X-Paste improves wound healing in diabetes via NF-E2-related factor/HO-1 signaling pathway.

BACKGROUND: Diabetic foot ulcers (DFU), as severe complications of diabetes mellitus (DM), significantly compromise patient health and carry risks of amputation and mortality. AIM: To offer new insights into the occurrence and development of DFU, focusing on the therapeutic mechanisms of X-Paste (XP) of wound healing in diabetic mice. METHODS: Employing traditional Chinese medicine ointment preparation methods, XP combines various medicinal ingredients. High-performance liquid chromatography (HPLC) identified XP's main components. Using streptozotocin (STZ)-induced diabetic, we aimed to investigate whether XP participated in the process of diabetic wound healing. RNA-sequencing analyzed gene expression differences between XP-treated and control groups. Molecular docking clarified XP's treatment mechanisms for diabetic wound healing. Human umbilical vein endothelial cells (HUVECs) were used to investigate the effects of Andrographolide (Andro) on cell viability, reactive oxygen species generation, apoptosis, proliferation, and metastasis in vitro following exposure to high glucose (HG), while NF-E2-related factor-2 (Nrf2) knockdown elucidated Andro's molecular mechanisms. RESULTS: XP notably enhanced wound healing in mice, expediting the healing process. RNA-sequencing revealed Nrf2 upregulation in DM tissues following XP treatment. HPLC identified 21 primary XP components, with Andro exhibiting strong Nrf2 binding. Andro mitigated HG-induced HUVECs proliferation, metastasis, angiogenic injury, and inflammation inhibition. Andro alleviates HG-induced HUVECs damage through Nrf2/HO-1 pathway activation, with Nrf2 knockdown reducing Andro's proliferative and endothelial protective effects. CONCLUSION: XP significantly promotes wound healing in STZ-induced diabetic models. As XP's key component, Andro activates the Nrf2/HO-1 signaling pathway, enhancing cell proliferation, tubule formation, and inflammation reduction.

Effects of low-dose methotrexate with MMI in patients with Graves' disease: results of a randomized clinical trial.

CONTEXT: Supplemental methotrexate (MTX) may affect the clinical course of Graves' disease (GD). OBJECTIVE: Evaluate efficacy of add-on MTX on medical treatment in GD. DESIGN: Prospective, open-label, randomized supplementation controlled trial. SETTING: Academic endocrine outpatient clinic. PATIENTS: One hundred and fifty-three untreated hyperthyroid patients with GD. INTERVENTION: Patients received MTX 10 mg/d with methimazole (MMI) or MMI only. MTX and MMI were discontinued at months 12-18 in euthyroid patients. MAIN OUTCOME MEASURES: Discontinuation rate at months 18 in each group. RESULTS: In the MTX with MMI group, the discontinuation rate was higher than the MMI group at months 15-18 (50.0 vs. 33.3%, P=0.043, 95% CI 1.020 to 3.922; and 55.6 vs 38.9%, P=0.045, 95%CI 1.011 to 3.815, respectively). The decrease in TRAb levels in the MTX with MMI group was significant from baseline to months 6 compared to the MMI alone group [MTX+MMI 67.22% (43.12-80.32), MMI 54.85% (33.18-73.76), P= 0.039) and became more significant from months 9 [MTX+MMI 77.79% (62.27-88.18), MMI 69.55% (50.50-83.22), P= 0.035] to months 18 (P < 0.01 in 15-18 months). A statistically significant difference between the levels of TRAb in the MTX with MMI group and the MMI group at 9-18 months. There were no significant differences in the levels of FT3, FT4 and TSH between two groups. No serious drug-related adverse events were observed in both groups(P=0.771). CONCLUSIONS: Supplemental MTX with MMI resulted in higher discontinuation rate and improvement in decreased TRAb levels to homeostatic levels faster than methimazole treatment alone at months 12-18.

Eruptive xanthomas in a patient with severe hypertriglyceridemia: A case report.

