Effects of polystyrene microspheres on the swimming behavior and metabolism of grass carp (Ctenopharyngodon idella).

Microplastics (MPs) are a heterogeneous class of pollutants fouling aquatic environments and they are hazardous to aquatic organisms. This study investigated the size-dependent effects of polystyrene microspheres (PSMPs) on the swimming ability, metabolism, and oxidative stress of juvenile grass carp (Ctenopharyngodon idella). Test fish were exposed to four sizes of PSMPs (0.07, 0.5, 5, and 20-µm), and swimming ability was tested after different exposure times (2, 7, and 15 days). To measure the effect on swimming ability, critical swimming speed (Ucrit) was determined, and to assess metabolic effects, oxygen consumption (MO2), routine metabolic rate (RMR), maximum oxygen consumption (MMR), and excess post-exercise oxygen consumption (EPOC) were determined. To assess the effects on oxidative stress, the activities of two antioxidant enzymes, superoxide dismutase (SOD) and catalase (CAT) were determined in the liver and gills of test fish. After exposure to 20 µm PSMPs, there was a significant drop in Ucrit compared to the control group (P<0.05), with decreases of 22 % on Day 2 and Day 7, and 21 % on Day 15. The RMR and MMR increased significantly (P<0.05), the RMR by 23.9 % on Day 2 and the MMR by 17.2 % on Day 2 and on Day 15, 44.7 % and 20.0 % respectively. The EPOC decreased with exposure time, by 31 % (0.07-µm), 45 %-(0.5-µm), 49 % (5-µm), and 57 % (20-µm) after 15 days. Exposure to the larger PSMPs increased CAT and SOD activity more than the smaller PSMPs and the increases began with SOD activity in the gills. The larger PSMPs were consistently more harmful to juvenile grass carp than the smaller PSMPs. Our results clearly show that PSMPs have detrimental effects on juvenile grass carp and provide additional scientific evidence that environmental monitoring and regulation of microplastic pollution is necessary.

Maternal Hypermethylated Genes Contribute to Intrauterine Growth Retardation of Piglets in Rongchang Pigs.

The placenta is a crucial determinant of fetal survival, growth, and development. Deficiency in placental development directly causes intrauterine growth retardation (IUGR). IUGR can lead to fetal growth restriction and an increase in the mortality rate. The genetic mechanisms underlying IUGR development, however, remain unclear. In the present study, we integrated whole-genome DNA methylation and transcriptomic analyses to determine distinct gene expression patterns in various placental tissues to identify pivotal genes that are implicated with IUGR development. By performing RNA-sequencing analysis, 1487 differentially expressed genes (DEGs), with 737 upregulated and 750 downregulated genes, were identified in IUGR pigs (H_IUGR) compared with that in normal birth weight pigs (N_IUGR) (p < 0.05); furthermore, 77 miRNAs, 1331 lncRNAs, and 61 circRNAs were differentially expressed. The protein-protein interaction network analysis revealed that among these DEGs, the genes GNGT1, ANXA1, and CDC20 related to cellular developmental processes and blood vessel development were the key genes associated with the development of IUGR. A total of 495,870 differentially methylated regions were identified between the N_IUGR and H_IUGR groups, which included 25,053 differentially methylated genes (DMEs); moreover, the overall methylation level was higher in the H_IUGR group than in the N_IUGR group. Combined analysis showed an inverse correlation between methylation levels and gene expression. A total of 1375 genes involved in developmental processes, tissue development, and immune system regulation exhibited methylation differences in gene expression levels in the promoter regions and gene ontology regions. Five genes, namely, ANXA1, ADM, NRP2, SHH, and SMAD1, with high methylation levels were identified as potential contributors to IUGR development. These findings provide valuable insights that DNA methylation plays a crucial role in the epigenetic regulation of gene expression and mammalian development and that DNA-hypermethylated genes contribute to IUGR development in Rongchang pigs.

