A holistic platform for accelerating sorbent-based carbon capture.

Reducing carbon dioxide (CO2) emissions urgently requires the large-scale deployment of carbon-capture technologies. These technologies must separate CO2 from various sources and deliver it to different sinks1,2. The quest for optimal solutions for specific source-sink pairs is a complex, multi-objective challenge involving multiple stakeholders and depends on social, economic and regional contexts. Currently, research follows a sequential approach: chemists focus on materials design3 and engineers on optimizing processes4,5, which are then operated at a scale that impacts the economy and the environment. Assessing these impacts, such as the greenhouse gas emissions over the plant's lifetime, is typically one of the final steps6. Here we introduce the PrISMa (Process-Informed design of tailor-made Sorbent Materials) platform, which integrates materials, process design, techno-economics and life-cycle assessment. We compare more than 60 case studies capturing CO2 from various sources in 5 global regions using different technologies. The platform simultaneously informs various stakeholders about the cost-effectiveness of technologies, process configurations and locations, reveals the molecular characteristics of the top-performing sorbents, and provides insights on environmental impacts, co-benefits and trade-offs. By uniting stakeholders at an early research stage, PrISMa accelerates carbon-capture technology development during this critical period as we aim for a net-zero world.

Winter fields antisense RNAs to kick off flowering.

FLOWERING LOCUS C (FLC), a MADS-box transcription factor, plays a major role in determining flowering time in Arabidopsis In this issue of Genes & Development, Zhao and colleagues (pp. 888-898) elucidate the role of COOLAIR antisense noncoding RNAs in FLC regulation through field trials and laboratory experiments. COOLAIR-mediated FLC silencing is induced by the first seasonal frost in the field and thus acts as a key molecular indicator during autumn for winter arrival.

LncRNA FLAIL affects alternative splicing and represses flowering in Arabidopsis.

How the noncoding genome affects cellular functions is a key biological question. A particular challenge is to distinguish the effects of noncoding DNA elements from long noncoding RNAs (lncRNAs) that coincide at the same loci. Here, we identified the flowering-associated intergenic lncRNA (FLAIL) in Arabidopsis through early flowering flail mutants. Expression of FLAIL RNA from a different chromosomal location in combination with strand-specific RNA knockdown characterized FLAIL as a trans-acting RNA molecule. FLAIL directly binds to differentially expressed target genes that control flowering via RNA-DNA interactions through conserved sequence motifs. FLAIL interacts with protein and RNA components of the spliceosome to affect target mRNA expression through co-transcriptional alternative splicing (AS) and linked chromatin regulation. In the absence of FLAIL, splicing defects at the direct FLAIL target flowering gene LACCASE 8 (LAC8) correlated with reduced mRNA expression. Double mutant analyses support a model where FLAIL-mediated splicing of LAC8 promotes its mRNA expression and represses flowering. Our study suggests lncRNAs as accessory components of the spliceosome that regulate AS and gene expression to impact organismal development.

Evidence for an atomic chiral superfluid with topological excitations.

Topological superfluidity is an important concept in electronic materials as well as ultracold atomic gases1. However, although progress has been made by hybridizing superconductors with topological substrates, the search for a material-natural or artificial-that intrinsically exhibits topological superfluidity has been ongoing since the discovery of the superfluid 3He-A phase2. Here we report evidence for a globally chiral atomic superfluid, induced by interaction-driven time-reversal symmetry breaking in the second Bloch band of an optical lattice with hexagonal boron nitride geometry. This realizes a long-lived Bose-Einstein condensate of 87Rb atoms beyond present limits to orbitally featureless scenarios in the lowest Bloch band. Time-of-flight and band mapping measurements reveal that the local phases and orbital rotations of atoms are spontaneously ordered into a vortex array, showing evidence of the emergence of global angular momentum across the entire lattice. A phenomenological effective model is used to capture the dynamics of Bogoliubov quasi-particle excitations above the ground state, which are shown to exhibit a topological band structure. The observed bosonic phase is expected to exhibit phenomena that are conceptually distinct from, but related to, the quantum anomalous Hall effect3-7 in electronic condensed matter.

Arabidopsis protein S-acyl transferases positively mediate BR signaling through S-acylation of BSK1.

