Author Correction: A new coronavirus associated with human respiratory disease in China.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A new coronavirus associated with human respiratory disease in China.

Emerging infectious diseases, such as severe acute respiratory syndrome (SARS) and Zika virus disease, present a major threat to public health1-3. Despite intense research efforts, how, when and where new diseases appear are still a source of considerable uncertainty. A severe respiratory disease was recently reported in Wuhan, Hubei province, China. As of 25 January 2020, at least 1,975 cases had been reported since the first patient was hospitalized on 12 December 2019. Epidemiological investigations have suggested that the outbreak was associated with a seafood market in Wuhan. Here we study a single patient who was a worker at the market and who was admitted to the Central Hospital of Wuhan on 26 December 2019 while experiencing a severe respiratory syndrome that included fever, dizziness and a cough. Metagenomic RNA sequencing4 of a sample of bronchoalveolar lavage fluid from the patient identified a new RNA virus strain from the family Coronaviridae, which is designated here 'WH-Human 1' coronavirus (and has also been referred to as '2019-nCoV'). Phylogenetic analysis of the complete viral genome (29,903 nucleotides) revealed that the virus was most closely related (89.1% nucleotide similarity) to a group of SARS-like coronaviruses (genus Betacoronavirus, subgenus Sarbecovirus) that had previously been found in bats in China5. This outbreak highlights the ongoing ability of viral spill-over from animals to cause severe disease in humans.

Listerin promotes cGAS protein degradation through the ESCRT pathway to negatively regulate cGAS-mediated immune response.

The enzyme cyclic GMP-AMP synthase (cGAS) is a key sensor for detecting misplaced double-stranded DNA (dsDNA) of genomic, mitochondrial, and microbial origin. It synthesizes 2'3'-cGAMP, which in turn activates the stimulator of interferon genes pathway, leading to the initiation of innate immune responses. Here, we identified Listerin as a negative regulator of cGAS-mediated innate immune response. We found that Listerin interacts with cGAS on endosomes and promotes its K63-linked ubiquitination through recruitment of the E3 ligase TRIM27. The polyubiquitinated cGAS is then recognized by the endosomal sorting complexes required for transport machinery and sorted into endosomes for degradation. Listerin deficiency enhances the innate antiviral response to herpes simplex virus 1 infection. Genetic deletion of Listerin also deteriorates the neuroinflammation and the ALS disease progress in an ALS mice model; overexpression of Listerin can robustly ameliorate disease progression in ALS mice. Thus, our work uncovers a mechanism for cGAS regulation and suggests that Listerin may be a promising therapeutic target for ALS disease.

Pterostilbene upregulates MICA/B via the PI3K/AKT signaling pathway to enhance the capability of natural killer cells to kill cervical cancer cells.

Natural killer (NK) cells are triggered by the innate immune response in the tumor microenvironment. The extensive set of stimulating and inhibiting receptors mediates the target recognition of NK cells, and controls the strength of the effector reaction countering specific targeted cells. Yet, lacking major MHC (histocompatibility complex) MICA/B class I chain-related proteins on the membrane of tumor cells results in the failure of NK cell recognition and ability to resist NK cell destruction. Searching databases and molecular docking suggested that in cervical cancer, pterostilbene (3,5-dimethoxy-40-hydroxystilbene; PTS) in Vaccinium corymbosum extract could constrain PI3K/AKT signaling and improving the MICA/B expression. In flow cytometry, MTT assay, viability/cytotoxicity assay, and colony development assays, PTS reduced the development of cervical cancer cells and increased apoptosis. The quantitative real-time PCR (qRT-PCR) and a Western blot indicate that PTS controlled the cytolytic action of NK cells in tumor cells via increasing the MICA/B expression, thus modifying the anti-tumor immune response in cervical cancer.

Estrogen-immuno-neuromodulation disorders in menopausal depression.

