Quantitative parameters of dual-layer spectral detector computed tomography for evaluating Ki-67 and human epidermal growth factor receptor 2 expression in colorectal adenocarcinoma.

Background: Ki-67 and human epidermal growth factor receptor 2 (HER2) are key biomarkers in evaluating the prognosis of colorectal adenocarcinoma (CRAC). The purpose of this study was to investigate the value of quantitative parameters in dual-layer spectral detector computed tomography (SDCT) for evaluating the expression of Ki-67 and HER2 in CRAC. Methods: In this retrospective, cross-sectional study, 88 eligible patients with pathologically confirmed CRAC were selected from Taicang Hospital of Traditional Chinese Medicine between May 2021 and April 2023. The study participants underwent enhanced SDCT of the whole abdomen within 2 weeks before to surgery, did not receive antitumor therapy, and had complete immunohistochemical (IHC) indexes. Patients with nonadenocarcinoma pathologic types, poor quality of spectral CT images, or no complete immunohistochemistry results were excluded. Spectral parameters including CT values at 40 and 100 keV, effective atomic number, iodine concentration (IC), the slope of the spectral Hounsfield unit (HU) curve (λHU), and normalized iodine concentration (NIC) in the arterial phase (AP) and venous phase (VP) were analyzed for their value in distinguishing between the high and low expression of Ki-67 and HER2-positive and -negative status in CRAC. The statistical significance of the SDCT parameters between the different groups of Ki-67 expression and those of HER2 status was assessed with the Mann-Whitney test. Spearman correlation analysis was used to analyze the correlation between the SDCT parameters and the extent of Ki-67 expression and HER2 expression status. The receiver operating characteristic (ROC) curve was used, and the area under the curve (AUC) was calculated. Results: The SDCT parameters of CT values at 40 keV, effective atomic number, IC, and the λHU in the VP showed significant differences between the Ki-67 high- and low-expression groups in CRAC (P=0.035, P=0.041, P=0.036, and P=0.044, respectively), with AUCs of 0.639 [95% confidence interval (CI): 0.512-0.766], 0.634 (95% CI: 0.508-0.761), 0.638 (95% CI: 0.510-0.766), and 0.633 (95% CI: 0.504-0.762), respectively. The expression of CRAC Ki-67 was positively correlated with CT values at 40 keV (r=0.227; P=0.034), effective atomic number (r=0.219; P=0.040), IC (r=0.225; P=0.035), and the λHU in VP (r=0.216; P=0.043). SDCT parameter values showed no statistical difference between negative and positive expression in HER2 (all P values >0.05). There was no significant correlation between SDCT parameters and the expression of HER2 in CRAC (all P values >0.05). Conclusions: The quantitative parameters of SDCT in the VP provide valuable information for distinguishing between the low expression and high expression of Ki-67 in CRAC.

Effect of small molecular crowders on dynamics of kinesin molecular motors.

Kinesin is a motor protein that can convert chemical energy of ATP hydrolysis into mechanical energy of moving processively on microtubules. Apart from the load and ATP concentration affecting the dynamics of the motor such as velocity, run length, dissociation rate, etc., the increase of solution viscosity by supplementing crowding agents of low molecular weight into the buffer can also affect the dynamics. Here, based on our proposed model for the chemomechanical coupling of the kinesin motor, a systematically theoretical study of the motor dynamics under the variation of the viscosity and load is presented. Both the load on the motor's stalk and that on one of the two heads are considered. The theoretical results provide a consistent explanation of the available contradictory experimental results, with some showing that increasing viscosity decreases sensitively the velocity whereas others showing that increasing viscosity has little effect on the velocity. The theoretical results reproduce quantitatively the puzzling experimental data showing that under different directions of the load on the stalk, increasing viscosity has very different effects on the change of run length or dissociation rate. The theoretical results predict that in both the pure and crowded buffers the dependence of the run length on the load acting one of the two heads has very different feature from that on the load acting on the stalk.

Oral direct thrombin inhibitors or oral factor Xa inhibitors versus conventional anticoagulants for the treatment of deep vein thrombosis.

