High-throughput single-microbe RNA sequencing reveals adaptive state heterogeneity and host-phage activity associations in human gut microbiome.

Microbial communities such as those residing in the human gut are highly diverse and complex, and many with important implications in health and diseases. The effects and functions of these microbial communities are determined not only by their species compositions and diversities but also by the dynamic intra- and inter-cellular states at the transcriptional level. Powerful and scalable technologies capable of acquiring single-microbe-resolution RNA sequencing information in order to achieve comprehensive understanding of complex microbial communities together with their hosts is therefore utterly needed. Here we report the development and utilization of a droplet-based smRNA-seq (single-microbe RNA sequencing) method capable of identifying large species varieties in human samples, which we name smRandom-seq2. Together with a triple-module computational pipeline designed for the bacteria and bacteriophage sequencing data by smRandom-seq2 in four human gut samples, we established a single-cell level bacterial transcriptional landscape of human gut microbiome, which included 29,742 single microbes and 329 unique species. Distinct adaptive responses states among species in Prevotella and Roseburia genus and intrinsic adaptive strategy heterogeneity in Phascolarctobacterium succinatutens were uncovered. Additionally, we identified hundreds of novel host-phage transcriptional activity associations in the human gut microbiome. Our results indicated the smRandom-seq2 is a high-throughput and high-resolution smRNA-seq technique that is highly adaptable to complex microbial communities in real-word situations and promises new perspectives in the understanding of human microbiomes.

Antiferromagnetic Chromium-Doped Tin Clusters.

The trend toward further miniaturization of micronano antiferromagnetic (AFM) spintronic devices has led to a strong demand for low-dimensional materials. The assembly of AFM clusters to produce such materials is a potential pathway that promotes studies on such clusters. In this work, we report on the discovery of the AFM Cr2Snx (x = 3-20) clusters with a stepwise growth at the density functional theory (DFT) level. In comparison, the two Cr atoms tend to stay together and be buried by Sn atoms, forming endohedral structures with one Cr atom encapsulated at size 9 and finally forming a full-encapsulated structure at size 17. Each successive cluster size is composed of its predecessor with an extra Sn atom adsorbed onto the face, giving evidence of stepwise growth. All these Cr2Snx (x = 3-20) clusters are antiferromagnets, except for the triplet-state ferrimagnetic Cr2Sn11, and all their singly negatively and positively charged ions are ferromagnets. The found stable Cr2Sn17 cluster can dimerize, yielding dimers and trimers without noticeably distorting the geometrical structure and magnetic properties of each of its constituent cluster monomers, making it possible as a building block for AFM materials.

Whole organism snRNA-seq reveals systemic peripheral changes in Alzheimer's Disease fly models.

Peripheral tissues become disrupted in Alzheimer's Disease (AD). However, a comprehensive understanding of how the expression of AD-associated toxic proteins, Aß42 and Tau, in neurons impacts the periphery is lacking. Using Drosophila, a prime model organism for studying aging and neurodegeneration, we generated the Alzheimer's Disease Fly Cell Atlas (AD-FCA): whole-organism single-nucleus transcriptomes of 219 cell types from adult flies neuronally expressing human Aß42 or Tau. In-depth analyses and functional data reveal impacts on peripheral sensory neurons by Aß42 and on various non-neuronal peripheral tissues by Tau, including the gut, fat body, and reproductive system. This novel AD atlas provides valuable insights into potential biomarkers and the intricate interplay between the nervous system and peripheral tissues in response to AD-associated proteins.

Directive giant upconversion by supercritical bound states in the continuum.

Photonic bound states in the continuum (BICs), embedded in the spectrum of free-space waves1,2 with diverging radiative quality factor, are topologically non-trivial dark modes in open-cavity resonators that have enabled important advances in photonics3,4. However, it is particularly challenging to achieve maximum near-field enhancement, as this requires matching radiative and non-radiative losses. Here we propose the concept of supercritical coupling, drawing inspiration from electromagnetically induced transparency in near-field coupled resonances close to the Friedrich-Wintgen condition2. Supercritical coupling occurs when the near-field coupling between dark and bright modes compensates for the negligible direct far-field coupling with the dark mode. This enables a quasi-BIC field to reach maximum enhancement imposed by non-radiative loss, even when the radiative quality factor is divergent. Our experimental design consists of a photonic-crystal nanoslab covered with upconversion nanoparticles. Near-field coupling is finely tuned at the nanostructure edge, in which a coherent upconversion luminescence enhanced by eight orders of magnitude is observed. The emission shows negligible divergence, narrow width at the microscale and controllable directivity through input focusing and polarization. This approach is relevant to various physical processes, with potential applications for light-source development, energy harvesting and photochemical catalysis.

