A pan-cancer analysis of anti-proliferative protein family genes for therapeutic targets in cancer.

The recently discovered APRO (anti-proliferative protein) family encodes a group of trans-membrane glycoproteins and includes 6 members: TOB1, TOB2, BTG1, BTG2, BTG3 and BTG4. The APRO family is reportedly associated with the initiation and progression of cancers. This study aims to undertake a comprehensive investigation of the APRO family of proteins as a prognostic biomarker in various human tumors. We performed a pan-cancer analysis of the APRO family based on The Cancer Genome Atlas (TCGA). With the bioinformatics methods, we explored the prognostic value of the APRO family and the correlation between APRO family expression and tumor mutation burden (TMB), microsatellite instability (MSI), drug sensitivity, and immunotherapy in numerous cancers. Our results show that the APRO family was primarily down-regulated in cancer samples. The expression of APRO family members was linked with patient prognosis. In addition, APRO family genes showed significant association with immune infiltrate subtypes, tumor microenvironment, and tumor cell stemness. Finally, our study also demonstrated the relationship between APRO family genes and drug sensitivity. This study provides comprehensive information to understand the APRO family's role as an oncogene and predictor of survival in some tumor types.

Hydrogen co-production via nickel-gold electrocatalysis of water and formaldehyde.

Hydrogen is one of the most promising future energy sources due to its highly efficient energy storage and carbon-free features. However, the energy input required for a hydrogen production protocol is an essential factor affecting its widespread adoption. Water electrolysis for hydrogen production currently serves a vital role in the industrial field, but the high overpotential of the oxygen evolution reaction (OER) dramatically impedes its practical application. The formaldehyde oxidation reaction (FOR) has emerged as a more thermodynamically favorable alternative, and the innovation of compatible electrodes may steer the direction of technological evolution. We have designed Au-Vo-NiO/CC as a catalyst that triggers the electrocatalytic oxidation of formaldehyde, efficiently producing H2 at the ultra-low potential of 0.47 V (vs. RHE) and maintaining long-term stability. Integrated with the cathodic hydrogen evolution reaction (HER), this bipolar H2 production protocol achieves a nearly 100% Faraday efficiency (FE).

[Discussion on the establishment of regional peacetime and wartime combined emergency hospital from the collaborative governance theory].

In the context of the prevention and control for coronavirus disease (COVID), public health emergency governance has been incorporated into an important part of the national governance system, and the "combination of peacetime and wartime" has become an important principle of public health emergency governance. Based on the experience of public health emergency management in large cities and the theory of collaborative governance, this study analyzed the problems and obstacles of general hospitals in coping with emerging respiratory infectious diseases. It is proposed to select general hospitals above tertiary level in the region to build peacetime and wartime combined emergency hospital, establish standardized conversion procedures and strengthen the construction of key elements of integrated emergency hospitals, so as to provide new ideas for the construction of emergency medical system "combination of peacetime and wartime" mechanism and improve the "combination of civilian and combat" public health emergency governance system.

Exosomal circ_0091741 promotes gastric cancer cell autophagy and chemoresistance via the miR-330-3p/TRIM14/Dvl2/Wnt/ß-catenin axis.

The importance of cancer cell-released exosomes in the treatment of various cancers has been well-characterized. The current study aims to examine the potential biological functions of gastric cancer (GC) cell-released exosomes delivering a novel circRNA circ_0091741 in GC and the underlying molecular mechanism. Expression of circ_0091741 was examined in the GC cells, (OXA)-resistant HGC-27 (HGC-27/OXA) cells, and isolated exosomes, after which its downstream miRNA was analyzed. The role and mechanism of the circ_0091741 transmitted by GC cells-derived exosomes in GC cell autophagy and chemoresistance were assessed using various molecular biological methods. A mouse tumor xenograft model was prepared to discern the effect of circ_0091741 on tumorigenesis in vivo. GC cells and their exosomes were characterized by upregulated circ_0091741 expression. circ_0091741 transferred by GC cell-derived exosomes induced the autophagy and OXA resistance of GC cells. circ_0091741 obstructed the binding of miR-330-3p to TRIM14 and increased the expression of TRIM14. TRIM14 could cause activation of the Wnt/ß-catenin signaling pathway by stabilizing Dvl2. By this mechanism, the autophagy and OXA resistance of GC cells were augmented. In vivo assay unfolded that orthotopic implantation of exosomal circ_0091741 overexpressed GC cells into nude mice enhanced tumorigenesis. In conclusion, our study emphasized the promotive role of exosomal circ_0091741 in autophagy and chemoresistance of GC cells, thus laying the basis for the development of novel therapeutic targets for GC treatment.

