Porous boron-doped graphitic carbon nitride-based label-free electrochemical immunoassay of vascular endothelial cadherin.

As a main connecting protein between endothelial cells, vascular endothelial cadherin (CD144) is involved in regulating vascular remodeling and maintaining vascular integrity. It is regarded as a marker of endothelial dysfunction and injury. Quantitative determination of CD144 is of importance in pathology research, diagnosis and treatment of vascular diseases. A label-free electrochemical method for the immunoassay of CD144 was developed in this work. CD144 antibodies were assembled on a glassy carbon electrode modified with porous boron-doped carbon nitride (B-GCN) and gold nanoparticles (AuNPs) in the presence of protein A. The binding of CD144 on the antibody-modified electrode induced serious steric hindrance, inhibiting the diffusion of ferri-/ferrocyanide from the bulk electrolyte to the electrode interface. The change of the differential pulse voltammetric response displayed a linear relationship with the concentration of CD144 between 0.500 and 400 ng mL-1. The new electrochemical sensor showed some good performances including good selectivity, high stability and satisfactory reproducibility. The cellular morphology observation and activity measurement showed that the dysfunction of vascular endothelial cells appeared in the presence of high-content NaCl. The electrochemical analysis reveals a positive correlation between the release amount of CD144 from the dysfunctional cells and the NaCl concentration in the growth medium.

FPS-ZM1 attenuates the deposition of lipid in the liver of diabetic mice by sterol regulatory element binding protein-1c.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) shares common pathogenic mechanisms of type 2 diabetes mellitus (T2DM) with upregulated advanced glycation end products (AGEs). Here, we aim to investigate the effect of FPS-ZM1, an inhibitor for receptor for AGEs (RAGE), on lipid deposition in the liver of mice. METHODS: KK-Ay mice were used as models of T2DM with NAFLD, while C57BL/6j mice were controls. Additionally, KK-Ay mice were treated with DMSO (with a concentration of 1%), with or without FPS-ZM1 (3 mg/kg/day, i.p). Lipid deposition in hepatocytes was observed using oil red O stain. Levels of AGEs and RAGE were measured. Sterol regulatory element-binding protein-1c (SREBP-1c), as well as nuclear factor κB p65 (p65 nfκb) and mitogen-activated protein kinase p38 (p38 MAPK), were also detected. RESULTS: Lipid deposition is increased in the hepatocytes of KK-Ay mice compared to C57BL/6j mice. In addition, not only were the levels of AGEs elevated in plasma, but also the levels of RAGE in liver tissue. Although total SREBP-1c levels did not change in the liver of diabetic mice, mature SREBP-1c increased in KK-Ay mice with diabetes mellitus. Moreover, diabetic mice showed increased levels of phosphorylated-p65 nfκb (p-p65 nfκb) and phosphorylated-p38 MAPK (p-p38 MAPK). On the contrary, FPS-ZM1 decreased lipid deposition in liver cells, as well as mature SREBP-1c, p-p65 nfκb and p-p38 MAPK levels in liver tissue. CONCLUSION: Generally, FPS-ZM1 may attenuate lipid deposition in hepatocytes of diabetic mice via SREBP-1c down-regulation. This may depend on the downregulation of p65 nfκb and p38 MAPK phosphorylation.

A Theory and Evidence-Based Artificial Intelligence-Driven Motivational Digital Assistant to Decrease Vaccine Hesitancy: Intervention Development and Validation.

Vaccine hesitancy is one of the top ten threats to global health. Artificial intelligence-driven chatbots and motivational interviewing skills show promise in addressing vaccine hesitancy. This study aimed to develop and validate an artificial intelligence-driven motivational digital assistant in decreasing COVID-19 vaccine hesitancy among Hong Kong adults. The intervention development and validation were guided by the Medical Research Council's framework with four major steps: logic model development based on theory and qualitative interviews (n = 15), digital assistant development, expert evaluation (n = 5), and a pilot test (n = 12). The Vaccine Hesitancy Matrix model and qualitative findings guided the development of the intervention logic model and content with five web-based modules. An artificial intelligence-driven chatbot tailored to each module was embedded in the website to motivate vaccination intention using motivational interviewing skills. The content validity index from expert evaluation was 0.85. The pilot test showed significant improvements in vaccine-related health literacy (p = 0.021) and vaccine confidence (p = 0.027). This digital assistant is effective in improving COVID-19 vaccine literacy and confidence through valid educational content and motivational conversations. The intervention is ready for testing in a randomized controlled trial and has high potential to be a useful toolkit for addressing ambivalence and facilitating informed decision making regarding vaccination.

