Tuning Fe3O4 for sustainable cathodic heterogeneous electro-Fenton catalysis by acetylated chitosan.

Peroxidase-like catalysts are safe and low-cost candidates to tackle the dilemma in constructing sustainable cathodic heterogeneous electro-Fenton (CHEF) catalysts for water purification, but the elusive structure-property relationship of enzyme-like catalysts constitutes a pressing challenge for the advancement of CHEF processes in practically relevant water and wastewater treatment. Herein, we probe the origins of catalytic efficiency in the CHEF process by artificially tailoring the peroxidase-like activity of Fe3O4 through a series of acetylated chitosan-based hydrogels, which serve as ecofriendly alternatives to traditional carbon shells. The optimized acetylated chitosan wrapping Fe3O4 hydrogel on the cathode shows an impressive activity and stability in CHEF process, overcoming the complicated and environmentally unfavored procedures in the electro-Fenton-related processes. Structural characterizations and theoretical calculations reveal that the amide group in chitosan can modulate the intrinsic redox capacity of surficial Fe sites on Fe3O4 toward CHEF catalysis via the neutral hydrogen bond. This work provides a sustainable path and molecule-level insight for the rational design of high-efficiency CHEF catalysts and beyond.

The additive function of YIGE2 and YIGE1 in regulating maize ear length.

Ear length (EL) is a key trait that greatly contributes to yield in maize. Although dozens of EL quantitative trait loci have been mapped, very few causal genes have been cloned, and the molecular mechanisms remain largely unknown. Our previous study showed that YIGE1 is involved in sugar and auxin pathways to regulate ear inflorescence meristem (IM) development and thus affects EL in maize. Here, we reveal that YIGE2, the paralog of YIGE1, regulates maize ear development and EL through auxin pathway. Knockout of YIGE2 causes a significant decrease of auxin level, IM length, floret number, EL, and grain yield. yige1 yige2 double mutants had even shorter IM and ears implying that these two genes redundantly regulate IM development and EL. The genes controlling auxin levels are differential expressed in yige1 yige2 double mutants, leading to lower auxin level. These results elucidated the critical role of YIGE2 and the redundancy between YIGE2 and YIGE1 in maize ear development, providing a new genetic resource for maize yield improvement.

Rice kinase OsMRLK63 contributes to drought tolerance by regulating reactive oxygen species production.

Drought is a major adverse environmental factor that plants face in nature but the molecular mechanism by which plants transduce stress signals and further endow themselves with tolerance remains unclear. Malectin/malectin-like domains containing receptor-like kinases (MRLKs) have been proposed to act as receptors in multiple biological signaling pathways, but limited studies show their roles in drought-stress signaling and tolerance. In this study, we demonstrate OsMRLK63 in rice (Oryza sativa L.) functions in drought tolerance by acting as the receptor of 2 rapid alkalization factors, OsRALF45 and OsRALF46. We show OsMRLK63 is a typical receptor-like kinase that positively regulates drought tolerance and reactive oxygen species (ROS) production. OsMRLK63 interacts with and phosphorylates several nicotinamide adenine dinucleotide phosphate (NADPH) oxidases with the primarily phosphorylated site at Ser26 in the N-terminal of RESPIRATORY BURST OXIDASE HOMOLOGUE A (OsRbohA). The application of the 2 small signal peptides (OsRALF45/46) on rice can greatly alleviate the dehydration of plants induced by mimic drought. This function depends on the existence of OsMRLK63 and the NADPH oxidase-dependent ROS production. The 2 RALFs interact with OsMRLK63 by binding to its extracellular domain, suggesting they may act as drought/dehydration signal sensors for the OsMRLK63-mediated process. Our study reveals a OsRALF45/46-OsMRLK63-OsRbohs module which contributes to drought-stress signaling and tolerance in rice.

Genome-wide association study implicates lipid pathway dysfunction in antipsychotic-induced weight gain: multi-ancestry validation.

