Search

Electrochemical imaging enables an in-depth analysis of the interface heterogeneity and reaction kinetics of single entities. However, electrode passivation during electrochemical reactions decreases the active sites and harms the long-term stability. Here, we introduce a method using laser-induced photothermal effects to restore the electrochemical activity, which is particularly displayed as enhanced micrometric patterns in electrochemiluminescence (ECL) microscopy. By co-localization characterization and X-ray photoelectron spectroscopy, the mechanism of active site regeneration is validated as the removal of the oxide film for restoring the local surface ECL reactivity under laser irradiation. The surface-confined and voltage-dependent features of ECL allows for easy pattern erasure and rewriting, and it shows good reversibility and anti-counterfeiting potential. This approach overcomes the passivation processes, evidently improves the image quality of single biological entities including Shewanella bacteria and cells, and makes the subtle contour structures more distinct. The renewable electrode interface also enhances the ECL signal of model bead-based bioassays. This approach not only showcases precise control in fabricating micron patterns but also holds promise for enhancing the sensitivity in electrochemical immunoassays and bioimaging., (© 2024 Wiley‐VCH GmbH.)

In this study, tungsten oxide nanosheets loaded with nitrogen-doped graphene oxide quantum dots (NGQDs/WO 3 NSs) were fabricated as SERS substrates. The promoted photo-induced charge transfer (PICT) and the strong π-π stacking effect resulting from the unique structure of the NGQDs contributed to the enhanced SERS signal.

The sewer system, despite being a significant source of methane emissions, has often been overlooked in current greenhouse gas inventories due to the limited availability of quantitative data. Direct monitoring in sewers can be expensive or biased due to access limitations and internal heterogeneity of sewer networks. Fortunately, since methane is almost exclusively biogenic in sewers, we demonstrate in this study that the methanogenic potential can be estimated using known sewer microbiome data. By combining data mining techniques and bioinformatics databases, we developed the first data-driven method to analyze methanogenic potentials using a data set containing 633 observations of 53 variables obtained from literature mining. The methanogenic potential in the sewer sediment was around 250-870% higher than that in the wet biofilm on the pipe and sewage water. Additionally, k -means clustering and principal component analysis linked higher methane emission rates (9.72 ± 51.3 kg CO 2  eq m -3 d -1 ) with smaller pipe size, higher water level, and higher potentials of sulfate reduction in the wetted pipe biofilm. These findings exhibit the possibility of connecting microbiome data with biogenic greenhouse gases, further offering insights into new approaches for understanding greenhouse gas emissions from understudied sources.

The global transition to net-zero emissions necessitates the integration of clean hydrogen as a key solution. To facilitate the required expansion of clean hydrogen production, sustainable water sources are required to support the electrolysis process. Utilizing nontraditional water sources such as water resource recovery facility (WRRF) effluents could potentially alleviate the water constraints and create cobenefits, but the real-world feasibility has not been explored in depth. Here, we investigated the geospatial interplay between WRRFs and H 2 users in a clean hydrogen economy. We developed an optimization framework for contiguous U.S. that would identify H 2 users-WRRF pairing through techno-economic constraint and multicriteria decision analysis, and we found that utilizing reclaimed water from WRRFs could save 66% (62-99%) of freshwater for clean hydrogen economy while accumulating $758 (275-1162) million annual national cost savings. The added benefits from H 2 users to WRRFs such as pure oxygen aeration would provide a compelling new opportunity for infrastructural symbiosis but warrant a future investigation on its technical and economic feasibilities.

Anaplasma phagocytophilum ( A. phagocytophilum ) is an emerging zoonotic pathogen causing human granulocytic anaplasmosis, linked to small mammal reservoirs that harbor various zoonotic pathogens, underscoring their importance in public health and ecology. This study seeks to determine the prevalence of A. phagocytophilum in small mammals using PCR, then sequence and genotype positive samples, and assess infection risk factors. Small mammals were seasonally captured and a nested polymerase chain reaction (nested-PCR) was conducted targeting the 16S rRNA gene on spleen samples to detect A. phagocytophilum infection from three counties in western Yunnan province, China. Positive samples were sequenced and genotyped, revealing genetic diversity and regional clustering of the pathogen. A total of 1,605 small mammals belonging to 30 species, 18 genera, 6 families, 3 orders were captured seasonally and screened in this region, yielding a 0.93% infection rate with A. phagocytophilum (15/1605). Significant variations in infection rates were observed across different species, counties, and habitats. The 16Sr RNA genes of A. phagocytophilum were categorized into two distinct clades, indicating notable genetic diversity. The identification of genetic variants in spleen samples underscores the potential public health risk and the critical importance of the One Health approach in disease surveillance. Our findings emphasize the necessity for continuous monitoring and highlight the value of nested-PCR testing on spleen samples for accurate prevalence assessment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhu, Zhang, Hong, Yu, Hong, Liu, Li and Yin.)

The fabrication of high-performance microbial fuel cells requires the evaluation of the activity of electrochemically active bacteria. However, this is challenging because of the time-consuming nature of biofilm formation and the invasive nature of labeling. To address this issue, we developed a fast, label-free, single-cell Raman spectroscopic method. This method involves investigating the "pure" linear Stark effect of endogenous CO in the silent region of biological samples, which allows for probing the intrinsic electric field in the outer-membrane cytochromes of live bacterial cells. We found that reduced outer-membrane cytochromes can generate an additional intrinsic electric field equivalent to an applied potential of +0.29 V. We also found that the higher the electrical activity of the cell, the larger the generated electric field. This was also reflected in the output current of the constructed microbial fuel cells. Raman spectroscopy was employed to facilitate the assessment of electrochemical activity at the single-cell level in highly-diluted bacterial samples. After analysis, inactive bacteria were ablated by laser heating, and 20 active cells were cultured for further testing. The rapid and high-throughput probing of the intrinsic electric field offers a promising platform for high-efficiency screening of electrochemically active bacterial cells for bioenergetic and photosynthetic research., (© 2024 Wiley-VCH GmbH.)

