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Abstract Aims To explore rare and difficult cases of undifferentiated embryonal sarcoma of the liver (UESL) in children in a single centre, summarize the diagnosis and treatment experience and analyse the role of a computer-assisted surgery system (Hisense CAS), thus providing a new global vision and three-dimensional perspective. Methods We retrospectively collected the clinical data including the diagnoses and treatment processes, of children with UESL confirmed by histopathological examination in our hospital from January 2009 to December 2020. The relationship between the tumour volume and important blood vessels and between the liver volume and tumour volume, as well as other three-dimensional characteristics in the reconstructed three-dimensional model were analysed using Hisense CAS. The findings from this analysis can be used to aid in surgical decision-making and preoperative planning. Results Four children—3 girls and 1 boy—with UESL were included in the study. The age at onset ranged from 6 to 8 years. All four children presented with symptoms of abdominal discomfort, and abdominal masses were detected during physical examination. Owing to the wishes of their parents and the possibility that the disease was benign, all four children underwent one-stage radical surgery. For patient 1, a three-dimensional reconstruction was created during the initial diagnosis, which made accurate evaluation and planning of the preoperative procedure challenging. In patient 2, the tumour was located in the middle lobe of the liver and involved the first and second hepatic hilum. For patient 3, the pathological diagnosis of the tumour after surgery was challenging, but eventually, the diagnosis was confirmed through histochemistry and consultation with higher-level hospitals. Patient 4 had a giant tumour, which had a preoperative simulated future liver remnant volume (FLV) that was 21.0% of the total volume of the liver and tumour (TLTV). According to the standard liver volume (SLV) for children, the FLV was 77.0% of the SLV, making surgery feasible. All four children underwent complete resection, and only patient 4 experienced recurrence below the diaphragm 19 months after surgery. Currently, the 3-year overall survival rate is 100%, and the 3-year event-free survival rate is 75%. Conclusion UESL in children is rare, and the key to diagnosis and treatment is complete surgical resection. Through individualized three-dimensional surgical planning, accurate and complete resection of difficult and complex UESL in children can be achieved, leading to a favourable prognosis.

Abstract Patients with advanced gastric and colorectal cancers have limited treatment options. Since mesothelin is highly expressed in these tumour types, we evaluated the therapeutic benefits of anti‐mesothelin hYP218 CAR T cells alone, and in combination with anti‐PD1 antibody, pembrolizumab. GEPIA analysis was performed using human gastric (n = 408) and colon cancer tumours (n = 275) in TCGA database, to evaluate mRNA expression of mesothelin, compared to normal tissues. Mesothelin expression in gastric and colorectal cancer cell‐lines (n = 5) was analysed using flow cytometry. In vitro efficacy by hYP218 CAR T cells was tested by cytotoxicity and cytokine release assays. In vivo anti‐tumour efficacy of hYP218 CAR T cells alone, and in combination with pembrolizumab, was evaluated in NSG mice bearing human gastric (HGC27) and colorectal (SW48) tumour xenografts. Additionally, hYP218 CAR‐T cell persistence, activation and exhaustion marker‐expression were studied. Mesothelin expression was significantly higher in gastric and colon cancer biopsies compared to normal tissues (p

The delicate plateau lake ecosystem has been further damaged by extensive human construction projects, leading to water pollution in Lake Dianchi, China. This serves as a prominent example of urbanization and human interference, drawing global scholarly interest. Restoring Lake Dianchi’s water quality remains a global challenge despite 40 years of treatment, with unclear links to surrounding land development. Therefore, this study constructed a GIS database, combined with 2013–2023 landsat-8/MODIS, Land Use/Land Cover (LULC) remote sensing data and multi-year water quality monitoring, to conduct a multi-scale analysis of the plateau Lake Dianchi and its surrounding land, and implemented it through a Self-Organizing Map (SOM). The classification of lakeshore pollution source clusters was further analyzed through Redundancy Analysis to explore the interaction and future trends between lake water quality and land development in the lakeshore zone. Research indicates the following: (1) According to cluster analysis, water quality in semi-urban lakeside areas (cluster 2) had the highest correlation with lakeside land use, followed by urban areas (cluster 1) and rural areas (cluster 3); (2) Lake water pollution was difficult to improve through the optimization of land development in the lakeshore zone. Combined with the results from (1), although semi-urban areas had a certain impact on water quality, over time, there was a trend of decorrelation between the steady state of water quality pollution and the development of urban construction. This trend indicates that urban development consistently contributes to single pollution sources in water quality; (3) At different scales, the water pollution index in semi-urban areas responded significantly to construction activities, indicating signs of tele-coupling; the response to farmland was complex, while the response to green space was small; (4) In the process of decorrelation between lake water quality and land development, the rate in urban areas (cluster 1) and rural areas (cluster 3) was faster than that in semi-urban lakeside areas (cluster 2). To sum up, it is difficult to restore the water quality of Lake Dianchi through optimizing urban land layout. Meanwhile, it is necessary to further prevent and control the impact of remote pollution sources on the water quality of Lake Dianchi. Protection of the plateau lake environment cannot remain at the optimization level; it should further realize the principles of multi-dimensional governance. This is also the key to addressing the lack of results in Lake Dianchi management for many years.

