Digital exclusion and cognitive impairment in older people: findings from five longitudinal studies.

OBJECTIVES: Older people are more likely to have digital exclusion, which is associated with poor health. This study investigated the relationship between digital exclusion and cognitive impairment in older adults from 23 countries across five longitudinal surveys. DESIGN AND MEASUREMENTS: Digital exclusion is defined as self-reported non-use of the Internet. We assessed cognitive impairment on three dimensions: orientation, memory, and executive function. We used generalized estimation equations fitting binary logistic regression with exchangeable correlations to study the relationship between digital exclusion and cognitive impairment, and apply the minimum sufficiently adjusted set of causally directed acyclic graphs as the adjusted variable. SETTING AND PARTICIPANTS: We pooled a nationally representative sample of older adults from five longitudinal studies, including the China Health and Retirement Longitudinal study (CHARLS), the English Longitudinal Study of Ageing (ELSA), the Health and Retirement Study (HRS), the Mexican Health and Ageing Study (MHAS) and the Survey of Health, Ageing and Retirement in European (SHARE). RESULTS: We included 62,413 participants from five longitudinal studies. Digital exclusion varied by country, ranging from 21.69% (SHARE) in Denmark to 97.15% (CHARLS) in China. In the original model, digital exclusion was significantly associated with cognitive impairment in all five studies. In the adjusted model, these associations remained statistically significant: CHARLS (Odds ratio [OR] = 2.81, 95% confidence interval [CI] 1.84-4.28, ELSA (1.92 [1.70-2.18]), HRS(2.48[2.28-2.71), MHAS (1.92 [1.74-2.12]), and SHARE (2.60 [2.34-2.88]). CONCLUSION: Our research shows that a significant proportion of older people suffer from digital exclusion, especially in China. Digital exclusion was positively correlated with cognitive impairment. These findings suggest that digital inclusion could be an important strategy to improve cognitive function and reduce the risk of cognitive impairment in older adults.

Heteroaggregation kinetics of nanoplastics and soot nanoparticles in aquatic environments.

Heteroaggregation between polystyrene nanoplastics (PSNPs) and soot nanoparticles (STNPs) in aquatic environments may affect their fate and transport. This study investigated the effects of particle concentration ratio, electrolytes, pH, and humic acid on their heteroaggregation kinetics. The critical coagulation concentration (CCC) ranked CCCPSNPs > CCCPSNPs-STNPs > CCCSTNPs, indicating that heteroaggregation rates fell between homoaggregation rates. In NaCl solution, as the PSNPs/STNPs ratio decreased from 9/1 to 3/7, heteroaggregation rate decreased and CCCPSNPs-STNPs increased from 200 to 220 mM due to enhanced electrostatic repulsion. Outlier was observed at PSNPs/STNPs= 1/9, where CCCPSNPs-STNPs= 170 mM and homoaggregation of STNPs dominated. However, in CaCl2 solution where calcium bridged with STNPs, heteroaggregation rate increased and CCCPSNPs-STNPs decreased from 26 to 5 mM as the PSNPs/STNPs ratio decreasing from 9/1 to 1/9. In composite water samples, heteroaggregation occurred only at estuarine and marine salinities. Acidic condition promoted heteroaggregation via charge screening. Humic acid retarded or promoted heteroaggregation in NaCl or CaCl2 solutions by steric hindrance or calcium bridging, respectively. Other than van der Waals attraction and electrostatic repulsion, heteroaggregation was affected by steric hindrance, hydrophobic interactions, π - π interactions, and calcium bridging. The results highlight the role of black carbon on colloidal stability of PSNPs in aquatic environments.

Vitamin D effects on Chlamydia trachomatis infection: a case-control and experimental study.

