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Diabetic wounds pose a clinical challenge due to persistent inflammation, severe bacterial infections, inadequate vascularization, and pronounced oxidative stress. Current therapeutic modalities fail to provide satisfactory outcomes in managing these conditions, resulting in considerable patient distress. Two-dimensional nanomaterials (2DNMs), characterized by their unique nanosheet structures, expansive surface areas, and remarkable physicochemical properties, have garnered considerable attention for their potential in therapeutic applications. Emerging 2DNMs can be loaded with various pharmacological agents, including small molecules, metal ions, and liposomes. Moreover, they can be integrated with various biomaterials such as hydrogels, microneedles, and microspheres, thus demonstrating unprecedented advantages in expediting the healing process of diabetic wounds. Moreover, 2DNMs exhibit exceptional performance characteristics, including high biocompatibility, effective antimicrobial properties, optimal phototherapeutic effects, and enhanced electrostimulation capabilities. These properties enable them to modulate the wound microenvironment, leading to widespread application in tissue repair with remarkable outcomes. This review delineates several emerging 2DNMs, such as graphene and its derivatives, black phosphorus, MXenes, and transition metal dichalcogenides, in the context of diabetic wound repair. Furthermore, it elucidates the translational challenges and future perspectives of 2DNMs in wound healing treatments. Overall, 2DNMs present a highly promising strategy for ameliorating diabetic wounds, thus providing novel avenues for diagnostic and therapeutic strategies in diabetic wound management.
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Peptide-based drugs hold great potential for cancer treatment, and their effectiveness is driven by mechanisms on how peptides target cancer cells and escape from potential lysosomal entrapment post-endocytosis. Yet, the mechanisms remain elusive, which hinder the design of peptide-based drugs. Here hendeca-arginine peptides (R11) are synthesized for targeted delivery in bladder carcinoma (BC), investigated the targeting efficiency and elucidated the mechanism of peptide-based delivery, with the aim of refining the design and efficacy of peptide-based therapeutics. It is demonstrated that the over-activated Piezo1/integrin ß1 (ITGB1) signaling axis significantly facilitates tumor-targeted delivery of R11 peptides via macropinocytosis. Furthermore, R11 peptides formed hydrogen bonds with integrin ß1, facilitating targeting and penetration into tumor cells. Additionally, R11 peptides protected integrin ß1 from lysosome degradation, promoting its recycling from cytoplasm to membrane. Moreover, this findings establish a positive feedback loop wherein R11 peptides activate Piezo1 by increasing membrane fusion, promoting Ca2+ releasing and resulting in enhanced integrin ß1-mediated endocytosis in both orthotopic models and clinical tissues, demonstrating effective tumor-targeted delivery. Eventually, the Piezo1/integrin ß1 signaling axis promoted cellular uptake and transport of peptides, establishing a positive feedback loop, promoting mechanical delivery to cancer and offering possibilities for drug modification in cancer therapy.
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OBJECTIVE: To evaluate the efficacy and safety of Wuda Granule (WDG) on recovery of gastrointestinal function after laparoscopic bowel resection in the setting of enhanced recovery after surgery (ERAS)-based perioperative care. METHODS: A total of 108 patients aged 18 years or older undergoing laparoscopic bowel resection with a surgical duration of 2 to 4.5 h were randomly assigned (1:1) to receive either WDG or placebo (10 g/bag) twice a day from postoperative days 1-3, combining with ERAS-based perioperative care. The primary outcome was time to first defecation. Secondary outcomes were time to first flatus, time to first tolerance of liquid or semi-liquid food, gastrointestinal-related symptoms and length of stay. Subgroup analysis of the primary outcome according to sex, age, tumor site, surgical time, histories of underlying disease or history of abdominal surgery was undertaken. Adverse events were observed and recorded. RESULTS: A total of 107 patients [53 in the WDG group and 54 in the placebo group; 61.7 ± 12.1 years; 50 males (46.7%)] were included in the intention-to-treat analysis. The patients in the WDG group had a significantly shorter time to first defecation and flatus [between-group difference -11.01 h (95% CI -20.75 to -1.28 h), P=0.012 for defecation; -5.41 h (-11.10 to 0.27 h), P=0.040 for flatus] than the placebo group. Moreover, the extent of improvement in postoperative gastrointestinal-related symptoms in the WDG group was significantly better than that in the placebo group (P<0.05). Subgroup analyses revealed that the benefits of WDG were significantly superior in patients who were male, or under 60 years old, or surgical time less than 3 h, or having no history of basic disease or no history of abdominal surgery. There were no serious adverse events. CONCLUSION: The addition of WDG to an ERAS postoperative care may be a viable strategy to enhance gastrointestinal function recovery after laparoscopic bowel resection surgery. (Registry No. ChiCTR2100046242).
