Mechanistic Exploration of Determinants for the Fullerene@FASnI3 Interface Stability: Surface Termination and Monovalent Cation Rotation.

The investigation into the interfacial properties between fullerene compounds and Sn-based perovskites (Sn-PVSK) holds extraordinary significance for advancing efficient and stable Pb-free perovskite solar cells. This study is the first theoretical exploration to examine their interfacial properties using Ab initio molecular dynamics (AIMD) simulations and trajectory analysis methods with C60@FASnI3 as a representative system. The impact of surface termination and FA+ rotation on interface stability has been assessed. Within the 10 ps AIMD simulations, the C60@FAI interface demonstrates greater stability compared to the C60@SnI interface due to the robustness of the single-bonded I on the FAI termination and weaker C60-FAI interactions. The C60@SnI interface has poor stability, but it can be enhanced by controlling the FA+ rotation, achieving optimal stability at a 45° rotation along the C-H bond axis. This is attributed to minimal hydrogen bond interactions and a reduced steric hindrance. This work not only substantiates the pivotal role of surface termination in maintaining interface stability but, most importantly, also reveals how FA+ rotational dynamics regulate the C60@SnI interface stability, providing valuable insights for further improving the efficiency of Sn-PVSK solar cells.

Loss of SELENOW aggravates muscle loss with regulation of protein synthesis and the ubiquitin-proteasome system.

Sarcopenia is characterized by accelerated muscle mass and function loss, which burdens and challenges public health worldwide. Several studies indicated that selenium deficiency is associated with sarcopenia; however, the specific mechanism remains unclear. Here, we demonstrated that selenoprotein W (SELENOW) containing selenium in the form of selenocysteine functioned in sarcopenia. SELENOW expression is up-regulated in dexamethasone (DEX)-induced muscle atrophy and age-related sarcopenia mouse models. Knockout (KO) of SELENOW profoundly aggravated the process of muscle mass loss in the two mouse models. Mechanistically, SELENOW KO suppressed the RAC1-mTOR cascade by the interaction between SELENOW and RAC1 and induced the imbalance of protein synthesis and degradation. Consistently, overexpression of SELENOW in vivo and in vitro alleviated the muscle and myotube atrophy induced by DEX. SELENOW played a role in age-related sarcopenia and regulated the genes associated with aging. Together, our study uncovered the function of SELENOW in age-related sarcopenia and provides promising evidence for the prevention and treatment of sarcopenia.

Efficacy and safety of denosumab and teriparatide versus oral bisphosphonates to treat postmenopausal osteoporosis: a systematic review and meta-analysis.

Study Design: A systematic review and Meta-analysis. Objective: To compare the efficacy and safety of denosumab and teriparatide versus oral bisphosphonates to treat postmenopausal osteoporosis. Summary of Background Data: While bisphosphonates have historically been the cornerstone of pharmacological management for bone protection in patients, emerging evidence suggests that teriparatide and denosumab warrant further investigation as potential first-line treatments. The optimal choice among denosumab, teriparatide, and oral bisphosphonates for the treatment of postmenopausal osteoporosis remains a subject of ongoing debate and controversy within the scientific community. Methods: This systematic review adhered meticulously to the rigorous standards outlined by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines as well as the Cochrane Collaboration recommendations. Additionally, it employed the AMSTAR (Assessing the methodological quality of systematic reviews) criteria to ensure methodological robustness and enhance the credibility of the findings. A systematic electronic search was conducted across Web of Science, PubMed, and the Cochrane Library databases from their inception dates up to February 2024. Results: In this meta-analysis of studies, our findings suggest that compared to bisphosphonates, both teriparatide and denosumab demonstrated notable increases in percentage changes in lumbar spine bone mineral density (BMD) among postmenopausal osteoporosis patients. Furthermore, denosumab exhibited superiority over teriparatide and oral bisphosphonates in enhancing percentage changes in both femoral neck and total hip BMD, indicating its potential as a more efficacious option. Regarding safety outcomes, no significant differences were observed in the incidence of serious adverse events among patients treated with teriparatide, denosumab, and bisphosphonates. However, teriparatide showed superiority over oral bisphosphonates in terms of a lower risk of general adverse events, suggesting a favorable safety profile. Conclusion: In conclusion, our study suggests that teriparatide and denosumab demonstrate comparable or potentially superior efficacy and safety profiles compared to oral bisphosphonates for the treatment of postmenopausal osteoporosis. Systematic Review Registration: PROSPERO, identifier CRD42024508382.

