Influence factors associated with fertility intention among people living with HIV in China and other regions: a systematic review and meta-analysis.

BACKGROUND: Advances in medical care and improved quality of life have fostered a growing desire for parenthood among people living with HIV (PLHIV). However, this desire remains inadequately addressed in China, highlighting a crucial research gap. Understanding the factors influencing fertility intentions in PLHIV is essential for informing policy development. METHODS: We conducted a systematic review of English and Chinese literature, analyzing articles from 2000 to 2024. The odds ratio (OR) with 95% confidence intervals (CIs) was used for pooled measurement. Subgroup analyses based on regional factors were performed, and publication bias was assessed using Egger's test. RESULTS: The review included 25 articles with 11,394 participants. Key factors associated with fertility intention included age (OR = 2.67, 95%CI: 2.04-3.48, P < 0.05), marital status (OR = 1.52, 95%CI: 1.14-2.02, P < 0.05), and number of children (OR = 5.28, 95%CI: 3.58-7.79, P < 0.05). Interestingly, education level did not significantly impact fertility desire (OR = 1.08, 95%CI: 0.72-1.41, P = 0.61). Subgroup analysis revealed that childlessness was a stronger influence in China (OR = 7.40, 95%CI: 3.76-14.58, P < 0.05) compared to developing and developed countries, where higher education levels had minimal or even negative effects on fertility intentions (OR = 0.98, 95%CI: 0.66-1.46, P = 0.93). No significant differences were observed regarding age and marital status between China and other regions. CONCLUSIONS: This study highlights the prominent roles of age, marital status, and number of children in shaping fertility intentions among PLHIV. In China, the social and national context uniquely influences these intentions. Given the limited number of studies and variability in educational classifications across countries, further in-depth research is warranted.

The role of an oxidized lithospheric mantle in gold mobilization.

Phanerozoic orogenic gold mineralization at craton margins is related to the metasomatism of the lithospheric mantle by crustal material. Slab subduction transfers Au from the crust to the metasomatized mantle and oxidizes the latter to facilitate the mobilization of Au into mantle melts. The role of volatiles in the mobilization of Au in the mantle is unclear because of the absence of direct geochemical evidence relating the mantle source of Au to Au mineralization in the overlying crust. This study uses lithium isotopes from a large suite of lamprophyres to characterize the mantle beneath the eastern North China Craton, which hosts giant Mesozoic gold deposits. Our results indicate a strong genetic link between carbonate metasomatism in the mantle and Au mineralization in the overlying crust. Although pre-enrichment of Au in the mantle is critical for forming giant Au provinces, the oxidation of the lithospheric mantle controls the mobilization of Au.

Isovalerylspiramycin I suppresses small cell lung cancer proliferation via ATR/CHK1 mediated DNA damage response and PERK/eIF2α/ATF4/CHOP mediated ER stress.

Small cell lung cancer (SCLC) urgently needs new therapeutic approaches. We found that the antibiotic-derived compound Isovalerylspiramycin I (ISP-I) has potent anti-tumor activity against SCLC cell lines H1048 and DMS53 both in vitro and in vivo. ISP-I induced apoptosis, G2/M phase cell cycle arrest, and mitochondrial respiratory chain dysfunction in both cell lines. Comprehensive RNA sequencing revealed that the anti-SCLC effects of ISP-I were primarily attributed to ATR/CHK1-mediated DNA damage response and PERK/eIF2α/ATF4/CHOP-mediated ER stress. Importantly, the induction of DNA damage, ER stress, and apoptosis by ISP-I was mitigated by the reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine (NAC), underscoring the critical role of ROS in the anti-SCLC mechanism of ISP-I. Moreover, ISP-I treatment induced immunogenic cell death (ICD) in SCLC cells, as evidenced by increased adenosine triphosphate (ATP) secretion, elevated release of high-mobility group box 1 (HMGB1), and enhanced exposure of calreticulin (CRT) on the cell surface. Additionally, network pharmacology analysis, combined with cellular thermal shift assay (CETSA) and cycloheximide (CHX) chase experiments, demonstrated that ISP-I acted as a ligand for apurinic/apyrimidinic endonuclease 1 (APEX1) and promoted its degradation, leading to the accumulation of ROS. In conclusion, our findings elucidate the multifaceted mechanisms underlying the anti-cancer effects of ISP-I, highlighting its potential as a promising therapeutic candidate for SCLC treatment.

