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Continuous SiC fibers with excellent mechanical properties and high‐temperature resistance possess immense potential as reinforcements for aeroengines. In this work, we prepared functionalized boron nitride nanosheet (F‐BNNS) composite SiC (F‐BNNS/SiC) fibers by polymer‐derived method. Due to the existence of F‐BNNS, the F‐BNNS/SiC fibers demonstrate an improved tensile strength up to 2300 MPa, representing a 25% increase compared to the original SiC fibers. Furthermore, owing to the chemical bonds established between the F‐BNNS and the SiCxOy network, the decomposition of the SiCxOy amorphous phase and the crystallization of SiC at high temperatures is effectively suppressed. The F‐BNNS/SiC fibers exhibit improved high‐temperature resistance, maintaining a tensile strength of 720 MPa up to 1500°C, while the SiC fibers completely degraded under the same conditions. The successful preparation of BNNS/SiC fibers may offer new insights into the performance enhancement of advanced ceramic fibers. [ABSTRACT FROM AUTHOR]

The strong potential of platinum single atom (PtSA) in gas sensor technology is primarily attributed to its high atomic economy. Nevertheless, it is imperative to conduct further exploration to understand the impact of PtSA on the active sites. In this study, the evolution of PtSA on (100)CeO2 and (111)CeO2 is examined, revealing notable disparities in the position and activity of surface PtSA on different crystal planes. The PtSA in (100)CeO2 surface can enhance the stability of Ce3+ and construct a frustrated Lewis pair (FLP) to form a double active site by combining the steric hindrance effect of oxygen vacancies, which increases the response value from 1.8 to 27 and reduce the response‐recovery time from 140–192 s to 25–26 s toward five ppm NO2 at room temperature. Conversely, PtSA tends to bind to terminal oxygen on the surface of (111)CeO2 and become an independent reaction site. The response value of PtSA‐(111)CeO2 surface only increased from 1.6 to 3.8. This research underscores the correlation between single atoms and crystal plane effects, laying the groundwork for designing and synthesizing ultra‐stable and efficient gas sensors. [ABSTRACT FROM AUTHOR]

The circular RNA (circRNA) family is a group of endogenous non-coding RNAs (ncRNAs) that have critical functions in multiple physiological and pathological processes, including inflammation, cancer, and cardiovascular diseases. However, their roles in regulating innate immune responses remain unclear. Here, we define Cell division cycle 42 (CDC42)−165aa, a protein encoded by circRNA circCDC42, which is overexpressed in Klebsiella pneumoniae (KP)-infected alveolar macrophages. High levels of CDC42-165aa induces the hyperactivation of Pyrin inflammasomes and aggravates alveolar macrophage pyroptosis, while the inhibition of CDC42-165aa reduces lung injury in mice after KP infection by inhibiting Pyrin inflammasome-mediated pyroptosis. Overall, these results demonstrate that CDC42-165aa stimulates Pyrin inflammasome by inhibiting CDC42 GTPase activation and provides a potential clinical target for pathogenic bacterial infection in clinical practice. The function of circular RNA (circRNA) in the innate immune system is not fully understood. Here the authors characterise a cell division cycle 42 (CDC42)-165aa protein encoded by circRNA circCDC42 that promotes Pyrin-inflammasome mediated pyroptosis in Klebsiella pneumoniae (KP) infection and inhibition of circCDC42 reduces KP induced lung injury in mice. [ABSTRACT FROM AUTHOR]

Primates exhibit complex brain structures that augment cognitive function. The neocortex fulfills high-cognitive functions through billions of connected neurons. These neurons have distinct transcriptomic, morphological, and electrophysiological properties, and their connectivity principles vary. These features endow the primate brain atlas with a multimodal nature. The recent integration of next-generation sequencing with modified patch-clamp techniques is revolutionizing the way to census the primate neocortex, enabling a multimodal neuronal atlas to be established in great detail: (1) single-cell/single-nucleus RNA-seq technology establishes high-throughput transcriptomic references, covering all major transcriptomic cell types; (2) patch-seq links the morphological and electrophysiological features to the transcriptomic reference; (3) multicell patch-clamp delineates the principles of local connectivity. Here, we review the applications of these technologies in the primate neocortex and discuss the current advances and tentative gaps for a comprehensive understanding of the primate neocortex. [ABSTRACT FROM AUTHOR]

The diffusion of credit cards may have relaxed households' liquidity constraints, thereby stimulating the diffusion of commercial insurance. By investigating Chinese urban households who had no commercial insurance in 2013, we find that their initial access to credit cards significantly increased the likelihood of their holding commercial insurance in 2015. Our instrumental variable (IV) estimations confirm the causality. This positive effect is more pronounced among more liquidity‐constrained households and among households with more financial knowledge. Last, the initial access to credit cards also significantly enhanced commercial insurance renewal in 2015 among those households who had commercial insurance in 2013. [ABSTRACT FROM AUTHOR]

One-dimensional silicon carbide (SiC) nanomaterials hold great promise for a series of applications, such as nanoelectronic devices, sensors, supercapacitors, and catalyst carriers, attributed to their unique electrical, mechanical, and physicochemical properties. Recent progress in their design and fabrication has led to a deep understanding of the structural evolution and structure–property correlation. Several unique attributes, such as high electron mobility, offer SiC nanomaterials an opportunity in the design of SiC-based sensors with high sensitivity. In this review, a brief introduction to the structure and properties of SiC is first presented, and the latest progress in design and fabrication of one-dimensional SiC nanomaterials is summarized. Then, the sensing applications of one-dimensional SiC nanomaterials are reviewed. Finally, our perspectives on the important research direction and future opportunities of one-dimensional SiC nanomaterial for sensors are proposed. [ABSTRACT FROM AUTHOR]

Geopolitical uncertainty imposes a significant impact on stock prices in the stock market. We construct dynamic estimations of geopolitical risk exposure of individual stocks listed in China and examine the relationship between individual geopolitical risk and future stock price crash risk. Our results show that geopolitical risk is a more prominent macro factor than economic policy uncertainty measure that affects stock price crash risk. Investigating the underlying mechanism, we find that firms with highly synchronized stock prices, low analyst coverage ratio, low institutional holdings, and large investor heterogeneity tend to be affected more by geopolitical shocks, leading to future stock price crashes. This study shows the importance of promoting efficient information transmission system and improving corporate governance. [ABSTRACT FROM AUTHOR]