Multiomics Reveals the Microbiota and Metabolites Associated with Sperm Quality in Rongchang Boars.

In this study, we investigated the correlation between the composition and function of the gut microbiota and the semen quality of Rongchang boars. Significant differences in gut microbial composition between boars with high (group H) and low (group L) semen utilization rates were identified through 16S rRNA gene sequencing, with 18 differential microbes observed at the genus level. Boars with lower semen utilization rates exhibited a higher relative abundance of Treponema, suggesting its potential role in reducing semen quality. Conversely, boars with higher semen utilization rates showed increased relative abundances of Terrisporobacter, Turicibacter, Stenotrophomonas, Clostridium sensu stricto 3, and Bifidobacterium, with Stenotrophomonas and Clostridium sensu stricto 3 showing a significant positive correlation with semen utilization rates. The metabolomic analyses revealed higher levels of gluconolactone, D-ribose, and 4-pyridoxic acid in the H group, with 4 pyridoxic acid and D-ribose showing a significant positive correlation with Terrisporobacter and Clostridium sensu stricto 3, respectively. In contrast, the L group showed elevated levels of D-erythrose-4-phosphate, which correlated negatively with Bifidobacterium and Clostridium sensu stricto 3. These differential metabolites were enriched in the pentose phosphate pathway, vitamin B6 metabolism, and antifolate resistance, potentially influencing semen quality. These findings provide new insights into the complex interplay between the gut microbiota and boar reproductive health and may offer important information for the discovery of disease biomarkers and reproductive health management.

The role of different nutrients in the prevention and treatment of cardiovascular diseases.

Cardiovascular health is a hot topic around the world, and as the incidence of cardiovascular disease increases each year, people are increasingly focusing on the management of their heart health. Dietary and lifestyle changes as non-pharmacological treatments have been increasingly recognized as important in the prevention of cardiovascular disease and in reducing the risk of cardiovascular accidents. Awareness of different nutrients and their effects on cardiovascular health is important for establishing a good dietary pattern. This review summarizes the effects of the five major nutrients in the daily diet, namely carbohydrates, proteins, dietary fats, vitamins, and minerals, on cardiovascular health, and aims to provide a more comprehensive understanding of the effects of a healthy dietary pattern on cardiovascular health.

Arthroscopic treatment of osteoid osteoma in the posterior proximal tibia: A case report and literature review.

BACKGROUND: Osteoid osteoma (OO) is a benign lesion characterized by an increased fibrous component in the bone marrow, presence of bone-like structures within the medullary cavity, and a surrounding sclerotic bone rim. Reports on OO located in the posterior proximal tibia are rare. CASE SUMMARY: Herein, we report the case of an 18-year-old male, admitted for the evaluation of right knee pain. The right knee pain had started 6 months prior without any apparent cause, which was notably severe at night, affecting sleep, and was exacerbated while climbing stairs or bearing weight. The patient also experienced pain on flexion. Three-dimensional computed tomography and magnetic resonance imaging revealed a nodular lesion beneath the cortical bone of the posterior medial plateau of the right tibia and an abnormal signal focus on the posterior lateral aspect of the right tibial plateau associated with extensive bone marrow edema. A small amount of fluid was present in the right knee joint capsule. The patient subsequently underwent arthroscopic excision of the OO. Postoperatively, there was significant relief of pain, and the knee range of motion returned to normal. CONCLUSION: Although OO in the posterior proximal tibia is a rare occurrence, it can be effectively excised through minimally invasive arthroscopic visualization.

Lactobacillus sp. participated in the adaptation of Rongchang piglets to cold stress.