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OBJECTIVE: To observe the effect of early cervical functional exercise (CFE) on clinical outcomes and safety of patients after anterior cervical discectomy and fusion (ACDF). METHODS: Sixty patients who underwent ACDF from September 2019 to September 2020 were analyzed and randomly divided into two groups: the CFE group (27 cases) and the usual care (UC) group (33 cases). Then, all patients in the two groups received routine postoperative guidance care at the same time. Besides, the patients of the CFE group underwent a cervical functional exercise program after on the third day after ACDF. The evaluation was conducted preoperatively and at 1 week, 1 month and 6 months after surgery. The Visual Analogue Scale (VAS), Neck Disability Index (NDI) and Japanese Orthopaedic Association scores (JOA) were used to assess clinical outcomes and the safety was confirmed with routine postoperative radiological visits to ensure intervertebral stability. RESULTS: The CFE group reported lower neck pain scores on VAS at 1 month after surgery (P = 0.02) and higher postoperative scores by JOA at 1 month and 6 months, neck disability on NDI at 1 week, 1 month and 6 months after surgery (P < 0.05) compared to the UC group. For postoperative dysfunction, the CFE group had more significant changes than the UC group at 1 month and 6 months after surgery (P < 0.05). There was no statistical difference in cervical curves, fusion rate and fusion status between the two groups, and no revision surgery was recorded although a patient has one screw partially back out in UC group. CONCLUSION: Our study suggested that the cervical functional exercise could decrease cervical pain and improve postoperative function in patients after ACDF. It was a safe and effective treatment for postoperative rehabilitation. The use of a postoperative collar, especially for one or two-level ACDF may not be needed. PROTOCOL IDENTIFYING NUMBER: This trial was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR1900025569) on 01/09/2019.
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Aims: Rotator cuff tear (RCT) is the leading cause of shoulder pain, primarily associated with age-related tendon degeneration. This study aimed to elucidate the potential differential gene expressions in tendons across different age groups, and to investigate their roles in tendon degeneration. Methods: Linear regression and differential expression (DE) analyses were performed on two transcriptome profiling datasets of torn supraspinatus tendons to identify age-related genes. Subsequent functional analyses were conducted on these candidate genes to explore their potential roles in tendon ageing. Additionally, a secondary DE analysis was performed on candidate genes by comparing their expressions between lesioned and normal tendons to explore their correlations with RCTs. Results: We identified 49 genes in torn supraspinatus tendons associated with advancing age. Among them, five age-related genes showed DE in lesioned tendons compared to normal tendons. Functional analyses and previous studies have highlighted their specific enrichments in biological functions, such as muscle development (e.g. myosin heavy chain 3 (MYH3)), transcription regulation (e.g. CCAAT enhancer binding brotein delta (CEBPD)), and metal ion homeostasis (e.g. metallothionein 1X (MT1X)). Conclusion: This study uncovered molecular aspects of tendon ageing and their potential links to RCT development, offering insights for targeted interventions. These findings enhance our understanding of the mechanisms of tendon degeneration, allowing potential strategies to be made for reducing the incidence of RCT.
