[Guidelines for traditional dietary care in autumn and winter].

The National Nutrition Plan(2017-2030) and the Healthy China Action Plan(2019-2030) propose to vigorously develop traditional dietary care services, fully leverage the role of traditional dietary care in modern nutrition, and guide citizens to develop dietary habits that are in line with the dietary characteristics of different regions in China. Traditional dietary care has a long history in China and is one of the brilliant treasures of Chinese cuisine and traditional Chinese medicine(TCM) culture. It has played an important role in disease prevention, treatment, and health preservation and longevity. To promote the traditional culture of TCM, and guide and standardize the application and promotion of dietary care, it is necessary to develop a dietary care guideline with TCM characteristics. Based on the theories and practices of TCM, the China Academy of Chinese Medical Sciences(CACMS) has developed this guideline, which is tailored to local conditions and combined with modern nutrition, and targets people with different physical constitutions. According to the principles of dialectical diet, tailored to people, times, and local conditions, reinforcing healthy qi, correction, the combination of meat and vegetables, and the combination of four qi and five flavors, suitable ingredients are recommended(including TCM materials that are both food and medicinal materials). By promoting the popularization and development of traditional dietary care, this guideline contributes to integrating the strength of TCM into a unique nutritional and health model with Chinese characteristics.

Proton dose calculation with LSTM networks in presence of a magnetic field.

OBJECTIVE: To present a long short-term memory (LSTM) network-based dose calculation method for magnetic resonance (MR)-guided proton therapy. APPROACH: 35 planning computed tomography (CT) images of prostate cancer patients were collected for Monte Carlo (MC) dose calculation under a perpendicular 1.5 T magnetic field. Proton pencil beams (PB) at three energies (150, 175, and 200 MeV) were simulated (7560 PBs at each energy). A 3D relative stopping power (RSP) cuboid covering the extent of the PB dose was extracted and given as input to the LSTM model, yielding a 3D predicted PB dose. Three single-energy (SE) LSTM models were trained separately on the corresponding 150/175/200 MeV datasets and a multi-energy (ME) LSTM model with an energy embedding layer was trained on either the combined dataset with three energies or a continuous energy (CE) dataset with 1 MeV steps ranging from 125 to 200 MeV. For each model, training and validation involved 25 patients and 10 patients were for testing. Two single field uniform dose prostate treatment plans were optimized and recalculated with MC and the CE model. RESULTS: Test results of all PBs from the three SE models showed a mean gamma passing rate (2%/2mm, 10% dose cutoff) above 99.9% with an average center-of-mass (COM) discrepancy below 0.4 mm between predicted and simulated trajectories. The ME model showed a mean gamma passing rate exceeding 99.8% and a COM discrepancy of less than 0.5 mm at the three energies. Treatment plan recalculation by the CE model yielded gamma passing rates of 99.6% and 97.9%. The inference time of the models was 9-10 ms per PB. SIGNIFICANCE: LSTM models for proton dose calculation in a magnetic field were developed and showed promising accuracy and efficiency for prostate cancer patients.

The transcription factor RUNT-like regulates pupal cuticle development via promoting a pupal cuticle protein transcription.

Holometabolous insects undergo morphological remodeling from larvae to pupae and to adults with typical changes in the cuticle; however, the mechanism is unclear. Using the lepidopteran agricultural insect Helicoverpa armigera, cotton bollworm, as a model, we revealed that the transcription factor RUNT-like (encoded by Runt-like) regulates the development of the pupal cuticle via promoting a pupal cuticle protein gene (HaPcp) expression. The HaPcp was highly expressed in the epidermis and wing during metamorphosis and was found being involved in pupal cuticle development by RNA interference (RNAi) analysis in larvae. Runt-like was also strongly upregulated in the epidermis and wing during metamorphosis. Knockdown of Runt-like produced similar phenomena, a failure of abdomen yellow envelope and wing formation, to those following HaPcp knockdown. The insect molting hormone 20-hydroxyecdysonen (20E) upregulated HaPcp transcription via RUNT-like. 20E upregulated Runt-like transcription via nuclear receptor EcR and the transcription factor FOXO. Together, RUNT-like and HaPCP are involved in pupal cuticle development during metamorphosis under 20E regulation.

Importance of the enhanced cooling system for more spherical ablation zones: Numerical simulation, ex vivo and in vivo validation.

