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Abstract Background Displaced tibial tubercle (TT) fractures in adolescents are typically treated with open reduction and internal fixation. While metallic screw (MS) fixation provides strong stability, it often results in a high incidence of postoperative screw head protrusion or irritation, leading to additional removal surgery. Bioabsorbable screw (BS) fixation presents an alternative that may avoid these issues, though its stability has not yet been extensively documented in the literature. This study aims to compare the efficacy of BS versus MS in the fixation of TT fractures. Methods A retrospective analysis was conducted on adolescent patients with TT fractures who underwent surgical treatment from September 2015 to September 2023. Patients were divided into two groups based on the fixation method: The BS group and the MS group. Data collected included patient demographics, fracture details, treatment strategies, radiological and clinical rehabilitation outcomes, and postoperative complications. Knee joint function was evaluated using the Lysholm and Tegner scores. Statistical analysis was performed to identify differences between the variables of the two groups. Results A total of 30 patients with 32 fractures were included, with 15 fractures in the BS group and 17 in the MS group. The average follow-up period was 42.1 (range: 12.0-109.5) months. The demographic characteristics, fracture details, and treatment strategies were comparable between the two groups. No significant differences were observed between the groups in fracture healing time, time to return to pre-injury activities, or knee joint function as assessed by the Lysholm and Tegner scores at the final follow-up. However, compared with the MS group, the BS group showed a shorter time to regain full range of motion (ROM) in the knee joint and experienced lower rates of postoperative hardware irritation and joint stiffness. Conclusions Both BS and MS fixations are safe and effective for treating adolescent TT fractures. BS fixation has the advantages of avoiding hardware irritation, facilitating earlier recovery of knee joint ROM, reducing the incidence of joint stiffness, and eliminating the need for additional removal surgery. Clinical trial number Not applicable.

Abstract PbI6 octahedron as a fundamental framework endows the perovskite with excellent photoelectric properties, but also the defective and flimsy surface. Here, we report that the treatment of perovskite surface by bidentate ligands molecules N, N’-Dimethyl-1,2-ethanediamine can in-situ form a lead iodide chelates layer with excellently robust chelated lead octahedron, leading to effectively stabilize and passivate the underlying perovskite. The strong chelation with the lead enables the surface to largely inhibit the defects generation, iodide ion migration and skeleton collapse under external stimuli. It also prolongs the carrier lifetime and adjusts the surface energy-level of perovskite. The resultant perovskite solar cells deliver a power conversion efficiency of 25.7% (certified 25.04%) and retain >90% of their initial value after almost 1000 hours aging at maximum power point under simulated AM1.5 illumination.

Healthy lifestyles and good living habits are effective strategies and important approaches to prevent chronic non-communicable diseases. With the development of evidence-based medicine, the evidence translation system has made some achievements in clinical practice. There is, however, no comprehensive, professional and efficient system for translating lifestyle evidence globally. Therefore, the Health Lifestyle Evidence (HLSE) Group of Lanzhou University constructed the HLSE Evidence Translation System (https://hlse.cn/), with the aim of synthesizing, evaluating, translating, and applying lifestyle-related evidence resources. This paper aims to introduce the functional module design of the evidence translation system, the system development process and testing, introduce the interface design and function demonstration, and explain the significance of constructing the HLSE.

Abstract Inflammation is a key pathological feature of many diseases, disrupting normal tissue structure and resulting in irreversible damage. Despite the need for effective inflammation control, current treatments, including stem cell therapies, remain insufficient. Recently, extracellular vesicles secreted by adipose-derived stem cells (ADSC-EVs) have garnered attention for their significant anti-inflammatory properties. As carriers of bioactive substances, these vesicles have demonstrated potent capabilities in modulating inflammation and promoting tissue repair in conditions such as rheumatoid arthritis, osteoarthritis, diabetes, cardiovascular diseases, stroke, and wound healing. Consequently, ADSC-EVs are emerging as promising alternatives to conventional ADSC-based therapies, offering advantages such as reduced risk of immune rejection, enhanced stability, and ease of storage and handling. However, the specific mechanisms by which ADSC-EVs regulate inflammation under pathological conditions are not fully understood. This review discusses the role of ADSC-EVs in inflammation control, their impact on disease prognosis, and their potential to promote tissue repair. Additionally, it provides insights into future clinical research focused on ADSC-EV therapies for inflammatory diseases, which overcome some limitations associated with cell-based therapies.

Abstract The present study aims to investigate the current trends in replacing conventional preservatives with multifunctional ingredients with antimicrobial properties for preservation of cosmetics for infants or sensitive population, to decrease their potential for contact dermatitis. We first reviewed the labels of cosmetics purchased from the Chinese market for conventional preservatives and multifunctional ingredients with antimicrobial properties, of which the actual contents were further quantified by chromatographic methods. We identified 7 traditional preservatives (phenoxyethanol, benzoic acid (salts), methylparaben, benzyl alcohol, sorbic acid (salts), propylparaben, and methylisothiazolinone), and 11 alternative ingredients with antimicrobial activities (ethylhexylglycerin, butylene glycol, caprylyl glycol, propylene glycol, 1,2-hexanediol, p-anisic acid, hydroxyacetophenone, pentylene glycol, decylene glycol, caprylhydroxamic acid, and aminomethyl propanol) in descending order of prevalence. The contents of all identified preservatives and ingredients were either below regulatory limits or in the range that is generally regarded to be safe. Further challenge with microorganisms indicated irrespective of the composition of preservation systems, product preservation could be compromised under test conditions. We conclude that multifunctional ingredients with antimicrobial properties in cosmetics have the potential to completely replace or significantly reduce the use of traditional preservatives while retaining comparative preservative efficacy. Future attentions may need to be shifted to the safety of those multifunctional ingredients with antimicrobial properties.

Phenols, parabens, and phthalates are commonly found in consumer products, yet there is limited research on their individual and combined effects on depressive symptoms, particularly regarding the role of inflammation in these associations. This study aimed to evaluate these effects and explore potential molecular mechanisms, with a focus on inflammation as a mediator. We conducted a cross-sectional analysis involving 2766 adult participants from the National Health and Nutrition Examination Survey (NHANES) 2013–2016. Urine samples were analyzed for 15 chemicals, including 3 phenols, 2 parabens, and 10 phthalates. Depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9). Statistical analyses included linear regression, restricted cubic splines, Bayesian Kernel Machine Regression and quantile g-computation models to investigate the relationships between chemical exposures and depressive symptoms. Additionally, mediation analysis was employed to explore the potential role of inflammation (immune cells, CRP, NLR) in these associations. The underlying molecular mechanisms were analyzed using bioinformatic approaches. Notably, BPA, MECPP, MEHHP, MiBP and MBP were found to be positively associated with depressive symptoms among females. Besides, BPA was the most significant positive contributor to the effect in the context of the chemical mixture, while the overall mixture effect was relatively weak. Furthermore, WBC were found to mediate a marginal portion (4 %) of the potential effects of MBP on depressive symptoms. The 15 genes identified are primarily involved in neurotransmission, mood regulation, and stress response. Further research is needed to elucidate the mechanisms underlying the observed associations.