Antipsychotic-induced weight gain (AIWG) is a common side effect of antipsychotic medication and may contribute to diabetes and coronary heart disease. To expand the unclear genetic mechanism underlying AIWG, we conducted a two-stage genome-wide association study in Han Chinese patients with schizophrenia. The study included a discovery cohort of 1936 patients and a validation cohort of 534 patients, with an additional 630 multi-ancestry patients from the CATIE study for external validation. We applied Mendelian randomization (MR) analysis to investigate the relationship between AIWG and antipsychotic-induced lipid changes. Our results identified two novel genome-wide significant loci associated with AIWG: rs10422861 in PEPD (P = 1.373 × 10-9) and rs3824417 in PTPRD (P = 3.348 × 10-9) in Chinese Han samples. The association of rs10422861 was validated in the European samples. Fine-mapping and functional annotation revealed that PEPD and PTPRD are potentially causal genes for AIWG, with their proteins being prospective therapeutic targets. Colocalization analysis suggested that AIWG and type 2 diabetes (T2D) shared a causal variant in PEPD. Polygenic risk scores (PRSs) for AIWG and T2D significantly predicted AIWG in multi-ancestry samples. Furthermore, MR revealed a risky causal effect of genetically predicted changes in low-density lipoprotein cholesterol (P = 7.58 × 10-4) and triglycerides (P = 2.06 × 10-3) caused by acute-phase of antipsychotic treatment on AIWG, which had not been previously reported. Our model, incorporating antipsychotic-induced lipid changes, PRSs, and clinical predictors, significantly predicted BMI percentage change after 6-month antipsychotic treatment (AUC = 0.79, R2 = 0.332). Our results highlight that the mechanism of AIWG involves lipid pathway dysfunction and may share a genetic basis with T2D through PEPD. Overall, this study provides new insights into the pathogenesis of AIWG and contributes to personalized treatment of schizophrenia.

ZmWAK02 encoding an RD-WAK protein confers maize resistance against gray leaf spot.

Gray leaf spot (GLS) caused by Cercospora zeina or C. zeae-maydis is a major maize disease throughout the world. Although more than 100 QTLs resistant against GLS have been identified, very few of them have been cloned. Here, we identified a major resistance QTL against GLS, qRglsSB, explaining 58.42% phenotypic variation in SB12×SA101 BC1 F1 population. By fine-mapping, it was narrowed down into a 928 kb region. By using transgenic lines, mutants and complementation lines, it was confirmed that the ZmWAK02 gene, encoding an RD wall-associated kinase, is the responsible gene in qRglsSB resistant against GLS. The introgression of the ZmWAK02 gene into hybrid lines significantly improves their grain yield in the presence of GLS pressure and does not reduce their grain yield in the absence of GLS. In summary, we cloned a gene, ZmWAK02, conferring large effect of GLS resistance and confirmed its great value in maize breeding.

FUSCA3-induced AINTEGUMENTA-like 6 manages seed dormancy and lipid metabolism.

FUSCA 3 (FUS3), a seed master regulator, plays critical role in seed dormancy and oil accumulation. However, its downstream regulation mechanisms remain poorly understood. Here, we explored the roles of AINTEGUMENTA-like 6 (AIL6), a seed transcription factor, in these processes. The activation of AIL6 by FUS3 was demonstrated by dual-LUC assay. Seeds of ail6 mutants showed alterations in fatty acid compositions, and both AtAIL6 (AIL6 from Arabidopsis thaliana) and BnaAIL6 (AIL6 from Brassica napus) rescued the phenotype. Over-expression (OE) of AIL6s reversed changes in seed fatty acid composition. Notably, OE lines showed low seed germination rates down to 12% compared to 100% of wild-type Col-0. Transcriptome analysis of the mutant and an OE line indicated widespread expression changes of genes involved in lipid metabolism and phytohormone pathways. In OE mature seeds, GA4 content decreased more than 15-fold, while abscisic acid and indole-3-acetic acid (IAA) contents clearly increased. Exogenous GA3 treatments did not effectively rescue the low germination rate. Nicking seed coats increased germination rates from 25% to nearly 80% while the wild-type rdr6-11 is 100% and 98% respectively, and elongation of storage time also improved seed germination. Furthermore, dormancy imposed by AIL6 was fully released in the della quintuple mutant. Together, our results indicate AIL6 acts as a manager downstream of FUS3 in seed dormancy and lipid metabolism.

