In Situ Synthesis and Self-Assembly of Peptide-PEG Conjugates: A Facile Method for the Construction of Fibrous Hydrogels.

Peptide-based hydrogels have gained considerable attention as a compelling platform for various biomedical applications in recent years. Their attractiveness stems from their ability to seamlessly integrate diverse properties, such as biocompatibility, biodegradability, easily adjustable hydrophilicity/hydrophobicity, and other functionalities. However, a significant drawback is that most of the functional self-assembling peptides cannot form robust hydrogels suitable for biological applications. In this study, we present the synthesis of novel peptide-PEG conjugates and explore their comprehensive hydrogel properties. The hydrogel comprises double networks, with the first network formed through the self-assembly of peptides to create a ß-sheet secondary structure. The second network is established through covalent bond formation via N-hydroxysuccinimide chemistry between peptides and a 4-arm PEG to form a covalently linked network. Importantly, our findings reveal that this hydrogel formation method can be applied to other peptides containing lysine-rich sequences. Upon encapsulation of the hydrogel with antimicrobial peptides, the hydrogel retained high bacterial killing efficiency while showing minimum cytotoxicity toward mammalian cells. We hope that this method opens new avenues for the development of a novel class of peptide-polymer hydrogel materials with enhanced performance in biomedical contexts, particularly in reducing the potential for infection in applications of tissue regeneration and drug delivery.

Well-Paired-Seq2: High-Throughput and High-Sensitivity Strategy for Characterizing Low RNA-Content Cell/Nucleus Transcriptomes.

Single-cell RNA sequencing (scRNA-seq) is a transformative technology that unravels the intricate cellular state heterogeneity. However, the Poisson-dependent cell capture and low sensitivity in scRNA-seq methods pose challenges for throughput and samples with a low RNA-content. Herein, to address these challenges, we present Well-Paired-Seq2 (WPS2), harnessing size-exclusion and quasi-static hydrodynamics for efficient cell capture. WPS2 exploits molecular crowding effect, tailing activity enhancement in reverse transcription, and homogeneous enzymatic reaction in the initial bead-based amplification to achieve 3116 genes and 8447 transcripts with an average of ∼20000 reads per cell. WPS2 detected 1420 more genes and 4864 more transcripts than our previous Well-Paired-Seq. It sensitively characterizes transcriptomes of low RNA-content single cells and nuclei, overcoming the Poisson limit for cell and barcoded bead capture. WPS2 also profiles transcriptomes from frozen clinical samples, revealing heterogeneous tumor copy number variations and intercellular crosstalk in clear cell renal cell carcinomas. Additionally, we provide the first single-cell-level characterization of rare metanephric adenoma (MA) and uncover potential specific markers. With the advantages of high sensitivity and high throughput, WPS2 holds promise for diverse basic and clinical research.

A highly sensitive ratiometric fluorescence immunoassay based on bioorthogonal nanozymes.

We designed a novel ratiometric fluorescence immunoassay based on bioorthogonal nanozymes for carcinoembryonic antigen detection. The analytical performance of our designed immunoassay showed a wide linear range, a low detection limit, good reproducibility, selectivity and stability. Thus, bioorthogonal nanozymes hold great potential applications in clinical diagnoses.

Reduced Cx43 Expression Induces Autophagy through Activation of the AMPK-mTOR-ULK1 Signaling Pathway in the Common Bile Duct Ligation Rat Heart.

