Exploration of Unconventional excitation wavelength and dynamic emission in rare-earth doped multilayer core-shell Structures: Application for optical "Hard" and "Soft" switching.

Optical switches are increasingly acknowledged for their potential advantages over mechanical counterparts in various domains. However, research on optical switches remains relatively nascent, primarily focusing on applications like anti-counterfeiting, switching chemical reactions, etc., while neglecting the control of photocurrent switching. Here, we have developed NaYF4:30 %Er-NaYF4-NaYF4:20 %Ho-NaYF4 core-shell nanocrystals with unique upconversion (UC) multi-color emission properties under 1530 nm, 980 nm and 1150 nm laser excitations. These nanocrystals allow for optical control of circuit switching by modulating photocurrent signals in photosensitive circuits. The UC emission is due to the self-sensitization of rare earth ions in the core and shell. By adjusting the intermediate shell thickness, we have optimized the luminescence and investigated the mechanism. Combining these nanocrystals with a WO3 quantum dots (QDs) photochromic hydrogel, dynamic variation of UC emissions could be realized. Moreover, by combining with a commercial silicon photodetector, we constructed a photosensitive circuit demonstrating the modulation of photocurrent signal output and realized the "hard switching" of rapid circuit cutoff. Furthermore, by using the photochromic effect of WO3 QDs, the "soft switching" of slow circuit cutoff and recovery were also achieved. This work has significant implications for the development and application such as energy management system and smart home of optical switches in various fields.

Role of Neurotropic Viruses in Brain Metastasis of Breast Cancer: Mechanisms and Therapeutic Implications.

Neurotropic viruses have been implicated in altering the central nervous system microenvironment and promoting brain metastasis of breast cancer through complex interactions involving viral entry mechanisms, modulation of the blood-brain barrier, immune evasion, and alteration of the tumour microenvironment. This narrative review explores the molecular mechanisms by which neurotropic viruses such as Herpes Simplex Virus, Human Immunodeficiency Virus, Japanese Encephalitis Virus, and Rabies Virus facilitate brain metastasis, focusing on their ability to disrupt blood-brain barrier integrity, modulate immune responses, and create a permissive environment for metastatic cell survival and growth within the central nervous system. Current therapeutic implications and challenges in targeting neurotropic viruses to prevent or treat brain metastasis are discussed, highlighting the need for innovative strategies and multidisciplinary approaches in virology, oncology, and immunology.

m6A-modified cenRNA stabilizes CENPA to ensure centromere integrity in cancer cells.

m6A modification is best known for its critical role in controlling multiple post-transcriptional processes of the mRNAs. Here, we discovered elevated levels of m6A modification on centromeric RNA (cenRNA) in cancerous cells compared with non-cancerous cells. We then identified CENPA, an H3 variant, as an m6A reader of cenRNA. CENPA is localized at centromeres and is essential in preserving centromere integrity and function during mitosis. The m6A-modified cenRNA stabilizes centromeric localization of CENPA in cancer cells during the S phase of the cell cycle. Mutations of CENPA at the Leu61 and the Arg63 or removal of cenRNA m6A modification lead to loss of centromere-bound CENPA during S phase. This in turn results in compromised centromere integrity and abnormal chromosome separation and hinders cancer cell proliferation and tumor growth. Our findings unveil an m6A reading mechanism by CENPA that epigenetically governs centromere integrity in cancer cells, providing potential targets for cancer therapy.

Implementing Optogenetic-Controlled Bacterial Systems in Drosophila melanogaster for Alleviation of Heavy Metal Poisoning.