A significant decrease in estrogen levels puts menopausal women at high risk for major depression, which remains difficult to cure despite its relatively clear etiology. With the discovery of abnormally elevated inflammation in menopausal depressed women, immune imbalance has become a novel focus in the study of menopausal depression. In this paper, we examined the characteristics and possible mechanisms of immune imbalance caused by decreased estrogen levels during menopause and found that estrogen deficiency disrupted immune homeostasis, especially the levels of inflammatory cytokines through the ERα/ERß/GPER-associated NLRP3/NF-κB signaling pathways. We also analyzed the destruction of the blood-brain barrier, dysfunction of neurotransmitters, blockade of BDNF synthesis, and attenuation of neuroplasticity caused by inflammatory cytokine activity, and investigated estrogen-immuno-neuromodulation disorders in menopausal depression. Current research suggests that drugs targeting inflammatory cytokines and NLRP3/NF-κB signaling molecules are promising for restoring homeostasis of the estrogen-immuno-neuromodulation system and may play a positive role in the intervention and treatment of menopausal depression.

Peripheral hemoglobin to albumin ratio predicts prognosis in patients with nasopharyngeal carcinoma underwent concurrent chemoradiotherapy.

BACKGROUND: Recently, the hemoglobin to albumin ratio (HAR) has been shown to be closely associated with the survival of certain malignancies. However, its prognostic value in nasopharyngeal carcinoma (NPC) remained to be elucidated. Herein, we aimed to explore the correlation between HAR and overall survival (OS) in NPC patients treated with concurrent chemoradiotherapy (CCRT). METHODS: This retrospective study included a total of 858 patients with NPC receiving CCRT between January 2010 and December 2014 in Sun Yat-sen University Cancer Center. We randomly divided them into the training cohort (N = 602) and the validation cohort (N = 206). We performed univariate and multivariate Cox regression analyses to identify variables associated with OS, based on which, a predictive nomogram was constructed and assessed. RESULTS: In both the training and validation cohorts, patients were classified into low- and high-HAR groups according to the cutoff value determined by the maximally selected rank statistics. This HAR cutoff value effectively divided patients into two distinct prognostic groups with significant differences. Multivariable Cox analysis revealed that higher T-stage, N-stage, and HAR values were significantly related to poorer prognosis in NPC patients and served as independent prognostic factors for NPC. Based on these, a predictive model was constructed and graphically presented as a nomogram, whose predictive performance is satisfactory with a C-index of 0.744 [95%CI: 0.679-0.809] and superior to traditional TNM staging system [C-index = 0.609, 95%CI: 0.448-0.770]. CONCLUSION: The HAR value was an independent predictor for NPC patients treated with CCRT, the predictive model based on HAR with superior predictive performance than traditional TNM staging system might improve individualized survival predictions.

Prognostic significance of the novel immunonutritional marker of cholesterol-to-lymphocyte ratio in patients with non-metastatic breast cancer.

BACKGROUND: Although there is a strong correlation between the novel cholesterol-to-lymphocyte ratio (CLR) and tumor survival, its prognostic significance in breast cancer (BC) is unknown. After analyzing the relationship between CLR and the overall survival (OS) of patients with BC, we created a predictive model. METHODS: Following retrospective enrollment, 1316 patients with BC were randomized into two cohorts: validation (n = 392) and training (n = 924). Distinct factors within the training dataset were identified for OS by univariate and multivariate Cox analyses; two-tailed P-value < 0.05 were considered to indicate statistical significance. On this premise, we developed novel signals for survival prediction and utilized the calibration curve, receiver operating characteristic curves, and concordance index (C-index) to validate their efficacy across both datasets. RESULTS: Patients with BC were categorized into two categories with differing prognoses based on the CLR score [hazard ratio = 0.492; 95% confidence interval (CI): 0.286-0.846, P = 0.009]. A prediction nomogram was created based on multivariate analysis, which showed that N stage, postoperative pathological categorization, and CLR score were all independently correlated with OS. In the training [C-index = 0.831 (95% CI: 0.788-0.874)] and validation [C-index = 0.775 (95% CI: 0.694-0.856)] cohorts, the nomogram demonstrated favorable performance in predicting OS. In both the training and validation cohorts, it outperformed the traditional staging system [C-index = 0.702 (95% CI: 0.623-0.782)] and [C-index = 0.709 (95% CI: 0.570-0.847)]. The accurate prediction by the signature was further demonstrated by the time-dependent receiver operating characteristic curves. CONCLUSIONS: The novel immunonutritional marker CLR could function as a simplified, cost-effective, easily accessible, non-invasive, and readily promotive prognostic indicator for patients with early-stage BC and demonstrates superior predictive power than the traditional staging system.

