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Abstract Objective To investigate the safety and efficacy of endoscopic subserosal dissection for patients with submucosal tumors in the upper gastrointestinal tract. Methods This retrospective single-center study included 16 patients who underwent ESSD. All patients were enrolled from July 2018 to Dec 2021. Parameters such as demographics, size, resection margin, complications, pathological features, procedure time and follow-up were investigated and analyzed. Results Our study achieved 100% en bloc resection and 100% R0 resection. The most common location was the corpus with a mean tumor size of 2.78 ± 1.56 cm. The mean age, procedure time, were 53.4 ± 10.3 years, 85.31 ± 46.64 min respectively. Acocording to National Institutes of Health classification, 7 (13, 53.85%), 5 (13, 38.46%) ,and 1 (13, 7.69%) objects belonged to the very low, low, and intermediate classification, respectively. Immunohistochemistry results showed a 100% positive rate of CD34, DOG-1, CD117, and Ki67. A mean follow-up of 9.3 ± 2.5 months showed no recurrence or metastasis. Conclusions ESSD is effective and safe surgical procedure for curative removal of gastrointestinal submucosal tumors in the upper gastrointestinal tract, and it can be preferred for patients with no metastasis.

Abstract Background Traditional topical drug delivery for treating inflammatory skin diseases suffers from poor skin penetration and long-term side effects. Metal nanoparticles show promising application in topical drug delivery for inflammatory skin diseases. Methods Here, we synthesized a new type of nanoparticles, azelamide monoethanolamine-functionalized gold nanoparticles (Au-MEA NPs), based on citrate-capped gold nanoparticles (Au-CA NPs) via the ligand exchange method. The physical and chemical properties of Au-CA NPs and Au-MEA NPs were characterized. In vivo studies were performed using imiquimod-induced psoriasis and LL37-induced rosacea animal models, respectively. For in vitro studies, a model of cellular inflammation was established using HaCaT cells stimulated with TNF-α. In addition, proteomics, gelatin zymography, and other techniques were used to investigate the possible therapeutic mechanisms of the Au-MEA NPs. Results We found that Au-MEA NPs exhibited better stability and permeation properties compared to conventional Au-CA NPs. Transcutaneously administered Au-MEA NPs exerted potent therapeutic efficacy against both rosacea-like and psoriasiform skin dermatitis in vivo without overt signs of toxicity. Mechanistically, Au-MEA NPs reduced the production of pro-inflammatory mediators in keratinocytes by promoting SOD activity and inhibiting the activity of MMP9. Conclusion Au-MEA NPs have the potential to be a topical nanomedicine for the effective and safe treatment of inflammatory skin diseases.

Abstract Quantum networks provide a prospective paradigm to connect separated quantum nodes, which relies on the distribution of long-distance entanglement and active feedforward control of qubits between remote nodes. Such approaches can be utilized to construct nonlocal quantum gates, forming building blocks for distributed quantum computing and other novel quantum applications. However, these gates have only been realized within single nodes or between nodes separated by a few tens of meters, limiting the ability to harness computing resources in large-scale quantum networks. Here, we demonstrate nonlocal photonic quantum gates between two nodes spatially separated by 7.0 km using stationary qubits based on multiplexed quantum memories, flying qubits at telecom wavelengths, and active feedforward control based on field-deployed fibers. Furthermore, we illustrate quantum parallelism by implementing the Deutsch-Jozsa algorithm and the quantum phase estimation algorithm between the two remote nodes. These results represent a proof-of-principle demonstration of quantum gates over metropolitan-scale distances and lay the foundation for the construction of large-scale distributed quantum networks relying on existing fiber channels.

Abstract In this study, we reported for the first time the dose-dependent dual effects of Alpha-Ketoglutarate (AKG) on cumulus oocyte complexes (COCs) during in vitro maturation (IVM). AKG at appropriate concentration (30 µM) has beneficial effects on IVM. This includes improved cumulus expansion, oocyte quality, and embryo development. These effects are mediated through multiple underlying mechanisms. AKG reduced the excessive accumulation of reactive oxygen species (ROS) in cumulus cells, reduced the consumption of GSH and NADPH. Cumulus GSH and NADPH were transported to oocytes via gap junctions, thereby reducing the oxidative stress, apoptosis and maintaining the redox balance in oocytes. In addition, AKG improved the mitochondrial function by regulating the mitochondrial complex 1 related gene expression in oocytes to maintain mitochondrial membrane potential and ATP production. On the other hand, oocyte generated GDF9 could also be transported to cumulus cells to promote cumulus expansion. Conversely, a high concentration of AKG (750 µM) exerted adverse effects on IVM and suppressed the cumulus expansion as well as reduced the oocyte quality. The suppression of the cumulus expansion caused by high concentration of AKG could be rescued with GDF9 supplementation in COCs, indicating the critical role of GDF9 in IVM. The results provide valuable information on the variable effects of AKG at different concentrations on reproductive physiology. Graphical abstract