Hepatic arterial infusion chemotherapy, lenvatinib plus programmed cell death protein-1 inhibitors: A promising treatment approach for high-burden hepatocellular carcinoma.

BACKGROUND: Hepatic arterial infusion chemotherapy (HAIC) has demonstrated remarkable local therapeutic efficacy in treating patients with large unresectable hepatocellular carcinoma (HCC). Additionally, the combination of lenvatinib and programmed cell death protein-1 (PD-1) inhibitors has demonstrated promising antitumor effects in unresectable HCC. Therefore, we conducted a retrospective analysis to evaluate the efficacy and safety of combining HAIC with lenvatinib and PD-1 inhibitors as a first-line therapeutic approach in high-burden HCC patients. METHODS: We conducted a retrospective analysis on patients diagnosed with high-burden HCC who had major portal vein tumor thrombosis (Vp3 and Vp4) or tumor occupancy exceeding 50% of the liver. These patients received a first-line treatment consisting of HAIC with a combination of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX), along with lenvatinib and PD-1 inhibitors between November 2020 and June 2023. The primary endpoints of this study included progression-free survival (PFS) and overall survival (OS), while the secondary endpoints were objective response rate (ORR), disease control rate (DCR), and treatment-related adverse events (TRAEs). RESULTS: Ninety-one patients were enrolled in this study, with a median PFS of 8.8 months (95% confidence interval [CI]: 5.75-11.78) and a median OS of 14.3 months (95% CI: 11.23-17.31). According to RECIST 1.1 criteria, the ORR was 52.7%, and DCR was 95.6%. According to the mRECIST criteria, the ORR was 72.5%, and the DCR was 96.5%. Among all patients, 86 (94.5%) experienced TRAEs, and there were no instances of treatment-related deaths. CONCLUSION: The combination of HAIC-FOLFOX with lenvatinib and PD-1 inhibitors as a first-line therapy has exhibited notable therapeutic efficacy and well-tolerated adverse events among patients with high-burden HCC.

25-hydroxycholesterol promotes proliferation and metastasis of lung adenocarcinoma cells by regulating ERß/TNFRSF17 axis.

Lung adenocarcinoma is the main type of lung cancer in women. Our previous findings have evidenced that 25-hydroxycholesterol (25-HC) promotes migration and invasion of lung adenocarcinoma cells (LAC), during which LXR as a 25-HC receptor plays an important role. Estrogen receptor beta (ERß) is a receptor of 27-hydroxycholesterol that is structurally analogous to 25-HC, but its role in the functional actions of 25-HC remained largely unknown. In this study, we demonstrated that 25-HC treatment triggered ERß expression in LAC. Knockdown of ERß inhibited 25-HC-mediated proliferation, migration and invasion, and reduced 25-HC-induced LAC metastasis in vivo. Further investigation revealed that ERß knockdown restrained the expression of TNFRSF17 (BCMA). In vivo experiments also confirmed that ERß knockdown blocked 25-HC-induced TNFRSF17 expression. TNFRSF17 knockdown also restrained 25-HC-induced proliferation, migration and invasion. Bioinformatic analysis showed that the levels of ERß and TNFRSF17 were elevated in lung adenocarcinoma, and were closely related to tumor stages and nodal metastasis status. These results suggested that 25-HC promoted the proliferation and metastasis of LAC by regulating ERß/TNFRSF17 axis.

Hsa_circ_0006260 Mediates Trophoblast Function by Fibronectin Type III Domains Containing Protein 5 via Interacting with miR-770-5p.

