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Abstract Cryo-electron microscopy (cryo-EM) has been widely used to reveal the structures of proteins at atomic resolution. One key challenge is that almost all proteins are predominantly adsorbed to the air-water interface during standard cryo-EM specimen preparation. The interaction of proteins with air-water interface will significantly impede the success of reconstruction and achievable resolution. Here, we highlight the critical role of impenetrable surfactant monolayers in passivating the air-water interface problems, and develop a robust effective method for high-resolution cryo-EM analysis, by using the superstructure GSAMs which comprises surfactant self-assembled monolayers (SAMs) and graphene membrane. The GSAMs works well in enriching the orientations and improving particle utilization ratio of multiple proteins, facilitating the 3.3-Å resolution reconstruction of a 100-kDa protein complex (ACE2-RBD), which shows strong preferential orientation using traditional specimen preparation protocol. Additionally, we demonstrate that GSAMs enables the successful determinations of small proteins (

Abstract Background In epigenetic modification, histone modification and DNA methylation coordinate the regulation of spermatogonium. Not only can methylcytosine dioxygenase 1 (TET1) function as a DNA demethylase, converting 5-methylcytosine to 5-hydroxymethylcytosine, it can also form complexes with other proteins to regulate gene expression. H3K27me3, one of the common histone modifications, is involved in the regulation of stem cell maintenance and tumorigenesis by inhibiting gene transcription. Methods we examined JMJD3 at both mRNA and protein levels and performed Chip-seq sequencing of H3K27me3 in TET1 overexpressing cells to search for target genes and signaling pathways of its action. Results This study has found that JMJD3 plays a leading role in spermatogonia self-renewal and proliferation: at one extreme, the expression of the self-renewal gene GFRA1 and the proliferation-promoting gene PCNA was upregulated following the overexpression of JMJD3 in spermatogonia; at the other end of the spectrum, the expression of differentiation-promoting gene DAZL was down-regulated. Furthermore, the fact that TET1 and JMJD3 can form a protein complex to interact with H3K27me3 has also been fully proven. Then, through analyzing the sequencing results of CHIP-Seq, we found that TET1 targeted Pramel3 when it interacted with H3K27me3. Besides, TET1 overexpression not only reduced H3K27me3 deposition at Pramel3, but promoted its transcriptional activation as well, and the up-regulation of Pramel3 expression was verified in JMJD3-overexpressing spermatogonia. Conclusion In summary, our study identified a novel link between TET1 and H3K27me3 and established a Tet1-JMJD3-H3K27me3-Pramel3 axis to regulate spermatogonia self-renewal and proliferation. Judging from the evidence offered above, we can safely conclude that this study provides new ideas for further research regarding the mechanism of spermatogenesis and spermatogenesis disorders on an apparent spectrum.

This paper models and analyzes the Complementary Metal Oxide Semiconductor (CMOS) cross-coupled differential-drive (CCDD) rectifier for Ultra-Low-Power ambient radio-frequency energy harvesters (RFEHs) working in the subthreshold region. In this paper, two closed-form equations of CCDD rectifier output voltage and input resistance in the subthreshold region were derived based on BSIM4 models of NMOS and PMOS. The model give insight to specify circuit parameters according to different inputs, transistor sizes, threshold voltages, numbers of stages, load conditions and compensation voltages, which can be used to optimize the rectifier circuit. There is a good agreement between the simulation results and these models, and these models have a maximum deviation of 10% in comparison with the simulation results in the subthreshold region. The measurement results of a single-stage CCDD rectifier reported in a previous paper were adopted to verify the model. The output voltage and input resistance predicted by these models provide excellent consistency with corresponding measurement results. The model can be employed to optimize the CCDD rectifier without expensive calculation in the design stage.

Differential evolution is capable of searching for the optimum for different types of optimization problems with a few inputs, which has gained worldwide popularity. In this paper, we propose a parameters adaptation scheme based on the stagnation ratio (PASR), which regards the stagnation ratio (STR) as the indicator for adjusting the control parameters and greediness parameter. To be specific, when the STR is larger than the predefined threshold, exploration is advocated. In this circumstance, larger control parameters and a greediness parameter are adopted. However, when the STR is smaller than the predefined threshold, exploitation is preferred. In this case, smaller control parameters and a greediness parameter are utilized. Further, when the stagnation lasts for a long period, a generation-based selection (GBS) scheme is developed to help it escape from the local optimum and stagnation. Comparative experiments have been implemented on the CEC2017 to testify the effectiveness of adaptive differential evolution with the stagnation termination mechanism (STMDE) and its components. The competitiveness of the STMDE is also verified via comparing it to top-performing DE variants in the practical optimization problem selected from the CEC2011.

