Programmable DNA Templates for Silver Nanoclusters Synthesis To Develop On-Demand FRET Aptasensor.

DNA-templated silver nanoclusters (AgNCs-DNA) can be synthesized via a one-pot method bypassing the tedious process of biomolecular labeling. Appending an aptamer to DNA templates results in dual-functionalized DNA strands that can be utilized for synthesizing aptamer-modified AgNCs, thereby enabling the development of label-free fluorescence aptasensors. However, a major challenge lies in the necessity to redesign the dual-functionalized DNA strand for each specific target, thus increasing the complexity and hindering widespread application of these aptasensors. To overcome this challenge, we designed six DNA strands (DNA1-DNA6) that incorporate the templates for AgNCs synthesis and A4-linker for further aptamer coupling. Among all the synthesized AgNCs-DNA samples, it was found that both AgNCs-DNA1 and AgNCs-DNA2 stood out for their excellent long-term stability. After capturing the T4-linker that connected with aptamer1 specific for aflatoxin B1 (AFB1), however, we found that only AgNCs-DNA1/aptamer1 maintained excellent long-term stability. This finding highlighted the potential of AgNCs-DNA1 as a versatile label-free fluorescence probe for the development of on-demand fluorescence aptasensors. To emphasize its benefits in aptasensing applications, we utilized AgNCs-DNA1/aptamer1 as the fluorescence probe and MoS2 nanosheets as the quencher to develop a FRET aptasensor for AFB1 detection. This aptasensor demonstrated remarkable sensitivity, enabling the detection of AFB1 within a wide concentration range of 0.03-120 ng/mL, with a limit of detection as low as 3.6 pg/mL (S/N = 3). The versatility of the aptasensor has been validated through the recognition of diverse targets, employing aptamer2 specific for ochratoxin A and aptamer3 specific for zearalenone, thereby showcasing its extensive applicability for on-demand detection. The universal applicability of this aptasensor holds great promise for future applications in diverse fields including food safety, environmental monitoring, and clinical diagnosis.

Isolated superior mesenteric artery dissection with concomitant vascular aberrancy: Extremely rare cases and clinical implications.

OBJECTIVE: Vascular aberrancy of superior mesenteric artery (SMA) may contribute to the occurrence of SMA dissection. However, there is no direct evidence to support this hypothesis. Etiology, natural history, classification, and treatment options of ISMAD are still in controversial at some degree. We also review the current understanding of ISMAD based on our results. METHODS: Out of 57 patients, 2 cases of isolated superior mesenteric artery dissection (ISMAD) which concomitant with replaced common hepatic artery with SMA origin, are first reported. RESULTS: Two patients have no any typical etiological factors, such as atherosclerosis, hypertension, long-term smoking, and connective tissue disease. The contrast-enhanced computed tomography and (or) angiography showed concomitant SMA aberrancy. They have 81.2°, 132.7° SMA angle, respectively. After conservative treatment of 4, 6 days, respectively, these 2 patients were discharged smoothly. CONCLUSION: Vascular aberrancy may be a new identified risk factor for ISMAD. Even in ISMAD cases with vascular aberrancy, conservative treatment still can be used as first line therapy.

Alpha-Asarone Ameliorates Neurological Dysfunction of Subarachnoid Hemorrhagic Rats in Both Acute and Recovery Phases via Regulating the CaMKII-Dependent Pathways.