Detection of consensus genomic regions and candidate genes for quality traits in barley using QTL meta-analysis.

Improving barley grain quality is a major goal in barley breeding. In this study, a total of 35 papers focusing on quantitative trait loci (QTLs) mapping for barley quality traits published since 2000 were collected. Among the 454 QTLs identified in these studies, 349 of them were mapped onto high-density consensus maps, which were used for QTL meta-analysis. Through QTL meta-analysis, the initial QTLs were integrated into 41 meta-QTLs (MQTLs) with an average confidence interval (CI) of 1. 66 cM, which is 88.9% narrower than that of the initial QTLs. Among the 41 identified MQTLs, 25 were subsequently validated in publications using genome-wide association study (GWAS). From these 25 validated MQTLs, ten breeder's MQTLs were selected. Synteny analysis comparing barley and wheat MQTLs revealed orthologous relationships between eight breeder's MQTLs and 45 wheat MQTLs. Additionally, 17 barley homologs associated with rice quality traits were identified within the regions of the breeder's MQTLs through comparative analysis. The findings of this study provide valuable insights for molecular marker-assisted breeding and the identification of candidate genes related to quality traits in barley.

Characteristic research of lower extremity injuries in elderly pedestrians during collisions.

PURPOSE: The aim of this research is to study the trend of pedestrian lower extremity injuries during vehicle-pedestrian collisions. METHODS: In this study, pedestrian's age, collision angle and pedestrian's position are considered influencing factors. Nine experiments using a novel lower extremity mechanical model are designed with the orthogonal experiment method. RESULTS: Under the same collision angle, collisions in the left and right positions caused more serious tibia injuries than the middle position. As for the collision angle, the tibial injury at +45° is more significant than the tibial injury at -45°, and the injury of oblique collisions is slightly greater than that at 0°. Moreover, tibial injury is more sensitive to research variables than femoral injury. When the collision angle and position are changed, the difference ratio of tibia stress is by 483.2% higher than that of femur stress. The axial force and bending moment of the quadriceps tendon in the left-position collision reach peak values, which are 3.83 kN and 165.98 Nm, respectively. The peak quadriceps tendon axial force is captured with the collision angle of -45°, and the peak quadriceps tendon bending moment is obtained with a collision angle of +45°. CONCLUSIONS: The effects of differences in impact position and angle on lower extremity injury in the elderly were analyzed, and the results of this study can be used as a reference for research on lower extremity protection.

Investigation of lower limb injury under different contact stiffness for drivers during frontal crash.

Lower extremity injuries in AIS2+ were the most costly injuries through the statistic analysis of traffic accidents. This study aimed to investigate the response characteristics of the lower limb with different contact stiffness, in which knee cushion and foot cushion were applied. First, a model with a human body and a car was established, and the muscle function was activated in lower extremity of human model. Second, the deceleration pulse with a peak of 186 m/s2 was applied to the car to simulate the frontal crash. Then, four sets of simulations with different contact stiffness are conducted to obtain the lower limb responses. Results indicate that the maximum loading of the left and right legs during the impact wes 1.29 and 1.22 kN, respectively. Meanwhile, the maximum moment were 28.82 and 52.17 Nm, respectively. The maximum stress of lower extremity was 87.35 MPa, and the maximum tibia index was 0.230. It was demonstrated that the injury risk of the femur in the groups with equipment of knee cushion and foot cushion was low, but the injury risk of the tibia increased at the same time. This study could provide a reference to the study of lower limb injury in a frontal impact.

Simultaneous analysis of 20 free amino acids by a single marker combined with an HPLC fingerprint evaluation of Dendrobium huoshanense.