Background: Ulcerative colitis (UC) is an increasing incidence of inflammatory disorder in the colon mucosa. One of the current research focuses is the alteration of metabolic networks in UC. One of the important aspects of this metabolic shift is the expression of purine metabolism genes (PMGs) vital for nucleic acid synthesis. Nevertheless, the precise function of PMGs in the pathophysiology of UC is not yet fully known. Methods: To this end, this study used state-of-the-art bioinformatics tools and approaches to discover and confirm the PMGs involved in UC. All the 114 candidate PMGs were compared for their expression levels. GSEA and GSVA were applied to define the functional and pathway implications of these PMGs. Lasso regression and SVM-RFE approaches were used for the identification of hub genes and to assess the diagnostic potential of eight PMGs in UC classification. The relationship between these critical PMGs and clinical features was also systematically evaluated as well. The expression levels of these eight PMGs were validated using datasets GSE206285 and GSE179285. Results: Using bioinformatics and machine learning, this work seeks to establish the involvement of PMGs in UC. From the LASSO and SVM models, 114 DE PMGs were selected and investigated to build a stable predictive model. Based on these studies, the following genes: IMPDH1, GUK1, POLE3, ADCY3, ADCY4, PDE6B, PNPT1 and PDE4D were suggested as potential biomarkers of UC. Gene ontology enrichment analysis revealed that these genes are implicated in the biological processes of particular relevance to immune and inflammatory responses. The study also provided a lot of information on the interaction between immune cells and PMGs indicating that these genes may control some immune-related pathways in UC. Moreover, drug-gene interaction analysis presents potential therapeutic opportunities for potential drug targets which were further confirmed through molecular docking. Mendelian randomization analysis revealed that ADCY4 and PDAZN are involved in PMG-related processes, thus opening new possibilities for treatment. Conclusions: This work reveals eight PMGs closely related to UC and provides new perspectives on possible markers of this inflammatory disease. These findings not only increase the understanding of the pathogenesis of UC but also offer potential for improving the surveillance of disease and its progression.

Abstract Although molecular vibronic spectra generation is pivotal for chemical analysis, tackling such exponentially complex tasks on classical computers remains inefficient. Quantum simulation, though theoretically promising, faces technological challenges in experimentally extracting vibronic spectra for molecules with multiple modes. Here, we propose a nontrivial algorithm to generate the vibronic spectra using states with zero displacements (squeezed vacuum states) coupled to a linear optical network, offering ease of experimental implementation. We also fabricate an integrated quantum photonic microprocessor chip as a versatile simulation platform containing 16 modes of single-mode squeezed vacuum states and a fully programmable interferometer network. Molecular vibronic spectra of formic acid and thymine under the Condon approximation are simulated using the quantum microprocessor chip with high reconstructed fidelity ( > 92%). Furthermore, vibronic spectra of naphthalene, phenanthrene, and benzene under the non-Condon approximation are also experimentally simulated. Such demonstrations could pave the way for solving complicated quantum chemistry problems involving vibronic spectra and computational tasks beyond the reach of classical computers.

Abstract The robust operation of quantum entanglement states is crucial for applications in quantum information, computing, and communications1–3. However, it has always been a great challenge to complete such a task because of decoherence and disorder. Here, we propose theoretically and demonstrate experimentally an effective scheme to realize robust operation of quantum entanglement states by designing quadruple degeneracy exceptional points. By encircling the exceptional points on two overlapping Riemann energy surfaces, we have realized a chiral switch for entangled states with high fidelity. Owing to the topological protection conferred by the Riemann surface structure, this switching of chirality exhibits strong robustness against perturbations in the encircling path. Furthermore, we have experimentally validated such a scheme on a quantum walk platform. Our work opens up a new way for the application of non-Hermitian physics in the field of quantum information.

The fabrication of high quality copper alloys using laser powder bed fusion (LPBF) technology remains challenging due to their low laser absorption and high thermal conductivity. LPBF often involves intrinsic defects, such as rough surface and internal pores, which largely deteriorate the performance of as-built copper alloy components. Here we studied the effect of scanning speed on the evolution of surface morphologies and internal pores of LPBF-fabricated CuSn10 alloy. The melt flow behaviors were studied by both experiments and in situ observations where combined a high-speed camera with an infrared thermal imager. With increasing the scanning speed, the morphology of melt track evolves from a continuous track to a discontinuous one, whereas the internal defects change from a great number of spherical pores to many irregular pores. A higher scanning speed decreases the peak temperature of the melt pool and causes less overlaps between neighboring melt tracks, thus deteriorating wetting behaviors. It is expected that the obtained results are beneficial for guiding the additive manufacturing of copper alloy parts with high metallurgical quality and thus promoting their industrial applications.

We report a new land snail species representing a new genus from the mountainous area of Zhejiang, China. The snail has a depressed shell with granules all over the surface. The soft part of the new taxon is characterized by the presence of a mantle lobe whose form is reviewed herein across a wide range of helicoid snails, the presence of a developed epiphallic papilla, and the absence of a penial sheath, a dart sac apparatus and a flagellum. As indicated by a molecular-based phylogeny (16S + ITS2), the new taxon is deeply nested in the eastern Asian camaenid genera and shows a close relationship with the camaenids distributed in Central China.

Conventional Al–Ti–B and Al–Ti–C refiners fail to refine Al–Si casting alloys with high Si content due to the well-known “Si-poisoning” effect. Developing a novel grain refiner with superior grain refinement efficiency for Al–Si casting alloys is the research focus in recent years. In this work, a superior anti Si-poisoning α-Al grain refiner Al–2La–1B alloy with fine LaB6 particles was successfully fabricated via the aluminum melt reaction method. The microstructural evolution, grain refinement performance and refinement mechanisms of the Al–2La–1B alloy were comprehensively investigated based on the experiment results and first-principles calculations. The currently designed Al–2La–1B refiner presents supreme grain refinement efficiency on Al–Si casting alloys. The average grain size of Al–7Si alloy inoculated with 0.5% Al–2La–1B alloy can be refined to 67 ± 5 μm. The superior grain refinement performance can be attributed to the presence of fine LaB6 particles in the refiner. These particles are highly stable in Al–Si alloy melt and can directly act as the potent nucleation sites for α-Al due to the small lattice misfit and low interfacial energy. Moreover, the nucleation potency of the LaB6 particles will not be influenced by the solute Si element. Our work provides an effective strategy for designing a superior α-Al grain refiner for Al–Si casting alloys.

Telangiectasia macularis multiplex acquisita is an acquired cutaneous telangiectasis of unknown aetiology, and it lacks both effective and cost-efficient treatment. This study aims to identify a novel potential associated factor of the disease and explore feasible therapeutic interventions. In this retrospective case series study, 46 Chinese patients diagnosed with telangiectasia macularis multiplex acquisita between 1 January 2007 and 18 May 2023 were included. The median age of onset was 43 years (23 to 60 years), and the male to female ratio was 10.5:1. Besides previously reported associations including chronic liver disorders, alcohol consumption, and smoking, a potential association was found between use of calcium channel blockers and development of telangiectasia macularis multiplex acquisita. Twenty-two of 27 hypertensive patients took calcium channel blockers, with 17 followed up. Ten out of 17 displayed a range of improvements following the cessation of calcium channel blockers; 1 patient reported no lesion change post-discontinuation of calcium channel blockers; 1 patient continued their medication but showed partial improvement after 2 pulsed dye laser treatments; 1 patient observed lesion colour lightening without altering hypertensive medication or other specific treatments; and another 4 kept their previous hypertensive regimen due to blood pressure stability concerns, with no change in their lesions. The study proposes that cessation of calcium channel blockers can be a novel therapeutic approach for affected individuals.

