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This study optimized a gas chromatography-tandem triple quadrupole mass spectrometry (GC-MS/MS) method for the determination of 21 persistent organic pollutants (POPs) in Irtysh River water, including 14 organochlorines (OCPs) and 7 polychlorinated biphenyls (PCBs). Factors such as column temperature ramping, selection of qualitative and quantitative ion pairs and collision energy were considered to achieve perfect separation and accurate quantification of all 21 target compounds. The limits of detection (LOD) for PCBs and OCPs ranged from 0.21 to 1.18 ng/L. Applying this method to detect POPs in the Irtysh River revealed concentrations of OCPs ranging from ND to 20.2 ng/L and PCBs from ND to 0.411 ng/L. Source analysis indicated that POPs in the Irtysh River mainly originate from historical industrial and agricultural activities, particularly the deliberate use of pesticides. To ensure ecological safety and human health, expanding the range of target analytes and monitoring periods is necessary. This study provides: • Qualitative and quantitative analysis methods for 7 PCBs and 14 OCPs. • Recoveries achieved ranged between 74.6 to 109 % with RSD less than 15 %. • Analysis of sources, transport pathways, accumulation status, and ecological risks of PCBs and OCPs in the Irtysh River.

IntroductionEnterocytozoon bieneusi is one of the most important zoonotic pathogens, responsible for nearly 90% of human infections. Its host spectrum is broad in China, encompassing humans, non-human primates, domestic animals, wildlife, and wastewater. Wild rodents have the potential to act as carriers of E. bieneusi, facilitating the parasite’s transmission to humans and domestic animals.MethodsThe present study involved the collection of 344 wild rodents, representing nine species, from three provinces in China. The prevalence and genotypes of E. bieneusi were determined through amplification of the ITS gene. Evolutionary analysis was conducted using Mega 5.0 with the neighbor-joining method (Kimura 2-parameter model, 1,000 replicates).ResultsAmong the sampled wild rodents, 41 (11.92%) were tested positive for E. bieneusi. Rattus flavipectus exhibited the highest prevalence (11/39), while Bandicota indica and Rattus rattus sladeni showed no infections (0/39 and 0/5, respectively), highlighting significant differences. Environmental factors strongly influenced E. bieneusi infection; rodents residing in lake beaches (10.27%, 15/146) and fields (19.95%, 18/95) were more susceptible compared to those in mountainous areas (7.77%, 8/103). The study identified four known genotypes (D, Type IV, SDD5, PigEBITS7) and five novel genotypes (HNRV-1 to HNRV-3, GXRL-1, GXRL-2) in the investigated wild rodents, with Genotype D exhibiting the highest prevalence.DiscussionRemarkably, this study reports the presence of E. bieneusi, R. flavipectus, M. fortis, A. agrarius, R. losea, and N. lotipes for the first time. These findings underscore the common occurrence of E. bieneusi infection in wild rodents in China, highlighting its diverse nature and significant potential for zoonotic transmission. Hence, it is imperative to conduct a comprehensive epidemiological investigation of rodent infection with E. bieneusi, particularly focusing on wild rodents that are closely associated with humans. Additionally, developing appropriate measures and monitoring strategies to minimize the risk of infection is essential.

The use of carbon fiber reinforced polymer (CFRP) strands as prestressed reinforcement in prestressed concrete (PC) structures offers an effective solution to the corrosion issues associated with prestressed steel strands. In this study, the flexural behavior of PC beams reinforced with prestressed CFRP strands and non-prestressed steel rebars was investigated using finite element modeling (FEM) and artificial neural network (ANN) methods. First, three-dimensional nonlinear FE models were developed. The FE results indicated that the predicted failure mode, load-deflection curve, and ultimate load agreed well with the previous test results. Variations in prestress level, concrete strength, and steel reinforcement ratio shifted the failure mode from concrete crushing to CFRP strand fracture. While the ultimate load generally increased with a higher prestressed level, an excessively high prestress level reduced the ultimate load due to premature fracture of CFRP strands. An increase in concrete strength and steel reinforcement ratio also contributed to a rise in the ultimate load. Subsequently, the verified FE models were utilized to create a database for training the back propagation ANN (BP-ANN) model. The ultimate moments of the experimental specimens were predicted using the trained model. The results showed the correlation coefficients for both the training and test datasets were approximately 0.99, and the maximum error between the predicted and test ultimate moments was around 8%, demonstrating that the BP-ANN method is an effective tool for accurately predicting the ultimate capacity of this type of PC beam.

IntroductionBlastocystis is one of the most critical intestinal protozoans in various hosts, including humans and mice. To determine the status of Blastocystis infection in wild rodents in China.MethodsA total of 344 faecal samples were collected from seven wild rodent species from three provinces, and the small subunit ribosomal RNA (SSU rRNA) genes of Blastocystis were amplified to determine their prevalence and subtypes.ResultsOf the 344 samples, 54 (15.70%) were detected as Blastocystis-positive. The prevalence of Blastocystis was 26.14% (40/153), 7.95% (7/88), and 6.80% (7/103) in wild rodents from Hunan Province, Yunnan Province, and Guangxi Province, respectively. The prevalence of Blastocystis in different wild rodent species varied from 0.00% (0/13) in Mus musculus to 40.00% (2/5) in Rattus rattus sladeni. The prevalence of Blastocystis in samples from the lake beach area (27.40%, 40/146) was significantly higher than in those from the mountain (6.80%, 7/103) and field regions (7.37%, 7/95). The prevalence in different seasons was 26.14% in summer (40/153), 7.95% in autumn (7/88), and 6.80% in winter (7/103). Moreover, a total of two Blastocystis subtypes were identified in the investigated wild rodents, including ST4 and ST5.DiscussionThe present study discovered the existence of Blastocystis infection in Rattus favipectus, Microtus fortis, Apodemus agrarius, Bandicota indica, Rattus rattus sladeni, and Rattus losea, expanding the host range of this parasite. The findings also demonstrate that wild rodents may be an important potential infection source for Blastocystis infection in humans and other animals.

Abstract Background Some medical conditions may increase the risk of developing pulmonary tuberculosis (PTB); however, no systematic study on PTB-associated comorbidities and comorbidity clusters has been undertaken. Methods A nested case-control study was conducted from 2013 to 2017 using multi-source big data. We defined cases as patients with incident PTB, and we matched each case with four event-free controls using propensity score matching (PSM). Comorbidities diagnosed prior to PTB were defined with the International Classification of Diseases-10 (ICD-10). The longitudinal relationships between multimorbidity burden and PTB were analyzed using a generalized estimating equation. The associations between PTB and 30 comorbidities were examined using conditional logistic regression, and the comorbidity clusters were identified using network analysis. Results A total of 4265 cases and 17,060 controls were enrolled during the study period. A total of 849 (19.91%) cases and 1141 (6.69%) controls were multimorbid before the index date. Having 1, 2, and ≥ 3 comorbidities was associated with an increased risk of PTB (aOR 2.85–5.16). Fourteen out of thirty comorbidities were significantly associated with PTB (aOR 1.28–7.27), and the associations differed by sex and age. Network analysis identified three major clusters, mainly in the respiratory, circulatory, and endocrine/metabolic systems, in PTB cases. Conclusions Certain comorbidities involving multiple systems may significantly increase the risk of PTB. Enhanced awareness and surveillance of comorbidity are warranted to ensure early prevention and timely control of PTB.

