Search

ABSTRACTFollowing the national dynamic zero-COVID strategy adjustment, the utilization of broad-spectrum nasal neutralizing antibodies may offer an alternative approach to controlling the outbreak of Omicron variants between late 2022 and early 2023 in China. This study involved an investigator-initiated trial (IIT) to assess the pharmacokinetic, safety and efficacy of the F61 nasal spray. A total of 2,008 participants were randomly assigned to receive F61 nasal spray (24 mg/0.8 mL/dose) or normal saline (0.8 mL/dose) and 1336 completed the follow-up in the IIT. Minimal absorption of F61 antibody into the bloodstream was detected in individuals receiving F61 nasal spray for seven consecutive days. No treatment-emergent adverse reactions of grade 3 severity or higher were reported. In the one-dose cohort, the 7-day cumulative SARS-CoV-2 infection rate was 79.0% in the F61 group and 82.6% in the placebo group, whereas, in the multiple-dose (once daily for 7 consecutive days) cohort, the rates were 6.55% in the F61 group and 23.83% in the placebo group. The laboratory-confirmed efficacy of F61 was 3.78% (−3.74%–10.75%) in the one-dose cohort and 72.19% (57.33%–81.87%) in the multiple-dose cohort. In the real-world study, 60,225 volunteers in four different regions were administered the F61 nasal spray based on the subject's wishes, over 90% efficacy rate was observed against different Omicron variants. The F61 nasal spray, with its favourable safety profile, could be a promising prophylactic monoclonal antibody against SARS-CoV-2 VOCs.

Abstract BackgroundVarious older adult care settings have embraced the use of the life story approach to enhance the development of comprehensive care plans. However, organizing life stories and extracting useful information is labor-intensive, primarily due to the repetitive, fragmented, and redundant nature of life stories gathered from everyday communication scenarios. Existing life story systems, while available, do not adequately fulfill the requirements of users, especially in the application of care services. ObjectiveThe objective of this study is to design, develop, and evaluate a digital system that provides caregivers with the necessary tools to view and manage the life stories of older adults, enabling expedited access to pertinent information effectively and visually. MethodsThis study used a multidisciplinary, user-centered design approach across 4 phases: initial design requirements, prototyping, prototype refinement workshops, and usability testing. During the initial phase, we conducted field research in the Hefei Tianyu Senior Living Service Nursing Home, China, to discover how caregivers currently store and use life stories and their needs, challenges, and obstacles in organizing and retrieving information. Subsequently, we designed a low-fidelity prototype according to the users’ requirements. A prototyping workshop involving 6 participants was held to collaboratively design and discuss the prototype’s function and interaction. User feedback from the workshops was used to optimize the prototype, leading to the development of the system. We then designed 2 rounds of usability testing with 7 caregivers to evaluate the system’s usability and effectiveness. ResultsWe identified 3 categories of functionalities that are necessary to include in the design of our initial low-fidelity prototype of life story visualizations: life story input, life story organization, and timeline generation. Subsequently, through the workshops, we identified 3 categories for functional optimization: feedback on user interface and usability, optimization suggestions for existing features, and the request for additional functionalities. Next, we designed a medium-fidelity prototype based on human-centered design. The Story Mosaic system underwent usability testing in the Hefei Tianyu Senior Living Service Nursing Home. Overall, 7 users recorded and organized 1123 life stories of 16 older adults. The usability testing results indicated that the system was accessible and easy to use for caregivers. Based on the feedback from the usability testing, we finalized the high-fidelity prototype. ConclusionsWe designed, developed, and evaluated the Story Mosaic system to support the visual management of older adults’ life stories. This system empowers caregivers through digital technology and innovative design, pioneering personal narrative integration in caregiving. This system can expand to include informal caregivers and family members for continued adaptability and empathy.

