Recombinase Polymerase Amplification and Target-Triggered CRISPR/Cas12a Assay for Sensitive and Selective Hepatitis B Virus DNA Analysis Based on Lanthanide Tagging and Inductively Coupled Plasma Mass Spectrometric Detection.

Herein, we report a target-triggered CRISPR/Cas12a assay by coupling lanthanide tagging and inductively coupled plasma mass spectrometry (ICP-MS) for highly sensitive elemental detection. Hepatitis B virus (HBV) DNA was chosen as a model analyte, and recombinase polymerase amplification (RPA) was used for target amplification. The double-stranded RPA amplicons containing a 5' TTTG PAM sequence can be recognized by Cas12a through a specific CRISPR RNA, activating the trans-cleavage activity of CRISPR/Cas12a and nonspecific cleavage of terbium (Tb)-ssDNA modified on magnetic beads (MBs). Following magnetic separation and acid digestion, the released Tb3+ ions were quantitated by ICP-MS and correlated to the concentration of HBV DNA. Taking advantage of the accelerated cleavage of Tb-ssDNA attached to the MB particles, RPA for target amplification, and ICP-MS for highly selective signal readout, this method permits the detection of 1 copy/µL of HBV DNA in serum with high specificity and holds great promise in the early diagnosis of viral infections or tumor development.

Electrochemical identification of reductive enantiomers in wood channels: A low-cost and scalable platform for chiral sensing.

Chirality, an inherent characteristic of natural substances (such as sugars, peptides, proteins, and nucleic acid), plays a vital role in human metabolism and exerts substantial impacts. In general, chiral drugs can display diverse pharmacological and pharmacokinetic properties. One enantiomer may exhibit therapeutic effects, while the other could cause adverse reactions. Selective recognition of enantiomers is thus a significant task in the biomolecular and pharmaceutical fields. Despite the development of several chiral identification techniques, low-cost enantioselective sensing methods remain highly desirable. Here, we designed and developed an electrochemical sensing device for reductive enantiomer identification using natural wood channels as the substrate. The wood channels were endowed with oxidase-like activity through the in-situ growth of cerium oxide nanoparticles (CeO2). Chiral recognition capability was further introduced by incorporating a layer of chiral ZIF-8 (L-ZIF) as the chiral selector. To demonstrate the enantioselective sensing performance, 3,4-dihydroxyphenylalanine (DOPA) enantiomers were employed as model analytes. Due to the oxidase-like activity and the confinement effect of the proposed channels, the captured DOPA enantiomers were effectively oxidized to their quinone structure, and the Ce(IV) in CeO2 was reduced to Ce(III). These changes led to alterations in the surface charge of the channels, thereby modulating their ionic transport properties. This sensing mechanism also proved useful for the identification of other reductive enantiomers. The limits of detection for l-DOPA and d-DOPA were determined as 2.41 nM and 1.56 nM, respectively. The resulting wood channel-based sensing device not only can be used for the recognition and detection of reductive enantiomers, but also is expected to be applied to the non-electochemically active substances. Moreover, this study offers a novel type of solid-state channel material with low cost, reproducibility, and easy accessibility for electrochemical chiral sensing.

Activation and antitumor immunity of CD8+ T cells are supported by the glucose transporter GLUT10 and disrupted by lactic acid.

CD8+ T cell activation leads to the rapid proliferation and differentiation of effector T cells (Teffs), which mediate antitumor immunity. Although aerobic glycolysis is preferentially activated in CD8+ Teffs, the mechanisms that regulate CD8+ T cell glucose uptake in the low-glucose and acidic tumor microenvironment (TME) remain poorly understood. Here, we report that the abundance of the glucose transporter GLUT10 is increased during CD8+ T cell activation and antitumor immunity. Specifically, GLUT10 deficiency inhibited glucose uptake, glycolysis, and antitumor efficiency of tumor-infiltrating CD8+ T cells. Supplementation with glucose alone was insufficient to rescue the antitumor function and glucose uptake of CD8+ T cells in the TME. By analyzing tumor environmental metabolites, we found that high concentrations of lactic acid reduced the glucose uptake, activation, and antitumor effects of CD8+ T cells by directly binding to GLUT10's intracellular motif. Disrupting the interaction of lactic acid and GLUT10 by the mimic peptide PG10.3 facilitated CD8+ T cell glucose utilization, proliferation, and antitumor functions. The combination of PG10.3 and GLUT1 inhibition or anti-programmed cell death 1 antibody treatment showed synergistic antitumor effects. Together, our data indicate that GLUT10 is selectively required for glucose uptake of CD8+ T cells and identify that TME accumulated lactic acid inhibits CD8+ T cell effector function by directly binding to GLUT10 and reducing its glucose transport capacity. Last, our study suggests disrupting lactate-GLUT10 binding as a promising therapeutic strategy to enhance CD8+ T cell-mediated antitumor effects.