A phenylhexyl isothiocyanate (PITC) precolumn derivatization quantitative analysis of multicomponents by a single marker (QAMS) strategy for the simultaneous analysis of 20 free amino acids (FAA) in Dendrobium huoshanense is proposed. The method was validated by the linearity, limit of detection (LDO), and limit of quantitation (LOQ), recovery, precision, and stability. The results showed that when applying the established method, the LOQ of the FFAs was lower than 1 ng/ml except threonine (1.32 ng) and cysteine (1.16 ng). The QAMS investigation revealed that, using any one of the 20 FAAs as the reference internal standard, no significant differences were observed between the external standard method and the QAMS method for the quantification of FAAs in D. huoshanense by PITC precolumn derivatization [The relative standard deviation (RSD, %) by QAMS and ESM were all below 5%]. HPLC fingerprint investigation combined with similar analysis (the similarity values for S1-S25 were >0.875) and quality fluctuation analysis showed that the cultivation environment might have a great effect on the accumulation of FAAs in D. huoshanense. Overall, our study showed that we might increase the accuracy and scope of the simultaneous quantification of multicomponents using the QAMS technique by being derivatized with a strong UV absorbing group, and QAMS combined with chromatographic fingerprinting can be considered good quality criteria for the quality control of D. huoshanense and may provide analytical technical support for research on Maillard Reaction during the further processing of D. huoshanense.

Thermal Properties and Key Groups Evolution of Low-Temperature Oxidation for Bituminous Coal under Lean-Oxygen Environment.

To deeply explore the spontaneous combustion disaster of coal caused by air leakage and oxygen supply, low-temperature coal oxidation experiments under different oxygen concentrations (DOC) were carried out. Within the coal spontaneous combustion characteristic measurement system, a synchronous thermal analyzer (STA) and a Fourier transform infrared spectrometer (FTIR), the macro laws of gas and heat generation under DOC are analyzed, and the mechanism of the development of coal spontaneous combustion restricted by the lean-oxygen environment is also revealed. The results show that the change of oxygen concentration (OC) does not affect the critical temperature value and gas index change trend, but the lean-oxygen environment reduces the gas concentration and heat production rate very obviously. According to the temperature of the intersection, OC needs to be lowered to less than 5% when preventing spontaneous combustion of coal. The chain thermal reaction lags in the lean-oxygen environment, and the pyrolysis activity is significantly reduced. Meanwhile, the temperature points at T 6 and T 7 show significant differences. Furthermore, with increasing OC and temperature, the content of the aliphatic hydrocarbon presents an overall trend of first increasing, then decreasing, and continuously increasing after stage IV. It is concluded that •OH, aliphatic hydrocarbons, aromatic hydrocarbons, and carboxyl groups are the key groups for the coal spontaneous combustion evolution under DOC. To combine the spontaneous combustion reaction of coal in the DOC environment, the reaction path of the index gas in the macroscopic phenomenon and the reason for the concentration differences are revealed, the mechanism for exotherm varies caused by OC is clarified, and the microscopic inhibition affection on the chain reaction within the lean-oxygen environment is also explored. The results put forward the key groups evolution mechanism under the DOC for coal oxidation, which could provide the technical guidance for the fire prevention and control on coal mines.

The Synergistic Effect of PM2.5 and CO2 Concentrations on Occupant Satisfaction and Work Productivity in a Meeting Room.

High indoor air quality is crucial for the health of human beings. The purpose of this work is to analyze the synergistic effect of particulate matter 2.5 (PM2.5) and carbon dioxide (CO2) concentration on occupant satisfaction and work productivity. This study carried out a real-scale experiments in a meeting room with exposures of up to one hour. Indoor environment parameters, including air temperature, relative humidity, illuminance, and noise level, were controlled at a reasonable level. Twenty-nine young participants were participated in the experiments. Four mental tasks were conducted to quantitatively evaluate the work productivity of occupants and a questionnaire was used to access participants' satisfaction. The Spearman correlation analysis and two-way analysis of variance were applied. It was found that the overall performance declined by 1% for every 10 µg/m3 increase in PM2.5 concentration. Moreover, for every 10% increase in dissatisfaction with air quality, productivity performance decreased by 1.1% or more. It should be noted that a high CO2 concentration (800 ppm) has a stronger negative effect on occupant satisfaction towards air quality than PM2.5 concentration in a non-ventilated room. In order to obtain optimal occupant satisfaction and work productivity, low concentrations of PM2.5 (<50 µg/m3) and CO2 (<700 ppm) are recommended.

