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AIM: To systematically evaluate the efficacy and safety of low-concentrations atropine eye drops in controlling adolescent myopia.METHODS:A computer search was conducted on Wanfang Data, CNKI, VIP, PubMed, Cochrane Library, and Embase databases from January 2010 to March 2024 on clinical studies on low-concentration atropine eye drops for controlling adolescent myopia. Two researchers independently screened trials, extracted data, evaluated risk of bias and quality, and used Review Manager5.4 software to perform Meta-analysis.RESULTS:A total of 17 articles, involving 3 764 cases and 3 952 eyes, were included. The Meta-analysis showed that compared with the control group, low concentrations of atropine could effectively slow down the growth of axial length [MD=-0.15, 95% CI(-0.20, -0.10), P

Abstract Computationally derived volcano curve has become the gold standard in catalysis, whose practical application usually relies on empirical interpretations of composition or size effects by the identical active site assumption. Here, we present a proof-of-concept study on disclosing both the support- and adsorbate-induced restructuring of Pt-Co bimetallic catalysts, and the related interplays among different interfacial sites to propose the synergy-dependent volcano curves. Multiple characterizations, isotopic kinetic investigations, and multiscale simulations unravel that the progressive incorporation of Co into Pt catalysts, driven by strong Pt-C bonding (metal-support interfaces) and Co-O bonding (metal-adsorbate interfaces), initiates the formation of Pt-rich alloys accompanied by isolated Co species, then Co segregation to epitaxial CoOx overlayers and adjacent Co3O4 clusters, and ultimately structural collapse into amorphous alloys. Accordingly, three distinct synergies, involving lattice oxygen redox from Pt-Co alloy/Co3O4 clusters, dual-active sites engineering via Pt-rich alloy/CoOx overlayer, and electron coupling within exposed alloy, are identified and quantified for CO oxidation (gas-phase), ammonia borane hydrolysis (liquid-phase), and hydrogen evolution reaction (electrocatalysis), respectively. The resultant synergy-dependent volcano curves represent an advancement over traditional composition-/size-dependent ones, serving as a bridge between theoretical models and experimental observations in bimetallic catalysis.

Abstract Epigenetic readers frequently affect gene regulation, correlate with disease prognosis, and hold significant potential as therapeutic targets for cancer. Zinc finger MYND-type containing 11 (ZMYND11) is notably recognized for reading the epigenetic marker H3.3K36me3; however, its broader functions and mechanisms of action in cancer remain underexplored. Here, we report that ZMYND11 downregulation is prevalent across various cancers and profoundly correlates with poorer outcomes in prostate cancer patients. Depletion of ZMYND11 promotes tumor cell growth, migration, and invasion in vitro, as well as tumor formation and metastasis in vivo. Mechanistically, we discover that ZMYND11 exhibits tumor suppressive roles by recognizing arginine-194-methylated HNRNPA1 dependent on its MYND domain, thereby retaining HNRNPA1 in the nucleus and preventing the formation of stress granules in the cytoplasm. Furthermore, ZMYND11 counteracts the HNRNPA1-driven increase in the PKM2/PKM1 ratio, thus mitigating the aggressive tumor phenotype promoted by PKM2. Remarkably, ZMYND11 recognition of HNRNPA1 can be disrupted by pharmaceutical inhibition of the arginine methyltransferase PRMT5. Tumors with low ZMYND11 expression show sensitivity to PRMT5 inhibitors. Taken together, our findings uncover a previously unexplored noncanonical role of ZMYND11 as a nonhistone methylation reader and underscore the critical importance of arginine methylation in the ZMYND11-HNRNPA1 interaction for restraining tumor progression, thereby proposing novel therapeutic targets and potential biomarkers for cancer treatment.

Reactive transport equations in porous media are critical in various scientific and engineering disciplines, but solving these equations can be computationally expensive when exploring different scenarios, such as varying porous structures and initial or boundary conditions. The deep operator network (DeepONet) has emerged as a popular deep learning framework for solving parametric partial differential equations. However, applying the DeepONet to porous media presents significant challenges due to its limited capability to extract representative features from intricate structures. To address this issue, we propose the Porous-DeepONet, a simple yet highly effective extension of the DeepONet framework that leverages convolutional neural networks (CNNs) to learn the solution operators of parametric reactive transport equations in porous media. By incorporating CNNs, we can effectively capture the intricate features of porous media, enabling accurate and efficient learning of the solution operators. We demonstrate the effectiveness of the Porous-DeepONet in accurately and rapidly learning the solution operators of parametric reactive transport equations with various boundary conditions, multiple phases, and multi-physical fields through five examples. This approach offers significant computational savings, potentially reducing the computation time by 50–1000 times compared with the finite-element method. Our work may provide a robust alternative for solving parametric reactive transport equations in porous media, paving the way for exploring complex phenomena in porous media.