Introduction: Vitamin D deficiency is the most common nutritional deficiency worldwide. Chronic vitamin D deficiency causes immune system dysfunction, which increases susceptibility to pathogens such as bacteria, especially intracellular parasites, and viruses. Chlamydia trachomatis (C. t) is an obligate intracellular parasitic bacterium that causes a variety of sequelae. We speculated that vitamin D might be associated with C. t infection. This study aimed to address this gap in knowledge by investigating the relationship between vitamin D and C. t infection using both in vitro and in vivo models. Methods and results: The addition of calcitriol to McCoy cell culture in vitro delayed and reduced the quantity and volume of inclusions compared to the control group. Macrophages of peritoneally lavaged mice co-cultured with McCoy decreased the infection rate and delayed the appearance of inclusions. In mice models of vitamin D deficiency, mice in the VD-group exhibited more severe genital tract inflammation and a longer duration of infection after inoculation with C. t in the genital tract. Supplementing these mice with vitamin D3 during treatment enhanced the therapeutic effect of antibiotics. We also conducted a case-control study involving 174 C. t-positive patients (95 males and 79 females) and 380 healthy volunteers (211 males and 169 females) aged 20-49 from January 2016 to March 15, 2017. Serum 25-(OH)D concentration was measured by assessing morning fasting blood samples of healthy volunteers and C. t-positive patients 1 day before antibiotic treatment and the next day after one course of treatment. The patients were followed up for 1 month and evaluated for recovery. The results showed that vitamin D deficiency was a risk factor for C. t infection and treatment failure. Conclusion: In summary, findings from experimental and clinical studies indicate a close association between vitamin D levels and C. t infection and treatment outcomes. Given the affordability and safety of vitamin D, both healthy individuals and patients should focus on vitamin D intake. Vitamin D supplementation could enhance treatment success and should be used as an adjunctive therapy alongside antibiotic therapy for C. t infections, pending confirmation in larger, prospective, randomized controlled trials.

The Main Mechanisms of Mesenchymal Stem Cell-Based Treatments against COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has a clinical manifestation of hypoxic respiratory failure and acute respiratory distress syndrome. However, COVID-19 still lacks of effective clinical treatments so far. As a promising potential treatment against COVID-19, stem cell therapy raised recently and had attracted much attention. Here we review the mechanisms of mesenchymal stem cell-based treatments against COVID-19, and provide potential cues for the effective control of COVID-19 in the future. METHODS: Literature is obtained from databases PubMed and Web of Science. Key words were chosen for COVID- 19, acute respiratory syndrome coronavirus 2, mesenchymal stem cells, stem cell therapy, and therapeutic mechanism. Then we summarize and critically analyze the relevant articles retrieved. RESULTS: Mesenchymal stem cell therapy is a potential effective treatment against COVID-19. Its therapeutic efficacy is mainly reflected in reducing severe pulmonary inflammation, reducing lung injury, improving pulmonary function, protecting and repairing lung tissue of the patients. Possible therapeutic mechanisms might include immunoregulation, anti-inflammatory effect, tissue regeneration, anti-apoptosis effect, antiviral, and antibacterial effect, MSC - EVs, and so on. CONCLUSION: Mesenchymal stem cells can effectively treat COVID-19 through immunoregulation, anti-inflammatory, tissue regeneration, anti-apoptosis, anti-virus and antibacterial, MSC - EVs, and other ways. Systematically elucidating the mechanisms of mesenchymal stem cell-based treatments for COVID-19 will provide novel insights into the follow-up research and development of new therapeutic strategies in next step.

CRISPR-Cas9 screening identifies INTS3 as an anti-apoptotic RNA-binding protein and therapeutic target for colorectal cancer.

Growing evidences indicate that RNA-binding proteins (RBPs) play critical roles in regulating the RNA splicing, polyadenylation, stability, localization, translation, and turnover. Abnormal expression of RBPs can promote tumorigenesis. Here, we performed a CRISPR screen using an RBP pooled CRISPR knockout library and identified 27 potential RBPs with role in supporting colorectal cancer (CRC) survival. We found that the deletion/depletion of INTS3 triggered apoptosis in CRC. The in vitro experiments and RNA sequencing revealed that INTS3 destabilized pro-apoptotic gene transcripts and contributed to the survival of CRC cells. INTS3 loss delayed CRC cells growth in vivo. Furthermore, delivery of DOTAP/cholesterol-mshINTS3 nanoparticles inhibited CRC tumor growth. Collectively, our work highlights the role of INTS3 in supporting CRC survival and provides several novel therapeutic targets for treatment.