INTRODUCTION: This study aimed to investigate the efficacy of a small-gauge microwave ablation antenna (MWA) with an enhanced cooling system (ECS) for generating more spherical ablation zones. METHODS: A comparison was made between two types of microwave ablation antennas, one with ECS and the other with a conventional cooling system (CCS). The finite element method was used to simulate in vivo ablation. Two types of antennas were used to create MWA zones for 5, 8, 10 min at 50, 60, and 80 W in ex vivo bovine livers (n = 6) and 5 min at 60 W in vivo porcine livers (n = 16). The overtreatment ratio, ablation aspect ratio, carbonization area, and other characteristcs of antennas were measured and compared using numerical simulation and gross pathologic examination. RESULTS: In numerical simulation, the ECS antenna demonstrated a lower overtreatment ratio than the CCS antenna (1.38 vs 1.43 at 50 W 5 min, 1.19 vs 1.35 at 50 W 8 min, 1.13 vs 1.32 at 50 W 10 min, 1.28 vs 1.38 at 60 W 5 min, 1.14 vs 1.32 at 60 W 8 min, 1.10 vs 1.30 at 60 W 10 min). The experiments revealed that the ECS antenna generated ablation zones with a more significant aspect ratio (0.92 ± 0.03 vs 0.72 ± 0.01 at 50 W 5 min, 0.95 ± 0.02 vs 0.70 ± 0.01 at 50 W 8 min, 0.96 ± 0.01 vs 0.71 ± 0.04 at 50 W 10 min, 0.96 ± 0.01 vs 0.73 ± 0.02 at 60 W 5 min, 0.94 ± 0.03 vs 0.71 ± 0.03 at 60 W 8 min, 0.96 ± 0.02 vs 0.69 ± 0.04 at 60 W 10 min) and a smaller carbonization area (0.00 ± 0.00 cm2 vs 0.54 ± 0.06 cm2 at 50 W 5 min, 0.13 ± 0.03 cm2 vs 0.61 ± 0.09 cm2 at 50 W 8 min, 0.23 ± 0.05 cm2 vs 0.73 ± 0.05 m2 at 50 W 10 min, 0.00 ± 0.00 cm2 vs 1.59 ± 0.41 cm2 at 60 W 5 min, 0.23 ± 0.22 cm2 vs 2.11 ± 0.63 cm2 at 60 W 8 min, 0.57 ± 0.09 cm2 vs 2.55 ± 0.51 cm2 at 60 W 10 min). Intraoperative ultrasound images revealed a hypoechoic area instead of a hyperechoic area near the antenna. Hematoxylin-eosin staining of the dissected tissue revealed a correlation between the edge of the ablation zone and that of the hypoechoic area. CONCLUSIONS: The ECS antenna can produce more spherical ablation zones with less charring and a clearer intraoperative ultrasound image of the ablation area than the CCS antenna.

Denoising of volumetric magnetic resonance imaging using multi-channel three-dimensional convolutional neural network with applications on fast spin echo acquisitions.

Background: Three-dimensional (3D) magnetic resonance imaging (MRI) can be acquired with a high spatial resolution with flexibility being reformatted into arbitrary planes, but at the cost of reduced signal-to-noise ratio. Deep-learning methods are promising for denoising in MRI. However, the existing 3D denoising convolutional neural networks (CNNs) rely on either a multi-channel two-dimensional (2D) network or a single-channel 3D network with limited ability to extract high dimensional features. We aim to develop a deep learning approach based on multi-channel 3D convolution to utilize inherent noise information embedded in multiple number of excitation (NEX) acquisition for denoising 3D fast spin echo (FSE) MRI. Methods: A multi-channel 3D CNN is developed for denoising multi-NEX 3D FSE magnetic resonance (MR) images based on the feature extraction of 3D noise distributions embedded in 2-NEX 3D MRI. The performance of the proposed approach was compared to several state-of-the-art MRI denoising methods on both synthetic and real knee data using 2D and 3D metrics of peak signal-to-noise ratio (PSNR) and structural similarity index measure (SSIM). Results: The proposed method achieved improved denoising performance compared to the current state-of-the-art denoising methods in both slice-by-slice 2D and volumetric 3D metrics of PSNR and SSIM. Conclusions: A multi-channel 3D CNN is developed for denoising of multi-NEX 3D FSE MR images. The superior performance of the proposed multi-channel 3D CNN in denoising multi-NEX 3D MRI demonstrates its potential in tasks that require the extraction of high-dimensional features.