Abstract Manipulation of confined water dynamics by voltage keeps great importance for diverse applications. However, limitations on the membrane functions, voltage-control range, and unclear dynamics need to be addressed. Herein, we report an anomalous electrically controlled gating phenomenon on cation-intercalated multi-layer Ti3C2 membranes and reveal the confined water dynamics. The water permeation rate was improved rapidly following the application and rise of voltage and finally reached a maximum rate at 0.9 V. The permeation rate starts to decrease from 0.9 V. Below 0.9 V, the electric field affects the charge and polarity of water molecules and then leads to ordered and denser rearrangement in the two-dimensional (2D) channel to accelerate the permeation rate. Above 0.9 V, with the assistance of metal cations, the surge in current induced aggregation of water molecules into clusters, thereby limiting the water mobility. Based on these findings, a high-performance humidity sensor was developed by simultaneously optimizing the response and recovery speeds through electric manipulation. This work provides flexible strategies in intelligent membrane design and nanofluidic sensing.

Abstract A novel method based on machine learning is proposed to estimate the electromagnetic radiation level at the ground plane near fifth‐generation (5G) base stations. The machine learning model was trained using data from various 5G base stations, enabling it to estimate the electric field intensity at any arbitrary radiation point when the base station provides service to different numbers of 5G terminals which are in different service modes. The inputs required for the model include the transmit power of the antenna, the antenna gain, the distance between the 5G base station and 5G terminals, terminal service modes, the number of 5G terminals and the environmental complexity around the 5G base station. Experimental results demonstrate the feasibility and effectiveness of the estimation method, with the mean absolute percentage error of the machine learning model being approximately 5.98%. This level of accuracy showcases the reliability of the approach. Moreover, the proposed method offers low costs when compared with on‐site measurements. The estimated results can be utilised to reduce test costs and provide valuable guidance for optimal site selection, thereby facilitating radio wave coverage or electromagnetic radiation regulation of 5G base stations.

Abstract The development of sustainable and anti-poisoning single-atom catalysts (SACs) is essential for advancing their research from laboratory to industry. Here, we present a proof-of-concept study on the poisoning of Au SACs, and the antidote of Au nanoparticles (NPs), with trace addition shown to reinforce and sustain propylene epoxidation. Multiple characterizations, kinetics investigations, and multiscale simulations reveal that Au SACs display remarkable epoxidation activity at a low propylene coverage, but become poisoned at higher coverages. Interestingly, Au NPs can synergistically cooperate with Au SACs by providing distinct active sites required for H2/O2 and C3H6 activations, as well as hydroperoxyl radical to restore poisoned SACs. The difference in reaction order between C3H6 and H2 (nC3H6-nH2) is identified as the descriptor for establishing the volcano curves, which can be fine-tuned by the intimacy and composition of SACs and NPs to achieve a rate-matching scenario for the formation, transfer, and consumption of hydroperoxyl. Consequently, only trace addition of Au NPs antidote (0.3% ratio of SACs) stimulates significant improvements in propylene oxide formation rate, selectivity, and H2 efficiency compared to SACs alone, offering a 56-fold, 3-fold, and 22-fold increase, respectively, whose performances can be maintained for 150 h.

BackgroundIt has been demonstrated that receptive cultural engagement, such as visits to theaters and museums, can reduce depression in older adults. However, the association between hobby engagement and lower rates of depressive symptoms (DS) remains unclear. The objective of this study was to investigate the potential relationship between hobby engagement and depressive symptoms.MethodsThe data for this prospective cross-sectional study were collected from participants in the China Longitudinal Study of Health and Retirement (CHARLS) wave 2020. To assess DS, a score of 10 or more on the Center for Epidemiological Studies Depression Scale was used to indicate depression. Hobby engagement was gaged by trained staff through the administration of a battery of standardized questions. Logistic regression and inverse probability of treatment weighting (IPTW) using the propensity score analyses were employed to investigate the relationship between hobby engagement and DS.ResultsA total of 16,057 participants were included, with a mean age of 62.4 ± 9.2 years. Of these, 7,699 were male and 8,358 were female. The proportion of individuals exhibiting depressive symptoms was 31.57% (1,286 out of 4,073) among those with hobby engagement, while it was 39.67% (4,754 out of 11,984) among those without hobby engagement. After adjusting for covariates, the odds ratio was 0.89 (95% CI: 0.82–0.97, p = 0.0109). Propensity-score analyses also supported these findings, with the odds ratio being 0.91 (95% CI: 0.84–0.99, p = 0.0204). The finding was consistent with multiple sensitivity analyses.ConclusionOur study found hobby engagement was associated with a reduced risk of depressive symptoms in Chinese middle-aged and older adults. Our findings need to be confirmed in future studies.

Abstract Graphitic carbon nitride (CN), as a nonmetallic photocatalyst, has gained considerable attention for its cost‐effectiveness and environmentally friendly nature in catalyzing solar‐driven CO2 conversion into valuable products. However, the photocatalytic efficiency of CO2 reduction with CN remains low, accompanied by challenges in achieving desirable product selectivity. To address these limitations, a two‐step hydrothermal‐calcination tandem synthesis strategy is presented, introducing carbon quantum dots (CQDs) into CN and forming ultra‐thin CQD/CN nanosheets. The integration of CQDs induces a distinct work function with CN, creating a robust interface electric field after the combination. This electric field facilitates the accumulation of photoelectrons in the CQDs region, providing an abundant source of reduced electrons for the photocatalytic process. Remarkably, the CQD/CN nanosheets exhibit an average CO yield of 120 µmol g−1, showcasing an outstanding CO selectivity of 92.8%. The discovery in the work not only presents an innovative pathway for the development of high‐performance photocatalysts grounded in non‐metallic CN materials employing CQDs but also opens new avenues for versatile application prospects in environmental protection and sustainable cleaning energy.

