Effects of soaking glutinous sorghum grains on physicochemical properties of starch.

Glutinous sorghum grains were soaked (60-80 °C, 2-8 h) to explore the effects of soaking, an essential step in industrial processing of brewing, on starch. As the soaking temperature increased, the peak viscosity and crystallinity of starch gradually decreased, while the enzymatic hydrolysis rate and storage modulus first increased and then decreased. At 70 °C, the content of amylose, the enzymatic hydrolysis rate of starch, and the final viscosity first increase and then decrease with the increase of soaking time, reaching their maximum at 6 h, increased by 53.1 %, 11.0 %, and 10.4 %, respectively, as compared with the non-soaked sample. At 80 °C (4 h), the laser confocal microscopy images showed a network structure formed between the denatured protein chains and the leached-out amylose chains. The molecular weights of starch before and after soaking were all in the range of 3.82-8.98 × 107 g/mol. Since 70 °C is lower than that of starch gelatinization and protein denaturation, when soaking for 6 h, the enzymatic hydrolysis rate of starch is the highest, and the growth of miscellaneous bacteria is inhibited, which is beneficial for subsequent processing technology. The result provides a theoretical basis for the intelligent control of glutinous sorghum brewing.

Preoperative pancreatic stent placement before the enucleation of insulinoma located in the head and neck of the pancreas in proximity to the main pancreatic duct: study protocol for a multicentre randomised clinical trial in Chinese tertiary medical centres.

INTRODUCTION: The surgical intervention approach to insulinomas in proximity to the main pancreatic duct remains controversial. Standard pancreatic resection is recommended by several guidelines; however, enucleation (EN) still attracts surgeons with less risk of late exocrine/endocrine insufficiency, despite a higher postoperative pancreatic fistula (POPF) rate. Recently, the efficacy and safety of preoperative pancreatic stent placement before the EN have been demonstrated. Thus, a multicentre open-label study is being conducted to evaluate the efficacy and safety of stent placement in improving the outcome of EN of insulinomas in proximity to the main pancreatic duct. METHODS AND ANALYSIS: This is a prospective, randomised, open-label, superiority clinical trial conducted at multiple tertiary centres in China. The major eligibility criterion is the presence of insulinoma located in the head and neck of the pancreas in proximity (≤2 mm) to the main pancreatic duct. Blocked randomisation will be performed to allocate patients into the stent EN group and the direct EN group. Patients in the stent EN group will go through stent placement by the endoscopist within 24 hours before the EN surgery, whereas other patients will receive EN surgery directly. The primary outcome is the assessment of the superiority of stent placement in reducing POPF rate measured by the International Study Group of Pancreatic Surgery standard. Both interventions will be performed in an inpatient setting and regular follow-up will be performed. The primary outcome (POPF rate) will be tested for superiority with the Χ2 test. The difference in secondary outcomes between the two groups will be analysed using appropriate tests. ETHICS AND DISSEMINATION: The study has been approved by the Peking Union Medical College Hospital Institutional Review Board (K23C0195), Ruijin Hospital Ethics Committee (2023-314), Peking University First Hospital Ethics Committee (2024033-001), Institutional Review Board of Xuanwu Hospital of Capital Medical University (2023223-002), Ethics Committee of the First Affiliated Hospital of Xi'an Jiaotong University (XJTU1AF2023LSK-473), Institutional Review Board of Tongji Medical College Tongji Hospital (TJ-IRB202402059), Ethics Committee of Tongji Medical College Union Hospital (2023-0929) and Shanghai Cancer Center Institutional Review Board (2309282-16). The results of the study will be published in an international peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05523778.

Bioluminescence Imaging of Potassium Ion Using a Sensory Luciferin and an Engineered Luciferase.