BACKGROUNDS: This study aimed to investigate the relationship between Cx43 expression and autophagy mediated by the AMPK-mTOR-Ulk1 signaling pathway in jaundice heart. METHODS: In this study, a jaundice model was established in common bile duct ligation (CBDL) rats. Cardiac injury was assessed using various methods including myocardial injury indicators, echocardiography, TEM, HE staining, Masson staining, IHC, and IF. We investigated the regulatory relationship between Cx43, autophagy, and the AMPK-mTOR-ULK pathway in vivo by administering autophagy agonists (Rapa), autophagy inhibitors (3-MA), and Cx43 inhibitors (Gap 26). In vitro, we observed the relationship between autophagy and the AMPK-mTOR-ULK1 pathway in cells by exposing them to the AMPK inhibitor Compound C and the AMPK activator AICAR. RESULTS: We found that CBDL induced autophagy through the AMPK-mTOR-ULK pathway, leading to the inhibition of myocardial dysfunction. Rapamycin pretreatment with CBDL3d exhibited a protective effect against myocardial injury and promoted autophagy. In contrast, 3-MA had no impact. Pretreatment with rapamycin at CBDL2w enhanced autophagy and aggravated cardiac injury; however, inhibition of autophagy using 3-MA attenuated cardiac injury. Cell viability was enhanced by AMPK inhibitors and inhibited by AMPK agonists. In addition, we observed that increased autophagy led to decreased Cx43 expression, which negatively affected cardiac function. CONCLUSIONS: CBDL induces myocardial injury in rats and activates autophagy through the AMPK-mTOR-ULK pathway, resulting in decreased Cx43 protein levels. A moderate increase in early autophagy in CBDL can improve cardiac injury, while late inhibition of autophagy can reduce myocardial injury.

SiONx Coating Regulates Mesenchymal Stem Cell Antioxidant Capacity via Nuclear Erythroid Factor 2 Activity under Toxic Oxidative Stress Conditions.

Healing in compromised and complicated bone defects is often prolonged and delayed due to the lack of bioactivity of the fixation device, secondary infections, and associated oxidative stress. Here, we propose amorphous silicon oxynitride (SiONx) as a coating for the fixation devices to improve both bioactivity and bacteriostatic activity and reduce oxidative stress. We aimed to study the effect of increasing the N/O ratio in the SiONx to fine-tune the cellular activity and the antioxidant effect via the NRF2 pathway under oxidative stress conditions. The in vitro studies involved using human mesenchymal stem cells (MSCs) to examine the effect of SiONx coatings on osteogenesis with and without toxic oxidative stress. Additionally, bacterial growth on SiONx surfaces was studied using methicillin-resistant Staphylococcus aureus (MRSA) colonies. NRF2 siRNA transfection was performed on the hMSCs (NRF2-KD) to study the antioxidant response to silicon ions. The SiONx implant surfaces showed a >4-fold decrease in bacterial growth vs. bare titanium as a control. Increasing the N/O ratio in the SiONx implants increased the alkaline phosphatase activity >1.5 times, and the other osteogenic markers (osteocalcin, RUNX2, and Osterix) were increased >2-fold under normal conditions. Increasing the N/O ratio in SiONx enhanced the protective effects and improved cell viability against toxic oxidative stress conditions. There was a significant increase in osteocalcin activity compared to the uncoated group, along with increased antioxidant activity under oxidative stress conditions. In NRF2-KD cells, there was a stunted effect on the upregulation of antioxidant markers by silicon ions, indicating a role for NRF2. In conclusion, the SiONx coatings studied here displayed bacteriostatic properties. These materials promoted osteogenic markers under toxic oxidative stress conditions while also enhancing antioxidant NRF2 activity. These results indicate the potential of SiONx coatings to induce in vivo bone regeneration in a challenging oxidative stress environment.

Value of magnetic resonance imaging radiomics features in predicting histologic grade of invasive ductal carcinoma of the breast.

