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Abstract [Objective] PEX (pollen extensin-like) gene is involved in controlling pollen development, which plays a crucial role in embryogenesis of pollen microspores and haploid culture. In this study, the authors isolated the CaPEX3 gene from pepper and analyzed its protein structure and expression pattern, which provides a theoretical foundation for further investigation into the function of the CaPEX3 gene. [Methods] CaPEX3 was cloned by PCR, and its protein structure, evolution, and gene regulation were analyzed by bioinformatics. Expression of CaPEX3 in different tissues and pollen of different varieties were detected by qRT-PCR. Pollen viability of different pepper varieties was detected by staining method and their relationship with CaPEX3 expression was analyzed. [Results] The coding region of CaPEX3 was 1 581 bp in length, encoding 526 amino acids, which belongs to the LRX (leucine-rich repeats/extensins) gene family. The protein had phosphorylation and glycosylation sites, signaling peptides, and transmembrane domains. The expression level of CaPEX3 was the highest in flowers, and the gene expression was higher in tissues with high pollen vitality. The regulatory network predicted that CaPEX3 might be involved in the regulation of pollen development through the action of genes related to flower development. [Conclusion] CaPEX3 was specifically expressed in flowers, and a correlation was observed between its expression level and the activity of pollen grains. The analysis of gene expression and the construction of related vectors provided a theoretical foundation and technical support for the subsequent investigation of gene function and mechanism of CaPEX3

Objective To analyze the changes in fertility trends of seasonally and calendar adjusted fertility rate (SAFR) in different countries before and after the COVID-19 pandemic outbreak and investigate the influence factors. Methods Monthly SAFR data of 28 countries during January 2012 and December 2022 were collected in the Human Fertility Database (HFD). The node of December 2020 (9-month delay in gestation from the start of the March 2020 outbreak) was used as the point of division for comparison between the pre- (2012.1-2020.11) and post-pandemic (2020.12-2022.12) periods. Interrupted time series was used to analyze whether fertility rate trends (short-term fluctuations and long-term trends) changed before and after the pandemic in each country. Wilcoxon test was employed to analyze whether pre-pandemic fertility rate, GDP per capita, public health and social measures (PHSM) and unemployment rate were associated with the changes in fertility trends. Results Nineteen out of the 28 countries experienced a short-term decline in fertility rate after the pandemic, which subsequently rebounded. With respect to long-term trends, 2 countries shifted from a declining trend to an increasing trend, 8 countries shifted from an increasing trend to a declining trend, and 6 countries had their SAFR unchanged. The SAFR decline was mainly observed in some of the countries of Central Europe and the Western Mediterranean, while its increase was mainly in Northern and Western Europe. Pre-pandemic SAFR was lower in the countries with no short-term fluctuations in SAFR than those with short-term fluctuations (P=0.041). The countries with declining rate of SAFR had significantly lower pre-pandemic SAFR (P=0.005) and GDP per capita (P=0.027) than the countries with increasing rate of SAFR. No association was found between short-term fluctuations or long-term trends in fertility rate and the PHSM severity index or unemployment rate. Conclusion The COVID-19 pandemic has had varying short- and long-term impacts on SAFR in 28 countries, with the countries with relatively low economic levels and pre-pandemic SAFRs more vulnerable to further blows. The longer-term impacts of the COVID-19 pandemic on the populations of each country deserve further attention. X

Abstract Background Different approach ultrasound-guided superior laryngeal nerve block was used to aid awake intubation, but little is known which approach was superior. We aimed to compare the parasagittal and transverse approaches for ultrasound-guided superior laryngeal nerve block in adult patients undergoing awake intubation. Methods Fifty patients with awake orotracheal intubation were randomized to receive either a parasagittal or transverse ultrasound-guided superior laryngeal nerve block. The primary outcome was patient’s quality of airway anesthesia grade during insertion of the tube into the trachea. The patients’ tube tolerance score after intubation, total procedure time, mean arterial pressure, heart rate, Ramsay sedation score at each time point, incidence of sore throat both 1 h and 24 h after extubation, and hoarseness before intubation, 1 h and 24 h after extubation were documented. Results Patients’ quality of airway anesthesia was significantly better in the parasagittal group than in the transverse group (median grade[IQR], 0 [0–1] vs. 1 [0–1], P = 0.036). Patients in the parasagittal approach group had better tube tolerance scores (median score [IQR],1[1–1] vs. 1 [1–1.5], P = 0.042) and shorter total procedure time (median time [IQR], 113 s [98.5–125.5] vs. 188 s [149.5–260], P

Employing crystal facets to regulate the catalytic properties in electrocatalytic carbon dioxide reduction reaction (eCO2RR) has been well demonstrated on electrocatalysts containing single metals but rarely explored for bimetallic systems. Here, we synthesize ZnSn(OH)6 (ZSO) microcrystals (MCs) with distinct facets and investigate the facet effects in eCO2RR. Electrochemical studies and in situ Fourier Transform Infrared Spectroscopy (in situ-FTIR) reveal that ZSO MCs produce mainly C1 products of HCOOH and CO. The {111} facet of the ZSO MCS exhibits higher selectivity and faradaic efficiency (FE) than that of the {100} facet over a wide range of potentials (−0.9 V ∼ −1.3 V versus RHE). Density Functional Theory (DFT) calculations elucidate that the {111} facet is favorable to the adsorption/activation of CO2 molecules, the formation of intermediate in the rate-determining step, and the desorption of C1 products of CO and HCOOH molecules.