Protein S-acyl transferases (PATs) catalyze S-acylation, a reversible post-translational modification critical for membrane association, trafficking, and stability of substrate proteins. Many plant proteins are potentially S-acylated but few have corresponding PATs identified. By using genomic editing, confocal imaging, pharmacological, genetic, and biochemical assays, we demonstrate that three Arabidopsis class C PATs positively regulate BR signaling through S-acylation of BRASSINOSTEROID-SIGNALING KINASE1 (BSK1). PAT19, PAT20, and PAT22 associate with the plasma membrane (PM) and the trans-Golgi network/early endosome (TGN/EE). Functional loss of all three genes results in a plethora of defects, indicative of reduced BR signaling and rescued by enhanced BR signaling. PAT19, PAT20, and PAT22 interact with BSK1 and are critical for the S-acylation of BSK1, and for BR signaling. The PM abundance of BSK1 was reduced by functional loss of PAT19, PAT20, and PAT22 whereas abolished by its S-acylation-deficient point mutations, suggesting a key role of S-acylation in its PM targeting. Finally, an active BR analog induces vacuolar trafficking and degradation of PAT19, PAT20, or PAT22, suggesting that the S-acylation of BSK1 by the three PATs serves as a negative feedback module in BR signaling.

Dual mutations in the whitefly nicotinic acetylcholine receptor ß1 subunit confer target-site resistance to multiple neonicotinoid insecticides.

Neonicotinoid insecticides, which target insect nicotinic acetylcholine receptors (nAChRs), have been widely and intensively used to control the whitefly, Bemisia tabaci, a highly damaging, globally distributed, crop pest. This has inevitably led to the emergence of populations with resistance to neonicotinoids. However, to date, there have been no reports of target-site resistance involving mutation of B. tabaci nAChR genes. Here we characterize the nAChR subunit gene family of B. tabaci and identify dual mutations (A58T&R79E) in one of these genes (BTß1) that confer resistance to multiple neonicotinoids. Transgenic D. melanogaster, where the native nAChR Dß1 was replaced with BTß1A58T&R79E, were significantly more resistant to neonicotinoids than flies where Dß1 were replaced with the wildtype BTß1 sequence, demonstrating the causal role of the mutations in resistance. The two mutations identified in this study replace two amino acids that are highly conserved in >200 insect species. Three-dimensional modelling suggests a molecular mechanism for this resistance, whereby A58T forms a hydrogen bond with the R79E side chain, which positions its negatively-charged carboxylate group to electrostatically repulse a neonicotinoid at the orthosteric site. Together these findings describe the first case of target-site resistance to neonicotinoids in B. tabaci and provide insight into the molecular determinants of neonicotinoid binding and selectivity.

Generation and characterization of mature hepatocyte organoids for liver metabolic studies.

Hepatocyte organoids (HOs) generated in vitro are powerful tools for liver regeneration. However, previously reported HOs have mostly been fetal in nature with low expression levels of metabolic genes characteristic of adult liver functions, hampering their application in studies of metabolic regulation and therapeutic testing for liver disorders. Here, we report development of novel culture conditions that combine optimized levels of triiodothyronine (T3) with the removal of growth factors to enable successful generation of mature hepatocyte organoids (MHOs) of both mouse and human origin with metabolic functions characteristic of adult livers. We show that the MHOs can be used to study various metabolic functions including bile and urea production, zonal metabolic gene expression, and metabolic alterations in both alcoholic liver disease and non-alcoholic fatty liver disease, as well as hepatocyte proliferation, injury and cell fate changes. Notably, MHOs derived from human fetal hepatocytes also show improved hepatitis B virus infection. Therefore, these MHOs provide a powerful in vitro model for studies of human liver physiology and diseases. The human MHOs are potentially also a robust research tool for therapeutic development.

Tertiary Lymphoid Structure-Associated B Cells Enhance CXCL13+CD103+CD8+ Tissue-Resident Memory T-Cell Response to Programmed Cell Death Protein 1 Blockade in Cancer Immunotherapy.

