A multi-tissue metabolome atlas of primate pregnancy.

Pregnancy induces dramatic metabolic changes in females; yet, the intricacies of this metabolic reprogramming remain poorly understood, especially in primates. Using cynomolgus monkeys, we constructed a comprehensive multi-tissue metabolome atlas, analyzing 273 samples from 23 maternal tissues during pregnancy. We discovered a decline in metabolic coupling between tissues as pregnancy progressed. Core metabolic pathways that were rewired during primate pregnancy included steroidogenesis, fatty acid metabolism, and arachidonic acid metabolism. Our atlas revealed 91 pregnancy-adaptive metabolites changing consistently across 23 tissues, whose roles we verified in human cell models and patient samples. Corticosterone and palmitoyl-carnitine regulated placental maturation and maternal tissue progenitors, respectively, with implications for maternal preeclampsia, diabetes, cardiac hypertrophy, and muscle and liver regeneration. Moreover, we found that corticosterone deficiency induced preeclampsia-like inflammation, indicating the atlas's potential clinical value. Overall, our multi-tissue metabolome atlas serves as a framework for elucidating the role of metabolic regulation in female health during pregnancy.

A 3D-printed transepidermal microprojection array for human skin microbiome sampling.

Skin microbiome sampling is currently performed with tools such as swabs and tape strips to collect microbes from the skin surface. However, these conventional approaches may be unable to detect microbes deeper in the epidermis or in epidermal invaginations. We describe a sampling tool with a depth component, a transepidermal microprojection array (MPA), which captures microbial biomass from both the epidermal surface and deeper skin layers. We leveraged the rapid customizability of 3D printing to enable systematic optimization of MPA for human skin sampling. Evaluation of sampling efficacy on human scalp revealed the optimized MPA was comparable in sensitivity to swab and superior to tape strip, especially for nonstandard skin surfaces. We observed differences in species diversity, with the MPA detecting clinically relevant fungi more often than other approaches. This work delivers a tool in the complex field of skin microbiome sampling to potentially address gaps in our understanding of its role in health and disease.

Comparison of children and adults in deep brain stimulation for Tourette Syndrome: a large-scale multicenter study of 102 cases with long-term follow-up.

BACKGROUND: Deep brain stimulation (DBS) is a promising therapy for refractory Gilles de la Tourette syndrome (GTS). However, its long-term efficacy, safety, and recommended surgical age remain controversial, requiring evidence to compare different age categories. METHODS: This retrospective cohort study recruited 102 GTS patients who underwent DBS between October 2006 and April 2022 at two national centers. Patients were divided into two age categories: children (aged < 18 years; n = 34) and adults (aged ≥ 18 years; n = 68). The longitudinal outcomes as tic symptoms were assessed by the YGTSS, and the YBOCS, BDI, and GTS-QOL were evaluated for symptoms of obsessive-compulsive disorder (OCD), depression, and quality of life, respectively. RESULTS: Overall, these included patients who finished a median 60-month follow-up, with no significant difference between children and adults (p = 0.44). Overall, the YGTSS total score showed significant postoperative improvements and further improved with time (improved 45.2%, 51.6%, 55.5%, 55.6%, 57.8%, 61.4% after 6, 12, 24, 36, 48, and ≥ 60 months of follow-up compared to baseline, respectively) in all included patients (all p < 0.05). A significantly higher improvement was revealed in children than adults at ≥ 60 months of follow-up in the YGTSS scores (70.1% vs 55.9%, p = 0.043), and the time to achieve 60% improvement was significantly shorter in the children group (median 6 months vs 12 months, p = 0.013). At the last follow-up, the mean improvements were 45.4%, 48.9%, and 55.9% and 40.3%, 45.4%, and 47.9% in YBOCS, BDI, and GTS-QOL scores for children and adults, respectively, which all significantly improved compared to baseline (all p < 0.05) but without significant differences between these two groups (all p > 0.05), and the children group received significantly higher improvement in GTS-QOL scores than adults (55.9% vs. 47.9%, p = 0.049). CONCLUSIONS: DBS showed acceptable long-term efficacy and safety for both children and adults with GTS. Surgeries performed for patients younger than 18 years seemed to show acceptable long-term efficacy and safety and were not associated with increased risks of loss of benefit compared to patients older than 18 at the time of surgery. However, surgeries for children should also be performed cautiously to ensure their refractoriness and safety.