Refining DIIS algorithms for Si and GaAs solar cells: incorporation of weight regularization, conjugate gradient, and reverse automatic differentiation techniques.

Pivotal enhancements in electronic minimization algorithms, which are vital for the advancement of computational materials science, are introduced in this research. Our research is dedicated to refining the DIIS algorithm specifically for electronic structure calculations of silicon (Si) and gallium arsenide (GaAs) solar cells, aiming to enhance their efficiency and stability. We have enriched DIIS by integrating a weight regularization factor, significantly bolstering its convergence stability. This modification enhances iteration robustness and curtails the average iteration duration, thus streamlining the convergence process. Furthermore, we have incorporated the conjugate gradient (CG) algorithm to proficiently resolve symmetric positive definite residual matrices. This inclusion substantially accelerates the solution-finding process within the DIIS framework. A novel aspect of our research is the application of reverse automatic differentiation (AD), deployed in two distinct methodologies: the construction of the Jacobian matrix and direct chain rule application for gradient computation. These approaches involve sophisticated mathematical techniques that enhance computational precision and efficiency specifically for Si and GaAs solar cell materials in determining the optimal weights for residual combinations during DIIS iterations. The integration of these advanced methods into the DIIS algorithm not only augments its convergence stability but also ensures a substantial reduction in total computational time. Our findings demonstrate that the enhanced DIIS, CG-enhanced DIIS, and AD-integrated DIIS methods collectively lead to a more efficient electronic minimization process. This balance of stability and efficiency is crucial in high-performance computational materials science, particularly for complex systems analysis. The findings of this research represent a notable advancement in computational strategies for Si and GaAs solar cell materials, providing enhanced methodologies and insights that significantly improve the efficiency and stability of electronic structure calculations in these critical components of renewable energy technologies.

Relationships among bacterial cell size, diversity, and taxonomy in rumen.

Introduction: The rumen microbial community plays a crucial role in the digestion and metabolic processes of ruminants. Although sequencing-based studies have helped reveal the diversity and functions of bacteria in the rumen, their physiological and biochemical characteristics, as well as their dynamic regulation along the digestion process in the rumen, remain poorly understood. Addressing these gaps requires pure culture studies to demystify the intricate mechanisms at play. Bacteria exhibit morphological differentiation associated with different species. Based on the difference in size or shape of microorganisms, size fractionation by filters with various pore sizes can be used to separate them. Methods: In this study, we used polyvinylidene difluoride filters with pore sizes of 300, 120, 80, 40, 20, 8, 6, 2.1, and 0.6 µm. Bacterial suspensions were successively passed through these filters for the analysis of microbial population distribution using 16S rRNA gene sequences. Results: We found that bacteria from the different pore sizes were clustered into four branches (> 120 µm, 40-120 µm, 6-20 µm, 20-40 µm, and < 0.6 µm), indicating that size fractionation had effects on enriching specific groups but could not effectively separate dominant groups by cell size alone. The species of unclassified Flavobacterium, unclassified Chryseobacterium, unclassified Delftia, Methylotenera mobilis, unclassified Caulobacteraceae, unclassified Oligella, unclassified Sphingomonas, unclassified Stenotrophomonas, unclassified Shuttleworthia, unclassified Sutterella, unclassified Alphaproteobacteria, and unclassified SR1 can be efficiently enriched or separated by size fractionation. Discussion: In this study, we investigated the diversity of sorted bacteria populations in the rumen for preliminary investigations of the relationship between the size and classification of rumen bacteria that have the potential to improve our ability to isolate and culture bacteria from the rumen in the future.

Changes in physiology, antioxidant system, and gene expression in Microcystis aeruginosa under fenoxaprop-p-ethyl stress.