BACKGROUND: Deep vein thrombosis (DVT) is a condition in which a clot forms in the deep veins, most commonly of the leg. It occurs in approximately one in 1000 people. If left untreated, the clot can travel up to the lungs and cause a potentially life-threatening pulmonary embolism (PE). Previously, a DVT was treated with the anticoagulants heparin and vitamin K antagonists. However, two forms of direct oral anticoagulants (DOACs) have been developed: oral direct thrombin inhibitors (DTIs) and oral factor Xa inhibitors, which have characteristics that may be favourable compared to conventional treatment, including oral administration, a predictable effect, lack of frequent monitoring or dose adjustment and few known drug interactions. DOACs are now commonly being used for treating DVT: recent guidelines recommended DOACs over conventional anticoagulants for both DVT and PE treatment. This Cochrane Review was first published in 2015. It was the first systematic review to measure the effectiveness and safety of these drugs in the treatment of DVT. This is an update of the 2015 review.  OBJECTIVES: To assess the effectiveness and safety of oral DTIs and oral factor Xa inhibitors versus conventional anticoagulants for the long-term treatment of DVT. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL databases and the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 1 March 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) in which people with a DVT, confirmed by standard imaging techniques, were allocated to receive an oral DTI or an oral factor Xa inhibitor compared with conventional anticoagulation or compared with each other for the treatment of DVT.  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were recurrent venous thromboembolism (VTE), recurrent DVT and PE. Secondary outcomes included all-cause mortality, major bleeding, post-thrombotic syndrome (PTS) and quality of life (QoL). We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We identified 10 new studies with 2950 participants for this update. In total, we included 21 RCTs involving 30,895 participants. Three studies investigated oral DTIs (two dabigatran and one ximelagatran), 17 investigated oral factor Xa inhibitors (eight rivaroxaban, five apixaban and four edoxaban) and one three-arm trial investigated both a DTI (dabigatran) and factor Xa inhibitor (rivaroxaban). Overall, the studies were of good methodological quality. Meta-analysis comparing DTIs to conventional anticoagulation showed no clear difference in the rate of recurrent VTE (odds ratio (OR) 1.17, 95% confidence interval (CI) 0.83 to 1.65; 3 studies, 5994 participants; moderate-certainty evidence), recurrent DVT (OR 1.11, 95% CI 0.74 to 1.66; 3 studies, 5994 participants; moderate-certainty evidence), fatal PE (OR 1.32, 95% CI 0.29 to 6.02; 3 studies, 5994 participants; moderate-certainty evidence), non-fatal PE (OR 1.29, 95% CI 0.64 to 2.59; 3 studies, 5994 participants; moderate-certainty evidence) or all-cause mortality (OR 0.66, 95% CI 0.41 to 1.08; 1 study, 2489 participants; moderate-certainty evidence). DTIs reduced the rate of major bleeding (OR 0.58, 95% CI 0.38 to 0.89; 3 studies, 5994 participants; high-certainty evidence).   For oral factor Xa inhibitors compared with conventional anticoagulation, meta-analysis demonstrated no clear difference in recurrent VTE (OR 0.85, 95% CI 0.71 to 1.01; 13 studies, 17,505 participants; moderate-certainty evidence), recurrent DVT (OR 0.70, 95% CI 0.49 to 1.01; 9 studies, 16,439 participants; moderate-certainty evidence), fatal PE (OR 1.18, 95% CI 0.69 to 2.02; 6 studies, 15,082 participants; moderate-certainty evidence), non-fatal PE (OR 0.93, 95% CI 0.68 to 1.27; 7 studies, 15,166 participants; moderate-certainty evidence) or all-cause mortality (OR 0.87, 95% CI 0.67 to 1.14; 9 studies, 10,770 participants; moderate-certainty evidence). Meta-analysis showed a reduced rate of major bleeding with oral factor Xa inhibitors compared with conventional anticoagulation (OR 0.63, 95% CI 0.45 to 0.89; 17 studies, 18,066 participants; high-certainty evidence).  AUTHORS' CONCLUSIONS: The current review suggests that DOACs may be superior to conventional therapy in terms of safety (major bleeding), and are probably equivalent in terms of efficacy. There is probably little or no difference between DOACs and conventional anticoagulation in the prevention of recurrent VTE, recurrent DVT, pulmonary embolism and all-cause mortality. DOACs reduced the rate of major bleeding compared to conventional anticoagulation. The certainty of evidence was moderate or high.

A Three-Year Prospective Study Assessing the Application of Chromosomal Microarray Analysis in 576 High-Risk Pregnant Women.

