TransGEM: a molecule generation model based on Transformer with gene expression data.

MOTIVATION: It is difficult to generate new molecules with desirable bioactivity through ligand-based de novo drug design, and receptor-based de novo drug design is constrained by disease target information availability. The combination of artificial intelligence and phenotype-based de novo drug design can generate new bioactive molecules, independent from disease target information. Gene expression profiles can be used to characterize biological phenotypes. The Transformer model can be utilized to capture the associations between gene expression profiles and molecular structures due to its remarkable ability in processing contextual information. RESULTS: We propose TransGEM (Transformer-based model from gene expression to molecules), which is a phenotype-based de novo drug design model. A specialized gene expression encoder is used to embed gene expression difference values between diseased cell lines and their corresponding normal tissue cells into TransGEM model. The results demonstrate that the TransGEM model can generate molecules with desirable evaluation metrics and property distributions. Case studies illustrate that TransGEM model can generate structurally novel molecules with good binding affinity to disease target proteins. The majority of genes with high attention scores obtained from TransGEM model are associated with the onset of the disease, indicating the potential of these genes as disease targets. Therefore, this study provides a new paradigm for de novo drug design, and it will promote phenotype-based drug discovery. AVAILABILITY AND IMPLEMENTATION: The code is available at https://github.com/hzauzqy/TransGEM.

Integrated Platform for Large-Scale Quantitative Profiling of Phosphotyrosine Signaling Complexes Based on Cofractionation/Mass Spectrometry and Complex-Centric Algorithm.

The scarcity and dynamic nature of phosphotyrosine (pTyr)-modified proteins pose a challenge for researching protein complexes with pTyr modification, which are assembled through multiple protein-protein interactions. We developed an integrated complex-centric platform for large-scale quantitative profiling of pTyr signaling complexes based on cofractionation/mass spectrometry (CoFrac-MS) and a complex-centric algorithm. We initially constructed a trifunctional probe based on pTyr superbinder (SH2-S) for specifically binding and isolation of intact pTyr protein complexes. Then, the CoFrac-MS strategy was employed for the identification of pTyr protein complexes by integrating ion exchange chromatography in conjunction with data independent acquisition mass spectrometry. Furthermore, we developed a novel complex-centric algorithm for quantifying protein complexes based on the protein complex elution curve. Utilizing this algorithm, we effectively quantified 216 putative protein complexes. We further screened 21 regulated pTyr protein complexes related to the epidermal growth factor signal. Our study engenders a comprehensive framework for the intricate examination of pTyr protein complexes and presents, for the foremost occasion, a quantitative landscape delineating the composition of pTyr protein complexes in HeLa cells.

Multichannel Nanogenerator-Driven Collaborative Metabolic Fingerprint Diagnostic Strategy for Early Screening and Risk Evaluation of Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD), along with its progressive forms nonalcoholic steatohepatitis (NASH) and NASH fibrosis, has emerged as a global health crisis. However, the absence of robust screening and risk evaluation tools contributes to the underdiagnosis of NAFLD. Herein, we reported a multichannel nanogenerator-assisted laser desorption/ionization mass spectrometry (LDI-MS) platform for early screening and risk evaluation of NAFLD. Specifically, titanium oxide nanosheets (TiNS) and covalent-organic framework nanosheets (COFNS) were employed as nanogenerators with excellent optical properties and exhibited efficient desorption/ionization during the LDI-MS process. Only ∼0.025 µL of serum without pretreatments and separation, serum metabolic fingerprints (SMFs) can be extracted within seconds. Notably, integrated SMFs from TiNS and COFNS significantly improved diagnostic performance and achieved the area under the curve (AUC) values of 1.000 with 100% sensitivity and 100% specificity for the validation sets of global diagnosis, early diagnosis, high-risk NASH, and NASH fibrosis evaluation. Additionally, four biomarker panels were identified, and their diagnostic AUC values were more than 0.944. Ultimately, key metabolic pathways indicating the change from simple NAFLD to high-risk NASH and NASH fibrosis were uncovered. This work provided a noninvasive and high-throughput screening and risk evaluation strategy for NAFLD healthcare management, thus contributing to the precise treatment of the NALFD.