BackgroundTraditional Chinese medicine (TCM) comprising herbal formulas has been used for millennia to treat various diseases, such as insomnia, based on distinct syndrome types. Although TCM has been proposed to be effective in insomnia through gut microbiota modulation in animal models, human studies remain limited. Therefore, this study employs machine learning and integrative network techniques to elucidate the role of the gut microbiome in the efficacies of two TCM formulas — center-supplementing and qi-boosting decoction (CSQBD) and spleen-tonifying and yin heat-clearing decoction (STYHCD) — in treating insomnia patients diagnosed with spleen qi deficiency and spleen qi deficiency with stomach heat.MethodsSixty-three insomnia patients with these two specific TCM syndromes were enrolled and treated with CSQBD or STYHCD for 4 weeks. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI) every 2 weeks. In addition, variations in gut microbiota were evaluated through 16S rRNA gene sequencing. Stress and inflammatory markers were measured pre- and post-treatment.ResultsAt baseline, patients exhibiting only spleen qi deficiency showed slightly lesser severe insomnia, lower IFN-α levels, and higher cortisol levels than those with spleen qi deficiency with stomach heat. Both TCM syndromes displayed distinct gut microbiome profiles despite baseline adjustment of PSQI, ISI, and IFN-α scores. The nested stratified 10-fold cross-validated random forest classifier showed that patients with spleen qi deficiency had a higher abundance of Bifidobacterium longum than those with spleen qi deficiency with stomach heat, negatively associated with plasma IFN-α concentration. Both CSQBD and STYHCD treatments significantly improved sleep quality within 2 weeks, which lasted throughout the study. Moreover, the gut microbiome and inflammatory markers were significantly altered post-treatment. The longitudinal integrative network analysis revealed interconnections between sleep quality, gut microbes, such as Phascolarctobacterium and Ruminococcaceae, and inflammatory markers.ConclusionThis study reveals distinct microbiome profiles associated with different TCM syndrome types and underscores the link between the gut microbiome and efficacies of Chinese herbal formulas in improving insomnia. These findings deepen our understanding of the gut-brain axis in relation to insomnia and pave the way for precision treatment approaches leveraging TCM herbal remedies.

Abstract Microbial production of monoterpenoid indole alkaloids (MIAs) provides a sustainable and eco‐friendly means to obtain compounds with high pharmaceutical values. However, efficient biosynthesis of MIAs in heterologous microorganisms is hindered due to low supply of key precursors such as geraniol and its derivative 8‐hydroxygeraniol catalyzed by geraniol 8‐hydroxylase (G8H). In this study, we developed a facile evolution platform to screen strains with improved yield of geraniol by using the SCRaMbLE system embedded in the Sc2.0 synthetic yeast and confirmed the causal role of relevant genomic targets. Through genome mining, we identified several G8H enzymes that perform much better than the commonly used CrG8H for 8‐hydroxygeraniol production in vivo. We further showed that the N‐terminus of these G8H enzymes plays an important role in cellular activity by swapping experiments. Finally, the combination of the engineered chassis, optimized biosynthesis pathway, and utilization of G8H led to the final strain with more than 30‐fold improvement in producing 8‐hydroxygeraniol compared with the starting strain. Overall, this study will provide insights into the construction and optimization of yeast cells for efficient biosynthesis of 8‐hydroxygeraniol and its derivatives.

Abstract In this multicenter, single-arm phase 2 trial (ChiCTR1900024428), patients with locally advanced gastric/gastroesophageal junction cancers receive one cycle of sintilimab (anti-PD1) and chemotherapy (S-1 and nab-paclitaxel), followed by 5 weeks of concurrent chemoradiotherapy and sintilimab, and another cycle of sintilimab and chemotherapy thereafter. Surgery is preferably scheduled within one to three weeks, and three cycles of adjuvant sintilimab and chemotherapy are administrated. The primary endpoint is the pathological complete response. Our results meet the pre-specified primary endpoint. Thirteen of 34 (38.2%) enrolled patients achieve pathological complete response (95% CI: 22.2-56.4). The secondary objectives include disease-free survival (DFS), major pathological response, R0 resection rate, overall survival (OS), event-free survival (EFS), and safety profile. The median DFS and EFS were 17.0 (95%CI: 11.1-20.9) and 21.1 (95%CI: 14.7-26.1) months, respectively, while the median OS was not reached, and the 1-year OS rate was 92.6% (95%CI: 50.1-99.5%). Seventeen patients (50.0%) have grade ≥3 adverse events during preoperative therapy. In prespecified exploratory biomarker analysis, CD3+ T cells, CD56+ NK cells, and the M1/M1 + M2-like macrophage infiltration at baseline are associated with pathological complete response. Here, we show the promising efficacy and manageable safety profile of sintilimab in combination with concurrent chemoradiotherapy for the perioperative treatment of locally advanced gastric/gastroesophageal junction adenocarcinoma.

Abstract Bilayer graphene (BLG) is intriguing for its unique properties and potential applications in electronics, photonics, and mechanics. However, the chemical vapor deposition synthesis of large-area high-quality bilayer graphene on Cu is suffering from a low growth rate and limited bilayer coverage. Herein, we demonstrate the fast synthesis of meter-sized bilayer graphene film on commercial polycrystalline Cu foils by introducing trace CO2 during high-temperature growth. Continuous bilayer graphene with a high ratio of AB-stacking structure can be obtained within 20 min, which exhibits enhanced mechanical strength, uniform transmittance, and low sheet resistance in large area. Moreover, 96 and 100% AB-stacking structures were achieved in bilayer graphene grown on single-crystal Cu(111) foil and ultraflat single-crystal Cu(111)/sapphire substrates, respectively. The AB-stacking bilayer graphene exhibits tunable bandgap and performs well in photodetection. This work provides important insights into the growth mechanism and the mass production of large-area high-quality BLG on Cu.

