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Abstract China ranks 160 out of 180 countries in terms of ecological efficiency, with an EPI score of 28.40 and a 10-year average change in score of 11.40. This article examines the impact of green finance and China’s natural resources on regional ecological efficiency using the Tobit regression model. The study uses the average yearly exchange rate to normalize dollar-related values and GDP to 2012 RMB using the price deflator. Variables used as explanatory tools include green financing, the availability of natural resources, and regional eco-efficiency. The results of the study imply that natural resources in eastern region of China are better managed as and have avoided the resource curse as compared to central and western regions. Resources temporarily support area economic and social growth. However, resource agglomeration locks many elements in the resource industry and degrades regional industrial development, generating environmental and social difficulties that may hinder regional economic progress. Given that Foreign Direct Investment (FDI) increases regional eco-efficiency after accounting for adjustment. The FDI positively correlated with ecological efficiency in the east zone, while central and western zones have negative correlations. The industrial development of the nation negatively impacts ecological efficiency in the East, Midwest, and West regions. Western results are distinctive, with ecological efficiency and regional economic growth frequently going hand in hand.

The aim of this study is to assess the impact of serum magnesium (Mg) levels on prognostic outcomes in patients with non-small cell lung cancer (NSCLC) undergoing treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). A cohort comprising 91 patients with NSCLC with epidermal growth factor receptor mutations received EGFR-TKI therapy. Assessments of liver and kidney function and electrolyte levels were conducted before treatment initiation and after completing two cycles of EGFR-TKI therapy. Data on variables such as age, gender, presence of distant metastasis, smoking history, other therapeutic interventions, and the specific TKI used were collected for analysis. Cox regression analysis revealed that patients with higher Mg levels prior to EGFR-TKI therapy had significantly longer progression-free survival (PFS) and overall survival (OS). Elevated Mg levels remained predictive of PFS and OS after two cycles of EGFR-TKI therapy. Multiple regression analysis confirmed these findings. Additionally, it was observed that smokers might represent a unique population, demonstrating a correlation between OS and Mg levels. Our findings indicate that serum Mg level is a prognostic factor in patients with NSCLC undergoing EGFR-TKI therapy. This may provide new insights into the underlying mechanisms of EGFR-TKI therapy related to electrolyte balance.

Objective: To Prepared of β-Cyclodextrin inclusion complex with Foeniculum vulgare（fennel） volatile ooil and study on its sstructural characterization and stability. Methods: Based on the inclusion rate, the inclusion yield and the content of trans-anethole in the inclusion compound, the comprehensive evaluation index was established, and the effects of the ratio of fennel volatile oil to β-cyclodextrin, inclusion temperature and inclusion time on it were explored. The preparation process was optimized by orthogonal test. It was characterized by scanning electron microscopy, thin layer chromatography, Fourier infrared spectroscopy and differential scanning calorimetry. Finally, the stability of the inclusion compound was investigated by light, high temperature and high humidity tests. Results: The optimum conditions obtained by saturated aqueous solution method were as follows: the ratio of volatile oil to β-cyclodextrin was 1∶8 (mL/g), the inclusion temperature was 40 ℃, the inclusion time was 60 min. Under these conditions, the inclusion rate of fennel volatile oil inclusion compound was 96.90%, the inclusion yield was 93. 61%, the content of trans-anethole was 6.81%, and the comprehensive score was 99.68. The inclusion compound was white powder with loose texture and good inclusion effect. The inclusion compound was characterized by scanning electron microscopy, thin layer chromatography, Fourier infrared spectroscopy and differential scanning calorimetry. Its stability was good within 5 days of illumination (4 000 lx), volatile components in the inclusion compound were easy to lose at high temperature (60 ℃) for a long time, and it would deliquesce and agglomerate when the relative humidity was more than 75%. Under the conditions of long illumination time, high temperature and high humidity, the inclusion rate and trans-anethole content were obviously reduced. Conclusion: The inclusion rate and inclusion yield of the above-mentioned optimal inclusion process are high, and the process is stable. When stored in a dry and sealed environment at room temperature, the β-cyclodextrin inclusion compound of fennel volatile oil has certain stability compared with the volatile oil.

Abstract Background There are emerging clinical evidence for umbilical cord blood mononuclear cells (UCBMNCs) intervention to improve preterm complications. The first critical step in cell therapy is to obtain high-quality cells. This retrospective study aimed to investigate the quantity and quality of UCBMNCs from very preterm infants (VPIs) for the purpose of autologous cell therapy in prevention and treatment of preterm complications. Methods Very preterm infants (VPIs) born in Guangdong Women and Children Hospital from January 1, 2017, to December 8, 2022, from whom cord blood was successfully collected and separated for public or private banking, were enrolled. The UCBMNCs characters from route cord blood tests performed in cord blood bank, impact of perinatal factors on UCBMNCs, the relationship between UCBMNCs characteristics and preterm outcomes, and the correlation of UCBMNCs characteristics and peripheral blood cells in VPIs were analyzed. Results Totally, 89 VPIs underwent UCB collection and processing successfully. The median cell number post processing was 2.6 × 108. To infuse a dose of 5 × 107 cells/kg, only 3.4% of infants required a volume of more than 20 mL/kg, which exceeded the maximum safe volume limit for VPIs. However, when infusing 10 × 107 cells/kg, 25.8% of infants required a volume of more than 20 ml/kg volume. Antenatal glucocorticoids use and preeclampsia was associated with lower original UCBMNCs concentration. Both CD34+ hematopoietic stem cells (HSC) frequency and colony forming unit - granulocyte and macrophage (CFU-GM) number correlated negatively with gestational age (GA). UCBMNCs characters had no significant effect on preterm outcomes, whereas a significant positive correlation was observed between UCBMNCs concentration and total white blood cell, neutrophil, lymphocyte and PLT counts in peripheral blood. Conclusion UCBMNCs collected from VPIs was feasible for autologous cell therapy in improving preterm complications. Setting the infusion dose of 5 × 107 cells/kg guaranteed a safe infusion volume in more than 95% of the targeted infants. UCBMNCs characters did not affect preterm complications; however, the effect of UCBMNCs concentration on peripheral blood classification count should be considered when evaluating the immunomodulation of UCBMNCs transfusion.

This research identified four amino acid residues (Leu174, Asn297, Tyr301, and Gln291) that contribute to substrate recognition by the high-affinity glucose transporter Xltr1p from Trichoderma reesei. Potential hotspots affecting substrate specificity were selected through homology modeling, evolutionary conservation analyses, and substrate-docking modeling of Xltr1p. Variants carrying mutations at these hotspots were subsequently obtained via in silico screening. Replacement of Leu174 or Asn297 in Xltr1p with alanine resulted in loss of hexose transport activity, indicating that Leu174 and Asn297 play essential roles in hexose transport. The Y301W variant exhibited accelerated mannose transport, but lost galactose transport capacity, and mutation of Gln291 to alanine greatly accelerated mannose transport. These results suggest that amino acids located in transmembrane α-helix 7 (Asn297, Tyr301, and Gln291) play critical roles in substrate recognition by the hexose transporter Xltr1p. Our results will help expand the potential applications of this transporter and provide insights into the mechanisms underlying its function and specificity.

General anesthesia, as a commonly used medical intervention, has been widely applied during surgical procedures to ensure rapid loss of consciousness and pain relief for patients. However, recent research suggests that general anesthesia may be associated with the occurrence of perioperative neurocognitive disorder (PND). PND is characterized by a decline in cognitive function after surgery, including impairments in attention, memory, learning, and executive functions. With the increasing trend of population aging, the burden of PND on patients and society’s health and economy is becoming more evident. Currently, the clinical consensus tends to believe that peripheral inflammation is involved in the pathogenesis of PND, providing strong support for further investigating the mechanisms and prevention of PND.

