Incidence of cardiovascular mortality among head and neck cancer patients.

BACKGROUND: While treatment advancements have prolonged the lives of patients with head and neck cancer, the subgroups of these patients at higher risk for cardiovascular disease (CVD) mortality remain unclear. METHODS: We analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database for patients diagnosed with head and neck cancer from 2000 to 2019. We compared their CVD mortality against the general US population using standardized mortality ratios (SMRs). RESULTS: Our analysis included 474,366 patients, identifying that 14% of deaths were due to CVD, with an SMR of 1.19. Notably, patients under the age of 39 had a CVD SMR increase of over 100-fold. Those with distant tumor stages showed the highest CVD SMR of 1.52 (95% CI 1.50-1.54). An upward trend in SMR to 2.53 (95% CI 2.51-2.56) was observed from 2011 to 2019. Within the initial 5-year post-diagnosis, the SMR for CVD was 3.17 (95% CI 3.14-3.20), which exceeded the general population's rates but declined in the 5-20-year range after diagnosis. Patients who did not any therapy had the greatest CVD SMR of 2.26 (95% CI 2.24-2.28). Hypopharyngeal cancer patients exhibited the highest CVD SMR of 1.54 (95% CI 1.52-1.56). CONCLUSIONS: The study highlights that head and neck cancer patients, especially younger individuals and those with advanced disease stages, face substantial CVD mortality risks. The CVD SMR peaks within 5 years following diagnosis. Patients abstaining from treatment bear the highest risk of CVD mortality. Cardioprotective measures should be considered critical for this patient population.

A validated model to predict spread through air space in lung adenocarcinoma.

Background: Spread through air space (STAS) is currently considered to be a significant predictor of a poor outcome of pulmonary adenocarcinoma. Preoperative prediction of STAS is of great importance for treatment planning. The aim of the present study was to establish a nomogram based on computed tomography (CT) features for predicting STAS in lung adenocarcinoma and to assess the prognosis of the patients with STAS. Methods: A retrospective cohort study was performed in Wuhan Union Hospital from December 2015 to March 2021. The sample was divided into training and testing cohorts. Clinicopathologic and radiologic variables were recorded. The independent risk factors for STAS were determined by stepwise regression and then incorporated into the nomogram. Receiver operating characteristic (ROC) curves and calibration curves analysed by the Hosmer-Lemeshow test were used to evaluate the performance of the model. Decision curve analysis (DCA) was conducted to determine the clinical value of the nomogram. The Kaplan-Meier method was used for survival analysis and the multivariable Cox proportional hazards regression model was used to identify independent predictors for recurrence-free survival (RFS) and overall survival (OS). Results: The sample included 244 patients who underwent surgical resection for primary lung adenocarcinoma. The training cohort included 199 patients (68 STAS-positive and 131 STAS-negative patients), and the testing cohort included 45 patients (15 STAS-positive and 30 STAS-negative patients). The preoperative CT features associated with STAS were shape, ground-glass opacity (GGO) ratio and spicules. The nomogram including these three factors had good discriminative power, and the areas under the ROC curve were 0.875 and 0.922 for the training and testing data sets, respectively, with well-fitted calibration curves. DCA showed that the nomogram was clinically useful. STAS-positive patients had significantly worse OS and RFS than STAS-negative patients (both P<0.01). OS and RFS at 5-year for STAS-positive patients were 63.1% and 59.5%, respectively. Multivariate analysis showed that age [hazard ratio (HR), 1.1; 95% confidence interval (CI): 1.035-1.169; P=0.002], diameter (HR, 1.06; 95% CI: 1.04-1.11; P=0.03) and surgical margin (HR, 32.8; 95% CI: 6.8-158.3; P<0.001) were independent risk factors for OS. Adjuvant therapy (HR, 7.345; 95% CI: 2.52-21.41; P<0.001), N stage (N2) (HR, 0.239; 95% CI: 0.069-0.828; P=0.02) and surgical margin (HR, 15.6; 95% CI: 5.9-41.1; P<0.001) were found to be independent risk factors for RFS. Conclusions: The outcome of STAS-positive patients was worse. The nomogram incorporating the identified CT features could be applied to facilitate individualized preoperative prediction of STAS and selection of rational therapy.

