-induced skin damage and epidermal dysbiosis, especially in S. aureus.

Dual mutations in the whitefly nicotinic acetylcholine receptor ß1 subunit confer target-site resistance to multiple neonicotinoid insecticides.

Neonicotinoid insecticides, which target insect nicotinic acetylcholine receptors (nAChRs), have been widely and intensively used to control the whitefly, Bemisia tabaci, a highly damaging, globally distributed, crop pest. This has inevitably led to the emergence of populations with resistance to neonicotinoids. However, to date, there have been no reports of target-site resistance involving mutation of B. tabaci nAChR genes. Here we characterize the nAChR subunit gene family of B. tabaci and identify dual mutations (A58T&R79E) in one of these genes (BTß1) that confer resistance to multiple neonicotinoids. Transgenic D. melanogaster, where the native nAChR Dß1 was replaced with BTß1A58T&R79E, were significantly more resistant to neonicotinoids than flies where Dß1 were replaced with the wildtype BTß1 sequence, demonstrating the causal role of the mutations in resistance. The two mutations identified in this study replace two amino acids that are highly conserved in >200 insect species. Three-dimensional modelling suggests a molecular mechanism for this resistance, whereby A58T forms a hydrogen bond with the R79E side chain, which positions its negatively-charged carboxylate group to electrostatically repulse a neonicotinoid at the orthosteric site. Together these findings describe the first case of target-site resistance to neonicotinoids in B. tabaci and provide insight into the molecular determinants of neonicotinoid binding and selectivity.

Clinical experience sharing on gastric microneuroendocrine tumors: A case report.

BACKGROUND: The majority of gastric neuroendocrine tumors (G-NENs) are present in various lesions under endoscopy, and they can be polypoid uplifts, submucosal tumors or papules, erosions, and ulcers. The lesions are mostly confined to the mucosal or submucosal layer, usually less than 2 cm, and exclusively localized to the gastric body or fundus. In type 1 G-NENs, about 22% of cases have no visible lesions under an endoscope, and such lesions can only be detected via biopsies (microcarcinoids). CASE SUMMARY: A 67-year-old female patient with appetite loss for more than half a year and personal history of hyperthyroidism was admitted to our hospital. After admission, a random multi-point biopsy was performed on the gastric body, fundus, angle, and antrum through gastroscopy. Pathological examination showed chronic severe atrophic gastritis in the fundus and body of the stomach. The small curvature of the gastric body, the anterior wall of the gastric body, and the posterior wall of the gastric body displayed proliferation of intestinal chromaffin cells. The curvature of the gastric body showed neuroendocrine tumor G1 (carcinoid), while the antrum and angle of the stomach showed mild atrophic gastritis with mild intestinal metaplasia. Immunohistochemical examination showed that the greater curvature of the gastric body was Syn (+), CgA (+), and Ki-67 (+, approximately 1%), which is consistent with neuroendocrine tumors (grade 1). Regular gastroscopy and biopsy should be performed every one to two years to monitor G-NENs. CONCLUSION: In the case under study, the patient did not have any visible raised lesions under a gastroscope, and the lesions were found only after a random biopsy. This article combines the endoscopic manifestations and clinical features of the lesions in this case to improve the diagnosis of G-NENs.

Machine learning identifies the risk of complications after laparoscopic radical gastrectomy for gastric cancer.

