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To explore the variation behaviour of anchor jointed rock subject to high in situ stress states, a coupling effect calculation model based on stress equality was established based on the original rheological model of rock by combining element combination theory and experiment, and the model was verified. The coupling effect between rock mass creep and bolt prestress loss is established by setting the deterioration function of bolt prestress loss. The uniaxial creep test is performed on specimens with different joint angles, and the results show that the prestress loss time in anchor rods decreases linearly with increasing stress level. With increasing stress level, the time of prestress loss decreases linearly with the increase in stress level. With increasing axial load, the deformation caused by the transverse expansion stress of the specimen can offset the compression deformation of the prestressed anchor rod. The relationship between prestress loss in anchors and creep of rock is solved theoretically, and the stability criterion for anchor jointed rock is proposed. The results of this study provide a scientific reference for anchor design of deep jointed rock mass.

The sulfonated covalent organic frameworks (COF@SO3H) have been synthesized by a simple one-step solvothermal reaction and used to adsorb Cd2+, Co2+, and Cr3+ metal ions from aqueous solution. The structure, composition and stability of as-prepared material were confirmed by FT-IR, PXRD, BET and TGA, and a fiber bundle-like COF@SO3H could be observed in the SEM and TEM images. The adsorption behaviors of Cd2+, Co2+, and Cr3+ onto COF@SO3H were studied through batch adsorption experiments, and the obtained data were analyzed using various models. The adsorption process of the three ions can be better described by the Langmuir isotherm and the pseudo-second-order kinetics than other models tested, and the maximum adsorption capacities for Cd2+, Co2+ and Cr3+ at 298 K are 81.97, 77.52, and 105.26 mg g−1, respectively. The thermodynamic parameters indicate that the adsorption of Cd2+ onto COF@SO3H is spontaneous, which is more favorable than Co2+ and Cr3+. Moreover, the adsorbed metal ions can be easily eluted by nitric acid or EDTA solution, and the COF@SO3H can be reused for more than 5 adsorption-elution cycles without obvious collapsing in structure and reducing in adsorption capacity. All the results suggested that the COF@SO3H could be used to the adsorption and removal of heavy metal ions from wastewater.

Introduction The evidence on efficacy of intravitreously administered Conbercept (IVC) monotherapy for diabetic macular degeneration was still limited. Methods A systematic review was conducted in November 2019 to summarize the current evidence on visual acuity (VA) changes with IVC monotherapy in the treatment of diabetic macular edema (DME) from Pubmed, ClinicalTrials.gov, EMbase, China National Knowledge Infrastructure (CNKI), Wanfang Database, Chin VIP Information (VIP), and Chinese Biomedical Database (CBM). Retrospective or prospective clinical studies which used IVC injection for the treatment of DME were included. Outcomes included in the analysis were change in best-corrected visual acuity (BCVA) and central macular thickness (CMT). A meta-regression was conducted to assess 1-year BCVA and CMT changes against numbers of injections. Results A total of 20 studies were included in current study. At 12-month follow-up, an overall increase of 0.67 logarithm of the minimum angle of resolution (logMAR) BCVA score [95% confidence interval (CI) 0.24–1.11; P = 0.003] and 1.03 Early Treatment Diabetic Retinopathy Study (ETDRS) letters (95% CI 0.69–1.38; P

In order to devise more effective penetration enhancers, 4-O-acylterpineol derivatives which were expected to be hydrolyzed into nontoxic metabolites by esterase in the living epidermis, were synthesized from 4-terpineol (4-TER) enantiomers and straight chain fatty acids. Their promoting activities on the SR-flurbiprofen and its enantiomers were tested across full-thickness rabbit skin, as well as to correlate under in vitro and in vivo conditions. The permeation studies indicated that both d-4-O-acylterpineol and l-4-O-acylterpineol had significant enhancing effects, interestingly, d-4-O-aclyterpineol had higher enhancing effects than l-4-O-aclyterpineol with the exception of d-4-methyl-1-(1-methylethyl)-3-cyclohexen-1-yl octadec-9-enoate (d-4-T-dC18). The mechanism of 4-O-acylterpineol facilitating the drug penetration across the skin was confirmed by Attenuated total reflection-Fourier transformed infrared spectroscopy (ATR-FTIR) and molecular simulation. The mechanism of penetration enhancers promoting drug release was explored by the in vitro release experiment. Finally, a relative safety skin irritation of enhancers was also investigated by in vivo histological evaluation. The present research suggested that d-4-O-aclyterpineol and l-4-O-aclyterpineol could significantly promote the penetration of SR-flurbiprofen and its enantiomers both in vitro and in vivo, with the superiorities of high flux and low dermal toxicity.

