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Objectives: This study aimed to assess the knowledge, attitudes, and practices (KAP) and the training requirements of pediatric intensive care nurses regarding intra-abdominal pressure (IAP) monitoring, in order to provide a reference for the development of relevant training programs and operational procedures in clinical practice. Methods: This descriptive cross-sectional survey was conducted from April 2023 to June 2023. A convenience sample was created by recruiting 212 pediatric intensive care nurses in eight hospitals in Zhejiang Province. A self-developed IAP monitoring KAP assessment tool was used for evaluation, which included knowledge (14 items), attitude (6 items), and practice (8 items), three dimensions, 28 items. Results: The overall KAP score was 60.73 ± 8.35; the knowledge score was 7.84 ± 2.35, with a scoring rate of 56.0%; the attitude score was 25.16 ± 3.23, with a scoring rate of 83.9%; and the practice score was 28.44 ± 6.46, with a scoring rate of 69.3%. Nurses wh-o have received IAP monitoring training have higher KAP score, knowledge score and practice score than those who have not received it (P 30 (P

Abstract Background Treatment efficacy may differ among patients with nasopharyngeal carcinoma (NPC) at similar tumor–node–metastasis stages. Moreover, end-of-treatment tumor regression is a reliable indicator of treatment sensitivity. This study aimed to investigate whether quantitative dual-energy computed tomography (DECT) parameters could predict sensitivity to neck–lymph node radiotherapy in patients with NPC. Methods Overall, 388 lymph nodes were collected from 98 patients with NPC who underwent pretreatment DECT. The patients were divided into complete response (CR) and partial response (PR) groups. Clinical characteristics and quantitative DECT parameters were compared between the groups, and the optimal predictive ability of each parameter was determined using receiver operating characteristic (ROC) analysis. A nomogram prediction model was constructed and validated using univariate and binary logistic regression. Results DECT parameters were higher in the CR group than in the PR group. The iodine concentration (IC), normalized IC, Mix-0.6, spectral Hounsfield unit curve slope, effective atomic number, and virtual monoenergetic images were significantly different between the groups. The area under the ROC curve of the DECT parameters was 0.73–0.77. Based on the binary logistic regression, a column chart was constructed using 10 predictive factors, including age, sex, N stage, maximum lymph node diameter, arterial phase NIC, venous phase NIC, λHU and spectral Hounsfield units at 70 keV. The area under the ROC curve value of the constructed model was 0.813, with a sensitivity and specificity of 85.6% and 81.3%, respectively. Conclusion Quantitative DECT parameters could effectively predict the sensitivity of NPC to radiotherapy. Therefore, DECT parameters and NPC clinical features can be combined to construct a nomogram with high predictive power and used as a clinical analytical tool.

Background Abnormalities in mitochondrial structure or function are closely related to the development of malignant tumors. Mitochondrial metabolic reprogramming provides precursor substances and energy for the vital activities of tumor cells, so that cancer cells can rapidly adapt to the unfavorable environment of hypoxia and nutrient deficiency. Mitochondria can enable tumor cells to gain the ability to proliferate, escape immune responses, and develop drug resistance by altering constitutive junctions, oxidative phosphorylation, oxidative stress, and mitochondrial subcellular relocalization. This greatly reduces the rate of effective clinical control of tumors. Purpose Explore the major role of mitochondria in cancer, as well as targeted mitochondrial therapies and mitochondria-associated markers. Conclusions This review provides a comprehensive analysis of the various aspects of mitochondrial aberrations and addresses drugs that target mitochondrial therapy, providing a basis for clinical mitochondria-targeted anti-tumor therapy.

Abstract The clinical significance of the combination of neutrophil–lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) is unclear. This study investigated the predictive value of pretreatment NLR (pre-NLR) combined with pretreatment PLR (pre-PLR) for the survival and prognosis of nasopharyngeal carcinoma (NPC). A total of 765 patients with non-metastatic NPC from two hospitals were retrospectively analyzed. The pre-NLR-PLR groups were as follows: HRG, high pre-NLR and high pre-PLR. MRG, high pre-NLR and low pre-PLR or low pre-NLR and high pre-PLR. LRG, neither high pre-NLR nor high pre-PLR. Receiver operating characteristic (ROC) curves were used to identify the cutoff-value and discriminant performance of the model. We compared survival rates and factors affecting the prognosis among different groups. The 5-year overall survival (OS), local regional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS) of NPC patients in HRG were significantly poorer than those in MRG and LRG. The pre-NLR-PLR score was positively correlated with T stage, clinical stage, ECOG, and pathological classification. Multivariate cox regression analysis showed that pre-NLR-PLR scoring system, ECOG, pre-ALB, pre-CRP and pre-LMR were independent risk factors affecting 5-year OS, LRRFS and DMFS. The ROC curve showed that area under the curve (AUC) values of pre-NLR-PLR of 5-year OS, LRRFS and DMFS were higher than those of pre-NLR and pre-PLR. pre-NLR-PLR is an independent risk factor for the prognosis of NPC. The pre-NLR-PLR scoring system can be used as an individualized clinical assessment tool to predict the prognosis of patients with non-metastatic NPC more accurately and easily.

Acute kidney injury (AKI) is in high prevalence worldwide but with no therapeutic strategies. Programmed cell death in tubular epithelial cells has been reported to accelerate a variety of AKI, but the major pathways and underlying mechanisms are not defined. Herein, we identified that pyroptosis was responsible for AKI progression and related to ATP depletion in renal tubular cells. We found that FAM3A, a mitochondrial protein that assists ATP synthesis, was decreased and negatively correlated with tubular cell injury and pyroptosis in both mice and patients with AKI. Knockout of FAM3A worsened kidney function decline, increased macrophage and neutrophil cell infiltration, and facilitated tubular cell pyroptosis in ischemia/reperfusion injury model. Conversely, FAM3A overexpression alleviated tubular cell pyroptosis, and inhibited kidney injury in ischemic AKI. Mechanistically, FAM3A promoted PI3K/AKT/NRF2 signaling, thus blocking mitochondrial reactive oxygen species (mt-ROS) accumulation. NLRP3 inflammasome sensed the overload of mt-ROS and then activated Caspase-1, which cleaved GSDMD, pro-IL-1β, and pro-IL-18 into their mature forms to mediate pyroptosis. Of interest, NRF2 activator alleviated the pro-pyroptotic effects of FAM3A depletion, whereas the deletion of NRF2 blocked the anti-pyroptotic function of FAM3A. Thus, our study provides new mechanisms for AKI progression and demonstrates that FAM3A is a potential therapeutic target for treating AKI.