The degenerative process in Parkinson's disease (PD) causes a progressive loss of dopaminergic neurons (DaNs) in the nigrostriatal system. Resolving the differences in neuronal susceptibility warrants an amenable PD model that, in comparison to post-mortem human specimens, controls for environmental and genetic differences in PD pathogenesis. Here we generated high-quality profiles for 250,173 cells from the substantia nigra (SN) and putamen (PT) of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonian macaques and matched controls. Our primate model of parkinsonism recapitulates important pathologic features in nature PD and provides an unbiased view of the axis of neuronal vulnerability and resistance. We identified seven molecularly defined subtypes of nigral DaNs which manifested a gradient of vulnerability and were confirmed by fluorescence-activated nuclei sorting. Neuronal resilience was associated with a FOXP2-centered regulatory pathway shared between PD-resistant DaNs and glutamatergic excitatory neurons, as well as between humans and nonhuman primates. We also discovered activation of immune response common to glial cells of SN and PT, indicating concurrently activated pathways in the nigrostriatal system. Our study provides a unique resource to understand the mechanistic connections between neuronal susceptibility and PD pathophysiology, and to facilitate future biomarker discovery and targeted cell therapy. Using animal models to mimic Parkinson's disease can advance our understanding of pathogenesis. Here, the authors combine single-cell genomics with a primate model of parkinsonism to provide insights into neuronal vulnerability and resilience. [ABSTRACT FROM AUTHOR]

Background: Neovascular age-related macular degeneration (AMD) is responsible for the majority of severe vision loss cases and is mainly caused by choroidal neovascularization (CNV). This condition persists or recurs in a subset of patients and regresses after 5 or more years of anti-vascular endothelial growth factor (VEGF) treatment. The precise mechanisms of CNV continue to be elucidated. According to our previous studies, macrophages play a critical role in CNV. Herein, we aimed to determine the morphological changes in macrophages in CNV to help us understand the dynamic changes. Methods: Mice were subjected to laser injury to induce CNV, and lesion expansion and macrophage transformation were examined by immunofluorescence and confocal analysis. Several strategies were used to verify the dynamic changes in macrophages. Immunofluorescence and confocal assays were performed on choroidal flat mounts to evaluate the morphology and phenotype of macrophages in different CNV phases, and the results were further verified by western blotting and RT–PCR. Results: The location of infiltrated macrophages changed after laser injury in the CNV mouse model, and macrophage morphology also dynamically changed. Branching macrophages gradually shifted to become round with the progression of CNV, which was certified to be an M2 phenotypic shift. Conclusions: Dynamic changes in macrophage morphology were observed during CNV formation, and the round-shaped M2 phenotype could promote neovascularization. In general, the changes in morphology we observed in this study can help us to understand the critical role of macrophages in CNV progression and exploit a potential treatment option for CNV indicated by a shift in macrophage polarity. [ABSTRACT FROM AUTHOR]

This study was conducted on the lesion-mimic mutant lm5, which was produced by mutagenesis of WYJ21 (WT) using ethyl methane sulfonate (EMS). The mutant lm5 was short in the seedling stage and displayed yellowish-brown disease-like spots on leaves that were yellowish-brown when the plant was at the tillering stage. The disease-like spots gradually grew larger as the plant grew until it reached maturity. Compared to WT, lm5 had considerably reduced the plant height, ear panicle length, tiller number, and 1000-grain weight. A single recessive gene was found to be in control of lm5, according to a genetic study. It was physically located 245 kb apart between the RM21160 and RM180 markers on chromosome 7. Using RiceData and other websites, analyze and sequence potential gene candidates. Exon 7 of LOC_Os07g10390 (OsLM5) was identified to have a mutation that changed the 1560 base from G to A, changing the 788 amino acids from Arg to Lys. The OsLM5 gene was found to be a new allele of the SPL5 gene, encoding the protein shear factor SF3b3. Studies showed that OsLM5 was localized in the nucleus, and OsLM5 was significantly expressed in leaves. Reactive oxygen species (ROS) accumulation occurred in the leaves and roots of mutant lm5, and qPCR results showed abnormal expression of genes related to chloroplast development as well as significantly increased expression of genes related to aging and disease course. The OsLM5 gene may have a significant impact on the regulation of apoptosis in rice cells. [ABSTRACT FROM AUTHOR]

Objective: Immune checkpoint inhibitors (ICIs) have been validated in epidermal growth factor receptor (EGFR) wild-type advanced non-small cell lung cancer (NSCLC) patients. However, there exists no evidence regarding NSCLC patients harboring EGFR mutations, experiencing EGFR-TKI (tyrosine kinase inhibitor) treatment failure. We collected clinical information from real world and conducted a time series-based meta-analysis to determine the efficacy and safety of ICIs in patients harboring EGFR mutations and experienced EGFR-TKIs resistance. Methods: Twenty-two NSCLC patients with EGFR mutations after TKI resistance were included from two hospitals. PubMed, Embase and Cochrane Library were searched for relevant literature published until December 31, 2021. Endpoint outcomes included mortality and progression-free survival (PFS) at different times of follow-up. Results: In total, 22 patients showed that the median PFS was 5.6 months (range 2.0–9.0 months). According to treatment strategies, the median PFS was 2.4 months (range 2.0–5.3 months) in the ICI monotherapy group and 5.9 months (range 2.8–9.0 months) in the ICI combined Chemotherapy group. Additionally, sixteen studies, including 5 trials, 10 controlled cohorts and 1 real-world study, were assessed, involving a total of ICI-treated NSCLC patients with EGFR mutation after TKI failure. The 6-month survival and PFS rate were 0.82 (95% CI 0.36–0.97) and 0.55 (95% CI 0.34–0.74), respectively. ICI combined chemotherapy showed the best survival outcome among these groups, as demonstrated by the 12-month survival rate and PFS. No new safety signals were identified with the combination therapy. The frequency of treatment-related adverse events was similar to that in previously reported studies of chemotherapy combined with checkpoint inhibitors. Conclusions: The addition of ICIs plus chemotherapy may significantly improve progression-free survival among patients with locally advanced or metastatic non-squamous NSCLC who EGFR-TKIs resistance. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) caused by acute bacterial infection remains a common life‐threatening lung disease. An increased inflammatory response is the basis for the occurrence and development of ALI. Most antibiotics can only reduce the bacterial load but do not protect from lung damage because of an excessive immune response. Chrysophanol (chrysophanic acid, Chr), as a natural anthraquinone extracted from Rheum palmatum L., has various biological functions, including anti‐inflammatory, anti‐cancer activities, and ameliorative effects on cardiovascular diseases. Considering these properties, we investigated the effect of Chr in Klebsiella pneumoniae (KP)‐induced ALI mice and its potential mechanism. Our results showed that Chr had protective effects against KP‐infected mice, including increased survival rate, decreased bacterial burden, reduced recruitment of immune cells, and reduced reactive oxygen species level of lung macrophages. Chr reduced the expression of inflammatory cytokines by inhibiting the toll‐like receptor 4/nuclear factor kappa‐B (TLR4/NF‐κB) signaling pathway and inflammasome activation and strengthening autophagy. Overactivation of the TLR4/NF‐κB signaling pathway by the activator Neoseptin 3 led to Chr losing control of inflammatory cytokines in cells, resulting in increased cell death. Similarly, overactivation of the c‐Jun N‐terminal kinase signaling pathway using the activator anisomycin resulted in Chr losing its inhibitory effect on NOD‐like receptor thermal protein domain associated protein 3 (NFRP3) inflammasome activation, and cell viability was reduced. In addition, autophagy was blocked by siBeclin1, so Chr could not reduce inflammatory factors, and cell viability was markedly inhibited. Collectively, this work unravels the molecular mechanism underpinning Chr‐alleviated ALI via inhibiting pro‐inflammatory cytokines. Thus, Chr is a potential therapeutic agent for KP‐induced ALI. [ABSTRACT FROM AUTHOR]

