Vision Improvement in Keratoconus Patients Trained with Perceptual Learning: A Randomized Controlled Trial.

BACKGROUND: Keratoconus (KC) is a corneal ectasia disease in which the vision of some patients cannot achieve satisfaction by spectacle corrections. However, not everyone can embrace contact lenses to achieve better vision. Perceptual learning (PL) is a potential treatment for vision improvement in such patients. PURPOSE: To investigate the effectiveness and maintenance of PL on vision improvement in KC patients corrected with spectacles. DESIGN: Randomized, double-blind clinical trial. PARTICIPANTS: Thirty-five non-progressive KC patients aged 9 years or older with unsatisfied spectacle-corrected vision were enrolled. METHODS: Non-progressive KC patients with best spectacle-corrected distance visual acuity (CDVA) of 0 to 1.0 logMAR (Snellen equivalent range 20/20 to 20/200) and contact lenses intolerant were enrolled. Eligible subjects were randomized into PL and control groups to receive PL and placebo training for 3 months, respectively. Spectacle-corrected visual acuity, contrast sensitivity function (CSF), stereoacuity, and visual functioning and quality of life questionnaires were measured at baseline, 3 months, and 6 months of follow-up. Statistics were analyzed following the intention-to-treat (ITT) principle. RESULTS: After 3 months of training, the CDVA of patients in the PL group improved as compared to the placebo group (0.17 ± 0.15 logMAR vs. 0.02 ± 0.06 logMAR; P = 0.0006). Eight out of seventeen (47.06 %) patients in the PL group reached CDVA improvement ≥ 2 lines (P=0.0010). This improvement persisted for at least 6 months (from baseline) as compared to the placebo group (0.17 ± 0.17 logMAR vs. 0.01 ± 0.07 logMAR; P = 0.0011). The increase of CSF in the PL group mainly was found for moderate spatial frequency (0.11 ± 0.17 log units at 3 cpd; 0.12 ± 0.19 log units at 6 cpd). Linear regression indicated that patients with worse initial CDVA achieved better gains in CDVA after PL (P = 0.009). No side effects were observed and no subjects quit because of training difficulties. CONCLUSION: Three-month perceptual learning improved vision in KC patients and the improvement maintained after 3 months of treatment cessation. The results indicate that perceptual learning may be a promising therapy for KC patients with unsatisfied spectacle-corrected visual acuity.

The Respiratory Burst Oxidase Homologue OsRBOHE is crucial for root hair formation, drought resistance and tillering in rice.

Respiratory Burst Oxidase Homologues (RBOHs) are involved in plant growth, development, and stress adaptation. How OsRBOHs affect root hair formation and consequently nutrient acquisition and drought resistance in rice is not well understood. We knocked out six OsRBOH genes in rice that were expressed in roots and identified OsRBOHE as the only one affecting root hair formation. OsRBOHE was strongly expressed in the root epidermis, root hairs and tiller buds. OsRBOHE is localised at the plasma membrane. Knockout of OsRBOHE decreased reactive oxygen species generation in the root hairs and tiller buds, downregulated genes involved in cell wall biogenesis, and decreased root hair length and tillering by 90% and 30%, respectively. Knockout of OsRBOHE decreased phosphorus acquisition only in low available P soil under aerobic conditions, but not in high P soil or under flooded conditions when P was likely not limited by diffusion. Knockout of OsRBOHE markedly decreased drought resistance of rice plants through the effect on root hair formation and the associated rhizosheath. Taken together, OsRBOHE is crucial for root hair formation and tillering and consequently on drought resistance in rice. The contribution of root hairs to P acquisition in rice is limited to aerobic soil.

Human leukocyte antigen evolutionary divergence as a novel risk factor for donor selection in acute lymphoblastic leukemia patients undergoing haploidentical hematopoietic stem cell transplantation.