Abstract Wind energy is one of the most important clean energies and the variable speed constant frequency technology is widely used in wind energy conversion systems. Maximum power point tracking (MPPT) is essential for a variable speed constant frequency wind power generation system. Concerning the current research on the MPPT algorithm, this paper studies the principle, characteristics, and reported improvement strategies of principal algorithms. Through the comparison of simulation results for selected control algorithms, the improved optimal torque control algorithm has been found to be the best MPPT algorithm for wind power generation systems because of its simplicity and efficiency. On this basis, further corresponding simulation runs are carried out to analyze the effect of the wind speed fluctuation characteristics on the systematic dynamic performance and power generation efficiency. The results show that the average wind speed, wind fluctuation frequency, and wind fluctuation amplitude can affect the performance of system operation and the efficiency of wind energy capture in different degrees, which has a great practical significance for the research of MPPT control strategy.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovitis and destruction of cartilage, promoted by sustained inflammation. However, current treatments remain unsatisfactory due to lacking of selective and effective strategies for alleviating inflammatory environments in RA joint. Inspired by neutrophil chemotaxis for inflammatory region, we therefore developed neutrophil-derived exosomes functionalized with sub-5 nm ultrasmall Prussian blue nanoparticles (uPB-Exo) via click chemistry, inheriting neutrophil-targeted biological molecules and owning excellent anti-inflammatory properties. uPB-Exo can selectively accumulate in activated fibroblast-like synoviocytes, subsequently neutralizing pro-inflammatory factors, scavenging reactive oxygen species, and alleviating inflammatory stress. In addition, uPB-Exo effectively targeted to inflammatory synovitis, penetrated deeply into the cartilage and real-time visualized inflamed joint through MRI system, leading to precise diagnosis of RA in vivo with high sensitivity and specificity. Particularly, uPB-Exo induced a cascade of anti-inflammatory events via Th17/Treg cell balance regulation, thereby significantly ameliorating joint damage. Therefore, nanoenzyme functionalized exosomes hold the great potential for enhanced treatment of RA in clinic.

Air-water interface and preferential orientation problems are crucial challenges in cryo-EM specimen preparation. Here, the authors utilize graphene-coated EM grids functionalized by salts with various electrostatic properties, successfully overcoming preferred orientation.

Abstract Background Early hepatocellular carcinoma (HCC) detection with non-invasive biomarkers remains an unmet clinical need. We aimed to construct a predictive model based on the pre-diagnostic levels of serum markers to predict the early-stage onset of HCC. Methods A total of 339 HCC patients (including 157 patients from Changzhou cohort and 182 patients from Wuxi cohort) were enrolled in our retrospective study. Levels of 25 baseline serum markers were collected. Propensity score matching (PSM) analysis was conducted to balance the distributions of patients’ gender, age, and the surveillance time between HCC group and control group. Then, Receiver operating characteristic (ROC) and Logistic regression analysis were performed to screen the independent predictive variables and construct a non-invasive predictive model. Subsequently, ROC curve and Kaplan–Meier (K–M) curve were used to evaluate the predictive values of the model. Clinical net benefit of the model was demonstrated by decision curve analysis (DCA) and clinical impact curve. Results Five independent predictive variables for HCC onset and two general characteristics of patients (age and gender) were incorporated into the score model. ROC and DCA curves showed that the score model had better predictive performance in discrimination and clinical net benefit compared with single variable or other score systems, with the area under the curve (AUC) of 0.890 (95% CI 0.856–0.925) in Changzhou cohort and 0.799 (95% CI 0.751–0.849) in Wuxi cohort. Meanwhile, stratification analysis indicated that the score model had good predictive values for patients with early tumor stage (AJCC stage I) or small tumors (

Defect-free integration of 2D materials onto semiconductor wafers is desired to implement heterogeneous electronic devices. Here, the authors report a method to transfer high-quality graphene on target wafers via gradient surface energy modulation, leading to improved structural and electronic properties.

Osteoporosis is the most common degenerative orthopedic disease in the elderly. Recently, the therapeutic methods for osteoporosis have shifted towards the regulation of local immunity in bone tissues, which could provide a suitable environment for the positive regulation of bone metabolism, promoting osteogenic differentiation and inhibiting osteoclast differentiation. Our previous work demonstrated that iron oxide nanoparticles (IONPs) could positively regulate bone metabolism in vitro. In this study, we further demonstrated that daily administration of IONPs relieved estrogen deficiency-induced osteoporosis via scavenging reactive oxygen species in vivo. Meanwhile, IONPs promoted the osteogenic differentiation of bone marrow mesenchymal stem cells and inhibited the osteoclast differentiation of monocytes from IONPs treated mice. Besides, alendronate, a clinically used anti-osteoporosis bisphosphate, was employed to precisely deliver the IONPs to the bone tissues and played a synergically therapeutic role. Eventually, we verified the bone targeting ability, therapeutic efficiency, and biocompatibility of the novel bone target iron oxides in ovariectomy-induced osteoporotic mice. By applying BTNPs, the OVX-induced osteoporosis was significantly revised in mice models via the positive regulation of bone metabolism.

