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Abstract ChatGPT has proven to facilitate computer programming tasks through the strategic use of prompts, which effectively steer the interaction with the language model towards eliciting relevant information. However, the impact of specifically designed prompts on programming learning outcomes has not been rigorously examined through empirical research. This study adopted a quasi-experimental framework to investigate the differential effects of prompt-based learning (PbL) versus unprompted learning (UL) conditions on the programming behaviors, interaction qualities, and perceptions of college students. The study sample consisted of 30 college students who were randomly assigned to two groups. A mixed-methods approach was employed to gather multi-faceted data. Results revealed notable distinctions between the two learning conditions. First, the PbL group students frequently engaged in coding with Python and employed debugging strategies to verify their work, whereas their UL counterparts typically transferred Python code from PyCharm into ChatGPT and posed new questions within ChatGPT. Second, PbL participants were inclined to formulate more complex queries independently, prompted by the guiding questions, and consequently received more precise feedback from ChatGPT compared to the UL group. UL students tended to participate in more superficial-level interactions with ChatGPT, yet they also obtained accurate feedback. Third, there were noticeable differences in perception observed before and after the ChatGPT implementation, UL group reported a more favorable perception in the perceived ease of use in the pre-test, while the PbL group experienced an improvement in their mean scores for perceived usefulness, ease of use, behavioral intention to utilize, and a significant difference regarding the attitude towards utilizing ChatGPT. Specifically, the use of structured output and delimiters enhanced learners’ understanding of problem-solving steps and made learning more efficient with ChatGPT. Drawing on these outcomes, the study offers recommendations for the incorporation of ChatGPT into future instructional designs, highlighting the structured prompting benefits in enhancing programming learning experience.

G protein-coupled receptors (GPCRs) are pivotal in mediating diverse physiological and pathological processes, rendering them promising targets for drug discovery. GPCRs account for about 40% of FDA-approved drugs, representing the most successful drug targets. However, only approximately 15% of the 800 human GPCRs are targeted by market drugs, leaving numerous opportunities for drug discovery among the remaining receptors. Cell expression systems play crucial roles in the GPCR drug discovery field, including novel target identification, structural and functional characterization, potential ligand screening, signal pathway elucidation, and drug safety evaluation. Here, we discuss the principles, applications, and limitations of widely used cell expression systems in GPCR-targeted drug discovery, GPCR function investigation, signal pathway characterization, and pharmacological property studies. We also propose three strategies for constructing genome-wide pan-GPCR cell libraries, which will provide a powerful platform for GPCR ligand screening, and facilitate the study of GPCR mechanisms and drug safety evaluation, ultimately accelerating the process of GPCR-targeted drug discovery.

Abstract To evaluate the efficacy and safety of digital therapy for children aged 6 to 12 years with attention deficit hyperactivity disorder (ADHD). From January to March 2023, 52 children aged 6 to 12 years with attention deficit hyperactivity disorder (ADHD) from Wuhan Children’s Hospital, Hubei Province, China were selected for intervention using the “MindPro1” attention training software developed by Jiangsu Ruinao Qizhi Medical Technology Co., Ltd. Before the intervention, the children were in a stable treatment state, and no modifications were made to the original treatment plan during the MindPro1 intervention. Subjects with severe mental illness or other conditions that may affect the implementation and evaluation of disease treatment were excluded. Subjects completed the planned 4-week intervention, and changes in attention-related variables were assessed using the Test of Attention Variables (TOVA) and the parent version of the 18-item SNAP-IV scale (Swanson, Nolan, and Pelham, version IV scale) before and after the intervention. After 4 weeks of intervention, the lower limit of the 95% confidence interval of the response rate of the 18-item SNAP-IV-Parent scale, which was ≥ 30% improvement from baseline, was higher than 27.5% (better than similar products on the market); the SNAP-IV parent score improved (P

Nano-controlled release formulations present a promising strategy to mitigate pesticide losses and enhance efficiency. In this study, a pH and GSH-responsive nanoplatform using mesoporous organosilica nanoparticles (MONs) as a carrier and poly(tannic acid) (PTA) as capping agent was established for controlling prochloraz (Pro) release. The obtained Pro@MON@PTA was characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA). The results indicate the successful preparation of Pro@MON@PTA nanoparticles, featuring uniform particle size (190 nm), excellent dispersibility, and a prochloraz loading efficiency of 17.2%. Evaluation of contact angle and adhesion work demonstrated superior adhesion of MON@PTA to rice leaves compared to MON. Controlled release studies revealed dual-responsive release properties of Pro@MON@PTA to acid and GSH. Additionally, photostability testing indicated effective ultraviolet light shielding by the carrier, reducing prochloraz degradation under irradiation. Bioassay results indicated equivalent fungicidal activity against Magnaporthe oryzae between Pro@MON@PTA and prochloraz technical and prochloraz EW after a 7-day treatment. However, in vivo experiments demonstrated that Pro@MON@PTA exhibited superior control efficacy compared to prochloraz EW. These findings suggested that MON@PTA holds significant potential for plant disease management.

To comprehensively assess the true visual function of clinical dry eye patients and the comprehensive impact of blinking characteristics on functional vision of the human eye, an intelligent vision measurement system has been designed and developed to detect and analyze blinks from the side. The system employs deep learning keypoint recognition technology to analyze eyelid features from a lateral perspective. It presents the data of identified key points for the upper and lower eyelids in a line chart format and annotates the trough of each blink. By setting benchmark values, the system automatically calculates the proportion of complete and incomplete blinks in the tested individuals. The results indicate that the system is stable in performance and accurate in measurement, successfully achieving the anticipated design objectives. It thereby provides reliable technical support for future clinical applications.

Summary: Natural killer (NK) cells play a pivotal role against cancer, both by direct killing of malignant cells and by promoting adaptive immune response though cytokine and chemokine secretion. In the lung tumor microenvironment (TME), NK cells are scarce and dysfunctional. By conducting single-cell transcriptomic analysis of lung tumors, and exploring pseudotime, we uncovered that the intratumoral maturation trajectory of NK cells is disrupted in a tumor stage-dependent manner, ultimately resulting in the selective exclusion of the cytotoxic subset. Using functional assays, we observed intratumoral NK cell death and a reduction in cytotoxic capacities depending on the tumor stage. Finally, our analyses of human public dataset on lung cancer corroborate these findings, revealing a parallel dysfunctional maturation process of NK cells during tumor progression. These results highlight additional mechanisms by which tumor cells escape from NK cell cytotoxicity, therefore paving the way for tailored therapeutic strategies.

Abstract The Rho GTPase activating protein family (ARHGAPs) is expressed in pancreatic adenocarcinoma (PAAD) but its function is unclear. The aim of this study was to explore the role and potential clinical value of ARHGAPs in PAAD. Using TCGA and GEO databases to analyze expression of ARHGAPs in PAAD and normal tissues. Survival curve was drawn by Kaplan–Meier. ARHGAPs were integrated analyzed by GEPIA2, TIMER, UCLCAN, cBioPortal and R language. Protein level and prognostic value were evaluated via IHC staining or survival analysis. We totally identify 18 differentially expressed (DE) ARHGAPs in PAAD. Among the 18 DE genes, 8 were positively correlated with tumor grade; abnorrmal expression of 5 was positively correlated with copy number variation; expression of 4 was positively correlated with promoter hypomethylation. Multivariate Cox regression identified ARHGAP5, ARHGAP11A, and ARHGAP12 as independent prognostic factors of PAAD. The function of ARHGAPs was mainly related to GTPase activity and signaling, axon guidance, proteoglycans in cancer and focal adhesion. Expression of 7 ARHGAPs was strongly correlated with immune infiltration. Immunohistochemistry showed increased protein levels of ARHGAP5, ARHGAP11A, and ARHGAP12 in PAAD tissues. Survival analysis confirmed a negative correlation between ARHGAP5, ARHGAP11A, and ARHGAP12 expression and patient prognosis. Multivariate Cox regression proved ARHGAP5, ARHGAP11A, and ARHGAP12 could serve as independent prognostic indicators for PAAD. Finally, this study verified ARHGAP5, ARHGAP11A, and ARHGAP12 as independent prognostic factors in PAAD, suggesting their significance for the diagnosis and treatment of PAAD.