Abstract Alternative polyadenylation plays an important role in cancer initiation and progression; however, current transcriptome-wide association studies mostly ignore alternative polyadenylation when identifying putative cancer susceptibility genes. Here, we perform a pan-cancer 3′ untranslated region alternative polyadenylation transcriptome-wide association analysis by integrating 55 well-powered (n > 50,000) genome-wide association studies datasets across 22 major cancer types with alternative polyadenylation quantification from 23,955 RNA sequencing samples across 7,574 individuals. We find that genetic variants associated with alternative polyadenylation are co-localized with 28.57% of cancer loci and contribute a significant portion of cancer heritability. We further identify 642 significant cancer susceptibility genes predicted to modulate cancer risk via alternative polyadenylation, 62.46% of which have been overlooked by traditional expression- and splicing- studies. As proof of principle validation, we show that alternative alleles facilitate 3′ untranslated region lengthening of CRLS1 gene leading to increased protein abundance and promoted proliferation of breast cancer cells. Together, our study highlights the significant role of alternative polyadenylation in discovering new cancer susceptibility genes and provides a strong foundational framework for enhancing our understanding of the etiology underlying human cancers.

Multimodal physiological signals play a pivotal role in drivers’ perception of work stress. However, the scarcity of labels and the multitude of modalities render the utilization of physiological signals for driving cognitive alertness detection challenging. We thus propose a multimodal physiological signal detection model based on self-supervised learning. First, in order to mine the intrinsic information of data and enable data to highlight effective information, we introduce a multiscale entropy (MSE) evoked attention mechanism. Secondly, the multimodal patches undergo processing through a novel cascaded attention mechanism. This attention mechanism is rooted in patch-level interactions within each modality, progressively integrating and interacting with other modalities in a cascading manner, thereby mitigating computational complexity. Moreover, a multimodal uncertainty-aware module is devised to effectively cope with intricate variations in the data. This module enhances its generalization ability through the incorporation of uncertain resampling. Experiments were conducted on the DriveDB dataset and the CogPilot dataset with both the linear probing and the fine-tuning evaluation protocols. Experimental results in subject-dependent setting show that our model significantly outperforms previous competitive baselines. In the linear probing evaluation, our model achieves on average 6.26%, 6.64%, and 7.75% improvements in Accuracy (Acc), Recall (Rec), and F1 Score. It also outperforms other models by 7.96% in Acc, 9.13% in Rec, and 9.2% in F1 using the fine-tuning evaluation. Furthermore, our model also demonstrates robust performance in subject-independent setting.

Background Anorexia nervosa (AN) has been characterised as a psychiatric disorder associated with increased control. Currently, it remains difficult to predict treatment response in patients with AN. Their cognitive abilities are known to be resistant to treatment. It has been established that the frontoparietal control network (FPCN) is the direct counterpart of the executive control network. Therefore, the resting-state brain activity of the FPCN may serve as a biomarker to predict treatment response in AN.Aims The study aimed to investigate the association between resting-state functional connectivity (RSFC) of the FPCN, clinical symptoms and treatment response in patients with AN.Methods In this case-control study, 79 female patients with AN and no prior treatment from the Shanghai Mental Health Center and 40 matched healthy controls (HCs) were recruited from January 2015 to March 2022. All participants completed the Questionnaire Version of the Eating Disorder Examination (version 6.0) to assess the severity of their eating disorder symptoms. Additionally, RSFC data were obtained from all participants at baseline by functional magnetic resonance imaging. Patients with AN underwent routine outpatient treatment at the 4th and 12th week, during which time their clinical symptoms were evaluated using the same measures as at baseline.Results Among the 79 patients, 40 completed the 4-week follow-up and 35 completed the 12-week follow-up. The RSFC from the right posterior parietal cortex (PPC) and dorsolateral prefrontal cortex (dlPFC) increased in 79 patients with AN vs 40 HCs after controlling for depression and anxiety symptoms. By multiple linear regression, the RSFC of the PPC to the inferior frontal gyrus was found to be a significant factor for self-reported eating disorder symptoms at baseline and the treatment response to cognitive preoccupations about eating and body image, after controlling for age, age of onset and body mass index. The RSFC in the dlPFC to the middle temporal gyrus and the superior frontal gyrus may be significant factors in the treatment response to binge eating and loss of control/overeating in patients with AN.Conclusions Alterations in RSFC in the FPCN appear to affect self-reported eating disorder symptoms and treatment response in patients with AN. Our findings offer new insight into the pathogenesis of AN and could promote early prevention and treatment.

Highlights The functional groups on graphene quantum dots (GQDs) for boosting the formation of MoS2 nanosheets via theoretical calculations were predicted. Near atom-layer-QD@SO3 with about 2 nm were synthesized using a functionalized GQD-induced in-situ bottom-up approach. Mechanistic insight on the role of functionalized GQDs was elaborated, namely, electron-withdrawing group functionalized GQDs facilitate the formation of nanosheet architectures of MoS2 compared to electron-donating group.

