Deep Learning-Assisted Spectrum-Structure Correlation: State-of-the-Art and Perspectives.

Spectrum-structure correlation is playing an increasingly crucial role in spectral analysis and has undergone significant development in recent decades. With the advancement of spectrometers, the high-throughput detection triggers the explosive growth of spectral data, and the research extension from small molecules to biomolecules accompanies massive chemical space. Facing the evolving landscape of spectrum-structure correlation, conventional chemometrics becomes ill-equipped, and deep learning assisted chemometrics rapidly emerges as a flourishing approach with superior ability of extracting latent features and making precise predictions. In this review, the molecular and spectral representations and fundamental knowledge of deep learning are first introduced. We then summarize the development of how deep learning assist to establish the correlation between spectrum and molecular structure in the recent 5 years, by empowering spectral prediction (i.e., forward structure-spectrum correlation) and further enabling library matching and de novo molecular generation (i.e., inverse spectrum-structure correlation). Finally, we highlight the most important open issues persisted with corresponding potential solutions. With the fast development of deep learning, it is expected to see ultimate solution of establishing spectrum-structure correlation soon, which would trigger substantial development of various disciplines.

A novel engineered IL-21 receptor arms T-cell receptor-engineered T cells (TCR-T cells) against hepatocellular carcinoma.

Strategies to improve T cell therapy efficacy in solid tumors such as hepatocellular carcinoma (HCC) are urgently needed. The common cytokine receptor γ chain (γc) family cytokines such as IL-2, IL-7, IL-15 and IL-21 play fundamental roles in T cell development, differentiation and effector phases. This study aims to determine the combination effects of IL-21 in T cell therapy against HCC and investigate optimized strategies to utilize the effect of IL-21 signal in T cell therapy. The antitumor function of AFP-specific T cell receptor-engineered T cells (TCR-T) was augmented by exogenous IL-21 in vitro and in vivo. IL-21 enhanced proliferation capacity, promoted memory differentiation, downregulated PD-1 expression and alleviated apoptosis in TCR-T after activation. A novel engineered IL-21 receptor was established, and TCR-T armed with the novel engineered IL-21 receptors (IL-21R-TCR-T) showed upregulated phosphorylated STAT3 expression without exogenous IL-21 ligand. IL-21R-TCR-T showed better proliferation upon activation and superior antitumor function in vitro and in vivo. IL-21R-TCR-T exhibited a less differentiated, exhausted and apoptotic phenotype than conventional TCR-T upon repetitive tumor antigen stimulation. The novel IL-21 receptor in our study programs powerful TCR-T and can avoid side effects induced by IL-21 systemic utilization. The novel IL-21 receptor creates new opportunities for next-generation TCR-T against HCC.

Phosphorus-rich CoP4@N-C nanoarrays for efficient nitrate-to-ammonia electroreduction.

The electrochemical nitrate reduction reaction (NO3-RR) is a novel green method for ammonia synthesis. However, the lack of sufficient catalysts has hindered the development of the NO3-RR. This research develops a transformation of porous CoP@N-C/CC into porous phosphorus-rich CoP4@N-C/CC through high-temperature calcination. Due to its unique phosphating-rich structure, CoP4@N-C/CC exhibits an excellent Faraday efficiency (FE: 92.3%) and NH3 yield (610.2 µmol h-1 cm-2). Such a catalyst with more P-P bonds can provide more active sites, effectively enhancing the adsorption and reaction processes of reactant molecules. In addition, the catalyst has good durability and catalytic stability, which provides a possibility for the future application of electrocatalytic ammonia production.

Effects of family dignity interventions combined with standard palliative care on family adaptability, cohesion, and anticipatory grief in adult advanced cancer survivors and their family caregivers: A randomized controlled trial.