Drosophila melanogaster (fruit fly) is an animal model chassis in biological and genetic research owing to its short life cycle, ease of cultivation, and acceptability to genetic modification. While the D. melanogaster chassis offers valuable insights into drug efficacy, toxicity, and mechanisms, several obvious challenges such as dosage control and drug resistance still limit its utility in pharmacological studies. Our research combines optogenetic control with engineered gut bacteria to facilitate the precise delivery of therapeutic substances in D. melanogaster for biomedical research. We have shown that the engineered bacteria can be orally administered to D. melanogaster to get a stable density of approximately 28,000 CFUs/per fly, leading to no detectable negative effects on the growth of D. melanogaster. In a model of D. melanogaster exposure to heavy metal, these orally administered bacteria uniformly express target genes under green light control to produce MtnB protein for binding and detoxifying lead, which significantly reduces the level of oxidative stress in the intestinal tract of Pb-treated flies. This pioneering study lays the groundwork for using optogenetic-controlled bacteria in the model chassis D. melanogaster to advance biomedical applications.

Optimizing trigeneration energy systems: Biogas-centric methanol production via direct CO2 hydrogenation with advanced integration of PEM electrolyzer and LNG cold technology.

Biogas, a sustainable alternative to fossil fuels, addresses issues of non-renewability and accessibility. Its structural similarity to fossil fuels makes it a potent option for energy systems. With this in mind, this paper discusses a novel trigeneration system that utilizes biogas and Liquefied natural gas cooling to produce methanol, electricity, cold water, hot water, oxygen, and natural gas. The system integrates various components such as a biogas burner, Kalina cycle, organic Rankine cycle, liquefied natural gas liquid gasification cycle, proton exchange membrane electrolyzer, and methanol synthesis unit. Simulation via Aspen HYSYS software includes an analysis of energy, exergy, economic, and environmental aspects. Efficiency assessment in single generation, cogeneration, trigeneration, and chemical trigeneration modes concludes chemical trigeneration as most efficient, with the proton exchange membrane electrolyzer being the most efficient subsystem. Key variables like Kalina cycle evaporator temperature, gas flow rate to the methanol reactor, and organic Rankine cycle working fluid pressure are assessed. Predictions on thermodynamic, environmental, and economic behaviors, along with their fluctuations, are made. Using a thermoeconomic approach, the economic analysis determines an exergy unit cost of 59.79 $/GJ and a total cost rate of 2764 $/h. Overall, this work presents a novel and efficient chemical trigeneration system that utilizes biogas and LNG cooling to produce multiple products.

DRPChain: A new blockchain-based trusted DRM scheme for image content protection.

The unauthorized replication and distribution of digital images pose significant challenges to copyright protection. While existing solutions incorporate blockchain-based techniques such as perceptual hashing and digital watermarking, they lack large-scale experimental validation and a dedicated blockchain consensus protocol for image copyright management. This paper introduces DRPChain, a novel digital image copyright management system that addresses these issues. DRPChain employs an efficient cropping-resistant robust image hashing algorithm to defend against 14 common image attacks, demonstrating an 85% success rate in watermark extraction, 10% higher than the original scheme. Moreover, the paper designs the K-Raft consensus algorithm tailored for image copyright protection. Comparative experiments with Raft and benchmarking against PoW and PBFT algorithms show that K-Raft reduces block error rates by 2%, improves efficiency by 300ms compared to Raft, and exhibits superior efficiency,decentralization, and throughput compared to PoW and PBFT. These advantages make K-Raft more suitable for digital image copyright protection. This research contributes valuable insights into using blockchain technology for digital copyright protection, providing a solid foundation for future exploration.

Enhancing electrochemical carbon dioxide capture with supercapacitors.

Supercapacitors are emerging as energy-efficient and robust devices for electrochemical CO2 capture. However, the impacts of electrode structure and charging protocols on CO2 capture performance remain unclear. Therefore, this study develops structure-property-performance correlations for supercapacitor electrodes at different charging conditions. We find that electrodes with large surface areas and low oxygen functionalization generally perform best, while a combination of micro- and mesopores is important to achieve fast CO2 capture rates. With these structural features and tunable charging protocols, YP80F activated carbon electrodes show the best CO2 capture performance with a capture rate of 350 mmolCO2 kg-1 h-1 and a low electrical energy consumption of 18 kJ molCO2-1 at 300 mA g-1 under CO2, together with a long lifetime over 12000 cycles at 150 mA g-1 under CO2 and excellent CO2 selectivity over N2 and O2. Operated in a "positive charging mode", the system achieves excellent electrochemical reversibility with Coulombic efficiencies over 99.8% in the presence of approximately 15% O2, alongside stable cycling performance over 1000 cycles. This study paves the way for improved supercapacitor electrodes and charging protocols for electrochemical CO2 capture.

