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The monoclonal antibody (mAb)-based treatment is a highly valued therapy against COVID-19, especially for individuals who may not have strong immune responses to the vaccine. However, with the arrival of the Omicron variant and its evolving subvariants, along with the occurrence of remarkable resistance of these SARS-CoV-2 variants to the neutralizing antibodies, mAbs are facing tough challenges. Future strategies for developing mAbs with improved resistance to viral evasion will involve optimizing the targeting epitopes on SARS-CoV-2, enhancing the affinity and potency of mAbs, exploring the use of non-neutralizing antibodies that bind to conserved epitopes on the S protein, as well as optimizing immunization regimens. These approaches can improve the viability of mAb therapy in the fight against the evolving threat of the coronavirus.

Background Infective endocarditis (IE) is a lethal disease which has been changing significantly over the past decades; however, information about IE in China remains scarce. This study surveyed the changes in clinical characteristics of IE at a tertiary hospital in south China over a period of nearly 18 years. Methods Medical records with IE patients consecutively hospitalized between June 2001 and June 2018 were selected from the electronic medical records system in Nanfang Hospital of Southern Medical University. Data were divided by admission time into two groups equally: early-period group, June 2001 to December 2009 and later-period group, January 2010 to July 2018. Results A Total of 313 IE patients were included in our study. Compared with the early-period group, patients in the later-period group included fewer intravenous drug users (IVDUs), older age at onset, reduced development of pulmonary embolism, less renal dysfunction, decreased proportion of Staphylococcus aureus infection and fewer vegetations observed in the right heart by echocardiography. The later-period group also showed a higher proportion of ischemic strokes and higher proportion of positive microbiological findings compared with the early-period group. The in-hospital mortality remained about the same between the two periods and the multivariate analysis identified intravenous drug addicted, prosthetic valve endocarditis, hemorrhagic stroke, acute congestive heart failure, renal insufficiency, left-sided endocarditis, early surgical as independent predictors of in-hospital mortality. Conclusions Our study demonstrated a dramatic change in the profile of IE over a period of 18 years at a tertiary hospital in south China and presented several independent predictors of in-hospital mortality. The geographic variations observed in our study will be of important value to profile the clinical feature of China and offer the reference for clinical decisions in our region.

The emergence of monkeypox has become a global health threat after the COVID‐19 pandemic. Due to the lack of available specifically treatment against MPV, developing an available vaccine is thus the most prospective and urgent strategy. Herein, a programmable macrophage vesicle based bionic self‐adjuvanting vaccine (AM@AEvs‐PB) is first developed for defending against monkeypox virus (MPV). Based on MPV‐related antigen‐stimulated macrophage‐derived vesicles, the nanovaccine is constructed by loading the mature virion (MV)‐related intracellular protein (A29L/M1R) and simultaneously modifying with the enveloped virion (EV) antigen (B6R), enabling them to effectively promote antigen presentation and enhance adaptive immune through self‐adjuvant strategy. Owing to the synergistic properties of bionic vaccine coloaded MV and EV protein in defensing MPV, the activation ratio of antigen‐presenting cells is nearly four times than that of single antigen in the same dose, resulting in stronger immunity in host. Notably, intramuscular injection uptake of AM@AEvs‐PB demonstrated vigorous immune‐protective effects in the mouse challenge attempt, offering a promising strategy for pre‐clinical monkeypox vaccine development. The monkeypox‐specific bionic vaccine (AM@AEvs‐PB) is consists of IMV antigens (A29L, M1R), the EEV antigen (B6R), and MPV‐preactivated macrophagederived vesicles. AM@AEvs‐PB can induce enhanced innate immune responses, promote cross‐presentation of antigens to dendritic cells (DCs), and elicit robust adaptive immune responses, realizing immunization protection against Monkeypox Virus.