Neutrophil extracellular traps mediated by platelet microvesicles promote thrombosis and brain injury in acute ischemic stroke.

AIMS: Neutrophil extracellular traps (NETs) have been implicated in thrombotic diseases. There is no definitive explanation for how NETs form during acute ischemic strokes (AIS). The purpose of our study was to investigate the potential mechanism and role of NETs formation in the AIS process. METHODS: As well as 45 healthy subjects, 45 patients with AIS had ELISA tests performed to detect NET markers. Expression of high-mobility group box 1 (HMGB1) on platelet microvesicles (PMVs) was analyzed by flow cytometry in healthy subjects and AIS patients' blood samples. We established middle cerebral artery occlusion (MCAO) mice model to elucidate the interaction between PMPs and NETs. RESULTS: A significant elevation in NET markers was found in patient plasma in AIS patients, and neutrophils generated more NETs from patients' neutrophils. HMGB1 expression was upregulated on PMVs from AIS patients and induced NET formation. NETs enhanced Procoagulant activity (PCA) through tissue factor and via platelet activation. Targeting lactadherin in genetical and in pharmacology could regulate the formation of NETs in MCAO model. CONCLUSIONS: NETs mediated by PMVs derived HMGB1 exacerbate thrombosis and brain injury in AIS. Video Abstract.

Interfacial Engineering of MoS2@CoS2 Heterostructure Electrocatalysts for Effective pH-Universal Hydrogen Evolution Reaction.

The practical utilization of the hydrogen evolution reaction (HER) necessitates the creation of electrocatalysts that are both efficient and abundant in earth elements, capable of operating effectively within a wide pH range. However, this objective continues to present itself as an arduous obstacle. In this research, we propose the incorporation of sulfur vacancies in a novel heterojunction formed by MoS2@CoS2, designed to exhibit remarkable catalytic performances. This efficacy is attributed to the advantageous combination of the low work function and space charge zone at the interface between MoS2 and CoS2 in the heterojunction. The MoS2@CoS2 heterojunction manifests outstanding hydrogen evolution activity over an extensive pH range. Remarkably, achieving a current density of 10 mA cm-2 in aqueous solutions 1.0 M KOH, 0.5 M H2SO4, and 1.0 M phosphate-buffered saline (PBS), respectively, requires only an overpotential of 48, 62, and 164 mV. The Tafel slopes for each case are 43, 32, and 62 mV dec-1, respectively. In this study, the synergistic effect of MoS2 and CoS2 is conducive to electron transfer, making the MoS2@CoS2 heterojunction show excellent electrocatalytic performance. The synergistic effects arising from the heterojunction and sulfur vacancy not only contribute to the observed catalytic prowess but also provide a valuable model and reference for the exploration of other efficient electrocatalysts. This research marks a significant stride toward overcoming the challenges associated with developing electrocatalysts for practical hydrogen evolution applications.

PHB2 Maintains the Contractile Phenotype of VSMCs by Counteracting PKM2 Splicing.