Development and validation of a nomogram for predicting rapid relapse in triple-negative breast cancer patients treated with neoadjuvant chemotherapy.

Background: Triple-negative breast cancer (TNBC) accounts for disproportionately poor outcomes in breast cancer, driven by a subset of rapid-relapse TNBC (rrTNBC) with marked chemoresistance, rapid metastatic spread, and poor survival. This study aimed to develop and validate a nomogram based on clinicopathological characteristics to predict rapid relapse in TNBC patients treated with neoadjuvant chemotherapy (NAC) first. Methods: The clinicopathological data of 504 TNBC patients treated with NAC first in Tianjin Medical University Cancer Hospital were analyzed retrospectively, with 109 rapid relapsed patients, and 395 non-rapid relapsed patients, respectively. Based on clinicopathologic characteristics, and follow-up data were analyzed. The independent predictors of clinicopathological characteristics were identified by logistic regression analysis and then used to build a nomogram. The concordance index (C-index), the area under the curve (AUC) of receiver operating characteristic (ROC), and calibration plots were used to evaluate the performance of the model. Results: Univariate and multivariate logistic regression analyses showed that age at diagnosis (age≥50 years, OR = 0.325,95% CI:0.137-0.771), Nodal staging (N3 staging, OR = 13.669,95% CI:3.693-50.592),sTIL expression levels (sTIL intermediate expression, OR = 0.272,95% CI:0.109-0.678; sTIL high expression, OR = 0.169,95% CI:0.048-0.594), and NAC response (ORR, OR = 0.059,95% CI:0.024-0.143) were independent predictors of rapid relapse in TNBC patients treated with NAC firstly. Among these independent predictors, age ≥ 50 years, sTIL intermediate expression, sTIL high expression, and ORR in NAC were independent protective factors for rapid relapse in TNBC NAC patients. N3 staging was an independent risk factor for rapid relapse in TNBC NAC patients. The ROC curve, calibration curve, and decision curve analysis were used to validate the model. The C-Index of the training sets and validation sets were 0.938 and 0.910, respectively. The Brier scores of the training sets and validation sets were 0.076 and 0.097, respectively. Conclusion: This study developed and verified a nomogram for predicting rapid relapse in TNBC NAC patients, and the predictive model had high discrimination and accuracy.

Clinical efficacy and safety of acupuncture combined with statin in dyslipidemia: A meta-analysis and system review.

BACKGROUND: This study aims to systematically evaluate the clinical efficacy and safety of acupuncture in combination with statin therapy compared to statin monotherapy for the treatment of dyslipidemia. METHODS: A comprehensive search for relevant randomized controlled trials assessing the clinical efficacy of acupuncture and statin combination in the treatment of dyslipidemia was conducted. Databases including PubMed, EMbase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, China Biology Medicine disc, Wanfang database, and China Science and Technology Journal Database were searched up to October 27, 2023. RESULTS: Sixteen Chinese-language studies involving a total of 1333 subjects were included for analysis. The meta-analysis revealed that the total effective rate of acupuncture combined with statin was significantly higher than that of statin alone (odds ratios = 3.32, 95% confidence intervals [CI] = 2.33 to 4.72). Furthermore, the combination of acupuncture with statin treatment resulted in a significant reduction in triglyceride levels (mean differences [MD] = -0.72 mmol/L, 95% CI = -1.05 to -0.4), total cholesterol levels (MD = -0.79 mmol/L, 95% CI = -1.07 to -0.51), low-density lipoprotein cholesterol levels (MD = -0.61 mmol/L, 95% CI = -0.95 to -0.27) and traditional Chinese medicine syndrome integral (MD = -1.32, 95% CI = -1.75 to -0.89), compared to statin treatment alone. Additionally, the high-density lipoprotein cholesterol level was higher in the combined acupuncture and statin treatment group than in the statin treatment alone group (MD = 0.44 mmol/L, 95% CI = 0.09 to 0.79). Notably, the rate of adverse reactions reported with combined acupuncture and statin treatment was lower than that with statin therapy alone. CONCLUSION: Our findings support the potential of acupuncture combined with statin as a viable clinical treatment option for dyslipidemia. However, it is important to note that current research on the mechanism of acupuncture for lipid-lowering has not yielded definitive results, and there are inherent biases in the conducted clinical studies.