Abstract Increased plasma homocysteine (Hcy) has been identified as one of the important risk factors for cardiovascular disease. However, the association between plasma Hcy and peripheral artery disease (PAD) is still controversial. This study aimed to investigate the association between plasma Hcy and PAD and the potential modifier factors in Chinese hypertensive adults. A total of 25 300 hypertensive patients aged 18 years or older were included in the analysis in this cross‐sectional study. The outcome was PAD, which defined as an ankle‐brachial index ≤0.90 in either limb. Multiple logistic regression was used to analyze the relationship between plasma Hcy and PAD. The median plasma Hcy was 14.00 (interquartile range: 11.60–17.80) μmol/L. There was a significant positive association between plasma Hcy and PAD (per SD increment; OR: 1.13; 95% CI: 1.06–1.19). Patients in the upper plasma Hcy tertile (≥16.16 μmol/L) were associated with a 53% increased risk of PAD compared with patients in the lower tertile (

Background Despite the high risk of eating disorder (ED)-related attitudes and behaviors among female dancers, targeted scientific dietary regimens are currently inadequate. Time-restricted eating (TRE), a popular intermittent fasting protocol, has been shown to be effective in enhancing body composition and exercise performance in athletes. In this study, TRE was employed as a dietary regimen to improve body composition and exercise performance and address ED attitudes and behaviors in DanceSport dancers.Methods Twenty female DanceSport dancers were recruited and divided into two groups: TRE (n = 10) and normal diet (ND) (n = 10). The TRE group consumed their self-selected necessary energy intake exclusively between 11 a.m. and 7 p.m. (utilizing a 16-hour fasting and 8-hour eating window) for 6 weeks, while the ND group maintained their regular dieting patterns. The consumption of water, black tea, or coffee without added sugar or milk was not restricted. Physical activity and calorie intake were systematically recorded during the TRE intervention. Body composition, aerobic and anaerobic performance, and ED attitudes and behaviors were assessed before and after the TRE intervention. The trial was registered in the Chinese Clinical Trial Registry under the identifier ChiCTR2200063780.Results The fixed effects tests (p 0.05). TRE resulted in a reduction in hip circumference (p = 0.039), fat mass (kg) (p = 0.0004), and body fat percentage (p = 0.0005), with no significant decrease in fat-free mass (p > 0.05). No significant improvement was observed in aerobic performance (p > 0.05). The average power (AP) (p = 0.01) and AP/Body weight ratio (p = 0.003) significantly increased. Additionally, the power drop decreased significantly (p = 0.019). Group-by-time interactions were observed for fat mass (kg) (p = 0.01), body fat percentage (p = 0.035), and AP/Body weight (p = 0.020).Conclusion TRE can be considered a feasible nutritional strategy for DanceSport dancers, facilitating improvements in body composition without compromising aerobic and anaerobic exercise performance or exacerbating ED attitudes and behaviors. Moreover, TRE may facilitate more favorable physiological adaptations, potentially contributing to improved exercise performance.

AbstractFabricating highly efficient and low-cost absorbents to remove organic contaminants in industrial effluents is urgent yet of great importance. Herein, a facile one-pot hydrothermal approach was developed to successfully construct magnesium silicate and bentonite composite (MS-Bt) with uniform multilayer porous structure by using Bt as structural promoter. The specific surface area of MS-Bt can reach up to 392 m2·g−1 along with an average pore diameter of 2.29 nm and a pore volume of 0.22 cm3·g−1. MS-Bt composite exhibits a maximal adsorption capacity of 253.92 mg·g−1 for methylene blue (MB) in model wastewater treatment. Adsorption behavior fitted well with Langmuir isotherm and pseudo-second-order kinetics adsorption equations. The adsorption pathways of MB on MS-Bt mainly include chemical precipitation by Mg-OH, electrostatic attraction and surface hydroxyl functional group capture. This work is anticipated to give a new insight into constructing organic contaminants adsorbent by using clay mineral material as an auxiliary agent.

Mouth floor cellulitis is a type of diffuse cellulitis involving the submandibular, submental, and sublingual spaces. This condition may cause asphyxia due to elevation and posterior deviation of the tissues of the floor of the mouth. The severity of submandibular gland infection often escalates in the presence of underlying comorbidities. Advanced age, hyperglycemia, and an immunocompromised status often lead to the rapid development of infection, resulting in complications such as acute upper airway obstruction. These complications increase treatment difficulty and the risk of mortality. We herein report a case involving an older adult with diabetes who developed mouth floor cellulitis secondary to a submandibular gland infection. Despite the severity of the submandibular gland infection, a timely, effective, and multidisciplinary approach improved the patient’s prognosis.

Zebrafish is a highly advantageous model animal for drug screening and toxicity evaluation thanks to its amenability to optical imaging (i.e., transparency), possession of organ structures similar to humans, and the ease with which disease models can be established. However, current zebrafish drug screening technologies and devices suffer from limitations such as low level of automation and throughput, and low accuracy caused by the heterogeneity among individual zebrafish specimens. To address these issues, we herein develop a high-throughput zebrafish drug screening system. This system is capable of maintaining optimal culturing conditions and simultaneously monitoring and analyzing the movement of 288 zebrafish larvae under various external conditions, such as drug combinations. Moreover, to eliminate the effect of heterogeneity, locomotion of participating zebrafish is assessed and grouped before experiments. It is demonstrated that in contrast to the experimental results without pre-selection, which shows ∼20 % damaged motor function (i.e., degree of attenuation), the drug-induced variations among zebrafish with equivalent mobility reaches ∼80 %. Overall, our high-throughput zebrafish drug screening system overcomes current limitations by improving automation, throughput, and accuracy, resulting in enhanced detection of drug-induced variations in zebrafish motor function.

Diabetic wound healing presents a significant clinical challenge due to the interplay of systemic metabolic disturbances and local inflammation, which hinder the healing process. Macrophages undergo a phenotypic shift from M1 to M2 during wound healing, a transition pivotal for effective tissue repair. However, in diabetic wounds, the microenvironment disrupts this phenotypic polarization, perpetuating inflammation, and impeding healing. Reprograming macrophages to restore their M2 phenotype offers a potential avenue for modulating the wound immune microenvironment and promoting healing. This review elucidates the mechanisms underlying impaired macrophage polarization toward the M2 phenotype in diabetic wounds and discusses novel strategies, including epigenetic and metabolic interventions, to promote macrophage conversion to M2. Hydrogels, with their hydrated 3D cross-linked structure, closely resemble the physiological extracellular matrix and offer advantageous properties such as biocompatibility, tunability, and versatility. These characteristics make hydrogels promising candidates for developing immunomodulatory materials aimed at addressing diabetic wounds. Understanding the role of hydrogels in immunotherapy, particularly in the context of macrophage reprograming, is essential for the development of advanced wound care solutions. This review also highlights recent advancements in immunotherapeutic hydrogels as a step toward precise and effective treatments for diabetic wounds.