Bioluminescent indicators are power tools for studying dynamic biological processes. In this study, we present the generation of novel bioluminescent indicators by modifying the luciferin molecule with an analyte-binding moiety. Specifically, we have successfully developed the first bioluminescent indicator for potassium ions (K+), which are critical electrolytes in biological systems. Our approach involved the design and synthesis of a K+-binding luciferin named potassiorin. Additionally, we engineered a luciferase enzyme called BRIPO (bioluminescent red indicator for potassium) to work synergistically with potassiorin, resulting in optimized K+-dependent bioluminescence responses. Through extensive validation in cell lines, primary neurons, and live mice, we demonstrated the efficacy of this new tool for detecting K+. Our research demonstrates an innovative concept of incorporating sensory moieties into luciferins to modulate luciferase activity. This approach has great potential for developing a wide range of bioluminescent indicators, advancing bioluminescence imaging (BLI), and enabling the study of various analytes in biological systems.

Preparation of nitrogen doped hyper-crosslinked polymer-based hard carbon for high performance Li+/Na+ battery anode.

Hyper cross-linked polymers (HCPs), as a key precursor of hard carbon (HC) anode materials, stand out because of their capacity for molecular-scale structural design and comparatively straightforward preparation techniques, which are not seen in other porous materials synthesized procedure. A novel synthesis method of HCPs is developed in this paper, which is through the incorporation of functional macromolecules, the structural control and heteroatom doping of the product has been achieved, thus augmenting its electrochemical performance in batteries. In this work, carbonized tetraphenylporphyrin zinc (TPP-Zn) doped HCP-based hard carbon (CTHCP) with stable structure was prepared by Friedel-Crafts reaction and carbonization by using naphthalene and trace TPP-Zn as monomers, dimethoxybenzene (DMB) as crosslinking agent and FeCl3 as catalyst. The introduction of TPP-Zn, a functional macromolecule with unique two-dimensional structure, realized the pore structure regulation and N doping of the raw carbonized HCP-based hard carbon (CHCP). The results showed that CTHCP had higher mesoporous volume, N content and wider layer spacing than CHCP. In addition, CTHCP anode exhibited excellent Li+/Na+ storage performance, initial reversible capacity, rate performance and long cycle life. More amount of N-containing (N-5) active sites and mesoporous content in CTHCP anode was the main reason for the improvement of Na+ storage effect. While the increased interlayer spacing had a greater effect on the lithium storage capacity. This study uncovered the design rules of HC anode materials suitable for Li+/Na+ batteries and provided a new idea for the preparation of high-performance HC anode materials.

Adsorption performance of mineral-carbon adsorbents derived from coal gasification fine ash: Prepared via low-temperature alkali fusion method.

To address the solid waste challenges associated with coal gasification fine ash, this study conducted a low-temperature alkali fusion de-ashing treatment to transform coal gasification fine ash into mineral-carbon adsorbent. The preparation process was simplified without grinding, carbonization and high-temperature (500-800 °C) activation treatment. The results demonstrate a positive linear correlation between the ash removal rate of the samples (measured during the preparation process, i.e., low-temperature alkaline fusion treatment of coal gasification fine ash) and their maximum equilibrium adsorption capacity for methylene blue. For the samples with an ash removal rate of 95.71 %, which exhibit a maximum adsorption capacity of 161.36 mg/g for methylene blue. The adsorption behavior of methylene blue on mineral-carbon adsorbent was a monolayer adsorption on the surface of homogeneous medium, involving both physical and chemical adsorption. The main adsorb rate-controlling steps for the samples with ash removal rates of 27.91-59.33 % and 95.71 % were the intra particle diffusion process and the liquid film diffusion process, respectively. The adsorption mechanism of methylene blue on the surface of mineral-carbon adsorbent involved electrostatic attraction and hydrogen bonding. The aforementioned results demonstrated the potential of coal gasification fine ash as an adsorbent material, providing new options for promoting the resource utilization and high-value applications of coal gasification fine ash.

Genetic Characteristics of Wuxiang Virus in Shanxi Province, China.