Flexible and high-strength bioactive glass fiber membrane for bone regeneration with the aid of alkoxysilane sol spinnability.

In this research, the spinnability of bioactive glass (BG) precursor solution was supplied by alkoxysilane sol with appropriate molar ratio of H2O/silicon (R) to prepare bioactive glass fiber membrane (BFM) using electrospinning (ES) technique. Alkoxysilane could form a linear or chain-like colloidal aggregation in hydrolysis-polycondensation with R = 2 or so, thereby exhibiting good spinnability. Therefore, the role of polymer binders could be largely replaced. Due to the significant decrease of polymer binder, the defects within the fibers are largely reduced and degree of fiber densification was improved after calcination, leading to BFM drastically enhanced strength and flexibility. The effect of R and calcination temperature on mechanical performance were investigated in detail. The tensile strength could reach the highest value 2.31 MPa with R = 2 and calcination at 700 °C. In addition, under this preparation condition, the BFM also possessed good flexibility with bending rigidity 37.7 mN. Furthermore, the great performance of promoting cell proliferation and osteogenesis could be observed from in vitro cellular experiment. The BFM calcined at 750 °C exhibited the best promoting osteogenic differentiation ability. The rat skull defect model revealed BFM could perform well in osteogenesis in vivo.

Broad-spectrum coronavirus neutralization induced by hetero RBD-Fc protein vaccine.

In the landscape of infectious diseases, human coronaviruses such as SARS-CoV, MERS-CoV, and SARS-CoV-2 pose significant threats, characterized by severe respiratory illnesses and notable resistance to conventional treatments due to their rapid evolution and the emergence of diverse variants, particularly within SARS-CoV-2. This study investigated the development of broad-spectrum coronavirus vaccines using heterodimeric RBD-Fc proteins engineered through the "Knob-into-Hole" technique. We constructed various recombinant proteins incorporating the receptor-binding domains (RBDs) of different coronaviruses. Heterodimers combining RBDs from SARS-CoV-2 with those of SARS-CoV or MERS-CoV elicited superior neutralizing responses compared to homodimeric proteins in murine models. Additionally, heterotetrameric proteins, specifically D614G_Delta/BA.1_XBB.1.5-RBD and MERS_D614G/BA.1_XBB.1.5-RBD, elicited remarkable breadth and potency in neutralizing all known SARS-CoV-2 variants, SARS-CoV, related sarbecoviruses like GD-Pangolin and WIV1, and even MERS-CoV pseudoviruses. Furthermore, these heterotetrameric proteins also demonstrated enhanced cellular immune responses. These findings underscore the potential of recombinant hetero proteins as a universal vaccine strategy against current and future coronavirus threats.

Branched hybridization chain reaction and tetrahedral DNA-based trivalent aptamer powered SERS sensor for ultra-highly sensitive detection of cancer-derived exosomes.

