Plasma Lipidomic Profiling Identifies Elevated Triglycerides as Potential Risk Factor in Chemotherapy-Induced Peripheral Neuropathy.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect of cytotoxic cancer treatment, often necessitating dose reduction (DR) or chemotherapy discontinuation (CD). Studies on peripheral neuropathy related to chemotherapy, obesity, and diabetes have implicated lipid metabolism. This study examined the association between circulating lipids and CIPN. METHODS: Lipidomic analysis was performed on plasma samples from 137 patients receiving taxane-based treatment. CIPN was graded using Total Neuropathy Score-clinical version (TNSc) and patient-reported outcome measure European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-CIPN (EORTC-QLQ-CIPN20). RESULTS: A significant proportion of elevated baseline lipids were associated with high-grade CIPN defined by TNSc and EORTC-QLQ-CIPN20 including triacylglycerols (TGs). Multivariable Cox regression on lipid species, adjusting for BMI, age, and diabetes, showed several elevated baseline TG associated with shorter time to DR/CD. Latent class analysis identified two baseline lipid profiles with differences in risk of CIPN (hazard ratio, 2.80 [95% CI, 1.50 to 5.23]; P = .0013). The higher risk lipid profile had several elevated TG species and was independently associated with DR/CD when modeled with other clinical factors (diabetes, age, BMI, or prior numbness/tingling). CONCLUSION: Elevated baseline plasma TG is associated with an increased risk of CIPN development and warrants further validation in other cohorts. Ultimately, this may enable therapeutic intervention.

CuPc-Fe@BSA nanocomposite: Intracellular acid-sensitive aggregation for enhanced sonodynamic and chemo-therapy.

Due to their rigid π-conjugated macrocyclic structure, organic sonosensitizers face significant aggregation in physiological conditions, hindering the production of reactive oxygen species (ROS). An acid-sensitive nanoassembly was developed to address this issue and enhance sonodynamic therapy (SDT) and emission. Initially, copper phthalocyanine (CuPc) was activated using a H2SO4-assisted hydrothermal method to introduce multiple functional groups (-COOH, -OH, and -SO3H), disrupting strong π-π stacking and promoting ROS generation and emission. Subsequently, negatively charged CuPc-SO4 was incorporated into bovine serum albumin (BSA) to form CuPc-Fe@BSA nanoparticles (10 nm) with Fe3+ ions serving as linkers. In acidic conditions, protonation of CuPc-SO4 and BSA weakened the interactions, leading to Fe3+ release and nanostructure dissociation. Protonated CuPc-SO4 tended to self-aggregate into nanorods. This acidity-sensitive aggregation is vital for achieving specific accumulation within the tumor microenvironment (TME), thereby enhancing retention and SDT efficacy. Prior to this, the nanocomposites demonstrated cycling stability under neutral conditions. Additionally, the released Fe ions exhibited mimicry of glutathione peroxidase and peroxidase activity for chemotherapy (CDT). The synergistic effect of SDT and CDT increased intracellular oxidative stress, causing mitochondrial injury and ferroptosis. Furthermore, the combined therapy induced immunogenic cell death (ICD), effectively activating anticancer immune responses and suppressing metastasis and recurrence.

Safety and efficacy of indocyanine green fluorescence imaging-guided laparoscopic para-aortic lymphadenectomy for left-sided colorectal cancer:A preliminary case-matched study.