Abstract Rosacea patients show facial hypersensitivity to stimulus factors (such as heat and capsaicin); however, the underlying mechanism of this hyperresponsiveness remains poorly defined. Here, we show capsaicin stimulation in mice induces exacerbated rosacea-like dermatitis but has no apparent effect on normal skin. Nociceptor ablation substantially reduces the hyperresponsiveness of rosacea-like dermatitis. Subsequently, we find that γδ T cells express Ramp1, the receptor of the neuropeptide CGRP, and are in close contact with these nociceptors in the skin. γδ T cells are significantly increased in rosacea skin lesions and can be further recruited and activated by neuron-secreted CGRP. Rosacea-like dermatitis is reduced in T cell receptor δ-deficient (Tcrd−/−) mice, and the nociceptor-mediated aggravation of rosacea-like dermatitis is also reduced in these mice. In vitro experiments show that CGRP induces IL17A secretion from γδ T cells by regulating inflammation-related and metabolism-related pathways. Finally, rimegepant, a CGRP receptor antagonist, shows efficacy in the treatment of rosacea-like dermatitis. In conclusion, our findings demonstrate a neuron-CGRP-γδT cell axis that contributes to the hyperresponsiveness of rosacea, thereby showing that targeting CGRP is a potentially effective therapeutic strategy for rosacea.

Taking the geoelectric field observation data of Yuanmou Julin of Chuxiong Earthquake Monitoring Center Station as the research object, combined with the ideas and specific contents of the two transformations since the geoelectric field observation，the observation data curve variation characteristics and data quality in three time periods before and after the two transformations are compared and analyzed，and the following experience is obtained，which can be used as a reference for the transformation and construction of other geoelectric field observation stations: ① The anti-interference ability and stability of solid non-polarized electrodes far exceed lead electrodes; ② Electrode buried depth need to consider more consistent soil electrical properties rather than pay attention to the buried depth，should do a good job in the construction of the site geological prospecting work，to ensure that the electrode buried after the grounding resistance without a big gap, but also should pay attention to the electrode lead buried depth must be greater than the farmers daily farming may touch the depth; ③ Double “L” type pole arrangement needs to be strictly in accordance with the construction specifications of the geoelectric station to arrange the long and short pole spacing; ④ For the insulation problem of overhead lines, it can be done between the hoop and the pole first through the insulation rubber pad insulation，and then between the hoop and the steel strand through the insulator re-insulating，especially the ground resistivity with the site observation station，more attention should be paid to the insulation of the steel strand.

Abstract Background The role of circRNAs in hepatocellular carcinoma (HCC) progression remains unclear. CircPIAS1 (circBase ID: hsa_circ_0007088) was identified as overexpressed in HCC cases through bioinformatics analysis. This study aimed to investigate the oncogenic properties and mechanisms of circPIAS1 in HCC development. Methods Functional analyses were conducted to assess circPIAS1’s impact on HCC cell proliferation, migration, and ferroptosis. Xenograft mouse models were employed to evaluate circPIAS1’s effects on tumor growth and pulmonary metastasis in vivo. Bioinformatics analysis, RNA immunoprecipitation, and luciferase reporter assays were utilized to elucidate the molecular pathways influenced by circPIAS1. Additional techniques, including RNA pulldown, fluorescence in situ hybridization (FISH), chromatin immunoprecipitation (ChIP), qPCR, and western blotting, were used to further explore the underlying mechanisms. Results CircPIAS1 expression was elevated in HCC tissues and cells. Silencing circPIAS1 suppressed HCC cell proliferation and migration both in vitro and in vivo. Mechanically, circPIAS1 overexpression inhibited ferroptosis by competitively binding to miR-455-3p, leading to upregulation of Nuclear Protein 1 (NUPR1). Furthermore, NUPR1 promoted FTH1 transcription, enhancing iron storage in HCC cells and conferring resistance to ferroptosis. Treatment with ZZW-115, an NUPR1 inhibitor, reversed the tumor-promoting effects of circPIAS1 and sensitized HCC cells to lenvatinib. Conclusion This study highlights the critical role of circPIAS1 in HCC progression through modulation of ferroptosis. Targeting the circPIAS1/miR-455-3p/NUPR1/FTH1 regulatory axis may represent a promising therapeutic strategy for HCC.