Abstract Objective To discuss the value of computed tomography (CT) iterative reconstruction technique combined with target scanning in the diagnosis of solid pseudopapillary tumor of the pancreas (SPTP). Methods The clinical information and CT examination data of 27 patients with SPTP were retrospectively analyzed, and the general condition and CT performance of the patients were observed. The CT image reconstruction algorithm of all patients used iterative reconstruction technique combined with the application of target scanning technique. Results A total of 27 patients were included in this study, including 6 males and 21 females, aged 14–72 years with a mean age of 39.6 ± 13.6 years. SPTP was more common in young and middle-aged females, with a low level of tumor markers, dominated by cystic-solid tumors. The combination of CT iterative reconstruction technology and targeted scanning revealed the following: the capsule of SPTP was clear and complete, where calcifications were visible, solid components were progressively enhanced, and rare pancreatic and bile duct dilation was seen. Tumors were cystic-solid in 18 of 27 patients with SPTP, of which the solid components showed isodensity or slightly low-density, with calcifications. The solid components and cyst walls were mildly enhanced during the arterial phase, and were progressively enhanced during the parenchymal phase, portal vein phase, and delayed phase, with their enhancement degree lower than that of normal pancreatic parenchyma, and pancreatic and bile duct dilation was rare. There were no statistical differences in tumor location, morphology, growth pattern, integrity of capsule, cystic or solid, calcifications, and enhancement features between the male group and the female group (P > 0.05). Conclusion The iterative reconstruction combined with target scanning clearly displayed the CT features of tumors, helping the diagnosis and clinical treatment of the disease.

Abstract Objective To investigate the diagnostic value of computed tomography (CT) and magnetic resonance imaging (MRI) in ovarian malignant mesothelioma (OMM). Methods The clinical and imaging data of 10 pathologically-confirmed OMM patients were analyzed retrospectively. Result (1) The patients were 27 years to 70 years old, with an average age of 57.2 ± 15.4 years. Seven patients reported abdominal distension and pain, 1 reported lower abdominal discomfort and decreased appetite, and 2 patients had no symptoms. (2) Two cases of localized OMM with incomplete semi-annular “capsule” observed around the localized OMM tumors were reported while 8 cases had diffuse OMM in which the tumor parenchyma showed isointense or slightly hypointense on T1WI, inhomogeneous hyperintense on T2WI, and obviously hyperintense on DWI, with obvious inhomogeneous enhancement after enhancement. Diffuse OMM was not mainly composed of ovarian masses and was mainly characterized by mild ovarian enlargement, nodular and irregular thickening of the peritoneum, cloudy omentum, unclear fat gap, and reticular or irregular thickening, which can fuse into a “cake-shape”. (3) All 10 patients underwent surgery, while 9 patients underwent systemic chemotherapy or immunotherapy after surgery. All patients with localized OMM survived. Out of the 8 diffuse-type patients, 5 died, 1 was lost to follow-up, and 2 survived. Conclusion OMM has certain clinical and imaging characteristics. There is no liquefaction, calcification, or partition in the tumor. The ovarian enlargement in the diffuse lesion is not significant. The diffuse thickening of the peritoneum and omentum with early appearance of mural nodules and ascites in the upper abdomen, help the diagnosis of OMM.

Mg-1 wt.% Li-1 wt.% Ca (LX11) and Mg-4 wt.% Li-1 wt.% Ca (LX41) alloys share the same hexagonal closed-packed crystalline structure. However, the differences in microstructure, mechanical properties, and degradation rates between the two alloys are not well understood. Hereby, the above three aspects of LX11 and LX41 alloys were studied via optical microscopy, tensile tests, and electrochemical polarization and electrochemical impedance spectroscopy, together with hydrogen evolution. The concentration of the released Mg2+, Ca2+, and Li+ ions was analyzed using a flame atomic absorption spectrophotometer. Results demonstrated that the LX11 alloy was composed of finer α-Mg grains, fewer twins, and smaller volume fractions of the intermetallic phases Mg2Ca than the LX41 alloy. The increasing Li concentration generated a weak decrease in the yield strength of the Mg–Li–Ca alloys, a remarkable increase in elongation to failure, and a stable ultimate tensile strength. The LX11 alloy had better corrosion resistance than the LX41 alloy. The release rate of the cations (Mg2+, Ca2+, and Li+) varied significantly with time. The release rate of metallic ions in Hank's solution cannot reflect the true corrosion rate of Mg–Li–Ca alloys due to the formation of the precipitated corrosion products and their difference in solubility. The dealloying corrosion mechanism of the Mg2Ca phase in Mg–Li–Ca alloys was proposed.

Abstract Background The current surveillance system only focuses on notifiable infectious diseases in China. The arrival of the big-data era provides us a chance to elaborate on the full spectrum of infectious diseases. Methods In this population-based observational study, we used multiple health-related data extracted from the Shandong Multi-Center Healthcare Big Data Platform from January 2013 to June 2017 to estimate the incidence density and describe the epidemiological characteristics and dynamics of various infectious diseases in a population of 3,987,573 individuals in Shandong province, China. Results In total, 106,289 cases of 130 infectious diseases were diagnosed among the population, with an incidence density (ID) of 694.86 per 100,000 person-years. Besides 73,801 cases of 35 notifiable infectious diseases, 32,488 cases of 95 non-notifiable infectious diseases were identified. The overall ID continuously increased from 364.81 per 100,000 person-years in 2013 to 1071.80 per 100,000 person-years in 2017 (χ 2 test for trend, P

Melanoma is the most aggressive skin malignancy with high morbidity. Anti-programmed cell death protein 1 (PD-1) monotherapy has been applied in metastatic melanoma. However, still most of the patients do not respond to anti-PD-1 and the availability of the present approved biomarkers therefore is limited. Here we combined the transcriptomic and clinical data of 163 advanced melanoma patients receiving anti-PD-1 from NIH Melanoma Genome Sequencing Project (phs000452, 122 patients) as the training and internal validation cohort, and Melanoma Institute Australia cohort (PRJEB23709, 41 patients) as the external validation cohort, respectively. Circular RNAs (circRNAs) are an evolutionarily conserved novel class of noncoding endogenous RNAs (ncRNAs) found in the eukaryotic transcriptome and were used based on RNAseq data for our analyses. 74,243 circular RNAs (circRNAs) were identified with NCLscan and CIRCexplorer2. Thereof, 70 circRNAs significantly associated with progression-free survival and overall survival. Further, a prognostic circRNAs signature consisting of HSA_CIRCpedia_1497, HSA_CIRCpedia_12559, HSA_CIRCpedia_43640, HSA_CIRCpedia_43070, and HSA_CIRCpedia_21660 could be determined with LASSO regression. This signature was a prognostic factor of overall survival and progression-free survival among the analyzed advanced melanoma patients. The concordance indexes (C-index of OStraining: 0.61, C-index of PFStraining: 0.68) also confirmed its credibility and accuracy. First enrichment analysis indicated that immune response and pathways related to tumor immune microenvironment were enriched. In conclusion, we succeeded to construct and validate novel prognostic circRNAs signature for advanced melanoma patients treated with anti-PD-1 immunotherapy.