Arterial Spin Labeling (ASL) MRI in Evaluating Pancreatic Blood Perfusion in Subjects With Different Glucose Tolerances.

BACKGROUND: The pancreas plays a central role in type 2 diabetes mellitus (T2DM), and its blood flow is usually associated with insulin release demand. PURPOSE: To noninvasively assess pancreatic blood flow (PBF) changes and modulation in people with different glucose tolerance following a glucose challenge using ASL MRI. STUDY TYPE: Prospective. SUBJECTS: Fourteen prediabetes, 22 T2DM, and 40 normal. FIELD STRENGTH/SEQUENCE: Pseudo-continuous ASL with a turbo gradient spin echo sequence at 3.0 T. ASSESSMENT: All normal and subjects (diagnosed by oral glucose tolerance test) underwent ASL after fasting for at least 6 hours. The normal and prediabetes groups additionally had ASL scans at 5, 10, 15, 20, and 25 minutes following oral glucose (50 mL, 5%). PBF maps were generated from the ASL data and measured at body and tail. The ability of baseline PBF (BL-PBF) of body, tail (BL-PBFtail), and their average to determine abnormal glucose tolerance and stage was assessed. STATISTICAL TESTS: ANOVA, Mann-Whitney U test, Kruskal-Wallis H test, paired sample t-test, intra-class correlation coefficient, repeated measures ANOVA, correlation analysis, receiver operating characteristic analysis, and logistic regression analysis. A P value <0.05 was considered significant. RESULTS: There were significant differences in BL-PBF among the three groups. The prediabetes group exhibited significantly lower PBF than the normal group at all time points; Both groups showed similar changing trends in PBF (peaking at the 15th minute and subsequently declining). The BL-PBFtail had the highest diagnostic performance when evaluating abnormal glucose tolerance or stage (area under the curves = 0.800, 0.584, respectively) and was an independent risk factor for glucose tolerance status. DATA CONCLUSION: ASL can noninvasively assess changes in PBF among individuals with varying glucose tolerance and in response to glucose challenge, which could be linked to insulin release demand and might help characterize changes in pancreatic endocrine function. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Second Near-Infrared Macrophage-Biomimetic Nanoprobes for Photoacoustic Imaging of Neuroinflammation.

Neuroinflammation is a significant pathological event involving the neurodegenerative process associated with many neurological disorders. Diagnosis and treatment of neuroinflammation in its early stage are essential for the prevention and management of neurological diseases. Herein, we designed macrophage membrane-coated photoacoustic (PA) probes (MSINPs), with targeting specificities based on naturally existing target-ligand interactions for the early diagnosis of neuroinflammation. The second near-infrared dye, IR1061, was doped into silica as the core and was encapsulated with a macrophage membrane. In vitro as well as in vivo, the MSINPs could target inflammatory cells via the inflammation chemotactic effect. PA imaging was used to trace the MSINPs in a neuroinflammation mouse model and showed a great targeted effect of MSINPs in the prefrontal cortex. Therefore, the biomimetic nanoprobe prepared in this study offers a new strategy for PA molecular imaging of neuroinflammation, which can enhance our understanding of the evolution of neuroinflammation in specific brain regions.

Strategy for the Preparation of ZnS/ZnO Composites Derived from Metal-Organic Frameworks toward Lithium Storage.