Objective To conduct a network meta-analysis on the effectiveness of first-line immunotherapy on patients with brain metastases from advanced non-small cell lung cancer (NSCLC). Methods Two investigators conducted a computerized search of Pubmed, Embase, Cochrane, and other databases to screen the literature, extract the information, and assess the risk of bias of the included studies. The included clinical trials were statistically analyzed using R (4.1.3) software. For the study outcome indicators OS and PFS, the risk ratios (HRs), and the 95% confidence intervals (CIs) were extracted from the included studies and logarithmically transformed into effect analysis statistics. Results Six randomized controlled trials were finally included, including 327 patients with non-excludable NSCLC brain metastases. Network meta-analysis suggested that PD-1 inhibitor + CTLA-4 was more advantageous than the conventional chemotherapy for enhancing patients’ OS (HR: 0.13, 95%CI: 0.03-0.71), followed by PD-L1 inhibitor (HR: 0.17, 95%CI: 0.04-0.74) and PD-1 inhibitor + chemotherapy (HR: 0.36, 95%CI: 0.2-0.63). PD-1 inhibitor + CTLA-4 was also more advantageous (HR: 0.37, 95%CI: 0.15-0.93) than the conventional chemotherapy for boosting patients’ PFS, followed by PD-L1 inhibitor + chemotherapy (HR: 0.44, 95%CI: 0.29-0.66) and PD-1 inhibitor (HR: 0.48, 95%CI: 0.27-0.86). Conclusion Immune checkpoint inhibitor therapy improves the survival of patients with brain metastases from advanced NSCLC. In particular, the combination of PD-1 inhibitor and CTLA-4 inhibitor show excellent survival benefit.

Abstract Background Targeting ferroptosis has been identified as a promising approach for the development of cancer therapies. Monounsaturated fatty acid (MUFA) is a type of lipid that plays a crucial role in inhibiting ferroptosis. Ficolin 3 (FCN3) is a component of the complement system, serving as a recognition molecule against pathogens in the lectin pathway. Recent studies have reported that FCN3 demonstrates inhibitory effects on the progression of certain tumors. However, whether FCN3 can modulate lipid metabolism and ferroptosis remains largely unknown. Methods Cell viability, BODIPY-C11 staining, and MDA assay were carried out to detect ferroptosis. Primary hepatocellular carcinoma (HCC) and xenograft models were utilized to investigate the effect of FCN3 on the development of HCC in vivo. A metabonomic analysis was conducted to assess alterations in intracellular and HCC intrahepatic lipid levels. Results Our study elucidates a substantial decrease in the expression of FCN3, a component of the complement system, leads to MUFA accumulation in human HCC specimens and thereby significantly promotes ferroptosis resistance. Overexpression of FCN3 efficiently sensitizes HCC cells to ferroptosis, resulting in the inhibition of the oncogenesis and progression of both primary HCC and subcutaneous HCC xenograft. Mechanistically, FCN3 directly binds to the insulin receptor β (IR-β) and its pro-form (pro-IR), inhibiting pro-IR cleavage and IR-β phosphorylation, ultimately resulting in IR-β inactivation. This inactivation of IR-β suppresses the expression of sterol regulatory element binding protein-1c (SREBP1c), which subsequently suppresses the transcription of genes related to de novo lipogenesis (DNL) and lipid desaturation, and consequently downregulates intracellular MUFA levels. Conclusions These findings uncover a novel regulatory mechanism by which FCN3 enhances the sensitivity of HCC cells to ferroptosis, indicating that targeting FCN3-induced ferroptosis is a promising strategy for HCC treatment.

Background & aims: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease characterized by hepatic steatosis, for which there is currently no effective treatment. ACY-1215 is a selective inhibitor of histone deacetylation 6, which has shown therapeutic potential in many tumors, as well as acute liver injury. However, no research about ACY-1215 on NAFLD has been published. Therefore, our study aims to explore the role and mechanism of ACY-1215 in the experimental model of NAFLD, to propose a new treatment strategy for NAFLD. Methods: We established cell and animal models of NAFLD and verified the effect of ACY-1215 on NAFLD. The mechanism of ACY-1215 on NAFLD was preliminarily explored through TMT relative quantitative proteomics, and then we verify the mechanism discovered in the experimental model of NAFLD. Results: ACY-1215 can reduce lipid aggregation, IL-1β, and TNF α mRNA levels in liver cells in vitro. ACY-1215 can reduce the weight gain and steatosis in the liver of the NAFLD mouse model, alleviate the deterioration of liver function, and reduce IL-1βs and TNF α mRNA levels in hepatocytes. TMT relative quantitative proteomics found that ACY-1215 decreased the expression of CD14 in hepatocytes. It was found that ACY-1215 can inhibit the activation level of CD14/TLR4/MyD88/MAPK/NFκB pathway in the NAFLD experimental model. Conclusions: ACY-1215 has a protective effect on the cellular model of NAFLD induced by fatty acids and lipopolysaccharide, as well as the C57BL/6J mouse model induced by a high-fat diet. ACY-1215 may play a protective role by inhibiting CD14/TLR4/MyD88/MAPK/NFκB signal pathway.

The core value of 5G in the field of digital distribution network is to give play to the technical advantages of 5G in ultra-high reliability and low latency, and provide high reliability and low latency communication for the control related business of distribution network. In order to provide a systematic theoretical analysis scheme for the latency and reliability of 5G communication deployment applications in the distribution network, a typical architecture of 5G communication in the distribution network in combination with digital distribution network services was given, the latency model for 5G communication in the distribution network was deeply analyzed. The end-to-end latency analysis for 5G frame structures of four operators in China was conducted with 5G reliability values of 3GPP Rel-15 and Rel-16 through 5G link level simulation. At last, a joint analysis method of time latency and reliability of 5G communication in distribution network was proposed.