Oxide ceramic fibers with softness and toughness are key materials in emerging fields like wearable devices and membrane technologies. However, the brittle failure of oxide ceramic fibers after thermal cycling leads to the loss of membrane architectures, which limits their long-term applications at high temperature. Here, we report a scalable approach of sol–gel electrospinning to synthesize a flexible and tough pyrochlore La1.85Al0.15Zr2O7 (L5AZO) nanofiber membrane (NFM) involving self-assembled 3D networks. The interactions between the nanoscale constituents lead to the assembled networks with high nodal connectivity and strong crosslinking between nanofibers, which may promote an enhancement of macroscopic mechanical properties by orders of magnitude. Ultrasonic dispersion and an amorphous secondary phase drive the formation of numerous L5AZO nuclei and soft grain boundaries, thus effectively refining grains and inhibiting crystallite growth. Indeed, the L5AZO NFM achieves both a high specific tensile modulus of ∼11.4 MPa cm3 g−1 and fracture toughness of ∼1032 J m−2, as well as high-temperature resistance above 1100 °C, which are advantageous for diverse structural applications. Furthermore, the simple processing technique of the NFM allows it to be fabricated into various functional devices, such as aerogels, thermal camouflage, and filtration membranes at high temperature. The mechanistic insights and manufacturability provided by this flexible and tough oxide NFM may create further opportunities for materials design and technological innovation. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii is a nosocomial pathogen associated with severe illness and death. Glucocorticoid aerosol is a common inhalation therapy in patients receiving invasive mechanical ventilation. We conducted a prospective cohort study to analyze the association between glucocorticoid aerosol therapy and A. baumannii isolation from ventilator patients in China. Of 497 enrolled patients, 262 (52.7%) received glucocorticoid aerosol, and A. baumannii was isolated from 159 (32.0%). Glucocorticoid aerosol therapy was an independent risk factor for A. baumannii isolation (hazard ratio 1.5, 95% CI 1.02-2.28; p = 0.038). Patients receiving glucocorticoid aerosol had a higher cumulative hazard for A. baumannii isolation and analysis showed that glucocorticoid aerosol therapy increased A. baumannii isolation in most subpopulations. Glucocorticoid aerosol was not a direct risk factor for 30-day mortality, but A. baumannii isolation was independently associated with 30-day mortality in ventilator patients. Physicians should consider potential A. baumannii infection when prescribing glucocorticoid aerosol therapy. [ABSTRACT FROM AUTHOR]

The primate neocortex exerts high cognitive ability and strong information processing capacity. Here, we establish a single-cell RNA sequencing dataset of 133,454 macaque visual cortical cells. It covers major cortical cell classes including 25 excitatory neuron types, 37 inhibitory neuron types and all glial cell types. We identified layer-specific markers including HPCAL1 and NXPH4, and also identified two cell types, an NPY-expressing excitatory neuron type that expresses the dopamine receptor D3 gene; and a primate specific activity-dependent OSTN + sensory neuron type. Comparisons of our dataset with humans and mice show that the gene expression profiles differ between species in relation to genes that are implicated in the synaptic plasticity and neuromodulation of excitatory neurons. The comparisons also revealed that glutamatergic neurons may be more diverse across species than GABAergic neurons and non-neuronal cells. These findings pave the way for understanding how the primary cortex fulfills the high-cognitive functions. The laminar organization of macaque V1 cortex is similar to that seen in humans. Here the authors describe a single-cell RNA sequencing dataset of macaque V1 cortex cells. [ABSTRACT FROM AUTHOR]

Objective. This study was aimed at studying the diagnostic value of aortic dissection (AD) risk score, coagulation function, and laboratory indicators in acute aortic dissection (AAD). Methods. In this retrospective study, 57 patients with AAD and 57 with an acute coronary syndrome (ACS). During the same period, 50 healthy subjects were selected as the control group admitted to our institution which were assessed for eligibility and recruited. They were assigned to an AD group (AAD patients) and an ACS group (ACS patients). The AD risk scores, coagulation function indexes, and laboratory indexes of the two groups were compared. With digital subtraction angiography- (DSA-) based diagnosis result as the gold standard, the receiver operating characteristic (ROC) curve was used to analyze the diagnostic value of various indexes for AD, and the sensitivity, specificity, and optimal diagnostic value (Youden index) of the diagnostic indexes were calculated. Additionally, the overall blood clot formation strength (MA), clotting factor function (R), platelet function (MAp), and functional fibrinogen (MAf) levels were evaluated. Results. AAD risk, AD screening, early diagnosis of AAD, fibrinogen degradation products (FDP), fibrinogen (Fib), prothrombin time (PT), activated partial thromboplastin time (APTT), tenascin C (TN-C), D-dimer (D-D), and N-terminal B-type natriuretic peptide precursor (NT-proBNP) in the three groups were statistically different (P < 0.05). Further pairwise comparisons showed that the AD patients got higher scores of AAD risk, AD screening, and early diagnosis of AAD versus ACS patients (P < 0.05). AD was associated with lower levels of fibrinogen degradation products (FDP) and fibrinogen (Fib), shorter prothrombin time (PT), and activated partial thromboplastin time (APTT) versus ACS (P < 0.05). AD also resulted in higher levels of tenascin C (TN-C), D-dimer (D-D), and N-terminal B-type natriuretic peptide precursor (NT-proBNP) versus ACS (P < 0.05). The three risk scores, various laboratory indicators, and various coagulation function indicators were of high diagnostic values for the diagnosis of AAD (A U C > 0.9 , P < 0.05). The sensitivity of the AD screening scale and TN-C expression level to the diagnosis of AAD was up to 100%, and the specificity of TN-C expression level was up to 98.25%. The influencing factors of AAD included Fib, FDP, PT, APTT, D-D, TN-C, and NT-proBNP. MA, MAf, and MAp displayed the same trend and reached the lowest point at T2. R was the opposite and reached the highest point at T2. At T4, a higher Map and a lower MAf were found than before surgery, and R and MA returned to preoperative levels. The positive detection rate of ACS by CT scan was positively correlated with the degree of stenosis (r = 0.814 , P < 0.05). Conclusion. AD screening scale, TN-C, and FDP are of the highest diagnostic value in the risk score of AD, laboratory indicators, and coagulation function. It has implications for the diagnosis of ADD. [ABSTRACT FROM AUTHOR]