Reliable transfer techniques are critical for the integration of 2D materials with arbitrary substrates. Here, the authors describe a method to transfer 4-inch and A4-sized defect-free graphene films onto rigid and flexible substrates with controllable conformal contact, leading to improved electrical properties and uniformity.

Abstract Objectives To analyze the changes of lower limb hemodynamics parameters before and after wearing graduated compression stockings (GCS) during ankle pump exercise in patients preparing for arthroplastic surgery. Method The leg veins of 16 patients awaiting arthroplasty were analyzed using a Sonosite M-Turbo ultrasound system during ankle pump exercise with or without GCS. The age of them was 70 ± 7 years (mean ± SD) (range 56—82 years) and body mass index was 25.8 ± 3.0 kg/m2 (range 18.0—30.5 kg/m2). Measured data including the cross-sectional area (CSA), anteroposterior (AP) diameter and lateromedial (LM) diameter of the soleus vein (SV), posterior tibial vein (PTV) and great saphenous vein (GSV). Additionally, the peak velocities of femoral vein (FV) were also measured. Results GCS could significantly decrease the cross-sectional area of SV, PTV and GSV in supine position at rest and maximum ankle plantar flexion. But the compression effect of GCS to SV and GSV was not observed during maximum ankle dorsiflexion. It was found that GCS application reduced the peak flow velocity of the femoral vein from 61.85 cm/s (95% CI = 50.94–72.75 cm/s) to 38.01 cm/s (95% CI = 28.42–47.59 cm/s) (P

Phagocyte oxidase plays an essential role in the first line of host defense against pathogens. It oxidizes intracellular NADPH to reduce extracellular oxygen to produce superoxide anions that participate in pathogen killing. The resting phagocyte oxidase is a heterodimeric complex formed by two transmembrane proteins NOX2 and p22. Despite the physiological importance of this complex, its structure remains elusive. Here, we reported the cryo-EM structure of the functional human NOX2-p22 complex in nanodisc in the resting state. NOX2 shows a canonical 6-TM architecture of NOX and p22 has four transmembrane helices. M3, M4, and M5 of NOX2, and M1 and M4 helices of p22 are involved in the heterodimer formation. Dehydrogenase (DH) domain of NOX2 in the resting state is not optimally docked onto the transmembrane domain, leading to inefficient electron transfer and NADPH binding. Structural analysis suggests that the cytosolic factors might activate the NOX2-p22 complex by stabilizing the DH in a productive docked conformation.

The differential evolution (DE) algorithm is a simple and efficient population-based evolutionary algorithm. In DE, the mutation strategy and the control parameter play important roles in performance enhancement. However, single strategy and fixed parameter are not universally applicable to problems and evolution stages with diverse characteristics; besides, the weakness of the advanced DE optimization framework, called selective-candidate framework with similarity selection rule (SCSS), is found by focusing on its single strategy and fixed parameter greedy degree (GD) setting. To address these problems, we mainly combine the multiple candidates generation with multi-strategy (MCG-MS) and the adaptive similarity selection (ASS) rule. On the one hand, in MCG-MS, two symmetrical mutation strategies, “DE/current-to-pbest-w/1” and designed “DE/current-to-cbest-w/1”, are utilized to build the multi-strategy to produce two candidate individuals, which prevents the over-approximation of the candidate in SCSS. On the other hand, the ASS rule provides the individual selection mechanism for multi-strategy to determine the offspring from two candidates, where parameter GD is designed to increase linearly with evolution to maintain diversity at the early evolution stage and accelerate convergence at the later evolution stage. Based on the advanced algorithm jSO, replacing its offspring generation strategy with the combination of MCG-MS and ASS rule, this paper proposes multi-strategy differential evolution algorithm with adaptive similarity selection rule (MSDE-ASS). It combines the advantages of two symmetric strategies and has an efficient individual selection mechanism without parameter adjustment. MSDE-ASS is verified under the Congress on Evolutionary Computation (CEC) 2017 competition test suite on real-parameter single-objective numerical optimization, and the results indicate that, of the 174 cases in total, it wins in 81 cases and loses in 30 cases, and it has the smallest performance ranking value, of 3.05. Therefore, MSDE-ASS stands out compared to the other state-of-the-art DEs.