Abstract Background Glioblastoma (GBM) is the most common brain tumor with the worst prognosis. Temozolomide is the only first-line drug for GBM. Unfortunately, the resistance issue is a classic problem. Therefore, it is essential to develop new drugs to treat GBM. As an oncogene, Skp2 is involved in the pathogenesis of various cancers including GBM. In this study, we investigated the anticancer effect of AAA237 on human glioblastoma cells and its underlying mechanism. Methods CCK-8 assay was conducted to evaluate IC50 values of AAA237 at 48, and 72 h, respectively. The Cellular Thermal Shift Assay (CETSA) was employed to ascertain the status of Skp2 as an intrinsic target of AAA237 inside the cellular milieu. The EdU-DNA synthesis test, Soft-Agar assay and Matrigel assay were performed to check the suppressive effects of AAA237 on cell growth. To identify the migration and invasion ability of GBM cells, transwell assay was conducted. RT-qPCR and Western Blot were employed to verify the level of BNIP3. The mRFP-GFP-LC3 indicator system was utilized to assess alterations in autophagy flux and investigate the impact of AAA237 on the dynamic fusion process between autophagosomes and lysosomes. To investigate the effect of compound AAA237 on tumor growth in vivo, LN229 cells were injected into the brains of mice in an orthotopic model. Results AAA237 could inhibit the growth of GBM cells in vitro. AAA237 could bind to Skp2 and inhibit Skp2 expression and the degradation of p21 and p27. In a dose-dependent manner, AAA237 demonstrated the ability to inhibit colony formation, migration, and invasion of GBM cells. AAA237 treatment could upregulate BNIP3 as the hub gene and therefore induce BNIP3-dependent autophagy through the mTOR pathway whereas 3-MA can somewhat reverse this process. In vivo, the administration of AAA237 effectively suppressed the development of glioma tumors with no side effects. Conclusion Compound AAA237, a novel Skp2 inhibitor, inhibited colony formation, migration and invasion of GBM cells in a dose-dependent manner and time-dependent manner through upregulating BNIP3 as the hub gene and induced BNIP3-dependent autophagy through the mTOR pathway therefore it might be a viable therapeutic drug for the management of GBM. Graphical Abstract

Abstract Dyes and heavy metals pollute the environment. Biochar-based hydrogel is an excellent adsorbent, but the competitive adsorption mechanism associated with the removal of pollutants using biochar is yet to be understood in detail. Biochar was prepared following the process of high-temperature lysis of marine green tide (Enteromorpha prolifera). The prepared biochar was cross-linked with water-soluble chitosan and compounded with nano-Fe3O4 to synthesize magnetically-modified Enteromorpha prolifera-based biochar hydrogel (MM-EBC-HD). The competitive removal performance of the hydrogel was studied, and the pollutant removal mechanism was analyzed against a binary system consisting of common environmental pollutants (methyl orange [MO] and hexavalent chromium [Cr (VI)]. The physical and chemical properties of the composites were studied before and after contaminant removal, and the associated pollutant removal mechanisms were analyzed by SEM, EDS, FTIR, XRD, and XPS techniques. The effects of pH, temperature and initial pollutant concentration on the adsorption performance of the materials were examined. The maximum adsorption of MO on MM-EBC-HD was 71.18 mg g−1, and adsorption equilibrium was attained at approximately 60 min. Electrostatic forces, hydrophobic bonds, and hydrogen bonds were exploited for MO adsorption. And the maximum adsorption amount of Cr (VI) was recorded to be 115.41 mg g−1, and equilibrium was attained in approximately 10 min. Electrostatic and ion exchange effects were exploited to adsorb Cr (VI) efficiently. The MO and Cr (VI) adsorption processes could be explained by the second-order kinetic model and Langmuir adsorption isotherms, respectively. The adsorption performance recorded for the binary adsorption system was poorer than that recorded for the single adsorption system for both pollutants. MO and Cr (VI) adsorption decreased from 74.88% to 47.65% and from 62.33% to 42.4%, respectively. Competition between MO and Cr (VI) in the dual system can be attributed to the presence of amino and hydroxyl groups. The MO–Cr complex, which was more compact in structure than a single contaminant, was formed, allowing few reactive groups to be exposed to the surface of the hydrogel. Additionally, MM-EBC-HD nanocomposites presented a recovery rate of 87% after 5 cycles and thus could be used to avoid adsorbents-caused environmental hazards. Graphical Abstract

Abstract Thermochromic smart windows have gained increasing popularity in light modulation and energy management in buildings. However, the fabrication of flexible thermochromic smart windows with high luminous transmittance (Tlum), tailorable critical temperature (τc), strong solar modulation ability (ΔTsol), and long‐term durability remains a huge challenge. In this study, hydrogel‐based thermochromic smart windows are fabricated by sandwiching thermochromic hydrogels of polyallylamine hydrochloride, polyacrylic acid, and carbonized polymer dots (CPDs) complexes between two pieces of transparent substrates. Benefiting from the incorporation of nanosized CPDs, the thermochromic hydrogel has an ultrahigh Tlum of ~98.7%, a desirable τc of ~24.2 °C, a ΔTsol of ~89.3% and a rapid transition time of ~3 s from opaque state to transparent state. Moreover, the thermochromic hydrogel exhibits excellent anti‐freezing ability, tight adhesion toward various substrates, and excellent self‐healing capability. The self‐healing capability enables the fabrication of large‐area smart windows by welding multiple hydrogel pieces. The smart windows retain their original thermochromic properties after being stored under ambient conditions for at least 147 days or undergoing 10,000 uninterrupted heating/cooling cycles. The model houses with smart windows can achieve a temperature reduction of 9.2 °C, demonstrating the excellent indoor temperature modulation performance of the smart windows.

In order to study the damage form and mechanism of coal mine roof, the stress distribution state in the stacked beam model was analyzed by using the stacked beam model and introducing the stress potential function; the model was simplified by using horizontal and vertical joints all over, and the damage range of coal seam roof was analyzed by combining Mohr-Coulomb strength criterion. The results show that the main factors of coal seam roof damage are layer separation caused by horizontal joints and fractures caused by vertical joints; the separation failure zone has a “hyperbolic-like” distribution with steep top and flat bottom, and the fracture damage zone has an “arch-shaped” distribution; with the increase of inter-bed friction coefficient with the increase of the interlayer friction coefficient, the height and width of the layer separation damage zone of the top plate decrease significantly, while the increase of the elastic modulus has less effect on the damage range of the top plate; meanwhile, with the increase of the indirect roof, the fracture height of the top plate gradually decreases and the layer separation width gradually increases.