Introduction: The human leukocyte antigen (HLA) evolutionary divergence (HED) reflects immunopeptidome diversity and has been shown to predict the response of tumors to immunotherapy. Its impact on allogeneic hematopoietic stem cell transplantation (HSCT) is controversial in different studies. Methods: In this study, we retrospectively analyzed the clinical impact of class I and II HED in 225 acute lymphoblastic leukemia patients undergoing HSCT from related haploidentical donors. The HED for recipient, donor, and donor-recipient pair was calculated based on Grantham distance, which accounts for variations in the composition, polarity, and volume of each amino acid within the peptide-binding groove of two HLA alleles. The median value of HED scores was used as a cut-off to stratify patients with high or low HED. Results: The class I HED for recipient (R_HEDclass I) showed the strongest association with cumulative incidence of relapse (12.2 vs. 25.0%, P = 0.00814) but not with acute graft-versus-host disease. The patients with high class II HED for donor-recipient (D/R_HEDclass II) showed a significantly higher cumulative incidence of severe aGVHD than those with low D/R_HEDclass II (24.0% vs. 6.1%, P = 0.0027). Multivariate analysis indicated that a high D/R_HEDclass II was an independent risk factor for the development of severe aGVHD (P = 0.007), and a high R_HEDclass I had a more than two-fold reduced risk of relapse (P = 0.028). However, there was no discernible difference in overall survival (OS) or disease-free survival (DFS) for patients with high or low HED, which was inconsistent with the previous investigation. Discussion: While the observation are limited by the presented single center retrospective cohort, the results show that HED has poor prognostic value in OS or DFS, as well as the associations with relapse and aGVHD. In haploidentical setting, class II HED for donor-recipient pair (D/R_HEDclass II) is an independent and novel risk factor for finding the best haploidentical donor, which could potentially influence clinical practice if verified in larger cohorts.

Pichia pastoris composition expressed aerolysin mutant of Aeromonas veronii as an oral vaccine evaluated in zebrafish (Danio rerio).

Vaccines are one of the most practical means to stop the spreading of Aeromonas veronii in aquaculture. In this study, virulence factor aerolysin mutant NTaer which has lost its hemolytic activity was used as a target antigen. Pichia pastoris constitutive secretory expression NTaer (GS115-NTaer) was used as a potential safe oral vaccine to evaluate its effectiveness on zebrafish immunity. The result shows that vaccination of GS115- NTaer for four weeks did not affect the growth performance of the host, while eliciting an effective immune protective response. Compared with the control group, the GS115-NTaer could significantly up-regulate the relative expression level of the intestinal tight junction protein 1α (TJP1α) gene, and significantly increased the contents of lysozyme (LYZ), complement C3 and C4 in the gut, indicating that the innate immune response of the fish was activated. The relative gene expression levels of macrophage-expressed gene 1 (MPEG1) and T cell receptor (TCR-α) in the gut, and MPEG1, CD4, CD8, TCR-α, GATA3, and T-bet in the spleen were all increased significantly, indicating that the cellular immune response of the fish was activated. Furthermore, the contents of serum IgM and intestinal mucosa IgZ antibodies were significantly increased, which showed that humoral immunity was also activated. Moreover, inoculation with GS115-NTaer significantly changed the structure of gut microbiota. In particular, the relative ratio of (Firmicutes + Fusobacteriota + Bacteroidota)/Proteobacteria was significantly higher than that of the control and GS115 groups. Lastly, the vaccinated fish were challenged with A. veronii, and the relative percent survival of GS115 and the GS115-NTear groups was 14.28% and 33.43%. This improvement of immunity was not only due to the specific immune response but also attributed to the improvement of innate immunity and the gut microbiota which was demonstrated by the germ-free zebrafish model. Collectively, this study provides information on the effectiveness of GS115-NTear as an oral vaccine for the green prevention and control of A. veronii infection in fish aquaculture.

Immune infiltration and prognosis in gastric cancer: role of NAD+ metabolism-related markers.