Fenoxaprop-p-ethyl (FE) is one of the typical aryloxyphenoxypropionate herbicides. FE has been widely applied in agriculture in recent years. Human health and aquatic ecosystems are threatened by the cyanobacteria blooms caused by Microcystis aeruginosa, which is one of the most common cyanobacteria responsible for freshwater blooming. Few studies have been reported on the physiological effects of FE on M. aeruginosa. This study analyzed the growth curves, the contents of chlorophyll a and protein, the oxidative stress, and the microcystin-LR (MC-LR) levels of M. aeruginosa exposed to various FE concentrations (i.e., 0, 0.5, 1, 2, and 5 mg/L). FE was observed to stimulate the cell density, chlorophyll a content, and protein content of M. aeruginosa at 0.5- and 1-mg/L FE concentrations but inhibit them at 2 and 5 mg/L FE concentrations. The superoxide dismutase and catalase activities were enhanced and the malondialdehyde concentration was increased by FE. The intracellular (intra-) and extracellular (extra-) MC-LR contents were also affected by FE. The expression levels of photosynthesis-related genes psbD1, psaB, and rbcL varied in response to FE exposure. Moreover, the expressions of microcystin synthase-related genes mcyA and mcyD and microcystin transportation-related gene mcyH were significantly inhibited by the treatment with 2 and 5 mg/L FE concentrations. These results might be helpful in evaluating the ecotoxicity of FE and guiding the rational application of herbicides in modern agriculture.

Integrated analysis of transcriptome and small RNAome reveals regulatory network of rapid and long-term response to heat stress in Rhododendron moulmainense.

MAIN CONCLUSION: The post-transcriptional gene regulatory pathway and small RNA pathway play important roles in regulating the rapid and long-term response of Rhododendron moulmainense to high-temperature stress. The Rhododendron plays an important role in maintaining ecological balance. However, it is difficult to domesticate for use in urban ecosystems due to their strict optimum growth temperature condition, and its evolution and adaptation are little known. Here, we combined transcriptome and small RNAome to reveal the rapid response and long-term adaptability regulation strategies in Rhododendron moulmainense under high-temperature stress. The post-transcriptional gene regulatory pathway plays important roles in stress response, in which the protein folding pathway is rapidly induced at 4 h after heat stress, and alternative splicing plays an important role in regulating gene expression at 7 days after heat stress. The chloroplasts oxidative damage is the main factor inhibiting photosynthesis efficiency. Through WGCNA analysis, we identified gene association patterns and potential key regulatory genes responsible for maintaining the ROS steady-state under heat stress. Finally, we found that the sRNA synthesis pathway is induced under heat stress. Combined with small RNAome, we found that more miRNAs are significantly changed under long-term heat stress. Furthermore, MYBs might play a central role in target gene interaction network of differentially expressed miRNAs in R. moulmainense under heat stress. MYBs are closely related to ABA, consistently, ABA synthesis and signaling pathways are significantly inhibited, and the change in stomatal aperture is not obvious under heat stress. Taken together, we gained valuable insights into the transplantation and long-term conservation domestication of Rhododendron, and provide genetic resources for genetic modification and molecular breeding to improve heat resistance in Rhododendron.

Effect of Sarcoplasmic Protein Solutions Dried at Different Times and Rates on Water Migration in Lamb Myofibril In Vitro.

