Two-Photon Cellular and Intravital Imaging of Hypochlorous Acid by Fluorescent Probes That Exhibit a Synergistic Excited-State Intramolecular Proton Transfer-Intramolecular Charge Transfer Mechanism Enabling Near-Infrared Emission with a Large Stokes Shift.

To develop highly effective molecular tools for intravital imaging of hypochlorous acid (HOCl), in this study, we initially designed two-photon hybrid fluorophores, SDP and P-SDP, by conjugating the classical dye 2-(2'-hydroxyphenyl)benzothiazole with the two-photon hydroxylphenyl-butadienylpyridinium fluorophore. The designed fluorophores exhibit a synergistic interaction between excited-state intramolecular proton transfer and intramolecular charge transfer mechanisms, enabling near-infrared (NIR) emission and significant Stokes shifts. Subsequently, using these fluorophores, we developed two HOCl fluorescent probes, SDP-SN and P-SDP-SN, by further incorporating N,N-dimethylthiocarbamate as a specific recognition group for HOCl. Toward HOCl, both SDP-SN and P-SDP-SN demonstrate an ultrafast response (less than 3 s), NIR emission at wavelengths of 714 and 682 nm, and remarkable Stokes shifts of 303 and 271 nm, respectively. Leveraging these advantages in conjunction with their ability to cross the blood-brain barrier, the probes find successful application in two-photon cellular and intravital imaging of HOCl. This includes visualizing endogenous generation of HOCl in cellular models related to inflammation, hyperglycemia, and ferroptosis, as well as mapping in vivo generation of HOCl within the brain and abdominal cavity using a murine model of systemic inflammation.

Imaging specific proteins in living cells with small unnatural amino acid attached Raman reporters.

Fluorescence labeling via fluorescent proteins (FPs) or immunofluorescence has been routinely applied for microscopic imaging of specific proteins. However, due to these over-weight and oversized labels (e.g. GFP, 238 aa, 27 kDa, ∼4 nm in size), the potential physiological malfunctions of the target proteins are largely underestimated in living cells. Herein, for living cells, we report a small and minimally-invasive Raman reporter (about 2 aa and <1 kDa), which can be site-specifically introduced into proteins by genetic codon expansion. After a single unnatural amino acid (UAA) is precisely incorporated into the target protein, the strained alkyne can rapidly undergo copper-free Diels-Alder cycloaddition reactions with the tetrazine-functionalized Raman reporter, which features a fine vibrational spectrum in contrast to fluorescence. In our experimental results, the UAA-based Raman tag was successfully incorporated into vimentin, histone 3.3 and huntingtin (Htt74Q) proteins in living HeLa cells and further utilized for stimulated Raman imaging. The site-specific bioorthogonal fusion of small Raman tags with intracellular proteins will pave the way for minimally-invasive protein labeling and multi-color imaging in living cells.

Liquid Bi-Sb-Sn Electrodes with Synergistic Stabilization Mechanism for Long-Lifespan Sodium-Based Liquid Metal Batteries.

Sodium-based liquid metal batteries are well suited for stationary energy storage due to their long life, intrinsic safety, and ease of scale-up. However, the irreversible alloying reaction between the positive current collector (PCC) and the cathodes at high temperatures leads to severe capacity degradation of the battery, severely limiting its scale-up application. In this work, a Bi-Sb-Sn alloy cathode based on a synergistic stabilization mechanism was designed for the first time. Due to the density difference of Bi, Sb, and Sn and the compatibility difference of Bi and Sn with the PCC, a part of Bi and Sn is spontaneously distributed in the region close to the PCC. The protection of Sb is realized by blocking the contact of Sb with the PCC as well as removing the PCC material dissolved in the cathode to prevent the loss of active material. Based on such protection, the Na||Bi36Sb24Sn40 cell maintained 99% Coulombic efficiency for 450 cycles at a rate of 0.75 C, with a capacity retention of 99.56% and a capacity decay rate of 0.001% per cycle. In addition, the interaction of Bi, Sb, and Sn during discharge also promotes capacity release and energy efficiency. At 0.3 C, the Na||Bi36Sb24Sn40 cell achieved 89% capacity utilization and 82% energy efficiency. These results provide an idea for the design of other batteries based on liquid metal electrodes.

