Crop root system architecture in drought response.

Drought is a natural disaster that has a profound impact on global agricultural production, significantly reduces crop yields and thereby poses a severe threat to worldwide food security. Addressing the challenge of effectively improving crop drought resistance (DR) to mitigate yield loss under drought conditions is a global issue. An optimal root system architecture (RSA) plays a pivotal role in enhancing crops' capacity to efficiently uptake water and nutrients, which consequently strengthens their resilience against environmental stresses. In this review, we discuss the compositions and roles of crop RSA and summarize the most recent developments in augmenting drought tolerance in crops by manipulating RSA-related genes. Based on current research, we propose the potential optimal RSA configuration that could be helpful in enhancing crop DR. Lastly, we discussed the existing challenges and future directions for breeding crops with enhanced DR capabilities through genetic improvements targeting RSA.

Synergistic Engineering of Energy Band Alignment and Interfacial Electric Field Distribution over Bi-bismuth-Based Hetero-nanofibers for Boosting Visible-Light-Driven Photocatalytic Ammonia Synthesis and Antibiotic Removal.

Synergistic engineering of energy band alignment and interfacial electric field distribution is essential for photocatalyst design but is still challenging because of the limitation on refined regulation in the nanoscale. This study addresses the issue by employing surface modification and thermal-induced phase transformation in Bi2MoO6/BixOyIz hetero-nanofiber frameworks. The energy band alignment switches from a type-II interface to a Z-scheme contact with stronger redox potentials and inhibited electron traps, and the optimized built-in electric field distribution could be reached based on experimental and theoretical investigations. The engineered hetero-nanofibers exhibit outstanding visible-light-driven photocatalytic nitrogen reduction activity (605 µmol/g/h) and tetracycline hydrochloride removal rate (81.5% within 30 min), ranking them among the top-performing bismuth series materials. Furthermore, the photocatalysts show promise in activating advanced oxidants for efficient organic pollutant degradation. Moreover, the Bi2MoO6/Bi5O7I hetero-nanofibers possess good recycling stability owing to their three-dimensional network structure. This research offers valuable insights into heterojunction design for environmental remediation and industrial applications.

Deficiency of leucine-rich repeat kinase 2 aggravates thioacetamide-induced acute liver failure and hepatic encephalopathy in mice.

BACKGROUND: Hepatic encephalopathy (HE) is closely associated with inflammatory responses. However, as a crucial regulator of the immune and inflammatory responses, the role of leucine-rich repeat kinase 2 (LRRK2) in the pathogenesis of HE remains unraveled. Herein, we investigated this issue in thioacetamide (TAA)-induced HE following acute liver failure (ALF). METHODS: TAA-induced HE mouse models of LRRK2 wild type (WT), LRRK2 G2019S mutation (Lrrk2G2019S) and LRRK2 knockout (Lrrk2-/-) were established. A battery of neurobehavioral experiments was conducted. The biochemical indexes and pro-inflammatory cytokines were detected. The prefrontal cortex (PFC), striatum (STR), hippocampus (HIP), and liver were examined by pathology and electron microscopy. The changes of autophagy-lysosomal pathway and activity of critical Rab GTPases were analyzed. RESULTS: The Lrrk2-/--HE model reported a significantly lower survival rate than the other two models (24% vs. 48%, respectively, p < 0.05), with no difference found between the WT-HE and Lrrk2G2019S-HE groups. Compared with the other groups, after the TAA injection, the Lrrk2-/- group displayed a significant increase in ammonium and pro-inflammatory cytokines, aggravated hepatic inflammation/necrosis, decreased autophagy, and abnormal phosphorylation of lysosomal Rab10. All three models reported microglial activation, neuronal loss, disordered vesicle transmission, and damaged myelin structure. The Lrrk2-/--HE mice presented no severer neuronal injury than the other genotypes. CONCLUSIONS: LRRK2 deficiency may exacerbate TAA-induced ALF and HE in mice, in which inflammatory response is evident in the brain and aggravated in the liver. These novel findings indicate a need of sufficient clinical awareness of the adverse effects of LRRK2 inhibitors on the liver.