To determine whether sarcoplasmic proteins affected water migration in myofibrils during air-drying, with protein denaturation as an indicator of sarcoplasmic protein changes, the extent of sarcoplasmic protein changes in lamb during air-drying was first studied. The results showed that sarcoplasmic protein's thermal stability decreased and secondary structure changed, indicating sarcoplasmic protein denatured in lamb during air-drying (35 °C, 60% RH, 3 m/s wind speed). Subsequently, the effect of sarcoplasmic protein solutions, dried at different times and rates, on myofibril protein-water interaction was studied in vitro. Two sets of sarcoplasmic protein solutions were dried for 0, 3, 6, and 9 h in a drying oven, resulting in different degrees of change. These two sets with higher or lower drying rates were achieved by controlling the contact area between sarcoplasmic protein solution and air. These dried sarcoplasmic protein solutions were then mixed with extracted myofibril and incubated for 2 h. The results showed a significant increase in T21 relaxation time of the incubation system when sarcoplasmic protein solution was dried at 35 °C for 3 h. This indicated that myofibrillar protein-water interaction was weakened, facilitating water migration from the inside to the outside of myofibrils. The denaturation degree of sarcoplasmic proteins was slowed by a higher drying rate, thereby alleviating the increase in the amount of immobile water within myofibrils when dried for 6 h. In conclusion, the properties of sarcoplasmic proteins were influenced by both drying rate and time, thereby influencing the water migration within myofibrils during air-drying.

Multiomics Analyses Provide New Insight into Genetic Variation of Reproductive Adaptability in Tibetan Sheep.

Domestication and artificial selection during production-oriented breeding have greatly shaped the level of genomic variability in sheep. However, the genetic variation associated with increased reproduction remains elusive. Here, two groups of samples from consecutively monotocous and polytocous sheep were collected for genome-wide association, transcriptomic, proteomic, and metabolomic analyses to explore the genetic variation in fecundity in Tibetan sheep. Genome-wide association study revealed strong associations between BMPR1B (p.Q249R) and litter size, as well as between PAPPA and lambing interval; these findings were validated in 1,130 individuals. Furthermore, we constructed the first single-cell atlas of Tibetan sheep ovary tissues and identified a specific mural granulosa cell subtype with PAPPA-specific expression and differential expression of BMPR1B between the two groups. Bulk RNA-seq indicated that BMPR1B and PAPPA expressions were similar between the two groups of sheep. 3D protein structure prediction and coimmunoprecipitation analysis indicated that mutation and mutually exclusive exons of BMPR1B are the main mechanisms for prolific Tibetan sheep. We propose that PAPPA is a key gene for stimulating ovarian follicular growth and development, and steroidogenesis. Our work reveals the genetic variation in reproductive performance in Tibetan sheep, providing insights and valuable genetic resources for the discovery of genes and regulatory mechanisms that improve reproductive success.

Assays on 3D tumor spheroids for exploring the light dosimetry of photodynamic effects under different gaseous conditions.

The multifaceted nature of photodynamic therapy (PDT) requires a throughout evaluation of a multitude of parameters when devising preclinical protocols. In this study, we constructed MCF-7 human breast tumor spheroid assays to infer PDT irradiation doses at four gradient levels for violet light at 408 nm and red light at 625 nm under normal and hypoxic oxygen conditions. The compacted three-dimensional (3D) tumor models conferred PDT resistance as compared to monolayer cultures due to heterogenous distribution of photosensitizers along with the presence of internal hypoxic region. Cell viability results indicated that the violet light was more efficient to kill cells in the spheroids under normal oxygen conditions, while cells exposed to the hypoxic microenvironment exhibited minimal PDT-induced death. The combination of 3D tumor spheroid assays and the multiparametric screening platform presented a solid framework for assessing PDT efficacy across a wide range of different physiological conditions and therapeutic regimes.

NIR-enhanced Pt single atom/g-C3N4 nanozymes as SOD/CAT mimics to rescue ATP energy crisis by regulating oxidative phosphorylation pathway for delaying osteoarthritis progression.