High-Throughput Metabolic Pattern Screening Strategy for Early Colorectal and Gastric Cancers Based on Covalent Organic Frameworks-Assisted Laser Desorption/Ionization Mass Spectrometry.

Precise early diagnosis and staging are conducive to improving the prognosis of colorectal cancer (CRC) and gastric cancer (GC) patients. However, due to intrusive inspections and limited sensitivity, the prevailing diagnostic methods impede precisely large-scale screening. In this work, we reported a high-throughput serum metabolic patterns (SMP) screening strategy based on covalent organic frameworks-assisted laser desorption/ionization mass spectrometry (hf-COFsLDI-MS) for early diagnosis and staging of CRC and GC. Notably, 473 high-quality SMP were extracted without any tedious sample pretreatment and coupled with multiple machine learning algorithms; the area under the curve (AUC) value is 0.938 with 96.9% sensitivity for early CRC diagnosis, and the AUC value is 0.974 with 100% sensitivity for early GC diagnosis. Besides, the discrimination of CRC and GC is accomplished with an AUC value of 0.966 for the validation set. Also, the screened-out features were identified by MS/MS experiments, and 8 metabolites were identified as the biomarkers for CRC and GC. Finally, the corresponding disordered metabolic pathways were revealed, and the staging of CRC and GC was completed. This work provides an alternative high-throughput screening strategy for CRC and GC and highlights the potential of metabolic molecular diagnosis in clinical applications.

Design and preparation of Ti-xFe antibacterial titanium alloys based on micro-area potential difference.

Fe was selected as an alloying element for the first time to prepare a new antibacterial titanium alloy based on micro-area potential difference (MAPD) antibacterial mechanism. The microstructure, the corrosion resistance, the mechanical properties, the antibacterial properties and the cell biocompatibility have been investigated in detail by optical microscopy, scanning electron microscopy, electrochemical testing, mechanical property test, plate count method and cell toxicity measurement. It was demonstrated that heat treatment had a significant on the compressive mechanical properties and the antibacterial properties. Ti-xFe (x = 3,5 and 9) alloys after 850 °C/3 h + 550 °C/62 h heat treatment exhibited strong antimicrobial properties with an antibacterial rate of more than 90% due to the MAPD caused by the redistribution of Fe element during the aging process. In addition, the Fe content and the heat treatment process had a significant influence on the mechanical properties of Ti-xFe alloy but had nearly no effect on the corrosion resistance. All Ti-xFe alloys showed non-toxicity to the MC3T3 cell line in comparison with cp-Ti, indicating that the microzone potential difference had no adverse effect on the corrosion resistance, cell proliferation, adhesion, and spreading. Strong antibacterial properties, good cell compatibility and good corrosion resistance demonstrated that Ti-xFe alloy might be a candidate titanium alloy for medical applications.

Prevalence, characteristics, and risk factors of venous thromboembolism in patients with brain tumor undergoing craniotomy: a meta-analysis.