Adprhl2 (OMIM: 610624) mutation associated stress-induced childhood-onset neurodegeneration with variable ataxia and seizures (CONDSIAS, OMIM: 618170) is a sporadic neurodegenerative disease with poor prognosis. ADPRHL2 encodes ADP-ribosylhydrolase 3 (ARH3), which participates in ADP-ribosylation to remove poly-ADP ribose (PAR). We found a new compound heterozygous mutation in the ADPRHL2 gene c.580C > T (p.Gln194Ter) and c.803-1G > A in a 30-month-old boy, who showed gait instability, abnormal EEG, and developmental delay after respiratory infection. He died of convulsions 4 months after onset. By constructing a mutant plasmid and using Western blot to detect the expression of ARH3 and PAR, it was demonstrated that the ADPRHL2 gene c.580C > T (p.Gln194Ter) and c.803-1G > A is pathogenic according to ACMG guidelines.

Accurate monitoring of fertilizer concentration and variable irrigation components is crucial for achieving precision irrigation through variable-rate fertigation. However, technological and cost constraints pose challenges in effectively managing mixed variable-rate fertigation. This study addresses these challenges by integrating machine learning (ML) with easily monitored physical parameters, such as electrical conductivity (EC), pH, and temperature, to predict fertilizer solution components and concentrations in mixed variable-rate fertigation. Cubic spline interpolation (CSI) was used to enhance the training dataset. Six ML algorithms—Multivariate Linear Regression (MLR), Support Vector Machines (SVM), K-Nearest Neighbors (KNN), Extremely Randomized Trees (ETs), Multilayer Perceptron (MLP), and Extreme Gradient Boosting (XGB)—were used to develop prediction models, with their performance evaluated using the coefficient of determination (R2), root mean square error (RMSE), and Akaike information criterion (AIC). The Extended Fourier Amplitude Sensitivity Test (EFAST) assessed the sensitivity of the ML models to physical parameters. All of the ML models, except for MLR, particularly SVM, demonstrated superior performance in predicting fertilizer solution components’ concentrations, with R2 values between 0.989 and 0.997 and RMSE values between 0.089 and 0.210. The CSI significantly enhanced model performance, resulting in larger R2 values and smaller RMSE values. The AIC results and sensitivity analysis confirmed the exceptional performance of SVM, emphasizing its suitability for predicting fertilizer components using easily measured physical parameters. The developed ML models offer valuable insights for decision-makers managing irrigation and fertilization in mixed variable-rate fertigation.

Background: Aim to investigate the impact of bedside assistant's work experience and learning curve on the short-term safety and efficacy in robotic-assisted laparoscopic radical hysterectomy for early-stage cervical cancer. Methods: Our research retrospectively retrieved 120 cases of early-stage cervical cancer patients who underwent robotic-assisted laparoscopic radical hysterectomy at the First Affiliated Hospital of Guangxi Medical University. According to the different work experiences of the two bedside assistants (BA), patients were divided into a research group (inexperienced BA 1) and a control group (experienced BA 2). Furthermore, the learning curves of these BAs were plotted separately and divided into two distinct phases by cumulative summation: the first learning phase and the second master phase. Result: In terms of work experience, comparing BA 1 with BA 2 who was more experienced, although the average operative time was prolonged by 29 min (P＜0.001), it did not increase the incidence of operative complication [24.4 % VS 29.1 %, P = 0.583], positive resection margin [4.9 % VS 7.6 %, P = 0.714], intraoperative organ damage [0 % VS 2.5 %, P = 0.546] and there was no significant difference in the number of lymph nodes [19 VS 15, P = 0.103]. Additionally, comparing two distinct phases of the same bedside assistant, there was no significant increasing rate in terms of operative complication, positive resection margin, intraoperative organ damage, and the number of lymph nodes (P＞0.05) neither BA 1 nor BA 2, except for a slight extension of operative time about 20 min in learning phase (P＜0.05). Conclusion: In robotic-assisted laparoscopic radical hysterectomy for early-stage cervical cancer, work inexperience and the learning phase of BA only result in a slight extension of operative time, without causing worse short-term surgical outcomes.

Abstract ChatGPT, an AI-based chatbot with automatic code generation abilities, has shown its promise in improving the quality of programming education by providing learners with opportunities to better understand the principles of programming. However, limited empirical studies have explored the impact of ChatGPT on learners’ programming processes. This study employed a quasi-experimental design to explore the possible impact of ChatGPT-facilitated programming mode on college students’ programming behaviors, performances, and perceptions. 82 college students were randomly divided into two classes. One class employed ChatGPT-facilitated programming (CFP) practice and the other class utilized self-directed programming (SDP) mode. Mixed methods were utilized to collect multidimensional data. Data analysis uncovered some intriguing results. Firstly, students in the CFP mode had more frequent behaviors of debugging and receiving error messages, as well as pasting console messages on the website and reading feedback. At the same time, students in the CFP mode had more frequent behaviors of copying and pasting codes from ChatGPT and debugging, as well as pasting codes to ChatGPT and reading feedback from ChatGPT. Secondly, CFP practice would improve college students’ programming performance, while the results indicated that there was no statistically significant difference between the students in CFP mode and the SDP mode. Thirdly, student interviews revealed three highly concerned themes from students' user experience about ChatGPT: the services offered by ChatGPT, the stages of ChatGPT usage, and experience with ChatGPT. Finally, college students’ perceptions toward ChatGPT significantly changed after CFP practice, including its perceived usefulness, perceived ease of use, and intention to use. Based on these findings, the study proposes implications for future instructional design and the development of AI-powered tools like ChatGPT.

Objective(s): The prognosis of endometrial cancer (EC) is significantly affected by tumor infiltration and metastasis. Cortactin (CTTN) regulates infiltration and metastasis in other tumors. Studies on the role and mechanism of CTTN in EC are limited and further studies are needed.Materials and Methods: Quantitative PCR and immunohistochemistry were used to detect Ras-associated C3 botulinum toxin substrate 1 (Rac1) and CTTN in EC and normal tissues. The relationship between the expression of these two genes and their prognostic factors was analyzed. A CTTN-RNAi lentiviral system was constructed and transfected into EC cells. Migration and invasion were evaluated by scratch assay, transwell migration, and invasion assays. Pseudopodia formation was observed by immunofluorescence staining. Western blotting was performed to detect the expression of Rac1.Results: The expression levels of Rac1 and CTTN in EC tissues were significantly higher than those in normal tissues. In the EC group, Rac1 and CTTN levels were correlated. The protein expression levels of Rac1 and CTTN were related to myometrial invasion and stage. After CTTN knockdown, the migration rate, invasiveness, and migratory ability of EC cells decreased significantly. Lamellipodia was observed to disappear with the appearance of blebs. Rac1 protein expression was decreased after CTTN knockdown.Conclusion: CTTN may promote the invasion and migration of EC by lamellipodia. This effect may be related to the regulation of Rac1 by CTTN.

Abstract Patients with HBeAg-negative chronic hepatitis B may experience an immune response after stopping nucleos(t)ide analogue (NA)therapy, which may potentially trigger HBsAg loss or off-therapy sustained viral control. The immunological mechanisms determining clinical response remain poorly understood. To identify inflammatory signatures associated with defined outcomes, we analysed plasma cytokines and chemokines from 57 HBeAg-negative patients enrolled in the Nuc-Stop Study at baseline and 12 weeks after NA cessation. Clinical response at 12 weeks was classified into four groups: immune control, viral relapse, evolving clinical relapse, and resolving clinical relapse. Twelve weeks after treatment cessation 17 patients (30%) experienced immune control, 19 (33%) viral relapse, 6 (11%) evolving clinical relapse, and 15 (26%) resolving clinical relapse. There was a significant increase in interferon-γ-induced protein 10 (IP-10; p = 0.012) and tumor necrosis factor (TNF; p = 0.032) in patients with evolving clinical relapse. Sparse partial least-squares multivariate analyses (sPLS-DA) showed higher first component values for the clinical relapse group compared to the other groups, separation was driven mainly by IP-10, TNF, IL-9, IFN-γ, MIP-1β, and IL-12. Our results demonstrate that evolving clinical relapse after NA cessation is associated with a systemic increase in the proinflammatory cytokines IP-10 and TNF. Clinical trial registration: ClinicalTrials.gov, Identifier: NCT03681132.