IntroductionSymptoms of gastric motility disorders are common clinical manifestations of functional gastrointestinal disorders (FGIDs), and are triggered and exacerbated by stress, but the neural pathways underpinning them remain unclear.MethodsWe set-up a mouse model by gastric dilation (GD) in which the gastric dynamics were assessed by installing strain gauges on the surface of the stomach. The neural pathway associated with gastric motility disorders was investigated by behavioral tests, electrophysiology, neural circuit tracing, and optogenetics and chemogenetics involving projections of the corticotropin-releasing hormone (CRH) from the paraventricular nucleus of the hypothalamus (PVN) to acetylcholine (ChAT) neurons in the dorsal motor nucleus of the vagus (DMV).ResultsWe found that GD induced gastric motility disorders were accompanied by activation of PVNCRH neurons, which could be alleviated by strategies that inhibits the activity of PVNCRH neurons. In addition, we identified a neural pathway in which PVNCRH neurons project into DMVChAT neurons, modulated activity of the PVNCRH→DMVChAT pathway to alleviate gastric motility disorders induced by GD.DiscussionThese findings indicate that the PVNCRH→DMVChAT pathway may mediate at least some aspects of GD related gastric motility, and provide new insights into the mechanisms by which somatic stimulation modulates the physiological functions of internal organs and systems.

Background/aims: Psychological and physiological stress can cause gastrointestinal motility disorders. Acupuncture has a benign regulatory effect on gastrointestinal motility. However, the mechanisms underlying these processes remain unclear.Methods: Herein, we established a gastric motility disorder (GMD) model in the context of restraint stress (RS) and irregular feeding. The activity of emotional center—central amygdala (CeA) GABAergic neurons and gastrointestinal center—dorsal vagal complex (DVC) neurons were recorded by electrophysiology. Virus tracing and patch clamp analysis of the anatomical and functional connection between the CeAGABA → dorsal vagal complex pathways were performed. Optogenetics inhibiting or activating CeAGABA neurons or the CeAGABA → dorsal vagal complex pathway were used to detect changes in gastric function.Results: We found that restraint stress induced delayed gastric emptying and decreased gastric motility and food intake. Simultaneously, restraint stress activated CeA GABAergic neurons, inhibiting dorsal vagal complex neurons, with electroacupuncture (EA) reversing this phenomenon. In addition, we identified an inhibitory pathway in which CeA GABAergic neurons project into the dorsal vagal complex. Furthermore, the use of optogenetic approaches inhibited CeAGABA neurons and the CeAGABA → dorsal vagal complex pathway in gastric motility disorder mice, which enhanced gastric movement and gastric emptying, whereas activation of the CeAGABA and CeAGABA → dorsal vagal complex pathway mimicked the symptoms of weakened gastric movement and delayed gastric emptying in naïve mice.Conclusion: Our findings indicate that the CeAGABA → dorsal vagal complex pathway may be involved in regulating gastric dysmotility under restraint stress conditions, and partially reveals the mechanism of electroacupuncture.

BackgroundThe prognostic value of the tumor burden score (TBS) in patients with combined hepatocellular-cholangiocarcinoma (cHCC-CCA) remains unknown. This study aimed to investigate the impact of TBS on long-term outcomes after surgery.MethodsPatients who underwent radical-intent resection between June 2013 and December 2019 were retrospectively reviewed. Kaplan–Meier curves were used to analyze patient survival, and disease-free survival (DFS) and overall survival (OS) were examined in relation to TBS.ResultsA total of 178 patients were included in this study, with 119 in the training cohort and 59 in the validation cohort. Kaplan–Meier curves showed that TBS was a strong prognostic indicator in patients with cHCC-CCA. Elevated TBS was associated with poorer DFS and OS (both P-value < 0.001) and was identified as an independent prognostic indicator. In addition, the prognostic value of TBS outperformed tumor size and number alone, microvascular invasion, and lymph node invasion. The prognostic significance of TBS was confirmed by the internal validation cohort.ConclusionsThe present study suggested the significance of tumor morphology in assessing the prognosis of patients with cHCC-CCA who undergoing curative resection. The TBS is a promising prognostic index in patients with cHCC-CCA. Elevated TBS was related to a lower long-term survival rate and was identified as an independent risk factor for poor DFS and OS. Further research is needed to verify our results.

In the electro-hydraulic servo control system, there are some problems, such as low position control accuracy, uncontrollable speed, speed impact, and asymmetric control due to the asymmetry of hydraulic cylinder. To solve the above problems, this paper proposes a Fuzzy PID control algorithm with load force compensation based on improved PSO optimization. This improved particle swarm optimization algorithm introduces crossover and mutation operations in genetic algorithm to improve the optimization performance of traditional particle swarm optimization algorithm. The mathematical model of valve controlled asymmetric cylinder is established, and the Amesim linearization analysis function is used to identify the system, establish the transfer function, and build the control system. The joint simulation and test results of Amesim and MATLAB show that the proposed control strategy can realize the simultaneous control of speed and position. Under different loads, different speeds, and different input follow signals, it does not need to adjust any parameters. Regardless of forward or reverse operation, the optimal dynamic performance and minimum steady-state error are obtained, which greatly improves the response speed of the system. The effectiveness and superiority of the improved PSO compound control strategy are verified.