ObjectiveClear cell renal cell carcinoma (ccRCC) is the most common type of renal cancer and currently lacks effective biomarkers. This research aims to analyze and identify RNA editing profile associated with ccRCC prognosis through bioinformatics and in vitro experiments.MethodsTranscriptome data and clinical information for ccRCC were retrieved from the TCGA database, and RNA editing files were obtained from the Synapse database. Prognostic models were screened, developed, and assessed using consistency index analysis and independent prognostic analysis, etc. Internal validation models were also constructed for further evaluation. Differential genes were investigated using GO, KEGG, and GSEA enrichment analyses. Furthermore, qPCR was performed to determine gene expression in human renal tubular epithelial cells HK-2 and ccRCC cells A-498, 786-O, and Caki-2.ResultsAn RNA editing-based risk score, that effectively distinguishes between high and low-risk populations, has been identified. It includes CHD3| chr17:7815229, MYO19| chr17:34853704, OIP5-AS1| chr15:41590962, MRI1| chr19:13883962, GBP4| chr1:89649327, APOL1| chr22:36662830, FCF1| chr14:75203040 edited sites or genes and could serve as an independent prognostic factor for ccRCC patients. qPCR results showed significant up-regulation of CHD3, MYO19, MRI1, APOL1, and FCF1 in A-498, 786-O, and Caki-2 cells, while the expression of OIP5-AS1 and GBP4 was significantly down-regulated.ConclusionRNA editing site-based prognostic models are valuable in differentiating between high and low-risk populations. The seven identified RNA editing sites may be utilized as potential biomarkers for ccRCC.

Glycation Stress (GS), induced by advanced glycation end-products (AGEs), significantly impacts aging processes. This study introduces a new model of GS of Caenorhabditis elegans by feeding them Escherichia coli OP50 cultured in a glucose-enriched medium, which better simulates human dietary glycation compared to previous single protein–glucose cross-linking methods. Utilizing WormCNN, a deep learning model, we assessed the health status and calculated the Healthy Aging Index (HAI) of worms with or without GS. Our results demonstrated accelerated aging in the GS group, evidenced by increased autofluorescence and altered gene expression of key aging regulators, daf-2 and daf-16. Additionally, we observed elevated pharyngeal pumping rates in AGEs-fed worms, suggesting an addictive response similar to human dietary patterns. This study highlights the profound effects of GS on worm aging and underscores the critical role of computer vision in accurately assessing health status and aiding in the establishment of disease models. The findings provide insights into glycation-induced aging and offer a comprehensive approach to studying the effects of dietary glycation on aging processes.

Abstract Mpox is a neglected zoonotic disease endemic in West and Central Africa. The Mpox outbreak with more than 90,000 cases worldwide since 2022 generated great concern about future outbreaks and highlighted the need for a simple and rapid diagnostic test. The Mpox virus, MPV, is a member of the Orthopoxvirus (OPV) genus that also contains other pathogenic viruses including variola virus, vaccinia virus, camelpox virus, and cowpox virus. Phylogenomic analysis of 200 OPV genomes identified 10 distinct phylogroups with the New World OPVs placed on a very long branch distant from the Old World OPVs. Isolates derived from infected humans were found to be distributed across multiple phylogroups interspersed with isolates from animal sources, indicating the zoonotic potential of these viruses. In this study, we developed a simple and sensitive colorimetric LAMP assay for generic detection of Old World OPVs. We also developed an MPV-specific probe that differentiates MPV from other OPVs in the N1R LAMP assay. In addition, we described an extraction-free protocol for use directly with swab eluates in LAMP assays, thereby eliminating the time and resources needed to extract DNA from the sample. Our direct LAMP assays are well-suited for low-resource settings and provide a valuable tool for rapid and scalable diagnosis and surveillance of OPVs and MPV.

Abstract Purpose Analyzing the prognostic value of Epstein-Barr virus (EBV) DNA load and platelet-to-lymphocyte ratio (PLR) in non-metastatic nasopharyngeal carcinoma (NPC) patients, thereby developing a reliable and effective marker. Methods We compared survival rates among different groups using the Kaplan-Meier method and the Log-rank test. The factors affecting the prognosis of NPC patients were determined using univariate and multivariate cox regression analysis. Receiver operating characteristic (ROC) curves were used to identify the cutoff-value and discriminant performance of the model. Results The ROC curve indicated a cut-off value of 775 copies/ml for EBV DNA and 203.3 for PLR. Kaplan-Meier and Log-rank tests showed that 3-year overall survival (OS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS) of NPC patients in high risk group (HRG) were significantly poorer than those in medium risk group (MRG) and low risk group (LRG). The 3-year OS of NPC patients was significantly correlated with age, N stage and EBV DNA-PLR. The 3-year LRFS were significantly correlated with sex, N stage, histology type, and EBV DNA-PLR. The 3-year DMFS were correlated with histology type. The ROC curve showed that area under the curve (AUC) values of EBV DNA-PLR of 3-year OS, LRFS and DMFS in NPC were higher than those of PLR and EBV DNA. Conclusion EBV DNA-PLR is an independent risk factor for the prognosis of NPC. Compared with PLR or EBV DNA alone, the combination of EBV DNA and PLR may be more accurate in predicting the prognosis of NPC patients.

Horizontal gene transfer (HGT) is a ubiquitous force in microbial evolution. Previous work has shown that the human gut is a hotspot for gene transfer between species, but the more subtle exchange of variation within species-also known as recombination-remains poorly characterized in this ecosystem. Here, we show that the genetic structure of the human gut microbiome provides an opportunity to measure recent recombination events from sequenced fecal samples, enabling quantitative comparisons across diverse commensal species that inhabit a common environment. By analyzing recent recombination events in the core genomes of 29 human gut bacteria, we observed widespread heterogeneities in the rates and lengths of transferred fragments, which are difficult to explain by existing models of ecological isolation or homology-dependent recombination rates. We also show that natural selection helps facilitate the spread of genetic variants across strain backgrounds, both within individual hosts and across the broader population. These results shed light on the dynamics of in situ recombination, which can strongly constrain the adaptability of gut microbial communities.