A series of studies have confirmed the relationship between circular RNAs (circRNAs) and metabolic diseases. Hsa_circ_0006260 has been reported to be lowly expressed in the placenta of gestational diabetes mellitus (GDM) patients, but the underlying mechanism and its biological functions remain obscure. Placental tissues were collected from 37 pregnant women with normal glucose tolerance (NGT) and 37 pregnant women with GDM. Expression changes of hsa_circ_0006260 in placentas and high glucose (HG)-stimulated HTR-8/SVneo cells were detected using real-time quantitative polymerase chain reaction. Cell viability and migration were determined by cell counting and transwell assays, respectively. Measurement of cytokines was done by enzyme-linked immunosorbent assay. Cell apoptosis was estimated by flow cytometry assay. The molecular mechanisms were identified using dual-luciferase reporter and RNA-binding protein immunoprecipitation assays. Hsa_circ_0006260 expression was remarkably lowered in GDM patient-derived placentas and HG-stimulated HTR-8/SVneo cells. Functionally, hsa_circ_0006260 overexpression weakened HG-mediated repression of HTR-8/SVneo cell viability and migration, as well as promotion of HTR-8/SVneo cell inflammatory response and apoptosis. Mechanistically, hsa_circ_0006260 functioned as a miR-770-5p decoy to mediate fibronectin type III domains containing protein 5 (FNDC5) expression. Ectopic expression of miR-770-5p weakened hsa_circ_0006260 overexpression-mediated repression of HG-induced HTR-8/SVneo cell dysfunction. Also, FNDC5 knockdown lessened miR-770-5p overexpression-mediated promotion of HG-induced HTR-8/SVneo cell dysfunction. Our findings manifested a novel mechanism by which hsa_circ_0006260 could lower HG-induced HTR-8/SVneo cell dysfunction by upregulating FNDC5 via binding to miR-770-5p, which shed new light on circRNA mediated GDM pathogenesis.

Bimetallic PtPd Atomic Clusters as Apoptosis/Ferroptosis Inducers for Antineoplastic Therapy through Heterogeneous Catalytic Processes.

Active polymetallic atomic clusters can initiate heterogeneous catalytic reactions in the tumor microenvironment, and the products tend to cause manifold damage to cell metabolic functions. Herein, bimetallic PtPd atomic clusters (BAC) are constructed by the stripping of Pt and Pd nanoparticles on nitrogen-doped carbon and follow-up surface PEGylation, aiming at efficacious antineoplastic therapy through heterogeneous catalytic processes. After endocytosed by tumor cells, BAC with catalase-mimic activity can facilitate the decomposition of endogenous H2O2 into O2. The local oxygenation not only alleviates hypoxia to reduce the invasion ability of cancer cells but also enhances the yield of •O2- from O2 catalyzed by BAC. Meanwhile, BAC also exhibit peroxidase-mimic activity for •OH production from H2O2. The enrichment of reactive oxygen species (ROS), including the radicals of •OH and •O2-, causes significant oxidative cellular damage and triggers severe apoptosis. In another aspect, intrinsic glutathione (GSH) peroxidase-like activity of BAC can indirectly upregulate the level of lipid peroxides and promote ferroptosis. Such deleterious redox dyshomeostasis caused by ROS accumulation and GSH consumption also results in immunogenic cell death to stimulate antitumor immunity for metastasis suppression. Collectively, this paradigm is expected to inspire more facile designs of polymetallic atomic clusters in disease therapy.

Co-inoculation of Soybean Seedling with Trichoderma asperellum and Irpex laceratus Promotes the Absorption of Nitrogen and Phosphorus.

Soybean are one of the main oil crops in the world. The study demonstrated that co-inoculation with Trichoderma asperellum (Sordariomycetes, Hypocreomycetidae) and Irpex laceratus (Basidiomycota, Polyporales) isolated from Kosteletzkya virginica can promote the growth of soybean seedlings. The two fungi were found to produce various enzymes, including cellulase, amylase, laccase, protease, and urease. Upon inoculation, T. asperellum mainly colonized within the phloem of the roots in soybean seedlings, while I. laceratus mainly in the xylem and phloem of the roots. Physiological parameters, such as plant height, root length, and fresh weight, were significantly increased in soybean seedlings co-inoculated with T. asperellum and I. laceratus. Moreover, the expression of key genes related to N and P absorption and metabolism was also increased, leading to improved N and P utilization efficiency in soybean seedlings. These results indicate that the two fungi may have complementary roles in promoting plant growth, co-inoculation with T. asperellum and I. laceratus can enhance the growth and nutrient uptake of soybean. These findings suggest that T. asperellum and I. laceratus have the potential to be used as bio-fertilizers to improve soybean growth and yield.

Nitrogen vacancy-rich carbon nitride anchored with iron atoms for efficient redox dyshomeostasis under ultrasound actuation.