BACKGROUND: Breast cancer has the second highest mortality rate of all cancers and occurs mainly in women. OBJECTIVE: To investigate the relationship between magnetic resonance imaging (MRI) radiomics features and histological grade of invasive ductal carcinoma (IDC) of the breast and to evaluate its diagnostic efficacy. METHODS: The two conventional MRI quantitative indicators, i.e. the apparent diffusion coefficient (ADC) and the initial enhancement rate, were collected from 112 patients with breast cancer. The breast cancer lesions were manually segmented in dynamic contrast-enhanced MRI (DCE-MRI) and ADC images, the differences in radiomics features between Grades I, II and III IDCs were compared and the diagnostic efficacy was evaluated. RESULTS: The ADC values (0.77 ± 0.22 vs 0.91 ± 0.22 vs 0.92 ± 0.20, F= 4.204, p< 0.01), as well as the B_sum_variance (188.51 ± 67.803 vs 265.37 ± 77.86 vs 263.74 ± 82.58, F= 6.040, p< 0.01), L_energy (0.03 ± 0.02 vs 0.13 ± 0.11 vs 0.12 ± 0.14, F= 7.118, p< 0.01) and L_sum_average (0.78 ± 0.32 vs 16.34 ± 4.23 vs 015.45 ± 3.74, F= 21.860, p< 0.001) values of patients with Grade III IDC were significantly lower than those of patients with Grades I and II IDC. The B_uniform (0.15 ± 0.12 vs 0.11 ± 0.04 vs 0.12 ± 0.03, F= 3.797, p< 0.01) and L_SRE (0.85 ± 0.07 vs 0.78 ± 0.03 vs 0.79 ± 0.32, F= 3.024, p< 0.01) values of patients with Grade III IDC were significantly higher than those of patients with Grades I and II IDC. All differences were statistically significant (p< 0.05). The ADC radiomics signature model had a higher area-under-the-curve value in identifying different grades of IDC than the ADC value model and the DCE radiomics signature model (0.869 vs 0.711 vs 0.682). The accuracy (0.812 vs 0.647 vs 0.710), specificity (0.731 vs 0.435 vs 0.342), positive predictive value (0.815 vs 0.663 vs 0.669) and negative predictive value (0.753 vs 0.570 vs 0.718) of the ADC radiomics signature model were all significantly better than the ADC value model and the DCE radiomics signature model. CONCLUSION: ADC values and breast MRI radiomics signatures are significant in identifying the histological grades of IDC, with the ADC radiomics signatures having greater value.

Use total portosystemic shunt to rescue an emergency PNF with intractable hypotension: A case report.

RATIONALE: Living donor allogeneic liver transplantation is a surgical treatment for patients with end-stage liver disease, wherein a healthy liver is implanted in the patient, facilitating the recovery of the liver function in patients with end-stage liver disease. However, primary nonfunction (PNF) may occur as a result of this procedure. PATIENT CONCERNS: A case of an 65-year-old Asian male with a medical history of cirrhosis and hepatocellular carcinoma is described. Intractable hypotension occurred after open hepatic portal anastomosis, and large doses of vasoactive substances did not improve the condition. DIAGNOSIS: PNF was diagnosed during surgery and it caused intractable hypotension. INTERVENTIONS: we promptly used the total portosystemic shunt to achieve a successful rescue. OUTCOMES: The strengthening of perioperative management and active treatment allowed second liver transplantation and anhepatic phase of up to 10 hours, following which the patient was rescued. LESSONS: The lesson we have learned is that total portosystemic shunt composited with careful anesthesia management can rescue the event of PNF with intractable hypotension in liver transplantation surgery. At the same time, we give attention to blood pressure, electrocardiogram, albumin, calcium, potassium, acidosis, coagulopathy, anti-infection, and protection of vital organs is essential for successful retransplant outcomes.

Theoretical and experimental investigation of Al3+ ion-suppressed phase-separation structures in rare-earth-doped high-phosphorus silica glasses.

Rare-earth-doped silica-based composite glasses (Re-SCGs) are widely used as high-quality laser gain media in defense, aerospace, energy, power, and medical applications. The variable regional chemical environments of Re-SCGs can induce new photoluminescence properties of rare-earth ions but can cause the selective aggregation of rare-earth ions, limiting the application of Re-SCGs in the field of high-power lasers. Here, topological engineering is proposed to adjust the degree of cross-linking of phase-separation network chains in Re-SCGs. A combination of experimental and theoretical characterization techniques suggested that the selective aggregation of rare-earth ions originates from the formation of phase-separated structures in glasses. The decomposition of nanoscale phase separation structures to the sub-nanometer scale, enabled by incorporating Al3+ ions, not only maintains the high luminescence efficiency of rare earth ions but also increases light transmittance and reduces light scattering. Furthermore, our investigation encompassed the exploration of the inhibitory mechanism of Al3+ ions on phase-separation structures, as well as their influence on the spectral characteristics of Re-SCGs. This work provides a new design concept for composite glass materials doped with rare-earth ions and could broaden their application in the field of high-power lasers.

Occurrence, structure, and function of short cells in maize leaf epidermis.