BACKGROUND & AIMS: Although the presence of tertiary lymphoid structures (TLS) correlates with positive responses to immunotherapy in many solid malignancies, the mechanism by which TLS enhances antitumor immunity is not well understood. The present study aimed to investigate the underlying cross talk circuits between B cells and tissue-resident memory T (Trm) cells within the TLS and to understand their role in the context of immunotherapy. METHODS: Immunostaining and H&E staining of TLS and chemokine (C-X-C motif) ligand 13 (CXCL13)+ cluster of differentiation (CD)103+CD8+ Trm cells were performed on tumor sections from patients with gastric cancer (GC). The mechanism of communication between B cells and CXCL13+CD103+CD8+ Trm cells was determined in vitro and in vivo. The effect of CXCL13+CD103+CD8+ Trm cells in suppressing tumor growth was evaluated through anti-programmed cell death protein (PD)-1 therapy. RESULTS: The presence of TLS and CXCL13+CD103+CD8+ Trm cells in tumor tissues favored a superior response to anti-PD-1 therapy in patients with GC. Additionally, our research identified that activated B cells enhanced CXCL13 and granzyme B secretion by CD103+CD8+ Trm cells. Mechanistically, B cells facilitated the glycolysis of CD103+CD8+ Trm cells through the lymphotoxin-α/tumor necrosis factor receptor 2 (TNFR2) axis, and the mechanistic target of rapamycin signaling pathway played a critical role in CD103+CD8+ Trm cells glycolysis during this process. Moreover, the presence of TLS and CXCL13+CD103+CD8+ Trm cells correlated with potent responsiveness to anti-PD-1 therapy in a TNFR2-dependent manner. CONCLUSIONS: This study further reveals a crucial role for cellular communication between TLS-associated B cell and CXCL13+CD103+CD8+ Trm cells in antitumor immunity, providing valuable insights into the potential use of the lymphotoxin-α/TNFR2 axis within CXCL13+CD103+CD8+ Trm cells for advancing immunotherapy strategies in GC.

14-3-3 proteins contribute to autophagy by modulating SINAT-mediated degradation of ATG13.

In multicellular eukaryotes, autophagy is a conserved process that delivers cellular components to the vacuole or lysosome for recycling during development and stress responses. Induction of autophagy activates AUTOPHAGY-RELATED PROTEIN 1 (ATG1) and ATG13 to form a protein kinase complex that initiates autophagosome formation. However, the detailed molecular mechanism underlying the regulation of this protein complex in plants remains unclear. Here, we determined that in Arabidopsis thaliana, the regulatory proteins 14-3-3λ and 14-3-3κ redundantly modulate autophagy dynamics by facilitating SEVEN IN ABSENTIA OF ARABIDOPSIS THALIANA (SINAT)-mediated proteolysis of ATG13a and ATG13b. 14-3-3λ and 14-3-3κ directly interacted with SINATs and ATG13a/b in vitro and in vivo. Compared to wild-type (WT), the 14-3-3λ 14-3-3κ double mutant showed increased tolerance to nutrient starvation, delayed leaf senescence, and enhanced starvation-induced autophagic vesicles. Moreover, 14-3-3s were required for SINAT1-mediated ubiquitination and degradation of ATG13a. Consistent with their roles in ATG degradation, the 14-3-3λ 14-3-3κ double mutant accumulated higher levels of ATG1a/b/c and ATG13a/b than the WT upon nutrient deprivation. Furthermore, the specific association of 14-3-3s with phosphorylated ATG13a was crucial for ATG13a stability and formation of the ATG1-ATG13 complex. Thus, our findings demonstrate that 14-3-3λ and 14-3-3κ function as molecular adaptors to regulate autophagy by modulating the homeostasis of phosphorylated ATG13.

Recent advances in the role of hydrogen sulfide in age-related diseases.

In recent years, the impact of age-related diseases on human health has become increasingly severe, and developing effective drugs to deal with these diseases has become an urgent task. Considering the essential regulatory role of hydrogen sulfide (H2S) in these diseases, it is regarded as a promising target for treatment. H2S is a novel gaseous transmitter involved in many critical physiological activities, including anti-oxidation, anti-inflammation, and angiogenesis. H2S also regulates cell activities such as cell proliferation, migration, invasion, apoptosis, and autophagy. These regulatory effects of H2S contribute to relieving and treating age-related diseases. In this review, we mainly focus on the pathogenesis and treatment prospects of H2S in regulating age-related diseases.