Background: This study endeavored to develop a nicotinamide adenine dinucleotide (NAD+) metabolism-related biomarkers in gastric cancer (GC), which could provide a theoretical foundation for prognosis and therapy of GC patients. Methods: In this study, differentially expressed genes (DEGs1) between GC and paraneoplastic tissues were overlapped with NAD+ metabolism-related genes (NMRGs) to identify differentially expressed NMRGs (DE-NMRGs). Then, GC patients were divided into high and low score groups by gene set variation analysis (GSVA) algorithm for differential expression analysis to obtain DEGs2, which was overlapped with DEGs1 for identification of intersection genes. These genes were further analyzed using univariate Cox and least absolute shrinkage and selection operator (LASSO) regression analyses to obtain prognostic genes for constructing a risk model. Enrichment and immune infiltration analyses further investigated investigate the different risk groups, and qRT-PCR validated the prognostic genes. Results: Initially, we identified DE-NMRGs involved in NAD biosynthesis, with seven (DNAJB13, CST2, THPO, CIDEA, ONECUT1, UPK1B and SNCG) showing prognostic significance in GC. Subsequent, a prognostic model was constructed in which the risk score, derived from the expression profiles of these genes, along with gender, emerged as robust independent predictors of patient outcomes in GC. Enrichment analysis linked high-risk patients to synaptic membrane pathways and low-risk to the CMG complex pathway. Tumor immune infiltration analysis revealed correlations between risk scores and immune cell abundance, suggesting a relationship between NAD+ metabolism and immune response in GC. The prognostic significance of our identified genes was validated by qRT-PCR, which confirmed their upregulated expression in GC tissue samples. Conclusion: In this study, seven NAD+ metabolism-related markers were established, which is of great significance for the development of prognostic molecular biomarkers and clinical prognosis prediction for gastric cancer patients.

Water Impact Dynamics and Mechanism Analysis of Polypropylene and Polypropylene/poly(ethylene-co-octene) Replica Surfaces with Nanowires under Low Temperature Conditions.

In this work, polypropylene (PP) and PP/poly(ethylene-co-octene) (PP/POE) blend replica surfaces with densely arranged nanowires are fabricated using a molding process. Morphology analysis shows that the nanowires on these replica surfaces have sharp tips and high aspect ratios. The droplet impact behaviors on the surfaces of the PP/POE blend replicas and PP replicas are investigated before and after freezing at -20 °C for 4 h. The height of the nanowires on the PP/POE blend replica surfaces is higher than that on the PP surface before and after freezing. The static wettability and droplet impact tests on the surfaces of PP/POE blend replicas and PP replica show that adding POE into the PP matrix can significantly increase the toughness of the nanowires on the PP/POE blend replica surfaces during the droplet impact at low temperatures. These investigations are favorable to broaden the practical applications of superhydrophobic surfaces in some severe environments.

Navigating the labyrinth of long non-coding RNAs in colorectal cancer: From chemoresistance to autophagy.

Long non-coding RNAs (lncRNAs), with transcript lengths exceeding 200 nucleotides and little or no protein-coding capacity, have been found to impact colorectal cancer (CRC) through various biological processes. LncRNA expression can regulate autophagy, which plays dual roles in the initiation and progression of cancers, including CRC. Abnormal expression of lncRNAs is associated with the emergence of chemoresistance. Moreover, it has been confirmed that targeting autophagy through lncRNA regulation could be a viable approach for combating chemoresistance. Two recent studies titled "Human ß-defensin-1 affects the mammalian target of rapamycin pathway and autophagy in colon cancer cells through long non-coding RNA TCONS_00014506" and "Upregulated lncRNA PRNT promotes progression and oxaliplatin resistance of colorectal cancer cells by regulating HIPK2 transcription" revealed novel insights into lncRNAs associated with autophagy and oxaliplatin resistance in CRC, respectively. In this editorial, we particularly focus on the regulatory role of lncRNAs in CRC-related autophagy and chemoresistance since the regulation of chemotherapeutic sensitivity by intervening with the lncRNAs involved in the autophagy process has become a promising new approach for cancer treatment.

Development and Validation of a Carbohydrate Metabolism-Related Model for Predicting Prognosis and Immune Landscape in Hepatocellular Carcinoma Patients.

