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Objective: Monitoring the disease status of Epstein–Barr virus (EBV)–related hemophagocytic lymphohistiocytosis (HLH) patients is crucial. This study aimed to investigate the different strategies and outcomes of patients with EBV-HLH and re-elevated EBV-DNA. Method: A retrospective analysis was conducted on 20 patients diagnosed with EBV-HLH. Clinical features, laboratory tests, treatments, plasma EBV-DNA levels, and outcomes were assessed. Three cases were highlighted for detailed analysis. Results: Nine of the 20 patients had a re-elevation of EBV-DNA during treatment, and 55.5 % (5/9) experienced relapses. Patients with persistently positive plasma EBV-DNA (n = 4) and those with re-elevated EBV-DNA after conversion (n = 9) showed a significantly higher relapse rate compared to those with persistently negative EBV-HLH (n = 7) (p < 0.05). Among the highlighted cases, Case 1 exhibited plasma EBV-DNA re-elevation after four weeks of treatment without relapse, maintaining stability with the original treatment regimen, and eventually, his plasma EBV-DNA turned negative. In Case 2, plasma EBV-DNA was elevated again with a recurrence of HLH after L-DEP. Consequently, she underwent allogeneic hematopoietic stem cell transplantation and eventually achieved complete remission (CR) with negative plasma EBV-DNA. Case 3 experienced plasma EBV-DNA re-elevation after L-DEP but remained in CR, discontinuing chemotherapy without relapse. Conclusion: The re-elevation of plasma EBV-DNA during EBV-HLH treatment poses challenges in determining disease status and treatment strategies. Optimal management decisions require a combination of the level of elevated EBV-DNA, the intensity of hyperinflammation, and the patient's immune function.

Abstract Nipah virus (NiV) is a zoonotic emergent paramyxovirus that can cause severe encephalitis and respiratory infections in humans, with a high fatality rate ranging from 40% to 75%. Currently, there are no approved human vaccines or antiviral drugs against NiV. Here, we designed a ferritin-based self-assembling nanoparticle displaying the NiV G head domain on the surface (NiV G-ferritin) and assessed immune responses elicited by the soluble NiV G head domain (NiV sG) or NiV G-ferritin. Immunization with NiV G-ferritin or NiV sG conferred complete protection against lethal NiV challenge without detection of viral RNA in Syrian golden hamsters. Compared to NiV sG, NiV G-ferritin induced significantly faster, broader, and higher serum neutralizing responses against three pathogenic henipaviruses (NiV-Malaysia, NiV-Bangladesh, and Hendra virus). Moreover, NiV G-ferritin induced a durable neutralizing immunity in mice as antisera potently inhibited NiV infection even after six months of the third immunization. Additionally, we isolated a panel of 27 NiV G-binding monoclonal antibodies (mAbs) from NiV G-ferritin immunized mice and found that these mAbs targeted four distinct antigenic sites on NiV G head domain with two sites that have not been defined previously. Notably, 25 isolated mAbs have potent neutralizing activity with 50% inhibitory concentrations less than 10 ng/mL against NiV pseudovirus. Collectively, these findings provide new insights into the immunogenicity of NiV G protein and reveal that NiV G-ferritin is a safe and highly effective vaccine candidate against Nipah virus infection.

Abstract The global epidemic of Mpox virus (MPXV) continues, and a local outbreak has occurred in Shenzhen city since June 2023. Herein, the evolutionary trajectory and characteristics of MPXV in 2023 were analyzed using 92 MPXV sequences from the Shenzhen outbreak and the available genomes from GISAID and GenBank databases. Phylogenetic tracing of the 92 MPXVs suggests that MPXVs in Shenzhen may have multiple sources of importation, and two main transmission chains have been established. The combination of phylogenetic relationships, epidemiological features, and mutation characteristics supports the emergence of a new lineage C.1.1. Together with the B.1 lineage diverging from the A.1 lineage, C.1.1 lineage diverging from the C.1 lineage may serve as another significant evolutionary events of MPXV. Moreover, increasing apolipoprotein B mRNA-editing catalytic polypeptide-like 3 (APOBEC3) related mutations, higher rate of missense mutations, and less mutations in the non-coding regions have been shown during MPXV evolution. Host regulation proteins of MPXV have accumulated considerable amino acid mutations since the B.1 lineage, and a lineage-defining APOBEC3-related mutation that disrupts the N2L gene encoding a viral innate immune modulator has been identified in the C.1.1 lineage. In summary, our study provides compelling evidence for the ongoing evolution of MPXV with specific features.