Galectin-3 impairs calcium transients and ß-cell function.

In diabetes, macrophages and inflammation are increased in the islets, along with ß-cell dysfunction. Here, we demonstrate that galectin-3 (Gal3), mainly produced and secreted by macrophages, is elevated in islets from both high-fat diet (HFD)-fed and diabetic db/db mice. Gal3 acutely reduces glucose-stimulated insulin secretion (GSIS) in ß-cell lines and primary islets in mice and humans. Importantly, Gal3 binds to calcium voltage-gated channel auxiliary subunit gamma 1 (CACNG1) and inhibits calcium influx via the cytomembrane and subsequent GSIS. ß-Cell CACNG1 deficiency phenocopies Gal3 treatment. Inhibition of Gal3 through either genetic or pharmacologic loss of function improves GSIS and glucose homeostasis in both HFD-fed and db/db mice. All animal findings are applicable to male mice. Here we show a role of Gal3 in pancreatic ß-cell dysfunction, and Gal3 could be a therapeutic target for the treatment of type 2 diabetes.

Discovery and pharmacological characterization of 1,2,3,4-tetrahydroquinoline derivatives as RORγ inverse agonists against prostate cancer.

The retinoic acid receptor-related orphan receptor γ (RORγ) is regarded as an attractive therapeutic target for the treatment of prostate cancer. Herein, we report the identification, optimization, and evaluation of 1,2,3,4-tetrahydroquinoline derivatives as novel RORγ inverse agonists, starting from high throughput screening using a thermal stability shift assay (TSA). The representative compounds 13e (designated as XY039) and 14a (designated as XY077) effectively inhibited the RORγ transcriptional activity and exhibited excellent selectivity against other nuclear receptor subtypes. The structural basis for their inhibitory potency was elucidated through the crystallographic study of RORγ LBD complex with 13e. Both 13e and 14a demonstrated reasonable antiproliferative activity, potently inhibited colony formation and the expression of AR, AR regulated genes, and other oncogene in AR positive prostate cancer cell lines. Moreover, 13e and 14a effectively suppressed tumor growth in a 22Rv1 xenograft tumor model in mice. This work provides new and valuable lead compounds for further development of drugs against prostate cancer.

Association of osteoporotic fractures of femoral neck and femoral neck geometric parameters in native Chinese women.

BACKGROUND: Although it is generally believed that the femoral neck fracture is related to the femoral neck geometric parameters (FNGPs), the association between the risk of osteoporotic fracture of the femoral neck and FNGPs in native Chinese women is still unclear. METHODS: A total of 374 female patients (mean age 70.2 ± 9.32 years) with osteoporotic fracture of the femoral neck, and 374 non-fracture control groups were completely matched with the case group according to the age ratio of 1:1. Using DXA bone densitometer to measured eight FNGPs: the outer diameter (OD), cross-sectional area (CSA), cortical thickness (CT), endocortical diameter (ED), buckling ratio (BR), section modulus (SM), cross-sectional moment of inertia (CSMI), and compressive strength index (CSI) at the narrowest point of the femoral neck. RESULTS: Compared with the control group, the average values of OD (2.9%), ED (4.5%), and BR (26.1%) in the patient group significantly increased (p = 0.015 to < 0.001), while CSA (‒15.3%), CT (‒18.2%), SM (‒10.3%), CSMI (‒6.4%), and CSI (‒10.8%) significantly decreased (all p < 0.001). The prevalence of osteoporosis in the lumbar spine, femoral neck, and total hip was, respectively, 82%, 81%, and 65% in fracture patients. Cox proportional hazard model analysis showed that in the age adjusted model, the fracture hazard ratio (HR) of CSA, CT, BR, SM, and CSI significantly increased (HRs = 1.60‒8.33; 95% CI = 1.08‒16.6; all p < 0.001). In the model adjusted for age and femoral neck BMD, HRs of CT (HRs = 3.90‒8.03; 95% CI = 2.45‒15.1; all p < 0.001) and BR (HRs = 1.62‒2.60; 95% CI = 1.20‒5.44; all p < 0.001) were still significantly increased. CONCLUSION: These results suggest that the majority of osteoporotic fractures of the femoral neck of native Chinese women occur in patients with osteoporosis. CT thinning or BR increase of FNGPs may be independent predictors of fragility fracture of femoral neck in native Chinese women unrelated to BMD.