Intercalation of Metal into Transition Metal Dichalcogenides in Molten Salts.

Van der Waals (vdW)-layered materials have drawn tremendous interests due to their unique properties. Atom intercalation in the vdW gap of layered materials can tune their electronic structure and generate unexpected properties. Here a chemical-scissor-mediated method that enables metal intercalation into transition metal dichalcogenides (TMDCs) in molten salts is reported. By using this approach, various guest metal atoms (Mn, Fe, Co, Ni, Cu, and Ag) are intercalated into various TMDC hosts (such as TiS2 , NbS2 , TaS2 , TiSe2 , NbSe2 , TaSe2 , and Ti0.5 V0.5 S2 ). The structure of the intercalated compound and intercalation mechanism are investigated. The results indicate that the vdW gap and valence state of TMDCs can be modified through metal intercalation, and the intercalation behavior is dictated by the electron work function. The adjustable charge transfer and intercalation endow a channel for rapid mass transfer to enhance the electrochemical performances. Such a chemical-scissor-mediated intercalation provides an approach to tune the physical and chemical properties of TMDCs, which may open an avenue in functional application ranging from energy conversion to electronics.

Realization of exciton-polariton optical chirality based on strong coupling between intrinsic chiral quasibound states in the continuum and monolayer WS2.

Hybrid quasiparticles produced by the strong interaction between nanostructures and excitons will exhibit optical chirality when one of the coupled components is chiral. Due to the tunability of hybrid states, the coupled system has potential applications in chiral devices and chiral sensing. However, reported chiral materials including chiral molecules and three-dimensional chiral structures in the coupled system limit the application due to the weak chiroptical responses and difficult fabrication, respectively. In this paper, we design chiral quasibound states in the continuum (q-BIC) metasurface by introducing planar symmetry-breaking and z-axis perturbation into an array structure whose unit cell is a C4 rotational symmetric disk. By tuning the polarization state of the eigenmode, a significant chiroptical response is obtained in our q-BIC metasurface. Furthermore, mode splitting is observed not only in the reflection spectrum but also in the circular dichroism (CD) spectrum in the chiral q-BIC and monolayer WS2 strong coupling system, which indicates the realization of the exciton-polariton optical chirality. More importantly, one order of magnitude difference in the reflection to left and right circularly polarized light is achieved resulting in significant CD signals. Our work provides a new strategy to realize the exciton polaritons with significant chiroptical responses, which exhibits promising applications in on-chip chiral devices.

Design of an ultrafast plasmonic nanolaser for high-intensity broadband emission operating at room temperature.

We propose a plasmonic nanolaser based on a metal-insulator-semiconductor-insulator-metal (MISIM) structure, which effectively confines light on a subwavelength scale (∼λ/14). As the pump power increases, the proposed plasmonic nanolaser exhibits broadband output characteristics of 20 nm, and the maximum output power can reach 20 µW. Furthermore, the carrier lifetime at the upper energy level in our proposed structure is measured to be about 400 fs using a double pump-probe excitation. The ultrafast characteristic is attributed to the inherent Purcell effect of plasmonic systems. Our work paves the way toward deep-subwavelength mode confinement and ultrafast femtosecond plasmonic lasers in spaser-based interconnected, eigenmode engineering of plasmonic nanolasers, nano-LEDs, and spontaneous emission control.

Ambient-Light-Promoted Stereospecific Synthesis of (Z)-Vinyl Thioesters under Solvent- and Catalyst-Free Conditions.

An ambient-light-promoted stereospecific olefinic C(sp2)-S bond construction of thioacids and 1,1-diarylethenes has been demonstrated, affording various (Z)-vinyl thioesters in 51-85% yields under solvent- and catalyst-free conditions. Mechanistic studies indicated that the formation of thioacid-olefin complexes is responsible for generating a carbonyl thiyl radical and dioxygen in the air participates in the reaction and functions as a traceless reagent. Moreover, synthetic applications have been demonstrated by the gram scale synthesis and aggregation-induced emission property of representative compound 3i.