Toward identity preserving in face sketch-photo synthesis using a hybrid CNN-Mamba framework.

The synthesis of facial sketch-photo has important applications in practical life, such as crime investigation. Many convolutional neural networks (CNNs) based methods have been proposed to address this issue. However, due to the substantial modal differences between sketch and photo, the CNN's insensitivity to global information, and insufficient utilization of hierarchical features, synthesized photos struggle to balance both identity preservation and image quality. Recently, State Space Sequence Models (SSMs) have achieved exciting results in computer vision (CV) tasks. Inspired by SSMs, we design a hybrid CNN-SSM model called FaceMamba for the Face Sketch-Photo Synthesis (FSPS) task. It includes an original Face Vision Mamba Attention for modeling in latent space using SSM. Additionally, it incorporates a general auxiliary method called Attention Feature Injection that combines encoding features, decoding features, and external auxiliary features using attention mechanisms. FaceMamba combines Mamba's modeling ability for long-range dependencies with CNN's powerful local feature extraction ability, and utilizes hierarchical features at the appropriate position. Adequate experimental and evaluation results reveal that FaceMamba has strong competitiveness in FSPS task, achieving the best balance between identity preservation and image quality.

Expanding clinical characteristics and genotypic profiling of Yao syndrome in Chinese patients.

Objectives: Yao syndrome (YAOS, OMIM# 617321) is a kind of systemic autoinflammatory diseases (SAIDs) linked to the nucleotide-binding oligomerization domain containing 2 (NOD2). Clinical reports of YAOS in China are sparse. Herein, we reported the largest YAOS cohort of Chinese patients to expand the understanding of its phenotype, genotype, and therapeutic responses. Methods: This study enrolled 15 adult patients diagnosed with YAOS at Peking Union Medical College Hospital from April 2015 to May 2024. Whole-exome sequencing was performed on all patients. Clinical data, genetic variations, and treatment responses were documented and compared with a Caucasian cohort. Results: The mean age of disease onset was 35 ± 17 years old. The most common clinical manifestations included recurrent high-grade fever (100%), gastrointestinal symptoms (73.3%), arthralgia/arthritis, fatigue, myalgia, and lower extremity swelling (46.7%). All patients exhibited elevated acute-phase reactants during episodes. 12 heterozygous NOD2 variants were identified, with Q902K in 4 patients, R471C in 3, and variants c.-14C>T, A110T, S127L, R311W, A432V, Y514H, R541P, A661P, K818Q, A886V each found in individual patients. 90% of the patients responded well to glucocorticoids, and 55.6% to sulfasalazine. 66.7% of patients who received TNF inhibitors achieved complete resolution of symptoms. Additionally, one patient each responded favorably to canakinumab and tocilizumab. Compared to the Caucasian cohort, our cohort exhibited a more balanced gender ratio and a higher proportion of recurrent fever, proteinuria/hematuria as well as more frequent leukocytosis, elevated acute phase reactants, and anemia. Lower proportions of arthralgia/arthritis, skin rashes, headaches, and sicca-like symptoms were noted in our cohort. Moreover, a higher proportion of patients in our cohort showed a good response to TNF inhibitors. Conclusion: Chinese patients with YAOS had more pronounced inflammatory manifestations compared to the Caucasian cohort. Variants c.-14C>T, A110T, S127L, A661P, K818Q, A886V, R471C, and A432V were identified as novel NOD2 variants in YAOS. TNF, IL-6, and IL-1 inhibitors are the promising treatment options. These findings expand the clinical spectrum, genetic profile, and treatment efficacy of YAOS, underscoring the need for heightened awareness of this disease in diverse populations.

Connexin 25 maintains self-renewal and functions of airway basal cells for airway regeneration.