Achieving Exceptional Volumetric Desalination Capacity Using Compact MoS2 Nanolaminates.

Capacitive deionization (CDI) has emerged as a promising technology for freshwater recovery from low-salinity brackish water. It is still inapplicable in specific scenarios (e.g., households, islands, or offshore platforms) due to too low volumetric adsorption capacities. In this study, we report a high-density semi-metallic molybdenum disulfide (1T'-MoS2) electrode with compact architecture obtained by restacking of exfoliated nanosheets, which achieved high capacitance up to ∼277.5 F cm-3 under an ultrahigh scan rate of 1000 mV s-1 with a lower charge-transfer resistance and nearly ten-fold higher electrochemical active surface area than the 2H-MoS2 electrode. Furthermore, 1T'-MoS2 electrode demonstrates exceptional volumetric desalination capacity of 65.1 mgNaCl cm-3 in CDI experiments. Ex-situ X-ray diffraction (XRD) reveal that the cation storage mechanism with the dynamic expansion of 1T'-MoS2 interlayer to accommodate cations such as Na+, K+, Ca2+, and Mg2+, which in turn enhances the capacity. Theoretical analysis unveils that 1T' phase is thermodynamically preferable over 2H phase, the ion hydration and channel confinement also play critical role in enhancing ion adsorption. Overall, this work provides a new method to design compact two-dimensional layered nanolaminates with high volumetric performance for CDI desalination. This article is protected by copyright. All rights reserved.

Astrocytic ALKBH5 in stress response contributes to depressive-like behaviors in mice.

Epigenetic mechanisms bridge genetic and environmental factors that contribute to the pathogenesis of major depression disorder (MDD). However, the cellular specificity and sensitivity of environmental stress on brain epitranscriptomics and its impact on depression remain unclear. Here, we found that ALKBH5, an RNA demethylase of N6-methyladenosine (m6A), was increased in MDD patients' blood and depression models. ALKBH5 in astrocytes was more sensitive to stress than that in neurons and endothelial cells. Selective deletion of ALKBH5 in astrocytes, but not in neurons and endothelial cells, produced antidepressant-like behaviors. Astrocytic ALKBH5 in the mPFC regulated depression-related behaviors bidirectionally. Meanwhile, ALKBH5 modulated glutamate transporter-1 (GLT-1) m6A modification and increased the expression of GLT-1 in astrocytes. ALKBH5 astrocyte-specific knockout preserved stress-induced disruption of glutamatergic synaptic transmission, neuronal atrophy and defective Ca2+ activity. Moreover, enhanced m6A modification with S-adenosylmethionine (SAMe) produced antidepressant-like effects. Our findings indicate that astrocytic epitranscriptomics contribute to depressive-like behaviors and that astrocytic ALKBH5 may be a therapeutic target for depression.

Phase Engineering of High-Entropy Alloy for Enhanced Electrocatalytic Nitrate Reduction to Ammonia.

Directly electrochemical conversion of nitrate (NO3-) is an efficient and environmentally friendly technology for ammonia (NH3) production but is challenged by highly selective electrocatalysts. High-entropy alloys (HEAs) with unique properties are attractive materials in catalysis, particularly for multi-step reactions. Herein, we first reported the application of HEA (FeCoNiAlTi) for electrocatalytic NO3- reduction to NH3 (NRA). The bulk HEA is active for NRA but limited by the unsatisfied NH3 yield of 0.36 mg h-1 cm-2 and Faradaic efficiency (FE) of 82.66%. Through an effective phase engineering strategy, uniform intermetallic nanoparticles are introduced on the bulk HEA to increase electrochemical active surface area and charge transfer efficiency.The resulting nanostructured HEA (n-HEA) delivers enhanced electrochemical NRA performance in terms of NH3 yield (0.52 mg h-1 cm-2) and FE (95.23%). Further experimental and theoretical investigations reveal that the multi-active sites (Fe, Co, and Ni) dominated electrocatalysis for NRA over the n-HEA. Notably, the typical Co sites exhibit the lowest energy barrier for NRA with *NO + H+ + e- → *NOH as the rate-determining step.

Corrigendum: Phenotypic and transcriptional characterization of F. tularensis LVS during transition into a viable but non-culturable state.

[This corrects the article DOI: 10.3389/fmicb.2024.1347488.].