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs), especially the latest Omicron, have exhibited severe antibody evasion. Broadly neutralizing antibodies with high potency against Omicron are urgently needed for understanding the working mechanisms and developing therapeutic agents. In this study, we characterized the previously reported F61, which was isolated from convalescent patients infected with prototype SARS-CoV-2, as a broadly neutralizing antibody against all VOCs including Omicron BA.1, BA.1.1, BA.2, BA.3 and BA.4 sublineages by utilizing antigen binding and cell infection assays. We also identified and characterized another broadly neutralizing antibody D2 with epitope distinct from that of F61. More importantly, we showed that a combination of F61 with D2 exhibited synergy in neutralization and protecting mice from SARS-CoV-2 Delta and Omicron BA.1 variants. Cryo-Electron Microscopy (Cryo-EM) structures of the spike-F61 and spike-D2 binary complexes revealed the distinct epitopes of F61 and D2 at atomic level and the structural basis for neutralization. Cryo-EM structure of the Omicron-spike-F61-D2 ternary complex provides further structural insights into the synergy between F61 and D2. These results collectively indicated F61 and F61-D2 cocktail as promising therapeutic antibodies for combating SARS-CoV-2 variants including diverse Omicron sublineages.

The life stories of older adults encapsulate an array of personal experiences that reflect their care needs. However, due to inherent fuzzy features, fragmented natures, repetition, and redundancies, the practical application of the life story approach poses challenges for caregivers in acquiring and comprehending these narratives. Addressing this challenge, our study introduces a novel approach called Life Story Hierarchies with Graph-Enhanced Event Feature Refinement (LSH-GEFR). LSH-GEFR constructs a bilayer graph. Firstly, the event element map leverages intricate relationships between event elements to extract environmental features, providing a detailed context for understanding each event element. Secondly, the event map explores the complex web of relationships between the events themselves, allowing LSH-GEFR to generate a comprehensive understanding of each event and enhance its representation. Subsequently, we conducted experiments on different datasets and found that, in comparison with four advanced event tree generation methods, the proposed LSH-GEFR method outperformed them in terms of path coherence, branch reasonableness, and overall readability when generating life story hierarchies. Over 84.91% of the structured life narratives achieved readability, marking a 5.96% increase over the best-performing approach at the baseline.

Abstract As the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to threaten public health worldwide, the development of effective interventions is urgently needed. Neutralizing antibodies (nAbs) have great potential for the prevention and treatment of SARS-CoV-2 infection. In this study, ten nAbs were isolated from two phage-display immune libraries constructed from the pooled PBMCs of eight COVID-19 convalescent patients. Eight of them, consisting of heavy chains encoded by the immunoglobulin heavy-chain gene-variable region (IGHV)3-66 or IGHV3-53 genes, recognized the same epitope on the receptor-binding domain (RBD), while the remaining two bound to different epitopes. Among the ten antibodies, 2B11 exhibited the highest affinity and neutralization potency against the original wild-type (WT) SARS-CoV-2 virus (KD = 4.76 nM for the S1 protein, IC50 = 6 ng/mL for pseudoviruses, and IC50 = 1 ng/mL for authentic viruses), and potent neutralizing ability against B.1.1.7 pseudoviruses. Furthermore, 1E10, targeting a distinct epitope on RBD, exhibited different neutralization efficiency against WT SARS-CoV-2 and its variants B.1.1.7, B.1.351, and P.1. The crystal structure of the 2B11–RBD complexes revealed that the epitope of 2B11 highly overlaps with the ACE2-binding site. The in vivo experiment of 2B11 using AdV5-hACE2-transduced mice showed encouraging therapeutic and prophylactic efficacy against SARS-CoV-2. Taken together, our results suggest that the highly potent SARS-CoV-2-neutralizing antibody, 2B11, could be used against the WT SARS-CoV-2 and B.1.1.7 variant, or in combination with a different epitope-targeted neutralizing antibody, such as 1E10, against SARS-CoV-2 variants.