Aim: We aimed to reveal the function of celastrol in the treatment of ovarian cancer using network pharmacology and molecular docking. Background: Ovarian cancer is a growth of cells that forms in the ovaries. Celastrol is a useful bioactive compound derived from the root of the thunder god vine. Method: Celastrol and ovarian cancer targets were determined by analyzing datasets. Protein–protein interaction (PPI) networks were obtained with network pharmacology. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed. Molecular docking using SWISS-MODEL, CB-Dock and Discovery Studio was conducted. A methylthiazolyltetrazolium bromide (MTT) assay was performed to evaluate cell proliferation. Cell apoptosis and cell cycle were measured with a fluorescence assay. Reverse transcription PCR (RT-PCR) and Western blot were performed to measure the expression of core targets. Result: Celastrol possessed 29 potential targets, while ovarian cancer possessed 471 potential targets. The core PPI network contained 163 nodes and 4,483 edges. The biological processes identified in the GO analysis indicated that the targets were related with the cellular response to DNA damage stimulus, DNA recombination, and cell proliferation, among other processes. The KEGG analysis indicated that the pathways were related with the cell cycle, viral carcinogenesis, and MAPK signaling pathway, among others. The three core targets shared between the core PPI network and celastrol targets were MYC, CDC37, and FN1. Celastrol directly combined with the targets according to the results from CB-Dock and Discovery Studio. Celastrol inhibited ovarian cancer cell proliferation and promoted ovarian cancer cell apoptosis in a dose-dependent manner. RT-PCR and Western blot analyses showed that celastrol inhibited core target expression. In addition, celastrol also influenced the related inflammatory signaling pathways in ovarian cancer cells. Conclusion: Celastrol exerts effective antitumor activity toward ovarian cancer. Celastrol regulated cell proliferation, DNA repair and replication, apoptotic processes, and inflammatory responses in ovarian cancer cells. [ABSTRACT FROM AUTHOR]

Background: The value of caregivers with respect to ensuring safety during home nasogastric tube (NGT) feeding is increasingly acknowledged. However, little attention has been given to the experience of caregivers. Methods: A qualitative descriptive design using semi‐structured interviews via purposive sampling at a comprehensive hospital in China was employed. Family caregivers of patients with home NGT feeding were recruited. Interviews were recorded, transcribed verbatim and analysed qualitatively using inductive content analysis. Results: Thirteen family caregivers of patients with home NGT feeding were interviewed. Four main themes were generated: negative experience (uncertainty and ambivalence, transition gaps between hospitals and home care services), new role: adapting to the lifestyle (participating in decision‐making, being responsible for everything, adjusting own life to NGT feeding), perceived benefit of caregiving (personal growth, development of positive attitudes and achievements) and expectations (expectations from continuity health system services, expectations from social support). Conclusions: The present study highlights the vulnerability and perceived benefits embedded in the role of a family caregiver. Improving communication and standardising practices between home and hospitals should be considered. [ABSTRACT FROM AUTHOR]

Aims: This clinical study was conducted to evaluate the impact of rifampicin on the pharmacokinetics of fuzuloparib. Methods: In this single‐centre, single‐arm, open‐label, fixed‐sequence study, healthy male subjects took a single 50 mg dose of fuzuloparib on two separate occasions: the first was on Day 1 as monotherapy, and the second was on Day 12 after oral administration of rifampicin 600 mg once daily for 8 days. Series of blood samples were obtained before and after fuzuloparib administration at different time points: pre‐dose, and 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, 36, 48 and 72 hours post‐dose. All samples were examined using liquid chromatography with tandem mass spectrometry. PK parameters were estimated by using a non‐compartmental method with Phoenix WinNonlin software. Safety was assessed by monitoring for changes in vital signs and laboratory tests, physical examinations, and incidences of adverse events (AEs). Results: A total of 16 Chinese male subjects were enrolled. Of these, 16 and 15 cases were evaluable for PK analysis following administration with fuzuloparib alone and pretreatment with rifampicin, respectively. Pretreatment with rifampicin resulted in a statistically significant reduction in the systemic exposure to fuzuloparib. The treatment ratio and 90% confidence intervals (CIs) for AUC0‐∞ and Cmax were 0.10 (0.095–0.115) and 0.32 (0.281–0.365), respectively. A single administration of fuzuloparib after multiple oral dosing of rifampicin was well‐tolerated, without severe AEs. Conclusion: The exposure of fuzuloparib was dramatically decreased when pretreated with rifampicin. Strong CYP3A4 inducers should be avoided during fuzuloparib treatment. [ABSTRACT FROM AUTHOR]

Background: Esophageal squamous cell carcinoma (ESCC) is the most predominant primary malignant tumor among worldwide, especially in China. To date, the successful treatment remains a mainly clinical challenge, it is imperative to develop successful therapeutic agents.Methods: The anti-proliferative effect of ivermectin on ESCC is investigated in cell model and in nude mice model. Cell apoptosis was assessed using flow cytometry, TUNEL assay and western blotting. Mitochondrial dysfunction was determined by reactive oxygen species accumulation, mitochondrial membrane potential and ATP levels.Results: Our results determined that ivermectin significantly inhibited the proliferation of ESCC cells in vitro and in vivo. Furthermore, we found that ivermectin markedly mediated mitochondrial dysfunction and induced apoptosis of ESCC cells, which indicated the anti-proliferative effect of ivermectin on ESCC cells was implicated in mitochondrial apoptotic pathway. Mechanistically, ivermectin significantly triggered ROS accumulation and inhibited the activation of NF-κB signaling pathway and increased the ratio of Bax/Bcl-2.Conclusions: These finding indicated that ivermectin has significant anti-tumour potential for ESSC and may be a potential therapeutic candidate against ESCC. [ABSTRACT FROM AUTHOR]