Experimental Investigation on Electrical Conductivity Variation of Carnosine and Zinc Chloride Aqueous Solutions under Microwave Irradiation.

The mechanism of biological effects of environmental electromagnetic radiation is still not completely clear. The chelation of biological small molecule peptides with metal ions plays a very important role in human metabolism. In this paper, a special experimental system was designed to measure the conductivity of carnosine and zinc chloride mixed aqueous solutions under different concentration ratios, microwave powers, and temperatures. The experimental results show that, first, different concentration ratios can alter the conductivity change rate of the mixed aqueous solution. The conductivity of the solution always increases under microwave irradiation at a concentration ratio of 1:1. However, the conductivity is reduced by -0.04% with a 1:5 concentration ratio and 6 W microwave power at 10 °C. Second, temperature can alter the conductivity change rate of the aqueous mixture. The higher the temperature, the smaller the conductivity change rate. Third, different microwave powers can alter the conductivity change rate of the mixed aqueous solution. In general, the conductivity change rate increases with an increase in microwave power. Experimentally observed reduction of the conductivity change rate in carnosine and zinc chloride aqueous solution under low microwave power and low temperature indicates that microwaves do affect the chelation of carnosine with zinc chloride. This work provides a new perspective for the mechanism of explanation of microwave biological effects.

Association of choroidal thickness and blood flow features with asymmetric axial lengths in children with unilateral myopic anisometropia.

BACKGROUND: Considering that changes in the choroidal thickness are closely related to ocular growth, we studied the choroidal thickness (CT) and the blood flow features in children with unilateral myopic anisometropia (UMA) as well as investigating the relationship between choroidal changes and myopia. METHODS: Subjective refractive, axial length (AL), and biometric parameters were measured in 98 UMA children (age: 8-15 years). CT and choroidal blood-flow features, including the choroidal vessel volume (CVV), choroidal vascularity index (CVI), and choriocapillaris perfusion area (CCPA), were measured through swept-source optical coherence tomography angiography. The macular region was categorized into four concentric circles of diameters 0-1 mm (central fovea), 1-3 mm (parafovea), 3-6 mm (perifovea), and 6-9 mm (extended), and further categorized into superior (S), inferior (I), temporal (T), and nasal (N) quadrants. RESULTS: The aforementioned four regions of myopic eyes displayed significantly lower CT, CVV, and CVI than those of non-myopic eyes. CCPA changes differed across different regions of both the eyes (parts of N and T quadrants). There was an inverse association between CT and the interocular AL difference (central and other regions S, T quadrant). No correlation was noted between CVV and CVI with interocular AL difference. CT and CVV were positively correlated in the 0-6-mm macular region of myopic eyes (Spearman correlation coefficient = 0.763, P < 0.001). CONCLUSIONS: In UMA children, CCT and blood flow may be related to myopia progression. A robust correlation between CT and CVV in the 0-6-mm macular region and reduced CT and diminished blood flow indicated an association with myopia.

Study on the intervention effect of HCH integrated SMG health management model on community high-risk group of cardiovascular disease.