The geological model of slope was established by taking the northern end of Baorixile Open-pit Mine as the research object. Based on the hydrothermal coupling theory, the thickness changes of frozen layer under different temperatures were analyzed by COMSOL finite element analysis software. GEO-slope software is used to analyze the slope stability under different thicknesses, revealing the influence law of slope angle change on slope stability, and determining the reasonable slope angle of slope mining in freezing period. The results show that the optimum mining period is from mid-February to mid-March, when the maximum frozen layer thickness is about 3.4 m. Under the action of 3.4 m frozen layer, the stability coefficient of slope in frozen period increases by 7.3% compared with that in non-frozen period. During the freezing period, the reasonable slope angle is 29°, and more than 84,000 t coal can be recovered. A transitional measure of increasing the width of the inner row step to 40 m is proposed to ensure the safety of the transition from freezing period to thawing period.

The objective of this study was to enhance the membrane permeability and anticancer effectiveness of (20S)-protopanaxadiol (PPD) by introducing triphenylphosphonium into the OH group at the C-3 site. This study shows that the anti-proliferation activity of CTPPPPD, with an IC50 value of 1.65 ± 0.10 μmol/L, was 33-times better than that of PPD (with an IC50 value of 54.56 ± 4.56 μmol/L) and superior to that of cisplatin (with an IC50 value of 1.82 ± 0.25 μmol/L) against A549 cells. Biological examinations suggested that CTPPPPD treatment reduced the growth rate of A549 cells, increased the permeability of cell membranes, and changed the structure of chromosomal DNA in a concentration-dependent manner. Annexin V/PI assay and flow cytometry were employed to detect the effect of CTPPPPD on the apoptosis of A549 cells. The results showed that CTPPPPD could induce the apoptosis of A549 cells, and the apoptosis rate of A549 cells treated with 0, 1.0, 2.0, and 4.0 μM of CTPPPPD for 24 h was 0%, 4.9%, 12.7%, and 31.0%, respectively. The integration of transcriptomics and metabolomics provided a systematic and detailed perspective on the induced antitumor mechanisms. A combined analysis of DEGs and DAMs suggested that they were primarily involved in the central carbon metabolism pathway in cancer, as well as the metabolism of aminoacyl-tRNA biosynthesis, alanine, aspartate, and glutamate. Central carbon metabolism in cancer-related genes, i.e., SLC16A3, FGFR3, LDHA, PGAM1, and SLC2A1, significantly reduced after treatment with CTPPPPD. In particular, the dominant mechanism responsible for total antitumor activity may be attributed to perturbations in the PI3K-AKT, MAPK, and P53 pathways. The findings derived from transcriptomics and metabolomics were empirically confirmed through q-PCR and molecular docking. Further analyses revealed that CTPPPPD could be a promising lead for the development of protopanaxadiol for non-small-cell lung cancer (NSCLC) drugs.

To study the relationship of external dump of opencast coal mine impacting on surrounding micrometeorological factors, and then provide the foundation acknowledge for the ecological restoration in mining area, the airflow movement and water distribution around the mine area were regarded as the influencing factors to furtherly explore the ecological effects of the scale and form of the external dump. Taking Hongshaquan open-pit coal mine as an example, using Fluent fluid simulation software, adopting large eddy simulation and component transfer model, the external dump models with different heights and angles were established for simulation. The monthly temperature and dew point data of the area in 2020 were obtained through the regional meteorological station where Hongshaquan open-pit coal mine located, thereby reaching the monthly condensation height of the area. By analyzing the cloud diagrams of air velocity and moisture mass fraction under different conditions, the influence law of different sizes of external dump on the surrounding air flow movement and water distribution was obtained, and compared with the condensation height in the area. The numerical simulation results showed that: with the increasing dump height, the air climbing speed increased slowly, while the maximum climbing height increased, as well as the moisture mass fraction on the windward slope and the dump top ascended. More and more obvious Karman vortex street phenomenon was formed along the leeward slope. The number of vortices increased and the influence range became larger. Both of the airflow velocity and moisture mass fraction in the vortex area increased and reached their maximum values. The increase in the angle of the external dump presented a significant impact on the maximum climb height of the airflow, but showed little impact on the surrounding micrometeorological factors. Under the condition of 360 m limit height, when the external dump Angle reached the critical value of 26°, the maximum airflow climbing height would reach the summer condensation height in this area. Alternatively, under the condition of 22° limit Angle of the outer dump, when the height of the outer dump reached the critical value of 380 m, the maximum climbing height of airflow would reach the summer condensation height of the region, thereby promoting the precipitation around the mining area

ObjectiveTo investigate the clinical application efficacy of hydroxybutyl chitosan as indocyanine green drug carrier in thoracoscopic pulmonary nodule localization. MethodsThe clinical data of 40 patients received preoperative thoracoscopic pulmonary nodule localization in Taikang Xianlin Drum Tower Hospital from January 2022 to October 2022 was retrospectively analyzed. Among them, 20 cases using hydroxybutyl chitosan drug loaded indocyanine green localization were selected as group A, while 20 cases using indocyanine green localization alone were selected as group B. The localization success rate, localization time, surgical resection time, and the incidence of complications were compared between the two groups. ResultsAll 20 nodules in group A were successfully localized, 2 nodules in group B failed to localize due to pleural contamination, resulting in a longer surgical resection time in group B compared to group A ［（42.30±23.75）min vs（21.25±4.39）min, t=3.898, P＜0.05］. There was no statistically significant difference in localization time, chest pain score, and incidence of complications （pulmonary hemorrhage, pneumothorax） between two groups （P＞0.05）. There was no occurrence of hemothorax or hemoptysis in both groups. ConclusionCompared with indocyanine green alone, hydroxybutyl chitosan drug loaded indocyanine green has a higher success rate and shorter surgical resection time in pulmonary nodule localization prior to video-assisted thoracoscopic surgery, with good safety.