The synergistic effect between multicomponent electrode materials often makes them have better lithium storage performance than single-component electrode materials. Therefore, to enhance surface reaction kinetics and encourage electron transfer, using multicomponent anode materials is a useful tactic for achieving high lithium-ion battery performance. In this article, ZnS/ZnO composites were synthesized by solvothermal sulfidation and calcination, with the utilization of metal-organic frameworks acting as sacrificial templates. From the point of material design, both ZnS and ZnO have high theoretical specific capacities, and the synergistic effect of ZnS and ZnO can promote charge transport. From the perspective of electrode engineering, the loose porous carbon skeleton that results from the calcination of metal-organic frameworks can enhance composite material conductivity as well as full electrolyte penetration and the area of contact between the electrolyte and active material, all of which are beneficial to enhancing lithium storage performance. As expected, ZnS/ZnO anode materials displayed remarkably high specific capacities and outstanding performance at different rates. Combining material design and electrode engineering, this paper provides another idea for preparing anode materials with excellent lithium storage properties.

The electronic and magnetic properties modulated by ferroelectric polarization switching in two-dimensional VSeTe/Sc2CO2 van der Waals heterostructures.

Exploring multiferroic materials that combine magnetic and ferroelectric properties is scientifically interesting and has important technical implications for many functions of nanoscale devices. In this work, spintronics and magnetoelectric coupling devices are proposed in two-dimensional (2D) layered ferromagnetic (FM)/ferroelectric (FE) van de Waals (vdW) heterostructures, VSeTe/Sc2CO2, employing density functional theory (DFT) calculations. The results indicate that the VSeTe/Sc2CO2 vdW heterostructure changes from a metal to a semiconductor in Sc2CO2-P↑ and Sc2CO2-P↓ polarization states. At the same time, the charge at the interface of the VSeTe/Sc2CO2 heterostructure will also be redistributed with the transformation of the ferroelectric polarization state, resulting in the change of the distribution of the electronic states near the Fermi level, and thus the change in the magnetic anisotropy energy (EMAE) of the heterostructure. Interestingly, biaxial strain brings reversibility and non-volatile regulation to the heterostructure of semiconductors and metals. The results provide an effective way to fabricate magnetoelectric coupling devices with 2D multiferroic heterostructures.

A mitochondrion-targeted cyanine agent for NIR-II fluorescence-guided surgery combined with intraoperative photothermal therapy to reduce prostate cancer recurrence.

Poorly identified tumor boundaries and nontargeted therapies lead to the high recurrence rates and poor quality of life of prostate cancer patients. Near-infrared-II (NIR-II) fluorescence imaging provides certain advantages, including high resolution and the sensitive detection of tumor boundaries. Herein, a cyanine agent (CY7-4) with significantly greater tumor affinity and blood circulation time than indocyanine green was screened. By binding albumin, the absorbance of CY7-4 in an aqueous solution showed no effects from aggregation, with a peak absorbance at 830 nm and a strong fluorescence emission tail beyond 1000 nm. Due to its extended circulation time (half-life of 2.5 h) and high affinity for tumor cells, this fluorophore was used for primary and metastatic tumor diagnosis and continuous monitoring. Moreover, a high tumor signal-to-noise ratio (up to ~ 10) and excellent preferential mitochondrial accumulation ensured the efficacy of this molecule for photothermal therapy. Therefore, we integrated NIR-II fluorescence-guided surgery and intraoperative photothermal therapy to overcome the shortcomings of a single treatment modality. A significant reduction in recurrence and an improved survival rate were observed, indicating that the concept of intraoperative combination therapy has potential for the precise clinical treatment of prostate cancer.

Malus toringoides (Rehd.) Hughes decoction alleviates isoproterenol-induced cardiac fibrosis by inhibiting cardiomyocyte inflammation and pyroptosis via the HK1/NLRP3 signaling pathway.