Early brain injury (EBI) is the leading cause of poor prognosis for patients suffering from subarachnoid hemorrhage (SAH), particularly learning and memory deficits in the repair phase. A recent report has involved calcium/calmodulin-dependent protein kinase II (CaMKII) in the pathophysiological process underlying SAH-induced EBI. Alpha-asarone (ASA), a major compound isolated from the Chinese medicinal herb Acorus tatarinowii Schott, was proven to reduce secondary brain injury by decreasing CaMKII over-phosphorylation in rats' model of intracerebral hemorrhage in our previous report. However, the effect of ASA on SAH remains unclear, and the role of CaMKII in both acute and recovery stages of SAH needs further investigation. In this work, we first established a classic SAH rat model by endovascular perforation and intraperitoneally administrated different ASA doses (10, 20, and 40 mg/kg) 2 h after successful modeling. Then, the short- and long-term neurobehavioral performances were blindly evaluated to confirm ASA's efficacy against SAH. Subsequently, we explored ASA's therapeutic mechanism in both acute and recovery stages using histopathological examination, TUNEL staining, flow cytometry, Western-blot, double-immunofluorescence staining, and transmission electron microscopy (TEM) observation. Finally, KN93, a selective CaMKII inhibitor, was applied in oxyhemoglobin-damaged HT22 cells to explore the role of CaMKII in ASA's neuroprotective effect. The results demonstrated that ASA alleviated short- and long-term neurological dysfunction, reduced mortality and seizure rate within 24 h, and prolonged 14-day survival in SAH rats. Histopathological examination showed a reduction of neuronal damage and a restoration of the hippocampal structure after ASA treatment in both acute and recovery phases of SAH. In the acute stage, the Western-blot and flow cytometer analyses showed that ASA restored E/I balance, reduced calcium overload and CaMKII phosphorylation, and inhibited mitochondrion-involved apoptosis, thus preventing neuronal damage and apoptosis underlying EBI post-SAH. In the recovery stage, the TEM observation, double-immunofluorescence staining, and Western-blot analyses indicated that ASA increased the numbers of synapses and enhanced synaptic plasticity in the ipsilateral hippocampi, probably by promoting NR2B/CaMKII interaction and activating subsequent CREB/BDNF/TrkB signaling pathways. Furthermore, KN93 notably reversed ASA's neuroprotective effect on oxyhemoglobin-damaged HT22 cells, confirming CaMKII a potential target for ASA's efficacy against SAH. Our study confirmed for the first time that ASA ameliorated the SAH rats' neurobehavioral deterioration, possibly via modulating CaMKII-involved pathways. These findings provided a promising candidate for the clinical treatment of SAH and shed light on future drug discovery against SAH.

Genome-wide identification of heat shock protein gene family and their responses to pathogen challenge in Trachinotus ovatus.

Heat Shock Proteins (HSPs) are a widely distributed family of proteins produced in response to heat and other stresses. To develop a deeper understanding of the mechanisms governing expression of HSPs in the bony fish Trachinotus ovatus, we carried out a whole genome analysis and identified 43 HSP genes. Based on their phylogenetic relationships with Danio rerio, Seriola dumerili, and Seriola lalandi, they were divided into four subfamilies: HSP20, HSP60, HSP70, and HSP90. We performed an analysis of the predicted physicochemical properties and subcellular localization of proteins encoded by these genes. The chromosomal localization results showed that the HSP genes are distributed across 20 chromosomes of T. ovatus.These genes were found to be expressed in different tissues, and they showed differential expression in the immune response against Streptococcus agalactiae. However, there was no significant differential expression in the different skin tissue locations of T. ovatus after infection by Cryptocaryon irritans Brown. This study provides basic information for further research on the evolution and structure and function of HSPs in teleosts.

Fabrication of a disposable aptasensing chip for simultaneous label-free detection of four common coexisting mycotoxins.