Prognostic and clinicopathological significance of pretreatment mean platelet volume in cancer: a meta-analysis.

OBJECTIVE: Our study aimed to evaluate the prognostic and clinicopathological significance of pretreatment mean platelet volume (MPV) on cancer by using meta-analysis of published studies. DESIGN: Meta-analysis. DATA SOURCES: Relevant studies available before 22 December 2019 were identified by searching MEDLINE, EMBASE. ELIGIBILITY CRITERIA: All published studies that assessed the prognostic and clinicopathological significance of pretreatment MPV on cancer were included. DATA EXTRACTION AND SYNTHESIS: Studies were identified and extracted by two reviewers independently. The HR/OR and its 95% CIs of survival outcomes and clinicopathological parameters were calculated. RESULTS: A total of 38 eligible studies (41 subsets) with 9894 patients with cancer were included in the final meta-analysis. MPV level was not significantly associated with both overall survival (HR 0.98, 95% CI 0.84 to 1.14) and disease-free survival (HR 1.22, 95% CI 0.86 to 1.73) of patients with cancer. Neither advanced nor mixed-stage tumour patients showed significant association between MPV and overall survival (HR 1.36, 95% CI 0.96 to 1.94, HR 0.90, 95% CI 0.74 to 1.09). However, high MPV had the strongest relationship with poor overall survival (HR 2.01; 95% CI 1.08 to 3.41) in gastric cancer, followed by pancreatic cancer (HR 1.54; 95% CI 1.31 to 1.82). Whereas in the subgroup using receiver operating characteristic curve method to define cut-off values, low MPV was significantly related to poor overall survival (HR 0.78, 95% CI 0.64 to 0.95). In addition, MPV had no significant association with age (OR 0.96, 95% CI 0.90 to 1.02), sex (OR 1.04, 95% CI 1.00 to 1.09), depth of cancer invasion (OR 0.90, 95% CI 0.77 to 1.04) and tumour stage (OR 0.91, 95% CI 0.78 to 1.07). CONCLUSIONS: Pretreatment MPV level is of no clearly prognostic significance in cancers and no significant association with clinicopathological parameters of patients with cancers.

Clinical significance of cell-free DNA concentration and integrity in serum of gastric cancer patients before and after surgery.

Early onset of gastric cancer (GC) is almost asymptomatic, thereby making early diagnosis and early treatment difficult. Blood samples were taken from 90 GC patients who had not undergone surgery, and from another set of 110 GC patients who had undergone surgery. The control consisted of 90 healthy individuals. Cell-free DNA (cfDNA) and its integrity were assayed using qPCR. The association between cfDNA levels and clinical presentations of GC was analyzed. In addition, cfDNA, carcino-embryonic antigen (CEA), carbohydrate antigen 724 (CA724), carbohydrate antigen 125 (CA125) and carbohydrate antigen 199 (CA199) were subjected to specificity and sensitivity analyses using ROC. The levels of cfDNA of GC patients before surgery were markedly higher than corresponding values in patients with GC after surgery. Post-surgery, the two indices were also significantly higher in GC patients than in the healthy group. The correlation between cfDNA concentration/integrity and gender, age, TNM stage, tumor differentiation, tumor location, neuronspecific enolase (NSE), or alpha fetoprotein (AFP) expression, was not significant in GC patients before or after surgery. However, the correlation between cfDNA and concentrations of CEA/CA125 was significant. The CA199 expression level was significantly correlated with cfDNA integrity. The AUC values of cfDNA concentration and integrity were higher than other tumor markers. Measurement of cfDNA concentration and integrity may be an ideal tumor screening method with higher sensitivity and specificity than traditional tumor biomarkers. The cfDNA concentration and integrity are significantly increased in plasma of GC patients, and may serve as promising indicators for GC.