AIM: This study is aimed to explore the safety and feasibility of indocyanine green (ICG) fluorescence imaging guidance in laparoscopic para-aortic lymph node (PALN) dissection for left-sided colorectal cancer (CRC) patients with clinically suspected PALN metastasis. METHOD: A total of 151 patients who underwent primary tumor resection and laparoscopic PALN dissection for left-sided CRC were included, with 20 patients in the ICG group and 131 patients in the non-ICG group. The surgical outcomes, postoperative complications, and pathological results, such as the number of harvested and metastatic lymph nodes were compared between groups after propensity score matching. RESULTS: Following propensity score matching, the ICG group had 20 patients, and the non-ICG group had 53 patients, and the two groups were similar in baseline characteristics. No significant differences were observed in overall intraoperative and postoperative complications between groups, except for chylous leakage, where the ICG group had a longer time to a normal diet. The number of harvested pericolic/perirectal and intermediate lymph nodes were comparable between the two groups, while the ICG group had a significantly higher number of total harvested lymph nodes (39 [14-78] vs. 29 [11-70], P = 0.001), inferior mesenteric artery lymph nodes (IMALN, 6 [0-17] vs. 3 [0-11], P = 0.006), and PALNs (9 [3-29] vs. 5 [1-37], P = 0.001). CONCLUSION: ICG fluorescence imaging could increase the retrieval of IMALN, PALN, and total lymph nodes, and potentially improve the completeness of laparoscopic PALN dissection in patients with left-sided CRC.

The loading of Fe ions on N-doped carbon nanosheets to boost photocatalytic cascade for water disinfection.

The pervasive presence of pathogenic bacteria in water environment poses a serious threat to public health. Here, a photocatalytic cascade was developed to reveal great water disinfection. Firstly, N-doped carbon nanosheets (N-CNSs) about 30-50 nm in size were synthesized by a hydrothermal strategy. It revealed wide-spectrum photocatalysis for H2O2 generation via a typical two-step single-electron process. A Fenton agent (Fe ion) was loaded, N-CNSs-Fe can in-situ convert photocatalytic H2O2 into ·OH with high oxidation potential. Moreover, its Fenton active is three times greater than pure Fe2+ owing to electron enrichment from N-CNSs to Fe for Fe3+/Fe2+ cycle. Further investigation displayed that Fe loading also could decrease bad gap and promote charge separation to boost photocatalysis. In addition, N-CNSs-Fe possesses positive surface potential to exhibit strong interaction with negative bacteria, facilitating the capture. Therefore, the nanocomposite can effectively inactivate E. coli with a lethality rate of 99.7 % under stimulated sunlight irradiation. In addition, it also was employed to treat a complex lake water sample, revealing great antibacterial (95.1 %) and dye-decolored (92.3 %) efficiency at the same time. With novel biocompatibility and antibacterial ability, N-CNSs-Fe possessed great potential for water disinfection.

A New δ-Globin Gene Variant: Hb A2-Yulin [δ46(CD5)Gly→Arg,HBD: C.139G > A].

We report a new δ-chain hemoglobin (Hb) variant observed in a 5-year-old female living in Yulin, Guangxi, China. Capillary electrophoresis revealed splitting of the Hb A2 peak into two fractions (Hb A2 and Hb A2 variant), and the Hb A2 variant was also detected by high-performance liquid chromatography. However, it could not be detected using matrix-assisted laser desorption lonization-time of flight mass spectrometry. CD41-42 (-TCTT) heterozygosity was observed on the HBB gene by PCR and reverse dot-blot hybridization. Sanger sequencing showed a new transition (G > A) at codon 46 of the HBD gene, resulting in glycine changing to arginine. Based on the patient's place of residence, the new variant was named Hb A2-Yulin [δ46(CD5)Gly→Arg,HBD:c.139G > A].

An Intelligent and Soluble Microneedle Composed of Bi/BiVO4 Schottky Heterojunction for Tumor Ct Imaging and Starvation/Gas Therapy-Promoted Synergistic Cancer Treatment.