This study provides current evidence for efficacy and safety of treating COVID‐19 with combined traditional Chinese medicine (TCM) and conventional western medicine (CWM). Six databases were searched from January 1 to December 31, 2020. Randomized controlled trials (RCTs), case–control studies (CCTs), and cohort studies on TCM or TCM combined with CWM treatment for COVID‐19 were included. The quality of included RCTs was assessed by Cochrane risk of bias tool, and the Newcastle‐Ottawa Scale (NOS) was used to assess the quality of cohort studies and CCTs. Review Manager 5.4 software was used to perform meta‐analysis. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. A total of 35 studies (3,808 patients) composing 19 RCTs and 16 observational studies were included. The results of meta‐analysis revealed that comparing with CWM alone, integrated TCM and CWM had significant improvement in total effective rate, improvement rate of chest CT, the rate of disease progression, as well as improvement of fever, fatigue and cough. The overall quality of evidence was very low to moderate. In conclusion, TCM combined with CWM was a potential treatment option for increasing clinical effective rate, improving the clinical symptoms, and preventing disease progression in COVID‐19 patients. High‐quality clinical trials are required in the further. [ABSTRACT FROM AUTHOR]

Canonical correlation analysis (CCA) has gained great success for fault detection (FD) in recent years. However, it cannot preserve the prior information of the underlying process. To cope with these difficulties, this paper proposes an improved CCA-based FD scheme using a novel multivariate statistical technique, called sparse collaborative regression (SCR). The core of the proposed method is to take the prior information as a supervisor, and then integrate it with CCA. Further, the ℓ2,1-norm is employed to reduce redundancy and avoid overfitting, which facilitates its interpretability. In order to solve the proposed SCR, an efficient alternating optimization algorithm is developed with convergence analysis. Finally, some experimental studies on a simulated example and the benchmark Tennessee Eastman process are conducted to demonstrate the superiority over the classical CCA in terms of the false alarm rate and fault detection rate. The detection results indicate that the proposed method is promising. [ABSTRACT FROM AUTHOR]

[Objective] The paper was to compare the indoor toxicities of sixteen fungicides on mycelial growth and spore germination of Monilinia fructicola, to screen out effective fungicides and to discuss use characteristics of various types of fungicides. [Method] The inhibitory activities of 16 fungicides on mycelial growth and spore germination were determined by mycelial growth rate method and spore germination method. [Result] The ECs(l values of 16 fungicides against mycelial growth ranged from 0.018 4 to 61.530 5 mg/L. Prochloraz, tetramycin, fenbuconazole and fludioxonil had strong inhibitory activities on mycelial growth, and their EC$, values were 0.018 4, 0-045 6, 0.053 1 and 0-081 4 mg/L, respectively, significantly lower than those of other 12 fungicides. The ECsc, values of 16 fungicides against spore germination ranged from 0.008 4 to 189.393 8 mg/L. Tetramycin and chlorothalonil had strong inhibitory activities on mycelial growth, and their EC® values were 0.008 4 and 0-037 8 mg/L, respectively, significantly lower than those of other 14 fungicides-[Conclusion] The 16 fungicides had great value in preventing and controlling peach brown rot. Benzimidazoles, diformimides and ergosterol inhibitors had good inhibitory' activities on mycelial growth. Strobilurins, succinate dehydrogenase inhibitors and multiple-site protective fungicides had good inhibitory' activities on spore germination. The agricultural antibiotics tetramycin, phenazine-l-carboxylic acid and pyrrole fungicide fludioxonil had good inhibitory activities on mycelial growth and spore germination. [ABSTRACT FROM AUTHOR]

Hydration mechanisms of hydratable alumina (HA) in citric acid at different pH are investigated in this study, aiming to improve rapid hydration process and massive hydration heat. By adding citric acid to adjust solution pHs to 2, 3, and 4, the crystal phase, morphologies, and microstructure of the HA hydrates are characterized by X-ray powder diffraction (XRD), differential scanning calorimetry (TG-DSC), and transmission electron microscopy (TEM), respectively. The results show that HA exhibits different hydration behaviors in different concentrations of acidic solutions. With decreasing pH of citric acid, the crystallinity of HA decreases whereas the dehydration process slows down. Excessive citric acid could displace hydroxyl which generates from pseudoboehmite gel. Meanwhile, the excess citrate ion can be absorbed on the surface of HA by forming numerous micelles, then compound to inhibit further hydration. Proper addition of citric acid helps to delay the hydration of HA and achieve better balance between bonding performance and hydration speed. [ABSTRACT FROM AUTHOR]

A simple, rapid, and sensitive liquid chromatography (LC)/mass spectrometry (MS) method was established and validated for simultaneous quantitation of pyrazinamide, isoniazid, rifampicin, and ethambutol in human blood sample. Samples were pretreated by a single-step precipitation with acetonitrile. Chromatographic separation was achieved on XSelecT HSS T3 column by gradient elution with a total run time of 5.0 min. MS detection was performed by a triple quadrupole tandem mass spectrometer in the multiple reaction monitoring mode with a positive electrospray ionization source. Isotope-labeled internal standard, especially rifampicin-D8, was applied to adjust for the loss during sample treatment. The established LC-MS/MS method showed a wide analytical range (pyrazinamide: 1.02∼60.0 μg/mL, isoniazid: 0.152∼10.0 μg/mL, rifampicin: 0.500∼30.0 μg/mL, and ethambutol: 0.0998∼5.99 μg/mL) and a good linearity (r > 0.99 for the four analytes) with acceptable accuracy and precision (90.15%∼104.62% and 94.00%∼104.02% for intra- and interaccuracy, respectively; RSD%: <12.46% and <6.43% for intra- and interprecision, respectively). It also showed excellent recoveries (79.24%∼94.16% for all analytes) and absence of significant matrix effect. This method was successfully applied to the quantification of four first-line antituberculosis (anti-TB) drugs, suggesting its suitability for therapeutic drug monitoring in the clinical practices. [ABSTRACT FROM AUTHOR]