Osteoarthritis (OA) progresses due to the excessive generation of reactive oxygen and nitrogen species (ROS/RNS) and abnormal ATP energy metabolism related to the oxidative phosphorylation pathway in the mitochondria. Highly active single-atom nanozymes (SAzymes) can help regulate the redox balance and have shown their potential in the treatment of inflammatory diseases. In this study, we innovatively utilised ligand-mediated strategies to chelate Pt4+ with modified g-C3N4 by π-π interaction to prepare g-C3N4-loaded Pt single-atom (Pt SA/C3N4) nanozymes that serve as superoxide dismutase (SOD)/catalase (CAT) mimics to scavenge ROS/RNS and regulate mitochondrial ATP production, ultimately delaying the progression of OA. Pt SA/C3N4 exhibited a high loading of Pt single atoms (2.45 wt%), with an excellent photothermal conversion efficiency (54.71%), resulting in tunable catalytic activities under near-infrared light (NIR) irradiation. Interestingly, the Pt-N6 active centres in Pt SA/C3N4 formed electron capture sites for electron holes, in which g-C3N4 regulated the d-band centre of Pt, and the N-rich sites transferred electrons to Pt, leading to the enhanced adsorption of free radicals and thus higher SOD- and CAT-like activities compared with pure g-C3N4 and g-C3N4-loaded Pt nanoparticles (Pt NPs/C3N4). Based on the use of H2O2-induced chondrocytes to simulate ROS-injured cartilage invitro and an OA joint model invivo, the results showed that Pt SA/C3N4 could reduce oxidative stress-induced damage, protect mitochondrial function, inhibit inflammation progression, and rebuild the OA microenvironment, thereby delaying the progression of OA. In particular, under NIR light irradiation, Pt SA/C3N4 could help reverse the oxidative stress-induced joint cartilage damage, bringing it closer to the state of the normal cartilage. Mechanistically, Pt SA/C3N4 regulated the expression of mitochondrial respiratory chain complexes, mainly NDUFV2 of complex 1 and MT-ATP6 of ATP synthase, to reduce ROS/RNS and promote ATP production. This study provides novel insights into the design of artificial nanozymes for treating oxidative stress-induced inflammatory diseases.

LiNAC100 contributes to linalool biosynthesis by directly regulating LiLiS in Lilium 'Siberia'.

MAIN CONCLUSION: The transcription factor LiNAC100 has a novel function of regulating floral fragrance by directly regulating linalool synthase gene LiLiS. Lilium 'Siberia', an Oriental hybrid, is renowned as both a cut flower and garden plant, prized for its color and fragrance. The fragrance comprises volatile organic compounds (VOCs), primarily monoterpenes found in the plant. While the primary terpene synthases in Lilium 'Siberia' were identified, the transcriptional regulation of these terpene synthase (TPS) genes remains unclear. Thus, understanding the regulatory mechanisms of monoterpene biosynthesis is crucial for breeding flower fragrance, thereby improving ornamental and commercial values. In this study, we isolated a nuclear-localized LiNAC100 transcription factor from Lilium 'Siberia'. The virus-induced gene silencing (VIGS) of LiNAC100 was found to down-regulate the expression of linalool synthase gene (LiLiS) and significantly inhibit linalool synthesis. Conversely, transient overexpression of LiNAC100 produced opposite effects. Additionally, yeast one-hybrid and dual-luciferase assays confirmed that LiNAC100 directly activates LiLiS expression. Our findings reveal that LiNAC100 plays a key role in monoterpene biosynthesis in Lilium 'Siberia', promoting linalool synthesis through the activation of LiLiS expression. These results offer insights into the molecular mechanisms of terpene biosynthesis in Lilium 'Siberia' and open avenues for biotechnological enhancement of floral scent.

The transcriptional landscape of Populus pattern/effector-triggered immunity and how PagWRKY18 involved in it.

Plants trigger a robust immune response by activating massive transcriptome reprogramming through crosstalk between PTI and ETI. However, how PTI and ETI contribute to the quantitative or/and qualitative output of immunity and how they work together when both are being activated were unclear. In this study, we performed a comprehensive overview of pathogen-triggered transcriptomic reprogramming by analyzing temporal changes in the transcriptome up to 144 h after Colletotrichum gloeosporioides inoculated in Populus. Moreover, we constructed a hierarchical gene regulatory network of PagWRKY18 and its potential target genes to explore the underlying regulatory mechanisms of PagWRKY18 that are not yet clear. Interestingly, we confirmed that PagWRKY18 protein can directly bind the W-box elements in the promoter of a transmembrane leucine-rich repeat receptor-like kinase, PagSOBIR1 gene, to trigger PTI. At the same time, PagWRKY18 functions in disease tolerance by modulation of ROS homeostasis and induction of cell death via directly targeting PagGSTU7 and PagPR4 respectively. Furthermore, PagPR4 can interact with PagWRKY18 to inhibit the expression of PagPR4 genes, forming a negative feedback loop. Taken together, these results suggest that PagWRKY18 may be involved in regulating crosstalk between PTI and ETI to activate a robust immune response and maintain intracellular homeostasis.