BACKGROUND: Coexisting multiple mycotoxins in food poses severe health risks on humans due to the augmented toxicity. Current multiplex detection methods for mycotoxins have evolved from instrumental analyses to rapid methods based on the specific recognition of antibody/aptamer using different signal transducers. However, nearly all of the reported aptasensors for multiple mycotoxins detection require external labels and can only simultaneous detection of two mycotoxins due to the limitation of distinguishable labels. The tedious labeling process definitely increases the operation complexity and the detection cost. Therefore, rapid method for simultaneous label-free detection of multiple mycotoxins in cereals is urgently needed. RESULTS: A disposable aptasensing chip was designed for simultaneous label-free detection of fumonisin B1 (FB1), aflatoxin B1 (AFB1), zearalenone (ZEN), and ochratoxin A (OTA) in one sample. Specifically, ITO conductive glass was divided into a rectangle (35 × 25 mm) and then etched by laser to set aside the required four ITO working electrodes (6 mm in diameter) with respective conductive channels. Gold nanoparticles were electrodeposited on the working electrodes to provide abundant anchoring sites for thiolated aptamers immobilization. On this basis, a disposable aptasensing chip for simultaneous label-free detection of four common coexisting mycotoxins has been developed, which used electrochemical impedance spectroscopy as transducer to measure direct biorecognition of the aptamer and corresponding target. This aptasensing chip provided wide linear ranges of 5-1000, 10-250, 10-1250, 10-1500 ng/mL for FB1, AFB1, ZEN, OTA, respectively, with the respective detection limit of 2.47, 3.19, 5.38, 4.87 ng/mL (S/N = 3). SIGNIFICANCE AND NOVELTY: This aptasensing chip shows fantastic characteristics of great simplicity and portability, easy operation, and multiple mycotoxins recognition. They are easy to produce on a large scale at low cost and the design concept can be easily expanded to screen a large panel of coexisting targets. This work provides a new avenue for multi-target detection and represents a substantial advance toward food quality and safety monitoring or other fields.

Immune Remodeling during Aging and the Clinical Significance of Immunonutrition in Healthy Aging.

Aging is associated with changes in the immune system and the gut microbiota. Immunosenescence may lead to a low-grade, sterile chronic inflammation in a multifactorial and dynamic way, which plays a critical role in most age-related diseases. Age-related changes in the gut microbiota also shape the immune and inflammatory responses. Nutrition is a determinant of immune function and of the gut microbiota. Immunonutrion has been regarded as a new strategy for disease prevention and management, including many age-related diseases. However, the understanding of the cause-effect relationship is required to be more certain about the role of immunonutrition in supporting the immune homeostasis and its clinical relevance in elderly individuals. Herein, we review the remarkable quantitative and qualitative changes during aging that contribute to immunosenescence, inflammaging and microbial dysbiosis, and the effects on late-life health conditions. Furthermore, we discuss the clinical significance of immunonutrition in the treatment of age-related diseases by systematically reviewing its modulation of the immune system and the gut microbiota to clarify the effect of immunonutrition-based interventions on the healthy aging.

Affine image registration of arterial spin labeling MRI using deep learning networks.

Convolutional neural networks (CNN) have demonstrated good accuracy and speed in spatially registering high signal-to-noise ratio (SNR) structural magnetic resonance imaging (sMRI) images. However, some functional magnetic resonance imaging (fMRI) images, e.g., those acquired from arterial spin labeling (ASL) perfusion fMRI, are of intrinsically low SNR and therefore the quality of registering ASL images using CNN is not clear. In this work, we aimed to explore the feasibility of a CNN-based affine registration network (ARN) for registration of low-SNR three-dimensional ASL perfusion image time series and compare its performance with that from the state-of-the-art statistical parametric mapping (SPM) algorithm. The six affine parameters were learned from the ARN using both simulated motion and real acquisitions from ASL perfusion fMRI data and the registered images were generated by applying the transformation derived from the affine parameters. The speed and registration accuracy were compared between ARN and SPM. Several independent datasets, including meditation study (10 subjects × 2), bipolar disorder study (26 controls, 19 bipolar disorder subjects), and aging study (27 young subjects, 33 older subjects), were used to validate the generality of the trained ARN model. The ARN method achieves superior image affine registration accuracy (total translation/total rotation errors of ARN vs. SPM: 1.17 mm/1.23° vs. 6.09 mm/12.90° for simulated images and reduced MSE/L1/DSSIM/Total errors of 18.07% / 19.02% / 0.04% / 29.59% for real ASL test images) and 4.4 times (ARN vs. SPM: 0.50 s vs. 2.21 s) faster speed compared to SPM. The trained ARN can be generalized to align ASL perfusion image time series acquired with different scanners, and from different image resolutions, and from healthy or diseased populations. The results demonstrated that our ARN markedly outperforms the iteration-based SPM both for simulated motion and real acquisitions in terms of registration accuracy, speed, and generalization.