Objective: Intraventricular hemorrhage (IVH) causes morbidity and mortality in preterm infants and prenatal exposure to inflammation contributes to brain injury. Moreover, prenatal exposure to severe inflammation increases the risk of IVH in preterm neonates. The current study investigated whether intrauterine exposure to inflammation affects cerebral angiogenesis and its underlying mechanisms. Methods: Wnt5a, flt1, and vascular endothelial growth factor (VEGF)-A levels in cord blood serum (stored in a bio-bank) of the enrolled patients were measured via enzyme-linked immunosorbent assay. A preterm prenatal inflammation exposure model was established in rats by intraperitoneal injection intraperitoneally during pregnancy. Angiogenesis of cerebral tissue was analyzed using immunohistochemistry. Wnt5a, flt1, and VEGF-A expression levels were measured via immunohistochemistry, immunofluorescence, or western blotting. The correlation between Wnt5a and flt1 expression and the cerebral vessel area was also analyzed. Results: The Wnt5a and flt1 levels in the cord blood serum were significantly higher in the amnionitis group than in the non-amnionitis group. The VEGF-A level in the cord blood serum was significantly lower in the amnionitis group. In the rat model, preterm rats in the prenatal inflammation group exhibited increased microglial cell infiltration and decreased vessel area and diameter in the cerebral tissue compared to the control group. Wnt5a was located in microglial cells, and Wnt5a and flt1 expression in brain tissue significantly increased after prenatal lipopolysaccharide (LPS) exposure. VEGF-A expression declined after prenatal LPS exposure. The cerebral vessel area was negatively correlated with Wnt5a and flt1 expression. Conclusion: Disordered cerebral angiogenesis is associated with increased Wnt5a-Flt1 activation in microglial cells after exposure to intrauterine inflammation.

In this paper, the predefined-time platoon control for multiple uncertain unmanned aerial vehicles (UAVs) under range-limited communication and external disturbance constraints is considered. A novel control scheme, which can guarantee communication connectivity, collision avoidance, and the predefined convergence time simultaneously, is proposed. To achieve disturbance robustness, an observer-based distributed control law is firstly proposed with a time-varying gain. Then, a radial basis function neural network (RBFNN) with an adaptive tuning law is applied to approximate uncertainties of the system. Under the time and error transformation techniques, uniformly ultimate boundedness (UUB) stability of the closed-loop system is guaranteed within predefined convergence time. Compared with the existing results, the proposed method allows the system to have UUB within any predefined time without depending on the initial conditions or system parameters. Finally, simulation results are presented to verify the derived theorem.

Abstract Experiencing a social threat, such as social exclusion, is a painful event. In contrast to previous studies providing insight into the processing of a single short-termed threat, we exposed healthy individuals to the simultaneous onset of different social threats. This approach allowed us to track whether these threats are processed independently—or whether they interact in a common system. Using a virtual ball-throwing game (Cyberball), electrophysiological (event-related brain potentials, ERPs) and behavioral (self-reports) responses were collected. We assigned undergraduates to three experimental groups: single threat exclusion (n = 24), single threat loss of control (n = 26), and joint onset of both threats (dual-threat, n = 25). Self-reports indicated an increase in threats (i.e., in perceived exclusion and loss-of-control) in the latter group. The ERPs disentangled the neural responses to each threat: In the dual-threat group, the amplitudes of the P3 responses to exclusionary and intervention events were enhanced. This indicates that individuals are sensitized to each of the threats when the other threat is present simultaneously. Our findings support the theoretical notion of a common cognitive system responding to violations in subjective expectations.

Abstract Aim To investigate the thrifty effects of subanesthetic‐dose S‐ketamine on postoperative opioids and its safety and analgesic efficacy. Methods Four‐hundred and twenty patients were divided into the control group (CON group), the S‐ketamine 0.2 mg/kg group (ES0.2 group), and the S‐ketamine 0.3 mg/kg group (ES0.3 group) randomly. Major indicators include the Visual Analogue Scale (VAS), the times of compression with analgesic pumps after surgery, and analgesic drug consumption from anesthesia induction to 48 h after surgery. Minor records include vital signs, the use of vasoactive drugs, the Ramsay scores, the occurrence of adverse events including nervous system reaction, and the patient's satisfaction with anesthesia. Results Compared with the CON group, VAS scores decreased in the ES0.2 and ES0.3 groups (p

Abstract Background TDP-43 (43-kD transactive response DNA-binding protein) is a DNA-/RNA-binding protein that plays an important role in several nervous system diseases, such as amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Whether it plays an important role in glioma patients is unknown. Methods Datasets were downloaded from the Chinese Glioma Genome Atlas (CGGA) website ( http://www.cgga.org.cn/ ). Cox survival analysis was performed to determine the relationship between TARDBP gene expression and the overall survival of glioma patients. GO analyses were performed to determine the biological functions of the TARDBP gene. Finally, we used PRS type, age, grade, IDH mutation status, 1p/19q codeletion status, and expression value of the TARDBP gene to construct a prediction model. With this model, we can predict patients’ 1-, 2-, 3-, 5-, and 10-year survival rates. Results The TARDBP gene plays an important role in glioma patients. The expression of the TARDBP gene has a significant correlation with glioma patient survival. We also constructed an ideal prediction model. Conclusion Our findings suggest that the TARDBP gene and the protein it encodes play important roles in glioma patients. The expression of the TARDBP gene has a significant correlation with the overall survival of glioma patients.

Pipe bursts in water distribution networks (WDNs) pose significant threats to the safety of distribution networks, driving attention to deep learning-based burst detection and localization. However, the applicability of different pressure features still needs to be compared and verified. A large number of nodes challenges deep learning with the excessive number of classification categories and low recognition accuracy. To address these problems, this paper extracts different burst pressure features, including pressure value, pressure difference, and pressure fluctuation ratio, and inputs one of these features into a Burst Diagnosis Multi-Stage Model (BDMM) based on three CS-LSTMs (a combination of the Cuckoo Search algorithm and a long short-term memory network). The first model addresses a binary classification problem, outputting labels indicating whether a pipe burst has occurred. The second one solves a multi-classification problem, outputting the label of the burst partition, and the third model also solves a multi-classification problem, outputting the ID of the bursting junction. The model is tested on a real network and outperforms ELM. For basic burst identification tasks using CS-LSTM, differences among the three features are minimal, while pressure difference and pressure fluctuation ratio exhibit superior performance to pressure value when resolving more complex problems like burst junction localization.

Abstract Aims/introduction As a common complication in elderly patients after surgery/anesthesia, postoperative cognitive dysfunction (POCD) is mainly characterized by memory, attention, motor, and intellectual retardation. Neuroinflammation is one of the most uncontroversial views in POCD. The sevoflurane-induced neurotoxicity has attracted widespread attention in recent years. However, its mechanism has not been determined. This study aimed to observe the effects of sevoflurane on cognitive function and the changes in inflammatory indices and autophagy protein expression in the prefrontal cortex in aged rats. Method Before the experiment, D-galactose was diluted with normal saline into a liquid with a concentration of 125 mg/kg and injected subcutaneously into the neck and back of rats for 42 days to establish the aging rat model. Morris water maze experiments were performed, including positioning navigation (5 days) and space exploration (1 day). The POCD model was established by 3.2% sevoflurane inhalation. The rats were treated with or without MCC950, a potent and selective nucleotide‐binding oligomerization domain‐like receptor protein 3 (NLRP3) inhibitor, followed by autophagy agonists and autophagy inhibitors. The expression levels of inflammasome-related protein NLRP3 and autophagy-related proteins LC3B and P62 were detected to test the behavior of rats with a water maze. Results We found that sevoflurane exposure affected learning and working memory ability in aged rats. We also observed microglia activation in the prefrontal cortex. NLRP3 protein expression was significantly upregulated after sevoflurane inhalation. NLRP3 inflammasome activation induced increased expression and mRNA expression of cleaved Caspase-1 and inflammatory cytokines IL-1β and IL-18, and increased secretion of peripheral proinflammatory cytokines. The inhibitor MCC950 was used to improve cognitive ability and inflammation in rats and inhibit the secretion of cytokines. In addition, we demonstrated that significant inhibition of autophagy (decreased LC3-II/I and increased P62) was accompanied by increased activation of NLRP3 inflammasomes and more severe neural cell damage. However, autophagy inhibitor rapamycin administration to activate autophagy resulted in the inhibition of NLRP3 inflammasomes, ultimately attenuating neuronal injury. Conclusions The activation of autophagy suppressed the formation of NLRP3 inflammasomes. It also alleviated cognitive impairment in aged rats.