BACKGROUND: Phenotypic transition of vascular smooth muscle cells (VSMCs) accounts for the pathogenesis of a variety of vascular diseases during the early stage. Recent studies indicate the metabolic reprogramming may be involved in VSMC phenotypic transition. However, the definite molecules that link energy metabolism to distinct VSMC phenotype remain elusive. METHODS: A carotid artery injury model was used to study postinjury neointima formation as well as VSMC phenotypic transition in vivo. RNA-seq analysis, cell migration assay, collagen gel contraction assay, wire myography assay, immunoblotting, protein interactome analysis, co-immunoprecipitation, and mammalian 2-hybrid assay were performed to clarify the phenotype and elucidate the molecular mechanisms. RESULTS: We collected cell energy-regulating genes by using Gene Ontology annotation and applied RNA-Seq analysis of transforming growth factor-ß or platelet-derived growth factor BB stimulated VSMCs. Six candidate genes were overlapped from energy metabolism-related genes and genes reciprocally upregulated by transforming growth factor-ß and downregulated by platelet-derived growth factor BB. Among them, prohibitin 2 has been reported to regulate mitochondrial oxidative phosphorylation. Indeed, prohibitin 2-deficient VSMCs lost the contractile phenotype as evidenced by reduced contractile proteins. Consistently, Phb2SMCKO mice were more susceptible to postinjury VSMC proliferation and neointima formation compared with Phb2flox/flox mice. Further protein interactome analysis, co-immunoprecipitation, and mammalian 2-hybrid assay revealed that prohibitin 2, through its C-terminus, directly interacts with hnRNPA1, a key modulator of pyruvate kinase M1/2 (PKM) mRNA splicing that promotes PKM2 expression and glycolysis. Prohibitin 2 deficiency facilitated PKM1/2 mRNA splicing and reversion from PKM1 to PKM2, and enhanced glycolysis in VSMCs. Blocking prohibitin 2-hnRNPA1 interaction resulted in increased PKM2 expression, enhanced glycolysis, repressed contractile marker genes expression in VSMCs, as well as aggravated postinjury neointima formation in vivo. CONCLUSIONS: Prohibitin 2 maintains VSMC contractile phenotype by interacting with hnRNPA1 to counteract hnRNPA1-mediated PKM alternative splicing and glucose metabolic reprogramming.

MiR-31-5p alleviates septic cardiomyopathy by targeting BAP1 to inhibit SLC7A11 deubiquitination and ferroptosis.

Septic cardiomyopathy is one of the most severe and common complications in patients with sepsis and poses a great threat to their prognosis. However, the potential mechanisms and effective therapeutic drugs need to be explored. The control of cardiac cell death by miRNAs has emerged as a prominent area of scientific interest in the diagnosis and treatment of heart disorders in recent times. In the present investigation, we discovered that overexpression of miR-31-5p prevented LPS-induced damage to H9C2 cells and that miR-31-5p could inhibit BAP1 production by binding to its 3'-UTR. BRCA1-Associated Protein 1 (BAP1) is a ubiquitin carboxy-terminal hydrolase. BAP1 upregulation blocked effect of miR-31-5p on H9C2 cell injury. Moreover, BAP1 inhibited the expression of solute carrier family 7 member 11 (SLC7A11) by deubiquitinating histone 2 A (H2Aub) on the promoter of SLC7A11. Furthermore, overexpression of miR-31-5p and downregulation of BAP1 inhibited SLC7A11 mediated ferroptosis. In addition, the downregulation of SLC7A11 reversed the inhibitory effect of miR-31-5p on the expression of myocardial injury and inflammatory factors, and cell apoptosis was reversed. In conclusion, these results indicate that miR-31-5p alleviates malignant development of LPS-induced H9C2 cell injury by targeting BAP1 and regulating SLC7A11 deubiquitination-mediated ferroptosis, which confirmed the protective effect of miR-31-5p on H9C2 cell injury and revealed potential mechanisms that may provide new targets for treatment of septic cardiomyopathy.

Golgi-targeted NIR fluorescent probe with large stokes shift for real-time monitoring of nitric oxide in depression model.