In the wake of the largest-ever recorded outbreak of mpox in terms of magnitude and geographical spread in human history since May 2022, we innovatively developed an automated online sewage virus enrichment and concentration robot for disease tracking. Coupled with an artificial intelligence (AI) model, our research aims to estimate mpox cases based on the concentration of the monkeypox virus (MPXV) in wastewater. Our research has revealed a compelling link between the levels of MPXV in wastewater and the number of clinically confirmed mpox infections, a finding that is reinforced by the ability of our AI prediction model to forecast cases with remarkable precision, capturing 87 % of the data’s variability. However, it is worth noting that this high precision in predictions may be related to the relatively high frequency of data acquisition and the relatively non-mobile isolated environment of the hospital itself. In conclusion, this study represents a significant step forward in our ability to track and respond to mpox outbreaks. It has the potential to revolutionize public health surveillance by utilizing innovative technologies for disease surveillance and prediction.

Abstract Timely and effective diagnosis of fungal keratitis (FK) is necessary for suitable treatment and avoiding irreversible vision loss for patients. In vivo confocal microscopy (IVCM) has been widely adopted to guide the FK diagnosis. We present a deep learning framework for diagnosing fungal keratitis using IVCM images to assist ophthalmologists. Inspired by the real diagnostic process, our method employs a two-stage deep architecture for diagnostic predictions based on both image-level and sequence-level information. To the best of our knowledge, we collected the largest dataset with 96,632 IVCM images in total with expert labeling to train and evaluate our method. The specificity and sensitivity of our method in diagnosing FK on the unseen test set achieved 96.65% and 97.57%, comparable or better than experienced ophthalmologists. The network can provide image-level, sequence-level and patient-level diagnostic suggestions to physicians. The results show great promise for assisting ophthalmologists in FK diagnosis.

Abstract Background Epstein-Barr virus DNA (EBV-DNA) is closely related to the pathogenesis and prognosis of EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH). The quantitative measurement of blood EBV-DNA is widely used in EBV-HLH, but there remains a lack of evidence to guide clinicians. Methods A retrospective analysis was conducted on clinical manifestations, laboratory tests, 310 blood EBV-DNA loads, and prognosis of 51 pediatric patients diagnosed with EBV-HLH. Receiver operating characteristic (ROC) curves were utilized to determine the optimal cutoff values of EBV-DNA for predicting mortality and evaluating the active status of EBV-HLH. Results EBV-positive- lymphoma-HLH had higher initial plasma EBV-DNA load(1.10 × 106copies/ml) compared to the EBV-HLH group (1.98 × 104 copies/ml) (P = 0.006), and experienced recurrently elevated plasma EBV-DNA levels during treatment. The optimal cut-off value of initial plasma EBV-DNA load in predicting mortality was 2.68 × 105 copies/ml, with a sensitivity of 88.57% and a specificity of 56.25%. For determining the active status of HLH, the optimal cutoff value of PBMC EBV-DNA load during treatment was 2.95 × 105 copies/ml, with a sensitivity of 69.14% and a specificity of 64.71%. The cut-off value of plasma EBV-DNA for determining active status was 1.32 × 103 copies/ml, with a sensitivity of 84.34%, and a specificity of 87.67%. Patients with higher PBMC and plasma EBV-DNA at initial and those with repeated elevated plasma EBV-DNA during treatment had worse prognoses (P