In this paper, the oxidation thermodynamics and oxidation kinetics of Au-20Sn solder at various temperatures were analyzed. The results indicated that the critical oxygen partial pressure to form SnO and SnO2 in Au-20Sn solder could be 1 × 10−44 Pascal (Pa) and 1 × 10−91 Pa at the temperature of 298 K, respectively. The oxidation kinetics analysis results indicated that the oxide on the surface of Au-20Sn solder consists mainly SnO2, while the major constituent of internal oxide is SnO. The reliability test results under salt spray environment have showed that the hermeticity of the package device gradually decreased with the increasing oxygen content in Au-20Sn solder. Meanwhile, the measured leakage rate of the packaging device could be lowered than 5 × 10−9 Pa·m–3·s–1 when the oxygen content in Au-20Sn solder is less than 28 ppm after high temperature aging.

Abstract Neuroinflammation is the main pathological mechanism of cognitive dysfunction caused by neurodegenerative diseases, and effective preventive and therapeutic measures are not available. We predicted the key targets of gastrodin’s effects upon neuroinflammation through Network Pharmacology and molecular docking. Then the predicted targets were used to study how gastrodin affected cognitive dysfunction triggered by lipopolysaccharide-induced neuroinflammation in rats and its mechanisms. Three-month-old male rats were intraperitoneally injected with lipopolysaccharide for 3 days (d), 7 d and 14 d respectively. Gastrodin improved learning and memory ability of rats with neuroinflammation. Lipopolysaccharide enhanced the levels of pro-inflammatory cytokines, such as TNF-α, IL-1β and IL-6, in rat hippocampus, which could be reversed by gastrodin. Gastrodin also inhibited the activation of microglia. Our findings suggested that gastrodin exerted neuroprotective effects in rats with neuroinflammation by impacting the TLR4-NF-kB-NLRP3 pathway. Therefore, gastrodin may be a potential therapeutic agent for neuroinflammation-induced cognitive dysfunction.

Most of the intensive human activities usually occur in lowlands. Here the authors report that human activity expansions also were widely distributed in Asian highlands in the 21st century and held dual effects, which provides new insights for regional human activity expansions.

Abstract Ketamine may become an important drug for multimodal analgesia regime again because of its strong analgesic effects and retaining the advantage of spontaneous breathing. The present study was designed to explore the influences of different dosages of S‐ketamine anesthesia induction regimes on psychiatric complications and postoperative prognosis in patients undergoing gynecological operations. In this prospective, triple‐blinded, randomized, controlled study, patients undergoing elective gynecological surgery were randomized to one of three treatment groups: low‐dose S‐ketamine (LDSK) group (a 0.3 mg/kg bolus for anesthesia induction), minimal‐dose S‐ketamine (MDSK) group (a 0.2 mg/kg bolus for anesthesia induction), and placebo (CON) group (a saline bolus for anesthesia induction). The main outcome measures were as follows: intraoperative vital signs, extubation time, anesthesia recovery time and postanesthesia care unit (PACU) stay duration, incidence of psychiatric complications, Ramsay sedation scale (RSS) 1, 2, 24, and 48 h, postoperatively, and overall prognosis. One hundred and eighty female participants were finally included in this study from April 2021 to December 2021. Significant differences were not observed in age, height, weight, American Society of Anesthesiologists physical status classification, or history of mental illness between the groups. No statistically significant differences were discovered with regard to intraoperative vital signs, extubation time and PACU stay duration, incidence of psychiatric complications, and RSS scores at 1, 2, 24, and 48 h postoperatively in the three groups. However, the visual analog scale (VAS) scores of the CON group at 10 min after extubation and at the time point leaving PACU were much higher than that of the LDSK and MDSK groups. The VAS scores at 48 h after surgery in the MDSK group were also lower than that of the CON group and the CON group had received more analgesic drug treatment in the surgical wards consequently. Postoperative nausea and vomiting (PONV) occurrence at 24 and 48 h, postoperatively, increased sharply in the CON group than in the other two experimental groups, which led to an increase in the use of postoperative antiemetic drugs in this group. According to the postoperative satisfaction survey, patients in the CON group had lower medical satisfaction. Our data demonstrate that a small dosage of S‐ketamine anesthesia induction can reduce postoperative pain and the incidence of PONV without increasing hemodynamic fluctuations or psychiatric complications.

Abstract CO2 cycloaddition with epoxides is a key catalytic procedure for CO2 utilization. Several metal‐based catalysts with cocatalysts are developed for photo‐driven CO2 cycloaddition, while facing difficulties in product purification and continuous reaction. Here, poly(ionic liquid)s are proposed as metal‐free catalysts for photo‐driven CO2 cycloaddition without cocatalysts. A series of poly(ionic liquid)s with donor–acceptor segments are fabricated and their photo‐driven catalytic performance (conversion rate of 83.5% for glycidyl phenyl ether) outstrips (≈4.9 times) their thermal‐driven catalytic performance (17.2%) at the same temperature. Mechanism studies confirm that photo‐induced charge separation is promoted by the donor–acceptor segments and can accelerate the CO2 cycloaddition reaction. This work paves the way for the further use of poly(ionic liquid)s as catalysts in photo‐driven CO2 cycloaddition.

Summary: Background: Bronchopulmonary dysplasia (BPD) is the primary severe complication of preterm birth. Severe BPD was associated with higher risks of mortality, more postnatal growth failure, long term respiratory and neurological developmental retardation. Inflammation plays a central role in alveolar simplification and dysregulated vascularization of BPD. There is no effective treatment to improve BPD severity in clinical practice. Our previous clinical study showed autologous cord blood mononuclear cells (ACBMNCs) infusion could reduce the respiratory support duration safely and potential improved BPD severity. Abundant preclinical studies have reported the immunomodulation effect as an important mechanism underlying the beneficial results of stem cell therapies in preventing and treating BPD. However, clinical studies assessing the immunomodulatory effect after stem cells therapy were rare. This study was to investigate the effect of ACBMNCs infusion soon after birth on prevention for severe BPD and long term outcomes in very preterm neonates. The immune cells and inflammatory biomarkers were detected to investigate the underlying immunomodulatory mechanisms. Methods: This single-center, prospective, investigator-initiated, non-randomized trial with blinded outcome assessment aimed to assess the effect of a single intravenous infusion of ACBMNCs in preventing severe BPD (moderate or severe BPD at 36 weeks of gestational age or discharge home) in surviving very preterm neonates less than 32 gestational weeks. Patients admitted to the Neonatal Intensive Care Unit (NICU) of Guangdong Women and Children Hospital from July 01, 2018 to January 1, 2020 were assigned to receiving a targeted dosage of 5 × 107 cells/kg ACBMNC or normal saline intravenously within 24 h after enrollment. Incidence of moderate or severe BPD in survivors were investigated as the primary short term outcome. Growth, respiratory and neurological development were assessed as long term outcomes at corrected age of 18–24 month-old. Immune cells and inflammatory biomarkers were detected for potential mechanism investigation. The trial was registered at ClinicalTrials.gov (NCT02999373). Findings: Six-two infants were enrolled, of which 29 were enrolled to intervention group, 33 to control group. Moderate or severe BPD in survivors significantly decreased in intervention group (adjusted p = 0.021). The number of patients needed to treat to gain one moderate or severe BPD-free survival was 5 (95% confidence interval: 3–20). Survivors in the intervention group had a significantly higher chance to be extubated than infants in the control group (adjusted p = 0.018). There was no statistical significant difference in total BPD incidence (adjusted p = 0.106) or mortality (p = 1.000). Incidence of developmental delay reduced in intervention group in long term follow-up (adjusted p = 0.047). Specific immune cells including proportion of T cells (p = 0.04) and CD4+ T cells in lymphocytes (p = 0.03), and CD4+ CD25+ forkhead box protein 3 (FoxP3)+ regulatory T cells in CD4+ T cells increased significantly after ACBMNCs intervention (p ＜ 0.001). Anti-inflammatory factor IL-10 was higher (p = 0.03), while pro-inflammatory factor such as TNF-a (p = 0.03) and C reactive protein (p ＜ 0.001) level was lower in intervention group than in control group after intervention. Interpretation: ACBMNCs could prevent moderate or severe BPD in surviving very premature neonates and might improve neurodevelopmental outcomes in long term. An immunomodulatory effect of MNCs contributed to the improvement of BPD severity. Funding: This work was supported by National Key R&D Program of China (2021YFC2701700), National Natural Science Foundation of China (82101817, 82171714, 8187060625), Guangzhou science and technology program (202102080104).

