CRY2 mediates the cognitive decline induced by sleep deprivation in 5xFAD mice.

BACKGROUND: Cryptochrome-2 (CRY2) is a core rhythm gene that plays a crucial role in DNA damage repair. The present study investigated the potential role of CRY2 in mediating sleep deprivation-induced cognitive decline in 5xFAD mice. METHODS: To assess the effects of SD on different brain regions of the mouse brain, we used 18F FDG PET-CT. Cognitive function was evaluated using the Morris water maze test and Y-maze. Lentivirus was used for the overexpression of CRY2, and small interfering RNA (siRNA) was used for the downregulation of CRY2 to verify the effect of CRY2. We used qRT‒PCR and Western blotting to identify the downstream factors of CRY2 and evaluated the cognitive function of mice to confirm the effects of these factors. RESULTS: The AD mice exhibited cognitive decline after 21 days of SD and had higher expression of CRY2 compared to AD mice with normal sleep. Overexpression of CRY2 led to decreased cognitive function in AD mice, and the downregulation of CRY2 attenuated the SD-induced cognitive decline in AD mice. CRY2 reduced the expression and function of CISH, which reduced the inhibition of STAT1 phosphorylation and led to synaptic dysfunction. CISH overexpression attenuated the impairing effect of sleep deprivation on cognitive function in AD mice. Furthermore, 18F FDG PET-CT revealed that SD significantly reduced glucose metabolism in different brain regions of AD mice. CONCLUSION: Our study demonstrated that sleep deprivation upregulated CRY2 in the hippocampus of AD mice, which resulted in synaptic dysfunction by decreasing CISH-mediated STAT1 phosphorylation.

Intraoperative hypotension is associated with decreased long-term survival in older patients after major noncardiac surgery: Secondary analysis of three randomized trials.

STUDY OBJECTIVE: To assess the association of intraoperative hypotension with long-term survivals in older patients after major noncardiac surgery mainly for cancer. DESIGN: A secondary analysis of databases from three randomized trials with long-term follow-up. SETTING: The underlying trials were conducted in 17 tertiary hospitals in China. PATIENTS: Patients aged 60 to 90 years who underwent major noncardiac thoracic or abdominal surgeries (≥ 2 h) in a single center were included in this analysis. EXPOSURES: Restricted cubic spline models were employed to determine the lowest mean arterial pressure (MAP) threshold that was potentially harmful for long-term survivals. Patients were arbitrarily divided into three groups according to the cumulative duration or area under the MAP threshold. The association between intraoperative hypotension exposure and long-term survivals were analyzed with the Cox proportional hazard regression models. MEASUREMENTS: Our primary endpoint was overall survival. Secondary endpoints included recurrence-free and event-free survivals. MAIN RESULTS: A total of 2664 patients (mean age 69.0 years, 34.9% female sex, 92.5% cancer surgery) were included in the final analysis. MAP < 60 mmHg was adopted as the threshold of intraoperative hypotension. Patients were divided into three groups according to duration under MAP < 60 mmHg (<1 min, 1-10 min, and > 10 min) or area under MAP <60 mmHg (< 1 mmHg⋅min, 1-30 mmHg⋅min, and > 30 mmHg⋅min). After adjusting confounders, duration under MAP < 60 mmHg for > 10 min was associated with a shortened overall survival when compared with the < 1 min patients (adjusted hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.09 to 1.57, P = 0.004); area under MAP < 60 mmHg for > 30 mmHg⋅min was associated with a shortened overall survival when compared with the < 1 mmHg⋅min patients (adjusted HR 1.40, 95% CI 1.16 to 1.68, P < 0.001). Similar associations exist between duration under MAP < 60 mmHg for > 10 min or area under MAP < 60 mmHg for > 30 mmHg⋅min and recurrence-free or event-free survivals. CONCLUSIONS: In older patients who underwent major noncardiac surgery mainly for cancer, intraoperative hypotension was associated with worse overall, recurrence-free, and event-free survivals.

The role of MNK1-mTORC1 pathway in modulating macrophage responses to Vibrio vulnificus infection.