ABSTRACT: A suite of ultramafic and mafic rocks developed in the Chigu Tso area, eastern Tethyan Himalaya. Baddeleyite and zircon U-Pb ages acquired by SIMS and LA-ICP-MS from olivine pyroxenite rocks in the Chigu Tso area are 138.9±3.0 Ma and 139.0±1.9 Ma, respectively. These two Early Cretaceous ages are similar with the ages of the more abundant mafic rocks in the eastern Tethyan Himalaya, indicating that this suite of ultramafic and mafic rocks in the Chigu Tso area should be included in the outcrop area of the Comei Large Igneous Province (LIP). These ultramafic rocks provide significant evidence that the involvement of mantle plume/hot spot activities in the formation of the Comei LIP. Baddeleyite U-Pb dating by SIMS is one reliable and convenient method to constrain the formation time of ultramafic rocks. The dating results of baddeleyite and zircon from the olivine pyroxenite samples in this paper are consistent with each other within analytical uncertainties, suggesting that baddeleyite and zircon were both formed during the same magmatic process. The consistency of baddeleyite U-Pb ages in the Chigu Tso area with zircon U-Pb ages for a large number of Early Cretaceous mafic rocks in the eastern Tethyan Himalaya further support that zircon grains from such mafic rocks yielding Early Cretaceous ages are also magmatic in origin.

Introduction: Although vaccines provide a cost-effective solution to vaccine-preventable diseases (VPDs), the disease burden of VPDs is still very high in most parts of the world. Methods: A population-based observational study was conducted in Shandong province, China, from 2013 to 2017, giving an insight into the epidemiological characteristics and disease burden of seven VPDs. The incidence trend was estimated using the Poisson regression model. The disease burden was calculated using the disability-adjusted life years (DALYs). Results: Most VPDs included in the China’s National Immunization Program had higher incidence density (ID) in inland cities. The ID of mumps decreased significantly, while herpes zoster increased (both P 50 years, while highest DALYs of hepatitis B were found in young adults. Conclusion: Inequalities in the vaccine coverage by geography, socio-economic status, and targeted population contribute to the increasing incidence and high burden of VPDs and call for renewed and sustained immunization strategies in China.

BackgroundNeuroinflammation and mitochondrial impairment play important roles in the neuropathogenesis of Parkinson’s disease (PD). The activation of NLRP3 inflammasome and the accumulation of α-synuclein (α-Syn) are strictly correlated to neuroinflammation. Therefore, the regulation of NLRP3 inflammasome activation and α-Syn aggregation might have therapeutic potential. It has been indicated that Dl-3-n-butylphthalide (NBP) produces neuroprotection against some neurological diseases such as ischemic stroke. We here intended to explore whether NBP suppressed NLRP3 inflammasome activation and reduced α-Syn aggregation, thus protecting dopaminergic neurons against neuroinflammation.MethodsIn our study, we established a MPTP-induced mouse model and 6-OHDA-induced SH-SY5Y cell model to examine the neuroprotective actions of NBP. We then performed behavioral tests to examine motor dysfunction in MPTP-exposed mice after NBP treatment. Western blotting, immunofluorescence staining, flow cytometry and RT-qPCR were conducted to investigate the expression of NLRP3 inflammasomes, neuroinflammatory cytokines, PARP1, p-α-Syn, and markers of microgliosis and astrogliosis.ResultsThe results showed that NBP exerts a neuroprotective effect on experimental PD models. In vivo, NBP ameliorated behavioral impairments and reduced dopaminergic neuron loss in MPTP-induced mice. In vitro, treatment of SH-SY5Y cells with 6-OHDA (100uM,24 h) significantly decreased cell viability, increased intracellular ROS production, and induced apoptosis, while pretreatment with 5uM NBP could alleviated 6-OHDA-induced cytotoxicity, ROS production and cell apoptosis to some extent. Importantly, both in vivo and in vitro, NBP suppressed the activation of the NLRP3 inflammasome and the aggregation of α-Syn, thus inhibited neuroinflammation ameliorated mitochondrial impairments.ConclusionsIn summary, NBP rescued dopaminergic neurons by reducing NLRP3 inflammasome activation and ameliorating mitochondrial impairments and increases in p-α-Syn levels. This current study may provide novel neuroprotective mechanisms of NBP as a potential therapeutic agent.

Charge mobility is an essential factor of organic crystalline materials. Although many investigators have made important progress, the exact relationship between the crystal structure and carrier mobility remains to be clarified. Fortunately, a series of bis-1,3,4-oxadiazole derivatives have been successfully prepared and reported. They have similar main molecular fragments but different crystal packing modes, which provide an ideal research objective for studying the effect of molecular packing on charge mobility in organic photoelectric conversion systems. In this work, the charge mobilities of these molecules are systematically evaluated from the perspective of first-principles calculation, and the effect of a molecular overlap on orbital overlap integral and final charge carrier mobility is fully discussed. It can be seen that the small intermolecular distance (less than 6 Å) is the decisive factor to achieve high electron mobility in π stacking, and better mobility can be obtained by increasing the hole migration distance appropriately. A larger dihedral angle of anisotropy is an important point limiting the charge mobility in the herringbone arrangement. It is hoped that the correlation results between the crystal structure and mobility can assist the experimental study and provide an effective way to improve the photoelectric conversion efficiency of the organic semiconductor devices and multiple basis for multiscale material system characterization and material information.

Madhuca hainanensis Chun & F.C.How is an endangered and endemic species in Hainan Island, and it was ranked as a VU (Vulnerable) species in China. In this study, we reported its complete chloroplast (cp) genome sequence based on high throughput sequencing data. The complete cp genome was 159,630 bp in length, containing two short inverted repeat (IRs) of 26,093 bp, a large single copy (LSC) region of 88,846 bp and a small single copy (SSC) region of 18,598 bp. Totally, the cp genome contained 131 genes, including 86 protein coding genes (PCG), eight rRNA genes and 37 tRNAs. The GC contents of this genome was 36.8%. A maximum likelihood (ML) phylogenetic analysis indicates that M. hainanensis is closely related to Sinosideroxylon wightianum.

Background: The objective of this study was to construct a risk classification system integrating cell-free Epstein-Barr virus (cfEBV) DNA with T- and N- categories for better prognostication in nasopharyngeal carcinoma (NPC). Methods: Clinical records of 10,149 biopsy-proven, non-metastatic NPC were identified from two cancer centers; this comprised a training ( N = 9,259) and two validation cohorts ( N = 890; including one randomized controlled phase 3 trial cohort). Adjusted hazard ratio (AHR) method using a two-tiered stratification by cfEBV DNA and TN-categories was applied to generate the risk model. Primary clinical endpoint was overall survival (OS). Performances of the models were compared against American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) 8th edition TNM-stage classification and two published recursive partitioning analysis (RPA) models, and were validated in the validation cohorts. Results: We chose a cfEBV DNA cutoff of ⩾2,000 copies for optimal risk discretization of OS, disease-free survival (DFS) and distant metastasis-free survival (DMFS) in the training cohort. AHR modeling method divided NPC into six risk groups with significantly disparate survival ( p

An essential gene may become non-essential when another gene is mutated. Here, the authors investigate this type of digenic interaction, termed ‘bypass of essentiality’, in the fission yeast Schizosaccharomyces pombe, and show that bypassable essential genes are common and share certain features.