DNA Processing in the Context of Noncoding Transcription.

RNA polymerase (RNAP)II frequently transcribes non-protein-coding DNA sequences in eukaryotic genomes into long noncoding RNA (lncRNA). Distinct molecular mechanisms linked to the position of lncRNA relative to the coding gene illustrate how noncoding transcription controls gene expression. Here, we focus on the impact of the act of lncRNA transcription on nearby functional DNA units. We review the biological significance of the act of lncRNA transcription on DNA processing, highlighting common themes, such as mediating cellular responses to environmental changes. This review combines the background of chromatin signaling with examples in several organisms to clarify when functions of ncDNA can be interpreted through the act of RNAPII transcription.

Does the liver facilitate aging-related cognitive impairment: Conversation between liver and brain during exercise?

Liver, an important regulator of metabolic homeostasis, is critical for healthy brain function. In particular, age-related neurodegenerative diseases seriously reduce the quality of life for the elderly. As population aging progresses rapidly, unraveling the mechanisms that effectively delay aging has become critical. Appropriate exercise is reported to improve aging-related cognitive impairment. Whereas current studies focused on exploring the effect of exercise on the aging brain itself, ignoring the persistent effects of peripheral organs on the brain through the blood circulation. The aim of this paper is to summarize the communication and aging processes of the liver and brain and to emphasize the metabolic mechanisms of the liver-brain axis about exercise ameliorating aging-related neurodegenerative diseases. A comprehensive understanding of the potential mechanisms about exercise ameliorating aging is critical for improving adaptation to age-related brain changes and formulating effective interventions against age-related cognitive decline.

Age-specific incidence trends of 32 cancers in China, 1983 to 2032: Evidence from Cancer Incidence in Five Continents.

The long-term incidence trends of 32 cancers in China remained unclear. Cancer statistics for young population were often presented in aggregate, masking important heterogeneity. We aimed to assess the incidence trends of 32 cancers in China from 1983 to 2032, stratified by sex and age groups. Data on cancer incidence from 1983 to 2017 were extracted from Cancer Incidence in Five Continents Volumes VI-XII. The age-period-cohort model was utilized to assess age and birth cohort effects on the temporal trends of 32 cancers in China, while the Bayesian age-period-cohort model was utilized to project future trends from 2018 to 2032. An increase in cohort effects is observed in some cancers such as thyroid and kidney cancers. Eight of the 12 obesity-related cancers may rise in the 0-14 age group, and nine in the 15-39 age group from 2013 to 2032. Liver and stomach cancers show an increasing trend among the younger population, contrasting with the observed declining trend in the middle-aged population. There has been a significant rise in the proportions of cervical cancer among females aged 40-64 (4.3%-19.1%), and prostate cancer among males aged 65+ (1.1%-11.8%) from 1983 to 2032. Cancer spectrum in China is shifting toward that in developed countries. Incidence rates of most cancers across different age groups may increase in recent cohorts. It is essential to insist effective preventive interventions, and promote healthier lifestyles, such as reducing obesity, especially among younger population.

Gain-of-function variants in GSDME cause pyroptosis and apoptosis associated with post-lingual hearing loss.

Gasdermin E (GSDME), a member of the gasdermin protein family, is associated with post-lingual hearing loss. All GSDME pathogenic mutations lead to skipping exon 8; however, the molecular mechanisms underlying hearing loss caused by GSDME mutants remain unclear. GSDME was recently identified as one of the mediators of programmed cell death, including apoptosis and pyroptosis. Therefore, in this study, we injected mice with GSDME mutant (MT) and examined the expression levels to assess its effect on hearing impairment. We observed loss of hair cells in the organ of Corti and spiral ganglion neurons. Further, the N-terminal release from the GSDME mutant in HEI-OC1 cells caused pyroptosis, characterized by cell swelling and rupture of the plasma membrane, releasing lactate dehydrogenase and cytokines such as interleukin-1ß. We also observed that the N-terminal release from GSDME mutants could permeabilize the mitochondrial membrane, releasing cytochromes and activating the mitochondrial apoptotic pathway, thereby generating possible positive feedback on the cleavage of GSDME. Furthermore, we found that treatment with disulfiram or dimethyl fumarate might inhibit pyroptosis and apoptosis by inhibiting the release of GSDME-N from GSDME mutants. In conclusion, this study elucidated the molecular mechanism associated with hearing loss caused by GSDME gene mutations, offering novel insights for potential treatment strategies.

