Bimetal Oxides Anchored on Carbon Nanotubes/Nanosheets as High-Efficiency and Durable Bifunctional Oxygen Catalyst for Advanced Zn-Air Battery: Experiments and DFT Calculations.

To meet increasing requirement for innovative energy storage and conversion technology, it is urgent to prepare effective, affordable, and long-term stable oxygen electrocatalysts to replace precious metal-based counterparts. Herein, a two-step pyrolysis strategy is developed for controlled synthesis of Fe2O3 and Mn3O4 anchored on carbon nanotubes/nanosheets (Fe2O3-Mn3O4-CNTs/NSs). The typical catalyst has a high half-wave potential (E1/2 = 0.87 V) for oxygen reduction reaction (ORR), accompanied with a smaller overpotential (η10 = 290 mV) for oxygen evolution reaction (OER), showing substantial improvement in the ORR and OER performances. As well, density functional theory calculations are performed to illustrate the catalytic mechanism, where the in situ generated Fe2O3 directly correlates to the reduced energy barrier, rather than Mn3O4. The Fe2O3-Mn3O4-CNTs/NSs-based Zn-air battery exhibits a high-power density (153 mW cm-2) and satisfyingly long durability (1650 charge/discharge cycles/550 h). This work provides a new reference for preparation of highly reversible oxygen conversion catalysts.

Spatial-temporal analysis of hepatitis E in Hainan Province, China (2013-2022): insights from four major hospitals.

Objective: Exploring the Incidence, Epidemic Trends, and Spatial Distribution Characteristics of Sporadic Hepatitis E in Hainan Province from 2013 to 2022 through four major tertiary hospitals in the Province. Methods: We collected data on confirmed cases of hepatitis E in Hainan residents admitted to the four major tertiary hospitals in Haikou City from January 2013 to December 2022. We used SPSS software to analyze the correlation between incidence rate and economy, population density and geographical location, and origin software to draw a scatter chart and SAS 9.4 software to conduct a descriptive analysis of the time trend. The distribution was analyzed using ArcMap 10.8 software (spatial autocorrelation analysis, hotspot identification, concentration, and dispersion trend analysis). SAS software was used to build an autoregressive integrated moving average model (ARIMA) to predict the monthly number of cases in 2023 and 2024. Results: From 2013 to 2022, 1,922 patients with sporadic hepatitis E were treated in the four hospitals of Hainan Province. The highest proportion of patients (n = 555, 28.88%) were aged 50-59 years. The annual incidence of hepatitis E increased from 2013 to 2019, with a slight decrease in 2020 and 2021 and an increase in 2022. The highest number of cases was reported in Haikou, followed by Dongfang and Danzhou. We found that there was a correlation between the economy, population density, latitude, and the number of cases, with the correlation coefficient |r| value fluctuating between 0.403 and 0.421, indicating a linear correlation. At the same time, a scatter plot shows the correlation between population density and incidence from 2013 to 2022, with r2 values fluctuating between 0.5405 and 0.7116, indicating a linear correlation. Global Moran's I, calculated through spatial autocorrelation analysis, showed that each year from 2013 to 2022 all had a Moran's I value >0, indicating positive spatial autocorrelation (p < 0.01). Local Moran's I analysis revealed that from 2013 to 2022, local hotspots were mainly concentrated in the northern part of Hainan Province, with Haikou, Wenchang, Ding'an, and Chengmai being frequent hotspot regions, whereas Baoting, Qiongzhong, and Ledong were frequent cold-spot regions. Concentration and dispersion analysis indicated a clear directional pattern in the average density distribution, moving from northeast to southwest. Time-series forecast modeling showed that the forecast number of newly reported cases per month remained relatively stable in 2023 and 2024, fluctuating between 17 and 19. Conclusion: The overall incidence of hepatitis E in Hainan Province remains relatively stable. The incidence of hepatitis E in Hainan Province increased from 2013 to 2019, with a higher clustering of cases in the northeast region and a gradual spread toward the southwest over time. The ARIMA model predicted a relatively stable number of new cases each month in 2023 and 2024.