Comparative performance analysis of large language models: ChatGPT-3.5, ChatGPT-4 and Google Gemini in glucocorticoid-induced osteoporosis.

BACKGROUNDS: The use of large language models (LLMs) in medicine can help physicians improve the quality and effectiveness of health care by increasing the efficiency of medical information management, patient care, medical research, and clinical decision-making. METHODS: We collected 34 frequently asked questions about glucocorticoid-induced osteoporosis (GIOP), covering topics related to the disease's clinical manifestations, pathogenesis, diagnosis, treatment, prevention, and risk factors. We also generated 25 questions based on the 2022 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis (2022 ACR-GIOP Guideline). Each question was posed to the LLM (ChatGPT-3.5, ChatGPT-4, and Google Gemini), and three senior orthopedic surgeons independently rated the responses generated by the LLMs. Three senior orthopedic surgeons independently rated the answers based on responses ranging between 1 and 4 points. A total score (TS) > 9 indicated 'good' responses, 6 ≤ TS ≤ 9 indicated 'moderate' responses, and TS < 6 indicated 'poor' responses. RESULTS: In response to the general questions related to GIOP and the 2022 ACR-GIOP Guidelines, Google Gemini provided more concise answers than the other LLMs. In terms of pathogenesis, ChatGPT-4 had significantly higher total scores (TSs) than ChatGPT-3.5. The TSs for answering questions related to the 2022 ACR-GIOP Guideline by ChatGPT-4 were significantly higher than those for Google Gemini. ChatGPT-3.5 and ChatGPT-4 had significantly higher self-corrected TSs than pre-corrected TSs, while Google Gemini self-corrected for responses that were not significantly different than before. CONCLUSIONS: Our study showed that Google Gemini provides more concise and intuitive responses than ChatGPT-3.5 and ChatGPT-4. ChatGPT-4 performed significantly better than ChatGPT3.5 and Google Gemini in terms of answering general questions about GIOP and the 2022 ACR-GIOP Guidelines. ChatGPT3.5 and ChatGPT-4 self-corrected better than Google Gemini.

Polystyrene nanoparticles regulate microbial stress response and cold adaptation in mainstream anammox process at low temperature.

Nanoplastic pollution has become one of the most pressing environmental issues, and its bioaccumulation in aquatic environment also causes a great difficulty in treatment. Therefore, this work investigated the microbial dynamics of mainstream anaerobic ammonia oxidizing (anammox) process to treat the wastewater containing typical nanoplastics, as well as the fate and regulation mechanism of polystyrene nanoparticles (PS-NPs) with different concentrations. The results showed that 0.1-0.5 mg L-1 of PS-NPs had no significant effect on the nitrogen removal efficiency (NRE). When the concentration of PS-NPs increased from 0.5 mg L-1 to 2 mg L-1, the NRE of R1 with PS-NPs decreased from 94.9 ± 2.3 % to 77.0 ± 1.6 %, while the control reactor R0 maintained a stable NRE. Notably, the relative abundance of Ca. Kuenenia decreased from 17.4 % to 14.8 %, and that of Ca. Brocadia slightly decreased from 5.9 % to 5.0 % in R1. In addition, PS-NPs induced oxidative stress in anammox consortia, leading to the significant increase in reactive oxygen species (ROS) and lactate dehydrogenase (LDH) as well as cell membrane damage. PS-NPs also downregulated the content of heme c and further inhibited anammox activity. Based on the molecular docking simulation and western blotting, cold shock proteins (CSPs) could bind to PS-NPs and reduce the performance of anammox processes at low temperatures.