Vibrio vulnificus (Vv) is known to cause life-threatening infections, particularly septicemia. These patients often exhibit elevated levels of pro-inflammatory cytokines. While it is established that mitogen-activated protein kinase (MAPK)-interacting kinase (MNK) contributes to the production of pro-inflammatory cytokines, the role of MNK in macrophages during Vv infection remains unclear. In this study, we investigate the impact of MNK on macrophages. We demonstrate that the inhibition of MNK in J774A.1 cells, when treated with lipopolysaccharide or Vv, resulted in decreased production of tumor necrosis factor alpha and interleukin-6, without affecting their transcription. Interestingly, treatment with MNK inhibitor CGP57380 led to enhanced phosphorylation of MNK1 but decreased phosphorylation of eIF4E. Moreover, MNK1 knockout cells exhibited an increased capacity for phagocytosis and clearance of Vv, with more acidic phagosomes than the parental cells. Notably, CGP57380 did not impact phagocytosis, bacterial clearance, or phagosome acidification in Vv-infected J774A.1 cells. Considering the reported association between MNK and mammalian target of rapamycin complex 1 (mTORC1) activation, we investigated the mTORC1 signaling in MNK1 knockout cells infected with Vv. Our results revealed that attenuation of the mTORC1 signaling in these cells and treatment with the mTORC1 inhibitor rapamycin significantly enhanced bacterial clearance in J774A.1 cells following Vv infection. In summary, our findings suggest that MNK promotes the Vv-induced cytokine production in J774A.1 cells without affecting their transcription levels. MNK1 appears to impair the phagocytosis, bacterial clearance, and phagosome acidification in Vv-infected J774A.1 cells through the MNK1-mTORC1 signaling pathway rather than the MNK1-eIF4E signaling pathway. Our findings highlight the importance of the MNK1-mTORC1 pathway in modulating macrophage responses to Vv infection. IMPORTANCE: Mitogen-activated protein kinase (MAPK)-interacting kinase (MNK) plays a role in promoting the production of tumor necrosis factor alpha and interleukin-6 in macrophages during Vibrio vulnificus (Vv) infection. Inhibition or knockout of MNK1 in J774A.1 cells resulted in reduced cytokine production without affecting their transcription levels. MNK1 also impairs phagocytosis, bacterial clearance, and phagosome acidification in Vv-infected cells through the MNK1-mammalian target of rapamycin complex 1 (mTORC1) signaling pathway. The findings highlight the importance of the MNK1-mTORC1 pathway in modulating macrophage responses to Vv infection.

Metformin induces tumor immunogenic cell death in ovarian cancer by activating AMPK pathway.

Inducing immunogenic cell death (ICD) process may be an important antitumor strategy in ovarian cancer (OC). Metformin (Met) has been shown to have antitumor effects in OC, but whether it mediates the ICD to inhibit OC process is unclear. Human OC cell lines (SKOV3 and A2780) were treated with Met. Dendritic cell (DC) and CD8+T cells were isolated from the peripheral blood mononuclear cells of volunteers. Cell counting kit 8 assay was used to measure cell viability, and immunofluorescence staining was performed to detect the percentages of membrane and intracellular calreticulin (CRT). CRT level, DC maturation and effector cell activation were evaluated by flow cytometry. The levels of IL-10 and IFN-γ, as well as the releasements of HMGB1 and ATP, were detected using corresponding kits. The protein levels of heat shock protein 70/90 (HSP70/90) and AMPKα were tested by western blot analysis, and the mRNA levels of CD80, CD86, IL-10, and IFN-γ were measured by quantitative real-time PCR. Colony formation assay was utilized for assessing cell cytotoxicity. Mice transplanted tumor model was constructed to assess the effect of Met on OC tumor growth, and immunohistochemistry staining was used to analyze CD80+ and CD86+ cells in mice tumor tissues. Our data showed that Met inhibited OC cell viability and induced CRT exposure. Besides, Met could promote the release of HMGB1 and ATP, as well as induce DC maturation. In vivo experiments suggested that Met restrained OC tumor growth via activating antitumor immune response. Moreover, Met activated AMPK pathway, and silenced AMPK pathway reversed the promoting effect of Met on CRT exposure and the releasements of HMGB1 and ATP in OC cells. In conclusion, Met induced ICD-mediated immune destruction in OC via activating AMPK pathway, indicating that Met might be used in the immunotherapy of OC.