Association of tooth loss and periodontal disease with all-cause mortality in cancer survivors: A cohort study based on NHANES.

Background: Increasing evidence supports the association between impaired oral health and elevated mortality. However, there is currently a lack of research on the impact of tooth loss and periodontal disease on survival outcomes in cancer survivors. This study aims to clarify the effect of tooth loss and periodontitis on all-cause mortality on cancer survivors. Methods: The clinical data of cancer survivors were collected from National Health and Nutrition Examination Survey (NHANES) 1999-2018. Mortality data were obtained by linking to records in the National Death Index until December 31, 2019. Receiver operating characteristic (ROC) curve analysis was performed to determine the optimal threshold for discriminating mortality based on the number of teeth lost. Kaplan-Meier survival curves and Cox regression analysis were performed to calculate hazard ratios (HRs) and 95 % confidence intervals (95 % CI) for tooth loss and periodontitis. Results: A total of 3271 cancer survivors were assessed for tooth loss status, while 1267 patients were evaluated for periodontitis status. The prevalence of any tooth loss and CDC-AAP periodontitis was 83.5 % and 47.2 %, respectively. The ROC curve showed the cut-off point of tooth loss for predicting mortality is > 5. Cancer survivors with tooth loss>5 had significantly lower bone density (1.06 vs. 1.13 g/cm2, P < 0.001), elevated C-reactive protein level (0.3 vs. 0.18 mg/dL, P < 0.001), and a trend of lower lean body mass (46.9 vs. 47.6 kg, P = 0.093). Besides, cancer survivors with severe periodontitis also exhibited elevated C-reactive protein level (0.34 vs. 0.21 mg/dL, P = 0.033). All-cause mortality significantly increased in cancer survivors with either tooth loss>5 (HR = 1.290, P = 0.001) or severe CDC-AAP periodontitis (HR = 1.682, P = 0.016) in the multivariate Cox regression analysis. Conclusion: Tooth loss and periodontitis are strong risk factors for reduced overall survival in cancer survivors. Cancer survivors should emphasize diligent oral hygiene and consistent dental check-ups to optimize long-term oral health. The causal relationship between oral health and survival rates in cancer survivors requires further validation through randomized controlled trials.

The diagnostic value of neutrophil to lymphocyte ratio, albumin to fibrinogen ratio, and lymphocyte to monocyte ratio in Parkinson's disease: a retrospective study.

Background: Parkinson's disease (PD) is a prevalent disorder of the central nervous system, marked by the degeneration of dopamine (DA) neurons in the ventral midbrain. In the pathogenesis of PD, inflammation hypothesis has been concerned. This study aims to investigate clinical indicators of peripheral inflammation in PD patients and to explore the diagnostic value of neutrophil-to-lymphocyte ratio (NLR), albumin-to-fibrinogen ratio (AFR), and lymphocyte-to-monocyte ratio (LMR) in assessing PD risk. Methods: This study included 186 patients with PD and 201 matched healthy controls (HC) with baseline data. Firstly, the differences of hematological indicators between PD group and healthy participants were compared and analyzed. Univariate and multivariate regression analyses were then conducted. Smooth curve fitting was applied to further validate the relationships between NLR, LMR, AFR, and PD. Subsequently, subgroup analysis was conducted in PD group according to different duration of disease and Hoehn and Yahr (H&Y) stage, comparing differences in clinical indicators. Finally, the receiver operating characteristic (ROC) curve was employed to assess the diagnostic value of NLR, LMR, and AFR in PD. Results: Compared to the HC group, the PD group showed significantly higher levels of hypertension, diabetes, neutrophil count, monocyte count, CRP, homocysteine, fibrinogen, and NLR. Conversely, levels of LMR, AFR, lymphocyte count, HDL, LDL, TG, TC, uric acid, and albumin were significantly lower. The multivariate regression model indicated that NLR (OR = 1.79, 95% CI: 1.39-2.31, p < 0.001), LMR (OR = 0.75, 95% CI: 0.66-0.85, p < 0.001), and AFR (OR = 0.79, 95% CI: 0.73-0.85, p < 0.001) were significant factors associated with PD. Smooth curve fitting revealed that NLR was positively linked to PD risk, whereas AFR and LMR were inversely associated with it. In ROC curve analysis, the AUC of AFR was 0.7290, the sensitivity was 63.98%, and the specificity was 76.00%. The AUC of NLR was 0.6200, the sensitivity was 50.54%, and the specificity was 71.50%. The AUC of LMR was 0.6253, the sensitivity was 48.39%, and the specificity was 73.00%. The AUC of the combination was 0.7498, the sensitivity was 74.19%, and the specificity was 64.00%. Conclusion: Our findings indicate that NLR, LMR, and AFR are significantly associated with Parkinson's disease and may serve as diagnostic markers.