Unexpected large charge transfer rate mediated by adenine in twisted DNA structure.

DNA exhibits remarkable charge transfer ability, which is crucial for its biological functions and potential electronic applications. The charge transfer process in DNA is widely recognized as primarily mediated by guanine, while the contribution of other nucleobases is negligible. Using the tight-binding models in conjunction with first-principles calculations, we investigated the charge transfer behavior of homogeneous GC and AT pairs. We found that the charge transfer rate of adenine significantly changes. With overstretching, the charge transfer rate of adenine can even surpass that of guanine, by as much as five orders of magnitude at a twist angle of around 26°. Further analysis reveals that it is attributed to the turnover of the relative coupling strength between homogeneous GC and AT base pairs, which is caused by the symmetry exchange between the two highest occupied molecular orbitals of base pairs occurring at different twist angles. Given the high degree of flexibility of DNA in vivo and in vitro conditions, these findings prompt us to reconsider the mechanism of biological functions concerning the charge transfer in DNA molecules and further open the potential of DNA as a biomaterial for electronic applications.

Beat-to-Beat Blood Pressure Variability Within 24 Hours of Ischemic Stroke Onset: A Potential Predictor of Functional Prognosis.

BACKGROUND: Beat-to-beat blood pressure variability (BPV) is based on each heartbeat and represents a dynamic equilibrium process modulated by artery and cardiac involvement of pressure-receptive reflexes. To date, there remains a lack of prospective studies illustrating the clinical value of beat-to-beat BPV within 24 hours of acute ischemic stroke onset. METHODS AND RESULTS: This study prospectively monitored beat-to-beat blood pressure and heart rate in patients with acute ischemic stroke within 24 hours of onset using a noninvasive plethysmograph and calculated beat-to-beat BPV, heart rate variability, and the cross-correlation baroreflex sensitivity. A modified Rankin Scale score of ≥2 at 90 days was defined as an unfavorable prognosis. Multivariate logistic regression was performed, and the nomogram model was developed by adding the beat-to-beat BPV to the traditional model for predicting prognosis. Beat-to-beat BPV increased significantly in the unfavorable outcome group (P<0.05) compared with that in the favorable outcome group, whereas no difference was observed in beat-to-beat heart rate variability and cross-correlation baroreflex sensitivity between both groups (P>0.05). Furthermore, beat-to-beat BPV within 24 hours of acute ischemic stroke onset was independently associated with unfavorable outcome at 90 days (P<0.005). The addition of beat-to-beat BPV to the traditional model for predicting prognosis enhanced the area under the receiver operating characteristic curve from 0.816 to 0.830. CONCLUSIONS: Increased beat-to-beat BPV within 24 hours of acute ischemic stroke onset was independently associated with a poor prognosis at 90 days and may be a potential predictor for discriminating unfavorable prognosis.

Brain network functional connectivity changes in long illness duration chronic schizophrenia.

Introduction: Chronic schizophrenia has a course of 5 years or more and has a widespread abnormalities in brain functional connectivity. This study aimed to find characteristic functional and structural changes in a long illness duration chronic schizophrenia (10 years or more). Methods: Thirty-six patients with a long illness duration chronic schizophrenia and 38 healthy controls were analyzed by independent component analysis of brain network functional connectivity. Correlation analysis with clinical duration was performed on six resting state networks: auditory network, default mode network, dorsal attention network, fronto-parietal network, somatomotor network, and visual network. Results: The differences in the resting state network between the two groups revealed that patients exhibited enhanced inter-network connections between default mode network and multiple brain networks, while the inter-network connections between somatomotor network, default mode network and visual network were reduced. In patients, functional connectivity of Cuneus_L was negatively correlated with illness duration. Furthermore, receiver operating characteristic curve of functional connectivity showed that changes in Thalamus_L, Rectus_L, Frontal_Mid_R, and Cerebelum_9_L may indicate a longer illness duration chronic schizophrenia. Discussion: In our study, we also confirmed that the course of disease is significantly associated with specific brain regions, and the changes in specific brain regions may indicate that chronic schizophrenia has a course of 10 years or more.