Liver cancer is one of the most common cancers in the world, and the rate of liver cancer is high due to the of its illness. The main risk factor for liver cancer is infection with the hepatitis B virus (HBV), but a considerable number of genetic and epigenetic factors are also directly or indirectly involved in the underlying pathogenesis of liver cancer. In particular, the apolipoprotein B mRNA editing enzyme, catalytic peptide-like protein (APOBEC) family (DNA or mRNA editor family), which has been the focus of virology research for more than a decade, has been found to play a significant role in the occurrence and development of various cancers, providing a new direction for the research of liver cancer. APOBEC3B is a cytosine deaminase that controls a variety of biological processes, such as protein expression, innate immunity, and embryonic development, by participating in the process of cytidine deamination to uridine in DNA and RNA. In humans, APOBEC3B has long been known as a DNA editor for limiting viral replication and transcription. APOBEC3B is widely expressed at low levels in a variety of normal tissues and organs, but it is significantly upregulated in different types of tumor tissues and tumor lines. Thus, APOBEC3B has received increasing attention in various cancers, but the role of APOBEC3B in the occurrence and development of liver cancer due to infection with HBV remains unclear. This review provides a brief introduction to the pathogenesis of hepatocellular carcinoma induced by HBV, and it further explores the latest results of APOBEC3B research in the development of HBV and liver cancer, thereby providing new directions and strategies for the treatment and prevention of liver cancer.

High-resolution electron microscopy requires robust and noise-free substrates to support the specimens. Here, the authors present a polymer- and transfer-free direct-etching method for fabrication of graphene grids with ultraclean surfaces and demonstrate cryo-EM at record high resolution.

Spermatogonia are the source of spermatogenic waves. Abnormal spermatogonia can cause ab-normal spermatogenic waves, which manifest as spermatogenic disorders such as oligospermia, hypospermia, and azoospermia. Among them, the self-renewal of spermatogonia serves as the basis for maintaining the process of spermatogenesis, and the closely regulated balance between self-renewal and differentiation of spermatogonia can maintain the continuous production of spermatozoa. Tet methylcytosine dioxygenase 1(TET1) is an important epitope modifying enzyme that catalyzes the conversion of 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC), thereby causing the methylation of specific genes site hydroxylation, enabling the DNA de-methylation process, and regulating gene expression. However, the hydroxymethylation sites at which TET1 acts specifically and the mechanisms of interaction affecting key differential genes are not clear. In the present study, we provide evidence that the expression of PLZF, a marker gene for spermatogonia self-renewal, was significantly elevated in the TET1 overexpression group, while the expression of PCNA, a proliferation-related marker gene, was also elevated at the mRNA level. Significant differential expression of SP1 was found by sequencing. SP1 expression was increased at both mRNA level and protein level after TET1 overexpression, while differential gene DAXX expression was downregulated at protein level, while the expression of its reciprocal protein P53 was upregulated. In conclusion, our results suggest that TET1 overexpression causes changes in the expression of SP1, DAXX and other genes, and that there is a certain antagonistic effect between SP1 and DAXX, which eventually reaches a dynamic balance to maintain the self-renewal state of spermatogonia for sustained sperm production. These findings may contribute to the understanding of male reproductive system disorders.

Background Early recurrence of hepatocellular carcinoma (HCC) is a major obstacle to improving the prognosis, and no widely accepted adjuvant therapy guideline for patients post-liver resection is available. Currently, all available methods and biomarkers are insufficient to accurately predict post-operation HCC patients’ risk of early recurrence and their response to adjuvant therapy. Methods In this study, we downloaded four gene expression datasets (GSE14520, GSE54236, GSE87630, and GSE109211) from the Gene Expression Omnibus database and identified 34 common differentially expressed genes associated with HCC dysregulation and response to adjuvant sorafenib. Then, we constructed a novel 11-messenger RNA predictive model by using ROC curves analysis, univariate Cox regression analysis, and LASSO Cox regression analysis. Furthermore, we validated the predictive values of the risk model in GSE14520 and TCGA-LIHC cohorts by using Kaplan–Meier survival analysis, multivariable Cox regression analysis, and decision curve analysis, respectively. Results The risk score model could identify patients with a high risk of HCC recurrence at the early stage and could predict the response of patients to adjuvant sorafenib. Patients with a high risk score had a worse recurrence rate in training cohorts (2-year: p < 0.0001, hazard ratio (HR): 4.658, confidence interval 95% CI [2.895–7.495]; 5-year: p < 0.0001, HR: 3.251, 95% CI [2.155–4.904]) and external validation cohorts (2-year: p < 0.001, HR: 3.65, 95% CI [2.001–6.658]; 5-year: p < 0.001, HR: 3.156, 95% CI [1.78–5.596]). The AUC values of the risk score model for predicting tumor early recurrence were 0.746 and 0.618, and that of the risk score model for predicting the response to adjuvant sorafenib were 0.722 and 0.708 in the different cohort, respectively. Multivariable Cox regression analysis and decision curve analysis also showed that the risk score model was superior to and independent of other clinicopathologic characteristics. Moreover, the risk score model had excellent abilities to predict the overall survival and HCC recurrence of patients with the same tumor stage category. Conclusions Our risk model is a reliable and superior predictive tool. With this model, we could optimize the risk stratification based on early tumor recurrence and could evaluate the response of patients to adjuvant sorafenib after liver resection.