Heat stress reduces brown adipose tissue activity by exacerbating mitochondrial damage in type 2 diabetic mice.

Epidemiological evidence shows that diabetic patients are susceptible to high temperature weather, and brown adipose tissue (BAT) activity is closely related to type 2 diabetes (T2DM). Activation of BAT under cold stress helps improve T2DM. However, the impact of high temperature on the activity of BAT is still unclear. The study aimed to investigate the impact of heat stress on glucose and lipid metabolism in T2DM mice by influencing BAT activity. High-fat feeding and injecting streptozotocin (STZ) induced model of T2DM mice. All mice were randomly divided into three groups: a normal(N) group, a diabetes (DM) group and a heat stress diabetes (DMHS) group. The DMHS group received heat stress intervention for 3 days. Fasting blood glucose, fasting serum insulin and blood lipids were measured in all three groups. The activity of BAT was assessed by using quantitative real-time PCR (qRT-PCR), electron microscopy, and PET CT. Furthermore, the UHPLC-Q-TOF MS technique was employed to perform metabolomics analysis of BAT on both DM group and DMHS group. The results of this study indicated that heat stress aggravated the dysregulation of glucose and lipid metabolism, exacerbated mitochondrial dysfunction in BAT and reduced the activity of BAT in T2DM mice. This may be related to the abnormal accumulation of branched-chain amino acids (BCAAs) in the mitochondria of BAT.

Logic "AND Gate Circuit"-Based Gasdermin Protein Expressing Nanoplatform Induces Tumor-Specific Pyroptosis to Enhance Cancer Immunotherapy.

Pyroptosis mediated by gasdermin protein has shown great potential in cancer immunotherapies. However, the low expression of gasdermin proteins and the systemic toxicity of nonspecific pyroptosis limit its clinical application. Here, we designed a synthetic biology strategy to construct a tumor-specific pyroptosis-inducing nanoplatform M-CNP/Mn@pPHS, in which a pyroptosis-inducing plasmid (pPHS) was loaded onto a manganese (Mn)-doped calcium carbonate nanoparticle and wrapped in a tumor-derived cell membrane. M-CNP/Mn@pPHS showed an efficient tumor targeting ability. After its internalization by tumor cells, the degradation of M-CNP/Mn@pPHS in the acidic endosomal environment allowed the efficient endosomal escape of plasmid pPHS. To trigger tumor-specific pyroptosis, pPHS was designed according to the logic "AND gate circuit" strategy, with Hif-1α and Sox4 as two input signals and gasdermin D induced pyroptosis as output signal. Only in cells with high expression of Hif-1α and Sox4 simultaneously will the output signal gasdermin D be expressed. Since Hif-1α and Sox4 are both specifically expressed in tumor cells, M-CNP/Mn@pPHS induces the tumor-specific expression of gasdermin D and thus pyroptosis, triggering an efficient immune response with little systemic toxicity. The Mn2+ released from the nanoplatform further enhanced the antitumor immune response by stimulating the cGAS-STING pathway. Thus, M-CNP/Mn@pPHS efficiently inhibited tumor growth with 79.8% tumor regression in vivo. We demonstrate that this logic "AND gate circuit"-based gasdermin nanoplatform is a promising strategy for inducing tumor-specific pyroptosis with little systemic toxicity.

Logical rotation of non-separable states via uniformly self-assembled chiral superstructures.