C-type lectin receptors (CLRs) are essential to execute host defense against fungal infection. Nevertheless, a comprehensive understanding of the molecular underpinnings of CLR signaling remains a work in progress. Here, we searched for yet-to-be-identified tyrosine-phosphorylated proteins in Dectin-1 signaling and linked the stress-response protein valosin containing protein (VCP)/p97 to Dectin-1 signaling. Knockdown of VCP expression or chemical inhibition of VCP's segregase activity dampened Dectin-1-elicited SYK activation in BMDMs and BMDCs, leading to attenuated expression of proinflammatory cytokines/chemokines such as TNF-α, IL-6 and CXCL1. Biochemical analyses demonstrated that VCP and its cofactor UFD1 form a complex with SYK and its phosphatase SHP-1 following Dectin-1 ligation, and knockdown of VCP led to a more prominent SYK and SHP-1 association. Further, SHP-1 became polyubiquitinated upon Dectin-1 activation, and VCP or UFD1 overexpression accelerated SHP-1 degradation. Conceivably, VCP may promote Dectin-1 signaling by pulling the ubiquitinated SHP-1 out of the SYK complex for degradation. Finally, genetic ablation of VCP in the neutrophil and macrophage compartment rendered the mice highly susceptible to infection by Candida albicans, an observation also phenocopied by administering the VCP inhibitor. These results collectively demonstrate that VCP is a previously unappreciated signal transducer of the Dectin-1 pathway and a crucial component of antifungal defense, and suggest a new mechanism regulating SYK activation.

The on-demand design of metamaterials such as lattices and bar structures is typically approached using computational methods due to their inherent complexity. An indispensable element of structural design is a reliable and easy to use FE simulation environment, which in turn not only benefits the design of underlying structures, but also, through easy customization and integration, propels the design of computational methods themselves. In response, this work provides a linear truss and beam FE simulation environment written in MATLAB. The simulation environment supports linear truss elements, Euler-Bernoulli besam elements, and Timoshenko beam elements. It further supports the introduction of self-weight and local truss buckling analysis. A variety of input methods are supported, these are specifically tailored towards simplifying the integration of the FE simulation environment in numerical optimization schemes. With this environment, researchers and design practitioners can easily simulate the mechanical response of complex bar structures without the need for interfacing with commercial FE software through cumbersome Application Programming Interfaces (APIs).

ABSTRACT Background Endoscopic submucosal dissection (ESD) is a widely utilized treatment for early esophageal cancer. However, the rising incidence of postoperative esophageal stricture poses a significant challenge, adversely affecting patients' quality of life and treatment outcomes. Developing precise predictive models is urgently required to enhance treatment outcomes. Materials and Methods This study retrospectively analyzed clinical data from 124 patients with early esophageal cancer who underwent ESD at Ningbo Medical Center Lihuili Hospital. Patients were followed up to assess esophageal stricture incidence. Binary logistic regression analysis was used to identify factors associated with post‐ESD esophageal stricture. A novel nomogram prediction model based on Systemic Immune‐inflammation Index (SII) was constructed and evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA). Results ROC curve analysis showed that the optimal value of SII for predicting esophageal stricture was 312.67. Both univariate and multivariate analyses identified lesion infiltration depth (

ABSTRACTElucidating the mechanisms underlying antifungal resistance in Aspergillus fumigatus, discovering new antifungal targets, and developing drugs to inhibit resistance are the key approaches to treating A. fumigatus infections. Here, we investigated the function of ctf1 (AFUA_1G03800), a gene encoding a C6 transcription factor. Homologous recombination replacement technology was employed to construct ctf1-knockout and revertant strains. Fungal morphological observations revealed that the growth of the knockout strain was slower, showing fewer conidia. The minimum inhibitory concentration of triazoles was determined by performing the E-test and by using the micro-liquid-based dilution method. The results indicated that ctf1 deletion decreased the susceptibility of A. fumigatus to voriconazole by 2-fold. The decreased antifungal sensitivity of Δctf1 can be attributed to the increased ergosterol content and the overexpression of mdr1, mdr2, and mdr4. Thus, our results on the function of ctf1 contribute to the elucidation of the mechanisms underlying A. fumigatus resistance and the factors associated with A. fumigatus virulence.

The high recurrence rate of cervical cancer is a leading cause of cancer deaths in women. 5-Fluorouracil (5-FU) is an antitumor drug used to treat many types of cancer, but its diminishing effectiveness and side effects limit its use. Norcantharidin (NCTD), a demethylated derivative of cantharidin, exhibits various biological activities. Here, we investigated whether NCTD could potentiate 5-FU to induce cervical cancer cell death. To assess the cell viability and synergistic effects of the drugs, cell counting kit-8 and colony formation assays were performed using HR-HPV-positive cervical cancer cell lines. Annexin V-FITC/PI staining and TUNEL assays were performed to confirm the induction of apoptosis. The synergistic effect of NCTD on the antitumor activity of 5-FU was analyzed using network pharmacology, molecular docking, and molecular dynamics simulations. Apoptosis-related proteins were examined using immunoblotting. The combination of NCTD and 5-FU was synergistic in cervical cancer cell lines. Network pharmacological analysis identified 10 common targets of NCTD and 5-FU for cervical cancer treatment. Molecular docking showed the strong binding affinity of both compounds with CA12, CASP9, and PTGS1. Molecular dynamics simulations showed that the complex system of both drugs with caspase-9 could be in a stable state. NCTD enhanced 5-FU-mediated cytotoxicity by activating apoptosis-related proteins. NCTD acts synergistically with 5-FU to inhibit cervical cancer cell proliferation. NCTD enhances 5-FU-induced apoptosis in cervical cancer cell lines via the caspase-dependent pathway.

Abstract Respiratory diseases, marked by structural changes in the airways and lung tissues, can lead to reduced respiratory function and, in severe cases, respiratory failure. The side effects of current treatments, such as hormone therapy, drugs, and radiotherapy, highlight the need for new therapeutic strategies. Traditional Chinese Medicine (TCM) offers a promising alternative, leveraging its ability to target multiple pathways and mechanisms. Active compounds from Chinese herbs and other natural sources exhibit anti-inflammatory, antioxidant, antitumor, and immunomodulatory effects, making them valuable in preventing and treating respiratory conditions. Ferroptosis, a unique form of programmed cell death (PCD) distinct from apoptosis, necrosis, and others, has emerged as a key area of interest. However, comprehensive reviews on how natural products influence ferroptosis in respiratory diseases are lacking. This review will explore the therapeutic potential and mechanisms of natural products from TCM in modulating ferroptosis for respiratory diseases like acute lung injury (ALI), asthma, pulmonary fibrosis (PF), chronic obstructive pulmonary disease (COPD), lung ischemia–reperfusion injury (LIRI), pulmonary hypertension (PH), and lung cancer, aiming to provide new insights for research and clinical application in TCM for respiratory health.