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter-2 inhibitors (SGLT-2I) are associated with significant cardiovascular benefit in type 2 diabetes (T2D). However, GLP-1RA or SGLT-2I alone may not improve some cardiovascular outcomes in patients with prior cardiovascular co-morbidities., Aim: To explore whether combining GLP-1RA and SGLT-2I can achieve additional benefit in preventing cardiovascular diseases in T2D., Methods: The systematic review was conducted according to PRISMA recommendations. The protocol was registered on PROSPERO (ID: 42022385007). A total of 107049 participants from eligible cardiovascular outcomes trials of GLP-1RA and SGLT-2I were included in network meta-regressions to estimate cardiovascular benefit of the combination treatment. Effect modification of prior myocardial infarction (MI) and heart failure (HF) was also explored to provide clinical insight as to when the combination treatment should be considered., Results: The estimated hazard ratios (HR) GLP-1RA/SGLT-2I vs Placebo (0.75-0.98) and HR Combination vs GLP-1RA/SGLT-2I (0.26-0.86) for primary and secondary cardiovascular outcomes suggested that the combination treatment may achieve additional cardiovascular benefit compared with GLP-1RA or SGLT-2I alone. In patients with prior MI or HF, the mono-therapies may not improve the overall cardiovascular outcomes, as the estimated HR MI+/HF+ (0.57-1.52) suggested that GLP-1RA or SGLT-2I alone may be associated with lower risks of hospitalization for HF but not cardiovascular death., Conclusion: Considering its greater cardiovascular benefit in T2D, the combination treatment of GLP-1RA and SGLT-2I might be prioritized in patients with prior MI or HF, where the monotherapies may not provide sufficient cardiovascular protection., Competing Interests: Conflict-of-interest statement: Zhu JJ and Gu XS have no conflict of interest or financial disclosures that are relevant to the content of this research report. Wilding JPH reports consultancy/advisory board work for the pharmaceutical industry contracted via the University of Liverpool (no personal payment) for Altimmune, AstraZeneca, Boehringer Ingelheim, Cytoki, Lilly, Napp, Novo Nordisk, Menarini, Pfizer, Rhythm Pharmaceuticals, Sanofi, Saniona, Tern, and Shionogi & Ysopia; research grants for clinical trials from AstraZeneca and Novo Nordisk and personal honoraria/lecture fees from AstraZeneca, Boehringer Ingelheim, Medscape, Napp, Novo Nordisk, and Rhythm. Wilding JPH is past president of the World Obesity Federation, a member of the Association for the Study of Obesity, Diabetes UK, EASD, ADA, Society for Endocrinology, and the Rank Prize Funds Nutrition Committee. Wilding JPH is national lead for the Metabolic and Endocrine Speciality Group of the UK NIHR Clinical Research Network., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Proteolysis-targeting chimeras (PROTACs) have accelerated drug development; however, some challenges still exist owing to their lack of tumor selectivity and on-demand protein degradation. Here, we developed a miRNA-initiated assembled pre-PROTAC (miRiaTAC) platform that enables the on-demand activation and termination of target degradation in a cell type-specific manner. Using miRNA-21 as a model, we engineered DNA hairpins labeled with JQ-1 and pomalidomide and facilitated the modular assembly of DNA-encoded pre-PROTACs through a hybridization chain reaction. This configuration promoted the selective polyubiquitination and degradation of BRD4 upon miR-21 initiation, highlighting significant tumor selectivity and minimal systemic toxicity. Furthermore, the platform incorporates photolabile groups, enabling the precise optical control of pre-PROTACs during DNA assembly/disassembly, mitigating the risk of excessive protein degradation. Additionally, by introducing a secondary ligand targeting CDK6, these pre-PROTACs were used as a modular scaffold for the programmable assembly of active miRiaTACs containing two different warheads in exact stoichiometry, enabling orthogonal multitarget degradation. The integration of near-infrared light-mediated photodynamic therapy through an upconversion nanosystem further enhanced the efficacy of the platform with potent in vivo anticancer activity. We anticipate that miRiaTAC represents a significant intersection between dynamic DNA nanotechnology and PROTAC, potentially expanding the versatility of PROTAC toolkit for cancer therapy., (© 2024 Wiley-VCH GmbH.)

Objective: To analyze the short-term clinical efficacy and safety of arsenic trioxide (ATO) combined with a modified N7 induction regimen in the treatment of children with high-risk neuroblastoma (NB). Methods: This study was a prospective, single-arm, multicenter phase Ⅱ clinical study. Sixty-seven high-risk NB children from eight units of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Wuhan Children's Hospital of Tongji Medical College of Huazhong University of Science and Technology, First Affiliated Hospital of Guangxi Medical University, Hainan General Hospital, Affiliated Hospital of Guangdong Medical University, Kunming Children's Hospital, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, and Guangdong Provincial Agricultural Reclamation Center Hospital were enrolled from January 2019 to August 2023 and were treated with ATO combined with a modified N7 induction regimen. The efficacy and adverse effects at the end of induction chemotherapy were assessed and analyzed, and the differences in the clinical characteristics were further compared between the treatment-responsive and treatment-unresponsive groups by using the Fisher's exact test. Results: Among 67 high-risk NB children, there were 40 males (60%) and 27 females (40%), with the age of disease onset of 3.5 (2.6, 4.8) years. Primary NB sites were mostly in retroperitoneum (including adrenal gland) (56/67, 84%) and the common metastases sites at initial diagnosis were distant lymph node in 25 cases (37%),bone in 48 cases (72%),bone marrow in 56 cases (84%) and intracalvarium in 3 cases (4%). MYCN gene amplification were detected in 28 cases (42%). At the end of induction, 33 cases (49%) achieved complete remission, 29 cases (43%) achieved partial remission, 1 case (1%) with stable disease, and 4 cases (6%) were assessed as progressive disease (PD). The objective remission rate was 93% (62/67) and the disease control rate was 94% (63/67). The percentage of central system metastases at the initial diagnosis was higher in the treatment-unresponsive group than in the treatment-responsive group (2/5 vs. 2% (1/62), P =0.013), whereas the difference in MYCN gene amplification was not statistically significant between two groups (3/5 vs. 40% (25/62), P =0.786). Grade Ⅲ or higher adverse reactions during the induction chemotherapy period were myelosuppression occurred in 60 cases (90%), gastrointestinal symptoms occurred in 33 cases (49%), infections occurred in 20 cases (30%), hepatotoxicity occurred in 4 cases (6%), and cardiovascular toxicity occurred in 1 case (2%). There were no chemotherapy-related deaths. Conclusion: ATO combined with N7-modified induction regimen had a superiority in efficacy and safety, which deserved further promotion in clinical practice.

Strategies based on nanomaterials for sterilization address the problem of antibiotic resistance faced by conventional antimicrobials, with the contribution of photocatalytic compounds being particularly prominent. Herein, to integrate multiple bactericidal techniques into a system for generating synergistic antibacterial effects, a novel photo-triggered AuAg@g-C 3 N 4 composite nanoplatform was constructed by anchoring AuAg on the surface of a g-C 3 N 4 layer. As the composite nanoplatform had a lower bandgap and superior visible light utilization efficiency, it could facilitate free electron transfer better and exhibit superior photocatalytic activity under light conditions. Moreover, the AuAg@g-C 3 N 4 composite nanoplatform integrated the bactericidal modes of silver ion toxicity, physical disruption of bacterial cell membranes by the multilayer structure, and excellent photocatalytic activity, exhibiting extremely superior bactericidal effects against Escherichia coli , Staphylococcus aureus , Pseudomonas aeruginosa and Bacillus subtilis , with a bactericidal efficiency of up to 100%.

Increasing the carbon sink capacity of terrestrial ecosystems is a primary strategy to mitigate climate change and achieve the "carbon neutrality" goal. Clarifying the status and future dynamics of carbon sink of terrestrial ecosystems in Northeast China is crucial for achieving "carbon neutrality" as this region is a core contributor to carbon sink in China's terrestrial ecosystems. Here, we systematically summarized current research on carbon sink of terrestrial ecosystems across Northeast China, including the measurements and spatial-temporal patterns of carbon sinks, driving mechanisms of carbon sinks, the assessments of carbon sink potential, and technologies for increasing carbon sequestration. There are substantial uncertainties in quantifying terrestrial ecosystem carbon sink in Northeast China due to differences in data sources and methods, especially for forest carbon sink measurements, ranging from 0.020 to 0.157 Pg C·a -1 . Carbon sink function depends on carbon exchange processes across plant-soil-atmosphere interfaces. The key pathways to enhance carbon sequestration in Northeast China under different temporal and spatial scales remains unclear. Improving terrestrial ecosystem quality is the key and core of carbon sequestration and sink enhancement. However, there is an urgent need to develop a multi-ecosystem collaborative carbon sequestration and sink enhancement technology system for the "dual carbon" goal. Future research needs to develop an accurate carbon sink measurement system that integrates multi-source data and multi-scale technologies to accurately assess the function and potential of carbon sink in Northeast China, focus on the multi-scale driving mechanism of carbon sink functions, develop new technical systems for coordinated enhancement of carbon sink for the Northeast terrestrial ecosystems, and carry out demonstrations of carbon sink enhancement technologies. These efforts will provide the scientific and technological supports for achieving the "carbon neutrality" goal.