Background: Family involvement and comfort are equally important in palliative care. Dignity undertook a new meaning and novel challenges as a result of restrictions on visits and companionship during the pandemic. Family-centered family dignity interventions have been shown to be effective in increasing patients' sense of dignity, increasing levels of hope, and reducing psychological distress; however, the effectiveness in enhancing family adaptability and intimacy in the survivor-caregiver binary and reducing expected grief have been inconclusive. Objectives: The primary objective of this study was to assess the efficacy of family dignity interventions on family adaptability and cohesion. The secondary objective was to explore the effects of the interventions on anticipatory grief and psychological distress, and the lasting effect 1 month after the intervention. Design: A single-blinded, two-arm parallel group, randomized controlled trial was conducted in China. Settings: and methods: Ninety-eight dyads who met the inclusion criteria were randomly assigned to the family dignity intervention (n = 51) or standard palliative care group (n = 47) between June and August 2022. Study outcomes were measured at baseline, immediately post-intervention, and at the 1-month follow-up post-intervention evaluation. Data were analyzed using the Kolmogorov-Smirnov test, chi-square test, Fisher's exact test, independent sample t-test, Wilcoxon rank-sum test, and generalized estimation equations. The Intention-To-Treat analysis was performed for all available data. Results: In comparison to the control group, significant improvements in family adaptability and cohesion and anticipatory grief over post-intervention and 1-month follow-up were demonstrated among the patients in the intervention group. The intervention group of caregivers had significant improvement in anticipatory grief at post-intervention and 1-month follow-up. The level of psychological distress was significantly lower in the intervention group than the control group (p < 0.05) at 1-month follow-up but the differences were not statistically significant at post-intervention. All outcomes showed clear differences from baseline after the intervention and at the 1-month follow-up evaluation but not between post-intervention and at the 1-month follow-up evaluation. Conclusion: This study further verifies the actual effect of family dignity intervention program through randomized controlled trials, and provides a reference for improving the family relationship between advanced cancer patients and their family caregivers, and improving their mental health. The addition of family dignity intervention to standard palliative care greatly increased the adaptability and cohesion between survivors and their families, lessened the anticipatory grief of the survivor-caregiver pair, and relieved caregivers' anxiety and despair. We did not detect a statistically significant difference between post-intervention and the 1-month follow-up evaluation, suggesting that the intervention may have a durable impact at least 1 month.

Atg5 deficiency in macrophages protects against kidney fibrosis via the CCR6-CCL20 axis.

BACKGROUND: Autophagy is a lysosome-dependent degradation pathway that regulates macrophage activation, differentiation, and polarization. Autophagy related 5 (Atg5) is a key protein involved in phagocytic membrane elongation in autophagic vesicles that forms a complex with Atg12 and Atg16L1. Alterations in Atg5 are related to both acute and chronic kidney diseases in experimental models. However, the role of macrophage-expressed Atg5 in acute kidney injury remains unclear. METHODS: Using a myeloid cell-specific Atg5 knockout (MΦ atg5-/-) mouse, we established renal ischemia/reperfusion and unilateral ureteral obstruction models to evaluate the role of macrophage Atg5 in renal macrophage migration and fibrosis. RESULTS: Based on changes in the serum urea nitrogen and creatinine levels, Atg5 deletion had a minimal effect on renal function in the early stages after mild injury; however, MΦ atg5-/- mice had reduced renal fibrosis and reduced macrophage recruitment after 4 weeks of ischemia/reperfusion injury and 2 weeks of unilateral ureteral obstruction injury. Atg5 deficiency impaired the CCL20-CCR6 axis after severe ischemic kidneys. Chemotactic responses of bone marrow-derived monocytes (BMDMs) from MΦ atg5-/- mice to CCL20 were significantly attenuated compared with those of wild-type BMDMs, and this might be caused by the inhibition of PI3K, AKT, and ERK1/2 activation. CONCLUSIONS: Our data indicate that Atg5 deficiency decreased macrophage migration by impairing the CCL20-CCR6 axis and inhibited M2 polarization, thereby improving kidney fibrosis.

Mesenchymal Stem Cell-Derived Extracellular Vesicles Alleviate Brain Damage Following Subarachnoid Hemorrhage via the Interaction of miR-140-5p and HDAC7.