A novel spherical GelMA-HAMA hydrogel encapsulating APET×2 polypeptide and CFIm25-targeting sgRNA for immune microenvironment modulation and nucleus pulposus regeneration in intervertebral discs.

METHODS: Single-cell transcriptomics and high-throughput transcriptomics were used to screen factors significantly correlated with intervertebral disc degeneration (IDD). Expression changes of CFIm25 were determined via RT-qPCR and Western blot. NP cells were isolated from mouse intervertebral discs and induced to degrade with TNF-α and IL-1ß. CFIm25 was knocked out using CRISPR-Cas9, and CFIm25 knockout and overexpressing nucleus pulposus (NP) cell lines were generated through lentiviral transfection. Proteoglycan expression, protein expression, inflammatory factor expression, cell viability, proliferation, migration, gene expression, and protein expression were analyzed using various assays (alcian blue staining, immunofluorescence, ELISA, CCK-8, EDU labeling, transwell migration, scratch assay, RT-qPCR, Western blot). The GelMA-HAMA hydrogel loaded with APET×2 polypeptide and sgRNA was designed, and its effects on NP regeneration were assessed through in vitro and mouse model experiments. The progression of IDD in mice was evaluated using X-ray, H&E staining, and Safranin O-Fast Green staining. Immunohistochemistry was performed to determine protein expression in NP tissue. Proteomic analysis combined with in vitro and in vivo experiments was conducted to elucidate the mechanisms of hydrogel action. RESULTS: CFIm25 was upregulated in IDD NP tissue and significantly correlated with disease progression. Inhibition of CFIm25 improved NP cell degeneration, enhanced cell proliferation, and migration. The hydrogel effectively knocked down CFIm25 expression, improved NP cell degeneration, promoted cell proliferation and migration, and mitigated IDD progression in a mouse model. The hydrogel inhibited inflammatory factor expression (IL-6, iNOS, IL-1ß, TNF-α) by targeting the p38/NF-κB signaling pathway, increased collagen COLII and proteoglycan Aggrecan expression, and suppressed NP degeneration-related factors (COX-2, MMP-3). CONCLUSION: The study highlighted the crucial role of CFIm25 in IDD and introduced a promising therapeutic strategy using a porous spherical GelMA-HAMA hydrogel loaded with APET×2 polypeptide and sgRNA. This innovative approach offers new possibilities for treating degenerated intervertebral discs.

Cluster headache: understandings of current knowledge and directions for whole process management.

Cluster headache (CH) is a common primary headache that severely impacts patients' quality of life, characterized by recurrent, severe, unilateral headaches often centered around the eyes, temples, or forehead. Distinguishing CH from other headache disorders is challenging, and its pathogenesis remains unclear. Notably, patients with CH often experience high levels of depression and suicidal tendencies, necessitating increased clinical attention. This comprehensive assessment combines various reports and the latest scientific literature to evaluate the current state of CH research. It covers epidemiology, population characteristics, predisposing factors, and treatment strategies. Additionally, we provide strategic insights into the holistic management of CH, which involves continuous, individualized care throughout the prevention, treatment, and rehabilitation stages. Recent advances in the field have revealed new insights into the pathophysiology of CH. While these findings are still evolving, they offer a more detailed understanding of the neurobiological mechanisms underlying this disorder. This growing body of knowledge, alongside ongoing research efforts, promises to lead to the development of more targeted and effective treatments in the future.

Investigation on the Adhesion Force between Tetrabutylammonium Bromide Hydrate Particles Using Atomic Force Microscopy.