In the helicopter hover refuelling system, the emergency breakaway device is an important component to ensure the safety of the helicopter. It requires automatic disconnection and sealing of the pipeline under the tension of 1700–2000 N. The claw type emergency breakaway device was designed, the three-dimensional model is established for dynamic analysis, and the optimal parameters of the breakaway device are obtained by orthogonal experiment. Then, the calculation equation of the braking force is obtained through analysis. The sealing structure of the emergency breakaway device adopts a pair of poppet valves. In order to verify the reliability of the braking force and the seal, the emergency breakaway device is subjected to a water-passing test. The results show that the emergency breakaway device is separated with the required breaking force and the leakage amount is zero after the breakaway.

Objective To compare the epidemiological characteristics and transmission dynamics in relation to interventions against the COVID-19 and severe acute respiratory syndrome (SARS) outbreak in mainland China.Design Comparative study based on a unique data set of COVID-19 and SARS.Setting Outbreak in mainland China.Participants The final database included 82 858 confirmed cases of COVID-19 and 5327 cases of SARS.Methods We brought together all existing data sources and integrated them into a comprehensive data set. Individual information on age, sex, occupation, residence location, date of illness onset, date of diagnosis and clinical outcome was extracted. Control measures deployed in mainland China were collected. We compared the epidemiological and spatial characteristics of COVID-19 and SARS. We estimated the effective reproduction number to explore differences in transmission dynamics and intervention effects.Results Compared with SARS, COVID-19 affected more extensive areas (1668 vs 230 counties) within a shorter time (101 vs 193 days) and had higher attack rate (61.8 vs 4.0 per million persons). The COVID-19 outbreak had only one epidemic peak and one epicentre (Hubei Province), while the SARS outbreak resulted in two peaks and two epicentres (Guangdong Province and Beijing). SARS-CoV-2 was more likely to infect older people (median age of 52 years), while SARS-CoV tended to infect young adults (median age of 34 years). The case fatality rate (CFR) of either disease increased with age, but the CFR of COVID-19 was significantly lower than that of SARS (5.6% vs 6.4%). The trajectory of effective reproduction number dynamically changed in relation to interventions, which fell below 1 within 2 months for COVID-19 and within 5.5 months for SARS.Conclusions China has taken more prompt and effective responses to combat COVID-19 by learning lessons from SARS, providing us with some epidemiological clues to control the ongoing COVID-19 pandemic worldwide.

Long non-coding RNAs (lncRNAs) are involved in a variety of biological functions through transcriptional and post-transcriptional regulation. However, little is known about their functions in the process of insect mediated virus transmission. In the present study, we analyzed using RNA-Seq, the lncRNAs that were differentially expressed in response to Rice black-streaked dwarf virus (RBSDV) infection in Laodelphax striatellus (Fallén) midgut. A total of 13,927 lncRNAs were identified and over 69% were assigned to intergenic regions. Among them, 176 lncRNAs were differentially expressed and predicted to target 168 trans-regulatory genes. Ten differentially expressed lncRNAs were selected and their expression changes were validated by RT-qPCR. KEGG analysis showed that these target genes were enriched in the essential biological process, such as Purine metabolism, Valine, leucine and isoleucine degradation, and Fatty acid elongation. The expression levels of the differentially expressed lncRNAs and the predicted target genes that were significantly enriched in the Human papillomavirus infection pathway were analyzed by RT-qPCR. The results showed that several lncRNAs were co-expressed with their target genes. One of the lncRNAs called MSTRG15394 and its target gene, encoding a secreted protease inhibitor (PI), were up-regulated at the transcriptional level after RBSDV infection. Knockdown of MSTRG15394 could down-regulate the PI expression at mRNA level. Inhibition of either MSTRG15394 or PI expression by RNA interference promoted RBSDV accumulation in L. striatellus midgut. Our finding provides new insights into the function of lncRNAs in regulating virus infection in an important insect vector.

Farmers' production behaviour is a key to ensuring the safety and quality of their final products, and cooperatives play an important role in shaping that behaviour. This paper aims to explore the determinants of pig farmers' safe production behaviour, giving special focus from the perspective of cooperatives' services. This study adopted cross sectional survey data from 27 pig cooperatives and their 540 farmers in China to test the influence of cooperatives' services on farmers' safe production behaviour. The hypotheses were tested using a logit regression model. The findings indicated that although the number of services is not a key determinant of farmers' safe production behaviour, service quality matters. When a cooperative is strongly capable of involving more farmers in certain services, and provides certain services in more frequency, member farmers behave more safely. The results also show that veterinarian and pig-selling services play an important role in ensuring farmers' safe production behaviour. For this study, the quality of cooperatives' services is implied to have a positive impact on farmers' safe production behaviour. Leaders/managers of cooperatives must try to improve the quality of their services instead of merely attempting to provide a large number of services. For government officials and policy makers, designing policies that encourage cooperatives to improve their service quality is important. This research contributes to the scant literature on how cooperative services could help farmers engage in safer production behaviour, which would improve the safety of pork products in the future.

Abstract Obesity-related traits have been associated with coronary artery disease (CAD) in observational studies, but these associations may be biased by confounding factors and reverse causation. In this study, we specifically conducted two-sample Mendelian randomization (MR) analyses to overcome these limitations and test the associations of obesity-related traits (other than body mass index (BMI)) (n = 322,154) with CAD (22,233 cases and 64,762 controls) by using summary-level data from previous studies. The methods utilized to estimate these associations included the inverse-variance weighted method, the weighted median method and MR-Egger regression. Our results supported causal effects of BMI, hip circumference (HC), waist circumference (WC), and waist-hip ratio (WHR) on CAD. The associations of BMI-adjusted HC and WC with CAD were reversed, unlike that of WHR. In MR analyses excluding overlapping single nucleotide polymorphisms (SNPs) from obesity-related traits, the associations of these traits with CAD were preserved. The associations of BMI-adjusted HC and WC with CAD require further investigation, as collider stratification may be occurring. Additionally, central adiposity (measured by WHR) separated from general adiposity (measured by BMI) and general adiposity might pose similar risks for CAD. In clinical practice, physicians should pay attention to the potential effects of different obesity-related traits on CAD.

The seismic vulnerability analysis of gravity dam can predict the probability of dam damage at different levels under different seismic loads. It is significant to evaluate the seismic safety, optimize the seismic design and develop the reinforcement measures of gravity dam. Based on the uncertainty of the material parameters of concrete and the earthquake, the seismic vulnerability analysis of the Koyna gravity dam with the strain rate effect is carried out. The dam vulnerability analysis method and the seismic vulnerability curve of Koyna gravity dam are given. The results show when the strain rate effect is considered, the probability of severe damage and dam break is less than without considering strain rate effect. Dam head break, dam heel crack and combination failure are the typical seismic damages of gravity dam, which is in line with the actual damage of the Koyna dam.The results show that the dam head, dam heel and slope break are the key parts to focus.