Depression is a debilitating mental illness that poses a serious threat to human health. Nitric Oxide (NO), as an important gasotransmitter, is closely associated with the pathogenesis of depressive disorders. Effective monitoring of NO fluctuation is beneficial for the diagnosis of depression and therapy assessment of antidepressants. Currently, there is a lack of effective methods for rapidly and sensitively identifying NO and elucidating its relationship with depression diseases. Herein, we developed a NIR dye TJ730-based fluorescent probe TJ730-Golgi-NO incorporating benzenesulfonamide as a Golgi-targeted moiety and the thiosemicarbazide group for NO detection. The probe exhibited turn-on fluorescence ability and a large Stokes shift of 158 nm, which shows high sensitivity, selectivity, and rapid response (<1 min) for NO detection. TJ730-Golgi-NO could detect exogenous and endogenous NO in cells stimulated by Glu and LPS, and target Golgi apparatus. Moreover, we disclose a significant increase of NO in the depression model and a weak fluorescence evidenced in the fluoxetine-treated depression mice. This study provides a competent tool for studying the function of NO and helping improve the effective treatment of depression diseases.

Perovskite light-emitting diodes with external quantum efficiency exceeding 20 per cent.

Metal halide perovskite materials are an emerging class of solution-processable semiconductors with considerable potential for use in optoelectronic devices1-3. For example, light-emitting diodes (LEDs) based on these materials could see application in flat-panel displays and solid-state lighting, owing to their potential to be made at low cost via facile solution processing, and could provide tunable colours and narrow emission line widths at high photoluminescence quantum yields4-8. However, the highest reported external quantum efficiencies of green- and red-light-emitting perovskite LEDs are around 14 per cent7,9 and 12 per cent8, respectively-still well behind the performance of organic LEDs10-12 and inorganic quantum dot LEDs13. Here we describe visible-light-emitting perovskite LEDs that surpass the quantum efficiency milestone of 20 per cent. This achievement stems from a new strategy for managing the compositional distribution in the device-an approach that simultaneously provides high luminescence and balanced charge injection. Specifically, we mixed a presynthesized CsPbBr3 perovskite with a MABr additive (where MA is CH3NH3), the differing solubilities of which yield sequential crystallization into a CsPbBr3/MABr quasi-core/shell structure. The MABr shell passivates the nonradiative defects that would otherwise be present in CsPbBr3 crystals, boosting the photoluminescence quantum efficiency, while the MABr capping layer enables balanced charge injection. The resulting 20.3 per cent external quantum efficiency represents a substantial step towards the practical application of perovskite LEDs in lighting and display.

A programmable pAgo nuclease with RNA target preference from the psychrotolerant bacterium Mucilaginibacter paludis.

Argonaute (Ago) proteins are programmable nucleases found in eukaryotes and prokaryotes. Prokaryotic Agos (pAgos) share a high degree of structural homology with eukaryotic Agos (eAgos), and eAgos originate from pAgos. Although eAgos exclusively cleave RNA targets, most characterized pAgos cleave DNA targets. This study characterized a novel pAgo, MbpAgo, from the psychrotolerant bacterium Mucilaginibacter paludis which prefers to cleave RNA targets rather than DNA targets. Compared to previously studied Agos, MbpAgo can utilize both 5'phosphorylated(5'P) and 5'hydroxylated(5'OH) DNA guides (gDNAs) to efficiently cleave RNA targets at the canonical cleavage site if the guide is between 15 and 17 nt long. Furthermore, MbpAgo is active at a wide range of temperatures (4-65°C) and displays no obvious preference for the 5'-nucleotide of a guide. Single-nucleotide and most dinucleotide mismatches have no or little effects on cleavage efficiency, except for dinucleotide mismatches at positions 11-13 that dramatically reduce target cleavage. MbpAgo can efficiently cleave highly structured RNA targets using both 5'P and 5'OH gDNAs in the presence of Mg2+ or Mn2+. The biochemical characterization of MbpAgo paves the way for its use in RNA manipulations such as nucleic acid detection and clearance of RNA viruses.

GFAP hyperpalmitoylation exacerbates astrogliosis and neurodegenerative pathology in PPT1-deficient mice.

