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Freshwater salinization is receiving increasing global attention due to its profound influence on nitrogen cycling in aquatic ecosystems and the accessibility of water resources. However, a comprehensive understanding of the changes in river salinization and the impacts of salinity on nitrogen cycling in arid and semi-arid regions of China is currently lacking. A meta-analysis was first conducted based on previous investigations and found an intensification in river salinization that altered hydrochemical characteristics. To further analyze the impact of salinity on nitrogen metabolism processes, we evaluated rivers with long-term salinity gradients based on in situ observations. The genes and enzymes that were inhibited generally by salinity, especially those involved in nitrogen fixation and nitrification, showed low abundances in three salinity levels. The abundance of genes and enzymes with denitrification and dissimilatory nitrate reduction to ammonium functions still maintained a high proportion, especially for denitrification genes/enzymes that were enriched under medium salinity. Denitrifying bacteria exhibited various relationships with salinity, while dissimilatory nitrate reduction to ammonium bacterium (such as Hydrogenophaga and Curvibacter carrying nirB) were more inhibited by salinity, indicating that diverse denitrifying bacteria could be used to regulate nitrogen concentration. Most genera exhibited symbiotic and mutual relationships, and the highest proportion of significant positive correlations of abundant genera was found under medium salinity. This study emphasizes the role of river salinity on environment characteristics and nitrogen transformation rules, and our results are useful for improving the availability of river water resources in arid and semi-arid regions.

Abstract Acetylcholine regulates various cognitive functions through broad cholinergic innervation. However, specific cholinergic subpopulations, circuits and molecular mechanisms underlying recognition memory remain largely unknown. Here we show that Ngfr + cholinergic neurons in the substantia innominate (SI)/nucleus basalis of Meynert (nBM)-medial prefrontal cortex (mPFC) circuit selectively underlies recency judgements. Loss of nerve growth factor receptor (Ngfr −/− mice) reduced the excitability of cholinergic neurons in the SI/nBM-mPFC circuit but not in the medial septum (MS)-hippocampus pathway, and impaired temporal order memory but not novel object and object location recognition. Expression of Ngfr in Ngfr −/− SI/nBM restored defected temporal order memory. Fiber photometry revealed that acetylcholine release in mPFC not only predicted object encounters but also mediated recency judgments of objects, and such acetylcholine release was absent in Ngfr −/− mPFC. Chemogenetic and optogenetic inhibition of SI/nBM projection to mPFC in ChAT-Cre mice diminished mPFC acetylcholine release and deteriorated temporal order recognition. Impaired cholinergic activity led to a depolarizing shift of GABAergic inputs to mPFC pyramidal neurons, due to disturbed KCC2-mediated chloride gradients. Finally, potentiation of acetylcholine signaling upregulated KCC2 levels, restored GABAergic driving force and rescued temporal order recognition deficits in Ngfr −/− mice. Thus, NGFR-dependent SI/nBM-mPFC cholinergic circuit underlies temporal order recognition memory.

Abstract The rising prevalence of diabetes mellitus has casted a spotlight on one of its significant sequelae: cognitive impairment. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally developed for diabetes management, are increasingly studied for their cognitive benefits. These benefits may include reduction of oxidative stress and neuroinflammation, decrease of amyloid burdens, enhancement of neuronal plasticity, and improved cerebral glucose utilization. The multifaceted effects and the relatively favorable side-effect profile of SGLT2 inhibitors render them a promising therapeutic candidate for cognitive disorders. Nonetheless, the application of SGLT2 inhibitors for cognitive impairment is not without its limitations, necessitating more comprehensive research to fully determine their therapeutic potential for cognitive treatment. In this review, we discuss the role of SGLT2 in neural function, elucidate the diabetes-cognition nexus, and synthesize current knowledge on the cognitive effects of SGLT2 inhibitors based on animal studies and clinical evidence. Research gaps are proposed to spur further investigation.

Abstract Background Type 2 diabetes mellitus (T2D) is associated with an increased risk of cognitive dysfunction. Angiopoietin-like protein 8 (ANGPTL8) is an important regulator in T2D, but the role of ANGPTL8 in diabetes-associated cognitive dysfunction remains unknown. Here, we explored the role of ANGPTL8 in diabetes-associated cognitive dysfunction through its interaction with paired immunoglobulin-like receptor B (PirB) in the central nervous system. Methods The levels of ANGPTL8 in type 2 diabetic patients with cognitive dysfunction and control individuals were measured. Mouse models of diabetes-associated cognitive dysfunction were constructed to investigate the role of ANGPTL8 in cognitive function. The cognitive function of the mice was assessed by the Barnes Maze test and the novel object recognition test, and levels of ANGPTL8, synaptic and axonal markers, and pro-inflammatory cytokines were measured. Primary neurons and microglia were treated with recombinant ANGPTL8 protein (rA8), and subsequent changes were examined. In addition, the changes induced by ANGPTL8 were validated after blocking PirB and its downstream pathways. Finally, mice with central nervous system-specific knockout of Angptl8 and PirB −/− mice were generated, and relevant in vivo experiments were performed. Results Here, we demonstrated that in the diabetic brain, ANGPTL8 was secreted by neurons into the hippocampus, resulting in neuroinflammation and impairment of synaptic plasticity. Moreover, neuron-specific Angptl8 knockout prevented diabetes-associated cognitive dysfunction and neuroinflammation. Mechanistically, ANGPTL8 acted in parallel to neurons and microglia via its receptor PirB, manifesting as downregulation of synaptic and axonal markers in neurons and upregulation of proinflammatory cytokine expression in microglia. In vivo, PirB −/− mice exhibited resistance to ANGPTL8-induced neuroinflammation and synaptic damage. Conclusion Taken together, our findings reveal the role of ANGPTL8 in the pathogenesis of diabetes-associated cognitive dysfunction and identify the ANGPTL8-PirB signaling pathway as a potential target for the management of this condition.

Objective To establish a nomogram model to predict the survival of elderly patients with colon cancer after radical resection, and to verify the predictive value of this model. Methods A total of 118 elderly patients with colon cancer who underwent radical surgery at the Xinjiang Medical University Affiliated Traditional Chinese Medicine Hospital from January 2015 to December 2017 were selected as the research subjects. The prognostic indicators of elderly patients with colorectal cancer after radical surgery were analyzed by univariate Cox regression analysis. The meaningful indicators with P0.05). Conclusion The nomogram model combined with differentiation degree, TNM/T staging, lymph node metastasis and VEGF can accurately predict postoperative disease-free survival and overall survival of elderly patients with colon cancer.

Abstract This study comprehensively explores the clinical characteristics, diagnostic approaches, and treatment methods for liver mucinous cystic neoplasms (MCN). A retrospective analysis was conducted on seven individuals diagnosed with MCN, admitted to the Fifth Medical Center of the PLA General Hospital between October 2016 and May 2023. Preoperative AFP was negative, while CA19-9 was elevated in two cases. Surgical resection was performed for all patients. The patients showed favorable postoperative recovery. Follow-up revealed an excellent overall survival rate, except for one case of invasive carcinoma resulting in tumor recurrence and metastasis 6 months after surgery. MCN poses a diagnostic challenge due to the absence of distinct clinical and radiological features, leading to potential misdiagnosis and inappropriate treatment. Patients with suspected liver cystic diseases should consider the possibility of MCN. Surgical resection has proven to be a practical approach with satisfactory therapeutic outcomes.