Subarachnoid hemorrhage (SAH) triggers severe neuroinflammation and cognitive impairment, where microglial M1 polarization exacerbates the injury and M2 polarization mitigates damage. Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs), carrying microRNA (miR)-140-5p, offer therapeutic promise by targeting the cAMP/PKA/CREB pathway and modulating microglial responses, demonstrating a novel approach for addressing SAH-induced brain injury. This research explored the role of miR-140-5p delivered by MSC-EVs in mitigating brain damage following SAH. Serum from SAH patients and healthy individuals was analyzed for miR-140-5p and cAMP levels. The association between miR-140-5p levels, brain injury severity, and patient survival was examined, along with the target relationship between miR-140-5p and histone deacetylases 7 (HDAC7). MSC-EVs were characterized for their ability to cross the blood-brain barrier and modulate the HDAC7/AKAP12/cAMP/PKA/CREB axis, reducing M1 polarization and inflammation. The therapeutic effect of MSC-EV-miR-140-5p was demonstrated in an SAH mouse model, showing reduced neuronal apoptosis and improved neurological function. This study highlights the potential of MSC-EV-miR-140-5p in mitigating SAH-induced neuroinflammation and brain injury, providing a foundation for developing MSC-EV-based treatments for SAH.

Anti-angiogenesis agents plus chemoradiotherapy for locally advanced nasopharyngeal cancer: a systematic review and meta-analysis.

PURPOSE: To evaluate literature evidences about the efficacy and safety of anti-angiogenesis agents plus chemoradiotherapy versus chemoradiotherapy in the treatment of locally advanced nasopharyngeal carcinoma. METHODS: The relevant literature was systematically searched from the date of establishment to April 2023 in PubMed, Embase, Web of Science, The Cochrane Library, Chinese National Knowledge Infrastructure, Chinese Biological Medicine, Wanfang and VIP database. Search terms included: Nasopharyngeal Neoplasms, Angiogenesis inhibitors, Endostar, Anlotinib, Apatinib, Bevacizumab, Sunitinib, Pazopanib, Chemoradiotherapy. The literature was strictly screened according to the inclusion and exclusion criteria, and 8 eligible studies were finally included in our meta-analysis (4 randomized controlled trials and 4 retrospective studies). RESULTS: A total of 642 patients were included, with 316 in the anti-angiogenesis agents plus chemoradiotherapy group and 326 in the chemoradiotherapy group. The results of our meta-analysis showed that compared with chemoradiotherapy group, the complete response rate (RR = 1.35, 95% CI 1.05-1.74, P = 0.02), objective response rate (RR = 1.26, 95% CI 1.12-1.43, P = 0.0002) in the anti-angiogenesis agents plus chemoradiotherapy group were significantly improved. In terms of safety, there was a higher incidence of cardiac arrhythmia (RR = 3.63, 95% CI 1.16-11.37, P = 0.03) and hypertension (RR = 1.85, 95% CI 1.04-3.27, P = 0.004) in the anti-angiogenesis agents plus chemoradiotherapy group, while no statistically significant differences were reported in other adverse reactions (all P > 0.05). CONCLUSION: Compared with chemoradiotherapy, anti-angiogenesis agents plus chemoradiotherapy could bring more benefits in terms of short-term efficacy, particularly by notably improving both complete response rate and objective response rate, and overall adverse reactions were acceptable. Anti-angiogenesis agents plus chemoradiotherapy may provide a promising direction for the treatment of locally advanced nasopharyngeal carcinoma. SYSTEMATIC REVIEW REGISTRATION: https://inplasy.com/inplasy-2023-8-0076/ , registration number INPLASY202380076.

Signal2signal: Pushing the Spatiotemporal Resolution to the Limit by Single Chemical Hyperspectral Imaging.