This study aims to evaluate the relationship between home parenting environment and the cognitive and psychomotor development in children under 5 years old by using meta-analysis. A systematic search of the Chinese and English databases including Pubmed, Embase, the Cochrane Library, CNKI, Weipu, Wanfang, and CBMdisc databases from January 1, 1990, to July 31, 2021, was performed. Articles concerning the relationship between home parenting environment and the cognitive and psychomotor development in children under 5 years old were included. Review Manager 5.4 was used for meta-analysis. Subgroup analysis in terms of age and region were performed. A total of 12 articles were included, including 11 in English and 1 in Chinese. Meta-analysis showed that there was significant relationship between home parenting environment and the cognitive and psychomotor development of children (r = 0.31; r = 0.21). Subgroup analysis showed that correlation between home parenting environment and the cognitive and psychomotor development of children was stronger in children over 18 months compared to those under 17 months [(r = 0.33, r = 0.21) vs. (r = 0.28, r = 0.17)]. The converted summary r value between home parenting environment and cognitive development in developing and developed countries was both 0.32. Conclusively, there is a positive correlation between the home parenting environment and the cognitive and psychomotor development of children under 5 years old. Improving the home parenting environment of children is beneficial to promote their early development.

Hydrogels, consisting of hydrophilic polymers, can be used as films, scaffolds, nanoparticles and drug carriers. They are one of the hot research topics in material science and tissue engineering and are widely used in the field of biomedical and biological sciences. Researchers are seeking for a type of material that is similar to human tissues and can partially replace human tissues or organs. The hydrogel has brought possibility to solve this problem. It has good biocompatibility and biodegradability. After entering the body, it does not cause immune and toxic reactions. The degradation time can be controlled, and the degradation products are nontoxic and nonimmunogenic; the final metabolites can be excreted outside the body. Owing to the lack of blood vessels and poor migration ability of chondrocytes, the self-healing ability of damaged cartilage is limited. Tissue engineering has brought a new direction for the regeneration of cartilage. Drug carriers and scaffolds made of hydrogels are widely used in cartilage tissue engineering. The present review introduces the natural hydrogels, which are often used for cartilage tissue engineering with respect to synthesis, modification and application methods. The translational potential of this article: This review introduces the natural hydrogels that are often used in cartilage tissue engineering with respect to synthesis, modification and application methods. Furthermore, the essential concepts and recent discoveries were demonstrated to illustrate the achievable goals and the current limitations. In addition, we propose the putative challenges and directions for the use of natural hydrogels in cartilage regeneration. Keywords: Alginate, Chitosan, Collagen, Gelatin, Hyaluronan, Natural hydrogel

Maximum power point tracking (MPPT) is the key to improve the conversion efficiency of wind energy. Concerning the current research on the MPPT control, based on the accurate tracking of rotor speed probability density function (PDF) shape for wind turbines, a novel MPPT algorithm was introduced in detail to improve the power capture and reduce mechanical damage for wind turbines. Considering the influence of wind speed distribution on the wind power generation system performance, this paper expounds a PDF shape control method of a stochastic system based on the Fokker–Planck–Kolmogorov (FPK) equation. Combining the conventional optimal torque (OT) control algorithm with the FPK equation solved by linear least-square (LLS) method, the novel MPPT control law is designed to make the PDF shape of rotor speed track the desired PDF shape as accurately as possible. The simulation verification of the novel MPPT method is carried out in the 1.5 MW wind turbine system. The results reveal that the novel MPPT method can improve the conversion efficiency of wind energy, reduce the frequent fluctuations of system variables, and significantly optimize the performance of wind power generation system.

Gold nanoparticles (GNPs) have attracted considerable attention in promoting osteogenic differentiation. However, little is known about their osteogenic effects on cells from various origins, and further in vivo investigation as a promising osteogenic agent upon hydrogel-conjugation is required. Herein, the effects of PEGylated GNPs with the sizes of 4, 18 and 45 nm on osteogenic differentiation in the pre-osteoblastic MC3T3-E1 cell line, human bone marrow-derived mesenchymal stem cells (hBMSCs) and rat bone marrow-derived mesenchymal stem cells (rBMSCs) were comprehensively evaluated. The results showed that GNPs with all of three different sizes had excellent biocompatibility, and their effects on induction of osteogenic differentiation of various cell types were dependent on size. Specifically, 45-nm GNPs showed more pronounced alkaline phosphatase (ALP) activity, mineralized nodule formation and expression of osteogenic marker genes compared with the 18-nm group, while 4-nm GNPs reduced the above osteogenic effects. Meanwhile, β-catenin and p-GSK-3β were upregulated by GNPs-45 nm and GNPs-18 nm, but suppressed by GNPs-4 nm, indicating that Wnt/β-catenin signaling pathway mighy play an important role in GNPs-induce osteogenic differentiation. In addition, specific blocking of Wnt/β-catenin signals by KYA1797K inhibited 45 nm GNPs-induced osteogenic differentiation of MC3T3-E1 cells. Furthermore, 45-nm GNPs conjugated with PEG-hydrogel were chosen for in vivo bone regeneration testing in rabbits with 4-mm femur defects. The results demonstrated that the GNPs stimulated bone regeneration rapidly and effectively. Such comprehensive evaluation of GNPs' effects on in vitro osteogenic differentiation and in vivo bone regeneration could promote their applications in clinical translation.