Objective: This study aimed to evaluate the integration of the Hospital-Community-Home (HCH) model with the Self-Mutual-Group (SMG) health management model for high-risk populations with cardiovascular disease in the Yuhua community of Shijiazhuang city. The study focused on implementing care interventions (HCH, SMG) with a specific emphasis on SMG to promote beneficial views/behaviors, enhance self-efficacy/agency, and address detrimental determinants of health, ultimately leading to durable changes and healthier lifestyles. Comparing the HCH model with the combined SMG model helps to comprehensively assess the strengths and weaknesses of different health management approaches. This comparison contributes to theoretical innovation and practical development in the field of health management, as well as improving patients' health outcomes and quality of life. Methods: This study employed a quasi-experimental design. Using stratified sampling, individuals who underwent health examinations in Community A and Community B from Shijiazhuang city between May 2023 and August 2023 were randomly selected. After informing the participants about the study and obtaining informed consent via telephone, high-risk patients with cardiovascular disease were screened based on their medical examination reports. Data on lifestyle behaviors, self-efficacy, medical responses, quality of life, and readmission rates were collected and compared before and after the intervention. Results: A total of 526 eligible participants were included, with 241 in the control group and 285 in the study group. After the intervention, there was no significant change in the proportions of smokers, alcohol consumers, and individuals engaging in leisure exercises in the control group. However, in the study group, the proportions of smokers and alcohol consumers significantly decreased, while the proportion of individuals engaging in leisure exercises significantly increased. After the intervention, both the study group and the control group showed significant increases in scores on the General Self-Efficacy Scale-Schwarzer (GSES) and the Seattle Angina Questionnaire (SAQ), with the study group scoring significantly higher than the control group. Avoidance and surrender scores significantly increased after the intervention, with the study group scoring significantly lower than the control group. Confrontation scores significantly increased after the intervention, with the study group scoring significantly higher than the control group. During the follow-up period, the study group had a significantly lower readmission rate than the control group. Conclusion: The integration of HCH with SMG health management model can significantly improve lifestyle behaviors, optimize medical responses, enhance self-efficacy and quality of life, and significantly reduce readmission rates among high-risk populations with cardiovascular disease.

The differences in cytokine signatures between severe fever with thrombocytopenia syndrome (SFTS) and hemorrhagic fever with renal syndrome (HFRS).

Severe fever with thrombocytopenia syndrome (SFTS) virus and hantavirus are categorized under the Bunyavirales order. The severe disease progression in both SFTS and hemorrhagic fever with renal syndrome (HFRS) is associated with cytokine storms. This study aimed to explore the differences in cytokine profiles and immune responses between the two diseases. A cross-sectional, single-center study involved 100 participants, comprising 46 SFTS patients, 48 HFRS patients, and 6 healthy controls. The study employed the Luminex cytokine detection platform to measure 48 cytokines. The differences in cytokine profiles and immune characteristics between the two diseases were further analyzed using multiple linear regression, principal component analysis, and random forest method. Among the 48 cytokines tested, 30 showed elevated levels in SFTS and/or HFRS compared to the healthy control group. Furthermore, there were 19 cytokines that exhibited significant differences between SFTS and HFRS. Random forest analysis suggested that TRAIL and CTACK were predictive of SFTS, while IL2Ralpha, MIG, IL-8, IFNalpha2, HGF, SCF, MCP-3, and PDGFBB were more common with HFRS. It was further verified by the receiver operating characteristic with area under the curve >0.8 and P-values <0.05, except for TRAIL. Significant differences were observed in the cytokine profiles of SFTS and HFRS, with TRAIL, IL2Ralpha, MIG, and IL-8 being the top 4 cytokines that most clearly distinguished the two diseases. IMPORTANCE: SFTS and HFRS differ in terms of cytokine immune characteristics. TRAIL, IL-2Ralpha, MIG, and IL-8 were the top 4 that differed markedly between SFTS and HFRS.

Supertough MXene/Sodium Alginate Composite Fiber Felts Integrated with Outstanding Electromagnetic Interference Shielding and Heating Properties.

The development of multifunctional MXene-based fabrics for smart textiles and portable devices has garnered significant attention. However, very limited studies have focused on their structure design and associated mechanical properties. Here, the supertough MXene fiber felts composed of MXene/sodium alginate (SA) fibers were fabricated. The fracture strength and bending stiffness of felts can be up to 97.8 MPa and 1.04 N mm2, respectively. Besides, the fracture toughness of felts was evaluated using the classic Griffith theory, yielding to a critical stress intensity factor of 1.79 MPam. In addition, this kind of felt presents outstanding electrothermal conversion performance (up to 119 °C at a voltage of 2.5 V), high cryogenic and high-temperature tolerance of photothermal conversion performance (-196 to 160 °C), and excellent electromagnetic interference (EMI) shielding effectiveness (54.4 dB in the X-band). This work provides new structural design concepts for high-performance MXene-based textiles, broadening their future applications.