On the basis of Löwner partial order and core partial order, we introduce a new partial order: LC partial order. By applying matrix decomposition, core inverse, core partial order, and Löwner partial order, we give some characteristics of LC partial order, study the relationship between LC partial order and Löwner partial order under constraint conditions, and illustrate its differences with some classical partial orders, such as minus, CL, and GL partial orders.

Software development based on message driven framework has become an important pattern for big data application system.The message management module which is an important part of whole framework was designed and implemented.The basic format of message and the standard of message management was defined,its function was realized,and the advantages through a case were shown.

Abstract Background We prepared an oral W/O microemulsion for the removal of colonic ammonia (ME-RCA). The effect of this microemulsion was influenced by the digestion process in the gastrointestinal tract. In this paper, we aim to show that stability was improved by using a microemulsion-based gel for the removal of colonic ammonia (MBG-RCA). Methods MBG-RCA was prepared by adding sodium alginate to the ME-RCA. MBG-RCA and ME-RCA were passed through a simulated gastrointestinal environment, and the amount of colonic ammonia present was then determined by titration with a standard solution of hydrochloric acid. The pH of the gastrointestinal fluid was measured using a pH test paper and the size and form of the microemulsions were examined under the microscope. 18 healthy rats were randomly divided into three groups, fasted for 24 hours and allowed to drink normally. Three-way pipes were placed at the gastroduodenal junction in Group I, and at the terminal ileum in Group II. After the intragastric administration of ME-RCA, the stomach contents in Group I, the effluent from the terminal ileum in Group II and discharge from the anus in Group III were collected. The pH values of the gastrointestinal juice were measured by the pH test paper and those of the colon were determined by a universal indicator. These animal experiments were also used to test the effect of MBG-RCA. Results MBG-RCA showed a better removal rate of artificial colonic ammonia than ME-RCA (P < 0.05). The decrease in pH value of the artificial small intestinal fluid due to ME-RCA did not occur when MBG-RCA was used. In the simulated gastrointestinal process, MBG-RCA maintained greater stability and released the emulsion (ME-RCA) in the colonic fluid. In the gastrointestinal tract of normal SD rats, ME-RCA decreased in size and lost its stable form after entering the small intestine, while MBG-RCA remained stable and intact emulsion-drops were observed from the anus. Neither substance had any effect on the pH of the stomach or colon of normal rats (partly because normal rats were fasted for 24 hours and allowed to drink normally, which resulted in a low level of ammonia production in the colon). Unlike ME-RCA, MBG-RCA did not reduce the pH of the small intestine. Conclusions MBG-RCA was more stable in the gastrointestinal tract and more effective at removing colonic ammonia when a higher concentration of ammonia was present. This made it possible to achieve the targeted removal of colonic ammonia and is a promising method to prevent hepatic encephalopathy (HE) in future studies.

A notable feature of volcanic activity in the Halmahera arc since the Middle Miocene is that eruptions have occurred episodically from south to north, rather than simultaneously. However, the dynamic cause of the volcanic age disparity between the northern and southern regions remains unresolved. To investigate this, thermal simulation methods were employed to calculate the temperature structures of the subducted slab and mantle wedge under varying movement rates of subduction and overriding plates. Simulation results indicate that arc magmatism is favored at lower subduction rates or higher overriding plate movement rates. During the Middle Miocene, the northward drift of the Australian plate propelled the Obi microplate southward via left-lateral strike-slip faults, accelerating its movement rate. In contrast, the movement rate of the Halmahera microplate in the north remained lower, unaffected by the Australian plate. The accelerated movement of the Obi microplate resulted in the rapid generation of a higher temperature zone, facilitating arc volcanism on Obi Island in the late Middle Miocene. Meanwhile, the lower movement rate of the Halmahera microplate delayed the formation of a favorable high-temperature zone for arc volcanism, leading to the emergence of volcanism on Halmahera Island in the late Pliocene. [ABSTRACT FROM AUTHOR]