BackgroundMyosteatosis is a well-established predictor of poor prognosis in many types of cancer, and a decreased Creatinine/Cystatin C ratio (CCR) is a known indicator of unfavorable outcomes in patients with metabolic disorders and cancer. Despite this knowledge, the significance of concurrent CCR and myosteatosis in predicting the prognosis of patients with cholangiocarcinoma (CCA) who undergo radical surgery remains uncertain.MethodData from 757 patients with cholangiocarcinoma who underwent the first radical resection in the Affiliated Hospital of Qingdao University from January 2017 to March 2022 were collected. According to the inclusion and exclusion criteria, 149 patients were finally included in the retrospective study cohort. Various clinicopathological, serological, and radiological data were collected at admission. Myosteatosis was evaluated using sliceOmatic software on computed tomography (CT) images. The study used receiver operating characteristic (ROC) curve analysis to determine the critical value of CCR, which predicts overall survival (OS) based on the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were employed to identify the risk factors associated with OS and RFS confidently.ResultsThe group identified as the myosteatosis cohort consisted of 79 patients with an average age of 64.3 ± 7.8 years. The ROC curve analysis revealed an optimal critical CCR value of 10.834. A low CCR ≤ 10.834 and myosteatosis were found to be associated with poor OS and RFS outcomes (P = 0.022; P = 0.017; P = 0.038; P = 0.030 respectively). Moreover, patients with myosteatosis and a CCR ≤ 10.834 had the worst OS and RFS outcomes (P = 0.035; P = 0.027).ConclusionAfter radical excision in CCA patients, the presence of myosteatosis and CCR had a negative correlation with prognosis. A more accurate prediction of OS and RFS was possible by combining CCR and myosteatosis, compared to CCR alone.

Neuroblastoma is a childhood cancer characterized by the formation of tumors derived from neuroblasts. Identifying the genetic mutations underlying neuroblastoma for genetic counseling and early diagnosis is essential. Thus, this study aimed to screen for pathogenic gene variants within a neuroblastoma family, aiming to contribute to genetic counseling practices. Clinical data was collected from a family affected by neuroblastoma, and peripheral blood DNA samples were obtained from all family members. A combination of whole-exome sequencing and Sanger sequencing was utilized to detect potential gene mutations. Proband 1 and her sister (Proband 2) were diagnosed with neuroblastoma, while their parents and siblings were unaffected. The analysis revealed a novel missense mutation, c.422G > A (p.Arg141Gln), in the PHOX2B gene, which was inherited from the mother. Notably, this mutation represents a previously unreported variant within the PHOX2B gene. Detecting the missense mutation c.422G > A (p.Arg141Gln) in the PHOX2B gene implies its potential pathogenic role within this neuroblastoma family. This finding widens the range of mutations observed in the PHOX2B gene and has important implications for early neuroblastoma diagnosis within this family.

Double-layer Ni-P coatings with low phosphorus content in the inner layer and high phosphorus content in the outer layer and Ni-Mo-P composite coatings are successfully prepared on the surface of AZ91D magnesium alloy by chemical plating process. The microstructures, friction and corrosion resistance of double-layer Ni-P and Ni-Mo-P coatings are studied in comparison. Meanwhile, the deposition and corrosion resistance mechanism for the coatings are investigated. Results convey that both Ni-P and Ni-Mo-P coatings showcase an amorphous structure. The coating possesses denser and more homogeneous structure with the co-doping of Mo. The micro-indentation hardness (859.7 HV) and friction coefficient (0.58) of Ni-Mo-P coatings show that the ternary alloy coating is firmly bonded to the magnesium alloy substrate. Besides, the Ni-Mo-P coatings demonstrate exceptional wear resistance attributed to Mo co-deposition, fostering grain refinement and facilitating the growth of passivation films.

In the process of urbanization, the low effectiveness of urban water governance has been driven by multiple causes. Among them, a perplexing and misunderstood issue has been that stabilization or even enhancement of urban water areas may often conceal detrimental changes in the ecological function of the urban hydrological system. To address this phenomenon, a typical plains river network city is taken as the research object against the background of China's urban development. Specifically, we studied the spatial evolution of the river system in the city of Luohe, China, over the past 30 years. We attempt to measure the impact of urbanization on the Luohe river system through remote sensing techniques across four dimensions: water area, number and class of rivers, and river grid density. The results show that, (1) from 1988 to 2022, the water area fluctuated and even increased slightly, with a rate of change of + 1.46 %. During this period the area of forest decreased, while the area of urbanized land increased. Given the stable area of the hydrological system it is easy to assume the river has not deteriorated in ecological structure and function. However, our further results show that (2) the length and number of rivers have decreased. (3) The river unit density decline rates were 13.89 %, 12.90 %, 11.11 %, 4.17 %, and 8.70 %, respectively, from 1988 to 2022. This indicates a regional simplification of the structure of the network of river systems in the area. (4) Morans’ I for the river unit density over six periods showed a positively correlated, indicating that the degree of concentration of river density decreased year by year, and the significant clustering distance of density grids increased, and the high-density centroid of gravity of the river network consistently shifted from north to southwest over the analysis period. In summary, our analyses showed that the structure of the Luohe river system has changed to few, wide and concentrated channels. Natural river geomorphology has been transformed to channelized and hardened channels, then to concentration into single main channels, with tributaries combined and concentrated into few main linear channels, explaining why smaller rivers system units have been eliminated and lost through attrition.