Phototherapy and sonodynamic therapy (SDT) are widely used for the synergistic treatment of tumors and have received considerable attention. However, an inappropriate tumor microenvironment, including pH, H2O2, oxygen, and glutathione levels, can reduce the therapeutic effects of synergistic phototherapy and SDT. Here, a novel Bi-based soluble microneedle (MN) is designed for the CT imaging of breast tumors and starvation therapy/gas therapy-enhanced phototherapy/SDT. The optimized Bi/BiVO4 Schottky heterojunction serves as the tip of the MN, which not only has excellent photothermal conversion ability and CT contrast properties, but its heterojunction can also avoid the rapid combination of electrons and hole pairs, thereby enhancing the photodynamic/sonodynamic effects. A degradable MN with excellent mechanical properties is fabricated by optimizing the ratios of poly(vinyl alcohol), poly(vinyl pyrrolidone), and sodium hyaluronate. Glucose oxidase (GOx) and diallyl trisulfide are loaded into the MN to achieve tumor starvation and gas therapy, respectively; And the controlled release of GOx and H2S can be achieved under ultrasound or near-infrared laser irradiation. The in vitro and in vivo results demonstrate that this multifunctional MN can achieve high therapeutic efficacy through starvation therapy/gas therapy-enhanced phototherapy/SDT. The designed multifunctional MN provides a prospective approach for synergistic phototherapy and SDT.

Interrater Agreement of CT Grading of Blunt Splenic Injuries: Does the AAST Grading Need to Be Reimagined?

Introduction: The Revised Organ Injury Scale (OIS) of the American Association for Surgery of Trauma (AAST) is the most widely accepted classification of splenic trauma. The objective of this study was to evaluate inter-rater agreement for CT grading of blunt splenic injuries. Methods: CT scans in adult patients with splenic injuries at a level 1 trauma centre were independently graded by 5 fellowship trained abdominal radiologists using the AAST OIS for splenic injuries - 2018 revision. The inter-rater agreement for AAST CT injury score, as well as low-grade (IIII) versus high-grade (IV-V) splenic injury was assessed. Disagreement in two key clinical scenarios (no injury versus injury, and high versus low grade) were qualitatively reviewed to identify possible sources of disagreement. Results: A total of 610 examinations were included. The inter-rater absolute agreement was low (Fleiss kappa statistic 0.38, P < 0.001), but improved when comparing agreement between low and high grade injuries (Fleiss kappa statistic of 0.77, P < .001). There were 34 cases (5.6%) of minimum two-rater disagreement about no injury vs injury (AAST grade ≥ I). There were 46 cases (7.5%) of minimum two-rater disagreement of low grade (AAST grade I-III) versus high grade (AAST grade IV-V) injuries. Likely sources of disagreement were interpretation of clefts versus lacerations, peri-splenic fluid versus subcapsular hematoma, application of adding multiple low grade injuries to higher grade injuries, and identification of subtle vascular injuries. Conclusion: There is low absolute agreement in grading of splenic injuries using the existing AAST OIS for splenic injuries.

PCPro: a clinically accessible, circulating lipid biomarker signature for poor-prognosis metastatic prostate cancer.

BACKGROUND: Using comprehensive plasma lipidomic profiling from men with metastatic castration-resistant prostate cancer (mCRPC), we have previously identified a poor-prognostic lipid profile associated with shorter overall survival (OS). In order to translate this biomarker into the clinic, these men must be identifiable via a clinically accessible, regulatory-compliant assay. METHODS: A single regulatory-compliant liquid chromatography-mass spectrometry assay of candidate lipids was developed and tested on a mCRPC Discovery cohort of 105 men. Various risk-score Cox regression prognostic models of OS were built using the Discovery cohort. The model with the highest concordance index (PCPro) was chosen for validation and tested on an independent Validation cohort of 183 men. RESULTS: PCPro, the lipid biomarker, contains Cer(d18:1/18:0), Cer(d18:1/24:0), Cer(d18:1/24:1), triglycerides and total cholesterol. Within the Discovery and Validation cohorts, men who were PCPro positive had significantly shorter OS compared to those who were PCPro negative (Discovery: median OS 12.0 months vs 24.2 months, hazard ratio (HR) 3.75 [95% confidence interval (CI) 2.29-6.15], p < 0.001, Validation: median OS 13.0 months vs 25.7 months, HR = 2.13 [95% CI 1.46-3.12], p < 0.001). CONCLUSIONS: We have developed PCPro, a lipid biomarker assay capable of prospectively identifying men with mCRPC with a poor prognosis. Prospective clinical trials are required to determine if men who are PCPro positive will benefit from therapeutic agents targeting lipid metabolism.