Aquaculture originates from ancient Chinese wisdom, and is considered the most efficient food-producing industry. About 70 years ago, New China proposed an industrial approach to fish production and made a policy decision to begin modern aquaculture development. As one of lucky persons since the early 1980s, I have committed my scholarly career to the studies on genetics and breeding biotechnology of polyploid gibel carp (Carassius gibelio). Here, several significant recent innovations, such as the proposition of the amphitriploid concept, the association of ploidy changes with reproduction transition, the finding of a unique ameiofusiongenesis mode, the establishment of a controllable fertility approach, the creation of intermuscular bonefree mutants, as well as the recreation of desirable goldfish, are introduced and emphasized from an active participant of these innovations. Additionally, some modern innovations and contributions are also highlighted in other aspects of aquaculture including feed development, disease control, facilities and equipment upgrading, as well as paradigm and mode changes. This comprehensive synthesis of ancient Chinese wisdom and modern innovations seeks to provide valuable insights into the field from a historical basis. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study is to analyze the factors affecting college students' subjective well-being and the relationship between research achievement motivation, self-efficacy and emotional well-being among college students. Design/Methodology/Approach: 1,082 students were selected from 10 universities in Guangxi Province using a convenience sampling method. Questionnaires were administered based on achievement motivation, self-efficacy and subjective well-being scales. The data were analyzed using SPSS 24.0 and AMOS 22.0. Findings: College students' achievement motivation has a significant positive effect on emotional well-being. Self-efficacy acts as a mediator in the relationship between achievement motivation and subjective well-being. Conclusion: Achievement motivation can stimulate positive actions and efforts in college students enabling them to face challenges and difficulties more confidently. Approving activities and increased confidence enhance students' self-efficacy improving their subjective well-being. Research Limitations The interpretation of study results and inferences is constrained in sampling because of the time and expertise of the researchers. Practical Implications: It is possible to effectively improve college students' subjective well-being by focusing on the development of achievement motivation, self-efficacy and social support. Contribution to the Literature: This study further clarifies the influence of achievement motivation on subjective well-being and the mechanism of self-efficacy which is a supplement to the current research in this field at the same time. It also helps to enrich and perfect the research on achievement motivation, self-efficacy and subjective well-being of college students. [ABSTRACT FROM AUTHOR]

In Southeast Asia, emerging subduction zones often appear to begin at the corners of small oceanic basins, which have a triangular‐indenter continent–ocean boundary geometry. To investigate the influence of a triangular corner on subduction initiation, we performed a series of three‐dimensional numerical simulations with varying corner angles and base lengths. The results show that the apex of the corner constitutes the initial location of subduction, irrespective of the angle or the extent of the corner. Smaller angle corners are more likely to facilitate subduction initiation. At the same time, wide acute angle corners are difficult to form. Our findings suggest that triangular corner structures may facilitate subduction initiation in smaller basins; however, the role such corners in subduction initiation is limited in larger basins. Our results emphasize the importance of accounting for the three‐dimensional geometry of a subduction zone when examining its subduction dynamics and geological features. Plain Language Summary: In Southeast Asia, new subduction zones near small ocean areas and near locations prone to subduction have a unique and common feature—subduction starts at triangular corner–shaped continent–ocean boundaries. To fully understand how these triangular corner shapes affect the initiation of subduction, we employed advanced computer simulations. We varied the angles and lengths of the corners in our models. We discovered that, no matter the size of the corner, subduction began at the apex of the corner. Interestingly, smaller corners are especially good at initiating subduction. However, forming a wide corner with small angles in nature appears to be very difficult. This study indicates that the corner shape helps subduction start in small ocean areas but is not as important in larger ocean areas. This insight helps us better understand how subduction works in different locations on the Earth. Key Points: In small ocean basins subduction initiates at the apex of the corner, regardless of its size or angle at the cornerThe smaller the angle of the corner in the oceanic basin, the more likely subduction is to initiateAn angle at the corner greater than 120° is less likely to lead to the subduction initiation [ABSTRACT FROM AUTHOR]