The homeostasis of protein palmitoylation and depalmitoylation is essential for proper physiological functions in various tissues, in particular the central nervous system (CNS). The dysfunction of PPT1 (PPT1-KI, infantile neuronal ceroid lipofuscinosis [INCL] mouse model), which catalyze the depalmitoylation process, results in serious neurodegeneration accompanied by severe astrogliosis in the brain. Endeavoring to determine critical factors that might account for the pathogenesis in CNS by palm-proteomics, glial fibrillary acidic protein (GFAP) was spotted, indicating that GFAP is probably palmitoylated. Questions concerning if GFAP is indeed palmitoylated in vivo and how palmitoylation of GFAP might participate in neural pathology remain unexplored and are waiting to be investigated. Here we show that GFAP is readily palmitoylated in vitro and in vivo; specifically, cysteine-291 is the unique palmitoylated residue in GFAP. Interestingly, it was found that palmitoylated GFAP promotes astrocyte proliferation in vitro. Furthermore, we showed that PPT1 depalmitoylates GFAP, and the level of palmitoylated GFAP is overwhelmingly up-regulated in PPT1-knockin mice, which lead us to speculate that the elevated level of palmitoylated GFAP might accelerate astrocyte proliferation in vivo and ultimately led to astrogliosis in INCL. Indeed, blocking palmitoylation by mutating cysteine-291 into alanine in GFAP attenuate astrogliosis, and remarkably, the concurrent neurodegenerative pathology in PPT1-knockin mice. Together, these findings demonstrate that hyperpalmitoylated GFAP plays critical roles in regulating the pathogenesis of astrogliosis and neurodegeneration in the CNS, and most importantly, pinpointing that cysteine-291 in GFAP might be a valuable pharmaceutical target for treating INCL and other potential neurodegenerative diseases.

Classification of Visually Induced Motion Sickness Based on Phase-Locked Value Functional Connectivity Matrix and CNN-LSTM.

To effectively detect motion sickness induced by virtual reality environments, we developed a classification model specifically designed for visually induced motion sickness, employing a phase-locked value (PLV) functional connectivity matrix and a CNN-LSTM architecture. This model addresses the shortcomings of traditional machine learning algorithms, particularly their limited capability in handling nonlinear data. We constructed PLV-based functional connectivity matrices and network topology maps across six different frequency bands using EEG data from 25 participants. Our analysis indicated that visually induced motion sickness significantly alters the synchronization patterns in the EEG, especially affecting the frontal and temporal lobes. The functional connectivity matrix served as the input for our CNN-LSTM model, which was used to classify states of visually induced motion sickness. The model demonstrated superior performance over other methods, achieving the highest classification accuracy in the gamma frequency band. Specifically, it reached a maximum average accuracy of 99.56% in binary classification and 86.94% in ternary classification. These results underscore the model's enhanced classification effectiveness and stability, making it a valuable tool for aiding in the diagnosis of motion sickness.

Genetic basis of resistance to southern corn leaf blight in the maize multi-parent population and diversity panel.

Southern corn leaf blight (SLB), caused by the necrotrophic pathogen Cochliobolus heterostrophus, is one of the maize foliar diseases and poses a great threat to corn production around the world. Identification of genetic variations underlying resistance to SLB is of paramount importance to maize yield and quality. Here, we used a random-open-parent association mapping population containing eight recombinant inbred line populations and one association mapping panel consisting of 513 diversity maize inbred lines with high-density genetic markers to dissect the genetic basis of SLB resistance. Overall, 109 quantitative trait loci (QTLs) with predominantly small or moderate additive effects, and little epistatic effects were identified. We found 35 (32.1%) novel loci in comparison with the reported QTLs. We revealed that resistant alleles were significantly enriched in tropical accessions and the frequency of about half of resistant alleles decreased during the adaptation process owing to the selection of agronomic traits. A large number of annotated genes located in the SLB-resistant QTLs were shown to be involved in plant defence pathways. Integrating genome-wide association study, transcriptomic profiling, resequencing and gene editing, we identified ZmFUT1 and MYBR92 as the putative genes responsible for the major QTLs for resistance to C. heterostrophus. Our results present a comprehensive insight into the genetic basis of SLB resistance and provide resistant loci or genes as direct targets for crop genetic improvement.