Exosomes have emerged as a promising noninvasive biomarker for early cancer diagnosis due to their ability to carry specific bioinformation related to cancer cells. However, accurate detection of trace amount of cancer-derived exosomes in complex blood remains a significant challenge. Herein, an ultra-highly sensitive SERS sensor, powered by the branched hybridization chain reaction (bHCR) and tetrahedral DNA-based trivalent aptamer (triApt-TDN), has been proposed for precise detection of cancer-derived exosomes. Taking gastric cancer SGC-7901 cells-derived exosomes as a test model, the triApt-TDNs were constructed by conjugating aptamers specific to mucin 1 (MUC1) protein with tetrahedral DNAs and subsequently immobilized on the surface of silver nanorods (AgNRs) arrays to create SERS-active sensing chips capable of specifically capturing exosomes overexpressing MUC1 proteins. The bHCR was further initiated by the trigger aptamers (tgApts) bound to exosomes, and as a result the SERS tags were assembled into AuNP network structures with abundant SERS hotspots. By optimizing the sensing conditions, the SERS sensor showed good performance in ultra-highly sensitive detection of target exosomes within 60 min detection time, with a broad response ranging of 1.44 to 1.44 × 104 particles·µL-1 and an ultralow limit of detection capable of detecting a single exosome in 2 µL sample. Furthermore, the SERS sensor exhibited good uniformity, repeatability and specificity, and capability to distinguish between gastric cancer (GC) patients and healthy controls (HC) through the detection of exosomes in clinical human serums, indicating its promising clinical potential for early diagnosis of gastric cancer.

Effects of Bushen Huoxue on integrin ß3 and integrin ß5 in the placental tissue of mice with repeated implantation failure caused by phospholipid antibodies.

BACKGROUND: This study aimed to investigate the effects of the Kidney-Tonifying and Blood-Activating Formula on combating the downregulation of integrin ß3 and integrin ß5 in mouse placental tissue induced by phospholipid antibodies. OBJECTIVE: This study aimed to investigate the effects of kidney-tonifying and blood-activating formulations on combating the downregulation of integrin ß3 and integrin ß5 in mouse placental tissue induced by phospholipid antibodies. METHODS: Mice in the phospholipid antibody group and phospholipid antibody + kidney-tonifying and blood-activating formula group underwent repeated implantation experiments, and the expression of integrin ß3 and integrin ß5 in placental tissue was observed. The effects of the kidney-tonifying and blood-activating formula on mouse placental tissue were evaluated through biochemical index tests, histopathological observations, and immunohistochemical staining. RESULTS: After intervention with the kidney-tonifying and blood-activating formula, the expression of integrin ß3 and integrin ß5 in placental tissue was notably upregulated, and placental structure was restored. Kidney-Tonifying and Blood-Activating Formula significantly improved abnormal biochemical indices and exerted a remarkable protective effect on placental tissue pathology. CONCLUSION: The kidney-tonifying and blood-activating formula effectively counteracted the downregulation of integrin ß3 and integrin ß5 in mouse placental tissue induced by phospholipid antibodies and alleviated placental tissue pathology through structural improvement and protection. Therefore, kidney-tonifying and blood-activating formulas may serve as potential therapeutic agents for recurrent implantation failure, offering new insights and approaches for clinical treatment.

Multi-Omics Integration Analysis Pinpoint Proteins Influencing Brain Structure and Function: Toward Drug Targets and Neuroimaging Biomarkers for Neuropsychiatric Disorders.