AimTo provide a comprehensive overview on emerging direct and alternative methods for intra-abdominal pressure (IAP) measurement techniques.MethodsThis was a scoping review study following Arksey and Malley's framework. The PubMed, EMBASE, Web of Science, EBSCO, Scopus and ProQuest databases were searched, and we only considered studies published from 2000 as we have extended the data from two previous reviews. Original studies that reported on the development, feasibility and credibility of IAP measurement techniques were included.ResultsForty-two of 9954 screened articles were included. IAP measurement techniques include three major categories: direct, indirect and less invasive measurement techniques. Agreement analyses were performed in most studies, and some explored the safety, time expenditure and reproducibility of IAP measurement techniques.ConclusionsClinical data assessing the validation of new IAP measurement techniques or the reliability of established measurement techniques remain lacking. Considering the cost and invasiveness, direct measurement is not recommended as a routine method for IAP measurement and should be preserved for critically ill patients where standard techniques are contraindicated or could be inaccurate. The measurement accuracy, reliability and sensitivity of the transrectal and transfemoral vein methods remain insufficient and cannot be recommended as surrogate IAP measures. Transvesical measurement is the most widely used method, which is the potentially most easy applicable technique and can be used as a reliable method for continuous and intermittent IAP measurement. Wireless transvaginal method facilitates the quantitative IAP measurement during exercise and activity, which laying the foundations for monitoring IAP outside of the clinic environment, but the accuracy of this technique in measuring absolute IAP cannot be determined at present. Less invasive technology will become a new trend to measure IAP and has substantial potential to replace traditional IAP measurement technologies, but further validation and standardization are still needed. Medical professionals should choose appropriate measurement tools based on the advantages and disadvantages of each IAP technique in combination with assessing specific clinical situations.

The positioning results of terrain matching in flat terrain areas will significantly deteriorate due to the influence of terrain nonlinearity and multibeam measurement noise. To tackle this problem, this study presents the Pulse-Coupled Neural Network (PCNN), which has been effectively utilized for image denoising. The interconnection of surface terrain data nodes is achieved through PCNN ignition, which serves to alleviate the reduction in terrain similarity caused by measurement error. This enables the efficient selection of terrain data, ensuring that points with high measurement accuracy are preserved for terrain matching and positioning operations. The simulation results illustrate that the suggested methodology effectively removes terrain data points with low measurement accuracy, thereby improving the performance of terrain matching and positioning.

The intermittent and volatile nature of wind power generation necessitates thermal power units to provide deep-peak shaving and fast frequency regulation services within the same grid. However, the current proportional integral differential (PID) control performance in the process control foundation of thermal power units falls short of meeting these requirements. Despite the lack of comprehensive research on engineering fastest control (EFC), this article aims to address this gap by studying and analyzing the mechanism and physical defects of the fast tracking filter (FTF), the output tracking input characteristics of EFTF reconstructed by FTF engineering, and the control performance of the constructed EFC. Through mathematical calculation analysis, simulation experiments, and real-world engineering practice, it is concluded that EFC surpasses the limitations of PID control performance and effectively enhances feedback control performance. As a result, it is deemed suitable for process control in thermal power units.

Carbon allocation in forest ecosystems is essential for the optimization of growth. However, remote-sensing-based research on the estimation of carbon allocation in forests is inadequate. This article considers forests in northeastern China as the research area and uses leaf area index (LAI) data combined with random forest and structural equation modelling methods to study the spatiotemporal distribution characteristics and driving factors of carbon allocation to leaves (ΔLAI) in deciduous broad-leaved forests (DBF), deciduous coniferous forests (DNF), and mixed forests (MF) during the green-up period (GUP) at a monthly scale during April, May, June, and July from 2001 to 2021, and clarifies the impact of leaf carbon allocation on gross primary productivity (GPP). The ΔLAI was the highest in DBF in April and in DNF and MF in May. The ΔLAI in April with an increasing trend year by year in DBF and MF, and the ΔLAI in May with an increasing trend in DNF. Among all the direct and indirect relationships that affect ΔLAI, temperature (TEM) has the highest path coefficient for DBF’s ΔLAI in April (−1.213) and the start of the season (SOS) has the highest path coefficient for DNF (−1.186) and MF (0.815). ΔLAI in the GUP has a significant positive impact on the GPP. In the MF, the higher ΔLAI in May was most conducive to an increase in GPP. During the critical period, that is April and May, carbon allocation to leaves effectively improves the carbon sequestration capacity of forestland. This information is of great value for the development and validation of terrestrial ecosystem models.

Abstract Background To retrospectively analyze the efficacy and safety of concurrent chemoradiotherapy (CCRT) plus recombinant human endostatin (Endostar, CCRT + E) versus CCRT alone in locally advanced nasopharyngeal carcinoma (LANPC). Methods A retrospective analysis of patients initially treated for LANPC from November 2016 to March 2019 was performed: trial group received CCRT + E and control group received CCRT. Prognoses and adverse effects were evaluated. Results Eighty-eight patients were included: 43 received CCRT + E and 45 received CCRT. The median follow-up time was 54.0 (range: 8.0–64.0) months. The survival data of the CCRT + E and CCRT groups were as follows: 3-year progression-free survival (PFS) rates, 81.4% and 63.6% (hazard ratio [HR] 0.418, 95%CI 0.181–0.963, P = 0.034); 3-year distant metastasis-free survival (DMFS) rates, 88.3% and 77.3% (HR 0.370, 95%CI 0.132–1.039, P = 0.049); 3-year overall survival rates, 88.2% and 81.9% (HR 0.437, 95%CI 0.151–1.260, P = 0.114); and 3-year locoregional failure-free survival rates, 87.8% and 86.9% (HR 0.795, 95%CI 0.242–2.616, P = 0.705). Three months after radiotherapy, the complete response (CR) rates of cervical lymph node regression were 97.7% and 82.2% for the CCRT + E and CCRT groups (P = 0.041). The corresponding CR rates were 100% and 80.0% for lymph node necrosis (P = 0.001) and 100% and 85.2% for extranodal extension (P = 0.041). The CCRT + E group had higher incidence of grade 3/4 leukopenia (32.6% vs. 13.3%, P = 0.031), with similar results for late toxicity. Conclusions CCRT + E significantly prolonged 3-year PFS and DMFS in LANPC, and patients had better lymph node regression.

Abstract Background Cisplatin-based concurrent chemoradiotherapy has been identified as the primary and standard treatment for locally advanced nasopharyngeal carcinoma (NPC). However, the side effects of cisplatin affect the compliance to therapy. Thus, the search for a platinum-based substitute for NPC has always been a research focus. However, there is a variability in the efficacy of different platinum-based chemotherapies in the treatment of NPC. We performed a meta-analysis to compare the efficacy and safety of cisplatin-based regimens and other platinum-based derivatives (carboplatin, nedaplatin, and lobaplatin) for locally advanced NPC. Methods PubMed, EMBASE, Cochrane Library, Web of Science, and ClinicalTrials.gov were systematically searched for all potentially eligible clinical trials as of February 15, 2022. The pooled hazard ratios, risk ratio, and 95% confidence interval were calculated using Review Manager Software version 5.4. Results A total of 1,907 patients with locally advanced NPC were eligible from the 1,265 retrieved records. This systematic review included eight articles, six of which were randomized controlled clinical trials. There was no significant difference in the 3- and 5-year overall survival, progression-free survival, distant metastasis-free survival, and locoregional relapse-free survival between cisplatin-based chemotherapy and other platinum-based chemotherapy. Severe acute hematological side effects (≥ grade 3) during treatment, such as neutropenia, leukopenia, and thrombocytopenia, were equivalent in both groups. However, the incidence of anemia was higher in patients receiving other platinum-based chemotherapies. The risk of nausea, vomiting and weight loss was higher in the cisplatin group; however, there was no significant difference in the other non-hematological and late side effects between the two groups. Conclusions Other types of platinum-based chemotherapies are as effective as cisplatin-based chemotherapy in the treatment of locally advanced NPC, thus acting as potential alternatives to cisplatin. Further studies providing high-level evidence are needed.