Rongchang piglets were easily induced to cold stress and diarrhoea in the winter when raised in an open hog house. However, they also gradually recovered under mid-cold stress. Other studies have suggested gut microbiome might be involved in the host energy metabolism to relieve stress. To study how to adapt Rongchang piglets to cold stress by gut microbiome, thirty Rongchang piglets were randomly divided into a mild cold stress group and a control group for 30 consecutive days. The findings revealed that the piglets had low growth performance and a high diarrhoea rate and mortality rate during the first half of the cold treatment, but subsequently stabilised. The level of cortisol (COR) also displayed a similar trend. In the mild cold stress group, the relative abundance of Muribaculaceae significantly increased on day 15, and the predominant bacterial on day 30 was Lactobacillus sp. Our results indicated that the Rongchang piglet's production performance and health were impaired at the start of the mild cold stress. However, as time passed, the body could progressively adapt to the low temperature, and Lactobacillus sp. participated in this process. This study provides new insight into how to alleviate health damage caused by cold stress.

Advancing cardiac regeneration through 3D bioprinting: methods, applications, and future directions.

Cardiovascular diseases (CVDs) represent a paramount global mortality concern, and their prevalence is on a relentless ascent. Despite the effectiveness of contemporary medical interventions in mitigating CVD-related fatality rates and complications, their efficacy remains curtailed by an array of limitations. These include the suboptimal efficiency of direct cell injection and an inherent disequilibrium between the demand and availability of heart transplantations. Consequently, the imperative to formulate innovative strategies for cardiac regeneration therapy becomes unmistakable. Within this context, 3D bioprinting technology emerges as a vanguard contender, occupying a pivotal niche in the realm of tissue engineering and regenerative medicine. This state-of-the-art methodology holds the potential to fabricate intricate heart tissues endowed with multifaceted structures and functionalities, thereby engendering substantial promise. By harnessing the prowess of 3D bioprinting, it becomes plausible to synthesize functional cardiac architectures seamlessly enmeshed with the host tissue, affording a viable avenue for the restitution of infarcted domains and, by extension, mitigating the onerous yoke of CVDs. In this review, we encapsulate the myriad applications of 3D bioprinting technology in the domain of heart tissue regeneration. Furthermore, we usher in the latest advancements in printing methodologies and bioinks, culminating in an exploration of the extant challenges and the vista of possibilities inherent to a diverse array of approaches.

Cardiac self-limiting rhabdomyomas in a neonatal patient with tuberous sclerosis complex: a case report with negative genetic testing.

Background: Tuberous Sclerosis Complex (TSC) is a hereditary condition that leads to the development of non-malignant neoplasms in various organs, including cardiac rhabdomyomas, which can cause significant complications. Case presentation: This report describes the case of a 15-day-old male neonate who was hospitalized due to intracardiac masses and brain lesions, despite the absence of TSC gene mutations. The patient's mother exhibited facial angiofibromas, a common feature of TSC. Over a 2-year follow-up period, spontaneous regression of the cardiac tumor was observed. Conclusions: This case illustrates that not all TSC cases exhibit detectable TSC gene mutations. Current treatment strategies, such as mTOR inhibitors, offer potential effectiveness in managing associated cardiac rhabdomyomas. Further research should focus on evaluating the therapeutic potential of these inhibitors.

Circulating miR-107 as a diagnostic biomarker of osteoporotic vertebral compression fracture increases bone formation in vitro and in vivo.

AIMS: This study aimed to examine the key circulating microRNAs (miRNAs) in the plasma of patients with osteoporotic vertebral compression fracture and assess their potential role as diagnostic biomarkers and explore their function in vitro and in vivo. METHODS: Weighted gene co-expression network analysis (WGCNA) was applied to identify hub miRNAs for subsequent analysis. The candidate miRNAs were tested using plasma from 144 patients and the results were applied to construct receiver operating characteristic (ROC) curves to assess their diagnostic value. In addition, the function of the target miRNA was validated in MC3T3-E1 cells, human bone marrow-derived mesenchymal stromal cells (BMSCs), and an ovariectomized (OVX) mouse model. KEY FINDINGS: Seven modules were obtained by WGCNA analysis. The expression levels of circulating miR-107 in the red module were significantly lower in osteoporotic patients than in healthy controls. In addition, miR-107 provided discrimination with an AUC > 85 % by ROC analyses to differentiate women osteoporosis patients from healthy controls and differentiate women osteoporotic patients with vertebral compression fractures from osteoporotic patients without vertebral compression fractures. In vitro experiments revealed that miR-107 levels were increased in osteogenically induced MC3T3-E1 cells and BMSCs and transfection with synthetic miR-107 could promote bone formation. Lastly, the bone parameters were improved by miR-107 upregulation in OVX mice. SIGNIFICANCE: Our findings show that circulating miR-107 plays an essential role in facilitating osteogenesis and may be a useful diagnostic biomarker and therapeutic target in osteoporosis.