Background: The use of chromosomal microarray analysis (CMA) in prenatal diagnosis of chromosomal and genetic diseases has resulted in a significant improvement in the diagnosis of genetically caused congenital malformations, neurodevelopmental disorders, and congenital anomalies, with a high diagnostic yield in selected prenatal cases. Objective: The objective of this study was to evaluate the application of CMA in the prenatal diagnosis of high-risk pregnant women. Method: A total of 576 pregnancies were selected from May 2018 to October 2020 in our hospital, including amniotic fluid chromosome, karyotype analysis, and CMA detection. The study group was divided into two groups based on the indications for testing: group A has 88 patients at the age of 35 years or older, and group B patients were in high-risk pregnancies, which consisted of 33 cases of bad pregnancy history, 252 high-risk serological screenings, 70 high-risk non-invasive prenatal testing (NIPT), 65 cases of B-ultrasound indicated fetal development abnormalities or ultrasonic soft marker abnormalities, and 68 other cases of pregnant women or both who have genetic or chromosomal abnormalities. At last, we have an analysis of the detection rate from different testing methods. Results: Based on the follow-up test, 576 high-risk pregnant women showed an amniotic fluid chromosome karyotype rate of 18.1% (104/576), and the remaining 472 of these cases suffered a CNV ratio of 14.2% (67/472). 472 women of low clinical relevance are at 4.87% (23/472), 16 people showed a clear cause ratio = 3.39% (16/472), and 28 of the 472 (5.93%) cases showed polymorphism. Conclusions: In our study, CMA significantly improved the fetal detection rate and diagnosis rate in high-risk pregnant women, which proved to be a very useful method in the diagnosis of genetically caused neurodevelopmental disorders and congenital anomalies. The use of CMA in high-risk pregnant women is justified, and these women can detect an additional (3.40%, 16/472) of pathogenic microdeletions and microduplications in the cases.

Linking the network topology of plant traits with community structure, functioning, and adaptive strategies of submerged macrophytes.

Plant trait network analysis can calculate the topology of trait correlations and clarify the complex relationships among traits, providing new insights into ecological topics, including trait dimensions and phenotypic integration. However, few studies have focused on the relationships between network topology and community structure, functioning, and adaptive strategies, especially in natural submerged macrophyte communities. In this study, we collected 15 macrophyte community-level traits from 12 shallow lakes in the Yangtze River Basin in the process of eutrophication and analyzed the changes in trait network structure (i.e., total phosphorus, TP) by using a moving window method. Our results showed that water TP significantly changed the topology of trait networks. Specifically, under low or high nutrient levels, the network structure was more dispersed, with lower connectance and higher modularity than that found at moderate nutrient levels. We also found that network connectance was positively correlated with community biomass and homeostasis, while network modularity was negatively correlated with community biomass and homeostasis. In addition, modules and hub traits also changed with the intensity of eutrophication, which can reflect the trait integration and adaptation strategies of plants in a stressful environment. At low or high nutrient levels, more modules were differentiated, and those modules with higher strength were related to community nutrition. Our results clarified the dynamics of community structure and functioning from a new perspective of plant trait networks, which is key to predicting the response of ecosystems to environmental changes.

Phosphorus accelerate the sulfur cycle by promoting the release of malodorous volatile organic sulfur compounds from Microcystis in freshwater lakes.

Volatile organic sulfur compounds (VSCs) released by algae are of great significance in sulfur cycle, climate regulation and biological information transmission, and they also caused taste and odor in freshwaters. However, the categories, sources, and environmental regulatory factors of VSCs in freshwaters were less known. Here, we show that eight common freshwater cyanobacterium Microcystis, which bloom in freshwaters over the world, are found to be important producers of VSCs. Dimethyl sulfide (DMS), dimethyl disulfide (DMDS) and isopropyl methyl sulfide (IPMS) are the main VSCs with the highest concentrations 184.81 nmol/L, 162.01 nmol/L and 101.55 nmol/L, respectively. The amount of VSCs released from those Microcystis varied greatly, M. elabens, M. panniformis and M. flos-aquae released the largest amount of VSCs (1260.52 nmol S/L, 1154.75 nmol S/L and 670.58 nmol S/L), and M. wesenbergii had the smallest release amount. We also found for the first time that phosphorus (P) was one of the important factors for the regulation VSCs from most Microcystis. P can elevate the release of DMS by promoting the biomass and DMS yields of most Microcystis in the range 0.05 mg/L to 0.5 mg/L. Similar results were also found in 16 lakes at three different spatiotemporal scales. Overall, we revealed that the common freshwater Microcystis were able to release diverse thioethers, and the major VSCs were significantly influenced by water P concentrations. In the context of global freshwater eutrophication and Microcystis bloom, freshwater cyanobacteria driven sulfur cycle and water odor will probably be further strengthened.

Epigenetic priming enhances antitumor immunity in platinum-resistant ovarian cancer.