BACKGROUND: Xanthomatosis, a metabolic disorder causing yellow growths (xanthomas), poses challenges in lipid metabolism. This case study introduces the first documented instance within China's Yi population, emphasizing the need to explore dietary habits and treatment strategies tailored to this specific community. CASE SUMMARY: Xanthomatosis is a metabolic disorder where lipid metabolism goes awry, resulting in the development of yellowish growths called xanthomas. A male patient, 47 years of age, from China's Yi population, who is obese, visited our dermatology clinic complaining of widespread, non-painful rashes that have been present for two weeks. The patient works as a chef and has a diet that frequently includes oily and greasy foods. This case represents the initial documentation of xanthomatosis within the Yi population in China, offering a theoretical foundation for understanding dietary patterns and treatment options specific to the Yi community. CONCLUSION: The first report of xanthomatosis in the Yi population in China lays a theoretical foundation for understanding Yi dietary patterns and treatment.

Serum beta2-microglobulin acts as a biomarker for severity and prognosis in glioma patients: a preliminary clinical study.

BACKGROUND: Gliomas are the deadliest malignant tumors of the adult central nervous system. We previously discovered that beta2-microglobulin (B2M) is abnormally upregulated in glioma tissues and that it exerts a range of oncogenic effects. Besides its tissue presence, serum B2M levels serve as biomarkers for various diseases. This study aimed to explore whether serum B2M levels can be used in the diagnosis and prognosis of gliomas. METHODS: Medical records from 246 glioma patients were retrospectively analyzed. The relationship between preoperative serum B2M levels and clinicopathological features was examined. Kaplan-Meier analysis, alongside uni- and multivariate Cox regression, assessed the association between B2M levels, systemic inflammatory markers, and glioma patient prognosis. Receiver operating characteristic (ROC) curve analysis evaluated the diagnostic significance of these biomarkers specifically for glioblastoma (GBM). RESULTS: Patients with malignant gliomas exhibited elevated preoperative serum B2M levels. Glioma patients with high serum B2M levels experienced shorter survival times. Multivariate Cox analysis determined the relationship between B2M levels (hazard ratio = 1.92, 95% confidence interval: 1.05-3.50, P = 0.034) and the overall survival of glioma patients. B2M demonstrated superior discriminatory power in distinguishing between GBM and non-GBM compared to inflammation indicators. Moreover, postoperative serum B2M levels were lower than preoperative levels in the majority of glioma patients. CONCLUSIONS: High preoperative serum B2M levels correlated with malignant glioma and a poor prognosis. Serum B2M shows promise as a novel biomarker for predicting patient prognosis and reflecting the therapeutic response.

The Role of Beta2-Microglobulin in Central Nervous System Disease.

Central nervous system (CNS) disorders represent the leading cause of disability and the second leading cause of death worldwide, and impose a substantial economic burden on society. In recent years, emerging evidence has found that beta2 -microglobulin (B2M), a subunit of major histocompatibility complex class I (MHC-I) molecules, plays a crucial role in the development and progression in certain CNS diseases. On the one hand, intracellular B2M was abnormally upregulated in brain tumors and regulated tumor microenvironments and progression. On the other hand, soluble B2M was also elevated and involved in pathological stages in CNS diseases. Targeted B2M therapy has shown promising outcomes in specific CNS diseases. In this review, we provide a comprehensive summary and discussion of recent advances in understanding the pathological processes involving B2M in CNS diseases (e.g., Alzheimer's disease, aging, stroke, HIV-related dementia, glioma, and primary central nervous system lymphoma).

Characterization of the exopolysaccharide produced by Pediococcus acidilactici S1 and its effect on the gel properties of fat substitute meat mince.