High-Throughput Host-Microbe Single-Cell RNA Sequencing Reveals Ferroptosis-Associated Heterogeneity during Acinetobacter baumannii Infection.

Interactions between host and bacterial cells are integral to human physiology. The complexity of host-microbe interactions extends to different cell types, spatial aspects, and phenotypic heterogeneity, requiring high-resolution approaches to capture their full complexity. The latest breakthroughs in single-cell RNA sequencing (scRNA-seq) have opened up a new era of studies in host-pathogen interactions. Here, we first report a high-throughput cross-species dual scRNA-seq technology by using random primers to simultaneously capture both eukaryotic and bacterial RNAs (scRandom-seq). Using reference cells, scRandom-seq can detect individual eukaryotic and bacterial cells with high throughput and high specificity. Acinetobacter baumannii (A.b) is a highly opportunistic and nosocomial pathogen that displays resistance to many antibiotics, posing a significant threat to human health, calling for discoveries and treatment. In the A.b infection model, scRandom-seq witnessed polarization of THP-1 derived-macrophages and the intracellular A.b-induced ferroptosis-stress in host cells. The inhibition of ferroptosis by Ferrostatin-1 (Fer-1) resulted in the improvement of cell vitality and resistance to A.b infection, indicating the potential to resist related infections. scRandom-seq provides a high-throughput cross-species dual single-cell RNA profiling tool that will facilitate future discoveries in unraveling the complex interactions of host-microbe interactions in infection systems and tumor micro-environments.

Turning Nonemissive CsPb2Br5 Crystals into High-Performance Scintillators through Alkali Metal Doping.

X-ray scintillators have utility in radiation detection, therapy, and imaging. Various materials, such as halide perovskites, organic illuminators, and metal clusters, have been developed to replace conventional scintillators due to their ease of fabrication, improved performance, and adaptability. However, they suffer from self-absorption, chemical instability, and weak X-ray stopping power. Addressing these limitations, we employ alkali metal doping to turn nonemissive CsPb2Br5 into scintillators. Introducing alkali metal dopants causes lattice distortion and enhances electron-phonon coupling, which creates transient potential energy wells capable of trapping photogenerated or X-ray-generated electrons and holes to form self-trapped excitons. These self-trapped excitons undergo radiative recombination, resulting in a photoluminescence quantum yield of 55.92%. The CsPb2Br5-based X-ray scintillator offers strong X-ray stopping power, high resistance to self-absorption, and enhanced stability when exposed to the atmosphere, chemical solvents, and intense irradiation. It exhibits a detection limit of 162.3 nGyair s-1 and an imaging resolution of 21 lp mm-1.

Discovery of a series of silicon-based ferrimagnets in CrMnSin (n = 4-20) clusters.

Herein, the structural evolution, electronic and magnetic properties of silicon clusters with two different dopants, CrMnSin (n = 4-20) clusters were investigated at density functional theory (DFT) level. Small-sized CrMnSin (n = 4-9) clusters tend to adopt bipyramid-based geometries, while clusters with sizes n = 10 and 11 prefer to opening cage-like structures. For sizes n = 12 to 14, the half-encapsulated structures gradually transform into closed-cage Cr@Sin structures, with the Mn atom exposed outside. Starting from size 15, both the Cr and Mn atoms are completely encapsulated by silicon atoms. Meanwhile, the Cr and Mn atoms in smaller-sized CrMnSin (n = 4-7) clusters tend to be separated, while they prefer to stay together for larger sizes. Cr atom always acts as electron donor, but not for Mn atom. From the average binding energies, one can conclude that it is easier to form larger size clusters. Smaller and larger sized CrMnSin (n = 4-9 and 19-20) clusters prefer to exhibit ferromagnetic Cr-Mn coupling, while sizes n = 10-18 always exhibit ferrimagnetic state. To our knowledge, the CrMnSin clusters is the first kind of neutral transition-metal doped semiconductor clusters that show ferrimagnetic state within a wide size range.