BackgroundImmune checkpoint inhibitors (ICIs) have modest activity in ovarian cancer (OC). To augment their activity, we used priming with the hypomethylating agent guadecitabine in a phase II study.MethodsEligible patients had platinum-resistant OC, normal organ function, measurable disease, and received up to 5 prior regimens. The treatment included guadecitabine (30 mg/m2) on days 1-4, and pembrolizumab (200 mg i.v.) on day 5, every 21 days. The primary endpoint was the response rate. Tumor biopsies, plasma, and PBMCs were obtained at baseline and after treatment.ResultsAmong 35 evaluable patients, 3 patients had partial responses (8.6%), and 8 (22.9%) patients had stable disease, resulting in a clinical benefit rate of 31.4% (95% CI: 16.9%-49.3%). The median duration of clinical benefit was 6.8 months. Long-interspersed element 1 (LINE1) was hypomethylated in post-treatment PBMCs, and methylomic and transcriptomic analyses showed activation of antitumor immunity in post-treatment biopsies. High-dimensional immune profiling of PBMCs showed a higher frequency of naive and/or central memory CD4+ T cells and of classical monocytes in patients with a durable clinical benefit or response (CBR). A higher baseline density of CD8+ T cells and CD20+ B cells and the presence of tertiary lymphoid structures in tumors were associated with a durable CBR.ConclusionEpigenetic priming using a hypomethylating agent with an ICI was feasible and resulted in a durable clinical benefit associated with immune responses in selected patients with recurrent OC.Trial registrationClinicalTrials.gov NCT02901899.FundingUS Army Medical Research and Material Command/Congressionally Directed Medical Research Programs (USAMRMC/CDMRP) grant W81XWH-17-0141; the Diana Princess of Wales Endowed Professorship and LCCTRAC funds from the Robert H. Lurie Comprehensive Cancer Center; Walter S. and Lucienne Driskill Immunotherapy Research funds; Astex Pharmaceuticals; Merck & Co.; National Cancer Institute (NCI), NIH grants CCSG P30 CA060553, CCSG P30 CA060553, and CA060553.

Perfluorohexanoic acid caused disruption of the hypothalamus-pituitary-thyroid axis in zebrafish larvae.

Perfluorohexanoic acid (PFHxA) has been recognized as an alternative to the wide usage of perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS) in the fluoropolymer industry for years. PFHxA has been frequently detected in the environment due to its wide application. However, the ecological safety of PFHxA, especially its toxicological effects on aquatic organisms, remains obscure. In the present study, PFHxA at different concentrations (0, 0.48, 2.4, and 12 mg/L) was added to the culture medium for zebrafish embryo/larval exposure at 96 h postfertilization (hpf). Zebrafish larvae showed a slow body growth trend and changes in thyroid hormone levels (THs) upon PFHxA exposure, indicating the interference effect of PFHxA on fish larval development. Moreover, the transcription levels of genes related to the hypothalamic-pituitary-thyroid (HPT) axis were also analyzed. The gene expression level of thyroid hormone receptor ß (trß) was upregulated in a dose-dependent manner. Exposure to 0.48 mg/L PFHxA increased the expression levels of the thyrotrophic-releasing hormone (trh) and thyroid hormone receptor α (trα). Significant increases in corticotrophin-releasing hormone (crh) and transthyretin (ttr) gene expression were also observed when the zebrafish larvae were treated with 12 mg/L PFHxA, except iodothyronine deiodinases (dio1), which decreased obviously at that point. There were significant declines in the transcription of both thyroid-stimulating hormone ß (tshß) and uridinediphosphate-glucuronosyltransferase (ugt1ab) upon exposure to 2.4 mg/L PFHxA. In addition, PFHxA induced a dose-related inhibitory effect on the transcription of sodium/iodide symporter (nis). Finally, the thyroid status will be destroyed after exposure to PFHxA, thus leading to growth impairment in zebrafish larvae.

Cascading effects of benthic fish impede reinstatement of clear water conditions in lakes: A mesocosm study.

In shallow eutrophic lakes, submersed macrophytes are essential for maintaining a clear water state, and they are affected markedly by fishes directly through herbivory and indirectly by fish-invertebrate-periphyton complexity, a pathway that presently is not well understood in subtropical lakes but probably vital to lake managements. We conducted a mesocosm study involving benthic fish (Misgurnus anguillicaudatus), snails (Radix swinhoei) and submersed macrophyte (Vallisneria natans), aiming to examine whether benthic fish is detrimental to reestablishment of clear-water macrophyte-dominated state in eutrophic degraded lakes. In addition, we aimed to investigate the cascading effect that benthic fish might have on periphyton and phytoplankton and to what extent snails can alleviate this effect. Our results showed that benthic fish promoted nutrient release from the sediment and thereby facilitated the growth of phytoplankton and periphyton, leading to reduced growth of submerged macrophytes due to shading. Snails consumed the periphyton attached on the leaves of macrophytes, thereby being beneficial to the plant growth, albeit it could not fully counteract the adverse effects from benthic fish. The water quality indicators in terms of nutrients concentrations, phytoplankton biomass and light extinction coefficient along the water column was affected primarily by benthic fish, followed by macrophytes and snails. To target a clear-water condition, the water quality was best at the presence of macrophytes alone or in combination with snails, and worst at the presence of benthic fish. Our results implied that the removal of benthic fish should be a useful ecological restoration method for rehabilitation of submersed macrophytes and water quality improvement in subtropic, eutrophic, shallow lakes following external nutrient loading reduction.