Abstract One-dimensional metallic transition-metal chalcogenide nanowires (TMC-NWs) hold promise for interconnecting devices built on two-dimensional (2D) transition-metal dichalcogenides, but only isotropic growth has so far been demonstrated. Here we show the direct patterning of highly oriented Mo6Te6 NWs in 2D molybdenum ditelluride (MoTe2) using graphite as confined encapsulation layers under external stimuli. The atomic structural transition is studied through in-situ electrical biasing the fabricated heterostructure in a scanning transmission electron microscope. Atomic resolution high-angle annular dark-field STEM images reveal that the conversion of Mo6Te6 NWs from MoTe2 occurs only along specific directions. Combined with first-principles calculations, we attribute the oriented growth to the local Joule-heating induced by electrical bias near the interface of the graphite-MoTe2 heterostructure and the confinement effect generated by graphite. Using the same strategy, we fabricate oriented NWs confined in graphite as lateral contact electrodes in the 2H-MoTe2 FET, achieving a low Schottky barrier of 11.5 meV, and low contact resistance of 43.7 Ω µm at the metal-NW interface. Our work introduces possible approaches to fabricate oriented NWs for interconnections in flexible 2D nanoelectronics through direct metal phase patterning.

Objective(s): Wnt5a, which regulates the activities of osteoblasts and osteoclasts, is reportedly overexpressed in osteoarthritis (OA) tissues. The purpose of this study was to elucidate its role in the development of OA by deleting Wnt5a in osteocalcin (OCN)-expressing cells.Materials and Methods: Knee OA was induced by anterior cruciate ligament transection (ACLT) in OCN-Cre;Wnt5afl/fl knockout (Wnt5a-cKO) mice and control littermates. Eight weeks after surgery, histological changes, cell apoptosis, and matrix metabolism of cartilage were evaluated by toluidine blue, TUNEL staining, and im-immunohistochemistry analyses, respectively. In addition, the subchondral bone microarchitecture of mice was examined by micro-computed tomography (micro-CT).Results: Histological scores show substantial cartilage degeneration occurred in ACLT knees, coupled with decreased collagen type II expression and enhanced matrix metalloproteinase 13 expression, as well as higher proportions of apoptotic cells. Micro-CT results show that ACLT resulted in decreased bone mineral density, bone volume/trabecular volume, trabecular number, and structure model index of subchondral bones in both Wnt5a-cKO and control littermates; although Wnt5a-cKO mice display lower BMD and BV/TV values, no significant difference was observed between Wnt5a-cKO and control mice for any of these values. Conclusion: Our findings indicate that Wnt5a deficiency in OCN-expressing cells could not prevent an osteoarthritic phenotype in a mouse model of post-traumatic OA.

Abstract Purpose This study aimed to investigate the feasibility of using computed tomography (CT) attenuation values to differentiate hypodense brain lesions, specifically acute ischemic stroke (AIS) from asymmetric leukoaraiosis (LA) and old cerebral infarction (OCI). Materials and methods This retrospective study included patients with indeterminate hypodense lesions identified via brain CT scans conducted between June 2019 and June 2021. All lesions were confirmed through head MRI/diffusion-weighted imaging within 48 h after CT. CT attenuation values of hypodense lesions and symmetrical control regions were measured. Additionally, CT attenuation value difference (ΔHU) and ratio (RatioHU) were calculated. One-way analysis of variance (ANOVA) was used to compare age and CT parameters (CT attenuation values, ΔHU and RatioHU) across the groups. Finally, receiver operating characteristic (ROC) analysis was performed to determine the cutoff values for distinguishing hypodense lesions. Results A total of 167 lesions from 146 patients were examined. The CT attenuation values for AIS(n = 39), LA(n = 53), and OCI(n = 75) were 18.90 ± 6.40 HU, 17.53 ± 4.67 HU, and 11.90 ± 5.92 HU, respectively. The time interval between symptom onset and CT scans for AIS group was 32.21 ± 26.85 h. ANOVA revealed significant differences among the CT parameters of the hypodense lesion groups (all P