BACKGROUND: Laparoscopic radical gastrectomy is widely used, and perioperative complications have become a highly concerned issue. AIM: To develop a predictive model for complications in laparoscopic radical gastrectomy for gastric cancer to better predict the likelihood of complications in gastric cancer patients within 30 days after surgery, guide perioperative treatment strategies for gastric cancer patients, and prevent serious complications. METHODS: In total, 998 patients who underwent laparoscopic radical gastrectomy for gastric cancer at 16 Chinese medical centers were included in the training group for the complication model, and 398 patients were included in the validation group. The clinicopathological data and 30-d postoperative complications of gastric cancer patients were collected. Three machine learning methods, lasso regression, random forest, and artificial neural networks, were used to construct postoperative complication prediction models for laparoscopic distal gastrectomy and laparoscopic total gastrectomy, and their prediction efficacy and accuracy were evaluated. RESULTS: The constructed complication model, particularly the random forest model, could better predict serious complications in gastric cancer patients undergoing laparoscopic radical gastrectomy. It exhibited stable performance in external validation and is worthy of further promotion in more centers. CONCLUSION: Using the risk factors identified in multicenter datasets, highly sensitive risk prediction models for complications following laparoscopic radical gastrectomy were established. We hope to facilitate the diagnosis and treatment of preoperative and postoperative decision-making by using these models.

Synthesis and Characterization of DOPO-Containing Poly(2,6-dimethyl-1,4-phenylene oxide)s by Oxidative Coupling Polymerization.

A set of polyphenylene oxides incorporating DOPO (9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide) functionality, denoted as DOPO-R-PPO, was synthesized by copolymerization of 2,6-dimethylphenol (2,6-DMP) with various DOPO-substituted tetramethyl bisphenol monomers. In the initial step, a Friedel-Crafts acylation reaction was employed to react 2,6-DMP with different acyl chlorides, leading to the formation of ketone derivatives substituted with 2,6-dimethylphenyl groups. Subsequently, the ketones, along with DOPO and 2,6-DMP, underwent a condensation reaction to yield a series of DOPO-substituted bisphenol derivatives. Finally, polymerizations of 2,6-dimethylphenol with these DOPO-substituted bisphenols were carried out in organic solvents using copper(I) bromide/N-butyldimethylamine catalysts (CuBr/DMBA) under a continuous flow of oxygen, yielding telechelic PPO oligomers with DOPO moieties incorporated into the polymer backbone. The chemical structures of the synthesized compounds were characterized using various analytical techniques, including Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (1H NMR), phosphorus nuclear magnetic resonance (31P NMR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). When compared to conventional poly(2,6-dimethyl-1,4-phenylene oxide)s with a similar molecular weight range, all DOPO-PPOs exhibited higher glass transition temperatures, enhanced thermal degradability, and increased char yield formation at 800 °C without compromising solubility in organic solvents.

Revolutionizing sphincter preservation in ultra-low rectal cancer: exploring the potential of transanal endoscopic intersphincteric resection (taE-ISR): a propensity score-matched cohort study.

BACKGROUND: With the optimization of neoadjuvant treatment regimens, the indications for intersphincteric resection (ISR) have expanded. However, limitations such as unclear surgical field, impaired anal function, and failure of anal preservation still exist. Transanal total mesorectal excision can complement the drawbacks of ISR. Therefore, this study combined these two techniques and proposed transanal endoscopic intersphincteric resection (taE-ISR), aiming to explore the value of this novel technique in anal preservation for ultra-low rectal cancer. MATERIAL AND METHODS: Four high-volume centres were involved. After 1:1 propensity score-matching, patients with ultra-low rectal cancer underwent taE-ISR ( n =90) or ISR ( n =90) were included. Baseline characteristics, perioperative outcomes, pathological results, and follow-up were compared between the two groups. A nomogram model was established to assess the potential risks of anal preservation. RESULTS: The incidence of adjacent organ injury (0.0% vs. 5.6%, P =0.059), positive distal resection margin (1.1% vs. 8.9%, P =0.034), and incomplete specimen (2.2% vs. 13.3%, P =0.012) were lower in taE-ISR group. Moreover, the anal preservation rate was significantly higher in taE-ISR group (97.8% vs. 82.2%, P =0.001). Patients in the taE-ISR group showed a better disease-free survival ( P =0.044) and lower cumulative recurrence ( P =0.022) compared to the ISR group. Surgery procedure, tumour distance, and adjacent organ injury were factors influencing anal preservation in patients with ultra-low rectal cancer. CONCLUSION: taE-ISR technique was safe, feasible, and improved surgical quality, anal preservation rate and survival outcomes in ultra-low rectal cancer patients. It held significant clinical value and showed promising application prospects for anal preservation.