Single-Cell Transcriptomics Reveals Crucial Cell Subsets and Functional Heterogeneity Associated With Carotid Atherosclerosis and Cerebrovascular Events.

BACKGROUND: Carotid atherosclerosis is a chronic inflammatory disorder and is responsible for the vast majority of ischemic strokes. Inappropriate innate and adaptive immune responses synergize with malfunctional vascular wall cells to cause atherosclerotic lesions. Yet, functional characteristics of specific immune and endothelial cell subsets associated with atherosclerosis and cerebrovascular events are poorly understood. METHODS: Here, using single-cell RNA sequencing, the unprecedentedly largest data set from 20 patients' carotid artery plaques and paired peripheral blood mononuclear cells was generated, with which an ultra-high-precision cellular landscape of the atherosclerotic microenvironment involving 372 070 cells was depicted. RESULTS: Compared with peripheral blood mononuclear cells, 3 plaque-specific T-cell subsets exhibiting proatherogenic features of both activation and exhaustion were identified. Strikingly, usually antiatherogenic, CD4+FOXP3+ regulatory T cells from plaques of patients with symptomatic disease acquired proinflammatory properties by probably converting to T helper 17 and T helper 9 cells, while CD4+NR4A1+/C0 and CD8+SLC4A10+ T cells related to cerebrovascular events possessed atherogenic attributes including proinflammation, polarization, and exhaustion. In addition, monocyte-macrophage dynamics dominated innate immune response. Two plaque-specific monocyte subsets performed diametrically opposed functions, EREG+ monocytes promoted cerebrovascular events while C3+ monocytes are anti-inflammatory. Similarly, IGF1+ and HS3ST2+ macrophages with classical proinflammatory M1 macrophage features were annotated and contributed to cerebrovascular events. Moreover, SULF1+ (sulfatase-1) endothelial cells were also found to participate in cerebrovascular events through affecting plaque vulnerability. CONCLUSIONS: This compendium of single-cell transcriptome data provides valuable insights into the cellular heterogeneity of the atherosclerotic microenvironment and the development of more precise cardiovascular immunotherapies.

Platelet distribution width as an useful indicator of influenza severity in children.

PURPOSE: The present study aims to investigate the potential of platelet distribution width as an useful parameter to assess the severity of influenza in children. METHODS: Baseline characteristics and laboratory results were collected and analyzed. Receiver operating characteristic (ROC) curve analysis was used to joint detection of inflammatory markers for influenza positive children, and the scatter-dot plots were used to compare the differences between severe and non-severe group. RESULTS: Influenza B positive children had more bronchitis and pneumonia (P < 0.05), influenza A infected children had more other serious symptoms (P = 0.007). Neutrophil count, lymphocyte count, neutrophil-to-lymphocyte ratio (NLR), and platelet parameters performed differently among < 4 years and ≥ 4 years children with influenza. Combined detection of platelet parameters and other indicators could better separate healthy children from influenza infected children than single indicator detection. The levels of platelet distribution width of children with severe influenza (A and B) infection was significantly dropped, compared with non-severe group (P < 0.05). CONCLUSIONS: Platelet distribution width could be a very useful and economic indicator in distinction and severity assessment for children with influenza.

Red blood cell extracellular vesicles deliver therapeutic siRNAs to skeletal muscles for treatment of cancer cachexia.