Wuxiang virus (WUXV) is the first sandfly-borne Phlebovirus isolated from Phlebotomus chinensis collected in China and has been established as a consistent viral presence in the local sandfly populations of both Wuxiang County and Yangquan City. However, its distribution in the Shanxi Province remains unclear. In this study, three novel WUXV strains were isolated from sandflies collected from Jiexiu City, Shanxi Province, China, in 2022. Subsequently, whole-genome sequences of these novel strains were generated using next-generation sequencing. The open reading frame (ORF) sequences of the WUXV strains from the three locations were subjected to gene analysis. Phylogenetic analysis revealed that WUXV belongs to two distinct clades with geographical differences. Strains from Wuxiang County and Yangquan City belonged to clade 1, whereas strains from Jiexiu City belonged to clade 2. Reassortment and recombination analyses indicated no gene reassortment or recombination between the two clades. However, four reassortments or recombination events could be detected in clade 1 strains. By aligning the amino acid sequences, eighty-seven mutation sites were identified between the two clades, with seventeen, sixty, nine, and one site(s) in the proteins RdRp, M, NSs, and N, respectively. Additionally, selection pressure analysis identified 17 positively selected sites across the entire genome of WUXV, with two, thirteen, one, and one site(s) in the proteins RdRp, M, NSs, and N, respectively. Notably, sites M-312 and M-340 in the M segment not only represented mutation sites but also showed positive selective pressure effects. These findings highlight the need for continuous nationwide surveillance of WUXV.

Engineering and Characterization of 3-Aminotyrosine-Derived Red Fluorescent Variants of Circularly Permutated Green Fluorescent Protein.

Introducing 3-aminotyrosine (aY), a noncanonical amino acid (ncAA), into green fluorescent protein (GFP)-like chromophores shows promise for achieving red-shifted fluorescence. However, inconsistent results, including undesired green fluorescent species, hinder the effectiveness of this approach. In this study, we optimized expression conditions for an aY-derived cpGFP (aY-cpGFP). Key factors like rich culture media and oxygen restriction pre- and post-induction enabled high-yield, high-purity production of the red-shifted protein. We also engineered two variants of aY-cpGFP with enhanced brightness by mutating a few amino acid residues surrounding the chromophore. We further investigated the sensitivity of the aY-derived protein to metal ions, reactive oxygen species (ROS), and reactive nitrogen species (RNS). Incorporating aY into cpGFP had minimal impact on metal ion reactivity but increased the response to RNS. Expanding on these findings, we examined aY-cpGFP expression in mammalian cells and found that reductants in the culture media significantly increased the red-emitting product. Our study indicates that optimizing expression conditions to promote a reduced cellular state proved effective in producing the desired red-emitting product in both E. coli and mammalian cells, while targeted mutagenesis-based protein engineering can further enhance brightness and increase method robustness.

Event-related alpha power in early stage of facial expression processing in social anxiety: Influence of language context.

Accurate interpretation of the emotional information conveyed by others' facial expressions is crucial for social interactions. Event-related alpha power, measured by time-frequency analysis, is a frequently used EEG index of emotional information processing. However, it is still unclear how event-related alpha power varies in emotional information processing in social anxiety groups. In the present study, we recorded event-related potentials (ERPs) while participants from the social anxiety and healthy control groups viewed facial expressions (angry, happy, neutral) preceded by contextual sentences conveying either a positive or negative evaluation of the subject. The impact of context on facial expression processing in both groups of participants was explored by assessing behavioral ratings and event-related alpha power (0-200 ms after expression presentation). In comparison to the healthy control group, the social anxiety group exhibited significantly lower occipital alpha power in response to angry facial expressions in negative contexts and neutral facial expressions in positive contexts. The influence of language context on facial expression processing in individuals with social anxiety may occur at an early stage of processing.

Single-cell transcriptome profiling of primary tumors and paired organoids of pancreatobiliary cancer.