Abstract The ionosphere can be artificially modified by employing ground-based high-power high-frequency electromagnetic waves to irradiate the ionosphere. This modification is achieved through the nonlinear interaction between the electromagnetic waves and the ionospheric plasma, leading to changes in the physical properties and structure of the ionosphere. The degree of artificial modification of the ionosphere is closely related to the heating energy density of high-frequency pump waves. Due to the high density of neutral constituents in the lower ionosphere and the high frequency of electron-neutral collisions, the energy of heating pump waves will be absorbed and attenuated during the penetration of the low ionosphere, seriously affecting the heating effect. This paper proposes a method to reduce the absorption of ionospheric heating pump waves by releasing electron attachment chemicals into low ionosphere to form a large-scale electron density hole. A model for mitigating pump waves absorption based on SF6 release is established, and the absorption at different frequencies is quantitatively calculated. The propagation characteristics of high-frequency signals in ionospheric holes are studied using a three-dimensional ray tracing method, and the results demonstrate that the chemical release method not only reduces the absorption attenuation of heating pump waves but also forms spherical electron density holes, which exhibit a focusing effect on the heating beam and enhance the heating effect. The results are of great significance for understanding the nonlinear interaction between electromagnetic wave and ionospheric plasma and improving the ionospheric heating efficiency.

Abstract Understanding of infection dynamics is important for public health measures against monkeypox virus (MPXV) infection. Herein, samples from multiple body sites and environmental fomites of 77 acute MPXV infections (HIV co-infection: N = 42) were collected every two to three days and used for detection of MPXV DNA, surface protein specific antibodies and neutralizing titers. Skin lesions show 100% positivity rate of MPXV DNA, followed by rectum (88.16%), saliva (83.78%) and oropharynx (78.95%). Positivity rate of oropharynx decreases rapidly after 7 days post symptom onset (d.p.o), while the rectum and saliva maintain a positivity rate similar to skin lesions. Viral dynamics are similar among skin lesions, saliva and oropharynx, with a peak at about 6 d.p.o. In contrast, viral levels in the rectum peak at the beginning of symptom onset and decrease rapidly thereafter. 52.66% of environmental fomite swabs are positive for MPXV DNA, with highest positivity rate (69.89%) from air-conditioning air outlets. High seropositivity against A29L (100%) and H3L (94.74%) are detected, while a correlation between IgG endpoint titers and neutralizing titers is only found for A29L. Most indexes are similar between HIV and Non-HIV participants, while HIV and rectitis are associated with higher viral loads in rectum.

The management of chronic wounds in diabetes remains challenging due to the complexity of impaired wound healing, delayed healing, susceptibility to infection, and elevated risk of reopening, highlighting the need for effective chronic wound management with innovative approaches such as multifunctional hydrogels. Here, we have produced HA-DA@rhCol hydrogels consisting of dopamine-modified hyaluronic acid and recombinant human collagen type-III (rhCol) by oxidative coupling of the catechol group using the H2O2/HRP catalytic system. The post-reactive hydrogel has a good porous structure, swelling rate, reasonable degradation, rheological and mechanical properties, and the catechol group and dopamine impart to the hydrogel tissue adhesiveness, antioxidant capacity, and excellent photothermal effects leading to superior in vitro antimicrobial activity. In addition, the ability of rhCol to confer hydrogels to promote angiogenesis and wound repair has also been investigated. Cytotoxicity and hemolysis tests demonstrated the good biocompatibility of the hydrogel. Wound closure, collagen deposition and immunohistochemical examination confirmed the ability of the hydrogel to promote diabetic wound healing. In summary, the adhesive hemostatic antioxidative hydrogel with rhCol to promote wound healing in diabetic rat is an excellent chronic wound dressing.