Exopolysaccharide produced by lactic acid bacteria has various functions. In the present study, one anti-oxidant polysaccharide fraction, namely S1-EPS, was extracted and purified from Pediococcus acidilactici S1, and its structure and its potential effect on the gel properties of fat substitute meat mince were investigated. The results showed that S1-EPS, one of homogeneous polysaccharides, was mainly composed of Gal, Glc, and Man in molar ratio of 7.61: 15.25: 77.13 and molecular weight of 46.975 kDa. The backbone of EPS-S1 contained →2,6)-α-D-Manp-(1→，→2)-α-D-Manp-(1→,→3)-α-D-Glcp-(1 → and a small amount of→6)-ß-D-Manp-(1→. The linkages of branches in EPS-S1 were mainly composed of α-D-Manp-(1→ attached to a sugar residue →2,6)-α-D-Manp-(1→O-2 or ß-D-Galp-(1→ attached to a sugar residue →2,6)-α-D-Manp-(1→O-6. Furthermore, as S1-EPS increased, the meat minced gel pores decreased, and the surface became smooth. A remarkable inhibitory effect on the lipid oxidation of meat minced gel was found as S1-EPS concentration increased. Overall, S1-EPS was found to have substantial potential in low-fat meat products by serving as a natural, anti-oxidant, and functional additive.

Nickel-Catalyzed Cross-Coupling Reaction of Aryl Bromides/Nitriles with Imidazolium Salts Involving Inert C-N Bond Cleavage.

We herein present a nickel-catalyzed cross-coupling reaction of aryl halides and nitriles with imidazolium salts. A series of 2-arylated imidazoles could be obtained in moderate to good yields through inert C-N bond cleavage. The imidazolium salt in this reaction acts as both a coupling partner and N-heterocyclic carbene (NHC) ligand precursor. Mechanistic studies reveal that consecutive steps of migratory insertion of the NHC into the aryl C-Ni bond and ß-C elimination might be involved in the proposed reaction mechanism.

A new perspective on prostate cancer treatment: the interplay between cellular senescence and treatment resistance.

The emergence of resistance to prostate cancer (PCa) treatment, particularly to androgen deprivation therapy (ADT), has posed a significant challenge in the field of PCa management. Among the therapeutic options for PCa, radiotherapy, chemotherapy, and hormone therapy are commonly used modalities. However, these therapeutic approaches, while inducing apoptosis in tumor cells, may also trigger stress-induced premature senescence (SIPS). Cellular senescence, an entropy-driven transition from an ordered to a disordered state, ultimately leading to cell growth arrest, exhibits a dual role in PCa treatment. On one hand, senescent tumor cells may withdraw from the cell cycle, thereby reducing tumor growth rate and exerting a positive effect on treatment. On the other hand, senescent tumor cells may secrete a plethora of cytokines, growth factors and proteases that can affect neighboring tumor cells, thereby exerting a negative impact on treatment. This review explores how radiotherapy, chemotherapy, and hormone therapy trigger SIPS and the nuanced impact of senescent tumor cells on PCa treatment. Additionally, we aim to identify novel therapeutic strategies to overcome resistance in PCa treatment, thereby enhancing patient outcomes.

Photodynamic therapy upregulates expression of HIF-1α and PD-L1 in related pathways and its clinical relevance in non-small-cell lung cancer.

BACKGROUND: Photodynamic therapy (PDT) is a promising interventional treatment approach that contributes to antitumor immunity. It has been reported that PDT can enhance the effectiveness of immune checkpoint inhibitors (ICIs), but its mechanism is yet unclear. Herein, we implemented bioinformatics analysis to detect common pathways and potential biomarkers in non-small cell lung cancer (NSCLC), PDT, and NSCLC immunotherapy to investigate potential links between PDT, immunotherapy and NSCLC, and their clinical impact. METHODS: Differentially expressed genes in NSCLC- and NSCLC immunotherapy-related data in the GEO database were intersected with PDT-related genes in the GeneCards database to obtain candidate genes and shared pathways. Enrichment analysis and protein-protein interaction were established to identify key genes in functionally enriched pathways. The expression profiles and the prognostic significance of key genes were depicted. RESULTS: Bioinformatics analysis showed that HIF-1α was screened as a prognostic gene in hypoxia, HIF-1, and PD-L1-related signaling pathways, which was associated with clinical response in NSCLC patients after PDT and immunotherapy. In vivo experiments showed that PDT could inhibit tumor growth and upregulate HIF-1α and PD-L1 expressions in NSCLC tissues with a positive correlation, which might influence the blocking activity of ICIs on the HIF-1, and PD-L1-related signaling pathways. CONCLUSIONS: PDT might improve the clinical response of ICIs by upregulating tumor HIF-1α and PD-L1 expressions in NSCLC.