Traditional Fe-based Fenton reaction for inducing oxidative stress is restricted by random charge transfer without oriental delivery, and the resultant generation of reactive oxygen species (ROS) is always too simplistic to realize a satisfactory therapeutic outcome. Herein, FeNv/CN nanosheets rich in nitrogen vacancies are developed for high-performance redox dyshomeostasis therapy after surface conjugation with polyethylene glycol (PEG) and cyclic Arg-Gly-Asp (cRGD). Surface defects in FeNv/CN serve as electron traps to drive the directional transfer of the excited electrons to Fe atom sites under ultrasound (US) actuation, and the highly elevated electron density promote the catalytic conversion of H2O2 into ·OH. Meanwhile, energy band edges of FeNv/CN favor the production of 1O2 upon interfacial redox chemistry, which is enhanced by the optimal separation/recombination dynamics of electron/hole pairs. Moreover, intrinsic peroxidase-like activity of FeNv/CN contributes to the depletion of reductant glutathione (GSH). Under the anchoring effect of cRGD, PEGylated FeNv/CN can be efficiently enriched in the tumorous region, which is ultrasonically activated for concurrent ROS accumulation and GSH consumption in cytosolic region. The deleterious redox dyshomeostasis not only eradicates primary tumor but also suppresses distant metastasis via antitumor immunity elicitation. Collectively, this study could inspire more facile designs of chalybeates for medical applications.

Vacancy-Rich Bismuth-Based Nanosheets for Mitochondrial Destruction via CO Poisoning, Ca2+ Dyshomeostasis, and Oxidative Damage.

Mitochondria are core regulators of tumor cell homeostasis, and their damage has become an arresting therapeutic modality against cancer. Despite the development of many mitochondrial-targeted pharmaceutical agents, the exploration of more powerful and multifunctional medications is still underway. Herein, oxygen vacancy-rich BiO2-x wrapped with CaCO3 (named BiO2-x @CaCO3 /PEG, BCP) is developed for full-fledged attack on mitochondrial function. After endocytosis of BCP by tumor cells, the CaCO3 shell can be decomposed in the acidic lysosomal compartment, leading to immediate Ca2+ release and CO2 production in the cytoplasm. Near-infrared irradiation enhances the adsorption of CO2 onto BiO2-x defects, which enables highly efficient photocatalysis of CO2 -to-CO. Meanwhile, such BiO2-x nanosheets possess catalase-, peroxidase- and oxidase-like catalytic activities under acidic pH conditions, allowing hypoxia relief and the accumulation of diverse reactive oxygen species (ROS) in the tumor microenvironment. Ca2+ overload-induced ion dyshomeostasis, CO-mediated respiratory chain poisoning, ROS-triggered oxidative stress aggravation, and cytosolic hyperoxia can cause severe mitochondrial disorders, which further lead to type I cell death in carcinoma. Not only does BCP cause irreversible apoptosis, but immunogenic cell death is simultaneously triggered to activate antitumor immunity for metastasis inhibition. Collectively, this platform promises high benefits in malignant tumor therapy and may expand the medical applications of bismuth-based nanoagents.

The stability of perennial grasses mediates the negative impacts of long-term warming and increasing precipitation on community stability in a desert steppe.

Background: Desert steppe, as an ecotone between desert and grassland, has few species and is sensitive to climate change. Climate change alters species diversity and the stability of functional groups, which may positively or negatively affect community stability. However, the response of plant community stability in the desert steppe to experimental warming and increasing precipitation remains largely unexplored. Methods: In a factorial experiment of warming and increasing precipitation for five to seven years (ambient precipitation (P0), ambient precipitation increased by 25% and 50% (P1 and P2), ambient temperature (W0), ambient temperature increased by 2°C and 4°C (W1 and W2)), we estimated the importance value (IV) of four functional groups (perennial grasses, semi-shrubs, perennial forbs and annual herbs), species diversity and community stability. Results: Compared to W0P0, the IV of perennial grasses was reduced by 37.66% in W2P2, whereas the IV of perennial forbs increased by 48.96%. Although increasing precipitation and experimental warming significantly altered species composition, the effect on species diversity was insignificant (P > 0.05). In addition, increasing precipitation and experimental warming had a significant negative impact on community stability. The stability of perennial grasses significantly explained community stability. Conclusion: Our results suggest that the small number of species in desert steppe limits the contribution of species diversity to regulating community stability. By contrast, maintaining high stability of perennial grasses can improve community stability in the desert steppe.

