Enhancing the activation of T cells through anti-CD3/CD28 magnetic beads by adjusting the antibody ratio.

The utilization of anti-CD3/CD28 magnetic beads for T cell expansion in vitro has been investigated for adoptive cell transfer therapy. However, the impact of the CD3/CD28 antibody ratio on T cell differentiation and function remains incompletely elucidated. This study seeks to address this knowledge gap. To begin with, CD3 antibodies with a relatively low avidity for Jurkat cells (Kd = 13.55 nM) and CD28 antibodies with a relatively high avidity (Kd = 5.79 nM) were prepared. Afterwards, anti-CD3/CD28 antibodies with different mass ratios were attached to magnetic beads to examine the impacts of different antibody ratios on T cell capture, and proliferation. The research demonstrated that the most significant expansion of T cells was stimulated by the anti-CD3/CD28 magnetic beads with a mass ratio of 2:1 for CD3 antibodies and CD28 antibodies. Moreover, CD25 and PD1 expression of expanded T cells increased and then decreased, with lower CD25 and PD1 expression in the later stages of expansion indicating that T cells were not depleted. These T cells, which are massively expanded in vitro and have excellent expansion potential, can be infused back into the patient to treat tumor patients. This study shows that altering the ratio of anti-CD3/CD28 antibodies can control the strength of T cell stimulation, thereby leading to the improvement of T cell activation. This discovery can be utilized as a guide for the creation of other T cell stimulation approaches, which is beneficial for the further development of tumor immunotherapy technology.

The spatial-temporal variations and influencing factors of COVID-19 case fatality rate: a worldwide study in 30 countries from February 2021 to May 2022.

To evaluate the variations in COVID-19 case fatality rates (CFRs) across different regions and waves, and the impact of public health interventions, social and economic characteristics, and demographic factors on COVID-19 CFRs, we collected data from 30 countries with the highest incidence rate in three waves. We summarized the CFRs of different countries and continents in each wave through meta-analysis. Spearman's correlation and multiple linear regression were employed to estimate the correlation between influencing factors and reduction rates of CFRs. Significant differences in CFRs were observed among different regions during the three waves (P < 0.001). An association was found between the changes in fully vaccinated rates (r s  = 0.41), population density (r s  = 0.43), the proportion of individuals over 65 years old (r s  = 0.43), and the reduction rates of case fatality rate. Compared to Wave 1, the reduction rates in Wave 2 were associated with population density (ß = 0.19, 95%CI: 0.05-0.33) and smoking rates (ß = -4.66, 95%CI: -8.98 - -0.33), while in Wave 3 it was associated with booster vaccine rates (ß = 0.60, 95%CI: 0.11-1.09) and hospital beds per thousand people (ß = 4.15, 95%CI: 1.41-6.89). These findings suggest that the COVID-19 CFRs varied across different countries and waves, and promoting booster vaccinations, increasing hospital bed capacity, and implementing tobacco control measures can help reduce CFRs.

Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia.

BACKGROUND: The initial cases of novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) occurred in Wuhan, Hubei Province, China, in December 2019 and January 2020. We analyzed data on the first 425 confirmed cases in Wuhan to determine the epidemiologic characteristics of NCIP. METHODS: We collected information on demographic characteristics, exposure history, and illness timelines of laboratory-confirmed cases of NCIP that had been reported by January 22, 2020. We described characteristics of the cases and estimated the key epidemiologic time-delay distributions. In the early period of exponential growth, we estimated the epidemic doubling time and the basic reproductive number. RESULTS: Among the first 425 patients with confirmed NCIP, the median age was 59 years and 56% were male. The majority of cases (55%) with onset before January 1, 2020, were linked to the Huanan Seafood Wholesale Market, as compared with 8.6% of the subsequent cases. The mean incubation period was 5.2 days (95% confidence interval [CI], 4.1 to 7.0), with the 95th percentile of the distribution at 12.5 days. In its early stages, the epidemic doubled in size every 7.4 days. With a mean serial interval of 7.5 days (95% CI, 5.3 to 19), the basic reproductive number was estimated to be 2.2 (95% CI, 1.4 to 3.9). CONCLUSIONS: On the basis of this information, there is evidence that human-to-human transmission has occurred among close contacts since the middle of December 2019. Considerable efforts to reduce transmission will be required to control outbreaks if similar dynamics apply elsewhere. Measures to prevent or reduce transmission should be implemented in populations at risk. (Funded by the Ministry of Science and Technology of China and others.).