Objective To systematically assess the applicability of the clinical practice guidelines (CPGs) integrating Chinese and western medicine, thereby providing reference for enhancing their future usability. Methods PubMed, Web of Science, Embase, SinoMed, WanFang Data, and CNKI databases were searched for guidelines for the integration of Chinese and western medicine. Supplementary searches of Chinese Medical Association, Chinese Medicine Administration, MedSci websites, Website of China Association of Chinese Medicine, Medlive, Website of Dangdang, Chinese Association of Integrative Medicine and World Federation of Traditional Chinese Medicine Societies were conducted. The search time frame was from inception of the databases to December 31, 2022. Four reviewers independently evaluated the implementability of clinical practice guidelines by using 'Clinical Practice Guideline (CPG) implementation evaluation tool'. Results A total of 61 integrative Chinese and western medicine guidelines were included. Of the guidelines assessed, 9 guidelines(14.75%) exhibited strong implementability, 40(65.57%) demonstrated average implementability, and 12 (19.67%) demonstrated poor implementability. Among the 5 domains, the dimensions of 'accessibility' and 'implementability' were found to be of high quality, while those of 'communication', 'ease of identification' and 'applicability' were relatively poor. Notably, compared to guidelines published between 2006—2016, those published between 2017—2022 showed improvements in the areas of 'identification' and 'application'. Conclusions The implementabilityof the existing clinical practice guidelines of the integrative Chinese and western medicine is average and needs to be improved. In the future, emphasis should be placed on the integration of medical education and research, publicity of the guidelines, continuous medical education and training, a more concise form of recommendations, application of the guidelines by clinicians, and the implementability of the integrative Chinese and western medicine guideline.

Returning corn straw to the field is beneficial for improving soil fertility, but the fermentation phase significantly affects the dissolved organic carbon (DOC) content. However, there is limited research on the effects of straw at different fermentation phases on soil microorganisms and soil nutrients. This study examined the effects of high-temperature fermentation phase straw (HF) and completely fermentation phase straw (CF) on soil nutrient activation and microorganism activity through pot experiments. The pot experiment results indicated a significant increase in soil DOC content following the application of corn straw, among which the high-temperature fermentation phase straw treatment (THF) exhibited the highest DOC content, which was 14% higher than the completely fermentation phase straw treatment (TCF). THF also significantly increased soil alkaline hydrolyzed nitrogen and available phosphorus content as well as urease and phosphatase, and promoted the uptake of nitrogen and phosphorus from soil by Brassica chinensis. THF significantly enhanced bacterial diversity and reduced the presence of pathogenic fungi. Compared to the TCF, the relative proportion of Fusarium under the THF decreased by 32.24%, effectively mitigating the impact of pathogenic fungi. THF also increased soil DOC content, enriched beneficial microbial community structure, increased soil enzyme activity, activated soil nutrients, thereby promoting the uptake of nitrogen and phosphorus by crops. Taken together, the results reveal that the application of high-temperature fermentation phase straw is conducive to soil fertilization and crop growth.

Accurate wind power forecasting is essential for maintaining the stability of a power system and enhancing scheduling efficiency in the power sector. To enhance prediction accuracy, this paper presents a hybrid wind power prediction model that integrates the improved complementary ensemble empirical mode decomposition (ICEEMDAN), the RIME optimization algorithm (RIME), sample entropy (SE), the improved dung beetle optimization (IDBO) algorithm, the bidirectional long short-term memory (BiLSTM) network, and multi-head attention (MHA). In this model, RIME is utilized to improve the parameters of ICEEMDAN, reducing data decomposition complexity and effectively capturing the original data information. The IDBO algorithm is then utilized to improve the hyperparameters of the MHA-BiLSTM model. The proposed RIME-ICEEMDAN-IDBO-MHA-BiLSTM model is contrasted with ten others in ablation experiments to validate its performance. The experimental findings prove that the proposed model achieves MAPE values of 5.2%, 6.3%, 8.3%, and 5.8% across four datasets, confirming its superior predictive performance and higher accuracy.

Urban spatial compactness is crucial for reducing carbon emissions and promoting sustainable urban development. However, the potential of and variations in spatial compactness in county-level carbon reduction have been largely overlooked. Taking the county-level areas in the Beijing–Tianjin–Hebei (BTH) region as an example, after reviewing the dimensions, scales, and pathways of the existing research, we quantifies the spatial compactness from 2005 to 2015 in terms of density, morphology, and function. The results reveal that, firstly, BTH county-level areas’ carbon emissions, both per land area (CO2/L) and per capita (CO2/P), have generally risen. Heterogeneity varied across spatial compactness indicators: urban density and functional compactness increased, while morphological compactness showed a minor fluctuation. Second, the correlations with CO2/L were stronger than those with CO2/P, ranking from urban density, functional compactness > morphological compactness. Additionally, the geographically and temporally weighted regression (GTWR) model revealed the spatial and temporal heterogeneity in the impact of spatial compactness on carbon emission intensity. The heterogeneity results provide insights into the mechanisms and general patterns of the differences in the factors influencing carbon emissions in four different types of county-level areas, namely, central, eastern, southern, and northwestern, offering policy guidance to promote the reductions in both CO2/L and CO2/P. This study is helpful for proposing urban spatial planning strategies for carbon reduction and formulating differentiated carbon reduction policies.

Topological phase has received considerable attention in recent decades. One of the crucial factors to determine the phase is symmetry. Such a concept involves mathematical, geometrical, and physical meanings, which displays many fascinating phases in Hermitian and non-Hermitian systems. In this paper, we first briefly review the symmetry-related topological phases in Hermitian and non-Hermitian systems. The study in this section focuses on the topological phase itself, not the realizations therein. Then, we present a thorough review of the observations about these symmetry-related topological phenomena in classical platforms. Accompanied by the rise of quantum technology, the combination of symmetry-related topological phase and quantum technology leads to an additional new avenue, in which quantum information tasks can be accomplished better. Finally, we provide comments about future research into symmetry-related topological phases.

Manganese (Mn) exposure is a common environmental risk factor for Parkinson's disease (PD), with pathogenic mechanisms associated with dopaminergic neuron damage and neuroinflammation. Mesenchymal stem cells (MSCs)-derived small extracellular vesicles (sEVs) have emerged as a novel therapeutic approach for neural damage repair. The functional sEVs released from MSCs when they are induced into dopaminergic progenitors may have a better repair effect on neural injury. Therefore, we collected sEVs obtained from primary human nasal mucosal mesenchymal stem cells (hnmMSC-sEVs) or cells in the process of dopaminergic progenitor cell differentiation (da-hnmMSC-sEVs), which were cultured in a 3D dynamic system, and observed their repair effects and mechanisms of Mn-induced neural damage by intranasal administration of sEVs. In Mn-exposed mice, sEVs could reach the site of brain injury after intranasal administration, da-hnmMSC enhanced the repair effects of sEVs in neural damage and behavioral competence, as evidenced by restoration of motor dysfunction, enhanced neurogenesis, decreased microglia activation, up-regulation of anti-inflammatory factors, and down-regulation of pro-inflammatory factors. The transcriptomics of hnmMSC-sEVs and da-hnmMSC-sEVs revealed that miRNAs, especially miR-494–3p in sEVs were involved in neuroprotective and anti-inflammatory effects. Overexpression of miR-494–3p in sEVs inhibited Mn-induced inflammation and neural injury, and its repair mechanism might be related to the down-regulation of CMPK2 and NLRP3 in vitro experiments. Thus, intranasal delivery of da-hnmMSC-sEVs is an effective strategy for the treatment of neural injury repair.