Retrospective analysis of patients with hepatocellular carcinoma complicated with human immunodeficiency virus infection after hepatectomy.

BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide, with a 5-year relative survival rate of approximately 18%. The similarity between incidence and mortality (830000 deaths per year) underscores the bleak prognosis associated with the disease. HCC is the fourth most common malignancy and the second leading cause of cancer death in China. Most patients with HCC have a history of chronic liver disease such as chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, alcoholism or alcoholic steatohepatitis, nonalcoholic fatty liver disease, or nonalcoholic steatohepatitis. Early diagnosis and effective treatment are the keys to improving the prognosis of patients with HCC. Although the total number of human immunodeficiency virus (HIV)-infected patients is declining globally the incidence of HCC is increasing in HIV-infected patients, especially those who are coinfected with HBV or HCV. As a result, people infected with HIV still face unique challenges in terms of their risk of developing HCC. AIM: To investigate the survival prognosis and clinical efficacy of surgical resection in patients with HCC complicated with HIV infection. METHODS: The clinical data of 56 patients with HCC complicated with HIV admitted to the Third Affiliated Hospital of Nantong University from January 2013 to December 2023 were retrospectively analyzed. Among these, 27 patients underwent hepatectomy (operation group) and 29 patients received conservative treatment (nonoperation group). All patients signed informed consents in line with the provisions of medical ethics. The general data, clinicopathological features and prognoses for the patients in the two groups were analyzed and the risk factors related to the prognoses of the patients in the operation group were identified. RESULTS: The median disease-free survival (DFS) and overall survival (OS) of HIV-HCC patients in the surgical group were 13 months and 17 months, respectively, and the median OS of patients in the nonsurgical group was 12 months. The OS of the surgical group was significantly longer than that of the control group (17 months vs 12 months, respectively; P < 0.05). The risk factors associated with DFS and OS in the surgical group were initial HIV diagnosis, postoperative microvascular invasion (MVI), a CD4+ T-cell count < 200/µL, Barcelona stage C-D, and men who have sex with men (MSM; P < 0.05). CONCLUSION: Hepatectomy can effectively prolong the survival of patients with HIV-HCC but MVI identified during postoperative pathological examination, late tumor detection, late BCLC stage, CD4+ T < 200/µL and MSM are risk factors affecting the survival and prognosis of patients undergoing hepatectomy. In addition, there were significant differences between the surgical group and the nonsurgical group in terms of the initial diagnosis of HIV, Child-Pugh score, alpha-fetoprotein measurement value, and HART-efficient antiretroviral therapy after the diagnosis of HIV (P < 0.05). Therefore, these factors may also affect the survival and prognosis of patients.

Dispersion leading potential energy surface of N2·NbN12-: Anion photoelectron spectroscopy and theoretical studies.

In order to understand the dispersion interactions between molecules and to provide information about the potential energy surface of geometry evolutions, NbN12- and N2·NbN12- complexes were investigated by using photoelectron spectroscopy and ab initio calculations. The experimental adiabatic detachment energy (ADE) and vertical detachment energy (VDE) of NbN12- were both measured to be 2.129 ± 0.030 eV. The experimental ADE and VDE of N2·NbN12- were measured to be 2.17 ± 0.05 and 2.23 ± 0.05 eV, respectively, which are slightly higher than those of NbN12-. The structures of NbN12-/0 were confirmed to be hexacoordinated octahedrons. The investigation of N2·NbN12- structures shows that it is stable for N2 to bind to the face or vertex site of octahedron NbN12-; the face-side-on structure has the lowest energy. The calculations based on symmetry-adapted perturbation theory suggest that the dispersion term is predominant and leads to the stability of N2·NbN12- complexes.

Discovery of pyrazolo[1,5-a]pyrimidine derivatives targeting TLR4-TLR4∗ homodimerization via AI-powered next-generation screening.