Sulfonyl-PYBOX Ligands Enable Kinetic Resolution of α-Tertiary Azides by CuAAC.

We report the first highly selective kinetic resolution of racemic α-chiral azides via Cu-catalyzed azide-alkyne cycloaddition (CuAAC). Newly developed pyridine-bisoxazoline (PYBOX) ligands, bearing a C4 sulfonyl group, enable effective kinetic resolution of racemic azides derived from privileged scaffolds such as indanone, cyclopentenone, and oxindole, and their asymmetric CuAAC to afford α-tertiary 1,2,3-triazoles with high to excellent ee values. DFT calculations and control experiments reveal that the C4 sulfonyl group decreases the Lewis basicity of the ligand and increases the electrophilicity of the copper center for better recognition of azides, and functions as a shielding group to make the chiral pocket of the catalyst more effective.

Identification and Risk Assessment of Priority Control Organic Pollutants in Groundwater in the Junggar Basin in Xinjiang, P.R. China.

The Junggar Basin in Xinjiang is located in the hinterland of Eurasia, where the groundwater is a significant resource and has important ecological functions. The introduction of harmful organic pollutants into groundwater from increasing human activities and rapid socioeconomic development may lead to groundwater pollution at various levels. Therefore, to develop an effective regulatory framework, establishing a list of priority control organic pollutants (PCOPs) is in urgent need. In this study, a method of ranking the priority of pollutants based on their prevalence (Pv), occurrence (O) and persistent bioaccumulative toxicity (PBT) has been developed. PvOPBT in the environment was applied in the screening of PCOPs among 34 organic pollutants and the risk assessment of screened PCOPs in groundwater in the Junggar Basin. The results show that the PCOPs in groundwater were benzo[a]pyrene, 1,2-dichloroethane, trichloromethane and DDT. Among the pollutants, benzo[a]pyrene, 1,2-dichloroethane and DDT showed high potential ecological risk, whilst trichloromethane represented low potential ecological risk. With the exception of benzo[a]pyrene, which had high potential health risks, the other screened PCOPs had low potential health risks. Unlike the scatter distribution of groundwater benzo[a]pyrene, the 1,2-dichloroethane and trichloromethane in groundwater were mainly concentrated in the central part of the southern margin and the northern margin of the Junggar Basin, while the DDT in groundwater was only distributed in Jinghe County (in the southwest) and Beitun City (in the north). Industrial and agricultural activities were the main controlling factors that affected the distribution of PCOPs.

Insights into rapidly recovering the autotrophic nitrogen removal performance of single-stage partial nitritation-anammox systems: Reconstructing granular sludge and its functional microbes synergy.

Partial nitritation-anammox (PNA) deteriorates easily and is difficult to recover. After an airlift inner-circulation partition bioreactor was impacted by low NH4+-N wastewater containing organic matter, Nitrospira and Denitratisoma propagated rapidly, granular sludge disintegrated, and the total nitrogen removal efficiency (TNRE) decreased from 68.27 % to 5.97 %. This study used a unique strategy to recover deteriorated single-stage PNA systems and explored the mechanism of rapid performance recovery. The TNRE of the system recovered up to 61.77 % in 43 days. The high nitrogen loading rate and hydraulic shear force from the airlift caused the sludge in the reactor to granulate again. The microbial community structure recovered, with a decrease in the abundance of Nitrospira (0.05 %) and enrichment of Candidatus Brocadia (8.82 %). A favorable synergy among functional microbes in the reactor was thus re-established, promoting the rapid recovery of the nitrogen removal performance. This study provides a feasible recovery strategy for PNA processes.