The worldwide outbreak of the monkeypox virus (MPXV) has become a \"Public Health Emergency of International Concern\" (PHEIC). Severe monkeypox virus infection can be fatal, however, effective therapeutic methods are yet to be developed. Mice were immunized with A35R protein and A29L protein of MPXV, and the binding and neutralizing activities of the immune sera against poxvirus-associated antigens and viruses were identified. A29L protein and A35R protein-specific monoclonal antibodies (mAbs) were generated and their antiviral activities of these mAbs were characterized in vitro and in vivo. Immunization with the MPXV A29L protein and A35R protein induced neutralizing antibodies against the orthopoxvirus in mice. None of the mAbs screened in this study against A35R could effectively neutralize the vaccinia virus (VACV), while three mAbs against A29L protein, 9F8, 3A1 and 2D1 were confirmed to have strong broad binding and neutralizing activities against orthopoxvirus, among which 9F8 showed the best neutralizing activity. 9F8, 3A1, and 2D1 recognized different epitopes on MPXV A29L protein, showing synergistic antiviral activity in vitro against the VACV Tian Tan and WR strains; the best activity was observed when the three antibodies were combined. In the vivo antiviral prophylactic and therapeutic experiments, 9F8 showed complete protective activity, whereas 3A1 and 2D1 showed partial protective activity. Similarly, the three antibodies showed synergistic antiviral protective activity against the two VACVs. In conclusion, three mAbs recognized different epitopes on MPXV A29L protein were developed and showed synergistic effects against orthopoxvirus.

In 2022, the monkeypox virus (mpox virus, MPXV) exhibited global dissemination across six continents, representing a notable challenge owing to the scarcity of targeted antiviral interventions. Passive immunotherapy, such as the use of monoclonal antibodies (mAbs) and bispecific antibodies (bsAbs), has emerged as a promising option for antiviral regimens. Here, we generated several mAbs against M1R and B6R of MPXV, and subsequently characterized the antiviral activity of these antibodies both and . Two neutralizing mAbs, M1H11 and M3B2, targeting M1R, and one B6R-specific mAb, B7C9, were identified. They exhibited varying antiviral efficacy against vaccinia virus (VACV) and . A cocktail comprising M1H11 and M3B2 demonstrated a superior protective effect . A bsAb, Bis-M1M3, was engineered by conjugating the fragment crystallizable (Fc) region of the human-mouse chimeric engineered M1H11 with the single-chain fragment variable (scFv) of M3B2. In mice challenged with MPXV, Bis-M1M3 showed a notable protective effects. Analysis of neutralization mechanism showed that these mAbs and Bis-M1M3 exerted virus-neutralizing effects before the virus infects cells. pharmacokinetic experiments showed that Bis-M1M3 has a long half-life in rhesus macaques. This study provides crucial insights for further research on broad-spectrum antiviral drugs against MPXV and other orthopoxviruses.

Background Infective endocarditis (IE) is a lethal disease that is difficult to diagnosis early. Although echocardiography is one of the most widely used diagnostic technique, it has limited sensitivity. This study surveyed the clinical features of IE patients who underwent surgery and compared transthoracic echocardiography and histological findings to explore the factors related to false-negative echocardiographic results. Methods Medical records were extracted from IE patients consecutively hospitalized between June 2001 and June 2018. Results A total of 182 patients with native valve IE who underwent surgery were included. Compared to the non-surgery group, the surgery group was more likely to have pre-existing valvular lesions and more serious cardiac conditions and a relative lack of signs of infection and cerebrovascular events, leading to a lower proportion of “definite cases” before surgery. The false-negative rate of echocardiography was 14.5%. Echocardiography has significant disadvantages in diagnosing perivalvular abscesses, valve perforations, and left-sided endocarditis, especially for subjects with both aortic and mitral valve infections. The multivariate analysis identified congenital heart disease and small vegetations (< 10 mm) as independent predictors of false-negative echocardiography results. Conversely, fever and heart murmurs on admission served as protective factors. Conclusions Under some circumstances, echocardiography provides inconsistent results compared with surgical findings, and negative echocardiography results do not rule out IE. The diagnosis of IE depends on comprehensive evaluations using multiple methods.

Monkeypox cases continue to increase globally, and there is an urgent need to develop a highly effective vaccine against monkeypox. This study investigated the binding and authentic-virus neutralizing activities of sera from mice immunized with EEV (extracellularly enveloped viruses) antigens B6R and A35R, and IMV (intrinsic material viruses) antigens M1R, A29L, E8L, and H3L against monkeypox virus. The results showed that immunizations of A35R and E8L could only induce lower titers of binding antibodies, in contrast, immunization of M1R induced the highest titers of binding antibodies, while immunization of B6R, H3L, and A29L induced moderate titers of binding antibodies. For the live monkeypox virus neutralization assay, the results showed that immunization with two doses of EEV antigen B6R did not effectively induce humoral immune responses to neutralize monkeypox live virus, immunization with EEV-A35R only induced weak monkeypox-neutralizing antibodies. In contrast, the immunization of the four types of monkeypox virus IMV antigens can all induce neutralizing antibodies against authentic monkeypox virus, among them, A29L and H3L induced the highest neutralizing antibody titers. The results of this study provide important references for the selection of antigens in the development of the next generation of monkeypox vaccines.