In this paper, we study the bifurcation of limit cycles from a class of cubic integrable non-Hamiltonian systems under arbitrarily small piecewise smooth perturbations of degree $n$. By using the averaging theory and complex method, the lower and upper bounds for the maximum number of limit cycles bifurcating from the period annulus of the unperturbed systems are given at first order in $\varepsilon$. It is also shown that in this case, the maximum number of limit cycles produced by piecewise smooth perturbations is almost twice the upper bound of the maximum number of limit cycles produced by smooth perturbations for the considered systems.

Actinidia arguta is a cold-resistant fruit tree but intolerant to waterlogging. Waterlogging stress is the major abiotic stress in A. arguta growth, and several pathways are involved in the response mechanisms. Fifteen physiological indices and transcriptome data of two A. arguta cultivars, which showed two forms under waterlogging, were used to identify the major factor following the leaf senescence in waterlogging. Through principal component analysis (PCA) of 15 physiological indices in ‘Kuilv’ and ‘Lvwang’, the hormone contents were selected as the most important principal component (PCA 2) out of four components in response to waterlogging stress. According to the analysis of transcriptome data, 21,750 differentially expressed genes were identified and 10 genes through WGCNA, including hormone metabolism and sucrose metabolism, were screened out on the 6th day of waterlogging. In particular, the ABA signal transduction pathway was found to be closely related to the response to waterlogging based on the correlation analysis between gene expression level and plant hormone content, which may have regulated physiological indicators and morphological changes together with other hormones. Overall, the phenomenon of leaves falling induced by ABA might be a protective mechanism. The results provided more insights into the response mechanism of coping with waterlogging stress in A. arguta.

Titanium dioxide (TiO2) has emerged as a candidate anode material for sodium-ion batteries (SIBs). However, their applications still face challenges of poor rate performance and low initial coulomb efficiency (ICE), which are induced by the unstable solid-electrolyte interface (SEI) and sluggish Na+ diffusion kinetics in conventional ester-based electrolytes. Herein, inspired by the electrode/electrolyte interfacial chemistry, tetrahydrofuran (THF) is exploited to construct an advanced electrolyte and reveal the relationship between the improved electrochemical performance and the derived SEI film on TiO2 anode. The robust and homogeneously distributed F-rich SEI film formed in THF electrolyte favors fast interfacial charge transfer dynamics and excellent interfacial stability. As a result, the THF electrolyte endows the TiO2 anode with greatly improved ICE (64.5%), exceptional rate capabilities (186 mAh g−1 at 5.0 A g−1), and remarkable cycling stability. This study elucidates the control of interfacial chemistry by rational electrolyte design and offers insights into the development of high-performance and long-lifetime TiO2 anode.

Root system architecture is pivotal for the acquisition of water and nutrients in maize, serving as an essential foundation for achieving high and stable yields. Identification of the genetic components and natural variations determining root traits may facilitate molecular breeding of maize varieties with better root traits. Melatonin plays an important role in plant physiology and development. In this study, nine melatonin biosynthesis genes were re-sequenced in 348 inbred lines, 68 landraces, and 32 teosintes to investigate variations related to maize root traits. The analysis of nucleotide diversity suggested that these genes may have undergone selection, particularly within their promoter regions. Marker–trait association analysis identified 26 variants significantly associated with six root traits. Five variations within the ZmTDC4 promoter were significantly correlated with both total root length (TRL) and lateral root length (LRL). Among these, SNP-1784 explained the most phenotypic variation of root traits, including TRL and LRL, that has undergone selection throughout maize domestication and improvement. Furthermore, knockout of ZmTDC4 in maize resulted in a pronounced reduction in root length, underscoring its critical role in root development. Collectively, these findings elucidate the role of melatonin synthesis genes in root development and identified favorable alleles, thus providing key loci for breeding maize varieties with superior root systems.

With the increase in global economic integration, high-quality economic development (HQED) has become a common goal of all countries. Based on these five development concepts, this paper uses the Gini coefficient, trend surface analysis, geographically weighted regression (GWR), the entropy weighting method, and standard deviation ellipse analysis to study the spatio-temporal pattern and driving mechanism of HQED in the Guangdong-Hong Kong-Macao Greater Bay Area (GBA). This paper examines the spatial and temporal patterns and driving mechanisms of HQED in the Guangdong-Hong Kong-Macao Greater Bay Area (GBA) based on five development concepts. The study revealed that (1) HQED is on the rise overall, but at the same time, it highlights the uneven development of multiple dimensions, especially in terms of significant differences in innovation, openness, and sharing. (2) HQED shows a clear center-periphery structure, with Guangzhou, Shenzhen, and Hong Kong as the core high-value areas; the growth rate of HQED capacity in the internal areas is significantly greater than that in the external areas, and HQED is prominent in the cities around Guangzhou, Shenzhen, and Hong Kong. (3) Factors such as agglomeration level, human capital, foreign investment, infrastructure development, financial and environmental protection expenditures, and financial inputs, and scientific, and technological inputs have a significant positive effect on HQED, and their interactions are further strengthened. This study reveals the importance of the realization of HQED in the GBA and the promotion of the overall development of the region.

Docetaxel (DOC) is one of the second-generation antineoplastic drugs of the taxanes family with excellent antitumor activity. However, the mechanism of DOC inducing tumor cell apoptosis and treating cancer diseases, especially its interaction with DNA in the nucleus, and its adjuvant or combined Doxorubicin (DOX) acting on DNA molecules are unclear. In this study, the interaction mechanism between DOC and DNA, as well as the synergistic effects and competitive relationships among DOC and DOX when they simultaneously interact with DNA molecules were studied by laser confocal Raman spectroscopy combined with UV–visible absorption spectroscopy and molecular docking technology. The spectroscopic results showed that the binding constant of DOC to DNA is 5.25 × 103 M−1, the binding modes of DOC and DNA are non-classical intercalation and electrostatic binding, and the DNA-DOC complex has good stability. When DOC or DOX interacts with DNA alone, both of them can bind with bases and phosphate backbone of DNA, and also lead to DNA conformation changes; when DOC and DOX interact with DNA at the same time, the orders of interaction not only affect their binding sites with DNA, but also cause changes in the surrounding environment of the binding sites. In addition, the molecular docking results further verified that DOC and DOX have synergy and competition when they interact with DNA molecules simultaneously. The docking energies of DNA-DOC and DNA-DOX indicate the important role of van der Waals forces and hydrogen bonds. This study has practical significance for the design and development of antitumor drugs with less toxic based on the taxanes family and the combination with other drugs for the treatment of cancer.