Urban-rural disparities in mortality due to stroke subtypes in China and its provinces, 2015-2020.

BACKGROUND: Death burden of stroke is severe in China with over one-third rural residents, but there is still a lack of specific national and high-quality reports on the urban-rural differences in stroke burden, especially for subtypes. We aimed to update the understanding of urban-rural differences in stroke deaths. METHODS: This is a descriptive observational study. Data from the national mortality surveillance system, which covers 323.8 million with 605 disease surveillance points (DSPs) across all 31 provinces, municipalities, and autonomous regions in China. All deaths from stroke as the underlying cause from 2015 to 2020 according to DSPs. Crude mortality rate and age-standardized mortality rate (ASMR) were estimated through DSPs. Average annual percentage change was used to explain the change in mortality rate. RESULTS: From 2015 to 2020, the majority of deaths from all stroke subtypes occurred in rural areas. There were significant differences between the changes of urban and rural ASMRs. On the whole, the changes in urban areas were evidently better, and the ASMR differences were basically expanding. Stroke ASMR in urban China decreased by 15.5%. The rural ASMR of ischemic stroke (IS) increased by 12.9%. The rural and urban ASMRs of intracerebral hemorrhage decreased by 24.9% and 27.4%, and those of subarachnoid hemorrhage decreased by 29.5% and 40.4%, respectively. The highest ASMRs of all stroke subtypes and the increasing trend of IS ASMR make rural males the focus of stroke management. CONCLUSIONS: The death burden of stroke varies greatly between urban and rural China. Rural residents face unique challenges.

LncSTPred: a predictive model of lncRNA subcellular localization and decipherment of the biological determinants influencing localization.

Introduction: Long non-coding RNAs (lncRNAs) play crucial roles in genetic markers, genome rearrangement, chromatin modifications, and other biological processes. Increasing evidence suggests that lncRNA functions are closely related to their subcellular localization. However, the distribution of lncRNAs in different subcellular localizations is imbalanced. The number of lncRNAs located in the nucleus is more than ten times that in the exosome. Methods: In this study, we propose a new oversampling method to construct a predictive dataset and develop a predictive model called LncSTPred. This model improves the Adaboost algorithm for subcellular localization prediction using 3-mer, 3-RF sequence, and minimum free energy structure features. Results and Discussion: By using our improved Adaboost algorithm, better prediction accuracy for lncRNA subcellular localization was obtained. In addition, we evaluated feature importance by using the F-score and analyzed the influence of highly relevant features on lncRNAs. Our study shows that the ANA features may be a key factor for predicting lncRNA subcellular localization, which correlates with the composition of stems and loops in the secondary structure of lncRNAs.

Effects of transcranial direct current stimulation on pain and physical function in patients with knee osteoarthritis: a systematic review and meta-analysis.