Abstract The unique structural features of hard carbon (HC) make it a promising anode candidate for sodium‐ion batteries (SIB). However, traditional methods of preparing HC require special equipment, long reaction times, and large energy consumption, resulting in low throughputs and efficiency. In our contribution, a novel synthesis method is proposed, involving the formation of HC nanosheets (NS‐CNs) within minutes by creating an anoxic environment through flame combustion and further introducing sulfur and nitrogen sources to achieve heteroatom doping. The effect of heterogeneous element doping on the microstructure of HC is quantitatively analyzed by high‐resolution transmission electron microscopy and image processing technology. Combined with density functional theory calculation, it is verified that the functionalized HC exhibits stronger Na+ adsorption ability, electron gain ability, and Na+ migration ability. As a result, NS‐CNs as SIB anodes provide an ultrahigh reversible capacity of 542.7 mAh g−1 at 0.1 A g−1, and excellent rate performance with a reversible capacity of 236.4 mAh g−1 at 2 A g−1 after 1200 cycles. Furthermore, full cell assembled with NS‐CNs as the can present 230 mAh g−1 at 0.5 A g−1 after 150 cycles. Finally, in/ex situ techniques confirm that the excellent sodium storage properties of NS‐CNs are due to the construction of abundant active sites based on the novel synthesis method for realizing the reversible adsorption of Na+. This work provides a novel strategy to develop novel carbons and gives deep insights for the further investigation of facile preparation methods to develop high‐performance carbon anodes for alkali‐ion batteries.

Candida species are significant causes of mucosal and systemic infections in immune compromised populations, including HIV-infected individuals and cancer patients. Drug resistance and toxicity have limited the use of anti-fungal drugs. A good comprehension of the nature of the immune responses to the pathogenic fungi will aid in the developing of new approaches to the treatment of fungal diseases. In recent years, extensive research has been done to understand the host defending systems to fungal infections. In this review, we described how pattern recognition receptors senses the cognate fungal ligands and the cellular and molecular mechanisms of anti-fungal innate immune responses. Furthermore, particular focus is placed on how anti-fungal signal transduction cascades are being activated for host defense and being modulated to better treat the infections in terms of immunotherapy. Understanding the role that these pathways have in mediating host anti-fungal immunity will be crucial for future therapeutic development.

The aims of developing rapid and living guidelines is to keep the recommendations in the guideline up-to-date. Compared with the conventional guideline, the rapid and living guideline can make better use of the existing evidence and apply and transform the evidence in a timely manner. This paper introduces the advantages and usage of rapid and living guidelines, the development process and existing challenges, and offers some insights, in order to provide reference for domestic organizations and scholars engaged in guideline development.

Abstract Recently, higher-order topological insulators (HOTIs) have been introduced, and were shown to host topological corner states under the theoretical framework of Benalcazar-Bernevig-Hughes. Here we unveil some topological effects in HOTIs by studying the three-dimensional (3D) non-Abelian Bloch oscillations (BOs). In HOTIs, BOs with a multiplied period occur when a force with a special direction is applied due to the effect of the non-Abelian Berry curvature. Along the direction of the oscillations we find a higher-order topological state that goes beyond the theoretical framework of multipole moments. The emergence of such a higher-order topological state coincides with the appearance of the 3D non-Abelian BOs. That is, the 3D non-Abelian BOs can be used as a tool to probe higher-order topological states. These phenomena are observed experimentally with designed electric circuit networks. Our work opens up a way to detect topological phases theoretically and experimentally.

Optimization algorithms are pivotal in addressing complex problems across diverse domains, including global optimization and feature selection (FS). In this paper, we introduce the Enhanced Crisscross Parrot Optimizer (ECPO), an improved version of the Parrot Optimizer (PO), designed to address these challenges effectively. The ECPO incorporates a sophisticated strategy selection mechanism that allows individuals to retain successful behaviors from prior iterations and shift to alternative strategies in case of update failures. Additionally, the integration of a crisscross (CC) mechanism promotes more effective information exchange among individuals, enhancing the algorithm’s exploration capabilities. The proposed algorithm’s performance is evaluated through extensive experiments on the CEC2017 benchmark functions, where it is compared with ten other conventional optimization algorithms. Results demonstrate that the ECPO consistently outperforms these algorithms across various fitness landscapes. Furthermore, a binary version of the ECPO is developed and applied to FS problems on ten real-world datasets, demonstrating its ability to achieve competitive error rates with reduced feature subsets. These findings suggest that the ECPO holds promise as an effective approach for both global optimization and feature selection.

In-depth quality assessment of 3D-printed parts is vital in determining their overall characteristics. This study focuses on the use of 2D X-Ray diffraction (2D-XRD) and X-Ray micro-computed tomography (micro-CT) techniques to evaluate the crystallography and internal defects of 316L SS parts fabricated by the powder-based direct energy deposition (DED) technique. The test samples were printed in a controlled argon environment with variable laser power and print speeds, using a customized deposition pattern to achieve a high-density print (>99%). Multiple features, including hardness, elastic modulus, porosity, crystallographic orientation, and grain morphology and size were evaluated as a function of print parameters. Micro-CT was used for in-depth internal defect analysis, revealing lack-of-fusion and gas-induced (keyhole) pores and no observable micro-cracks or inclusions in most of the printed body. Some porosity was found mostly concentrated in the initial layers of print and decreased along the build direction. 2D-XRD was used for phase analysis and grain size determination. The phase analysis revealed single phase γ-austenitic FCC phase without any detectable presence of the δ-ferrite phase. A close correlation was found between Electron Backscatter Diffraction (EBSD) and 2D-XRD results on the average size distribution and the crystallographic orientation of grains in the sample. This work demonstrates the fast and reliable as-printed crystallography analysis using 2D-XRD compared to the EBSD technique, with potential for in-line integration.

Land image recognition and classification and land environment detection are important research fields in remote sensing applications. Because of the diversity and complexity of different tasks of land environment recognition and classification, it is difficult for researchers to use a single model to achieve the best performance in scene classification of multiple remote sensing land images. Therefore, to determine which model is the best for the current recognition classification tasks, it is often necessary to select and experiment with many different models. However, finding the optimal model is accompanied by an increase in trial-and-error costs and is a waste of researchers’ time, and it is often impossible to find the right model quickly. To address the issue of existing models being too large for easy selection, this paper proposes a multi-path reconfigurable network structure and takes the multi-path reconfigurable residual network (MR-ResNet) model as an example. The reconfigurable neural network model allows researchers to selectively choose the required modules and reassemble them to generate customized models by splitting the trained models and connecting them through modules with different properties. At the same time, by introducing the concept of a multi-path input network, the optimal path is selected by inputting different modules, which shortens the training time of the model and allows researchers to easily find the network model suitable for the current application scenario. A lot of training data, computational resources, and model parameter experience are saved. Three public datasets, NWPU-RESISC45, RSSCN7, and SIRI-WHU datasets, were used for the experiments. The experimental results demonstrate that the proposed model surpasses the classic residual network (ResNet) in terms of both parameters and performance.