BACKGROUND: The formation of stem cell clones enables close contact of stem cells inside. The gap junctions in such clone spheres establish a microenvironment that allows frequent intercellular communication to maintain self-renewal and functions of stem cells. Nevertheless, the essential gap junction protein for molecular signaling in clones is poorly known. METHODS: Primary human airway basal cells (hBCs) were isolated from brushing samples through bronchoscopy and then cultured. A tightly focused femtosecond laser was used to excite the local Ca2+ in an individual cell to initiate an internal Ca2+ wave in a clone to screen gap junction proteins. Immunoflourescence staining and clonogenicity assay were used to evaluate self-renewal and functions. RNA and protein levels were assessed by PCR and Western blot. Air-liquid interface assay was conducted to evaluate the differentiation potential. A Naphthalene injury mouse model was used to assess the regeneration potential. RESULTS: Herein, we identify Connexin 25 (Cx25) dominates intercellular Ca2+ communications in clones of hBCs in vitro to maintain the self-renewal and pluripotency of them. The self-renewal and in vitro differentiation functions and in vivo regeneration potential of hBCs in an airway damage model are both regulated by Cx25. The abnormal expression of Cx25 is validated in several diseases including IPF, Covid-19 and bronchiectasis. CONCLUSION: Cx25 is essential for hBC clones in maintaining self-renewal and functions of hBCs via gap junctions.

PerturbDB for unraveling gene functions and regulatory networks.

Perturb-Seq combines CRISPR (clustered regularly interspaced short palindromic repeats)-based genetic screens with single-cell RNA sequencing readouts for high-content phenotypic screens. Despite the rapid accumulation of Perturb-Seq datasets, there remains a lack of a user-friendly platform for their efficient reuse. Here, we developed PerturbDB (http://research.gzsys.org.cn/perturbdb), a platform to help users unveil gene functions using Perturb-Seq datasets. PerturbDB hosts 66 Perturb-Seq datasets, which encompass 4 518 521 single-cell transcriptomes derived from the knockdown of 10 194 genes across 19 different cell lines. All datasets were uniformly processed using the Mixscape algorithm. Genes were clustered by their perturbed transcriptomic phenotypes derived from Perturb-Seq data, resulting in 421 gene clusters, 157 of which were stable across different cellular contexts. Through integrating chemically perturbed transcriptomes with Perturb-Seq data, we identified 552 potential inhibitors targeting 1409 genes, including an mammalian target of rapamycin (mTOR) signaling inhibitor, retinol, which was experimentally verified. Moreover, we developed a 'Cancer' module to facilitate the understanding of the regulatory role of genes in cancer using Perturb-Seq data. An interactive web interface has also been developed, enabling users to visualize, analyze and download all the comprehensive datasets available in PerturbDB. PerturbDB will greatly drive gene functional studies and enhance our understanding of the regulatory roles of genes in diseases such as cancer.

Mechanism of norcantharidin intervention in gastric cancer: analysis based on antitumor proprietary Chinese medicine database, network pharmacology, and transcriptomics.

BACKGROUND: Combining antitumor proprietary Chinese medicine (pCm) with radiotherapy and chemotherapy can effectively improve tumor cure rates and enhance patients' quality of life. Gastric cancer (GC) severely endangers public health. Despite satisfactory therapeutic effects achieved by using antitumor pCm to treat GC, its underlying mechanism remains unclear. OBJECTIVE: To integrate existing research data, construct a database of antitumor pCm, and study the intervention mechanisms in GC by focusing on their monomer components. METHODS: We constructed an antitumor pCm database based on China's medical insurance catalog, and employed network pharmacology, molecular docking methods, cell experiments, transcriptomics, and bioinformatics to investigate the intervention mechanisms of effective pCm components for GC. RESULTS: The study built an antitumor pCm database including 55 pCms, 171 Chinese herbal medicines, 1955 chemical components, 2104 targets, and 32 disease information. Network pharmacology and molecular docking technology identified norcantharidin as an effective component of antitumor pCm. In vitro experiments showed that norcantharidin effectively inhibited GC cell proliferation, migration, and invasion; blocked the G2/M cell cycle phase; and induced GC cell apoptosis. Transcriptomic results revealed that norcantharidin affected biological processes, such as cell adhesion, migration, and inflammatory responses by influencing PI3K-AKT, NF-κB, JAK-STAT, TNF-α signaling pathways, and EMT-related pathways. Core molecules of norcantharidin involved in GC intervention include SERPINE1, SHOX2, SOX4, PRDM1, TGFR3, TOX, PAX9, IL2RB, LAG3, and IL15RA. Additionally, the key target SERPINE1 was identified using bioinformatics methods. CONCLUSION: Norcantharidin, as an effective component of anti-tumor pCm, exerts its therapeutic effects on GC by influencing biological processes such as cell adhesion, migration, and inflammation. This study provides a foundation and research strategy for the post-marketing re-evaluation of antitumor pCms.