BACKGROUND: Keen Osteoarthritis (KOA) is a common chronic disabling disease characterized by joint pain and dysfunction, which seriously affects patients' quality of life. Recent studies have shown that transcranial direct current stimulation (tDCS) was a promising treatment for KOA. PURPOSE: Investigate the effects of tDCS on pain and physical function in patients with KOA. METHODS: Randomized controlled trials related to tDCS and KOA were systematically searched in the PubMed, Embase, Medline, Cochrane Library, CINHL, and Web of Science databases from inception to July 23, 2024. The pain intensity was evaluated using the visual analog scale or the numeric rating scale, and the pain sensitivity was assessed using conditioned pain modulation, pressure pain threshold, heat pain threshold, or heat pain tolerance. The physical function outcome was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index or the Knee injury and Osteoarthritis Outcome Score. Statistical analysis was performed using Review Manager 5.4. RESULTS: Seven studies with a total of 503 participants were included. Compared to sham tDCS, tDCS was effective in reducing the short-term pain intensity (SMD: -0.58; 95% CI: -1.02, -0.14; p = 0.01) and pain sensitivity (SMD: -0.43; 95% CI: -0.70, -0.16; p = 0.002) but failed to significantly improve the long-term pain intensity (SMD: -0.26; 95% CI: -0.59, 0.08; p = 0.13) in KOA patients. In addition, tDCS did not significantly improve the short-term (SMD: -0.13; 95% CI: -0.35, 0.08; p = 0.22) and long-term (SMD: 0.02; 95% CI: -0.22, 0.25; p = 0.90) physical function in patients with KOA. CONCLUSIONS: The tDCS can reduce short-term pain intensity and sensitivity but fails to significantly relieve long-term pain intensity and improve the physical function in patients with KOA. Thus, tDCS may be a potential therapeutic tool to reduce short-term pain intensity and pain sensitivity in patients with KOA.

[Niche and interspecific association of main woody plants in Cunninghamia lanceolata plantation community in Jianfengling, China]. / 尖峰岭杉木人工林群落主要木本植物的生态位和种间联结.

Studies on niche and interspecific association can reveal plant interspecific relationship in the community, and provide theoretical support for promoting the transformation and development of plantation to natural forest. Based on Cunninghamia lanceolata investigation data of permanent plots of plantation in Jianfengling area of Hainan Tropical Rainforest National Park, we analyzed niche and interspecific association of the top 20 woody species in the community according to their importance values. The results showed that there were 163 species of woody species belonging to 101 genera and 55 families in the C. lanceolata plantation community, with complex species composition. As a constructive species, C. lanceolata had the highest importance value and niche breadth, and thus was the absolute dominant species in the community. It had a large niche overlap and niche similarity with many other species, among which the highest was observed in Adinandra hainanensis. The average niche overlap and niche similarity of the community were 0.54 and 0.49, respectively. The change trends of those two niche indicators were basically the same, indicating that some species were similar in resource demands. The overall association of main woody species was significantly positive. The χ2 test, association coefficient, Pearson correlation coefficient, and Spearman rank correlation coefficient suggested that the amounts of pairs with positive association were more than that with negative ones. The proportion of significant association species pairs was relatively low, indicating that the community stability was strong, species could coexist stably, and most species did not form close ties. On the whole, C. lanceolata had inhibited the regeneration of original tree species, and A. hainanensis, Garcinia oblongifolia, and Heptapleurum heptaphyllum could be used in natural transformation and restoration of C. lanceolata plantation in the Hainan Tropical Rainforest National Park.

Physics-Informed Inverse Design of Programmable Metasurfaces.

Emerging reconfigurable metasurfaces offer various possibilities for programmatically manipulating electromagnetic waves across spatial, spectral, and temporal domains, showcasing great potential for enhancing terahertz applications. However, they are hindered by limited tunability, particularly evident in relatively small phase tuning over 270°, due to the design constraints with time-intensive forward design methodologies. Here, a multi-bit programmable metasurface is demonstrated capable of terahertz beam steering facilitated by a developed physics-informed inverse design (PIID) approach. Through integrating a modified coupled mode theory (MCMT) into residual neural networks, the PIID algorithm not only significantly increases the design accuracy compared to conventional neural networks but also elucidates the intricate physical relations between the geometry and the modes. Without decreasing the reflection intensity, the method achieves the enhanced phase tuning as large as 300°. Additionally, the inverse-designed programmable beam steering metasurface is experimentally validated, which is adaptable across 1-bit, 2-bit, and tri-state coding schemes, yielding a deflection angle up to 68° and broadened steering coverage. The demonstration provides a promising pathway for rapidly exploring advanced metasurface devices, with potentially great impact on communication and imaging technologies.