Differential evolution (DE) is a simple, effective, and robust algorithm, which has demonstrated excellent performance in dealing with global optimization problems. However, different search strategies are designed for different fitness landscape conditions to find the optimal solution, and there is not a single strategy that can be suitable for all fitness landscapes. As a result, developing a strategy to adaptively steer population evolution based on fitness landscape is critical. Motivated by this fact, in this paper, a novel adaptive DE based on fitness landscape (FL-ADE) is proposed, which utilizes the local fitness landscape characteristics in each generation population to (1) adjust the population size adaptively; (2) generate DE/current-to-pcbest mutation strategy. The adaptive mechanism is based on local fitness landscape characteristics of the population and enables to decrease or increase the population size during the search. Due to the adaptive adjustment of population size for different fitness landscapes and evolutionary processes, computational resources can be rationally assigned at different evolutionary stages to satisfy diverse requirements of different fitness landscapes. Besides, the DE/current-to-pcbest mutation strategy, which randomly chooses one of the top p% individuals from the archive cbest of local optimal individuals to be the pcbest, is also an adaptive strategy based on fitness landscape characteristic. Using the individuals that are approximated as local optimums increases the algorithm’s ability to explore complex multimodal functions and avoids stagnation due to the use of individuals with good fitness values. Experiments are conducted on CEC2014 benchmark test suit to demonstrate the performance of the proposed FL-ADE algorithm, and the results show that the proposed FL-ADE algorithm performs better than the other seven highly performing state-of-art DE variants, even the winner of the CEC2014 and CEC2017. In addition, the effectiveness of the adaptive population mechanism and DE/current-to-pcbest mutation strategy based on landscape fitness proposed in this paper are respectively verified.

Lignin-carbohydrate complex (LCC) is the biological macromolecule that has been demonstrated to exert multiple biological functions, including antioxidant, anti-inflammation and anti-tumorigenesis, which support its broad application in the bioengineering field. However, it remains elusive the involvements of LCC in human neurological disorders, especially those with the overproduction of reactive oxygen species (ROS), such as spinocerebellar ataxias (SCAs). In this study, we found a previously undetermined anti-protein aggregation activity of LCC. Initially, two individual LCC preparations and carbohydrate-free lignin were isolated from the water-extracted waste residues of Chionanthus retusus (C. retusus) tender leaves. The chemical compositional analysis revealed that lignin (61.5%) is the predominant constituent in the lignin-rich LCC (LCC-L-CR), whereas the carbohydrate-rich LCC (LCC-C-CR) is mainly composed of carbohydrate (60.9%) with the xylan as the major constituent (42.1%). The NMR structural characterization showed that LCC-L-CR preparation is enriched in benzyl ether linkage, while phenyl glycoside is the predominant type of linkage in LCC-C-CR. Both LCC and lignin preparations showed antioxidant activities as exemplified by their abilities to scavenge free radicals in cultured mammalian cells and ROS in zebrafish. We further demonstrated a pronounced capability of LCC-L-CR in inhibiting the aggregation of expanded Ataxin-3, disease protein of SCA type 3, in human neuronal cells. Taken together, our study highlights the antioxidant and novel anti-protein aggregation activities of the C. retusus tender leaves-derived LCC.

Abstract An improved model based on Biot poroelastic theory is presented incorporating the initial seepage flow in the matrix. The proposed model quantifies wave propagation in the oil field development process as VSP, transient well tests, and seismic production technology. Porosity variation, fluid–solid compressibility, and pseudo-threshold pressure gradient in low permeability reservoir are simultaneously considered, resulting in a modified form of continuity and motion equations. Integrating the equations and decomposition for the fluid–solid displacements helps to derive the analytical wave vectors of the fast P, slow P, and S waves in porous media. The sensitivity of affecting factors, such as petrophysical parameter, fluid property, and vibration frequency, on the wave velocity and attenuation is subsequently evaluated. Furthermore, the Biot model can be considered a special situation when the initial flow rate in this model tends to zero. The increase in initial percolating rate, expressed by the ratio of initial flow rate and solid scalar potential, causes an obvious decrease in the fast P wave velocity and an increase in its quality factor. Propagation of the slow P wave and the S wave is scarcely influenced. Low vibration frequency and low permeability also contribute to a large difference between the wave propagation parameters of the improved and Biot models. Cognition of the proportion in the inertia and viscosity effects is helpful in analyzing the complicated multiple mechanisms in wave propagation in the actual developed layer.

In underwater wireless sensor networks, time synchronization and localization are basic requirements in many applications. A joint synchronization and localization framework is expected to provide better accuracy. In this paper, we propose a unified framework to execute synchronization and localization simultaneously taking stratification effect into account. In this method, the stratification effect of underwater medium is modeled using a ray tracing approach. The maximum likelihood (ML) estimator is derived, which is shown to be highly nonlinear and nonconvex. Therefore, we employ the Gauss-Newton algorithm to solve the original nonconvex ML problem in an iterative manner. Furthermore, the Cramér-Rao lower bound for this problem is derived as a benchmark. Simulation results indicate that the proposed method outperforms the existing methods in both accuracy and energy efficiency.