Revealing the effect of biofilm formation in partial nitritation-anammox systems: Start-up, performance stability, and recovery.

Successful application of partial nitritation-anammox (PNA) processes is currently and primarily associated with biofilm systems. Biofilm characteristics significantly influence start-up, performance stability, and recovery. Here, two PNA systems with and without carriers were implemented simultaneously for treating wastewater containing 50 mg-NH4/L. The performance characteristics of these two PNA systems were compared. Stable nitrogen removal efficiencies of 76.3 ± 2.8% and 72.9 ± 1.6% were obtained for suspended sludge and biofilm systems, respectively. The slow process of biofilm colonization resulted in a long start-up time in the biofilm system. Biofilm enrichment and protection conferred stable performance when exposed to aeration shock. The suspended sludge system displayed good elasticity during performance recovery after shock compared to the slow recovery in the biofilm system. Moreover, suitable control of dissolved oxygen could improve the activity and abundance of the functional microbes. This study provides new insights into the operation and control of PNA systems for treating mainstream wastewater.

Dual inner circulation and multi-partition driving single-stage autotrophic nitrogen removal in a bioreactor.

The single-stage autotrophic nitrogen removal (ANR) process is impeded by a long start-up cycle and unstable operation performance. In this study, an airlift inner-circulation partition bioreactor (AIPBR) was operated continuously for 215 days to explore methods of strengthening the performance and stable operation of the single-stage ANR system. AIPBR start-up period took around 38 days, the total nitrogen removal efficiency was > 85% on day 35. With the decrease of hydraulic retention time and the increase of aeration rate, the nitrogen removal rate increased to 0.85 ± 0.02 kg-N/m3/day. The sludge morphology gradually changed into dark-red floc-coupled granular sludge. Nitrosomonas (9.95%) and Candidatus Brocadia (6.41%) were dominant in the sludge. During long-term operation, AIPBR achieved the dual inner circulation of sewage and sludge and then formed effective dissolved oxygen and sludge partitions to provide a suitable growth environment for various functional bacteria, promote synergy between them, and strengthen the ANR performance.

Redox-Based Strategy for Selectively Inducing Energy Crisis Inside Cancer Cells: An Example of Modifying Dietary Curcumin to Target Mitochondria.

Reprograming of energy metabolism is a major hallmark of cancer, but its effective intervention is still a challenging task due to metabolic heterogeneity and plasticity of cancer cells. Herein, we report a general redox-based strategy for meeting the challenge. The strategy was exemplified by a dietary curcumin analogue (MitoCur-1) that was designed to target mitochondria (MitoCur-1). By virtue of its electrophilic and mitochondrial-targeting properties, MitoCur-1 generated reactive oxygen species (ROS) more effectively and selectively in HepG2 cells than in L02 cells via the inhibition of mitochondrial antioxidative thioredoxin reductase 2 (TrxR2). The ROS generation preferentially mediated the energy crisis of HepG2 cells in a dual-inhibition fashion against both mitochondrial and glycolytic metabolisms, which could hit the metabolic plasticity of HepG2 cells. The ROS-dependent energy crisis also allowed its preferential killing of HepG2 cells (IC50 = 1.4 µM) over L02 cells (IC50 = 9.1 µM), via induction of cell-cycle arrest, apoptosis and autophagic death, and its high antitumor efficacy in vivo, in nude mice bearing HepG2 tumors (15 mg/kg). These results highlight that inhibiting mitochondrial TrxR2 to produce ROS by electrophiles is a promising redox-based strategy for the effective intervention of cancer cell energy metabolic reprograming.