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In the vanguard of neuromorphic engineering, we develop a paradigm of biocompatible polymer memcapacitors using a seamless solution process, unleashing comprehensive synaptic capabilities depending on both the stimulation form and history. Like the human brain to learn and adapt, the memcapacitors exhibit analogue-type and evolvable capacitance shifts that mirror the complex flexibility of synaptic strengthening and weakening. With increasing frequency and intensity of the stimulation, the memcapacitors demonstrate an evolution from short-term plasticity (STP) to long-term plasticity (LTP), and even to metaplasticity (MP) at a higher level. A physical picture, featuring the stimulus-controlled spatiotemporal ion redistribution in the polymer, elaborates the origin of the memcapacitive prowess and resultant versatile synaptic plasticity. The distinctive MP behavior endows the memcapacitors with a dynamic learning rate (LR), which is utilized in an artificial neural network. The superiority of implementing a dynamic LR compared with conventional practices of using constant LR shines light on the potential of the memcapacitors to exploit organic neuromorphic computing hardware.
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AIMS: Microglia activation after spinal cord injury (SCI) is a double-edged sword, modulation of the activated microglia populations toward pro-regenerative phenotypes highlights the potential therapeutic implications. P2Y12, a microglia-specific marker, remains underexplored in its capacity to polarize microglial activation populations in SCI repair. We aimed to explore the effects of modulating P2Y12 on microglia function after spinal cord injury, and further on axonal regeneration and motor recovery after spinal cord injury. MATERIALS AND METHODS: The study employed both in vitro and in vivo models, using BV2 cells and a mouse model of SCI, respectively. Ticagrelor, a P2Y12 antagonist, was administered via a collagen scaffold to ensure stable and sustained release. Transcriptome sequencing analysis, immunofluorescence staining, and Basso Mouse Scale (BMS) scores were used to assess microglial activation, axonal regeneration, and functional recovery. KEY FINDINGS: Herein, we observed P2Y12+ microglia localized predominantly at the lesion periphery within 3â¯days post injury (dpi), manifesting a pro-inflammatory phenotype, but not anti-inflammatory phenotype. In vitro investigations revealed that P2Y12 inhibition of the activated microglia curtailed pro-inflammatory differentiation while augmenting anti-inflammatory differentiation. SIGNIFICANCE: Leveraging this insight, we engineered a collagen scaffold-based delivery system for sustained release of the P2Y12 antagonist, ticagrelor, at the injury site in a mouse complete SCI model. Notably, P2Y12 suppression markedly enhanced axonal regeneration within the injured site and ameliorated lower limb motor functions in SCI mice. Collectively, our findings illuminate P2Y12-targeted microglial modulation as a promising therapeutic approach for SCI.
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Treatment options for patients with relapsed extensive-stage small cell lung cancer (ES-SCLC) remain scarce. This study aims to evaluate the efficacy and safety of combining anlotinib and sintilimab plus chemotherapy as a second line or later therapy for ES-SCLC patients. This is a phase II clinical trial (ChiCTR2100049390) conducting at Shandong Cancer Hospital. Patients with ES-SCLC and received at least one prior systemic treatment were enrolled. The trial design involved a combination therapy (sintilimab, anlotinib, and nab-paclitaxel) administered over six 21-day cycles, followed by maintenance sintilimab therapy. The primary endpoint was objective response rate (ORR). Circulating tumor DNA sequencing was employed for exploratory analysis. From July 2021 to April 2023, 25 eligible patients were enrolled. The confirmed ORR was 60% (95% CI: 38.7-78.9%) and the DCR was 76% (95% CI: 54.9-90.6%). The mPFS was 6.0 months (95% CI: 5.4-9.7), and the 6-month PFS rate was 49.2%. The mOS was 13.4 months (95% CI: 11.8-NR), with a 12-month survival rate of 62.2%. Treatment-related adverse events (TRAEs) of any grade occurred in 80% of patients, with the most common being fatigue (40%) and nausea (32%). TRAEs of Grade 3 or higher were reported in 12% of patients. ctDNA analysis indicated that low on-treatment blood tumor mutation burden was associated with longer PFS and OS and a potential role of KMT2D mutation in treatment resistance. This combination therapy shows promising efficacy and a manageable safety profile as a second-line or later treatment for ES-SCLC, with genomic insights providing potential biomarkers for treatment response.