Wheat grain yields, quality, and nitrous oxide (N2O) emissions were controlled through the type and application rate of nitrogen (N) fertilizer. Here, we investigated the optimal management of N fertilization by examining the combined effects of organic and N fertilizers on wheat yields, quality, and N2O emissions. Field trials under six treatments were located on campus farms at Anhui Science and Technology University, including farmer’s common practice (270 kg N ha-1, N270), 2/3 reduction in N270 (90 kg N ha-1, N90), organic fertilizer with equal N270 (OF270), 2/3 reduction in OF270 (OF90), 4/5 reduction OF270 + 1/5 reduction N270 (20% OF270 + 80% N270), and 4/5 reduction OF90 + 1/5 reduction N90 (20% OF90 + 80% N90) were applied to winter wheat. The plots were arranged in a randomized complete block experimental design. The N2O emissions were quantified under different fertilization measures in the peak wheat growing season during sowing, jointing, and grain filling stages, respectively. Compared with N270 and N90 treatments, N2O emissions were significantly decreased by 18.6% and 27.2%, respectively, under 20% OF270 + 80% N270% and 20% OF90 + 80% N90 (p < 0.05). Further, N2O emissions in N270 were increased by 50.8% relative to N90. Wheat yields increased significantly under 20% OF90 + 80% N90 by 27.6% (N270) and 16.4% (N90), and were considerably enhanced under 20% OF270 + 80% N270 by 40.6% (N270) and 12.7% (N90) in contrast to OF270 and N270 (p < 0.05). Compared with N90, the content of wet gluten, protein and starch under 20% OF90 + 80% N90 treatment significantly increased by 7.7%, 13.8% and 7.9%, and enhanced by 7.6%, 4.8%, 8.0% relative to OF90, respectively (p < 0.05). The starch content increased significantly by 2.0%, whereas the settlement value decreased considerably by 2.9% under 20% OF270 + 80% N270 (p < 0.05), and there was no notable difference in the wet gluten and protein contents (p > 0.05). Our findings indicated that organic fertilizer mixed with N fertilizer can effectively reduce N2O emissions, increase both the grain yields and quality in wheat field compared with N fertilizer alone.

Abstract The uneven growth of lithium dendrites not only compromise the performance of lithium metal batteries, but also has security risks. In this sutudy, double coating with MgF2 and hydroxypropyl methylcellulose was synthesized on the surface of polyethylene separator through a simple soaking and in‐situ chemical precipitation method, achieve the purpose of protecting lithium metal anode. Utilizing the MgF2/HPMC@PE separator, the Li||Li symmetric cell was capable of cycling for over 1000 hours with a voltage hysteresis of only 11.4 mV, comparing the voltage hysteresis based on the cell use of PE separator increases rapidly after 200 h. Furthermore, the initial discharge capacity of Li||LiNi0.6Co0.2Mn0.2O2(NCM622) is 144.6 mAh g−1 and the capacity retention is 87.2 % after 200 cycles at 1 C, which is higher than that of the PE separator (135.3 mAh g−1, with retention of 74.9 %). All improvements can be credited with the formation of stable solid electrolyte interphase(SEI) film induced by HPMC/MgF2 double coating, which is reduced the Li nucleation overpotential and ultimately promoted uniform Li deposition. This study provides a simple and effective strategy for improving the cycling performance and safety of lithium metal batteries.

IntroductionMultidrug-resistant tuberculosis (MDR-TB) remains a challenge in the TB program of Taiwan, where 0.5% of new cases and 2.1% of previously treated cases were resistant to at least rifampin (RIF) and isoniazid (INH). Since >80% of our MDR-TB are new cases, genotyping of MDR Mycobacterium tuberculosis is implemented to facilitate contact investigation, cluster identification, and outbreak delineation.MethodsThis is a population-based retrospective cohort study analyzing MDR-TB cases from 2019 to 2022. Whole genome sequencing (WGS) was performed using the Illumina MiSeq and analyzed using the TB Profiler. A single nucleotide polymorphism (SNP) threshold of ≤ 12 and phylogenetic methods were used to identify putative transmission clusters. An outbreak was confirmed using genomic data and epidemiologic links.ResultsOf the 297 MDR-TB cases, 246 (82.8%), 45 (15.2%), and 6 (2.0%) were simple MDR, extensively drug-resistant tuberculosis (pre-XDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), respectively. The sublineage 2.2 modern Beijing was the predominant (48.8%) MDR-TB strain in Taiwan. Phylogenetic analysis identified 25.3% isolates in 20 clusters, with cluster sizes ranging from 2 to 13 isolates. Nevertheless, only 2 clusters, one household and one community, were confirmed as outbreaks. In this study, we found that males had a higher risk of MDR-TB transmission compared to females, and those infected with the sublineage 2.1-proto-Beijing genotype isolates were at a higher risk of transmission. Furthermore, 161 (54.2%) isolates harbored compensatory mutations in the rpoC and non-rifampicin resistant determinant region (non-RRDR) of the rpoB gene. MDR-TB strains containing rpoB S450L and other compensatory mutations concurrently were significantly associated with clusters, especially the proto-Beijing genotype strains with the compensatory mutation rpoC E750D or the modern Beijing genotype strains with rpoC D485Y/rpoC E1140D.DiscussionRoutine and continuous surveillance using WGS-based analysis is recommended to warn of risks and delineate transmission clusters of MDR-TB. We proposed the use of compensatory mutations as epidemiological markers of M. tuberculosis to interrupt putative MDR-TB transmission.