There is growing interest in developing a high-performance self-supervised denoising algorithm for real-time chemical hyperspectral imaging. With a good understanding of the working function of the zero-shot Noise2Noise-based denoising algorithm, we developed a self-supervised Signal2Signal (S2S) algorithm for real-time denoising with a single chemical hyperspectral image. Owing to the accurate distinction and capture of the weak signal from the random fluctuating noise, S2S displays excellent denoising performance, even for the hyperspectral image with a spectral signal-to-noise ratio (SNR) as low as 1.12. Under this condition, both the image clarity and the spatial resolution could be significantly improved and present an almost identical pattern with a spectral SNR of 7.87. The feasibility of real-time denoising during imaging was well demonstrated, and S2S was applied to monitor the photoinduced exfoliation of transition metal dichalcogenide, which is hard to accomplish by confocal Raman spectroscopy. In general, the real-time denoising capability of S2S offers an easy way toward in situ/in vivo/operando research with much improved spatial and temporal resolution. S2S is open-source at https://github.com/3331822w/Signal2signal and will be accessible online at https://ramancloud.xmu.edu.cn/tutorial.

Novel insights into macrophage immunometabolism in nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH), an inflammatory subtype of nonalcoholic fatty liver disease (NAFLD), is characterized by liver steatosis, inflammation, hepatocellular injury and different degrees of fibrosis, and has been becoming the leading cause of liver-related morbidity and mortality worldwide. Unfortunately, the pathogenesis of NASH has not been completely clarified, and there are no approved therapeutic drugs. Recent accumulated evidences have revealed the involvement of macrophage in the regulation of host liver steatosis, inflammation and fibrosis, and different phenotypes of macrophages have different metabolic characteristics. Therefore, targeted regulation of macrophage immunometabolism may contribute to the treatment and prognosis of NASH. In this review, we summarized the current evidences of the role of macrophage immunometabolism in NASH, especially focused on the related function conversion, as well as the strategies to promote its polarization balance in the liver, and hold promise for macrophage immunometabolism-targeted therapies in the treatment of NASH.

Effect of pretreatment with a small dose of esketamine on sufentanil-induced cough during anesthesia induction: a randomized controlled trial.

BACKGROUND: Sufentanil-induced cough is common during the induction of anesthesia. The objective of this study was to determine whether pretreatment with a small dose of esketamine is effective in treating sufentanil-induced cough. METHODS: 220 patients were screened, and 200 patients who had scheduled elective surgery and were between 18 and 70 years old were randomly divided into two groups. Before sufentanil was administered, esketamine group (group K) was injected with 0.15 mg/kg esketamine at 5 s, and control group (group C) was administered with the same volume. Within 1 min after sufentanil(0.4ug/kg) injection during induction, cough incidence and severity were evaluated. After sufentanil was injected, we recorded its hemodynamic changes and side effects. RESULTS: In the esketamine group (group K) and control group (group C), there was an incidence of cough of 5 and 34%, respectively. The esketamine group (group K) had a significantly lower incidence and severity of cough compared to the control group (group C) immediately after sufentanil injection (P < 0.05). MAP and HR did not differ significantly between the two groups during three different times of general anesthesia induction (P > 0.05). CONCLUSION: In our study, we found that sufentanil-induced cough was significantly reduced by pretreatment with 0.15 mg/kg esketamine, but with no significant changes in the hemodynamic status. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2200063821, registered date: 17/09/2022), http://www.chictr.org.cn.

Factors influencing family resilience in adult patients with acute leukemia undergoing chemotherapy: A qualitative study.

Objective: To explore the factors influencing family resilience in adult patients with acute leukemia undergoing chemotherapy, with the aim of providing a theoretical basis for the development of strategies to strengthen their family resilience. Methods: A descriptive phenomenological qualitative research method was used to select 11 adult acute leukemia chemotherapy patients for semi-structured interviews. Colaizzi 7-step analysis and NVivo 12.0 were used to summarize information and refine themes. Results: The main outcomes consisted of two themes and 11 sub-themes: protective factors for family resilience (positive traits, cognitive restructuring, positive family beliefs, organizational flexibility, clear communication, and social support) and risk factors for family resilience (symptom burden, self-concealment, role overload, economic distress, and social alienation). Conclusions: Health care professionals should pay attention to screening protective and risk factors for family resilience in adult acute leukemia chemotherapy patients, affirming the positive role of internal and external resources available in the family in stressful situations, alleviating patients' negative experiences, and promoting the recovery of family function.