Traumatic distal anterior cerebral artery (dACA) aneurysm is rare and can be easily neglected and misdiagnosed in patients with trauma. The aim of this study was to explore the radiologic characteristics of and therapeutic strategies for traumatic dACA aneurysm and to improve our understanding of unusual complications after trauma. The clinical data of nine cases of traumatic dACA aneurysm from our neurosurgical department from July 1, 2010, to July 1, 2018, were retrospectively analysed. All 9 patients had a history of brain trauma. The initial computed tomography scan immediately after trauma showed subarachnoid haemorrhage in 8 cases. Among these cases, delayed intracranial haemorrhage occurred in 7 cases. The average interval between injury and diagnosis was 13.67 ± 9.43 days. All 9 cases were confirmed as traumatic dACA aneurysm by computed tomography angiography (CTA) and/or digital subtraction angiography. According to Lehecka’s classification system, traumatic dACA aneurysm located in the A3 and A4 segment was found in 3 and 6 cases, respectively. Surgical treatment was performed in 8 cases, including neck clipping, with or without wrapping in 3 cases, trapping in 4 cases, aneurysm excision and suturing in 1 case and conservative treatment in 1 case. Three patients required a ventriculoperitoneal shunt due to severe hydrocephalus. According to the Glasgow Outcome Scale scoring system, good recovery was achieved in 4 cases, moderate disability in 2 cases, severe disability in 1 case, and death in 2 cases. Traumatic dACA aneurysm is a rare complication of brain trauma. Delayed intracranial haemorrhage and the sudden deterioration of neurologic function were the typical characteristics in patients with traumatic dACA aneurysm. CTA is the first-line screening modality for patients who present with intracerebral haemorrhage in the corpus callosum after trauma, particularly for patients who are older, in a poorer or critical condition. When the aneurysm is located in the A4 segment or involves a small branch, surgical trapping is the preferred definitive therapy to prevent further growth and disastrous bleeding. Early diagnosis and prompt treatment could help to improve clinical outcomes.

Background The phenotypes and genotypes of Streptococcus pneumoniae isolated from invasive pneumococcal diseases (IPDs) were changing all the time. To monitor these changes of phenotypes and genotypes of S. pneumoniae isolates from children, we examined antibiotic susceptibility, serotype distribution and sequence types (STs) of S. pneumoniae, which were isolated before the 13-valent pneumococcal conjugate vaccine (PCV13) introduced into China. Methods Strains were isolated from children less than 14 years old between January 2013 and May 2017 from Shenzhen Children’s Hospital. Serotypes, antibiotic resistance, and genotypes of these isolates were determined using capsular swelling, E-test, and multi-locus sequence typing, respectively. Results A total of 94 S. pneumoniae strains were isolated, which belonged to 15 serotypes. The five most prevalent serotypes were 19F (25.5%), 19A (19%), 14 (17%), 23F (7.5%), and 6B (9.6%). We found 42 STs for these isolates. The most abundant STs were ST271 (24.4%), ST876 (17%), and ST320 (10.6%), mainly related to 19F, 14, and 19A, respectively. The potential coverage of PCV13 was 87.2%. Among non-meningitis isolates, the resistance rates to penicillin and ceftriaxone were 0% and 2%. However, the meningitis isolates showed high resistance to penicillin (80%) and ceftriaxone (20%). Most of these isolates (95.7%) were resistant to erythromycin, and 66 (70.2%) strains carried the ermB gene and 24 (25.5%) strains carried both the ermB and mefA/E genes. Serotype 19A showed the highest mean minimum inhibitory concentration (MIC) for penicillin (MIC = 1.486) than the other serotypes, but no significant difference in penicillin MIC among the three main STs (ST271, ST320, and ST876). Conclusions The phenotypes and genotypes of invasive pneumococcal isolates from Shenzhen Children’s Hospital have changed with the passage of time. Compared with PCV7, PCV13 can more effectively protect Chinese children from IPDs. To some extent, these changes are possibly related to the usage of antibiotics and vaccines.

