Genomic architecture of autism from comprehensive whole-genome sequence annotation.

Fully understanding autism spectrum disorder (ASD) genetics requires whole-genome sequencing (WGS). We present the latest release of the Autism Speaks MSSNG resource, which includes WGS data from 5,100 individuals with ASD and 6,212 non-ASD parents and siblings (total n = 11,312). Examining a wide variety of genetic variants in MSSNG and the Simons Simplex Collection (SSC; n = 9,205), we identified ASD-associated rare variants in 718/5,100 individuals with ASD from MSSNG (14.1%) and 350/2,419 from SSC (14.5%). Considering genomic architecture, 52% were nuclear sequence-level variants, 46% were nuclear structural variants (including copy-number variants, inversions, large insertions, uniparental isodisomies, and tandem repeat expansions), and 2% were mitochondrial variants. Our study provides a guidebook for exploring genotype-phenotype correlations in families who carry ASD-associated rare variants and serves as an entry point to the expanded studies required to dissect the etiology in the ∼85% of the ASD population that remain idiopathic.

Multifunctional ytterbium oxide buffer for perovskite solar cells.

Perovskite solar cells (PSCs) comprise a solid perovskite absorber sandwiched between several layers of different charge-selective materials, ensuring unidirectional current flow and high voltage output of the devices1,2. A 'buffer material' between the electron-selective layer and the metal electrode in p-type/intrinsic/n-type (p-i-n) PSCs (also known as inverted PSCs) enables electrons to flow from the electron-selective layer to the electrode3-5. Furthermore, it acts as a barrier inhibiting the inter-diffusion of harmful species into or degradation products out of the perovskite absorber6-8. Thus far, evaporable organic molecules9,10 and atomic-layer-deposited metal oxides11,12 have been successful, but each has specific imperfections. Here we report a chemically stable and multifunctional buffer material, ytterbium oxide (YbOx), for p-i-n PSCs by scalable thermal evaporation deposition. We used this YbOx buffer in the p-i-n PSCs with a narrow-bandgap perovskite absorber, yielding a certified power conversion efficiency of more than 25%. We also demonstrate the broad applicability of YbOx in enabling highly efficient PSCs from various types of perovskite absorber layer, delivering state-of-the-art efficiencies of 20.1% for the wide-bandgap perovskite absorber and 22.1% for the mid-bandgap perovskite absorber, respectively. Moreover, when subjected to ISOS-L-3 accelerated ageing, encapsulated devices with YbOx exhibit markedly enhanced device stability.

Genome-wide chromatin interaction profiling reveals a vital role of super-enhancers and rearrangements in host enhancer contacts during BmNPV infection.

As influential regulatory elements in the genome, enhancers control gene expression under specific cellular conditions, and such connections are dynamic under different conditions. However, because of the lack of a genome-wide enhancer-gene connection map, the roles and regulatory pattern of enhancers were poorly investigated in insects, and the dynamic changes of enhancer contacts and functions under different conditions remain elusive. Here, combining Hi-C, ATAC-seq, and H3K27ac ChIP-seq data, we generate the genome-wide enhancer-gene map of silkworm and identify super-enhancers with a role in regulating the expression of vital genes related to cell state maintenance through a sophisticated interaction network. Additionally, a radical attenuation of chromatin interactions is found after infection of Bombyx mori nucleopolyhedrovirus (BmNPV), the main pathogen of silkworm, which directly rearranges the enhancer contacts. Such a rearrangement disturbs the intrinsic enhancer-gene connections in several antiviral genes, resulting in reduced expression of these genes, which accelerates viral infection. Overall, our results reveal the regulatory role of super-enhancers and shed new light on the mechanisms and dynamic changes of the genome-wide enhancer regulatory network.

Nutrition-dependent juvenile hormone sensitivity promotes flight-muscle degeneration during the aphid dispersal-reproduction transition.