Objective: This study constitutes a pioneering systematic review and meta analysis delving into the clinical efficacy and safety of the combined therapy involving Wuhu Decoction and azithromycin for treating Mycoplasma pneumoniae pneumonia in pediatric patients.Methods: This study conducted a comprehensive computerized search, covering 6 Chinese databases and 6 English databases, to collect randomized controlled trials related to the combined use of Wuhu Decoction and azithromycin for treating Mycoplasma pneumoniae pneumonia in pediatric patients. The search was extended until August 2023. Two independent researchers were involved in literature screening, data extraction, and bias risk assessment. Meta-analysis was performed using Stata 14.0 and RevMan 5.4 software. Additionally, meta-regression analysis and subgroup analysis were carried out on primary outcomes to identify potential sources of heterogeneity and confounding factors.Results: A total of 22 randomized controlled trials involving 2,026 patients were included in this study. The combined therapy of Wuhu Decoction and azithromycin demonstrated superior efficacy compared to azithromycin alone (RR = 1.17, 95% CI [1.13, 1.21], p < 0.00001; low certainty of evidence). Additionally, patients receiving the combination therapy experienced significantly reduced the disappearance time of fever (MD = −1.42, 95% CI [−1.84, −1.00], p < 0.00001; very low certainty of evidence), disappearance time of cough (MD = −2.08, 95% CI [−2.44, −1.71], p < 0.00001; very low certainty of evidence), disappearance of pulmonary rales (MD = −1.97, 95% CI [−2.31, −1.63], p < 0.00001; very low certainty of evidence), and disappearance time of wheezing (MD = −1.47, 95% CI [−1.72, −1.22], p < 0.00001; very low certainty of evidence). Meta-regression analysis suggested that course of disease, sample size, and age might be sources of heterogeneity. Subgroup and sensitivity analyses reaffirmed the stability of these results. Furthermore, analyses of secondary outcomes such as T lymphocytes, serum inflammatory factors, and the incidence rate of adverse reactions consistently favored the combination therapy of WHD and azithromycin over azithromycin alone, with statistically significant differences.Conclusion: Based on our meta-analysis findings, the combined therapy of Wuhu Decoction and azithromycin for treating pediatric Mycoplasma pneumoniae pneumonia exhibited superior overall efficacy in comparison to azithromycin monotherapy. However, in the included 22 studies, the majority of evaluated factors showed unclear bias risks, and a persistent bias risk was consistently present within one category. Moreover, due to the low quality of evidence, interpreting these results should be approached with caution. Hence, we emphasize the necessity for future high-quality, multicenter, and large-sample clinical randomized controlled trials. These trials are essential to provide more robust data for evidence-based research and to establish higher-quality evidence support.Systematic Review Registration:https://www.crd.york.ac.uk/prospero/, identifier CRD42023465606

Abstract Background Chinese/Mandarin language instruction to undergraduate students from non-Chinese speaking countries has become a topic of increasing interest, driven by China’s influential role in global political and economic dynamics. With Mandarin being the language spoken by approximately 70% of Chinese speakers, it is not only taught within China but also in institutions around the world. While teaching any second or foreign language presents unique challenges, the specific challenges faced in Mandarin language education have not received comprehensive scrutiny, prompting the need for further investigation. Objectives The primary objective of this study was to explore the challenges associated with teaching and learning Mandarin from the perspectives of non-native Mandarin language teachers. By adopting a qualitative (phenomenological) research approach, we aimed to uncover the multifaceted challenges that confront both educators and learners in the context of Mandarin language instruction. Methodology The research methodology employed for this study involved the use of semi-structured interviews conducted with 15 Mandarin language teachers, who were chosen through theoretical sampling. These interviews were transcribed into text files and subsequently subjected to qualitative data analysis, which was facilitated by the use of MAQDA software. This approach allowed us to identify and categorize the various challenges and problems encountered in the teaching and learning of Mandarin. Findings The research findings revealed a range of challenges and problems experienced in Mandarin language education. These challenges were grouped into two primary thematic categories: psycho-linguistic and educational challenges. The linguistic challenges are deeply rooted in the distinctive features of the Mandarin language, presenting obstacles that necessitate innovative teaching strategies and materials. Educational challenges extend beyond native speaker proficiency, emphasizing the requirement for a comprehensive pedagogical skill set among instructors. Implications : The implications of this research extend to various stakeholders in the field of Chinese/Mandarin language education, including policymakers, educators, curriculum designers, and learners. Understanding the linguistic, educational, and psychological challenges can inform the development of more effective teaching methods, curriculum design, and motivation-enhancing strategies, ultimately promoting a more successful and engaging Mandarin language learning experience for non-native speakers.

Abstract Background GeneXpert MTB/RIF (Xpert) assay was applied widely to detect Mycobacterium tuberculosis (MTB) and rifampicin resistance. Methods Retrospectively investigated the association among treatment histories, phenotypic drug susceptibility testing (pDST) results, and clinical outcomes of patients infected with probe A absent mutation isolate confirmed by Xpert. Results 63 patients with only probe A absent mutation and 40 with additional pDST results were analyzed. 24 (60.0%) patients had molecular-phenotypic discordant rifampicin (RIF) susceptibility testing results, including 12 (12/13, 92.3%) new tuberculosis (TB) patients and 12 (12/27, 44.4%) retreated ones. 28 (28/39, 71.8%) retreated patients received first-line treatment regime within two years with failed outcomes. New patients had better treatment outcomes than retreated ones (successful: 83.3% VS. 53.8%; P value = 0.02). The clinical results of RIF-susceptible TB confirmed by pDST were not better than RIF-resistant TB (successful: 62.5% VS. 50.0%; P value = 0.43). INH-resistant TB and INH-susceptible TB had similar treatment outcomes too (successful: 61.5% VS. 50.0%; P value = 0.48). 11 (11/12, 91.7%) new patients treated with the short treatment regimen (STR) had successful outcomes. Conclusions More than half of mono probe A absent isolates had RIF molecular-phenotypic discordance results, especially in new patients. Probe A mutations were significantly associated with unsuccessful clinical outcomes, whether the pDST results were RIF susceptible or not. STR was the best choice for new patients. Trial registration retrospectively registered in Wuhan Jinyintan Hospital (No. 2021-KY-16).

Abstract To properly repair and maintain implants, which are bone tissue implants that replace natural tooth roots, it is crucial to accurately identify their brand and specification. Deep learning has demonstrated outstanding capabilities in analysis, such as image identification and classification, by learning the inherent rules and degrees of representation of data models. The purpose of this study is to evaluate deep learning algorithms and their supporting application software for their ability to recognize and categorize three dimensional (3D) Cone Beam Computed Tomography (CBCT) images of dental implants. By using CBCT technology, the 3D imaging data of 27 implants of various sizes and brands were obtained. Following manual processing, the data were transformed into a data set that had 13,500 two-dimensional data. Nine deep learning algorithms including GoogleNet, InceptionResNetV2, InceptionV3, ResNet50, ResNet50V2, ResNet101, ResNet101V2, ResNet152 and ResNet152V2 were used to perform the data. Accuracy rates, confusion matrix, ROC curve, AUC, number of model parameters and training times were used to assess the efficacy of these algorithms. These 9 deep learning algorithms achieved training accuracy rates of 100%, 99.3%, 89.3%, 99.2%, 99.1%, 99.5%, 99.4%, 99.5%, 98.9%, test accuracy rates of 98.3%, 97.5%, 94.8%, 85.4%, 92.5%, 80.7%, 93.6%, 93.2%, 99.3%, area under the curve (AUC) values of 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00, 1.00. When used to identify implants, all nine algorithms perform satisfactorily, with ResNet152V2 achieving the highest test accuracy, classification accuracy, confusion matrix area under the curve, and receiver operating characteristic curve area under the curve area. The results showed that the ResNet152V2 has the best classification effect on identifying implants. The artificial intelligence identification system and application software based on this algorithm can efficiently and accurately identify the brands and specifications of 27 classified implants through processed 3D CBCT images in vitro, with high stability and low recognition cost.