Background: Vancomycin is the standard therapy for methicillin-resistant Staphylococcus aureus (MRSA) infection; however, nephrotoxicity happened with a high incidence of 15%~40%. Weighting the risk before receiving vancomycin treatment facilitates timely prevention of nephrotoxicity, but no standardized strategy exists for this purpose.Methods: A retrospective cohort study was performed. A total of 524 hospitalized patients treated with vancomycin were included in this study. They were divided into derivation cohort (n=341) and externally validation cohort (n=183) according to their admission time. Using univariate and multivariable logistic regression, we identified potential predictors of vancomycin-associated acute kidney injury (AKI) and developed a risk score by plotting nomogram. The predictive performance of this novel risk score was assessed and validated by discrimination and calibration. Besides, the risk score was also compared with existing prediction models according to integrated discrimination index (IDI) and net reclassification index (NRI).Results: The incidence of AKI was 16.1% (55/341) in the derivation cohort and 16.4% (30/183) in the validation cohort. Three factors (vancomycin serum trough concentration, piperacillin/tazobactam and furosemide) were determined as predictors for vancomycin-associated AKI. The established three-item risk score showed a comparable discrimination in both derivation cohort (AUC=0.793, 95% CI: 0.732-0.855) and validation cohort (AUC=0.788, 95% CI: 0.698-0.877). The risk score also demonstrated a good calibration in the derivation cohort (χ2=6.079, P=0.638>0.05) and validation cohort (χ2=5.665, P=0.686>0.05). Compared with prediction by Cmin alone, this risk score significantly improved reclassification accuracy (IDI=0.050, 95% CI: 0.024-0.076, P<0.001, NRI=0.166, 95% CI: 0.044-0.289, P=0.007).Conclusion: The established model in this study is a simplified three-item risk score, which provides a robust tool for the prediction of AKI after receiving vancomycin treatment. [ABSTRACT FROM AUTHOR]

Rhizoctonia cerealis, Bipolaris sorokiniana, and Fusarium spp. are three wheat-damaging soil-borne fungal pathogens causing sharp eyespot, common root rot, and crown rot, respectively. This study aimed to develop a multiplex PCR (mPCR) system to simultaneously detect these fungal pathogens. The mPCR assay was performed on wheat seedlings collected from a field in the Shandong Province. Specific primers were designed on the basis of the sequences of following genes: internal transcribed spacer (ITS) of R. cerealis, ITS of B. sorokiniana, and translation elongation factor (TEF1-α) of Fusarium spp., generating amplicons of 174, 418, and 600 bp, respectively. The mPCR system was optimized through an orthogonal design L18 (37) (three levels of five factors: three sets of primers, Taq DNA polymerase, and dNTPs) and statistical analysis. No nonspecific products were obtained upon amplification of nontarget species of the fungi. Sensitivity analysis revealed that the limit of detection of the mPCR assay for each pathogen was 100 pg. The mPCR results were further confirmed via subsequent visual diagnosis. The system developed herein provides a rapid, effective, and valuable method to simultaneously detect three soil-borne pathogens, thus facilitating prompt treatment and prevention of root diseases of wheat. [ABSTRACT FROM AUTHOR]

Aluminum borate ceramics (ABCs) with a skeleton structure of rod‐like crystals were established via a solid‐state reaction synthesis. The influence of heat treatment systems on the phase composition and microstructural evolution of an anisotropic grain were firstly studied. Next, the impact of boric acid content on the activation energy of reaction, microstructure, mechanical properties, and neutron shielding capability were investigated. The results demonstrate that orthorhombic Al18B4O33 formed between 900°C and 1000°C which was the stable phase during heating treatment. In addition, increasing the boric acid content was favorable for reducing the activation energy of forming aluminum borate, resulting in increased in situ formation and growth of aluminum borate whiskers in fired samples. Next, mircropores could be generated by the decomposition of boric acid at high temperatures, which had a considerable influence on the physical properties of the sample. Furthermore, the Monte Carlo particle transport program simulation and neutron shielding experiments showed that the prepared ABCs could shield neutron effectively manifested as possessing a high neutron absorption cross‐section in the case of porous materials. Moreover, ABCs have potential application value as thermal insulation material in the nuclear energy field. [ABSTRACT FROM AUTHOR]

Gentamicin, one of the most widely used aminoglycoside antibiotics, is known to have toxic effects on the inner ear. Taken up by cochlear hair cells and spiral ganglion neurons (SGNs), gentamicin induces the accumulation of reactive oxygen species (ROS) and initiates apoptosis or programmed cell death, resulting in a permanent and irreversible hearing loss. Since the survival of SGNs is specially required for cochlear implant, new procedures that prevent SGN cell loss are crucial to the success of cochlear implantation. ROS modulates the activity of the mammalian target of rapamycin (mTOR) signaling pathway, which mediates apoptosis or autophagy in cells of different organs. However, whether mTOR signaling plays an essential role in the inner ear and whether it is involved in the ototoxic side effects of gentamicin remain unclear. In the present study, we found that gentamicin induced apoptosis and cell loss of SGNs in vivo and significantly decreased the density of SGN and outgrowth of neurites in cultured SGN explants. The phosphorylation levels of ribosomal S6 kinase and elongation factor 4E binding protein 1, two critical kinases in the mTOR complex 1 (mTORC1) signaling pathway, were modulated by gentamicin application in the cochlea. Meanwhile, rapamycin, a specific inhibitor of mTORC1, was co-applied with gentamicin to verify the role of mTOR signaling. We observed that the density of SGN and outgrowth of neurites were significantly increased by rapamycin treatment. Our finding suggests that mTORC1 is hyperactivated in the gentamicin-induced degeneration of SGNs, and rapamycin promoted SGN survival and outgrowth of neurites. [ABSTRACT FROM AUTHOR]

Background: Adjuvant chemotherapy treatment for different endometrial cancer stages is still debated. We aimed to evaluate the outcome of early (FIGO I-II) vs late stage (FIGO III-IV) endometrial cancer in an institutional experience using chemotherapy only after surgery.Method: Charts of patients with endometrial carcinoma who underwent surgery with postoperative chemotherapy between February 2012 and December 2017 were retrospectively identified, and the recurrence as well as prognosis were assessed.Result: Of the 272 eligible endometrioid adenocarcinoma (EA) patients, 127 had received chemotherapy, 145 did not receive chemotherapy; 37 were in late stage (FIGO III-IV) and 235 were in early stage (FIGO I-II). In the late stage group, patients with no chemotherapy had worse overall survival (OS) and recurrence-free survival (RFS) as compared to the patients taking chemotherapy (OS, 28.6% vs 76.4%, P = 0.059; RFS, 17.1% vs 66.4%, P = 0.053). However, in the early stage group, there was no significant difference between the OS and RFS between the patients that were receiving and not receiving chemotherapy (OS, 84.1% vs 93.3%, P = 0.789; RFS, 76.7% vs 72.4%, P = 0.924). Independent predictive factors of recurrence were age over 53 years, histological grade G3, as well as late stages (FIGO III-IV), while independent predictive factors of OS were age over 53 years, deeper depth of myometrial invasion, and late stages (FIGO III-IV).Conclusion: In late stages, patients with chemotherapy had lower recurrence rate and favorable OS as compared to patients not taking chemotherapy, which was the benefit of postoperative adjuvant chemotherapy, and chemotherapy might be strongly considered in late stage EA. [ABSTRACT FROM AUTHOR]