Evaluating the performance of city construction not only helps optimize city functions and improve city quality, but it also contributes to the development of sustainable cities. However, most of the scoring rules for evaluating the performance of city construction are overly cumbersome and demand very high data integrity. Moreover, the properties, change scale, and scope of different evaluation indicators of city construction often lead to uncertain and ambiguous results. In this study, a hybrid fuzzy method is proposed to conduct the performance evaluation of city construction in two phases. Firstly, a city performance index (CPI) was developed by combining the means and standard deviations of indicators of city construction to address the volatility of historical statistical data as well as different types of data. Considering the sampling errors in data analysis, the parameter estimation method was used to derive the 100% × (1 − α) confidence interval of the CPI. Buckley’s fuzzy approach was then adopted to extend the statistical estimators from the CPI into fuzzy estimators, after which a fuzzy CPI was proposed. To identify the specific improvement directions for city construction, the fuzzy axiom design (fuzzy AD) method was applied to explore the relationship between the targets set by city managers and actual performance. Finally, an example of six cities in China is provided to illustrate the effectiveness and practicality of the proposed method. The results show that the performance of Chongqing on several evaluation indicators is lower than that of other cities. The proposed method takes into account the issues of uniformity and diversity in the performance evaluation of city construction. It can enable a quantitative assessment of the city construction level in all cities and provide theoretical support and a decision-making basis for relevant government departments to optimize city construction planning and scientifically formulate city construction policies.

Poliovirus (PV) is on the brink of eradication due to global vaccination programs utilizing live-attenuated oral and inactivated polio vaccines. Recombinant PV virus-like particles (VLPs) are emerging as a safe next-generation vaccine candidate for the impending polio-free era. In this study, we investigate the production, antigenicity, thermostability, immunogenicity, and structures of VLPs derived from PV serotype 2 (PV2) wildtype strain and thermally stabilized mutant (wtVLP and sVLP, respectively). Both PV2 wtVLP and sVLP are efficiently produced in Pichia pastoris yeast. The PV2 sVLP displays higher levels of D-antigen and significantly enhanced thermostability than the wtVLP. Unlike the wtVLP, the sVLP elicits neutralizing antibodies in mice at levels comparable to those induced by inactivated polio vaccine. The addition of an aluminum hydroxide adjuvant to sVLP results in faster induction and a higher magnitude of neutralizing antibodies. Furthermore, our cryo-EM structural study of both sVLP and wtVLP reveals a native conformation for the sVLP and a non-native expanded conformation for the wtVLP. Our work not only validates the yeast-produced PV2 sVLP as a promising vaccine candidate with high production potential but also sheds light on the structural mechanisms that underpin the assembly and immunogenicity of the PV2 sVLP. These findings may expedite the development of sVLP-based PV vaccines.

Weeds have a detrimental effect on crop yield. However, the prevailing chemical weed control methods cause pollution of the ecosystem and land. Therefore, it has become a trend to reduce dependence on herbicides; realize a sustainable, intelligent weed control method; and protect the land. In order to realize intelligent weeding, efficient and accurate crop and weed recognition is necessary. Convolutional neural networks (CNNs) are widely applied for weed and crop recognition due to their high speed and efficiency. In this paper, a multi-path input skip-residual network (SkipResNet) was put forward to upgrade the classification function of weeds and crops. It improved the residual block in the ResNet model and combined three different path selection algorithms. Experiments showed that on the plant seedling dataset, our proposed network achieved an accuracy of 95.07%, which is 0.73%, 0.37%, and 4.75% better than that of ResNet18, VGG19, and MobileNetV2, respectively. The validation results on the weed–corn dataset also showed that the algorithm can provide more accurate identification of weeds and crops, thereby reducing land contamination during the weeding process. In addition, the algorithm is generalizable and can be used in image classification in agriculture and other fields.

This research highlights that street layouts, including the vegetation ratio, street orientation, and aspect ratio, are key in diminishing urban heat islands (UHIs), building energy use, and carbon emissions. The optimal street layout for minimal building energy consumption, carbon emissions, and maximal outdoor thermal comfort in Tianjin was established via field measurements, ENVI-met 5.6.1, Energy Plus simulations, and correlation analysis. The findings indicate the following: (1) The carbon emissions of winter residential heating energy consumption are 2.9–3.2 times higher than those for summer cooling. Urban design should thus prioritize winter energy efficiency and summer thermal comfort outdoors. (2) The summer street PET (physiological equivalent temperature) inversely correlates with the vegetation ratio and aspect ratio. Winter heating energy use inversely correlates with the street orientation and directly correlates with the aspect ratio. Adequate vegetation and proper orientation can decrease energy and carbon output while enhancing summer outdoor comfort. (3) Streets with an NW–SE orientation, H/W = 0.9, and 50% trees in summer yield the best thermal comfort, while those with an NE–SW orientation, H/W = 0.3, and 50% vegetative trees in winter produce the lowest carbon emissions. These insights are instrumental in refining urban streets and building designs in cold zones.

Abstract Background Oncolytic viruses are now well recognized as potential immunotherapeutic agents against cancer. However, the first FDA-approved oncolytic herpes simplex virus 1 (HSV-1), T-VEC, showed limited benefits in some patients in clinical trials. Thus, the identification of novel oncolytic viruses that can strengthen oncolytic virus therapy is warranted. Here, we identified a live-attenuated swine pseudorabies virus (PRV-LAV) as a promising oncolytic agent with broad-spectrum antitumor activity in vitro and in vivo. Methods PRV cytotoxicity against tumor cells and normal cells was tested in vitro using a CCK8 cell viability assay. A cell kinase inhibitor library was used to screen for key targets that affect the proliferation of PRV-LAV. The potential therapeutic efficacy of PRV-LAV was tested against syngeneic tumors in immunocompetent mice, and against subcutaneous xenografts of human cancer cell lines in nude mice. Cytometry by time of flight (CyTOF) and flow cytometry were used to uncover the immunological mechanism of PRV-LAV treatment in regulating the tumor immune microenvironment. Results Through various tumor-specific analyses, we show that PRV-LAV infects cancer cells via the NRP1/EGFR signaling pathway, which is commonly overexpressed in cancer. Further, we show that PRV-LAV kills cancer cells by inducing endoplasmic reticulum (ER) stress. Moreover, PRV-LAV is responsible for reprogramming the tumor microenvironment from immunologically naïve (“cold”) to inflamed (“hot”), thereby increasing immune cell infiltration and restoring CD8+ T cell function against cancer. When delivered in combination with immune checkpoint inhibitors (ICIs), the anti-tumor response is augmented, suggestive of synergistic activity. Conclusions PRV-LAV can infect cancer cells via NRP1/EGFR signaling and induce cancer cells apoptosis via ER stress. PRV-LAV treatment also restores CD8+ T cell function against cancer. The combination of PRV-LAV and immune checkpoint inhibitors has a significant synergistic effect. Overall, these findings point to PRV-LAV as a serious potential candidate for the treatment of NRP1/EGFR pathway-associated tumors.