Determination of Ground State Structures of Snx - (x=21-35) Clusters.

In this work, an unbiased global search with a homemade genetic algorithm was performed to investigate the structural evolution and electronic properties of Snx - (x=21-35) clusters with density functional theory (DFT) calculations. All the ground-state structures for all these Snx - (x=21-35) clusters have been confirmed by the comparison of the experimental and simulated photoelectron spectra (PESs). It has been revealed that all Snx - (x=21-35) clusters are tricapped trigonal prism (TTP)-based structures consisting of two (for sizes x=21-28) or three (for x=29-35) TTP units, with the remaining atoms adsorbed on the surface or inserted between TTP units. The gradually decreasing HOMO-LUMO gaps indicate that these clusters are undergoing semiconductor-to-metal transformation. The average binding energies show that the structural stabilities of Snx - clusters are not as good as that of silicon and germanium clusters. It found that sizes x=23, 25, 29, 33 show high relative stability.

Promoted Growth and Multiband Emission in Heterostructured Perovskites Through Cs+ -Sublattice Interaction.

Precise control of exciton confinement in metal halide perovskites is critical to the development of high-performance, stable optoelectronic devices. A significant hurdle is the swift completion of ionic metathesis reactions, often within seconds, making consistent control challenging. Herein, the introduction of different steric hindrances in a Cs+ sublattice within CsYb2 F7 is reported, which effectively modulates the reaction rate of Cs+ with lead (Pb2+ ) and halide ions in solution, extending the synthesis time for perovskite nanostructures to tens of minutes. Importantly, the Cs+ sublattice provides a crystal facet-dependent preference for perovskite growth and thus exciton confinement, allowing the simultaneous occurrence of up to six emission bands of CsPbBr3 . Moreover, the rigid CsYb2 F7 nano template offers high activation energy and enhances the stability of the resulting perovskite nanostructures. This methodology provides a versatile approach to synthesizing functional heterostructures. Its robustness is demonstrated by in-situ growth of perovskite nanostructures on Cs+ -mediated metal-organic frameworks.

Pan-Cancer Single-Nucleus Total RNA Sequencing Using snHH-Seq.

Tumor heterogeneity and its drivers impair tumor progression and cancer therapy. Single-cell RNA sequencing is used to investigate the heterogeneity of tumor ecosystems. However, most methods of scRNA-seq amplify the termini of polyadenylated transcripts, making it challenging to perform total RNA analysis and somatic mutation analysis.Therefore, a high-throughput and high-sensitivity method called snHH-seq is developed, which combines random primers and a preindex strategy in the droplet microfluidic platform. This innovative method allows for the detection of total RNA in single nuclei from clinically frozen samples. A robust pipeline to facilitate the analysis of full-length RNA-seq data is also established. snHH-seq is applied to more than 730 000 single nuclei from 32 patients with various tumor types. The pan-cancer study enables it to comprehensively profile data on the tumor transcriptome, including expression levels, mutations, splicing patterns, clone dynamics, etc. New malignant cell subclusters and exploring their specific function across cancers are identified. Furthermore, the malignant status of epithelial cells is investigated among different cancer types with respect to mutation and splicing patterns. The ability to detect full-length RNA at the single-nucleus level provides a powerful tool for studying complex biological systems and has broad implications for understanding tumor pathology.

Adaptive Gravity Compensation Framework Based on Human Upper Limb Model for Assistive Robotic Arm Extender.

The Assistive Robotic Arm Extender (ARAE) is an upper limb assistive and rehabilitation robot that belongs to the end-effector type, enabling it to assist patients with upper limb movement disorders in three-dimensional space. However, the problem of gravity compensation for the human upper limb with this type of robot is crucial, which directly affects the deployment of the robot in the assistive or rehabilitation field. This paper presents an adaptive gravity compensation framework that calculates the compensated force based on the estimated human posture in 3D space. First, we estimated the human arm joint angles in real-time without any wearable sensors, such as inertial measurement unit (IMU) or magnetic sensors, only through the kinematic data of the robot and established human model. The performance of the estimation method was evaluated through a motion capture system, which validated the accuracy of joint angle estimation. Second, the estimated human joint angles were input to the rigid link model to demonstrate the support force profile generated by the robot. The force profile showed that the support force provided by the developed ARAE robot could adaptively change with human arm postures in 3D space. The adaptive gravity compensation framework can improve the usability and feasibility of the 3D end-effector rehabilitation or assistive robot.