Firefighters' muscle activity change during firefighting training program.

BACKGROUND: Research on muscle activity to reduce injuries during firefighting training has getting increasing attention. OBJECTIVE: The purpose of this study was to assess the activity changes in nine muscles of firefighters during the seven firefighting training programs, and to analyze the influence of different firefighting training programs on muscle activity. METHODS: Ten healthy male firefighters were recruited to measure the field surface electromyographic activities (including the percentage of Maximum Voluntary Contraction electromyography (% MVC) and the integrated electromyography value (iEMG)) during all the firefighting training programs. RESULTS: The results showed that the electromyographic activity of gastrocnemius (GA) was stronger in climbing the hooked ladder and climbing the six-meter long ladder training programs. Arms, shoulders, and lower limb muscles were more activated, myoelectric activities were more intense, and fatigue in these areas was more likely to occur during climbing five-story building with loads. Compared with other muscles, erector spine (ES) had a higher degree of activation during different postures of water shooting. The Borg scale scores of shoulders, trunk, thighs and calves were also higher. CONCLUSION: After completing all training programs, GA, tibialis anterior (TA), trapezius (TR), and ES were strongly activated, and all muscles had obvious force. The % MVC and iEMG analyses correspond well with the Borg Scale score. The results can provide certain reference for reducing the musculoskeletal injury of firefighters, carrying out scientific training and formulating effective injury prevention measures for them.

Identification of ibuprofen targeting CXCR family members to alleviate metabolic disturbance in lipodystrophy based on bioinformatics and in vivo experimental verification.

Background: Lipodystrophy is a rare disease that is poorly diagnosed due to its low prevalence and frequent phenotypic heterogeneity. The main therapeutic measures for patients with clinical lipodystrophy are aimed at improving general metabolic complications such as diabetes mellitus, insulin resistance, and hypertriglyceridemia. Therefore, there is an urgent need to find new biomarkers to aid in the diagnosis and targeted treatment of patients with congenital generalized lipodystrophy (CGL). Methods: Dataset GSE159337 was obtained via the Gene Expression Omnibus database. First, differentially expressed genes (DEGs) between CGL and control samples were yielded via differential expression analysis and were analyzed for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment to explore the functional pathways. Next, protein-protein interaction analysis and the MCC algorithm were implemented to yield candidate genes, which were then subjected to receiver operating characteristic (ROC) analysis to identify biomarkers with an area under the curve value exceeding 0.8. Moreover, random forest (RF), logistic regression, and support vector machine (SVM) analyses were carried out to assess the diagnostic ability of biomarkers for CGL. Finally, the small-molecule drugs targeting biomarkers were predicted, and ibuprofen was further validated in lipodystrophy mice. Results: A total of 71 DEGs in GSE159337 were sifted out and were involved in immune receptor activity, immune response-regulating signaling pathway, and secretory granule membrane. Moreover, CXCR2, TNFSF10, NLRC4, CCR2, CEACAM3, TLR10, TNFAIP3, and JUN were considered as biomarkers by performing ROC analysis on 10 candidate genes. Meanwhile, RF, logistic regression, and SVM analyses further described that those biomarkers had an excellent diagnosis capability for CGL. Eventually, the drug-gene network included ibuprofen-CXCR1, ibuprofen-CXCR1, cenicriviroc-CCR2, fenofibrate-JUN, and other relationship pairs. Ibuprofen treatment was also validated to downregulate CXCR1 and CXCR2 in peripheral blood mononuclear cells (PBMCs) and improve glucose tolerance, hypertriglyceridemia, hepatic steatosis, and liver inflammation in lipodystrophy mice. Conclusion: Eight biomarkers, namely, CXCR2, TNFSF10, NLRC4, CCR2, CEACAM3, TLR10, TNFAIP3, and JUN, were identified through bioinformatic analyses, and ibuprofen targeting CXCR1 and CXCR2 in PBMCs was shown to improve metabolic disturbance in lipodystrophy, contributing to studies related to the diagnosis and treatment of lipodystrophy.

Curcumin protects against cadmium-induced germ cell death in the testis of rats.