Thermosensitive and injectable chitosan-based hydrogel embedding umbilical cord mesenchymal stem cells for ß-cell repairing in type 2 diabetes mellitus.

A thermosensitive and injectable hydrogel composed of chitosan (CS), chitosan biguanide hydrochloride (CSG) and collagen (CO) could embed umbilical cord mesenchymal stem cells (UC-MSCs), then was applied for the type 2 diabetes mellitus (T2DM) treatment in vivo. UC-MSCs could adhere well on CS/CSG/CO hydrogel surface and cell division could be clearly observed. Especially, UC-MSCs maintained alive till they grew in CS/CSG/CO hydrogel for 8 days, while the amount of UC-MSCs was limited due to the steric hindrance in hydrogel. To T2DM mice contrastive treatment by intraperitoneal injection for thirteen weeks, UC-MSCs + Hydrogel group could improve the impaired glucose tolerance, maintain glucose homeostasis in vivo, and restore islet morphology for T2DM mice. The immunofluorescence staining and western blot experiments further displayed that both the nuclear antigen Ki67 for cell proliferation and pancreatic duodenal homeobox-1 (Pdx1) expression in UC-MSCs + Hydrogel group were significantly higher than the expressions in untreated T2DM group and treated UC-MSCs + PBS group, which indicated that UC-MSCs + Hydrogel elevated ß cell transcriptional activity. Moreover, the positivity rates of iNOS and CD163 in UC-MSCs + Hydrogel group were generally decreased and increased, respectively, compared to those in untreated T2DM group and treated UC-MSCs + PBS group. It displayed that UC-MSCs + Hydrogel could reduce M1 macrophage expression and increase M2 macrophage polarization in T2DM mice.

Genomic and Metagenomic Insights into the Distribution of Nicotine-degrading Enzymes in Human Microbiota.

Introduction: Nicotine degradation is a new strategy to block nicotine-induced pathology. The potential of human microbiota to degrade nicotine has not been explored. Aims: This study aimed to uncover the genomic potentials of human microbiota to degrade nicotine. Methods: To address this issue, we performed a systematic annotation of Nicotine-Degrading Enzymes (NDEs) from genomes and metagenomes of human microbiota. A total of 26,295 genomes and 1,596 metagenomes for human microbiota were downloaded from public databases and five types of NDEs were annotated with a custom pipeline. We found 959 NdhB, 785 NdhL, 987 NicX, three NicA1, and three NicA2 homologs. Results: Genomic classification revealed that six phylum-level taxa, including Proteobacteria, Firmicutes, Firmicutes_A, Bacteroidota, Actinobacteriota, and Chloroflexota, can produce NDEs, with Proteobacteria encoding all five types of NDEs studied. Analysis of NicX prevalence revealed differences among body sites. NicX homologs were found in gut and oral samples with a high prevalence but not found in lung samples. NicX was found in samples from both smokers and non-smokers, though the prevalence might be different. Conclusion: This study represents the first systematic investigation of NDEs from the human microbiota, providing new insights into the physiology and ecological functions of human microbiota and shedding new light on the development of nicotine-degrading probiotics for the treatment of smoking-related diseases.

Alkaline phosphatase-activated prodrug system based on a bifunctional CuO NP tandem nanoenzyme for on-demand bacterial inactivation and wound disinfection.