Cancer cachexia is a multifactorial syndrome characterized by a significant loss of skeletal muscle, which negatively affects the quality of life. Inhibition of myostatin (Mstn), a negative regulator of skeletal muscle growth and differentiation, has been proven to preserve muscle mass in muscle atrophy diseases, including cachexia. However, myostatin inhibitors have repeatedly failed clinical trials because of modest therapeutic effects and side effects due to the poor efficiency and toxicity of existing delivery methods. Here, we describe a novel method for delivering Mstn siRNA to skeletal muscles using red blood cell-derived extracellular vesicles (RBCEVs) in a cancer cachectic mouse model. Our data show that RBCEVs are taken up by myofibers via intramuscular administration. Repeated intramuscular administrations with RBCEVs allowed the delivery of siRNAs, thereby inhibiting Mstn, increasing muscle growth, and preventing cachexia in cancer-bearing mice. We observed the same therapeutic effects when delivering siRNAs against malonyl-CoA decarboxylase, an enzyme driving dysfunctional fatty acid metabolism in skeletal muscles during cancer cachexia. We demonstrate that intramuscular siRNA delivery by RBCEVs is safe and non-inflammatory. Hence, this method is useful to reduce the therapeutic dose of siRNAs, to avoid toxicity and off-target effects caused by systemic administration of naked siRNAs at high doses.

The Mechanism and Fine-Tuning of Chiral Plexcitons in the Strong Coupling Regime.

Chiral plexcitons, produced by the strong interaction between plasmonic nanocavities and chiral molecules, can provide a promising direction for controlling chiroptical responses on the nanoscale. Here, we reveal the chiral origin and electromagnetic hybridization process in chiral strongly coupled systems. The mechanism and unique advantages of chiral plexcitons for fine-tuning circular dichroism (CD) responses are demonstrated, providing a rule for controlling chiral light-matter interactions in complex chiral nanosystems. Furthermore, we experimentally demonstrate the fine-tuning of chiral plexcitons in hybrid systems consisting of plasmonic nanoparticles and chiral J-aggregates. Continuous and precise tuning of the CD resonance positions was successfully achieved in a given structure. Compared with the previous work, the CD spectral tuning accuracy has been improved by an order of magnitude, which can reach the level of 1 nm. Our findings provide a feasible strategy and theoretical basis for accurately controlling chirality in multiple dimensions.

Engineering Ti3C2-MXene Surface Composition for Excellent Li+ Storage Performance.

Exploiting novel materials with high specific capacities is crucial for the progress of advanced energy storage devices. Intentionally constructing functional heterostructures based on a variety of two-dimensional (2D) substances proves to be an extremely efficient method for capitalizing on the shared benefits of these materials. By elaborately designing the structure, a greatly escalated steadiness can be achieved throughout electrochemical cycles, along with boosted electron transfer kinetics. In this study, chemical vapor deposition (CVD) was utilized to alter the surface composition of multilayer Ti3C2Tx MXene, contributing to contriving various layered heterostructure materials through a precise adjustment of the reaction temperature. The optimal composite materials at a reaction temperature of 500 °C (defined as MX500), incorporating MXene as the conductive substrate, exhibited outstanding stability and high coulombic efficiency during electrochemical cycling. Meanwhile, the reactive sites are increased by using TiS2 and TiO2 at the heterogeneous interfaces, which sustains a specific capacity of 449 mAh g-1 after 200 cycles at a current density of 0.1 A g-1 and further demonstrates their exceptional electrochemical characteristics. Additionally, the noted pseudocapacitive properties, like MXene materials, further highlight the diverse capabilities of intuitive material design. This study illuminates the complex details of surface modification in multilayer MXene and offers a crucial understanding of the strategic creation of heterostructures, significantly impacting sophisticated electrochemical applications.

Flexible aqueous Cr-ion hybrid supercapacitors with remarkable electrochemical properties in all climates.

The integration of hostless battery-like metal anodes for hybrid supercapacitors is a realistic design method for energy storage devices with promising future applications. With significant Cr element deposits on Earth, exceptionally high theoretical capacity (1546 mAh g-1), and accessible redox potential (-0.74 V vs. reversible hydrogen electrode) of Cr metals, the design of Cr anodes has rightly come into our focus. This work presents a breakthrough design of a flexible Cr-ion hybrid supercapacitor (CHSC) based on a porous graphitized carbon fabric (PGCF) substrate prepared by K2FeO4 activation. In the CHSC device, PGCF acts as both a current collector and cathode material due to its high specific surface area and superior conductivity. The use of a highly concentrated LiCl-CrCl3 electrolyte with high Cr plating/stripping efficiency and excellent antifreeze properties enables the entire PGCF-based CHSC to achieve well-balanced performance in terms of energy density (up to 1.47 mWh cm-2), power characteristics (reaching 9.95 mW cm-2) and durability (95.4% capacity retention after 30,000 cycles), while realizing it to work well under harsh conditions of -40 °C. This work introduces a new concept for low-temperature energy storage technology and confirms the potential application of Cr anodes in hybrid supercapacitors.