Background: The notable decline in the number of Tregs within Necrotizing enterocolitis (NEC) intestinal tissues，contribute to excessive inflammation and necrosis, yet the precise underlying factors remain enigmatic. Ferroptosis, a novel cell death stemming from a disrupted lipid redox metabolism, is the focus of this investigation. Specifically, this study delves into the ferroptosis of Treg cells in the context of NEC and observes the protective effects exerted by vitamin E intervention, which aims to mitigate ferroptosis of Treg cells. Methods: To investigate the reduction of Treg cells in NEC intestine, we analyzed its association with ferroptosis from multiple angles. We constructed a mouse with a specific knockout of Gpx4 in Treg cells, aiming to examine the impact of Treg cell ferroptosis on NEC intestinal injury and localized inflammation. Ultimately, we employed vitamin E treatment to mitigate ferroptosis in NEC intestine's Treg cells, monitoring the subsequent amelioration in intestinal inflammatory damage. Results: The diminution of Treg cells in NEC is attributed to ferroptosis stemming from diminished GPX4 expression. Gpx4-deficient Treg cells exhibit impaired immunosuppressive function and are susceptible to ferroptosis. This ferroptosis of Treg cells exacerbates intestinal damage and inflammatory response in NEC. Notably, Vitamin E can inhibit the ferroptosis of Treg cells, subsequently alleviating intestinal damage and inflammation in NEC. Additionally, Vitamin E bolsters the anti-lipid peroxidation capability of Treg cells by upregulating the expression of GPX4. Conclusion: In the context of NEC, the ferroptosis of Treg cells represents a significant factor contributing to intestinal tissue damage and an exaggerated inflammatory response. GPX4 is pivotal for the viability and functionality of Treg cells. Vitamin E exhibits the capability to mitigate the ferroptosis of Treg cells, thereby enhancing their number and function, which plays a crucial role in mitigating intestinal tissue damage and inflammatory response in NEC.

BackgroundDigital technologies have impacted health care delivery globally, and are increasingly being deployed in clinical practice. However, there is limited research on patients’ expectations of doctors’ clinical competencies when using digital health care technologies (DHTs) in medical care. Understanding these expectations can reveal competency gaps, enhance patient confidence, and contribute to digital innovation initiatives. ObjectiveThis study explores patients’ perceptions of doctors’ use of DHTs in clinical care. Using Singapore as a case study, it examines patients’ expectations regarding doctors’ communication, diagnosis, and treatment skills when using telemedicine, health apps, wearable devices, electronic health records, and artificial intelligence. MethodsFindings were drawn from individual semistructured interviews with patients from outpatient clinics. Participants were recruited using purposive sampling. Data were analyzed qualitatively using thematic analysis. ResultsTwenty-five participants from different backgrounds and with various chronic conditions participated in the study. They expected doctors to be adept in handling medical data from apps and wearable devices. For telemedicine, participants expected a level of assessment of their medical conditions akin to in-person consultations. In addition, they valued doctors recognizing when a physical examination was necessary. Interestingly, eye contact was appreciated but deemed nonessential by participants across all age bands when electronic health records were used, as they valued the doctor’s efficiency more than eye contact. Nonetheless, participants emphasized the need for empathy throughout the clinical encounter regardless of DHT use. Furthermore, younger participants had a greater expectation for DHT use among doctors compared to older ones, who preferred DHTs as a complement rather than a replacement for clinical skills. The former expected doctors to be knowledgeable about the algorithms, principles, and purposes of DHTs such as artificial intelligence technologies to better assist them in diagnosis and treatment. ConclusionsBy identifying patients’ expectations of doctors amid increasing health care digitalization, this study highlights that while basic clinical skills remain crucial in the digital age, the role of clinicians needs to evolve with the introduction of DHTs. It has also provided insights into how DHTs can be integrated effectively into clinical settings, aligning with patients’ expectations and preferences. Overall, the findings offer a framework for high-income countries to harness DHTs in enhancing health care delivery in the digital era.