Safely opening university campuses has been a major challenge during the COVID-19 pandemic. Here, the authors describe a program of public health measures employed at a university in the United States which, combined with other non-pharmaceutical interventions, allowed the university to stay open in fall 2020 with limited evidence of transmission.

IntroductionB-cell lymphoma-2 (Bcl-2) is the first identified member of the Bcl-2 family that performs an anti-apoptotic function in mammals. However, its role in teleosts is not fully understood. In this study, Bcl-2 of Trachinotus ovatus (TroBcl2) was cloned, and its role in apoptosis was investigated.MethodsIn this study, Bcl-2 of Trachinotus ovatus (TroBcl2) was cloned by PCR. Quantitative real-time PCR (qRT-PCR) was used to detect its mRNA expression level in healthy condition and after LPS stimulation. Subcellular localization was performed by transfecting the pTroBcl2-N3 plasmid into golden pompano snout (GPS) cells and observed under an inverted fluorescence microscope DMi8 and further verified by immunoblotting. In vivo overexpression and RNAi knockdown method were performed to evaluate the role of TroBcl2 in apoptosis. The anti-apoptotic activity of TroBcl2 was detected by flow cytometry. The effect of TroBcl2 on the mitochondrial membrane potential (MMP) was measured by an enhanced mitochondrial membrane potential assay kit with JC-1. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) method was performed to evaluate the role of TroBcl2 in the DNA fragmentation. Immunoblotting was used to verify whether TroBcl2 inhibits the release of cytochrome c from mitochondria into the cytoplasm. The Caspase 3 and Caspase 9 Activity Assay Kits were used to investigate the effect of TroBcl2 on caspase 3 and caspase 9 activities. The effects of TroBcl2 on the expression of apoptosis-related and nuclear factor- κB (NF-κB) signaling pathway-related genes in vitro were evaluated by qRT-PCR and Enzyme linked immunosorbent assay (ELISA). Luciferase reporter assay was used to evaluate the activity in NF-κB signaling pathway.Results and discussionThe full-length coding sequence of TroBcl2 contains 687 bp and encodes a protein containing 228 amino acids. Four conserved Bcl-2 homology (BH) domains and one invariant “NWGR” motif located in BH1 were identified in TroBcl2. In healthy T. ovatus, TroBcl2 was widely distributed in the eleven tested tissues, and higher expression levels were found in immune-related tissues, such as spleen and head kidney tissues. After stimulation with lipopolysaccharide (LPS), the expression of TroBcl2 in the head kidney, spleen, and liver was significantly upregulated. In addition, subcellular localization analysis revealed that TroBcl2 was localized in both the cytoplasm and nucleus. Functional experiments showed that TroBcl2 inhibited apoptosis, possibly by reducing mitochondrial membrane potential loss, decreasing DNA fragmentation, preventing cytochrome c release into cytoplasm, and reducing the caspase 3 and caspase 9 activations. Moreover, upon LPS stimulation, overexpression of TroBcl2 suppressed the activation of several apoptosis-related genes, such as BOK, caspase-9, caspase-7, caspase-3, cytochrome c, and p53. Furthermore, knockdown of TroBcl2 significantly increased the expression of those apoptosis-related genes. In addition, TroBcl2 overexpression or knockdown induced or inhibited, respectively, the transcription of NF-κB and regulated the expression of genes (such as NF-κB1 and c-Rel) in the NF-κB signaling pathway as well as the expression of the downstream inflammatory cytokine IL-1β. Overall, our study suggested that TroBcl2 performs its conserved anti-apoptotic function via the mitochondrial pathway and may serve as an anti-apoptotic regulator in T. ovatus.

Puffer fish is a type of precious high-end aquatic product, is widely popular in Asia, especially in China and Japan, even though it naturally harbors a neurotoxin known as tetrodotoxin (TTX) that is poisonous to humans and causes food poisoning. With the increasing trade demand, which frequently exceeds existing supply capacities, fostering fraudulent practices, such as adulteration of processed products with non-certified farmed wild puffer fish species. To determine the authenticity of puffer fish processed food, we developed a real-time qPCR method to detect five common puffer fish species in aquatic products: Lagocephalus inermis, Lagocephalus lagocephalus, Lagocephalus gloveri, Lagocephalus lunaris, and Lagocephalus spadiceus. The specificity, cross-reactivity, detection limit, efficiency, and robustness of the primers and probes created for five species of puffer fish using TaqMan technology have been determined. No cross-reactivity was detected in the DNA of non-target sample materials, and no false-positive signal was detected; the aquatic products containing 0.1% of a small amount of wild puffer fish materials without certification can be reliably tracked; the statistical p-value for each method’s Ct value was greater than 0.05. The developed qPCR method was sensitive, highly specific, robust, and reproducibility, which could be used to validate the authenticity of wild puffer fish in aquatic products sold for commercial purposes.

Grassland ecosystem dominates in the Mongolian Plateau, mostly located in its arid and semi-arid regions. Although the ecosystem is an important source for agriculture, it is also a fragile system ecologically. This system is one of the most sensitive areas to global climate change. Precipitation (PPT) and soil moisture (SM) are important water sources in the grassland ecosystem, and their changes would greatly affect vegetation growth. This paper generates the precipitation use efficiency (PUE) and soil water use efficiency (SWUE) of Mongolian Plateau grassland based on multi-source remote sensing data to investigate the spatio-temporal distribution pattern and identify the driving factors. Results showed four main findings. Firstly, two water use efficiency (WUE) indicators show a generally increasing trend from 2000 to 2018, with average PUE and SWUE 1.07 gC·m−2·mm−1 and 1.03 gC/kg·H2O, respectively. They have similar spatial distribution patterns, consistent with the available water resources, decreasing from northeast to southwest. However, grassland vegetation growth is more sensitive to soil moisture than precipitation, and the dynamic change of SWUE is smoother and more significant than PUE. Secondly, due to the higher species richness, better vegetation biological characteristics and less severe growth environment, meadow grassland has the highest PUE and SWUE, followed by typical grassland and desert steppe. Thirdly, PUE and SWUE are relatively low in extremely arid and humid regions. In areas with relatively moderate water conditions (PPT in 148–360 mm, SM in 0.14–0.35 cm3/cm3), two indicators increase with the abundance of moisture conditions and reach the maximum. Fourthly, there is a positive linear relationship between PUE (SWUE) with precipitation and a unimodal correlation between PUE (SWUE) with temperature across the entire grassland. However, a varying correlation exists in different grassland ecosystems, especially meadow grassland. Together with analyzing past and future trends, this study provides strong evidence to reflect the impact of global climate change and the management and protection of the grassland ecosystems in arid and semi-arid regions.