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Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Indoles , Neoplasias Pulmonares , Quinolinas , Carcinoma Pulmonar de Células Pequeñas , Humanos , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/patología , Femenino , Masculino , Persona de Mediana Edad , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Anciano , Indoles/administración & dosificación , Indoles/uso terapéutico , Indoles/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quinolinas/administración & dosificación , Quinolinas/uso terapéutico , Quinolinas/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Adulto , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Paclitaxel/uso terapéutico , Estadificación de Neoplasias , AlbúminasRESUMEN
OBJECTIVE: Otolaryngologists are at a significantly greater risk of being sued than most other physicians. To date, there is a lack of studies characterizing trends in otolaryngology malpractice claims. To assess these trends and risk variables, this study examined malpractice claims against otolaryngologists. STUDY DESIGN: Retrospective database review. SETTING: LexisNexis Jury Verdicts and Settlements. METHODS: The LexisNexis legal database was used to locate jury verdicts and settlements related to medical malpractice in otolaryngology, from 2018 to 2024. The study did not include any claims covered by the Social Security Disability Insurance, Workers' Compensation, Healthcare Law, or Criminal Law and Procedure categories. Temporal trends were evaluated, and logistic regression was used to identify independent risk factors. RESULTS: Out of 903 items, 79 reported malpractice cases were included (mean age 44.5; 60.3% female). The most sued subspecialty was head and neck oncology (32.5%). Negligence (93.7%) was the primary cause of action. Of cases sent to the jury, 87.7% of them resulted in a verdict in favor of the defendant. The mean plaintiff verdict payout was $7,432,508.06 and the mean identified settlement amount was $1,562,500.00. Physical injury (62.0%) was the highest type of harm. Regional analysis indicated a higher percentage of cases from New York favored the defendant (21.1% vs 13.6%; P = .034). CONCLUSION: This study highlights key trends in otolaryngology malpractice claims, emphasizing the prevalence in cases of head and neck surgery, primarily attributed to negligence. By identifying trends and risk factors, otolaryngologists can get a better understanding of the dynamics surrounding malpractice.
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TTFields is a novel FDA-approved technology utilized for treating glioblastoma multiforme (GBM) within the brain. Presently, the effectiveness of therapy is evaluated through MRI imaging at random two-month intervals. Electrical impedance is an important and effective parameter for reflecting changes in tissue properties. In TTFields treatment for brain tumors, electrodes attached to the scalp deliver electric field energy to the tumor region. We hypothesize that these electrodes can also serve as sensors to detect impedance changes caused by tumor alterations in real time, thus continuously assessing the effectiveness of the treatment. In this work, we propose and scrutinize this hypothesis by conducting an in silico study to confirm the potential feasibility of the proposed concept. Our results indicate that the impedance amplitude change measured between opposing TTFields electrode arrays utilizing voltage and frequency of 50 V and 200 kHz (typical TTFields treatment parameters), has enough resolution (> 1mm) and Signal-to-Noise Ratio (> 40 dB) to evaluate tumor size change in the head. The impedance detection technique may be a significant augmentation to TTFields cancer treatment, enabling the continuous evaluation of safety and efficacy throughout the procedure.
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OBJECTIVES: Endoscopic necrosectomy (EN) is a promising minimally invasive approach for treating infected walled-off pancreatic necrosis (WOPN). Multiple EN approaches are currently available, though criteria for selecting the optimal approaches are lacking. We aimed to propose a rational selection strategy of EN and to retrospectively evaluate its safety and effectiveness. METHODS: Altogether 101 patients who underwent EN for infected WOPN at a tertiary hospital between June 2009 and February 2023 were retrospectively included for analysis. Demographic characteristics, details of the EN procedures, procedure-related adverse events, and clinical outcomes were investigated. RESULTS: Among these 101 patients with WOPN, 56 (55.4%) underwent transluminal EN, 38 (37.6%) underwent percutaneous EN, and seven (6.9%) underwent combined approach, respectively. Clinical success was achieved in 94 (93.1%) patients. Seven (6.9%) experienced procedure-related adverse events, and seven (6.9%) died during the treatment period. During a median follow-up of 50 months, 5 (5.3%) of the 94 patients had disease recurrence, 17.0% (16/94) had new-onset diabetes mellitus, and 6.4% (6/94) needed oral pancreatic enzyme supplementation. The clinical success rate, procedure-related adverse event rate, and long-term follow-up outcomes were not significantly different among the three groups. High APACHE-II scores (≥15) and organ failure were identified as factors related to treatment failure. CONCLUSIONS: A selection strategy for EN approaches, based on the extent of necrosis and its distance from the gastrointestinal lumen (using a threshold of 15 mm), is safe and effective for treating infected WOPN in both short-term and long-term outcomes.