We have developed a whole-cell bioconversion system for the production of D-1,2,4-butanetriol (BT) from renewable biomass. A plasmid pETduet-xylB-yjhG-T7-adhP-T7-mdlC was constructed and transformed to Escherichia coli BL21(DE3) to obtain the whole cells of E. coli BL21-XYMA capable of bioconversion D-xylose to BT. Then, the factors including carbon sources, nitrogen sources, metal ions, and culture conditions (pH, temperature, IPTG) were identified, and their effects on the whole-cell activity for BT production were investigated. To obtain the highest whole-cell activity, the optimal cultivation parameters are: 15 g·L-1 yeast extract, 5 g·L-1 sucrose, 3 g·L-1 KH2PO4, 5 g·L-1 NaCl, 3 g·L-1 NH4Cl, 0.25 g·L-1 MgSO4·7H2O and 1 mL·L-1 the mixture of trace elements. With the optimized whole cells of E. coli BL21-XYMA, 60 g·L-1 of xylose was converted to 28 g·L-1 BT with a molar yield of 66 %, which is higher than those reported in the biotechnological system. [ABSTRACT FROM AUTHOR]

Chronic constipation is often accompanied by emotional disorders such as depression and anxiety. The aim of this study was to determine whether administration of a multispecies probiotic can decrease depressive behaviors through the gut-brain axis and identify any underlying mechanisms. A mouse model of constipation induced by loperamide (5 mg·kg−1,i.p.) was used. For that purpose, 36 ICR male mice were divided into three groups: control, constipation and probiotic groups. The probiotic group received treatment with a probiotic once per day for 14 days via a gavage. All other groups were given an equal volume of normal saline. The fecal parameters and intestinal transit ratio were recorded. The forced swimming test and tail suspension test were used to detect changes in depressive behaviors. Total superoxide dismutase (T-SOD) activity and malondialdehyde (MDA) levels were measured by assay kits. We also detected neuronal survival, as well as phosphorylated Ser/Thr protein kinase (p-AKT), Bcl-2, Bcl-2 associated X protein (Bax) and cleaved caspase-3 levels in the hippocampus. The results showed that administration of a probiotic could ameliorate depressive behaviors and relieve neuronal cell injury in the hippocampal CA3 regions. Moreover, probiotic treatment decreased MDA levels and increased SOD activity. Furthermore, probiotic administration increased p-AKT and Bcl-2 levels in the hippocampus of the constipated mice, while decreasing the concentrations of Bax and cleaved caspase-3, so as to inhibit the neural apoptosis. In the present study, we confirm that probiotics can alleviate depression induced by constipation through protecting neuronal health via activation of the AKT signaling pathway. [ABSTRACT FROM AUTHOR]

Premise of the Study: Polymorphic microsatellite primers were developed for greater duckweed, Spirodela polyrhiza (Lemnaceae), to investigate genetic diversity and structure for application in a bioremediation program. Methods and Results: A total of 401 publicly available S. polyrhiza whole‐genome shotgun sequences were searched for simple sequence repeat loci of two or more nucleotides. Of these, 60 primer pairs were selected to analyze 68 individuals of S. polyrhiza from three populations. Nineteen polymorphic microsatellite loci were developed. A total of 108 alleles were detected with an average of 5.7 alleles per locus. The levels of expected and observed heterozygosity were 0.0511–0.8669 and 0–0.8750, respectively. Ten loci also successfully amplified in 16 individuals of Lemna perpusilla. Conclusions: The results demonstrate the broad utility of these microsatellite loci for studying population genetics in S. polyrhiza. [ABSTRACT FROM AUTHOR]

The auditory function develops and matures after birth in many mammalian species. After hearing onset, environmental sounds exert profound and long-term effects on auditory functions. However, the effects of the acoustic environment on the functional development of the peripheral auditory system, especially the cochlear sensory hair cells, are still unclear. In the present study, we exposed mouse pups to frequency-enriched acoustic environments in postnatal days 0–14. The results indicated that the acoustic environment significantly decreased the threshold of the auditory brainstem response in a frequency-specific manner. Compared with controls, no difference was found in the number and alignment of inner and outer hair cells or in the length of hair bundles after acoustic overstimulation. The expression and function of prestin, the motor protein of outer hair cells (OHCs), were specifically increased in OHCs activated by acoustic stimulation at postnatal days 7–11. We analyzed the postnatal maturation of ribbon synapses in the hair cell areas. After acoustic stimulation, the number of ribbon synapses was closer to the mature stage than to the controls. Taken together, these data indicate that early acoustic exposure could promote the functional maturation of cochlear hair cells and the development of hearing. [ABSTRACT FROM AUTHOR]

[Objective] The study was to evaluate the indoor toxicity and field efficacy of five Strobilurins fungicides including pyraclostrobin 250 g/L EC, azoxystrobin 250 g/L SC, kresoxim-methyl 50% WG, picoxystrobin 22,5% SC and trifloxystrobin 50% WG against Phomopsis asparagi (Sacc.) Bubak, and to screen out effective fungicides. [Method] The toxicity was tested by mycelial growth rate method. The field trials were carried out by routine spraying method. [Result] The indoor toxicities successively were pyraclostrobin > kresoxim-methyl > picoxystrobin > trifloxystrobin > azoxystrobin. The EC% values were 6.102 9, 52.559 1, 83.825 7, 129.861 6 and 252.121 4 mg/L, respectively, all significantly higher than that of benzimidazole fungicide carbendazim (753.365 0 mg/L). The field efficacies successively were pyraclostrobin > kresoxim-methyl ≥ picoxystrobin ≥ azoxystrobin ≥ trifloxystrobin. The control effects were 81.20%, 77.95%, 74.80%, 71.69% and 68.54%, respectively, all significantly higher than that of benzimidazole fungicide carbendazim(48.27%). [Conclusion] The five Strobilurins fungicides all have good toxicity and field efficacy against P. asparagi. [ABSTRACT FROM AUTHOR]