BACKGROUND: Brain tumor patients undergoing craniotomy are significantly associated with the development of venous thromboembolism (VTE), while the contributing factors remains controversial. Our study aimed to investigate the prevalence and risk factors for VTE in postoperational brain tumor patients. METHODS: We searched the PubMed, Embase, Web of Science, Medline, and Cochrane Library databases from their inception to July 2023. Article selection, data extraction, and study quality assessment were performed independently by two reviewers. Publication bias was assessed using Egger's and Begg's tests. Stata 15.0 software was used for data analysis. RESULTS: A total of 25 studies were considered, with a total of 49,620 brain tumor individuals. The pooled prevalence of VTE during hospitalization in postoperational brain tumor patients was 9% [95% CI: (0.08, 0.10)]. Moreover, our results demonstrated that patients with VTE were older than those without VTE [mean difference [MD] = 8.14, 95% CI: (4.97, 11.30)]. The following variables were significantly associated with VTE: prior history of VTE [OR = 7.81, 95% CI: (3.62, 16.88)], congestive heart failure [OR = 2.33, 95% CI: (1.08-5.05)], diabetes [OR = 1.87, 95% CI: (1.12-3.10)], hypertension [OR = 1.27, 95% CI: (1.07-1.50)], steroid use [OR = 1.63, 95% CI: (1.41, 1.88)], high white blood cells counts [MD = 0.32, 95% CI: (0.01, 0.63)], and high fibrinogen levels [MD = 0.19, 95% CI: (0.08, 0.30)]. CONCLUSION: This meta-analysis identified risk factors for postoperational VTE in patients with brain tumor, which can serve as a theoretical foundation for medical staff to manage and treat VTE. TRIAL REGISTRATION: CRD42023357459.

Comparison of Locking Plate Alone and Locking Plate Combined with 3D Printed Polymethylmethacrylate Augmentation in Treating Proximal Humerus Fractures in the Elderly.

BACKGROUND: Locking plates are widely used in open reduction internal fixation (ORIF) for proximal humeral fracture (PHF). However, the optimal surgical treatment of unstable, displaced PHF in elderly patients remains controversial. This study aimed to compare the radiological and clinical outcomes of surgical treatment of PHF in the elderly with locking plate (LP) alone and locking plate combined with 3D printed polymethylmethacrylate (PMMA) prosthesis augmentation (LP-PA). METHODS: From May 2015 to April 2021, a total of 97 patients aged ≥ 60 years with acute unstable PHF who underwent osteosynthesis with either LP (46 patients) or LP-PA (51 patients) were retrospectively analyzed. For the LP-PA group, a customized proximal humeral prosthesis made of PMMA cement was intra-operatively fabricated by a three-dimensional (3D) printed prototype mold for the humeral medial support. Radiological outcomes were analyzed by measuring the value of neck-shaft angle (NSA) and humeral head height (HHH). The clinical outcomes were evaluated using Constant-Murley Score (CMS), Disabilities of the Arm Shoulder and Hand (DASH) score, American Shoulder and Elbow Surgeons (ASES) score, and the shoulder range of motion (ROM). Pain was measured using a visual analogue scale (VAS). RESULTS: At the one-year follow-up, all fractures healed radiologically and clinically. The mean changes of NSA and HHH over the follow-up period were markedly smaller in the LP-PA group (3.8 ± 0.9° and 1.7 ± 0.3 mm) than those in the LP group (9.7 ± 2.1° and 3.2 ± 0.6 mm, both P < 0.0001). The LP-PA group also presented lower DASH score (17.1 ± 3.6), higher ASES score (89.5 ± 11.2) and better ROM in forward elevation (142 ± 26°) and external rotation (59 ± 11°) compared to the LP group (28.9 ± 4.8 for DASH score, P < 0.0001; 82.3 ± 9.0 for ASES score, P < 0.001; 129 ± 21° for forward elevation, P = 0.008; and 52 ± 9° for external rotation, P = 0.001). There was no significant difference in overall complication rate between the two groups, although the complication rate of screw perforation was higher in the LP-PA group (P = 0.172). CONCLUSIONS: For PHF in elderly patients, the combination of LP fixation and PMMA prosthesis augmentation effectively improved humeral head support and reduction maintenance, providing satisfactory outcomes both radiologically and clinically. This technique also reduced the incidence of screw perforation associated with plate fixation alone, making it a reasonable option to ensure satisfactory clinical outcomes.

Study on the correlation between serum indole-3-propionic acid levels and the progression and prognosis of acute ischemic stroke.