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Chemical moderate preoxidation for algae-laden water is an economical and prospective strategy for controlling algae and exogenous pollutants, whereas it is constrained by a lack of effective on-line evaluation and quick-response feedback method. Herein, excitation-emission matrix parallel factor analysis (EEM-PARAFAC) was used to identify cyanobacteria fluorophores after preoxidation of sodium hypochlorite (NaClO) at Excitation/Emission wavelength of 260(360)/450 nm, based on which the algal cell integrity and intracellular organic matter (IOM) release were quantitatively assessed. Machine learning modeling of fluorescence spectral data for prediction of moderate preoxidation using NaClO was established. The optimal NaClO dosage for moderate preoxidation depended on algal density, growth phases, and organic matter concentrations in source water matrices. Low doses of NaClO (<0.5 mg/L) led to short-term desorption of surface-adsorbed organic matter (S-AOM) without compromising algal cell integrity, whereas high doses of NaClO (≥0.5 mg/L) quickly caused cell damage. The optimal NaClO dosage increased from 0.2-0.3 mg/L to 0.9-1.2 mg/L, corresponding to the source water with algal densities from 0.1 × 106 to 2.0 × 106 cells/mL. Different growth stages required varying NaClO doses: stationary phase cells needed 0.3-0.5 mg/L, log phase cells 0.6-0.8 mg/L, and decaying cells 2.0-2.5 mg/L. The presence of natural organic matter and S-AOM increased the NaClO dosage limit with higher dissolved organic carbon (DOC) concentrations (1.00 mg/L DOC required 0.8-1.0 mg/L NaClO, while 2.20 mg/L DOC required 1.5-2.0 mg/L). Compared to other predictive models, the machine learning model (Gaussian process regression-Matern (0.5)) performed best, achieving R2 values of 1.000 and 0.976 in training and testing sets. Optimal preoxidation followed by coagulation effectively removed algal contaminants, achieving 91%, 92%, and 92% removal for algal cells, turbidity, and chlorophyll-a, respectively, thereby demonstrating the effectiveness of moderate preoxidation. This study introduces a novel approach to dynamically adjust NaClO dosage by monitoring source water qualities and tracking post-preoxidation fluorophores, enhancing moderate preoxidation technology application in algae-laden water treatment.
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Tea plants are a perennial crop with significant economic value. Chlorophyll, a key factor in tea leaf color and photosynthetic efficiency, is affected by the photoperiod and usually exhibits diurnal and seasonal variations. In this study, high-throughput transcriptomic analysis was used to study the chlorophyll metabolism, under different photoperiods, of tea plants. We conducted a time-series sampling under a skeleton photoperiod (6L6D) and continuous light conditions (24 L), measuring the chlorophyll and carotenoid content at a photoperiod interval of 3 h (24 h). Transcriptome sequencing was performed at six time points across two light cycles, followed by bioinformatics analysis to identify and annotate the differentially expressed genes (DEGs) involved in chlorophyll metabolism. The results revealed distinct expression patterns of key genes in the chlorophyll biosynthetic pathway. The expression levels of CHLE (magnesium-protoporphyrin IX monomethyl ester cyclase gene), CHLP (geranylgeranyl reductase gene), CLH (chlorophyllase gene), and POR (cytochrome P450 oxidoreductase gene), encoding enzymes in chlorophyll synthesis, were increased under continuous light conditions (24 L). At 6L6D, the expression levels of CHLP1.1, POR1.1, and POR1.2 showed an oscillating trend. The expression levels of CHLP1.2 and CLH1.1 showed the same trend, they both decreased under light treatment and increased under dark treatment. Our findings provide potential insights into the molecular basis of how photoperiods regulate chlorophyll metabolism in tea plants.