Malus toringoides (Rehd.) Hughes, called "Eseye (Ese)," is a traditional medicinal plant from the Tibet province of China that has proven effective in treating cardiac conditions due to its anti-inflammatory, antioxidative, and antiapoptotic properties. In this study, we explored the underlying protective mechanisms of Ese decoction in isoproterenol (ISO)-induced cardiac fibrosis (CF) and established the fact that treatment with an Ese decoction attenuated tissue injury, decreased the release of IL-1ß, IL-18, TNF-α, and caspase-3, and elevated the Bax/Bcl-2 ratio in CF mice. We also found that with Ese treatment damage to the mitochondrial ultrastructure of myocardium was alleviated, and the level of reactive oxygen species was markedly diminished. Ese inhibited the expression of proteins associated with pyroptosis by the HK1/NLRP3 signaling pathway and also improved CF. Due to the anti-inflammatory, antioxidative, and antiapoptotic characteristics of Ese decoction, we found that Ese protected against ISO-induced CF, by inhibiting inflammation and pyroptosis as mediated by the HK1/NLRP3 signaling pathway.

The hysteresis damage of cold exposure on tissue and transcript levels in mice.

OBJECTIVES: Although cold stress-induced damage to the heart and thyroid has been reported, specific organ associations between the heart and thyroid with delayed injury mechanisms have not been investigated. In this study, we determined the damage time and transcript levels of a large number of genes in the heart and thyroid after cold exposure. Meanwhile, we analysed the relationship between heart and thyroid injury in human medical records to determine the association of delayed injury from cold exposure. METHODS: Mice were exposed to cold stress and hysteresis injury. Gene changes at the transcriptional level were detected using high throughput sequencing technology. The most variable genes were verified at the protein level using Western Blotting and medical records were collected and analysed. RESULTS: The damage was the most severe when the animals were allowed to recover to room temperature for 4 h after exposure to cold stress. During this process, STAT1 and ATF3 genes were acutely up-regulated. Analysis of human medical records showed the highest correlation between AST and T4 under cold stress (p = 0.0011). CONCLUSIONS: Exposure to cold increases blood level of free thyroid hormone and biomarkers of myocardial injury, as well as related mRNA levels. These changes were more pronounced after return to room temperature.

High-Density Lipoprotein Subclasses and Their Role in the Prevention and Treatment of Cardiovascular Disease: A Narrative Review.

The association between high-density lipoprotein cholesterol (HDL-C) and cardiovascular disease (CVD) is controversial. HDL-C is one content type of high-density lipoprotein (HDL). HDL consists of diverse proteins and lipids and can be classified into different subclasses based on size, shape, charge, and density, and can change dynamically in disease states. Therefore, HDL-C levels alone cannot represent HDLs' cardioprotective role. In this review, we summarized the methods for separating HDL subclasses, the studies on the association between HDL subclasses and cardiovascular risk (CVR), and the impact of lipid-modifying medications and nonpharmacological approaches (exercise training, dietary omega fatty acids, and low-density lipoprotein apheresis) on HDL subclasses. As HDL is a natural nanoplatform, recombinant HDLs (rHDLs) have been used as a delivery system in vivo by loading small interfering RNA, drugs, contrast agents, etc. Therefore, we further reviewed the HDL subclasses used in rHDLs and their advantages and disadvantages. This review would provide recommendations and guidance for future studies on HDL subclasses' cardioprotective roles.

Construction of cellulose-based hybrid hydrogel beads containing carbon dots and their high performance in the adsorption and detection of mercury ions in water.

Cellulose-based adsorbents have been extensively developed in heavy metal capture and wastewater treatment. However, most of the reported powder adsorbents suffer from the difficulties in recycling due to their small sizes and limitations in detecting the targets for the lack of sensitive sensor moieties in the structure. Accordingly, carbon dots (CDs) were proposed to be encapsulated in cellulosic hydrogel beads to realize the simultaneous detection and adsorption of Hg (II) in water due to their excellent fluorescence sensing performance. Besides, the molding of cellulose was beneficial to its recycling and further reduced the potential environmental risk generated by secondary pollution caused by adsorbent decomposition. In addition, the detection limit of the hydrogel beads towards Hg (II) reached as low as 8.8 × 10-8 M, which was below the mercury effluent standard declared by WHO, exhibiting excellent practicability in Hg (II) detection and water treatment. The maximum adsorption capacity of CB-50 % for Hg (II) was 290.70 mg/g. Moreover, the adsorbent materials also had preeminent stability that the hydrogel beads could maintain sensitive and selective sensing performance towards Hg (II) after 2 months of storage. Additionally, only 3.3% of the CDs leaked out after 2 weeks of immersion in water, ensuring the accuracy of Hg (II) evaluation. Notably, the adsorbent retained over 80% of its original adsorption capacity after five consecutive regeneration cycles, underscoring its robustness and potential for sustainable environmental applications.