OBJECTIVE: The activities and products of carbohydrate metabolism are involved in key processes of cancer. However, its relationship with hepatocellular carcinoma (HCC) is unclear. METHODS: The cancer genome atlas (TCGA)-HCC and ICGC-LIRI-JP datasets were acquired via public databases. Differentially expressed genes (DEGs) between HCC and control samples in the TCGA-HCC dataset were identified and overlapped with 355 carbohydrate metabolism-related genes (CRGs) to obtain differentially expressed CRGs (DE-CRGs). Then, univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses were applied to identify risk model genes, and HCC samples were divided into high/low-risk groups according to the median risk score. Next, gene set enrichment analysis (GSEA) was performed on the risk model genes. The sensitivity of the risk model to immunotherapy and chemotherapy was also explored. RESULTS: A total of 8 risk model genes, namely, G6PD, PFKFB4, ACAT1, ALDH2, ACYP1, OGDHL, ACADS, and TKTL1, were identified. Moreover, the risk score, cancer status, age, and pathologic T stage were strongly associated with the prognosis of HCC patients. Both the stromal score and immune score had significant negative/positive correlations with the risk score, reflecting the important role of the risk model in immunotherapy sensitivity. Furthermore, the stromal and immune scores had significant negative/positive correlations with risk scores, reflecting the important role of the risk model in immunotherapy sensitivity. Eventually, we found that high-/low-risk patients were more sensitive to 102 drugs, suggesting that the risk model exhibited sensitivity to chemotherapy drugs. The results of the experiments in HCC tissue samples validated the expression of the risk model genes. CONCLUSION: Through bioinformatic analysis, we constructed a carbohydrate metabolism-related risk model for HCC, contributing to the prognosis prediction and treatment of HCC patients.

Polysaccharide fraction from Triplostegia glandulifera Wall and its renoprotective effect in streptozotocin-induced diabetic mice by attenuating oxidative stress.

Triplostegia glandulifera Wall (T. glandulifera) is an ethnomedicine commonly used by ethnic minorities in Yunnan, China, to treat kidney disease. However, there are few reports on the renoprotective effects of this substance, and the active ingredients remain unclear. In this study, we extracted the polysaccharide fractions TGB and TGC using the water extraction-alcohol precipitation method and determined their molecular weight (Mw) and monosaccharide composition. The study investigated the protective effects of TGB and TGC fractions against diabetic nephropathy (DN) using an in vitro high glucose-induced HRMCs model and an in vivo STZ-induced diabetic mouse model. HPLC analysis revealed that TGB contained D-galacturonic acid, D-glucose, D-galactose, and D-arabinose, and had a lower Mw than TGC. In vitro, TGB showed concentration-dependent antioxidant activity and effectively reduced abnormal proliferation and while attenuating oxidative stress in HRMCs. In mice with diabetes, TGB corrected the dysregulation of glucose-lipid metabolism and alleviated oxidative stress in the kidneys. Additionally, it improved renal function and reduced renal tissue damage. The study suggests that the low Mw polysaccharides (TGB) have better activity against DN through the antioxidative stress mechanism.

Isotropic Quantum Griffiths Singularity in Nd_{0.8}Sr_{0.2}NiO_{2} Infinite-Layer Superconducting Thin Films.

This work reports on the emergence of quantum Griffiths singularity (QGS) associated with the magnetic field induced superconductor-metal transition (SMT) in unconventional Nd_{0.8}Sr_{0.2}NiO_{2} infinite layer superconducting thin films. The system manifests isotropic SMT features under both in-plane and perpendicular magnetic fields. Importantly, after scaling analysis of the isothermal magnetoresistance curves, the obtained effective dynamic critical exponents demonstrate divergent behavior when approaching the zero-temperature critical point B_{c}^{*}, identifying the QGS characteristics. Moreover, the quantum fluctuation associated with the QGS can quantitatively explain the upturn of the upper critical field around zero temperature for both the in-plane and perpendicular magnetic fields in the phase boundary of SMT. These properties indicate that the QGS in the Nd_{0.8}Sr_{0.2}NiO_{2} superconducting thin film is isotropic. Moreover, a higher magnetic field gives rise to a metallic state with the resistance-temperature relation R(T) exhibiting lnT dependence among the 2-10 K range and T^{2} dependence of resistance below 1.5 K, which is significant evidence of Kondo scattering. The interplay between isotropic QGS and Kondo scattering in the unconventional Nd_{0.8}Sr_{0.2}NiO_{2} superconductor can illustrate the important role of rare region in QGS and help to uncover the exotic superconductivity mechanism in this system.