Large-Scale Observations Support Aboveground Vegetation as an Important Biological Mercury Sink in the Tibetan Plateau.

Mercury, a pervasive global pollutant, primarily enters the atmosphere through human activities and legacy emissions from the land and oceans. A significant portion of this mercury subsequently settles on land through vegetation uptake. Characterizing mercury storage and distribution within vegetation is essential for comprehending regional and global mercury cycles. We conducted an unprecedented large-scale aboveground vegetation mercury survey across the expansive Tibetan Plateau. We find that mosses (31.1 ± 0.5 ng/g) and cushion plants (15.2 ± 0.7 ng/g) outstood high mercury concentrations. Despite exceptionally low anthropogenic mercury emissions, mercury concentrations of all biomes exceeded at least one-third of their respective global averages. While acknowledging the role of plant physiological factors, statistical models emphasize the predominant impact of atmospheric mercury on driving variations in mercury concentrations. Our estimations indicate that aboveground vegetation on the plateau accumulates 32-12+21 Mg (interquartile range) mercury. Forests occupy the highest biomass and store 82% of mercury, while mosses, representing only 3% of the biomass, disproportionally contribute 13% to mercury storage and account for 43% (2.5-1.4+3.0 Mg/year) of annual mercury assimilation by vegetation. Additionally, our study underscores that extrapolating aboveground vegetation mercury storage from lower-altitude regions to the Tibetan Plateau can lead to substantial overestimation, inspiring further exploration in alpine ecosystems worldwide.

Porous Molybdenum Nitride Nanosphere as Carrier-Free and Efficient Nitric Oxide Donor for Synergistic Nitric Oxide and Chemo/Sonodynamic Therapy.

Given its abundant physiological functions, nitric oxide (NO) has attracted much attention as a cancer therapy. The sensitive release and great supply capacity are significant indicators of NO donors and their performance. Here, a transition metal nitride (TMN) MoN@PEG is adopted as an efficient NO donor. The release process starts with H+-triggered denitrogen owing to the high electronegativity of the N atom and weak Mo-N bond. Then, these active NHx are oxidized by O2 and other reactive oxygen species (ROS) to form NO, endowing specific release to the tumor microenvironment (TME). With a porous nanosphere structure (80 nm), MoN@PEG does not require an extra carrier for NO delivery, contributing to ultrahigh atomic utilization for outstanding release ability (94.1 ± 5.6 µM). In addition, it can also serve as a peroxidase and sonosensitizer for anticancer treatment. To further improve the charge separation, MoN-Pt@PEG was prepared to enhance the sonodynamic therapy (SDT) effect. Accordingly, ultrasound (US) further promotes NO generation due to more ROS generation, facilitating in situ peroxynitrite (·ONOO-) generation with great cytotoxicity. At the same time, the nanostructure also degrades gradually, leading to high elimination (94.6%) via feces and urine within 14-day. The synergistic NO and chemo-/sono-dynamic therapy brings prominent antitumor efficiency and further activates the immune response to inhibit metastasis and recurrence. This work develops a family of NO donors that would further widen the application of NO therapy in other fields.

Significant impacts of river inputs on the distributions and transports of mercury and methylmercury in nearshore and open seas - Simulation based on field surveys and mass balance modeling.