Short cells are specialised epidermal cells of grasses and they include cork and silica cells. The time of occurrence, distribution, and number of short cells differ among plants or tissues of the same plant. The present study aimed to assess the occurrence, structure, and function of short cells in the epidermis of maize (Zea mays L.) leaves from cultivar "Zhengdan 958″ under field and potted experimental conditions. Results showed that short cells occurred synchronously in multiple maize leaves. Few short cells occurred at the base of the fifth leaf; most were found at the middle and base of the sixth leaf, and throughout the seventh leaf. The accumulation of K+ and H2O2 in cork cells changed periodically with stomatal opening and closure, which was consistent with the accumulation of K+ and H2O2 in subsidiary cells; whereas no accumulation was observed in silica cells. Moreover, photosynthetic parameters and stomatal aperture were significantly higher in leaves containing short cells than in those without them in the same parts of different leaves or in different leaves at the same leaf position. Accumulation of K+ and H2O2 in cork cells increased with increasing water stress. In conclusion, short cells not only improved leaf mechanical support and photosynthetic performance, and maize drought resistance, but they also participated in stomatal regulation.

Riboflavin-loaded carbon cloth aids the anaerobic digestion of cow dung by promoting direct interspecies electron transfer.

Cow dung generates globally due to increased beef and milk consumption, but its treatment efficiency remains low. Previous studies have shown that riboflavin-loaded conductive materials can improve anaerobic digestion through enhance direct interspecies electron transfer (DIET). However, its effect on the practical anaerobic digestion of cow dung remained unclear. In this study, carbon cloth loaded with riboflavin (carbon cloth-riboflavin) was added into an anaerobic digester treating cow dung. The carbon cloth-riboflavin reactor showed a better performance than other two reactors. The metagenomic analysis revealed that Methanothrix on the surface of the carbon cloth predominantly utilized the CO2 reduction for methane production, further enhanced after riboflavin addition, while Methanothrix in bulk sludge were using the acetate decarboxylation pathway. Furthermore, the carbon cloth-riboflavin enriched various major methanogenic pathways and activated a large number of enzymes associated with DIET. Riboflavin's presence altered the microbial communities and the abundance of functional genes relate to DIET, ultimately leading to a better performance of anaerobic digestion for cow dung.

Pseudolaric acid B exerts an antifungal effect and targets SIRT1 to ameliorate inflammation by regulating Nrf2/NF-κB pathways in fungal keratitis.

Fungal keratitis (FK) is a vision-threatening infection. We aimed to explore the antifungal and anti-inflammatory effects of pseudolaric acid B (PAB) on FK and the underlying mechanisms involved. Network pharmacology utilized to acquire the potential target genes, and silent information regulator 1 (SIRT1) was consistently downregulated in Gene Expression Omnibus dataset and clinical samples. Molecular docking analysis showed that PAB and SIRT1 had good binding activity. No toxicity was observed in vivo and in vitro with a PAB concentration below 0.3 µM. PAB exerted its antifungal activity by destroying the integrity of hyphae, and alleviated the severity of FK in rats by decreasing clinical scores, fungal burden and inhibiting inflammatory cell infiltration. PAB increased SIRT1 to regulate the crosstalk between nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa-B (NF-κB), decreasing the levels of inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6; and pattern recognition receptors, C-type lectin domain containing 7A (Dectin-1), lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1), toll like receptor (TLR)-2, and TLR4 both in vivo and in vitro. However, this anti-inflammatory effect of PAB was abolished by the SIRT1 inhibitor EX527. This study provides new evidence that PAB has antifungal and anti-inflammatory effects in FK and may provide a novel therapeutic strategy for the treatment of FK.

Reaction mechanism of the ethynylation of formaldehyde on copper terminated Cu2O(100) surfaces: a DFT study.

1,4-Butanediol (BDO) is an important chemical raw material for a series of high-value-added products. And the ethynylation of formaldehyde is the key step for the production of BDO by the Reppe process. However, little work has been done to reveal the reaction mechanism. In this work, the reaction mechanism for the ethynylation of formaldehyde process on copper-terminated Cu2O(100) surfaces was investigated with density functional theory (DFT). The reaction network of the ethynylation of formaldehyde was constructed first and the adsorption properties of the related species were calculated. Then the energy barrier and reaction energy of the related reactions and the geometric configuration were calculated. It is a consecutive reaction including two processes. For the propargyl alcohol (PA) formation process, the most favorable pathway is the direct addition of acetylene to formaldehyde followed by a hydrogen transfer reaction. And the rate control step is the hydrogen transfer reaction with an energy barrier of 1.43 eV. For the 1,4-butynediol (BYD) formation process, the most competitive pathway is the addition of PA to CH2OH, including formaldehyde hydrogenation to form CH2OH, coupling addition, and dehydrogenation reaction. The rate control step of this pathway is the dehydrogenation reaction with an energy barrier of 1.51 eV.