Introduction: Cadmium (Cd) has been shown to disrupt the reproductive system. In this study, we evaluated the protective effects of Curcumin (Cur) against Cd-induced reproductive toxicity. Methods: Exploring the role of Cur in Cd-treated rat models. Results: The study demonstrated that Cd treatment impaired the seminiferous epithelium, leading to increased apoptosis of germ cells. Interestingly, pretreatment with Cur ameliorated the histological damage and decreased the germ cell apoptosis induced by Cd. Furthermore, after Cd exposure, B-cell lymphoma-2 expression was significantly decreased while Bax expression was increased. Pretreatment of rats with Cur protected against germ cell apoptosis by improving the expression of B-cell lymphoma-2 and reducing Bax. Additionally, Cd treatment increased reactive oxygen species, resulting in a decrease in antioxidant enzymes. However, pretreatment of rats with Cur followed by Cd administration led to a substantial decrease in reactive oxygen species levels and increased activities of antioxidant enzymes. Ultrastructural investigations revealed that damage to the mitochondrial structure was significantly ameliorated by Cur pretreatment in Cd-treated rats. Notably, Cur significantly activated the peroxisome proliferator-activated receptor gamma coactivator 1a/Sirtuins-3 signaling pathway. Conclusions: Overall, our data suggest that Cd induces germ cell apoptosis through mitochondrial-induced oxidative stress, but Cur pretreatment offers strong protection against Cd-induced reproductive toxicity.

Disease Progression and Multiparametric Imaging Characteristics of Spinocerebellar Ataxia Type 3 With Spastic Paraplegia.

Background and Objectives: Spinocerebellar ataxia type 3 (SCA3) is a hereditary ataxia that occurs worldwide. Clinical patterns were observed, including the one characterized by marked spastic paraplegia. This study investigated the clinical features, disease progression, and multiparametric imaging aspects of patients with SCA3. Methods: We retrospectively analyzed 249 patients with SCA3 recruited from the Organization for Southeast China for cerebellar ataxia research between October 2014 and December 2020. Of the 249 patients, 145 were selected and assigned to 2 groups based on neurologic examination: SCA3 patients with spastic paraplegia (SCA3-SP) and SCA3 patients with nonspastic paraplegia (SCA3-NSP). Participants underwent 3.0-T brain MRI examinations, and voxel-wise and volume-of-interest-based approaches were used for the resulting images. A tract-based spatial statistical approach was used to investigate the white matter (WM) alterations using diffusion tensor imaging, neurite orientation dispersion, and density imaging metrics. Multiple linear regression analyses were performed to compare the clinical and imaging parameters between the 2 groups. The longitudinal data were evaluated using a linear mixed-effects model. Results: Forty-three patients with SCA3-SP (mean age, 37.58years ± 11.72 [SD]; 18 women) and 102 patients with SCA3-NSP (mean age, 47.42years ± 12.50 [SD]; 39 women) were analyzed. Patients with SCA3-SP were younger and had a lower onset age but a larger cytosine-adenine-guanine repeat number, as well as higher clinical severity scores (all corrected p < 0.05). The estimated progression rates of the Scale for the Assessment and Rating of Ataxia (SARA) and International Cooperative Ataxia Rating Scale scores were higher in the SCA3-SP subgroup than in the SCA3-NSP subgroup (SARA, 2.136 vs 1.218 points; ICARS, 5.576 vs 3.480 points; both p < 0.001). In addition, patients with SCA3-SP showed gray matter volume loss in the precentral gyrus with a decreased neurite density index in the WM of the corticospinal tract and cerebellar peduncles compared with patients with SCA3-NSP. Discussion: SCA3-SP differs from SCA3-NSP in clinical features, multiparametric brain imaging findings, and longitudinal follow-up progression.

Network Pharmacology and Molecular Docking Validation to Explore the Pharmacological Mechanism of Zhuling Decoction against Nephrotic Syndrome.