Satellite data and algorithms directly affect the accuracy of phenological estimation; therefore, it is necessary to compare and verify existing phenological models to identify the optimal combination of data and algorithms across the Mongolian Plateau (MP). This study used five phenology fitting algorithms—double logistic (DL) and polynomial fitting (Poly) combined with the dynamic threshold method at thresholds of 35% and 50% (DL-G35, DL-G50, Poly-G35, and Poly-G50) and DL combined with the cumulative curvature extreme value method (DL-CUM)—and two data types—the enhanced vegetation index (EVI) and solar-induced chlorophyll fluorescence (SIF)—to identify the start (SOS), peak (POS), and end (EOS) of the growing season in alpine meadow (ALM), desert steppe (DRS), forest vegetation (FV), meadow grassland (MEG), and typical grassland (TYG) of the MP. The optimal methods for identifying the SOS, POS, and EOS of typical grassland areas were Poly-G50 (NSE = 0.12, Pbias = 0.22%), DL-G35/50 (NSE = −0.01, Pbias = −0.06%), and Poly-G35 (NSE = 0.02, Pbias = 0.08%), respectively, based on SIF data. The best methods for identifying the SOS, POS, and EOS of desert steppe areas were Poly-G35 (NSE = −0.27, Pbias = −1.49%), Poly-G35/50 (NSE = −0.58, Pbias = −1.39%), and Poly-G35 (NSE = 0.29, Pbias = −0.61%), respectively, based on EVI data. The data source explained most of the differences in phenological estimates. The accuracy of polynomial fitting was significantly greater than that of the DL method, while all methods were better at identifying SOS and POS than they were at identifying EOS. Our findings can help to facilitate the establishment of a phenological estimation system suitable for the Mongolian Plateau and improve the observation methods of vegetation phenology.

Centralized manufacturing and global supply chains have emerged as an efficient strategy for large-scale production of goods throughout the 20th century. However, while this system of production is highly efficient, it is not resilient. The COVID-19 pandemic has seen numerous supply chains fail to adapt to sudden changes in supply and demand, including those for goods critical to the pandemic response such as personal protective equipment. Here, we consider the production of the non-woven polypropylene filtration media used in face filtering respirators (FFRs). The FFR supply chain's reliance on non-woven media sourced from large, centralized manufacturing facilities led to a supply chain failure. In this study, we present an alternative manufacturing strategy that allows us to move towards a more distributed manufacturing practice that is both scalable and robust. Specifically, we demonstrate that a fiber production technique known as centrifugal melt spinning can be implemented with modified, commercially-available cotton candy machines to produce nano- and microscale non-woven fibers. We evaluate several post processing strategies to transform the produced material into viable filtration media and then characterize these materials by measuring filtration efficiency and breathability, comparing them against equivalent materials used in commercially-available FFRs. Additionally, we demonstrate that waste plastic can be processed with this technique, enabling the development of distributed recycling strategies to address the growing plastic waste crisis. Since this method can be employed at small scales, it allows for the development of an adaptable and rapidly deployable distributed manufacturing network for non-woven materials that is financially accessible to more people than is currently possible.

Effective management of the COVID-19 pandemic requires widespread and frequent testing of the population for SARS-CoV-2 infection. Saliva has emerged as an attractive alternative to nasopharyngeal samples for surveillance testing as it does not require specialized personnel or materials for its collection and can be easily provided by the patient. We have developed a simple, fast, and sensitive saliva-based testing workflow that requires minimal sample treatment and equipment. After sample inactivation, RNA is quickly released and stabilized in an optimized buffer, followed by reverse transcription loop-mediated isothermal amplification (RT-LAMP) and detection of positive samples using a colorimetric and/or fluorescent readout. The workflow was optimized using 1,670 negative samples collected from 172 different individuals over the course of 6 months. Each sample was spiked with 50 copies/μL of inactivated SARS-CoV-2 virus to monitor the efficiency of viral detection. Using pre-defined clinical samples, the test was determined to be 100% specific and 97% sensitive, with a limit of detection of 39 copies/mL. The method was successfully implemented in a CLIA laboratory setting for workplace surveillance and reporting. From April 2021-February 2022, more than 30,000 self-collected samples from 755 individuals were tested and 85 employees tested positive mainly during December and January, consistent with high infection rates in Massachusetts and nationwide.

Abstract Background During infection by intracellular pathogens, a highly complex interplay occurs between the infected cell trying to degrade the invader and the pathogen which actively manipulates the host cell to enable survival and proliferation. Many intracellular pathogens pose important threats to human health and major efforts have been undertaken to better understand the host-pathogen interactions that eventually determine the outcome of the infection. Over the last decades, the unicellular eukaryote Dictyostelium discoideum has become an established infection model, serving as a surrogate macrophage that can be infected with a wide range of intracellular pathogens. In this study, we use high-throughput RNA-sequencing to analyze the transcriptional response of D. discoideum when infected with Mycobacterium marinum and Legionella pneumophila. The results were compared to available data from human macrophages. Results The majority of the transcriptional regulation triggered by the two pathogens was found to be unique for each bacterial challenge. Hallmark transcriptional signatures were identified for each infection, e.g. induction of endosomal sorting complexes required for transport (ESCRT) and autophagy genes in response to M. marinum and inhibition of genes associated with the translation machinery and energy metabolism in response to L. pneumophila. However, a common response to the pathogenic bacteria was also identified, which was not induced by non-pathogenic food bacteria. Finally, comparison with available data sets of regulation in human monocyte derived macrophages shows that the elicited response in D. discoideum is in many aspects similar to what has been observed in human immune cells in response to Mycobacterium tuberculosis and L. pneumophila. Conclusions Our study presents high-throughput characterization of D. discoideum transcriptional response to intracellular pathogens using RNA-seq. We demonstrate that the transcriptional response is in essence distinct to each pathogen and that in many cases, the corresponding regulation is recapitulated in human macrophages after infection by mycobacteria and L. pneumophila. This indicates that host-pathogen interactions are evolutionary conserved, derived from the early interactions between free-living phagocytic cells and bacteria. Taken together, our results strengthen the use of D. discoideum as a general infection model.