Comprehensive analysis of differentially expressed lncRNAs as diagnostic and prognostic markers for colorectal cancer.

Colorectal cancer (CRC) is the third most common type of cancer worldwide. Recent studies had revealed the important roles of long non-coding RNAs (lncRNAs) in a variety of human cancers, including CRC. However, the molecular mechanisms associated with CRC remain largely undetermined. In the current study, the GSE21510 dataset was analyzed to identify differentially expressed mRNAs and lncRNAs in CRC samples. The Database for Annotation, Visualization and Integrated Discovery was used to perform Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway bioinformatics analysis. Furthermore, protein-protein interaction networks were constructed to reveal interactions among differentially expressed proteins. Kaplan-Meier analysis was subsequently performed to determine the association between key lncRNA expression and the overall survival of patients with CRC. A total of 107 upregulated lncRNAs and 43 downregulated lncRNAs were identified in CRC. A lncRNA mediated co-expression network was also constructed in CRC. Bioinformatics analysis indicated that lncRNAs were associated with a series of biological processes, including 'xenobiotic glucuronidation', 'rRNA processing', 'sister chromatid cohesion', 'cell proliferation', 'mitotic nuclear division' and 'cell cycle regulation'. Furthermore, a higher expression of small nucleolar RNA host gene 17, tetratricopeptide repeat domain 2B-antisense RNA (AS) 1, erythrocyte membrane protein band 4.1 like 4A-AS2, deleted in lymphocytic leukemia 2, and a lower expression of muscle blind like splicing regulator 1-AS1 and LOC389332 were associated with shorter overall survival time in CRC samples. The present study provides useful information that can be used in the identification of novel biomarkers for CRC.

Quantitative determination of corosolic acid in rat plasma by LC-MS/MS-ESI: application to a pharmacokinetic study.

A sensitive and robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of corosolic acid (CRA) in rat plasma. The plasma samples were prepared by a simple protein precipitation treatment. Chromatographic separation was performed on an Agela MG-C18 column (50 mm × 4.6 mm; i.d., 5 µm) at 30°C. The mobile phase consisting of methanol-10 mM ammonium acetate-formic acid (80:20:0.1, v/v/v; pH=3.8) was delivered with a flow rate of 0.6 ml/min and a running time of 2.5 min. Quantification was performed with positive electrospray ionization (ESI) in the multiple-reaction monitoring (MRM) mode at m/z 490 → m/z 205 for CRA, and m/z 471 → m/z 203 for TEOA (internal standard, IS), respectively. Linearity was evaluated over the concentration range of 1.00-1000 ng/ml with a lower limit of quantification (LLOQ) of 1.00 ng/ml. The validated method was successfully applied to the pharmacokinetic study of CRA after the drug was orally administered in Sprague-Dawley rats.

Simultaneous determination and pharmacokinetic study of stachydrine and leonurine in rat plasma after oral administration of Herba Leonuri extract by LC-MS/MS.

A simple, sensitive and specific method was developed for simultaneous determination of stachydrine and leonurine in rat plasma using diphenhydramine as an internal standard (IS). The separation was performed on an Agilent ZORBAX Eclipse XDB-C(18) column (150mm×4.6mm, i.d., 5µm) at a flow rate of 0.6mL/min, and the mixture of methanol-water containing 0.1% formic acid was used as the mobile phase. The lower limits of quantitation (LLOQs) in rat plasma were 0.895 and 0.287ng/mL for stachydrine and leonurine, respectively. Intra- and inter-day precisions were within 14.4% and accuracies were not more than 3.0%. After single oral administration of 14.5g/kg Herba Leonuri extract, C(max) of stachydrine and leonurine in rat plasma were respectively 1608±267 and 43.3±8.2ng/mL, while T(max) values were respectively 0.75±0.27 and 0.83±0.26h. The results demonstrated that the present LC-MS/MS method was sensitive enough for pharmacokinetic study of stachydrine and leonurine following oral administration of Herba Leonuri extract.