BACKGROUND: In recent years, the incidence and prevalence of Nephrotic Syndrome (NS) have been increasing. Zhuling decoction (ZLD), a classical Chinese medicine, has been clinically proven to be effective for the treatment of NS. However, its underlying mechanism and pharmacodynamic substances remain unclear. OBJECTIVE: This study aimed to explore the mechanism of action and chemical components of ZLD against NS using network pharmacology and molecular docking. METHODS: Traditional Chinese Medicine Systems Pharmacology (TCMSP), Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicines (BATMAN-TCM), and SwissTargetPrediction databases were used to screen the principal ingredients and the associated targets of ZLD. NS-related targets were obtained from the Online Mendelian Inheritance in Man (OMIM), GeneCards, Therapeutic Target Database (TTD), and Drugbank databases. Shared targets were derived by the intersection of ZLD- and NS-associated targets. Protein-interaction relationships were analyzed using the STRING database and Cytoscape. A visualized drug-active compound-target network of ZLD was established using Cytoscape. Analyses of gene enrichment were performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) methods by the Database for Annotation, Visualization, and Integrated Discovery (DAVID) database. Molecular docking was performed to assess the binding activity between active components and hub targets. RESULTS: Polyporusterone E, cerevisterol, alisol B, and alisol B 23-acetate were the primary potential ingredients of ZLD. HMGCR, HSD11B1, NOS2, NR3C1, and NR3C2 were the hub targets of ZLD against NS. Molecular docking showed that polyporusterone E, cerevisterol, and alisol B had high binding activities with targets HMGCR, HSD11B1, and NOS2. CONCLUSION: In summary, this study suggests that the main active compounds (polyporusterone E, cerevisterol, alisol B) may have important roles for ZLD acting against NS by binding to hub targets (HMGCR, HSD11B1, and NOS2) and modulating PI3K-Akt, Ras, MAPK, and HIF-1 signaling pathways.

Defect Regulation Strategy of Porous Persistent Phosphors for Multiple and Dynamic Information Encryption.

Optical encryption technologies based on persistent luminescence material have currently drawn increasing attention due to the distinctive and long-lived optical properties, which enable multi-dimensional and dynamic optical information encryption to improve the security level. However, the controlled synthesis of persistent phosphors remains largely unexplored and it is still a great challenge to regulate the structure for optical properties optimization, which inevitably sets significant limitations on the practical application of persistent luminescent materials. Herein, a controlled synthesis method is proposed based on defect structure regulation and a series of porous persistent phosphors is obtained with different luminous intensities, lifetime, and wavelengths. By simply using diverse templates during the sol-gel process, the oxygen vacancy defects structures are successfully regulated to improve the optical properties. Additionally, the obtained series of porous Al2O3 are utilized for multi-color and dynamic optical information encryption to increase the security level. Overall, the proposed defect regulation strategy in this work is expected to provide a general and facile method for optimizing the optical properties of persistent luminescent materials, paving new ways for broadening their applications in multi-dimensional and dynamic information encryption.

Early diagnosis and staging of paraquat-induced pulmonary fibrosis using [18F]F-FAPI-42 PET/CT imaging.

BACKGROUND: Paraquat (PQ) -induced pulmonary fibrosis poses a significant medical challenge due to limited treatment options and high mortality rates. Consequently, there is an urgent need for early diagnosis and accurate staging to facilitate appropriate treatment strategies. In this study, we assessed the diagnostic potential of [18F]F-FAPI-42 PET/CT imaging for early detection and disease staging in a rat model of PQ-induced lung fibrosis. METHODS: After administering 80 mg/kg of PQ orally to Sprague-Dawley rats, we intravenously injected 3-3.5 MBq of [18F]F-FAPI-42 on day 7, 14, and 21 post-dosing. Dynamic PET/CT imaging was carried out for one hour immediately after the administration of [18F]F-FAPI-42. Subsequently, the lung tissues were collected for Hematoxylin and Eosin (HE) staining, Masson's trichrome staining, and NOTA-FAPI-04-MB fluorescent probe staining. Data analysis was performed using the Imalytics preclinical software, and the mean standardized uptake value (SUVmean) was calculated. RESULTS: PET signals revealed that in areas with evident lesions on CT, the SUVmean on day 14 was significantly higher than on day 7 and 21, indicating that changes in fibrosis activity levels contribute to the staging of pulmonary fibrosis. Additionally, the NOTA-FAPI-04-MB fluorescent probe staining also demonstrated the most pronounced probe uptake on day 14. In regions without apparent lesions on CT, the SUVmean gradually increased from day 7 to day 21, reflecting ongoing fibrotic activity. Moreover, HE staining and Masson's trichrome staining did not reveal pulmonary fibrosis, while PET imaging was able to detect it, serving the purpose of early diagnosis. At 30 min and 60 min, the target-to-background ratio (TBR) of the PQ groups on day 7, 14, and 21 was significantly higher than the control group, suggesting a high specificity of [18F]F-FAPI-42 binding to activated fibroblasts. CONCLUSION: [18F]F-FAPI-42 PET/CT imaging enables early diagnosis and staging of PQ-induced pulmonary fibrosis, demonstrating its feasibility and potential for characterizing early disease stages.