Aplastic anemia (AA), is a rare but potentially life-threatening disease characterized by pancytopenia and a hypocellular bone marrow. Pulmonary mucormycosis (PM) is a rare but life-threatening fungal infection observed in immunocompromised patients, particularly those with neutropenia and those using corticosteroids, with a high mortality rate from 40 to 80%. However, PM diagnosis and treatment remain challenging. This study reports a case of very severe aplastic anemia (VSAA) in a male child with PM. The innovation of this article lies in the following aspects: the patient exhibited typical clinical manifestations, the reverse halo sign (RHS) on chest computed tomography (CT), and a positive metagenomic next-generation sequencing (mNGS) analysis; despite aggressive anti-infective treatment and left lower lobectomy, he experienced a poor clinical outcome. Reflecting on cases with poor prognosis can indeed offer valuable insights and opportunities for learning. This study underlines the diagnostic challenges in mucormycosis, which should be considered in persistent fever that is unresponsive to standard antibiotic and antifungal therapies, and conduct a comprehensive examination to achieve early detection, diagnosis and treatment. It was concluded that, in addition to antifungal treatment, early surgery is essential for treating mucormycosis.

IntroductionHypoxia due to reduced partial pressure of oxygen from high-altitude exposure affects the cognitive function of high-altitude migrants. Executive function is an important component of human cognitive function, characterized by high oxygen consumption during activity, and its level can be measured using cognitive control capacity (CCC). In addition, there is evidence for the potential value of hyperbaric oxygen (HBO) interventions in improving cognitive decline on the plateau. Therefore, the objective of this study was to investigate the effect of long-term high-altitude exposure on CCC in high-altitude newcomers and whether hyperbaric oxygen intervention has an ameliorative effect.MethodsThis study measured the magnitude of participants’ CCC using a Backward Masking Majority Function Task (MFT-M). Study 1 was a controlled study of different altitude conditions, with 64 participants in the high-altitude newcomer group and 64 participants in the low-altitude resident group, each completing the MFT-M task once. Study 2 was a controlled HBO intervention study in which newcomers who had lived at a high altitude for 2 years were randomly divided into the HBO group (n = 28) and control group (n = 28). 15 times hyperbaric oxygen interventions were performed in the HBO group. Subjects in both groups completed the MFT-M task once before and once after the intervention.ResultsStudy 1 showed that CCC was significantly higher in the low-altitude resident group than in the high-altitude newcomer group (p = 0.031). Study 2 showed that the CCC in the HBO group was significantly higher after 15 hyperbaric interventions than before (p = 0.005), while there was no significant difference in the control group (p = 0.972). The HBO group had significantly higher correct task rates than the control group after the intervention (p = 0.001).ConclusionThis study confirms that long-term high-altitude exposure leads to impairment of CCC in high-altitude newcomers and that hyperbaric oxygen intervention is effective in improving CCC.

Abstract Background Endovascular thrombectomy (EVT) is a standard treatment for acute ischemic stroke (AIS) with large vessel occlusion. Hypertension and increased blood pressure variability within the first 24 h after successful reperfusion are related to a higher risk of symptomatic intracerebral hemorrhage and higher mortality. AIS patients might suffer from ischemia-reperfusion injury following reperfusion, especially within 24 h. Dexmedetomidine (DEX), a sedative commonly used in EVT, can stabilize hemodynamics by inhibiting the sympathetic nervous system and alleviate ischemia-reperfusion injury through anti-inflammatory and antioxidative properties. Postoperative prolonged sedation for 24 h with DEX might be a potential pharmacological approach to improve long-term prognosis after EVT. Methods This single-center, open-label, prospective, randomized controlled trial will include 368 patients. The ethics committee has approved the protocol. After successful reperfusion (modified thrombolysis in cerebral infarction scores 2b–3, indicating reperfusion of at least 50% of the affected vascular territory), participants are randomly assigned to the intervention or control group. In the intervention group, participants will receive 0.1~1.0 μg/kg/h DEX for 24 h. In the control group, participants will receive an equal dose of saline for 24 h. The primary outcome is the functional outcome at 90 days, measured with the categorical scale of the modified Rankin Scale, ranging from 0 (no symptoms) to 6 (death). The secondary outcome includes (1) the changes in stroke severity between admission and 24 h and 7 days after EVT, measured by the National Institute of Health Stroke Scale (ranging from 0 to 42, with higher scores indicating greater severity); (2) the changes in ischemic penumbra volume/infarct volume between admission and 7 days after EVT, measured by neuroimaging scan; (3) the length of ICU/hospital stay; and (4) adverse events and the all-cause mortality rate at 90 days. Discussion This randomized clinical trial is expected to verify the hypothesis that postoperative prolonged sedation with DEX after successful reperfusion may promote the long-term prognosis of patients with AIS and may reduce the related socio-economic burden. Trial registration ClinicalTrials.gov NCT04916197. Prospectively registered on 7 June 2021.