Phosphorus enrichment affects trait network topologies and the growth of submerged macrophytes.

Significant differences in the morphological and physiological characteristics of submerged macrophytes have been studied following nutrient addition, but little research has investigated the changes in plant trait network topology structures and trait interactions at the whole-plant perspective along nutrient gradients. Plant trait interactions and coordination strongly determine ecosystem structure and functioning. Thirty plant traits were collected from a three-month experiment to construct plant trait networks to clarify the variations in trait connections and network organization arising from five total phosphorus (TP) addition concentrations in water, including a control (CK), 0.1 (TP1), 0.2 (TP2), 0.4 (TP3), and 0.8 (TP4) mg L-1. Nonmetric multidimensional scaling analysis showed a clear difference in the distribution of plant trait space among the different TP treatments. Distinct network structures showed that water TP-deficiency and TP-repletion changed the plant trait network into loose assemblages of more modules, which was related to low plant carbohydrate levels. Most plant functions involving biomass accumulation and carbohydrate synthesis were reduced under high TP conditions compared to moderate TP enrichment. Moreover, the percentage of significant relationships between plant functions and corresponding network modules was lower in the CK and TP4 treatments. These results suggested that low plant carbohydrates in high TP environments induced by high water chlorophyll a and tissue phosphorus could not support rapid resource transport among organs and thus inefficiently performed plant functions. Plant carbohydrates were a vital variable that impacted the network edge density, trait interactions, and plant growth. In summary, we demonstrated that high water TP enrichment reduces plant trait network connectedness and plant functional potentials, which may be correlated with reducing tissue carbohydrates. This study explores the correlations between plant trait network topology and functions to improve our understanding of physiological and ecological rules regulating trait interactions among organs and plant growth under eutrophic conditions.

Expression of Tspan8 in Patients with Intrahepatic Cholangiocarcinoma and Its Relationship with Clinicopathological Features and Prognosis.

The incidence and mortality of intrahepatic cholangiocarcinoma (ICC) are increasing worldwide. High invasion and metastasis are one of the main causes of death in patients. The selection of reasonable and effective molecular markers to evaluate the prognosis of patients with ICC has important clinical guiding significance. In this study, the expression of Tspan protein in ICC and normal tissues was compared, the correlation between Tspan expression and pathological features of patients was analyzed by the logistic regression model using multivariate analysis, and the relationship between Tspan8 expression and prognosis of ICC patients was analyzed by the Kaplan-Meier survival curve. The results showed that Tspan8 is highly positive in ICC tissues, TNM stage, degree of tumor differentiation, lymph node metastasis, and Tspan8 protein expression were independently correlated, and the overexpression of Tspan was associated with the prognosis of ICC invasion and metastasis. This provides a new idea for clinical treatment.

Stoichiometric and physiological mechanisms that link hub traits of submerged macrophytes with ecosystem structure and functioning.

Eutrophication strongly influences plant stoichiometric characteristics and physiological status by altering nutrient and light availability in the water column. However, the mechanisms linking plant functional traits with ecosystem structure and functioning to clarify the decline of submerged macrophytes have not been fully elucidated to date. Therefore, based on a field investigation of 26 macrophytic shallow lakes on the Yangtze Plain, we first constructed a plant trait network at the whole-plant level to determine the hub traits of submerged macrophytes that play central regulatory roles in plant phenotype. Our results suggested that organ (leaf, stem, and root) phosphorus (P), starch, and total nonstructural carbohydrate (TNC) contents were hub traits. Organ starch and TNC were consistent with those in the experiment-based network obtained from a three-month manipulation experiment. Next, the mechanisms underlying the relationships between the hub traits and vital aspects of ecological performance were carefully investigated using field investigation data. Specifically, stoichiometric homeostasis of P (HP), starch, and TNC were positively associated with dominance and biomass at the species level, and community biomass at the community level. Additionally, structural equation modeling clarified not only a hypothesized pathway from eutrophication to water clarity and community TNC, but also combined effects of community TNC and HP on community biomass. That is, ecosystems dominated by more homeostatic communities tended to have more carbon (C)-rich compounds in relatively oligotrophic conditions, which promoted the primary production of macrophytes. Eutrophication was determined to affect community structure by inhibiting the predominance of more homeostatic species and the production of carbohydrates. Finally, reduced community biomass and increased nutrient contents and nutrient:C ratios in plants induced by eutrophication implied a decrease in the C sink in biomass and may potentially lead to an enhancement of litter decomposition rates and nutrient cycling rates. By adjusting plant responses to eutrophication, stoichiometric and physiological mechanisms linking plant traits with ecosystem structure have important implications for understanding ecosystem processes, and these results may contribute to practical management to achieve the restoration of submerged macrophytes and ecosystem services.