In insects, the loss of flight typically involves a dispersal-reproduction transition, but the underlying molecular mechanisms remain poorly understood. In the parthenogenetic pea aphid Acyrthosiphon pisum, winged females undergo flight-muscle degeneration after flight and feeding on new host plants. Similarly, topical application of a juvenile hormone (JH) mimic to starved aphids also induces flight-muscle degeneration. We found that feeding preferentially upregulated the expression of the JH receptor gene Met and a JH-inducible gene, Kr-h1, in the flight muscles, and, thus, enhanced tissue-specific JH sensitivity and signaling. RNAi-mediated knockdown of Kr-h1 prevented flight-muscle degeneration. Likewise, blocking nutritional signals by pharmacological inhibition of the target of rapamycin complex 1 (TORC1) impaired JH sensitivity of the flight muscles in feeding aphids and subsequently delayed muscle degeneration. RNA-sequencing analysis revealed that enhanced JH signaling inhibited the transcription of genes involved in the tricarboxylic acid cycle, likely resulting in reduction of the energy supply, mitochondrial dysfunction and muscle-fiber breakdown. This study shows that nutrient-dependent hormone sensitivity regulates developmental plasticity in a tissue-specific manner, emphasizing a relatively underappreciated mechanism of hormone sensitivity in modulating hormone signaling.

A gain-of-function allele of a DREB transcription factor gene ameliorates drought tolerance in wheat.

Drought is a major environmental factor limiting wheat production worldwide. However, the genetic components underlying wheat drought tolerance are largely unknown. Here, we identify a DREB transcription factor gene (TaDTG6-B) by genome-wide association study that is tightly associated with drought tolerance in wheat. Candidate gene association analysis revealed that a 26-bp deletion in the TaDTG6-B coding region induces a gain-of-function for TaDTG6-BDel574, which exhibits stronger transcriptional activation, protein interactions, and binding activity to dehydration-responsive elements (DRE)/CRT cis-elements than the TaDTG6-BIn574 encoded by the allele lacking the deletion, thus conferring greater drought tolerance in wheat seedlings harboring this variant. Knockdown of TaDTG6-BDel574 transcripts attenuated drought tolerance in transgenic wheat, whereas its overexpression resulted in enhanced drought tolerance without accompanying phenotypic abnormalities. Furthermore, the introgression of the TaDTG6-BDel574 elite allele into drought-sensitive cultivars improved their drought tolerance, thus providing a valuable genetic resource for wheat breeding. We also identified 268 putative target genes that are directly bound and transcriptionally regulated by TaDTG6-BDel574. Further analysis showed that TaDTG6-BDel574 positively regulates TaPIF1 transcription to enhance wheat drought tolerance. These results describe the genetic basis and accompanying mechanism driving phenotypic variation in wheat drought tolerance, and provide a novel genetic resource for crop breeding programs.

ATG12 conjugation to ATG3 regulates mitochondrial homeostasis and cell death.

ATG12, an ubiquitin-like modifier required for macroautophagy, has a single known conjugation target, another autophagy regulator called ATG5. Here, we identify ATG3 as a substrate for ATG12 conjugation. ATG3 is the E2-like enzyme necessary for ATG8/LC3 lipidation during autophagy. ATG12-ATG3 complex formation requires ATG7 as the E1 enzyme and ATG3 autocatalytic activity as the E2, resulting in the covalent linkage of ATG12 onto a single lysine on ATG3. Surprisingly, disrupting ATG12 conjugation to ATG3 does not affect starvation-induced autophagy. Rather, the lack of ATG12-ATG3 complex formation produces an expansion in mitochondrial mass and inhibits cell death mediated by mitochondrial pathways. Overall, these results unveil a role for ATG12-ATG3 in mitochondrial homeostasis and implicate the ATG12 conjugation system in cellular functions distinct from the early steps of autophagosome formation.

CEBPD aggravates apoptosis and oxidative stress of neuron after ischemic stroke by Nrf2/HO-1 pathway.