Association of metabolites on ischemic stroke subtypes: a 2-sample Mendelian randomization study.

Background: Metabolomics is increasingly being utilized in IS research to elucidate the intricate metabolic alterations that occur during ischemic stroke (IS). However, establishing causality in these associations remains unclear between metabolites and IS subtypes. In this study, we employ Mendelian randomization (MR) to identify specific metabolites and investigate potential causal relationships between metabolites and IS subtypes. Methods: MR analysis was conducted using genome-wide association study (GWAS) summary data. We obtained 1,091 blood metabolites and 309 metabolite ratios from the GWAS Catalog (GCST90199621-90201020), which gene sequencing data from 8,299 individuals from the Canadian Longitudinal Study. We obtained GWAS summary statistics for IS subtypes which include large artery stroke (LAS), cardioembolic stroke (CES), and small vessel stroke (SVS) from the MEGASTROKE consortium that included 446,696 cases of European ancestry and 406,111 controls of European ancestry. The primary analysis utilized inverse-variance weighted (IVW) method. To validate our results, we performed supplementary analyses employing the MR-Egger, weighted median, simple mode, and weighted mode methods. Heterogeneity and pleiotropy were assessed through Cochran's Q test, MR-Egger intercept test, and leave-one-out analysis. Results: The study assessed the possible causality of serum metabolites in the risk of IS subtypes. The discovery of significant causal links between 33 metabolites and 3 distinct IS subtypes. Conclusion: Metabolites show significant potential as circulating metabolic biomarkers and offer promise for clinical applications in the prevention and screening of IS subtypes. These discoveries notably advance our comprehension of the molecular processes specific to IS subtypes and create avenues for investigating targeted treatment approaches in the future.

Hypoxia induces ROS-resistant memory upon reoxygenation in vivo promoting metastasis in part via MUC1-C.

Hypoxia occurs in 90% of solid tumors and is associated with metastasis and mortality. Breast cancer cells that experience intratumoral hypoxia are 5x more likely to develop lung metastasis in animal models. Using spatial transcriptomics, we determine that hypoxic cells localized in more oxygenated tumor regions (termed 'post-hypoxic') retain expression of hypoxia-inducible and NF-kB-regulated genes, even in the oxygen-rich bloodstream. This cellular response is reproduced in vitro under chronic hypoxic conditions followed by reoxygenation. A subset of genes remains increased in reoxygenated cells. MUC1/MUC1-C is upregulated by both HIF-1α and NF-kB-p65 during chronic hypoxia. Abrogating MUC1 decreases the expression of superoxide dismutase enzymes, causing reactive oxygen species (ROS) production and cell death. A hypoxia-dependent genetic deletion of MUC1, or MUC1-C inhibition by GO-203, increases ROS levels in circulating tumor cells (CTCs), reducing the extent of metastasis. High MUC1 expression in tumor biopsies is associated with recurrence, and MUC1+ CTCs have lower ROS levels than MUC1- CTCs in patient-derived xenograft models. This study demonstrates that therapeutically targeting MUC1-C reduces hypoxia-driven metastasis.

A method for quantitative spatial analysis of immunolabeled fibers at regenerative electrode interfaces.

BACKGROUND: Regenerative electrodes are being explored as robust peripheral nerve interfaces for neuro-prosthetic control and sensory feedback. Current designs differ in electrode number, spatial arrangement, and porosity which impacts the regeneration, activation, and spatial distribution of fibers at the device interface. Knowledge of sensory and motor fiber distributions are important in optimizing selective fiber activation and recording. NEW METHOD: We use confocal microscopy and immunofluorescence methods to conduct spatial analysis of immunolabeled fibers across whole nerve cross sections. RESULTS: This protocol was implemented to characterize motor fiber distribution within 3 macro-sieve electrode regenerated (MSE), 3 silicone-conduit regenerated, and 3 unmanipulated control rodent sciatic nerves. Total motor fiber counts were 1485 [SD: +/- 50.11], 1899 [SD: +/- 359], and 5732 [SD: +/- 1410] for control, MSE, and conduit nerves respectively. MSE motor fiber distributions exhibited evidence of deviation from complete spatial randomness and evidence of dispersion and clustering tendencies at varying scales. Notably, MSE motor fibers exhibited clustering within the central portion of the cross section, whereas conduit regenerated motor fibers exhibited clustering along the periphery. COMPARISON WITH EXISTING METHODS: Prior exploration of fiber distributions at regenerative interfaces was limited to either quadrant-based density analysis of randomly sampled subregions or qualitative description. This method extends existing sample preparation and microscopy techniques to quantitatively assess immunolabeled fiber distributions within whole nerve cross-sections. CONCLUSIONS: This approach is an effective way to examine the spatial organization of fiber subsets at regenerative electrode interfaces, enabling robust assessment of fiber distributions relative to electrode arrangement.