Background: Surgical site infection (SSI) hampers the advantages of surgical management, which requires early forecast particularly in patients receiving colorectal surgery. This study is to explore potential relationship between individual abdominal anatomic characteristics including subcutaneous fat thickness (SFT), rectus abdominis thickness (RAT), and abdomen depth (AD), with the incidence of SSI in elective radical resection of colon malignancy.Materials and Methods: This retrospective case-control study has recruited 55 patients in each SSI and non-SSI group with propensity score match method. Demographics, clinical attributes, and pre- and intra-operative information were compared between groups with univariate analysis to elicit significant parameters, which were subsequently brought into logistic regression and receiver-operating characteristic (ROC) analysis.Results: Patients with SSI showed lower preoperative albumin (p = 0.0022), higher RAT (p = 0.014), AD (p = 0.029), and the multiplied value (RAT × AD) (p = 0.0026) contrasted with patients without SSI. Logistic regression demonstrated RAT × AD as an independent risk factor for SSI (OR = 1.007, p < 0.001) and a biomarker for SSI prediction (AUC = 0.83, 95% CI: 0.74 ~ 0.91).Conclusions: Preoperative RAT and abdomen depth are associated with the risk of postoperative SSI in patients receiving elective radical resection of colon cancer.Trial Registration:www.researchregistry.com, identifier researchregistry3669

A combined strategy of torque error feed-forward control and blade-pitch angle servo control is proposed to improve the dynamic power capture for wind turbine maximum power point tracking (MPPT). Aerodynamic torque is estimated using the unscented Kalman filter (UKF). Wind speed and tip speed ratio (TSR) are estimated using the Newton−Raphson method. The error between the estimated aerodynamic torque and the steady optimal torque is used as the feed-forward signal to control the generator torque. The gain parameters in the feed-forward path are nonlinearly regulated by the estimated generator speed. The estimated TSR is used as the reference signal for the optimal blade-pitch angle regulation at non-optimal TSR working points, which can improve the wind power capture for a wider non-optimal TSR range. The Fatigue, Aerodynamics, Structures, and Turbulence (FAST) code is used to simulate the aerodynamics and mechanical aspects of wind turbines while MATLAB/SIMULINK is used to simulate the doubly-fed induction generator (DFIG) system. The example of a 5 MW wind turbine model reveals that the new method is able to improve the dynamic response of wind turbine MPPT and wind power capture.

Foam injection is widely applied in amounts of fields to drilling, production, and formation protection. Sometimes, the application result is disappointing, which is caused by the failure of bubble generation in foam flooding. Therefore, it is necessary to seek ways for improving the performance of foam injection. An increased disturbance to the stratum, like the vibration caused by a seismic oil recovery technique, would be helpful. In the current work, the seepage of air foam in porous media under low frequency (LF) vibration is analyzed with experiments and an investigation of bubble creation/destruction rate change is carried out using mathematical modeling. The resistance factor of foam flooding under indoor vibration increases by 1.5 times and the valid time is obviously extended compared with when no vibration is used. The optimal vibrating acceleration and frequency of 0.7 m/s2 and the natural frequency of the cores-nearby of 18 Hz are achieved in the indoor experiments. Under vibration, the bubble generation rate increases, while bubble break rate by internal expansion or by gas diffusion and transfer decreases. An interesting phenomenon is also observed, which might develop a power level formula between the initially defined dimensionless MRF (maximum foam flooding resistance factor) and dimensionless DMRF (duration of maximum foam flooding resistance factor). The power product and sum of the power exponents of the above formula both equal approximately to 1. With the assistance of LF vibration, the increase of security, adaptability, and efficiency in foam injection may improve the reservoir recovery and extend its application.

Using active control methods for load mitigation in wind turbines could greatly reduce the cost of per kilowatt hour of wind power. In this work, the combined pitch and trailing edge flap control (CPFC) for load mitigation of wind turbines is investigated. The CPFC includes an individual pitch control (IPC) loop and a trailing edge flap control (TEFC) loop, which are combined by a load frequency division control algorithm. The IPC loop is mainly used to mitigate the low frequency loads, and the TEFC loop is mainly used to mitigate the high frequency loads. The CPFC adopts both an azimuth angle feed-forward and a loads feedback control strategy. The azimuth angle feed-forward control strategy should mitigate the asymmetrical loads caused by observable disturbances. and the loads feedback control strategy should decrease asymmetrical loads by closed loop control. A simulation is carried out on the joint platform of FAST and MATLAB. The simulation results show that the damage equivalent load (DEL) of blade root out-of-plane bending moment is reduced by 53.7% while using CPFC, compared to collective pitch control (CPC); and the standard deviation of blade tip out-of-plane deflection is reduced by 50.2% while using CPFC, compared to CPC. The results demonstrate that the CPFC can mitigate the fatigue loads of wind turbines as anticipated.