Astrocyte-derived SerpinA3N promotes neuroinflammation and epileptic seizures by activating the NF-κB signaling pathway in mice with temporal lobe epilepsy.

Impaired activation and regulation of the extinction of inflammatory cells and molecules in injured neuronal tissues are key factors in the development of epilepsy. SerpinA3N is mainly associated with the acute phase response and inflammatory response. In our current study, transcriptomics analysis, proteomics analysis, and Western blotting showed that the expression level of Serpin clade A member 3N (SerpinA3N) is significantly increased in the hippocampus of mice with kainic acid (KA)-induced temporal lobe epilepsy, and this molecule is mainly expressed in astrocytes. Notably, in vivo studies using gain- and loss-of-function approaches revealed that SerpinA3N in astrocytes promoted the release of proinflammatory factors and aggravated seizures. Mechanistically, RNA sequencing and Western blotting showed that SerpinA3N promoted KA-induced neuroinflammation by activating the NF-κB signaling pathway. In addition, co-immunoprecipitation revealed that SerpinA3N interacts with ryanodine receptor type 2 (RYR2) and promotes RYR2 phosphorylation. Overall, our study reveals a novel SerpinA3N-mediated mechanism in seizure-induced neuroinflammation and provides a new target for developing neuroinflammation-based strategies to reduce seizure-induced brain injury.

Plexcitonic optical chirality in the chiral plasmonic structure-microcavity-exciton strong coupling system.

Chiral plexcitonic systems exhibit a novel chiroptical phenomenon, which can provide a new route to design chiroptical devices. Reported works focused on the two-mode strong coupling between chiral molecules and nanoparticles, while multiple-mode coupling can provide richer modulation. In this paper, we proposed a three-mode coupling system consisting of a chiral Au helices array, a Fabry-Pérot cavity, and monolayer WSe2, which can provide an extra chiral channel, a more widely tunable region, and more tunable methods compared to two-mode coupled systems. The optical response of this hybrid system was investigated based on the finite element method. Mode splitting observed in the circular dichroism (CD) spectrum demonstrated that the chiroptical response successfully shifted from the resonant position of the chiral structure to three plexcitons through strong coupling, which provided a new route for chiral transfer. Furthermore, we used the coupled oscillator model to obtain the energy and Hopfield coefficients of the plexciton branches to explain the chiroptical phenomenon of the hybrid system. Moreover, the tunability of the hybrid system can be achieved by tuning the temperature and period of the helices array. Our work provides a feasible strategy for chiral sensing and modulation devices.

Strong coupling of second harmonic generation scattering spectrum in a diexcitionic nanosystem.

Diexcitonic strong coupling between quantum emitters and localized surface plasmon has attracted more attention recently because it can provide multiple qubit states for future quantum information technology at room temperature. In a strong coupling regime, nonlinear optical effects can offer new routes for developing quantum devices, but it is rarely reported. In this paper, we established the hybrid system consisting of J-aggregates-WS2-cuboid Au@Ag nanorods, which can realize diexcitonic strong coupling and second harmonic generation (SHG). We find that multimode strong coupling has been achieved not only in the fundamental frequency scattering spectrum but also in the SHG scattering spectrum. SHG scattering spectrum shows three plexciton branches, similar to the splitting in the fundamental frequency scattering spectrum. Furthermore, the SHG scattering spectrum can be modulated by tuning the armchair direction of the crystal lattice, pump polarization direction, and plasmon resonance frequency, which makes our system very promising in the quantum device at room temperature. Moreover, we develop coupled nonlinear harmonic oscillator model theory to explain the nonlinear diexcitonic strong coupling mechanism. The calculated results by the finite element method accord well with our theory. The nonlinear optical properties of the diexcitonic strong coupling can provide potential applications such as quantum manipulation, entanglement, and integrated logic devices.