We consider robust smoothing for nonlinear state space models in which both the process and measurement noises have heavy tails. To improve the robustness of Kalman smoothing, we formulate the robust smoothing problem by replacing the quadratic loss in the conventional Gaussian Kalman smoother by Huber’s cost function. However, the Huber based smoother cannot be directly implemented within the Kalman smoothing framework, which has well recognized benefits in computational efficiency and stability. To address this issue, we introduce an auxiliary parameter to construct a surrogate function for the Huber cost function, leading to a reformulation of the robust Kalman smoothing problem. The reformulated robust smoothing is solved by an alternating minimization method, which iterates between a simple auxiliary parameter update step and a modified conventional Kalman smoothing step. Simulation results show that the proposed method achieves a performance improvement over several conventional and existing robust smoothers with a slight increase of computational time.

Esophageal cancer (EC) is the sixth leading cause of cancer-related deaths worldwide. Western medicine has played a leading role in its treatment, but its prognosis remains unsatisfactory. Therefore, the development of effective therapies is important. Traditional Chinese medicine (TCM) has been practiced for thousands of years, and involves taking measures before diseases occur, deteriorate, and recur. Interestingly, there is growing evidence that TCM can improve the therapeutic effects in reversing precancerous lesions, inhibiting the recurrence and metastasis of EC. In this article, we review traditional Chinese herbs and formulas that have preventive and therapeutic effects on EC, summarize the application and research status of TCM in patients with EC, and discuss its shortcomings and prospects in the context of translational, evidence-based, and precision medicine.

Introduction. Brucea javanica oil emulsion injection (BJOEI) is an antitumor drug extracted from the traditional Chinese medicinal plant Brucea javanica, which has broad prospects as an adjuvant treatment for gastric cancer (GC); however, its efficacy and safety are still controversial. We plan to conduct a systematic review and meta-analysis to summarise the clinical efficacy and safety of BJOEI in the treatment of GC and provide credible evidence for the clinical application and subsequent studies of BJOEI. Methods and Analysis. This systematic review will include articles identified by electronically searching the following databases: PubMed, EMBASE, CENTRAL, Web of Science, the Chinese Biomedical Literature Database (CBM), the China National Knowledge Infrastructure (CNKI), Wanfang Database, and Chinese Scientific Journals Database (VIP Database) from inception to 31 July 2021. The primary outcomes of this research will be the clinical total effective rate, performance status, and adverse drug reactions (ADRs). The systematic review will be performed using RevMan 5 software. Finally, we will use the Grading of Recommendations Assessment, Development and Evaluation System (GRADE) to assess the quality of evidence. Ethics and Dissemination. Ethical approval is not required for literature-based studies. The results of this systematic review will be published in a peer-reviewed journal. PROSPERO registration number: CRD42021265646.

In severe traumatic brain injury (sTBI), acute oxidative stress and inflammatory cascades rapidly spread to cause irreversible brain damage and low survival rate within minutes. Therefore, developing a feasible solution for the quick-treatment of life-threatening emergency is urgently demanded to earn time for hospital treatment. Herein, Janus catalysis-driven nanomotors (JCNs) are carefully constructed via plasma-induced alloying technology and sputtering-caused half-coating strategy. The theoretical calculation and experiment results indicate that the heteroatom-doping alloyed engine endows JCNs with much higher catalytic activity for removing reactive oxygen species and reactive nitrogen species than common Pt-based engines. When JCNs are dropped to the surface of the ruptured skull, they can effectively catalyze endogenous hydrogen peroxide, which induces movement as fuels to promote JCNs to deep brain lesions for further nanocatalyst-mediated cascade-blocking therapy. The results demonstrate that the JCNs successfully block the inflammatory cascades, thereby reversing multiple behavioral defects and dramatically declining the mortality of sTBI mice. This work provides a revolutionary nanomotor-based strategy to sense brain injury and scavenge oxidative stress. Meanwhile, the JCNs provide a feasible strategy to adapt various first-aid scenarios due to their self-propelled movement combined with highly multienzyme-like catalytic activity, exhibiting tremendous therapeutic potential to help people for emergency pretreatment.

With the unique advantages in structure and property, covalent organic frameworks have been widely employed for separation and enrichment. In this work, the thiosemicarbazide-linked covalent organic framework (TpTc) was prepared by using 1,3,5-triformylphloroglucinol and non-rigid thiosemicarbazide as building blocks for the first time. The as-prepared TpTc COF was fully characterized, presenting an agaric-like structure, large specific surface area (63.5 m2 g-1), uniform pore size distribution (1.36 nm), inherent porosity and ordered crystallinity. The potential of TpTc as adsorbent for metal ions capture was investigated by static batch adsorption experiment using the one-factor procedure. The maximum adsorption capacities of 73.50, 56.53 and 94.13 mg g-1 were obtained for Cu (II), Pb (II) and Cd (II) at natural pH, respectively. The anchoring of three metal ions onto TpTc is a multi-layer sorption involving chemical adsorption, and obeys the Freundlich and pseudo-second-order model. According to XPS analysis, the adsorption mechanism may be attributed to the coordination and electrostatic interaction between metal ions and N, O and S atoms on TpTc COF. This work not only provides a candidate for the application of COFs in metal ions capture, but also a reference for exploring functional design of COFs .