OBJECTIVE: This study aimed to explore the correlation between the serum level of indole-3-propionic acid (IPA) and the progression and prognosis of acute cerebral infarction (ACI). METHODS: This study enrolled 197 patients with ACI, and 53 participants from a community-based stroke screening program during the same period were included as the control group. The patients with ACI were divided into quartiles of serum IPA. A logistic regression model was used for comparison. Receiver operating characteristic (ROC) curves were drawn to evaluate the predictive value of the IPA. RESULTS: Compared with the healthy control group, the ACI group had lower serum IPA (P < 0.05). The serum IPA was an independent factor for acute ischemic stroke (OR=0.992, 95% CI: 0.984-0.999, P=0.035). The serum IPA was lower in patients with progressive stroke or poor prognosis than in patients with stable stroke or good prognosis (P < 0.05). Patients with ACI with low serum IPA are prone to progression and poor prognosis. The best cutoff value for predicting progression was 193.62 pg/mL (sensitivity, 67.5%; specificity 83.7%), and that for poor prognosis was 193.77 pg/mL (sensitivity, 71.1%; specificity, 72.5%). CONCLUSION: The serum level of IPA was an independent predictor of ACI and had certain clinical value for predicting stroke progression and prognosis in patients with ACI.

Mechanisms of Cardiovascular Toxicities Induced by Cancer Therapies and Promising Biomarkers for Their Prediction: A Scoping Review.

AIM: With the advancement of anti-cancer medicine, cardiovascular toxicities due to cancer therapies are common in oncology patients, resulting in increased mortality and economic burden. Cardiovascular toxicities caused by cancer therapies include different severities of cardiomyopathy, arrhythmia, myocardial ischaemia, hypertension, and thrombosis, which may lead to left ventricular dysfunction and heart failure. This scoping review aimed to summarise the mechanisms of cardiovascular toxicities following various anti-cancer treatments and potential predictive biomarkers for early detection. METHODS: PubMed, Cochrane, Embase, Web of Science, Scopus, and CINAHL databases were searched for original studies written in English related to the mechanisms of cardiovascular toxicity induced by anti-cancer therapies, including chemotherapy, targeted therapy, immunotherapy, radiation therapy, and relevant biomarkers. The search and title/abstract screening were conducted independently by two reviewers, and the final analysed full texts achieved the consensus of the two reviewers. RESULTS: A total of 240 studies were identified based on their titles and abstracts. In total, 107 full-text articles were included in the analysis. Cardiomyocyte and endothelial cell apoptosis caused by oxidative stress injury, activation of cell apoptosis, blocking of normal cardiovascular protection signalling pathways, overactivation of immune cells, and myocardial remodelling were the main mechanisms. Promising biomarkers for anti-cancer therapies related to cardiovascular toxicity included placental growth factor, microRNAs, galectin-3, and myeloperoxidase for the early detection of cardiovascular toxicity. CONCLUSION: Understanding the mechanisms of cardiovascular toxicity following various anti-cancer treatments could provide implications for future personalised treatment methods to protect cardiovascular function. Furthermore, specific early sensitive and stable biomarkers of cardiovascular system damage need to be identified to predict reversible damage to the cardiovascular system and improve the effects of anti-cancer agents.

Domino Reactions Enabling Sulfur-Mediated Gradient Interphases for High-Energy Lithium Batteries.

Silicon (Si)-based anodes are currently considered a feasible solution to improve the energy density of lithium-ion batteries owing to their sufficient specific capacity and natural abundance. However, Si-based anodes exhibit low electric conductivities and large volume changes during cycling, which could easily trigger continuous breakdown/reparation of the as-formed solid-electrolyte-interphase (SEI) layer, seriously hampering their practical application in current battery technology. To control the chemoelectrochemical instability of the conventional SEI layer, we herein propose the introduction of elemental sulfur into nonaqueous electrolytes, aiming to build a sulfur-mediated gradient interphase (SMGI) layer on Si-based anodes. The SMGI layer is generated through the domino reactions (i.e., electrochemical cascade reactions) involving the electrochemical reductions of elemental sulfur followed by nucleophilic substitutions of fluoroethylene carbonate, which endows the corresponding SEI layer with strong elasticity and chemomechanical stability and enables rapid transportation of Li+ ions. Consequently, the prototype Si||LiNi0.8Co0.1Mn0.1O2 cells attain a high-energy density of 622.2 W h kg-1 and a capacity retention of 88.8% after 100 cycles. Unlike previous attempts based on sophisticated chemical modifications of electrolyte components, this study opens a new avenue in interphase design for long-lived and high-energy rechargeable batteries.