Construction of organic/GaN heterostructures for DUV-to-NIR broadband photodetection.

Herein, a broadband photodetector (BPD) is constructed with consistent and stable detection abilities for deep ultraviolet to near-infrared spectral range. The BPD integrates the GaN template with a hybrid organic semiconductor, PM6:Y6, via the spin-coating process, and is fabricated in the form of asymmetric metal-semiconductor-metal structure. Under an optimal voltage, the device shows consistent photoresponse within 254 to 850 nm, featuring high responsivity (10 to 60 A/W), photo-to-dark-current ratio over 103, and fast response time. These results show the potential of such organic/GaN heterojunctions as a simple and effective strategy to build BPDs for a reliable photo-sensing application in the future.

Alkynylation of Isatin Derivatives Catalyzed by a Silver-Chiral Quaternary Ammonium Salt Derived from Quinine.

Asymmetric addition of terminal alkynes catalyzed by a transition metal to isatins obviously is an efficient and economic method for the synthesis of 3-alkynyl-3-hydroxy-2-oxindoles. The new dimeric chiral quaternary ammoniums derived from a natural chiral alkaloid, quinine, can be used as cationic inducers of the enantioselectivity for the Ag(I)-catalyzed alkynylation of isatin derivatives under mild conditions. The desired chiral 3-alkynyl-3-hydroxy-2-oxindoles can be obtained in good to high yields with high to excellent enantioselectivites (≤99% ee). A variety of aryl-substituted terminal alkynes and substituted isatins are tolerated in this reaction.

XAI-enabled neural network analysis of metabolite spatial distributions.

We used deep neural networks to process the mass spectrometry imaging (MSI) data of mouse muscle (young vs aged) and human cancer (tumor vs normal adjacent) tissues, with the aim of using explainable artificial intelligence (XAI) methods to rapidly identify biomarkers that can distinguish different classes of tissues, from several thousands of metabolite features. We also modified classic neural network architectures to construct a deep convolutional neural network that is more suitable for processing high-dimensional MSI data directly, instead of using dimension reduction techniques, and compared it to seven other machine learning analysis methods' performance in classification accuracy. After ascertaining the superiority of Channel-ResNet10, we used a novel channel selection-based XAI method to identify the key metabolite features that were responsible for its learning accuracy. These key metabolite biomarkers were then processed using MetaboAnalyst for pathway enrichment mapping. We found that Channel-ResNet10 was superior to seven other machine learning methods for MSI analysis, reaching > 98% accuracy in muscle aging and colorectal cancer datasets. We also used a novel channel selection-based XAI method to find that in young and aged muscle tissues, the differentially distributed metabolite biomarkers were especially enriched in the propanoate metabolism pathway, suggesting it as a novel target pathway for anti-aging therapy.

Role of the gut microbiota and their metabolites in hemodialysis patients.

High serum phosphate levels in chronic kidney disease (CKD) are linked to adverse health outcomes, including cardiovascular disease, kidney disease progression, and all-cause mortality. This study is aimed to find out which microorganisms or microbial functions have a significant impact on higher calcium-phosphorus product (Ca x P) after they undergo hemodialysis (HD) treatment. Feces samples from 30 healthy controls, 15 dialysis patients with controlled Ca xP (HD), and 16 dialysis patients with higher Ca xP (HDHCP) were collected to perform in 16S amplicon sequencing. We found gut microbial composition was significantly different between hemodialysis patients and healthy controls. Three phyla including Firmicutes, Actinobacteria, and Proteobacteria were significantly enriched in hemodialysis patients. Although only one genus, Lachnospiraceae_FCS020_group, was significantly increased in higher Ca xP group, there were four metabolic pathways predicted by PICRUSt significantly increased in higher Ca xP group and associated with causing VC, including the pentose phosphate pathway, steroid biosynthesis, terpenoid backbone biosynthesis, and fatty acid elongation pathway. Characterizing dysbiosis of gut microbiome played the important role in hemodialysis patients.