To explore the structure-activity connections of amphiphilic permeation enhancers containing the length of the hydrophobic chains as well as the properties of the polar head

Background: The effect of SARS-CoV-2 on existing respiratory pathogens in circulation remains uncertain. This study aimed to assess the impact of SARS-CoV-2 on the prevalence of respiratory pathogens among hospitalized children.Methods: This study enrolled hospitalized children with acute respiratory infections in Shenzhen Children’s Hospital from September to December 2019 (before the COVID-19 epidemic) and those from September to December 2020 (after the COVID-19 epidemic). Nasopharyngeal swabs were collected, and respiratory pathogens were detected using multiplex PCR. The absolute case number and detection rates of 11 pathogens were collected and analyzed.Results: A total of 5696 children with respiratory tract infection received multiplex PCR examination for respiratory pathogens: 2298 from September to December 2019 and 3398 from September to December 2020. At least one pathogen was detected in 1850 (80.5%) patients in 2019, and in 2380 (70.0%) patients in 2020; the detection rate in 2020 was significantly lower than that in 2019. The detection rates reflected changes in these pathogens when the COVID-19 epidemic was well controlled. The Influenza A (InfA) detection rate was 5.6% in 2019, but 0% in 2020. The detection rates of Mycoplasma pneumoniae, Human adenovirus, and Human rhinovirus also decreased from 20% (460), 8.9% (206), and 41.8% (961) in 2019 to 1.0% (37), 2.1% (77), and 25.6% (873) in 2020, respectively. In contrast, the detection rates of Human respiratory syncytial virus, Human parainfluenza virus, and Human metapneumovirus increased from 6.6% (153), 9.9% (229), and 0.5% (12) in 2019 to 25.6% (873), 15.5% (530), and 7.2% (247) in 2020, respectively (p < 0.0001).Conclusions: The emergence of SARS-CoV-2 was associated with the substantial reduction in the circulation of respiratory pathogens including influenza virus, rhinovirus, adenovirus, and Mycoplasma pneumoniae, as well as with the increase in respiratory syncytial virus, parainfluenza, and human metapneumovirus in Shenzhen. The reasons for this phenomenon require further studies.

Significance Each year, the global mortality rates for fungal diseases now exceed those for malaria and breast cancer and are currently comparable to those for tuberculosis and HIV. The limited scope of currently available antifungal drugs is the major factor underlying the observed high mortality rate. Here, we provide evidence that Myosin IF (MYO1F) plays a critical role in the mediating of signaling molecules “trafficking from membrane to cytoplasm,” and this process is essential for the antifungal signaling pathway activation. Moreover, we provide evidence that Sirt2 deacetylase inhibitors promote antifungal immunity and protect mice from lethal Candida albicans infection, which indicates that the Sirt2 could be a good therapeutic target for the antifungal drug development., Opportunistic fungal infections have become one of the leading causes of death among immunocompromised patients, resulting in an estimated 1.5 million deaths each year worldwide. The molecular mechanisms that promote host defense against fungal infections remain elusive. Here, we find that Myosin IF (MYO1F), an unconventional myosin, promotes the expression of genes that are critical for antifungal innate immune signaling and proinflammatory responses. Mechanistically, MYO1F is required for dectin-induced α-tubulin acetylation, acting as an adaptor that recruits both the adaptor AP2A1 and α-tubulin N-acetyltransferase 1 to α-tubulin; in turn, these events control the membrane-to-cytoplasm trafficking of spleen tyrosine kinase and caspase recruitment domain-containing protein 9. Myo1f-deficient mice are more susceptible than their wild-type counterparts to the lethal sequelae of systemic infection with Candida albicans. Notably, administration of Sirt2 deacetylase inhibitors, namely AGK2, AK-1, or AK-7, significantly increases the dectin-induced expression of proinflammatory genes in mouse bone marrow–derived macrophages and microglia, thereby protecting mice from both systemic and central nervous system C. albicans infections. AGK2 also promotes proinflammatory gene expression in human peripheral blood mononuclear cells after Dectin stimulation. Taken together, our findings describe a key role for MYO1F in promoting antifungal immunity by regulating the acetylation of α-tubulin and microtubules, and our findings suggest that Sirt2 deacetylase inhibitors may be developed as potential drugs for the treatment of fungal infections.