Abstract Background Cognitive decline following surgery is a common concern among elderly individuals. Leukocyte telomere length (LTL) can be assessed as a biological clock connected to an individual lifespan. However, the mechanisms causing this inference are still not fully understood. As a result of this, LTL has the potential to be useful as an aging-related biomarker for assessing delayed neurocognitive recovery (dNCR) and related diseases. Methods For this study, 196 individuals over 60 who were scheduled due to major non-cardiac surgical operations attended neuropsychological testing before surgery, followed by additional testing one week later. The finding of dNCR was based on a measured Z-score ≤ -1.96 on two or more separate tests. The frequency of dNCR was presented as the primary outcome of the study. Secondly, we evaluated the association between dNCR and preoperative LTL. Results Overall, 20.4% [40/196; 95% confidence interval (CI), 14.7–26.1%] of patients exhibited dNCR 1-week post-surgery. Longer LTL was identified as a predictor for the onset of early cognitive impairment resulting in postoperative cognitive decline [odds ratio (OR), 14.82; 95% CI, 4.01–54.84; P

Abstract Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that is becoming increasingly prevalent, and it ranges from simple steatosis to cirrhosis. However, there is still a lack of pharmacotherapeutic strategies approved by the Food and Drug Administration, which results in a higher risk of death related to carcinoma and cardiovascular complications. Of note, it is well established that the pathogenesis of NAFLD is tightly associated with whole metabolic dysfunction. Thus, targeting interconnected metabolic conditions could present promising benefits to NAFLD, according to a number of clinical studies. Here, we summarize the metabolic characteristics of the development of NAFLD, including glucose metabolism, lipid metabolism and intestinal metabolism, and provide insight into pharmacological targets. In addition, we present updates on the progresses in the development of pharmacotherapeutic strategies based on metabolic intervention globally, which could lead to new opportunities for NAFLD drug development.

Objective: With the Polygonatum sibiricum as raw material, to develop a process for the combined extraction of Polygonatum sibiricum sponins (PSSs) and polysaccharides (PSPs), and the inhibitory activities of the extract and their complexes (PSSs-PSPs) on α-glucosidase and α-amylase were investigated. Methods: PSSs and PSPs were performed using ultrasound combined with enzymatic hydrolysis. The effects of solid-liquid ratio, ultrasonic time, and ultrasonic temperature on the yield of PSSs, the types of multi-enzymes, the proportion of complex enzymes, enzymolysis time, enzyme dosage, solid-liquid ratio, hot water extraction time, and hot water extraction temperature on the yield of PSPs were investigated, and the Box-Behnken experiment design was used to optimize the extraction of PSSs and PSPs. Results: The optimum extraction parameters of PSSs and PSPs were as follows: ultrasonic temperature was 50 ℃, ultrasonic time was 50 min, ultrasonic solid-liquid ratio was 1∶25 (g/mL), enzymolysis time was 2 h, enzyme dosage was 3 053 U/g, solid-liquid ratio was 1∶25 (g/mL), hot water extraction temperature was 80 ℃, and hot water extraction time was 1 h. Under the control of these conditions, the total yield of PSSs and PSPs was 12.22% and the 27.07%. The inhibitory activities of the extract and their complexes (PSSs-PSPs) on α-glucosidase and α-amylase were verified, and their complexes also have a good inhibitory effect on those enzymes. Conclusion: The process conditions for the efficient synergistic extraction of polygonatin and polysaccharide were obtained after optimization. Compared with a single component, the hypoglycemic activity of their complexes was improved.

In an effort to enhance the efficiency and safety of open-pit mines, this study explores the optimization of end slope road parameters and slope structures, specifically focusing on unmanned driving lanes. A significant aspect of the study is the development of a truck trajectory offset model, which considers the different reaction times between automated sensors and human drivers in adapting to environmental changes. To test these concepts, the study uses numerical simulations to confirm the stability of the proposed end slope designs. Using Victory West Mine No. 1 as a case study, the research determines the optimized width for unmanned driving lanes and the maximum angle for the safe steepening of end slopes. The findings indicate that the optimized unmanned lane width for NTE240 mining dump trucks is 1743 mm, allowing for a 2-degree increase in the slope angle at the south end slope. This optimization leads to a steep mining stripping volume of 3.2735 million m3 and a coal output of 2.49628 million tons, maintaining a stripping ratio of 1.31 m3/t. These results demonstrate that unmanned driving road width optimization not only ensures slope safety but also significantly boosts the economic benefits of steep mining in open-pit mines.

Abstract Background Inhibition of hepatic lipogenesis is widely regarded as an effective treatment for metabolic-associated fatty liver disease (MAFLD), although numerous related drugs have failed to reach clinical application. The goal of this study is to identify a novel small compound that can effectively treat MAFLD. Methods Primary hepatocytes were first exposed to palmitic acid and oleic acid, then treated with compounds prior to high through screening for cellular lipid content. The efficacy of these compounds was measured by Nile Red staining and triglyceride analysis. The potential cellular toxicity caused by these compounds was evaluated by CCK8 assay. qPCR and Western blot were used to determine expression of RNAs and proteins, respectively. The compound was intraperitoneally injected into diet-induced obese (DIO) mice to examine its efficacy in vivo. Results We identified the dimethyl 1-methyl-2-thioxoindoline-3,3-dicarboxylate (TOIDC) as a powerful chemical to reduce cellular lipid with minimal cellular toxicity. When injected intraperitoneally, TOIDC effectively ameliorates MAFLD in DIO mice. Mechanically, TOIDC suppresses de novo lipogenesis through inhibiting sterol regulatory element-binding protein 1 (SREBP1). Conclusions Our findings indicate that TOIDC could be a promising lead compound to develop new drugs to treat MAFLD. Graphical Abstract