The association between the fibrinogen-to-albumin ratio and delirium after deep brain stimulation surgery in Parkinson's disease.

Introduction: Postoperative delirium (POD) remains one of the most prevalent neuropsychiatric complications after deep brain stimulation (DBS) surgery. The fibrinogen-to-albumin ratio (FAR) has been shown to significantly correlate with the prognosis of many diseases related to inflammation. However, the association between FAR and POD remains unclear. We aimed to explore the association between POD and FAR in patients with Parkinson's disease (PD) undergoing DBS surgery. Methods: Patients with PD who underwent DBS surgery in our hospital were included in this retrospective study. FAR was calculated from the blood sample collected on admission. The association between baseline FAR and delirium after surgery was assessed by binary logistic regression analysis, interaction analysis, and stratified analyses. Results: Of 226 patients, 37 (16.4%) suffered from delirium after surgery. The average age of the participants was 63.3 ± 7.2 years, and 51.3% were male patients. Multivariate logistic regression analysis indicated that patients in the highest FAR tertile had a higher risk of POD compared with patients in the lowest FAR tertile (OR = 3.93, 95% CI: 1.24 ~ 12.67). Subgroup analysis demonstrated that FAR and the preoperative Mini-Mental State Examination score (p = 0.013) had an association with delirium after surgery. Conclusion: Our data suggest that a higher preoperative FAR was significantly associated with delirium after DBS surgery. FAR on admission is a useful candidate biomarker to identify patients with PD who are at a high risk of delirium following DBS surgery.

Gfi-1 modulates HMGB1-Mediated autophagy to overcome oxaliplatin resistance in colorectal cancer.

Background: Resistance to oxaliplatin (L-OHP) is a major barrier in the treatment of colorectal cancer (CRC). Autophagy is the main cause of L-OHP tolerance in CRC cells. Method: The human colon cancer cell lines HCT116 and SW480 were treated with L-OHP to obtain the drug-resistant cell lines HCT116/L-OHP and SW480/L-OHP, respectively. To probe the relationship between autophagy and L-OHP tolerance of growth factor independent 1 (Gfi-1) and high-mobility group protein 1 (HMGB1) in CRC cells, gene knockout or overexpression was performed, and Western blotting was used to determine the levels of drug tolerance interrelated proteins. Transwell and CCK-8 assays were employed to analyze the proliferation of cancer cells. Immunofluorescence detection of LC3 reflected autophagy levels. Finally, the relationship between Gfi-1 and HMGB1 was detected by chromatin immunoprecipitation (ChIP). Result: Compared to normal CRC cells, L-OHP-tolerant CRC cells exhibited greater autophagy (8.2 times greater in HCT116/L-OHP cells and 7.4 times greater in SW480/L-OHP cells). In addition, we detected low levels of Gfi-1 (0.6-fold for HCT116/L-OHP cells and 0.4-fold for SW480/L-OHP cells), and OE-Gfi-1 decreased HMGB1 levels (0.6-fold for HCT116/L-OHP + OE-Gfi-1 cells and 0.5-fold for SW480/L-OHP + OE-Gfi-1 cells). The inhibition of Gfi-1 further enhanced cell viability (1.7 times in HCT116+sh-Gfi-1 cells and 1.2 times in SW480+sh-Gfi-1 cells) and invasion (1.8 times in HCT116+sh-Gfi-1 cells and 2.1 times in SW480+sh-Gfi-1 cells) in CRC cells, thus promoting oxaliplatin resistance in these cells. The autophagy inhibitor 3-MA reversed the above effects. Furthermore, we noted that Gfi-1 can restrain HMGB1 expression by binding to its promoter (0.5 times in HCT116+OE-Gfi-1 cells and 0.5 times in SW480+OE-Gfi-1 cells). The inhibitory influence of 3-MA on HMGB1 reversed the influence of Gfi-1 on autophagy and malignant progression in CRC cells. Conclusion: Our study suggested that Gfi-1 inhibited HMGB1 to reduce CRC autophagy levels, increasing CRC sensitivity to L-OHP.