Abstract Background Beneficial associations between plants and soil microorganisms are critical for crop fitness and resilience. However, it remains obscure how microorganisms are assembled across different root compartments and to what extent such recruited microbiomes determine crop performance. Here, we surveyed the root transcriptome and the root and rhizosphere microbiome via RNA sequencing and full-length (V1–V9) 16S rRNA gene sequencing from genetically distinct monogenic root mutants of maize (Zea mays L.) under different nutrient-limiting conditions. Results Overall transcriptome and microbiome display a clear assembly pattern across the compartments, i.e., from the soil through the rhizosphere to the root tissues. Co-variation analysis identified that genotype dominated the effect on the microbial community and gene expression over the nutrient stress conditions. Integrated transcriptomic and microbial analyses demonstrated that mutations affecting lateral root development had the largest effect on host gene expression and microbiome assembly, as compared to mutations affecting other root types. Cooccurrence and trans-kingdom network association analysis demonstrated that the keystone bacterial taxon Massilia (Oxalobacteraceae) is associated with root functional genes involved in flowering time and overall plant biomass. We further observed that the developmental stage drives the differentiation of the rhizosphere microbial assembly, especially the associations of the keystone bacteria Massilia with functional genes in reproduction. Taking advantage of microbial inoculation experiments using a maize early flowering mutant, we confirmed that Massilia-driven maize growth promotion indeed depends on flowering time. Conclusion We conclude that specific microbiota supporting lateral root formation could enhance crop performance by mediating functional gene expression underlying plant flowering time in maize. Video Abstract

Abstract Background Osteoporosis is a chronic bone disease characterized by bone loss and decreased bone strength. However, current anti‐resorptive drugs carry a risk of various complications. The deep learning‐based efficacy prediction system (DLEPS) is a forecasting tool that can effectively compete in drug screening and prediction based on gene expression changes. This study aimed to explore the protective effect and potential mechanisms of cinobufotalin (CB), a traditional Chinese medicine (TCM), on bone loss. Methods DLEPS was employed for screening anti‐osteoporotic agents according to gene profile changes in primary osteoporosis. Micro‐CT, histological and morphological analysis were applied for the bone protective detection of CB, and the osteogenic differentiation/function in human bone marrow mesenchymal stem cells (hBMMSCs) were also investigated. The underlying mechanism was verified using qRT‐PCR, Western blot (WB), immunofluorescence (IF), etc. Results A safe concentration (0.25 mg/kg in vivo, 0.05 μM in vitro) of CB could effectively preserve bone mass in estrogen deficiency‐induced bone loss and promote osteogenic differentiation/function of hBMMSCs. Both BMPs/SMAD and Wnt/β‐catenin signaling pathways participated in CB‐induced osteogenic differentiation, further regulating the expression of osteogenesis‐associated factors, and ultimately promoting osteogenesis. Conclusion Our study demonstrated that CB could significantly reverse estrogen deficiency‐induced bone loss, further promoting osteogenic differentiation/function of hBMMSCs, with BMPs/SMAD and Wnt/β‐catenin signaling pathways involved.

Abstract Due to their high reliability and cost‐efficiency, submarine pipelines are widely used in offshore oil and gas resource engineering. Due to the interaction of waves, currents, seabed, and pipeline structures, the soil around submarine pipelines is prone to local scour, severely affecting their operational safety. With the Yellow River Delta as the research area and based on the renormalized group (RNG) k‐ε turbulence model and Stokes fifth‐order wave theory, this study solves the Navier–Stokes (N–S) equation using the finite difference method. The volume of fluid (VOF) method is used to describe the fluid‐free surface, and a three‐dimensional numerical model of currents and waves–submarine pipeline–silty sandy seabed is established. The rationality of the numerical model is verified using a self‐built waveflow flume. On this basis, in this study, the local scour development and characteristics of submarine pipelines in the Yellow River Delta silty sandy seabed in the prototype environment are explored and the influence of the presence of pipelines on hydrodynamic features such as surrounding flow field, shear stress, and turbulence intensity is analyzed. The results indicate that (1) local scour around submarine pipelines can be divided into three stages: rapid scour, slow scour, and stable scour. The maximum scour depth occurs directly below the pipeline, and the shape of the scour pits is asymmetric. (2) As the water depth decreases and the pipeline suspension height increases, the scour becomes more intense. (3) When currents go through a pipeline, a clear stagnation point is formed in front of the pipeline, and the flow velocity is positively correlated with the depth of scour. This study can provide a valuable reference for the protection of submarine pipelines in this area.

Abstract Purpose Thyroid disorders have been reported in hypercortisolism patients. Endogenous Cushing’s syndrome (CS) potentially complicates its metabolic sequelae. We investigated thyroid function in CS patients to determine this relationship. Methods In this cross-sectional study, we screened CS patients from 2016 to 2019 at our hospital. Patient demographic, medical history, and laboratory data were collected. Additionally, we performed a meta-analysis to demonstrate the prevalence of thyroid dysfunction in patients with CS. Results Among 129 CS patients, 48.6% had triiodothyronine (TT3), 27.9% had thyroxine (TT4), 24.6% had free T3 (FT3), 27.7% had free T4 (FT4), and 6.2% had thyroid-stimulating hormone (TSH) levels below the reference values. Those with clinical CS showed more pronounced thyroid suppression than did those with subclinical CS. Cortisol levels were markedly greater in patients with pituitary hypothyroidism (P

Epigenetic modifications play an important role in cellular senescence, and enhancer of zeste homolog 2 (EZH2) is a key methyltransferase involved in epigenetic remodeling in multiple myeloma (MM) cells. We have previously demonstrated that GSK126, a specific EZH2 inhibitor, exhibits anti-MM therapeutic efficacy and safety in vivo and in vitro; however, its specific mechanism remains unclear. This study shows that GSK126 induces cellular senescence in MM, which is characterized by the accumulation of senescence-associated heterochromatin foci (SAHF) and p21, and increased senescence-associated β galactosidase activity. Furthermore, EZH2 is inhibited in ribonucleotide reductase regulatory subunit M2 (RRM2)-overexpressing OCI-MY5 and RPMI-8226 cells. RRM2 overexpression inhibits the methyltransferase function of EZH2 and promotes its degradation through the ubiquitin-proteasome pathway, thereby inducing cellular senescence. In this senescence model, Lamin B1, a key component of the nuclear envelope and a marker of senescence, does not decrease but instead undergoes aberrant accumulation. Meanwhile, phosphorylation of extracellular signal-regulated protein kinase (ERK1/2) is significantly increased. The inhibition of ERK1/2 phosphorylation in turn partially restores Lamin B1 level and alleviates senescence. These findings suggest that EZH2 inhibition increases Lamin B1 level and induces senescence by promoting ERK1/2 phosphorylation. These data indicate that EZH2 plays an important role in MM cellular senescence and provide insights into the relationships among Lamin B1, p-ERK1/2, and cellular senescence.

Abstract Statins are thought to have positive effects on migraine but existing data are inconclusive. We aimed to evaluate the causal effect of such drugs on migraines using Mendelian randomization. We used four types of genetic instruments as proxies for HMG-CoA reductase inhibition. We included the expression quantitative trait loci of the HMG-CoA reductase gene and genetic variation within or near the HMG-CoA reductase gene region. Variants were associated with low-density lipoprotein cholesterol, apolipoprotein B, and total cholesterol. Genome-wide association study summary data for the three lipids were obtained from the UK Biobank. Comparable data for migraine were obtained from the International Headache Genetic Consortium and the FinnGen Consortium. Inverse variance weighting method was used for the primary analysis. Additional analyses included pleiotropic robust methods, colocalization, and meta-analysis. Genetically determined high expression of HMG-CoA reductase was associated with an increased risk of migraines (OR = 1.55, 95% CI 1.30–1.84, P = 6.87 × 10−7). Similarly, three genetically determined HMG-CoA reductase-mediated lipids were associated with an increased risk of migraine. These conclusions were consistent across meta-analyses. We found no evidence of bias caused by pleiotropy or genetic confounding factors. These findings support the hypothesis that statins can be used to treat migraine.