Carbohydrate Ligands for COVID-19 Spike Proteins.

An outbreak of SARS-CoV-2 coronavirus (COVID-19) first detected in Wuhan, China, has created a public health emergency all over the world. The pandemic has caused more than 340 million confirmed cases and 5.57 million deaths as of 23 January 2022. Although carbohydrates have been found to play a role in coronavirus binding and infection, the role of cell surface glycans in SARS-CoV-2 infection and pathogenesis is still not understood. Herein, we report that the SARS-CoV-2 spike protein S1 subunit binds specifically to blood group A and B antigens, and that the spike protein S2 subunit has a binding preference for Lea antigens. Further examination of the binding preference for different types of red blood cells (RBCs) indicated that the spike protein S1 subunit preferentially binds with blood group A RBCs, whereas the spike protein S2 subunit prefers to interact with blood group Lea RBCs. Angiotensin converting enzyme 2 (ACE2), a known target of SARS-CoV-2 spike proteins, was identified to be a blood group A antigen-containing glycoprotein. Additionally, 6-sulfo N-acetyllactosamine was found to inhibit the binding of the spike protein S1 subunit with blood group A RBCs and reduce the interaction between the spike protein S1 subunit and ACE2.

Liquid Warping GAN With Attention: A Unified Framework for Human Image Synthesis.

We tackle human image synthesis, including human motion imitation, appearance transfer, and novel view synthesis, within a unified framework. It means that the model, once being trained, can be used to handle all these tasks. The existing task-specific methods mainly use 2D keypoints (pose) to estimate the human body structure. However, they only express the position information with no ability to characterize the personalized shape of the person and model the limb rotations. In this paper, we propose to use a 3D body mesh recovery module to disentangle the pose and shape. It can not only model the joint location and rotation but also characterize the personalized body shape. To preserve the source information, such as texture, style, color, and face identity, we propose an Attentional Liquid Warping GAN with Attentional Liquid Warping Block (AttLWB) that propagates the source information in both image and feature spaces to the synthesized reference. Specifically, the source features are extracted by a denoising convolutional auto-encoder for characterizing the source identity well. Furthermore, our proposed method can support a more flexible warping from multiple sources. To further improve the generalization ability of the unseen source images, a one/few-shot adversarial learning is applied. In detail, it first trains a model in an extensive training set. Then, it finetunes the model by one/few-shot unseen image(s) in a self-supervised way to generate high-resolution ( 512 ×512 and 1024 ×1024) results. Also, we build a new dataset, namely Impersonator (iPER) dataset, for the evaluation of human motion imitation, appearance transfer, and novel view synthesis. Extensive experiments demonstrate the effectiveness of our methods in terms of preserving face identity, shape consistency, and clothes details. All codes and dataset are available on https://impersonator.org/work/impersonator-plus-plus.html.

MicroRNA-214-5p aggravates sepsis-related acute kidney injury in mice.

Acute kidney injury (AKI) is a devastating comorbidity in sepsis and correlates with a very poor prognosis and increased mortality. Currently, we use lipopolysaccharide (LPS) to establish sepsis-related AKI and try to demonstrate the pathophysiological role of microRNA-214-5p (miR-214-5p) in this process. Mice were intravenously injected with the miR-214-5p agomir, antagomir or negative controls for three consecutive days and then received a single intraperitoneal injection of LPS (10 mg/kg) for 24 h to induce AKI. Besides, the Boston University mouse proximal tubular cell lines were stimulated with LPS (10 µg/ml) for 8 h to investigate the role of miR-214-5p in vitro. To inhibit adenosine monophosphate-activated protein kinase (AMPK), compound C (CpC) was used in vivo. For glucagon-like peptide-1 receptor (GLP-1R) silence, cells were transfected with the small interfering RNA against GLP-1R. miR-214-5p level was upregulated in LPS-treated kidneys and proximal tubular cell lines. The miR-214-5p antagomir reduced LPS-induced renal inflammation and oxidative stress, thereby preventing renal damage and dysfunction. In contrast, the miR-214-5p agomir aggravated LPS-induced inflammation, oxidative stress and AKI in vivo and in vitro. Mechanistically, we found that the miR-214-5p antagomir prevented septic AKI via activating AMPK and that CpC treatment completely abrogated its renoprotective effect in mice. Further detection showed that miR-214-5p directly bound to the 3'-untranslational region of GLP-1R to inhibit GLP-1R/AMPK axis. Our data identify miR-214-5p as a promising therapeutic candidate to treat sepsis-related AKI.