Cancer and Autism: How PTEN Mutations Degrade Function at the Membrane and Isoform Expression in the Human Brain.

Mutations causing loss of PTEN lipid phosphatase activity can promote cancer, benign tumors (PHTS), and neurodevelopmental disorders (NDDs). Exactly how they preferentially trigger distinct phenotypic outcomes has been puzzling. Here, we demonstrate that PTEN mutations differentially allosterically bias P loop dynamics and its connection to the catalytic site, affecting catalytic activity. NDD-related mutations are likely to sample conformations of the functional wild-type state, while sampled conformations for the strong, cancer-related driver mutation hotspots favor catalysis-primed conformations, suggesting that NDD mutations are likely to be weaker, and our large-scale simulations show why. Prenatal PTEN isoform expression data suggest exons 5 and 7, which harbor NDD mutations, as cancer-risk carriers. Since cancer requires more than a single mutation, our conformational and genomic analysis helps discover how same protein mutations can foster different clinical manifestations, articulates a role for co-occurring background latent driver mutations, and uncovers relationships of splicing isoform expression to life expectancy.

Potential mechanisms of non-suicidal self-injury (NSSI) in major depressive disorder: a systematic review.

Background: Non-suicidal self-injury (NSSI) is a frequent and prominent phenomenon in major depressive disorder (MDD). Even though its prevalence and risk factors are relatively well understood, the potential mechanisms of NSSI in MDD remain elusive. Aims: To review present evidence related to the potential mechanisms of NSSI in MDD. Methods: According to Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, articles for this systematic review were searched on Medline (through PubMed), Embase (through Elsevier), PsycINFO (through OVID) and Web of Science databases for English articles, as well as China National Knowledge Infrastructure (CNKI), SinoMed, Wanfang Data, and the Chongqing VIP Chinese Science and Technology Periodical (VIP) Databases for Chinese articles published from the date of inception to 2 August 2022. Two researchers (BW, HZ) independently screened studies based on inclusion and exclusion criteria and assessed their quality. Results: A total of 25 157 studies were searched. Only 25 of them were ultimately included, containing 3336 subjects (1535 patients with MDD and NSSI, 1403 patients with MDD without NSSI and 398 HCs). Included studies were divided into 6 categories: psychosocial factors (11 studies), neuroimaging (8 studies), stress and hypothalamic-pituitary-adrenal (HPA) axis (2 studies), pain perception (1 study), electroencephalogram (EEG) (2 studies) and epigenetics (1 study). Conclusions: This systematic review indicates that patients with MDD and NSSI might have specific psychosocial factors, aberrant brain functions and neurochemical metabolisms, HPA axis dysfunctions, abnormal pain perceptions and epigenetic alterations.

Droplet-based high-throughput single microbe RNA sequencing by smRandom-seq.

Bacteria colonize almost all parts of the human body and can differ significantly. However, the population level transcriptomics measurements can only describe the average bacteria population behaviors, ignoring the heterogeneity among bacteria. Here, we report a droplet-based high-throughput single-microbe RNA-seq assay (smRandom-seq), using random primers for in situ cDNA generation, droplets for single-microbe barcoding, and CRISPR-based rRNA depletion for mRNA enrichment. smRandom-seq showed a high species specificity (99%), a minor doublet rate (1.6%), a reduced rRNA percentage (32%), and a sensitive gene detection (a median of ~1000 genes per single E. coli). Furthermore, smRandom-seq successfully captured transcriptome changes of thousands of individual E. coli and discovered a few antibiotic resistant subpopulations displaying distinct gene expression patterns of SOS response and metabolic pathways in E. coli population upon antibiotic stress. smRandom-seq provides a high-throughput single-microbe transcriptome profiling tool that will facilitate future discoveries in microbial resistance, persistence, microbe-host interaction, and microbiome research.

WNK1 mediates amphiregulin-induced MMP9 expression and cell invasion in human extravillous trophoblast cells.