The widespread utilization of fossil fuels has emitted large amounts of CO 2 into the atmosphere since the Industrial Revolution, leading to climate warming and frequent occurrence of extreme climate events. To effectively alleviate climate change, the international community has made various efforts to reduce carbon emissions and eliminate CO 2 from the atmosphere. In 2020, the Chinese government announced that carbon emission peaking and carbon neutrality will be achieved by 2030 and 2060, respectively. According to the current forecast, by the time carbon neutrality is achieved in 2060, even under the minimum conditions of fossil energy use, production, and living emissions, China will still have to emit about 1/4 of the current total emissions. These carbon must primarily be absorbed by ecosystems. Furthermore, approximately 140 ppm increase in CO 2 in the atmosphere since the Industrial Revolution still needs to be removed by ecosystems. Forests are the main component of terrestrial ecosystems, contributing more than 80% of the carbon sequestration capacity of all terrestrial ecosystems. However, due to the long periodicity, complexity and dynamic variability of forests, the basic concepts of ecosystem carbon sink and its time effect are still unclear, leading to problems, such as lacking technologies for improving carbon sink capacity and disorganized rules in the carbon sink trading market. In this review, we introduced carbon sink concept according to the processes of absorbing and fixing CO 2 by plant photosynthesis in forest ecosystems. Then, we analyzed the processes of time-scale-dependent carbon sinks of forest ecosystems, discussed the time effects of forest carbon sinks, and suggested using "t-year" as the unit of carbon sink (taking 3-6 months as the minimum measurement time, i.e ., the beginning of carbon sequestration). Third, we proposed the approaches to improve the carbon sink capacity of forest ecosystems. One way is to improve the carbon sink capacity (expanding forest area, improving forest quality, and increasing forest soil carbon storage) of forest ecosystems. Another approach is to maintain the carbon sink of forest ecosystems as long as possible, i.e ., to reduce temporary carbon sink (definition: carbon in the forest ecosystems emit into the atmosphere for a certain period) and to increase persistent carbon sink (definition: carbon in the forest ecosystems no longer emit into the atmosphere for a certain period; according to the relevant provisions of the Paris Agreement, the upper time limit for carbon sink measurement can be considered to be the year 2100. In order to maintain the persistent carbon sink, strateges such as efficient use of wood products (replace steel, cement, plastic with wood), control of forest fires or other disturbances-induced emissions, and turning forest biomass into biochar should be taken. Finally, we proposed to develop climate-smart forestry driven by artificial intelligence (AI), which would provide new theoretical and technical support for improving the carbon sink of forest ecosystems and facilitating sustainable forest management.

Background: Adjacent segment disease (ASD) after fusion surgery is frequently manifests as a cranial segment instability, disc herniation, spinal canal stenosis, spondylolisthesis or retrolisthesis. The risk factors and mechanisms of ASD have been widely discussed but never clearly defined., Aim: To investigate the risk factors and clinical significance of retrograde movement of the proximal vertebral body after lower lumbar fusion., Methods: This was a retrospective analysis of the clinical data of patients who underwent transforaminal lumbar interbody fusion surgery between September 2015 and July 2021 and who were followed up for more than 2 years. Ninety-one patients with degenerative lumbar diseases were included (22 males and 69 females), with an average age of 52.3 years (40-73 years). According to whether there was retrograde movement of the adjacent vertebral body on postoperative X-rays, the patients were divided into retrograde and nonretrograde groups. The sagittal parameters of the spine and pelvis were evaluated before surgery, after surgery, and at the final follow-up. At the same time, the Oswestry Disability Index (ODI) and Visual Analogue Scale (VAS) were used to evaluate the patients' quality of life., Results: Nineteen patients (20.9%) who experienced retrograde movement of proximal adjacent segments were included in this study. The pelvic incidence (PI) of the patients in the retrograde group were significantly higher than those of the patients in the nonretrograde group before surgery, after surgery and at the final follow-up ( P < 0.05). There was no significant difference in lumbar lordosis (LL) between the two groups before the operation, but LL in the retrograde group was significantly greater than that in the nonretrograde group postoperatively and at the final follow-up. No significant differences were detected in terms of the |PI-LL|, and there was no significant difference in the preoperative lordosis distribution index (LDI) between the two groups. The LDIs of the retrograde group were 68.1% ± 11.5% and 67.2% ± 11.9%, respectively, which were significantly lower than those of the nonretrograde group (75.7% ± 10.4% and 74.3% ± 9.4%, respectively) ( P < 0.05). Moreover, the patients in the retrograde group had a greater incidence of a LDI < 50% than those in the nonretrograde group ( P < 0.05). There were no significant differences in the ODI or VAS scores between the two groups before the operation, but the ODI and VAS scores in the retrograde group were significantly worse than those in the nonretrograde group after the operation and at the last follow-up, ( P < 0.05)., Conclusion: The incidence of posterior slippage after lower lumbar fusion was approximately 20.9%. The risk factors are related to a higher PI and distribution of lumbar lordosis. When a patient has a high PI and insufficient reconstruction of the lower lumbar spine, adjacent segment compensation via posterior vertebral body slippage is one of the factors that significantly affects surgical outcomes., Competing Interests: Conflict-of-interest statement: All the authors declare no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The reliable detection of organophosphorus pesticides (OPs) in complex matrices remains an enormous challenge due to inevitable interference of sample matrices and testing factors. To address this issue, we designed a nanozyme-coated mesoporous COF with guest molecule loading, and successfully used it to construct a dual-ratio dual-mode sensor through target-regulated signal generation. The multifunctional COF-based composite (MB/COF@MnO 2 , MCM) featured high loading of methylene blue (MB), oxidase-like MnO 2 coatings as gatekeepers, and specific recognition of thiocholine (TCh). TCh, a regulator produced from acetylcholinesterase (AChE)-catalyzed hydrolysis of acetylthiocholine, could decompose MnO 2 coatings, triggering the release of abundant MB and oxidation of few o-phenylenediamine (OPD). OPs, strong inhibitors of AChE, could restrain TCh production and MnO 2 decomposition, thereby controlling the release of less MB and oxidation of more OPD. This regulation boosted the dual-ratio dual-mode assay of OPs by using the released MB and oxidized OPD in the solution as testing signals, measured by both fluorescent and electrochemical methods. Experimental results demonstrated the sensitive detection of dichlorvos with LODs of 0.083 and 0.026 ng/mL via the fluorescent/electrochemical mode, respectively. This study represented a creative endeavor to develop dual-ratio dual-mode sensors for OPs detection in complex samples, offering high sensitivity, excellent selectivity, and good reliability., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Arterial endothelial cells (AECs) are the founder cells for intraembryonic haematopoiesis. Here, we report a method for the efficient generation of human haemogenic DLL4+ AECs from pluripotent stem cells (PSC). Time-series single-cell RNA-sequencing reveals the dynamic evolution of haematopoiesis and lymphopoiesis, generating cell types with counterparts present in early human embryos, including stages marked by the pre-haematopoietic stem cell genes MECOM/EVI1, MLLT3 and SPINK2. DLL4+ AECs robustly support lymphoid differentiation, without the requirement for exogenous NOTCH ligands. Using this system, we find IL7 acts as a morphogenic factor determining the fate choice between the T and innate lymphoid lineages and also plays a role in regulating the relative expression level of RAG1. Moreover, we document a developmental pathway by which human RAG1+ lymphoid precursors give rise to the natural killer cell lineage. Our study describes an efficient method for producing lymphoid progenitors, providing insights into their endothelial and haematopoietic ontogeny, and establishing a platform to investigate the development of the human blood system., (© 2024. The Author(s).)