Emission of CO2 and its related carbonate system dynamics in a hotspot area during winter and summer: The Changjiang River estuary.

The carbonate chemistry in river-dominated marginal seas is highly heterogeneous, and there is ongoing debate regarding the definition of atmospheric CO2 source or sink. On this basis, we investigated the carbonate chemistry and air-sea CO2 fluxes in a hotspot estuarine area: the Changjiang Estuary during winter and summer. The spatial characteristics of the carbonate system were influenced by water mixing of three end-members in winter, including the Changjiang freshwater with low total alkalinity (TA) concentration, the less saline Yellow Sea Surface Water with high TA, and the saline East China Sea (ECS) offshore water with moderate TA. While in summer with increased river discharge, the carbonate system was regulated by simplified two end-member mixing between the Changjiang freshwater and the ECS offshore water. By performing the end-member mixing model on DIC variations in the river plume region, significant biological addition of DIC was found in winter with an estimation of -120 ± 113 µmol kg-1 caused by wintertime organic matter remineralization from terrestrial source. While this biological addition of DIC shifted to DIC removal due to biological production in summer supported by the increased nutrient loading from Changjiang River. The pCO2 dynamics in the river plume and the ECS offshore were both subjected to physical mixing of freshwater and seawater, whether in winter and summer. In the inner estuary without horizontal mixing, the pCO2 dynamics were mainly influenced by biological uptake in winter and temperature in summer. The inner estuary, the river plume, and the ECS offshore were sources of atmospheric CO2, with their contributions varying seasonally. The Changjiang runoff enhanced the inner estuary's role as a CO2 source in summer, while intensive biological uptake reduced the river plume's contribution.

Liver receptor homolog-1: structures, related diseases, and drug discovery.

Liver receptor homolog-1 (LRH-1), a member of the nuclear receptor superfamily, is a ligand-regulated transcription factor that plays crucial roles in metabolism, development, and immunity. Despite being classified as an 'orphan' receptor due to the ongoing debate surrounding its endogenous ligands, recent researches have demonstrated that LRH-1 can be modulated by various synthetic ligands. This highlights the potential of LRH-1 as an attractive drug target for the treatment of inflammation, metabolic disorders, and cancer. In this review, we provide an overview of the structural basis, functional activities, associated diseases, and advancements in therapeutic ligand research targeting LRH-1.

Clarifying the relationship and analyzing the influential factors of bronchial asthma in children with attention-deficit hyperactivity disorder.