CCAAT enhancer binding protein delta (CEBPD) is a transcription factor and plays an important role in apoptosis and oxidative stress, which are the main pathogenesis of ischemic stroke. However, whether CEBPD regulates ischemic stroke through targeting apoptosis and oxidative stress is unclear. Therefore, to answer this question, rat middle cerebral artery occlusion (MCAO) reperfusion model and oxygen-glucose deprivation/reoxygenation (OGD/R) primary cortical neuron were established to mimic ischemic reperfusion injury. We found that CEBPD was upregulated and accompanied with increased neurological deficit scores and infarct size, and decreased neuron in MCAO rats. The siRNA targeted CEBPD inhibited CEBPD expression in rats, and meanwhile lentivirus system was used to blocked CEBPD expression in primary neuron. CEBPD degeneration decreased neurological deficit scores, infarct size and brain water content of MCAO rats. Knockdown of CEBPD enhanced cell viability and reduced apoptosis as well as oxidative stress in vivo and in vitro. CEBPD silencing promoted the translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) to the nucleus and the expression of heme oxygenase 1 (HO-1). Newly, CEBPD facilitated the transcription of cullin 3 (CUL3), which intensified ischemic stroke through Nrf2/HO-1 pathway that was proposed by our team in the past. In conclusion, targeting CEBPD-CUL3-Nrf2/HO-1 axis may be contributed to cerebral ischemia therapy.

Concentration-Driven Interfacial Amorphization toward Highly Stable and High-Rate Zn Metal Batteries.

The interfacial structure holds great promise in suppressing dendrite growth and parasitic reactions of zinc metal in aqueous media. Current advancements prioritize novel component fabrication, yet the local crystal structure significantly impacts the interfacial properties. In addition, there is still a critical need for scalable synthesis methods for expediting the commercialization of aqueous zinc metal batteries (AZMBs). Herein, we propose a scalable concentration-controlled method for realizing crystalline to amorphous transformation of the Zn metal interface with exceptional scalability (>1 m2) and processing consistency (>30 trials). Theoretical and experimental analyses highlight the advantages of amorphous ZnO, which exhibits moderate adsorption energy, strong desolvation ability, and hydrophilicity. Employing the amorphous ZnO-coated zinc metal anode (AZO-Zn) significantly enhances the cycling performance, impressively maintaining 1000 cycles at 100 mA cm-2. The prototype AZO-Zn||MnO2@CNT pouch cell demonstrates a capacity of 15.7 mAh and maintains 91% of its highest capacity over 100 cycles, presenting promising avenues for the future commercialization of AZMBs.

Dual-Parasitic Effect Enables Highly Reversible Zn Metal Anode for Ultralong 25,000 Cycles Aqueous Zinc-Ion Batteries.

The use of electrolyte additives is an efficient approach to mitigating undesirable side reactions and dendrites. However, the existing electrolyte additives do not effectively regulate both the chaotic diffusion of Zn2+ and the decomposition of H2O simultaneously. Herein, a dual-parasitic method is introduced to address the aforementioned issues by incorporating 1-ethyl-3-methylimidazolium trifluoromethanesulfonate ([EMIm]OTf) as cosolvent into the Zn(OTf)2 electrolyte. Specifically, the OTf- anion is parasitic in the solvent sheath of Zn2+ to decrease the number of active H2O. Additionally, the EMIm+ cation can construct an electrostatic shield layer and a hybrid organic/inorganic solid electrolyte interface layer to optimize the deposition behavior of Zn2+. This results in a Zn anode with a reversible cycle life of 3000 h, the longest cycle life of full cells (25,000 cycles), and an extremely high initial capacity (4.5 mA h cm-2), providing a promising electrolyte solution for practical applications of rechargeable aqueous zinc-ion batteries.

Suffering makes you weaker: Limited evolutionary adaptation in competitively inferior populations.

Interspecific competition can hinder populations from evolutionarily adapting to abiotic environments, particularly by reducing population size and niche space; and feedback may arise between competitive ability and evolutionary adaptation. Here we studied populations of two model bacterial species, Escherichia coli and Pseudomonas fluorescens, that evolved in monocultures and cocultures for approximately 2400 generations at three temperatures. The two species showed a reversal in competitive dominance in cocultures along the temperature gradient. Populations from cocultures where they had been competitively dominant showed the same magnitude of fitness gain as those in monocultures. However, competitively inferior populations in cocultures showed limited abiotic adaptation compared with those in monocultures. The inferior populations in cocultures were also more likely to evolve weaker interspecific competitive ability, or go extinct. The possible competitive ability-adaptation feedback may have crucial consequences for population persistence.

Detection of circulating plasma cells in peripheral blood using deep learning-based morphological analysis.