Traditional Chinese Medicine Decoctions Significantly Reduce the Mortality in Severe and Critically Ill Patients with COVID-19: A Retrospective Cohort Study.

Coronavirus disease (COVID-19) is a new infectious disease associated with high mortality, and traditional Chinese medicine decoctions (TCMDs) have been widely used for the treatment of patients with COVID-19 in China; however, the impact of these decoctions on severe and critical COVID-19-related mortality has not been evaluated. Therefore, we aimed to address this gap. In this retrospective cohort study, we included inpatients diagnosed with severe/critical COVID-19 at the Tongren Hospital of Wuhan University and grouped them depending on the recipience of TCMDs (TCMD and non-TCMD groups). We conducted a propensity score-matched analysis to adjust the imbalanced variables and treatments and used logistic regression methods to explore the risk factors associated with in-hospital death. Among 282 patients with COVID-19 who were discharged or died, 186 patients (66.0%) received TCMD treatment (TCMD cohort) and 96 (34.0%) did not (non-TCMD cohort). After propensity score matching at a 1:1 ratio, 94 TCMD users were matched to 94 non-users, and there were no significant differences in baseline clinical variables between the two groups of patients. The all-cause mortality was significantly lower in the TCMD group than in the non-TCMD group, and this trend remained valid even after matching (21.3% [20/94] vs. 39.4% [37/94]). Multivariable logistic regression model showed that disease severity (odds ratio: 0.010; 95% CI: 0.003, 0.037; [Formula: see text]¡ 0.001) was associated with increased odds of death and that TCMD treatment significantly decreased the odds of in-hospital death (odds ratio: 0.115; 95% CI: 0.035, 0.383; [Formula: see text]¡ 0.001), which was related to the duration of TCMD treatment. Our findings show that TCMD treatment may reduce the mortality in patients with severe/critical COVID-19.

Effects of acute exposure to microcystins on hypothalamic-pituitary-adrenal (HPA), -gonad (HPG) and -thyroid (HPT) axes of female rats.

Microcystins (MCs) are common, well-known cyanobacterial toxins that can affect health of humans. Recently, it has been reported that MCs affect endocrine functions. In the present study, for the first time, histopathology, concentrations of hormones and transcription of genes along the hypothalamic-pituitary-adrenal (HPA), hypothalamic-pituitary-gonad (HPG) and hypothalamic-pituitary-thyroid (HPT) axes were examined in rats exposed to microcystin-LR (MC-LR). Female, Sprague-Dawley (SD) rats were exposed acutely to MC-LR by a single intraperitoneal (i.p.) injection at doses of 0.5, 0.75, or 1 median lethal dose (LD50), i.e. 36.5, 54.75, or 73 µg MC-LR/kg body mass (bm) then euthanized 24 hours after exposure. Acute exposure to MC-LR significantly increased relative mass of adrenal in a dose-dependent manner, but relative mass of hypothalamus, pituitary, ovary and thyroid were not significantly different from respective mass in controls. However, damage to all these tissues was observed by histology. Along the HPA axis, lesser concentrations of corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) were observed in blood serum of exposed individuals, relative to controls. For the HPG axis, concentrations of gonadotropin-releasing hormone (GnRH) and estradiol (E2) were significantly less in rats treated with MC-LR, but greater concentrations of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and testosterone (T) were observed. Along the HPT axis, MC-LR caused greater concentrations of thyroid-stimulating hormone (TSH), but lesser concentrations of thyrotropin-releasing hormone (TRH), free tetra-iodothyronine (fT4) and tri-iodothyronine (fT3). Significant positive/negative correlations of concentrations of hormones were observed among the HPA, HPG and HPT axes. In addition, profiles of transcription of genes for synthesis of hormones along the endocrine axes and nuclear hormone receptors in adrenal, ovary and thyroid were significantly altered. Therefore, these results suggested that MC-LR affected HPA, HPG and HPT axes and exerted endocrine-disrupting effects. Effects of MC-LR on crosstalk among these three axes need further studies.

In-situ responses of phytoplankton to graphene photocatalysis in the eutrophic lake Xingyun, southwestern China.