[Multiple verruca plantaris treated with modified fire-needle technique and herbal bathing-repairing therapy of TCM: a randomized controlled trial].

OBJECTIVE: To observe the clinical effect of modified fire-needle technique and herbal bathing-repairing therapy of TCM on multiple verruca plantaris. METHODS: Seventy patients with multiple verruca plantaris were randomly divided into an observation group (35 cases, 1 case was eliminated) and a control group (35 cases, 2 cases dropped out). In the control group, the herbal bathing-repairing therapy of TCM was adopted. In the observation group, besides the treatment as the control group, fire needling and cauterization were delivered on the base of skin lesion or the sites with rich blood vessels under the dermoscope. The intervention was provided once a week, one course of treatment was composed of 3 weeks, and two courses were required in each group. The score of the self-designed symptom scale, the score of dermatology life quality index (DLQI) and the area of typical skin lesion were observed before and after treatment. The clinical effect was evaluated after treatment and the recurrence was assessed 2 months after treatment completion in the two groups. RESULTS: After treatment, the scores of the self-designed symptom scale and DLQI were lower and the area of typical skin lesion was smaller compared with those before treatment in the two groups (P<0.05). The scores of the self-designed symptom score and DLQI in the observation group were reduced (P<0.05), and the area of typical lesion was smaller (P<0.05) in comparison with those in the control group. The total effective rate was 91.2% (31/34) in the observation group, higher than that in the control group (60.6%, 20/33, P<0.05). The recurrence rate was 6.5% (2/31) in the observation group, lower than that in the control group (35.0%, 7/20, P<0.05). CONCLUSION: Modified fire-needle technique combined with herbal bathing-repairing therapy ameliorates clinical symptoms and the quality of life in the patients with multiple verruca plantaris and reduces the recurrence of the disease.

Prevalence and genotype distribution of HPV infection from Hangzhou of Zhejiang Province pre- and during COVID-19 pandemic.

Limited data exist on HPV prevalence and genotyping during the COVID-19 pandemic. A total of 130,243 samples from 129, 652 women and 591 men who visited the First People's Hospital of Linping District between 2016 and 2022 were recruited. HPV genotypes were detected by polymerase chain reaction (PCR) amplification and nucleic acid molecular hybridization. Then the prevalence characteristics of HPV genotypes and trends in HPV infection rates from 2016 to 2022 were analyzed. Results showed that among the study population, the overall prevalence of HPV infection was 15.29%, with 11.25% having single HPV infections and 4.04% having multiple HPV infections, consistent with previous findings. HPV genotypes exhibited similar distribution patterns in both male and female groups, with HPV16, HPV52, HPV58, HPV18, and HPV39 being the most prevalent. Age-related analysis unveiled a bimodal pattern in HPV prevalence, with peaks in infection rates observed in individuals below 20 and those aged 61-65 years. Comparing the pre- and during COVID-19 periods revealed significant disparities in HPV infections, with variations in specific HPV genotypes, including 16, 18, 35, 45, 52, 58, 59, and 68. This study provides valuable insights into the prevalence, distribution, and epidemiological characteristics of HPV infections in a large population. It also highlights the potential impact of the COVID-19 pandemic on HPV trends.

CLCuMuV subverts the processing of hydroxyproline-rich systemin to suppress tobacco defenses against insect vectors.