TLR4 signaling is instrumental in orchestrating multiple aspects of innate immunity. Developing small molecule inhibitors targeting the TLR4 pathway holds potential therapeutic promise for TLR4-related disorders. Herein, an artificial intelligence (AI)-powered next-generation screening approach, employing HelixVS and HelixDock, was utilized to focus on the TLR4-TLR4∗ (a second copy of TLR4) homodimerization surface, leading to the identification of a potent pyrazolo[1,5-a]pyrimidine derivative, designated as compound 1. An extensive structure-activity relationship (SAR) exploration culminated in the discovery of the lead compound TH023, which effectively blocked the LPS-stimulated NF-κB activation and nitric oxide overproduction in HEK-Blue hTLR4 and RAW264.7 cells, with IC50 values of 0.354 and 1.61 µM, respectively. Molecular dynamic (MD) simulations indicated that TH023 stabilized TLR4-MD-2 and disrupted its association with TLR4∗. Moreover, TH023 alleviated the lung injury and decreased pro-inflammatory cytokine levels in LPS-induced septic mice. These findings not only illuminated the strategic advantage of HelixDock in advancing the frontiers of AI-driven drug discovery, but also provided valuable structural insights for the rational design of TLR4-TLR4∗ protein-protein interaction (PPI) inhibitors based on the pyrazolo[1,5-a]pyrimidine scaffold. Overall, this study validated a new strategy for TLR4 signaling regulation by targeting its dimerization, thereby underscoring the therapeutic promise of TH023 in treating TLR4-mediated inflammatory diseases.

Unveiling the mysteries of HER2-low expression in breast cancer: pathological response, prognosis, and expression level alterations.

BACKGROUND: The novel anti-HER2 antibody drug conjugates (ADCs) can effectively improve the long-term survival of patients with HER2-low expression breast cancer. However, pathological responses to neoadjuvant therapy (NAT) within HER2-low expression breast cancer, the relationship between pathological response and prognosis and the transformation of HER2 status are all now poorly understood. METHODS: The patients with HER2-0 and HER2-low expression breast cancer receiving NAT at Harbin Medical University Cancer Hospital between Jan. 2014 and Nov. 2018 were retrospectively explored. HER2 low expression refers to the IHC 1 + or 2 + and FISH negative. The Kappa test was utilized for analyzing the consistency rate of HER2 expression. To evaluate disease-free survival (DFS) and overall survival (OS), this research employed both the Kaplan-Meier analysis and the Cox regression. RESULTS: In this study, 178 patients with HER2-0 and 344 patients with HER2-low expression breast cancer were included. In comparison with the HER2-0 group, it is shown that patients in the HER2-low group have more possibility to be younger compared to those 50 years old (P < 0.014), have more premenopausal patients (P < 0.001), a higher proportion of hormone receptor (HR) positive patients (P < 0.001), and less proportion of stage III V patients (P < 0.034). When NAT was finished, the pCR rate became 23.6% in the HER2-0 group while 22.1% in the HER2-low group, and there was also a higher pCR rate in HR- patients in comparison with that in HR + patients (P < 0.01). Considering HER2 expression inconsistency, the overall HER2 inconsistency rate was 30.4% (Kappa = 0.431, P < 0.01). Among patients initially diagnosed as HER2-0, 34% (N = 61) were re-diagnosed as HER2-low after NAT. After stratification by HR expression status, HR+/HER2-0 patients transformed to HER2-low after NAT in 37%, and 32% of HR- patients changed from HER2-0 to HER2-low. In this survival analysis, there were both better DFS rates (P = 0.009) and OS rates (P = 0.026) in the HR-/HER2-low patients in comparison with the HR-/HER2-0 patients, while the HER2-0 and HER2-low patients in the HR + group had no significant survival difference. Additionally, for non-pCR patients, there was better DFS (P = 0.029) and OS (P = 0.038) in the HER2-low group in comparison with that of the HER2-0 group, while no significant survival difference exists between pCR patients. CONCLUSION: After HR stratification, there are unique clinical characteristics and prognostic outcomes in HER2-low expression breast cancer, which indicates the potential to become a specific molecular subtype of breast cancer. The significant instability of HER2-low expression status between primary tumor and residual invasive disease suggests that multiple detections of HER2 status should be emphasized in NAT strategies.

Association of mid-pregnancy ferritin levels with postpartum glucose metabolism in women with gestational diabetes.