BACKGROUND: Bronchial asthma is closely related to the occurrence of attention-deficit hyperactivity disorder (ADHD) in children, which can easily have adverse effects on children's learning and social interactions. Studies have shown that childhood asthma can increase the risk of ADHD and the core symptoms of ADHD. Compared with children with ADHD alone, children with asthma and ADHD are more likely to show high levels of hyperactivity, hyperactive-impulsive and other externalizing behaviors and anxiety in clinical practice and have more symptoms of somatization and emotional internalization. AIM: To explore the relationship between ADHD in children and bronchial asthma and to analyze its influencing factors. METHODS: This retrospective cohort study was conducted at Dongying People's Hospital from September 2018 to August 2023. Children diagnosed with ADHD at this hospital were selected as the ADHD group, while healthy children without ADHD who underwent physical examinations during the same period served as the control group. Clinical and parental data were collected for all participating children, and multivariate logistic regression analysis was employed to identify risk factors for comorbid asthma in children with ADHD. RESULTS: Significant differences were detected between the ADHD group and the control group in terms of family history of asthma and allergic diseases, maternal complications during pregnancy, maternal use of asthma and allergy medications during pregnancy, maternal anxiety and depression during pregnancy, and parental relationship status (P < 0.05). Out of the 183 children in the ADHD group, 25 had comorbid asthma, resulting in a comorbidity rate of 13.66% (25/183), compared to the comorbidity rate of 2.91% (16/549) among the 549 children in the control group. The difference in the asthma comorbidity rate between the two groups was statistically significant (P < 0.05). The results of the multivariate logistic regression analysis indicated that family history of asthma and allergic diseases, maternal complications during pregnancy, maternal use of asthma and allergy medications during pregnancy, maternal anxiety and depression during pregnancy, and parental relationship status are independent risk factors increasing the risk of comorbid asthma in children with ADHD (P < 0.05). CONCLUSION: Children with ADHD were more likely to have comorbid asthma than healthy control children were. A family history of asthma, adverse maternal factors during pregnancy, and parental relationship status were identified as risk factors influencing the comorbidity of asthma in children with ADHD. Clinically, targeted interventions based on these factors can be implemented to reduce the risk of comorbid asthma. This information is relevant for results sections of abstracts in scientific articles.

A visceral organ function-focused therapeutic strategy using a 6-hour time window for patients with acute type a aortic dissection complicated by mesenteric malperfusion.

BACKGROUND: Acute type A aortic dissection (ATAAD) complicated by mesenteric malperfusion is a critical and complicated condition. The optimal treatment strategy remains controversial, debate exists as to whether aortic dissection or mesenteric malperfusion should be addressed first, and the exact time window for mesenteric ischemia intervention is still unclear. To solve this problem, we developed a new concept based on the pathophysiological mechanism of mesenteric ischemia, using a 6-hour time window to divide newly admitted patients by the time from onset to admission, applying different treatment protocols to improve the clinical outcomes of patients with ATAAD complicated by mesenteric malperfusion. METHODS: This was a retrospective study that covered a five-year period. From July 2018 to December 2020(phase I), all patients underwent emergency open surgery. From January 2021 to June 2023(phase II), patients with an onset within 6 h all underwent open surgical repair, followed by immediately postoperative examination if the malperfusion is suspected, while the restoration of mesenteric perfusion and visceral organ function was performed first, followed by open repair, in patients with an onset beyond 6 h. RESULTS: There were no significant differences in baseline and surgical data. In phase I, eleven patients with mesenteric malperfusion underwent open surgery, while in phase II, our novel strategy was applied, with sixteen patients with an onset greater than 6 h and eleven patients with an onset less than 6 h. During the waiting period, none died of aortic rupture, but four patients died of organ failure, twelve patients had organ function improvement and underwent surgery successfully survived. The overall mortality rate decreased with the use of this novel strategy (54.55% vs. 18.52%, p = 0.047). Furthermore, the surgical mortality rate between the two periods showed even stronger statistical significance (54.55% vs. 4.35%, p = 0.022). Moreover, the proportions of patients with sepsis and multiorgan failure also showed differences. CONCLUSIONS: Our novel strategy for patients with ATAAD complicated by mesenteric malperfusion not only improves the surgical success rate but also reduces the overall mortality rate.

YTHDF1 promotes gallbladder cancer progression via post-transcriptional regulation of the m6A/UHRF1 axis.