Single-cell RNA-seq (scRNA-seq) and cancer organoid model have shown promise in investigating tumor microenvironment heterogeneity and facilitating chemotherapeutic drug testing to inform treatment selection. It is still unknown whether the scRNA-seq results based on organoid can faithfully reflect the heterogeneity of primary pancreatobiliary cancer. To reveal the similarities and differences between primary tumors and their matched organoids at transcriptome level, we conducted scRNA-seq for paired primary tumors and organoids from one cholangiocarcinoma (CCA) and two pancreatic ductal adenocarcinoma (PDAC) patients. We identified inter-patient and intra-tumor heterogeneity and found that the organoids retained copy number variation (CNV) patterns of primary tumors. There was no significant difference in cancer stem cell (CSC) properties between the primary tumors and the organoids, whereas organoid from one PDAC case had increased mesenchymal-score and decreased epithelial-score compared with the primary tumors. All organoids showed a transition tendency from the classical subtype to the basal-like subtype in the transcriptional level. Organoids and primary tumors differed in metabolic and unfolded protein response (UPR) signatures. In addition, we revealed the heterogeneity of cancer associated fibroblasts (CAFs) and T cells, and explored the developmental trajectory of T cells. Our findings facilitate further understanding of organoid model and confirm its application prospects in pancreatobiliary cancer.

Machine learning algorithm integrates bulk and single-cell transcriptome sequencing to reveal immune-related personalized therapy prediction features for pancreatic cancer.

Pancreatic cancer (PC) is a digestive malignancy with worse overall survival. Tumor immune environment (TIME) alters the progression and proliferation of various solid tumors. Hence, we aimed to detect the TIME-related classifier to facilitate the personalized treatment of PC. Based on the 1612 immune-related genes (IRGs), we classified patients into Immune_rich and Immune_desert subgroups via consensus clustering. Patients in distinct subtypes exhibited a difference in sensitivity to immune checkpoint blockers (ICB). Next, the immune-related signature (IRS) model was established based on 8 IRGs (SYT12, TNNT1, TRIM46, SMPD3, ANLN, AFF3, CXCL9 and RP1L1) and validated its predictive efficiency in multiple cohorts. RT-qPCR experiments demonstrated the differential expression of 8 IRGs between tumor and normal cell lines. Patients who gained lower IRS score tended to be more sensitive to chemotherapy and immunotherapy, and obtained better overall survival compared to those with higher IRS scores. Moreover, scRNA-seq analysis revealed that fibroblast and ductal cells might affect malignant tumor cells via MIF-(CD74+CD44) and SPP1-CD44 axis. Eventually, we identified eight therapeutic targets and one agent for IRS high patients. Our study screened out the specific regulation pattern of TIME in PC, and shed light on the precise treatment of PC.

Single-cell RNA-seq reveals characteristics in tumor microenvironment of PDAC with MSI-H following neoadjuvant chemotherapy with anti-PD-1 therapy.

Accumulating evidence suggests the minority of patients with advanced pancreatic ductal adenocarcinoma (PDAC) that have microsatellite instability high (MSI-H) can benefit from immune checkpoint inhibitors (ICIs). However, the effects of ICIs on the tumor microenvironment (TME) of PDAC remain elusive. We conducted single-cell RNA-seq (scRNA-seq) analysis on a residual lesion from a MSI-H PDAC patient who received a radical operation after eight cycles of neoadjuvant treatment (nab-paclitaxel/gemcitabine plus pembrolizumab). Multiple tumor subclusters were identified in residual lesion after neoadjuvant treatment, one of which was mainly composed of cells in the S and G2M phases. This subcluster also had enriched expression of MKI67 and PCNA and cell cycle-related signatures and was thus defined as a proliferating tumor subcluster. This subcluster had higher S_score, Fatty acid_score, UPR_score, and Glycolysis_score than others. We also identified characteristics of the TME after neoadjuvant treatment by comparing the excised primary tumors form nontreated PDAC and the residual lesion. The residual lesion was characterized with activated pancreatic stellate cells (PSCs) and exhausted T cells (Tex). We compared the receptor-ligand interactions between the two groups, and found that no checkpoint receptor-ligand pairs between T cells and tumor cells were identified in the residual lesion, while there were many checkpoint receptor-ligand pairs in the nontreated primary PDAC. In conclusion, our findings revealed the characteristics of residual lesion of advanced PDAC with MSI-H upon combination treatment of chemotherapy and immunotherapy, which might provide some valuable clues for solving the puzzle of ICI in PDAC.