BACKGROUND: Ferritin, a key indicator of body iron levels, has been reported to associate with type 2 diabetes (T2DM) and the onset of Gestational diabetes mellitus (GDM). However, limited research explores the association between mid-pregnancy ferritin levels and the risk of postpartum abnormal glucose metabolism (AGM) in patients with GDM. METHODS: A retrospective cohort study was conducted in 1514 women with GDM recruited from January 2016 to January 2021, and 916 women were included. Demographic characteristics, medical history and family history, pregnancy complications were recorded. Multiple logistic regression models were performed to assess the association between mid-pregnancy ferritin levels and the risk of postpartum AGM. RESULTS: Following the postpartum oral glucose tolerance test, 307 (33.5%) exhibited AGM. The AGM group had higher mid-pregnancy serum ferritin levels [AGM vs NGT: 23 (11.7, 69) µg/L vs 17.80 (9.85, 40.7) µg/L, P < 0.001] and had a larger proportion of women with ferritin levels ≥30 µg/L (AGM vs NGT: 43.6% vs 31.4%, P < 0.001). Logistic regression analysis demonstrated that women with ferritin levels≥ 30 µg/L had a 1.566 times higher risk of developing postpartum AGM. CONCLUSIONS: These findings indicate that elevated mid-pregnancy ferritin levels are significantly and independently associated with increased postpartum AGM risk in women with previous GDM. Consequently, cautious consideration is necessary for prescribing iron supplements in prenatal care, particularly for non-anemic women with GDM at high risk of developing diabetes after delivery.

Typical Morphological Characteristics of the Immunohistochemistrical Subtypes of Pituitary Microadenomas: A dual center study.

PURPOSE: This study aimed to investigate the relation of magnetic resonance image (MRI) features and immunohistochemistrical subtypes of pituitary microadenomas (PMAs) characterized by location and growth pattern. MATERIALS AND METHODS: A double-center, retrospective review of MRI characteristics was conducted in 57 PMA cases recorded from February 2014 to September 2023 and identified on the basis of 2017 WHO classification of pituitary gland tumors. The geometric center of the tumor was defined, and the possibility of PMA vertical or lateral growth pattern was evaluated according to ratio of maximum diameter between the X and Y axes. RESULTS: Among the PMAs, somatotroph adenomas (STAs) significantly frequented the lateral-anteroinferior portion of pituitary gland (P=0.036). Lactotroph adenomas (LTAs) showed significant locational preference for the lateral-posteroinferior portion (P=0.037), and gonadotroph adenomas (GTAs) were predominately located in the central-anteroinferior portion (P=0.022). Furthermore, the PMAs in the suprasellar portion exhibited vertical extension with statistical significance (P=0.0). CONCLUSION: In our cohort, the micro-STAs were predominately located in the lateral-anteroinferior portion of pituitary gland, the micro-LTAs in the lateral-posteroinferior portion, and the micro-GTAs in the central-anteroinferior portion. The growth pattern of the PMAs was highly correlated with their vertical position instead of their immunohistochemistrical subtypes. Therefore, MRI shows potential in differentiating partial PMA subgroups, especially the cases in silent groups.

The Multifaceted Role of Alpha-Lipoic Acid in Cancer Prevention, Occurrence, and Treatment.

Alpha-lipoic acid (ALA) is a naturally occurring compound synthesized by mitochondria and widely distributed in both animal and plant tissues. It primarily influences cellular metabolism and oxidative stress networks through its antioxidant properties and is an important drug for treating metabolic diseases associated with oxidative damage. Nevertheless, research indicates that the mechanism by which ALA affects cancer cells is distinct from that observed in normal cells, exhibiting pro-oxidative properties. Therefore, this review aims to describe the main chemical and biological functions of ALA in the cancer environment, including its mechanisms and effects in tumor prevention and anticancer activity, as well as its role as an adjunctive drug in cancer therapy. We specifically focus on the interactions between ALA and various carcinogenic and anti-carcinogenic pathways and discuss ALA's pro-oxidative capabilities in the unique redox environment of cancer cells. Additionally, we elaborate on ALA's roles in nanomedicine, hypoxia-inducible factors, and cancer stem cell research, proposing hypotheses and potential explanations for currently unresolved issues.

Bile acid metabolism modulates intestinal immunity involved in ulcerative colitis progression.