Gallbladder cancer is a rare but fatal malignancy. However, the mechanisms underlying gallbladder carcinogenesis and its progression are poorly understood. The function of m6A modification and its regulators was still unclear for gallbladder cancer. The current study seeks to investigate the function of YTH m6A RNA-binding protein 1 (YTHDF1) in gallbladder cancer. Transcriptomic analysis and immunochemical staining of YTHDF1 in gallbladder cancer tissues revealed its upregulation compared to paracancerous tissues. Moreover, YTHDF1 promotes the proliferation assays, Transwell migration assays, and Transwell invasion assays of gallbladder cancer cells in vitro. And it also increased tumour growth in xenograft mouse model and metastases in tail vein injection model in vivo. In vitro, UHRF1 knockdown partly reversed the effects of YTHDF1 overexpression. Mechanistically, dual-luciferase assays proved that YTHDF1 promotes UHRF1 expression via direct binding to the mRNA 3'-UTR in a m6A-dependent manner. Overexpression of YTHDF1 enhanced UHRF1 mRNA stability, as demonstrated by mRNA stability assays, and Co-IP studies confirmed a direct interaction between YTHDF1 and PABPC1. Collectively, these findings provide new insights into the progression of gallbladder cancer as well as a novel post-transcriptional mechanism of YTHDF1 via stabilizing target mRNA.

Effects of female bone marrow transplantation on male reproductive organs.

Graft-versus-host disease (GVHD), an adverse effect after bone marrow transplantation (BMT), may affect male reproductive function. It is hypothesized that a sex-mismatched BMT induces GVHD in male reproductive organs because female immune cells are not immunologically tolerant to specific antigens of the male organs. However, this hypothesis has not been experimentally verified using male (M) recipient animals following BMT from the female (F) donors. Therefore, the aim of the present study is to examine whether the female BMT to males (F→M group) induces some GVHD reactions in the testis and the other male reproductive organs. The results showed that no inflammation was found in recipients of the male BMT to males (M→M group), whereas significant inflammatory cell responses lasting for at least 4 months were induced in testis, epididymis, prostate and preputial gland in some mice of F→M group. The most severe lesion was found in the preputial gland, in which lymphocytic inflammation was accompanied by loss of glandular acini, thickening of the interstitum and increased cytokines such as TNF-α and IFN-γ. Western blot analyses revealed that sera from the F→M group reacted with various antigens of the male reproductive organs. These results indicate that transplanted female immune cells may recognize the male reproductive organs as immunologically foreign ones and induce chronic GVHD, which may affect male reproductive function.

Removal effect of pollutants from stormwater runoff in shallow bioretention system with gramineous plants.

The bioretention system is one of the most widely used low impact development (LID) facilities with efficient purification capacity for stormwater, and its planting design has been a hot spot for research at home and abroad. In this paper, ryegrass (Lolium perenne L.), bermuda (Cynodon dactylon Linn.), bahiagrass (Paspalum notatum Flugge), and green grass (Cynodon dactylon × C .transadlensis 'Tifdwarf') were chosen as plant species to construct a shallow bioretention system. The growth traits and nutrient absorption ability of four gramineous plants were analyzed. Their tolerance, enrichment, and transportation capacity were also evaluated to compare plant species and their absorptive capacity of heavy metals (Cu, Pb, and Zn). Results showed that the maximum absorption rate (Imax) ranged from 22.1 to 42.4 µg/(g·h) for P and ranged from 65.4 to 104.8 µg/(g·h) for NH4+-N; ryegrass had the strongest absorption capacity for heavy metals and the maximum removal rates of Cu, Pb, and Zn by four grasses were 78.4, 59.4, and 51.3%, respectively; the bioretention cell with ryegrass (3#) was significantly more effective in purifying than the unplanted bioretention cell (1#) during the simulated rainfall test. Overall, the system parameters were optimized to improve the technical application of gramineous plants in the bioretention system.