Introduction to nanoclusters: from theory to application.

Yi Gao, Daojian Cheng and Zhigang Wang introduce the Nanoscale Advances themed collection on Nanoclusters: from theory to application.

Central nervous system involvement in chronic lymphocytic leukemia: a case report and review of literature.

BACKGROUND: Central nervous system involvement in chronic lymphocytic leukemia rarely occurs, and there is no standard therapy for central nervous system involvement in chronic lymphocytic leukemia. This article aims to analyze the diagnosis and treatment of central nervous system involvement in chronic lymphocytic leukemia. CASE PRESENTATION: It reports two cases of central nervous system involvement in chronic lymphocytic leukemia describing the clinical course, therapy, and prognosis. Case 1 is a 67-year-old Asian male patient, he experienced complications with central nervous system involvement after developing resistance to ibrutinib, bendamustine, and rituximab (BR) chemotherapies. The central nervous system lesion was controlled with high-dose methotrexate combined with pomalidomide, but Richter transformation occurred several months later. Case 2 is a 62-year-old Asian female patient, she had central nervous system involvement at initial diagnosis, and bone marrow and central nervous system lesions were controlled by ibrutinib therapy. CONCLUSION: Central nervous system involvement in chronic lymphocytic leukemia is rare and can be diagnosed on the basis of clinical features, cerebrospinal fluid testing, and radiographic evaluation. Ibrutinib, pomalidomide, and other drugs that can cross the blood-brain barrier may be effective for treating central nervous system involvement in chronic lymphocytic leukemia.

Dynamics of sensory and decisional biases in perceptual decision making: Insights from the face distortion illusion.

Bias in perceptual decision making can have both sensory and decisional origins. These distinct sources of bias are typically seen as static and stable over time. However, human behavior is dynamic and constantly adapting. Yet it remains unclear how sensory and decisional biases progress in distinct ways over time. We addressed this question by tracking the dynamics of sensory and decisional biases during a task that involves a visual illusion. Observers saw multiple pairs of peripherally presented faces that induce a strong illusion making the faces appear distorted and grotesque. The task was to judge whether one of the last two faces had true physical distortion (experimentally introduced in half of the trials). Initially, participants classified most faces as distorted as exemplified by a liberal response bias. However, over the course of the experiment, this response bias gradually disappeared even though the distortion illusion remained equally strong, as demonstrated by a separate subjective rating task without artificially distorted faces. The results suggest that the sensory bias was progressively countered by an opposite decisional bias. This transition was accompanied by an increase in reaction times and a decrease in confidence relative to a condition that does not induce the visual illusion. All results were replicated in a second experiment with inverted faces. These findings demonstrate that participants dynamically adjust their decisional bias to compensate for sensory biases, and that these two biases together determine how humans make perceptual decisions.

Radiotherapy-triggered reduction of platinum-based chemotherapeutic prodrugs in tumours.

Pt(II) drugs are a widely used chemotherapeutic, yet their side effects can be severe. Here we show that the radiation-induced reduction of Pt(IV) complexes to cytotoxic Pt(II) drugs is rapid, efficient and applicable in water, that it is mediated by hydrated electrons from water radiolysis and that the X-ray-induced release of Pt(II) drugs from an oxaliplatin prodrug in tumours inhibits their growth, as we show with nearly complete tumour regression in mice with subcutaneous human tumour xenografts. The combination of low-dose radiotherapy with a Pt(IV)-based antibody-trastuzumab conjugate led to the tumour-selective release of the chemotherapeutic in mice and to substantial therapeutic benefits. The radiation-induced local reduction of platinum prodrugs in the reductive tumour microenvironment may expand the utility of radiotherapy.

A pan-KRAS degrader for the treatment of KRAS-mutant cancers.