Benzene, 1,2,4-Trimethoxy-5-(2-Methyl-1-Propen-1-yl) Attenuates D-galactose/AlCl3-induced Cognitive Impairment by Inhibiting Inflammation, Apoptosis, and improving Expression of Memory-Related Proteins.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by decreased learning ability and memory deficits. Our previous findings suggested that benzene, 1,2,4-trimethoxy-5-(2-methyl-1-propen-1-yl) (BTY) can ameliorate the dysfunction of GABAergic inhibitory neurons associated with neurological diseases. On this basis, we investigated the neuroprotective effect of BTY on AD and explored the underlying mechanism. This study included in vitro and in vivo experiments. BTY could maintain cell morphology, improve cell survival rate, reduce cell damage, and inhibit cell apoptosis in vitro experiments. Further, BTY has good pharmacological activity in vivo experiments, of which behavioral experiments showed that BTY could improve AD-like mice's learning and memory abilities. Besides, histopathological experiments indicated that BTY could maintain the morphology and function of neurons, reduce amyloid ß-protein 42 (Aß42) and phosphorylated tau (p-tau) accumulation, and decrease the levels of inflammatory cytokines. Finally, western blot experiments showed that BTY could inhibit the expression of apoptosis-related proteins and promote the expression of memory-related proteins. In conclusion, this study indicated that BTY may be a promising drug candidate for AD.

Construction of an alanine dehydrogenase gene deletion strain for vaccine development against Nocardia seriolae in hybrid snakehead (Channa maculata ♀ × Channa argus ♂).

Nocardia seriolae is the main pathogen of fish nocardiosis. In our previous study, alanine dehydrogenase was identified as a potential virulence factor of N. seriolae. On the basis of this fact, the alanine dehydrogenase gene of N. seriolae (NsAld) was knocked out to establish the strain ΔNsAld for vaccine development against fish nocardiosis in this study. The LD50 of strain ΔNsAld was 3.90 × 105 CFU/fish, higher than that of wild strain (5.28 × 104 CFU/fish) significantly (p < 0.05). When the strain ΔNsAld was used as a live vaccine to immunize hybrid snakehead (Channa maculata ♀ × Channa argus ♂) at 2.47 × 105 CFU/fish by intraperitoneal injection, the non-specific immune indexes (LZM, CAT, AKP, ACP and SOD activities), specific antibody (IgM) titers and several immune-related genes (CD4, CD8α, IL-1ß, MHCIα, MHCIIα and TNFα) were up-regulated in different tissues, indicating that this vaccine could induce humoral and cell-mediated immune responses. Furthermore, the relative percentage survival (RPS) of ΔNsAld vaccine was calculated as 76.48% after wild N. seriolae challenge. All these results suggest that the strain ΔNsAld could be a potential candidate for live vaccine development to control fish nocardiosis in aquaculture.

Prognostic value of preoperative circulating tumor cells for hepatocellular carcinoma with portal vein tumor thrombosis: A propensity score analysis.