This work investigates the adhesion force between tetrabutylammonium bromide (TBAB) hydrate particles dispersed in decane at different temperatures and TBAB concentrations using an atomic force microscopy. The thickness of the quasi-liquid layer (QLL) on the surface of the hydrate particles is calculated based on an adhesion force model. The results of force measurements indicate that the adhesion force between the hydrate particles increases with increasing temperature when TBAB concentration is 30 wt %. The increment of adhesion force between particles could be due to the increase in the QLL thickness on the particle surfaces. Furthermore, the force results also reveal that the adhesion force between hydrate particles(ice) at 253 K decreases when TBAB concentration increases from 0 to 30 wt %. The calculation indicates that QLL on the surface of formed hydrate particles becomes thinner at higher TBAB concentrations, which could be due to the conversion rate of water to hydrate within particles. The thickness of QLL is directly influenced by the temperature and TBAB concentration, which contributes to the adhesion force between hydrate particles.

Cyclic di-GMP incorporates the transcriptional factor FleQ03 in Pseudomonas syringae MB03 to elicit biofilm-dependent resistance in response to Caenorhabditis elegans predation.

Bacteria usually form biofilms as a defense mechanism against predation by bacterivorous nematodes. In this context, the second messenger c-di-GMP from the wild-type Pseudomonas syringae MB03 actuates the transcriptional factor FleQ03 to elicit biofilm-dependent nematicidal activity against Caenorhabditis elegans N2. P. syringae MB03 cells exhibited nematicidal activity and c-di-GMP content in P. syringae MB03 cells was increased after feeding to nematodes. Expression of a diguanylate cyclase (DGC) gene in P. syringae MB03 resulted in an increased c-di-GMP content, biofilm yield and nematicidal activity, whereas converse effects were obtained when expressing a phosphodiesterase (PDE) gene. Molecular docking and isothermal titration calorimetry assays verified the affinity activity between c-di-GMP and the FleQ03 protein. The disruption of the fleQ03 gene in P. syringae MB03, while increasing c-di-GMP content, significantly diminished both biofilm formation and nematicidal activity. Interestingly, P. syringae MB03 formed a full-body biofilm around the worms against predation, probably extending from the tail to the head, whereas it was not observed in the fleQ03 gene disrupted cells. Thus, we hypothesized that c-di-GMP incorporated FleQ03 to reinforce bacterial biofilm and biofilm-dependent pathogenicity in response to C. elegans predation, providing insights into a possible means of resisting bacterivorous nematodes by bacteria in natural ecosystems.

Chronic social isolation leads to abnormal behavior in male mice through the hippocampal METTL14 mediated epitranscriptomic RNA m6A modifications.

BACKGROUND: Social isolation not only increases the risk of mortality in later life but also causes depressive symptoms, cognitive and physical disabilities. Although RNA m6A modifications are suggested to play key roles in brain development, neuronal signaling and neurological disorders, both the roles of m6A and the enzymes that regulate RNA m6A modification in social isolation induced abnormal behavior is unknown. The present study aims to explore the possible epitranscriptomic role of RNA m6A modifications and its enzymes in social isolation induced impaired behavior. METHODS: 3-4 weeks mice experiencing 8 weeks social isolation stress (SI) were used in the present study. We quantified m6A levels in brain regions related to mood and cognitive behavior. And the expression of hippocampal m6A enzymes was also determined. The role of hippocampal m6A and its enzymes in SI induced abnormal behavior was further verified by the virus tool. RESULTS: SI led to not only depressive and anxiety-like behaviors but also cognitive impairment, with corresponding decreases in hippocampal m6A and METTL14. Hippocampal over-expression METTL14 with lentivirus not only rescued these behaviors but also enhanced the hippocampal m6A level. Hippocampal over-expression METTL14 resulted in increased synaptic related genes. CONCLUSIONS: We provide the first evidence that post-weaning social isolation reduces hippocampal m6A level and causes altered expression of m6A enzyme in mice. Importantly, hippocampal METTL14 over-expression alleviated the SI-induced depression/anxiety-like and impaired cognitive behaviors and enhanced m6A level and synaptic related genes expression.

Synergistic antitumor activity of baicalein combined with almonertinib in almonertinib-resistant non-small cell lung cancer cells through the reactive oxygen species-mediated PI3K/Akt pathway.