Abstract Objective Mild therapeutic hypothermia (MTH) is an important method for perioperative prevention and treatment of myocardial ischemia–reperfusion injury (MIRI). Modifying mitochondrial proteins after protein translation to regulate mitochondrial function is one of the mechanisms for improving myocardial ischemia–reperfusion injury. This study investigated the relationship between shallow hypothermia treatment improving myocardial ischemia–reperfusion injury and the O-GlcNAcylation level of COX10. Methods We used in vivo Langendorff model and in vitro hypoxia/reoxygenation (H/R) cell model to investigate the effects of MTH on myocardial ischemia–reperfusion injury. Histological changes, myocardial enzymes, oxidative stress, and mitochondrial structure/function were assessed. Mechanistic studies involved various molecular biology methods such as ELISA, immunoprecipitation (IP), WB, and immunofluorescence. Results Our research results indicate that MTH upregulates the O-GlcNACylation level of COX10, improves mitochondrial function, and inhibits the expression of ROS to improve myocardial ischemia–reperfusion injury. In vivo, MTH effectively alleviates ischemia–reperfusion induced cardiac dysfunction, myocardial injury, mitochondrial damage, and redox imbalance. In vitro, the OGT inhibitor ALX inhibits the OGT mediated O-GlcNA acylation signaling pathway, downregulates the O-Glc acylation level of COX10, promotes ROS release, and counteracts the protective effect of MTH. On the contrary, the OGA inhibitor ThG showed opposite effects to ALX, further confirming that MTH activated the OGT mediated O-GlcNAcylation signaling pathway to exert cardioprotective effects. Conclusions In summary, MTH activates OGT mediated O-glycosylation modified COX10 to regulate mitochondrial function and improve myocardial ischemia–reperfusion injury, which provides important theoretical basis for the clinical application of MTH.

Abstract Background Parkinson’s disease (PD) is a progressive neurodegenerative disease with increasing prevalence. Effective diagnostic markers and therapeutic methods are still lacking. Exploring key molecular markers and mechanisms for PD can help with early diagnosis and treatment improvement. Methods Three datasets GSE174052, GSE77668, and GSE168496 were obtained from the GEO database to search differentially expressed circRNA (DECs), miRNAs (DEMis), and mRNAs (DEMs). GO and KEGG enrichment analyses, and protein–protein interaction (PPI) network construction were implemented to explore possible actions of DEMs. Hub genes were selected to establish circRNA-related competing endogenous RNA (ceRNA) networks. Results There were 1005 downregulated DECs, 21 upregulated and 21 downregulated DEMis, and 266 upregulated and 234 downregulated DEMs identified. The DEMs were significantly enriched in various PD-associated functions and pathways such as extracellular matrix organization, dopamine synthesis, PI3K-Akt, and calcium signaling pathways. Twenty-one hub genes were screened out, and a PD-related ceRNA regulatory network was constructed containing 31 circRNAs, one miRNA (miR-371a-3p), and one hub gene (KCNJ6). Conclusion We identified PD-related molecular markers and ceRNA regulatory networks, providing new directions for PD diagnosis and treatment.

Objective To summarize the clinical characteristics of Vogt-Koyanagi-Harada syndrome (VKHS) combing with meningitis/encephalitis patients. Methods and Results The clinical data of the inpatients of Beijing Tongren Hospital, Capital Medical University from January 2009 to December 2022 with VKHS combing with meningitis/encephalitis were retrospectively analyzed. A total of 23 patients were included in the study, of which 20 patients (86.96%) had neurological symptoms, with headache being the most common (19 cases, 82.61%), 11 patients (47.83%) had increased cerebrospinal fluid (CBF) pressure, 14 patients (60.87%) had increased CBF white blood cells, and 11 patients (47.83%) had increased CBF protein. The brain MRI mainly showed white matter demyelination (8/14 cases). Optic nerve MRI showed inflammatory lesions of optic nerve and optic papilla (12/14 cases). The visual evoked potential (VEP) mainly showed prolonged latency (10/16 cases). The optical coherence tomography (OCT) showed retinal exudation (8/15 cases) and retinal neurocortical detachment (7/15 cases). The main results of fundus photography were disc edema (17/18 cases). The main manifestation of fundus fluorescein angiography (FFA) was uveitis (9/15 cases). After intravenous hormone and intravenous immunoglobulin (IVIg) treatment, 14 patients were followed up, and neurological symptoms were completely relieved, 11 patients had good visual prognosis, and 3 patients had no obvious visual improvement. Conclusions VKHS might present with meningitis/encephalitis symptoms, and the CSF characteristics of these patients were similar to those of viral meningitis. For those with early suspicions of VKHS, CBF examination and imaging examination might assist in early diagnosis and treatment.

Abstract Precise orchestration of cell fate determination underlies the success of scaffold-based skeletal regeneration. Despite extensive studies on mineralized parenchymal tissue rebuilding, regenerating and maintaining undifferentiated mesenchyme within calvarial bone remain very challenging with limited advances yet. Current knowledge has evidenced the indispensability of rebuilding suture mesenchymal stem cell niches to avoid severe brain or even systematic damage. But to date, the absence of promising therapeutic biomaterials/scaffolds remains. The reason lies in the shortage of fundamental knowledge and methodological evidence to understand the cellular fate regulations of scaffolds. To address these issues, in this study, we systematically investigated the cellular fate determinations and transcriptomic mechanisms by distinct types of commonly used calvarial scaffolds. Our data elucidated the natural processes without scaffold transplantation and demonstrated how different scaffolds altered in vivo cellular responses. A feasible scaffold, polylactic acid electrospinning membrane (PLA), was next identified to precisely control mesenchymal ingrowth and self-renewal to rebuild non-osteogenic suture-like tissue at the defect center, meanwhile supporting proper osteointegration with defect bony edges. Especially, transcriptome analysis and cellular mechanisms underlying the well-orchestrated cell fate determination of PLA were deciphered. This study for the first time cellularly decoded the fate regulations of scaffolds in suture-bony composite defect healing, offering clinicians potential choices for regenerating such complicated injuries.

Abstract Background Protein arginine methyltransferase 6 (PRMT6) plays a crucial role in various pathophysiological processes and diseases. Glioblastoma (GBM; WHO Grade 4 glioma) is the most common and lethal primary brain tumor in adults, with a prognosis that is extremely poor, despite being less common than other systemic malignancies. Our current research finds PRMT6 upregulated in GBM, enhancing tumor malignancy. Yet, the specifics of PRMT6’s regulatory processes and potential molecular mechanisms in GBM remain largely unexplored. Methods PRMT6’s expression and prognostic significance in GBM were assessed using glioma public databases, immunohistochemistry (IHC), and immunoblotting. Scratch and Transwell assays examined GBM cell migration and invasion. Immunoblotting evaluated the expression of epithelial-mesenchymal transition (EMT) and Wnt-β-catenin pathway-related proteins. Dual-luciferase reporter assays and ChIP-qPCR assessed the regulatory relationship between PRMT6 and YTHDF2. An in situ tumor model in nude mice evaluated in vivo conditions. Results Bioinformatics analysis indicates high expression of PRMT6 and YTHDF2 in GBM, correlating with poor prognosis. Functional experiments show PRMT6 and YTHDF2 promote GBM migration, invasion, and EMT. Mechanistic experiments reveal PRMT6 and CDK9 co-regulate YTHDF2 expression. YTHDF2 binds and promotes the degradation of negative regulators APC and GSK3β mRNA of the Wnt-β-catenin pathway, activating it and consequently enhancing GBM malignancy. Conclusions Our results demonstrate the PRMT6-YTHDF2-Wnt-β-Catenin axis promotes GBM migration, invasion, and EMT in vitro and in vivo, potentially serving as a therapeutic target for GBM.

Abstract There has recently been a surge of interest in studying the superconducting diode effect (SDE) partly due to the possibility of uncovering the intrinsic properties of a material system. A change of sign of the SDE at finite magnetic field has previously been attributed to different mechanisms. Here, we observe the SDE in epitaxial Al-InAs Josephson junctions with strong Rashba spin-orbit coupling (SOC). We show that this effect strongly depends on the orientation of the in-plane magnetic field. In the presence of a strong magnetic field, we observe a change of sign in the SDE. Simulation and measurement of supercurrent suggest that depending on the superconducting widths, W S, this sign change may not necessarily be related to 0–π or topological transitions. We find that the strongest sign change in junctions with narrow W S is consistent with SOC-induced asymmetry of the critical current under magnetic-field inversion, while in wider W S, the sign reversal could be related to 0–π transitions and topological superconductivity.