Lysosomal iron accumulation and subsequent lysosomes-mitochondria iron transmission mediate PFOS-induced hepatocyte ferroptosis.

Perfluorooctane sulfonate (PFOS) is known as a persistent organic pollutant. A significant correlation between PFOS and liver ferroptosis has been unveiled, but the precise mechanism needs to be elucidated. In prior research, we found that PFOS treatment provoked mitochondrial iron overload. In this study, we observed a gradual increase in lysosomal iron in L-O2 cells after exposure to PFOS for 0.5-24 h. In PFOS-exposed L-O2 cells, suppressing autophagy relieved the lysosomal iron overload. Inhibiting transient receptor potential mucolipin 1 (TRPML1), a calcium efflux channel on the lysosomal membrane, led to a further rise in lysosomal iron levels and decreased mitochondrial iron overload during PFOS treatment. Suppressing VDAC1, a subtype of voltage-dependent anion-selective channels (VDACs) on the outer mitochondrial membrane, had no impact on PFOS-triggered mitochondrial iron overload, whereas restraining VDAC2/3 relieved this condition. Although silencing VDAC2 relieved PFOS-induced mitochondrial iron overload, it had no effect on PFOS-triggered lysosomal iron overload. Silencing VDAC3 alleviated PFOS-mediated mitochondrial iron overload and led to an additional increase in lysosomal iron. Therefore, we regarded VDAC3 as the specific VDACs subtype that mediated the lysosomes-mitochondria iron transfer. Additionally, in the presence of PFOS, an enhanced association between TRPML1 and VDAC3 was found in mice liver tissue and L-O2 cells. Our research unveils a novel regulatory mechanism of autophagy on the iron homeostasis and the effect of TRPML1-VDAC3 interaction on lysosomes-mitochondria iron transfer, giving an explanation of PFOS-induced ferroptosis and shedding some light on the role of classic calcium channels in iron transmission.

The phosphorylation of Smad3 by CaMKIIγ leads to the hepatocyte pyroptosis under perfluorooctane sulfonate exposure.

Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant and accumulated in the liver of mammals. PFOS exposure is closely associated with the development of pyroptosis. Nevertheless, the underlying mechanism is unclear. We found here that PFOS induced pyroptosis in the mice liver and L-02 cells as demonstrated by activation of the NOD-like receptor protein 3 inflammasome, gasdermin D cleavage and increased release of interleukin-1ß and interleukin-18. The level of cytoplasmic calcium was accelerated in hepatocytes upon exposure to PFOS. The phosphorylated/activated form of calcium/calmodulin-dependent protein kinase II (CaMKII) was augmented by PFOS in vivo and in vitro. PFOS-induced pyroptosis was relieved by CaMKII inhibitor. Among various CaMKII subtypes, we identified that CaMKIIγ was activated specifically by PFOS. CaMKIIγ interacted with Smad family member 3 (Smad3) under PFOS exposure. PFOS increased the phosphorylation of Smad3, and CaMKII inhibitor or CaMKIIγ siRNA alleviated PFOS-caused phosphorylation of Smad3. Inhibiting Smad3 activity was found to alleviate PFOS-induced hepatocyte pyroptosis. This study puts forward that CaMKIIγ-Smad3 is the linkage between calcium homeostasis disturbance and pyroptosis, providing a mechanistic explanation for PFOS-induced pyroptosis.

The decoder design and performance comparative analysis for closed-loop brain-machine interface system.