Electrocatalytic upgrading of biomass-derived platform molecules has emerged as a sustainable and environmentally benign route to produce high-value chemicals. The main challenge lies in developing efficient catalysts for the selective activation of designated chemical bonds in the presence of various reducible groups. This work demonstrated a high-efficiency electrochemical conversion of 5-hydroxymethylfurfural (HMF) to 2,5-bis(hydroxymethyl)furan (BHMF), an important industrial synthetic reagent. A highly porous Cu-based catalyst was developed that achieved nearly 100% BHMF selectivity and long-term stability. Through comprehensive operando and ex-situ structural characterizations, an electrochemically generated catalyst with abundant Cu/Cu2O interfaces was identified as a catalytically active phase for HMF conversion. Deuterated BHMF, with the potential to produce deuterated drugs, was also synthesized using D2O as the deuterium source. Density functional theory calculations show that the Cu/Cu2O interface structure exhibits relatively low energy barriers for the hydrogenation of HMF to BHMF. This work provides insights into the origin of electrocatalytic hydrogenation activity and highlights the promising potential of the electrocatalytic synthesis of high-value chemicals.

Abstract We evaluate the efficacy of antimicrobial Photodynamic Therapy (APDT) for inactivating a variety of antibiotic-resistant clinical strains from diabetic foot ulcers. Here we are focused on APDT based on organic light-emitting diodes (OLED). The wound swabs from ten patients diagnosed with diabetic foot ulcers were collected and 32 clinical strains comprising 22 bacterial species were obtained. The isolated strains were identified with the use of mass spectrometry coupled with a protein profile database and tested for antibiotic susceptibility. 74% of isolated bacterial strains exhibited adaptive antibiotic resistance to at least one antibiotic. All strains were subjected to the APDT procedure using an OLED as a light source and 16 µM methylene blue as a photosensitizer. APDT using the OLED led to a large reduction in all cases. For pathogenic bacteria, the reduction ranged from 1.1-log to > 8 log (Klebsiella aerogenes, Enterobacter cloaca, Staphylococcus hominis) even for high antibiotic resistance (MRSA 5-log reduction). Opportunistic bacteria showed a range from 0.4-log reduction for Citrobacter koseri to > 8 log reduction for Kocuria rhizophila. These results show that OLED-driven APDT is effective against pathogens and opportunistic bacteria regardless of drug resistance.

The development of intelligent transportation technology has provided a significant impetus for autonomous driving technology. Currently, autonomous vehicles based on Model Predictive Control (MPC) employ motion control strategies based on sampling time, which fail to fully utilize the spatial information of obstacles. To address this issue, this paper proposes a dual-layer MPC vehicle collision-free trajectory tracking control strategy that integrates spatial kinematics and vehicle dynamics. To fully utilize the spatial information of obstacles, we designed a vehicle model based on spatial kinematics, enabling the upper-layer MPC to plan collision avoidance trajectories based on distance sampling. To improve the accuracy and safety of trajectory tracking, we designed an 8-degree-of-freedom vehicle dynamic model. This allows the lower-layer MPC to consider lateral stability and roll stability during trajectory tracking. In collision avoidance trajectory tracking experiments using three scenarios, compared to two advanced time-based algorithms, the trajectories planned by the proposed algorithm in this paper exhibited predictability. The proposed algorithm can initiate collision avoidance at predetermined positions and can avoid collisions in predetermined directions, with all state variables within safe ranges. In terms of time efficiency, it also outperformed the comparative algorithms.

Defect-engineered carbon materials have been emerged as promising electrocatalysts for oxygen reduction reaction (ORR) in metal-air batteries. Developing a facile strategy for the preparation of highly active nanocarbon electrocatalysts remains challenging. Herein, a low-cost and simple route is developed to synthesize defective graphene by pyrolyzing the mixture of glucose and carbon nitride. Molecular dynamics simulations reveal that the graphene formation is ascribed to two-dimensional layered feature of carbon nitride, and high compatibility of carbon nitride/glucose systems. Structural measurements suggest that the graphene possesses rich edge and topological defects. The graphene catalyst exhibits higher power density than commercial Pt/C catalyst in a primary Zn-air battery. Combining experimental results and theoretical thermodynamic analysis, it is identified that graphitic nitrogen-modified topological defects at carbon framework edges are responsible for the decent ORR performance. The strategy presented in this work can be can be scaled up readily to fabricate defective carbon materials.

Attaining high selectivity for CO2 electroreduction in acid is usually difficult due to competing hydrogen evolution. Here, the authors demonstrate efficient CO2 reduction to multicarbon products in strongly acidic medium (pH ≤ 1) on a porous Cu catalyst by combining confinement and cation effects.