Uptake of the core outcome set on polycystic ovary syndrome before and after its publication.

STUDY QUESTION: Does the core outcome set (COS) on polycystic ovary syndrome (PCOS) impact the selection of research outcomes? SUMMARY ANSWER: Following the publication of the COS on PCOS, an increasing number of trials are reporting both the generic domain and body mass index; however, the uptake of this COS has not been as extensive as expected. WHAT IS KNOWN ALREADY: The COS on PCOS included 33 core outcomes in the following seven domains: the generic (3), metabolic (8), reproductive (7), pregnancy (10), psychological (3), oncological (1), and long-term (1). This was done to improve consistency in outcome selection and definition. However, thus far, no studies have investigated the effectiveness of this COS in the above-mentioned tasks. STUDY DESIGN, SIZE, DURATION: A methodological study based on the trial registries, including 395 eligible clinical trials registered between 1 January 2018 and 21 September 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 1258 registered clinical studies on PCOS were retrieved from the World Health Organization International Clinical Trials Registry Platform. Of those, 395 were selected according to the inclusion and exclusion criteria, and divided into two groups based on the publication date of the COS on PCOS (4 February 2020): pre-publication and post-publication. The practical uptake of this COS was explored after data collation, assessment, comparison of the uptake of core outcomes or domains before and after the publication of this COS, and correlation analysis between the domains. MAIN RESULTS AND THE ROLE OF CHANCE: There were 26 out of 33 core outcomes and five out of seven domains reported in the 395 trials. The highest uptake was observed for the reproductive domain and the reproductive hormonal profile (63.0% and 38.7%, respectively). After the publication of the COS on PCOS, the uptake of the generic domain and body mass index increased from 24.1% to 35.8% (P = 0.011) and 17.8% to 26.5% (P = 0.039), respectively. The total number of reported core outcomes in the generic domain met statistical significance (P = 0.012). Moreover, multivariable analyses still supported the above finding in the generic domain. Correlation analysis showed that most of the domains were positively correlated with each other. However, the pregnancy domain was negatively correlated with the metabolic domain. Reasons responsible for the unsatisfactory uptake may be the absence of specific definitions of core outcomes, as well as the lack of awareness among researchers regarding this COS. LIMITATIONS, REASONS FOR CAUTION: Due to the lack of standardized definition of outcomes, it was difficult to avoid some subjectivity in the process of consistency assessment. WIDER IMPLICATIONS OF THE FINDINGS: Two years after its publication, there was no substantial improvement in the uptake of the COS on PCOS. This suggests that this COS may require further revision, refinement, and promotion to improve the comparability of PCOS studies. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by Beijing Municipal Health Science and Technology Achievements and Appropriate Technology Promotion Project (BHTPP2022069), and the special fund of Beijing Key Clinical Specialty Construction Project. The authors do not have conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

High-Throughput CRISPR/Cas9 Mutagenesis Streamlines Trait Gene Identification in Maize.

Maize (Zea mays) is one of the most important crops in the world. However, few agronomically important maize genes have been cloned and used for trait improvement, due to its complex genome and genetic architecture. Here, we integrated multiplexed CRISPR/Cas9-based high-throughput targeted mutagenesis with genetic mapping and genomic approaches to successfully target 743 candidate genes corresponding to traits relevant for agronomy and nutrition. After low-cost barcode-based deep sequencing, 412 edited sequences covering 118 genes were precisely identified from individuals showing clear phenotypic changes. The profiles of the associated gene-editing events were similar to those identified in human cell lines and consequently are predictable using an existing algorithm originally designed for human studies. We observed unexpected but frequent homology-directed repair through endogenous templates that was likely caused by spatial contact between distinct chromosomes. Based on the characterization and interpretation of gene function from several examples, we demonstrate that the integration of forward and reverse genetics via a targeted mutagenesis library promises rapid validation of important agronomic genes for crops with complex genomes. Beyond specific findings, this study also guides further optimization of high-throughput CRISPR experiments in plants.