Brain-machine interface (BMI) can convert electroencephalography signals (EEGs) into the control instructions of external devices, and the key of control performance is the accuracy and efficiency of decoder. However, the performance of different decoders obtaining control instructions from complex and variable EEG signals is very different and irregular in the different neural information transfer model. Aiming at this problem, the off-line and on-line performance of eight decoders based on the improved single-joint information transmission (SJIT) model is compared and analyzed in this paper, which can provide a theoretical guidance for decoder design. Firstly, in order to avoid the different types of neural activities in the decoding process on the decoder performance, eight decoders based on the improved SJIT model are designed. And then the off-line decoding performance of these decoders is tested and compared. Secondly, a closed-loop BMI system which combining by the designed decoder and the random forest encoder based on the improved SJIT model is constructed. Finally, based on the constructed closed-loop BMI system, the on-line decoding performance of decoders is compared and analyzed. The results show that the LSTM-based decoder has better on-line decoding performance than others in the improved SJIT model.

The use of matrine to inhibit osteosarcoma cell proliferation via the regulation of the MAPK/ERK signaling pathway.

Background: Matrine is an alkaloid extracted from Sophorus beans of the legume family, and it has significant effects and a variety of pharmacological activities. Osteosarcoma(OS) is a common malignant bone tumor that is characterized by high incidence and rapid progression. There have been some preliminary studies on the therapeutic effect of matrine on OS, but the specific mechanism remains unclear. Objective: The aim of this study was to investigate the antitumor effect of matrine on HOS cells and the underlying molecular mechanism. Methods: The effects of matrine on the proliferation, apoptosis and cell cycle progression of HOS cells were determined by CCK-8 assay, TUNEL assay and flow cytometry in vitro. Wound healing and Transwell invasion assays were used to observe the effect of matrine on the migration and invasion of HOS cells. The mechanism underlying the antitumor effect of matrine on HOS cells was investigated by Western blotting. Results: Matrine significantly inhibited HOS cell proliferation, promoted HOS cell apoptosis, and arrested HOS cells in the G1 phase of the cell cycle. Both wound healing and Transwell invasion assays showed that matrine inhibited HOS cell migration and invasion. Western blotting results showed that matrine inhibited the activation of the MAPK/ERK signaling pathway. We found that matrine also downregulated Bcl-2 expression, which may be related to protein synthesis inhibition. Conclusion: Matrine can inhibit the proliferation of HOS cells, arrest HOS cells in the G1 phase, and promote HOS cell apoptosis through the MAPK/ERK signaling pathway.

Case report: Macrophage activation syndrome in a patient with Kabuki syndrome.

Macrophage activation syndrome (MAS), is a severe and fatal complication of various pediatric inflammatory disorders. Kabuki syndrome (KS), mainly caused by lysine methyltransferase 2D (KMT2D; OMIM 602113) variants, is a rare congenital disorder with multi-organ deficiencies. To date, there have been no reported cases of MAS in patients with KS. This report describes a case of a 22-year-old male with Kabuki syndrome (KS) who developed MAS. This unique case not only deepens the understanding of the involvement of KMT2D in immune regulation and disease, but expands the phenotype of the adult patient to better understand the natural history, disease burden, and management of patients with KS complicated with autoimmune disorders.

Identification and characterization of new Siberian subtype of tick-borne encephalitis virus isolates revealed genetic variations of the Chinese strains.

Tick-borne encephalitis virus (TBEV) is a pathogen that causes febrile infectious diseases and neurological damage to humans. TBEVs are prevalent from Europe to Far Eastern Asia, including Northeastern China. The understanding of TBEV phylogeny in China has been limited owing to insufficient genomic data on Chinese TBEV strains. Here, six TBEV strains were isolated from ticks collected in Inner Mongolia. The transmission electron microscopy revealed spherical particles with an enveloped structure of 50-60 nm in diameter. Phylogenetic analysis showed that, two strains were classified as the Siberian subtype, while the remaining four were identified as the Far Eastern subtype. Migration analyses based on TBEV ORF and envelope (E) protein sequences revealed that Chinese TBEV strains were migrated from Russia and/or Kazakhstan into China. Hulun Buir and Mudanjiang, the northeastern region of China, are considered hotspots with multiple import and export routes of Chinese TBEV strains. These results promote the understanding of TBEV genetic variations and phylogeny in China and suggest the importance of improving investigation of TBEV prevalence, which would instrumental for vaccine design strategies and better preparation for controlling TBEV infection in humans.

Design, Construction, and Test of Compact, Distributed-Charge, X-Band Accelerator Systems that Enable Image-Guided, VHEE FLASH Radiotherapy.