Objective: To investigate the topological properties of the white matter network in the drug-naive first-episode children and adolescent with obsessive-compulsive disorder (OCD). Methods: This study was a case-control study. First-episode OCD childhren and adolescents(OCD group) who were treated in the outpatient or inpatient department of the Second Affiliated Hospital of Xinxiang Medical University from July 2018 to October 2023 were collected as the research subjects. Healthy controls (control group)matched by gender, age and education level were used as controls. Deterministic tractography technique was used to construct the whole brain white matter structural network, and graph theory analysis method was used to analyze the topological attributes of the whole brain white matter structure network in OCD children and adolescents. A network-based statistical method was used to examine the inter-group differences in the functional connectivity strength of the whole brain network. Results: Finally, 31 cases were included in the obsessive-compulsive disorder group, including 22 males and 9 females, with an age of (13.5±1.6) years; There were 34 cases in the control group, including 22 males and 12 females, with an age of (12.7±1.4) years. The global efficiency and local efficiency of the OCD group (0.62±0.03, 0.70±0.07) were significantly higher than those of the control group (0.50±0.06, 0.54±0.21) [both P <0.01, false discovery rate(FDR)correction]; while the characteristic path length (1.77±0.08) was significantly smaller than that of the control group (2.10±0.23) ( P <0.01, FDR correction).The centrality comparison of nodal betweenness centrality showed that in the OCD group, the connections were enhanced in the left lateral orbitofrontal gyrus, right dorsal agranular insula, left dorsal granular insula, right granular insula, right posterior central gyrus main area of parietal lobe, left ventral granular insula, granular insula, left ventral granulosa, left granular insula, and left dorsal agranular insula [all P <0.001, family wise error (FWE) correction], while the connection of right thalamic was weakened ( P <0.001, FWE correction), There were sub-networks characterized by significantly enhanced connection strength of relevant nodes in subcortical, visual network, and default mode network ( P <0.05, permutation test 5 000 times). Conclusions: The topological properties of the brain's functional network in children and adolescents with OCD exhibit abnormalities, indicating an immature state of brain functional connectivity.

C-C coupling is of utmost importance in the electrocatalytic reduction of CO 2 , as it governs the selectivity of diverse product formation. Nevertheless, the difficulties to directly observe C-C coupling pathways at a specific nanocavity hinder the advances in catalysts and electrolyzer design for efficient high-value hydrocarbon production. Here we develop a nano-confined Raman technology to elucidate the influence of the local electric field on the evolution of C-C coupling intermediates. Through precise adjustments to the Debye length in nanocavities of a copper catalyst, the overlapping of electrical double layers drives a transition in the C-C coupling pathway at a specific nanocavity from *CHO-*CO coupling to the direct dimerization of *CO species. Experimental evidence and simulations validate that a reduced potential drop across the compact layer promotes a higher yield of CO and promotes the direct dimerization of *CO species. Our findings provide insights for the development of highly selective catalyst materials tailored to promote specific products., (© 2024. The Author(s).)

A facile cation modulation strategy is proposed for the synthesis of copper/cobalt bimetallic sulfides dispersed on hierarchical carbon nanoflowers, which exhibit excellent oxygen electrocatalysis capacity to drive electrochemiluminescence for cytosensing.

HER2-positive and triple-negative breast cancers (TNBC) are difficult to treat and associated with poor prognosis. Despite showing initial response, HER2-positive breast cancers often acquire resistance to HER2-targeted therapies, and TNBC lack effective therapies. To overcome these clinical challenges, we evaluated the therapeutic utility of co-targeting TrkA and JAK2/STAT3 pathways in these breast cancer subtypes. Here, we report the novel combination of FDA-approved TrkA inhibitors (Entrectinib or Larotrectinib) and JAK2 inhibitors (Pacritinib or Ruxolitinib) synergistically inhibited in vitro growth of HER2-positive breast cancer cells and TNBC cells. The Entrectinib-Pacritinib combination inhibited the breast cancer stem cell subpopulation, reduced expression of stemness genes, SOX2 and MYC, and induced apoptosis. The Entrectinib-Pacritinib combination suppressed orthotopic growth of HER2-positive Trastuzumab-refractory breast cancer xenografts and basal patient-derived xenograft (PDXs), reduced tumoral SOX2 and MYC, and induced apoptosis in both mouse models. The Entrectinib-Pacritinib combination inhibited overall metastatic burden, and brain and bone metastases of intracardially inoculated TNBC cells without toxicity. Together, our results demonstrate for the first time that co-inhibition of TrkA and JAK2 synergistically suppresses breast cancer growth and metastasis, thereby providing preclinical evidence that supports future clinical evaluations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To assess the clinical features and effectiveness of antiviral therapy in newborns with sensorineural hearing loss (SNHL) caused by congenital congenital cytomegalovirus (cCMV) infection, and to speculate the risk factors for poor hearing outcomes. Methods: A multicenter prospective cohort study wasconducted, enrolling 176 newborns diagnosed with cCMV at four research centers in Zhejiang Province from March 1, 2021, to April 30, 2024. Clinical characteristics at birth were recorded and hearing was followed up. The children were divided into groups based on their condition at birth, specifically into asymptomatic, mild symptom, and moderate to severe symptom groups. Additionally, they were divided into SNHL and normal hearing groups based on the results of air conduction brainstem audiometry at birth. And they were also divided into treatment and untreated groups according to antiviral treatment. Mann Whitney U test, and chi square test were used for inter group comparison to analyze the differences in clinical features between different disease groups, and to analyze the effects of clinical features, antiviral therapy, and other factors on hearing improvement. Logistic regression analysis was employed to identify the risk factors influencing hearing outcomes. Results: Among the cohort of 176 children diagnosed infection with cCMV, 90 cases were male and 86 cases were female. Of these, 79 cases were asymptomatic, 12 cases classified as mild cCMV and 85 cases as moderate to severe cCMV. Fifty cases belonged to SNHL group, with different degrees of severity, including 30 cases of mild, 9 cases of moderate, 5 cases of severe, and 6 cases of extremely severe SNHL. Among the 121 cases in the normal hearing group, 2 cases (1.7%) exhibited late-onset hearing loss despite having normal hearing at birth. Among 81 cases (46.0%) who completed the hearing follow-up, 71 cases (87.7%) had good hearing outcomes and 10 cases (12.3%) had poor hearing outcomes. Among the 81 children, 29 cases (35.8%) had SNHL at birth. During follow-up, the hearing threshold improved in 19 cases (65.5%), remained stable in 7 cases (24.1%) and progressed in 3 cases (10.3%). A total of 26 cases in the treatment group and 55 cases in the untreated group completed the hearing follow-up assessment. The rate of hearing improvement in the treatment group was found to be higher compared to the untreated group (13 cases (50.0%) vs. 6 cases (10.9%), χ 2 =15.00, P <0.01), with individuals in the treatment group having a 4.58 times greater likelihood of experiencing hearing improvement ( RR =4.58,95% CI 1.96-10.70, P <0.05). However, no statistically significant difference was observed in hearing outcomes between the antiviral treatment group and the untreated group ( RR =0.90, 95% CI 0.57-1.41, P =0.517). Multivariate analysis further confirmed SNHL ( OR =11.58, 95% CI 2.10-63.93, P =0.005) and preterm birth ( OR =4.98, 95% CI 1.06-23.41, P =0.042) as independent risk factors for poor hearing outcomes. Conclusions: SNHL resulting from cCMV infection presents symptoms at birth and can be improved by antiviral therapy. Poor hearing outcomes are associated with SNHL and prematurity.