Flexible broadcast UWOC system using an LCVR-based tunable optical splitter.

For underwater wireless optical communication (UWOC) systems, using an omnidirectional light source to construct a broadcast system will require considerable energy due to high geometric loss and water attenuation. In addition, high-sensitivity photon detectors usually have a limited dynamic range, therefore limiting communication distance. In this Letter, a broadcast UWOC system, based on liquid crystal variable retarders (LCVRs) and polarization beam splitters (PBSs), is proposed to allocate user power in accordance with user-specific channel conditions. By adjusting the driving alternating current (AC) voltage of LCVRs to change the input light polarization, different proportions of light can be allocated to different PBS ports before broadcasting to different users. In a dual-user transmitter for the proof-of-concept, the output power dynamic range and the additional insertion loss for the first user are 19.17 dB and 0.91 dB, respectively. For the second user, the performance degrades to 17.33 dB and 1.26 dB, respectively. The step size of power adjustment is less than 0.063 dB. To verify the effectiveness of power adjustment in UWOC systems, a 7-m/243.2-Mbps single-user UWOC system is designed with a water attenuation coefficient ranging from 0.50 dB/m to 2.35 dB/m. All bit error rates (BERs) can decrease to below the forward error correction (FEC) limit by adjusting the LCVR driving voltage. The adjustable range of communication distance could be extended from 4.2 m to 13.19 m with a channel attenuation coefficient of 1.44 dB/m. Finally, a dual-user UWOC experiment is conducted and proves that the proposed system can still work in a multi-user system. The proposed system is proven to be effective for improving the anti-jamming capability and flexibility of UWOC networks.

Glucose transporter 3 (GLUT3) promotes lactylation modifications by regulating lactate dehydrogenase A (LDHA) in gastric cancer.

OBJECTIVES: Glucose transporter 3 (GLUT3) plays a major role in glycolysis and glucose metabolism in cancer cells. We aimed to investigate the correlation between GLUT3 and histone lactylation modification in the occurrence and progression of gastric cancer. MATERIALS AND METHODS: We initially used single-cell sequencing data to determine the expression levels of GLUT3 and lactate dehydrogenase A (LDHA) in primary tumor, tumor-adjacent normal, and metastasis tumor tissues. Immunohistochemistry analysis was conducted to measure GLUT3, LDHA, and L-lactyl levels in gastric normal and cancer tissues. Transwell and scratch assays were performed to evaluate the metastatic and invasive capacity of gastric cancer cell lines. Western blotting was used to measure L-lactyl and histone lactylation levels in gastric cancer cell lines. RESULTS: Single-cell sequencing data showed that GLUT3 expression was significantly increased in primary tumor and metastasis tumor tissues. In addition, GLUT3 expression was positively correlated with that of LDHA expression and lactylation-related pathways. Western blotting and immunohistochemistry analyses revealed that GLUT3 was highly expressed in gastric cancer tissues and cell lines. GLUT3 knockdown in gastric cancer cell lines inhibited their metastatic and invasive capacity to various degrees. Additionally, the levels of LDHA, L-lactyl, H3K9, H3K18, and H3K56 significantly decreased after GLUT3 knockdown, indicating that GLUT3 affects lactylation in gastric cancer cells. Moreover, LDHA overexpression in a GLUT3 knockdown cell line reversed the levels of lactylation and EMT-related markers, and the EMT functional phenotype induced by GLUT3 knockdown. The in vivo results were consistent with the in vitro results. CONCLUSIONS: This study suggests the important role of histone lactylation in the occurrence and progression of gastric cancer, and GLUT3 may be a new diagnostic marker and therapeutic target for gastric cancer.