Nanozymes are promising antimicrobials, as they produce reactive oxygen species (ROS). However, the intrinsic lack of selectivity of ROS in distinguishing normal flora from pathogenic bacteria deprives nanozymes of the necessary selectivities of ideal antimicrobials. Herein, we exploit the physiological conditions of bacteria (high alkaline phosphatase (ALP) expression) using a novel CuO nanoparticle (NP) nanoenzyme system to initiate an ALP-activated ROS prodrug system for use in the on-demand precision killing of bacteria. The prodrug strategy involves using 2-phospho-L-ascorbic acid trisodium salt (AAP) that catalyzes the ALP in pathogenic bacteria to generate ascorbic acid (AA), which is converted by the CuO NPs, with intrinsic ascorbate oxidase- and peroxidase-like activities, to produce ROS. Notably, the prodrug system selectively kills Escherichia coli (pathogenic bacteria), with minimal influence on Staphylococcus hominis (non-pathogenic bacteria) due to their different levels of ALP expression. Compared to the CuO NPs/AA system, which generally depletes ROS during storage, CuO NPs/AAP exhibits a significantly higher stability without affecting its antibacterial activity. Furthermore, a rat model is used to indicate the applicability of the CuO NPs/AAP fibrin gel in wound disinfection in vivo with negligible side effects. This study reveals the therapeutic precision of this bifunctional tandem nanozyme platform against pathogenic bacteria in ALP-activated conditions.

SIRT3 sulfhydration using hydrogen sulfide inhibited angiotensin II-induced atrial fibrosis and vulnerability to atrial fibrillation via suppression of the TGF-ß1/smad2/3 signalling pathway.

Atrial fibrosis is associated with the occurrence of atrial fibrillation (AF) and regulated by the transforming growth factor-ß1 (TGF-ß1)/Smad2/3 signalling pathway. Unfortunately, the mechanisms of regulation of TGF-ß1/Smad2/3-induced atrial fibrosis and vulnerability to AF remain still unknown. Previous studies have shown that sirtuin3 (SIRT3) sulfhydration has strong anti-fibrotic effects. We hypothesised that SIRT3 sulfhydration inhibits angiotensin II (Ang-II)-induced atrial fibrosis via blocking the TGF-ß1/Smad2/3 signalling pathway. In this study, we found that SIRT3 expression was decreased in the left atrium of patients with AF compared to that in those with sinus rhythm (SR). In vitro, SIRT3 knockdown by small interfering RNA significantly expanded Ang-II-induced atrial fibrosis and TGF-ß1/Smad2/3 signalling pathway activation, whereas supplementation with Sodium Hydrosulfide (NaHS, exogenous hydrogen sulfide donor and sulfhydration agonist) and SIRT3 overexpression using adenovirus ameliorated Ang-II-induced atrial fibrosis. Moreover, we observed suppression of the TGF-ß1/Smad2/3 pathway when Ang-II was combined with NaHS treatment, and the effect of this co-treatment was consistent with that of Ang-II combined with LY3200882 (Smad pathway inhibitor) on reducing atrial fibroblast proliferation and cell migration in vitro. Supplementation with dithiothreitol (DTT, a sulfhydration inhibitor) and adenovirus SIRT3 shRNA blocked the ameliorating effect of NaHS and AngII co-treatment on atrial fibrosis in vitro. Finally, continued treatment with NaHS in rats ameliorated atrial fibrosis and remodelling, and further improved AF vulnerability induced by Ang-II, which was reversed by DTT and adenovirus SIRT3 shRNA, suggesting that SIRT3 sulfhydration might be a potential therapeutic target in atrial fibrosis and AF.

Liver-on-a-Chip Integrated with Label-Free Optical Biosensors for Rapid and Continuous Monitoring of Drug-Induced Toxicity.