Background/Objective: This is a multicentre, randomised, double-blind, placebo-controlled clinical trial to investigate the safety and efficacy of Chinese herbal Fufang Xian Ling Gu Bao (XLGB) with antiadipogenic compounds for the prevention of corticosteroid (CS)-induced osteonecrosis of femoral head (ONFH). Methods: Patients of both genders, aged between 18 and 65 years, with diseases such as systemic lupus erythematosus, nephrosis, dermatosis and rheumatoid arthritis indicated for CS treatment and who did not show magnetic resonance imaging of ONFH at baseline were recruited into the study and then randomised into either XLGB group (n = 129) with daily oral administration of XLGB or placebo group (n = 146). Results: Magnetic resonance imaging revealed a total of 30 ONFH cases at 6 months after CS treatment, with 6.98% (9 of 129 cases) and 14.4% (21 of 146 cases) in the XLGB group and placebo group, respectively, (p

Background: Investigate into the medical expenditures of chronic kidney disease (CKD) patients through path analysis method of three consecutive years within a Grade-A tertiary hospital in Beijing to conduct the main influencing factors in diagnosis-related groups (DRGs) grouping of the diagnosis, and reassess the present grouping process to provide information and reference on cost control for hospitals and medical management departments. Methods: Eight hundred and fifty-five inpatient cases whose first diagnosis were defined as CKD in the year 2014–2016 within the hospital were selected as the sample of the study, multiple linear regression and path analysis method were adopted in DRGs grouping process to investigate the main influencing factors of total medical expenditures and DRGs grouping process. Results: The maximum proportion of the medical costs within CKD patients was the costs on treatment, with the highest of 35.3% on the year 2014, the second was the costs on drug, which accounted for

Inspired by the performance of the ostrich in terms of loading and high-speed moving ability, the purpose of this study was to design a structure and material on the forefoot and heel of the middle soles of sports shoes based on the high cushioning quality of the ostrich toe pad by applying bionic engineering technology. The anatomical dissection method was used to analyze the ostrich foot characteristics. The structure and material of the bionic shock absorption midsole were designed according to the principles of bionic engineering and reverse engineering. F-Scan and numerical simulation were used to evaluate the bionic shock absorption midsole performance. The results showed that the bionic shock absorption midsole decreased the peak pressure (6.04–12.27%), peak force (8.62–16.03%), pressure–time integral (3.06–12.66%), and force–time integral (4.06–10.58%) during walking and brisk walking. In this study, the biomechanical effects to which the bionic shock absorption midsole structure was subjected during walking and brisk walking exercises were analyzed. The bionic midsole has excellent shock resistance. It is beneficial for the comfort of the foot during exercise and might reduce the risk of foot injuries during exercise.

Abstract Background Infection with the hepatitis B virus (HBV) is closely associated with the development of hepatocellular carcinoma (HCC). The osmoregulatory transcription factor nuclear factor of activated T-cells 5 (NFAT5) has been shown to play an important role in the development of many types of human cancers. The role of NFAT5 in HBV-associated HCC has never previously been investigated. Methods We compared expression profiles of NFAT5, DARS2 and miR-30e-5p in HCC samples, adjacent nontumor tissues and different hepatoma cell lines by quantitative real-time polymerase chain reaction and /or Western blot. Clinical data of HCC patients for up to 80 months were analyzed. The regulatory mechanisms upstream and convergent downstream pathways of NFAT5 in HBV-associated HCC were investigated by ChIP-seq, MSP, luciferase report assay and bioinformation anaylsis. Results We first found that higher levels of NFAT5 expression predict a good prognosis, suggesting that NFAT5 is a potential tumor-suppressing gene, and verified that NFAT5 promotes hepatoma cell apoptosis and inhibits cell growth in vitro. Second, our results showed that HBV could suppress NFAT5 expression by inducing hypermethylation of the AP1-binding site in the NFAT5 promoter in hepatoma cells. In addition, HBV also inhibited NFAT5 through miR-30e-5p targeted MAP4K4, and miR-30e-5p in turn inhibited HBV replication. Finally, we demonstrated that NFAT5 suppressed DARS2 by directly binding to its promoter. DARS2 was identified as an HCC oncogene that promotes HCC cell cycle progression and inhibits HCC cell apoptosis. Conclusion HBV suppresses NFAT5 through the miR-30e-5p/mitogen-activated protein kinase (MAPK) signaling pathway upstream of NFAT5 and inhibits the NFAT5 to enhance HCC tumorigenesis via the downstream target genes of DARS2.

Background/Aims: The study aimed to investigate the protective effect of curcumin against oxidative stress-induced injury of Parkinson’s disease (PD) through the Wnt/β-catenin signaling pathway in rats. Methods: The successfully established PD rat models and normal healthy rats were randomly assigned into the 6-hydroxydopamine (6-OHDA), the curcumin (Cur) and the control groups. Immunohistochemistry was used to detect the positive expression of tyrosine hydroxylase (TH), dopamine transporter (DAT) and glial fibrillary acidic protein (GFAP). Deutocerebrum primary cells were extracted and classified into the control, 6-OHDA, Cur (5, 10, 15 µmol/L), Dickkopf-1 (DKK-1) and Cur + DKK-1 groups. MTT assays, adhesion tests and TUNEL staining were used to assess cell viability, adhesion and apoptosis, respectively. Western blotting and qRT-PCR were used to examine the protein and mRNA expressions of Wnt3a and β-catenin and the c-myc and cyclinD1 mRNA expressions. Results: TH and DAT expressions in the Cur group were elevated and GFAP was reduced compared with the 6-OHDA group. Curcumin enhanced viability, survival and adhesion and attenuated apoptosis of deutocerebrum primary cells by activating the Wnt/β-catenin signaling pathway. Higher Wnt3a and β-catenin mRNA and protein expressions and c-myc and cyclinD1 mRNA expressions, enhanced superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) contents, decreased malondialdehyde (MDA) content and elevated mitochondrial membrane potential (∆ψm) were found in the 10 and 15 µmol/L Cur groups compared with the 6-OHDA group. However, opposite tendencies were found in the Cur + DKK-1 group compared to the 10 µmol/L Cur group. Conclusion: This study suggests that curcumin could protect against oxidative stress-induced injury in PD rats via the Wnt/β-catenin signaling pathway.