ATP5O Hypo-crotonylation Caused by HDAC2 Hyper-Phosphorylation Is a Primary Detrimental Factor for Downregulated Phospholipid Metabolism under Chronic Stress.

Objective. Chronic stress (CS)-induced abnormal metabolism and other subsequent aspects of abnormality are threatening human health. Little is known regarding whether and how protein post-translational-modifications (PTMs) correlate with abnormal metabolism under CS. The aim of this study was to address this issue and also identify novel key protein PTM. Methods. First, we screened which pan-PTM had significant change between control and CS female mice and whether clinical CS females had similar pan-PTM change. Second, we performed quantitative PTM-omics and metabolomics to verify the correlation between abnormal protein PTMs and atypical metabolism. Third, we performed quantitative phospho-omics to identify the key PTM-regulating enzyme and investigate the interaction between PTM protein and PTM-regulating enzyme. Fourth, we attempted to rectify the abnormal metabolism by correcting the activity of the PTM-regulating enzyme. Finally, we examined whether the selected key protein was also correlated with stress scores and atypical metabolism in clinical women. Results. We initially found that multiple tissues of CS female mice have downregulated pan-crotonylation, and verified that the plasma of clinical CS females also had downregulated pan-crotonylation. Then we determined that ATP5O-K51 crotonylation decreased the most and also caused gross ATP5O decrement, whereas the plasma of CS mice had downregulated phospholipids. Next, downregulating ATP5O crotonylation partially recapitulated the downregulated phospholipid metabolism in CS mice. Next, we verified that HDAC2-S424 phosphorylation determined its decrotonylation activity on ATP5O-K51. Furthermore, correcting HDAC2 hyper-phosphorylation recovered the gross ATP5O level and partially rescued the downregulated phospholipid metabolism in CS mice. Finally, the ATP5O level was also significantly lower and correlated with high stress scores and downregulated phospholipid metabolism in clinical female plasma. Conclusion. This study discovered a novel PTM mechanism involving two distinct types of PTM in CS and provided a novel reference for the clinical precautions and treatments of CS.

A feminizing switch in a hemimetabolous insect.

The mechanism of sex determination remains poorly understood in hemimetabolous insects. Here, in the brown planthopper (BPH), Nilaparvata lugens, a hemipteran rice pest, we identified a feminizing switch or a female determiner (Nlfmd) that encodes a serine/arginine-rich protein. Knockdown of Nlfmd in female nymphs resulted in masculinization of both the somatic morphology and doublesex splicing. The female-specific isoform of Nlfmd, Nlfmd-F, is maternally deposited and zygotically transcribed. Depletion of Nlfmd by maternal RNAi or CRISPR-Cas9 resulted in female-specific embryonic lethality. Knockdown of an hnRNP40 family gene named female determiner 2 (Nlfmd2) also conferred masculinization. In vitro experiments showed that an Nlfmd2 isoform, NlFMD2340, bound the RAAGAA repeat motif in the Nldsx pre-mRNA and formed a protein complex with NlFMD-F to modulate Nldsx splicing, suggesting that NlFMD2 may function as an RNA binding partner of the feminizing switch NlFMD. Our results provide novel insights into the diverse mechanisms of insect sex determination.