Utility of dexmedetomidine on surgical site wound pain undergoing thoracoscopic surgery: A meta-analysis.

We conducted this study aimed to evaluate the analgesic effect of dexmedetomidine in thoracoscopic surgery on postoperative wound pain, and to provide a reference for clinical use of the drug. We searched PubMed, Embase, Cochrane Library, Web of Science, Wanfang, Chinese Biomedical Literature Database and China National Knowledge Infrastructure databases, and supplemented with manual searching. We searched from database inception to October 2023, to collect the randomised controlled trials (RCTs) on dexmedetomidine application in thoracoscopic surgery. Two researchers screened all the literature according to the inclusion and exclusion criteria and the literature included in the study was evaluated for quality, extracted information and required data. Stata 17.0 software was employed for data analysis and the outcomes were 2 6, 12, 24 and 48 h postoperative wound visual analog scores (VAS). Twenty-four RCTs totalling 2246 patients undergoing thoracoscopic surgery were finally included. The analysis revealed dexmedetomidine applied to thoracoscopic surgery significantly reduced the postoperative wound VAS scores at 2 h (SMD: -0.96, 95% CI: -1.57 to -0.36, p = 0.002), 6 h (SMD: -0.98, 95% CI: -1.27 to -0.69, p < 0.001), 12 h (SMD: -1.19, 95% CI: -1.44 to -0.94, p < 0.001), 24 h (SMD: -0.91, 95% CI: -1.16 to -0.66, p < 0.001) and 48 h (SMD: -0.75, 95% CI: -1.02 to -0.48, p < 0.001). Our results suggest dexmedetomidine applied to thoracoscopic surgery can significantly reduce postoperative wound pain, which is worthy of clinical application.

Co-expression of transcription factors ZmC1 and ZmR2 establishes an efficient and accurate haploid embryo identification system in maize.

Because of their high efficiency during chromosome doubling, immature haploid maize (Zea mays L.) embryos are useful for doubled haploid production. The R1-nj marker is commonly used in doubled haploid breeding and has improved the efficiency of haploid identification. However, its effectiveness is limited by genetic background and environmental factors. We addressed this technical challenge by developing an efficient and accurate haploid embryo identification marker through co-expression of two transcription factor genes (ZmC1 and ZmR2) driven by the embryo-aleurone-specific bidirectional promoter PZmBD1 ; these factors can activate anthocyanin biosynthesis in the embryo and aleurone layer during early seed development. We developed a new haploid inducer, Maize Anthocyanin Gene InduCer 1 (MAGIC1), by introducing the transgenes into the haploid inducer line CAU6. MAGIC1 could identify haploids at 12 days after pollination, which is nine days earlier than CAU6. Importantly, MAGIC1 increased haploid identification accuracy to 99.1%, compared with 88.3% for CAU6. In addition, MAGIC1 could effectively overcome the inhibition of anthocyanin synthesis in some germplasms. Furthermore, an upgraded anthocyanin marker was developed from ZmC1 and ZmR2 to generate MAGIC2, which could identify haploids from diploids due to differential anthocyanin accumulation in immature embryos, coleoptiles, sheaths, roots, leaves, and dry seeds. This haploid identification system is more efficient and accurate than the conventional R1-nj-based method, and it simplifies the haploid identification process. Therefore, this system provides technical support for large-scale doubled haploid line production.

ZmCOI2a and ZmCOI2b redundantly regulate anther dehiscence and gametophytic male fertility in maize.