Biting flies, including stable flies and horn flies, are considered important pests of livestock, companion animals, and humans by inflicting painful bites and interrupting normal animal behavior and human recreational/outdoor activities. It is estimated that they cause an annual loss of over 3 billion dollars in the US livestock industry. Both groups of pest flies further transmit various infectious diseases to animals and humans. The present review summarizes recent research advancements in stable and horn fly chemical and sensory ecology, especially in the discovery of novel attractants and repellents, as well as their controls for these blood-sucking flies and beyond., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cardiac myosin-binding protein C (cMyBP-C) is a novel cardiac marker of acute myocardial infarction (AMI) and acute cardiac injuries (ACI). Construction of point-of-care testing techniques capable of sensing cMyBP-C with high sensitivity and precision is urgently needed. Herein, we synthesized an Au@NGQDs@Au/Ag multi-shell nanoUrchins (MSNUs), and then applied it in a colorimetric/SERS dual-mode immunoassay for detection of cMyBP-C. The MSNUs displayed superior stability, colorimetric brightness, and SERS enhancement ability with an enhanced factor of 5.4 × 10 9 , which were beneficial to improve the detection capability of test strips. The developed MSNU-based test strips can achieve an ultrasensitive immunochromatographic assay of cMyBP-C in both colorimetric and SERS modes with the limits of detection as low as 19.3 and 0.77 pg/mL, respectively. Strikingly, this strip was successfully applied to analyze actual plasma samples with significantly better sensitivity, negative predictive value, and accuracy than commercially available gold test strips. Notably, this method possessed a wide range of application scenarios via combining with a color recognizer application named Color Grab on the smartphone, which can meet various needs of different users. Overall, our MSNU-based test strip as a mobile health monitoring tool shows excellent sensitivity, reproducibility, and rapid detection of the cMyBP-C, which holds great potential for the early clinic diagnosis of AMI and ACI.

Pregnancy requires metabolic adaptations in order to meet support fetal growth with nutrient availability. In this study, the influence of pregnancy on metabolically active organs (adipose tissues in particular) was investigated. Our results showed that maternal weight and adipose mass presented dynamic remodeling in the periparturient mice. Meanwhile, pregnancy mice displayed obvious glucose intolerance and insulin resistance in late pregnancy as compared to non-pregnancy, which were partially reversed at parturition. Further analyses revealed that different fat depots exhibited site-specific adaptions of morphology and functionality as pregnancy advanced. Brown and inguinal white adipose tissue (BAT and IngWAT) exhibited obviously decreased thermogenic activity; by contrast, gonadal white adipose tissue (GonWAT) displayed remarkably increased lipid mobilization. Notably, we found that mammary gland differentiation was enhanced in IngWAT, followed by BAT but not in GonWAT. These result indicated that brown and white adipose tissues might synergistically play a crucial role in maintaining the maximum of energy supply for mother and fetus, which facilitates the mammary duct luminal epithelium development as well as the growth and development of fetus. Accompanied with adipose adaptation, however, our results revealed that the liver and pancreas also displayed significant metabolic adaptability, which together tended to trigger the risk of maternal metabolic diseases. Importantly, pregnancy-dependent obesity in our mice model resembled the disturbed metabolic phenotypes of pregnant women such as hyperglyceridemia and hypercholesterolemia. Our findings in this study could provide valuable clues for better understanding the underlying mechanisms of metabolic maladaptation and facilitate the development of the prevention and treatment of metabolic diseases.

Solving the Hamiltonian of a system yields the energy dispersion and eigenstates. The geometric phase of the eigenstates generates many novel effects and potential applications. However, the geometric properties of the energy dispersion go unheeded. Here, we provide geometric insight into energy dispersion and introduce a geometric amplitude, namely, the geometric density of states (GDOS) determined by the Riemann curvature of the constant-energy contour. The geometric amplitude should accompany various local responses, which are generally formulated by the real-space Green's function. Under the stationary phase approximation, the GDOS simplifies the Green's function into its ultimate form. In particular, the amplitude factor embodies the spinor phase information of the eigenstates, favoring the extraction of the spin texture for topological surface states under an in-plane magnetic field through spin-polarized STM measurements. This work opens a new avenue for exploring the geometric properties of electronic structures and excavates the unexplored potential of spin-polarized STM measurements to probe the spinor phase information of eigenstates from their amplitudes.

PROteolysis TArgeting Chimeras have received increasing attention due to their capability to induce potent degradation of various disease-related proteins. However, the effective and controlled cytosolic delivery of current small-molecule PROTACs remains a challenge, primarily due to their intrinsic shortcomings, including unfavorable solubility, poor cell permeability, and limited spatiotemporal precision. Here, we develop a near-infrared light-controlled PROTAC delivery device (abbreviated as USDPR) that allows the efficient photoactivation of PROTAC function to achieve enhanced protein degradation. The nanodevice is constructed by encapsulating the commercial BRD4-targeting PROTACs (dBET6) in the hollow cavity of mesoporous silica-coated upconversion nanoparticles, followed by coating a Rose Bengal (RB) photosensitizer conjugated poly-L-lysine (PLL-RB). This composition enables NIR light-activatable generation of cytotoxic reactive oxygen species due to the energy transfer from the UCNPs to PLL-RB, which boosts the endo/lysosomal escape and subsequent cytosolic release of dBET6. We demonstrate that USDPR is capable of effectively degrading BRD4 in a NIR light-controlled manner. This in combination with NIR light-triggered photodynamic therapy enables an enhanced antitumor effect both in vitro and in vivo . This work thus presents a versatile strategy for controlled release of PROTACs and codelivery with photosensitizers using an NIR-responsive nanodevice, providing important insight into the design of effective PROTAC-based combination therapy.

Objective: To investigate the clinicopathological and genetic features of confined placental mosaicism (CPM) and its effect on fetal intrauterine growth. Methods: Fourteen CPM cases of Haidian Maternal and Children Health Hospital were collected from May 2018 to March 2022. Clinicopathological examination on placental specimens and molecular genetic analysis were performed. Results: The age of the parturient women ranged from 27 to 34 years, with an average age of (30.0±3.54) years. The gestational weeks ranged from 35 +1 to 41 +2 weeks. There were 4 premature births and 10 term births, among which 6 were female and 8 were male fetuses. Nine cases (9/14) had adverse pregnancy outcomes, including 7 cases of fetal growth restriction. The weight of CPM placenta decreased, with 6 cases below the 10th percentile of weight standards and 5 cases between the 10th and 25th percentile. All 14 CPM placental specimens showed morphological changes of perfusion dysfunction to varying degrees, with mainly placental-maternal vascular malperfusion followed by placental-fetal vascular malperfusion. The mosaic chromosomes in different CPM cases varied, with 16-trisomy/monosomy mosaicism being the most common followed by 7-trisomy and 21-trisomy/monosomy mosaicism. The mosaic proportion was unequal in different parts of the same CPM placenta, with the mosaic proportion of umbilical cord, fetal membranes, fetal surface, maternal surface, and edge ranging from 1% to 70%. Conclusions: The mosaic chromosomes in different CPM cases vary, and the mosaic proportion is unequal in different parts of the same CPM placenta. The pathological morphology is mainly manifested as perfusion dysfunction, which can lead to adverse pregnancy outcomes such as fetal growth restriction and preterm birth.