Background: Infective endocarditis (IE) is a lethal disease which has been changing significantly over the past decades; however, information about IE in China remains scarce. This study surveyed the changes in clinical characteristics of IE at a tertiary hospital in southern China over a period of nearly eighteen years. Methods: Medical records with IE patients consecutively hospitalized between June 2001 and June 2018 were selected from the electronic medical records system in Nanfang Hospital of Southern Medical University. Data were divided by admission time into two groups: early-period group, June 2001 to December 2009 and later-period group, January 2010 to July 2018. Results: A Total of 313 IE patients were included in our study. Compared with the early-period group, patients in the later-period group included fewer intravenous drug users (IVDU), older age at onset, reduced development of pulmonary embolism, less renal dysfunction, decreased proportion of Staphylococcus aureus infection and fewer vegetations observed in the right heart by echocardiography. The later-period group also showed a higher proportion of ischemic strokes and higher rate of whole-blood culture positive compared with the early-period group. The in-hospital mortality rate remained about the same between the two periods. Conclusions: Our study demonstrated a dramatic change in the profile and characteristics of IE over a period of eighteen years at a tertiary hospital in southern China, especially the decrease in intravenous drug users (IVDU), which might be responsible for many other changes.

Background: Infective endocarditis (IE) is a lethal disease that is difficult to diagnosis early. Although echocardiography is one of the most widely used diagnostic technique, it has limited sensitivity. This study surveyed the clinical features of IE patients who underwent surgery and compared transthoracic echocardiography and histological findings to explore the factors related to false-negative echocardiographic results. Methods: Medical records were extracted from IE patients consecutively hospitalized between June 2001 and June 2018. Results: A total of 182 patients with native valve IE who underwent surgery were included. Compared to the non-surgery group, the surgery group was more likely to have pre-existing valvular lesions and more serious cardiac conditions and a relative lack of signs of infection and cerebrovascular events, leading to a lower proportion of “definite cases” before surgery. The false-negative rate of echocardiography was 14.5%. Echocardiography has significant disadvantages in diagnosing perivalvular abscesses, valve perforations, and left-sided endocarditis, especially for subjects with both aortic and mitral valve infections. The multivariate analysis identified congenital heart disease and small vegetations (<10 mm) as independent predictors of false-negative echocardiography results. Conversely, fever and heart murmurs on admission served as protective factors. Conclusions: Under some circumstances, echocardiography provides inconsistent results compared with surgical findings, and negative echocardiography results do not rule out IE. The diagnosis of IE depends on comprehensive evaluations using multiple methods.

Alzheimer’s disease (Alzheimer’s disease, AD) is a progressive neurological disorder characterized by memory loss and cognitive impairment. It is characterized by the formation of tau protein neurofibrillary tangles and β-amyloid plaques. Recent studies have found that mitochondria in neuronal cells of AD patients exhibit various dysfunctions, including reduced numbers, ultrastructural changes, reduced enzyme activity, and abnormal kinetics. These abnormal mitochondria not only lead to the loss of normal neuronal cell function, but are also a major driver of AD progression. In this review, we will focus on the advances of mitochondria and their multi-omics in AD research, with particular emphasis on how mitochondrial dysfunction in AD drives disease progression. At the same time, we will focus on summarizing how mitochondrial genomics technologies have revealed specific details of these dysfunctions and how therapeutic strategies targeting mitochondria may provide new directions for future AD treatments. By delving into the key mechanisms of mitochondria in AD related to energy metabolism, altered kinetics, regulation of cell death, and dysregulation of calcium-ion homeostasis, and how mitochondrial multi-omics technologies can be utilized to provide us with a better understanding of these processes. In the future, mitochondria-centered therapeutic strategies will be a key idea in the treatment of AD.