Abstract The focus of this study was to explore the association between the non-HDL-cholesterol to HDL-cholesterol (non-HDLc/HDLc) ratio and mortality in septic patients. This was a retrospective cohort study of patients with sepsis in the eICU Collaborative Research Database (eICU-CRD) from 208 distinct ICUs across the United States between 2014 and 2015 that explored. All-cause mortality within 28 days after ICU admission. A multivariable logistic regression model was used to estimate the risk of death. Of the 724 patients with a median age of 68 years, 43 (5.94%) died within 28 days after ICU admission. When the non-HDLc/HDLc ratio was

Due to the diversity of landforms, an appropriate threshold should be selected for the simplification of different landforms. The distribution of simplified index was obtained by preprocessing the terrain data, and the distribution was used as a reference for threshold selection. In order to study the influence of terrain simplification on the prediction of complex electromagnetic environment, a visibility algorithm used in the regular model of terrain and a probability-based power propagation model are proposed. The visibility algorithm used in the regular model of terrain is based on the relationship between planes and triangular planes in three-dimensional space. The visible triangular surfaces and the corresponding visible area of the triangular surfaces in the terrain can be calculated with the visibility algorithm. The probability-based power propagation model uses the results of the visibility algorithm to calculate the propagation probability and calculates the change of receiver power in combination with the radio wave propagation characteristics. The spatial visibility algorithm and the probability-based power propagation model can be applied to the complex electromagnetic environment to analyze the influence of terrain simplification on prediction accuracy. The minimum error between the simulation result of the probability-based power propagation model and the Wireless InSite simulation result is 0.5018dB, and the average error is 1.5039dB.

BackgroundHigh-density lipoprotein cholesterol (HDL-C) has long been viewed as a protective factor for cardiovascular health. Yet, higher HDL-C was not necessarily beneficial. The purpose of this study was to investigate the relationship between HDL-C levels and intertrochanter bone mineral density.MethodsThe study collected the most recent data from the 2017-2020 National Health and Nutrition Examination Survey (NHANES). Weighted multiple regression analysis was used to evaluate the relationship between HDL-C and intertrochanter BMD, and further subgroup analysis and threshold effect analysis were conducted. Finally, the relationship between HDL-C and intertrochanter BMD was analyzed by fitting smooth curves.ResultsThe study included 3,345 people ranging in age from 50 to 80. HDL-C was discovered to be negatively correlated with intertrochanter BMD (β = -0.03, 95%CI: -0.04, -0.01, P = 0.0002). In subgroup analysis, the negative correlation was found among 60-70-year-olds (β = -0.04, 95%CI: -0.06, -0.02, P = 0.0010), additionally, non-Hispanic whites (β = -0.03, 95%CI: -0.05, -0.01, P = 0.0140), and obese individuals (β = -0.03, 95%CI: -0.05, -0.01, P = 0.0146). The negative correlation, on the other hand, remained significant and consistent across genders, menstruation status, hormone usage, and long-term use of steroids. The relationship between HDL-C and intertrochanter BMD was an inverted U-shaped curve in men and hormone users, with inflection points of 1.01 mmol/L and 1.71 mmol/L, and an U-shaped curve in other Hispanic and premenopausal individuals, with inflection points of 0.96 mmol/L and 1.89 mmol/L.ConclusionsHDL-C was negatively associated with intertrochanter BMD in people over 50 years of age, non-Hispanic whites, and obesity.

Purpose: It has been reported that serotonergic systems and parenting styles are involved in the pathogenesis of anorexia nervosa (AN). The present study made attempts to examine the DNA methylation profiles in the promoter region of serotonin transporter (5-HTT) encoding gene SLC6A4, and explore the association between the methylation level and severity of symptoms, 5-HTT linked polymorphic region (5-HTTLPR) genotypes and parenting styles in untreated Chinese Han AN patients. Methods: Ninety-one untreated female AN patients (ANs) and eighty-seven matched healthy controls (HCs) were analyzed for DNA methylation status at CpG islands in the promoter region of SLC6A4 using MassARRY EpiTYPER, and genotypes of 5-HTTLPR using PCR-RFLP. The severity of eating disorder (ED) symptoms was evaluated by body mass index (BMI) and Questionnaire Version of the Eating Disorders Examination (EDE-Q 6.0), and part of participants were assessed parenting styles using the short Chinese Egna Minnen av Barndoms Uppfostra (s-EMBU-C). Results: ANs had greater methylation levels at CpG26.27.28, CpG 31.32, and CpG 37 than HCs (P = 0.039, 0.042, 0.018 respectively). A positive association of methylation level at CpG26.27.28 with ED symptoms detected by EDEQ-6.0 was discovered in AN group (r = 0.216, P = 0.047). Methylation level at CpG26.27.28 was showed to be or tend to be positively correlated with the parenting styles of paternal rejection (r = 0.425, P = 0.038) and paternal overprotection (r = 0.362, P = 0.062) in ANs. No significant differences were found in SLC6A4 promoter region methylation levels among 5-HTTLPR genotypes in our samples (P > 0.05) and no interaction effect between 5-HTTLPR genotypes and parenting styles on SLC6A4 promoter region methylation was observed (P > 0.05). Conclusions: This study suggested that hypermethylation of SLC6A4 promoter region may be implicated in the pathological mechanisms of untreated Chinese Han female ANs, which is possibly associated with poor parenting styles. This finding may provide a direction for the epigenetic and family treatments for ANs and further investigation with larger samples is warranted.