BACKGROUND: The presence of circulating plasma cells (CPCs) is an important laboratory indicator for the diagnosis, staging, risk stratification, and progression monitoring of multiple myeloma (MM). Early detection of CPCs in the peripheral blood (PB) followed by timely interventions can significantly improve MM prognosis and delay its progression. Although the conventional cell morphology examination remains the predominant method for CPC detection because of accessibility, its sensitivity and reproducibility are limited by technician expertise and cell quantity constraints. This study aims to develop an artificial intelligence (AI)-based automated system for a more sensitive and efficient CPC morphology detection. METHODS: A total of 137 bone marrow smears and 72 PB smears from patients with at Zhongshan Hospital, Fudan University, were retrospectively reviewed. Using an AI-powered digital pathology platform, Morphogo, 305,019 cell images were collected for training. Morphogo's efficacy in CPC detection was evaluated with additional 184 PB smears (94 from patients with MM and 90 from those with other hematological malignancies) and compared with manual microscopy. RESULTS: Morphogo achieved 99.64% accuracy, 89.03% sensitivity, and 99.68% specificity in classifying CPCs. At a 0.60 threshold, Morphogo achieved a sensitivity of 96.15%, which was approximately twice that of manual microscopy, with a specificity of 78.03%. Patients with CPCs detected by AI scanning had a significantly shorter median progression-free survival compared with those without CPC detection (18 months vs. 34 months, p< .01). CONCLUSIONS: Morphogo is a highly sensitive system for the automated detection of CPCs, with potential applications in initial screening, prognosis prediction, and posttreatment monitoring for MM patients. PLAIN LANGUAGE SUMMARY: Diagnosing and monitoring multiple myeloma (MM), a type of blood cancer, requires identifying and quantifying specific cells called circulating plasma cells (CPCs) in the blood. The conventional method for detecting CPCs is manual microscopic examination, which is time-consuming and lacks sensitivity. This study introduces a highly sensitive CPC detection method using an artificial intelligence-based system, Morphogo. It demonstrated remarkable sensitivity and accuracy, surpassing conventional microscopy. This advanced approach suggests that early and accurate CPC detection is achievable by morphology examination, making efficient CPC screening more accessible for patients with MM. This innovative system has the potential to be used in the diagnosis and risk assessment of MM.

Validation of the RSClin risk calculator in the National Cancer Data Base.

BACKGROUND: Guidelines recommend the use of genomic assays such as OncotypeDx to aid in decisions regarding the use of chemotherapy for hormone receptor-positive, HER2-negative (HR+/HER2-) breast cancer. The RSClin prognostic tool integrates OncotypeDx and clinicopathologic features to predict distant recurrence and chemotherapy benefit, but further validation is needed before broad clinical adoption. METHODS: This study included patients from the National Cancer Data Base (NCDB) who were diagnosed with stage I-III HR+/HER2- breast cancer from 2010 to 2020 and received adjuvant endocrine therapy with or without chemotherapy. RSClin-predicted chemotherapy benefit was stratified into low (<3% reduction in distant recurrence), intermediate (3%-5%), and high (>5%). Cox models were used to model mortality adjusted for age, comorbidity index, insurance, and race/ethnicity. RESULTS: A total of 285,441 patients were identified for inclusion from the NCDB, with an average age of 60 years and a median follow-up of 58 months. Chemotherapy was associated with improved overall survival only for those predicted to have intermediate (adjusted hazard ratio [aHR], 0.68; 95% confidence interval [CI], 0.60-0.79) and high benefit per RSClin (aHR, 0.66; 95% CI, 0.61-0.72). Consistent benefit was seen in the subset with a low OncotypeDx score (<26) and intermediate (aHR, 0.66; 95% CI, 0.53-0.82) or high (aHR, 0.71; 95% CI, 0.58-0.86) RSClin-predicted benefit. No survival benefit with chemotherapy was seen in patients with a high OncotypeDx score (≥26) and low benefit per RSClin (aHR, 1.70; 95% CI, 0.41-6.99). CONCLUSIONS: RSClin may identify high-risk patients who benefit from treatment intensification more accurately than OncotypeDx, and further prospective study is needed.

Effects of 6-month customized home-based exercise on motor development, bone strength, and parental stress in children with simple congenital heart disease: a single-blinded randomized clinical trial.