The design and optimization of laser-Compton x-ray systems based on compact distributed charge accelerator structures can enable micron-scale imaging of disease and the concomitant production of beams of Very High Energy Electrons (VHEEs) capable of producing FLASH-relevant dose rates. The physics of laser-Compton x-ray scattering ensures that the scattered x-rays follow exactly the trajectory of the incident electrons, thus providing a route to image-guided, VHEE FLASH radiotherapy. The keys to a compact architecture capable of producing both laser-Compton x-rays and VHEEs are the use of X-band RF accelerator structures which have been demonstrated to operate with over 100 MeV/m acceleration gradients. The operation of these structures in a distributed charge mode in which each radiofrequency (RF) cycle of the drive RF pulse is filled with a low-charge, high-brightness electron bunch is enabled by the illumination of a high-brightness photogun with a train of UV laser pulses synchronized to the frequency of the underlying accelerator system. The UV pulse trains are created by a patented pulse synthesis approach which utilizes the RF clock of the accelerator to phase and amplitude modulate a narrow band continuous wave (CW) seed laser. In this way it is possible to produce up to 10 µA of average beam current from the accelerator. Such high current from a compact accelerator enables production of sufficient x-rays via laser-Compton scattering for clinical imaging and does so from a machine of "clinical" footprint. At the same time, the production of 1000 or greater individual micro-bunches per RF pulse enables > 10 nC of charge to be produced in a macrobunch of < 100 ns. The design, construction, and test of the 100-MeV class prototype system in Irvine, CA is also presented.

Thrombocytopenia in SFTS due to platelets with altered function undergoing cell death pathways.

BACKGROUND: Thrombocytopenia is the major clinical feature associated with the severity of SFTS, but the mechanism by which it occurs remains unclear. METHODS: RNA transcriptome analyses were performed on platelets purified from SFTS patients and SFTSV-infected mice. The functions of differentially expressed genes (DEGs) in the platelets were characterized. ELISA, flow cytometry, and qRT-PCR were used to measure the levels of platelet activation, SFTSV infection in platelets, formation of neutrophil extracellular traps (NETs), transcription of DEGs and percent of platelets undergoing cell death. RESULTS: Enhanced neutrophil activation and interferon (IFN) signaling involved in the viral life cycle were common platelet responses in SFTS, which may consume increasing numbers of platelets. Other functional changes may be associated with different outcomes of SFTS. SFTSV infection led to platelet destruction by pyroptosis, apoptosis, necroptosis, and autophagy. In contrast to SFTS patients, platelets in SFTSV-infected mice mainly play a role in adaptive immunity, and platelet death was not as severe as in humans. CONCLUSIONS: The altered functions of platelets, such as mediating leukocyte activation and undergoing cell death, contribute to thrombocytopenia in SFTS patients. The different mechanisms of thrombocytopenia in mice, suggest that platelet functions should be considered in experimental animal models.

Increased Expression of Mevalonate Pathway-Related Enzymes in Angiotensin II-Induced Abdominal Aortic Aneurysms.

Abdominal aortic aneurysm (AAA) is characterized by permanent luminal expansion and a high mortality rate due to aortic rupture. Despite the identification of abnormalities in the mevalonate pathway (MVA) in many diseases, including cardiovascular diseases, the potential impact of this pathway on AAA remains unclear. This study aims to investigate whether the expression of the MVA-related enzyme is altered during the progression of angiotensin II (Ang II) -induced AAA.Ang II 28D and Ang II 5D groups were continuously perfused with Ang II for 28 days and 5 days, respectively, and the Sham group was perfused with saline. The general and remodeling characteristics of AAA were determined by biochemical and histological analysis. Alteration of MVA-related enzyme expressions was revealed by western blot and single-cell RNA sequencing (scRNA-seq).The continuous Ang II infusion for 28 days showed significant aorta expansion and arterial remodeling. Although the arterial diameter slightly increased, the aneurysm formation was not found in Ang II induction for 5 days. MVA-related enzyme expression and activation of small GTP-binding proteins were significantly increased after Ang II-induced. As verified by scRNA-seq, the key enzyme gene expression was also higher in Ang II 28D. Similarly, it was detected that the expression levels of the above enzymes and the activity of small G proteins were elevated in the early stage of AAA as induced by Ang II infusion for 5 days.Continuous Ang II infusion-induced abdominal aortic expansion and arterial remodeling were accompanied by altered expression of key enzymes in the MVA.