Abstract Toughening of Fe-based amorphous coatings meanwhile maintaining a good corrosion resistance remains challenging. This work reports a novel approach to improve the toughness of a FeCrMoCBY amorphous coating through in-situ formation of amorphous carbon reinforcement without reducing the corrosion resistance. The Fe-based composite coating was prepared by high velocity oxy-fuel (HVOF) thermal spraying using a pre-mixed Fe-based amorphous/nylon-11 polymer feedstock powders. The nylon-11 powders were in-situ carbonized to amorphous carbon phase during thermal spraying process, which homogeneously distributed in the amorphous matrix leading to significant enhancement of toughness of the coating. The mechanical properties, including hardness, impact resistance, bending and fatigue strength, were extensively studied by using a series of mechanical testing techniques. The results revealed that the composite coating reinforced by amorphous carbon phase exhibited enhanced impact resistance and nearly twice-higher fatigue strength than that of the monolithic amorphous coating. The enhancement of impact toughness and fatigue properties is owed to the dumping effect of the soft amorphous carbon phase, which alleviated stress concentration and decreased crack propagation driving force.

AIM: To observe the efficacy of single time intravitreal injection of ranibizumab(IVR)in patients with diabetic macular edema(DME).METHODS: Twenty-nine cases of DME patients who complied with diagnostic criteria for clinically significant macular edema were enrolled in this retrospective study. All the patients receive single dose IVR(0.05mL, 10mg/mL), and no other eye treatments were performed before this operation. All data were recorded before and after injection of 4, 8, and 16wk. Best corrected visual acuity(BCVA), central foveal thickness(CFT), the integrity of the foveal photoreceptor layer on optical coherence tomography were analyzed. The data of photoreceptor integrity and photoreceptor defect group also were recorded and analyzed.RESULTS: BCVA was significantly improved at 4 and 8wk after IVR(P=0.009,0.003), macular edema was relieved, and CFT was significantly lower in the same time(PP=0.001). But the drug action was weakened in 16wk, BCVA was poorer than that in 4 and 8wk(P=0.043,0.019), macular edema recurred CFT increased(PP=0.005). BCVA and CFT value were not statistically significant different between 4 and 8wk(P=0.074,0.420). There was no significant change in BCVA before and after surgery in photoreceptor complete group(P=0.076), but CFT was lower obviously(P=0.001). BCVA and CFT value were better in photoreceptor defect group after IVR in 4wk(PPP=0.015, 0.024). CONCLUSION: Patients with DME treated with ranibizumab obtained great improvements in vision and macular edema in the short term. Macular photoreceptor integrity was closely related to the vision. IVR may also repair the macular photoreceptor damage.

Background. The aim of this study was to investigate the effects of human umbilical cord mesenchymal stem cell activated by curcumin (hUC-MSCs-CUR) on Parkinson’s disease (PD). hUC-MSCs can differentiate into many types of adult tissue cells including dopaminergic (DA) neurons. CUR could protect DA neurons from apoptosis induced by 6-hydroxydopamine (6-OHDA). Therefore, we used the hUC-MSCs activated by CUR for the treatment of PD in an animal model. Methods. The hUC-MSCs-CUR was transplanted into the MPTP-induced PD mouse models via the tail vein. We found that hUC-MSCs-CUR significantly improved the motor ability, increased the tyrosine hydroxylase (TH), dopamine (DA), and Bcl-2 levels, and reduced nitric oxide synthase, Bax, and cleaved caspase 3 expression in PD mice. The supernatant of hUC-MSCs-CUR (CM-CUR) was used to stimulate the SH-SY5Y cellular model of PD; cell proliferation, differentiation, TH, and neuronal-specific marker microtubular-associated protein 2 (MAP2) expressions were examined. Results. Our data showed that CM-CUR significantly promoted cell proliferation and gradually increased TH and MAP2 expression in SH-SY5Y PD cells. The beneficial effects could be associated with significant increase of rough endoplasmic reticulum in the hUC-MSCs-CUR, which secretes many cytokines and growth factors beneficial for PD treatment. Conclusions. Transplantation of hUC-MSCs-CUR could show promise for improving the motor recovery of PD.

An amendment to this paper has been published and can be accessed via the original article.

As a traditional Chinese medicine, Drynariae rhizoma (Kunze ex Mett.) J. Sm. has been used to treat osteoporosis and bone resorption for 2500 years. Based on the previous study and literature references, flavonoids were proved to be the most abundant and main active compounds of Drynariae rhizoma for osteoporosis treatment. In order to make good and rational use of Drynariae rhizoma in future, a rapid, sensitive, and selective ultraperformance liquid chromatography-mass spectrometry (UPLC-MS/MS) method was developed to investigate the pharmacokinetics of eight main flavonoids in rat plasma after oral administration of the Drynariae rhizoma extract, including neoeriocitrin, luteolin-7-O-β-D-glucoside, astragalin, naringin, eriodictyol, luteolin, naringenin, and kaempferol. Plasma samples’ pretreatment involved a solid-phase extraction column. The separation was performed on an ACQUITY UPLCTM BEH C18 column with a gradient mobile-phase system of acetonitrile and 1% acetic acid in water. The detection was performed using a triple quadrupole tandem mass spectrometer equipped with an electrospray ionization interface (ESI) by multiple reaction monitoring (MRM) in the positive ion mode. All calibration curves exhibited good linearity (r2 > 0.9990) over the measured ranges. The intraday and interday precisions (RSD) were within 13.87%, and the accuracy (RE) ranged from −14.57% to −0.25% at three quality control levels. Extraction recovery, matrix effect, and stability were satisfactory. The pharmacokinetic characteristics of the eight flavonoids of interest were clearly elucidated.

AIM: To investigate the morphological changes and the expression of hypoxia-inducible factor-1 alpha(HIF-1α)subunit during embryonic development of rat lens and explore the role of HIF-1α in lens development process. METHODS: Thirty clean pregnant Wistar rats were divided into 6 embryon groups,10-d, 12-d, 14-d, 16-d, 18-d and 20-d embryo. Two embryons were randomized obtained from every pregnant rat. One of the eyeball samples that were parallel to sagittal axis of optic nerve were cut into serial sections, used HE staining and examined by light microscope. Expression of HIF-1α protein in lens was detected by immunohistochemistry. The positive expression of HIF-1α mRNA of the other eyeball samples was detected by real-time PCR.RESULTS:In the 10th d of embryo(E10), the formation of lens vesicle were recognized under the light microscope. In the 12th d of embryo(E12), the anteriorly situated cells and posteriorly situated cells have already differentiated. The anteriorly situated cells were epithelium. In the 14th d of embryo(E14), primary fibers which came from posteriorly situated cells were examined. In the 16th d of embryo(E16), the lens epithelium undergoes extensive proliferation, and enlongate into the secondary fibers. In the 20th d of embryo(E20), the lens was maturation. By immunohistochemistry staining, the HIF-1α was highly expressed in the lens embryonic development. The expression was gradually promoting from E10 to E16, then reducing. The lens epithelium expressed more HIF-1α than fibers. The highest mean density was at E16, the lowest at E20. The difference was significant among of the 6 groups(PP>0.05). The other groups were compared with each other, finding significant difference(PPP>0.05). The other groups were compared with each other, finding significant difference(P<0.05). CONCLUSION:The lens of Wistar rats differentiate from the E10 when the vesicle formed through the embryo phase. The lens is basic mature before birth. The HIF-1α in the lens embryonic development is highly expressed and changeful. The varies of HIF-1α expression is depend upon rat embryo development indicating that HIF-1α might participate in the process of development of rat lens.