BACKGROUND: New "noncardiac" problems in children with congenital heart disease (CHD), such as developmental delay or long-term neurodevelopmental impairments, have attracted considerable attention in recent years. It is hypothesized that exercise might attenuate CHD-associated neurodevelopmental impairments; however, this has not been thoroughly investigated. The objective of this prospective, single-blinded, randomized controlled experiment was to evaluate the impact of customized home-based exercise for children with CHD. METHODS: Children aged 0-5 years with echocardiography-confirmed simple CHD subtypes who were scheduled to undergo cardiac catheterization were screened for enrolment. Among 420 screened CHD children, 192 were enrolled and randomly assigned at a 1:1 ratio to receive a 6-month intervention (30 min daily customized home-based exercise program with supervision for no less than 5 days per week, combined with home-based exercise education) or control treatment (home-based education). The primary outcome was motor development (gross motor quotient (GMQ), fine motor quotient (FMQ), and total motor quotient (TMQ)). The secondary outcomes were cardiac function and structure, bone quality, physical development, parental anxiety, caregiver burden, and quality of life. Children and their families were assessed before and 1, 3, and 6 months after catheterization; 183 (95.3%) children were included in the primary analysis. RESULTS: After 6-month treatment, the intervention group significantly increased their motor quotient, which was consistently higher than that of the control group (GMQ p < 0.0001, FMQ p = 0.02, TMQ p < 0.001). The physical developments in height, weight, and circumferences of the upper-arm, chest, and head were also significantly improved by exercise (all p < 0.017). No significant improvements in the bone strength or the cardiac structure and function were found among patients in the intervention group (all p > 0.017). For parents, higher quality of life level (total score p = 0.016) was observed in the intervention group; while effects of exercise on the anxiety (rude score p = 0.159, standard score p = 0.159) or the Zarit caregiver burden scale score (p = 0.404) were non-significant. No adverse events occurred during the study period. CONCLUSIONS: Customized home-based exercise improved motor development in children with CHD. While the long-term effects of parent training in home-based exercise are unknown, the study results suggest positive outcomes. TRIAL REGISTRATION: A home-based exercise program in congenital heart disease children with cardiac catheterization: a randomized controlled trial. ( http://www.chictr.org.cn/ , ChiCTR-IOR-16007762, January 14, 2016).

LiPF6 Induces Phosphorization of Garnet-Type Solid-State Electrolyte for Stable Lithium Metal Batteries.

Garnet solid electrolyte Li6.4 La3 Zr1.4 Ta0.6 O12 (LLZTO) is an excellent inorganic ceramic-type solid electrolyte; however, the presence of Li2 CO3 impurities on its surface hinders Li-ion transport and increases the interface impedance. In contrast to traditional methods of mechanical polishing, acid corrosion, and high-temperature reduction for removing Li2 CO3 , herein, a straightforward "waste-to-treasure" strategy is proposed to transform Li2 CO3 into Li3 PO4 and LiF in LiPF6 solution under 60 °C. It is found that the formation of Li3 PO4 during LLZTO pretreatment facilitates rapid Li-ion transport and enhances ionic conductivity, and the LLZTO/PAN composite polymer electrolyte shows the highest Li-ion transference number of 0.63. Additionally, the dense LiF layer serves to safeguard the internal garnet solid electrolyte against solvent decomposition-induced chemical adsorption. Symmetric Li/Li cells assembled with treated LLZTO/PAN composite electrolyte exhibit a critical current density of 1.1 mA cm-2 and a long lifespan of up to 700 h at a current density of 0.2 mA cm-2 . The Li/LiFePO4 solid-state cells demonstrate stable cycling performances for 141 mAh g-1 at 0.5 C, with capacity retention of 93.6% after 190 cycles. This work presents a novel approach to converting waste into valuable resources, offering the advantages of simple processes, and minimal side reactions.

Highly accelerated multi-shot intravoxel incoherent motion diffusion-weighted imaging in brain enabled by parametric POCS-based multiplexed sensitivity encoding.