Endoscopic cyanoacrylate injection therapy for refractory high-risk peptic ulcer bleeding by conventional endoscopic therapy.

OBJECTIVE: To evaluate the efficacy and safety of endoscopic cyanoacrylate injection therapy for refractory high-risk peptic ulcer bleeding by conventional endoscopic therapy. METHODS: 154 patients with refractory high-risk peptic ulcer bleeding by conventional endoscopic therapy at the Affiliated Hospital of Zunyi Medical Univesity and the People's Hospital of Liupanshui City from January 2018 to December 2021were enrolled in this study. Endoscopic intracellular cyanoacrylate injection was first carried out. When failure, perintravascullar injection was carried out. The data were retrospectively collected. RESULTS: Among the 154 patients, 102 patients (66.23%) obtained successful intravascular injection and perivascular injection was performed in 52 patients (33.77%). Immediate hemostatic rate for active bleeding achieved 93.18%. Overall rebleeding rate within 30 days was 12.99% and successful hemostasis rate achieved 87.01%. Immediate hemostatic rate and successful hemostasis rate in intravascular injection patients were markedly superior over perivascular injection. Rebleeding rate in intravascular injection patients was markedly lower than that in perivascular injection patients. 14 patients complicated abdominal pain and no other complication occurred. CONCLUSION: Endoscopic cyanoacrylate injection therapy, especial intravascular injection, was effective and safe, with high successful hemostasis rate for refractory high-risk peptic ulcer bleeding by conventional endoscopic therapy.

Social vulnerability, impacts and adaptations strategies in the face of natural hazards: insight from riverine islands of Bangladesh.

BACKGROUND: Bangladesh is one of the countries at risk of natural disasters due to climate change. In particular, inhabitants of its riverine islands (char) confront ongoing climatic events that heighten their vulnerability. This study aims to assess social vulnerability, impacts, and adaptation strategies to climate change in the riverine island areas of Bangladesh. METHODS: A mixed-method approach incorporating qualitative and quantitative procedures was used on data collected from 180 households of riverine islands in Gaibandha, Bangladesh. The social vulnerability of riverine island communities was assessed based on their adaptation capacity, sensitivity, and exposure to climatic stressors. RESULTS: The findings show that char dwellers' vulnerability, impacts, and adaptation capability to climate change vary significantly depending on their proximity to the mainland. Social vulnerability factors such as geographical location, fragile and low-grade housing conditions, illiteracy and displacement, climate-sensitive occupation and low-income level, and so on caused to the in-height vulnerability level of these particular areas. This study also displays that climate change and its associated hazards cause severe life and livelihood concerns for almost all households. In this case, the riverine dwellers employed several adaptation strategies to enhance their way of life to the disaster brought on changing climate. However, low education facilities, deficiency of useful information on climate change, poor infrastructure, and shortage of money are still the supreme hindrance to the sustainability of adaptation. CONCLUSION: The findings underscore the importance of evaluating the susceptibility of local areas to climate change and emphasize the need for tailored local initiatives and policies to reduce vulnerability and enhance adaptability in communities residing in char households.

"Green" Extraction and On-Site Rapid Detection of Aflatoxin B1, Zearalenone and Deoxynivalenol in Corn, Rice and Peanut.

The common mycotoxins in polluted grains are aflatoxin B1(AFB1), zearalenone (ZEN) and deoxynivalenol (DON). Because of the potential threat to humans and animals, it is necessary to detect mycotoxin contaminants rapidly. At present, later flow immunoassay (LFIA) is one of the most frequently used methods for rapid analysis. However, multistep sample pretreatment processes and organic solvents are also required to extract mycotoxins from grains. In this study, we developed a one-step and "green" sample pretreatment method without using organic solvents. By combining with LFIA test strips and a handheld detection device, an on-site method for the rapid detection of AFB1, ZEN and DON was developed. The LODs for AFB1, ZEN and DON in corn are 0.90 µg/kg, 7.11 µg/kg and 10.6 µg/kg, respectively, and the working ranges are from 1.25 µg/kg to 40 µg/kg, 20 µg/kg to 2000 µg/kg and 35 µg/kg to 1500 µg/kg, respectively. This method has been successfully applied to the detection of AFB1, ZEN and DON in corn, rice and peanut, with recoveries of 89 ± 3%-106 ± 3%, 86 ± 2%-108 ± 7% and 90 ± 2%-106 ± 10%, respectively. The detection results for the AFB1, ZEN and DON residues in certified reference materials by this method were in good agreement with their certificate values.