MicroRNAs (miRNAs) could regulate various biological processes. Nervous necrosis virus (NNV) is one of the primary germs of the Humpback grouper (Cromileptes altivelis), a commercial fish of great importance for Asian aquaculture. However, there is limited available information on the host-virus interactions of C. altivelis. miRNAs have been shown to play key roles in the host response to infection by a variety of pathogens. To better understand the regulatory mechanism of miRNAs, we constructed miRNA transcriptomes and identified immune-related miRNAs of C. altivelis spleen in response to NNV infection. Reads from the three libraries were mapped onto the Danio rerio reference genome. As a result, a total of 942 mature miRNAs were determined, with 266 known miRNAs and 676 novel miRNAs. Among them, thirty-two differentially expressed miRNAs (DEmiRs) were identified compared to the PBS control. These DEmiRs were targeted on 895 genes, respectively, by using miRanda v3.3a. Then, 14 DEmiRs were validated by qRT-PCR and showed consistency with those obtained from high-throughput sequencing. In order to study the relationship between viral infection and host miRNA, a cell line from C. altivelis brain (CAB) was used to examine the expressions of five known DEmiRs (miR-132-3p, miR-194a, miR-155, miR-203b-5p, and miR-146) during NNV infection. The results showed that one miRNA, cal-miRNA-155, displayed significantly increased expression in response to the virus infection. Subsequently, it was proved that overexpression of cal-miR-155 enhanced cell apoptosis with or without NNV infection and inhibited virus replication in CAB cells. Oppositely, the cal-miRNA-155 inhibitor markedly suppressed apoptosis in CAB cells. The results of the apoptosis-related genes mRNA expression also showed the regulation of cal-miR-155 on the apoptosis process in CAB cells. These findings verify that miR-155 might exert a function as a pro-apoptotic factor in reply to NNV stimulation in CAB cells and help us further study the molecular mechanisms of the pathogenesis of NNV in C. altivelis.

Due to the advantages of high transmission rate, lower power consumption, high security, etc., underwater wireless optical communication (UWOC) has been widely studied and considered as a potential technique for underwater communication. However, its performance is severely degraded by oceanic turbulence due to refractive index fluctuations, which is caused by the change of inhomogeneous ocean environment. Within our derived spatial power spectrum model under anisotropic oceanic turbulence, we conducted a detailed investigation for a spherical wave propagating in weak anisotropic turbulence in this paper. Based on the derived oceanic spectrum, we proposed a scintillation index model for spherical wave in anisotropic oceanic turbulence considering the aperture averaging effect at non-zero inner scale and limited outer scale. Besides, we analyze the aperture averaging scintillation index under the influence of channel parameters such as inner and outer scales. Simulation results reveal that the scintillation index increases with the increase of the outer scale, while the inner scale induces an opposite trend on the scintillation index. Moreover, the inner scale exhibits a larger impact than the outer scale on the UWOC system over weak oceanic turbulence.

The purpose of this study was to explore the drying kinetics, effective moisture diffusivity, activation energy, color variation, and the thermal degradation properties of anthocyanins of blood-flesh peach under hot air drying for the first time. The results showed that the hot air-drying process of blood-flesh peach belongs to reduced-speed drying. The Page model could accurately predict the change of moisture ratio of blood-flesh peach. The effective moisture diffusivity during hot air drying of blood-flesh peach was in the range between 1.62 × 10−10 and 2.84 × 10−10 m2/s, and the activation energy was 25.90 kJ/mol. Fresh samples had the highest content (44.61 ± 4.76 mg/100 g) of total monomeric anthocyanins, and it decreased with the increase of drying temperature. Cyanidin-3-O-glucoside and delphinidin-3-O-galactoside were the main anthocyanins of blood-flesh peach as identified and quantified by UPLC-QqQ-MS. Interestingly, during the drying process, the content of cyanidin-3-O-glucoside increased at the beginning, and then decreased. However, the content of delphinidin-3-O-galactoside kept decreasing during the whole drying process. Considering the drying efficiency, fruit color and quality, 70 °C would be a suitable temperature for drying blood-flesh peach. This research will provide beneficial information for understanding the anthocyanin degradation of blood-flesh peach during drying, and guide the production of high-quality dried products.

River blindness, a disease affecting millions throughout the tropics, is caused by parasitic worms. Here, Yuet al. report the discovery and structural characterization of potent macrocyclic peptide inhibitors of iPGM, a nematode-specific phosphoglycerate mutase, as potential leads for novel antimicrobial agents.

Combined with the research of mass customization and cloud manufacturing mode, this paper discussed the production planning of mass customization enterprises in the context of cloud manufacturing in detail, analyzed the attribute index of manufacturing resource combination, and given a system considering the characteristics of batch production in mass customization and the decentralization of manufacturing resources in cloud manufacturing environment. Then, a multiobjective optimization model has been constructed according to the product delivery date, product cost, and product quality that customers care most about. The Pareto solution set of production plan has been obtained by using NSGA-II algorithm. This paper established a six-tier attribute index system evaluation model for the optimization of production planning scheme set of mass customization enterprises in cloud manufacturing environment. The weight coefficients of attribute indexes were calculated by combining subjective and objective weights with analytic hierarchy process (AHP) and entropy weight method. Finally, the combined weights calculated were applied to the improved TOPSIS method, and the optimal production planning scheme has been obtained by ranking. This paper validated the effectiveness and feasibility of the multiobjective model and NSGA-II algorithm by the example of company A. The Pareto effective solution has been obtained by solving the model. Then the production plan set has been sorted synthetically according to the comprehensive evaluation model, and the optimal production plan has been obtained.

Wolbachia is an unculturable, intracellular bacterium that persists within an extremely broad range of arthropod and parasitic nematode hosts, where it is transmitted maternally to offspring via vertical transmission. In the filarial nematode Brugia malayi, a causative agent of human lymphatic filariasis, Wolbachia is an endosymbiont, and its presence is essential for proper nematode development, survival, and pathogenesis. While the elucidation of Wolbachia:nematode interactions that promote the bacterium's intracellular persistence is of great importance, research has been hampered due to the fact that Wolbachia cannot be cultured in the absence of host cells. The Wolbachia endosymbiont of B. malayi (wBm) has an active Type IV secretion system (T4SS). Here, we have screened 47 putative T4SS effector proteins of wBm for their ability to modulate growth or the cell biology of a typical eukaryotic cell, Saccharomyces cerevisiae. Five candidates strongly inhibited yeast growth upon expression, and 6 additional proteins showed toxicity in the presence of zinc and caffeine. Studies on the uptake of an endocytic vacuole-specific fluorescent marker, FM4-64, identified 4 proteins (wBm0076 wBm00114, wBm0447 and wBm0152) involved in vacuole membrane dynamics. The WAS(p)-family protein, wBm0076, was found to colocalize with yeast cortical actin patches and disrupted actin cytoskeleton dynamics upon expression. Deletion of the Arp2/3-activating protein, Abp1p, provided resistance to wBm0076 expression, suggesting a role for wBm0076 in regulating eukaryotic actin dynamics and cortical actin patch formation. Furthermore, wBm0152 was found to strongly disrupt endosome:vacuole cargo trafficking in yeast. This study provides molecular insight into the potential role of the T4SS in the Wolbachia endosymbiont:nematode relationship.