Curdlan is a natural exopolysaccharide produced by microorganisms without branching structure which is composed of glucose linked with β-1,3 glycosidic bonds, and used as a stabilizer, thickener in the food industry. Curdlan exhibits excellent functional properties such as gelling ability, anti-digestion and immunomodulatory effects, but the water-insoluble property of curdlan greatly limits its wide applications. Modification of curdlan can enhance its functional properties, especially the water-soluble ability of curdlan, which will expand its development and utilization in food area. In this review, the effects of modification methods on the functional properties of curdlan are discussed from three aspects: Physical modification, chemical modification and enzymatic modification. Moreover, this review highlights the recent research trends in curdlan applications in the food industry in recent years from four perspectives: Food packing materials, improving food texture, developing bionic food and functional food carrier. Overall, curdlan has great potential to be used in food industries. This review provides a reasonable reference for the further development and application of curdlan.

Abstract Although the closed pore structure plays a key role in contributing low-voltage plateau capacity of hard carbon anode for sodium-ion batteries, the formation mechanism of closed pores is still under debate. Here, we employ waste wood-derived hard carbon as a template to systematically establish the formation mechanisms of closed pores and their effect on sodium storage performance. We find that the high crystallinity cellulose in nature wood decomposes to long-range carbon layers as the wall of closed pore, and the amorphous component can hinder the graphitization of carbon layer and induce the crispation of long-range carbon layers. The optimized sample demonstrates a high reversible capacity of 430 mAh g−1 at 20 mA g−1 (plateau capacity of 293 mAh g−1 for the second cycle), as well as good rate and stable cycling performances (85.4% after 400 cycles at 500 mA g−1). Deep insights into the closed pore formation will greatly forward the rational design of hard carbon anode with high capacity.

Background Mutations in the mitochondrial transfer RNA (mt-tRNA) gene are a hotspot for mitochondrial DNA (mtDNA) mutations and are most common in mitochondrial diseases.

This paper introduces a new high-sensitivity curvature fiber sensor based on a miniature two-path Mach–Zehnder interferometer (MTP-MZI). The sensor is fabricated by coupling and fusing the multimode fiber (MMF) with the single-mode fiber (SMF) using arc fusion technology (AFT), resulting in a centimeter-level two-path MZI structure. The sensor represents an innovative approach to MZI coupling technology, which reduces device size, simplifies manufacturing, and lowers costs. In curvature-sensing experiments, the MTP-MZI sensor achieves a maximum curvature sensitivity of −96.70 dB/m−1 in the curvature range of 0.0418 m−1 to 0.0888 m−1, which is an extremely high sensitivity among intensity-modulated curvature sensors. Additionally, temperature-sensing measurements of the MTP-MZI sensor show a maximum temperature sensitivity of 212 pm/°C in the range of 30 °C to 70 °C, which is low temperature sensitivity and solves the cross-sensitivity problem. Thanks to the miniature two-path structure of the MTP-MZI, it provides a new perspective for developing multidimensional and multiparameter measurement methods in MZI fiber sensors.

The dynamic characteristics of single DNA molecules translocating within micro/nano-channels are fundamental for a wide range of applications such as stretching, separating, mapping, and even sequencing of DNA molecules. In this study, a type of tapered microchannel chip with uniform height for all configurations was fabricated, with the major tapered structure having a length of 13 μm and a width that tapers from 5 μm to 20 μm. The dynamic characteristics such as the trajectories and velocities of λ-DNA molecules translocating from different positions driven by an external DC electric field force were systematically investigated by single-molecule fluorescence imaging technology. Some dynamic characteristics of DNA molecules translocation were found. Considering simply the effects of electrophoretic force and electro-osmotic force on the DNA molecules, the dynamic characteristics of DNA molecules are well understood. For example, the velocity of the DNA molecule is inversely proportional to the diameter of the tapered channel and the turning phenomena of the trajectory of the DNA molecules translocating through microchannels. This study is helpful and proposes new ideas for the design and development of microfluidic chips for the quantitative manipulation of DNA molecules.

Abstract Background Climate affects the thermal adaptation and distribution of hosts, and drives the spread of Chytridiomycosis—a keratin-associated infectious disease of amphibians caused by the sister pathogens Batrachochytrium dendrobatidi (Bd) and B. salamandrivorans (Bsal). We focus on their climate-pathogen relationships in Eurasia, the only region where their geographical distributions overlap. Eurasia harbours invaded and native areas of both pathogens and the natural habitats where they co-exist, making it an ideal region to examine their environmental niche correlations. Our understanding of how climate change will affect their distribution is broadened by the differences in climate correlates and niche characteristics between Bd and Bsal in Asia and Europe. This knowledge has potential conservation implications, informing future spread of the disease in different regions. Results We quantified the environmental niche overlap between Bd and Bsal in Eurasia using niche analyses. Results revealed partial overlap in the niche with a unique 4% of non-overlapping values for Bsal, suggesting segregation along certain climate axes. Bd tolerates higher temperature fluctuations, while Bsal requires more stable, lower temperature and wetter conditions. Projections of their Realized Climatic Niches (RCNs) to future conditions show a larger expansion of suitable ranges (SRs) for Bd compared to Bsal in both Asia and Europe, with their centroids shifting in different directions. Notably, both pathogens' highly suitable areas in Asia are expected to shrink significantly, especially under the extreme climate scenarios. In Europe, they are expected to expand significantly. Conclusions Climate change will impact or increase disease risk to amphibian hosts, particularly in Europe. Given the shared niche space of the two pathogens across available climate gradients, as has already been witnessed in Eurasia with an increased range expansion and niche overlap due to climate change, we expect that regions where Bsal is currently absent but salamanders are present, and where Bd is already prevalent, may be conducive for the spread of Bsal.

Abstract Bioinsecticides and transgenic crops based on the bacterial pathogen Bacillus thuringiensis (Bt) can effectively control diverse agricultural insect pests, nevertheless, the evolution of resistance without obvious fitness costs has seriously eroded the sustainable use of these Bt products. Recently, it has been discovered that an increased titer of juvenile hormone (JH) favors an insect host (Plutella xylostella) to enhance fitness whilst resisting the Bt pathogen, however, the underlying regulatory mechanisms of the increased JH titer are obscure. Here, the involvement of N6‐methyladenosine (m6A) RNA modification in modulating the availability of JH in this process is defined. Specifically, it is found that two m6A methyltransferase subunit genes, PxMettl3 and PxMettl14, repress the expression of a key JH‐degrading enzyme JH esterase (JHE) to induce an increased JH titer, mitigating the fitness costs associated with a robust defense against the Bt pathogen. This study identifies an as‐yet uncharacterized m6A‐mediated epigenetic regulator of insect hormones for maintaining fitness during pathogen defense and unveils an emerging Bt resistance‐related m6A methylation atlas in insects, which further expands the functional landscape of m6A modification and showcases the pivotal role of epigenetic regulation in host‐pathogen interactions.

KCNH5 gene encodes for the voltage-gated potassium channel protein Kv10.2. Here, we investigated the clinical features of developmental and epileptic encephalopathy (DEE) in five Chinese pediatric patients with a missense mutation (p.R327H) in KCNH5 gene. These patients had undergone video EEG to evaluate background features and epileptiform activity, as well as 3.0 T MRI scans for structural analysis and intelligence assessments using the Gesell Developmental Observation or Wechsler Intelligence Scale for Children. Seizure onset occurs between 4 and 10 months of age, with focal and generalized tonic-clonic seizures being common. Initial EEG findings showed multiple multifocal sharp waves, sharp slow waves or spike slow waves, and spike waves. Brain MRI revealed widened extracerebral space in only one patient. Mechanistically, the KCNH5 mutation disrupts the two hydrogen bonds between Arg327 and Asp304 residues, potentially altering the protein’s structural stability and function. Almost 80 % of patients receiving add-on valproic acid (VPA) therapy experienced a reduction in epileptic seizure frequency. Altogether, this study presents the first Chinese cohort of pediatric DEE patients with the KCNH5 p.R327H mutation, highlighting focal seizures as the predominant seizure type and incomplete mutation penetrance. Add-on VPA therapy was likely effective in the early stages of DEE pathogenesis.