KRAS mutations are highly prevalent in a wide range of lethal cancers, and these mutant forms of KRAS play a crucial role in driving cancer progression and conferring resistance to treatment. While there have been advancements in the development of small molecules to target specific KRAS mutants, the presence of undruggable mutants and the emergence of secondary mutations continue to pose challenges in the clinical treatment of KRAS-mutant cancers. In this study, we developed a novel molecular tool called tumor-targeting KRAS degrader (TKD) that effectively targets a wide range of KRAS mutants. TKD is composed of a KRAS-binding nanobody, a cell-penetrating peptide selectively targeting cancer cells, and a lysosome-binding motif. Our data revealed that TKD selectively binds to KRAS in cancer cells and effectively induces KRAS degradation via a lysosome-dependent process. Functionally, TKD suppresses tumor growth with no obvious side effects and enhances the antitumor effects of PD-1 antibody and cetuximab. This study not only provides a strategy for developing drugs targeting "undruggable" proteins but also reveals that TKD is a promising therapeutic for treating KRAS-mutant cancers.

CELLULOSE SYNTHASE-LIKE C proteins modulate cell wall establishment during ethylene-mediated root growth inhibition in rice.

The cell wall shapes plant cell morphogenesis and affects the plasticity of organ growth. However, the way in which cell wall establishment is regulated by ethylene remains largely elusive. Here, by analyzing cell wall patterns, cell wall composition and gene expression in rice (Oryza sativa, L.) roots, we found that ethylene induces cell wall thickening and the expression of cell wall synthesis-related genes, including CELLULOSE SYNTHASE-LIKE C1, 2, 7, 9, 10 (OsCSLC1, 2, 7, 9, 10) and CELLULOSE SYNTHASE A3, 4, 7, 9 (OsCESA3, 4, 7, 9). Overexpression and mutant analyses revealed that OsCSLC2 and its homologs function in ethylene-mediated induction of xyloglucan biosynthesis mainly in the cell wall of root epidermal cells. Moreover, OsCESA-catalyzed cellulose deposition in the cell wall was enhanced by ethylene. OsCSLC-mediated xyloglucan biosynthesis likely plays an important role in restricting cell wall extension and cell elongation during the ethylene response in rice roots. Genetically, OsCSLC2 acts downstream of ETHYLENE-INSENSITIVE3-LIKE1 (OsEIL1)-mediated ethylene signaling, and OsCSLC1, 2, 7, 9 are directly activated by OsEIL1. Furthermore, the auxin signaling pathway is synergistically involved in these regulatory processes. These findings link plant hormone signaling with cell wall establishment, broadening our understanding of root growth plasticity in rice and other crops.

High-yield porphyrin production through metabolic engineering and biocatalysis.

Porphyrins and their derivatives find extensive applications in medicine, food, energy and materials. In this study, we produced porphyrin compounds by combining Rhodobacter sphaeroides as an efficient cell factory with enzymatic catalysis. Genome-wide CRISPRi-based screening in R. sphaeroides identifies hemN as a target for improved coproporphyrin III (CPIII) production, and exploiting phosphorylation of PrrA further improves the production of bioactive CPIII to 16.5 g L-1 by fed-batch fermentation. Subsequent screening and engineering high-activity metal chelatases and coproheme decarboxylase results in the synthesis of various metalloporphyrins, including heme and the anti-tumor agent zincphyrin. After pilot-scale fermentation (200 L) and setting up the purification process for CPIII (purity >95%), we scaled up the production of heme and zincphyrin through enzymatic catalysis in a 5-L bioreactor, with CPIII achieving respective enzyme conversion rates of 63% and 98% and yielding 10.8 g L-1 and 21.3 g L-1, respectively. Our strategy offers a solution for high-yield bioproduction of heme and other valuable porphyrins with substantial industrial and medical applications.

Identification of proteins related to SIS3 by iTRAQ and PRM-based comparative proteomic analysis in cisplatin-induced acute kidney injury.