Polymer hetero-electrolyte enabled solid-state 2.4-V Zn/Li hybrid batteries.

The high redox potential of Zn0/2+ leads to low voltage of Zn batteries and therefore low energy density, plaguing deployment of Zn batteries in many energy-demanding applications. Though employing high-voltage cathode like spinel LiNi0.5Mn1.5O4 can increase the voltages of Zn batteries, Zn2+ ions will be immobilized in LiNi0.5Mn1.5O4 once intercalated, resulting in irreversibility. Here, we design a polymer hetero-electrolyte consisting of an anode layer with Zn2+ ions as charge carriers and a cathode layer that blocks the Zn2+ ion shuttle, which allows separated Zn and Li reversibility. As such, the Zn‖LNMO cell exhibits up to 2.4 V discharge voltage and 450 stable cycles with high reversible capacity, which are also attained in a scale-up pouch cell. The pouch cell shows a low self-discharge after resting for 28 days. The designed electrolyte paves the way to develop high-voltage Zn batteries based on reversible lithiated cathodes.

Bioinspired Adaptive Microdrugs Enhance the Chemotherapy of Malignant Glioma: Beyond Their Nanodrugs.

Solid nanoparticle-mediated drug delivery systems are usually confined to nanoscale due to the enhanced permeability and retention (EPR) effect. However, they remain a great challenge for malignant glioma chemotherapy because of poor drug delivery efficiency and insufficient tumor penetration resulting from the blood-brain barrier/blood-brain tumor barrier (BBB/BBTB). Inspired by biological microparticles (e.g., cells) with excellent adaptive deformation, we demonstrate that the adaptive microdrugs (even up to 3.0 µm in size) are more efficient than their nanodrugs (less than 200 nm in size) to cross BBB/BBTB and penetrate into tumor tissues, achieving highly efficient chemotherapy of malignant glioma. The distinct delivery of the adaptive microdrugs is mainly attributed to the enhanced interfacial binding and endocytosis via adaptive deformation. As expected, the obtained adaptive microdrugs exhibited enhanced accumulation, deep penetration, and cellular internalization into tumor tissues in comparison with nanodrugs, significantly improving the survival rate of glioblastoma mice. We believe that the bioinspired adaptive microdrugs enable them to efficiently cross physiological barriers and deeply penetrate tumor tissues for drug delivery, providing an avenue for the treatment of solid tumors. This article is protected by copyright. All rights reserved.

Coupling High Hardness and Zn Affinity in Amorphous-Crystalline Diamond for Stable Zn Metal Anodes.

The highly reversible plating/stripping of Zn is plagued by dendrite growth and side reactions on metallic Zn anodes, retarding the commercial application of aqueous Zn-ion batteries. Herein, a distinctive nano dual-phase diamond (NDPD) comprised of an amorphous-crystalline heterostructure is developed to regulate Zn deposition and mechanically block dendrite growth. The rich amorphous-crystalline heterointerfaces in the NDPD endow modified Zn anodes with enhanced Zn affinity and result in homogeneous nucleation. In addition, the unparalleled hardness of the NDPD effectively overcomes the high growth stress of dendrites and mechanically impedes their proliferation. Moreover, the hydrophobic surfaces of the NDPD facilitate the desolvation of hydrate Zn2+ and prevent water-mediated side reactions. Consequently, the Zn@NDPD presents an ultrastable lifespan exceeding 3200 h at 5 mA cm-2 and 1 mAh cm-2. The practical application potential of Zn@NDPD is further demonstrated in full cells. This work exhibits the great significance of a chemical-mechanical synergistic anode modification strategy in constructing high-performance aqueous Zn-ion batteries.

The Role of MXene Surface Terminations on Peptide Transportation in Nanopore Sensing.

Nanopores with two-dimensional materials have various advantages in sensing, but the fast translocation of molecules hinders their scale-up applications. In this work, we investigate the influence of -F, -O, and -OH surface terminations on the translocation of peptides through MXene nanopores. We find that the longest dwell time always occurs when peptides pass through the Ti3C2O2 nanopores. This elongated dwell time is induced by the strongest interaction between peptides and the Ti3C2O2 membrane, in which the van der Waals interactions dominate. Compared to the other two MXene nanopores, the braking effect is indicated during the whole translocation process, which evidence the advantage of Ti3C2O2 in nanopore sensing. Our work demonstrates that membrane surface chemistry has a great influence on the translocation of peptides, which can be introduced in the design of nanopores for a better performance.