In Situ Capturing and Counting Device for the Specific Depletion and Purification of Cancer-Derived Exosomes.

From metabolic waste to biological mediators, exosomes have emerged as the key player in a variety of pathological processes, particularly in oncogenesis. The exosome-mediated communication network involves nearly every step of cancer progression, promoting the proliferation and immune escape of cancer cells. Therefore, the removal of cancer-derived exosomes has profound clinical significance. Current methods for exosome separation and enrichment are either for large-scale samples or require complex pretreatment processes, lacking effective methods for trace-volume exosome capture in situ. Herein, we have developed an in situ exosome capturing and counting device based on the antibody-functionalized capillary. Specific antibodies targeting exosome biomarkers were immobilized to the inner wall of the capillary via biotin-streptavidin interaction for direct cancer exosome capturing. Subsequent exosome staining enabled imaging and enumeration. Acceptable linearity and reproducibility were achieved with our device, with the capturing and detective range between 3.3 × 104 and 3.3 × 108 particles, surpassing the nanoparticle tracking analysis by 2 orders of magnitude while requiring merely 30 µL sample. We demonstrated that MCF-7-derived exosomes induced epithelial-mesenchymal transition of epithelial cells MCF-10A, and our method was able to completely or partially reverse the transition by complete depletion or specific depletion of cancer exosomes without any preprocessing. Moreover, both whole exosomes and cancer-specific exosomes alone from mimic blood samples were successfully captured and counted, without obvious non-specific adsorption. In all, our approach realized the in situ depletion and number-counting of cancer-derived exosomes directly from the complex humoral environment, having the potential to provide a comprehensive tumor therapeutic and prognosis evaluation tool by targeted hemodialysis and counting of tumor-derived exosomes.

New Method for Counting and Picking Out Single Circulating Tumor Cells from Microliter-Volume Samples for Tumor Progression Surveillance and Single-Cell Heterogeneity Analysis.

Circulating tumor cells (CTCs) are crucial in tumor progression and metastasis, but the knowledge of their roles grows slowly at single-cell levels. Characterizing the rarity and fragility of CTCs by nature, highly stable and efficient single-CTC sampling methods are still lacking, which impedes the development of single-CTC analysis. Herein, an improved, capillary-based single-cell sampling (SiCS) method, the so-called bubble-glue single-cell sampling (bubble-glue SiCS), is introduced. Benefiting from the characteristic that the cells tend to adhere to air bubbles in the solution, single cells can be sampled with bubbles as low as 20 pL with a self-designed microbubble-volume-controlled system. Benefiting from the excellent maneuverability, single CTCs are sampled directly from 10 µL volume of real blood samples after fluorescent labeling. Meanwhile, over 90% of the CTCs obtained survived and well proliferated after the bubble-glue SiCS process, which showed considerable superiority for downstream single-CTC profiling. Furthermore, a highly metastatic breast cancer model of the 4T1 cell line in vivo was employed for the real blood sample analysis. Increases in CTC numbers were observed during the tumor progression process, and significant heterogeneities among individual CTCs were discovered. In all, we propose a novel avenue for target SiCS and provide an alternative technique route for CTC separation and analysis.

Density Functional Theory and Raman Spectroscopy Studies of Adsorption Sites of Au Nanoparticles with Alectinib.