Risk Factors for Death Among the First 80 543 Coronavirus Disease 2019 (COVID-19) Cases in China: Relationships Between Age, Underlying Disease, Case Severity, and Region.

BACKGROUND: Knowledge of COVID-19 epidemiology remains incomplete and crucial questions persist. We aimed to examine risk factors for COVID-19 death. METHODS: A total of 80 543 COVID-19 cases reported in China, nationwide, through 8 April 2020 were included. Risk factors for death were investigated by Cox proportional hazards regression and stratified analyses. RESULTS: Overall national case-fatality ratio (CFR) was 5.64%. Risk factors for death were older age (≥80: adjusted hazard ratio, 12.58; 95% confidence interval, 6.78-23.33), presence of underlying disease (1.33; 1.19-1.49), worse case severity (severe: 3.86; 3.15-4.73; critical: 11.34; 9.22-13.95), and near-epicenter region (Hubei: 2.64; 2.11-3.30; Wuhan: 6.35; 5.04-8.00). CFR increased from 0.35% (30-39 years) to 18.21% (≥70 years) without underlying disease. Regardless of age, CFR increased from 2.50% for no underlying disease to 7.72% for 1, 13.99% for 2, and 21.99% for ≥3 underlying diseases. CFR increased with worse case severity from 2.80% (mild) to 12.51% (severe) and 48.60% (critical), regardless of region. Compared with other regions, CFR was much higher in Wuhan regardless of case severity (mild: 3.83% vs 0.14% in Hubei and 0.03% elsewhere; moderate: 4.60% vs 0.21% and 0.06%; severe: 15.92% vs 5.84% and 1.86%; and critical: 58.57% vs 49.80% and 18.39%). CONCLUSIONS: Older patients regardless of underlying disease and patients with underlying disease regardless of age were at elevated risk of death. Higher death rates near the outbreak epicenter and during the surge of cases reflect the deleterious effects of allowing health systems to become overwhelmed.

Impact of climate change on human health: evidence from riverine island dwellers of Bangladesh.

This study aims to explore the impact of climate change on health, including local adaptation strategies. A mixed-method approach has been used in this study. The results reveal that increasing the frequency of flooding, severity of riverbank erosion and drought, and rising disease outbreak are the highest indicators of climate change perceived by riverine island (char) dwellers, which is similar to the observed data. It also uncovers, approximately all respondents encounter several health-related issues during different seasons where prevailing cold and cough with fever, skin diseases, and diarrhoea are the leading ailments. Several adaptation strategies are accommodated by char inhabitants in order to enhance resilience against the climate change health impacts, but the paucity of money, disrupted communication, lack of formal health-care centre are the most obstacles to the sustainability of adaptation. This research recommends that healthcare-associated project should be performed through proper monitoring for exterminating char dwellers' health issues.

One Hundred Days of Coronavirus Disease 2019 Prevention and Control in China.

The epidemic of novel coronavirus disease was first reported in China in late December 2019 and was brought under control after some 2 months in China. However, it has become a global pandemic, and the number of cases and deaths continues to increase outside of China. We describe the emergence of the pandemic, detail the first 100 days of China's response as a phase 1 containment strategy followed by phase 2 containment, and briefly highlight areas of focus for the future. Specific, simple, and pragmatic strategies used in China for risk assessment, prioritization, and deployment of resources are described. Details of implementation, at different risk levels, of the traditional public health interventions are shared. Involvement of society in mounting a whole country response and challenges experienced with logistics and supply chains are described. Finally, the methods China is employing to cautiously restart social life and economic activity are outlined.

Development of a quantum dot-based lateral flow immunoassay with high reaction consistency to total aflatoxins in botanical materials.

Total aflatoxins (AFTs) are an important safety indicator for botanical materials, but at present, rapid detection technology for AFTs is seldom reported. In this study, the monoclonal antibody with similar reactivity to total aflatoxins was produced, and the quantum dot-based lateral flow immunoassay (QD-LFIA) coupled with a portable device was developed to rapidly determine AFT residues in botanical materials. The half maximal inhibitory concentrations (IC50) of the QD-LFIA for AFB1, AFB2, AFG1, AFG2, AFM1, and AFM2 were 10.57, 12.64, 11.34, 12.67, 10.13, and 12.75 µg kg-1, respectively, which show high reaction consistency to total aflatoxins. For different botanical materials, the sample was simply extracted with methanol-water and diluted with PBS, and the sample solution was directly loaded onto the QD-LFIA strip for determination. To overcome interference from the matrix effects, specific standard curves were established for each kind of botanical material. The detection limit of AFTs in 6 different botanical materials was 0.95~2.03 µg kg-1 with a linear range of 2~120 µg kg-1. The spiked recoveries of AFTs in botanical materials of different species and localities of growth were 75~105% with a coefficient of variation below 15%. The test results of the actual samples are consistent with the Chinese national standard test method. This study provides an easy-to-use method to rapidly determine AFTs in different botanical materials. Graphical abstract.