Pembrolizumab Versus Placebo as Adjuvant Therapy in Resected Stage IIB or IIC Melanoma: Final Analysis of Distant Metastasis-Free Survival in the Phase III KEYNOTE-716 Study.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.Pembrolizumab adjuvant therapy was shown to significantly improve recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) in patients with resected stage IIB or IIC melanoma in earlier analyses of the randomized, double-blind, phase III KEYNOTE-716 study (ClinicalTrials.gov identifier: NCT03553836). We report results of the protocol-specified final analysis of DMFS for KEYNOTE-716. Overall, 976 patients were randomly allocated to pembrolizumab (n = 487) or placebo (n = 489). As of January 4, 2023, median follow-up was 39.4 months (range, 26.0-51.4 months). The median DMFS was not reached in either treatment group, and the estimated 36-month DMFS was 84.4% for pembrolizumab and 74.7% for placebo (hazard ratio [HR], 0.59 [95% CI, 0.44 to 0.79]). The median RFS was not reached in either treatment group, and the estimated 36-month RFS was 76.2% for pembrolizumab and 63.4% for placebo (HR, 0.62 [95% CI, 0.49 to 0.79]). DMFS and RFS results were consistent across most prespecified subgroups, including stage IIB and stage IIC melanoma. The safety profile of pembrolizumab was manageable and consistent with previous reports. These results continue to support the use of pembrolizumab adjuvant therapy in patients with resected stage IIB or IIC melanoma.

[Diffuse Hepatoid Adenocarcinoma in the Peritoneal Cavity:Report of One Case].

Hepatoid adenocarcinoma is a rare and unique type of adenocarcinoma,resembling hepatocellular carcinoma in histopathology.Most cases occur in the stomach,lacking specific clinical and imaging manifestations,which leads to high rates of missed diagnosis and misdiagnosis.Hepatoid adenocarcinoma in the peritoneal cavity is even rarer.This article reports a case of hepatoid adenocarcinoma with the manifestation of diffuse peritoneal thickening,aiming to provide reference for clinical diagnosis and treatment.

Fat mass and obesity-associated protein (FTO) mediated m6A modification of circFAM192A promoted gastric cancer proliferation by suppressing SLC7A5 decay.

Gastric cancer (GC) is a common malignant tumor worldwide, especially in East Asia, with high incidence and mortality rate. Epigenetic modifications have been reported to participate in the progression of gastric cancer, among which m6A is the most abundant and important chemical modification in RNAs. Fat mass and obesity-associated protein (FTO) is the first identified RNA demethylase but little is known about its role in gastric cancer. In our study, data from TCGA and clinical samples showed that FTO was highly expressed in gastric cancer tissues. Kaplan-Meier plotter suggested that patients with the high level of FTO had a poor prognosis. In vitro and in vivo experiments confirmed the role of FTO in promoting gastric cancer cell proliferation. Mechanistically, we found that FTO bound to circFAM192A at the specific site and removed the m6A modification in circFAM192A, protecting it from degradation. CircFAM192A subsequently interacted with the leucine transporter solute carrier family 7 member 5 (SLC7A5) and enhancing its stability. As a result, an increased amount of SLC7A5 was on the membrane, which facilitated leucine uptake and activated the mTOR signaling pathway. Therefore, our study demonstrated that FTO promoted gastric cancer proliferation through the circFAM192A/SLC7A5 axis in the m6A-dependent manner. Our study shed new light on the role of FTO in gastric cancer progression.

The plant-like protein phosphatase PPKL regulates parasite replication and morphology in Toxoplasma gondii.