Objective: To investigate the evolution of inflammation under conditions and the effects of ginsenosides on macrophages subjected to the simulated weightlessness, with the aim of mitigating the inflammation. Methods: Initially, genes related to weightlessness, inflammation, and immunity were identified in the GeneCards database. Then, Search Tool for the Retrieval of Interaction Gene/Proteins (STRING) protein network analysis was conducted to determine the core targets involved in the weightlessness-induced inflammation. Subsequently, Label-Free Quantitative (LFQ) proteomics was carried out to discern the distinctive genes within ginsenoside-treated Tohoku Hospital Pediatrics-1 (THP-1) cells. Next, utilizing the outcomes of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, the biological processes and signaling pathways in which ginsenosides predominately engaged were scrutinized, and the primary targets of ginsenosides in combating weightlessness-induced inflammation were examined. Finally, enzyme-linked immunosorbent assay (ELISA) was performed to detect the secretion levels of interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α from lipopolysaccharide (LPS)-induced THP-1 cells under simulated weightlessness conditions, as well as during the weightlessness recovery period following treatment with ginsenosides. Results: A total of 2 933 genes associated with inflammation, 425 genes linked to weightlessness, and 4 564 genes connected to immunity were retrieved from the GeneCards database. Protein-protein interaction (PPI) networks were generated to identify pivotal targets associated with weightlessness-induced inflammation such as IL-1β, IL-6, TNF, and albumin (ALB). It was found that ginsenosides primarily participated in the regulation of various inflammation-related signaling pathways and pathways related to pathogenic microorganism infections. Moreover, it has a significant impact on the expression of proteins such as cluster of differentiation 40 (CD40), IL-1β, and poly ADP-ribose polymerase 1 (PARP1). As revealed in the simulated weightlessness cell test, ginsenosides exhibited a remarkable capacity to attenuate the secretion of inflammatory factors, specifically IL-6 and TNF-α (P < 0.000 1), in THP-1 macrophages following induction by LPS under simulated weightlessness conditions. In addition, it reduced the secretion of IL-1β, IL-6, IL-8, and TNF-α (P < 0.000 1) during the weightlessness recovery phase. Conclusion: Weightlessness can disrupt several inflammation-related signaling pathways, but ginsenosides were shown to mitigate the release of various inflammatory factors in macrophages subjected to simulated weightlessness, thereby exerting a protective role against inflammation. This study has laid a theoretical groundwork for further exploring the potential application of ginsenosides in safeguarding against LPS induced inflammation in a weightlessness environment.

Abstract Defects passivation is widely devoted to improving the performance of formamidinium lead triiodide perovskite solar cells; however, the effect of various defects on the α-phase stability is still unclear. Here, using density functional theory, we first reveal the degradation pathway of the formamidinium lead triiodide perovskite from α to δ phase and investigate the effect of various defects on the energy barrier of phase transition. The simulation results predict that iodine vacancies are most likely to trigger the degradation, since they obviously reduce the energy barrier of α-to-δ phase transition and have the lowest formation energies at the perovskite surface. A water-insoluble lead oxalate compact layer is introduced on the perovskite surface to largely suppress the α-phase collapse through hindering the iodine migration and volatilization. Furthermore, this strategy largely reduces the interfacial nonradiative recombination and boosts the efficiency of the solar cells to 25.39% (certified 24.92%). Unpackaged device can maintain 92% of its initial efficiency after operation at maximum power point under simulated air mass 1.5 G irradiation for 550 h.

Abstract Daqing Oilfield as the world’s largest application area of alkali–surfactant–polymer (ASP) flooding, in recent years, with the increase in aging wells, the eccentric wear and deformation of sucker rod and pipe during oil production has become more and more serious. In order to study the effect of emulsion lubrication in ternary composite flooding on eccentric wear of sucker rod and tubing, this paper establishes a calculation model for the depth of tubing wear under different emulsion lubrication conditions through indoor friction and wear experiments combined with White and Dawson wear efficiency theory. Based on this, the finite element method is used to predict the safe wear life of tubing under different component emulsion lubrication. The results show that compared to intact oil pipes, the residual internal pressure strength of oil pipes with defects decreases, and stress concentration occurs at the edges and middle of the defects. The wear life of oil pipes decreases with the increase in pump depth and wear coefficient under emulsion lubrication. The water content and alkali concentration have the most significant effects on the wear life of oil pipes under emulsion lubrication conditions. The safe wear life of sucker rod pipes under emulsion lubrication with a water content of 75% will be increased by 37.8% compared to those in emulsion lubrication with a water content of 95%, and under emulsion lubrication with an alkali concentration of 500 mg/l, the safe wear life will be increased by 50.6% compared to those in emulsion lubrication with a concentration of 2000 mg/l. The research results can provide theoretical and technical support for oilfield enterprises to reduce rod and pipe wear in ASP flooding oil wells, improve the pump inspection cycle of pumping wells, and ensure the safety of oil well work.

Abstract Metabolism vulnerability of cisplatin resistance in BCa cells remains to be discovered, which we applied integrated multi-omics analysis to elucidate the metabolism related regulation mechanism in bladder cancer (BCa) microenvironment. Integrated multi-omics analysis of metabolomics and proteomics revealed that MAT2A regulated methionine metabolism contributes to cisplatin resistance in BCa cells. We further validated MAT2A and cancer stem cell markers were up-regulated and circARHGAP10 was down-regulated through the regulation of MAT2A protein stability in cisplatin resistant BCa cells. circARHGAP10 formed a complex with MAT2A and TRIM25 to accelerate the degradation of MAT2A through ubiquitin-proteasome pathway. Knockdown of MAT2A through overexpression of circARHGAP10 and restriction of methionine up-take was sufficient to overcome cisplatin resistance in vivo in immuno-deficiency model but not in immuno-competent model. Tumor-infiltrating CD8+ T cells characterized an exhausted phenotype in tumors with low methionine. High expression of SLC7A6 in BCa negatively correlated with expression of CD8. Synergistic inhibition of MAT2A and SLC7A6 could overcome cisplatin resistance in immuno-competent model in vivo. Cisplatin resistant BCa cells rely on methionine for survival and stem cell renewal. circARHGAP10/TRIM25/MAT2A regulation pathway plays an important role in cisplatin resistant BCa cells while circARHGAP10 and SLC7A6 should be evaluated as one of the therapeutic target of cisplatin resistant BCa.

Abstract Mutations in OTOFERLIN (OTOF) lead to the autosomal recessive deafness 9 (DFNB9). The efficacy of adeno‐associated virus (AAV)‐mediated OTOF gene replacement therapy is extensively validated in Otof‐deficient mice. However, the clinical safety and efficacy of AAV‐OTOF is not reported. Here, AAV‐OTOF is generated using good manufacturing practice and validated its efficacy and safety in mouse and non‐human primates in order to determine the optimal injection dose, volume, and administration route for clinical trials. Subsequently, AAV‐OTOF is delivered into one cochlea of a 5‐year‐old deaf patient and into the bilateral cochleae of an 8‐year‐old deaf patient with OTOF mutations. Obvious hearing improvement is detected by the auditory brainstem response (ABR) and the pure‐tone audiometry (PTA) in these two patients. Hearing in the injected ear of the 5‐year‐old patient can be restored to the normal range at 1 month after AAV‐OTOF injection, while the 8‐year‐old patient can hear the conversational sounds. Most importantly, the 5‐year‐old patient can hear and recognize speech only through the AAV‐OTOF‐injected ear. This study is the first to demonstrate the safety and efficacy of AAV‐OTOF in patients, expands and optimizes current OTOF‐related gene therapy and provides valuable information for further application of gene therapies for deafness.