Introduction: An accurate knowledge of the isomeric yield ratio (IR) induced by the photonuclear reaction is crucial to study the nuclear structure and reaction mechanisms. 165Ho is a good candidate for the investigation of the IR since the Ho target has a natural abundance of 100% and the residual nuclide has a good decay property.Methods: In this study, the photoneutron production of 164m, gHo induced by laser-accelerated electron beams is investigated experimentally. The γ-ray spectra of activated Ho foils are off-line detected. Since the direct transitions from the 164mHo are not successfully observed, we propose to extract the IRs of the 164m, gHo using only the photopeak counts from the ground-state decay.Results: The production yields of 164m, gHo are extracted to be (0.45 ± 0.10) × 106 and (1.48 ± 0.14) × 106 per laser shot, respectively. The resulting IR is obtained to be 0.30 ± 0.08 at the effective γ-ray energy of 12.65 MeV.Discussion: The present data, available experimental data, and TALYS calculations are then compared to examine the role of the excitation energy. It is found that besides the giant dipole resonance, the excitation energy effect also plays a key role in the determination of the IRs.

Hypereutectic high chromium cast iron (HHCCI) coatings were prepared by flux-cored arc welding (FCAW) under 230 °C, 80 °C and 30 °C interlayer temperatures, and an extra liquid nitrogen cooling was used to obtain −125 °C terminal cooling temperature. The microstructure evolution mainly primary carbide (P–C) and matrix, and abrasive wear behavior were evaluated. For natural air cooling, the amount of primary carbide increased, and the size and the mean free path between P–C decreased, with the decrease of the interlayer temperature. Due to the anisotropy in the P–C shape, the volume fraction of P–C, expressed by the area fraction, was significantly affected by the growth orientation. Liquid nitrogen cooling further optimized the morphology of P–C, in terms of the amount, size and distribution. Due to the −125 °C terminal cooling temperature, the martensitic transformation developed in the matrix, showing a body-centered tetragonal structure and exhibiting a Kurjumov-Sachs (K–S) orientation relationship with parent austenite. The linear relationship between wear resistance and P–C was investigated by Pearson's correlation coefficient, and the amount, size and mean free path expressed a strong correlation with wear resistance. Finally, the coating cooled by liquid nitrogen showed the best wear resistance, owing to the excellent morphology of P–C, and the strengthened matrix.

The influence of vertical changes in water depth on emerging pollutants distribution and microbial food web remains elusive. We investigated the influence of vertical transition in water depth on the environmental variables, antibiotics and antibiotic resistomes, and microbial community structures in estuary and marine ecosystems (0–50 m). Stepwise multiple linear regression model showed that among investigated environmental variables, change in water salinity was the most influential factor dictating the fluoroquinolone and macrolides concentrations, while dissolved oxygen and turbidity were the key influencers of sulfonamides and beta-lactam concentrations, respectively. Bacterial and eukaryotic diversity and niche breadth significantly increased with the increasing water depth. Ecosystem food web structure at the bottom depths was more stable than at the middle and surface depths. At the surface depth, the top 5 keystone genera were Cryothecomonas, Syndiniales, Achromobacter, Pseudopirsonia, and Karlodinium. Whereas Eugregarinorida, Neptuniibacter, Mychonastes, Novel_Apicomplexa_Class_1, Aplanochytrium and Dietzia, Halodaphnea, Luminiphilus, Aplanochytrium, Maullinia dominated the top 5 genera at the middle and the bottom depth, respectively. Absolute abundance of antibiotic resistance genes (ARGs) was drastically increased at the surface depth compared with the middle and bottom depths. Abundance of the top 10 ARGs and mobile genetic elements (MGEs) detected including tnpA-05, aadA2-03, mexF, aadA1, intI-1(clinic), qacEdelta1-02, aadA-02, qacEdelta1-01, cmlA1-01, and aadA-01 were amplified at the surface depth. This study demonstrated that ARGs abundance was disproportionate to bacterial diversity, and anthropogenic disturbances, confinement, MGEs, and ecosystem stability play primary roles in the fate of ARGs. The findings of this study also implicate that vertical changes in the water depth on environmental conditions can influence antibiotic concentrations and microbial community dramatically.

Maximizing rice yield potential has always been the focus of high-yield rice cultivation research. For high-yield rice cultivation and breeding, more research into the link between yield and yield components is essential. In this experiment, 38 rice varieties with different yield types and 185 rice varieties as materials were chosen. The relationships between yield and yield components were studied. The regulation effects of total nitrogen application rate (TNAR) on yield and yield components were observed. The results showed that (1) the grain yield of high-yield varieties was 189.3−195.6%, 76.1−77.7%, and 27.0−28.7% higher than that of super-low-yield, low-yield, and medium-yield varieties, respectively. Compared with rice varieties with other yield types, rice varieties with high-yield type have a higher total number of spikelets. (2) The spikelet number per panicle and total number of spikelets were significantly positively linked with grain yield, but significantly negatively correlated with filled grains and grain weight. (3) With an increase in TNAR (0−340 kg ha−1), the panicles, spikelet number per panicle, and total spikelets of rice varieties with different yield types increased gradually, and the filled grains and grain weight decreased gradually. The higher the TNAR, the more obvious the decrease in filled grains and grain weight. The grain yield of rice varieties with different yield types was the highest under the TNAR at 250 kg ha−1. The main factor contributing to its high yield was the substantial increase in total spikelets. The above results showed that increasing the spikelet number per panicle and total spikelets played a material role in improving rice yield.