In higher plants, the generation and release of viable pollen from anthers is vital for double fertilization and the initiation of seed development. Thus, the characterization of genes related to pollen development and anther dehiscence in plants is of great significance. The F-box protein COI1 plays a crucial role in the jasmonate (JA) signaling pathway and interacts with many JAZ family proteins in the presence of jasmonoyl-isoleucine (JA-Ile) or coronatine (COR). The mutation of AtCOI1 in Arabidopsis leads to defective anther dehiscence and male sterility (MS), although COI has not been shown to affect fertility in Zea mays (maize). Here we identified two genes, ZmCOI2a and ZmCOI2b, that redundantly regulate gametophytic male fertility. Both ZmCOI2a and ZmCOI2b are highly homologous and constitutively expressed in all tissues tested. Subcellular localization revealed that ZmCOI2a and ZmCOI2b were located in the nucleus. The coi2a coi2b double mutant, generated by CRISPR/Cas9, had non-dehiscent anthers, delayed anther development and MS. In addition, coi2a coi2b male gametes could not be transmitted to the next generation because of severe defects in pollen germination. The JA content of coi2a coi2b anthers was unaltered compared with those of the wild type, and the exogenous application of JA could not rescue the fertility defects of coi2a coi2b. Transcriptome analysis showed that the expression of genes involving the JA signaling transduction pathway, including ZmJAZ3, ZmJAZ4, ZmJAZ5 and ZmJAZ15, was affected in coi2a coi2b. However, yeast two-hybrid assays showed that ZmJAZs interacted with ZmCOI1s, but not with ZmCOI2s. In conclusion, ZmCOI2a and ZmCOI2b redundantly regulate anther dehiscence and gametophytic male fertility in maize.

Myeloid-specific fatty acid transport protein 4 deficiency induces a sex-dimorphic susceptibility for nonalcoholic steatohepatitis in mice fed a high-fat, high-cholesterol diet.

Newborns with FATP4 mutations exhibit ichthyosis prematurity syndrome (IPS), and adult patients show skin hyperkeratosis, allergies, and eosinophilia. We have previously shown that the polarization of macrophages is altered by FATP4 deficiency; however, the role of myeloid FATP4 in the pathogenesis of nonalcoholic steatohepatitis (NASH) is not known. We herein phenotyped myeloid-specific Fatp4-deficient (Fatp4M-/-) mice under chow and high-fat, high-cholesterol (HFHC) diet. Bone-marrow-derived macrophages (BMDMs) from Fatp4M-/- mice showed significant reduction in cellular sphingolipids in males and females, and additionally phospholipids in females. BMDMs and Kupffer cells from Fatp4M-/- mice exhibited increased LPS-dependent activation of proinflammatory cytokines and transcription factors PPARγ, CEBPα, and p-FoxO1. Correspondingly, these mutants under chow diet displayed thrombocytopenia, splenomegaly, and elevated liver enzymes. After HFHC feeding, Fatp4M-/- mice showed increased MCP-1 expression in livers and subcutaneous fat. Plasma MCP-1, IL4, and IL13 levels were elevated in male and female mutants, and female mutants additionally showed elevation of IL5 and IL6. After HFHC feeding, male mutants showed an increase in hepatic steatosis and inflammation, whereas female mutants showed a greater severity in hepatic fibrosis associated with immune cell infiltration. Thus, myeloid-FATP4 deficiency led to steatotic and inflammatory NASH in males and females, respectively. Our work offers some implications for patients with FATP4 mutations and also highlights considerations in the design of sex-targeted therapies for NASH treatment.NEW & NOTEWORTHY FATP4 deficiency in BMDMs and Kupffer cells led to increased proinflammatory response. Fatp4M-/- mice displayed thrombocytopenia, splenomegaly, and elevated liver enzymes. In response to HFHC feeding, male mutants were prone to hepatic steatosis, whereas female mutants showed exaggerated fibrosis. Our study provides insights into a sex-dimorphic susceptibility to NASH by myeloid-FATP4 deficiency.