Clinical characteristics of liver injury induced by immune checkpoint inhibitors in patients with advanced biliary tract carcinoma.

Immune-related liver injuries are closely associated with the liver's fundamental state. Patients with advanced biliary tract carcinoma (BTC) have poor liver function. We evaluated the clinical data of immune-related liver injury in patients with advanced BTC and gastric cancer (GC) during immune checkpoint inhibitor (ICI) treatment between February 2019 and July 2022 at Peking University First Hospital. Twenty-five patients with advanced BTC were identified. Fifteen patients (60%) experienced immune-related liver injury during ICI treatment. We also evaluated the clinical status of patients with GC in another group receiving immunotherapy. The results demonstrated that the incidence of immune-related liver injury was higher in patients with BTC than in GC cancer (p=0.040). Multivariate analysis suggested that the type of malignant tumor and baseline liver function status were high-risk factors for grade 2 and higher immune-related liver injuries. Two patients were diagnosed with immune-related cholangitis. Both biliary enzymes can be decreased to a certain degree by corticosteroid and ursodeoxycholic acid (UDCA) therapy but are difficult to reduce to normal levels. Liver function normalized, and symptoms improved after local treatment for cholestasis (stent implantation or PTBD). We observed a higher incidence of immune-related liver injury after ICI treatment in patients with advanced BTC. Effect of baseline liver function on the incidence of liver injury associated with immunotherapy. Interventional therapy provides rapid relief from cholestasis and is an indispensable and effective approach to the treatment of immune-related cholangitis.

Sustainable preparation of high-calorific value and low-N and S energy products through the low-temperature alkali fusion of coal gasification fine ash.

Coal gasification fine ash (CGFA) is characterized by high yield, high carbon content, and difficult recovery. This results in waste of coal resources and serious environmental pollution. To address this issue, a novel green deashing process is proposed in this study to modify CGFA into deashed carbon (DAC) with a high calorific value and an ash content of less than 5% through a low-temperature alkaline fusion process. Compared with traditional alkaline fusion (which is carried out at 600-1000 °C), low-temperature alkaline fusion treatment can efficiently remove ash minerals in the temperature range of 300-450 °C, which is beneficial to the efficient recovery of residual carbon in DA, while simultaneously improving the physicochemical properties and energy characteristics of DAC, thereby improving its combustion performance. At an alkali fusion temperature of 350 °C, a NaOH:DA ratio of 4.5:1, and a reaction time of 40 min, the resulting DAC product had ash content of 2.28%, combustible material recovery (CMR) of 82.03%, higher heating value (HHV) of 31.07 MJ kg-1, and SBET of 445.43 m2 g-1. In comparison, it was found that low-temperature alkali fusion significantly improved the deashing of CGFA when compared to existing deashing technologies. These results strongly suggest that this innovative deashing method can modify CGFA into a high-calorific value and low-N and S fuel, thereby providing a cost-effective and sustainable utilization method for CGFA.

Cross-species scRNA-seq reveals the cellular landscape of retina and early alterations in type 2 diabetes mice.

Single-cell RNA sequencing (scRNA-seq) analysis have provided an unprecedented resolution for the studies on diabetic retinopathy (DR). However, the early changes in the retina in diabetes remain unclear. A total of 8 human and mouse scRNA-seq datasets, containing 276,402 cells were analyzed individually to comprehensively delineate the retinal cell atlas. The neural retinas were isolated from the type 2 diabetes (T2D) and control mice, and scRNA-seq analysis was conducted to evaluate the early effects of diabetes on the retina. Bipolar cell (BC) heterogeneity were identified. We found some stable BCs across multiple datasets, and explored their biological functions. A new RBC subtype (Car8_RBC) in the mouse retina was validated using the multi-color immunohistochemistry. AC149090.1 was significantly upregulated in the rod cells, ON cone BCs (CBCs), OFF CBCs, and RBCs in T2D mice. Additionally, the interneurons, especially BCs, were the most vulnerable cells to diabetes by integrating scRNA-seq and genome-wide association studies (GWAS) analyses. In conclusion, this study delineated a cross-species retinal cell atlas and uncovered the early pathological alterations in the retina of T2D mice.