Preventing local tumor recurrence while promoting bone tissue regeneration is an urgent need for osteosarcoma treatment. However, the therapeutic efficacy of traditional photosensitizers is limited, and they lack the ability to regenerate bone. Here, a piezo-photo nanoheterostructure is developed based on ultrasmall bismuth/strontium titanate nanocubes (denoted as Bi/SrTiO3), which achieve piezoelectric field-driven fast charge separation coupling with surface plasmon resonance to efficiently generate reactive oxygen species. These hybrid nanotherapeutics are integrated into injectable biopolymer hydrogels, which exhibit outstanding anticancer effects under the combined irradiation of NIR and ultrasound. In vivo studies using patient-derived xenograft models and tibial osteosarcoma models demonstrate that the hydrogels achieve tumor suppression with efficacy rates of 98.6 % and 67.6 % in the respective models. Furthermore, the hydrogel had good filling and retention capabilities in the bone defect region, which exerted bone repair therapeutic efficacy by polarizing and conveying electrical stimuli to the cells under mild ultrasound radiation. This study provides a comprehensive and clinically feasible strategy for the overall treatment and tissue regeneration of osteosarcoma.

CO2 capture by microalgae is a feasible strategy to reduce CO2 emissions. However, large amounts of cell-free supernatant will be produced after microalgal harvesting, which may be harmful to the environment if it is disorderly discharged. In this study, Chlorella vulgaris (C. vulgaris) was cultivated under three common cultivation modes (autotrophic culture (AC), heterotrophic culture (HC) and mixotrophic culture (MC)), and the obtained supernatant was used as fertilizer to investigate its effect on the growth of lettuce. The biomass concentration of C. vulgaris cultivated under MC and HC was 3.25 and 2.59 times that of under AC, respectively. The contents of macronutrients in supernatant obtained from AC were higher than those of MC and HC. However, the contents of amino acids and hormones in supernatant obtained from MC and HC were higher than those of AC. The fresh shoot weight, fresh root weight and root length of lettuce treated with supernatant were significantly higher than that of control treatment. In addition, the contents of chlorophyll, soluble sugar and soluble protein in lettuce treated with supernatant were also higher than that of control treatment. However, the contents of nitrate in lettuce treated with supernatant was lower than that of control treatment. These results showed that the supernatant could promote the growth of lettuce and was a potential of fertilizer for crop planting.

Abstract Simultaneously achieving high‐energy‐density and high‐power‐density is a crucial yet challenging objective in the pursuit of commercialized power batteries. In this study, atomic layer deposition (ALD) is employed combined with a coordinated thermal treatment strategy to construct a densely packed, electron‐ion dual conductor (EIC) protective coating on the surface of commercial LiNi0.5Co0.2Mn0.3O2 (NCM523) cathode material, further enhanced by gradient Al doping (Al@EIC‐NCM523). The ultra‐thin EIC effectively suppresses side reactions, thereby enhancing the stability of the cathode‐electrolyte interphase (CEI) at high‐voltages. The EIC's dual conduction capability provides a potent driving force for Li+ transport at the interface, promoting the formation of rapid ion deintercalation pathways within the Al@EIC‐NCM523 bulk phase. Moreover, the strategic gradient doping of Al serves to anchor the atomic spacing of Ni and O within the structure of Al@EIC‐NCM523, curbing irreversible phase transitions at high‐voltages and preserving the integrity of its layered structure. Remarkably, Al@EIC‐NCM523 displays an unprecedented rate capability (114.7 mAh g−1 at 20 C), and a sustained cycling performance (capacity retention of 74.72% after 800 cycles at 10 C) at 4.6 V. These findings demonstrate that the proposed EIC and doping strategy holds a significant promise for developing high‐energy‐density and high‐power‐density lithium‐ion batteries (LIBs).

Suspended particulate matter (SPM) concentrations and associated estuarine high turbidity zones (HTZ) play crucial role in maintaining delta land building, coastal wetlands and marine ecosystems. In the background of new water-sediment delivery regime and major geomorphological transition in delta, the long-term change characteristics and driving mechanisms of SPM and HTZ in the Yellow River Estuary (YRE) are not clarified. In this study, it was found that the existing SPM models could not be adapted to the extremely turbid YRE, for which a novel SPM retrieval algorithm and HTZ extraction method were developed. Spatiotemporal dynamics of SPM and HTZ in YRE from 1984 to 2023 were investigated using 798 Landsat TM/ETM+/OLI imageries. Results indicated that our proposed SPM algorithm outperformed all the previous models of YRE (R2 > 0.95, relative percentage difference (RPD)< 22%), and high accuracies were achieved for both satellite-derived SPM (RPD = 33.01%) and HTZ (overall accuracy = 94%). Over the last four decades, both SPM concentration and HTZ distribution area in YRE had demonstrated an increasing and then decreasing trend, reaching a peak around 1996. HTZ experienced four morphological transformations involving the circular shape surrounding coast (1984–1993), the enlarged southeasterly ovoid shape (1994–2007), the circle-like shape (2007–2017) and the thin northeasterly ovoid shape (2018–2023). Riverine sediment load and strong-wind frequency controlled 67% of interannual SPM variability in the study area, and the former contributed more. Moreover, combination of weakening ocean dynamics and coastal erosion, coarsening of sediments, and coastal defense structures led to an exponential decline of SPM concentrations in northern subregion. High sediment discharge and rapid accretion of estuarine spit in 1984–1996 resulted in increased SPM concentrations in southern subregion and a quick expansion of HTZ into Laizhou Bay. With the geomorphological evolution of new and old estuaries, the high velocity zone and strong bottom shear stress zone were consequently adjusted, which explained the interannual variability of SPM and HTZ in the region. This study will contribute to understanding of the long-term evolutionary patterns of the coupled system consisting of runoff-tidal dynamics, sediment transport and geomorphological development in the estuary.

As a deep connection between agriculture and energy, the rural integrated energy system (RIES) is a micro-scale supply–distribution–storage–demand network, which provides an important means to realize the utilization of rural clean energy. This paper proposes a day-ahead scheduling model of the RIES to improve its economical effectiveness, where three energy carriers, namely, biogas, electric power, and heat, are integrated. To address the source and load uncertainties composed of photovoltaic power, power load, and heat load, this paper develops a constrained distributionally robust optimization (CDRO), which optimizes the cost expectation related to the extreme distribution to enhance the robustness, while limiting the loss of cost expectation in the historical distribution to ensure economical effectiveness. In addition, an ambiguous set of the source and load uncertainties incorporating 1-norm and infinity-norm constraints is established, which realizes a flexible adjustment for the conservativeness of CDRO. The distributionally robust dispatch is formulated as a deterministic programming in a two-stage solving framework, where the subproblem uploads its extreme probability distribution to the master problem, and these two problems are iteratively optimized until the convergence. Finally, the numerical simulations in a modern farm park prove the performance of the constructed dispatch model and the flexibility of CDRO in balancing the economical effectiveness and robustness of the dispatch.