The bile acids (BA) in the intestine promote inflammation by interacting with immune cells, playing a crucial role in the progression of UC, but the specific mechanism between the two remains elusive. This study aims to explore the relationship between BAMand UC inflammation and determine its potential mechanisms.Firstly, we employed a hybrid approach using Lasso regression and support vector machine (SVM) feature selection in bioinformatics to identify genes linked to UC and BAM. The relationship between these genes and immune infiltration was explored, along with their correlation with immune factors in the Tumor-Immune System Interaction Database (TISIDB) database. Gene Set Enrichment Analysis (GSEA) pathway enrichment analysis was then used to predict signaling pathways associated with key genes in UC. Single-cell data from the GSE13464 dataset was also analyzed. Finally, Five differentially expressed genes (DEGs) related to BAM (APOA1, AMACR, PEX19, CH25H, and AQP9) were significantly upregulated/downregulated in UC immune cells. The expression of important genes in UC tissue was confirmed in the experimental validation section and AQP9, which showed significant differential expression, was chosen for further validation. The results showed that the AQP9 gene may regulate the IFN - γ/JAK signaling axis, thereby promoting CD8+T cell activation. This research has greatly advanced our comprehension of the pathogenesis and underlying mechanism of BAM in immune cells linked to UC.

High-strength alginate fibers wet-spun from pre-crosslinked sodium alginate solutions.

Facing the severe problem of microplastic pollution, there is an urgent need to develop biodegradable fibers to replace the petrochemical fibers. Sodium alginate, a biomass polysaccharide, has gained widespread attentions recently for the fiber manufacture. However, the limited mechanical strength of alginate fibers restricts their usages as load-bearing fabrics and reinforcement fibers. Here, we develop a novel strategy to prepare alginate multifilaments using pre-crosslinked sodium alginate solutions. The increase in the pre-crosslinking ratio effectively hinders the disentanglement of sodium alginate chains at high stretches, causing an increase in the shear viscosity of the solution ascertained from the capillarity-driven thinning process from 4.5 Pa·s to 9.9 Pa·s and facilitating the high alignment and orientation of sodium alginate chains. The resultant fibers possess a breaking strength of 474 MPa, elongation at break of 16 %, Young's modulus of 14.4 GPa, and toughness of 51.8 MJ/m3, exceeding most biomass fibers without reinforcement additives. The high orientation degree of 0.865 and high spinnability of alginate multifilaments enable their applications in multi-channel encryption fabrics that exhibit distinct information under various optical conditions. This rheological regulation of spinning solutions provides a facile yet effective strategy to enhance the mechanical performance and broaden application scenarios of alginate fibers.

Maternal gestational diabetes mellitus associates with altered gut microbiome composition and head circumference abnormalities in male offspring.

The impact of gestational diabetes mellitus (GDM) on maternal or infant microbiome trajectory remains poorly understood. Utilizing large-scale longitudinal fecal samples from 264 mother-baby dyads, we present the gut microbiome trajectory of the mothers throughout pregnancy and infants during the first year of life. GDM mothers had a distinct microbiome diversity and composition during the gestation period. GDM leaves fingerprints on the infant's gut microbiome, which are confounded by delivery mode. Further, Clostridium species positively correlate with a larger head circumference at month 12 in male offspring but not females. The gut microbiome of GDM mothers with male fetuses displays depleted gut-brain modules, including acetate synthesis I and degradation and glutamate synthesis II. The gut microbiome of female infants of GDM mothers has higher histamine degradation and dopamine degradation. Together, our integrative analysis indicates that GDM affects maternal and infant gut composition, which is associated with sexually dimorphic infant head growth.

HDAC Inhibition Sensitize Hepatocellular Carcinoma to Lenvatinib via Suppressing AKT Activation.

Hepatocellular carcinoma (HCC) is a deadly malignancy with limited treatment options. As a first-line treatment for advanced HCC, Lenvatinib has been applicated in clinic since 2018. Resistance to Lenvatinib, however, has severely restricted the clinical benefits of this drug. Therefore, it is urgent to explore the potential resistance mechanisms of Lenvatinib and identify appropriate methods to reduce resistance for the treatment of HCC. We identified SAHA, a HDAC inhibitor, to have effective anti-tumor activity against Lenvatinib-resistant HCC organoids by screening a customized drug library. Mechanism analysis revealed that SAHA upregulates PTEN expression and suppresses AKT signaling, which contributes to reversing Lenvatinib resistance in liver cancer cells. Furthermore, combinational application of Lenvatinib and HDAC inhibitor or AKT inhibitor synergistically inhibits HCC cell proliferation and induces cell apoptosis. Finally, we confirmed the synergistic effects of Lenvatinib and SAHA, or AZD5363 in primary liver cancer patient derived organoids. Collectively, these findings may enable the development of Lenvatinib combination therapies for HCC.