Heart failure with Sarcopenia: A Bibliometric review from 1995 to 2022.

This study aimed to dynamically track the priorities and potential research hotspots in the field of heart failure with sarcopenia. Using CiteSpace, we analyzed the literature on heart failure with sarcopenia from the Web of Science database from 1995 to 2022. The analysis encompassed 507 records, revealing an overall upward trend in annual publication volume. Europe and the United States emerged as the primary regions for publishing, particularly driven by contributions from developed countries such as the United States, Germany, and Italy. Productive institutions included the Charite Universitatsmedizin Berlin, University Medical Center Gottingen, the German Center for Cardiovascular Research (DZHK), Universita Cattolica del Sacro Cuore, and the National Institute on Aging (NIA). Noteworthy academic groups have formed around these institutions; von Haehling S, Anker Stefan D, Springer J, and Doehner W frequently collaborated. The core journals that frequently published articles in this area included Circulation, European Heart Journal, and The Journals of Gerontology Series A-Biological Sciences and Medical Sciences. Based on the keyword analysis, we identified three key research areas. First, the diagnosis and definition of sarcopenia emerged as significant themes. Second, researchers have focused on exploring the mechanisms underlying heart failure with sarcopenia, including inflammation, insulin resistance, and oxidative stress. Finally, treatment strategies, such as physical activity and nutritional support, constitute another critical research theme. Furthermore, potential research hotspots within this field include clinical randomized controlled trials, investigations into inflammatory mechanisms, cardiac rehabilitation, studies on physical activity, androgen receptor modulators, and investigations into clinical outcomes such as cognitive impairment.

Lipase and pH-responsive diblock copolymers featuring fluorocarbon and carboxyl betaine for methicillin-resistant staphylococcus aureus infections.

The emergence of multidrug-resistant bacteria along with their resilient biofilms necessitates the development of creative antimicrobial remedies. We designed versatile fluorinated polymer micelles with surface-charge-switchable properties, demonstrating enhanced efficacy against Methicillin-Resistant Staphylococcus Aureus (MRSA) in planktonic and biofilm states. Polymethacrylate diblock copolymers with pendant fluorocarbon chains and carboxyl betaine groups were prepared using reversible addition-fragmentation chain transfer polymerization. Amphiphilic fluorinated copolymers self-assembled into micelles, encapsulating ciprofloxacin in their cores (CIP@FCBMs) for antibacterial and antibiofilm applications. As a control, fluorine-free copolymer micelles loaded with ciprofloxacin (CIP@BCBMs) were prepared. Although both CIP@FCBMs and CIP@BCBMs exhibited pH-responsive surface charges and lipase-triggered drug release, CIP@FCBMs exhibited powerful antimicrobial and antibiofilm activities in vitro and in vivo, attributed to superior serum stability, higher drug loading, enhanced fluorination-facilitated cellular uptake, and lipase-triggered drug release. Collectively, reversing surface charge, on-demand antibiotic release, and fluorination-mediated nanoparticles hold promise for treating bacterial infections and biofilms.

Patch-Based Convolutional Encoder: A Deep Learning Algorithm for Spectral Classification Balancing the Local and Global Information.