Drug toxicity assays using conventional 2D static cultures and animal studies have limitations preventing the translation of potential drugs to the clinic. The recent development of organs-on-a-chip platforms provides promising alternatives for drug toxicity/screening assays. However, most studies conducted with these platforms only utilize single endpoint results, which do not provide real-time/ near real-time information. Here, a versatile technology is presented that integrates a 3D liver-on-a-chip with a label-free photonic crystal-total internal reflection (PC-TIR) biosensor for rapid and continuous monitoring of the status of cells. This technology can detect drug-induced liver toxicity by continuously monitoring the secretion rates and levels of albumin and glutathione S-transferase α (GST-α) of a 3D liver on-a-chip model treated with Doxorubicin. The PC-TIR biosensor is based on a one-step antibody functionalization with high specificity and a detection range of 21.7 ng mL-1 to 7.83 x 103 ng mL-1 for albumin and 2.20 ng mL-1 to 7.94 x 102 ng mL-1 for GST-α. This approach provides critical advantages for the early detection of drug toxicity and improved temporal resolution to capture transient drug effects. The proposed proof-of-concept study introduces a scalable and efficient plug-in solution for organ-on-a-chip technologies, advancing drug development and in vitro testing methods by enabling timely and accurate toxicity assessments.

SLC13A3 is a major effector downstream of activated ß-catenin in liver cancer pathogenesis.

Activated Wnt/ß-catenin pathway is a key genetic event in liver cancer development. Solute carrier (SLC) transporters are promising drug targets. Here, we identify SLC13A3 as a drug-targetable effector downstream of ß-catenin in liver cancer. SLC13A3 expression is elevated in human liver cancer samples with gain of function (GOF) mutant CTNNB1, the gene encoding ß-catenin. Activation of ß-catenin up-regulates SLC13A3, leading to intracellular accumulation of endogenous SLC13A3 substrates. SLC13A3 is identified as a low-affinity transporter for glutathione (GSH). Silencing of SLC13A3 downregulates the leucine transporter SLC7A5 via c-MYC signaling, leading to leucine depletion and mTOR inactivation. Furthermore, silencing of SLC13A3 depletes GSH and induces autophagic ferroptosis in ß-catenin-activated liver cancer cells. Importantly, both genetic inhibition of SLC13A3 and a small molecule SLC13A3 inhibitor suppress ß-catenin-driven hepatocarcinogenesis in mice. Altogether, our study suggests that SLC13A3 could be a promising therapeutic target for treating human liver cancers with GOF CTNNB1 mutations.

Immunogenomic profiles and therapeutic options of the pan-programmed cell death-related lncRNA signature for patients with bladder cancer.

Programmed cell death (PCD) is a process that eliminates infected, damaged, or possibly neoplastic cells to sustain homeostatic multicellular organisms. Although long noncoding RNAs (lncRNAs) are involved in various types of PCD and regulate tumor growth, invasion, and migration, the role of PCD-related lncRNAs in bladder cancer still lacks systematic exploration. In this research, we integrated multiple types of PCD as pan-PCD and identified eight pan-PCD-related lncRNAs (LINC00174, HCP5, HCG27, UCA1, SNHG15, GHRLOS, CYB561D2, and AGAP11). Then, we generated a pan-PCD-related lncRNA prognostic signature (PPlncPS) with excellent predictive power and reliability, which performed equally well in the E-MTAB-4321 cohort. In comparison with the low-PPlncPS score group, the high-PPlncPS score group had remarkably higher levels of angiogenesis, matrix, cancer-associated fibroblasts, myeloid cell traffic, and protumor cytokine signatures. In addition, the low-PPlncPS score group was positively correlated with relatively abundant immune cell infiltration, upregulated expression levels of immune checkpoints, and high tumor mutation burden (TMB). Immunogenomic profiles revealed that patients with both low PPlncPS scores and high TMB had the best prognosis and may benefit from immune checkpoint inhibitors. Furthermore, for patients with high PPlncPS scores, docetaxel, staurosporine, and luminespib were screened as potential therapeutic candidates. In conclusion, we generated a pan-PCD-related lncRNA signature, providing precise and individualized prediction for clinical prognosis and some new insights into chemotherapy and immune checkpoint inhibitor therapy for bladder cancer.

Seasonal variations affect the ecosystem functioning and microbial assembly processes in plantation forest soils.