Background: Cisplatin is a commonly used nephrotoxic drug and can cause acute kidney injury (AKI). In the present study, isobaric tags for relative and absolute quantification (iTRAQ) and parallel reaction monitoring (PRM)-based comparative proteomics were used to analyze differentially expressed proteins (DEPs) to determine the key molecular mechanism in mice with cisplatin-induced AKI in the presence or absence of SIS3, a specific p-smad3 inhibitor, intervention. Methods: The cisplatin-induced AKI mouse model was established and treated with SIS3. We used iTRAQ to search for DEPs, PRM to verify key DEPs and combined Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) for bioinformatics analysis. We then assessed lipid deposition, malondialdehyde (MDA) and reactive oxygen species (ROS) and detected the expression of SREBF1, SCD1, CPT1A, PPARα and NDRG1 in vitro. Results: Proteomic analysis showed that the identified DEPs were mainly enriched in energy metabolism pathways, especially in lipid metabolism. When SIS3 was applied to inhibit the phosphorylation of Smad3, the expression of NDRG1 and fatty acid oxidation key proteins CPT1A and PPARα increased, the expression of lipid synthesis related proteins SREBF1 and SCD1 decreased and the production of lipid droplets, MDA and ROS decreased. Conclusion: SIS3 alleviates oxidative stress, reduces lipid accumulation and promotes fatty acid oxidation through NDRG1 in cisplatin-induced AKI. Our study provides a new candidate protein for elucidating the molecular mechanisms of fatty acid metabolism disorders in cisplatin-induced acute kidney injury.

Colorimetric array sensor based on bimetallic nitrogen-doped carbon-based nanozyme material to detect multiple antioxidants.

Copper-cobalt bimetallic nitrogen-doped carbon-based nanoenzymatic materials (CuCo@NC) were synthesized using a one-step pyrolysis process. A three-channel colorimetric sensor array was constructed for the detection of seven antioxidants, including cysteine (Cys), uric acid (UA), tea polyphenols (TP), lysine (Lys), ascorbic acid (AA), glutathione (GSH), and dopamine (DA). CuCo@NC with peroxidase activity was used to catalyze the oxidation of TMB by H2O2 at three different ratios of metal sites. The ability of various antioxidants to reduce the oxidation products of TMB (ox TMB) varied, leading to distinct absorbance changes. Linear discriminant analysis (LDA) results showed that the sensor array was capable of detecting seven antioxidants in buffer and serum samples. It could successfully discriminate antioxidants with a minimum concentration of 10 nM. Thus, multifunctional sensor arrays based on CuCo@NC bimetallic nanoenzymes not only offer a promising strategy for identifying various antioxidants but also expand their applications in medical diagnostics and environmental analysis of food.

Fine hippocampal morphology analysis with a multi-dataset cross-sectional study on 2911 subjects.

CA1 subfield and subiculum of the hippocampus contain a series of dentate bulges, which are also called hippocampus dentation (HD). There have been several studies demonstrating an association between HD and brain disorders. Such as the number of hippocampal dentation correlates with temporal lobe epilepsy. And epileptic hippocampus have a lower number of dentation compared to contralateral hippocampus. However, most studies rely on subjective assessment by manual searching and counting in HD areas, which is time-consuming and labor-intensive to process large amounts of samples. And to date, only one objective method for quantifying HD has been proposed. Therefore, to fill this gap, we developed an automated and objective method to quantify HD and explore its relationship with neurodegenerative diseases. In this work, we performed a fine-scale morphological characterization of HD in 2911 subjects from four different cohorts of ADNI, PPMI, HCP, and IXI to quantify and explore differences between them in MR T1w images. The results showed that the degree of right hippocampal dentation are lower in patients with Alzheimer's disease than samples in mild cognitive impairment or cognitively normal, whereas this change is not significant in Parkinson's disease progression. The innovation of this paper that we propose a quantitative, robust, and fully automated method. These methodological innovation and corresponding results delineated above constitute the significance and novelty of our study. What's more, the proposed method breaks through the limitations of manual labeling and is the first to quantitatively measure and compare HD in four different brain populations including thousands of subjects. These findings revealed new morphological patterns in the hippocampal dentation, which can help with subsequent fine-scale hippocampal morphology research.

Association of adverse childhood experiences with poor health condition among middle-aged and elderly adults in the United States: A nationally retrospective cohort study.