BACKGROUND: The protozoan parasite Toxoplasma gondii encodes dozens of phosphatases, among which a plant-like phosphatase absent from mammalian genomes named PPKL, which is involved in regulating brassinosteroid signaling in Arabidopsis, was identified in the genome. Among the Apicomplexa parasites, T. gondii is an important and representative pathogen in humans and animals. PPKL was previously identified to modulate the apical integrity and morphology of the ookinetes and parasite motility and transmission in another important parasite, Plasmodium falciparum. However, the exact function of PPKL in the asexual stages of T. gondii remains unknown. METHODS: The plant auxin-inducible degron (AID) system was applied to dissect the phenotypes of PPKL in T. gondii. We first analyzed the phenotypes of the AID parasites at an induction time of 24 h, by staining of different organelles using their corresponding markers. These analyses were further conducted for the parasites grown in auxin for 6 and 12 h using a quantitative approach and for the type II strain ME49 of AID parasites. To further understand the phenotypes, the potential protein interactions were analyzed using a proximity biotin labeling approach. The essential role of PPKL in parasite replication was revealed. RESULTS: PPKL is localized in the apical region and nucleus and partially distributed in the cytoplasm of the parasite. The phenotyping of PPKL showed its essentiality for parasite replication and morphology. Further dissections demonstrate that PPKL is required for the maturation of daughter parasites in the mother cells, resulting in multiple nuclei in a single parasite. The phenotype of the daughter parasites and parasite morphology were observed in another type of T. gondii strain ME49. The substantial defect in parasite replication and morphology could be rescued by genetic complementation, thus supporting its essential function for PPKL in the formation of parasites. The protein interaction analysis showed the potential interaction of PPKL with diverse proteins, thus explaining the importance of PPKL in the parasite. CONCLUSIONS: PPKL plays an important role in the formation of daughter parasites, revealing its subtle involvement in the proper maturation of the daughter parasites during division. Our detailed analysis also demonstrated that depletion of PPKL resulted in elongated tubulin fibers in the parasites. The important roles in the parasites are potentially attributed to the protein interaction mediated by kelch domains on the protein. Taken together, these findings contribute to our understanding of a key phosphatase involved in parasite replication, suggesting the potential of this phosphatase as a pharmaceutic target.

The Emotion Regulation of Acupuncture in Chronic Low Back Pain: A Clinical Neuroimaging Protocol.

Introduction: Acupuncture is effective for patients with chronic low back pain (CLBP), which can relieve pain intensity and regulate negative emotional states such as pain-related anxiety and depression. Previous studies mainly discuss the analgesic mechanism of acupuncture treatment of CLBP, but there are multiple dimensions to pain, including sensation, emotion and cognition. Therefore, this study aims to investigate the central mechanism of acupuncture for CLBP from the perspective of emotional regulation by functional magnetic resonance imaging (fMRI). Methods and Analysis: A total of 72 patients with CLBP will be recruited in the study and randomly assigned to the verum acupuncture group or the sham acupuncture group. The trail will last for 18 weeks including a 2-week baseline, a 4-week treatment and a 12-week for follow-up period. The primary outcomes are the visual analog scale (VAS) and the Japanese Orthopaedic Association Scores (JOA) score. The secondary outcomes are the 12-item short form health survey (SF-12), the state trait anxiety inventory (STAI), the self-rating anxiety scale (SAS) and self-rating depression scale (SDS). The VAS, JOA, STAI SAS and SDS will be collected at baseline, week 2, week 4, and after follow-up. The SF-12 will be evaluated at baseline, week 2 and week 4. Functional magnetic resonance imaging (MRI) data will be collected at baseline and the end of treatment. Emotion-related brain regions will be chosen as regions of interest (ROIs). The gray matter volume (GMV), amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), functional connectivity (FC), and large-scale functional brain network based on these ROIs will be analyzed within and between the two groups. Discussion: This study will verify the emotional regulation of acupuncture and explore the mechanism of acupuncture for emotion regulation in patients with CLBP. Trial Registration Number: https://www.chictr.org.cn/showproj.html?proj=195486, identifier: ChiCTR2300070557.