The interactions of insect vector-virus-plant have important ecological and evolutionary implications. The constant struggle of plants against viruses and insect vectors has driven the evolution of multiple defense strategies in the host as well as counter-defense strategies in the viruses and insect vectors. Cotton leaf curl Multan virus (CLCuMuV) is a major causal agent of cotton leaf curl disease in Asia and is exclusively transmitted by the whitefly Bemisia tabaci. Here, we report that plants infected with CLCuMuV and its betasatellite, cotton leaf curl Multan betasatellite (CLCuMuB) enhance the performance of B. tabaci vector, and ßC1 encoded by CLCuMuB plays an important role in begomovirus-whitefly-tobacco tripartite interactions. We showed that CLCuMuB ßC1 suppresses the jasmonic acid signaling pathway by interacting with the subtilisin-like protease 1.7 (NtSBT1.7) protein, thereby enhancing whitefly performance on tobacco plants. Further studies revealed that in the wild type plants, NtSBT1.7 could process tobacco preprohydroxyproline-rich systemin B (NtpreproHypSysB). After CLCuMuB infection, CLCuMuB ßC1 could interfere with the processing of NtpreproHypSysB by NtSBT1.7, thereby impairing plant defenses against whitefly. These results contribute to our understanding of the tripartite interactions among virus, plant, and whitefly, thus offering ecological insights into the spread of vector insect populations and the prevalence of viral diseases.

Viral strategies to antagonize the host antiviral innate immunity: an indispensable research direction for emerging virus-host interactions.

The public's health is gravely at risk due to the current global outbreak of emerging viruses, specifically SARS-CoV-2 and MPXV. Recent studies have shown that SARS-CoV-2 mutants (such as Omicron) exhibit a higher capability to antagonize the host innate immunity, increasing their human adaptability and transmissibility. Furthermore, current studies on the strategies for MPXV to antagonize the host innate immunity are still in the initial stages. These multiple threats from emerging viruses make it urgent to study emerging virus-host interactions, especially the viral antagonism of host antiviral innate immunity. Given this, we selected several representative viruses that significantly threatened human public health and interpreted the multiple strategies for these viruses to antagonize the host antiviral innate immunity, hoping to provide ideas for molecular mechanism research that emerging viruses antagonize the host antiviral innate immunity and accelerate the research progress. The IAV, SARS-CoV-2, SARS-CoV, MERS-CoV, EBOV, DENV, ZIKV, and HIV are some of the typical viruses. Studies have shown that viruses could antagonize the host antiviral innate immunity by directly or indirectly blocking antiviral innate immune signaling pathways. Proviral host factors, host restriction factors, and ncRNAs (microRNAs, lncRNAs, circRNAs, and vtRNAs) are essential in indirectly blocking antiviral innate immune signaling pathways. Furthermore, via controlling apoptosis, ER stress, stress granule formation, and metabolic pathways, viruses may antagonize it. These regulatory mechanisms include transcriptional regulation, post-translational regulation, preventing complex formation, impeding nuclear translocation, cleavage, degradation, and epigenetic regulation.

Validation and refinement of cropland map in southwestern China by harnessing ten contemporary datasets.

Accurate cropland map serves as the cornerstone of effective agricultural monitoring. Despite the continuous enrichment of remotely sensed cropland maps, pervasive inconsistencies have impeded their further application. This issue is particularly evident in areas with limited valid observations, such as southwestern China, which is characterized by its complex topography and fragmented parcels. In this study, we constructed multi-sourced samples independent of the data producers, taking advantage of open-source validation datasets and sampling to rectify the accuracy of ten contemporary cropland maps in southwestern China, decoded their inconsistencies, and generated a refined cropland map (CroplandSyn) by leveraging ten state-of-the-art remotely sensed cropland maps released from 2021 onwards using the self-adaptive threshold method. Validations, conducted at both prefecture and county scales, underscored the superiority of the refined cropland map, aligning more closely with national land survey data. The refined cropland map and samples are publicly available to users. Our study offers valuable insights for improving agricultural practices and land management in under-monitored areas by providing high-quality cropland maps and validation datasets.

Steering and cloaking of hyperbolic polaritons at deep-subwavelength scales.

Polaritons are well-established carriers of light, electrical signals, and even heat at the nanoscale in the setting of on-chip devices. However, the goal of achieving practical polaritonic manipulation over small distances deeply below the light diffraction limit remains elusive. Here, we implement nanoscale polaritonic in-plane steering and cloaking in a low-loss atomically layered van der Waals (vdW) insulator, α-MoO3, comprising building blocks of customizable stacked and assembled structures. Each block contributes specific characteristics that allow us to steer polaritons along the desired trajectories. Our results introduce a natural materials-based approach for the comprehensive manipulation of nanoscale optical fields, advancing research in the vdW polaritonics domain and on-chip nanophotonic circuits.