Accurate detection of filarial parasites in humans is essential for the implementation and evaluation of mass drug administration programs to control onchocerciasis and lymphatic filariasis. Determining the infection levels in vector populations is also important for assessing transmission, deciding when drug treatments may be terminated and for monitoring recrudescence. Immunological methods to detect infection in humans are available, however, cross-reactivity issues have been reported. Nucleic acid-based molecular assays offer high levels of specificity and sensitivity, and can be used to detect infection in both humans and vectors. In this study we developed loop-mediated isothermal amplification (LAMP) tests to detect three different filarial DNAs in human and insect samples using pH sensitive dyes for enhanced visual detection of amplification. Furthermore, reactions were performed in a portable, non-instrumented nucleic acid amplification (NINA) device that provides a stable heat source for LAMP. The efficacy of several strand displacing DNA polymerases were evaluated in combination with neutral red or phenol red dyes. Colorimetric NINA-LAMP assays targeting Brugia Hha I repeat, Onchocerca volvulus GST1a and Wuchereria bancrofti LDR each exhibit species-specificity and are also highly sensitive, detecting DNA equivalent to 1/10-1/5000th of one microfilaria. Reaction times varied depending on whether a single copy gene (70 minutes, O. volvulus) or repetitive DNA (40 min, B. malayi and W. bancrofti) was employed as a biomarker. The NINA heater can be used to detect multiple infections simultaneously. The accuracy, simplicity and versatility of the technology suggests that colorimetric NINA-LAMP assays are ideally suited for monitoring the success of filariasis control programs.

Background and objective For the assessment of elderly patients can tolerate lung cancer operation, there is no clear standard. To evaluate the clinical validity of POSSUM (Physiological and Operative Severity Score for the Umeration of Mortality and Morbidity) in elderly non-small cell lung cancer (NSCLC) surgery patients, we want to provide an important basis for operation treatment decisions. Methods A total of 138 patients, with 88 males and 50 females, with elderly NSCLC surgery between December 2007 and December 2013, are included in PLA general hospital. Using the multivariate Logistic regression analysis, we evaluate the value of each factor on the actual postoperative complications mortality and morbidity. The scorings on standard POSSUM and modified POSSUM in the complication group are compared with the non-complication group using the group t test. Drawing receiver operating characteristic (ROC) curve in standard POSSUM group and modified POSSUM group, calculating the area under the curve (AUC), AUC in standard group is compared with modified group using t test. Judge if the modified POSSUM prediction is consistent with the actual mortality and morbidity. Results Among 138 patients, there were 77 postoperative complications in 59 patients, 2 cases of death. According to the Logistic regression analysis, 17 of 18 factors in standard POSSUM, pulmonary function, different TNM stage are predictors for postoperative complications (P

Polypharmacy is a problem of growing interest in geriatrics with the increase in drug consumption in recent years, is defined according to the WHO criteria as the, ''concurrent use of five or more different prescription medication". We investigated the clinical characteristics of polypharmacy and identified the effects of polypharmacy on clinical outcome among patients aged 80+ admitted to Chinese PLA general hospital.Older men aged ≥80 years (n = 1562) were included in this study. The included participants attended a structured clinical examination and an interview carried out by a geriatrician and trained nurses. A follow-up survey in 2014 was carried out on survivors in the same way as in 2009. The clinical outcome measured were adverse drug reactions, falls, frailty, disability, cognitive impairment, mortality. The association between polypharmacy and clinical outcome was assessed by logistic regression.The mean (range) age of the included participants was 85.2 (80-104) years. Medication exposure was reported by 100% of the population. Mean number of medications reported in this population was 9.56±5.68. The prevalence of polypharmacy (≥6 medications) in the present study was 70%. At the time of the follow-up survey, an increase in the number of taken medicines had occurred among half of the survivors. The risk of different outcomes in relation to number of medications rises significantly, the odds ratios were 1.21 (95% confidence interval [CI]1.17-1.28) for adverse drug reactions, 1.18 (95% CI 1.10-1.26) for falls, 1.16 (95% CI 1.09-1.24) for disability, and 1.19 (95% CI 1.12-1.23) for mortality. There was no association between increasing number of medications and cognitive impairment.Our study demonstrates that polypharmacy is very common in the very old patients, and observed that number of medications was a factor associated with difference clinical outcome independently of the age, type of medications prescribed and accompanied comorbidities.

Myristoylation is a lipid modification involving the addition of a 14-carbon unsaturated fatty acid, myristic acid, to the N-terminal glycine of a subset of proteins, a modification that promotes their binding to cell membranes for varied biological functions. The process is catalyzed by myristoyl-CoA:protein N-myristoyltransferase (NMT), an enzyme which has been validated as a drug target in human cancers, and for infectious diseases caused by fungi, viruses and protozoan parasites. We purified Caenorhabditis elegans and Brugia malayi NMTs as active recombinant proteins and carried out kinetic analyses with their essential fatty acid donor, myristoyl-CoA and peptide substrates. Biochemical and structural analyses both revealed that the nematode enzymes are canonical NMTs, sharing a high degree of conservation with protozoan NMT enzymes. Inhibitory compounds that target NMT in protozoan species inhibited the nematode NMTs with IC50 values of 2.5-10 nM, and were active against B. malayi microfilariae and adult worms at 12.5 µM and 50 µM respectively, and C. elegans (25 µM) in culture. RNA interference and gene deletion in C. elegans further showed that NMT is essential for nematode viability. The effects observed are likely due to disruption of the function of several downstream target proteins. Potential substrates of NMT in B. malayi are predicted using bioinformatic analysis. Our genetic and chemical studies highlight the importance of myristoylation in the synthesis of functional proteins in nematodes and have shown for the first time that NMT is required for viability in parasitic nematodes. These results suggest that targeting NMT could be a valid approach for the development of chemotherapeutic agents against nematode diseases including filariasis.