Rivers are important sources of Hg for adjacent seas, and seafood from nearshore waters is a major source of Hg exposure for humans. There is thus a key scientific concern regarding how much riverine Hg inputs influence Hg loads in nearshore waters as well as how far the impact range can extend from the river to the open sea. In addition, it is important to understand the influence of anthropogenic hydro-facilities and activities on Hg levels in downstream seas. Because of the concise mass exchange pattern between the seas and the previously demonstrated intensive Hg inputs under anthropogenic regulation from the Yellow River, the Bohai and Yellow Seas, which are key fishery and marine breeding areas for China, are an ideal research area for exploring the impacts of riverine Hg on nearshore and adjacent open seas. Field surveys were conducted in eight major rivers and two seas, and 433 water samples were collected. The main Hg input and output terms (rivers, ocean currents, underground discharge, sewage, coastal erosion, atmospheric deposition, surface evasion, sedimentation, and fisheries) were quantified in the Bohai and Yellow Seas. Owing to the high inputs from the Yellow and Yalu Rivers, elevated THg concentrations were found. Apart from direct MeHg discharge, riverine nutrients may also seemingly affect nearshore MeHg. Using mass balance models, we found that the Yellow River (9.8 t) was the dominant Hg source in the Bohai Sea, which accounted for more than half of all contributions, and the Bohai Sea played the role of a secondary source of Hg to the Yellow Sea, with a flux of 3.3 t. Anthropogenic hydro-activities in large rivers could significantly influence Hg outputs and loads in the nearshore and even open seas. This study provides useful information for water resource management applications to reduce potential MeHg risks.

Pathways of lymph node metastasis and prognosis after right hemicolectomy for cecal cancer: results from a retrospective single center.

BACKGROUND: The recommended operation for cecum cancer (CC) is right hemicolectomy (RH) in some Western countries while the principle of D3 lymphadenectomy in Japan recommends resecting approximately 10 cm from the tumor edge. Therefore, the optimal surgical approach for cecum cancer (CC) remains controversial. We conducted this retrospective study to explore the pattern of lymph node metastasis and better surgical procedures for CC. METHODS: A total of 224 cecum cancer patients from January 1, 2014, to December 31, 2021, were retrospectively included in the final study. The pattern of lymph node metastasis (LNM) was investigated. RESULTS: A total of 113 (50.4%, 113/224) patients had pathologically confirmed LNM. The most frequent metastatic site was no. 201 lymph node (46%, 103/224), while 20 (8.9%, 20/224) patients had LNM in no. 202 lymph node, and 8 (3.6%, 8/224) patients had LNM in no. 203 lymph node. Only 1 (0.4%, 1/224) patient had LNM in no. 221 lymph node, four (1.8, 4/224%) patients had LNM in no. 223 lymph node, and no patients had LNM in no. 222 lymph node. LNM in no. 223 lymph node was significantly associated with a poor prognosis. Multivariate analysis indicated that LNM in no. 223 lymph node (HR = 4.59, 95% CI 1.18-17.86, P = 0.028) was the only independent risk factor associated with worse disease-free survival (DFS). CONCLUSIONS: The LNM in no. 223 lymph node for cecum cancer was rare. Therefore, standard right hemicolectomy excision is too extensive for most CC cases.

Impacts of autochthonous dissolved organic matter on the accumulation of methylmercury by phytoplankton and zooplankton in a eutrophic coastal ecosystem.

The bioaccumulation of methylmercury (MeHg) within the pelagic food webs is a crucial determinant of the MeHg concentration in the organisms at higher trophic levels. Dissolved organic matter (DOM) is recognized for its influence on mercury (Hg) cycling in the aquatic environment because of its role in providing metabolic substrate for heterotrophic organism and serving as a strong ligand for MeHg. However, the impact of DOM on MeHg bioaccumulation in pelagic food chains remain controversial. Here, we explored MeHg bioaccumulation within a pelagic food web in China, in the eutrophic Bohai Sea and adjacent seas, covering a range of DOM concentrations and compositions. Our findings show that elevated concentrations of dissolved organic carbon (DOC) and phytoplankton biomass may contribute to a reduction in MeHg uptake by phytoplankton. Moreover, we observe that a higher level of autochthonous DOM in the water may result in more significant MeHg biomagnification in zooplankton. This can be explained by alterations in the structure of pelagic food webs and/or an increase in the direct consumption of DOM and particulate organic matter (POM) containing MeHg. Our study offers direct field monitoring evidence of dual roles played by DOM in regulating MeHg transfers from water to phytoplankton and zooplankton in coastal pelagic food webs. A thorough understanding of the intricate interactions is essential for a more comprehensive evaluation of ecological risks associated with MeHg exposure in coastal ecosystems.