Objectives: Glioblastomas (GBM) are the most common primary invasive neoplasms of the brain. Distinguishing between lesion recurrence and different types of treatment related changes in patients with GBM remains challenging using conventional MRI imaging techniques. Therefore, accurate and precise differentiation between true progression or pseudoresponse is crucial in deciding on the appropriate course of treatment. This retrospective study investigated the potential of apparent diffusion coefficient (ADC) map values derived from diffusion-weighted imaging (DWI) as a noninvasive method to increase diagnostic accuracy in treatment response., Methods: A cohort of 21 glioblastoma patients (mean age: 59.2 ± 11.8, 12 Male, 9 Female) that underwent treatment with bevacizumab were selected. The ADC values were calculated from the DWI images obtained from a standardized brain protocol across 1.5-T and 3-T MRI scanners. Ratios were calculated for rADC values. Lesions were classified as bevacizumab-induced cytotoxicity based on characteristic imaging features (well-defined regions of restricted diffusion with persistent diffusion restriction over the course of weeks without tissue volume loss and absence of contrast enhancement). The rADC value was compared to these values in radiation necrosis and recurrent lesions, which were concluded in our prior study. The nonparametric Wilcoxon signed rank test with p < 0.05 was used for significance., Results: The mean ± SD age of the selected patients was 59.2 ± 11.8. ADC values and corresponding mean rADC values for bevacizumab-induced cytotoxicity were 248.1 ± 67.2 and 0.39 ± 0.10, respectively. These results were compared to the ADC values and corresponding mean rADC values of tumor progression and radiation necrosis. Significant differences between rADC values were observed in all three groups ( p < 0.001). Bevacizumab-induced cytotoxicity had statistically significant lower ADC values compared to both tumor recurrence and radiation necrosis., Conclusion: The study demonstrates the potential of ADC values as noninvasive imaging biomarkers for differentiating recurrent glioblastoma from radiation necrosis and bevacizumab-induced cytotoxicity.

Electrochemical reduction of carbon dioxide (CO 2 ) or carbon monoxide (CO) to valuable multi-carbon (C 2+ ) products like acetate is a promising approach for a sustainable energy economy. However, it is still challenging to achieve high activity and selectivity for acetate production, especially in neutral electrolytes. Herein, a bioinspired hemin/Cu hybrid catalyst was developed to enhance the surface *CO coverage for highly efficient electroreduction of CO to acetate fuels. The hemin/Cu electrocatalyst exhibits a remarkable faradaic efficiency of 45.2% for CO-to-acetate electroreduction and a high acetate partial current density of 152.3 mA cm -2 . Furthermore, the developed hybrid catalyst can operate stably at 200 mA cm -2 for 14.6 hours, producing concentrated acetate aqueous solutions (0.235 M, 2.1 wt%). The results of in situ Raman spectroscopy and theoretical calculations proved that the Fe-N 4 structure of hemin could enhance the CO adsorption and enrich the local concentration of CO, thereby improving C-C coupling for acetate production. In addition, compared to the unmodified Cu catalysts, the Cu catalysts functionalized with cobalt phthalocyanine with a Co-N 4 structure also exhibit improved acetate performance, proving the universality of this bioinspired molecule-enhanced strategy. This work paves a new way to designing bioinspired electrolysis systems for producing specific C 2+ products from CO 2 or CO electroreduction.

DNA-based theragnostic platforms have attracted more and more attention, while their applications are still impeded by nonspecific interference and insufficient therapeutic efficacy. Herein, we fabricate an integrated "dual-key-and-lock" DNA nanodevice (DKL-DND) which is composed of the inner Dox/Hairpin/Aptazyme-Au@Ag@Au probes and the outer metal-organic frameworks loaded with Fuel strand. Once internalized into human breast cancer cells (MCF-7), the DKL-DND is activated by cascaded endogenous stimuli (acidic pH in the lysosome and high expression of ATP in the cytoplasm), leading to spatially controlled optical/magnetic resonance multimodal imaging and gene/chemo/small molecule combined cancer therapy. By engineering pH and ATP-responsive units as cascaded locks on the DKL-DND, the operating status of the nanodevice and accessibility of encapsulated anti-tumour drugs can be precisely regulated in the specified physiological states, avoiding the premature activation and release during assembly and delivery. Both in vitro and in vivo assessments demonstrate that the DKL-DND with excellent stimuli-responsive ability, biocompatibility, stability and accumulation behaviour was capable of simultaneously affording accurate tumour diagnosis and efficient tumour growth inhibition. This integrated DKL-DND exhibits great promise in constructing self-adaptive nanodevices for multimodal imaging-guided combination therapy., Competing Interests: The authors declare no competing interests., (This journal is © The Royal Society of Chemistry.)

Background: Although the combination of lenvatinib and PD-1 inhibitors has become the standard regimen for the treatment of advanced hepatocellular carcinoma (HCC), real data on the impact of baseline hepatitis B virus (HBV)-DNA levels on the clinical efficacy of this regimen is still limited., Aim: To evaluate the effectiveness of camrelizumab combined with lenvatinib in patients with HCC at varying levels of HBV-DNA., Methods: One hundred and twenty patients with HCC who received camrelizumab and lenvatinib treatment were categorized into two cohorts: HBV-DNA ≤ 2000 ( n = 66) and HBV-DNA > 2000 ( n = 54). The main outcomes measured were overall survival (OS) and progression-free survival (PFS), while additional outcomes included the rate of objective response rate (ORR), disease control rate (DCR), and any negative events. Cox proportional hazards regression analysis revealed independent predictors of OS, leading to the creation of a nomogram incorporating these variables., Results: The median PFS was 8.32 months for the HBV-DNA ≤ 2000 group, which was similar to the 7.80 months observed for the HBV DNA > 2000 group ( P = 0.88). Likewise, there was no notable variation in the median OS between the two groups, with durations of 13.30 and 14.20 months respectively ( P = 0.14). The ORR and DCR were compared between the two groups, showing ORR of 19.70% vs 33.33% ( P = 0.09) and DCR of 72.73% vs 74.07% ( P = 0.87). The nomogram emphasized the importance of antiviral treatment as the main predictor of patient results, with portal vein tumor thrombus and Barcelona Clinic Liver Cancer staging following closely behind., Conclusion: The clinical outcomes of patients with HBV-associated HCC treated with camrelizumab in combination with lenvatinib are not significantly affected by HBV viral load., Competing Interests: Conflict-of-interest statement: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Early metastasis of pancreatic cancer (PaC) is a major cause of its high mortality rate. Previous studies have shown that AHNAK2 is involved in the progression of some tumors and is predicted to be an independent prognostic factor for PaC; however, the specific mechanisms through which AHNAK2 regulates PaC remain unclear. In this study, we examined the role of AHNAK2 in PaC and its potential molecular mechanisms. AHNAK2 mRNA and protein expression in PaC tissues and cells were measured using qRT-PCR and western blot analysis. After AHNAK2 knockdown using small interfering RNA, PaC cells were subjected to CCK-8 scratch, and Transwell assays to assess cell proliferation, migration, and invasion, respectively. Furthermore, the validation of the mechanistic pathway was achieved by western blot analysis. AHNAK2 mRNA and protein levels were up-regulated in PaC and silencing AHNAK2 significantly inhibited the proliferation, migration, and invasion of PaC cells. Mechanistically, AHNAK2 knockdown decreased the expression of phosphorylated p65, phosphorylated IκBα, and matrix metalloproteinase-9 (MMP-9), suggesting that activation of the NF-κB/MMP-9 signaling pathway was inhibited. Importantly, activation of NF-κB reversed the effects of AHNAK2 knockdown. Our findings indicate that AHNAK2 promotes PaC progression through the NF-kB/MMP-9 pathway and provides a theoretical basis for targeting AHNAK2 for the treatment of PaC., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Pervaporation (PV) is an effective membrane separation process for organic dehydration, recovery, and upgrading. However, it is crucial to improve membrane materials beyond the current permeability-selectivity trade-off. In this research, we introduce machine learning (ML) models to identify high-potential polymers, greatly improving the efficiency and reducing cost compared to conventional trial-and-error approach. We utilized the largest PV data set to date and incorporated polymer fingerprints and features, including membrane structure, operating conditions, and solute properties. Dimensionality reduction, missing data treatment, seed randomness, and data leakage management were employed to ensure model robustness. The optimized LightGBM models achieved RMSE of 0.447 and 0.360 for separation factor and total flux, respectively (logarithmic scale). Screening approximately 1 million hypothetical polymers with ML models resulted in identifying polymers with a predicted permeation separation index >30 and synthetic accessibility score <3.7 for acetic acid extraction. This study demonstrates the promise of ML to accelerate tailored membrane designs.