BACKGROUND: The specific effects of adverse childhood experiences (ACEs) in adulthood and senectitude were less known. We aim to examine the relationship between early ACEs and overall health condition as well as specific dimensions in the middle-aged and elderly population. METHODS: In the 2019-2021 Behavioral Risk Factor Surveillance System Study, robust Poisson regression models were used to estimate the relationship between ACE exposure and current health status among adults aged 45 ≥ years. RESULTS: Of the 195,472 participants, 53.8 % were female and the mean age was 65.0 years. Compared to populations without ACE, ACE exposures were more significantly associated with depression (PR: 2.03, 95 %CI: 1.94-2.21), frequent mental health (PR: 1.85, 95 %CI: 1.74-1.97) and subject cognitive decline (PR: 1.99, 95 %CI:1.85-2.14) than with physical health (PR: 1.37, 95 %CI: 1.32-1.44), with dose-response patterns. The association with mental disorder was especially significant among the elderly population. CONCLUSION: Early ACEs are associated with adverse health outcomes that persist into later life, particularly mental disorders and cognitive decline. Poor mental health may indirectly influence associations with ACEs and cognitive decline as well as physical health. Our findings emphasize the importance of lifelong psychological screening and support for the ACE-exposed middle-aged and elderly population.

A Novel 10-Base Pair Deletion in the First Exon of GmHY2a Promotes Hypocotyl Elongation, Induces Early Maturation, and Impairs Photosynthetic Performance in Soybean.

Plants photoreceptors perceive changes in light quality and intensity and thereby regulate plant vegetative growth and reproductive development. By screening a γ irradiation-induced mutant library of the soybean (Glycine max) cultivar "Dongsheng 7", we identified Gmeny, a mutant with elongated nodes, yellowed leaves, decreased chlorophyll contents, altered photosynthetic performance, and early maturation. An analysis of bulked DNA and RNA data sampled from a population segregating for Gmeny, using the BVF-IGV pipeline established in our laboratory, identified a 10 bp deletion in the first exon of the candidate gene Glyma.02G304700. The causative mutation was verified by a variation analysis of over 500 genes in the candidate gene region and an association analysis, performed using two populations segregating for Gmeny. Glyma.02G304700 (GmHY2a) is a homolog of AtHY2a in Arabidopsis thaliana, which encodes a PΦB synthase involved in the biosynthesis of phytochrome. A transcriptome analysis of Gmeny using the Kyoto Encyclopedia of Genes and Genomes (KEGG) revealed changes in multiple functional pathways, including photosynthesis, gibberellic acid (GA) signaling, and flowering time, which may explain the observed mutant phenotypes. Further studies on the function of GmHY2a and its homologs will help us to understand its profound regulatory effects on photosynthesis, photomorphogenesis, and flowering time.

TREM1+ tumor-associated macrophages secrete CCL7 to promote hepatocellular carcinoma metastasis.

PURPOSE: Tumor-associated macrophages (TAMs) play a critical role in hepatocellular carcinoma (HCC) progression and metastasis. Systematic investigation of the cross-talk between TAMs and HCC may help in searching for the critical target to guard against HCC metastasis. METHODS AND RESULTS: Herein, we found that TREM1 highly expressed in HCC tissue by analyzing the data obtain from GEO database. Interestingly, the results indicated that TREM1 was primarily expressed by monocytes. Immune infiltration studies further validated that TREM1 expression was positively related with increased infiltration of macrophages in HCC tissues. In vitro, we observed that TREM1 knockdown significantly abrogated the effect of TAMs in promoting the metastasis and epithelial-mesenchymal transition (EMT) of HCC cells. Additionally, cytokine array detection identified CCL7 as the main responsive cytokine following with TREM1 knockdown in TAMs. CONCLUSION: Taken together, our findings strongly suggested that high expression of TREM1 was positively associated with metastasis and poor prognosis of HCC. Furthermore, TAMs expressing TREM1 contribute to EMT-based metastasis through secreting CCL7. These results provide a novel insight into the potential development of targeting the TREM1/CCL7 pathway for preventing metastatic HCC.