Genome-wide identification analysis in wild-type Solanum pinnatisectum reveals some genes defending against Phytophthora infestans.

Solanum pinnatisectum exhibits strong resistance to late blight caused by Phytophthora infestans but only an incomplete genome assembly based on short Illumina reads has been published. In this study, we generated the first chromosome-level draft genome for the wild-type potato species S. pinnatisectum in China using Oxford Nanopore technology sequencing and Hi-C technology. The high-quality assembled genome size is 664 Mb with a scaffold N50 value of 49.17 Mb, of which 65.87% was occupied by repetitive sequences, and predominant long terminal repeats (42.51% of the entire genome). The genome of S. pinnatisectum was predicted to contain 34,245 genes, of which 99.34% were functionally annotated. Moreover, 303 NBS-coding disease resistance (R) genes were predicted in the S. pinnatisectum genome to investigate the potential mechanisms of resistance to late blight disease. The high-quality chromosome-level reference genome of S. pinnatisectum is expected to provide potential valuable resources for intensively and effectively investigating molecular breeding and genetic research in the future.

Prognosis and factors related to severe secondary hyperparathyroidism in long-term peritoneal dialysis patients.

Secondary hyperparathyroidism (SHPT) can progress to severe SHPT (sSHPT), which affects the survival rate and quality of life of patients. This retrospective cohort study investigated risk factors for sSHPT and the association between SHPT and mortality (all-cause and infection-related) among 771 clinically stable patients (421 male patients; mean age, 51.2 years; median dialysis vintage, 28.3 months) who underwent >3 months of regular peritoneal dialysis (PD) between January 2013 and March 2021. The sSHPT and non-sSHPT groups comprised 75 (9.7%) (median progression, 35 months) and 696 patients, respectively. sSHPT was defined as a serum intact parathyroid hormone (PTH) level >800 pg/mL observed three times after active vitamin D pulse therapy. The influence of sSHPT on the prognosis of and risk factors for sSHPT progression were evaluated using logistic and Cox regression analyses. After adjusting for confounding factors, higher (each 100-pg/mL increase) baseline PTH levels (95% confidence interval (CI) 1.206-1.649, p < .001), longer (each 1-year increase) dialysis vintages (95% CI 1.013-1.060, p = .002), higher concomitant diabetes rates (95% CI 1.375-10.374, p = .010), and lower (each 1-absolute unit decrease) Kt/V values (95% CI 0.859-0.984, p = .015) were independent risk factors for progression to sSHPT in patients on PD. During follow-up, 211 deaths occurred (sSHPT group, n = 35; non-sSHPT group, n = 176). The sSHPT group had significantly higher infection-related mortality rates than the non-sSHPT group (12.0% vs. 4.3%; p < .05), and sSHPT was associated with increased infection-related mortality. In conclusion, patients with sSHPT are at higher risk for death and infection-related mortality than patients without sSHPT.

Sleep fragmentation exacerbates myocardial ischemia‒reperfusion injury by promoting copper overload in cardiomyocytes.

Sleep disorders increase the risk and mortality of heart disease, but the brain-heart interaction has not yet been fully elucidated. Cuproptosis is a copper-dependent type of cell death activated by the excessive accumulation of intracellular copper. Here, we showed that 16 weeks of sleep fragmentation (SF) resulted in elevated copper levels in the male mouse heart and exacerbated myocardial ischemia-reperfusion injury with increased myocardial cuproptosis and apoptosis. Mechanistically, we found that SF promotes sympathetic overactivity, increases the germination of myocardial sympathetic nerve terminals, and increases the level of norepinephrine in cardiac tissue, thereby inhibits VPS35 expression and leads to impaired ATP7A related copper transport and copper overload in cardiomyocytes. Copper overload further leads to exacerbated cuproptosis and apoptosis, and these effects can be rescued by excision of the sympathetic nerve or administration of copper chelating agent. Our study elucidates one of the molecular mechanisms by which sleep disorders aggravate myocardial injury and suggests possible targets for intervention.