Introduction: Almonertinib is an important third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) exhibiting high selectivity to EGFR-sensitizing and T790M-resistant mutations. Almonertinib resistance is a major obstacle in clinical use. Baicalein possesses antitumor properties, but its mechanism of antitumor action against almonertinib-resistant non-small cell lung cancer (NSCLC) remains unelucidated. Methods: CCK-8 assay was used to examine the survival rate of H1975/AR and HCC827/AR cells following treatment for 24 h with different concentrations of baicalein, almonertinib or their combination. The changes in colony formation ability, apoptosis, and intracellular reactive oxygen species (ROS) levels of the treated cells were analyzed using colony formation assay and flow cytometry. Western blotting was performed to detect the changes in protein expressions in the cells. The effects of pre-treatment with NAC on proliferation, apoptosis, and PI3K/Akt signaling pathway were observed in baicalein- and/or almonertinib-treated cells. A nude mouse model bearing subcutaneous HCC827/AR cell xenograft were treated with baicalein (20 mg/kg) or almonertinib (15 mg/kg), and the tumor volume and body mass changes was measured. Results: Both baicalein and almonertinib represses the viability of HCC827/AR and H1975/AR cells in a concentration-dependent manner. Compared with baicalein or almonertinib alone, the combined application of the two drugs dramatically attenuates cell proliferation; triggers apoptosis; causes cleavage of Caspase-3, PARP, and Caspase-9; downregulates the protein expressions of p-PI3K and p-Akt; and significantly inhibits tumor growth in nude mice. Furthermore, baicalein combined with almonertinib results in massive accumulation of reactive oxygen species (ROS) and preincubation with N-acetyl-L-cysteine (ROS remover) prevents proliferation as well as inhibits apoptosis induction, with partial recovery of the decline of p-PI3K and p-Akt. Discussion: The combination of baicalein and almonertinib can improve the antitumor activity in almonertinib-resistant NSCLC through the ROS-mediated PI3K/Akt pathway.

Lipases are differentially regulated by hormones to maintain free fatty acid homeostasis for insect brain development.

BACKGROUND: Free fatty acids (FFAs) play vital roles as energy sources and substrates in organisms; however, the molecular mechanism regulating the homeostasis of FFA levels in various circumstances, such as feeding and nonfeeding stages, is not fully clarified. Holometabolous insects digest dietary triglycerides (TAGs) during larval feeding stages and degrade stored TAGs in the fat body during metamorphosis after feeding cessation, which presents a suitable model for this study. RESULTS: This study reported that two lipases are differentially regulated by hormones to maintain the homeostasis of FFA levels during the feeding and nonfeeding stages using the lepidopteran insect cotton bollworm Helicoverpa armigera as a model. Lipase member H-A-like (Lha-like), related to human pancreatic lipase (PTL), was abundantly expressed in the midgut during the feeding stage, while the monoacylglycerol lipase ABHD12-like (Abhd12-like), related to human monoacylglycerol lipase (MGL), was abundantly expressed in the fat body during the nonfeeding stage. Lha-like was upregulated by juvenile hormone (JH) via the JH intracellular receptor methoprene-tolerant 1 (MET1), and Abhd12-like was upregulated by 20-hydroxyecdysone (20E) via forkhead box O (FOXO) transcription factor. Knockdown of Lha-like decreased FFA levels in the hemolymph and reduced TAG levels in the fat body. Moreover, lipid droplets (LDs) were small, the brain morphology was abnormal, the size of the brain was small, and the larvae showed the phenotype of delayed pupation, small pupae, and delayed tissue remodeling. Knockdown of Abhd12-like decreased FFA levels in the hemolymph; however, TAG levels increased in the fat body, and LDs remained large. The development of the brain was arrested at the larval stage, and the larvae showed a delayed pupation phenotype and delayed tissue remodeling. CONCLUSIONS: The differential regulation of lipases expression by different hormones determines FFAs homeostasis and different TAG levels in the fat body during the feeding larval growth and nonfeeding stages of metamorphosis in the insect. The homeostasis of FFAs supports insect growth, brain development, and metamorphosis.

Development of the insect adult fat body relies on glycolysis, lipid synthesis, cell proliferation, and cell adhesion.