IntroductionAtmospheric nitrogen (N) deposition can impact the levels of soil organic carbon (SOC) and total nitrogen (total N) by altering the soil N availability. However, the effect of N input on the mineralization of SOC and total N in various soil aggregate size fractions requires further clarification.MethodsThe soil samples were collected from a Pinus massoniana plantation situated in the Three Gorges Reservoir Area of China. Over a period of three years, the soils from the plantation were subjected to four different levels of nitrogen addition (0 [N0], 30 [N30], 60 [N60], and 90 [N90] kg N ha−1 yr−1). The impact of N addition on the mineralization of SOC and total N in aggregates was evaluated through an incubation experiment, encompassing four aggregate sizes (2000 − 8000, 1000 − 2000, 250 − 1000, and < 250 μm).ResultsThe < 250 μm fraction showed the highest levels of cumulative C mineralization, while the lowest levels were observed in the 2000 − 8000 μm fraction. Compared to the < 250 um fraction, a drop of 9 − 21% in cumulative C mineralization was observed in the 2000 − 8000 μm fraction, indicating that soil aggregates enhance the stability of C in the soil. Cumulative N mineralization levels were consistently at their lowest in the 2000 − 8000 μm fraction, indicating aggregates reducing mineralization-related N loss. Adding N to forest soil samples led to a reduction in cumulative C mineralization. In contrast, an opposite trend was observed in the cumulative N mineralization after adding N in microaggregates. Nitrification was the main contributor to net N mineralization. SOC and total levels increased in response to N30 and N60. N addition leads to an increase in the weight ratio of the 1000 − 2000 μm fraction. Moreover, N90 was linked to decreases in microbial biomass C and N.DiscussionThese findings confirm that the structural characteristics of soil aggregates play a crucial role in sequestering organic carbon and total N sequestration in the presence of N deposition, while highlighting N loss from the soil caused by N input.

The region coverage control problem of multiple stratospheric airships system is firstly addressed in this paper. Towards it, we propose a two-layer control framework with the artificial potential field (APF)-based region coverage control law and the adaptive tracking control law. The APF-based region coverage control law ensures the coverage task is achieved until every single stratospheric airship ends up performing station keeping where near the respective global minimum point, in which an innovative solution to the local minimum problem is put forward. The adaptive tracking control law is designed to realize motion control using tracking the desired velocity and angular velocity given by coverage control law, with the consideration of several practical control problems as unknown individual differences and external disturbances. To save resources, the combined self-/event-triggered mechanism designed therein significantly reduces the times of state information transmission and control law calculation. The effectiveness of the proposed control framework is verified through simulations.

Estrogens can affect the immune inflammatory response through estrogen receptor alpha (ERα), but the specific role of estrogen member receptor G-protein coupled receptor 1 (GPER1) in this process remains unclear. In this study, we evaluated the effects of tetrachlorobisphenol A (TCBPA), which has estrogen activity, on immune inflammatory-related indicators of Jurkat cells, as well as investigated the role of GPER1 in these effects. The results showed that TCBPA at lower concentrations significantly promoted the viability of Jurkat cells, whereas higher concentrations decreased cell viability. TCBPA at concentrations ranging from 1 to 25 μM increased the intracellular reactive oxygen species (ROS) levels. Additionally, treatment with 10 μM TCBPA increased the protein expression of ERα and GPER1, elevated the phosphorylation of protein kinase B (p-Akt), and upregulated the mRNA levels of GPER1, Akt, and phosphoinositide 3-kinase (PI3K) genes. Treatment with 10 μM TCBPA also upregulated the protein or gene expression of pro-inflammatory cytokines, such as interleukins (IL1β, IL2, IL6, IL8, IL12α) and tumor necrosis factor alpha (TNFα) in Jurkat cells. Furthermore, pretreatment with a GPER1 inhibitor G15 significantly reduced the mRNA levels of Akt induced by 10 μM TCBPA. Moreover, the upregulation of mRNA expression of RelA (p65), TNFα, IL6, IL8, and IL12α induced by 10 μM TCBPA was also significantly attenuated after G15 pretreatment. These findings suggest that TCBPA upregulates the expression of genes related to inflammatory responses by activating the GPER1-mediated PI3K/Akt signaling pathway. This study provides new insights into the mechanism of TCBPA-induced inflammatory response.

Influenza virus is one of the main pathogens causing respiratory diseases in humans. Vaccines are the most effective ways to prevent viral diseases. However, the limited protective efficacy of current influenza vaccines highlights the importance of novel, safe, and effective universal influenza vaccines. With the progress of the COVID-19 pandemic, live-attenuated vaccines delivered through respiratory mucosa have shown robustly protective efficacy. How to obtain a safe and effective live-attenuated vaccine has become a major challenge. Herein, using the influenza virus as a model, we have established a strategy to quickly obtain a live-attenuated vaccine by mutating the cleavage site of the influenza virus. This mutated influenza virus can be specifically cleaved by chymotrypsin. It has similar biological characteristics to the original strain in vitro, but the safety is improved by at least 100 times in mice. It can effectively protect against lethal doses of both homologous H1N1 and heterologous H5N1 viruses post mucosal administration, confirming that the vaccine generated by this strategy has good safety and broad-spectrum protective activities. Therefore, this study can provide valuable insights for the development of attenuated vaccines for respiratory viruses or other viruses with cleavage sites.

Abstract OTOF mutations are the principal causes of auditory neuropathy. There are reports on Otof‐related gene therapy in mice, but there is no preclinical research on the drug evaluations. Here, Anc80L65 and the mouse hair cell‐specific Myo15 promoter (mMyo15) are used to selectively and effectively deliver human OTOF to hair cells in mice and nonhuman primates to evaluate the efficacy and safety of OTOF gene therapy drugs. A new dual‐AAV‐OTOF‐hybrid strategy to transfer full‐length OTOF is generated, which can stably restore hearing in adult OTOFp.Q939*/Q939* mice with profound deafness, with the longest duration being at least 150 days, and the best therapeutic effect without difference in hearing from wild‐type mice. An AAV microinjection method into the cochlea of cynomolgus monkeys without hearing impairment is further established and found the OTOF can be safely and effectively driven by the mMyo15 promoter in hair cells. In addition, the therapeutic dose of AAV drugs has no impact on normal hearing and does not cause significant systemic toxicity both in mouse and nonhuman primates. In summary, this study develops a potential gene therapy strategy for DFNB9 patients in the clinic and provides complete, standardized, and systematic research data for clinical research and application.

Fungal infections have emerged as a major concern among immunocompromised patients, causing approximately 2 million deaths each year worldwide. However, the regulatory mechanisms underlying antifungal immunity remain elusive and require further investigation. The E3 ligase Trim26 belongs to the tripartite motif (Trim) protein family, which is involved in various biological processes, including cell proliferation, antiviral innate immunity, and inflammatory responses. Herein, we report that Trim26 exerts protective antifungal immune functions after fungal infection. Trim26-deficient mice are more susceptible to fungemia than their wild-type counterparts. Mechanistically, Trim26 restricts inflammatory neutrophils infiltration and limits proinflammatory cytokine production, which can attenuate kidney fungal load and renal damage during Candida infection. Trim26-deficient neutrophils showed higher proinflammatory cytokine expression and impaired fungicidal activity. We further demonstrated that excessive neutrophils infiltration in the kidney was because of the increased production of chemokines CXCL1 and CXCL2, which are mainly synthesized in the macrophages or dendritic cells of Trim26-deficient mice after Candida albicans infections. Together, our study findings unraveled the vital role of Trim26 in regulating antifungal immunity through the regulation of inflammatory neutrophils infiltration and proinflammatory cytokine and chemokine expression during candidiasis.