Integrating protein quantitative trait loci (pQTL) data and summary statistics from genome-wide association studies (GWAS) of brain image-derived phenotypes (IDPs) can benefit in identifying IDP-related proteins. Here, we developed a systematic omics-integration analytic framework by sequentially using proteome-wide association study (PWAS), Mendelian randomization (MR), and colocalization (COLOC) analyses to identify the potentially causal brain and plasma proteins for IDPs, followed by pleiotropy analysis, mediation analysis, and drug exploration analysis to investigate potential mediation pathways of pleiotropic proteins to neuropsychiatric disorders (NDs) as well as candidate drug targets. A total of 201 plasma proteins and 398 brain proteins were significantly associated with IDPs from PWAS analysis. Subsequent MR and COLOC analyses further identified 313 potentially causal IDP-related proteins, which were significantly enriched in neural-related phenotypes, among which 91 were further identified as pleiotropic proteins associated with both IDPs and NDs, including EGFR, TMEM106B, GPT, and HLA-B. Drug prioritization analysis showed that 6.33% of unique pleiotropic proteins had drug targets or interactions with medications for NDs. Nine potential mediation pathways were identified to illustrate the mediating roles of the IDPs in the causal effect of the pleiotropic proteins on NDs, including the indirect effect of TMEM106B on Alzheimer's disease (AD) risk via radial diffusivity (RD) of the posterior limb of the internal capsule (PLIC), with the mediation proportion being 11.18%, and the indirect effect of EGFR on AD through RD of PLIC, RD of splenium of corpus callosum (SCC), and fractional anisotropy (FA) of SCC, with the mediation proportion being 18.99%, 22.79%, and 19.91%, respectively. These findings provide novel insights into pathogenesis, drug targets, and neuroimaging biomarkers of NDs.

Breaking the Conversion-Selectivity Trade-Off in Methanol Synthesis from CO2 Using Dual Intimate Oxide/Metal Interfaces.

The selective hydrogenation of carbon dioxide (CO2) to value-added chemicals, e.g., methanol, using green hydrogen retrieved from renewable resources is a promising approach for CO2 emission reduction and carbon resource utilization. However, this process suffers from the competing side reaction of reverse water-gas shift (RWGS) and methanol decomposition, which often leads to a strong conversion-selectivity trade-off and thus a poor methanol yield. Here, we report that InOx coating of PdCu bimetallic nanoparticles (NPs) to construct intimate InOx/Cu and InOx/PdIn dual interfaces enables the break of conversion-selectivity trade-off by achieving ∼80% methanol selectivity at ∼20% CO2 conversion close to the thermodynamic limit, far superior to that of conventional metal catalysts with a single active metal/oxide interface. Comprehensive microscopic and spectroscopic characterization revealed that the InOx/PdIn interface favors the activation of CO2 to formate, while the adjacent InOx/Cu interface readily converts formate intermediates to methoxy species in tandem, which thus cooperatively boosts methanol production. These findings of dual-interface synergies via oxide coating of bimetallic NPs open a new avenue to the design of active and selective catalysts for advanced catalysis.

Polarization of Macrophages in Tumor Microenvironment Using High-Throughput Single-Cell Metabolomics.

Macrophages consist of a heterogeneous population of functionally distinct cells that participate in many physiological and pathological processes. They exhibit prominent plasticity by changing their different functional phenotypes represented by proinflammatory (M1) and anti-inflammatory (M2) in response to different environmental stimuli. Emerging evidence illustrates the importance of intracellular metabolic pathways in macrophage polarizations and functions. In the tumor microenvironment (TME), macrophages tend to M2 polarization, which promotes tumor growth and leads to adverse physiological effects. Due to the lack of highly specific antigens in M1 and M2 macrophages, significant challenges present in isolating these subtypes from clinical samples or in vitro coculture models of tumor-immune cells. In reverse, the single-cell technique provides the possibility to investigate the factors influencing macrophage polarization in the TME. In this research, we employed inertial microfluidic chip-mass spectrometry (IMC-MS) to conduct single-cell metabolomics analysis of macrophages polarized into the two major phenotypes, respectively, and 213 metabolites were identified in total. Subsequently, differential metabolites between macrophage phenotypes were analyzed using volcano plots and binary logistic regression models. Glutamine was pinpointed as a key metabolite for the M1 and M2 phenotypes. Experimental results from both monoculture and coculture cell models demonstrated that M1 polarization is more reliant on the presence of glutamine in the culture environment than M2 polarization. Glutamine deficiency resulted in failed M1 polarization, while its absence had a less pronounced effect on M2 polarization. Replenishing an appropriate amount of glutamine during the intermediate stages of coculture models significantly enhanced the proportion of M1 polarization and suppressed the growth of tumor cells. This research elucidated glutamine as a key factor influencing macrophage polarization in the TME via single-cell metabolomics based on IMC-MS, offering promising insights and targets for tumor therapies.