ABSTRACT For facilitating tuberculosis (TB) control, we used a whole-genome sequencing (WGS)-based approach to delineate transmission networks in a country with an intermediate burden of TB. A cluster was defined as Mycobacterium tuberculosis isolates with identical genotypes, and an outbreak was defined as clustered cases with epidemiological links (epi-links). To refine a cluster predefined using space oligonucleotide typing and mycobacterial interspersed repetitive unit variable tandem repeat typing, we analyzed one pansusceptible TB (C1) and three multidrug-resistant (MDR)-TB (C2-C4) clusters from different scenarios. Pansusceptible TB cluster (C1) consisting of 28 cases had ≤5 single nucleotide polymorphisms (SNPs) difference between their isolates. C1 was a definite outbreak, with cases attending the same junior high school in 2012. Three MDR-TB clusters (C2-C4) with distinct genotypes were identified, each consisting of 12–22 cases. Some of the cases had either ≤5 or ≤15 SNPs difference with clear or probable epi-links. Of note, even though WGS could effectively assist TB contact tracing, we still observed missing epi-links in some cases within the same cluster. Our results showed that thresholds of ≤5 and ≤15 SNPs difference between isolates were used to categorize definite and probable TB transmission, respectively. Furthermore, a higher SNP threshold might be required to define an MDR-TB outbreak. WGS still needs to be combined with classical epidemiological methods for improving outbreak investigations. Importantly, different SNP thresholds have to be applied to define outbreaks.IMPORTANCETB is a chronic disease. Depending on host factors and TB burden, clusters of cases may continue to increase for several years. Conventional genotyping methods overestimate TB transmission, hampering precise detection of outbreaks and comprehensive surveillance. WGS can be used to obtain SNP information of M. tuberculosis to improve discriminative limitations of conventional methods and to strengthen delineation of transmission networks. It is important to define the country-specific SNP thresholds for investigation of transmission. This study demonstrated the use of thresholds of ≤5 and ≤15 SNPs difference between isolates to categorize definite and probable transmission, respectively. Different SNP thresholds should be applied while a higher cutoff was required to define an MDR-TB outbreak. The utilization of SNP thresholds proves to be crucial for guiding public health interventions, eliminating the need for unnecessary public health actions, and potentially uncovering undisclosed TB transmissions.

Abstract In systems exhibiting the non-Hermitian skin effect (NHSE), the bulk spectrum under open boundary conditions (OBC) significantly differs from that of its periodic counterpart. This disparity renders the conventional bulk-boundary correspondence (BBC) inapplicable. Here we propose an intuitive approach called doubling and swapping to restore the BBC, using the non-Hermitian Su-Schrieffer-Heeger model as an example. Explicitly, we construct a modified system free of NHSE by swapping the asymmetric intracell hoppings in every second primitive unit cell. Importantly, this change does not alter the OBC spectrum. As a result, the modified periodic system can serve as the bulk for defining topological invariants that accurately predict edge states and topological phase transitions. The basic principle is applicable to many other systems. By extending the study to disordered systems in which the asymmetric hoppings are randomly swapped, we show that two types of winding numbers can also be defined to account for the NHSE and topological edge states, respectively.

Abstract GCG ((−)‐gallocatechin gallate) and EGCG ((−)‐epigallocatechin‐3‐gallate) are main biologically active polyphenolic compounds in tea leaves, and EGCG has been studied for its potential effects on alleviating diabetic nephropathy (DN). Previous studies showed that GCG exhibited better hypoglycemic and antioxidant efficacy than EGCG. However, the efficacy and molecular mechanisms of GCG in the protection of DN are unknown. In this study, db/db mice were administered with EGCG or GCG orally for 20 weeks to comparatively investigate their effects on DN. These results revealed that GCG was significantly more effective than EGCG in decreasing water intake and urine excretion, reducing fasting blood glucose levels and systolic blood pressure, improving mesenteric artery contractility, enhancing the right renal hemodynamics, and improving key renal function markers. Through transcriptome analysis, S100A8/S100A9, two regulators of interstitial fibrosis, were identified and found to be more sensitive to GCG intervention, which was further confirmed by mRNA and protein expression data. In addition, the molecular docking analysis results demonstrated that GCG displayed a superior binding affinity toward S100A8/S100A9 in comparison to EGCG. Overall, our study found that GCG holds significant potential for the treatment of DN and outperforms EGCG in terms of efficacy.