Association between sensory processing sensitivity and quality of life among cancer patients: a mediation and moderation of resilience and social determinants.

BACKGROUND: Individuals with sensory processing sensitivity (SPS) tend to be overreactive in response to negative environmental stimuli. More is known about the positive relationship between SPS and quality of life (QoL); nevertheless, less is known regarding the roles of resilience and social determinants in this association. This research aimed to investigate the potential mediation effect of resilience and the moderation effect of social determinants on the relationship between SPS and QoL in a large sample of Chinese cancer patients. METHODS: We used the most recent datasets from an ongoing project conducted in southwest China. A two-stage random sampling strategy with a probability proportionate to sample size (PPS) design was adopted. The associations between resilience, SPS, and QoL were evaluated using a linear regression model. Path analysis was adopted to examine the mediation of resilience. RESULTS: Resilience was positively associated with quality of life, while increased sensory processing sensitivity was negatively associated with quality of life. The restricted cubic spline analysis revealed that as resilience increased, the coefficients of quality of life rapidly increased across all domains. Conversely, the coefficients for quality of life gradually decreased with the escalation of sensory processing sensitivity. Resilience was a significant mediator, accounting for 21.88% of the total SPS-QoL association. The mediation effect of resilience varied across ethnicity and sex. CONCLUSION: Sensory processing sensitivity was significantly associated with quality of life in cancer patients, and promoting resilience could mitigate this negative impact. However, the effect of resilience varies across sex and ethnicity. Therefore, targeted resilience promotion interventions, especially those integrating social characteristics, should be considered for implementation.

[One-stage posterior debridement and spinal internal fixation for the treatment of lumbar Brucellar spondylitis].

OBJECTIVE: To explore the clinical efficacy and safety of one-stage posterior lesion removal and internal spinal fixation in patients with lumbar Brucellosis spondylitis. METHODS: The clinical data of 24 patients admitted from October 2017 to October 2022 were retrospectively analyzed, 2 patients were lost to follow-up at 10 months after surgery, at the final 22 cases were included in the study, including 13 males and 9 females with an average age of (52.00±6.89) years old, were treated with one-stage posterior lesion removal and internal spinal fixation. The operation time, intraoperative bleeding, follow-up time, erythrocyte sedimentation rate(ESR) and C-reactive protein(CRP) before and after operation were recorded. The pain visual analogue scale(VAS), Oswestry disability index(ODI), the Japanese Orthopaedic Association(JOA) score for neurofunction, American Spinal Injury Association(ASIA) spinal cord injury grade and modified MacNab criteria were ussed to evaluate the efficacy. RESULTS: All patients were followed up from 12 to 30 months with an average of (17.41±4.45) months. The operation time was 70 to 155 min with an average of (116.59±24.32) min;the intraoperative bleeding volume was 120 to 520 ml with an average of (275.00±97.53) ml. CRP and ESR levels decreased more significantly at 1 week and at the final follow-up than preoperative levels(P<0.05). VAS, JOA score and ODI at 1 week and at the latest follow-up were more significantly improved than preoperative results(P<0.05). There was no significant difference between ASIA preoperative and 1 week after operation(P>0.05), and a significant difference between preoperative and last follow-up(P<0.05). In the final follow-up, 21 patients had excellent efficacy, 1 patient had fair, and there was no recurrence during the follow-up. CONCLUSION: One-stage transpedicular lesion removal and internal spinal fixation, with few incisions and short operation time, helps the recovery of neurological function, and the prognosis meets the clinical requirements, which can effectively control Brucella spondylitis.