Parasitic nematodes are responsible for devastating illnesses that plague many of the world's poorest populations indigenous to the tropical areas of developing nations. Among these diseases is lymphatic filariasis, a major cause of permanent and long-term disability. Proteins essential to nematodes that do not have mammalian counterparts represent targets for therapeutic inhibitor discovery. One promising target is trehalose-6-phosphate phosphatase (T6PP) from Brugia malayi. In the model nematode Caenorhabditis elegans, T6PP is essential for survival due to the toxic effect(s) of the accumulation of trehalose 6-phosphate. T6PP has also been shown to be essential in Mycobacterium tuberculosis. We determined the X-ray crystal structure of T6PP from B. malayi. The protein structure revealed a stabilizing N-terminal MIT-like domain and a catalytic C-terminal C2B-type HAD phosphatase fold. Structure-guided mutagenesis, combined with kinetic analyses using a designed competitive inhibitor, trehalose 6-sulfate, identified five residues important for binding and catalysis. This structure-function analysis along with computational mapping provided the basis for the proposed model of the T6PP-trehalose 6-phosphate complex. The model indicates a substrate-binding mode wherein shape complementarity and van der Waals interactions drive recognition. The mode of binding is in sharp contrast to the homolog sucrose-6-phosphate phosphatase where extensive hydrogen-bond interactions are made to the substrate. Together these results suggest that high-affinity inhibitors will be bi-dentate, taking advantage of substrate-like binding to the phosphoryl-binding pocket while simultaneously utilizing non-native binding to the trehalose pocket. The conservation of the key residues that enforce the shape of the substrate pocket in T6PP enzymes suggest that development of broad-range anthelmintic and antibacterial therapeutics employing this platform may be possible.

The human filarial parasite Brugia malayi harbors an endosymbiotic bacterium Wolbachia (wBm) that is required for parasite survival. Consequently, targeting wBm is a promising approach for anti-filarial drug development. The Type IV secretion system (T4SS) plays an important role in bacteria-host interactions and is under stringent regulation by transcription factors. In wBm, most T4SS genes are contained in two operons. We show the wBm is active since the essential assembly factor virB8-1, is transcribed in adult worms and larval stages, and VirB8-1 is present in parasite lysates. We also identify two transcription factors (wBmxR1 and wBmxR2) that bind to the promoter region of several genes of the T4SS. Gel shift assays show binding of wBmxR1 to regions upstream of the virB9-2 and wBmxR2 genes, whereas wBmxR2 binds to virB4-2 and wBmxR1 promoter regions. Interestingly, both transcription factors bind to the promoter of the ribA gene that precedes virB8-1, the first gene in operon 1 of the wBm T4SS. RT-PCR reveals ribA and virB8-1 genes are co-transcribed as one operon, indicating the ribA gene and T4SS operon 1 are co-regulated by both wBmxR1 and wBmxR2. RibA encodes a bi-functional enzyme that catalyzes two essential steps in riboflavin (Vitamin B2) biosynthesis. Importantly, the riboflavin pathway is absent in B. malayi. We demonstrate the pathway is functional in wBm, and observe vitamin B2 supplementation partially rescues filarial parasites treated with doxycycline, indicating Wolbachia may supply the essential vitamin to its worm host. This is the first characterization of a transcription factor(s) from wBm and first report of co-regulation of genes of the T4SS and riboflavin biosynthesis pathway. In addition, our results demonstrate a requirement of vitamin B2 for worm health and fertility, and imply a nutritional role of the symbiont for the filarial parasite host.

The use of antibiotics targeting the obligate bacterial endosymbiont Wolbachia of filarial parasites has been validated as an approach for controlling filarial infection in animals and humans. Availability of genomic sequences for the Wolbachia (wBm) present in the human filarial parasite Brugia malayi has enabled genome-wide searching for new potential drug targets. In the present study, we investigated the cell division machinery of wBm and determined that it possesses the essential cell division gene ftsZ which was expressed in all developmental stages of B. malayi examined. FtsZ is a GTPase thereby making the protein an attractive Wolbachia drug target. We described the molecular characterization and catalytic properties of Wolbachia FtsZ. We also demonstrated that the GTPase activity was inhibited by the natural product, berberine, and small molecule inhibitors identified from a high-throughput screen. Furthermore, berberine was also effective in reducing motility and reproduction in B. malayi parasites in vitro. Our results should facilitate the discovery of selective inhibitors of FtsZ as a novel anti-symbiotic approach for controlling filarial infection. NOTE: The nucleotide sequences reported in this paper are available in GenBank™ Data Bank under the accession number wAlB-FtsZ (JN616286).

There has been a proliferation of online newspapers over recent years. Despite this, or perhaps because of it, factors affecting the quality of online newspapers remain only partially understood. Based on a two-factor model of hygiene and motivator factors, this paper examines quality for online newspapers giving attention to differences across culture, sex, and age. Hygiene factors are essential requirements whose absence causes dissatisfaction, while motivators are desirable elements that add value and increase user satisfaction. The paper presents findings from an empirical study of eighty-four Web users. Results show that hygiene factors for our respondents were: Timeliness, Content attractiveness, Content coverage, Usefulness, and Navigation, while motivators were: Writing style, Layout, Archives, Services, Interactivity, and Multimedia presentation. Four factors were borderline: Journalism ethics, Ease of use, Front page and headlines, and Locating information. However, the research reveals some differences in classification of factors across culture, sex, and age.

Filarial diseases, including lymphatic filariasis and onchocerciasis, are considered among the most devastating of all tropical diseases, affecting over 86 million people worldwide. To control and more rapidly eliminate onchocerciasis requires treatments that target the adult stage of the parasite. Drug discovery efforts are challenged by the lack of preclinical animal models using the human-pathogenic filariae, requiring the use of surrogate parasites for Onchocerca volvulus for both ex vivo and in vivo evaluation. Herein, we describe a platform utilizing phenotypic ex vivo assays consisting of the free-living nematode Caenorhabditis elegans, microfilariae and adult filariae of the bovine filariae Onchocerca lienalis and Onchocerca gutturosa, respectively, as well as microfilariae and adult filariae of the feline filariae Brugia pahangi, the rodent filariae Litomosoides sigmodontis and the human-pathogenic filariae Brugia malayi to assess activity across various surrogate parasites. Utilization of those surrogate nematodes for phenotypic ex vivo assays in order to assess activity across various parasites led to the successful establishment of a screening cascade and identification of multiple compounds with potential macrofilaricidal activity and desirable physicochemical, MW = 200-400 and low lipophilicity, logP <4, and pharmacokinetic properties, rat and human liver S9 stability of ≥70% remaining at 60 min, and AUC exposures above 3 μM h. This platform demonstrated the successful establishment of a screening cascade which resulted in the discovery of potential novel macrofilaricidal compounds for futher drug discovery lead optimization efforts. This screening cascade identified two distinct chemical series wherein one compound produced a significant 68% reduction of adult Litomosoides sigmodontis in the mouse model. Successful demonstration of efficacy prompted lead optimization medicinal chemistry efforts for this novel series., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)