The aim of this investigation was to develop an etomidate intravenous lipid emulsion (ETM-ILE) and evaluate its properties in vitro and in vivo. Etomidate (ETM) is a hydrophobic drug, and organic solvents must be added to an etomidate injectable solution (ETM-SOL) to aid dissolution, that causes various adverse reactions on injection. Lipid emulsions are a novel drug formulation that can improve drug loading and reduce adverse reactions. ETM-ILE was prepared using high-pressure homogenization. Univariate experiments were performed to select key conditions and variables. The proportion of oil, egg lecithin, and poloxamer 188 (F68) served as variables for the optimization of the ETM-ILE formulation by central composite design response surface methodology. The optimized formulation had the following characteristics: particle size, 168.0 ± 0.3 nm; polydispersity index, 0.108 ± 0.028; zeta potential, −36.4 ± 0.2 mV; drug loading, 2.00 ± 0.01 mg/mL; encapsulation efficiency, 97.65% ± 0.16%; osmotic pressure, 292 ± 2 mOsmol/kg and pH value, 7.63 ± 0.07. Transmission electron microscopy images showed that the particles were spherical or spheroidal, with a diameter of approximately 200 nm. The stability study suggested that ETM-ILE could store at 4 ± 2 °C or 25 ± 2 °C for 12 months. Safety tests showed that ETM-ILE did not cause hemolysis or serious vascular irritation. The results of the pharmacokinetic study found that ETM-ILE was bioequivalent to ETM-SOL. However, a higher concentration of ETM was attained in the liver, spleen, and lungs after administration of ETM-ILE than after administration of ETM-SOL. This study found that ETM-ILE had great potential for clinical applications.

This study investigates phase separation behavior and pattern formation in a binary fluid with chemical reaction controlled by thermal diffusion. By incorporating the Arrhenius equation into the lattice Boltzmann method (LBM), the coupling effects of the pre-exponential factor K, viscosity $$\eta $$ , and thermal diffusion D on phase separation were successfully evaluated. The effect of the competition between thermal diffusion and concentration on the phase separation morphology and dynamics of binary mixtures under a chemically reacting controlled by slow cooling is assessed based on the extended LBM. The calculations indicated that increases in viscosity and thermal diffusion can obtain interconnected structures (ISs) and lamellar structures (LSs) for cases with small K. However, concentric phase-separated structures (CSs) were observed in cases with large K. The increase in the degree and efficiency of phase separation were significantly greater in cases with decreased viscosity and increased thermal diffusion.

Adaptation of tumors to therapeutic interventions contributes to dismal long-term patient outcomes. Adaptation to therapy involves co-action of functionally related proteins that together activate cell survival programs and compensate for the therapeutic impact. Oncogenic dependencies to such adaptive events, however, can generate new therapeutic vulnerabilities that can be targeted with drug combinations. The precision medicine approaches in which targeted drugs are matched to pre-existing genomic aberrations fail to address the adaptive responses and resulting vulnerabilities. Here, we provide the mathematical formulation, implementation and validation of the TargetScore method. The TargetScore identifies collective adaptive responses to targeted interventions as concurrent changes of phospho-proteins that are connected within a signaling network. Based on the adaptive responses, the method predicts drug-induced vulnerabilities. Using TargetScore, we inferred the adaptive responses with short-term (i.e., days) stress and long-term (i.e., months) acquired resistance to inhibitors of anti-apoptotic mediators, MCL1 and BCL2. With experiments guided by the predictions, we identified synergistic interactions between inhibitors of PARP, SHP2, and MCL1 in breast cancer cells. TargetScore is readily applicable to existing precision oncology efforts by matching targeted drug combinations to emerging molecular signatures under therapeutic stress.

To study more fully the characteristic law of deformation and failure of tuff jointed rock mass of prefabricated parallel discontinuous joint test specimens, the uniaxial compression test was used. The stress–strain curve, peak intensity, deformation parameters, energy characteristics, etc., of the rock test specimens were systematically studied under different combinations of joint dip angle and joint spacing. The research found that: (1) during the failure process of tuff, the peak intensity and elastic modulus followed a U-shaped change pattern and the minimum value was reached when α = 60°; (2) the fracture modes of test specimens with different joint dip angles were different. When α = 30° and 45°, failure characteristics were mixed modes of tensile or tensile shear failure. When α = 60°, failure characteristics were shear. At α = 75°, the failure characteristic was tensile shear failure. (3) The absorbed and dissipated energy of the rock increased nonlinearly at each stage of deformation. (4) We quantified rock energy damage through a correlation between dissipated energy and absorbed energy of the rock in the process of energy evolution, and obtained an evolution of the relationship between the dissipated energy ratio, crack dip angle and crack spacing. Based on different fracture distribution methods and according to the strain equivalence principle, the constitutive equation of the pre-peak rock damage was obtained.