Nuclear isomers play a key role in the creation of the elements in the universe and potentially have significant applications related to the controlled release of nuclear energy on demand. Particularly, ^{93m}Mo is a good candidate for studying the depletion of nuclear isomers via nuclear excitation by electron capture. Therefore, it is necessary to explore the efficient approach of ^{93m}Mo production. In this paper, we experimentally demonstrate an efficient production of ^{93m}Mo via ^{93}Nb(p,n) reaction induced by an intense laser pulse. Employing the picosecond-duration, 100 J laser pulse, the ^{93m}Mo isomer at 2425 keV (21/2^{+}, T_{1/2}=6.85h) is generated with a high yield of 1.8×10^{6} particles/shot. The resulting peak production efficiency reaches 10^{17} particles/s, which is at least five orders of magnitude higher than that obtained using the classical accelerator. The impacts of the production and destruction of ^{93m}Mo to the astrophysical p-nuclide ^{92}Mo are studied. It is found that the ^{93}Nb(p,n)^{93m}Mo reaction is an important production path of ^{93m}Mo, which could further influence the production of ^{92}Mo. In addition, a direct measurement of the (p,n) reaction rate is proposed using the laser-induced proton beam of which the energies follow the Maxwell-Boltzmann distribution well. It is believed that the laser-induced proton beam opens an avenue for the production of nuclear isomers with high peak efficiency used for the studies of p-nuclei nucleosynthesis.

As a widely cultivated vegetable in China and Southeast Asia, the breeding of non-heading Chinese cabbage (Brassica campestris ssp. chinensis Makino) is widespread; more than 400 varieties have been granted new plant variety rights (PVRs) in China. Distinctness is one of the key requirements for the granting of PVRs, and molecular markers are widely used as a robust supplementary method for similar variety selection in the distinctness test. Although many genome-wide molecular markers have been developed, they have not all been well used in variety identification and tests of distinctness of non-heading Chinese cabbage. In this study, by using 423 non-heading Chinese cabbage varieties collected from different regions of China, 287 simple sequence repeat (SSR) markers were screened for polymorphisms, and 23 core markers were finally selected. The polymorphic information content (PIC) values of the 23 SSR markers ranged from 0.555 to 0.911, with an average of 0.693, and the average number of alleles per marker was 13.65. Using these 23 SSR markers, 418 out of 423 varieties could be distinguished, with a discrimination rate of 99.994%. Field tests indicated that those undistinguished varieties were very similar and could be further distinguished by a few morphological characteristics. According to the clustering results, the 423 varieties could be divided into three groups: pak-choi, caitai, and tacai. The similarity coefficient between the SSR markers and morphological characteristics was moderate (0.53), and the efficiency of variety identification was significantly improved by using a combination of SSR markers and morphological characteristics.

In order to study the effect of the freeze-thaw cycle on the integrity and dynamic mechanical performance of rubber concrete, the wave speed of rubber concrete specimens with 10% rubber volume was measured by a nonmetallic ultrasonic detector. The impact tests were also performed on rubber concrete specimens with different numbers of freeze-thaw cycles (0, 25, 50, 75, 100, and 125) at different impact air pressures (0.3, 0.4, 0.5, and 0.6 MPa) using a 74 mm diameter split Hopkinson pressure bar (SHPB) device, peak stress, ultimate strain dynamic intensity enhancement factor (DIF), and energy absorption effect. The results show that with the increase of freeze-thaw cycles, the wave speed decreases, and the freeze-thaw action will damage the rubber concrete and reduce the longitudinal wave velocity. Under the same freeze-thaw cycles, with the rise of strain rate, the peak stress, limit strain, DIF, and absorbed energy increase, and there is an obvious strain rate effect; under the pressure of 0.6 MPa, the peak stress of 25, 50, 75, 100, and 125 freeze-thaw cycles decreases by 25.1%, 37.1%, 46%, 52.5%, and 54.8%. With the increase of the freeze-thaw cycles, the peak stress of the specimen decreases, and the decrease gradually decreases. After the number of cycles exceeds 100, the stress decrease of the specimen is no longer obvious, the limit strain increases, and the absorbed energy decreases. The freeze-thaw environment significantly reduces the strength and integrity of rubber concrete specimens.