Observation of Agonistic Behavior in Pacific White Shrimp (Litopenaeus vannamei) and Transcriptome Analysis.

Agonistic behavior has been identified as a limiting factor in the development of intensive L. vannamei aquaculture. However, the characteristics and molecular mechanisms underlying agonistic behavior in L. vannamei remain unclear. In this study, we quantified agonistic behavior through a behavioral observation system and generated a comprehensive database of eyestalk and brain ganglion tissues obtained from both aggressive and nonaggressive L. vannamei employing transcriptome analysis. The results showed that there were nine behavior patterns in L. vannamei which were correlated, and the fighting followed a specific process. Transcriptome analysis revealed 5083 differentially expressed genes (DEGs) in eyestalk and 1239 DEGs in brain ganglion between aggressive and nonaggressive L. vannamei. Moreover, these DEGs were primarily enriched in the pathways related to the energy metabolism process and signal transduction. Specifically, the phototransduction (dme04745) signaling pathway emerges as a potential key pathway for the adjustment of the L. vannamei agonistic behavior. The G protein-coupled receptor kinase 1-like (LOC113809193) was screened out as a significant candidate gene within the phototransduction pathway. Therefore, these findings contribute to an enhanced comprehension of crustacean agonistic behavior and provide a theoretical basis for the selection and breeding of L. vannamei varieties suitable for high-density aquaculture environments.

Synthesis of fluorescent AuNCs with RNA as template.

Although nucleic acids have been widely used as templates for the synthesis of nanomaterials, the synthesis of RNA-templated gold nanoclusters (AuNCs) has not been explored. In this work, we developed a simple strategy for synthesis of RNA-templated fluorescent AuNCs. We first evaluated the adsorption of different nucleoside monophosphates (NMP) on gold atoms. Our density function theory simulation and isothermal titration calorimetry measurements demonstrated that adenosine monophosphate (AMP) is a superior gold binder than other NMPs or deoxyadenosine monophosphate. Afterwards, NMP-templated synthesis of AuNCs was conducted in various pH environments, and our results indicated that bright green light-emitting AMP-templated AuNCs can be obtained at pH ∼6.0. In order to study the synthesis mechanism of AuNCs, we investigated the effects of reducing agent type and addition time, and the negative charge carried by template nucleotides on the fluorescence of AuNCs. Finally, we extended the template AMP into RNA hairpin structure, the fluorescence intensity was the highest when the cyclic bases were poly 16 A. This study opens new routes to synthesize fluorescent AuNCs using RNA templates.

YHP: Y-chromosome Haplogroup Predictor for predicting male lineages based on Y-STRs.

Human Y chromosome reflects the evolutionary process of males. Male lineage tracing by Y chromosome is of great use in evolutionary, forensic, and anthropological studies. Identifying the male lineage based on the specific distribution of Y haplogroups narrows down the investigation scope, which has been used in forensic scenarios. However, existing software aids in familial searching using Y-STRs (Y-chromosome short tandem repeats) to predict Y-SNP (Y-chromosome single nucleotide polymorphism) haplogroups, they often lack resolution. In this study, we developed YHP (Y Haplogroup Predictor), a novel software offering high-resolution haplogroup inference without requiring extensive Y-SNP sequencing. Leveraging existing datasets (219 haplogroups, 4064 samples in total), YHP predicts haplogroups with 0.923 accuracy under the highest haplogroup resolution, employing a random forest algorithm. YHP, available on Github (https://github.com/cissy123/YHP-Y-Haplogroup-Predictor-), facilitates high-resolution haplogroup prediction, haplotype mismatch analysis, and haplotype similarity comparison. Notably, it demonstrates efficacy in East Asian populations, benefiting from training data from eight distinct East Asian ethnic populations. Moreover, it enables seamless integration of additional training sets, extending its utility to diverse populations.

Development and validation of the PLNA score to predict cytokine storm in acute-phase SFTS patients: A single-center cohort study.