Development a novel nomogram model for predicting significant hepatic histological changes in chronic hepatitis B virus carriers.

A proportion of chronic hepatitis B virus (HBV) carriers with normal alanine transaminase (ALT) present with significant liver histological changes (SLHC). To construct a noninvasive nomogram model to identify SLHC in chronic HBV carriers with different upper limits of normal (ULNs) for ALT. The training cohort consisted of 732 chronic HBV carriers who were stratified into four sets according to different ULNs for ALT: chronic HBV carriers I, II, III, and IV. The external validation cohort comprised 277 chronic HBV carriers. Logistic regression and least absolute shrinkage and selection operator analyses were applied to develop a nomogram model to predict SLHC. A nomogram model-HBGP (based on hepatitis B surface antigen, gamma-glutamyl transpeptidase, and platelet count) demonstrated good performance in diagnosing SLHC with area under the curve (AUCs) of 0.866 (95% confidence interval [CI]: 0.839-0.892) and 0.885 (95% CI: 0.845-0.925) in the training and validation cohorts, respectively. Furthermore, HBGP displayed high diagnostic values for SLHC with AUCs of 0.866 (95% CI: 0.839-0.892), 0.868 (95% CI: 0.838-0.898), 0.865 (95% CI: 0.828-0.901), and 0.853 (95% CI: 0.798-0.908) in chronic HBV carriers I, II, III, and IV, respectively. Additionally, HBGP showed greater ability in predicting SLHC compared with the existing predictors. HBGP has shown high predictive performance for SLHC, and thus may lead to an informed decision on the initiation of antiviral treatment.

Multi-Omic Integration of Blood-Based Tumor-Associated Genomic and Lipidomic Profiles Using Machine Learning Models in Metastatic Prostate Cancer.

PURPOSE: To determine prognostic and predictive clinical outcomes in metastatic hormone-sensitive prostate cancer (mHSPC) and metastatic castrate-resistant prostate cancer (mCRPC) on the basis of a combination of plasma-derived genomic alterations and lipid features in a longitudinal cohort of patients with advanced prostate cancer. METHODS: A multifeature classifier was constructed to predict clinical outcomes using plasma-based genomic alterations detected in 120 genes and 772 lipidomic species as informative features in a cohort of 71 patients with mHSPC and 144 patients with mCRPC. Outcomes of interest were collected over 11 years of follow-up. These included in mHSPC state early failure of androgen-deprivation therapy (ADT) and exceptional responders to ADT; early death (poor prognosis) and long-term survivors in mCRPC state. The approach was to build binary classification models that identified discriminative candidates with optimal weights to predict outcomes. To achieve this, we built multi-omic feature-based classifiers using traditional machine learning (ML) methods, including logistic regression with sparse regularization, multi-kernel Gaussian process regression, and support vector machines. RESULTS: The levels of specific ceramides (d18:1/14:0 and d18:1/17:0), and the presence of CHEK2 mutations, AR amplification, and RB1 deletion were identified as the most crucial factors associated with clinical outcomes. Using ML models, the optimal multi-omics feature combination determined resulted in AUC scores of 0.751 for predicting mHSPC survival and 0.638 for predicting ADT failure; and in mCRPC state, 0.687 for prognostication and 0.727 for exceptional survival. The models were observed to be superior than using a limited candidate number of features for developing multi-omic prognostic and predictive signatures. CONCLUSION: Using a ML approach that incorporates multiple omic features improves the prediction accuracy for metastatic prostate cancer outcomes significantly. Validation of these models will be needed in independent data sets in future.

The mediating effect of psychological empowerment on the relationship between work environment and clinical decision-making among midwives: a multicentre cross-sectional study.