In pancreatic cancer, KRAS G12D can trigger pancreatic cancer initiation and development. Rapid tumor growth is often accompanied by excess intracellular reactive oxygen species (ROS) production, which is unfavorable to tumor. However, the regulation of intracellular ROS levels in KRAS mutant pancreatic cancer remains unclear. In this study, we establish BxPC3 stable cell strains expressing KRAS wild type (WT) and G12D mutation and find unchanged ROS levels despite higher glycolysis and proliferation viability in KRAS mutant cells than KRAS WT cells. The key hydrogen sulfide (H 2S)-generating enzyme cystathionine-γ-lyase (CSE) is upregulated in KRAS mutant BxPC3 cells, and its knockdown significantly increases intracellular ROS levels and decreases cell glycolysis and proliferation. Nuclear factor erythroid 2-related factor 2 (Nrf2) is activated by KRAS mutation to promote CSE transcription. An Nrf2 binding site (‒47/‒39 bp) in the CSE promoter is verified. CSE overexpression and the addition of NaHS after Nrf2 knockdown or inhibition by brusatol decreases ROS levels and rescues cell proliferation. Our study reveals the regulatory mechanism of intracellular ROS levels in KRAS mutant pancreatic cancer cells, which provides a potential target for pancreatic cancer therapy.

Hemostasis markers associated with tumors have been widely studied. However, the associations between the coagulation factors and papillary thyroid carcinoma (PTC) prognosis remain unclear. The aim of the present study was to investigate these associations.

Background: Liver injury is a severe liver lesion caused by various etiologies and is one of the main areas of medical research. Panax ginseng C.A. Meyer has traditionally been used as medicine to treat diseases and regulate body functions. Ginsenosides are the main active components of ginseng, and their effects on liver injury have been extensively reported.Methods: Preclinical studies meeting the inclusion criteria were retrieved from PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Wan Fang Data Knowledge Service Platforms. The Stata 17.0 was used to perform the meta-analysis, meta-regression, and subgroup analysis.Results: This meta-analysis included ginsenosides Rb1, Rg1, Rg3, and compound K (CK), in 43 articles. The overall results showed that multiple ginsenosides significantly reduced alanine aminotransferase (ALT) and aspartate aminotransferase (AST), affected oxidative stress-related indicators, such as superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GSH-Px), and catalase (CAT), and reduced levels of inflammatory factor, such as factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6). Additionally, there was a large amount of heterogeneity in the meta-analysis results. Our predefined subgroup analysis shows that the animal species, the type of liver injury model, the duration of treatment, and the administration route may be the sources of some of the heterogeneity.Conclusion: In a word, ginsenosides have good efficacy against liver injury, and their potential mechanisms of action target antioxidant, anti-inflammatory and apoptotic-related pathways. However, the overall methodological quality of our current included studies was low, and more high-quality studies are needed to confirm their effects and mechanisms further.

Objective: To improve the separation efficiency of constricted clam shell and meat. Methods: Taking Lianyungang double-headed razor as the test object, taking frequency, amplitude, and sieve surface inclination as the test factors, and taking the screening efficiency and the ratio of the shell in the meat as the main control targets, a single-factor test was carried out, and the test results were analyzed by Design-Expert software. An analysis of variance was performed to establish a regression model matching the frequency, amplitude, and inclination of the screen surface to the screening efficiency and the ratio of husks in the meat. Using the response surface optimization analysis method, the optimal matching of working parameters for the separation and screening device of constricted razor shell and meat was obtained. Results: When the discharge rate was controlled at 1.2 kg/s, the shell opening rate was controlled at 97%, the frequency was set at 21.6 Hz, the amplitude was set at 3.6 mm, and the screen inclination angle was set at 9°, the screening efficiency of constricted razor was improved, with the screen efficiency of 97.60%, and the shell-on ratio of the meat of 4.52%. Conclusion: The designed vibrating screening device for constricted razor has high screening efficiency and good adaptability, which can meet the preliminary processing requirements.

Objective: To explore the methodology of the evidence-based expert consensus formulation process of traditional Chinese medicine (TCM) nursing taking stroke as an example. Methods: First, preliminary and comprehensive presentation of all stroke-related symptoms and corresponding TCM nursing techniques involved were revealed through bibliometric analysis. Then, selection of stroke symptoms and TCM nursing techniques for inclusion in the consensus was performed using an expert consultation method. Next, we determined the search strategy for a precise evidence search; conducted an evaluation of evidence quality and the grade of the evidence; and completed evidence extraction, evidence analysis, and evidence synthesis based on the included symptoms and TCM nursing techniques. The Delphi method was then applied to determine the strength of each recommendation and the choice of nursing care points by referring to the Grading of Recommendations, Assessment, Development, and Evaluations grid. Finally, we conducted an external expert validation of the Delphi results to form an expert consensus guideline. Results: Through the bibliometric analysis, 22 stroke symptoms and 18 TCM nursing techniques were identified in the literature. Then, after expert consultation, 22 symptoms and 111 pairs of symptoms combined with TCM nursing techniques were selected for the evidence search. Evidence integration yielded 10 stroke symptoms corresponding to 29 bodies of evidence; these 10 symptoms were retained through the Delphi consultation, and recommendation strength results for 26 recommendations were obtained. A total of 9 symptoms were further retained for expert external validation to form 24 recommendations, with a recommendation process score range of 7.64–9.99 points and a more scientific and standardized recommendation-formation process. Conclusion: Owing to the current limited conditions of evidence-based resources for TCM nursing, the present consensus-building process represents only a preliminary exploration of an evidence-based expert consensus for TCM nursing to provide a reference for a more scientific and standardized methodology.