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease known for its high mortality rate and its correlation with Cytokine Storms (CS). Timely detection of CS is crucial for improving the prognosis of the disease. The objective of this investigation was to develop a model for identifying cytokine storms in the acute phase of SFTS. METHODS: A total of 245 patients diagnosed with SFTS were included in this study between January 2020 and July 2022. Among them, 184 patients were part of the training set, while 61 patients were part of the validation set. Variables identified by LASSO were subsequently included in a multivariate logistic regression analysis to determine independent predictors. Subsequently, a nomogram was then developed to predict the likelihood of CS in SFTS patients. The predictive efficacy and clinical applicability of the nomogram model were further assessed through ROC analysis and the DCA curve. RESULTS: Following LASSO analysis, a total of 11 indicators were included in multivariate logistic regression analysis. The findings indicated that PLT (OR 0.865, P < 0.001), LDH (OR 1.002, P < 0.001), Na+ (OR 1.155, P = 0.005), and ALT (OR 1.019, P < 0.001) serve as independently predictors of CS in the acute phase of SFTS. Furthermore, a nomogram named the PLNA was constructed by integrating these four factors. The PLNA model exhibited favorable predictive accuracy with an AUC of 0.958. Moreover, the PLNA model exhibited excellent clinical applicability in both the training and validation sets, as evidenced by the DCA curve. CONCLUSIONS: The PLNA model, constructed using clinical indicators, can predict the probability of cytokine storm in the acute phase of SFTS patients.

Construction of Nanoflower Cobalt-Based Catalyst for Methane-Free CO Hydrogenation to Hydrocarbon Reaction.

Methane and its oxidation product (i. e., CO2) are both greenhouse gases. In the product chain of CO hydrogenation to hydrocarbon reaction, methane is also an unwanted product due to its poor added value. Herein we investigated the effect of structure-directing agent urotropine on cobalt-based catalyst supported on Al-O-Zn type carrier and achieved an initial and pioneering exploration of methane-free CO hydrogenation to hydrocarbon reaction at mild CO conversion range. The catalyst modified by urotropine has a nanoflower micromorphology and can significantly change the reaction performance, almost completely eliminating the ability of the catalyst to inhibit C-C coupling within a mild CO conversion range, that is, it can produce no or less C1-C4 gaseous hydrocarbons, while rich in condensed hydrocarbons (i. e., C5+ hydrocarbon selectivity can reach as high as 92.8 %-100.0 %).

HDAC Inhibition Increases CXCL12 Secretion to Recruit Natural Killer Cells in Peripheral T-cell Lymphoma.

Peripheral T-cell lymphoma (PTCL) is a heterogeneous and aggressive disease with a poor prognosis. Histone deacetylase (HDAC) inhibitors have shown inhibitory effects on PTCL. A better understanding of the therapeutic mechanism underlying the effects of HDAC inhibitors could help improve treatment strategies. Herein, we found that high expression of HDAC3 is associated with poor prognosis in PTCL. HDAC3 inhibition suppressed lymphoma growth in immunocompetent mice but not in immunodeficient mice. HDAC3 deletion delayed the progression of lymphoma, reduced the lymphoma burden in the thymus, spleen, and lymph nodes, and prolonged the survival of mice bearing N-methyl-N-nitrosourea-induced lymphoma. Furthermore, inhibiting HDAC3 promoted the infiltration and enhanced the function of natural killer (NK) cells. Mechanistically, HDAC3 mediated ATF3 deacetylation, enhancing its transcriptional inhibitory activity. Targeting HDAC3 enhanced CXCL12 secretion through an ATF3-dependent pathway to stimulate NK-cell recruitment and activation. Finally, HDAC3 suppression improved the response of PTCL to conventional chemotherapy. Collectively, this study provides insights into the mechanism by which HDAC3 regulates ATF3 activity and CXCL12 secretion, leading to immune infiltration and lymphoma suppression. Combining HDAC3 inhibitors with chemotherapy may be a promising strategy for treating PTCL. Significance: Targeting HDAC3 suppresses progression of T-cell lymphoma by activating ATF3 to induce secretion of CXCL12 and promote infiltration of NK cells, providing an immunostimulatory approach for treating T-cell lymphoma patients.