Alectinib is an ALK tyrosine kinase inhibitor, which is mainly used in patients with crizotinib-resistant nonsmall cell lung cancer. Alectinib has attracted much clinical attention for its longest progression-free survival time and the best therapeutic effect. The chemical adsorption of Au nanoclusters (AuNPs) with alectinib molecules is studied by density functional theory (DFT) and surface-enhanced Raman scattering spectroscopy (SERS) experiments. DFT/B3LYP-D3/6-311G** was used for optimization and vibration analysis of alectinib-Au6 complexes, as well as molecular electrostatic potential, frontier molecular orbital, and electro-optic-based charge transfer descriptors. Comparing the results of the DFT theory and SERS experiment, alectinib and AuNPs can form Au-N6 bonds primarily through chemical adsorption of N6 atoms, and the experimental results showed that the enhancement factor (EFCHEM) could reach 4.27. The results provide a theoretical basis for exploring the mechanism of chemical enhancement between AuNPs and alectinib.

Structural Transformation and Photoluminescent Property of Manganese-Doped Bismuth-Based Perovskites.

Here, we synthesized pure Cs3Bi2Cl9 (CBC) and manganese (Mn)-doped crystals with different feeding ratios, leading to changes in structure and luminescence. The crystals Cs3Bi2Cl9-Mn (CBCM) formed by doping a minor amount of Mn2+ (Bi/Mn = 8:1) maintain the orthorhombic phase structure of the host, but when Bi/Mn = 2:1, the crystal structure is more inclined to form Cs4MnBi2Cl12 (CMBC) of a trigonal phase. Combined with density functional theory (DFT) calculation, the results demonstrate that a moderate amount of Mn2+ doping can create impurity energy levels in the forbidden band. However, as the structure transitions, the type of energy band structure changes from indirect to direct, with completely different electronic orbital features. Temperature-dependent time-resolved and steady-state photoluminescence spectroscopies are used to explore the structure-related thermal properties and transitional process. Differences energy transfer routes are revealed, with CBCM relying on intersystem energy transfer and CMBC mainly depending on direct excitation of Mn2+ to produce d-d transitions. Furthermore, since CMBC is temperature-sensitive, we perform the first photoluminescent (PL) lifetime temperature measurement using CBMC and obtain a maximum relative sensitivity of 1.7 %K-1 and an absolute sensitivity of 0.0099 K-1. Our work provides insight into the mechanism of Mn2+ doping-induced luminescence and offers a potentially effective doping strategy for improving the PL properties of lead-free metal halide perovskites.

Development and validation of KASP markers for resistance to Phytophthora capsici in Capsicum annuum L.

Resistance of Capsicum annuum to Phytophthora blight is dependent on the genetic background of the resistance source and the Phytophthora capsici isolate, which poses challenges for development of generally applicable molecular markers for marker-assisted selection. In this study, the resistance to P. capsici of C. annuum was genetically mapped to chromosome 5 within a 1.68-Mb interval by genome-wide association study analysis of 237 accessions. In this candidate region, 30 KASP markers were developed using genome resequencing data for a P. capsici-resistant line (0601 M) and a susceptible line (77,013). Seven of these KASP markers, located in the coding region of a probable leucine-rich repeats receptor-like serine/threonine-protein kinase gene (Capana05g000704), were validated in the 237 accessions, which showed an average accuracy of 82.7%. The genotyping of the seven KASP markers strongly corresponded with the phenotype of 42 individual plants in a pedigree family (PC83-163) developed from the P. capsici-resistant line CM334. This research provides a set of efficient and high-throughput KASP markers for marker-assisted selection of resistance to P. capsici in C. annuum. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01367-3.

Chromosomal genome and population genetic analyses to reveal genetic architecture, breeding history and genes related to cadmium accumulation in Lentinula edodes.