High-efficiency all-fluorescent white organic light-emitting diode based on TADF material as a sensitizer.

The use of TADF materials as both sensitizers and emitters is a promising route to achieve high-efficiency all-fluorescent white organic light-emitting diodes (WOLEDs). In this study, the thermally-activated delayed-fluorescent (TADF) material DMAC-TRZ (9,9-dimethyl-9,10-dihydroacridine-2,4,6-triphenyl-1,3,5-triazine) was selected as a sensitizer for the conventional fluorescent emitter DCJTB (4-(dicyanomethylene)-2-t-butyl-6-(1,1,7,7-tetramethyljulolidyl-9-enyl)-4H-pyran), which was co-doped in a wide bandgap host of DPEPO (bis[2-(diphenylphosphino)phenyl]ether oxide) to fabricate WOLEDs. For the emitting layer of DPEPO:DMAC-TRZ:DCJTB, the DPEPO host can dilute the exciton concentration formed on the DMAC-TRZ sensitizer, which benefits the suppression of exciton quenching. The effect of the doping concentration of DCJTB on the carrier recombination and energy transfer process was investigated. With an optimized doping concentration of DCJTB as 0.8%, highly efficient WOLED was achieved with a maximum external quantum efficiency (EQE), power efficiency (PE), and current efficiency (CE) of 11.05%, 20.83 lm W-1, and 28.83 cd A-1, respectively, corresponding to the Commission Internationale de I' Eclairage (CIE) coordinates of (0.45, 0.46). These superior performances can be ascribed to the fact that the hole-trapping effect of the emitter and Dexter energy transfer (DET) from sensitizer to emitter can be suppressed simultaneously by the extremely low doping concentration.

IL-24 is the key effector of Th9 cell-mediated tumor immunotherapy.

Th9 cells are powerful effector T cells for cancer immunotherapy. However, the underlying antitumor mechanism of Th9 cells still needs to be further elucidated. Here, we show that Th9 cells express high levels of not only IL-9, but also IL-24. We found that knockout of Il24 gene in Th9 cells promotes Th9 cell proliferation in vitro, but decreases Th9 cell survival in vitro and in vivo. Interestingly, knockout of Il24 gene in Th9 cells decreases the tumor-specific cytotoxicity of Th9 cells in vitro. In addition, immunotherapy with Il24 knockout Th9 cells exhibit less tumor inhibition than regular Th9 cells in mouse tumor models. We found that inhibition of Foxo1 by a specific inhibitor downregulates IL-24 expression in Th9 cells and decreases Th9 cell antitumor efficacy in vivo. Our results identify IL-24 as a powerful antitumor effector of Th9 cells and provide a target in Th9 cell-mediated tumor therapy.

Interleukin-10 increases macrophage-mediated chemotherapy resistance via FABP5 signaling in multiple myeloma.

Macrophages (MΦs) protect multiple myeloma (MM) cells from chemotherapy-induced apoptosis, and interleukin-10 (IL-10) is frequently elevated in the MM microenvironment. However, the role of IL-10 in MΦ-induced tumor chemotherapy resistance has not yet been clarified. In the present study, bone marrow-derived MΦs were treated with IL-10 (IL10-MΦs), and IL10-MΦ-induced MM chemotherapy resistance was evaluated. IL-10 promoted MΦ-mediated resistance to MM chemotherapy. In addition, IL-10 treatment increased lipid accumulation and fatty acid ß-oxidation in MΦs. Mechanistically, IL-10 increased fatty acid binding protein 5 (FABP5) expression in MΦs, and targeting FABP5 decreased MM chemotherapy resistance induced by IL10-MΦs in vitro and enhanced chemotherapeutic efficacy in vivo. Inhibition of FABP5 decreased the expression of Carnitine Palmitoyltransferase 1A (CPT1A) in IL10-MΦs. In addition, inhibition of CPT1A in IL10-MΦs decreased IL10-MΦ-mediated MM chemotherapy resistance. Peroxisome proliferator-activated receptor γ (PPARγ) is upstream of FABP5 signaling. Inhibition of PPARγ in IL10-MΦs decreased IL10-MΦ-mediated MM chemotherapy resistance in vitro. Collectively, our work indicates that IL-10 enhances MΦ-mediated MM chemotherapy resistance via FABP5 signaling and targeting FABP5 has potentially important clinical implications.