Rhodium-Catalyzed C(sp2)-H Amidation of Azine with Sulfonamides.

Direct C-H amidation of azine with sulfonamide was developed for the first time. The reactions proceeded smoothly under benign conditions and gave the corresponding products with high selectivity. This approach shows high regioselectivity, wide substrate scope, and functional group tolerance. Additionally, this transformation can also be scaled up to the gram level. This strategy allows for the direct preparation of ortho-sulfonamide-substituted ketone products, thus providing a good complement to previous C-H amidation.

Selection, identification, and application of DNA aptamers against bovine pregnancy-associated glycoproteins 4.

The bovine pregnancy-associated glycoproteins (bPAGs) have been widely used as robust markers for early diagnosis of pregnancy in the cattle. The current immune recognition methods for detecting bPAGs are limited and, to a certain extent, are associated with high costs and poor stability of the antibody. Aptamers that are more stable and easily synthesized than antibodies might serve as suitable candidates for the development of rapid detection methods. This paper describes selection and characterization of bPAG4 aptamers and theirs applicability to detect bPAG4 in the serum. In this work, the recombinant bovine pregnancy-associated glycoproteins 4 (bPAG4) with a relative molecular mass of about 48 kDa was successfully expressed in human embryonic kidney 293 (HEK 293) cells. Subsequently, the ssDNA aptamers were selected by systematic evolution of ligands by exponential enrichment (SELEX) using magnetic beads (MB) coated with bPAG4 as target. After 9 rounds of selection, three aptamers with high affinity to bPAG4 (Kd = 11.7~40.2 nM) were identified. The selected aptamers were successfully used in enzyme-linked aptamer assay (ELAA) to detect bPAG4 at a detection limit of 0.09 ng/mL. Meanwhile, it has been successfully applied for the detection of bPAG4 in serum samples. This work demonstrated that the selected aptamers could be used as promising affinity probes in the development of inexpensive, simple, and sensitive analysis methods for detecting bPAGs. Graphical abstract.

Colorimetric enzyme-linked aptamer assay utilizing hybridization chain reaction for determination of bovine pregnancy-associated glycoproteins.

DNA aptamers that bind to bovine pregnancy-associated glycoproteins (bPAGs) were selected by the systematic evolution of ligands by exponential enrichment (SELEX) procedure coupled to surface plasmon resonance (SPR) and high-throughput sequencing (HTS) technology. After seven rounds of selection using carboxylated magnetic beads (MB) coated with bovine pregnancy-associated glycoproteins 9 (bPAG9) and bovine serum albumin (BSA) as target and counter targets, respectively, two aptamers designated as A1 and A24 showed high affinities to bPAG9 (Kd = 1.04 and 2.5 nM). Moreover, the specificity was determined by testing the non-targets bPAG4, bPAG6, bPAG16, BSA, and ovalbumin (OVA). Results showed that two aptamers demonstrated broad group specificity to bPAG family. Subsequently, a colorimetric sandwich enzyme-linked aptamer assay was developed for ultrasensitive detection of bPAG9 based on hybridization chain reaction (HCR) amplification strategy. The method exhibited a broad determination from 0.134 to 134 ng/mL with a detection limit of 0.037 ng/mL. The method has been successfully applied to determine bPAGs in real samples. The results demonstrate that the developed aptamers could be used as promising molecular probes for the development of pregnancy diagnostic tools. Graphical abstract In this study, we first selected aptamers against bovine pregnancy-associated glycoproteins (bPAGs) as molecular recognition elements and then developed a colorimetric enzyme-linked aptamer assay utilizing hybridization chain reaction to detect bPAGs in the serum.The GA can't be deleted, the modified GA can not upload. So themodified GA and figures will be send to CorrAdmin3@spi-global.com.

UAV Swarm Mission Planning in Dynamic Environment Using Consensus-Based Bundle Algorithm.