BACKGROUND: Clinical decision-making is considered an essential behaviour in clinical practice. However, no research has been done to examine the associations among midwives' clinical decision-making, work environment and psychological empowerment. Thus, this study aimed to determine the influence of work environment on midwives' clinical decision-making and confirm the mediating role of psychological empowerment. METHOD: This study was designed as a multicentre cross-sectional study, and included 602 registered midwives from 25 public hospitals in China. A sociodemographic questionnaire, Work Environment Scale, Psychological Empowerment Scale and Clinical decision-making Scale were applied. A structural equation model was conducted to estimate the hypothesis model of the clinical decision-making among midwives and explore the potential mediating mechanism of midwives' clinical decision-making. This model was employed maximum likelihood estimation method and bootstrapping to examine the statistical significance. RESULTS: The mean score of clinical decision-making among midwives was 143.03 ± 14.22, at an intermediate level. The data of this hypothesis model fitted well, and the results showed that work environment positively affected psychological empowerment, which in turn positively affected clinical decision-making; psychological empowerment partly mediated the relationship between work environment and clinical decision-making among midwives. CONCLUSIONS: Midwives' clinical decision-making could be promoted directly or indirectly by providing a healthy work environment and improving psychological empowerment. It is essential for hospital managers to pay attention to the assessment of the midwives' work environment and actively improve it, such as establishing a supportive, fair and just workplace, and maintaining effective communication with midwives. Furthermore, managers can also promote midwives' clinical decision-making behaviour by enhancing their psychological empowerment via enhancing job autonomy.

Defect-Rich Ni-CoO@PEG Porous Hexagonal Nanosheets: Multi-enzyme and Ultrasound Catalysis for Synergistic Anticancer Treatment.

Given the similarity with photocatalysis, sonodynamic therapy (SDT) can be defined as ultrasonic (US) catalysis. Encouraged by the principles of photocatalysis and defect chemistry, defect-rich nickel (Ni)-doped cobaltous oxide (Ni-CoO@PEG) porous hexagonal nanosheets have been synthesized as a sonosensitizer. The doping of Ni decreases the band gap that is testified by density functional theory to increase the US-generated charges. Under US irradiation, Ni-CoO@PEG nanosheets produce 1O2 as an active species that is determined by dissolved O2 and electrons. Moreover, the doping also brings abundant oxygen vacancies (OV) that not only are in favor of efficient separation of electron-hole but also enhance the interaction toward O2, boosting 1O2 generation. In addition, Ni-CoO@PEG shows robust mimic catalase (CAT) and peroxidase characterization to effectively improve the intratumor O2 content and oxidation stress. What is more, the nanosheets also possess glucose oxidase activity that can consume glucose to elevate the H2O2/acid level and to block the intracellular energy supply. The tandem nanozyme behaviors would further regulate the tumor microenvironment for assisting anticancer treatment. It is noted that Ni-CoO@PEG reveals a novel half-metallic feature endowing great magnetism and magnetic resonance imaging capacity. The above synergistic treatments exhibit outstanding anticancer performance that also evokes antitumor immunity to suppress metastasis and recurrence, efficiently.

NIR-II driven photocatalytic hydrogen peroxide-supply on metallic copper-nickel selenide (Cu-Ni0.85Se) nanoparticle for synergistic therapy.

Currently, finite intratumoral H2O2 content has restricted the efficacy of chemodynamic therapy (CDT). Here, Cu-Ni0.85Se@PEG nanoparticles are constructed to display intracellular NIR-II photocatalytic H2O2 supplement. The formation mechanism is explored to discover that H2O2 generation is dominated by photo-excited electrons and dissolved O2 via a typical sequential single-electron transfer process. Both density functional theory calculation and experimental data confirm its metallic feature that endows the great NIR-II absorption and photothermal conversion efficiency (59.6 %, 1064 nm). Furthermore, the photothermal-assisting consecutive interband and intraband transition in metallic catalyst contributes to the high redox capacity and efficient separation/transfer ability of photo-generated charges, boosting H2O2 production under 1064 nm laser irradiation. In addition, Cu-Ni0.85Se@PEG possess mimic peroxidase and catalase activity, leading to in-situ H2O2 activation to produce ∙OH and O2 for the enhanced CDT and hypoxia relief. What's more, the nanomaterials reveal novel biodegradation that is derived from oxidation from insolvable selenide into soluble selenate, resulting in elimination via feces and urine within 2 weeks. Synergistic CDT and photothermal therapy (PTT) further lead to great tumor inhibition and immune response for anti-tumor. The antitumor mechanism and the potential biological process also are investigated by high-throughput sequencing of expressed transcripts (RNAseq). The great treatment performance is responsible for the regulation of related oxidative stress and stimulus genes to induce organelle (mitochondrial) and membrane dysfunction. Besides, the synergistic therapy also can efficiently evoke immune response to further fight against tumor.