EWS-WT1 fusion isoforms establish oncogenic programs and therapeutic vulnerabilities in desmoplastic small round cell tumors.

EWS fusion oncoproteins underlie several human malignancies including Desmoplastic Small Round Cell Tumor (DSRCT), an aggressive cancer driven by EWS-WT1 fusion proteins. Here we combine chromatin occupancy and 3D profiles to identify EWS-WT1-dependent gene regulation networks and target genes. We show that EWS-WT1 is a powerful chromatin activator controlling an oncogenic gene expression program that characterizes primary tumors. Similar to wild type WT1, EWS-WT1 has two isoforms that differ in their DNA binding domain and we find that they have distinct DNA binding profiles and are both required to generate viable tumors that resemble primary DSRCT. Finally, we identify candidate EWS-WT1 target genes with potential therapeutic implications, including CCND1, whose inhibition by the clinically-approved drug Palbociclib leads to marked tumor burden decrease in DSRCT PDXs in vivo. Taken together, our studies identify gene regulation programs and therapeutic vulnerabilities in DSRCT and provide a mechanistic understanding of the complex oncogenic activity of EWS-WT1.

Enhanced interleukin-16-CD4 signaling in CD3 T cell mediates neuropathic pain via activating astrocytes in female mice.

Immune cells and interleukins play a crucial role in female-specific pain signaling. Interleukin 16 (IL-16) is a cytokine primarily associated with CD4+ T cell function. While previous studies have demonstrated the important role of spinal CD4+ T cells in neuropathic pain, the specific contribution of IL-16 to neuropathic pain remains unclear. In this study, by using a spinal nerve ligation (SNL)-induced neuropathic pain mice model, we found that SNL induced an increase in IL-16 mRNA levels, which persisted for a longer duration in female mice compared to male mice. Immunofluorescence analysis further confirmed enhanced IL-16- and CD4-positive signals in the spinal dorsal horn following SNL surgery in female mice. Knockdown of spinal IL-16 by siRNA or inhibition of CD4 by FGF22-IN-1, a CD4 inhibitor, attenuated established mechanical and thermal pain hypersensitivity induced by SNL. Furthermore, female mice injected with IL-16 intrathecally exhibited significant spontaneous pain, mechanical and thermal hyperalgesia, all of which could be alleviated by FGF22-IN-1 or a CD3 antibody. Additionally, IL-16 induced astrocyte activation but not microglial activation in the spinal dorsal horn of female mice. Meanwhile, astrocyte activation could be suppressed by the CD3 antibody. These results provide compelling evidence that IL-16 promotes astrocyte activation via CD4 on CD3+ T cells, which is critical for maintaining neuropathic pain in female mice.

Lewis Acid-Driven Multicomponent Reactions Enable 2-Alkyl Chromanones with Anticancer Activities.

2-Alkyl chromanone scaffold has become prominent in pharmaceuticals and natural compounds. Consequently, devising robust strategies for synthesizing 2-alkyl chromanones remains crucial. Here, multicomponent reactions were employed to synthesize 2-alkyl chromanones containing an oxazole moiety using 3-formylchromones, amines, and N-propargylamides as reactants. This method utilizes readily available feedstocks with a catalytic amount of Zn(OTf)2 and exhibits an impressive substrate scope compared to existing methods. Importantly, the synthesized compounds demonstrated highly selective anticancer activity against the DU145 cell line.

Suicidal incidence and gender-based discrepancies in prolonged grief disorder: insights from a meta-analysis and systematic review.