Objective: To establish a high performance liquid chromatography-electrochemical detection (HPLC-ECD) method for the determination of polyphenolic compounds in the leaves of Houttuynia cordata and investigate the contribution of different compounds to the antioxidant activity by the correlation analysis. Methods: The leaves of Houttuynia cordata were extracted by ultrasonic extraction with 80% (v/v) methanol, and the content of 12 polyphenolic compounds was determined by the established HPLC-ECD method. The total phenolics content of Houttuynia cordata leaves was determined by the Folin-ciocalteu method. The antioxidant activities were evaluated by radical scavenging ability and ferric reducing antioxidant power (FRAP). Cluster heat map and gray correlation analysis were used for multivariate statistical analysis. Results: The established HPLC-ECD method showed good linearity, precision, repeatability and stability, with an average recovery of 93.25%~103.97% and RSD value of 1.99%~4.47%. The total phenolic content of Houttuynia cordata leaves from different sources ranged from 5.98~52.86 mg GAE/g, which was significantly correlated with ABTS+, DPPH radical scavenging ability and ferric ion reduction ability (P

AbstractThis study proposed an interpretable model that combines Random Forest (RF), Optuna hyperparameter optimization, and SHapley Additive exPlanations (SHAP) to achieve optimal landslide susceptibility evaluation and provide explanations in the northwest region of Yunnan Province in China. First, an inventory of 4447 landslides and 23 related factors was considered for the landslide susceptibility assessment. Subsequently, a hyperparameter-optimized RF model was developed using the Optuna framework and the training dataset to generate landslide susceptibility maps. The performance of the models were evaluated using accuracy (ACC), precision (PPV), recall (TPR), F1-score (F1), and the Area Under the Curve (AUC) based on the Receiver Operating Characteristic. Furthermore, the interpretability of the model was enhanced through the implementation of SHAP. The proposed model demonstrated outstanding performance on the test set, achieving an ACC of 0.7792, PPV of 0.7448, TPR of 0.8769, F1 of 0.8055, and an AUC of 0.8387. The interpretability analysis revealed that elevation, population density, distance from roads, and normalized difference vegetation index were the primary factors influencing landslide occurrences in the study area. This study provides a comprehensive framework for evaluating landslide susceptibility in specific regions and offers invaluable insights for the prevention and management of landslide disasters.

ObjectiveTo accurately verify the pathogenicity of variants of uncertain significance (VUS) in MUT and MMACHC genes through mass spectrometry and silico analysis.MethodsThis multicenter retrospective study included 35 participating units (ClinicalTrials.gov ID: NCT06183138). A total of 3,071 newborns (within 7 days of birth) were sorted into carrying pathogenic/likely pathogenic (P/LP) variants and carrying VUS, non-variant groups. Differences in metabolites among the groups were calculated using statistical analyses. Changes in conservatism, free energy, and interaction force of MMUT and MMACHC variants were analyzed using silico analysis.ResultsThe percentage of those carrying VUS cases was 68.15% (659/967). In the MMUT gene variant, we found that C3, C3/C2, and C3/C0 levels in those carrying the P/LP variant group were higher than those in the non-variant group (p < 0.000). The conservative scores of those carrying the P/LP variant group were >7. C3, C3/C0, and C3/C2 values of newborns carrying VUS (c.1159A>C and c.1286A>G) were significantly higher than those of the non-variant group and the remaining VUS newborns (p < 0.005). The conservative scores of c.1159A>C and c.1286A>G calculated by ConSurf analysis were 9 and 7, respectively. Unfortunately, three MMA patients with c.1159A>C died during the neonatal period; their C3, C3/C0, C3/C2, and MMA levels were significantly higher than those of the controls.ConclusionCommon variants of methylmalonic acidemia in the study population were categorized as VUS. In the neonatal period, the metabolic biomarkers of those carrying the P/LP variant group of the MUT gene were significantly higher than those in the non-variant group. If the metabolic biomarkers of those carrying VUS are also significantly increased, combined with silico analysis the VUS may be elevated to a likely pathogenic variant. The results also suggest that mass spectrometry and silico analysis may be feasible screening methods for verifying the pathogenicity of VUS in other inherited metabolic diseases.

Interaction of the lanthanide nitrates M(NO3)3 (M = Gd, Eu) with methylcucurbit[5]uril (Me10Q[5]) in the presence of transition metal chlorides (ZnCl2 and FeCl3) in acidic media resulted in the isolation of the complexes [Me10Q[5]Gd(H2O)2Cl Gd(H2O)6](ZnCl4)2∙Cl∙8.9H2O (1) and [Me10Q[5]Eu(H2O)3Cl(H3O)](FeCl4)3 (2). The molecular structures of 1 and 2 have been determined by single crystal X-ray crystallography, and reveal discrete complexes which are involved in dense stacking with adjacent Me10Q[5]s linked via H-bonding and/or metal anions resulting in a supramolecular assembly.