Smart cities improve services for businesses, among many other benefits. A comprehensive understanding and effective utilization of these advantages is crucial for promoting business development. Using panel data from Chinese listed companies (2010-2020), this study employs a multi-stage DiD model to investigate the impact of smart cities on corporate earnings management. The findings indicate that the smart city pilot policy has significantly reduced corporate earnings management. Further analysis suggests that smart cities primarily reduce earnings management by improving firms' external information environments. Additionally, the results show that the policy impact of smart cities is more significant in regions with lower regulatory intensity or higher marketization levels, compared to regions with higher regulatory intensity or lower marketization levels. Similarly, firms in less concentrated markets or those more closely related to smart city development tend to experience greater reductions in earnings management due to smart city construction, unlike firms in more concentrated markets or those less involved. Finally, this paper offers several brief suggestions.

Summary: Background: Personal protective equipment (PPE) helps protect healthcare workers (HCWs) from infection and prevents cross-contamination. Knowledge of the contamination dynamics of PPE during the management of COVID-19 patients in a makeshift hospital is limited. Aim: To describe the rate of SARS-CoV-2 contamination in PPE and to assess the change of contamination at different time points. Methods: HCWs were followed up for up to 4 hours with hourly collection of swab samples from PPE surfaces in a makeshift COVID-19 hospital setting. Swabs were tested using quantitative reverse transcription polymerase chain reaction (RT-qPCR) for SARS-CoV-2 RNA. Results: SARS-CoV-2 was detected on 50.9% of the 1620 swabbed samples from 9 different sites of full-body PPE worn by HCWs. The proportion of sites contaminated with SARS-CoV-2 RNA varied from 10.6% to 95.6%. Viral RNA was most frequently detected from the sole of the outer foot cover (95.6%) and least frequently on the face shield (10.6%). The median Ct values among positive samples were 34.20 (IQR, 32.61–35.22) and 34.05 (IQR, 32.20–35.39) for ORF1ab and N genes, respectively. The highest rate of contamination with SARS-CoV-2 RNA for the PPE swab samples was found after 3 hours of use. The positive rate of outer surface of HEPA filters from air supply device was 82.1% during the full capacity period of the makeshift hospital. Conclusion: A higher rate of contamination was identified at 3 hours after the entrance to the COVID-19 patient care area. Virus-containing aerosols were trapped in the HEPA filter of air supply equipment, representing a potential protective factor against infection to HCWs.

A novel pretreatment strategy utilizing a combination of NaOH and 1-Butyl-3-methylimidazolium chloride ([Bmim]Cl) was proposed to enhance the enzymatic hydrolysis of abandoned Medium-density fiberboard (MDF). The synergistic effect of NaOH and [Bmim]Cl pretreatment significantly improved the glucose yield, reaching 445.8 mg/g within 72 h, which was 5.04 times higher than that of the untreated samples. The working mechanism was elucidated according to chemical composition, as well as FTIR, 13C NMR, XRD, and SEM analyses. The combined effects of NaOH and [Bmim]Cl led to lignin degradation, hemicellulose removal, the destruction and erosion of crystalline regions, pores, and an irregular microscopic morphology. In addition, by comparing the enzymatic hydrolysis sugar yield and elemental nitrogen content of untreated MDF samples, eucalyptus, and hot mill fibers (HMF), it was demonstrated that the presence of adhesives and additives in waste MDF significantly influences its hydrolysis process. The sugar yield of untreated MDF samples (88.5 mg/g) was compared with those subjected to hydrothermal pretreatment (183.2 mg/g), Ionic liquid (IL) pretreatment (406.1 mg/g), and microwave-assisted ionic liquid pretreatment (MWI) (281.3 mg/g). A long water bath pretreatment can reduce the effect of adhesives and additives on the enzymatic hydrolysis of waste MDF. The sugar yield produced by the combined pretreatment proposed in this study and the removal ability of adhesives and additives highlight the great potential of our pretreatment technology in the recycling of waste fiberboard.

Combinatorial drug therapy has emerged as a critically important strategy in medical research and patient treatment and involves the use of multiple drugs in concert to achieve a synergistic effect. This approach can enhance therapeutic efficacy while simultaneously mitigating adverse side effects. However, the process of identifying optimal drug combinations, including their compositions and dosages, is often a complex, costly, and time-intensive endeavor. To surmount these hurdles, we propose a novel microfluidic device capable of simultaneously generating multiple drug concentration gradients across an interlinked array of culture chambers. This innovative setup allows for the real-time monitoring of live cell responses. With minimal effort, researchers can now explore the concentration-dependent effects of single-agent and combination drug therapies. Taking neural stem cells (NSCs) as a case study, we examined the impacts of various growth factors—epithelial growth factor (EGF), platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF)—on the differentiation of NSCs. Our findings indicate that an overdose of any single growth factor leads to an upsurge in the proportion of differentiated NSCs. Interestingly, the regulatory effects of these growth factors can be modulated by the introduction of additional growth factors, whether singly or in combination. Notably, a reduced concentration of these additional factors resulted in a decreased number of differentiated NSCs. Our results affirm that the successful application of this microfluidic device for the generation of multi-drug concentration gradients has substantial potential to revolutionize drug combination screening. This advancement promises to streamline the process and accelerate the discovery of effective therapeutic drug combinations.

The deployment of Li–S batteries in the commercial sector faces obstacles due to their low electrical conductivity, slow redox reactions, quick fading of capacity, and reduced coulombic efficiency. These issues stem from the “shuttle effect” associated with lithium polysulfides (LiPSs). In this work, a haystack-like CeO2 derived from a cerium-based metal-organic framework (Ce-MOF) is obtained for the modification of a polypropylene separator. The carbon framework and CeO2 coexist in this haystack-like structure and contribute to a synergistic effect on the restriction of LiPSs shuttling. The carbon network enhances electron transfer in the conversion of LiPSs, improving the rate performance of the battery. Moreover, CeO2 enhances the redox kinetics of LiPSs, effectively reducing the “shuttle effect” in Li–S batteries. The Li–S battery with the optimized CeO2 modified separator shows an initial discharge capacity of 870.7 mAh/g at 2 C, maintaining excellent capacity over 500 cycles. This research offers insights into designing functional separators to mitigate the “shuttle effect” in Li–S batteries.

Revealing the interaction mechanisms between anticancer drugs and target DNA molecules at the single-molecule level is a hot research topic in the interdisciplinary fields of biophysical chemistry and pharmaceutical engineering. When fluorescence imaging technology is employed to carry out this kind of research, a knotty problem due to fluorescent dye molecules and drug molecules acting on a DNA molecule simultaneously is encountered. In this paper, based on self-made novel solid active substrates NpAA/(ZnO-ZnCl2)/AuNPs, we use a surface-enhanced Raman spectroscopy method, inverted fluorescence microscope technology, and a molecular docking method to investigate the action of the fluorescent dye YOYO-1 and the drug DOX on calf thymus DNA (ctDNA) molecules and the influencing effects and competitive relationships of YOYO-1 on the binding properties of the ctDNA-DOX complex. The interaction sites and modes of action between the YOYO-1 and the ctDNA-DOX complex are systematically examined, and the DOX with the ctDNA-YOYO-1 are compared, and the impact of YOYO-1 on the stability of the ctDNA-DOX complex and the competitive mechanism between DOX and YOYO-1 acting with DNA molecules are elucidated. This study has helpful experimental guidance and a theoretical foundation to expound the mechanism of interaction between drugs and biomolecules at the single-molecule level.