Acute type A aortic dissection (aTAAD) is a common aortic disease with a very high mortality rate. Due to its frequent involvement of vessels above aortic arch, it is highly prone to cause neurological complications. This review comprehensively elaborates on the possible risk factors of aTAAD combined with neurological complications, and summarizes the commonly used surgical treatment strategies, in order to provide a theoretical basis for finding intervention methods for aTAAD combined with neurological complications.

BackgroundRadiogenomics is an emerging technology that integrates genomics and medical image–based radiomics, which is considered a promising approach toward achieving precision medicine. ObjectiveThe aim of this study was to quantitatively analyze the research status, dynamic trends, and evolutionary trajectory in the radiogenomics field using bibliometric methods. MethodsThe relevant literature published up to 2023 was retrieved from the Web of Science Core Collection. Excel was used to analyze the annual publication trend. VOSviewer was used for constructing the keywords co-occurrence network and the collaboration networks among countries and institutions. CiteSpace was used for citation keywords burst analysis and visualizing the references timeline. ResultsA total of 3237 papers were included and exported in plain-text format. The annual number of publications showed an increasing annual trend. China and the United States have published the most papers in this field, with the highest number of citations in the United States and the highest average number per item in the Netherlands. Keywords burst analysis revealed that several keywords, including “big data,” “magnetic resonance spectroscopy,” “renal cell carcinoma,” “stage,” and “temozolomide,” experienced a citation burst in recent years. The timeline views demonstrated that the references can be categorized into 8 clusters: lower-grade glioma, lung cancer histology, lung adenocarcinoma, breast cancer, radiation-induced lung injury, epidermal growth factor receptor mutation, late radiotherapy toxicity, and artificial intelligence. ConclusionsThe field of radiogenomics is attracting increasing attention from researchers worldwide, with the United States and the Netherlands being the most influential countries. Exploration of artificial intelligence methods based on big data to predict the response of tumors to various treatment methods represents a hot spot research topic in this field at present.

The lysine-specific demethylase 1 (KDM1A) is reported to be a regulator in learning and memory. However, the effect of KDM1A in oxycodone rewarding memory has yet to be studied. In our study, rewarding memory was assessed by using conditioned place preference (CPP) in male mice. Next generation sequencing and chromatin immunoprecipitation-PCR were used to explore the molecular mechanisms. Oxycodone significantly decreased PP1α mRNA and protein levels in hippocampal neurons. Oxycodone significantly increased KDM1A and H3K4me1 levels, while significantly decreased H3K4me2 levels in a time- and dose-dependent manner. Behavioral data demonstrated that intraperitoneal injection of ORY-1001 (KDM1A inhibitor) or intra-hippocampal injection of KDM1A siRNA/shRNA blocked the acquisition and expression of oxycodone CPP and facilitated the extinction of oxycodone CPP. The decrease of PP1α was markedly blocked by the injection of ORY-1001 or KDM1A siRNA/shRNA. Oxycodone-induced enhanced binding of CoRest with KDM1A and binding of CoRest with the PP1α promoter was blocked by ORY-1001. The level of H3K4me2 demethylation was also decreased by the treatment. The results suggest that oxycodone-induced upregulation of KDM1A via demethylation of H3K4me2 promotes the binding of CoRest with the PP1α promoter, and the subsequent decrease in PP1α expression in hippocampal neurons may contribute to oxycodone reward.