PURPOSE: The role of circulating tumor cells (CTCs) in hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is not fully understood. METHODS: In this retrospective analysis, we included 316 HCC patients who underwent hepatectomy and preoperative CTC detection. We selected 41 pairs of matched HCC patients with and without PVTT using propensity score matching (PSM) analysis. We compared the preoperative CTC counts in patients from both the full cohort and the PSM model. We also analyzed their associations with disease-free survival (DFS) and overall survival (OS). RESULTS: Before and after PSM analysis, the preoperative CTC counts in the HCC with PVTT group were substantially higher than in the HCC without PVTT group. In both the full cohort of patients and the PSM model, patients with CTC ≥ 2 had significantly shorter OS and DFS than patients with CTC < 2. The outcomes of HCC patients with PVTT could be well differentiated by preoperative CTC levels. HCC patients with CTC ≥ 2 had noticeably shorter OS (9.9 months vs. 24.6 months, P = 0.0003) and DFS (6.0 months vs. 12.3 months, P = 0.0041) than those with CTC < 2. Moreover, preoperative CTC ≥ 2 remained an independent predictor in all groups' multivariate analysis. CONCLUSION: We discovered a link between preoperative CTC counts and the occurrence of PVTT and confirmed the prognostic significance of preoperative CTC in HCC patients with PVTT. These findings suggest that preoperative CTC counts have the potential to assist in identifying patients with HCC and PVTT who may benefit from surgery.

Computational Modeling to Determine the Effect of Phenotypic Heterogeneity in Tumors on the Collective Tumor-Immune Interactions.

Tumor immunotherapy aims to maintain or enhance the killing capability of CD8+ T cells to clear tumor cells. The tumor-immune interactions affect the function of CD8+ T cells. However, the effect of phenotype heterogeneity of a tumor mass on the collective tumor-immune interactions is insufficiently investigated. We developed the cellular-level computational model based on the principle of cellular Potts model to solve the case mentioned above. We considered how asymmetric division and glucose distribution jointly regulated the transient changes in the proportion of proliferating/quiescent tumor cells in a solid tumor mass. The evolution of a tumor mass in contact with T cells was explored and validated by comparing it with previous studies. Our modeling exhibited that proliferating/quiescent tumor cells, exhibiting distinct anti-apoptotic and suppressive behaviors, redistributed within the domain accompanied by the evolution of a tumor mass. Collectively, a tumor mass prone to a quiescent state weakened the collective suppressive functions of a tumor mass on cytotoxic T cells and triggered a decline of apoptosis of tumor cells. Although quiescent tumor cells did not sufficiently do their inhibitory functions, the possibility of long-term survival was improved due to their interior location within a mass. Overall, the proposed model provides a useful framework to investigate collective-targeted strategies for improving the efficiency of immunotherapy.

Investigation and Countermeasures Research of Hospital Information Construction of Tertiary Class-A Public Hospitals in China: Questionnaire Study.

BACKGROUND: Medical informatization has initially demonstrated its advantages in improving the medical service industry. Over the past decade, the Chinese government have made a lot of effort to complete infrastructural information construction in the medical and health domain, and smart hospitals will be the next priority according to policies released by Chinese government in recent years. OBJECTIVE: To provide strategic support for further development of medical information construction in China, this study aimed to investigate the current situation of medical information construction in tertiary class-A public hospitals and analyze the existing problems and countermeasures. METHODS: This study surveyed 23 tertiary class-A public hospitals in China who voluntarily responded to a self-designed questionnaire distributed in April 2020 to investigate the current medical information construction status. Descriptive statistics were used to summarize the current configurations of hospital information department, hospital information systems, hospital internet service and its application, and the satisfaction of hospital information construction. Interviews were also conducted with the respondents in this study for requirement analysis. RESULTS: The results show that hospital information construction has become one of the priorities of the hospitals' daily work, and the medical information infrastructural construction and internet service application of the hospitals are good; however, a remarkable gap among the different level of hospitals can be observed. Although most hospitals had built their own IT team to undertake information construction work, the actual utilization rate of big data collected and stored in the hospital information system was not satisfactory. CONCLUSIONS: Support for the construction of information technology in primary care institutions should be increased to balance the level of development of medical informatization in medical institutions at all levels. The training of complex talents with both IT and medical backgrounds should be emphasized, and specialized disease information standards should be developed to lay a solid data foundation for data utilization and improve the utilization of medical big data.

Neuroprotection of boropinol-B in cerebral ischemia-reperfusion injury by inhibiting inflammation and apoptosis.