To deal with serious environmental pollution resulting from plastic packaging materials, biodegradable films using chitosan (CS) are gaining considerable increase gradually. However, chitosan films lack important properties to meet the preserved demands. This study aimed to develop new bio-based films incorporated with carboxymethyl chitosan-ZnO (CMCS-ZnO) nanoparticles and sodium alginate (SA) to overcome the weakness of CS films. CMCS-ZnO nanoparticles were successfully synthesized in the matrix of CMCS through direct precipitation method, which showed an average diameter of 100 nm. Multilayer films with CS film as the outer layer and SA film as the inner layer were prepared by solution casting method. The addition of CMCS-ZnO nanoparticles led to enhanced tensile strength, and to better water vapor resistance. The as-prepared films exhibited distinctive antibacterial activity against S. aureus and E. coli. The results suggested that the as-prepared film is expected to be a promising material for food packaging.

We consider the robust smoothing problem for a state-space model with outliers in measurements. A unified framework for robust smoothing based on M-estimation is developed, in which the robust smoothing problem is formulated by replacing the quadratic loss for measurement fitting in the conventional Kalman smoother by a robust cost function from robust statistics. The majorization-minimization method is employed to iteratively solve the formulated robust smoothing problem. In each iteration, a surrogate function is constructed for the robust cost, which enables the states update procedure to be implemented in a similar way as that in a conventional Kalman smoother with a reweighted measurement covariance. Numerical experiments show that the proposed robust approach outperforms the traditional Kalman smoother and several robust filtering methods.

In this paper, we investigate optimal linear approximations ( n -approximation numbers) of the embeddings from the Sobolev spaces H r ( r > 0 ) for various equivalent norms and the Gevrey type spaces G α , β ( α , β > 0 ) on the sphere S d and on the ball B d , where the approximation error is measured in the L 2 -norm. We obtain preasymptotics, asymptotics, and strong equivalences of the above approximation numbers as a function in n and the dimension d . We emphasize that all equivalence constants in the above preasymptotics and asymptotics are independent of the dimension d and n . As a consequence we obtain that for the absolute error criterion the approximation problems I d : H r → L 2 are weakly tractable if and only if r > 1 , not uniformly weakly tractable, and do not suffer from the curse of dimensionality. We also prove that for any α , β > 0 , the approximation problems I d : G α , β → L 2 are uniformly weakly tractable, not polynomially tractable, and quasi-polynomially tractable if and only if α ≥ 1 .

We study d -variate problems in the average case setting with respect to a zero-mean Gaussian measure. The covariance kernel of this Gaussian measure is a product of univariate kernels and satisfies some special properties. We study ( s , t ) -weak tractability of this multivariate problem under the absolute or normalized error criterion, and obtain a necessary and sufficient condition for s > 0 and t ∈ ( 0 , 1 ) . Our result can apply to the problems with covariance kernels corresponding to Euler and Wiener integrated processes, Korobov kernels, and analytic Korobov kernels.

In the study, amorphous calcium phosphate (ACP) nanoparticles were prepared by the coprecipitation method to optimize release profile of curcumin (Cur) and avoid burst releases, which were used to overcome the weakness of Cur, such as poor chemical stability and bioavailability. To find the best preparation condition, the influence of reaction concentration, temperature, time and pH on crystal phase of the samples was investigated by XRD and FTIR. The results showed that amorphous calcium phosphate (ACP) was obtained, when pH value and the concentration of PO43− were 8 and 0.024 mM, prepared at 30 °C for 10 min. In vitro drug release assay, ACP nanoparticles showed high loading capacity of Cur and favorable pH-responsive drug release properties. Furthermore, the Cur-load ACP nanoparticles showed an excellent ability to scavenge free radical and damage A549 cells, resulting in a high antioxidant properties and low cell viability. Therefore, the as-prepared nanoparticles have promising applications in the food and biomedical fields.