BACKGROUND: Lentinula edodes (Berk.) is the second most productive mushroom in the world. It contains compounds effective for antiviral, antitumor, antioxidant and immune regulation. Although genomes have previously been reported for this species, a high-quality chromosome-level reference for L. edodes is unavailable. This hinders detailed investigation of population genetics, breeding history of strains and genes related to environmental stress responses. RESULTS: A high-quality chromosome-level genome was constructed. We separated a monokaryon from protoplasts of the commercial L. edodes strain L808 and assembled the genome of L. edodes using PacBio long-read and Illumina short-read sequencing, along with the high-throughput chromatin conformation capture (Hi-C) technique. We assembled a 45.87 Mb genome, and 99% of the sequences were anchored onto 10 chromosomes. The contig and scaffold N50 length were 2.17 and 4.94 Mb, respectively. Over 96% of the complete Benchmarking Universal Single-Copy Orthologs (BUSCO) were identified, and 9853 protein-coding genes were predicted. We performed population genome resequencing using 34 wild strains and 65 commercial cultivars of L. edodes originating from China, Japan, the United States and Australia. Based on whole-genome variants, we showed substantial differences in the Chinese wild population, which divided into different branches according to the main areas of their geographical distribution. We also determined the breeding history of L. edodes at the molecular level, and demonstrated that the cultivated strains in China mainly originated from wild strains from China and Northeast Asia. Phenotypic analysis showed that 99 strains exhibited differences on the Cd accumulation. Three significant loci in the of L. edodes genome were identified using the genome-wide association study (GWAS) of Cd accumulation traits. Functional genes associated with Cd accumulation traits were related to DNA ligase and aminoacyl tRNA synthetase, indicating that DNA damage repair and in vivo protein translation may be responses to Cd stress. CONCLUSIONS: A high-quality chromosome-level genome and population genetic data of L. edodes provide genetic resources for functional genomic, evolutionary and artificial breeding studies for L. edodes.

Designer Cathode Additive for Stable Interphases on High-Energy Anodes.

Rechargeable lithium-based batteries built with high-energy anode materials (e.g., silicon-based and silicon-derivative materials) are considered a feasible solution to satisfy the stringent requirements imposed by emerging markets, including electric vehicles and grid storage, due to their higher energy density compared to contemporary lithium-ion batteries. The robustness of the solid electrolyte interphase (SEI) layer on high-energy anodes is critical to achieve long-term and stable cycling performances of the batteries. Herein, we propose a new type of designer cathode additive (DCA), i.e., an ultrathin coating layer of elemental sulfur on the cathode, for the in situ formation of a thin and robust SEI layer on various types of high-energy anodes. The DCA elemental sulfur undergoes simultaneous oxidation and reduction paths, forming lithium alkyl sulfate (R-OSO2OLi) and poly(ethylene oxide) (PEO)-like polymers on the anode surface. The as-formed R-OSO2OLi/PEO-modified SEI layer has good lithium cation (Li+) permeability to facilitate fast ion transportation across the interphases and superior elasticity to adapt to large volume changes, which is particularly effective for improving the cycling efficiency of high-energy anodes (e.g., ca. 14-35% increase in capacity retention for the silicon-carbon composite (SiC) or silicon-tin alloy (Si-Sn)||LiFePO4 cells). The present work opens a new avenue toward the practical deployment of high-energy rechargeable lithium-based batteries.

Counting Protein Number in a Single Cell by a Picoliter Liquid Operating Technology.