Molecular vibrational spectroscopies, including infrared absorption and Raman scattering, provide molecular fingerprint information and are powerful tools for qualitative and quantitative analysis. They benefit from the recent development of deep-learning-based algorithms to improve the spectral, spatial, and temporal resolutions. Although a variety of deep-learning-based algorithms, including those to simultaneously extract the global and local spectral features, have been developed for spectral classification, the classification accuracy is still far from satisfactory when the difference becomes very subtle. Here, we developed a lightweight algorithm named patch-based convolutional encoder (PACE), which effectively improved the accuracy of spectral classification by extracting spectral features while balancing local and global information. The local information was captured well by segmenting the spectrum into patches with an appropriate patch size. The global information was extracted by constructing the correlation between different patches with depthwise separable convolutions. In the five open-source spectral data sets, PACE achieved a state-of-the-art performance. The more difficult the classification, the better the performance of PACE, compared with that of residual neural network (ResNet), vision transformer (ViT), and other commonly used deep learning algorithms. PACE helped improve the accuracy to 92.1% in Raman identification of pathogen-derived extracellular vesicles at different physiological states, which is much better than those of ResNet (85.1%) and ViT (86.0%). In general, the precise recognition and extraction of subtle differences offered by PACE are expected to facilitate vibrational spectroscopy to be a powerful tool toward revealing the relevant chemical reaction mechanisms in surface science or realizing the early diagnosis in life science.

Dose-response association of diabetic kidney disease with routine clinical parameters in patients with type 2 diabetes mellitus: a systematic review and meta-analysis.

Background: Diabetic kidney disease (DKD) is a leading cause of end-stage kidney disease and is associated with high mortality rates. The influence of routine clinical parameters on DKD onset in patients with type 2 diabetes mellitus (T2DM) remains uncertain. Methods: In this systematic review and meta-analysis, we searched multiple databases, including PubMed, Embase, Scopus, Web of Science, and Cochrane Library, for studies published from each database inception until January 11, 2024. We included cohort studies examining the association between DKD onset and various clinical parameters, including body mass index (BMI), hemoglobin A1c (HbA1c), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and serum uric acid (UA). Random-effect dose-response meta-analyses utilizing one-stage and/or cubic spline models, were used to estimate correlation strength. This study is registered in PROSPERO (CRD42022326148). Findings: This analysis of 46 studies involving 317,502 patients found that in patients with T2DM, the risk of DKD onset increased by 3% per 1 kg/m2 increase in BMI (relative risk (RR) = 1.03, confidence interval (CI) [1.01-1.04], I2 = 70.07%; GRADE, moderate); a 12% increased risk of DKD onset for every 1% increase in HbA1c (RR = 1.12, CI [1.07-1.17], I2 = 94.94%; GRADE, moderate); a 6% increased risk of DKD onset for every 5 mmHg increase in SBP (RR = 1.06. CI [1.03-1.09], I2 = 85.41%; GRADE, moderate); a 2% increased risk of DKD onset per 10 mg/dL increase in TG (RR = 1.02, CI [1.01-1.03], I2 = 78.45%; GRADE, low); an 6% decreased risk of DKD onset per 10 mg/dL increase in HDL (RR = 0.94, CI [0.92-0.96], I2 = 0.33%; GRADE, high), and a 11% increased risk for each 1 mg/dL increase in UA (RR = 1.11, CI [1.05-1.17], I2 = 79.46%; GRADE, moderate). Subgroup analysis revealed a likely higher risk association of clinical parameters (BMI, HbA1c, LDL, and UA) in patients with T2DM for less than 10 years. Interpretation: BMI, HbA1c, SBP, TG, HDL and UA are potential predictors of DKD onset in patients with T2DM. Given high heterogeneity between included studies, our findings should be interpreted with caution, but they suggest monitoring of these clinical parameters to identify individuals who may be at risk of developing DKD. Funding: Shenzhen Science and Innovation Fund, the Hong Kong Research Grants Council, and the HKU Seed Funds, and Scientific and technological innovation project of China Academy of Chinese Medical Sciences.

Atovaquone enhances antitumor efficacy of TCR-T therapy by augmentation of ROS-induced ferroptosis in hepatocellular carcinoma.