Ischemic stroke is the leading cause of death and disability worldwide. The activation of gamma-aminobutyric acid A (GABAA) receptors can attenuate cerebral ischemia-reperfusion injury (CI/RI). Boropinol-B, originally isolated from Boronia pinnata Sm. (Rutaceae), has been proved the ability to activate GABAA receptors synergistically. However, whether boropinol-B has neuroprotection in CI/RI remains unknown. Here we reported the neuroprotective effect of boropinol-B on CI/RI and its underlying mechanism, focusing on inhibiting inflammation and apoptosis. The oxygen and glucose deprivation and reperfusion (OGD/R) cell model showed that boropinol-B could improve cell viability, mitigate cell injury, and inhibit apoptosis. In rats, the transient ischemic model was induced by middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion. Our results indicated that boropinol-B improved neurological scores, reduced cerebral infarction and neuronal necrosis of rats 24 h after ischemia, and prolonged median survival time after continuous administration for 14 days. Furthermore, we found that boropinol-B inhibited the over-activation of microglia and astrocytes, reduced the release of pro-inflammatory factors, and down-regulated the expression of matrix metalloproteinases-3/9, thus alleviating cerebral edema and blood-brain barrier dysfunction. Also, it suppressed apoptosis by increasing Bcl-2 expression and decreasing the expression of Bax, Active Caspase-3, and Cytochrome C. In conclusion, boropinol-B demonstrated anti-inflammatory and anti-apoptotic properties that contributed to the neuroprotective effect against CI/RI, suggesting that it may be an up-and-coming drug candidate to treat ischemic stroke.

Postoperative outcomes and recurrence patterns of intermediate-stage hepatocellular carcinoma dictated by the sum of tumor size and number.

BACKGROUND: The selection criteria for Barcelona Clinic Liver Cancer (BCLC) intermediate-stage hepatocellular carcinoma (HCC) patients who would truly benefit from liver resection (LR) remain undefined. AIM: To identify BCLC-B HCC patients more suitable for LR. METHODS: We included patients undergoing curative LR for BCLC stage A or B multi-nodular HCC (MNHCC) and stratified BCLC-B patients by the sum of tumor size and number (N + S). Overall survival (OS), recurrence-free survival (RFS), recur-rence-to-death survival (RTDS), recurrence patterns, and treatments after recurrence in BCLC-B patients in each subgroup were compared with those in BCLC-A patients. RESULTS: In total, 143 patients who underwent curative LR for MNHCC with BCLC-A (n = 25) or BCLC-B (n = 118) were retrospectively analyzed. According to the N + S, patients with BCLC-B HCC were divided into two subgroups: BCLC-B1 (N + S ≤ 10, n = 83) and BCLC-B2 (N + S > 10, n = 35). Compared with BCLC-B2 patients, those with BCLC-B1 had a better OS (5-year OS rate: 67.4% vs 33.6%; P < 0.001), which was comparable to that in BCLC-A patients (5-year OS rate: 67.4% vs 74.1%; P = 0.250), and a better RFS (median RFS: 19 mo vs 7 mo; P < 0.001), which was worse than that in BCLC-A patients (median RFS: 19 mo vs 48 mo; P = 0.022). Further analysis of patients who developed recurrence showed that both BCLC-B1 and BCLC-A patients had better RTDS (median RTDS: Not reached vs 49 mo; P = 0.599), while the RTDS in BCLC-B2 patients was worse (median RTDS: 16 mo vs not reached, P < 0.001; 16 mo vs 49 mo, P = 0.042). The recurrence patterns were similar between BCLC-B1 and BCLC-A patients, but BCLC-B2 patients had a shorter recurrence time and a higher proportion of patients had recurrence with macrovascular invasion and/or extrahepatic metastasis, both of which were independent risk factors for RTDS. CONCLUSION: BCLC-B HCC patients undergoing hepatectomy with N + S ≤ 10 had mild recurrence patterns and excellent OS similar to those in BCLC-A MNHCC patients, and LR should be considered in these patients.