Depolarizing current injections produced a rhythmic bursting of action potentials - a bursting oscillation - in a set of local interneurons in the lateral geniculate nucleus (LGN) of rats. The current dynamics underlying this firing pattern have not been determined, though this cell type constitutes an important cellular component of thalamocortical circuitry, and contributes to both pathologic and non-pathologic brain states. We thus investigated the source of the bursting oscillation using pharmacological manipulations in LGN slices in vitro and in silico . 1. Selective blockade of calcium channel subtypes revealed that high-threshold calcium currents I L and I P contributed strongly to the oscillation. 2. Increased extracellular K + concentration (decreased K + currents) eliminated the oscillation. 3 . Selective blockade of K + channel subtypes demonstrated that the calcium-sensitive potassium current ( I A H P ) was of primary importance. A morphologically simplified, multicompartment model of the thalamic interneuron characterized the oscillation as follows: 1. The low-threshold calcium current I T provided the strong initial burst characteristic of the oscillation. 2. Alternating fluxes through high-threshold calcium channels and I A H P then provided the continuing oscillation's burst and interburst periods respectively. This interplay between I L and I A H P contrasts with the current dynamics underlying oscillations in thalamocortical and reticularis neurons, which primarily involve I T and I H , or I T and I A H P respectively. These findings thus point to a novel electrophysiological mechanism for generating intrinsic oscillations in a major thalamic cell type. Because local interneurons can sculpt the behavior of thalamocortical circuits, these results suggest new targets for the manipulation of ascending thalamocortical network activity.

Cathepsin L (CTSL) is a promising therapeutic target for metabolic disorders. Current pharmacological interventions targeting CTSL have demonstrated potential in reducing body weight gain, serum insulin levels, and improving glucose tolerance. However, the clinical application of CTSL inhibitors remains limited. In this study, we used a combination of artificial intelligence and experimental methods to identify new CTSL inhibitors from natural products. Through a robust deep learning model and molecular docking, we screened 150 molecules from natural products for experimental validation. At a concentration of 100 µM, we found that 36 of them exhibited more than 50 % inhibition of CTSL. Notably, 13 molecules displayed over 90 % inhibition and exhibiting concentration-dependent effects. The molecular dynamics simulation on the two most potent inhibitors, Plumbagin and Beta-Lapachone, demonstrated stable interaction at the CTSL active site. Enzyme kinetics studies have shown that these inhibitors exert an uncompetitive inhibitory effect on CTSL. In conclusion, our research identifies Plumbagin and Beta-Lapachone as potential CTSL inhibitors, offering promising candidates for the treatment of metabolic disorders and illustrating the effectiveness of artificial intelligence in drug discovery., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Hydrogen production by photosynthetic hybrid systems (PBSs) offers a promising avenue for renewable energy. However, the light-harvesting efficiency of PBSs remains constrained due to unclear intracellular kinetic factors. Here, we present an operando elucidation of the sluggish light-harvesting behavior for existing PBSs and strategies to circumvent them. By quantifying the spectral shift in the structural color scattering of individual PBSs during the photosynthetic process, we observe the accumulation of product hydrogen bubbles on their outer membrane. These bubbles act as a sunshade and inhibit light absorption. This phenomenon elucidates the intrinsic constraints on the light-harvesting efficiency of PBSs. The introduction of a tension eliminator into the PBSs effectively improves the bubble sunshade effect and results in a 4.5-fold increase in the light-harvesting efficiency. This work provides valuable insights into the dynamics of transmembrane transport gas products and holds the potential to inspire innovative designs for improving the light-harvesting efficiency of PBSs.

Small molecule-based photothermal agents (PTAs) hold promising future for photothermal therapy; however, unexpected inactivation exerts negative impacts on their application clinically. Herein, a self-regenerating PTA strategy is proposed by integrating 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS •+ ) with a thermodynamic agent (TDA) 2,2'-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH). Under NIR laser, the photothermal effect of ABTS •+ accelerates the production of alkyl radicals by AIPH, which activates the regeneration of ABTS •+ , thus creating a continuous positive feedback loop between photothermal and thermodynamic effects. The combination of ABTS •+ regeneration and alkyl radical production leads to the tandem photothermal and thermodynamic tumor therapy. In vitro and in vivo experiments confirm that the synergistic action of thermal ablation, radical damage, and oxidative stress effectively realizes tumor suppression. This work offers a promising approach to address the unwanted inactivation of PTAs and provides valuable insights for optimizing combination therapy., (© 2024 Wiley‐VCH GmbH.)

The endoperoxide group of artemisinins is universally accepted an essential group for their anti-cancer effects. In this study, a series of D-ring-contracted artemisinin derivatives were constructed by combining ring-contracted artemisinin core with fragments of functional heterocyclic molecules or classical CDK4/6 inhibitors to identify more efficacious breast cancer treatment agents. Twenty-six novel hybridized molecules were synthesized and characterized by HRMS, IR, 1 H-NMR and 13 C NMR. In antiproliferative activities and kinase inhibitory effects assays, we found that the antiproliferative effects of B01 were close to those of the positive control Palbociclib, with GI 50 values of 4.87±0.23 μM and 9.97±1.44 μM towards T47D cells and MDA-MB-436 cells respectively. In addition, the results showed that B01 was the most potent compound against CDK6/cyclin D3 kinase, with an IC 50 value of 0.135±0.041 μM, and its activity was approximately 1/3 of the positive control Palbociclib., (© 2024 Wiley-VHCA AG, Zurich, Switzerland.)