T-cell receptor (TCR) engineered T-cell therapy has recently emerged as a promising adoptive immunotherapy approach for tumor treatment, yet hindered by tumor immune evasion resulting in poor therapeutic efficacy. The introduction of ferroptosis-targeted inducers offers a potential solution, as they empower T cells to induce ferroptosis and exert influence over the tumor microenvironment. Atovaquone (ATO) stands as a prospective pharmaceutical candidate with the potential to target ferroptosis, effectively provoking an excessive generation and accumulation of reactive oxygen species (ROS). In this study, we evaluated the effectiveness of a combination therapy comprising ATO and TCR-T cells against hepatocellular carcinoma (HCC), both in vitro and in vivo. The results of lactate dehydrogenase and cytokine assays demonstrated that ATO enhanced cytotoxicity mediated by AFP-specific TCR-T cells and promoted the release of IFN-γ in vitro. Additionally, in an established HCC xenograft mouse model, the combined therapy with low-dose ATO and TCR-T cells exhibited heightened efficacy in suppressing tumor growth, with no apparent adverse effects, comparable to the results achieved through monotherapy. The RNA-seq data unveiled a significant activation of the ferroptosis-related pathway in the combination therapy group in comparison to the TCR-T cells group. Mechanistically, the synergy between ATO and TCR-T cells augmented the release of IFN-γ by TCR-T cells, while concurrently elevating the intracellular and mitochondrial levels of ROS, expanding the labile iron pool, and impairing the integrity of the mitochondrial membrane in HepG2 cells. This multifaceted interaction culminated in the potentiation of ferroptosis within the tumor, primarily induced by an excess of ROS. In summary, the co-administration of ATO and TCR-T cells in HCC exhibited heightened vulnerability to ferroptosis. This heightened susceptibility led to the inhibition of tumor growth and the stimulation of an anti-tumor immune response. These findings suggest that repurposing atovaquone for adoptive cell therapy combination therapy holds the potential to enhance treatment outcomes in HCC.

Unraveling the Molecular Basis of Color Variation in Dioscorea alata Tubers: Integrated Transcriptome and Metabolomics Analysis.

Dioscorea alata L. (Dioscoreaceae) is a widely cultivated tuber crop with variations in tuber color, offering potential value as health-promoting foods. This study focused on the comparison of D. alata tubers possessing two distinct colors, white and purple, to explore the underlying mechanisms of color variation. Flavonoids, a group of polyphenols known to influence plant color and exhibit antioxidant properties, were of particular interest. The total phenol and total flavonoid analyses revealed that purple tubers (PTs) have a significantly higher content of these metabolites than white tubers (WTs) and a higher antioxidant activity than WTs, suggesting potential health benefits of PT D. alata. The transcriptome analysis identified 108 differentially expressed genes associated with the flavonoid synthesis pathway, with 57 genes up-regulated in PTs, including CHS, CHI, DFR, FLS, F3H, F3'5'H, LAR, ANS, and ANR. The metabolomics analysis demonstrated that 424 metabolites, including 104 flavonoids and 8 tannins, accumulated differentially in PTs and WTs. Notably, five of the top ten up-regulated metabolites were flavonoids, including 6-hydroxykaempferol-7-O-glucoside, pinocembrin-7-O-(6″-O-malonyl)glucoside, 6-hydroxykaempferol-3,7,6-O-triglycoside, 6-hydroxykaempferol-7-O-triglycoside, and cyanidin-3-O-(6″-O-feruloyl)sophoroside-5-O-glucoside, with the latter being a precursor to anthocyanin synthesis. Integrating transcriptome and metabolomics data revealed that the 57 genes regulated 20 metabolites within the flavonoid synthesis pathway, potentially influencing the tubers' color variation. The high polyphenol content and antioxidant activity of PTs indicate their suitability as nutritious and health-promoting food sources. Taken together, the findings of this study provide insights into the molecular basis of tuber color variation in D. alata and underscore the potential applications of purple tubers in the food industry and human health promotion. The findings contribute to the understanding of flavonoid biosynthesis and pigment accumulation in D. alata tubers, opening avenues for future research on enhancing the nutritional quality of D. alata cultivars.