This paper presents a theoretical and numerical study on the stress intensity factors for double-edged cracked steel plates strengthened with fiber reinforced polymer (FRP) plates. Based on the stress intensity factor solution for infinite center-cracked steel plates strengthened with FRP plates, expressions of the stress intensity factors were proposed for double-edged cracked steel plates strengthened with FRP plates by introducing two correction factors: β and f. A finite element (FE) simulation was carried out to calculate the stress intensity factors of the steel plate specimens. Numerous combinations of the specimen width, crack length, FRP thickness and Young’s modulus, adhesive thickness, and shear modulus were considered to conduct the parametric investigation. The FE results were used to investigate the main influencing factors of the stress intensity factors and the correction factor, β. The expression of the correction factor, β, was formulated and calibrated based on the FE results. The proposed expressions of the stress intensity factors were a function of the applied stress, the crack length, the ratio between the crack length and the width of the steel plate, the stiffness ratio between the FRP plate and steel plate, the adhesive thickness, and the shear modulus. Finally, the theoretical results and numerical results were compared to validate the proposed expressions.

Escopoletin, a phenolic compound belonging to anthocyanin family shows promising antioxidant activities. In the present study, anti-cancer effects of escopoletin treatment in DU145 cells were investigated. The sulphorhodamine-B staining and annexin V and propidium iodide were respectively used for the analysis of cell viability and death. The results revealed a significantly higher cytotoxicity by escopoletin that caused cell death in DU145 cells. Escopoletin treatment in DU145 cells markedly inhibited cell growth through non-apoptotic cell death and induced significant reactive oxygen species (ROS) production. It also induced G1 cell cycle arrest and cyclin D1 accumulation through the enhanced expression of p21. However, the effect of escopoletin on DU145 cells was reversed by pretreatment with glutathione antioxidant. This suggests that escopoletin induced generation of ROS is responsible for the increased cytotoxicity in DU145 cells. Thus, escopoletin exhibits potential therapeutic efficacy for the treatment of prostate cancer.

After multistage fracturing, the flowback of fracturing fluid will cause two-phase flow through hydraulic fractures in shale gas reservoirs. With the consideration of two-phase flow and desorbed gas transient diffusion in shale gas reservoirs, a two-phase transient flow model of multistage fractured horizontal well in shale gas reservoirs was created. Accurate solution to this flow model is obtained by the use of source function theory, Laplace transform, three-dimensional eigenvalue method, and orthogonal transformation. According to the model’s solution, the bilogarithmic type curves of the two-phase model are illustrated, and the production decline performance under the effects of hydraulic fractures and shale gas reservoir properties are discussed. The result obtained in this paper has important significance to understand pressure response characteristics and production decline law of two-phase flow in shale gas reservoirs. Moreover, it provides the theoretical basis for exploiting this reservoir efficiently.

Structure-specific nucleases play crucial roles in many DNA repair pathways. They must be precisely controlled to ensure optimal repair outcomes; however, mechanisms of their regulation are not fully understood. Here, we report a fission yeast protein, Pxd1, that binds to and regulates two structure-specific nucleases: Rad16XPF-Swi10ERCC1 and Dna2-Cdc24. Strikingly, Pxd1 influences the activities of these two nucleases in opposite ways: It activates the 3' endonuclease activity of Rad16-Swi10 but inhibits the RPA-mediated activation of the 5' endonuclease activity of Dna2. Pxd1 is required for Rad16-Swi10 to function in single-strand annealing, mating-type switching, and the removal of Top1-DNA adducts. Meanwhile, Pxd1 attenuates DNA end resection mediated by the Rqh1-Dna2 pathway. Disabling the Dna2-inhibitory activity of Pxd1 results in enhanced use of a break-distal repeat sequence in single-strand annealing and a greater loss of genetic information. We propose that Pxd1 promotes proper DNA repair by differentially regulating two structure-specific nucleases.

During eukaryotic DNA damage response (DDR), one of the earliest events is the phosphorylation of the C-terminal SQ motif of histone H2AX (H2A in yeasts). In human cells, phosphorylated H2AX (γH2AX) is recognized by MDC1, which serves as a binding platform for the accumulation of a myriad of DDR factors on chromatin regions surrounding DNA lesions. Despite its important role in DDR, no homolog of MDC1 outside of metazoans has been described. Here, we report the characterization of Mdb1, a protein from the fission yeast Schizosaccharomyces pombe, which shares significant sequence homology with human MDC1 in their C-terminal tandem BRCT (tBRCT) domains. We show that in vitro, recombinant Mdb1 protein binds a phosphorylated H2A (γH2A) peptide, and the phospho-specific binding requires two conserved phospho-binding residues in the tBRCT domain of Mdb1. In vivo, Mdb1 forms nuclear foci at DNA double strand breaks (DSBs) induced by the HO endonuclease and ionizing radiation (IR). IR-induced Mdb1 focus formation depends on γH2A and the phospho-binding residues of Mdb1. Deleting the mdb1 gene does not overtly affect DNA damage sensitivity in a wild type background, but alters the DNA damage sensitivity of cells lacking another γH2A binder Crb2. Overexpression of Mdb1 causes severe DNA damage sensitivity in a manner that requires the interaction between Mdb1 and γH2A. During mitosis, Mdb1 localizes to spindles and concentrates at spindle midzones at late mitosis. The spindle midzone localization of Mdb1 requires its phospho-binding residues, but is independent of γH2A. Loss of Mdb1 or mutating its phospho-binding residues makes cells more resistant to the microtubule depolymerizing drug thiabendazole. We propose that Mdb1 performs dual roles in DDR and mitotic spindle regulation.

The molecule of the title compound, C14H9Cl2FN2O, exists in a trans configuration with respect to the methylidene unit and the benzene rings form a dihedral angle of 8.1 (2)°. In the crystal, molecules are linked through N—H...O hydrogen bonds into C(4) chains propagating in [100].

The title arsenatomolybdate, K5[Mo8O24(OH)2(AsO4)]·2H2O, which was obtained hydrothermally, features an [AsMo8O28(OH)2]5− anion, which is formed by two Mo4O14(OH) units that are linked by As in a sandwich-like fashion. The overall symmetry of the anion is m2m. The {Mo4O14(OH)} core is composed of two pairs of confacial bioctahedral {Mo2O9} units with two μ4-O atoms which have been characterized as hydroxyl groups. The anions are further interconnected by potassium cations, forming a three-dimensional network structure with the uncoordinated water molecules occupying the channels. The structure is further stabilized by O—H...O hydrogen bonding.