ObjectiveBased on the investigation of the core capacity development of health emergency response of Shanghai disease prevention and control institutions after the COVID-19 pandemic， to analyze the shortcomings of health emergency response capacity of Shanghai disease prevention and control institutions， and to put forward suggestions to improve the core capacity of Shanghai's disease prevention and control system in the face of public health emergencies.MethodsUsing questionnaire surveys， investigations and evaluations were conducted on the emergency system development， epidemic monitoring and risk assessment， emergency team manpower and equipment， and actual response to COVID-19 in 16 district-level disease prevention and control institutions in Shanghai.ResultsThe overall public health emergency response capacity building of the district-level disease control agencies in Shanghai is relatively good， and the effect of capacity building has been proven during the handling of the new coronavirus. But at the same time， it also exposed some specific problems such as imperfect system construction， lack of emergency personnel and materials， insufficient on-site handling capabilities of personnel， and uneven allocation of emergency personnel and materials among different agencies.ConclusionShanghai district-level disease control should focus on the specific problems， such as strengthening the development of health emergency system， improving the human resources and material reserves of the emergency teams， and optimizing the laboratory testing ability， to further improve the core health emergency capacity of Shanghai disease control system.

Porous covalent organic frameworks have arisen as tunable photocatalysts for H2 production. Here, authors report frameworks engineered with co-catalyst binding sites to improve photocatalytic H2 evolution performances.

Abstract Background Methotrexate (MTX) has a protective effect against cardiovascular diseases (CVD), but the mechanism is unclear. Objective To investigate the effect of MTX on lipid profiles and the difference between psoriasis without arthritis (PsO) and psoriatic arthritis (PsA). Methods In this prospective study, we recruited 288 psoriatic patients (136 PsA and 152 PsO) who completed 12 weeks of MTX treatment. Total cholesterol (TC), triglycerides (TG), lipoprotein A [LP(a)], high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL), apolipoprotein A1 (ApoA1), and ApoB were measured. Results Compared with sex- and age-matched healthy controls, psoriatic patients had significantly (p < 0.0001) higher levels of proatherogenic lipids and lower levels of anti-atherogenic lipids. PsA patients had a higher ApoB/ApoA1 ratio than PsO patients (p < 0.05). Stepwise regression analysis found a positive correlation between the inflammatory marker hCRP and the Psoriasis Area Severity Index (PASI), ApoB/ApoA1 ratio, BMI, and smoking. ApoB was positively associated with concomitant arthritis, diabetes, and hypertension. MTX decreased the levels of pro-atherogenic and anti-atherogenic lipids. However, a significant reduction of the ApoB/ApoA1 ratio by MTX was only observed in male patients. Conclusion PsA patients had a significantly higher percentage of concomitant disease than PsO. The decrease of MTX on CVD might be related with sex. Trial registration ChiCTR2000036192

Abstract Purpose To develop and validate a radiomics nomogram for the preoperative prediction of lymph node (LN) metastasis in pancreatic ductal adenocarcinoma (PDAC). Materials and methods In this retrospective study, 225 patients with surgically resected, pathologically confirmed PDAC underwent multislice computed tomography (MSCT) between January 2014 and January 2017. Radiomics features were extracted from arterial CT scans. The least absolute shrinkage and selection operator method was used to select the features. Multivariable logistic regression analysis was used to develop the predictive model, and a radiomics nomogram was built and internally validated in 45 consecutive patients with PDAC between February 2017 and December 2017. The performance of the nomogram was assessed in the training and validation cohort. Finally, the clinical usefulness of the nomogram was estimated using decision curve analysis (DCA). Results The radiomics signature, which consisted of 13 selected features of the arterial phase, was significantly associated with LN status (p

PurposeTo evaluate the diagnostic performance of radiomics model based on fully automatic segmentation of pancreatic tumors from non-enhanced magnetic resonance imaging (MRI) for differentiating pancreatic adenosquamous carcinoma (PASC) from pancreatic ductal adenocarcinoma (PDAC).Materials and methodsIn this retrospective study, patients with surgically resected histopathologically confirmed PASC and PDAC who underwent MRI scans between January 2011 and December 2020 were included in the study. Multivariable logistic regression analysis was conducted to develop a clinical and radiomics model based on non-enhanced T1-weighted and T2-weighted images. The model performances were determined based on their discrimination and clinical utility. Kaplan-Meier and log-rank tests were used for survival analysis.ResultsA total of 510 consecutive patients including 387 patients (age: 61 ± 9 years; range: 28–86 years; 250 males) with PDAC and 123 patients (age: 62 ± 10 years; range: 36–84 years; 78 males) with PASC were included in the study. All patients were split into training (n=382) and validation (n=128) sets according to time. The radiomics model showed good discrimination in the validation (AUC, 0.87) set and outperformed the MRI model (validation set AUC, 0.80) and the ring-enhancement (validation set AUC, 0.74).ConclusionsThe radiomics model based on non-enhanced MRI outperformed the MRI model and ring-enhancement to differentiate PASC from PDAC; it can, thus, provide important information for decision-making towards precise management and treatment of PASC.

With the development of IoT and 5G, the smart grid, as one of the key component for the smart city, can provide the uninterrupted and reliable electricity service by properly adjusting the electricity supply according to the consumption of users. The advanced metering infrastructure (AMI), as an important part of smart grid system, is a complete network and system for measuring, collecting, storing and analyzing the electricity consumption information of users. The security of AMI plays a vital role in the smooth operation of smart grid. In this paper, we study how to establish the secure communication between two entities in AMI, namely the smart meter and the electricity service provider. Although, there are many authentication and key management protocols for AMI, the high complexity and computation overhead of these protocols hinder their application in the smart grid environment. Based on identity cryptosystem and elliptic curve cryptography (ECC), we put forward a lightweight and dynamic authenticated key agreement and management protocol, which can significantly reduce the computation overhead of the resource-constrained smart meters. In addition, we utilize a one-way key tree technique to efficiently generate and update the group key in the multicast communication. We give a systematic proof to show that our designed protocol not only guarantees the confidentiality and integrity of transmitted messages, but also resists various attacks from an adversary. Finally, we carry out some simulated experiments to demonstrate the high efficiency of our designed protocol.