Background Although computed tomography (CT)-defined emphysema is considered a predictor of lung cancer risk, it is not fully clear whether CT-defined emphysema is associated with the prognosis of lung cancer. We aimed to assess the clinical impact of CT-defined emphysema on the survival of lung cancer. Methods In the prospective cohort study of nonsmall cell lung cancer (NSCLC), the correlation between CT-defined emphysema and clinical variables was analysed. A multivariable Cox regression model was built to assess the association between CT-defined emphysema and overall survival (OS) for up to 8.8 years. The differences in survival analyses were derived by Kaplan–Meier analysis and log-rank testing. Low attenuation area (LAA%) was defined as the per cent of voxels below −950 HU. Results 854 patients were included and CT-defined emphysema was present in 300 (35.1%) at diagnosis. Epidermal growth factor receptor (EGFR) wild-type (OR 1.998; p17% displayed poorer survival than those with LAA% ≤17% (median 432 versus 670 days; HR 1.564; p=0.020). Conclusions CT-defined emphysema, especially CLE with LAA%>17%, is an independent predictor of NSCLC prognosis. Moreover, prospective studies are needed to further explore this association.

IntroductionRanavirus disease, caused by viruses within the genus Ranavirus (Iridoviridae), is considered a globally emerging infectious disease linked to mass mortality events in both wild and cultured ectothermic vertebrates. Surveillance work is, however, limited in Asia hence prevalence and the dynamics of the disease remain poorly understood. To understand disease burden and the potential biotic and abiotic drivers in southern China region, we conducted a systematic surveillance of the ranavirus across Guangxi Zhuang Autonomous region (GAR).MethodsFor this, we used a multifaceted approach involving screening of amphibians and other potential hosts, diagnostic tests, phylogenetic analyses, prevalence estimation, co-infection assessments, and climatic niche analyses. Over one thousand individuals were sampled across 25 sampling sites.ResultsWe found ninety-two individuals from 18 species of ectothermic vertebrates to be infected with ranavirus. Two lineages were responsible – Rana nigromaculata ranavirus and tiger frog virus were identified using phylogenetic analysis based on the major capsid protein (MCP) gene fragment. Out of these two lineages, the presence of tiger frog virus is rare as we came across only one case. We also found evidence of a co-infection with ranavirus and Batrachochytrium dendrobatidis that can be highly detrimental to host populations; possibly the first such documentation in Asia. Our niche modelling analysis suggests that precipitation seasonality plays an important role in ranavirus prevalence in GAR – southwestern, southeastern, central and northeastern regions of GAR can be considered to be optimum habitats for ranaviruses. Infection rates in wild frog species have reached 100% in some areas, even in nature reserves.DiscussionOur research also indicates that culture facilities and pet markets are frequently infected, serving as likely vectors for the regional and global spread of ranaviruses. The knowledge generated suggests the need for systematic surveillance, stringent biosecurity measures, and control of international animal trade to prevent further transmission and protection of biodiversity and aquaculture industries across Asia.

Climate warming has increased the frequency of droughts and excessive precipitation, adversely affecting crop growth, particularly under traditional intensive tillage. No-till improves crop tolerance to extreme events by reducing soil evaporation and improving soil structural stability to enhance soil water storage capacity and crop resistance, but long-term mono-no-till cakes the soil, reducing crop yield. Combining intensive tillage with no-till can compensate for some deficiencies arising from conventional tillage or single no-till. A three-year field experiment was conducted in wet (2020) and normal (2019 and 2021, where a drought event occurred in 2021) years to study the effect of tillage practices on summer maize productivity under different precipitation types. Treatments included conventional tillage (CT), no-tillage (NT), ridge cultivation with no-tillage (RNT), and conventional tillage of winter wheat combined with no-tillage of summer maize (NC). Compared with NT, NC and RNT significantly reduced soil bulk density and increased soil porosity in the 0–20 cm soil layer. Compared with CT, NC and RNT significantly improved aggregate stability, NC increased available soil water storage by 19.7% in the dry season (P

IntroductionNeuronal surface antibody syndromes (NSAS) encompass a growing set of autoimmune neurological disorders, with their predominant clinical presentation being autoimmune encephalitis (AE). The most extensively documented form within NSAS is anti-N-methyl-D-aspartate receptor (NMDAR) autoimmunity. In contrast, other NSAS, such as anti-metabotropic glutamate receptor-5 (mGluR5) autoimmunity, are less common and less comprehensively characterized, particularly in pediatric cases.Case descriptionIn this instance, we present the case of a 7-year-old girl who exhibited abnormal behaviors following hematopoietic stem cell transplantation (HSCT). She received a diagnosis of anti-mGluR5 AE, and her Electroencephalogram (EEG) displayed an increased number of generalized slow waves during wakefulness. Treatment involved intravenous administration of gamma globulin and methylprednisolone, followed by oral prednisone tablets. Levetiracetam was introduced as an antiepileptic therapy during the pulse steroid therapy. Notably, the abnormal behaviors exhibited significant improvement after treatment.ConclusionsTo the best of our knowledge, this is the first report of rare pediatric NSAS involving anti-mGluR5 AE following HSCT. Enhancing our understanding and characterization of this condition may facilitate its recognition and treatment in children. Serum antibody testing could enable early identification and treatment of anti-mGluR5 AE.

Objective: To investigate the details of environmental contamination status by SARS-CoV-2 in a makeshift COVID-19 hospital.Methods: Environmental samples were collected from a makeshift hospital. The extent of contamination was assessed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) for SARS-CoV-2 RNA from various samples.Results: There was a wide range of total collected samples contaminated with SARS-CoV-2 RNA, ranging from 8.47% to 100%. Results revealed that 70.00% of sewage from the bathroom and 48.19% of air samples were positive. The highest rate of contamination was found from the no-touch surfaces (73.07%) and the lowest from frequently touched surfaces (33.40%). The most contaminated objects were the top surfaces of patient cubic partitions (100%). The median Ct values among strongly positive samples were 33.38 (IQR, 31.69–35.07) and 33.24 (IQR, 31.33–34.34) for ORF1ab and N genes, respectively. SARS-CoV-2 relic RNA can be detected on indoor surfaces for up to 20 days.Conclusion: The findings show a higher prevalence and persistence in detecting the presence of SARS-CoV-2 in the makeshift COVID-19 hospital setting. The contamination mode of droplet deposition may be more common than contaminated touches.

In this study, a novel artificial intervertebral disc implant with modified “Bucklicrystal” structure was designed and 3D printed using thermoplastic polyurethane. The new implant has a unique auxetic structure with building blocks joined “face-to-face”. The accompanied negative Poisson’s ratio enables its excellent energy absorption and stability under compression. The deformation and load distribution behavior of the implant under various loading conditions (bending, torsion, extension and flexion) has been thoroughly evaluated through finite element method. Results show that, compared to natural intervertebral disc and conventional 3D implant, our new implant exhibits more effective stress transfer and attenuation under practical loading conditions. The implant's ability to contract laterally under compression can be potentially used to alleviate the symptoms of lumbar disc herniation. Finally, the biocompatibility of the implant was assessed in vitro and its ability to restore the physiological function of the disc segment was validated in vivo using an animal model.