Carbonate cements formed at different stages in sandstone have different mineral compositions, structural characteristics and carbon and oxygen isotope compositions. Carbon stable isotope compositions in cements can be used to indicate the source of carbon in diagenetic fluids, while oxygen stable isotope can be used to estimate the temperature and the source of fluid at the time of crystallization. In order to obtain the carbon and oxygen isotope compositions of different kinds of carbonates in sandstone cements, off-line selective acid extraction method was usually used to extract and test the carbon and oxygen isotope compositions of each carbonate. In order to overcome the shortcomings of the off-line method such as cumbersome process and low efficiency, the temperature and time experiments of the reaction of the mixture sample with 100% phosphoric acid were carried out for the first time by using Gasbench-IRMS with different ratios of quartz, calcite and dolomite mixture samples in this study. When the particle size of the sample is mainly about 63-75 μm, the reaction temperature is 25 ℃ and the reaction time is 2 h, the generated CO2 represents the carbon and oxygen isotopic compositions of calcite. When the reaction temperature is 25 ℃, there is almost no CO2 generated in reaction of dolomite with 100% phosphoric acid for 1 h, and the yield of CO2 is only about 3% for 2 h. The mixture experiment showed that this method is only suitable for the mixture samples with more calcite than dolomite. When the content of calcite is higher than that of dolomite, Gasbench-IRMS can be used to separate calcite and dolomite mixture samples online, and test C and O isotope compositions. The carbon dioxide produced at 25 ℃ for 2 h represents the C and O isotope compositions of calcite. The CO2 gas is removed after another 2 h of reaction, then the carbon dioxide produced at 50 ℃ for 18 h represents δ13C and δ18O of dolomite. The precision of δ13C and δ18O is better than 0.15‰ (1σ) and 0.20‰ (1σ), respectively.

The porosity of the cold sprayed deposits reflects the deformation degree of the sprayed particles and the bonding degree between them, which has an important influence on the deposit properties such as hardness, elastic modulus, friction and wear performance, corrosion resistance, fatigue property and so on. Hence, the porosity of deposits is very important for evaluating the comprehensive properties of deposits and optimizing the cold spraying process parameters, and it is one of the important indicators to evaluate the quality of deposits. Although previous review articles have summarized the influence of cold spraying process on the cold sprayed deposits performance, there were few review articles involving pores in cold sprayed deposits and their control methods. Referring to dozens of articles, this article aimed to review the formation of pores in cold sprayed deposits, the measurement methods, the influence factors and summarize the influence of porosity on the properties of deposits and the measures to reduce the porosity of deposits.

A clear understanding of landslide mechanisms and stability analyses is of great significance for landslide monitoring, prediction, and control. A large-scale end wall landslide occurred and its area reached 47,752 m2 on August 7–20, 2020, in the Manglai open-pit coal mine, China. In this paper, the engineering geological survey, mechanical test, large-deformation finite element numerical method, limit equilibrium method and analytical formula are used to analyze how the groundwater level rise caused this end wall failure and landslide. The engineering geological conditions, hydrogeological conditions, landslide activity signs and physical and mechanical parameter calibration of the sliding mass are investigated in detail and tested. Three-dimensional and two-dimensional numerical models of slopes are established, and an analytical formula calculation method to calculate the factor of safety (FoS) is proposed when sliding cracks are located on the top and toe of a slope. The results indicate that the fault fracture zone, soft strata, continuous heavy rainfall, and groundwater were the main contributors to this landslide. The three-dimensional numerical calculation results are consistent with the deformation and failure process of the slope observed in the field, which shows a retrogressive progressive failure mode. The calculation results of SLOPE/W and the analytical formula are consistent; i.e., when the groundwater level rises to +950, the stability of the end wall reaches the critical stability state. With the passage of time, the creep of the sliding surface accelerates until the entire end wall landslide.

Abstract Redox-responsive drug delivery system emerges as a hopeful platform for tumor treatment. Dihydroartemisinin (DHA) has been investigated as an innovative tumor therapeutic agent. Herein, a DHA dimeric prodrug bridged with disulfide bond as linker (DHA2-SS) has been designed and synthesized. The prepared prodrugs could self-assemble into nanoparticles (SS NPs) with high DHA content (> 90%) and robust stability. These SS NPs display sensitive redox responsive capability and can release DHA under the tumor heterogeneity microenvironment. SS NPs possess preferable antitumor therapeutic activity in contrast with free DHA. Moreover, the possible anti-cancer mechanism of SS NPs was investigated through RNA-seq analysis, bioinformatics and molecular biological method. SS NPs could induce apoptosis via mitochondrial apoptosis pathway, as well as glycolysis inhibition associate with the regulation of PI3K/AKT/HIF-1α signal path, which may offer an underlying therapeutic target for liver cancer. Our study highlights the potential of using redox responsive prodrug nanoparticles to treat cancer, meanwhile provides insights into the anti-cancer mechanism of DHA prodrug. Graphical Abstract