Enhanced cellular therapy: revolutionizing adoptive cellular therapy.

Enhanced cellular therapy has emerged as a novel concept following the basis of cellular therapy. This treatment modality applied drugs or biotechnology to directly enhance or genetically modify cells to enhance the efficacy of adoptive cellular therapy (ACT). Drugs or biotechnology that enhance the killing ability of immune cells include immune checkpoint inhibitors (ICIs) / antibody drugs, small molecule inhibitors, immunomodulatory factors, proteolysis targeting chimera (PROTAC), oncolytic virus (OV), etc. Firstly, overcoming the inhibitory tumor microenvironment (TME) can enhance the efficacy of ACT, which can be achieved by blocking the immune checkpoint. Secondly, cytokines or cytokine receptors can be expressed by genetic engineering or added directly to adoptive cells to enhance the migration and infiltration of adoptive cells to tumor cells. Moreover, multi-antigen chimeric antigen receptors (CARs) can be designed to enhance the specific recognition of tumor cell-related antigens, and OVs can also stimulate antigen release. In addition to inserting suicide genes into adoptive cells, PROTAC technology can be used as a safety switch or degradation agent of immunosuppressive factors to enhance the safety and efficacy of adoptive cells. This article comprehensively summarizes the mechanism, current situation, and clinical application of enhanced cellular therapy, describing potential improvements to adoptive cellular therapy.

TaoHe ChengQi decoction ameliorates sepsis-induced cardiac dysfunction through anti-ferroptosis via the Nrf2 pathway.

BACKGROUND: Sepsis-induced cardiac dysfunction (SICD) is a serious complication of sepsis that is associated with increased mortality. Ferroptosis has been reported in the SICD. TaoHe ChengQi decoction (THCQD), a classical traditional Chinese medicinal formula, has multiple beneficial pharmacological effects. The potential effects of THCQD on the SICD remain unknown. PURPOSE: To investigate the effect of THCQD on SICD and explore whether this effect is related to the regulation of myocardial ferroptosis through nuclear factor erythroid 2-related factor 2 (Nrf2) activation. METHODS: We induced sepsis in a mouse model using cecal ligation and puncture (CLP) and administered THCQD (2 and 4 g/kg) and dexamethasone (40 mg/kg). Mice mortality was recorded and survival curves were plotted. Echocardiography, hematoxylin and eosin staining, and analysis of serum myocardial injury markers and inflammatory factors were used to evaluate cardiac pathology. Myocardial ferroptosis was detected by quantifying specific biomarker content and protein levels. Through HPLC-Q-Exactive-MS analysis, we identified the components of the THCQD. Network pharmacology analysis and Cellular Thermal Shift Assay (CETSA) were utilized to predict the targets of THCQD for treating SICD. We detected the expression of Nrf2 using Western blotting or immunofluorescence. An RSL3-induced ferroptosis model was established using neonatal rat cardiomyocytes (NRCMs) to further explore the pharmacological mechanism of THCQD. In addition to measuring cell viability, we observed changes in NRCM mitochondria using electron microscopy and JC-1 staining. NRF2 inhibitor ML385 and Nrf2 knockout mice were used to validate whether THCQD exerted protective effects against SICD through Nrf2-mediated ferroptosis signaling. RESULTS: THCQD reduced mortality in septic mice, protected against CLP-induced myocardial injury, decreased systemic inflammatory response, and prevented myocardial ferroptosis. Network pharmacology analysis and CETSA experiments predicted that THCQD may protect against SICD by activating the Nrf2 signaling pathway. Western blotting and immunofluorescence showed that THCQD activated Nrf2 in cardiac tissue. THCQDs consistently mitigated RSL3-induced ferroptosis in NRCM, which is related to Nrf2. Furthermore, the pharmacological inhibition of Nrf2 and genetic Nrf2 knockout partially reversed the protective effects of THCQD on SICD and ferroptosis. CONCLUSION: The effect of THCQD on SICD was achieved by activating Nrf2 and its downstream pathways.