Background: Hepatocellular carcinoma (HCC) has a poor long-term prognosis. The competition of circular RNAs (circRNAs) with endogenous RNA is a novel tool for predicting HCC prognosis. Based on the alterations of circRNA regulatory networks, the analysis of gene modules related to HCC is feasible., Methods: Multiple expression datasets and RNA element targeting prediction tools were used to construct a circRNA-microRNA-mRNA network in HCC. Gene function, pathway, and protein interaction analyses were performed for the differentially expressed genes (DEGs) in this regulatory network. In the protein-protein interaction network, hub genes were identified and subjected to regression analysis, producing an optimized four-gene signature for prognostic risk stratification in HCC patients. Anti-HCC drugs were excavated by assessing the DEGs between the low- and high-risk groups. A circRNA-microRNA-hub gene subnetwork was constructed, in which three hallmark genes, KIF4A, CCNA2, and PBK, were subjected to functional enrichment analysis., Results: A four-gene signature (KIF4A, CCNA2, PBK, and ZWINT) that effectively estimated the overall survival and aided in prognostic risk assessment in the The Cancer Genome Atlas (TCGA) cohort and International Cancer Genome Consortium (ICGC) cohort was developed. CDK inhibitors, PI3K inhibitors, HDAC inhibitors, and EGFR inhibitors were predicted as four potential mechanisms of drug action (MOA) in high-risk HCC patients. Subsequent analysis has revealed that PBK, CCNA2, and KIF4A play a crucial role in regulating the tumor microenvironment by promoting immune cell invasion, regulating microsatellite instability (MSI), and exerting an impact on HCC progression., Conclusions: The present study highlights the role of the circRNA-related regulatory network, identifies a four-gene prognostic signature and biomarkers, and further identifies novel therapy for HCC., (Copyright © 2023 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Our study aimed to evaluate the safety of CoronaVac, an inactivated vaccine made by Sinovac, in children aged 7-14. We conducted a parent-administered online survey to monitor adverse reactions after vaccinating children in Taizhou, China, from February 15, 2021, to January 19, 2022. 767 parents completed the survey after receiving a questionnaire via WeChat. Overall, 15.3 % (117/767) of children experienced adverse effects after the first dose, and 12.2 % (88/724) after the second. Muscle pain was the most common adverse reaction post-first dose (10.0 %), while localized pain or itching at the injection site was most common after the second dose (7.6 %). In conclusion, the vaccine has a low incidence of side effects. The mild to moderate, transient, and common nature of these effects further boosts parents' confidence in vaccinating their children., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Breast cancer poses the significance of early diagnosis and treatment. Here, we developed an innovative photoelectrochemical (PEC) immunosensor characterized by high-level dual photocurrent signals and exceptional sensitivity. The PEC sensor, denoted as MIL&Ag 2 S, was constructed by incorporating Ag 2 S into a metal-organic framework of MIL-101(Cr). This composite not only enhanced electron-hole separation and conductivity but also yielded robust and stable dual photocurrent signals. Through the implementation of signal switching, we achieved the combined detection of cancer antigen 15-3 (CA15-3) and carcinoembryonic antigen (CEA) with outstanding stability, reproducibility, and specificity. The results revealed a linear range for CEA detection spanning 0.01-32 ng/mL, with a remarkably low detection limit of 0.0023 ng/mL. Similarly, for CA15-3 detection, the linear range extended from 0.1 to 320 U/mL, with a low detection limit of 0.014 U/mL. The proposed strategy introduces new avenues for the development of highly efficient, cost-effective, and user-friendly PEC sensors. Furthermore, it holds promising prospects for early clinical diagnosis, contributing to potential breakthroughs in medical detection and ultimately improving patient outcomes.

Simultaneous profiling of redox-regulated markers at different cellular sublocations is of great significance for unraveling the upstream and downstream molecular mechanisms of oxidative stress in living cells. Herein, by synchronizing dual target-triggered DNA machineries in one nanoentity, we engineered a DNA walker-driven mass nanotag (MNT) assembly system (w-MNT-AS) that can be sequentially activated by oxidative stress-associated mucin 1 (MUC1) and apurinic/apyrimidinic endonuclease 1 (APE1) from plasma membrane to cytoplasm and induce recycled assembly of MNTs for multiplex detection of the two markers by matrix-assisted laser desorption ionization mass spectrometry (MALDI MS). In the working cascade, the sensing process governs the separate activation of w-MNT-AS by MUC1 and APE1 in diverse locations, while the assembly process contributes to the parallel amplification of the ion signal of the characteristic mass tags. In this manner, the differences between MCF-7, HeLa, HepG2, and L02 cells in membrane MUC1 expression and cytoplasmic APE1 activation were fully characterized. Furthermore, the oxidative stress level and dynamics caused by exogenous H 2 O 2 , doxorubicin, and simvastatin were comprehensively demonstrated by tracking the fate of the two markers across different cellular locations. The proposed w-MNT-AS coupled MS method provides an effective route to probe multiple functional molecules that lie at different locations while participating in the same cellular event, facilitating the mechanistic studies on cellular response to oxidative stress and other disease-related cellular processes.

Irritable bowel syndrome (IBS) is a prevalent functional gastrointestinal disease characterized by chronic visceral pain with a complex etiology and challenging treatment. Although accumulating evidence supports the involvement of central nervous system sensitization in the development of visceral pain, the precise molecular mechanisms remain incompletely understood. In this study, we highlight the critical regulatory role of lysine-specific demethylase 6B (KDM6B) in the anterior cingulate cortex (ACC) in chronic visceral pain. To simulate clinical IBS conditions, we utilized the neonatal maternal deprivation (NMD) mouse model. Our results demonstrated that NMD induced chronic visceral pain and anxiety-like behaviors in mice. Notably, the protein expression level of KDM6B significantly increased in the ACC of NMD mice, leading to a reduction in the expression level of H32K7me3. Immunofluorescence staining revealed that KDM6B primarily co-localizes with neurons in the ACC, with minimal presence in microglia and astrocytes. Injecting GSK-J4 (a KDM6B-specific inhibitor) into ACC of NMD mice, resulted in a significant alleviation in chronic visceral pain and anxiety-like behaviors, as well as a remarkable reduction in NR2B expression level. ChIP assay further indicated that KDM6B regulates NR2B expression by influencing the demethylation of H3K27me3. In summary, our findings underscore the critical role of KDM6B in regulating chronic visceral pain and anxiety-like behaviors in NMD mice. These insights provide a basis for further understanding the molecular pathways involved in IBS and may pave the way for targeted therapeutic interventions.

The image of a tourist destination is considered a vital aspect of international travel experiences, yet research in this area remains limited. Adopting a combination of netography and qualitative research methodology, this study aims to contribute to the scientific knowledge of destination image development in Thailand by analysing online travelogues to evaluate how Chinese tourists interpret the idea of destination image. To achieve this goal, 146,641 words of Chinese internet comments containing the keyword "Thailand" from four major media sources and Chinese bloggers were gathered and analysed using netography methodology. The findings showed that there was a rise in public interest, in public forums, in the destination image of Thailand among Chinese outbound tourists. The study's results may provide important fundamental theoretical insights and inspire further investigation into the issue of destination image construction., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhu, Shan. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The unique virus-cell interaction in Epstein-Barr virus (EBV)-associated malignancies implies targeting the viral latent-lytic switch is a promising therapeutic strategy. However, the lack of specific and efficient therapeutic agents to induce lytic cycle in these cancers is a major challenge facing clinical implementation. We develop a synthetic transcriptional activator that specifically activates endogenous BZLF1 and efficiently induces lytic reactivation in EBV-positive cancer cells. A lipid nanoparticle encapsulating nucleoside-modified mRNA which encodes a BZLF1-specific transcriptional activator (mTZ3-LNP) is synthesized for EBV-targeted therapy. Compared with conventional chemical inducers, mTZ3-LNP more efficiently activates EBV lytic gene expression in EBV-associated epithelial cancers. Here we show the potency and safety of treatment with mTZ3-LNP to suppress tumor growth in EBV-positive cancer models. The combination of mTZ3-LNP and ganciclovir yields highly selective cytotoxic effects of mRNA-based lytic induction therapy against EBV-positive tumor cells, indicating the potential of mRNA nanomedicine in the treatment of EBV-associated epithelial cancers., (© 2024. The Author(s).)