Abstract Postoperative cognitive dysfunction (POCD) is a common clinical manifestation that is a severe complication characterized by decreased learning ability and deterioration of memory following anesthesia and surgery. However, the precise mechanisms of POCD are not completely understood. Rats were divided into blank control group (Con, n = 12) and sevoflurane group (Sev, n = 12). Morris water maze test was performed to evaluate the ability of learning and memory in two groups of rats; immunohistochemical staining was used to detect the expression of ion calcium‐binding adaptor molecule‐1 (Iba‐1) in rat prefrontal cortex (PFC); Western blot analysis was applied respectively to investigate Iba‐1, inducible nitric oxide synthase (iNOS), arginase‐1 (ARG1), inflammatory cytokines interleukin‐1β (IL‐1β), and tumor necrosis factor‐α (TNF‐α) expression; The expression of iNOS, ARG1, IL‐1β, and TNF‐α in sera of rats was detected by enzyme‐linked immunosorbent assay. We found that sevoflurane induced learning and memory impairment assessed by morris water maze test, anesthesia up‐regulated the expression of iNOS, IL‐1β and TNF‐α inflammasome in microglia, as indicated by increased activation of Iba‐1 and reduced the level of ARG1 in the PFC. We conclude that the cognitive function of rats after inhaling anesthesia was likely associated with M1/M2 polarization of microglia, which was triggered by sevoflurane.

BackgroundCerebral microbleeds (CMBs) are common in the hypertensive population and can only be detected with magnetic resonance imaging (MRI). The anticoagulation and thrombolytic regimens for patients with >5 CMBs are different from those for patients with ≤ 5 CMBs. However, MRI is not suitable for evaluating CMBs in patients with MRI contraindications or acute ischemic stroke urgently requiring thrombolysis. We aimed to develop and validate a nomogram combining clinical and brain computed tomography (CT) characteristics for predicting >5 CMBs in a hypertensive population.Materials and methodsIn total, 160 hypertensive patients from 2016 to 2020 who were confirmed by MRI to have >5 (77 patients) and ≤ 5 CMBs (83) were retrospectively analyzed as the training cohort. Sixty-four hypertensive patients from January 2021 to February 2022 were included in the validation cohort. Multivariate logistic regression was used to evaluate >5 CMBs. A combined nomogram was constructed based on the results, while clinical and CT models were established according to the corresponding characteristics. Receiver operating characteristic (ROC) and calibration curves and decision curve analysis (DCA) were used to verify the models.ResultsIn the multivariable analysis, the duration of hypertension, level of homocysteine, the number of lacunar infarcts (LIs), and leukoaraiosis (LA) score were included as factors associated with >5 CMBs. The clinical model consisted of the duration of hypertension and level of homocysteine, while the CT model consisted of the number of LIs and LA. The combined model consisted of the duration of hypertension, level of homocysteine, LI, and LA. The combined model achieved an area under the curve (AUC) of 0.915 (95% confidence interval [CI]: 0.860–0.953) with the training cohort and 0.887 (95% CI: 0.783–0.953) with the validation cohort, which were higher than those of the clinical model [training cohort: AUC, 0.797 (95% CI: 0.726, 0.857); validation cohort: AUC, 0.812 (95% CI: 0.695, 0.899)] and CT model [training cohort: AUC, 0.884 (95% CI: 0.824, 0.929); validation cohort: AUC, 0.868 (95% CI: 0.760, 0.940)]. DCA showed that the clinical value of the combined model was superior to that of the clinical model and CT model.ConclusionA combined model based on clinical and CT characteristics showed good diagnostic performance for predicting >5 CMBs in hypertensive patients.

Heavy metal pollution caused by industrial wastewater such as mining and metallurgical wastewater is a major global concern. Therefore, this study used modified lignite as a low-cost adsorbent for heavy metal ions. Pingzhuang lignite was dissolved and modified using Fusarium lignite B3 to prepare a biotransformed-lignite adsorbent (BLA). The O, H, and N contents of the BLA increased after transformation, and the specific surface area increased from 1.81 to 5.66 m2·g−1. Various adsorption properties were investigated using an aqueous solution of Cu(Ⅱ). The kinetic and isothermal data were well-fitted by pseudo-second-order and Langmuir models, respectively. The Langmuir model showed that the theoretical Cu(II) adsorption capacity was 71.47 mg·g−1. Moreover, large particles and a neutral pH were favorable for the adsorption of heavy metal ions. The adsorption capacities of raw lignite and BLA were compared for various ions. Microbial transformation greatly improved the adsorption capacity, and the BLA had good adsorption and passivation effects with Cu(II), Mn(II), Cd(II), and Hg(II). Investigation of the structural properties showed that the porosity and specific surface area increased after biotransformation, and there were more active groups such as –COOH, Ar–OH, and R–OH, which were involved in the adsorption performance.

Abstract Background Biomarkers for distinguishing psoriatic arthritis (PsA) from psoriasis without arthritis (PsO) are still lacking. Methods We applied isobaric tags for relative and absolute quantification (iTRAQ) and LC–MS/MS to analyze the proteome profile of peripheral blood mononuclear cells (PBMCs) collected from patients with PsO, patients with PsA, and healthy controls. Bioinformatics analysis and western blotting were performed to identify and validate differentially expressed proteins. Results We identified 389, 199, 291, and 60 significantly differentially expressed proteins (adj.p

As one of the most common geological disasters, rockfalls seriously threaten the safety of linear projects such as roads, railways, and oil and natural gas pipelines. The rigid protective structures that are used for disaster reduction are easily damaged by the impact of rockfalls, which affects the service life of structures. Consequently, the buffer layer has been introduced to resolve this problem. In this work, numerical simulations were carried out by the discrete element method to study the interaction between falling rocks and the granular medium of a soil cushion layer that is installed on a rigid structure. The falling rock is modeled as a single sphere and the soil cushion layer is modeled as a component composed of a collection under the action of gravity, where the filled particles of the soil cushion layer are based on superquadric spheres generated by the superquadric surface equation. This paper uses three shapes (i.e., spheres, cubes, and cylinders) to mix and match as the soil cushion layer. The buffer performance of different mixed material buffer layers is investigated by analyzing the pressure of the bottom plate. The force chain propagation process is investigated by analyzing the comparison of the force chains of the soil cushion layers with different thickness and different filling particles after being impacted. The energy propagation process was studied by analyzing the evolution of the kinetic energy of the particles after the impact of the soil cushion layer.

Cells respond to and actively remodel the extracellular matrix (ECM). The dynamic and bidirectional interaction between cells and ECM, especially their mechanical interactions, has been found to play an essential role in triggering a series of complex biochemical and biomechanical signal pathways and in regulating cellular functions and behaviours. The collagen gel contraction assay (CGCA) is a widely used method to investigate cell–ECM interactions in 3D environments and provides a mechanically associated readout reflecting 3D cellular contractility. In this review, we summarize various versions of CGCA, with an emphasis on recent high-throughput and low-consumption CGCA techniques. More importantly, we focus on the technique of force monitoring during the contraction of collagen gel, which provides a quantitative characterization of the overall forces generated by all the resident cells in the collagen hydrogel. Accordingly, we present recent biological applications of the CGCA, which have expanded from the initial wound healing model to other studies concerning cell–ECM interactions, including fibrosis, cancer, tissue repair and the preparation of biomimetic microtissues.