Diagnostic value of contrast-enhanced ultrasound in judging the survival of graft after heteroautoplasty for secondary hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is one of the common complications of end-stage renal disease-uremia, and is mainly manifested as parathyroid hyperplasia and abnormal secretion of parathyroid hormone (PTH). OBJECTIVE: To investigate the value and advantages of contrast-enhanced ultrasound (CEUS) in evaluating the survival of autografts after parathyroidectomy + parathyroid autotransplantation. METHODS: In this study, 125 patients with renal failure due to polycystic kidney disease, chronic nephritis, diabetic nephropathy, lupus nephritis, and atherosclerotic nephropathy were enrolled as the participants and each of them had 4 secondary hyperactive parathyroid glands and underwent parathyroid autotransplantation. One parathyroid gland was taken from each patient and equally divided into 4 parts and placed in the subcutaneous fat of one forearm for transplantation. CEUS was performed 14 days after the transplantation to observe the micro blood supply of the graft and assess the survival and secretory function of the transplanted parathyroid. The grafts were divided into the partial survival group and the total survival group based on the enhancement characteristics. The survival of the grafts was determined by comparing the parathyroid hormone level in bilateral elbow cephalic veins 1 month after surgery. RESULTS: Among the 125 patients, 112 had linear or punctate enhancement of 2-4 parathyroid glands 14 days after surgery, and 13 patients had linear or punctate enhancement of 0-1 parathyroid gland. There were statistically significant differences in the perfusion pattern, enhancement uniformity, and parathyroid hormone levels in the cephalic veins at the elbow on both the graft and non-graft sides among all groups (P< 0.05). CONCLUSION: Compared to the detection of the difference in the parathyroid hormone level in the cephalic vein of bilateral elbows 1 month after surgery, CEUS can reflect the parathyroid survival after transplantation more quickly and accurately 2 weeks later, and provide a more rapid and agile non-invasive clinical diagnosis method.

Inflammation causes insulin resistance in mice via interferon regulatory factor 3 (IRF3)-mediated reduction in FAHFA levels.

Obesity-induced inflammation causes metabolic dysfunction, but the mechanisms remain elusive. Here we show that the innate immune transcription factor interferon regulatory factor (IRF3) adversely affects glucose homeostasis through induction of the endogenous FAHFA hydrolase androgen induced gene 1 (AIG1) in adipocytes. Adipocyte-specific knockout of IRF3 protects male mice against high-fat diet-induced insulin resistance, whereas overexpression of IRF3 or AIG1 in adipocytes promotes insulin resistance on a high-fat diet. Furthermore, pharmacological inhibition of AIG1 reversed obesity-induced insulin resistance and restored glucose homeostasis in the setting of adipocyte IRF3 overexpression. We, therefore, identify the adipocyte IRF3/AIG1 axis as a crucial link between obesity-induced inflammation and insulin resistance and suggest an approach for limiting the metabolic dysfunction accompanying obesity.

Stretchable Tb-Tb Distance Regulates the Piezofluorochromic Behavior of Chiral Tb(III)-MOF upon Compression.

Luminescent chiral Tb-MOF microcrystals with the Tb2(COO)4 subunit indicated strong green mechano-luminescence under compression. Furthermore, piezofluorochromic behavior in the diamond anvil cell was observed, with the intensity tendency of decreasing-increasing-decreasing and a shortened lifetime upon compression, due to the reversible stretchable Tb-Tb interactions. The Tb-Tb distance upon compression was refined through in situ high-pressure X-ray absorption spectra, which was consistent with the tendency of the piezofluorochromic intensity. In situ high-pressure UV-vis absorption spectra, Fourier transform infrared spectra, and powder X-ray diffraction demonstrated the full recovery of Tb-MOF after over 10 GPa compressions due to the semiflexible ligand. This work not only provided an ultrastable Tb-MOF but also illustrated the relationship of the piezofluorochromic behavior with the detailed structural transformation for the first time.