Background: In the aftermath of bereavement, our research explores the subtleties of Prolonged Grief Disorder (PGD), focusing particularly on its correlation with suicidal behaviors and their variation across genders. This study seeks to elucidate the impact of gender on these behaviors among individuals suffering from PGD, thereby enhancing our understanding and facilitating the development of tailored therapeutic interventions. Methods: By November 24th, 2023, we had rigorously reviewed key databases such as PubMed, Web of Science, Cochrane Library, PsycINFO, and Embase. Independently, two researchers conducted detailed interviews and filled out questionnaires with participants to gather demographic information and record instances of prolonged grief disorder. The study also meticulously tracked occurrences of suicidal ideation, suicide attempts, suicide deaths, and self-injury among the participants. Results: The findings indicate that 22.34% of males reported suicidal ideation (95% CI: 21.33-23.35), a figure that rises to 26.84% among females (95% CI: 25.99-27.69). Notably, 12.11% of males attempted suicide (95% CI: 11.49-12.72), marginally surpassing the 9.60% observed in females (95% CI: 9.17-10.04). More striking disparities were observed in suicide deaths, with rates for males at 3.66% (95% CI: 3.32-4.00) compared to a notably higher 7.12% for females (95% CI: 6.44-7.81). Furthermore, the incidence of self-injury was lower among males, at 2.48% (95% CI: 2.03-2.94), than in females, who reported a rate of 5.09% (95% CI: 4.69-5.49). These patterns underscore the critical need for gender-specific interventions aimed at reducing these significant disparities. Conclusion: This study distinctly underscores the profound impact of gender on the manifestation of suicidal behaviors in individuals afflicted with prolonged grief disorder. It reveals that females are more prone to suicidal ideation, self-injury, and suicide deaths, while males predominantly exhibit a higher incidence of suicide attempts and risk-taking behaviors. These unmediated trends highlight the necessity for gender-specific clinical interventions tailored to address particular behaviors and modify prevalent patterns that typically resist conventional approaches. Systematic review registration: PROSPERO (york.ac.uk), identifier CRD42023480035.

Identification and Prediction of Differentially Expressed MicroRNAs Associated with Detoxification Pathways in Larvae of Spodoptera frugiperda.

Spodoptera frugiperda poses a severe threat to crops, causing substantial economic losses. The increased use of chemical pesticides has led to resistance in S. frugiperda populations. Micro ribonucleic acids (MicroRNAs or miRNAs) are pivotal in insect growth and development. This study aims to identify miRNAs across different developmental stages of S. frugiperda to explore differential expression and predict target gene functions. High-throughput sequencing of miRNAs was conducted on eggs, 3rd instar larvae, pupae, and adults. Bioinformatics analyses identified differentially expressed miRNAs specifically in larvae, with candidate miRNAs screened to predict target genes, particularly those involved in detoxification pathways. A total of 184 known miRNAs and 209 novel miRNAs were identified across stages. Comparative analysis revealed 54, 15, and 18 miRNAs differentially expressed in larvae, compared to egg, pupa, and adult stages, respectively. Eight miRNAs showed significant differential expression across stages, validated by quantitative reverse transcription PCR (qRT-PCR). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses predicted target genes' functions, identifying eight differentially expressed miRNAs targeting 10 gene families associated with detoxification metabolism, including P450s, glutathione S-transferase (GSTs), ATP-binding cassette (ABC) transporters, and sodium channels. These findings elucidate the species-specific miRNA profiles and regulatory mechanisms of detoxification-related genes in S. frugiperda larvae, offering insights and strategies for effectively managing this pest.

Discovery of a novel Xanthone derivative P24 for anti-AD via targeting sTGFBR3.