BackgroundAmong bone diseases, osteoporosis-like skeleton, such as trabecular thinning, fracture and so on, is the main pathological change of cadmium-induced osteoporosis(Cd-OP), accompanied by brittle bone and increased fracture rate. However, the mechanism underlying cadmium-induced osteoporosis has remained elusive. Compound Lurong Jiangu Capsule (CLJC) is an experienced formula for the treatment of bone diseases, which has the effect of tonifying kidney and strengthening bones, promoting blood circulation and relieving pain.ObjectiveNetwork pharmacology and molecular docking technology combined with experiments were used to investigate the potential mechanism of CLJC in treating Cd-OP.MethodThe active compounds and corresponding targets of each herb in CLJC were searched in the TCMSP and BATMAN-TCM databases. The DisGeNet, OMIM, and GeneCards databases searched for Cd-OP targets. The relationship between both of them was visualized by establishing an herb-compound-target network using Cytoscape 3.9.1 software. Gene ontology (GO), and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses were performed after determining the intersection of the targets from CLJC and Cd-OP. What’s more, molecular docking was performed to validate the results. All of them were aim to obtain hud signaling pathways for further study. Finally, BAX, BCL-2, and CASPASE-3 were screened and selected for further experiments, which included bone imaging and reconstruction analysis (Micro-CT), hematoxylin-eosin Staining (HE), and western blot (WB).Results106 common targets from CLJC and Cd-OP targets were identified. KEGG pathway analysis suggested that multiple signaling pathways, such as the pathways in cancer, may play roles in treatment. Verification of the molecular docking was successful. Here we showed that Cd-OP displayed Tb.Th and Tb.N significantly reduced and even broke, irregular proliferation of bone cortex, uneven and loose trabecular bone arrangement, changed in apoptosis-related proteins, such as significant upregulation of CASPASE-3, BAX protein and significant downregulation of BCL-2 protein in vivo, while CLJC rescued these phenotypes.ConclusionThis study revealed that CLJC can reduce the expression of apoptosis-related proteins, and multiple components and multiple targets inhibit Cd-OP through apoptosis signaling pathway.

Abstract Long-wavelength, near-infrared small-molecule dyes are attractive in biophotonics. Conventionally, they rely on expanded aromatic structures for redshift, which comes at the cost of application performance such as photostability, cell permeability, and functionality. Here, we report a ground-state antiaromatic strategy and showcase the concise synthesis of 14 cationic aminofluorene dyes with mini structures (molecular weights: 299–504 Da) and distinct spectra covering 700–1600 nm. Aminofluorene dyes are cell-permeable and achieve rapid renal clearance via a simple 44 Da carboxylation. This accelerates optical diagnostics of renal injury by 50 min compared to existing macromolecular approaches. We develop a compact molecular sensing platform for in vivo intracellular sensing, and demonstrate the versatile applications of these dyes in multispectral fluorescence and optoacoustic imaging. We find that aromaticity reversal upon electronic excitation, as indicated by magnetic descriptors, not only reduces the energy bandgap but also induces strong vibronic coupling, resulting in ultrafast excited-state dynamics and unparalleled photostability. These results support the argument for ground-state antiaromaticity as a useful design rule of dye development, enabling performances essential for modern biophotonics.

The Al–50Si alloy, designed for effective heat dissipation in electronic components, was subjected to a two-stage heat treatment process to optimize its microstructure and achieve high thermal conductivity (TC). Two distinct temperature stages were strategically chosen: 850 °C and 550 °C, respectively, with the former operating above and the latter below the eutectic point. The first stage at 850 °C led to the isolation of independent Si particles, each closely associated with individual Al crystal with grain size of approximately 1 mm. Subsequent heat treatment at 550 °C skillfully eliminated introduced eutectic Si through Ostwald ripening. Consequently, the impediments posed by grain boundaries to the movement of electrons and phonons were significantly reduced, yielding an exceptionally high TC of approximately 180 Wm−1K−1, closely approaching the theoretical TC value (∼193 Wm−1K−1) for the Al–50Si alloy. This work paved a new path for the design of outstanding thermal properties in Al–Si electronic packaging materials.

Objective·To evaluate the quality of clinical practice guidelines of obstructive sleep apnea (OSA) published worldwide.Methods·The guidelines of OSA were retrieved in PubMed, Embase, China National Knowledge Infrastructure (CNKI), Wanfang Data, SinoMed, MedSci, The Cochrane Library, and the websites such as Medlive, U. S. Preventive Services Task Force (USPSTF), National Institute for Health and Care Excellence (NICE), New Zealand Guidelines Group (NZGG), Scottish Intercollegiate Guidelines Network (SIGN), and Guidelines International Network (GIN) from establishment to December 2022. Two reviewers screened the literature and extracted the main information independently, using the Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ) and Reporting Items for Practice Guidelines in Healthcare (RIGHT) to evaluate the quality of the included OSA guidelines. Subgroup analysis was performed according to the publication regions of guidelines. The inter-evaluator consistency test was also performed and the results were expressed as the intra-class correlation coefficient (ICC). All the included guidelines were read entirely and the clinical questions they raised were summarized.Results·A total of 35 OSA guidelines were included. The ICC value of 0.975 showed a good inter-evaluator agreement. The results of AGREE Ⅱ showed that the average score of all guidelines was (63.60±16.45)%, with a minimum of 23.40% and a maximum of 91.67%. In the six domains, the scores of "Rigor of development" [(56.07±25.89)%] and "Applicability" [(53.57±15.52)%] were relative low. The average reporting rate of RIGHT of all the included guidelines was (67.84±20.03)%, with a minimum of 14.29% and a maximum of 94.29%, and the three domains with the lowest reporting rates were "Review and quality assurance" [(31.40±45.51)%], "Funding and conflict of interest declaration and management" [(56.43±33.95)%] and "Other aspects" [(56.19±36.85)%]. Subgroup analysis showed that guidelines in Asian had a lower score in "Rigor of development" and a lower overall score of AGREE Ⅱ than the guidelines in America and Europe (both P

Background: Atrial fibrillation (AF) is a major public health problem with high rates of morbidity, disability and mortality, especially in the elderly population. This study explored the diagnosis and treatment status of AF in adults aged ≥65 years in the community through wearable dynamic electrocardiogram (ECG) monitoring. Methods: We conducted a cross-sectional study in 4 random communities within the Qingpu district of Shanghai, China. Between January 1, 2020 and June 30, 2022, the ECGs of 3852 adults aged 65 years or older were examined through wearable dynamic ECG monitoring. Data from 3839 participants were ultimately analyzed. Multivariate logistic regression was used to determine the independent predictors of AF. Results: Wearable dynamic ECG monitoring detected AF in 360 elderly people, 78 of whom were diagnosed with AF for the first time. Multivariate logistic regression analysis revealed that snoring, renal dysfunction, coronary heart disease and high CHA2DS2-VASc score were independent risk factors for AF. Among patients with unknown AF, 68 (87.20 %) met the criteria for anticoagulant therapy based on the CHA2DS2-VASc score. Only 4 (5.88 %) patients were taking anticoagulants. Of the patients with a clear history of AF, 249 (84.98 %) needed an anticoagulant strategy, but only 18 (7.23 %) took oral anticoagulants. Conclusion: Many elderly people have silent AF, and wearable dynamic ECG monitoring can be used to screen for AF effectively.

Abstract The treatment of critical-size bone defects with irregular shapes remains a major challenge in the field of orthopedics. Bone implants with adaptability to complex morphological bone defects, bone-adhesive properties, and potent osteogenic capacity are necessary. Here, a shape-adaptive, highly bone-adhesive, and ultrasound-powered injectable nanocomposite hydrogel is developed via dynamic covalent crosslinking of amine-modified piezoelectric nanoparticles and biopolymer hydrogel networks for electrically accelerated bone healing. Depending on the inorganic-organic interaction between the amino-modified piezoelectric nanoparticles and the bio-adhesive hydrogel network, the bone adhesive strength of the prepared hydrogel exhibited an approximately 3-fold increase. In response to ultrasound radiation, the nanocomposite hydrogel could generate a controllable electrical output (-41.16 to 61.82 mV) to enhance the osteogenic effect in vitro and in vivo significantly. Rat critical-size calvarial defect repair validates accelerated bone healing. In addition, bioinformatics analysis reveals that the ultrasound-responsive nanocomposite hydrogel enhanced the osteogenic differentiation of bone mesenchymal stem cells by increasing calcium ion influx and up-regulating the PI3K/AKT and MEK/ERK signaling pathways. Overall, the present work reveals a novel wireless ultrasound-powered bone-adhesive nanocomposite hydrogel that broadens the therapeutic horizons for irregular bone defects.