Immune checkpoint inhibitors (ICIs) are essential for urothelial carcinoma (UC) treatment. Fibroblast growth factor receptor (FGFR) alterations, as common oncogenic drivers in UC, have been reported to drive T cell depletion of UC immune microenvironment via up-regulating FGFR signaling, which indicated FGFR alterations potentially result in reduced response to ICIs. In addition, the selective pan-FGFR inhibitor showed better clinical benefit in clinical trials, indicating FGFR has emerged as critical therapeutic target via inhibiting FGFR signaling. The present study aims to evaluate prognosis and response to ICIs between FGFR-altered UC patients and FGFR-wildtype UC patients via 1963 UC patients and offers new insights into personalized precision therapy and combination therapy for UC.

Purpose: Conduct a bibliometric analysis to review the knowledge structure and research trends regarding the association between periodontal disease and cardiovascular disease (CVD). Methods: The Web of Science Core collection database was searched for retrieving publications related to periodontitis and CVD between January 1, 2003 and December 31, 2022. The VOSviewer, CiteSpace, and R software package “bibliometrix” were employed for the bibliometric analysis. Results: In total, 3447 articles were collected from 98 countries over the past 20 years, with the United States (1,003), Japan (377), and China (321) contributing the most publications. The literature in this field exhibited exponential growth. The University of Helsinki (n = 125, 1.37 %) holds the distinction of being the research institution with the highest number of publications, with a predominant representation from institutions in the United States. Notably, the Journal of Periodontology emerges as the most popular journal in the field, whereas the Journal of Clinical Periodontology takes the lead in terms of citations. These publications originated from 15,236 authors, with Pussinen (n = 40) having the highest number of published papers and Tonetti (n = 976) garnering the most citations. The visualization analysis of keywords identified “oral microbiome,” “inflammation,” and “porphyromonas gingivalis” as emerging research hotspots in exploring the relationship between periodontitis and CVDs. Conclusion: Through a comprehensive bibliometric analysis, this study posits that periodontitis may heighten the risk of cardiovascular events, offering valuable academic references for scholars investigating the link between periodontitis and CVDs.

Abstract The ongoing mutations of the SARS‐CoV‐2 pose serious challenges to the efficacy of the available antiviral drugs, and new drugs with fantastic efficacy are always deserved investigation. Here, a nanobody called IBT‐CoV144 is reported, which exhibits broad neutralizing activity against SARS‐CoV‐2 by inducing the conformation of spike trimer dimers. IBT‐CoV144 was isolated from an immunized alpaca using the RBD of wild‐type SARS‐CoV‐2, and it showed strong cross‐reactive binding and neutralizing potency against diverse SARS‐CoV‐2 variants, including Omicron subvariants. Moreover, the prophylactically and therapeutically intranasal administration of IBT‐CoV144 confers fantastic protective efficacy against the challenge of Omicron BA.1 variant in BALB/c mice model. The structure analysis of the complex between spike (S) protein, conducted using Cryo‐EM, revealed a special conformation known as the trimer dimers. This conformation is formed by two trimers, with six RBDs in the “up” state and bound by six VHHs. IBT‐CoV144 binds to the lateral region of the RBD on the S protein, facilitating the aggregation of S proteins. This aggregation results in steric hindrance, which disrupts the recognition of the virus by ACE2 on host cells. The discovery of IBT‐CoV144 will provide valuable insights for the development of advanced therapeutics and the design of next‐generation vaccines.