Abstract Background We analyzed the results of a 3-year surveillance study on the epidemiological and clinical characteristics of healthcare associated-infections (HAIs) in elderly inpatients in a large tertiary hospital in China. Methods Real-time surveillance was performed from January 1, 2015 to December 31, 2017. All HAIs were identified by infection control practitioners and doctors. Inpatient data were collected with an automatic surveillance system. Results A total of 134,637 inpatients including 60,332 (44.8%) elderly ≥60 years were included. The overall incidence of HAI was 2.0%. The incidence of HAI in elderly patients was significantly higher than that in non-elderly patients (2.6% vs. 1.5%, χ2 = 202.421, P

AlCoCrFeNiTi high-entropy alloys (HEAs) have attracted much attention because of their excellent mechanical properties. Here, we systemically studied the effects of elements on the microstructure and mechanical properties of AlCoCrFeNiTi HEAs. The results showed that the phase composition and morphology are significantly affected by the elements. With increasing Ti addition, the lattice parameters of the solid solution phase increased slightly, and lattice distortion occurred. Al changes the crystal structure of FCC to BCC and reduces the lattice distortion energy of the alloy. The BCC phase obviously increases with increasing Al content. However, excessive Al, Ti and Cr promote the formation of intermetallic compound phases, while Ni, Fe and Co promote the transformation of the alloy into a solid solution. The properties of AlCoCrFeNiTi HEAs are closely related to their phase composition and morphology. When HEAs consist only of FCC and BCC phases, their ductility and strength are greatly improved. The presence of an intermetallic compound phase in the microstructure can significantly reduce the configurational entropy of adjacent solid solutions, thus reducing the strengthening effect of solid solutions. Additionally, the AlCoCrFeNiTi HEAs with different microstructures show different deformation mechanisms. The deformation of FCC + BCC HEAs with cellular structures is uniform and presents great plasticity and strength. When the cellular-structure HEAs contain equiaxed BCC, thick lamellar BCC/FCC or intermetallic compound phases, cracks tend to occur and propagate along the phase boundary due to the local nonuniform deformation. For AlCoCrFeNiTi HEAs with dendrite structures, after initiation at the phase boundary, the crack does not easily spread to the dendrite FCC phase but causes the interdendritic BCC phase to crack.

Objective: Diagnostic tools in emergency medicine have been widely studied. As a non-invasive and quick tool, ultrasound plays a role in the field of emergency medicine. Thus, it is significant to understand the global scientific output of this topic. An analysis of publications on the use of ultrasound in emergency medicine over the past decade was performed and summarized to track the current hotspots and highlight future directions.Methods: Globally relevant publications on ultrasound in emergency medicine from 2009 to 2020 were extracted from the Web of Science collection database. VOSviewer software and CiteSpace were employed to visualize and predict the trends in the research on the topic.Results: The overall volume of global publications is on the rise; furthermore, the United States published the most publications in this field and had the most citations and H-index. University of California at San Francisco in the United States has most publications in terms of institutions. The American Journal of Emergency Medicine published the most papers related to ultrasound in emergency medicine in terms of journals. Pulmonary embolism was once the main research direction, and importantly, “point-of-care ultrasound” was determined to be a new research hotspot.Conclusion: Altogether, the number of publications on ultrasound in emergency medicine will rise in the future. In addition, the findings reported here shed new light on the major progress on ultrasound in emergency medicine, which may be mutually cooperative in various fields. Moreover, this bibliometric study provides further indications for the topic of “point-of-care ultrasound”.

Background: Rapidly progressive interstitial lung disease (RP-ILD) is a fatal complication of dermatomyositis (DM) and clinically amyopathic DM (CADM). The objective of this study was to evaluate risk markers associated with RP-ILD incidence in patients with DM/CADM and to develop a RP-ILD risk prediction (RRP) model.Methods: The clinical records of 229 patients with DM/CADM from Peking University People's Hospital, and 97 patients from four other independent clinical centers were retrospectively reviewed. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors associated with later RP-ILD incidence to build a risk score model. The concordance index (C-index) and calibration curve were calculated to evaluate the predictive accuracy of the RRP model.Results: A multiparametric RRP model was established based on weighted clinical features, including fever (yes, 5; no, 0), periungual erythema (yes, 6; no, 0), elevated CRP (yes, 5; no, 0), anti-MDA5 antibody (positive, 8; negative, 0), and anti-Ro-52 antibody (positive, 6; negative, 0). Patients were divided into three risk groups according to the RRP total score: low, 0–9; medium, 10–19; high, 20–30. The C-index and calibration curve of the RRP model showed a promising predictive accuracy on the incidence of RP-ILD.Conclusion: The RRP model might promisingly predict the incidence of RP-ILD in DM/CADM patients to guide early individual treatment and further improve the prognosis of DM/CADM patients.

Abstract Background The elderly inpatients are in high risk of suffering health-care associated infection (HAI). The study aimed to analyze the risk factors of health-care associated infection (HAI) in elderly hospitalized patients to prevent it and improve the recovery rate of elderly patients. Methods The study was a Retrospective Cohort Study based on a 3-year surveillance in elderly inpatients in a large tertiary hospital in China. A retrospective review of the elderly inpatients ≥60 years with or without HAI were conducted. Binary multivariable logistic regression was used to evaluate the potential association between HAI and risk factors. Results We investigated a total of 60,332 subjects aged 60 years old or above. The incidence of HAI in elderly was 2.62%. With adjustment for some factors, advanced age, hospital days before HAI, intensive care unit (ICU) admission, use of ventilator, central line catheter or urinary catheter and cerebral hemorrhage, cerebral infarction, brain neoplasms, diabetes mellitus, coronary artery disease, malignant tumor and malignant hematonosis had significantly increased odds ratios (OR) of suffering from HAI compared with the control group but body weight and operation decreased OR. Conclusion Our findings suggested that advanced age, accompanied by some neurological and chronic noncommunicable diseases, hospital days before HAI, ICU admission, and use of devices were risk factors of suffering HAI in the elderly but the body weight and operation were the potential protective factors in this sample.