The emergence of drug resistance in cutaneous leishmaniasis (CL) has become a major problem over the past decades. The spread of resistant phenotypes has been attributed to the wide misuse of current antileishmanial chemotherapy, which is a serious threat to global health. Photodynamic therapy (PDT) has been shown to be effective against a wide spectrum of drug-resistant pathogens. Due to its multi-target approach and immediate effects, it may be an attractive strategy for treatment of drug-resistant Leishmania species. In this study, we sought to evaluate the activity of PDT in vitro using the photosensitizer 1,9-dimethyl methylene blue (DMMB), against promastigotes of two Leishmania amazonensis strains: the wild-type (WT) and a lab induced miltefosine-resistant (MFR) strain. The underlying mechanisms of DMMB-PDT action upon the parasites was focused on the changes in the lipid metabolism of both strains, which was conducted by a quantitative lipidomics analysis. We also assessed the production of ROS, mitochondrial labeling and lipid droplets accumulation after DMMB-PDT. Our results show that DMMB-PDT produced high levels of ROS, promoting mitochondrial membrane depolarization due to the loss of membrane potential. In addition, both untreated strains revealed some differences in the lipid content, in which MFR parasites showed increased levels of phosphatidylcholine, hence suggesting this could also be related to their mechanism of resistance to miltefosine. Moreover, the oxidative stress and consequent lipid peroxidation led to significant phospholipid alterations, thereby resulting in cellular dysfunction and parasite death. Thus, our results demonstrated that DMMB-mediated PDT is effective to kill L. amazonensis MFR strain and should be further studied as a potential strategy to overcome antileishmanial drug resistance.

Abstract Giant cell tumor of bone (GCTB) is an aggressive osteolytic bone tumor characterized by the within-tumor presence of osteoclast-like multinucleated giant cells (MGCs), which are induced by the neoplastic stromal cells and lead to extensive bone destruction. However, the underlying mechanism of the pathological process of osteoclastogenesis in GCTB is poorly understood. Here we show that the proteoglycan Serglycin (SRGN) secreted by neoplastic stromal cells plays a crucial role in the formation of MGCs and tumorigenesis in GCTB. Upregulated SRGN expression and secretion are observed in GCTB tumor cells and patients. Stromal-derived SRGN promotes osteoclast differentiation from monocytes. SRGN knockdown in stromal cells inhibits tumor growth and bone destruction in a patient-derived orthotopic xenograft model of mice. Mechanistically SRGN interacts with CD44 on the cell surface of monocytes and thus activates focal adhesion kinase (FAK), leading to osteoclast differentiation. Importantly, blocking CD44 with a neutralizing antibody reduces the number of MGCs and suppresses tumorigenesis in vivo. Overall, our data reveal a mechanism of MGC induction in GCTB and support CD44-targeting approaches for GCTB treatment.

Electrochemical conversion of CO2 to fuels is a promising strategy to reduce the ever-increasing CO2 emission. Here, the authors developed graphene quantum dots (GQDs) catalysts to efficiently convert CO2 to CH4 and revealed the significance of electron-donating functional groups in regulating the reactivity of GQDs.

Abstract Seawater electrolysis is an attractive technique for mass production of high‐purity hydrogen considering the abundance of seawater. Nevertheless, due to the complexity of seawater environment, efficient anode catalyst, that should be, cost effective, highly active for oxygen evolution reaction (OER) but negligible for Cl2/ClO– formation, and robust toward chlorine corrosion, is urgently demanded for large‐scale application. Although catalysis typically appears at surface, while the bulk properties and morphology structure also have a significant impact on the performance, thus requiring a systematic optimization. Herein, a multiscale engineering approach toward the development of cost‐effective and robust OER electrocatalyst for operation in seawater is reported. Specifically, the engineering of hollow‐sphere structure can facilitate the removal of gas product, while atom‐level synergy between Co and Fe can promote Co sites transforming to active phase, and in situ transformation of sulfate ions layer protects catalysts from corrosion. As a result, the as‐developed hollow‐sphere structured CoFeSx electrocatalyst can stably operate at a high current density of 100 mA cm–2 in the alkaline simulated seawater (pH = 13) for 700 h and in a neutral seawater for 20 h without attenuation. It provides a new strategy for the development of electrocatalysts with a broader application potential.

BackgroundThe angiotensin-receptor neprilysin inhibitor (ARNI) sacubitril/valsartan was shown to be superior to the angiotensin receptor blocker (ARB) valsartan in terms of reversing heart failure classification (NYHA classification), reducing N-terminal pro-brain natriuretic peptide (NT-proBNP) level and cardiovascular mortality in many studies. Yet, the efficacy of ARNI did not come from patients with acute myocardial infarction (AMI).MethodsWe searched databases for research published from inception to July 29, 2022, that reported cardiac reverse remodeling (CRR) or security indices. Two reviewers independently screened literature, extracted data, and assessed the risk of bias. Nine studies enrolling 1,369 patients were included to perform a meta-analysis. There were 716 patients in the ARNI group and 653 in the ARB group.ResultsARNI outperformed ARBs in terms of CRR indices, with striking changes in left ventricular ejection fraction (EF) (MD: 4.12%, 95%CI: 2.36, 5.88, P < 0.0001), diameter (MD: –3.40 mm, 95%CI: –4.30, –2.94, P < 0.00001, I2 = 0%) and left atrial diameter (MD: –2.41 mm, 95%CI: –3.85, –0.97, P = 0.001, I2 = 0%), other indices there showed no significant improvements. The incidences of major adverse cardiac events (RR: 0.47, 95%CI: 0.34–0.65, P < 0.00001, I2 = 0%), the heart failure (RR: 0.37, 95%CI: 0.23–0.61, P < 0.0001, I2 = 0%), readmission (RR: 0.54, 95%CI: 0.36–0.80, P = 0.003, I2 = 29%) in the sacubitril/valsartan group were lower than the ARB group, while the incidences of cardiac death (RR: 0.56, 95%CI: 0.28, 1.09, P = 0.09), the myocardial infarction (RR: 0.83, 95% CI: 0.39, 1.77, P = 0.63), adverse side effects (RR: 1.67, 95% CI: 0.89, 3.13, P = 0.11) showed no difference.ConclusionThis research indicated that early initiation of sacubitril/valsartan in patients after AMI was superior to ARBs in reducing the risks of major adverse cardiac events, heart failure, readmission, and enhancing left ventricular EF, decreasing diameter, left atrial diameter. As for the other outcomes (the incidences of cardiac death, myocardial infarction, and adverse side effects), sacubitril/valsartan demonstrated no obvious advantage over ARBs.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier [CRD42022307237].