Abstract The gradual aging of the global population has led to a surge in age-related diseases, which seriously threaten human health. Researchers are dedicated to understanding and coping with the complexities of aging, constantly uncovering the substances and mechanism related to aging like chronic low-grade inflammation. The NOD-like receptor protein 3 (NLRP3), a key regulator of the innate immune response, recognizes molecular patterns associated with pathogens and injury, initiating an intrinsic inflammatory immune response. Dysfunctional NLRP3 is linked to the onset of related diseases, particularly in the context of aging. Therefore, a profound comprehension of the regulatory mechanisms of the NLRP3 inflammasome in aging-related diseases holds the potential to enhance treatment strategies for these conditions. In this article, we review the significance of the NLRP3 inflammasome in the initiation and progression of diverse aging-related diseases. Furthermore, we explore preventive and therapeutic strategies for aging and related diseases by manipulating the NLRP3 inflammasome, along with its upstream and downstream mechanisms.

Abstract Cardiac fibroblasts (CFs) are the primary cells tasked with depositing and remodeling collagen and significantly associated with heart failure (HF). TEAD1 has been shown to be essential for heart development and homeostasis. However, fibroblast endogenous TEAD1 in cardiac remodeling remains incompletely understood. Transcriptomic analyses revealed consistently upregulated cardiac TEAD1 expression in mice 4 weeks after transverse aortic constriction (TAC) and Ang-II infusion. Further investigation revealed that CFs were the primary cell type expressing elevated TEAD1 levels in response to pressure overload. Conditional TEAD1 knockout was achieved by crossing TEAD1-floxed mice with CFs- and myofibroblasts-specific Cre mice. Echocardiographic and histological analyses demonstrated that CFs- and myofibroblasts-specific TEAD1 deficiency and treatment with TEAD1 inhibitor, VT103, ameliorated TAC-induced cardiac remodeling. Mechanistically, RNA-seq and ChIP-seq analysis identified Wnt4 as a novel TEAD1 target. TEAD1 has been shown to promote the fibroblast-to-myofibroblast transition through the Wnt signalling pathway, and genetic Wnt4 knockdown inhibited the pro-transformation phenotype in CFs with TEAD1 overexpression. Furthermore, co-immunoprecipitation combined with mass spectrometry, chromatin immunoprecipitation, and luciferase assays demonstrated interaction between TEAD1 and BET protein BRD4, leading to the binding and activation of the Wnt4 promoter. In conclusion, TEAD1 is an essential regulator of the pro-fibrotic CFs phenotype associated with pathological cardiac remodeling via the BRD4/Wnt4 signalling pathway.

In the paper, we presented a data-driven optimal control method for the sub-satellite deployment of tethered satellite systems during the release phase, with the objective of reducing the libration angle fluctuation during system work. First, the dynamic equation of the tethered satellite system was established and processed dimensionless. Considering the presence of noise when sensors were put on the satellite to measure the libration angle, the corresponding state equation was derived. Next, we estimated the system state using an unscented Kalman filter and established a performance index and the Hamilton function. Based on the index, we designed an optimal control strategy and provided sufficient conditions for the asymptotic stability of the closed-loop system. We used critic-actor neural networks based on measurement data to implement the data-driven control algorithm to approximate the performance index function and the control policy, respectively. Finally, taking a tethered satellite system as an example, a simulation showed that the unscented Kalman filter can effectively estimate the system state and improve the impact of noise on the system, and the proposed optimal control strategy ensured that the tethered satellite system is stable, which shows the applicability and effectiveness of the control strategy in reducing the tether vibration of the disturbed system.

Abstract A two-dimensional (2D) Dirac semimetal with concomitant superconductivity has been long sought but rarely reported. It is believed that light-element materials have the potential to realize this goal owing to their intrinsic lightweight and metallicity. Here, based on the recently synthesized β 12 hydrogenated borophene, we investigate its counterpart named β 12-B5H3. Our first-principles calculations suggest it has good stability. β 12-B5H3 is a scarce Dirac semimetal demonstrating a strain-tunable phase transition from three Dirac cones to a single Dirac cone. Additionally, β 12-B5H3 is also a superior phonon-mediated superconductor with a superconducting critical temperature of 32.4 K and can be further boosted to 42 K under external strain. The concurrence of Dirac fermions and superconductivity, supplemented with dual tunabilities, reveals β 12-B5H3 is an attractive platform to study either quantum phase transition in 2D Dirac semimetal or the superconductivity or the exotic physics brought about by their interplay.

Abstract Transmembrane serine protease 6 (Tmprss6) has been correlated with the occurrence and progression of tumors, but any specific molecular mechanism linking the enzyme to oncogenesis has remained elusive thus far. In the present study, we found that Tmprss6 markedly inhibited mouse neuroblastoma N2a (neuro-2a) cell proliferation and tumor growth in nude mice. Tmprss6 inhibits Smad1/5/8 phosphorylation by cleaving the bone morphogenetic protein (BMP) co-receptor, hemojuvelin (HJV). Ordinarily, phosphorylated Smad1/5/8 binds to Smad4 for nuclear translocation, which stimulates the expression of hepcidin, ultimately decreasing the export of iron through ferroportin 1 (FPN1). The decrease in cellular iron levels in neuro-2a cells with elevated Tmprss6 expression limited the availability of the metal forribo nucleotide reductase activity, thereby arresting the cell cycle prior to S phase. Interestingly, Smad4 promoted nuclear translocation of activating transcription factor 3 (ATF3) to activate the p38 mitogen-activated protein kinases signaling pathway by binding to ATF3, inducing apoptosis of neuro-2a cells and inhibiting tumor growth. Disruption of ATF3 expression significantly decreased apoptosis in Tmprss6 overexpressed neuro-2a cells. Our study describes a mechanism whereby Tmprss6 regulates the cell cycle and apoptosis. Thus, we propose Tmprss6 as a candidate target for inhibiting neuronal tumor growth.

Brain iron homeostasis plays a vital role in maintaining brain development and controlling neuronal function under physiological conditions. Many studies have shown that the imbalance of brain iron homeostasis is closely related to the pathogenesis of neurodegenerative diseases (NDs), such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Recent advances have revealed the importance of iron transporters and regulatory molecules in the pathogenesis and treatment of NDs. This review summarizes the research progress on brain iron overload and the aberrant expression of several key iron transporters and regulators in AD and PD, emphasizes the pathological roles of these molecules in the pathogenesis of AD and PD, and highlights the therapeutic prospects of targeting these iron transporters and regulators to restore brain iron homeostasis in the treatment of AD and PD. A comprehensive understanding of the pathophysiological roles of iron, iron transporters and regulators, and their regulations in NDs may provide new therapeutic avenues for more targeted neurotherapeutic strategies for treating these diseases.

Alzheimer's and Parkinson's diseases are two of the most frequent neurological diseases. The clinical features of AD are memory decline and cognitive dysfunction, while PD mainly manifests as motor dysfunction such as limb tremors, muscle rigidity abnormalities, and slow gait. Abnormalities in cholesterol, sphingolipid, and glycerophospholipid metabolism have been demonstrated to directly exacerbate the progression of AD by stimulating Aβ deposition and tau protein tangles. Indirectly, abnormal lipids can increase the burden on brain vasculature, induce insulin resistance, and affect the structure of neuronal cell membranes. Abnormal lipid metabolism leads to PD through inducing accumulation of α-syn, dysfunction of mitochondria and endoplasmic reticulum, and ferroptosis. Great progress has been made in targeting lipid metabolism abnormalities for the treatment of AD and PD in recent years, like metformin, insulin, peroxisome proliferator-activated receptors (PPARs) agonists, and monoclonal antibodies targeting apolipoprotein E (ApoE). This review comprehensively summarizes the involvement of dysregulated lipid metabolism in the pathogenesis of AD and PD, the application of Lipid Monitoring, and emerging lipid regulatory drug targets. A better understanding of the lipidological bases of AD and PD may pave the way for developing effective prevention and treatment methods for neurodegenerative disorders.