Graphene photocatalysis is receiving increased attention for its potential to be used as a novel green technology for mitigating harmful algae in highly eutrophic waters. However, graphene is seldom applied to in situ aquatic ecosystems for environmental applications. Here, the impacts of graphene photocatalysis on phytoplankton and environmental conditions were evaluated through an in situ macrocosm experiment in the eutrophic Lake Xingyun, southwestern China. The graphene photocatalysis treated area had significantly reduced conductivity, total nitrogen (TN), total phosphorus (TP) and dissolved phosphorus concentrations, as well as increased dissolved oxygen (DO) concentrations. The abundances of all species of the genus Microcystis were significantly reduced in the graphene photocatalysis-treated area; in contrast, the abundances of all species of the diazotrophic genera, including Anabaena and Aphanizomenon, greatly increased after treatment with graphene photocatalysis. Eukaryotic algae, especially Chlorophyta, Euglenophyta and Pyrrophyta, as well as Cryptophyta, had significantly higher abundances in the graphene photocatalysis-treated area, whereas most of the eutrophic diatom species had lower abundances in the treated area. These observed differences in eukaryotic algae between the two groups might be related to their sensitivity to graphene photocatalysis and their tolerance of nutrients. Generally, graphene photocatalysis can make a great contribution to the improvement of eutrophic water, as evidenced by the reduction in cyanobacteria abundance and phosphorus concentration, as well as the increase in species richness and the dissolved oxygen concentration in the treated area. However, the mechanisms underlying these differences in phytoplankton community structure and environmental conditions require further study.

Inhibition of Drp1 SUMOylation by ALR protects the liver from ischemia-reperfusion injury.

Hepatic ischemic reperfusion injury (IRI) is a common complication of liver surgery. Although an imbalance between mitochondrial fission and fusion has been identified as the cause of IRI, the detailed mechanism remains unclear. Augmenter of liver regeneration (ALR) was reported to prevent mitochondrial fission by inhibiting dynamin-related protein 1 (Drp1) phosphorylation, contributing partially to its liver protection. Apart from phosphorylation, Drp1 activity is also regulated by small ubiquitin-like modification (SUMOylation), which accelerates mitochondrial fission. This study aimed to investigate whether ALR-mediated protection from hepatic IRI might be associated with an effect on Drp1 SUMOylation. Liver tissues were harvested from both humans and from heterozygous ALR knockout mice, which underwent IRI. The SUMOylation and phosphorylation of Drp1 and their modulation by ALR were investigated. Hepatic Drp1 SUMOylation was significantly increased in human transplanted livers and IRI-livers of mice. ALR-transfection significantly decreased Drp1 SUMOylation, attenuated the IRI-induced mitochondrial fission and preserved mitochondrial stability and function. This study showed that the binding of transcription factor Yin Yang-1 (YY1) to its downstream target gene UBA2, a subunit of SUMO-E1 enzyme heterodimer, was critical to control Drp1 SUMOylation. By interacting with YY1, ALR inhibits its nuclear import and dramatically decreases the transcriptional level of UBA2. Consequently, mitochondrial fission was significantly reduced, and mitochondrial function was maintained. This study showed that the regulation of Drp1 SUMOylation by ALR protects mitochondria from fission, rescuing hepatocytes from IRI-induced apoptosis. These new findings provide a potential target for clinical intervention to reduce the effects of IRI during hepatic surgery.

Challenges of using blooms of Microcystis spp. in animal feeds: A comprehensive review of nutritional, toxicological and microbial health evaluation.

Microcystis spp., are Gram-negative, oxygenic, photosynthetic prokaryotes which use solar energy to convert carbon dioxide (CO2) and minerals into organic compounds and biomass. Eutrophication, rising CO2 concentrations and global warming are increasing Microcystis blooms globally. Due to its high availability and protein content, Microcystis biomass has been suggested as a protein source for animal feeds. This would reduce dependency on soybean and other agricultural crops and could make use of "waste" biomass when Microcystis scums and blooms are harvested. Besides proteins, Microcystis contain further nutrients including lipids, carbohydrates, vitamins and minerals. However, Microcystis produce cyanobacterial toxins, including microcystins (MCs) and other bioactive metabolites, which present health hazards. In this review, challenges of using Microcystis blooms in feeds are identified. First, nutritional and toxicological (nutri-toxicogical) data, including toxicity of Microcystis to mollusks, crustaceans, fish, amphibians, mammals and birds, is reviewed. Inclusion of Microcystis in diets caused greater mortality, lesser growth, cachexia, histopathological changes and oxidative stress in liver, kidney, gill, intestine and spleen of several fish species. Estimated daily intake (EDI) of MCs in muscle of fish fed Microcystis might exceed the provisional tolerable daily intake (TDI) for humans, 0.04 µg/kg body mass (bm)/day, as established by the World Health Organization (WHO), and is thus not safe. Muscle of fish fed M. aeruginosa is of low nutritional value and exhibits poor palatability/taste. Microcystis also causes hepatotoxicity, reproductive toxicity, cardiotoxicity, neurotoxicity and immunotoxicity to mollusks, crustaceans, amphibians, mammals and birds. Microbial pathogens can also occur in blooms of Microcystis. Thus, cyanotoxins/xenobiotics/pathogens in Microcystis biomass should be removed/degraded/inactivated sufficiently to assure safety for use of the biomass as a primary/main/supplemental ingredient in animal feed. As an ameliorative measure, antidotes/detoxicants can be used to avoid/reduce the toxic effects. Before using Microcystis in feed ingredients/supplements, further screening for health protection and cost control is required.