While afforestation mitigates climate concerns, the impact of afforestation on ecological assembly processes and multiple soil functions (multifunctionality) in afforested areas remains unclear. The Xiong'an New Area plantation forests (Pinus and Sophora forests) in North China were selected to examine the effects of plantation types across four distinct seasons on soil microbiomes. Three functional categories (nutrient stocks, organic matter decomposition, and microbial functional genes) of multifunctionality and the average (net) multifunctionality were quantified. All these categories are directly related to soil functions. The results showed that net soil multifunctionality as a broad function did not change seasonally, unlike other narrow functional categories. Bacterial communities were deterministically (variable selection and homogenous selection) structured, whereas the stochastic process of dispersal limitation was mainly responsible for the assembly and turnover of fungal and protist communities. In Pinus forests, winter initiates a sudden shift from deterministic to stochastic processes in bacterial community assembly, accompanied by decreased Shannon diversity and heightened nutrient cycling (nutrient stocks and organic matter decomposition). This indicates the potential vulnerability of deterministic assembly to seasonal fluctuations, particularly in environments rich in nutrients. The results predicted that protist community composition was uniquely structured with C-related functional activities relative to bacterial and fungal ß-diversity variations, which were mostly explained by seasonal variations. Our study highlighted the importance of the protist phagocytosis process on soil microbial interactions through the predicted impact of protist α-diversity on microbial cooccurrence network parameters. This association might be driven by the high abundance of protist consumers as the main predators of bacterial and fungal lineages in our sampling plots. Our findings reveal that the complexity of microbial co-occurrence interactions was considerably higher in spring, perhaps attributing thermal variability and increased resource availability within spring that foster microbial diversity and network complexity. This study contributes to local ecosystem prospects to model the behavior of soil biota seasonally and their implied effects on soil functioning and microbial assembly processes, which will benefit global-scale afforestation programs by promoting novel, precise, and rational plantation forests for future environmental sustainability and self-sufficiency.

Fabrication of a novel nanofiltration membrane using an Mg-Fe layered double hydroxide for dye/salt separation.

Mg-Fe layered hydroxide (LDH) was synthesized by the double titration method and added to trimesoyl chloride (TMC) to prepare an Mg-Fe LDH-modified polyamide nanofiltration (NF) membrane by interfacial polymerization (IP). Compared to the pure polyamide NF membrane, the Mg-Fe LDH-modified membrane presented a wrinkled structure and a comparatively smooth surface. Additionally, the permeation flux and rejection rate of the modified NF membrane for 1000 mg L-1 Na2SO4 solution were 61.7 L m-2 h-1 and 95.9%, respectively. When the Mg-Fe LDH modified NF membrane was used to separate dye/NaCl mixed solutions, the rejection of NaCl was less than 17% and the rejection rate of Coomassie Brilliant Blue (CBB) molecules was close to 100%. At the same time, the concentration of CBB increased from 500 mg L-1 to 1151 mg L-1 which means that the LDH modified NF membrane could separate CBB/NaCl effectively and could concentrate CBB at the same time.

Targeting Notch signaling pathways with natural bioactive compounds: a promising approach against cancer.

Notch signaling pathway is activated abnormally in solid and hematological tumors, which perform essential functions in cell differentiation, survival, proliferation, and angiogenesis. The activation of Notch signaling and communication among Notch and other oncogenic pathways heighten malignancy aggressiveness. Thus, targeting Notch signaling offers opportunities for improved survival and reduced disease incidence. Already, most attention has been given to its role in the cancer cells. Recent research shows that natural bioactive compounds can change signaling molecules that are linked to or interact with the Notch pathways. This suggests that there may be a link between Notch activation and the growth of tumors. Here, we sum up the natural bioactive compounds that possess inhibitory effects on human cancers by impeding the Notch pathway and preventing Notch crosstalk with other oncogenic pathways, which provoke further study of these natural products to derive rational therapeutic regimens for the treatment of cancer and develop novel anticancer drugs. This review revealed Notch as a highly challenging but promising target in oncology.