FGD5 in basal cells induces CXCL14 secretion that initiates a feedback loop to promote murine mammary epithelial growth and differentiation.

The interactions of environmental compartments with epithelial cells are essential for mammary gland development and homeostasis. Currently, the direct crosstalk between the endothelial niche and mammary epithelial cells remains poorly understood. Here, we show that faciogenital dysplasia 5 (FGD5) is enriched in mammary basal cells (BCs) and mediates critical interactions between basal and endothelial cells (ECs) in the mammary gland. Conditional deletion of Fgd5 reduced, whereas conditional knockin of Fgd5 increased, the engraftment and expansion of BCs, regulating ductal morphogenesis in the mammary gland. Mechanistically, murine mammary BC-expressed FGD5 inhibited the transcriptional activity of activating transcription factor 3 (ATF3), leading to subsequent transcriptional activation and secretion of CXCL14. Furthermore, activation of CXCL14/CXCR4/ERK signaling in primary murine mammary stromal ECs enhanced the expression of HIF-1α-regulated hedgehog ligands, which initiated a positive feedback loop to promote the function of BCs. Collectively, these findings identify functionally important interactions between BCs and the endothelial niche that occur through the FGD5/CXCL14/hedgehog axis.

4-Octyl itaconate alleviates dextran sulfate sodium-induced ulcerative colitis in mice via activating the KEAP1-NRF2 pathway.

Ulcerative colitis (UC) is a chronic idiopathic inflammatory bowel disease with a relapsing-remitting course. Although its etiology remains unknown, excessive oxidative stress in colon is a major intermediate factor that can promote the progression of UC. In the present study, we investigated the effect and the underlying mechanisms of 4-Octyl itaconate (OI) on dextran sulfate sodium (DSS)-induced UC in mice. Our work identified that OI alleviated the colitis by reducing the oxidative stress and the apoptosis in colon tissue, then increasing the tight junction proteins expression and in turn enhancing the intestinal barrier function, thereby creating less severe inflammatory responses. Moreover, our results demonstrated that OI reduced the Kelch-like ECH-associated protein 1 (KEAP1) expression and subsequent upregulated nuclear factor E2-related factor (NRF2) expression and its nuclear translocation which in turn induced the expression of glutathione S-transferase (GST) and NAD(P)H: quinone oxidoreductase 1 (NQO1). In addition, ML385, a NRF2 antagonist, can inhibit the protective effects of OI on UC, indicating that the role of OI in this colitis model could be dependent on the activation of KEAP1-NRF2 pathway. Notably, OI co-administration significantly enhanced the therapeutic effects of mesalazine or 1400W on UC. Collectively, itaconate may have a great potential for use in the treatment of IBD.

MCP-3 as a prognostic biomarker for severe fever with thrombocytopenia syndrome: a longitudinal cytokine profile study.

Introduction: Severe fever with thrombocytopenia syndrome (SFTS) is characterized by a high mortality rate and is associated with immune dysregulation. Cytokine storms may play an important role in adverse disease regression, this study aimed to assess the validity of MCP-3 in predicting adverse outcomes in SFTS patients and to investigate the longitudinal cytokine profile in SFTS patients. Methods: The prospective study was conducted at Yantai Qishan Hospital from May to November 2022. We collected clinical data and serial blood samples during hospitalization, patients with SFTS were divided into survival and non-survival groups based on the clinical prognosis. Results: The levels of serum 48 cytokines were measured using Luminex assays. Compared to healthy controls, SFTS patients exhibited higher levels of most cytokines. The non-survival group had significantly higher levels of 32 cytokines compared to the survival group. Among these cytokines, MCP-3 was ranked as the most significant variable by the random forest (RF) model in predicting the poor prognosis of SFTS patients. Additionally, we validated the predictive effects of MCP-3 through receiver operating characteristic (ROC) curve analysis with an AUC of 0.882 (95% CI, 0.787-0.978, P <0.001), and the clinical applicability of MCP-3 was assessed favorably based on decision curve analysis (DCA). The Spearman correlation analysis indicated that the level of MCP-3 was positively correlated with ALT, AST, LDH, α-HBDH, APTT, D-dimer, and viral load (P<0.01). Discussion: For the first time, our study identified and validated that MCP-3 could serve as a meaningful biomarker for predicting the fatal outcome of SFTS patients. The longitudinal cytokine profile analyzed that abnormally increased cytokines were associated with the poor prognosis of SFTS patients. Our study provides new insights into exploring the pathogenesis of cytokines with organ damage and leading to adverse effects.