Abstract Idiopathic short stature (ISS) is a common childhood condition with largely unknown underlying causes. Recent research highlights the role of circulating exosomes in the pathogenesis of various disorders, but their connection to ISS remains unexplored. In the experiments, human chondrocytes are cocultured with plasma exosomes from ISS patients, leading to impaired chondrocyte growth and bone formation. Elevated levels of a specific long non‐coding RNA (lncRNA), ISSRL, are identified as a distinguishing factor in ISS, boasting high specificity and sensitivity. Silencing ISSRL in ISS plasma exosomes reverses the inhibition of chondrocyte proliferation and bone formation. Conversely, overexpression of ISSRL in chondrocytes impedes their growth and bone formation, revealing its mechanism of action through the miR‐877‐3p/GZMB axis. Subsequently, exosomes (CT‐Exo‐siISSRL‐oeGH) with precise cartilage‐targeting abilities are engineered, loaded with customized siRNA for ISSRL and growth hormone. This innovative approach offers a therapeutic strategy to address ISS by rectifying abnormal non‐coding RNA expression in growth plate cartilage and delivering growth hormone with precision to promote bone growth. This research provides valuable insights into ISS diagnosis and treatment, highlighting the potential of engineered exosomes.

In recent years, long-short term memory (LSTM) networks have emerged as a promising tool for time-series analysis, offering the ability to capture temporal dependencies effectively, especially for the fault detection in power facilities which is crucial for maintaining operational integrity and ensuring continuous power supply. This paper presents a study on the utilization of LSTM networks for fault detection in power facilities, focusing on evaluating the detection accuracy as a performance metric. We propose a novel LSTM-based fault detection framework that utilizes historical operational data to identify abnormal patterns indicative of faults or anomalies. The framework is trained on labeled data to learn the normal operational behavior of the power facility, enabling it to detect deviations from expected patterns in practical data streams. To assess the effectiveness of the proposed approach, extensive experiments are conducted using real-world operational data from diverse power facilities. We systematically evaluate the detection accuracy of the LSTM-based fault detection system under various operating conditions, including different types of faults and levels of noise in the data. Comparative analyses are performed against traditional fault detection methods to demonstrate the superiority of the LSTM-based approach in terms of accuracy. Moreover, sensitivity analyses are conducted to investigate the impact of key parameters, such as network architecture and training data size, on the detection performance. The results illustrate the robustness and effectiveness of the proposed LSTM-based fault detection framework, highlighting its potential for enhancing the reliability and efficiency of power facility operations.

Spinocerebellar ataxia is a phenotypically and genetically heterogeneous group of autosomal dominant-inherited degenerative disorders. The gene mutation spectrum includes dynamic expansions, point mutations, duplications, insertions, and deletions of varying lengths. Dynamic expansion is the most common form of mutation. Mutations often result in indistinguishable clinical phenotypes, thus requiring validation using multiple genetic testing techniques. Depending on the type of mutation, the pathogenesis may involve proteotoxicity, RNA toxicity, or protein loss-of-function. All of which may disrupt a range of cellular processes, such as impaired protein quality control pathways, ion channel dysfunction, mitochondrial dysfunction, transcriptional dysregulation, DNA damage, loss of nuclear integrity, and ultimately, impairment of neuronal function and integrity which causes diseases. Many disease-modifying therapies, such as gene editing technology, RNA interference, antisense oligonucleotides, stem cell technology, and pharmacological therapies are currently under clinical trials. However, the development of curative approaches for genetic diseases remains a global challenge, beset by technical, ethical, and other challenges. Therefore, the study of the pathogenesis of spinocerebellar ataxia is of great importance for the sustained development of disease-modifying molecular therapies.

Background: With the spread of COVID-19, concerns regarding its adverse effects have arisen. Based on affect regulation theory and construal level theory, this study explored how COVID-19 affects intertemporal choice in the health and economy domains, self-other differences for intertemporal choice were also inspected. The study examined whether psychological safety can moderate the relationship between COVID-19 and intertemporal choice. Methods: A 2 (COVID-19 status: pre-COVID-19, during-COVID-19) × 2 (decision maker role: decision for self, decision for others) × 2 (domain: health, economy) three-factor hybrid experiment was employed. Results: (1) Individuals in during-COVID-19 condition preferred more immediate options. (2) Delayed options were preferred more in the health domain. Preference for immediate money options enhanced during than before COVID-19. However, COVID-19 status did not affect choices related to health. (3) Delayed options were preferred more when making intertemporal choices for others than for oneself under the pre-COVID-19 condition. Self-other differences for intertemporal choice disappeared during COVID-19. (4) Psychological safety moderated the effect of COVID-19 on intertemporal choice. Conclusions: During COVID-19, individuals’ impulsive preference of intertemporal choice increased. COVID-19 affected intertemporal choice regarding economy and the self-other differences for intertemporal choice. Psychological safety could buffer the effect of COVID-19 on intertemporal choice. Value: This study can provide empirical evidence to affect regulation theory and level of explanation theory as well as guide individuals in making scientific decisions in health and economic domains under public health emergencies.

In order to realize the optimal planning of grid–resource–storage for distribution networks (DNs) with high penetrated distributed photovoltaics (PVs), a cluster partition-based two-layer expansion planning for DNs is proposed. First, a comprehensive cluster partition index-based cluster partition method is proposed, which involves the indexes such as electrical distance, power balance of the cluster, and cluster size. Second, a cluster partition-based two-layer expansion planning model is proposed. In the upper layer, a line planning model for clusters is established to carry out the planning of cluster connection lines. In the lower layer, a robust source-storage planning model is established with the uncertainty of PVs and loads, and then, the optimal location and capacity of PVs and energy storages (ESs) can be obtained. In addition, the uncertainty regulation parameter is utilized to control the range of uncertainty sets, which can reduce the conservatism of the optimization. Finally, the proposed method is carried out in a real DN in China, which can effectively improve the economy of DN planning.

Cisplatin-induced acute kidney injury (CIAKI) is a major dose-limiting toxicity of cisplatin treatment. The mechanisms of CIAKI involve the production of inflammation, apoptosis and oxidative stress. Palmatine, an isoquinoline alkaloid has anti-inflammatory activity. Here, we investigated the protective effect and underlying mechanism of palmatine on CIAKI by in vitro and in vivo experiments based on network pharmacology. Network pharmacology was used to analyze the relationship and potential mechanisms of palmatine and CIAKI. The protective effect of palmatine was validated in cisplatin induced 293 T cell injury model and mice model. Furthermore, the mechanism of palmatine on CIAKI was determined by detecting inflammatory factors and related signaling pathways. A total of 61 targets of palmatine against CIAKI and the closely related signaling pathways including oxidative stress, MAPK and Akt were found. Palmatine effectively protected 293 T cells and mouse kidney against CIAKI. Mechanistically, palmatine reduced CIAKI inflammation by suppressing the NF-κB/MAPK pathway. Meanwhile, palmatine inhibited apoptosis by activating the Akt pathway and reduced oxidative stress. The results of in vitro and in vivo experiments were consistent with those of network pharmacology. Furthermore, the cytotoxicity of cisplatin to H460 and HCT116 cells was slightly improved by palmatine. In conclusion, palmatine protects against CIAKI by inhibiting inflammation and apoptosis through regulation of NF-κB/MAPK and Akt pathways. Palmatine is a potential adjunctive treatment during the use of cisplatin.