Conductive and alignment-optimized porous fiber conduits with electrical stimulation for peripheral nerve regeneration.

Autologous nerve transplantation (ANT) is currently considered the gold standard for treating long-distance peripheral nerve defects. However, several challenges associated with ANT, such as limited availability of donors, donor site injury, mismatched nerve diameters, and local neuroma formation, remain unresolved. To address these issues comprehensively, we have developed porous poly(lactic-co-glycolic acid) (PLGA) electrospinning fiber nerve guide conduits (NGCs) that are optimized in terms of alignment and conductive coating to facilitate peripheral nerve regeneration (PNR) under electrical stimulation (ES). The physicochemical and biological properties of aligned porous PLGA fibers and poly(3,4-ethylenedioxythiophene):polystyrene sodium sulfonate (PEDOT:PSS) coatings were characterized through assessments of electrical conductivity, surface morphology, mechanical properties, hydrophilicity, and cell proliferation. Material degradation experiments demonstrated the biocompatibility in vivo of electrospinning fiber films with conductive coatings. The conductive NGCs combined with ES effectively facilitated nerve regeneration. The designed porous aligned NGCs with conductive coatings exhibited suitable physicochemical properties and excellent biocompatibility, thereby significantly enhancing PNR when combined with ES. This combination of porous aligned NGCs with conductive coatings and ES holds great promise for applications in the field of PNR.

Effect of Akkermansia muciniphila on pancreatic islet ß-cell function in rats with prediabetes mellitus induced by a high-fat diet.

Prediabetes is an important stage in the development of diabetes. It is necessary to find a safe, effective and sustainable way to delay and reverse the progression of prediabetes. Akkermansia muciniphila (A. muciniphila) is one of the key bacteria associated with glucose metabolism. Recent studies mainly focus on the effect of A. muciniphila on obesity and insulin resistance, but there is no research on the effect of A. muciniphila on pancreatic ß-cell function and its mechanism in prediabetes. In this study, we investigated the effects of A. muciniphila on ß-cell function, apoptosis and differentiation, as well as its effects on the gut microbiome, intestinal barrier, metaflammation and the expression of Toll-like receptors (TLRs) in a high-fat diet (HFD)-induced prediabetic rat model. The effect of A. muciniphila was compared with dietary intervention. The results showed both A. muciniphila treatment and dietary intervention can reduce metaflammation by repairing the intestinal barrier in rats with prediabetes induced by an HFD and improve ß-cell secretory function, apoptosis and differentiation through signaling pathways mediated by TLR2 and TLR4. Additionally, A. muciniphila can further elevate ß-cell secretion, attenuate apoptosis and improve differentiation and the TLR signaling pathway on the basis of diet.

Sulfite-Assisted Acetate Conversion from CO Electroreduction.

The efficient acetate conversion from CO electroreduction is challenging due to the poor selectivity at high reaction rate, which requires the competition with H2 and other C2+ (i. e., ethylene, ethanol, n-propanol) reduction products. Electrolyte engineering is one of the efficient strategies to regulate the reaction microenvironment. In this work, the adding of sulfite (SO3 2-) with high nucleophilicity in KOH electrolytes was demonstrated to enable improving the CO-to-acetate conversion via generating a S-O chemical bond between SO3 2- and oxygenated *C2 intermediates (i. e., *CO-CO, *CO-COH) compared with that in pure KOH system on both synthesized Cu(200)- and normal commercial Cu(111)-facets-exposed metallic Cu catalysts. As a result, the prepared Cu(200)-facets-exposed metallic Cu catalyst with surface ions modification showed an superior Faradaic efficiency of 63.6 % at -0.6 A ⋅ cm-2, and extraordinary absolute value of peak partial current density as high as 1.52 A ⋅ cm-2 with adding SO3 2- in KOH electrolytes, compared to the best reported values in both CO and CO2 electroreduction. Our work suggests an attractive strategy to introduce the oxyanion with high nucleophilicity in electrolytes to regulate the microenvironment for industrial-current-density electrosynthesis of acetate from CO electroreduction.