The fat body of the holometabolous insect is remodeled by the degradation of the larval fat body and the development of the adult fat body during metamorphosis. However, the mechanism of adult fat body development is quite unclear. Using the agricultural pest Helicoverpa armigera, the cotton bollworm, as a model, we revealed that the development of adult fat body was regulated by glycolysis, triglyceride (triacylglycerol [TAG]) synthesis, cell proliferation, and cell adhesion. RNA sequencing detected a set of genes that were upregulated in the 8-d late pupal fat body at a late metamorphic stage compared with the 2-d pupal fat body at an earlier metamorphic stage. The pathways for glycolysis, TAG synthesis, cell proliferation, and cell adhesion were enriched by the differentially expressed genes, and the key genes linked with these pathways showed increased expression in the 8-d pupal fat body. Knockdown of phosphofructokinase (Pfk), acetyl-CoA carboxylase (Acc1), phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit (P110) and collagen alpha-1(IV) chain (Col4a1) by RNA interference resulted in abnormal eclosion and death at pupal stages, and repressed lipid droplets accumulation and adult fat body development. The expression of Acc1, P110, and Col4a1 was repressed by the insect steroid hormone 20-hydroxyecdysone (20E). The critical genes in the 20E pathway appeared to decrease at the late pupal stage. These data suggested that the development of the insect adult fat body is regulated by glycolysis, lipids synthesis, cell proliferation, and cell adhesion at the late pupal stage when the 20E signal decreases.

Integrated Comparative Transcriptome and Weighted Gene Co-Expression Network Analysis Provide Valuable Insights into the Mechanisms of Pinhead Initiation in Chinese Caterpillar Mushroom Ophiocordyceps sinensis (Ascomycota).

The initiation and formation of the "pinhead" is the key node in growth process of Ophiocordyceps sinensis (Chinese Cordyceps). The research on the mechanism of changes in this growth stage is the basis for realizing the industrialization of its artificial cultivation. Clarifying the mechanisms of pinhead initiation is essential for its further application. Here, we performed a comprehensive transcriptome analysis of pinhead initiation process in O. sinensis. Comparative transcriptome analysis revealed remarkable variation in gene expression and enriched pathways at different pinhead initiation stages. Gene co-expression network analysis by WGCNA identified 4 modules highly relevant to different pinhead initiation stages, and 23 hub genes. The biological function analysis and hub gene annotation of these identified modules demonstrated that transmembrane transport and nucleotide excision repair were the topmost enriched in pre-pinhead initiation stage, carbohydrate metabolism and protein glycosylation were specially enriched in pinhead initiation stage, nucleotide binding and DNA metabolic process were over-represented after pinhead stage. These key regulators are mainly involved in carbohydrate metabolism, synthesis of proteins and nucleic acids. This work excavated the candidate pathways and hub genes related to the pinhead initiation stage, which will serve as a reference for realizing the industrialization of artificial cultivation in O. sinensis.

[Improving effect of selenium on spermatogenesis in mice with cyclophosphamide-induced spermatogenic impairment and its underlying mechanism].