Soil Moisture Content Dominates the Photosynthesis of C3 and C4 Plants in a Desert Steppe after Long-Term Warming and Increasing Precipitation.

Plant photosynthesis has a non-negligible influence on forage quality and ecosystem carbon sequestration. However, the influence of long-term warming, increasing precipitation, and their interactions on the photosynthesis of dominant species in desert steppe remains unclear, and the main factors regulating plant photosynthesis in desert steppes have remained unrevealed. Therefore, we measured the photosynthetic parameters and specific leaf area of the dominant species and calculated the water and nitrogen content of leaves and soil in a desert steppe after long-term warming and increasing precipitation (air temperature, W0, air temperature increases of 2 °C and 4 °C, W1 and W2; natural precipitation, P0, natural precipitation increases of 25% and 50%, P1 and P2). Results showed that warming and increasing precipitation significantly enhanced photosynthesis in C3 and C4 species (p < 0.05). Compared to W0P0, the net photosynthetic rate of C3 and C4 species in W2P2 increased by 159.46% and 178.88%, respectively. Redundancy analysis showed that soil water content significantly explained the photosynthesis of C3 and C4 plants (the degree of explanation was 48% and 67.7%), followed by soil-available nitrogen content (the degree of explanation was 19.6% and 5.3%). Therefore, our study found that climate change enhanced photosynthesis in C3 and C4 plants, and soil water content plays a critical role in regulating photosynthesis in desert steppes.

Gibberellin confers to the expression of TaGA-6D and negatively regulates the fertility of wheat with Aegilops juvenalis cytoplasm.

As the trace signal molecules widely existing in plants, plant hormones can regulate physiological responses of plants at low concentrations. At present, the effect of plant endogenous hormones on wheat male fertility has attracted attention, but the molecular mechanism underlying fertility regulation is unclear. Given this, the anthers of five isonuclear alloplasmic male sterile lines and their maintainer line were RNA-sequenced. A gene TaGA-6D encoding gibberellin (GA) regulated protein was isolated, which was located to the nucleus, cell wall and/or cell membrane, and predominantly highly expressed in the anther of Ju706A, a male sterile line with Aegilops juvenalis cytoplasm. By spraying assay of GA with different concentrations on fertility line Ju706R, it was found that with the increase of exogenous GA concentration, the content of endogenous GA and expression level of TaGA-6D in anther gradually increased, and the fertility decreased. However, silencing of TaGA-6D partially restore the fertility of Ju706R sprayed with 1000 ng/µl GA, and indicating that gibberellin can promote the expression of TaGA-6D and negatively regulates the fertility of wheat with Aegilops juvenalis cytoplasm, which providing new insights for understanding hormone regulation of male fertility in wheat.

Aspirin induces immunogenic cell death and enhances cancer immunotherapy in colorectal cancer.

The use of aspirin is associated with reduced incidence of colorectal cancer (CRC). However, the detailed mechanism remains unclear. In this study, we reported that colon cancer cells treated with aspirin showed the hallmarks of immunogenic cell death (ICD), including surface expression of calreticulin (CRT) and heat shock protein 70 (HSP70). Mechanistically, aspirin induced endoplasmic reticulum (ER) stress in colon cancer cells. In addition, aspirin decreased the expression of the glucose transporters, GLUT3, and reduced the key enzyme of glycolysis, including HK2, PFKM, PKM2 and LDHA. The changes of tumor glycolysis after aspirin treatment were associated with c-MYC downregulation. Moreover, aspirin potentiated the antitumor efficacy of anti-PD-1 antibody and anti-CTLA-4 antibody in CT26 tumors. However, this antitumor activity of aspirin in combination with anti-PD-1 antibody was abolished by the depletion of CD8+ T cells. Vaccination with tumor antigens is one of the strategies for activating T-cell response against tumors. Here, we demonstrated that aspirin-treated tumor cells in combination with tumor antigens (AH1 peptide) or protective substituted peptide (A5 peptide) could be served as a potent vaccine to eradicate tumors. Overall, our data indicated that aspirin can be used as an inducer of ICD for CRC therapy.

Serum Uric Acid Levels Are Related to Diabetic Peripheral Neuropathy, Especially for Motor Conduction Velocity of Tibial Nerve in Type 2 Diabetes Mellitus Patients.