Thermal-Response Proton Conduction in Schiff Base-Incorporated Metal-Organic Framework Hybrid Membranes under Low Humidity Based on the Excited-State Intramolecular Proton Transfer Mechanism.

Stimulus-responsive proton conduction materials have attracted enormous interest as a new kind of "smart material". It is desirable to develop the appropriate stimulus signal and high proton-conducting materials with an excellent proton-conducting switch ratio (γ), but it remains a great challenge. Here, it can be found for the first time that 4-((2-hydroxybenzylidene)amino)benzenesulfonic acid (HBABSA) has obvious thermal isomerization when porous solids act as matrixes at the ambient temperatures, which is different from that in the crystalline state at 77 K. Therefore, we proposed a host-guest metal-organic framework (MOF) composite, namely, MOF-808 incorporated with HBABSA (HBABSA@MOF-808), which has a proton-conducting switch ratio (γ) of 16 between 338 and 343 K due to the thermally induced isomerization of HBABSA molecules in the MOF pores. The strong binding between the keto-type HBABSA and MOF at the relatively low temperatures can efficiently suppress the proton conduction, while the enol-type one provides more mobile protons for conduction at the high temperatures due to the excited-state intramolecular proton transfer mechanism. Further, the HBABSA@MOF-808 as a filler is blended into polyvinyl alcohol and poly(2-acrylamide-2-methyl-1-propane sulfonic acid) to form hybrid membranes. The hybrid membrane with the highest content of the MOF composite displays a high proton conductivity of 5.57 × 10-3 S·cm-1 under 353 K and 57% RH along with a good switch ratio of 5.4. The development of thermal-response proton-conducting MOF materials is opening up a unique pathway for remote control, thermal sensing, intelligent batteries, and other fields.

Hollow CoP@N-Carbon Nanospheres: Heterostructure and Glucose-Enhanced Charge Separation for Sonodynamic/Starvation Therapy.

Sonodynamic therapy (SDT) can be described as ultrasonic (US) catalysis. Adequate charge separation is considered as effective means to promote reactive oxygen species (ROS). Here, hollow CoP@N-carbon@PEG (CPCs@PEG) nanospheres (∼60 nm) are prepared as sonosensitizers, showing greater ROS generation than pure CoP@PEG under US irradiation. Both 1O2 and ·O2- are activation species that are determined by O2 and electrons. The great SDT performance of CPCs@PEG is ascribed to the heterostructure which promotes the separation and transfer for US-generated electrons and holes. In addition, holes can be further captured by endogenous glucose that is in favor of electron aggregation and ROS generation. Moreover, the consumption of glucose would decrease intracellular ATP for starvation therapy. Given the higher oxidation ability of Co3+, CPCs@PEG nanospheres possess catalase (CAT) activity to convert H2O2 into O2 for assisting ROS generation. Moreover, they also can oxidize glutathione (GSH) as a mimic GSH oxidase to break intratumor redox balance, facilitating oxidative stress. More importantly, the nanocomposites reveal good degradation ability dominated by the oxidation from insoluble phosphide into soluble phosphate, accelerating elimination via urine and feces within 14 days. CPCs@PEG nanospheres integrate the above effects not only to reveal great tumor inhibition ability but also to excite immune activation for anticancer.