Phytoplankton structure in spring in the moats of Dinghai District, Zhoushan City was investigated in April 2016. Firstly, the species composition and dominant species of phytoplankton were analyzed, and then the water quality of the moats was evaluated by cell density, water-quality indicator species, biodiversity index method, and saprobic index method. The results show that there were 114 species of phytoplankton in the moats of Dinghai District in spring, belonging to 70 genera, 38 families, and 7 phyla, of which Bacillarophyta, Chlorophyta and Cyanophyta were dominant; the main dominant species were Synedra acus, Aphanizomenon flosaquae, Microcytis flos-aquae, etc. The cell density of phytoplankton in the moats ranged from 1.07 million to 13.7 million cells/L. Shannon-Wiener diversity index, Margalef richness index, Pielou evenness index, and saprobic index averaged 0.93, 2.53, 0.12, and 2.61 respectively. On the whole, river water in the moats of Dinghai District was polluted seriously, but there was no obvious difference between the four rivers in water pollution. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) is a serious post-surgery complication; however, few preoperative risk models for AKI have been developed for hypertensive patients undergoing general surgery. Thus, in this study involving a large Chinese cohort, we developed and validated a risk model for surgery-related AKI using preoperative risk factors. Methods and Findings: This retrospective cohort study included 24,451 hypertensive patients aged ≥18 years who underwent general surgery between 2007 and 2015. The endpoints for AKI classification utilized by the KDIGO (Kidney Disease: Improving Global Outcomes) system were assessed. The most discriminative predictor was selected using Fisher scores and was subsequently used to construct a stepwise multivariate logistic regression model, whose performance was evaluated via comparisons with models used in other published works using the net reclassification index (NRI) and integrated discrimination improvement (IDI) index. Results: Surgery-related AKI developed in 1994 hospitalized patients (8.2%). The predictors identified by our Xiang-ya Model were age, gender, eGFR, NLR, pulmonary infection, prothrombin time, thrombin time, hemoglobin, uric acid, serum potassium, serum albumin, total cholesterol, and aspartate amino transferase. The area under the receiver-operating characteristic curve (AUC) for the validation set and cross validation set were 0.87 (95% CI 0.86–0.89) and (0.89; 95% CI 0.88–0.90), respectively, and was therefore similar to the AUC for the training set (0.89; 95% CI 0.88–0.90). The optimal cutoff value was 0.09. Our model outperformed that developed by Kate et al., which exhibited an NRI of 31.38% (95% CI 25.7%-37.1%) and an IDI of 8% (95% CI 5.52%-10.50%) for patients who underwent cardiac surgery (n = 2101). Conclusions/Significance: We developed an AKI risk model based on preoperative risk factors and biomarkers that demonstrated good performance when predicting events in a large cohort of hypertensive patients who underwent general surgery. [ABSTRACT FROM AUTHOR]

Purpose: To explore the readability and content integrity of informed consent forms (ICFs) used in China and to compare the quality of Chinese local ICFs with that of international ICFs. Methods: The length, readability and content of 155 consent documents from phase II-IV drug clinical trials from the Third Xiangya Hospital Ethics Committee from November 2009 to January 2015 were evaluated. Reading difficulty was tested using a readability formula adapted for the Chinese language. An ICF checklist containing 27 required elements was successfully constructed to evaluate content integrity. The description of alternatives to participation was assessed. The quality of ICFs from different sponsorships were also compared. Results: Among the 155 evaluable trials, the ICFs had a median length of 5286 words, corresponding to 7 pages. The median readability score was 4.31 (4.02–4.41), with 63.9% at the 2nd level and 36.1% at the 3rd level. Five of the 27 elements were frequently neglected. The average score for the description of alternatives to participation was 1.06, and 27.7% of the ICFs did not mention any alternatives. Compared with Chinese local ICFs, international ICFs were longer, more readable and contained more of the required elements (P < 0.05). Conclusion: The ICFs used in China were difficult to read for most participants. These forms had poor description of alternatives to participation, and failed to provide a high degree of information disclosure, including an explanation of informed consent, follow-up processing of the data/sample, inclusion/exclusion criteria, double blinding, and unpredictable risks. International ICFs had better readability and content integrity than Chinese local ICFs. More efforts should thus be made to improve the quality of consent documents in China. [ABSTRACT FROM AUTHOR]

As persistent organic pollutants, polychlorinated biphenyls (PCBs) accumulate in the bodies of animals and humans, resulting in toxic effects on the reproductive, immune, nervous, and endocrine systems. The biological and toxicological characteristics of enantiomers of chiral PCBs may differ, but these enantioselective effects of PCBs have not been fully characterized. In this study, we performed metabolomics analysis, using ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) to investigate the enantioselective toxic effects of PCB95 in zebrafish (Danio rerio) embryos after exposure to three dose levels of 0.1, 1, and 10 μg/L for 72 h. Multivariate analysis directly reflected the metabolic perturbations caused by PCB95. The effects of (-)-PCB95 and (+)-PCB95 were more prominent than those of the racemate in zebrafish embryos. A total of 26 endogenous metabolites were selected as potential marker metabolites with variable importance at projection values larger than 1 and significant differences (p<0.05). These metabolites included amino acids, organic acids, nucleosides, betaine, and choline. The changes in these biomarkers were dependent on the enantiomer-specific structures of PCB95. Fifteen metabolic pathways were significantly affected, and several nervous and immune system-related metabolites were significantly validated after exposure. These metabolic changes indicated that the toxic effects of PCB95 may be associated with the interaction of PCB95 with the nervous and immune systems, thus resulting in disruption of energy metabolism and liver function. [ABSTRACT FROM AUTHOR]

The efficiencies of free and immobilized microbial consortia in the degradation of different types of petroleum hydrocarbons were investigated. In this study, the biodegradation rates of naphthalene, phenanthrene, pyrene and crude oil reached about 80%, 30%, 56% and 48% under the optimum environmental conditions of free microbial consortia after 7 d. We evaluated five unique co-metabolic substances with petroleum hydrocarbons, α-lactose was the best co-metabolic substance among glucose, α-lactose, soluble starch, yeast powder and urea. The orthogonal biodegradation analysis results showed that semi-coke was the best immobilized carrier followed by walnut shell and activated carbon. Meanwhile, the significance of various factors that contribute to the biodegradation of semi-coke immobilized microbial consortia followed the order of: α-lactose ＞ semi-coke ＞ sodium alginate ＞ CaCl2. Moreover, the degradation rate of the immobilized microbial consortium (47%) was higher than that of a free microbial consortium (26%) under environmental conditions such as the crude oil concentration of 3 g L−1, NaCl concentration of 20 g L−1, pH at 7.2–7.4 and temperature of 25 °C after 5 d. SEM and FTIR analyses revealed that the structure of semi-coke became more porous and easily adhered to the microbial consortium; the functional groups (e.g., hydroxy and phosphate) were identified in the microbial consortium and were changed by immobilization. This study demonstrated that the ability of microbial adaptation to the environment can be improved by immobilization which expands the application fields of microbial remediation. [ABSTRACT FROM AUTHOR]