Prereplicative complex (pre-RC) formation during G1 is fundamental for cell replication. Here the authors report a role for cyclin K in regulating pre-RC formation in mammalian cells by affecting cyclin E1 activity.

Background/Aims: Hyperphosphatemia is common in patients on hemodialysis. The efficacy of lanthanum carbonate (LC) in the treatment of hyperphosphatemia in these patients remains controversial. The objective of this meta-analysis was to evaluate the effect of LC on all-cause mortality in patients on maintenance hemodialysis. Methods: We electronically searched the PubMed, EMBASE, and Cochrane Library databases for all randomized controlled trials (RCTs) comparing LC with other phosphate binders used in adult hemodialysis patients, including calcium carbonate, calcium acetate, and sevelamer. Results: Nine RCTs involving 2813 patients were suitable for inclusion. Our results showed that all-cause mortality was significantly lower in patients who received LC than in those who received standard therapy (odds ratio [OR]: 0.45, 95% confidence interval [CI]: 0.32–0.63, P

Abstract Background Maturity-onset diabetes of the young (MODY) is an early-onset, autosomal dominant form of non-insulin dependent diabetes. Genetic diagnosis of MODY can transform patient management. Earlier data on the genetic predisposition to MODY have come primarily from familial studies in populations of European origin. Methods In this study, we carried out a comprehensive genomic analysis of 289 individuals from India that included 152 clinically diagnosed MODY cases to identify variants in known MODY genes. Further, we have analyzed exome data to identify putative MODY relevant variants in genes previously not implicated in MODY. Functional validation of MODY relevant variants was also performed. Results We found MODY 3 (HNF1A; 7.2%) to be most frequently mutated followed by MODY 12 (ABCC8; 3.3%). They together account for ~ 11% of the cases. In addition to known MODY genes, we report the identification of variants in RFX6, WFS1, AKT2, NKX6–1 that may contribute to development of MODY. Functional assessment of the NKX6–1 variants showed that they are functionally impaired. Conclusions Our findings showed HNF1A and ABCC8 to be the most frequently mutated MODY genes in south India. Further we provide evidence for additional MODY relevant genes, such as NKX6–1, and these require further validation.

Abstract Background The selective lignin-degrading white-rot fungi are regarded to be the best lignin degraders and have been widely used for reducing the saccharification recalcitrance of lignocellulose. However, the biological delignification and conversion of lignocellulose in biorefinery is still limited. It is necessary to develop novel and more efficient bio-delignification systems. Results Physisporinus vitreus relies on a new versatile peroxidase (VP)-based delignification strategy to remove enzymatic recalcitrance of corn stover efficiently, so that saccharification of corn stover was significantly enhanced to 349.1 mg/g biomass (yield of glucose) and 91.5% (hydrolysis yield of cellulose) at 28 days, as high as levels reached by thermochemical treatment. Analysis of the lignin structure using pyrolysis–gas chromatography–mass spectrometry (Py–GC/MS) showed that the total abundance of lignin-derived compounds decreased by 54.0% and revealed a notable demethylation during lignin degradation by P. vitreus. Monomeric and dimeric lignin model compounds were used to confirm the ligninolytic capabilities of extracellular ligninases secreted by P. vitreus. The laccase (Lac) from P. vitreus could not oxidize nonphenolic lignin compounds and polymerized β-O-4 and 5-5′ dimers to precipitate which had a negative effect on the enzymatic hydrolysis of corn stover in vitro. However, the VP from P. vitreus could oxidize both phenolic and nonphenolic lignin model compounds as well as break the β-O-4 and 5-5′ dimers into monomeric compounds, which were measured by high-performance liquid chromatography–electrospray ionization–mass spectrometry (LC–ESI–MS). Moreover, we showed that addition of purified VP in vitro improved the enzymatic hydrolysis of corn stover by 14.1%. Conclusions From the highly efficient system of enzymatic recalcitrance removal by new white-rot fungus, we identified a new delignification strategy based on VP which could oxidize both phenolic and nonphenolic lignin units and break different linkages in lignin. In addition, this is the first evidence that VP could break 5-5′ linkage efficiently in vitro. Moreover, VP improved the enzymatic hydrolysis of corn stover in vitro. The remarkable lignin-degradative potential makes VP attractive for biotechnological applications.

Abstract Background Technological advances have enabled transcriptome characterization of cell types at the single-cell level providing new biological insights. New methods that enable simple yet high-throughput single-cell expression profiling are highly desirable. Results Here we report a novel nanowell-based single-cell RNA sequencing system, ICELL8, which enables processing of thousands of cells per sample. The system employs a 5,184-nanowell-containing microchip to capture ~1,300 single cells and process them. Each nanowell contains preprinted oligonucleotides encoding poly-d(T), a unique well barcode, and a unique molecular identifier. The ICELL8 system uses imaging software to identify nanowells containing viable single cells and only wells with single cells are processed into sequencing libraries. Here, we report the performance and utility of ICELL8 using samples of increasing complexity from cultured cells to mouse solid tissue samples. Our assessment of the system to discriminate between mixed human and mouse cells showed that ICELL8 has a low cell multiplet rate (< 3%) and low cross-cell contamination. We characterized single-cell transcriptomes of more than a thousand cultured human and mouse cells as well as 468 mouse pancreatic islets cells. We were able to identify distinct cell types in pancreatic islets, including alpha, beta, delta and gamma cells. Conclusions Overall, ICELL8 provides efficient and cost-effective single-cell expression profiling of thousands of cells, allowing researchers to decipher single-cell transcriptomes within complex biological samples.