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Clorofila , Ritmo Circadiano , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Fotoperiodo , Transcriptoma , Clorofila/metabolismo , Ritmo Circadiano/genética , Camellia sinensis/genética , Camellia sinensis/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
INTRODUCTION: Keverprazan is a novel potassium-competitive acid blocker, whose advantages as a potent acid suppressor in Helicobacter pylori (H. pylori) eradication has not yet been demonstrated. This study aimed to evaluate the efficacy of Keverprazan as a component of bismuth quadruple therapy in H. pylori treatment. METHODS: Adult patients with H. pylori infection were enrolled and randomized to take Keverprazan (KEV group) or Esomeprazole (ESO group)-quadruple therapy (regimen contains Keverprazan 20 mg or Esomeprazole 20 mg, clarithromycin 500 mg, amoxicillin 1000 mg, bismuth potassium citrate 240 mg) twice daily for 14 days. The primary endpoint was the H. pylori eradication rate at 4 weeks after treatment. RESULTS: Full analysis set showed the H. pylori eradication rates were 87.8% (252/287) and 82.52% (236/286) for KEV group and ESO group, respectively (difference: 5.29%; 95% CI: -0.55% to 11.18%). Superiority of Keverprazan over Esomeprazole in terms of eradication rate was observed in the per-protocol set (P=0.0382). The eradication rates for patients resistant or not resistant to clarithromycin were both numerically higher in KEV group than ESO group (83.45% vs. 76.98% for clarithromycin-resistance; 96.67 vs. 93.38% for clarithromycin-nonresistance). The incidence of adverse events was similar in KEV and ESO group (76.31% vs. 77.62%), with most adverse events (>90%) being mild in severity and leading to no deaths. CONCLUSIONS: Keverprazan 20 mg twice daily, used as a component of bismuth quadruple therapy provided effective H. pylori eradication and was non-inferior to Esomeprazole-based regimen.
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To understand the adaptation of water use strategy of plant community to habitat heterogeneity, we measured the δD and δ18O values of xylem water of shrubs and potential water sources (soil water in different layers or groundwater) of Ammopiptanthus mongolicus communities on sand dune and Gobi from April to September in 2021 in the Ulan Buh Desert. Employing the MixSIAR model, we examined the seasonal dynamics of water source of each shrub by quantifying the contribution of different potential water sources. The results showed that A. mongolicus and Artemisia xerophytica on sand dune mainly used soil water of 10-25 cm in April and May after heavy rain in early spring, whereas Artemisia ordosica mainly used soil water of 10-200 cm. During the drought event within summer from June to August, A. mongolicus increasingly used soil water of 100-200 cm and groundwater, but A. xerophytica and A. ordosica increased the usage of 50-200 cm soil water. After the moderate rain in September, A. mongolicus evenly used soil water in all layers and groundwater, whereas two Artemisia shrubs preferred soil water of 10-50 cm. On Gobi, A. mongolicus and Nitraria sphaerocarpa evenly used soil water in all layers in April and May, mainly used 50-150 cm soil water from June to August and used 10-50 cm soil water in September. Convolvulus tragacanthoides mainly used soil water of 10-50 cm (from April to May), 25-150 cm (from June to August), and 10-25 cm (in September), separately. There were seasonal differences in water use of three shrubs on sand dune and Gobi A. mongolicus communities. During drought, A. mongolicus on sand dune could use deep soil water and groundwater, and that on Gobi relied only on deep soil water, which was more sensitive to rainfall.