Recently, intravoxel incoherent motion (IVIM) diffusion-weighted imaging (DWI) has also been demonstrated as an imaging tool for applications in neurological and neurovascular diseases. However, the use of single-shot diffusion-weighted echo-planar imaging for IVIM DWI acquisition leads to suboptimal data quality: for instance, geometric distortion and deteriorated image quality at high spatial resolution. Although the recently commercialized multi-shot acquisition methods, such as multiplexed sensitivity encoding (MUSE), can attain high-resolution and high-quality DWI with signal-to-noise ratio (SNR) performance superior to that of the conventional parallel imaging method, the prolonged scan time associated with multi-shot acquisition is impractical for routine IVIM DWI. This study proposes an acquisition and reconstruction framework based on parametric-POCSMUSE to accelerate the four-shot IVIM DWI with 70% reduction of total scan time (13 min 8 s versus 4 min 8 s). First, the four-shot IVIM DWI scan with 17 b values was accelerated by acquiring only one segment per b value except for b values of 0 and 600 s/mm2 . Second, an IVIM-estimation scheme was integrated into the parametric-POCSMUSE to enable joint reconstruction of multi-b images from under-sampled four-shot IVIM DWI data. In vivo experiments on both healthy subjects and patients show that the proposed framework successfully produced multi-b DW images with significantly higher SNRs and lower reconstruction errors than did the conventional acceleration method based on parallel imaging. In addition, the IVIM quantitative maps estimated from the data produced by the proposed framework showed quality comparable to that of fully sampled MUSE-reconstructed images, suggesting that the proposed framework can enable highly accelerated multi-shot IVIM DWI without sacrificing data quality. In summary, the proposed framework can make multi-shot IVIM DWI feasible in a routine MRI examination, with reasonable scan time and improved geometric fidelity.

Specific Alterations in Brain White Matter Networks and Their Impact on Clinical Function in Pediatric Patients With Thoracolumbar Spinal Cord Injury.

BACKGROUND: The alternation of brain white matter (WM) network has been studied in adult spinal cord injury (SCI) patients. However, the WM network alterations in pediatric SCI patients remain unclear. PURPOSE: To evaluate WM network changes and their functional impact in children with thoracolumbar SCI (TSCI). STUDY TYPE: Prospective. SUBJECTS: Thirty-five pediatric patients with TSCI (8.94 ± 1.86 years, 8/27 males/females) and 34 age- and gender-matched healthy controls (HCs) participated in this study. FIELD STRENGTH/SEQUENCE: 3.0 T/DTI imaging using spin-echo echo-planar and T1-weighted imaging using 3D T1-weighted magnetization-prepared rapid gradient-echo sequence. ASSESSMENT: Pediatric SCI patients were evaluated for motor and sensory scores, injury level, time since injury, and age at injury. The WM network was constructed using a continuous tracing method, resulting in a 90 × 90 matrix. The global and regional metrics were obtained to investigate the alterations of the WM structural network. topology. STATISTICAL TESTS: Two-sample independent t-tests, chi-squared test, Mann-Whitney U-test, and Spearman correlation. Statistical significance was set at P < 0.05. RESULTS: Compared with HCs, pediatric TSCI patients displayed decreased shortest path length (Lp = 1.080 ± 0.130) and normalized Lp (λ = 5.020 ± 0.363), and increased global efficiency (Eg = 0.200 ± 0.015). Notably, these patients also demonstrated heightened regional properties in the orbitofrontal cortex, limbic system, default mode network, and several audio-visual-related regions. Moreover, the λ and Lp values negatively correlated with sensory scores. Conversely, nodal efficiency values in the right calcarine fissure and surrounding cortex positively correlated with sensory scores. The age at injury positively correlated with node degree in the left parahippocampal gyrus and nodal efficiency in the right posterior cingulate gyrus. DATA CONCLUSION: Reorganization of the WM networks in pediatric SCI patients is indicated by increased global and nodal efficiency, which may provide promising neuroimaging biomarkers for functional assessment of pediatric SCI. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 5.

Midbrain FA initiates neuroinflammation and depression onset in both acute and chronic LPS-induced depressive model mice.