The next generation of high-capacity, multi-task optical informatics requires sophisticated manipulation of multiple degrees of freedom (DoFs) of light, especially when they are coupled in a non-separable way. Vector beam, as a typical non-separable state between the spin and orbital angular momentum DoFs, mathematically akin to entangled qubits, has inspired multifarious theories and applications in both quantum and classical regimes. Although qubit rotation is a vital and ubiquitous operation in quantum informatics, its classical analogue is rarely studied. Here, we demonstrate the logical rotation of vectorial non-separable states via the uniform self-assembled chiral superstructures, with favorable controllability, high compactness and exemption from formidable alignment. Photonic band engineering of such 1D chiral photonic crystal renders the incident-angle-dependent evolution of the spatially-variant polarizations. The logical rotation angle of a non-separable state can be tuned in a wide range over 4π by this single homogeneous device, flexibly providing a set of distinguished logic gates. Potential applications, including angular motion tracking and proof-of-principle logic network, are demonstrated by specific configuration. This work brings important insight into soft matter photonics and present an elegant strategy to harness high-dimensional photonic states.

Predictive Analysis of Linoleic Acid in Red Meat Employing Advanced Ensemble Models of Bayesian and CNN-Bi-LSTM Decision Layer Fusion Based Hyperspectral Imaging.

Rapid non-destructive testing technologies are effectively used to analyze and evaluate the linoleic acid content while processing fresh meat products. In current study, hyperspectral imaging (HSI) technology was combined with deep learning optimization algorithm to model and analyze the linoleic acid content in 252 mixed red meat samples. A comparative study was conducted by experimenting mixed sample data preprocessing methods and feature wavelength extraction methods depending on the distribution of linoleic acid content. Initially, convolutional neural network Bi-directional long short-term memory (CNN-Bi-LSTM) model was constructed to reduce the loss of the fully connected layer extracted feature information and optimize the prediction effect. In addition, the prediction process of overfitting phenomenon in the CNN-Bi-LSTM model was also targeted. The Bayesian-CNN-Bi-LSTM (Bayes-CNN-Bi-LSTM) model was proposed to improve the linoleic acid prediction in red meat through iterative optimization of Gaussian process acceleration function. Results showed that best preprocessing effect was achieved by using the detrending algorithm, while 11 feature wavelengths extracted by variable combination population analysis (VCPA) method effectively contained characteristic group information of linoleic acid. The Bi-directional LSTM (Bi-LSTM) model combined with the feature extraction data set of VCPA method predicted 0.860 Rp2 value of linoleic acid content in red meat. The CNN-Bi-LSTM model achieved an Rp2 of 0.889, and the optimized Bayes-CNN-Bi-LSTM model was constructed to achieve the best prediction with an Rp2 of 0.909. This study provided a reference for the rapid synchronous detection of mixed sample indicators, and a theoretical basis for the development of hyperspectral on-line detection equipment.

Targeting Cellular Senescence in Aging and Age-Related Diseases: Challenges, Considerations, and the Emerging Role of Senolytic and Senomorphic Therapies.

Cellular senescence is characterized by the permanent arrest of cell proliferation and is a response to endogenous and exogenous stress. The continuous accumulation of senescent cells (SnCs) in the body leads to the development of aging and age-related diseases (such as neurodegenerative diseases, cancer, metabolic diseases, cardiovascular diseases, and osteoarthritis). In the face of the growing challenge of aging and age-related diseases, several compounds have received widespread attention for their potential to target SnCs. As a result, senolytics (compounds that selectively eliminate SnCs) and senomorphics (compounds that alter intercellular communication and modulate the behavior of SnCs) have become hot research topics in the field of anti-aging. In addition, strategies such as combination therapies and immune-based approaches have also made significant progress in the field of anti-aging therapy. In this article, we discuss the latest research on anti-aging targeting SnCs and gain a deeper understanding of the mechanism of action and impact of different anti-aging strategies on aging and age-related diseases, with the aim of providing more effective references and therapeutic ideas for clinical anti-aging treatment in the face of the ever-grave challenges of aging and age-related diseases.