Background/Aims: Cancer stem cells (CSCs) exhibit enhanced proliferative capacity and resistance to chemotherapy; however, choriocarcinoma CSCs have not yet been reported. In this study the human choriocarcinoma cell line JEG-3 was cultured in serum free media, and the characteristics of suspension and parental adherent JEG-3 cells were compared. Methods: Cell proliferation, colony-formation, soft agar clonogenicity, and transwell invasion assays were performed in vitro, and tumor xenografts in BALB/c nude mice were used to evaluate stem cell properties. Results: In serum-supplemented medium (SSM), JEG-3 cells were 4.51 ± 1.71% CD44+, 7.67 ± 2.67% CD133+, and 13.85 ± 2.95% ABCG2+. In serum-free medium (SFM), the expression of these markers increased to 53.08 ± 3.15%, 47.40 ± 2.67%, and 78.70 ± 7.16%, respectively. Moreover, suspension JEG-3 cells exhibited enhanced colony-formation capability as well as invasive and proliferative ability in vitro, alongside enhanced tumorigenic properties in vivo. Suspension JEG-3 cells also exhibited resistance to the chemotherapeutic drugs methotrexate, fluorouracil and etoposide. When seeded in serum supplemented medium, suspension JEG-3 cells readopted an adherent phenotype and continued to differentiate with no significant difference in the morphology between suspension and parent cells. Conclusion: In this study, choriocarcinoma stem-like cells (CSLCs) were isolated from the human choriocarcinoma JEG-3 cell line by SFM culture and characterized.

Although some studies have indicated that climate changes can affect Pinus koraiensis mixed forest, the responses of composition and structure of Pinus koraiensis mixed forests to climatic changes are unknown and the key climatic factors controlling the composition and structure of Pinus koraiensis mixed forest are uncertain.Field survey was conducted in the natural Pinus koraiensis mixed forests along a latitudinal gradient and an elevational gradient in Northeast China. In order to build the mathematical models for simulating the relationships of compositional and structural attributes of the Pinus koraiensis mixed forest with climatic and non-climatic factors, stepwise linear regression analyses were performed, incorporating 14 dependent variables and the linear and quadratic components of 9 factors. All the selected new models were computed under the +2°C and +10% precipitation and +4°C and +10% precipitation scenarios. The Max Temperature of Warmest Month, Mean Temperature of Warmest Quarter and Precipitation of Wettest Month were observed to be key climatic factors controlling the stand densities and total basal areas of Pinus koraiensis mixed forest. Increased summer temperatures and precipitations strongly enhanced the stand densities and total basal areas of broadleaf trees but had little effect on Pinus koraiensis under the +2°C and +10% precipitation scenario and +4°C and +10% precipitation scenario.These results show that the Max Temperature of Warmest Month, Mean Temperature of Warmest Quarter and Precipitation of Wettest Month are key climatic factors which shape the composition and structure of Pinus koraiensis mixed forest. Although the Pinus koraiensis would persist, the current forests dominated by Pinus koraiensis in the region would all shift and become broadleaf-dominated forests due to the dramatic increase of broadleaf trees under the future global warming and increased precipitation.

Germ cell and embryonic stem cells are inextricably linked in many aspects. Remarkably both can generate all somatic cell types in organisms. Yet the molecular regulation accounting for these similarities is not fully understood. Cyclin K was previously thought to associate with CDK9 to regulate gene expression. However, we and others have recently shown that its cognate interacting partners are CDK12 and CDK13 in mammalian cells. We further demonstrated that cyclin K is essential for embryonic stem cell maintenance. In this study, we examined the expression of cyclin K in various murine and human tissues. We found that cyclin K is highly expressed in mammalian testes in a developmentally regulated manner. During neonatal spermatogenesis, cyclin K is highly expressed in gonocytes and spermatogonial stem cells. In adult testes, cyclin K can be detected in spermatogonial stem cells but is absent in differentiating spermatogonia, spermatids and spermatozoa. Interestingly, the strongest expression of cyclin K is detected in primary spermatocytes. In addition, we found that cyclin K is highly expressed in human testicular cancers. Knockdown of cyclin K in a testicular cancer cell line markedly reduces cell proliferation. Collectively, we suggest that cyclin K may be a novel molecular link between germ cell development, cancer development and embryonic stem cell maintenance.

The mesothelin (MSLN) gene encodes a 71 kilodalton (kDa) precursor protein that is processed into megakaryocytic potentiating factor (MPF), a 31 kDa protein that is secreted from the cell, and mature mesothelin (mMSLN), a 40 kDa cell surface protein. The mMSLN binds to CA125, an interaction that has been implicated in the intra-cavitary spread of mesothelioma and ovarian cancer. To better define the role of MPF and mMSLN, growth of the lung cancer cell line A549 was evaluated in immuno-deficient mice with inactivation of the Msln gene. We observed that Msln-/- mice xenografted with intraperitoneal A549 tumors survive significantly long than tumor-bearing Msln+/+ mice. When tumor-bearing Msln-/- mice are supplemented with recombinant MPF (and to a lesser extent mMSLN), most of this survival advantage is lost. These studies demonstrate that MPF and mMSLN have an important role in the growth of lung cancer cells in vivo and raise the possibility that inactivation of MPF may be a useful treatment for lung and other MSLN expressing cancers.