OBJECTIVE: To investigate the effect of selenium on cyclophosphamide (CTX)-induced spermatogenic impairment (SI) in mice and its underlying mechanism. METHODS: We equally randomized 36 male KM mice into 3 SI model and 3 control groups, the first 3 treated by intraperitoneal injection of CTX at 100 mg/kg (the SI model control group), CTX plus SI model control group, selenium deficient model group (－Se SI), selenium supplemented model group (+Se SI), while latter 3 by intraperitoneal injection of normal saline (the normal control), selenium deficiency control group (－Se control), selenium addition control group (+Se control), respectively, all once a week for 6 successive weeks. Then we observed the histopathological changes in the testes of all the mice by HE staining, obtained the sperm count in the epididymides, determined the expressions of glutathione peroxidase 4 (GPx4) and SLC7A11 proteins by Western blot and ferroptosis-related genes by RT-qPCR, and examined the changes in the expressions of ferroptosis-related proteins and genes in the GC2-spd cells treated with ferroptosis inhibitors and inducers in combination with different concentrations of inorganic sodium selenite (SeS) and organic selenomethionine (SeM). RESULTS: Compared with the normal controls, the SI model mice showed significantly decreased testicular and prostatic organ coefficients, reduced spermatogenic layers, increased voids, decreased serum ferritin concentration (P<0.05), and elevated transferrin concentration (P<0.05). The organ coefficients were significantly higher in the +Se SI and +Se control than in the －Se SI and －Se control groups (P<0.05, P<0.01), with evident pathological improvement of the testis tissue in the +Se controls. The expressions of the GPx4 and solute carrier family 7 members 11（SLC7A11） genes in the testis were dramatically down-regulated in the SI model controls (P<0.01), but up-regulated in the +Se SI and +Se control compared with those in the －Se SI and －Se control group (P<0.01 and P<0.05), but there were no statistically significant differences between their protein expressions. The results of in vitro GC2 spd cell experiments indicated that the GPx4 gene and GPx4 protein levels in the - Se group were significantly lower than those in the normal control group (P<0.05), while the SLC7A11 gene level decreased (P<0.01). Different doses of SeS and SeM significantly increased the GPx4 protein expression compared to the average Se group. Low doses of SeM promoted a significant increase in GPx4 gene levels, while high doses of SeS increased the expression levels of SLC7A11 gene and SLC7A11 protein (P<0.05, P<0.01). The Se group showed a significant decrease in the levels of acsl4 and ptgs2 genes compared to the normal control group. SeM promoted the expression of acsl4, while SeS promoted the expression of ptgs2 and fth1 (P<0.01, P<0.05). The intervention results of GC2 spd showed that the Erastin group had a decrease in ptgs2 compared to the normal control group, while the SeS+Erastin and SeM+Erastin groups had an increase in ptgs2 gene expression compared to the Erastin group. However, the ptgs2 expression of Fer-1 was lower than that of the normal control group, and the ptgs2 gene level of SeS+Fer-1 and SeM+Fer-1 groups was lower than that of Fer-1 group (P<0.05); The gene quantity of GPx4 in the SeM+Erastin and SeM+Fer-1 groups increased compared to the Erastin and Fer-1 groups (P<0.01, P<0.05); SeM+Erastin and SeS+Erastin showed a decrease in SLC7A11 compared to the Erastin group, as well as SeM+Fer-1 and SeS+Fer-1 groups compared to the Fer-1 group, accompanied by an increase in acsl4 and fth1 (P<0.01). CONCLUSION: Selenium deficiency causes the reduction of the SLC7A11 and GPx4 gene levels, disorder of ferroptosis-related genes and down-regulation of the GPx4 protein expression in the mouse testis and spermatocytes. Selenium can promote the expression of GPx4, up-regulate the level of SLC7A11, and improve spermatogenesis in the testis of the mouse with SI. There are differences between organic SeM and inorganic SeS in regulating the ferroptosis pathway-related genes.

Self-supervised learning-enhanced deep learning method for identifying myopic maculopathy in high myopia patients.

Accurate detection and timely care for patients with high myopia present significant challenges. We developed a deep learning (DL) system enhanced by a self-supervised learning (SSL) approach to improve the automatic diagnosis of myopic maculopathy (MM). Using a dataset of 7,906 images from the Shanghai High Myopia Screening Project and a public validation set of 1,391 images from MMAC2023, our method significantly outperformed conventional techniques. Internally, it achieved 96.8% accuracy, 83.1% sensitivity, and 95.6% specificity, with AUC values of 0.982 and 0.999. Externally, it maintained 89.0% accuracy, 71.7% sensitivity, and 87.8% specificity, with AUC values of 0.978 and 0.973. The model's Cohen's kappa values exceeded 0.8, indicating substantial agreement with retinal experts. Our SSL-enhanced DL approach offers high accuracy and potential to enhance large-scale myopia screenings, demonstrating broader significance in improving early detection and treatment of MM.

Unveiling the Therapeutic Potential of hUCMSC-Derived EVs in Intervertebral Disc Degeneration through MALAT1/miR-138-5p/SLC7A11 Coexpression Regulation.

Intervertebral disc degeneration (IVDD) is a prevalent chronic condition causing spinal pain and functional impairment. This study investigates the role of extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (hUCMSCs) in regulating IVDD. Using RNA-seq, we analyzed differential expressions of lncRNA and miRNA in nucleus pulposus tissues from various mouse groups. We identified key regulatory molecules, MALAT1 and miRNA-138-5p, which contribute to IVDD. Further experiments demonstrated that MALAT1 can up-regulate SLC7A11 expression by competitively binding to miR-138-5p, forming a MALAT1/miR-138-5p/SLC7A11 coexpression regulatory network. This study elucidates the molecular mechanism by which hUCMSC-derived EVs regulate IVDD and could help develop novel therapeutic strategies for treating this condition. Our findings demonstrate that hUCMSCs-EVs inhibit ferroptosis in nucleus pulposus cells, thereby improving IVDD. These results highlight the therapeutic potential of hUCMSCs-EVs in ameliorating the development of IVDD, offering significant scientific and clinical implications for new treatments.