Metastatic merkel cell carcinoma to the thyroid gland: Case report and review of the literature.

BACKGROUND: Merkel cell carcinoma (MCC) is an aggressive and rare neuroendocrine tumor, accounting for less than 1% of skin cancers. Metastasis primarily manifests in the cervical lymph nodes but rarely affect the thyroid. METHODS: We report a case of primary head and neck cutaneous MCC with metastasis to the thyroid gland. A review of the literature of MCC with thyroid metastasis was conducted. RESULTS: We identified five cases of MCC with thyroid metastasis. Primary sites included the distal upper and lower extremities, axilla, buttock, and groin. Treatment courses varied including thyroidectomy, immunotherapy, and expectant palliative measures. Time from initial diagnosis to thyroid metastasis ranged from four months to four years. Tissue diagnosis was achieved in 5 of 6 cases. CONCLUSIONS: MCC with thyroid metastasis is rare and likely represents aggressive disease. Despite advances in treatment and surveillance, outcomes for MCC remain poor. Ongoing research may establish predictors for treatment response.

Optimal risk management considering environmental and climatic changes.

Climate change presents challenges to policy and economic stability, necessitating effective trading strategies to reduce environmental risks. This article addresses gaps in existing studies by using a Markov-switching model to consider climate risk. Backward stochastic differential equations are used to optimize utility with three hedging strategies based on the concept of risk aversion. Numerical scenarios confirm the model's superiority in incorporating exogenous events, with our risk-averse strategy outperforming classical approaches. Our strategy outperforms classical strategies by taking a flexible risk trading when investors face risk-averse behavior due to climate risk events. The findings presented in this article have important implications for the development of more resilient investment portfolios and can contribute to climate policy.

Double S-scheme Cu2-xSe/twinned-Cd0.5Zn0.5S homo-heterojunctions with surface plasmon effects for efficient photocatalytic H2 evolution.

The enhancement of charge separation and utilization efficiency in both the bulk phase and interface of semiconductor photocatalysts, as well as the expansion of light absorption range, are crucial research topics in the field of photocatalysis. To address this issue, twinned Cd0.5Zn0.5S (T-CZS) homojunctions consisting of wurtzite Cd0.5Zn0.5S (WZ-CZS) and zinc blende Cd0.5Zn0.5S (ZB-CZS) were synthesized via a hydrothermal method to facilitate the bulk-phase charge separation. Meanwhile, Cu2-xSe with localized surface plasmon resonance effect (LSPR) generated by Cu vacancies was also obtained through a hydrothermal process. Due to their opposite electronegativity, a solvent evaporation strategy was employed to combine Cu2-xSe and T-CZS by intermolecular electrostatic. After optimization, the photocatalytic hydrogen (H2) evolution rate of 5 wt% Cu2-xSe/T-CZS reached an impressive value of 60 mmol∙h-1∙g-1, which was 4.6 and 66.6 times higher than that of pure Cu2-xSe and T-CZS, respectively. Furthermore, this composites demonstrated a remarkable rate of 0.46 mmol∙h-1∙g-1 under near-infrared (NIR) wavelength (>800 nm). The enhanced performance observed in Cu2-xSe/T-CZS can be attributed to its unique and efficient double S-scheme charge transfer mechanism which effectively suppresses rapid recombination of electron-hole pairs both within the bulk phase and at the surface interfaces; this conclusion is supported by Density Functional Theory (DFT) calculations as well as electron paramagnetic resonance spectroscopy analysis. Moreover, incorporation of Cu2-xSe enables effective utilization ultraviolet visible-near infrared (UV-Vis-NIR) light by the composites while facilitating injection "hot electrons" into T-CZS for promoting photocatalytic reactions. This study provides a potential strategy for achieving efficient solar energy conversion through synergistic integration of non-stoichiometric plasmonic materials with photocatalysts with twinned-twinned structures.

Regulating the Electron Distribution of Metal-Oxygen for Enhanced Oxygen Stability in Li-rich Layered Cathodes.