Importance: A cluster of influenza-associated deaths occurred among children during pandemic 2009 influenza A (H1N1) in China, but the risk factors and causes for death have not been clarified. Objective: We describe the clinical findings regarding 2009 influenza A (H1N1)-associated pediatric deaths in China, including the risk factors for death. Methods: The definition of 2009 influenza A (H1N1)-associated pediatric death is death in a child who is younger than 14 years and has laboratory-confirmed influenza. We collected data of total 810 hospitalized patients with 2009 influenza A (H1N1) infection from September 2009 to February 2010 in 17 hospitals across China. The clinical characteristics, laboratory abnormalities, and treatment course were retrospectively studied. Results: Of the 810 patients hospitalized with 2009 influenza A (H1N1) infection, 19 (2.3%) died. Ten patients died from severe pneumonia and acute respiratory distress syndrome; eight died from encephalopathy/encephalitis; one died from secondary fungal meningitis. Patients who died were more likely than patients who survived to have neutrophilia, lymphopenia, elevated C-reactive protein, and elevations of lactate dehydrogenase, creatine kinase, creatine kinase-MB, aspartate aminotransferase and alanine aminotransferase. There were no significant differences in the median age, median time from onset of illness to admission, underlying chronic disease, and initiation of antiviral therapy within 48 hours of illness onset, between patients who died and those who survived. Interpretation: The risk factors for pediatric death associated with 2009 influenza A (H1N1) infection are different from those of seasonal influenza. The most common causes of death are viral pneumonia, acute respiratory distress syndrome, and encephalopathy/encephalitis. Key words: 2009 influenza A (H1N1); Mortality rates; Children

Purpose This study aims to explore the characteristics, related factors and risk factors of insomnia of patients after operation for gastric cancer. Methods A cross-sectional survey was carried out and finally 115 patients with insomnia after operation for gastric cancer were included. The general information, gastric cancer related information, sleep quality and other symptoms were investigated. Results ①The Pittsburgh sleep quality index score of most insomnia patients after gastric cancer surgery was 11–15 points, the sleep quality rating was “Poor”. ②The sleep quality of patients with insomnia after surgery for gastric cancer is related to the number of chemotherapy cycles, fatigue and depression. ③The risk of reduced sleep quality with the number of chemotherapy cycles > 6 is 3.640 times that of ≤ 6. The risk of reduced sleep quality during moderate to severe fatigue was 4.390 times that of patients with no or mild fatigue. Conclusion Attention to related factors and risk factors may be associated with improvement of sleep quality in patients with gastric cancer after surgery.

We study multivariate approximation in the average case setting with the error measured in the weighted $L_2$ norm. We consider algorithms that use standard information $\Lambda^{\rm std}$ consisting of function values or general linear information $\Lambda^{\rm all}$ consisting of arbitrary continuous linear functionals. We investigate the equivalences of various notions of algebraic and exponential tractability for $\Lambda^{\rm std}$ and $\Lambda^{\rm all}$ for the absolute error criterion, and show that the power of $\Lambda^{\rm std}$ is the same as that of $\Lambda^{\rm all}$ for all notions of algebraic and exponential tractability without any condition. Specifically, we solve Open Problems 116-118 and almost solve Open Problem 115 as posed by E.Novak and H.Wo\'zniakowski in the book: Tractability of Multivariate Problems, Volume III: Standard Information for Operators, EMS Tracts in Mathematics, Z\"urich, 2012., Comment: 23 pages. arXiv admin note: substantial text overlap with arXiv:2101.03665

Additional file 2 Table S2. Ct values of human adenovirus (HADV) detected in the BAL fluid.

Invasive fungal infections have become a leading cause of death among immunocompromised patients, leading to around 1.5 million deaths per year globally. The molecular mechanisms by which hosts defend themselves against fungal infection remain largely unclear, which impedes the development of antifungal drugs and other treatment options. In this article, we show that the tyrosine kinase receptor EPH receptor B2 (EPHB2), together with dectin-1, recognizes β-glucan and activates downstream signaling pathways. Mechanistically, we found that EPHB2 is a kinase for Syk and is required for Syk phosphorylation and activation after dectin-1 ligand stimulation, whereas dectin-1 is critical for the recruitment of Syk. Ephb2-deficient mice are susceptible to Candida albicans–induced fungemia model, which also supports the role of EPHB2 in antifungal immunity. Overall, we provide evidence that EPHB2 is a coreceptor for the recognition of dectin-1 ligands and plays an essential role in antifungal immunity by phosphorylating Syk.