Abstract Background Homocysteine, folate, and vitamin B12 involved in 1-carbon metabolism are associated with cognitive disorders. We sought to investigate the relationships between these factors and delayed neurocognitive recovery (dNCR) after non-cardiac surgery. Methods This was a prospective observational study of patients (n = 175) who were ≥ 60 years of age undergoing non-cardiac surgery. Patients were evaluated preoperatively and for 1 week postoperatively by using neuropsychological tests and were divided into dNCR or non-dNCR groups according to a Z-score ≤ − 1.96 on at least two of the tests. The relationship between the occurrence of dNCR and preoperative levels of homocysteine, folate, and vitamin B12 was analyzed. Univariate and multivariable logistic regression analyses were conducted to identify factors associated with dNCR. Results Delayed neurocognitive recovery was observed in 36 of 175 patients (20.6%; 95% confidence interval [CI], 14.5–26.6%) 1 week postoperatively. Patients who developed dNCR had significantly higher median [interquartile range (IQR)] homocysteine concentrations (12.8 [10.9,14.4] μmol/L vs 10.6 [8.6,14.7] μmol/L; P = 0.02) and lower folate concentrations (5.3 [4.2,7.3] ng/mL vs 6.9 [5.3,9.5] ng/mL; P = 0.01) than those without dNCR. Compared to the lowest tertile, the highest homocysteine tertile predicted dNCR onset (odds ratio [OR], 3.9; 95% CI, 1. 3 to 11.6; P = 0.02), even after adjusting for age, sex, education, and baseline Mini Mental State Examination. Conclusions Elderly patients with high homocysteine levels who underwent general anesthesia for non-cardiac surgery have an increased risk of dNCR. This knowledge could potentially assist in the development of preventative and/or therapeutic measures. Trial registration NCT03084393 ( https://www.clinicaltrials.gov )

Abstract Background Enhanced recovery after surgery (ERAS) protocols were rapidly adopted in many surgeries such as fast-track arthroplasty. The study aimed to investigate the impact of ERAS protocols on the clinical effect of total knee arthroplasty (TKA) via the midvastus approach. Methods A total of 69 patients who underwent primary unilateral TKA via the midvastus approach from October 2018 to June 2019 were enrolled and randomly divided into two groups: ERAS group and Control group. The ERAS protocols were adopted for the ERAS group and consisted of pure juice drinking 2 h before the surgery, optimization of the preoperative anesthesia plan, phased use of tourniquets, and the use of tranexamic acid as well as a drug cocktail. The operative time, first postoperative walking time, first straight leg elevation time, postoperative hospitalization time, visual analogue scale score (VAS score), Hospital for Special Surgery score (HSS score), conventional Knee Society score (KSS), and knee range of motion (ROM) were used to assess the clinical effects in the two groups. All the included patients were followed up for 12 months. Results There were no significant differences in the basic demographic information and operation time between the ERAS and Control groups (P > 0.05). The first postoperative walking time (2.11 ± 0.11 h) and first postoperative straight leg elevation time (6.14 ± 1.73 h) in the ERAS group were significantly earlier than those in the Control group (P

IntroductionSchwannomas are tumors arising from Schwan cells of the neural sheath, which rarely occur in the gastrointestinal tract. The aim of the present study was to analyze the clinicopathological features and treatment outcomes of gastrointestinal schwannomas (GISs).MethodsPatients who were diagnosed with GISs in our hospital from January 2010 to December 2021 were selected. Data about demographic characteristics, clinical symptoms, treatment methods and outcomes, pathological results, and follow-up results were retrospectively collected and analyzed.ResultsA total of 78 patients with 79 GISs were included, the female-to-male ratio was 55:23, and the average age was 52.12 ± 12.26 years. One-third (26/78) of the patients were asymptomatic. A total of 79 GISs were removed, and the average size was 3.63 ± 2.03 cm (range, 0.3–10 cm). As for tumor location, 54 GISs were located in the stomach, 14 in the esophagus, 2 in the duodenum, 6 in the colorectum (4 in the colon and 2 in the rectum), and the other 3 in the small intestine. A total of 23 and 55 patients underwent endoscopic and surgical resections, respectively. Compared with surgical resection, endoscopic resection is associated with a smaller diameter, lower cost, and shorter hospital stay. Pathological results revealed that S100 was positive in all the GISs. No recurrence was noticed during a median follow-up of 45 months (range, 6–148 months).ConclusionGISs are rare gastrointestinal tumors with favorable prognoses, which are most commonly seen in the stomach and diagnosed by pathological findings with immunohistochemical staining. Surgical resection remains the standard method for removing GISs, while endoscopic resection may serve as an alternative method for selected patients with GISs and may be attempted in GISs with a diameter of

The purpose of this study is to explore and determinants the risk management and prevention in credit card business of Malaysian commercial banks. There were five factors derived through the literature and experimental investigation that are affecting the banks due to credit card which are External Fraud Risk, Internal Operational Risk, Credit Risk of Cardholders, Science and Technology and Intermediary Agency Trades Risk. Hence, 250 respondents participated in this study from state of Selangor and Federal Capital Kuala Lumpur. The data was collected and analyzed by SPPS software and it was concluded that that External fraud risk, Internal operational risk, Credit risk of Cardholder, Science and technology are positively correlated with the Credit card business risks of commercial Banks in Malaysia. These papers have highlighted suggestion for future research to develop this study further by considering the data derived from this study by using Delphi Technique