Abstract Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous clonal disease associated with unmet medical needs. Paralleling the pathology of other cancers, AML tumorigenesis and propagation can be ascribed to dysregulated cellular processes, including apoptosis. This function and others are regulated by tumor suppressor P53, which plays a pivotal role in leukemogenesis. Opposing P53-mediated activities is the mouse double minute 2 homolog (MDM2), which promotes P53 degradation. Because the TP53 mutation rate is low, and MDM2 frequently overexpressed, in patients with leukemia, targeting the MDM2-P53 axis to restore P53 function has emerged as an attractive AML treatment strategy. APG-115 is a potent MDM2 inhibitor under clinical development for patients with solid tumors. In cellular cultures and animal models of AML, we demonstrate that APG-115 exerted substantial antileukemic activity, as either a single agent or when combined with standard-of-care (SOC) hypomethylating agents azacitidine (AZA) and decitabine (DAC), or the DNA-damaging agent cytarabine (Ara-C). By activating the P53/P21 pathway, APG-115 exhibited potent antiproliferative and apoptogenic activities, and induced cell cycle arrest, in TP53 wild-type AML lines. In vivo, APG-115 significantly reduced tumor burden and prolonged survival. Combinations of APG-115 with SOC treatments elicited synergistic antileukemic activity. To explain these effects, we propose that APG-115 and SOC agents augment AML cell killing by complementarily activating the P53/P21 pathway and upregulating DNA damage. These findings and the emerging mechanism of action afford a sound scientific rationale to evaluate APG-115 (with or without SOC therapies) in patients with AML.

Abstract Background Complement component(C7) gene has been shown to influence the prognosis in Hepatocellular carcinoma (HCC) patients. The association between C7 and HCC recurrence after orthotopic liver transplantation (OLT), however, is still unknown. The purpose of this study was to evaluate whether the donor and recipient C7 gene polymorphisms are related to HCC recurrence after OLT in the Han Chinese population. Methods A total of 73 consecutive patients with HCC who had undergone OLT, both donors and recipients, were involved in this research. A single nucleotide polymorphism of C7, rs9292795, was genotyped using Sequenom MassARRAY in the cohort. The expression of C7 and the association between C7 gene polymorphisms and HCC recurrence following OLT were analyzed by bioinformatics and statistical analysis, respectively. Results As shown in database, the expression of C7 was higher in HCC tissues than that in normal tissues, and represented a worse prognosis. We also found that recipient C7 rs9292795 polymorphism, rather than the donor, was significantly associated with HCC recurrence after OLT. Multivariate logistic regression analysis confirmed that TNM stage (P = 0.001), Milan criteria (P = 0.000) and recipient rs9292795 genotype (TT vs AA/AT, P = 0.008) were independent risk factors for HCC recurrence. Furthermore, the recipient carrying AA/AT showed higher recurrence-free survival (RFS) and overall survival (OS) than that carrying TT (P

Meta‐analysis has been recognized as the best means to evaluate objectively and study the evidence for a particular issue. In order to give researchers a better understanding of the Meta process, we present an overall introduction to Meta‐analysis in terms of comprehensive assessment of the literature, goals, advantages, main steps, and article structure.

Background Hypoxic‐ischemic encephalopathy (HIE) could induce exacerbated changes and unpredictable effects in brain cells, and the mechanism remains unclear. Methods HIE model was established in neonatal rats, Zea‐Longa score and TTC staining were used to observe the neurobehavior and brain infarct volume in rats subjected to cerebral hypoxia‐ischemia (HI). Primary cortical neurons were then cultured in vitro to establish an oxygen and glucose deprivation model. To determine the role of synaptosomal‐associated protein‐25 (SNAP25) in HIE, PC12 cells were cultured and effective siRNA fragments were screened, and SNAP25 was transfected into primary neurons. Then, quantitative real‐time polymerase chain reaction was used to detect the mRNA expression level and immunofluorescence staining was used to observe the morphological changes of neurons before and after the injury. Finally, the abundance values of SNAP25 and its associated genes were filtered using the NCBI and GeneMANIA, respectively. Results HI leads to a decrease in neuronal number and an increase in SNAP25 expression. Whereas, the interference of SNAP25 caused marked decrease in neuronal number and the length of neurite. Moreover, the expression levels of CREB and SYP were significantly decreased after interference of SNAP25. Conclusion SNAP25 exhibited several neuroprotective effects to neuronal protection in neonatal cerebral HI by regulating CREB and SYP.

AA9 lytic polysaccharide monooxygenases (LPMOs) are copper-dependent metalloenzymes that play a major role in cellulose degradation and plant infection. Understanding the AA9 LPMO mechanism would facilitate the improvement of plant pathogen control and the industrial application of LPMOs. Herein, via point mutation, we investigated the role of glycine 2 residue in cellulose degradation by Thermoascus aurantiacus AA9 LPMOs (TaAA9). A computational simulation showed that increasing the steric properties of this residue by replacing glycine with threonine or tyrosine altered the H-bonding network of the copper center and copper coordination geometry, decreased the surface charge of the catalytic center, weakened the TaAA9-substrate interaction, and enhanced TaAA9-product binding. Compared with wild-type TaAA9, G2T-TaAA9 and G2Y-TaAA9 variants showed attenuated copper affinity, reduced oxidative product diversity and decreased substrate Avicel binding, as determined using ITC, MALDI-TOF/TOF MS and cellulose binding analyses, respectively. Consistently, the enzymatic activity and synergy with cellulase of the G2T-TaAA9 and G2Y-TaAA9 variants were lower than those of TaAA9. Hence, the investigated residue crucially affects the catalytic activity of AA9 LPMOs, and we propose that the electropositivity of copper may correlate with AA9 LPMO activity. Thus, the relationship among the amino acid at position 2, surface charge and catalytic activity may facilitate an understanding of the proteins in AA9 LPMOs.

Leakage detection is an important task to ensure the operational safety of water distribution networks. Leakage characteristic extraction based on high-frequency data has been widely used for leakage detection in experimental networks. However, the accuracy of single-feature-based methods is limited by the interference of background pressure fluctuations in networks. In addition, the setting of leakage diagnosis thresholds has been insufficiently studied, but influences leakage detection performance greatly. Hence, a new method of leakage detection is proposed based on multi-feature extraction. The multi-features of leakage are composed of instantaneous characteristics (ICs) and trend characteristics (TCs), which constitute comprehensive leakage information. The levels of the instantaneous and trend pressure drops in background pressure fluctuations in network environments are quantified for the setting of leakage diagnosis thresholds. In addition, ICs and TCs are used for leakage degree prediction. The proposed method was applied to an experimental network. Compared with the single-feature-based method and the cumulative sum (CUSUM) method, the proposed method achieved increases of 6.01% and 13.66% in F-Scores, respectively, and showed better adaptability to background pressure fluctuations in complex network environments.

Cloud removal in optical remote sensing imagery is essential for many Earth observation applications. To recover the cloud obscured information, some preconditions must be satisfied. For example, the cloud must be semitransparent or relationships between contaminated and cloud-free pixels must be assumed. Due to the inherent imaging geometry features in satellite remote sensing, it is impossible to observe the ground under the clouds directly; therefore, cloud removal algorithms are always not perfect owing to the loss of ground truth. Recently, the use of passenger aircraft as a platform for remote sensing has been proposed by some researchers and institutes, including Airbus and the Japan Aerospace Exploration Agency. Passenger aircraft have the advantages of short visitation frequency and low cost. Additionally, because passenger aircraft fly at lower altitudes compared to satellites, they can observe the ground under the clouds at an oblique viewing angle. In this study, we examine the possibility of creating cloud-free remote sensing data by stacking multiangle images captured by passenger aircraft. To accomplish this, a processing framework is proposed, which includes four main steps: first, multiangle image acquisition from passenger aircraft, second, cloud detection based on deep learning semantic segmentation models, third, cloud removal by image stacking, and fourth, image quality enhancement via haze removal. This method is intended to remove cloud contamination without the requirements of reference images and predetermination of cloud types. The proposed method was tested in multiple case studies, wherein the resultant cloud- and haze-free orthophotos were visualized and quantitatively analyzed in various land cover type scenes. The results of the case studies demonstrated that the proposed method could generate high quality, cloud-free orthophotos. Therefore, we conclude that this framework has great potential for creating cloud-free remote sensing images when the cloud removal of satellite imagery is difficult or inaccurate.