Background: Oxidative stress is one of the most critical factors that contribute to the pathogenesis of neuronal damage, including diabetic peripheral neuropathy (DPN). Uric acid is a kind of natural antioxidant that plays a major role in the antioxidant capacity against oxidative stress. Here, we aim to determine the role of serum uric acid (SUA) in the DPN of patients with type 2 diabetes mellitus (T2DM). Patients and Methods. 106 patients with T2DM were recruited and divided into the DPN group and the control group. Clinical parameters, especially for motor nerve fiber conduction velocity and sensory nerve fiber conduction velocity, were collected. Differences between T2DM patients with and without DPN were compared. Correlation and regression analyses were performed to explore the association between SUA and DPN. Results: Compare with 57 patients with DPN, 49 patients without DPN showed lower HbA1c and elevated SUA levels. Additionally, SUA levels are negatively associated with the motor conduction velocity of tibial nerve with or without adjusting for HbA1c. Besides, it is suggested that decreased SUA levels may influence the motor conduction speed of the tibial nerve by multiple linear regression analysis. Moreover, we demonstrated that decreased SUA level is a risk factor for DPN in patients with T2DM by binary logistic regression analysis. Conclusion: Lower SUA is a risk factor for DPN in patients with T2DM. Additionally, decreased SUA may influence the damage of peripheral neuropathy, especially for motor conduction velocity of the tibial nerve.

Structural basis of membrane skeleton organization in red blood cells.

The spectrin-based membrane skeleton is a ubiquitous membrane-associated two-dimensional cytoskeleton underneath the lipid membrane of metazoan cells. Mutations of skeleton proteins impair the mechanical strength and functions of the membrane, leading to several different types of human diseases. Here, we report the cryo-EM structures of the native spectrin-actin junctional complex (from porcine erythrocytes), which is a specialized short F-actin acting as the central organizational unit of the membrane skeleton. While an α-/ß-adducin hetero-tetramer binds to the barbed end of F-actin as a flexible cap, tropomodulin and SH3BGRL2 together create an absolute cap at the pointed end. The junctional complex is strengthened by ring-like structures of dematin in the middle actin layers and by patterned periodic interactions with tropomyosin over its entire length. This work serves as a structural framework for understanding the assembly and dynamics of membrane skeleton and offers insights into mechanisms of various ubiquitous F-actin-binding factors in other F-actin systems.

CYP27A1 deficiency promoted osteoclast differentiation.

Background: The elevating osteoclast differentiation can lead to an imbalance in bone homeostasis, which was responsible for bone loss and bone diseases, such as osteoporosis. Multiple pathways and molecules have been involved in osteoclast formation, but the role of CYP27A1 in osteoclast differentiation has never been explored. Methods: CYP27A1 deficient mice were constructed using CRISPR-Cas9 system. Osteoclast differentiation was detected by TRAP staining. Differentially expressed genes (DEGs) were identified using RNA-seq analysis and were confirmed by qRT-PCR and Western blot. Results: The results showed that CYP27A1 knockout (KO) promoted osteoclast differentiation and bone loss. The transcriptomic analysis revealed that CYP27A1 KO led to differential expression of multiple genes, including ELANE, LY6C2, S100A9, GM20708, BGN, SPARC, and COL1A2, which were confirmed by qRT-PCR and Western blot. Enrichment analysis indicated that these differential genes were significantly associated with osteogenesis-related pathways, such as PPAR signaling, IL-17 signaling, and PI3K/AKT signaling, which were confirmed by qRT-PCR and Western blot. Conclusions: These results suggested that CYP27A1 was involved in osteoclast differentiation, providing a novel therapeutic target for osteoclast-related diseases.

Is repeat sentinel lymph node biopsy possible for surgical axillary staging among patients with ipsilateral breast tumor recurrence?