Benzene, 1,2,4-Trimethoxy-5-(2-Methyl-1-Propen-1-yl), a New Neuroprotective Agent, Treats Intracerebral Hemorrhage by Inhibiting Apoptosis, Inflammation, and Oxidative Stress.

The highest disability rates and mortality among neurodegenerative diseases were caused by intracerebral hemorrhage (ICH). We previously proved that Benzene, 1,2,4-trimethoxy-5-(2-methyl-1-propen-1-yl) (BTY) has an inhibitory effect on sodium ion channel and an activation effect on GABAA receptor, which were related to the brain injury. Based on this, we aimed to investigate BTY's neuroprotection on intracerebral hemorrhage and its underlying mechanism. In the in vivo study, a stereotactic injection of collagenase VII in Sprague Dawley rats (0.5 U) induced ICH and the BTY was intraperitoneally injected at 2 h after ICH. The neurological deficit scores, blood-brain barrier (BBB) permeability, and other indicators were assessed 24 h after ICH. The results showed that the BTY reduced brain edema and hematoma volume, improved neurological function and BBB permeability, and inhibited inflammatory factors and neuron apoptosis. The cell experiments proved that the BTY suppressed oxidative stress, cell apoptosis, intracellular calcium influx, and stabilized mitochondrial membrane potential by reducing glutamate's excitotoxicity. This study for the first time exhibited desirable neuroprotection of BTY, indicating it may be a promising neuroprotective agent for ICH therapy.

Induction of attenuated Nocardia seriolae and their use as live vaccine trials against fish nocardiosis.

Nocardia seriolae, a Gram-positive facultative intercellular pathogen, has been identified as the causative agent of fish nocardiosis, causing substantial mortality and morbidity of a wide range of fish species. Looking into that fact, the effective vaccine against this pathogen is urgently needed to control the significant losses in aquaculture practices. In order to induct attenuated strains for developing the potential live vaccines, the mutagenic N. seriolae strain S-250 and U-20 were obtained from wild-type strain ZJ0503 through continuous passaging and ultraviolet (UV) irradiation, respectively. Additionally, the biological characteristic, virulence, stability, mediating immune response and supplying protective efficacy to hybrid snakehead of the S-250 and U-20 strains were determined in the present study. The results showed that U-20 strain displayed dramatic changes in morphological characteristic and significant decreased in the virulence to hybrid snakehead, while that of S-250 strain had no obvious different in comparison to ZJ0503 strain. When hybrid snakehead were intraperitoneally injected with ZJ0503, S-250 and U-20 strains at their respective sub-clinical dosage, the non-specific immunity parameters (serum LYZ, POD, ACP, AKP and SOD activities), specific antibody (IgM) titers production and immune-related genes (CC1, CC2, IL-1ß, IL-8, TNFα, IFNγ, MHCIα, MHCIIα, CD4, CD8α, TCRα and TCRß) expression were up-regulated, indicating that they were able to trigger humoral and cell-mediated immune responses. Furthermore, the protective efficacy in hybrid snakehead after vaccination with ZJ0503, S-250 and U-20 strains, in terms of relative percentage survival (RPS), were 28.85%, 56.89% and 89.65% respectively. Taken together, two attenuated N. seriolae strains S-250 and U-20 were obtained successfully and they could elicit strong immune response and supply protective efficacy to hybrid snakehead against N. seriolae, which suggested that these two attenuated strains were the potential candidates for live vaccine development to control fish nocardiosis in aquaculture.

More to Less (M2L): Enhanced Health Recognition in the Wild with Reduced Modality of Wearable Sensors.