Summary: Premature ovarian failure (POF) is a complex and heterogeneous disease that causes infertility and subfertility. However, the molecular mechanism of POF has not been fully elucidated. Here, we show that the loss of adenylyl cyclase III (Adcy3) in female mice leads to POF and a shortened reproductive lifespan. We found that Adcy3 is abundantly expressed in mouse oocytes. Adcy3 knockout mice exhibited the excessive activation of primordial follicles, progressive follicle loss, follicular atresia, and ultimately POF. Mechanistically, we found that mitochondrial oxidative stress in oocytes significantly increased with age in Adcy3-deficient mice and was accompanied by oocyte apoptosis and defective folliculogenesis. In contrast, compared with wild-type female mice, humanized ADCY3 knock-in female mice exhibited improved fertility with age. Collectively, these results reveal that the previously unrecognized Adcy3 signaling pathway is tightly linked to female ovarian aging, providing potential pharmaceutical targets for preventing and treating POF.

In this study odour-less additive were added to modify the asphalt properties in order to reduce the asphalt flue gas produced during the application process.Three different brands of No. 70 asphalt were chosen as the base asphalt and different dosages of odour-less additive were added to prepare the odour-less asphalt. The effect of the odour-less additive on VOCs, CO, H2S, NO and SO2 were tested by a portable detector to determine the optimal dosage. Then, a gas chromatography was adopted to further analyze the effect of odour-less additive on the compounds in the VOCs. SEM was used to investigate the mechanism of odour-less asphalt. Finally, the effect of odour-less additive on the basic performance of asphalt and on the road performance of asphalt mixtures were analyzed. Research results indicate that the optimal dosage of odour-less additive for No.70 asphalt is 0.04%; The odour-less ratio of the total emissions of the five gases can reach up to 52.9%; Crude oil and the processing technology exert relative huge influence on the concentration of VOCs and the higher the concentration of the compound, the better the odour-less effect, and the odour-less ratio of ethanethiol can reach up to 73.7%. The odour-less asphalt inhibits the volatilization of small molecular substances by increasing the specific surface area of asphalt and improving the inter-molecular cohesion, thereby achieving the purpose of reducing asphalt flue gas; odour-less additive yields little effect on the performance of asphalt and asphalt mixtures.

Community parks in old urban areas have problems such as outdated facilities and low quality, which inhibit the development of healthy aging. However, limited research has examined the correlation between such park characteristics and park satisfaction among elderly individuals. Additionally, the mechanisms underlying this association remain unclear. In this investigation, a moderated mediation framework grounded in self-determination theory was formulated to probe the interplay between these variables, with a specific focus on the mediating influence of social self-efficacy among the elderly and the moderating effect of use intention. A questionnaire survey (N = 319) was conducted in Shamian Park, Guangzhou, employing structural equation modeling for data analysis. Findings indicate that, even after controlling for demographic factors, park characteristics not only exert a direct influence on satisfaction but also exhibit an indirect impact through the mediation of social self-efficacy, with both pathways being moderated by use intention. This study has implications for how to improve the design of community parks in old urban areas in developing countries to better meet the basic needs of the elderly and promote healthy aging.

The dynamics of excited‐state charge transfer (CT) in second near‐infrared (NIR‐II) fluorophore proceeds with conformational change that govern fluorescence. Unveiling the relationship between CT dynamics and conformational change in excited state is of great fundamental significance in optimizing NIR‐II fluorescence but remains less explored. This study unveils the pivotal role of large conformational change in promoting the evolution of emissive CT state into nonemissive CT state in NIR‐II fluorophore (CA‐BBT). Spectroscopic and computational results reveal that large conformational rotation/twisting leads to a pronounced increase in the CT character in excited state. This heightened CT character in CA‐BBT enables a rapid evolution of emissive CT state into a nonemissive CT state within 1.4 ps, as observed by ultrafast spectroscopy. Subsequently, this nonemissive state dominates nonradiative decay, resulting in very low NIR‐II fluorescence. Preventing such detrimental evolution by constraining the conformational dynamics of CA‐BBT results in a 10‐fold enhancement of NIR‐II fluorescence, enabling high‐resolution dynamic visualization of vasculature within osteosarcoma. This study offers a profound understanding of the relationship between CT dynamics and conformational changes in NIR‐II fluorescence, presenting innovative perspectives to develop bright NIR‐II fluorophores.