BACKGROUND: There is a lack of studies assessing the survival of repeat sentinel lymph node biopsy (rSLNB) versus axillary lymph node dissection (ALND) for surgical axillary staging among patients with ipsilateral breast tumor recurrence (IBTR). METHODS: We retrospectively identified patients with IBTR from the Surveillance, Epidemiology, and End Results database from 2000 to 2017. The primary outcome was overall survival (OS) between the rSLNB and ALND groups. RESULTS: Of the 2141 women with IBTR after lumpectomy and SLNB, 524 did not receive surgical axillary staging (nonsurgery group) and 1617 patients who did undergo axilla surgery received either rSLNB or ALND as axillary staging (1268 with rSLNB and 349 with ALND). The 10-year OS rates were 61.9% for the nonsurgery and 73.8% for axilla surgery groups (p = .001). In the 1:1 matched cohorts, the 10-year OS rates were 61.4% for the nonsurgery and 69.1% for axilla surgery groups (p = .072). After adjusting for other factors, axillary surgery treatment of IBTR was an independent favorable factor for OS (hazard ratio [HR], 0.71; 95% CI, 0.56-0.90; p = .004). Within the axilla surgery group, rSLNB presented a comparable 10-year OS to the ALND cohort (log-rank test p = .054). Multivariate Cox analysis, as well as subgroup analysis, showed that rSLNB had a similar benefit to ALND (10-year OS; HR, 1.18; 95% CI, 0.88-1.58; p = .268). CONCLUSIONS: The results of this cohort study suggested that receiving surgical axillary staging was associated with better survival of IBTR patients, and rSLNB had a similar long-term survival outcome as ALND. rSLNB might be considered for surgical axillary staging among patients with IBTR after lumpectomy and initial SLNB.

Ultrasound-Activatable g-C3 N4 -Anchored Titania Heterojunction as an Intracellular Redox Homeostasis Perturbator for Augmented Oncotherapy.

Energy band structure of inorganic nano-sonosensitizers is usually optimized by surface decoration with noble metals or metal oxide semiconductors, aiming to enhance interfacial charge transfer, augment spin-flip and promote radical generation. To avoid potential biohazards of metallic elements, herein, metal-free graphitic carbon nitride quantum dots (g-C3 N4 QDs) are anchored onto hollow mesoporous TiO2 nanostructure to formulate TiO2 @g-C3 N4 heterojunction. The direct Z-scheme charge transfer significantly improves the separation/recombination dynamics of electron/hole (e- /h+ ) pairs upon ultrasound (US) stimulation, which promotes the yield of singlet oxygen (1 O2 ) and hydroxyl radicals (·OH). The conjugated g-C3 N4 QDs with peroxidase-mimic activity further react with the elevated endogenous H2 O2 and aggravate oxidative stress. After loading prodrug romidepsin (RMD) in TiO2 @g-C3 N4 , stimulus-responsive drug delivery can be realized by US irradiation. The disulfide bridge of the released RMD tends to be reduced by glutathione (GSH) into a monocyclic dithiol, which arrests cell cycle in G2/M phase and evokes apoptosis through enhanced histone acetylation. Importantly, reactive oxygen species accumulation accompanied by GSH depletion is devoted to deleterious redox dyshomeostasis, leading to augmented systemic oncotherapy by eliciting antitumor immunity. Collectively, this paradigm provides useful insights in optimizing the performance of TiO2 -based nano-sonosensitizers for tackling critical diseases.

Overlooked impacts of natural organic matter conversion in a Fe(II)-induced peroxymonosulfate activation system for river water remediation.

The peroxymonosulfate (PMS) process may be hindered severely due to natural organic matter (NOM) conversion in the treatment of emerging pollutants from river water, becoming a critical engineering and technical issue. In this study, a Fe(II)-induced river water (RW)/PMS catalytic system was constructed for investigating molecular transformation of NOM and related influence mechanism to sulfamethoxazole (SMX) degradation. Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) analysis indicated that NOM molecules containing no more than one heteroatom in river may be attacked by hydroxyl radicals (OH) and then polymerized, converting into molecules with two or three heteroatoms during PMS oxidation. Based on the correlation analysis, CHONP-NOM, CHOSP-NOM and CHONSP-NOM showed a significant inhibition against SMX degradation, while CHONS-NOM exhibited a moderate inhibitory effect. Besides, more condensed aromatic structures, carbohydrates and tannins were generated via reactive species (OH and sulfate radicals (SO4-)) oxidation, radical addition and polymerization reactions. Notably, condensed aromatic structures, carbohydrates and tannins presented weak, modest and strong inhibition to SMX degradation, respectively. Based on the current results, the inhibition of target pollutants degradation would be mitigated via regulation of NOM molecules in a Fe(II)-induced PMS activation system, providing valuable information to reduce NOM impact. In addition, this study paves the way to achieve efficient removal of emerging pollutants from river water.