Li-rich Mn-based layered oxides (LLO) hold great promise as cathode materials for lithium-ion batteries (LIBs) due to their unique oxygen redox (OR) chemistry, which enables additional capacity. However, the LLOs face challenges related to the instability of their OR process due to the weak transition metal (TM)-oxygen bond, leading to oxygen loss and irreversible phase transition that results in severe capacity and voltage decay. Herein, a synergistic electronic regulation strategy of surface and interior structures to enhance oxygen stability is proposed. In the interior of the materials, the local electrons around TM and O atoms may be delocalized by surrounding Mo atoms, facilitating the formation of stronger TM─O bonds at high voltages. Besides, on the surface, the highly reactive O atoms with lone pairs of electrons are passivated by additional TM atoms, which provides a more stable TM─O framework. Hence, this strategy stabilizes the oxygen and hinders TM migration, which enhances the reversibility in structural evolution, leading to increased capacity and voltage retention. This work presents an efficient approach to enhance the performance of LLOs through surface-to-interior electronic structure modulation, while also contributing to a deeper understanding of their redox reaction.

Carbon dioxide capture and functionalization by bis(N-heterocyclic carbene)-borylene complexes.

Derivatives of free monocoordinated borylenes have attracted considerable interest due to their ability to exhibit transition-metal-like reactivity, in particular small molecules capture. However, such complexes are rare as the formation is either endergonic, or the resulting adduct is a transient intermediate that is prone to reaction. Here, we present the synthesis of two bis(N-heterocyclic carbene)-borylene complexes capable of capturing and functionalizing carbon dioxide. The capture and subsequent functionalization of CO2 by the bis(NHC)-disilylamidoborylene 1 is demonstrated by the formation of the bis(NHC)-isocyanatoborylene-carbon dioxide complex 3. Reversible capture of CO2 is observed using the bis(NHC)-mesitylborylene 2, and the persistent bis(NHC)-mesitylborylene-carbon dioxide adduct 4 can be stabilized by hydrogen bonding with boric acid. The reactions of 4 with ammonia-borane and aniline demonstrate that the captured CO2 can be further functionalized.

Proteomics-Derived Biomarker Panel Facilitates Distinguishing Primary Lung Adenocarcinomas With Intestinal or Mucinous Differentiation From Lung Metastatic Colorectal Cancer.

The diagnosis of primary lung adenocarcinomas with intestinal or mucinous differentiation (PAIM) remains challenging due to the overlapping histomorphological, immunohistochemical (IHC), and genetic characteristics with lung metastatic colorectal cancer (lmCRC). This study aimed to explore the protein biomarkers that could distinguish between PAIM and lmCRC. To uncover differences between the two diseases, we used tandem mass tagging-based shotgun proteomics to characterize proteomes of formalin-fixed, paraffin-embedded tumor samples of PAIM (n = 22) and lmCRC (n = 17).Then three machine learning algorithms, namely support vector machine (SVM), random forest, and the Least Absolute Shrinkage and Selection Operator, were utilized to select protein features with diagnostic significance. These candidate proteins were further validated in an independent cohort (PAIM, n = 11; lmCRC, n = 19) by IHC to confirm their diagnostic performance. In total, 105 proteins out of 7871 proteins were significantly dysregulated between PAIM and lmCRC samples and well-separated two groups by Uniform Manifold Approximation and Projection. The upregulated proteins in PAIM were involved in actin cytoskeleton organization, platelet degranulation, and regulation of leukocyte chemotaxis, while downregulated ones were involved in mitochondrial transmembrane transport, vasculature development, and stem cell proliferation. A set of ten candidate proteins (high-level expression in lmCRC: CDH17, ATP1B3, GLB1, OXNAD1, LYST, FABP1; high-level expression in PAIM: CK7 (an established marker), NARR, MLPH, S100A14) was ultimately selected to distinguish PAIM from lmCRC by machine learning algorithms. We further confirmed using IHC that the five protein biomarkers including CDH17, CK7, MLPH, FABP1 and NARR were effective biomarkers for distinguishing PAIM from lmCRC. Our study depicts PAIM-specific proteomic characteristics and demonstrates the potential utility of new protein biomarkers for the differential diagnosis of PAIM and lmCRC. These findings may contribute to improving the diagnostic accuracy and guide appropriate treatments for these patients.