Abstract Graphitic carbon nitride (g‐C3N4) is a highly recognized two‐dimensional semiconductor material known for its exceptional chemical and physical stability, environmental friendliness, and pollution‐free advantages. These remarkable properties have sparked extensive research in the field of energy storage. This review paper presents the latest advances in the utilization of g‐C3N4 in various energy storage technologies, including lithium‐ion batteries, lithium‐sulfur batteries, sodium‐ion batteries, potassium‐ion batteries, and supercapacitors. One of the key strengths of g‐C3N4 lies in its simple preparation process along with the ease of optimizing its material structure. It possesses abundant amino and Lewis basic groups, as well as a high density of nitrogen, enabling efficient charge transfer and electrolyte solution penetration. Moreover, the graphite‐like layered structure and the presence of large π bonds in g‐C3N4 contribute to its versatility in preparing multifunctional materials with different dimensions, element and group doping, and conjugated systems. These characteristics open up possibilities for expanding its application in energy storage devices. This article comprehensively reviews the research progress on g‐C3N4 in energy storage and highlights its potential for future applications in this field. By exploring the advantages and unique features of g‐C3N4, this paper provides valuable insights into harnessing the full potential of this material for energy storage applications.

BackgroundCell transplants as a treatment for Parkinson’s disease have been studied for decades, and stem cells may be the most promising cell sources for this treatment. We aimed to investigate whether stem cell transplantation contributes to the cure for Parkinson’s disease and the factors that may influence the efficacy for this therapy.MethodsPubMed, Embase, Cochrane Library, Web of Science, SinoMed, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and ChinaInfo were thoroughly searched to find controlled trials or randomized controlled trials performing stem cell transplantation in patients with Parkinson’s disease. The pooled effects were analyzed to evaluate the weighted mean difference (WMD) with 95% confidence intervals.ResultsNine articles were identified including 129 individuals. Stem cell transplantation was an effective treatment for Parkinson’s disease (WMD = −14.86; 95% CI: −16.62 to −13.10; p

Background: EEPD1 is vital in homologous recombination, while its role in cancer remains unclear. Methods: We performed multiple pan-cancer analyses of EEPD1 with bioinformatics methods, such as gene expression, gene alterations, Prognosis and enrichment analysis, tumor microenvironment, immune cell infiltration, TMB, MSI, immunotherapy, co-expression of genes, and drug resistance. Finally, RT-qPCR, EdU, and transwell assays helped investigate the impact of EEPD1 on CRC cells. Results: EEPD1 was dysregulated and correlated with bad prognosis in several cancers. GSVA and GSEA revealed that EEPD1 was primarily associated with the ''WNT_BETA_CATENIN_SIGNALING,'' ''ribonucleoprotein complex biogenesis,'' ''Ribosome,'' and ''rRNA processing.'' The infiltration of CD8+ T cells, MAIT cells, iTreg cells, NK cells, Tc cells, Tex cells, Tfh cells, and Th1 cells were negatively correlated with EEPD1 expression. Additionally, EEPD1 is significantly associated with TMB and MSI in COAD, while enhanced CRC cell proliferation and migration. Conclusions: EEPD1 was dysregulated in human cancers and correlated with various cancer patient prognoses. The dysregulated EEPD1 expression can affect tumor-infiltrating immune cells and immunotherapy response. Therefore, EEPD1 could act as an oncogene associated with immune cell infiltration in CRC.

Under the dual pressure of energy shortage and environmental pollution, relying only on increasing the installed capacity of units and line transmission capacity cannot cope with the conflict between the growth of power demand and the difficulty of grid expansion in the long run. Demand response conducts users to change their energy consumption habits through system-issued electricity prices or incentives, so that the demand of the load side can be adjusted flexibly, which can further enhance the consumption of wind power and improve system economics. Based on the background of diversified energy use, this paper proposes a day-ahead optimal scheduling strategy for integrated electricity and thermal system considering multiple types of demand response. Firstly, the dispatch framework of integrated electricity and thermal system with the situation awareness technology is constructed to address uncertainties of Renewable Energy Sources, thus helping system mitigate uncertain risks. Secondly, the demand response mechanism of power system and regional thermal inertia of thermal system are modeled, respectively, to uncover the principles of load regulation of different energy systems; Then, a day-ahead optimal scheduling model for the integrated thermal and electricity system is developed, and the consumption evaluation index is integrated to indicate energy utilization efficiency; Finally, a combined electric-heat system model with 39-node grid and 6-node heat network is developed, and the positive effects of considering multiple types of demand response and situation awareness technology on promoting the consumption of renewable energy and improving the energy efficiency of the system are verified through the case study.

In response to the underutilization of energy and insufficient flexible operation capability of rural energy supply systems in China, this study proposes an optimal dispatch approach for a rural multi-energy supply system (RMESS) considering virtual energy storage (VES). First, to enable the flexible utilization of rural biomass resources and the thermal inertia of residential building envelopes, this study constructed VES-I and VES-II models that describe electrical-thermal and electrical-gas coupling from an electrical viewpoint. Subsequently, an RMESS model encompassing these two types of VES was formulated. This model delineates the intricate interplay of multi-energy components within the RMESS framework and facilitates the precise assessment of the adjustable potential for optimizing RMESS operations. Based on the above models, a day-ahead optimal dispatch model for an RMESS considering a VES is proposed to achieve optimal economic performance while ensuring efficient energy allocation. Comparative simulations validated the effectiveness of the VES modeling and the day-ahead optimal dispatch approach for the RMESS.

The effect of the combination of 10-Hydroxycamptothecin (HCPT) and crizotinib (CRI) on EGFR- and KRAS-mutant lung cancer cells was investigated and the conjugates of the two drugs were synthesised. HCPT combined with CRI synergistically inhibited the cell growth and proliferation of H1975, HCC827, and H460 without aggravating adverse effect on the normal cells. The combination synergistically enhanced the cell apoptosis rate through releasing Cyto-C by activation of Bcl-2 family-mediated mitochondrial signalling, which was associate with inactivating of EGFR related downstream signalling pathways including AKT, ERK, JNK, and p38 MAPK. Based on this synergy, the conjugates of HCPT and CRI (compounds CH-1 and CH-2) with different chemical bonds were synthesised. Compound CH-1 exhibited stronger cytotoxicity than HCPT and CRI alone or in combination. The combination of HCPT and CRI might be a promising therapeutic regimen and the conjugate CH-1was a potential target drug for the treatment of lung cancer.

Abstract Background Copper (Cu) homeostasis and Cu-induced cell death are gaining recognition as crucial processes in the pathogenesis of cardiovascular disease (CVD). Circulating Cu associated with CVD and mortality is yet to be fully elucidated. Objective This national prospective cohort study is to estimate relationship between serum Cu and the risk of CVD and all-cause mortality. Methods This study included participants from the National Health and Nutrition Examination Survey 2011–2016. Weighted Cox proportional hazards regression analysis and exposure-response curves were applied. Results This included 5,412 adults, representing 76,479,702 individuals. During a mean of 5.85 years of follow-up (31,653 person-years), 96 CVD and 356 all-cause mortality events occurred. Age and sex-adjusted survival curves showed that individuals with higher levels of serum Cu experienced increased CVD and all-cause death rates (tertiles, p

In recent years, with the continuous improvement of China’s urbanization level, the transfer of agricultural population to cities has stepped up, and the number and scale of grain stored by farmers have shown a significant downward trend. However, the problem of grain postpartum loss caused by improper storage of farmers is still prominent every year. This paper mainly conducts in-depth investigation and analysis on the characteristics, loss rate and loss causes of the front-end storage links of farmers’ grain in China. The study found out that at present, the scale of grain storage of farmers in China is gradually decreasing, but the total scale is still large. The purpose of grain storage of farmers is mostly used for rations and feed grain, and a small amount is to wait for a better time to sell grain. There are regional differences in the number and scale of grain storage of farmers, which is mainly manifested in the fact that the main production area is higher than the production and marketing balance area and the main sales area. The study also found that the loss rate of grain storage in China’s farmers showed a downward trend, and there were significant differences in the loss rate of grain storage among farmers. Due to the poor storage facilities of farmers, improper storage management, weak scientific storage awareness, lack of storage technology and other reasons, the loss of rodents, mildew and pests is large, among which the loss of rodents is the most serious. Finally, the study also puts forward some countermeasures and suggestions for targeted derogation management.