Many theoretical researches predicted that the larch species would decrease drastically in China under future climatic changes. However, responses of the structural and compositional changes of Gmelin larch (Larix gmelinii var. gmelinii) forests to climatic changes have rarely been reported.Field survey was conducted to examine the structures and compositions of natural Gmelin larch forests along a climatic gradient. Stepwise linear regression analyses incorporating linear and quadratic components of climatic and non-climatic factors were performed on the structural and compositional attributes of those natural Gmelin larch forests. Isothermality, Max Temperature of Warmest Month (TempWarmestMonth), Precipitation of Wettest Month (PrecipWettestMonth), Precipitation Seasonality (PrecipSeasonality) and Precipitation of Driest Quarter (PrecipDriestQuarter) were observed to be effective climatic factors in controlling structure and composition of Gmelin larch forests. Isothermality significantly affected total basal area of larch, while TempWarmestMonth, PrecipWettestMonth and PrecipSeasonality significantly affected total basal area of Mongolian pine, and PrecipDriestQuarter significantly affected mean DBH of larch, stand density of larch and total basal area of spruce and fir.The summer and winter temperatures and precipitations are all predicted to increase in future in Northeast China. Our results showed the increase of total basal area of spruce and fir, the suppression of regeneration and the decrease of stand density of larch under increased winter precipitation, and the decrease of total basal area of larch under increased summer temperature in the region of current Gmelin larch forest. Therefore, we suggest that larch would decrease and spruce and fir would increase in the region of future Gmelin larch forest.

Although semi-arid and arid regions account for about 40% of terrestrial surface of the Earth and contain approximately 10% of the global soil organic carbon stock, our understanding of soil organic carbon dynamics in these regions is limited.A field experiment was conducted to compare soil organic carbon dynamics between a perennial grass community dominated by Cleistogenes squarrosa and an adjacent shrub community co-dominated by Reaumuria soongorica and Haloxylon ammodendron, two typical plant life forms in arid ecosystems of saline-alkaline arid regions in northwestern China during the growing season 2010. We found that both fine root biomass and necromass in two life forms varied greatly during the growing season. Annual fine root production in the perennial grasses was 45.6% significantly higher than in the shrubs, and fine root turnover rates were 2.52 and 2.17 yr(-1) for the perennial grasses and the shrubs, respectively. Floor mass was significantly higher in the perennial grasses than in the shrubs due to the decomposition rate of leaf litter in the perennial grasses was 61.8% lower than in the shrubs even though no significance was detected in litterfall production. Soil microbial biomass and activity demonstrated a strong seasonal variation with larger values in May and September and minimum values in the dry month of July. Observed higher soil organic carbon stocks in the perennial grasses (1.32 Kg C m(-2)) than in the shrubs (1.12 Kg C m(-2)) might be attributed to both greater inputs of poor quality litter that is relatively resistant to decay and the lower ability of microorganism to decompose these organic matter.Our results suggest that the perennial grasses might accumulate more soil organic carbon with time than the shrubs because of larger amounts of inputs from litter and slower return of carbon through decomposition.

Tumor microenvironments present significant barriers to penetration by antibodies and immunoconjugates. Tumor microenvironments, however, are difficult to study in vitro. Cells cultured as monolayers exhibit less resistance to therapy than those grown in vivo and an alternative research model more representative of the in vivo tumor is more desirable. SS1P is an immunotoxin composed of the Fv portion of a mesothelin-specific antibody fused to a bacterial toxin that is presently undergoing clinical trials in mesothelioma.Here, we examined how the tumor microenvironment affects the penetration and killing activity of SS1P in a new three-dimensional (3D) spheroid model cultured in vitro using the human mesothelioma cell line (NCI-H226) and two primary cell lines isolated from the ascites of malignant mesothelioma patients. Mesothelioma cells grown as monolayers or as spheroids expressed comparable levels of mesothelin; however, spheroids were at least 100 times less affected by SS1P. To understand this disparity in cytotoxicity, we made fluorescence-labeled SS1P molecules and used confocal microscopy to examine the time course of SS1P penetration within spheroids. The penetration was limited after 4 hours. Interestingly, we found a significant increase in the number of tight junctions in the core area of spheroids by electron microscopy. Expression of E-Cadherin, a protein involved in the assembly and sealing of tight junctions and highly expressed in malignant mesothelioma, was found significantly increased in spheroids as compared to monolayers. Moreover, we found that siRNA silencing and antibody inhibition targeting E-Cadherin could enhance SS1P immunotoxin therapy in vitro.This work is one of the first to investigate immunotoxins in 3D tumor spheroids in vitro. This initial description of an in vitro tumor model may offer a simple and more representative model of in vivo tumors and will allow for further investigations of the microenvironmental effects on drug penetration and tumor cell killing. We believe that the methods developed here may apply to the studies of other tumor-targeting antibodies and immunoconjugates in vitro.