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Artemisia , Clima Desértico , Ecosistema , Suelo , Agua , China , Agua/análisis , Artemisia/crecimiento & desarrollo , Suelo/química , Estaciones del Año , Agua Subterránea/análisis , Agua Subterránea/química , Sequías , LluviaRESUMEN
Spinal cord injury (SCI) is a severe neurological disorder that can lead to paralysis or death. Oxidative stress during SCI is a critical phase causing extensive nerve cell damage and apoptosis, thereby impairing spinal cord healing. Thus, a primary goal of SCI drug therapy is to mitigate oxidative stress. Curculigoside (CUR), a phenolic glucoside extracted from the dried root and rhizome of Curculigo orchioides Gaertn, possesses neuroprotective and antioxidant properties. This study aimed to investigate whether CUR effectively promotes the recovery of spinal cord tissue following SCI and elucidate its mechanism. We employed a hydrogen peroxide (H2O2)-induced PC12 cell model and an SCI rat model to observe the effects of CUR on oxidation and apoptosis. The results demonstrated that CUR significantly reduced the expression of apoptosis-related proteins (Bax and Caspase-3), Annexin V/propidium iodide (PI), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), while increasing the expression of the anti-apoptotic protein Bcl-2. Moreover, CUR effectively enhanced levels of antioxidants (glutathione [GSH)] and decreased reactive oxygen species (ROS) in vitro. Furthermore, CUR facilitated functional recovery through its anti-apoptotic and anti-oxidative stress effects on spinal cord tissues in SCI rats. These effects were mediated via the Nrf2/NQO1 signaling pathway. Therefore, our study showed that CUR acted as an anti-apoptotic and anti-oxidative stress agent, inhibiting astrocyte activation and promoting neuronal reconstruction and functional recovery. These findings may contribute significantly to the development of SCI treatments and advance the field of SCI drug therapy.
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Recently the FDA conducted a risk investigation and labeled the Boxed Warning for all BCMA- and CD19-directed CAR-T cell therapy, so does it mean that the public must take risk of secondary cancer to receive cell therapy? Here, without lentivirus and professional antigen presenting cell application, a novel tumor-specific T-cell therapy was successfully developed only by co-culturing MHC+ cancer cells and Naïve-T cells under the CD28 co-stimulatory signals. These tumor-specific T-cells could be separated through cell size and abundantly produced from peripheral blood, and would spontaneously attack target cells that carrying the same tumor antigen while avoiding others in vitro test. Moreover, it markedly decreased 90% tumor nodules companying with greatly improving overall survival (76 days vs 30 days) after twice infusion back to mice. This work maximally avoided the risks of secondary cancer and non-specific killing, and might open a revolutionary beginning of natural tumor-specific T-cell therapy.
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2,5-Diformylfuran (DFF) is a significant biomass-derived compound with diverse applications in novel furan-based materials, fragrances, fuel additives, and drug synthesis. A pivotal challenge in DFF synthesis is developing a method to produce DFF under mild conditions using sustainable feedstocks. In this study, an affordable 4-hydroxy-2,2,6,6-tetramethylpiperidine (TEMPOL)- assisted Cu(OAc)2 catalytic system for aerobic oxidation reaction of HMF to DFF in liquid sunlight methanol solvent was developed. The effects of parameters such as metal species, catalyst amount, solvent species, ligand structure, and reaction temperature were systematically investigated. The evolution of product distribution in the reaction solution at various times was monitored and analyzed using 1H-NMR spectroscopy. FT-IR and ESI-MS characterizations were employed to integrate experimental findings and elucidate the reaction mechanism. The highest DFF yield of 96% and complete conversion of HMF were obtained. Furthermore, a total DFF yield of 68.6% was achieved from fructose using a two-steps method, demonstrating the potential for scalable production. The establishment of this catalytic system presents a novel approach for the selective preparation of DFF from sustainable feedstocks.
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BACKGROUND: Saccharomyces cerevisiae is a fungus widely used in the food industry and biofuel industry, whereas it is usually exposed to high sugar stress during the fermentation process. Ca2+ is a key second messenger of the cell, it can regulate cell metabolism. The present study investigated the effect of the Ca2+ signal on the activity of key enzymes of carbon metabolism and related gene expression in yeast under high sugar fermentation. RESULTS: The expression of genes encoding hexokinase was up-regulated in the high sugar environment, the activity of hexokinase was increased, glucose transmembrane transport capacity was enhanced, the ability of glucose to enter into glycolytic metabolism was increased, and the expression of genes related to pentose phosphate metabolism, glycerol metabolism and trehalose metabolism was up-regulated in the high glucose with Ca2+ group. CONCLUSION: Ca2+ signal regulates the cellular metabolism of glycerol and trehalose and optimizes the allocation of carbon flow by regulating the key enzymes and related gene expression to enhance the resistance of yeast to high sugar stress. © 2024 Society of Chemical Industry.