BackgroundClinically, the diagnosis and treatment of cholangiocarcinoma are generally different according to the location of occurrence, and the studies rarely consider the differences between different pathological types. Cholangiocarcinomas in large- and middle-sized intrahepatic bile ducts are mostly mucinous, while in small sized bile duct are not; mucinous extrahepatic cholangiocarcinomas are also more common than mucinous intrahepatic cholangiocarcinoma. However, it is unclear whether these pathological type differences are related to the prognosis.MethodsData of total 22509 patients was analyzed from Surveillance, Epidemiology, and End Results program database out of which 22299 patients were diagnosed with common adeno cholangiocarcinoma while 210 were diagnosed with mucinous cholangiocarcinoma. Based on the propensity score matching (PSM) analysis, between these two groups’ clinical, demographic, and therapeutic features were contrasted. The data were analyzed using Cox and LASSO regression analysis and Kaplan-Meier survival curves. Ultimately, overall survival (OS) and cancer specific survival (CSS) related prognostic models were established and validated in test and external datasets and nomograms were created to forecast these patients’ prognosis.ResultsThere was no difference in prognosis between mucinous cholangiocarcinoma and adeno cholangiocarcinoma. Therefore, we constructed prognostic model and nomogram that can be used for mucinous and adeno cholangiocarcinoma at the same time. By comparing the 9 independent key characteristics i.e. Age, tumor size, the number of primary tumors, AJCC stage, Grade, lymph node status, metastasis, surgery and chemotherapy, risk scores were calculated for each individual. By integrating these two pathological types in OS and CSS prognostic models, effective prognosis prediction results could be achieved in multiple datasets (OS: AUC 0.70–0.87; CSS: AUC 0.74–0.89).ConclusionAge, tumor size, the number of primary tumors, AJCC stage, Grade, lymph node status, metastasis, surgery and chemotherapy are the independent prognostic factors in OS or CSS of the patients with mucinous and ordinary cholangiocarcinoma. Nomogram that can be used for mucinous and adeno cholangiocarcinoma at the same time is of significance in clinical practice and management of cholangiocarcinoma.

The Nipah virus (NiV), a highly deadly bat-borne paramyxovirus, poses a substantial threat due to recurrent outbreaks in specific regions, causing severe respiratory and neurological diseases with high morbidity. Two distinct strains, NiV-Malaysia (NiV-M) and NiV-Bangladesh (NiV-B), contribute to outbreaks in different geographical areas. Currently, there are no commercially licensed vaccines or drugs available for prevention or treatment. In response to this urgent need for protection against NiV and related henipaviruses infections, we developed a novel homotypic virus-like nanoparticle (VLP) vaccine co-displaying NiV attachment glycoproteins (G) from both strains, utilizing the self-assembling properties of ferritin protein. In comparison to the NiV G subunit vaccine, our nanoparticle vaccine elicited significantly higher levels of neutralizing antibodies and provided complete protection against a lethal challenge with NiV infection in Syrian hamsters. Remarkably, the nanoparticle vaccine stimulated the production of antibodies that exhibited superior cross-reactivity to homologous or heterologous henipavirus. These findings underscore the potential utility of ferritin-based nanoparticle vaccines in providing both broad-spectrum and long-term protection against NiV and emerging zoonotic henipaviruses challenges.

This study presents a groundbreaking approach to modeling the Hall-Héroult cathode used in aluminum production. Our innovative model is grounded in a sophisticated porous electrode methodology coupled with state-of-the-art numerical simulations. This enables us to capture the intricate physicochemical processes within the system precisely, encompassing the migration, diffusion, and convection of ionic species. A key feature of our model is the integration of detailed electrochemical reaction kinetics at the microscale, providing a nuanced understanding of the internal dynamics of the cathode. Furthermore, we have incorporated a unique penalization method that rigorously enforces the principles of electroneutrality and ionic thermodynamic equilibrium, ensuring the model's fidelity to real-world phenomena. Computational simulation using the finite element method (FEM) serves as the backbone of our model, offering unparalleled accuracy and robustness. This has been confirmed through validation against empirical data, underlining the model's potential to significantly enhance both the efficiency and sustainability of aluminum production processes. • Development of an advanced porous electrode model for the Hall-Héroult process, utilizing numerical simulations42 to unravel complex physicochemical dynamics. • Incorporation of a novel penalization method for ensuring electroneutrality and thermodynamic equilibrium, enhancing 44 model accuracy. • Validation of the model against empirical data using FEM, demonstrating potential improvements in aluminum 46 production efficiency and sustainability.