ROS-responsive nanoparticle delivery of ferroptosis inhibitor prodrug to facilitate mesenchymal stem cell-mediated spinal cord injury repair.

Spinal cord injury (SCI) is a traumatic condition that results in impaired motor and sensory function. Ferroptosis is one of the main causes of neural cell death and loss of neurological function in the spinal cord, and ferroptosis inhibitors are effective in reducing inflammation and repairing SCI. Although human umbilical cord mesenchymal stem cells (Huc-MSCs) can ameliorate inflammatory microenvironments and promote neural regeneration in SCI, their efficacy is greatly limited by the local microenvironment after SCI. Therefore, in this study, we constructed a drug-release nanoparticle system with synergistic Huc-MSCs and ferroptosis inhibitor, in which we anchored Huc-MSCs by a Tz-A6 peptide based on the CD44-targeting sequence, and combined with the reactive oxygen species (ROS)-responsive drug nanocarrier mPEG-b-Lys-BECI-TCO at the other end for SCI repair. Meanwhile, we also modified the classic ferroptosis inhibitor Ferrostatin-1 (Fer-1) and synthesized a new prodrug Feborastatin-1 (Feb-1). The results showed that this treatment regimen significantly inhibited the ferroptosis and inflammatory response after SCI, and promoted the recovery of neurological function in rats with SCI. This study developed a combination therapy for the treatment of SCI and also provides a new strategy for the construction of a drug-coordinated cell therapy system.

High-Entropy Strategy to Achieve Electronic Band Convergence for High-Performance Thermoelectrics.

Multiband convergence has attracted significant interest due to its positive effects on further improving thermoelectric performance. However, the current research mainly focuses on two- or three-band convergence in lead chalcogenides through doping and alloying. Therefore, exploring a new strategy to facilitate more-band convergence has instructive significance and practical value in thermoelectric research. Herein, we first propose a high-entropy strategy to achieve four-band convergence for optimizing thermoelectric performance. Taking high-entropy AgSbPbSnGeTe5 as an example, we found that the emergence of more-band convergence occurs as the configuration entropy increases; in particular, the four-band convergence occurs in high-entropy AgSbPbSnGeTe5. The overlap of multiatom orbitals in the high-entropy sample contributes to the convergence of four valence bands, promoting the improvement of electrical performance. Meanwhile, due to large lattice distortion and disordered atoms, the phonon mean free path is effectively compressed, resulting in low lattice thermal conductivity of high-entropy AgSbPbSnGeTe5. Consequently, AgSbPbSnGeTe5 achieved an intrinsically high ZT value of 1.22 at 673 K, providing a cornerstone for further optimizing thermoelectric performance. For example, by generally optimizing the carrier concentration, a peak ZT value of ∼1.75 at 723 K is achieved. These insights offer a comprehensive understanding of the band structure affected by unique structures of high-entropy materials and also shed useful light on innovation mechanisms and functionalities for future improvement of thermoelectric performance.

In-situ observation of silk nanofibril assembly via graphene plasmonic infrared sensor.

Silk nanofibrils (SNFs), the fundamental building blocks of silk fibers, endow them with exceptional properties. However, the intricate mechanism governing SNF assembly, a process involving both protein conformational transitions and protein molecule conjunctions, remains elusive. This lack of understanding has hindered the development of artificial silk spinning techniques. In this study, we address this challenge by employing a graphene plasmonic infrared sensor in conjunction with multi-scale molecular dynamics (MD). This unique approach allows us to probe the secondary structure of nanoscale assembly intermediates (0.8-6.2 nm) and their morphological evolution. It also provides insights into the dynamics of silk fibroin (SF) over extended molecular timeframes. Our novel findings reveal that amorphous SFs undergo a conformational transition towards ß-sheet-rich oligomers on graphene. These oligomers then connect to evolve into SNFs. These insights provide a comprehensive picture of SNF assembly, paving the way for advancements in biomimetic silk spinning.