AimsTo assess whether MTHFR rs1801131 and rs1801133 SNPs are associated with concomitant psoriatic arthritis (PsA) and investigate the efficacy and hepatotoxicity of MTX in patients with psoriasis in the Han Chinese population.MethodsThis prospective, single-arm, interventional study recruited a total of 309 patients with psoriasis, 163 with psoriatic arthritis and 146 without psoriatic arthritis, who completed a 12-week MTX treatment and 1,031 healthy controls. Patients' characteristics including age, gender, disease duration, height, weight, smoking status, alcohol consumption, medical history, disease severity and liver function test results were accessed and recorded. Single nucleotide polymorphism (SNP) genotyping of rs1801131 and rs1801133 in the MTHFR gene was performed.ResultsThe rs1801133 CC genotype was more frequent in patients with PsA than those with PsO and healthy controls (42.3% vs. 28.8% vs. 33.1%, p < 0.05). The 90% reduction from baseline PASI score (PASI 90) response rates to MTX were significantly higher in patients with the rs1801133 TT genotype than those with the CT and CC genotype (33.96% vs. 19.31% vs. 14.41%, OR = 2.76, p = 0.006). The rs1801133 CT+TT genotype was more frequent in PsA patients with abnormal liver function than in those with normal liver function (p < 0.05). In addition, patients with the rs1801131 CT genotype had lower PASI 75 response rates to MTX (OR = 0.49, p = 0.01), and lower risk of ALT elevation (OR = 0.46, p = 0.04).ConclusionsThis study provided some evidence for MTHFR polymorphism association with the risk of PsA and the efficacy and hepatotoxicity of the low-dose MTX in the Chinese population. Given the relatively small sample size and potentially missed diagnosis of PsA, the results from this study warrant further investigation.

Background Diabetes mellitus is a growing global health challenge and affects patients of all ages. Treatment aims to keep blood glucose levels close to normal and to prevent or delay complications. However, adherence to antidiabetic medicines is often unsatisfactory. Purpose Here, we established and internally validated a medication nonadherence risk nomogram for use in Chinese type 2 diabetes mellitus (T2DM) patients. Methods This cross-sectional study was carried out from July–December 2020 on randomly selected T2DM patients visiting a diabetes clinic and included 753 participants. Adherence was analyzed based on an eight-item Morisky Medication Adherence Scale (MMAS-8). Other data, including patient demographics, treatment, complications, and comorbidities, were also collected on questionnaires. Optimization of feature selection to develop the medication nonadherence risk model was achieved using the least absolute shrinkage and selection operator regression model (LASSO). A prediction model comprising features selected from LASSO model was designed by applying multivariable logistic regression analysis. The decision curve analysis, calibration plot, and C-index were utilized to assess the performance of the model in terms of discrimination, calibration, and clinical usefulness. Bootstrapping validation was applied for internal validation. Results The prediction nomogram comprised several factors including sex, marital status, education level, employment, distance, self-monitoringofbloodglucose, disease duration, and dosing frequency of daily hypoglycemics (pills, insulin, or glucagon-like peptide-1). The model exhibited good calibration and good discrimination (C-index = 0.79, 95% CI [0.75–0.83]). In the validation samples, a high C-index (0.75) was achieved. Results of the decision curve analysis revealed that the nonadherence nomogram could be applied in clinical practice in cases where the intervention is decided at a nonadherence possibility threshold of 12%. Conclusion The number of patients who adhere to anti-diabetes therapy was small. Being single male, having no formal education, employed, far from hospital, long disease duration, and taking antidiabetics twice or thrice daily, had significant negative correlation with medication adherence. Thus, strategies for improving adherence are urgently needed.

Carbon catabolite repression (CCR), which is mainly mediated by Cre1 and triggered by glucose, leads to a decrease in cellulase production in Trichoderma reesei. Many studies have focused on modifying Cre1 for alleviating CCR. Based on the homologous alignment of CreA from wild-type Penicillium oxalicum 114–2 (Po-0) and cellulase hyperproducer JUA10-1(Po-1), we constructed a C-terminus substitution strain—Po-2—with decreased transcriptional levels of cellulase and enhanced CCR. Results revealed that the C-terminal domain of CreAPo−1 plays an important role in alleviating CCR. Furthermore, we replaced the C-terminus of Cre1 with that of CreAPo−1 in T. reesei (Tr-0) and generated Tr-1. As a control, the C-terminus of Cre1 was truncated and Tr-2 was generated. The transcriptional profiles of these transformants revealed that the C-terminal chimera greatly improves cellulase transcription in the presence of glucose and thus upregulates cellulase in the presence of glucose and weakens CCR, consistent with truncating the C-terminus of Cre1 in Tr-0. Therefore, we propose constructing a C-terminal chimera as a new strategy to improve cellulase production and alleviate CCR in the presence of glucose.

Abstract Oligosaccharides have important therapeutic applications. A useful route for oligosaccharides synthesis is reverse hydrolysis by β-glucosidase. However, the low conversion efficiency of disaccharides from monosaccharides limits its large-scale production because the equilibrium is biased in the direction of hydrolysis. Based on the analysis of the docking results, we hypothesized that the hydropathy index of key amino acid residues in the catalytic site is closely related with disaccharide synthesis and more hydrophilic residues located in the catalytic site would enhance reverse hydrolysis activity. In this study, positive variants TrCel1bI177S, TrCel1bI177S/I174S, and TrCel1bI177S/I174S/W173H, and one negative variant TrCel1bN240I were designed according to the Hydropathy Index For Enzyme Activity (HIFEA) strategy. The reverse hydrolysis with TrCel1bI177S/I174S/W173H was accelerated and then the maximum total production (195.8 mg/mL/mg enzyme) of the synthesized disaccharides was increased by 3.5-fold compared to that of wild type. On the contrary, TrCel1bN240I lost reverse hydrolysis activity. The results demonstrate that the average hydropathy index of the key amino acid residues in the catalytic site of TrCel1b is an important factor for the synthesis of laminaribiose, sophorose, and cellobiose. The HIFEA strategy provides a new perspective for the rational design of β-glucosidases used for the synthesis of oligosaccharides.

Most existing sewer pipeline condition assessment methods determine the presence and types of faults via examination of videos, which is a time-consuming and labor-intensive process. A few automatic methods based on image processing techniques can be used to detect specific faults. However, these methods have limitations due to the presence of unpredictable sewer pipeline fault patterns. Deep learning methods have also been applied to sewer pipeline fault detection. However, these methods require a large amount of annotated data to obtain reliable results. In this paper, we propose a fault detection method that applies unsupervised machine learning based anomaly detection algorithms with feature extraction to videos recorded by new sewer pipeline visual inspection equipment. The recorded videos are regarded as sequence signals, which are converted into feature vectors, followed by application of an anomaly detection algorithm. Unlike existing methods, the proposed method is computationally efficient as it does not require an annotated fault sample database for training fault detection models. We evaluate various anomaly detection algorithms and feature combinations on real sewer pipeline data collected in Shenzhen, with an overall accuracy result of above 90%. The proposed method provides a new and fast technique for surveying urban sewer pipelines, and to facilitate further research in this area, we have made the code and data used in this paper publicly available.