Association between cations and anions plays an important role in the interfacial structure of room-temperature ionic liquids (ILs) and their electrochemical performance. Whereas great efforts have been devoted to investigating the association effect on the equilibrium properties of ILs, a molecular-level understanding of the charging dynamics is yet to be established. Here, we propose a theoretical procedure combining reaction kinetics and the modified Poisson-Nernst-Planck (MPNP) equations to study the influences of ionic association on the dynamics of electrical double layer (EDL) in response to an applied voltage. The ionic association introduces a new decay length λS and relaxation time scale τRC=λSL/D, where L is the system size and D is ion diffusivity, that are distinctively different those corresponding to non-associative systems. Analytical expressions have been obtained to reveal the quantitative relations between the dynamic timescales and the association strength.

Understanding the mechanisms and properties of various transport processes in the electrolyte, porous electrode, and at the interface between electrode and electrolyte plays a crucial role in guiding the improvement of electrolytes, materials and microstructures of electrode. Nanoscale equilibrium properties and nonequilibrium ion transport are substantially different to that in the bulk, which are difficult to observe from experiments directly. In this paper, we introduce equilibrium and no-equilibrium thermodynamics for electrolyte in porous electrodes or electrolyte–electrode interface. The equilibrium properties of electrical double layer (EDL) including the EDL structure and capacitance are discussed. In addition, classical non-equilibrium thermodynamic theory is introduced to help us understand the coupling effect of different transport processes. We also review the recent studies of nonequilibrium ion transport in porous electrode by molecular and continuum methods, among these methods, dynamic density functional theory (DDFT) shows tremendous potential as its high efficiency and high accuracy. Moreover, some opportunities for future development and application of the non-equilibrium thermodynamics in electrochemical system are prospected.

Cancer stem-like cells are the culprits of tumour recurrence and metastasis, but their regulatory mechanisms are not fully understood. Here, the authors show that the scaffold protein SH3RF3 enhances the stem-like properties of breast cancer by facilitating activation of the JNK-JUN pathway and PTX3 expression.

Summary: Background: Since late 2019, SARS-CoV-2 infection has resulted in COVID-19 accompanied by diverse clinical manifestations. However, the underlying mechanism of how SARS-CoV-2 interacts with host and develops multiple symptoms is largely unexplored. Methods: Bioinformatics analysis determined the sequence similarity between SARS-CoV-2 and human genomes. Diverse fragments of SARS-CoV-2 genome containing Human Identical Sequences (HIS) were cloned into the lentiviral vector. HEK293T, MRC5 and HUVEC were infected with laboratory-packaged lentivirus or transfected with plasmids or antagomirs for HIS. Quantitative RT-PCR and chromatin immunoprecipitation assay detected gene expression and H3K27ac enrichment, respectively. UV-Vis spectroscopy assessed the interaction between HIS and their target locus. Enzyme-linked immunosorbent assay evaluated the hyaluronan (HA) levels of culture supernatant and plasma of COVID-19 patients. Findings: Five short sequences (24–27 nt length) sharing identity between SARS-CoV-2 and human genome were identified. These RNA elements were highly conserved in primates. The genomic fragments containing HIS were predicted to form hairpin structures in silico similar to miRNA precursors. HIS may function through direct genomic interaction leading to activation of host enhancers, and upregulation of adjacent and distant genes, including cytokine genes and hyaluronan synthase 2 (HAS2). HIS antagomirs and Cas13d-mediated HIS degradation reduced HAS2 expression. Severe COVID-19 patients displayed decreased lymphocytes and elevated D-dimer, and C-reactive proteins, as well as increased plasma hyaluronan. Hymecromone inhibited hyaluronan production in vitro, and thus could be further investigated as a therapeutic option for preventing severe outcome in COVID-19 patients. Interpretation: HIS of SARS-CoV-2 could promote COVID-19 progression by upregulating hyaluronan, providing novel targets for treatment. Funding: The National Key R&D Program of China (2018YFC1005004), Major Special Projects of Basic Research of Shanghai Science and Technology Commission (18JC1411101), and the National Natural Science Foundation of China (31872814, 32000505).