CRIP1 regulates osteogenic differentiation of bone marrow stromal cells and pre-osteoblasts via the Wnt signaling pathway.

With the aging of the global demographic, the prevention and treatment of osteoporosis are becoming crucial issues. The gradual loss of self-renewal and osteogenic differentiation capabilities in bone marrow stromal cells (BMSCs) is one of the key factors contributing to osteoporosis. To explore the regulatory mechanisms of BMSCs differentiation, we collected bone marrow cells of femoral heads from patients undergoing total hip arthroplasty for single-cell RNA sequencing analysis. Single-cell RNA sequencing revealed significantly reduced CRIP1 (Cysteine-Rich Intestinal Protein 1) expression and osteogenic capacity in the BMSCs of osteoporosis patients compared to non-osteoporosis group. CRIP1 is a gene that encodes a member of the LIM/double zinc finger protein family, which is involved in the regulation of various cellular processes including cell growth, development, and differentiation. CRIP1 knockdown resulted in decreased alkaline phosphatase activity, mineralization and expression of osteogenic markers, indicating impaired osteogenic differentiation. Conversely, CRIP1 overexpression, both in vitro and in vivo, enhanced osteogenic differentiation and rescued bone mass reduction in ovariectomy-induced osteoporosis mice model. The study further established CRIP1's modulation of osteogenesis through the Wnt signaling pathway, suggesting that targeting CRIP1 could offer a novel approach for osteoporosis treatment by promoting bone formation and preventing bone loss.

Chimeric virus-like particles of human norovirus constructed by structure-guided epitope grafting elicit cross-reactive immunity against both GI.1 and GII.4 genotypes.

IMPORTANCE: Human norovirus (HuNoV) is highly infectious and can result in severe illnesses in the elderly and children. So far, there is no effective antiviral drug to treat HuNoV infection, and thus, the development of HuNoV vaccines is urgent. However, NoV evolves rapidly, and currently, at least 10 genogroups with numerous genotypes have been found. The genetic diversity of NoV and the lack of cross-protection between different genotypes pose challenges to the development of broadly protective vaccines. In this study, guided by structural alignment between GI.1 and GII.4 HuNoV VP1 proteins, several chimeric-type virus-like particles (VLPs) were designed through surface-exposed loop grafting. Mouse immunization studies show that two of the designed chimeric VLPs induced cross-immunity against both GI.1 and GII.4 HuNoVs. To our knowledge, this is the first designed chimeric VLPs that can induce cross-immune activities across different genogroups of HuNoV, which provides valuable strategies for the development of cross-reactive HuNoV vaccines.

Deep learning tackles single-cell analysis-a survey of deep learning for scRNA-seq analysis.

Since its selection as the method of the year in 2013, single-cell technologies have become mature enough to provide answers to complex research questions. With the growth of single-cell profiling technologies, there has also been a significant increase in data collected from single-cell profilings, resulting in computational challenges to process these massive and complicated datasets. To address these challenges, deep learning (DL) is positioned as a competitive alternative for single-cell analyses besides the traditional machine learning approaches. Here, we survey a total of 25 DL algorithms and their applicability for a specific step in the single cell RNA-seq processing pipeline. Specifically, we establish a unified mathematical representation of variational autoencoder, autoencoder, generative adversarial network and supervised DL models, compare the training strategies and loss functions for these models, and relate the loss functions of these models to specific objectives of the data processing step. Such a presentation will allow readers to choose suitable algorithms for their particular objective at each step in the pipeline. We envision that this survey will serve as an important information portal for learning the application of DL for scRNA-seq analysis and inspire innovative uses of DL to address a broader range of new challenges in emerging multi-omics and spatial single-cell sequencing.