The invasion of human extravillous trophoblast (EVT) cells is a critical event required for a successful pregnancy. Amphiregulin, a ligand of the epidermal growth factor receptor (EGFR), has been shown to stimulate cell invasion in an immortalized human EVT cell line, HTR-8/SVneo. The with-no-lysine kinase 1 (WNK1) is involved in regulating cell invasion. It is known that WNK1 is expressed in the human placenta, but its role in human EVT cells remains unknown. In the present study, we show that AREG treatment phosphorylated WNK1 at Thr60 in both HTR-8/SVneo and primary human EVT cells. The stimulatory effect of AREG on WNK1 phosphorylation was mediated by the activation of PI3K/AKT, but not the ERK1/2 signaling pathway. AREG upregulated matrix metalloproteinase 9 (MMP9) but not MMP2. In addition, cell invasiveness was increased in response to the treatment of AREG. Using the siRNA-mediated knockdown approach, our results showed that the knockdown of WNK1 attenuated the AREG-induced upregulation of MMP9 expression and cell invasion. Moreover, the expression of WNK1 was downregulated in the placentas with preeclampsia, a disease resulting from insufficiency of EVT cell invasion during pregnancy. This study discovers the physiological function of WNK1 in human EVT cells and provides important insights into the regulation of MMP9 and cell invasion in human EVT cells.

Aging Fly Cell Atlas identifies exhaustive aging features at cellular resolution.

Aging is characterized by a decline in tissue function, but the underlying changes at cellular resolution across the organism remain unclear. Here, we present the Aging Fly Cell Atlas, a single-nucleus transcriptomic map of the whole aging Drosophila. We characterized 163 distinct cell types and performed an in-depth analysis of changes in tissue cell composition, gene expression, and cell identities. We further developed aging clock models to predict fly age and show that ribosomal gene expression is a conserved predictive factor for age. Combining all aging features, we find distinctive cell type-specific aging patterns. This atlas provides a valuable resource for studying fundamental principles of aging in complex organisms.

Resveratrol stimulates StAR expression and progesterone production by GPER-mediated downregulation of Snail expression in human granulosa cells.

Steroidogenic acute regulatory protein (StAR) plays a critical role in the regulation of progesterone (P4) production. Resveratrol (RSV), a natural polyphenol, has beneficial effects on reproductive function. However, its effects on StAR expression and P4 production in human granulosa cells remain undetermined. In this study, we showed that treatment of RSV upregulated StAR expression in human granulosa cells. G protein-coupled estrogen receptor (GPER) and ERK1/2 signaling were involved in RSV-stimulated StAR expression and P4 production. In addition, the expression of a transcriptional repressor, Snail, was downregulated by RSV, which contributed to the RSV-induced inductions of StAR expression and P4 production.

Volumetric Nanocrystal Lattice Reconstruction through Dynamic Metal Complex Docking.

Vacancies pose a major challenge in the production of high-quality crystals, particularly at the nanoscale. To address this problem, we report a convenient strategy that involves volumetric lattice reconstruction and dynamic metal complex docking to produce ultrasmall (10 nm) and bright core-shell upconversion nanoparticles (UCNPs). This strategy involves the formation of lanthanide ion-oleic acid complexes during postannealing in solution, which effectively removes vacancies in nanocrystals. The removal of vacancies restricts the diffusion of lanthanide sensitizers and emitters within the core, thus minimizing surface quenching. Our volumetric lattice reconstruction strategy provides fundamental insights into lattice engineering and presents a general strategy for purifying functional nanocrystals for applications in fields such as single-molecule tracking, quantum optics, energy conversion, and others.

High-throughput single nucleus total RNA sequencing of formalin-fixed paraffin-embedded tissues by snRandom-seq.

Formalin-fixed paraffin-embedded (FFPE) tissues constitute a vast and valuable patient material bank for clinical history and follow-up data. It is still challenging to achieve single cell/nucleus RNA (sc/snRNA) profile in FFPE tissues. Here, we develop a droplet-based snRNA sequencing technology (snRandom-seq) for FFPE tissues by capturing full-length total RNAs with random primers. snRandom-seq shows a minor doublet rate (0.3%), a much higher RNA coverage, and detects more non-coding RNAs and nascent RNAs, compared with state-of-art high-throughput scRNA-seq technologies. snRandom-seq detects a median of >3000 genes per nucleus and identifies 25 typical cell types. Moreover, we apply snRandom-seq on a clinical FFPE human liver cancer specimen and reveal an interesting subpopulation of nuclei with high proliferative activity. Our method provides a powerful snRNA-seq platform for clinical FFPE specimens and promises enormous applications in biomedical research.