Accurately recognizing health-related conditions from wearable data is crucial for improved healthcare outcomes. To improve the recognition accuracy, various approaches have focused on how to effectively fuse information from multiple sensors. Fusing multiple sensors is a common choice in many applications, but may not always be feasible in real-world scenarios. For example, although combining biosignals from multiple sensors (i.e., a chest pad sensor and a wrist wearable sensor) has been proved effective for improved performance, wearing multiple devices might be impractical in the free-living context. To solve the challenges, we propose an effective more to less (M2L) learning framework to improve testing performance with reduced sensors through leveraging the complementary information of multiple modalities during training. More specifically, different sensors may carry different but complementary information, and our model is designed to enforce collaborations among different modalities, where positive knowledge transfer is encouraged and negative knowledge transfer is suppressed, so that better representation is learned for individual modalities. Our experimental results show that our framework achieves comparable performance when compared with the full modalities. Our code and results will be available at https://github.com/comp-well-org/More2Less.git.

Design and implementation of a highly integrated dual hemisphere capsule robot.

To achieve cancer screening in any appointed position in 3D regions of the gastrointestinal (GI) tract such as esophagus, stomach and colon, a highly integrated dual hemisphere capsule robot (DHCR) with a novel three-layer nested structure is proposed. Based on tracking effect, in which the robotic axis is likely to be approximately coincident with the orientation of the space universal rotating magnetic field (SURMF) using the gyroscope dynamic balance, the dual hemisphere structure realizes the observation at a fixed-point in the passive mode and the rolling locomotion in the active mode by the dynamic posture control of the SURMF manipulation. The image acquisition module, wireless transmission module and driving actuator are tuned in a spherical structure, making the DHCR more compact and less invasive. To verify the maneuverability of the innovative DHCR both for observation at a fixed-point and navigation in curved intestine by aid of image, experiments are conducted in the simulated GI tract environment. The results show that the DHCR achieves effective conversion between posture adjustment and rolling locomotion, which lays a foundation for all-over inspection and medical operation inside 3D regions of the GI tract of human body.

Myrothecol A, a new alkylresorcinol with cytotoxicity from Myrothecium sp.

A new alkylresorcinol, myrothecol A (1), along with two known ones (2 and 3), were isolated from a fungal strain Myrothecium sp. GY170016. Their structures were elucidated by extensive spectroscopic analysis. The absolute configuration of 1 was determined by electronic circular dichroism experiment. This is the first case of the presence of alkylresorcinols in genus Myrothecium. All the isolates were evaluated for their cytotoxic activities against human cancer cell line MCF-7 with IC50 values of 16.7, 13.2, 21.3 µM, respectively.

Occupational health risk assessment of BTEX in municipal solid waste landfill based on external and internal exposure.

Benzene, toluene, ethylbenzene, and xylenes (BTEX) released from landfills have received increased attention because of their health risks. In this study, individual external and internal exposures of BTEX in a municipal solid waste (MSW) landfill were simultaneously studied for the first time. Eight workers from the landfill (as the case group) and eight control subjects were enrolled in the study. In total, 88 air samples and 232 urine samples (194 samples from the case group and 38 samples from the control group) were obtained from 2018 to 2019. According to the results of external exposure monitoring, benzene was the predominant component of BTEX, and the exposure level was higher in winter than in other seasons. Carcinogenic (RiskT) and noncarcinogenic (HIT) risks were calculated based on a dose-response model. The RiskT (1.64 × 10-8-1.09 × 10-6) might exceeded the limit, whereas HIT (9.84 × 10-4-1.40 × 10-2) was within their thresholds. Benzene was the major contributor to both RiskT and HIT. Internal exposures were evaluated by measuring urinary metabolites of BTEX. Levels of urinary BTEX metabolites for case group were higher than those for control group. A remarkable increase in urinary metabolites was observed from the urine samples of the case group after their shift compared with those before their shift. t,t-MA, the metabolite of benzene, was found to exceed the biomonitoring guidance limits of both China and the United States of America. Landfills can be considered as a potential BTEX exposure source for landfill employees. Minimizing occupational exposures and appropriate personal protective equipment are needed in reducing BTEX exposures.