Increased Hepatocyte Growth Factor Secretion by Placenta-Derived Mesenchymal Stem Cells Improves Ovarian Function in an Ovariectomized Rat Model via Vascular Remodeling by Wnt Signaling Activation.

The vascular network contributes to the development of follicles. However, the therapeutic mechanism between vascular remodeling and ovarian functions is still unclear. Therefore, we demonstrated whether increased HGF by placenta-derived mesenchymal stem cells (PD-MSCs) improves ovarian function in an ovariectomized rat model via vascular remodeling by Wnt signaling activation. We established a half-ovariectomized rat model in which damaged ovaries were induced by ovariectomy of half of each ovary, and PD-MSCs (5 × 105 cells) were transplanted by intravenous injection. Three weeks after transplantation, rats in all groups were sacrificed. We examined the secretion of HGF by PD-MSCs through culture medium. The vascular structure in injured ovarian tissues was restored to a greater extent in the PD-MSC transplantation (Tx) group than in the nontransplantation (NTx) group (* p < 0.05). The expression of genes related to Wnt signaling (e.g., LRP6, GSK3ß, ß-catenin) was significantly increased in the Tx group compared to the NTx group (* p < 0.05). However, the expression of genes related to vascular permeability (e.g., Asef, ERG3) was significantly decreased in the Tx group compared to the NTx group (* p < 0.05). Follicular development was improved in the Tx group compared to the NTx group (* p < 0.05). Furthermore, to evaluate vascular function, we cocultivated PD-MSCs after human umbilical vein endothelial cells (HUVECs) with lipopolysaccharide (LPS), and we analyzed the vascular formation assay and dextran assay in HUVECs. Cocultivation of PD-MSCs with injured HUVECs enhanced vascular formation and decreased endothelial cell permeability (* p < 0.05). Also, cocultivation of PD-MSCs with explanted ovarian tissues improved follicular maturation compared to cocultivation of the Wnt inhibitor-treated PD-MSCs with explanted ovarian tissues. Therefore, HGF secreted by PD-MSCs improved ovarian function in rats with ovarian dysfunction by decreasing vascular permeability via Wnt signaling.

Increased IGFBP2 Levels by Placenta-Derived Mesenchymal Stem Cells Enhance Glucose Metabolism in a TAA-Injured Rat Model via AMPK Signaling Pathway.

The insulin resistance caused by impaired glucose metabolism induces ovarian dysfunction due to the central importance of glucose as a source of energy. However, the research on glucose metabolism in the ovaries is still lacking. The objectives of this study were to analyze the effect of PD-MSCs on glucose metabolism through IGFBP2-AMPK signaling and to investigate the correlation between glucose metabolism and ovarian function. Thioacetamide (TAA) was used to construct a rat injury model. PD-MSCs were transplanted into the tail vein (2 × 106) 8 weeks after the experiment started. The expression of the IGFBP2 gene and glucose metabolism factors (e.g., AMPK, GLUT4) was significantly increased in the PD-MSC group compared to the nontransplantation (NTx) group (* p < 0.05). The levels of follicular development markers and the sex hormones AMH, FSH, and E2 were also higher than those in the TAA group. Using ex vivo cocultivation, the mRNA and protein expression of IGFBP2, AMPK, and GLUT4 were significantly increased in the cocultivation with the PD-MSCs group and the recombinant protein-treated group (* p < 0.05). These findings suggest that the increased IGFBP2 levels by PD-MSCs play an important role in glucose metabolism and ovarian function through the IGFBP2-AMPK signaling pathway.