Noninvasive electrical stimulation as a neuroprotective strategy in retinal diseases: a systematic review of preclinical studies.

BACKGROUND: Electrical activity has a crucial impact on the development and survival of neurons. Numerous recent studies have shown that noninvasive electrical stimulation (NES) has neuroprotective action in various retinal disorders. OBJECTIVE: To systematically review the literature on in vivo studies and provide a comprehensive summary of the neuroprotective action and the mechanisms of NES on retinal disorders. METHODS: Based on the PRISMA guideline, a systematic review was conducted in PubMed, Web of Science, Embase, Scopus and Cochrane Library to collect all relevant in vivo studies on "the role of NES on retinal diseases" published up until September 2023. Possible biases were identified with the adopted SYRCLE's tool. RESULTS: Of the 791 initially gathered studies, 21 articles met inclusion/exclusion criteria for full-text review. The results revealed the neuroprotective effect of NES (involved whole-eye, transcorneal, transscleral, transpalpebral, transorbital electrical stimulation) on different retinal diseases, including retinitis pigmentosa, retinal degeneration, high-intraocular pressure injury, traumatic optic neuropathy, nonarteritic ischemic optic neuropathy. NES could effectively delay degeneration and apoptosis of retinal neurons, preserve retinal structure and visual function with high security, and its mechanism of action might be related to promoting the secretion of neurotrophins and growth factors, decreasing inflammation, inhibiting apoptosis. The quality scores of included studies ranged from 5 to 8 points (a total of 10 points), according to SYRCLE's risk of bias tool. CONCLUSION: This systematic review indicated that NES exerts neuroprotective effects on retinal disease models mainly through its neurotrophic, anti-inflammatory, and anti-apoptotic capabilities. To assess the efficacy of NES in a therapeutic setting, however, well-designed clinical trials are required in the future.

Gut microbiota-derived short-chain fatty acids regulate group 3 innate lymphoid cells in HCC.

BACKGROUND AND AIMS: Type 3 innate lymphoid cells (ILC3s) are essential for host defense against infection and tissue homeostasis. However, their role in the development of HCC has not been adequately confirmed. In this study, we investigated the immunomodulatory role of short-chain fatty acids (SCFAs) derived from intestinal microbiota in ILC3 regulation. APPROACH AND RESULTS: We report that Lactobacillus reuteri was markedly reduced in the gut microbiota of mice with HCC, accompanied by decreased SCFA levels, especially acetate. Additionally, transplantation of fecal bacteria from wild-type mice or L. reuteri could promote an anticancer effect, elevate acetate levels, and reduce IL-17A secretion in mice with HCC. Mechanistically, acetate reduced the production of IL-17A in hepatic ILC3s by inhibiting histone deacetylase activity, increasing the acetylation of SRY (sex-determining region Y)-box transcription factor 13 (Sox13) at site K30, and decreasing expression of Sox13. Moreover, the combination of acetate with programmed death 1/programmed death ligand 1 blockade significantly enhanced antitumor immunity. Consistently, tumor-infiltrating ILC3s correlated with negative prognosis in patients with HCC, which could be functionally mediated by acetate. CONCLUSIONS: These findings suggested that modifying bacteria, changing SCFAs, reducing IL-17A-producing ILC3 infiltration, and combining with immune checkpoint inhibitors will contribute to the clinical treatment of HCC.

Isthmin: A multifunctional secretion protein.

Isthmin is a polypeptide secreted by adipocytes that was first detected in Xenopus gastrula embryos. Recent studies have focused on the biological functions of isthmin in growth and development, angiogenesis, and metabolism. Distinct spatiotemporal expression of isthmin-1 (ISM-1) was observed during growth and development. ISM-1 plays an important role in the occurrence and development of cancer by regulating cell proliferation, migration, angiogenesis, and immune microenvironments. Moreover, ISM-1, as a newly identified insulin-like adipokine, increases adipocyte glucose uptake and inhibits hepatic lipid synthesis. However, the biological function of ISM-1 remains largely unknown. In this review, we highlight the structure and physiological functions of isthmin and explore its application potential, contributing to a better understanding of its function and providing prevention and treatment strategies for various diseases.