To solve the real-time complex mission-planning problem for Multiple heterogeneous Unmanned Aerial Vehicles (UAVs) in the dynamic environments, this paper addresses a new approach by effectively adapting the Consensus-Based Bundle Algorithms (CBBA) under the constraints of task timing, limited UAV resources, diverse types of tasks, dynamic addition of tasks, and real-time requirements. We introduce the dynamic task generation mechanism, which satisfied the task timing constraints. The tasks that require the cooperation of multiple UAVs are simplified into multiple sub-tasks to perform by a single UAV independently. We also introduce the asynchronous task allocation mechanism. This mechanism reduces the computational complexity of the algorithm and the communication time between UAVs. The partial task redistribution mechanism has been adopted for achieving the dynamic task allocation. The real-time performance of the algorithm is assured on the premise of optimal results. The feasibility and real-time performance of the algorithm are validated by conducting dynamic simulation experiments.

Expression profile analysis of microRNAs during hair follicle development in the sheep foetus.

MicroRNAs (miRNAs) regulate the development and growth cycle of hair follicles (HFs). The molecular mechanism by which miRNAs determine the development of HFs in the sheep foetus remains elusive. In this study, the expression profiles of miRNAs at 11 development periods (45, 55, 65, 75, 85, 95, 105, 115, 125, 135 and 145 d) in sheep foetus skin were analysed by high-throughput sequencing and bioinformatics analysis. A total of 72 conserved miRNAs, 44 novel miRNAs and 32 known miRNAs were significantly differentially expressed. qRT-PCR results for 18 miRNAs were consistent with the sequencing data. 85 d of foetal development was the starting point for secondary hair follicle (SF) development according to tissue morphology and cluster analysis. In SF development, the prolactin signalling pathway and platelet activation played important roles, and 10 miRNAs were potential candidate miRNAs in SF initiation.

The comparison of reproductive hormone receptor expressions of the sheep ovary and hormone concentrations in two Chinese breeds.

The aim of this research was to investigate the changes in reproductive hormone receptor expressions of the ovary and hormone concentrations between oestrous cycle pattern of two different sheep breeds in China. Ovarian tissues were collected from Chinese Merino (Junken type) and Hu sheep with different reproductive states in spring and autumn. Serum samples were assayed for oestrogen (E2), progesterone (P), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations by radioimmunoassay during spring. The ovarian expression of hormone receptors (ERα, ERß, PR, LHR and FSHR) was analysed using real-time reverse transcription polymerase chain reaction (RT-PCR). In Chinese Merino, there was no corpora lutea and ovulation point on the surfaces of ovaries in spring and low basal levels of both LH and P in serum. ERα, ERß and FSHR were expressed significantly higher in Merino ovaries during anoestrus compared with oestrous or luteal phases of Hu sheep (p < 0.05 or p < 0.01). However, both varieties of sheep exhibited a similar tendency to secrete E2 and FSH. Compared with Hu sheep, FSH levels were slightly higher in Merino serum. In Hu sheep, ERα, ERß, FSHR, LHR and PR expressed in luteal phase ovaries during spring were significantly lower (p < 0.05, p < 0.01 or p < 0.001) than autumn. Interestingly, LHR and PR expressed in anoestrous ovaries were similar to that in oestrous phase of both sheep breeds. The above results suggest that seasonal reproductive sheep increased the expression of E2 and FSH receptors in ovary during spring may enhance the effects of E2 and FSH on follicular development. It is likely that this enhancement prevents the ovary from progressing to the luteal phase.

Risk factors for long-term post-traumatic stress disorder among medical rescue workers appointed to the 2008 Wenchuan earthquake response in China.

This study aims to determine the risk factors for clinically-significant post-traumatic stress disorder (PTSD) among Chinese medical rescue workers one year after the response to the Wenchuan earthquake on 12 May 2008. A sample of 337 medical workers who performed response work within the first three months of the event completed an online questionnaire, which included information on demographics, social support, the management and organisation of the disaster response, and an assessment of PTSD. Symptoms consistent with PTSD were prevalent in 17 per cent of the rescue workers. Those who developed PTSD symptoms were more likely to have been injured, experienced a water shortage, been disconnected from family and friends during the response, and have passive coping styles and neurotic personalities. Factors that cannot be changed easily, such as personality traits, should be evaluated prior to deployment to ensure that rescue workers at higher risk of PTSD are provided with adequate support before and during deployment.