Soluble transforming growth factor beta receptor 3 (sTGFBR3) antagonist is a new focus in the research and development of Alzheimer's disease (AD) drugs. Our previous studies have identified sTGFBR3 as a promising new target for AD, with few targeted antagonists identified. In this study, we performed structural modeling of sTGFBR3 using AlphaFold2, followed by high-throughput virtual screening and surface plasmon resonance assays. which collectively identified Xanthone as potential compounds for targeting sTGFBR3. After optimizing the sTGFBR3-Xanthone complex using molecular dynamics (MD) simulations, we prepared a series of novel Xanthone derivatives and evaluated their anti-inflammatory activity, toxicity, and structure-activity relationship in BV2 cell model induced by lipopolysaccharides (LPS) or APP/PS1/tau mouse brain extract (BE). Several derivatives with the most potent anti-inflammatory activity were tested for blood-brain barrier permeability and sTGFBR3 affinity. Derivative P24, selected for its superior properties, was further evaluated in vitro. The results indicated that P24 increased the activation of TGF-ß signaling and decreased the activation of IκBα/NF-κB signaling by targeting sTGFBR3, thereby regulating the inflammation-phagocytosis balance in microglia. Moreover, the low acute toxicity, long half-life, and low plasma clearance of P24 suggest that it can be sustained in vivo. This property may render P24 a more effective treatment modality for chronic diseases, particularly AD. The study demonstrates P24 serve as potential novel candidates for the treatment of AD via antagonizing sTGFBR3.

Research on the mechanism of sea buckthorn leaf Fu tea in the treatment of hyperlipidemia.

Background: Hyperlipidemia (HLP) presents a significant challenge to global public health. Mounting evidence suggests that statins, the recommended first-line lipid-lowering agents, have significant adverse effects. Consequently, the quest for natural and efficacious alternative therapies is steadily emerging as a research priority for HLP prevention and treatment. Consumption of tea, which is rich in diverse biologically active compounds with the capacity to regulate lipid metabolism and combat obesity, has emerged as a promising alternative therapy. Sea buckthorn leaves are rich in a multitude of biologically active substances, have a hypolipidemic effect, and can be used as a raw material for tea because of their unique flavor. There is a suggestion that combining Aspergillus cristatus with tea could modify or boost the lipid-lowering active compounds present in tea, thereby increasing its efficacy in regulating lipid metabolism. Results: Sea Buckthorn Leaf Fu Tea (SBLFT) was obtained by fermentation when sea buckthorn leaves contained 42 % moisture, inoculated with Aspergillus cristatus 0.2 mL/g, and incubated for 8 d at constant temperature. Animal experiments demonstrated that SBLFT significantly inhibited body weight gain in HLP rats and reduced lipid content and serum oxidative stress. In addition, liver tissue sections and functional indices showed that SBLFT can improve liver morphology and function abnormalities. Reverse transcription-polymerase chain reaction results indicated that the expression of Liver kinase B1 (LKB1), adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK), acetyl CoA carboxylase 1 (ACC1), and sterol-regulatory element binding protein-1 (SREBP1c) gene related to lipid metabolism was altered. Conclusion: SBLFT improved HLP, specifically via promoting the expression of LKB1 in the liver of HLP rats, activating AMPK, and inhibiting ACC1 and SREBP1c expression, resulting in the inhibition of fatty acid and triglyceride synthesis-related enzymes at the transcriptional level.

New insights into the evolution and local adaptation of the genus Castanea in east Asia.

Chestnut plants (Castanea) are important nut fruit trees worldwide. However, little is known regarding the genetic relationship and evolutionary history of different species within the genus. How modern chestnut plants have developed local adaptation to various climates remains a mystery. The genomic data showed that Castanea henryi first diverged in the Oligocene ~31.56 million years ago, followed by Castanea mollissima, and the divergence between Castanea seguinii and Castanea crenata occurred in the mid-Miocene. Over the last 5 million years, the population of chestnut plants has continued to decline. A combination of selective sweep and environmental association studies was applied to investigate the genomic basis of chestnut adaptation to different climates. Twenty-two candidate genes were associated with temperature and precipitation. We also revealed the molecular mechanism by which CmTOE1 interacts with CmZFP8 and CmGIS3 to promote the formation of non-glandular trichomes for adaptation to low temperature and high altitudes. We found a significant expansion of CER1 genes in Chinese chestnut (C. mollissima) and verified the CmERF48 regulation of CmCER1.6 adaptation to drought environments. These results shed light on the East Asian chestnut plants as a monophyletic group that had completed interspecific differentiation in the Miocene, and provided candidate genes for future studies on adaptation to climate change in nut trees.