LC-MS/MS determination and pharmacokinetic study of bergenin, the main bioactive component of Bergenia purpurascens after oral administration in rats.

Bergenin, a C-glucoside of 4-O-methyl gallic acid from Bergenia purpurascens, is a naturally antitussive and expectorant agent. A rapid and sensitive liquid chromatography tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the determination of the active component-bergenin, in rat plasma after oral administration of aqueous B. purpurascens extract. The plasma samples were pretreated by protein precipitation with acetonitrile and chromatographic separation was achieved on a Diamonsil® C18 column (150 mm×4.6 mm, 5 µm) with isocratic elution using a mobile phase consisting of water-methanol (30:70, v/v) at a flow rate of 0.6 mL/min. The detection was accomplished by a triple-quadrupole tandem mass spectrometer in multiple-reaction monitoring (MRM) scanning via an electrospray ionization (ESI) source operating in the negative mode. The optimized mass transition ion-pairs (m/z) for quantitation were 327.3/192.0 for bergenin, and 431.1/311.1 for IS. The time for each analysis run was only 3.5 min between injections. The calibration curve exhibited good linearity (r2>0.99) over a range of 1.00-2000 ng/mL for bergenin. The lower limit of quantitation (LLOQ) was 1.00 ng/mL. The intra- and inter-day precisions were no more than 11.8%, and relative errors (RE) were within the range of 0.0-4.4%. The validated method was successfully applied to investigate the pharmacokinetics of bergenin after oral administration of B. purpurascens extract in rats.

Simultaneous determination of 5 major bioactive components in hugu capsule by HPLC-DAD.

OBJECTIVE: To develop a qualitative and quantitative determination of multiple components for quality control of Hugu Capsule, a composite prescription in TCM. METHODS: HPLC analysis was performed on a Kromasil C18 column (5.0 microm, 250 mm x 4.6 mm) by gradient elution with methanol-acetonitrile-1% glacial acetic acid as the mobile phase at a flow-rate of 0.8 mL/min,the detection wavelengths were set at 270, 283, 320 and 325 nm at the temperature of 30 degrees C. RESULTS: Five components: chlorogenic acid, tetrahydroxy stilbene glucoside, ferulaic acid, naringin and icariin were simultaneously analyzed in this study. The calibration curves were exhibited linear regressions of at least r > 0.9992. The injection precision,the intra-day precisions and the analysis repeatability were evaluated with the RSD values were all less than 5%. The mean recoveries of the five components were ranged from 97.4% to 99.4%, and RSD values all were less than 1.72%. CONCLUSION: This method is found to be convenient, fast, accurate, and is applicable to analyze the multi-constituents in Hugu Capsule.

Dispersion-optimized optical fiber for high-speed long-haul dense wavelength division multiplexing transmission.

Four non-zero-dispersion-shifted fibers with almost the same large effective area (A(eff)) and optimized dispersion properties are realized by novel index profile designing and modified vapor axial deposition and modified chemical vapor deposition processes. An A(eff) of greater than 71 µm(2) is obtained for the designed fibers. Three of the developed fibers with positive dispersion are improved by reducing the 1550 nm dispersion slope from 0.072 ps/nm(2)/km to 0.063 ps/nm(2)/km or 0.05 ps/nm(2)/km, increasing the 1550 nm dispersion from 4.972 ps/nm/km to 5.679 ps/nm/km or 7.776 ps/nm/km, and shifting the zero-dispersion wavelength from 1500 nm to 1450 nm. One of these fibers is in good agreement with G655D and G.656 fibers simultaneously, and another one with G655E and G.656 fibers; both fibers are beneficial to high-bit long-haul dense wavelength division multiplexing systems over S-, C-, and L-bands. The fourth developed fiber with negative dispersion is also improved by reducing the 1550 nm dispersion slope from 0.12 ps/nm(2)/km to 0.085 ps/nm(2)/km, increasing the 1550 nm dispersion from -4 ps/nm/km to -6.016 ps/nm/km, providing facilities for a submarine transmission system. Experimental measurements indicate that the developed fibers all have excellent optical transmission and good macrobending and splice performances.