Association between systemic immune-inflammation index and serum neurofilament light chain: a population-based study from the NHANES (2013-2014).

Background: The systemic immune-inflammation index (SII) is a novel inflammatory marker used to assess the immune-inflammatory status of the human body. The systemic immune inflammation has an interplay and mutual relationship with neurological disorders. Serum neurofilament light chain (sNfL) is widely regarded as a potential biomarker for various neurological diseases. The study aimed to examine the association between SII and sNfL. Methods: This cross-sectional investigation was conducted in a population with complete data on SII and sNfL from the 2013-2014 National Health and Nutrition Examination Survey (NHANES). The SII was calculated by dividing the product of platelet count and neutrophil count by the lymphocyte count. Multivariate linear regression models and smooth curves were used to explore the linear connection between SII and sNfL. Sensitivity analyses, interaction tests, and diabetes subgroup smoothing curve fitting were also performed. Results: A total of 2,025 participants were included in our present research. SII showed a significant positive association with the natural logarithm-transformed sNfL (ln-sNfL) in crude model [0.17 (0.07, 0.28)], partially adjusted model [0.13 (0.03, 0.22)], and fully adjusted model [0.12 (0.02, 0.22)]. In all participants, the positive association between SII and ln-sNfL served as a linear relationship, as indicated by a smooth curve. Interaction tests showed that age, gender, BMI, hypertension, and diabetes did not have a significant impact on this positive association (p for interaction >0.05). The subgroup analysis of diabetes was conducted using smooth curve fitting. It was found that compared to the group without diabetes and the group in a pre-diabetic state, the effect was more pronounced in the group with diabetes. Conclusion: Our findings suggest that there is a positive association between SII and sNfL. Furthermore, in comparison to individuals without diabetes and those in a pre-diabetic state, the positive association between SII and sNfL was more pronounced in individuals with diabetes. Further large-scale prospective studies are needed to confirm the association between SII and sNfL.

Chemically programmed metabolism drives a superior cell fitness for cartilage regeneration.

The rapid advancement of cell therapies underscores the importance of understanding fundamental cellular attributes. Among these, cell fitness-how transplanted cells adapt to new microenvironments and maintain functional stability in vivo-is crucial. This study identifies a chemical compound, FPH2, that enhances the fitness of human chondrocytes and the repair of articular cartilage, which is typically nonregenerative. Through drug screening, FPH2 was shown to broadly improve cell performance, especially in maintaining chondrocyte phenotype and enhancing migration. Single-cell transcriptomics indicated that FPH2 induced a super-fit cell state. The mechanism primarily involves the inhibition of carnitine palmitoyl transferase I and the optimization of metabolic homeostasis. In animal models, FPH2-treated human chondrocytes substantially improved cartilage regeneration, demonstrating well-integrated tissue interfaces in rats. In addition, an acellular FPH2-loaded hydrogel proved effective in preventing the onset of osteoarthritis. This research provides a viable and safe method to enhance chondrocyte fitness, offering insights into the self-regulatory mechanisms of cell fitness.

[Advances in Imaging-Based Evaluation of Solid Tumors Treated With Immune Checkpoint Inhibitors].

Immune checkpoint inhibitors have shown remarkable benefits in the treatment of solid tumors,while the occurrence of atypical response patterns and immune-related adverse events during treatment challenges the accuracy of therapeutic evaluation.Medical imaging is crucial for the evaluation of immunotherapy.It enables the assessment of treatment efficacy via both morphological and functional ways and offers unique a predictive value when being combined with artificial intelligence.Here we review the recent research progress in imaging-based evaluation of solid tumors treated with immune checkpoint inhibitors.