BackgroundThe association between grip strength (GS) and non-alcoholic fatty liver disease (NAFLD) has been reported by recent epidemiological studies, however, the results of these studies are inconsistent. This meta-analysis was conducted to collect all available data and estimate the risk of NAFLD among people with low GS, as well as the risk of low GS among patients with NAFLD.MethodsWe systematically searched several literature databases including PubMed, Web of Science, Cochrane Library, and Embase from inception to March 2022. These observational studies reported the risk of NAFLD among people with low GS and/or the risk of low GS among patients with NAFLD. Qualitative and quantitative information was extracted, statistical heterogeneity was assessed using the I2 test, and potential for publication bias was assessed qualitatively by a visual estimate of a funnel plot and quantitatively by calculation of the Begg’s test and the Egger’s test.ResultsOf the citations, 10 eligible studies involving 76,676 participants met inclusion criteria. The meta-analysis of seven cross-section studies (69,757 participants) showed that people with low GS had increased risk of NAFLD than those with normal GS (summary OR = 3.32, 95% CI: 1.91–5.75). In addition, the meta-analysis of four studies (14,920 participants) reported that the risk of low GS patients with NAFLD was higher than those in normal people (summary OR = 3.31, 95% CI: 2.45–4.47).ConclusionIn this meta-analysis, we demonstrated a strong relationship between low GS and NAFLD. We found an increased risk of NAFLD among people with low GS, and an increased risk of lower GS among NAFLD patients.Systematic review registration[www.crd.york.ac.uk/prospero], identifier [CRD42022334687].

BACKGROUND The measurement of 40Ar content in K-Ar dilution method includes sample melting and releasing gas, gas purification and enrichment, mass spectrometry measurement. With the application of a newly designed double vacuum furnace and gas purification system, the experiment process gradually changes from manual operation to automatic program control, but the parameters are unclear. OBJECTIVES To determine the parameters by conditional experiments and establish a complete measurement method of 40Ar content in K-Ar dilution method. METHODS Parameters were determined by releasing and absorbing an air standard in activated carbon cold finger with different times, melting different types of samples with different temperatures of the double vacuum furnace. The method reliability was verified by K-Ar dating for SK01 sanidine standard. RESULTS The optimal heating release time for activated carbon cold finger was 500s, and the adsorption time was 200s. Using these conditions, the gas produced by the melting in the furnace can be completely transferred and released to avoid isotope fractionation. The corresponding melting temperature was used for different types of samples to ensure that the samples were completely melted and outgassed, the melting temperature of the furnace for clay minerals, biotite, and muscovite should be set to 1400℃, and 1500℃ for amphibole, 1550℃ for basic rock, and 1600℃for potassium feldspar. The K-Ar dating of 10 sets of SK01 sanidine standards showed that the results were consistent with 40Ar-39Ar dating ages. CONCLUSIONS The obtained condition parameters meet the accurate measurement of 40Ar content using the K-Ar dilution method.

In tunnel design and construction, the stability evaluation of tunnel roof wedge usually adopts traditional deterministic analysis methods, which cannot appropriately reflect the spatial variability of rock mass. Based on limit equilibrium method, an efficient approach for evaluating the safety factor integral expression of tunnel roof wedge is presented in this study. This approach considers the influence of spatial variability of rock mass joint friction angle and is validated by universal distinct element code (UDEC). Based on random field method and Monte Carlo simulation (MCS), a generated random field is substituted into the established safety factor integral expression to calculate the safety factor of the tunnel wedge, in which the spatial variability of rock mass joint friction angle is well considered. The failure probability of roof wedge is calculated with consideration of geological and geometry parameters uncertainties. The results indicate that the spatial variability of rock mass joint friction angle has a significant influence on the failure probability of tunnel roof wedge. Ignoring the spatial variability of rock mass mechanical parameters will cause an overestimated failure probability of tunnel roof wedge.

Objective To determine the effect of knocking out zebrafish rpl15 gene by CRISPR/Cas9 editing technique on zebrafish erythroid hematopoietic development. Methods Guide RNA was designed and prepared for rpl15 gene of zebrafish and the mixture of gRNA and Cas9 protein was microinjected into zebrafish zygote at single cell stage. Genomic DNA was extracted after 72 h and the target fragment was amplified by PCR. Editing effect was evaluated by T7E1 restriction enzyme digestion of the PCR products followed by DNA sequencing. Hemoglobin synthesis was analyzed by O-dianisidine staining, neutrophil production was analyzed by neutrophil staining, and the expression of p53, mdm2, hsp70 and hematopoiesis related transcription factor genes was detected by real-time PCR. Results The rpl15 gRNA was successfully prepared and the rpl15 mutants were selected. The results showed that zebrafish rpl15 gene knockout juveniles showed a phenotype of shortened body length, curved tail, smaller head and eyes, and pericardial edema. Hematopoietic lineage staining showed that hemoglobin synthesis in rpl15 mutant was significantly decreased, but neutrophil production was not affected. The mRNA expression levels of rpl15 mutant p53 and mdm2 were significantly increased (P < 0.01, P < 0.05), while those of α-globin, gata 1 and hsp70 were obviously down-regulated (P < 0.01, P < 0.05, P < 0.05). There were no significant differences between the rpl15 mutant and the control group in the mRNA expression levels of hematopoiesis-related transcription factors except erythroid-related ones. Conclusion The rpl15 gene of zebrafish is successfully edited by CRISPR/Cas9 technique, and the mutant produces a phenotype similar to Diamoncl-Blackfan anemia disease. At the same time, it is suggested that p53 and hsp70 may be involved in regulating the formation of mutant phenotype.

Migraine is a common clinical chronic neurovascular disease, which seriously affects the quality of life of patients. Studies have shown that patent foramen ovale (PFO) may be related to migraine, such as transient hypoxemia caused by patent foramen ovale related right ⁃ to ⁃ left shunt, or vasoactive substances passing through an unclosed oval foramen, avoiding lung tissue metabolism and directly entering the arterial system, and contradictory micro ⁃ embolism and other mechanisms may be related to migraines related to patent foramen ovale, especially migraine with aura. The closure of patent foramen ovale can benefit some migraine patients. This article intends to outline the relationship between patent foramen ovale and migraine, and its mechanism, prevention and treatment.