Ultra-low-copy number proteins play a crucial role in exploring cellular heterogeneity and the insight of protein biomarkers in a single cell. However, counting ultra-low-copy number target proteins in a single cell remains a grand challenge. Herein, we developed a so-called single-cell picoliter liquid operating technology for counting target proteins in a single cell. An ingenious volume-controllable sampling technique was employed to capture a single cell for subsequent analysis. Remarkably, 50 pL of sample volume was employed for sample preparation, single-cell capture, in-droplet lysis, and target protein immobilization on a functionalized coverslip in a monolayer. Then, target protein antibodies coupled with quantum dots were added and incubated to label those immobilized proteins. After clean-up, a single-view image under 100× objective was taken, and the 80 × 80 µm2 view image was then applied to count the precise copy number of the target proteins in the single cell. Furthermore, good linearity and repeatability were achieved for ultra-low-copy number proteins, ranging from 1 to 1500. Finally, the expression level of human epidermal growth factor receptor 2 in single cells from both MCF-7 and MDA-MB-231 cell lines was also analyzed. In a word, this work stimulated the development of capillary-based single-cell analysis and updated the connotation of counting ultra-low-copy number proteins.

Fine mapping of Rf2, a minor Restorer-of-fertility (Rf) gene for cytoplasmic male sterility in chili pepper G164 (Capsicum annuum L.).

KEY MESSAGE: Genome re-sequencing and recombination analyses identified Capana06g000193 as a strong candidate for the minor male fertility restoration locus Rf2 in chili pepper G164 harboring two dominant male fertility restoration genes. Male fertility restoration genes of chili pepper restorer line G164 (Capsicum annuum L.) were studied using molecular marker genotypes of an F2 population (7G) of G164 crossed with the cytoplasmic male sterility line 77013A. The ratio of sterile to fertile single plants in the F2 population was 1:15. This result indicates that chili pepper G164 has two dominant restoration genes, which we designated as Rf1 and Rf2. An individual plant recessive for Rf1 and heterozygous for Rf2, 7G-112 (rf1rf1Rf2rf2), was identified by molecular marker selection and genetic analysis, and a single Rf2 gene-segregating population with a 3:1 ratio of fertile to sterile plants was developed from the self-pollination of male fertile individuals of 77013A and 7G-112 hybrid progeny. Bulk segregant analysis of fertile and sterile pools from the segregating populations was used to genetically map Rf2 to a 3.1-Mb region on chromosome 6. Rf2 was further narrowed to a 179.3-kb interval through recombination analysis of molecular markers and obtained the most likely candidate gene, Capana06g000193.

Serum Exosomal mir-340-5p Promotes Angiogenesis in Brain Microvascular Endothelial Cells During Oxygen-Glucose Deprivation.

Ischemic stroke (IS) is a cerebrovascular disease with high morbidity, recurrence, and mortality. The purpose of the present study was to investigate the role and mechanism of human serum exosomes on angiogenesis after IS. The middle cerebral artery occlusion (MCAO) in vivo model and oxygen-glucose deprivation (OGD) in vitro model were established. Human serum exosomes from healthy samples (NC-exo) and IS samples (IS-exo) were injected into MCAO mice. Neurobehavioral tests were performed to assess the extent of neurological deficits. The infarct volume was assessed by 2,3,5-triphenyl tetrazolium chloride (TTC) staining, and the levels of inflammatory cytokines were analyzed by enzyme-linked immunosorbent assay (ELISA). In addition, human serum exosomes were cocultured with brain microvascular endothelial cells (BMECs). Cell Counting Kit-8 (CCK-8), Transwell, and tubule formation assays were performed to investigate the proliferation, migration, invasion, length, and branching of BMECs. The miRNA expression profiles of NC-exo and IS-exo were analyzed by high-throughput sequencing and compared. Bioinformatics and luciferase reporter assays were performed to evaluate the relationship between miR-340-5p and CD147. Serum NC-exo and IS-exo had protective effects on IS injury and promoted BMEC angiogenesis. Interestingly, the protective effect of IS-exo was weaker than that of NC-exo. In addition, miR-340-5p was downregulated in IS-exo, and miR-340-5p accelerated angiogenesis of BMECs after OGD. Mechanistically, CD147 was confirmed as a direct target of miR-340-5p. Finally, miR-340-5p promoted angiogenesis by directly targeting CD147. Serum exosome-derived miR-340-5p promote angiogenesis in OGD-induced BMECs by targeting CD147.