Therapeutic options for treatment of basal-like breast cancers remain limited. Here, we demonstrate that bromodomain and extra-terminal (BET) inhibition induces an adaptive response leading to MCL1 protein-driven evasion of apoptosis in breast cancer cells. Consequently, co-targeting MCL1 and BET is highly synergistic in breast cancer models. The mechanism of adaptive response to BET inhibition involves the upregulation of lipid synthesis enzymes including the rate-limiting stearoyl-coenzyme A (CoA) desaturase. Changes in lipid synthesis pathway are associated with increases in cell motility and membrane fluidity as well as re-localization and activation of HER2/EGFR. In turn, the HER2/EGFR signaling results in the accumulation of and vulnerability to the inhibition of MCL1. Drug response and genomics analyses reveal that MCL1 copy-number alterations are associated with effective BET and MCL1 co-targeting. The high frequency of MCL1 chromosomal amplifications (30%) in basal-like breast cancers suggests that BET and MCL1 co-targeting may have therapeutic utility in this aggressive subtype of breast cancer.

IL-17A plays an essential role in the pathogenesis of many autoimmune diseases, including psoriasis and multiple sclerosis. Act1 is a critical adaptor in the IL-17A signaling pathway. In this study, we report that an anti-sense long noncoding RNA

The resurgence ofIn this study, whole-genome sequencing analysis was performed for 388This study revealed that lineage V diverged about 50 years ago in China, while lineage IV is dominant in the other countries. It also revealed that the erythromycin-resistant sub-lineages Va, Vb, and Vc with limited genomic variation emerged 11 ~ 12 years ago. These three sub-lineages were identified after the co-purified acellular vaccines (cp-ACVs) completely replaced the previous whole cell vaccines (WCVs) after the national immunization program of 2012. It suggests that the cp-ACVs cannot induce immunity that is potent enough to restrict the spread of the lineage V, antibiotic abuse further favors the spread of this lineage in China.These findings demand a reassessment of the immunization strategy and development of new vaccines in China to stop the resurgence and drug resistance of

Alagille syndrome (AGS) is an autosomal dominant multisystem disorder caused by mutations in theEight adults diagnosed with AGS at our hospital between June 2016 and June 2019 were included in the study. Clinical data, biochemical results, imaging results, liver histopathology, and genetic testing were analyzed.Three female and five male patients with a median age of 24.5 years at the time of diagnosis were included in the analysis. The clinical manifestations were adult-onset (62.5%, 5/8), cholestasis (50%, 4/8), butterfly vertebrae (62.5%, 5/8), systolic murmurs (12.5%, 1/8), typical facies (12.5%, 1/8), posterior embryotoxon, and renal abnormalities (0/8). Genetic sequencing showed that all patients had mutations, with four occurring in theThe clinical manifestations highlighted by the current diagnostic criteria for most adults with AGS are atypical. Those who do not meet the criteria but are highly suspicious of having AGS need further evaluation, especially genetic testing.

Human Adenovirus (AdV) infection is very common and usually has a significant impact on children. AdV-induced inflammation is believed to be one of the main causes of severe symptoms. However, an inflammatory response profile in the airway in AdV-infected children is still lacking, and the mechanism underlying AdV-induced inflammation in the airway is also poorly understood. In the current study, we determined the expression of a panel of inflammation cytokines in the airway samples from AdV 7 infected children and further investigated the molecular mechanism underlying AdV 7-induced cytokine expression. Our results showed that eight out of 13 tested inflammatory cytokines were significantly increased in nasal washes of AdV 7-infected children comparing to healthy control, with IL-6 showing the highest enhancement. AdV 7 infection of bronchial epithelial cell line and primary airway epithelial cells confirmed that AdV 7 increased IL-6 mRNA and protein expression in an infection dose-dependent manner. Promoter analysis revealed that AdV 7 infection transactivated IL-6 promoter and a NF-κB binding site in IL-6 promoter was involved in the transactivation. Further analysis showed that upon AdV 7 infection, NF-κB p65 was phosphorylated and translocated into nucleus and bound onto IL-6 promoter. Signaling pathway analysis revealed that p38/NF-κB pathway was involved in AdV 7 infection induced IL-6 elevation. Taken together, our study shows that AdV 7 infection triggers the expression of a range of inflammatory cytokines including IL-6 in the airway of infected children, and AdV 7 enhances IL-6 expression by transactivating IL-6 promoter via p38/NF-κB signaling pathway. Findings of our current study have provided more information toward a better understanding of AdV-induced airway inflammation, which might also benefit the development of intervention strategies.