The benefits of neoadjuvant therapy for patients with resectable pancreatic cancer: an updated systematic review and meta-analysis.

Neoadjuvant therapy (NAT) was effective in improving overall survival (OS) of borderline resectable pancreatic cancer. However, its application in resectable pancreatic cancer remains controversial. This study aimed to determine whether NAT has a greater advantage over conventional upfront surgery (US) in terms of resection rate, R0 resection rate, positive lymph node rate, and OS. We identified articles before October 7, 2022, by searching four electronic databases. The studies included in the meta-analysis all met the inclusion and exclusion criteria. The Newcastle-Ottawa scale was used to evaluate the quality of the articles. OS, DFS, resection rate, R0 resection rate and positive lymph nodes rate were extracted. Odds ratio (OR), hazard ratio (HR) and 95% confidence intervals (CI) were calculated, and sensitivity analysis and publication bias were used to assess the sources of heterogeneity. In total, 24 studies, involving 1384 (35.66%) patients assigned to NAT and 2497 (64.43%) patients assigned to US, were included in the analysis. NAT could effectively prolong OS (HR 0.73, 95% CI 0.65-0.82, P < 0.001) and DFS (HR 0.72, 95% CI 0.62-0.84, P < 0.001). Subgroup analysis results of 6 randomized controlled trials (RCTs) also showed that RPC patients could benefit from NAT in the long term (HR 0.72, 95% CI 0.58-0.90, P = 0.003). NAT decreased resection rate (OR 0.43, 95% CI 0.33-0.55, P < 0.001), but was associated with increased R0 resection rate (OR 2.05, 95% CI 1.47-2.88, P < 0.001) and decreased positive lymph node rate (OR 0.38, 95% CI 0.27-0.52, P < 0.001). Although the application of NAT increases the risk of patients not being able to undergo surgical resection, it can prolong the OS and delay tumor progression in RPC. Therefore, we still expect larger and higher-quality RCTs to confirm the effectiveness of NAT.

Identification of novel prognostic model based on homologous recombination deficiency associated lncRNAs in lung adenocarcinoma.

Background: Non-small cell lung cancer with homologous recombination deficiency (HRD) was revealed to have better response to immunotherapy. Long non-coding RNAs (lncRNAs) modulate multiple processes including HRD acting as potential biomarkers in tumors. The function of HRD-associated lncRNAs in lung cancer arouses our interests. Methods: Two independent cohorts were enrolled containing 838 lung adenocarcinoma (LUAD) patients. HRD-associated lncRNAs were defined as the lncRNAs that were differential expressed in high-HRD group and low-HRD group which were classified in accordance with the HRD score. The least absolute shrinkage and selection operator cox regression was employed to construct a signature according to prognostic HRD-associated lncRNAs. The signature robustness was evaluated by using the prognosis analysis, multivariate-cox analysis, ROC curve, and nomogram. The participating pathways were estimated by gene set enrichment analysis and KEGG pathway analysis. The infiltration of immune cells was estimated by using xCell. The tumor immune dysfunction and exclusion (TIDE) and immunophenoscore (IPS) were both utilized for the prediction of immunotherapy response. Results: Seventeen HRD-associated lncRNAs were screened to classify the LUAD patients into two groups with variant survival that inferior overall survival was found in high-risk patients comparing to those with low-risk. Our model not only was the independent prognostic factor in LUAD but also had better performance on the prognosis prediction when making a comparison with other clinical and molecular signatures. Additionally, the high-risk group was suggested to have increased genomic instability and less response to immunotherapy. Conclusion: A great predicative efficient prognostic signature was established based on 17 HRD-associated lncRNAs in LUAD. The signature might be the predictor for genomic instability and immunotherapy response in LUAD. Our findings provided new insight for the improvement of clinical stratification in LUAD.