Knowledge mapping of application of image-guided surgery in prostate cancer: a bibliometric analysis (2013-2023).

BACKGROUND: Image-guided surgery (IGS) refers to surgery navigated by medical imaging technology, helping doctors better clarify tumor boundaries, identify metastatic lymph nodes and preserve surrounding healthy tissue function. Recent studies have provided expectable momentum of the application of IGS in prostate cancer (PCa). The authors aim to comprehensively construct a bibliometric analysis of the application of IGS in PCa. METHOD: The authors searched publications related to application of IGS in PCa from 2013 to 2023 on the web of science core collection (WoSCC) databases. VOSviewer, CiteSpace, and R package 'bibliometrix' were used for bibliometric analysis. RESULTS: Two thousand three eighty-nine articles from 75 countries and 2883 institutions led by the United States were included. The number of publications related to the application of IGS in PCa kept high in the last decade. Johns Hopkins University is the top research institutions. Journal of Nuclear Medicine has the highest popularity as the selection of journal and co-cited journal. Pomper Martin G. had published the most paper. Ali Afshar-Oromieh was co-cited most frequently. The clinical efficacy of PSMA-PET/CT in PCa diagnosis and treatment are main topics in this research field, with emerging focuses on the use of fluorescence imaging guidance technology in PCa. 'PSMA' and 'PET/CT' are the main keywords as long-term research hotspots. CONCLUSION: This study is the first bibliometric analysis of researches on application of IGS in PCa with three recognized bibliometric software, providing an objective description and comprehensive guidance for the future relevant investigations.

Designer Lithium Reservoirs for Ultralong Life Lithium Batteries for Grid Storage.

The minimization of irreversible active lithium loss stands as a pivotal concern in rechargeable lithium batteries, particularly in the context of grid-storage applications, where achieving the utmost energy density over prolonged cycling is imperative to meet stringent demands, notably in terms of life cost. Departing from conventional methodologies advocating electrode prelithiation and/or electrolyte additives, a new paradigm is proposed here: the integration of a designer lithium reservoir (DLR) featuring lithium orthosilicate (Li4SiO4) and elemental sulfur. This approach concurrently addresses active lithium consumption through solid electrolyte interphase (SEI) formation and mitigates minor yet continuous parasitic reactions at the electrode/electrolyte interface during extended cycling. The remarkable synergy between the Li-ion conductive Li4SiO4 and the SEI-favorable elemental sulfur enables customizable compensation kinetics for active lithium loss throughout continuous cycling. The introduction of a minute quantity of DLR (3 wt% Li4SiO4@S) yields outstanding cycling stability in a prototype pouch cell (graphite||LiFePO4) with an ampere-hour-level capacity (≈2.3 Ah), demonstrating remarkable capacity retention (≈95%) even after 3000 cycles. This utilization of a DLR is poised to expedite the development of enduring lithium batteries for grid-storage applications and stimulate the design of practical, implantable rechargeable batteries based on related cell chemistries.

A pH-regulated fluorescence covalent organic framework for quantitative water content detection in methanol.