Sandwich-Like Flexible Breathable Strain Sensor with Tunable Thermal Regulation Capability for Human Motion Monitoring.

High-performance flexible strain sensors with synergistic and outstanding thermal regulation function are poised to make a significant impact on next-generation multifunctional sensors. However, it has long been intractable to optimize the sensing performance and high thermal conductivity simultaneously. Herein, a novel flexible sandwich-like strain sensor with advanced thermal regulation capability was prepared by assembling electrospun thermoplastic polyurethane (TPU) fibrous membrane, MXene layer, and TPU/boron nitride nanosheet (BNNS) composite films. The as-prepared sensor demonstrates a wide strain working range (∼100% strain), an ultrahigh gauge factor (2080.9), and a satisfactory reliability. Meanwhile, benefiting from the uniform dispersion and promising orientation of BNNSs in TPU composites, the sensor possesses a high thermal conductivity of 1.5 W·m-1·K-1, guaranteeing wearer comfort. Additionally, the unique structure endows the sensor with high stretchability, breathability, biocompatibility, and tunable electromagnetic interference shielding performances. Furthermore, an integrated wireless motion monitoring device based on this sensor is rationally designed. It exhibits a fast response time, a wide recognition range, and the ability to maintain skin temperature during prolonged physical activity. These encouraging findings provide a new and feasible approach to designing high-performance and versatile flexible strain sensors with broad applications in advanced wearable technology.

Selective lithium extraction from spent lithium-ion batteries through polyvinyl chloride thermal decomposition-based gas-solid reaction.

The recovery of valuable metals from waste battery materials and the thermal decomposition of PVC both require significant energy and material consumption. In this study, we propose an innovative strategy that integrates the lithium extraction process from spent LiNi0.85Co0.15Al0.05O2 (S-NCA) with PVC pyrolysis, resulting in a substantial reduction in energy consumption and chemical additive. Various characterization techniques, including SEM, TEM, XRD, and XPS, are employed to investigate the mechanism of gas-solid lithium extraction and provide valuable insights into the migration pathway of lithium from S-NCA to soluble LiCl. The optimal conditions for the process were determined as follows: a temperature of 600 °C, S-NCA/PVC mass ratio of 1:4, and a baking time of 2 h, achieving a lithium extraction efficiency of 94.37 %. The research provides valuable insights for the valorization of PVC thermal decomposition and lithium extraction from NCA, presenting a novel approach for future applications.

A sodium alginate intervention strategy to enhance therapeutic effects of bone-targeted alpha therapy via remodeling 223RaCl2 distribution.

Radium-223 dichloride is the first approved alpha particle-emitting radiopharmaceutical for patients with castration-resistant prostate cancer with symptomatic bone metastases and no known visceral metastases. A large percentage of intestinal enrichment and a slow clearance rate were the main causes of gastrointestinal adverse events after 223RaCl2 administration. The molecular weight of sodium alginate in aqueous solution was determined to be 656 kDa. Sodium alginate exhibits a higher affinity for adsorbing Ra2+ compared to other metal ions belonging to the second main group. Sodium alginate as low as 0.5 g/rat reduced intestinal damage by remodeling 223RaCl2 distribution without affecting bone resorption. Intestinal villi were preserved and enterocyte activity was maintained after sodium alginate intervention. Sodium alginate reduced DNA oxidative damage and lipid peroxidation and maintained endogenous antioxidant status by increasing superoxide dismutase levels and total antioxidant capacity. Furthermore, sodium alginate treatment mitigated DNA damage and apoptosis. The administration of sodium alginate effectively maintained the integrity of the intestinal microbiota, which had undergone perturbations due to radiation exposure. This study demonstrated that sodium alginate could be applied to reduce the adverse effects caused by radiation exposure to the intestine during 223RaCl2-treated and reduced intestinal damage resulted from 223RaCl2 accumulation without affecting bone uptake.