Immune profiling and prognostic model of pancreatic cancer using quantitative pathology and single-cell RNA sequencing.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a complex tumor immune microenvironment (TIME), the clinical value of which remains elusive. This study aimed to delineate the immune landscape of PDAC and determine the clinical value of immune features in TIME. METHODS: Univariable and multivariable Cox regression analyses were performed to evaluate the clinical value of immune features and establish a new prognostic model. We also conducted single-cell RNA sequencing (scRNA-seq) to further characterize the immune profiles of PDAC and explore cell-to-cell interactions. RESULTS: There was a significant difference in the immune profiles between PDAC and adjacent noncancerous tissues. Several novel immune features were captured by quantitative pathological analysis on multiplex immunohistochemistry (mIHC), some of which were significantly correlated with the prognosis of patients with PDAC. A risk score-based prognostic model was established based on these immune features. We also constructed a user-friendly nomogram plot to predict the overall survival (OS) of patients by combining the risk score and clinicopathological features. Both mIHC and scRNA-seq analysis revealed PD-L1 expression was low in PDAC. We found that PD1 + cells were distributed in different T cell subpopulations, and were not enriched in a specific subpopulation. In addition, there were other conserved receptor-ligand pairs (CCL5-SDC1/4) besides the PD1-PD-L1 interaction between PD1 + T cells and PD-L1 + tumor cells. CONCLUSION: Our findings reveal the immune landscape of PDAC and highlight the significant value of the combined application of mIHC and scRNA-seq for uncovering TIME, which might provide new clues for developing immunotherapy combination strategies.

A genetically encoded far-red fluorescent indicator for imaging synaptically released Zn2.

Synaptic zinc ion (Zn2+) has emerged as a key neuromodulator in the brain. However, the lack of research tools for directly tracking synaptic Zn2+ in the brain of awake animals hinders our rigorous understanding of the physiological and pathological roles of synaptic Zn2+. In this study, we developed a genetically encoded far-red fluorescent indicator for monitoring synaptic Zn2+ dynamics in the nervous system. Our engineered far-red fluorescent indicator for synaptic Zn2+ (FRISZ) displayed a substantial Zn2+-specific turn-on response and low-micromolar affinity. We genetically anchored FRISZ to the mammalian extracellular membrane via a transmembrane (TM) ⍺ helix and characterized the resultant FRISZ-TM construct at the mammalian cell surface. We used FRISZ-TM to image synaptic Zn2+ in the auditory cortex in acute brain slices and awake mice in response to electric and sound stimuli, respectively. Thus, this study establishes a technology for studying the roles of synaptic Zn2+ in the nervous system.

In situ Ti assisted graphitization approach for the preparation of graphite foam with light weight and high thermal conductivity.

The state-of-the-art graphite foams (GFs) are afflicted by large bulk density and low thermal conductivity, restricting their practical application. To alleviate the above problem, herein, an issue-oriented scheme, i.e., an in situ titanium (Ti) assisted catalytic graphitization strategy was proposed by using AR mesophase pitch (ARMP) as a precursor. In a typical preparation process, the mixture of Ti and ARMP underwent a pressurized foam, carbonization, and graphitization procedure successively to obtain GFs. The results showed that the Ti content played an important role in the development of the graphitic microcrystal structure due to the catalytic graphitization of Ti. According to the XRD analysis and molecular dynamics (MD) simulation, we confirmed that Ti promoted graphitization mainly by the generation of TiC during the high-temperature graphitization. The GFs obtained with 11 wt% Ti exhibited the most perfect graphitic crystal structure, with the highest graphitization degree. Thanks to the improved graphitization degree, the thermal conductivity of GFs increased with the added amount of Ti increasing from 0 to 11 wt%. The highest thermal conductivity of 60.8 W m-1 K-1 and the low bulk density of 0.36 g cm-3 could be achieved when the addition amount of Ti was 11 wt%. Meanwhile, apart from the optimization of thermal conductivity and bulk density, the compressive strength was also enhanced as the amount of Ti increased from 0 to 15 wt%. Our work provided a facile and scalable approach to preparing GFs with low density and high thermal conductivity.