Both exogenous gaseous and liquid forms of formaldehyde (FA) can induce depressive-like behaviors in both animals and humans. Stress and neuronal excitation can elicit brain FA generation. However, whether endogenous FA participates in depression occurrence remains largely unknown. In this study, we report that midbrain FA derived from lipopolysaccharide (LPS) is a direct trigger of depression. Using an acute depressive model in mice, we found that one-week intraperitoneal injection (i.p.) of LPS activated semicarbazide-sensitive amine oxidase (SSAO) leading to FA production from the midbrain vascular endothelium. In both in vitro and in vivo experiments, FA stimulated the production of cytokines such as IL-1ß, IL-6, and TNF-α. Strikingly, one-week microinfusion of FA as well as LPS into the midbrain dorsal raphe nucleus (DRN, a 5-HT-nergic nucleus) induced depressive-like behaviors and concurrent neuroinflammation. Conversely, NaHSO3 (a FA scavenger), improved depressive symptoms associated with a reduction in the levels of midbrain FA and cytokines. Moreover, the chronic depressive model of mice injected with four-week i.p. LPS exhibited a marked elevation in the levels of midbrain LPS accompanied by a substantial increase in the levels of FA and cytokines. Notably, four-week i.p. injection of FA as well as LPS elicited cytokine storm in the midbrain and disrupted the blood-brain barrier (BBB) by activating microglia and reducing the expression of claudin 5 (CLDN5, a protein with tight junctions in the BBB). However, the administration of 30 nm nano-packed coenzyme-Q10 (Q10, an endogenous FA scavenger), phototherapy (PT) utilizing 630-nm red light to degrade FA, and the combination of PT and Q10, reduced FA accumulation and neuroinflammation in the midbrain. Moreover, the combined therapy exhibited superior therapeutic efficacy in attenuating depressive symptoms compared to individual treatments. Thus, LPS-derived FA directly initiates depression onset, thereby suggesting that scavenging FA represents a promising strategy for depression treatment.

Modulation of fatty acid elongation in cockroaches sustains sexually dimorphic hydrocarbons and female attractiveness.

Insect cuticular hydrocarbons (CHCs) serve as important intersexual signaling chemicals and generally show variation between the sexes, but little is known about the generation of sexually dimorphic hydrocarbons (SDHCs) in insects. In this study, we report the molecular mechanism and biological significance that underlie the generation of SDHC in the German cockroach Blattella germanica. Sexually mature females possess more C29 CHCs, especially the contact sex pheromone precursor 3,11-DimeC29. RNA interference (RNAi) screen against the fatty acid elongase family members combined with heterologous expression of the genes in yeast revealed that both BgElo12 and BgElo24 were involved in hydrocarbon (HC) production, but BgElo24 is of wide catalytic activities and is able to provide substrates for BgElo12, and only the female-enriched BgElo12 is responsible for sustaining female-specific HC profile. Repressing BgElo12 masculinized the female CHC profile, decreased contact sex pheromone level, and consequently reduced the sexual attractiveness of female cockroaches. Moreover, the asymmetric expression of BgElo12 between the sexes is modulated by sex differentiation cascade. Specifically, male-specific BgDsx represses the transcription of BgElo12 in males, while BgTra is able to remove this effect in females. Our study reveals a novel molecular mechanism responsible for the formation of SDHCs and also provide evidences on shaping of the SDHCs by sexual selection, as females use them to generate high levels of contact sex pheromone.

Methyl Acetate Boosts the Low-Temperature Performance of Li4Ti5O12/Graphite Dual-Ion Batteries.

Methyl acetate (MA) is a suitable solvent for low-temperature electrolyte solutions, but its poor stability against lithium metal is a big problem. Herein, a simple and cheap solution of LiPF6 dissolved in MA was successfully employed for Li4Ti5O12/graphite dual-ion batteries (DIBs). This cell has a long cycle life with 93.1% capacity retention after 1000 cycles. Moreover, it has superior performance at low temperatures (-40 °C) compared to other reported DIBs. The storage behavior of PF6- solvated by MA in graphite cathode has been investigated in detail by in situ X-ray diffraction (XRD) in combination with electrochemical dilatometry (ECD).

LiNi0.5Mn1.5O4 Joins to Alleviate Self-Discharge of Anion-Graphite Intercalation Compounds.

A straightforward hybrid approach of a blend cathode is put forward to alleviate self-discharged anion-graphite intercalation compounds in dual-ion batteries. The self-discharge mechanism of the LiNi0.5Mn1.5O4/graphite blend cathode is investigated by conventional electrochemical tests and in situ X-ray diffraction measurements. A charging behavior between electrode materials during self-discharge has been discovered. This work will contribute to advancing the practical implementation of dual-ion batteries and provide valuable theoretical support for the research of blend electrodes.