Microsurgery for drug resistance epilepsy due to temporal lobe lesions in a resource limited condition: a cross-sectional study.

Epilepsy is a prevalent neurological condition that affects individuals of all ages and genders worldwide. Surgical intervention for drug-resistant epilepsy has been found to improve quality of life, with patient independence being of utmost importance. Methods: The study was a retrospective and prospective cross-sectional study of 35 cases of drug-resistant temporal lobe epilepsy. All patients were operated on by the primary author between May 2018 and September 2022. The study evaluated various factors including clinical characteristics, electroencephalogram, magnetic resonance imaging, surgical outcomes, and histopathology. Results: The success rate of the surgeries (74.3%) is similar to those reported in high-income countries. 51.4% underwent selective amygdalohippocampectomy for cases that localized to the mesial temporal lobe. Lateral/neocortical lesions underwent lesionectomy (48.6%). Our study found a complication rate of 17.1%: meningitis (8.5%), trainset focal paralysis (2.9%), and soft tissue infection (5.7%). There were no mortalities. Conclusions: The article showcases an international collaborative effort that demonstrates the possibility of providing highly effective and safe surgical care for temporal lobe epilepsy even in low-resource environments. The authors hope that this model can be replicated in other areas with similar resource limitations.

Temporal Lobe Surgery for Epilepsy in a Resource-Limited Vietnamese Cohort.

BACKGROUND: Epilepsy surgery is traditionally difficult to pursue in resource-limited countries but is nevertheless essential in the treatment of medication-refractory, surgically amenable epilepsy. METHODS: With the help of international collaboration, a successful epilepsy program was started in Vietnam. This article comprises a retrospective chart review, combined with prospective longitudinal follow-up of 35 cases of unilateral drug-resistant epilepsy in the temporal lobe who underwent temporal lobectomy, in Viet Duc University Hospital from May 2018 to September 2022. RESULTS: The female/male ratio was 0.6:1, and focal seizures with impaired awareness accounted for 97.14% of patients. Of patients with focal awareness seizures, 51.41% were localized and detected by electroencephalography. Postoperatively, 80% of patients were seizure free (Engel I) at 1 year, and the remaining 20% had worthwhile seizure improvement (Engel II). Postoperative temporal lobe pathology was categorized as follows: mesial temporal sclerosis (48.57%), focal cortical dysplasia (25.71%), and low-grade neoplasms (25.71%). Of patients, 17.14% had postoperative complications (5 infections and 1 transient extremity paresis), and there were no deaths. CONCLUSIONS: Even in low-resource environments, effective and safe surgical care can be provided for drug-resistant epilepsy caused by temporal lobe disease. This study serves as a model of international collaboration and support for future hospitals in low-resource environments to replicate.

Research progress on reactive oxygen species production mechanisms in tumor sonodynamic therapy.

In recent years, because of the growing desire to improve the noninvasiveness and safety of tumor treatments, sonodynamic therapy has gradually become a popular research topic. However, due to the complexity of the therapeutic process, the relevant mechanisms have not yet been fully elucidated. One of the widely accepted possibilities involves the effect of reactive oxygen species. In this review, the mechanism of reactive oxygen species production by sonodynamic therapy (SDT) and ways to enhance the sonodynamic production of reactive oxygen species are reviewed. Then, the clinical application and limitations of SDT are discussed. In conclusion, current research on sonodynamic therapy should focus on the development of sonosensitizers that efficiently produce active oxygen, exhibit biological safety, and promote the clinical transformation of sonodynamic therapy.