In this paper, we designed and synthesized a two-dimensional fluorescent covalent organic framework (TAPB-DMTP-COF) for the precise determination of H2O content in methanol. The COF was synthesized using two typical monomers by grinding method, which significantly reduced the synthesis time. By adjusting the pH value of the COF suspension to 4.0, the portion of the COF material structure is disrupted, thereby mitigating π-π stacking and resolving the aggregation-caused quenching (ACQ) effect. Consequently, the non-fluorescent TAPB-DMTP-COF exhibited blue-purple fluorescence emission in methanol. At the same time, it is observed that in the presence of H2O, there is a red shift in the maximum fluorescence emission peak of TAPB-DMTP-COF, which correlates with the H2O content within a specific range. Notably, this redshift demonstrates a linear relationship with H2O content from 4% to 80% in methanol. Our work presents novel insights for efficient analysis and detection of H2O content in methanol and could be used for H2O detection in other organic solvents.

Selective detection of ascorbic acid by tuning the composition and fluorescence of the cesium lead halide perovskite nanocrystals.

Lead halide perovskite nanocrystals (PNCs) have attracted intense attention due to their excellent optoelectronic properties. In this work, a series of water-stable CsPb(Br/I)3PNCs fluorescent probes were prepared using an anion exchange method. It was found that the PNCs probes could be used to detect ascorbic acid (AA) in water, and interestingly, the FL spectra of the PNCs probes can be adjusted by controlling the concentration of KI in anion exchange to improve the detection selectivity of AA. The high sensitivity and selectivity make CsPb(Br/I)3PNCs an ideal material for AA sensing. The concentration of AA can be linearly measured in the range from 0.01 to 50µM, with a detection limit of 4.2 nM. The reason for the enhanced FL of CsPb(Br/I)3PNCs was studied, and it is considered that AA causes the aggregation of CsPb(Br/I)3PNCs. This strategy of improving the selectivity of the probe to the substrate by adjusting the spectrum will significantly expand the application of PNCs in the field of analysis and detection.

Chiral Assembly of Perovskite Nanocrystals: Sensitive Discrimination of Amino Acid Enantiomers.

Chirality is a widespread phenomenon in nature and in living organisms and plays an important role in living systems. The sensitive discrimination of chiral molecular enantiomers remains a challenge in the fields of chemistry and biology. Establishing a simple, fast, and efficient strategy to discriminate the spatial configuration of chiral molecular enantiomers is of great significance. Chiral perovskite nanocrystals (PNCs) have attracted much attention because of their excellent optical activity. However, it is a challenge to prepare perovskites with both chiral and fluorescence properties for chiral sensing. In this work, we synthesized two chiral fluorescent perovskite nanocrystal assembly (PNA) enantiomers by using l- or d-phenylalanine (Phe) as chiral ligands. PNA exhibited good fluorescence recognition for l- and d-proline (Pro). Homochiral interaction led to fluorescence enhancement, while heterochiral interaction led to fluorescence quenching, and there is a good linear relationship between the fluorescence changing rate and l- or d-Pro concentration. Mechanism studies show that homochiral interaction-induced fluorescence enhancement is attributed to the disassembly of chiral PNA, while no disassembly of chiral PNA was found in heterochiral interaction-induced fluorescence quenching, which is attributed to the substitution of Phe on the surface of chiral PNA by heterochiral Pro. This work suggests that chiral perovskite can be used for chiral fluorescence sensing; it will inspire the development of chiral nanomaterials and chiral optical sensors.

Clinical Practice of Photodynamic Therapy for Non-Small Cell Lung Cancer in Different Scenarios: Who Is the Better Candidate?

BACKGROUND: Photodynamic therapy (PDT) is a relatively safe and highly selectivity antitumor treatment, which might be increasingly used as a supplement to conventional therapies. A clinical overview and detailed comparison of how to select patients and lesions for PDT in different scenarios are urgently needed to provide a basis for clinical treatment. SUMMARY: This review demonstrates the highlights and obstacles of applying PDT for lung cancer and underlines points worth considering when planning to initiate PDT. The aim was to make out the appropriate selection and help PDT develop efficacy and precision through a better understanding of its clinical use. KEY MESSAGES: Increasing evidence supports the feasibility and safety of PDT in the treatment of non-small cell lung cancer. It is important to recognize the factors that influence the efficacy of PDT to develop individualized management strategies and implement well-designed procedures. These important issues should be worth considering in the present and further research.