The nucleoside analog 4'-fluorouridine suppresses the replication of multiple enteroviruses by targeting 3D polymerase.

Human enteroviruses are the major pathogens causing hand-foot-and-mouth disease in infants and young children throughout the world, and infection with enterovirus is also associated with severe complications, such as aseptic meningitis and myocarditis. However, there are no antiviral drugs available to treat enteroviruses infection at present. In this study, we found that 4'-fluorouridine (4'-FlU), a nucleoside analog with low cytotoxicity, exhibited broad-spectrum activity against infections of multiple enteroviruses with EC50 values at low micromolar levels, including coxsackievirus A10 (CV-A10), CV-A16, CV-A6, CV-A7, CV-B3, enterovirus A71 (EV-A71), EV-A89, EV-D68, and echovirus 6. With further investigation, the results indicated that 4'-FlU directly interacted with the RNA-dependent RNA polymerase of enterovirus, the 3D pol, and impaired the polymerase activity of 3D pol, hence inhibiting viral RNA synthesis and significantly suppressing viral replication. Our findings suggest that 4'-FlU could be promisingly developed as a broad-spectrum direct-acting antiviral agent for anti-enteroviruses therapy.

Targeting FTO induces colorectal cancer ferroptotic cell death by decreasing SLC7A11/GPX4 expression.

Ferroptosis is a newly identified iron-dependent form of death that is becoming increasingly recognized as a promising avenue for cancer therapy. N6-methyladenosine (m6A) is the most abundant reversible methylation modification in mRNA contributing to tumorigenesis. However, the crucial role of m6A modification in regulating ferroptosis during colorectal cancer (CRC) tumorigenesis remains elusive. Herein, we find that m6A modification is increased during ferroptotic cell death and correlates with the decreased m6A demethylase fat mass and obesity-associated protein (FTO) expression. Functionally, we demonstrate that suppressing FTO significantly induces CRC ferroptotic cell death, as well as enhancing CRC cell sensitivity to ferroptosis inducer (Erastin and RSL3) treatment. Mechanistically, high FTO expression increased solute carrier family 7 member 11 (SLC7A11) or glutathione peroxidase 4 (GPX4) expressions in an m6A-YTHDF2 dependent manner, thereby counteracting ferroptotic cell death stress. In addition, we identify Mupirocin as a novel inhibitor of FTO, and Mupirocin induces CRC ferroptosis and inhibits tumor growth. Clinically, the levels of FTO, SLC7A11, and GPX4, are highly correlated expression in CRC tissues. Our findings reveal that FTO protects CRC from ferroptotic cell death in promoting CRC tumorigenesis through triggering SLC7A11/GPX4 expression.

A DFT study on regulating the active center of v-Ti2XT2 MXene through surface modification for efficient nitrogen fixation.

The electrochemical conversion of nitrogen to ammonia provides an encouraging method to substitute the traditional Haber-Bosch process, owing to its high efficiency and mild reaction conditions. The search for high-performance catalysts and comprehension of catalytic mechanisms remains significant challenges. Herein, we conduct a systematic theoretical calculation of the NRR performance and mechanism of 24 Ti2XT2 (X = B, C, N; T = F, Cl, Br, I, O, S, Se, Te) MXenes with a T-vacancy to explore the influence of surface functional terminations and non-metallic center elements. Our findings demonstrate that surface functionalization significantly reduces the limiting potential by altering the rate-determining step. This change ranges from -1.24 V (Ti2NF2) to -0.21 V (Ti2BSe2), signifying the remarkable efficacy of modification of the surrounding environment of the exposed transition metal active center in promoting electrocatalytic performance. Detailed investigation of the charge density difference and orbital interaction reveals that the different NRR performance originates from the surface termination and non-metallic atoms regulate the electronic properties of the active Ti atoms. We also introduce the free energy change of *NNH2 (ΔG*NNH2) as a descriptor to predict the performance of NRR, which exhibits satisfactory linear relationship with free energy change of different intermediates and displays favourable volcano plot with limiting potential. Moreover, we highlight the pivotal role of work function in tuning the energy barrier of the rate-determining step, which can be regulated through the surface modification of MXenes. Our study not only offers a comprehensive understanding of the crucial impact of surface modification on the catalytic activities of defective MXenes, but also provides a rational perspective for designing efficient NRR catalysts.