Immunodiagnostics have been widely used in the detection of disease biomarkers. The conventional immunological tests in central laboratories require expensive equipment and, for non-specialists, the tests are technically demanding and time-consuming, which has prevented their use by the public. Thus, point-of-care tests (POCT), such as lateral flow immunoassays, are being, or have been, developed as more convenient and low-cost methods for immunodiagnostics. However, the sensitivity of such tests is often a concern. Here, a fluorescence-linked immunosorbent assay (FLISA) using organic light-emitting diodes (OLEDs) as excitation light sources was investigated as a way forward for the development of compact and sensitive POCTs. Phycoerythrin (PE) was selected as the fluorescent dye, and OLEDs were designed with different emission spectra. The leakage light of different OLEDs for exciting PE was then investigated to reduce the background noise and improve the sensitivity of the system. Finally, as proof-of-principle that OLED-based technology can be successfully further developed for POCT, antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in human serum was detected by OLED−FLISA.

In the study of hyperspectral image classification based on machine learning theory and techniques, the problems related to the high dimensionality of the images and the scarcity of training samples are widely discussed as two main issues that limit the performance of the data-driven classifiers. These two issues are closely interrelated, but are usually addressed separately. In our study, we try to kill two birds with one stone by constructing an ensemble of lightweight base models embedded with spectral feature refining modules. The spectral feature refining module is a technique based on the mechanism of channel attention. This technique can not only perform dimensionality reduction, but also provide diversity within the ensemble. The proposed ensemble can provide state-of-the-art performance when the training samples are quite limited. Specifically, using only a total of 200 samples from each of the four popular benchmark data sets (Indian Pines, Salinas, Pavia University and Kennedy Space Center), we achieved overall accuracies of 89.34%, 95.75%, 93.58%, and 98.14%, respectively.

BackgroundType 2 diabetes mellitus increases the risk of cardiovascular disease including myocardial infarction (MI). Inflammation and apoptosis have been implicated in the pathophysiology of MI. In the present study, the effects of astragaloside IV (AS-IV) on MI in diabetic mice were evaluated.MethodsHigh glucose/high fat (HG/HF) and hypoxia culture condition were established to mimic diabetic condition. After administration of AS-IV to H9c2 myocytes, the cell apoptosis, viability, and activation of mitogen-activated protein kinase (MAPK) signaling pathways were detected. MI was induced in streptozotocin-induced diabetic mice. After administration of AS-IV to mice, cardiac function, cardiac fibrosis, inflammation, and activation of MAPK signaling pathway were detected.ResultsAstragaloside IV treatment significantly inhibited HG/HF and hypoxia-induced apoptosis of H9c2. AS-IV inhibited activation of JNK and p38 signaling pathway while promoting the activation of EKR signaling pathway. AS-IV treatment rescued cardiac function, suppressed cardiac fibrosis and inflammation, and differently regulated the activation of MAPK signaling pathways.ConclusionAstragaloside IV prevented apoptosis and restored cardiac function in MI, which may be due to the regulation of MAPK signaling pathway in diabetes.

OLED is ready for photodynamic therapy Flexible OLED technology is becoming increasingly mature and is ready to open new directions in antimicrobial photodynamic therapy. An international team led by Prof Ifor Samuel from University of St Andrews, UK presents a comprehensive study to show that flexible organic light-emitting diodes (OLEDs) are ideal light sources to be used in photodynamic therapy to kill bacteria. They design the OLED device structure to enable large area, high uniformity, low driving voltage, long operational lifetime, adequate shelf-life and colour tunability and address all the requirements of photodynamic therapy. Actual biological experiments show killing rates of more than 99% for S. aureus bacteria. The approach clearly demonstrates the huge potential of OLEDs for treatment of bacterial infections and future wearable healthcare devices.

Acute myeloid leukemia (AML) is as a highly aggressive and heterogeneous hematological malignancy. MiR-20a-5p has been reported to function as an oncogene or tumor suppressor in several tumors, but the clinical significance and regulatory mechanisms of miR-20a-5p in AML cells have not been fully understood. In this study, we found miR-20a-5p was significantly decreased in bone marrow from AML patients, compared with that in healthy controls. Moreover, decreased miR-20a-5p expression was correlated with risk status and poor survival prognosis in AML patients. Overexpression of miR-20a-5p suppressed cell proliferation, induced cell cycle G0/G1 phase arrest and apoptosis in two AML cell lines (THP-1 and U937) using CCK-8 assay and flow cytometry analysis. Moreover, miR-20a-5p overexpression attenuated tumor growth in vivo by performing tumor xenograft experiments. Luciferase reporter assay and western blot demonstrated that protein phosphatase 6 catalytic subunit (PPP6C) as a target gene of miR-20a-5p was negatively regulated by miR-20a-5p in AML cells. Furthermore, PPP6C knockdown imitated, while overexpression reversed the effects of miR-20a-5p overexpression on AML cell proliferation, cell cycle G1/S transition and apoptosis. Taken together, our findings demonstrate that miR-20a-5p/PPP6C represent a new therapeutic target for AML and a potential diagnostic marker for AML therapy.

Light-driven carbon dioxide conversion into fuels provides a nature-inspired strategy to combat climate change, but how materials do so remains a challenge. Here, the authors prepare metal–semiconductor composites and find platinum-nanoparticle size controls fuel selectivity and activity.