A systematic review and meta-analysis of the efficacy and safety of arbidol in the treatment of coronavirus disease 2019.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is highly contagious, and the epidemic has spread to hundreds of countries around the world, and seriously threatens the life safety of people around the world. Arbidol is an antiviral drug with high potential against COVID-19, but evidence of effectiveness and safety is lacking. The systematic review protocol aims to formulate a research plan that can evaluate the efficacy and safety of arbidol for COVID-19. METHODS: The retrieval time will be from the database establishment to June 2020. The retrieval database will include the Cochrane Library, PubMed, Embase, OVID, CNKI, Wanfang, VIP, CBM, etc. The primary outcome will be clinical efficacy, and the secondary results will be accompanying symptoms, time for the temperature to return to normal, time of novel coronavirus nucleic acid turning negative, blood sample test, Computed Tomography examination, length of hospitalization, adverse reactions, and adverse events. RevManV.5.3 software will be used for meta-analysis, and fixed effects model, random-effects model, subgroup analysis, and descriptive analysis will be adopted according to the heterogeneity of the research results. RESULTS: To provide the latest evidence of clinical efficacy and safety of arbidol in the treatment of COVID-19. CONCLUSION: Our study will provide the latest evidence analysis of the efficacy and safety of arbidol for COVID-19, to provide evidence-based medicine for the prevention and control of this epidemic. REGISTRATION DETAILS: PROSPERO CRD42020189203.

A systematic review and meta-analysis of the efficacy and safety of western medicine routine treatment combined with Chinese herbal medicine in the treatment of COVID-19.

BACKGROUND: COVID-19 is a global public health emergency. At present, there is no highly effective medicine for the prevention and treatment of 2019-nCoV. Western medicine for COVID-19 is mainly based on symptomatic support therapy. Chinese herbal medicine has been used to prevent infectious diseases for thousands of years in China. Western medicine routine treatment combined with Chinese herbal medicine is an alternative clinical option but lacks evidence-based medical evidence. The systematic review protocol aims to formulate a research plan that can evaluate the efficacy and safety of western medicine routine treatment combined with Chinese herbal medicine for COVID-19. METHODS: We will search the following eight databases: Cochrane Library, PubMed, Embase, Medline, CNKI, Wanfang, VIP, and CBM. The search time is up to the end of July 2020. Two authors will independently complete literature screening, data extraction, and risk of bias assessment. In case of disagreement, the third author will assist in the judgment. The primary outcome will be the clinical cure rate. The secondary outcome will be accounting symptoms, fever time, time of virus nucleic acid turning negative, check the condition by drawing blood, pneumonia absorption rate, patient hospitalization time, severe conversion rate and case fatality rate, adverse reactions, and adverse events. Revman 5.3 will be used for systematic reviews and meta-analysis. The report of the protocol will follow the PRISMA-P statement, and the report of the systematic review and meta-analysis will follow the PRISMA statement. RESULTS: We will provide evidence-based medical evidence of the efficacy and safety of western medicine routine treatment combined with Chinese herbal medicine for COVID-19. The findings will be published in peer-reviewed journals. REGISTRATION DETAILS: CRD42020190106.

Sodium tanshinone IIA sulfonate prevents radiation-induced damage in primary rat cardiac fibroblasts.

This study investigated the effects of X-ray irradiation on primary rat cardiac fibroblasts (CFs) and its potential mechanism, as well as whether sodium tanshinone IIA sulfonate (STS) has protective effect on CFs and its possible mechanism. Our data demonstrated that X-rays inhibited cell growth and increased oxidative stress in CFs, and STS mitigated X-ray-induced injury. Enzyme-linked immuno-sorbent assay showed that X-rays increased the levels of secreted angiotensin II (Ang II) and brain natriuretic peptide (BNP). STS inhibited the X-ray-induced increases in Ang II and BNP release. Apoptosis and cell cycle of CFs were analyzed using flow cytometry. X-rays induced apoptosis in CFs, whereas STS inhibited apoptosis in CFs after X-ray irradiation. X-rays induced S-phase cell cycle arrest in CFs, which could be reversed by STS. X-rays increased the expression of phosphorylated-P38/P38, cleaved caspase-3 and caspase-3 as well as decreased the expression of phosphorylated extracellular signal-regulated kinase 1/2 (ERK 1/2)/ERK 1/2 and B cell lymphoma 2 (Bcl-2)/Bcl-2 associated X protein (BAX) in CFs, as shown by Western blotting. STS mitigated the X-ray radiation-induced expression changes of these proteins. In conclusion, our results demonstrated that STS may potentially be developed as a medical countermeasure to mitigate radiation-induced cardiac damage.