AbstractWe performed the first sequencing of the complete mitogenome of Botyodes diniasalis by high-throughput sequencing. A circular DNA molecule of 15,219 bp in size, encoding 2 rRNAs, 22 tRNAs, and 13 PCGs, contains a non-coding AT-rich region. The overall nucleotide composition of the genome is A (39.5%), T (41.3%), C (11.3%), and G (7.8%). Phylogenetic analysis based on mitogenomic data suggest that the species B. diniasalis has a close evolutionary relationship with B. principalis in Margaroniini. The complete mitogenome of B. diniasalis will serve as a valuable resource for future studies on evolution, taxonomy, genetic conservation, and utilization of Botyodes.

Rich observation data generated by ubiquitous sensors are vital for wetland monitoring, spanning from the prediction of natural disasters to emergency response. Such sensors use different data acquisition and description methods and, if combined, could provide a comprehensive description of the wetland. Unfortunately, these data remain hidden in isolated silos, and their variety makes integration and interoperability a significant challenge. In this work, we develop a semantic model for wetland monitoring data using an agile and modular approach, namely, wetland monitoring ontology (WMO), which contains five modules: wetland ecosystem, monitoring indicator, monitoring context, geospatial context, and temporal context. The proposed ontology supports the semantic interoperability and integration of wetland monitoring data from multiple sources, domains, modes, and spatiotemporal scales. We also provide two real-world use cases to validate the WMO and demonstrate the WMO’s usability and reusability.

Red honeybush tea (RHT) is a tea product developed from Cyclopia spp. which is endemic to South Africa. Aside refreshment, RHT has over the years been used traditionally in the treatment of various diseases including type 2 diabetes. This study investigated the in vivo antioxidant and anti-diabetic activity of RHT concentrated hot water extract in type 2 diabetes (T2D) model of rats. T2D was induced starting with feeding 10 % fructose solution ad libitum for 2 weeks followed by a single intraperitoneal injection of streptozotocin (40 mg/kg body weight (BW)). Five weeks of treatment of RHT led to significant (P < 0.05) elevation in serum insulin, pancreatic β-cell function, HDL-c levels with concomitant decrease in AST, ALT, ALP, urea, CK-MB, fructosamine, total cholesterol, triglycerides, LDL-c, and insulin resistance in diabetic rats. RHT also significantly (P < 0.05) decreased MDA levels and enhanced level of GSH, activity of SOD, catalase, GR in most of organs (pancreas, liver, kidneys, and heart). Significantly (P < 0.05) improved morphological changes in the islets and β-cells were observed in rats treated with RHT. The data of this study suggest that RHT demonstrates an outstanding antioxidant and anti-diabetic effects in STZ-induced T2D model of rats.

Nanozymes with superior antioxidant properties offer new hope for treating oxidative stress-related inflammatory skin diseases. However, lacking sufficient catalytic activity or having complex material designs limit the application of current metallic nanozymes in inflammatory skin diseases. Here, we report a simple and effective twin-defect platinum nanowires (Pt NWs) enzyme with multiple mimetic enzymes and broad-spectrum ROS scavenging capability for the treatment of inflammatory skin diseases in mice (including psoriasis and rosacea). Pt NWs with simultaneous superoxide dismutase, glutathione peroxidase and catalase mimetic enzyme properties exhibit cytoprotective effects against ROS-mediated damage at extremely low doses and significantly improve treatment outcomes in psoriasis- and rosacea-like mice. Meanwhile, these ultrasmall sizes of Pt NWs allow the nanomaterials to effectively penetrate the skin and do not produce significant biotoxicity. Therefore, Pt NWs have potential applications in treating diseases related to oxidative stress or inflammation.

Accurate monitoring of agricultural droughts in data-scarce areas remains a challenge due to their intricate spatiotemporal patterns. Deep learning represents a promising approach for developing efficient drought monitoring models. In this study, a hybrid deep learning model, combining convolutional neural network and random forest (CNN-RF), is proposed to monitor agricultural droughts in a mountainous region located in Southwest China. The model integrates multisource data obtained from the Moderate Resolution Imaging Spectroradiometer (MODIS) satellite sensor, Global Land Data Assimilation System (GLDAS), Climate Hazards Group InfraRed Precipitation with Station Data (CHIRPS) and digital elevation model (DEM) to reproduce a station-based 3-month Standardized Precipitation Evapotranspiration Index (SPEI-3) during 2001–2020. Performance evaluation of the proposed model utilized an in situ soil moisture dataset and grain yields as benchmarks. The results demonstrated the superiority of the CNN-RF model over both the CNN and RF models in terms of estimating SPEI-3 and forecasting drought categories, as quantified by the lowest root mean square error (RMSE0.9) and the multi-class receiver operating characteristic (ROC) based area under curves (AUC) (AUC=0.86). The CNN-RF model successfully reproduced the spatial heterogeneity of the drought pattern while maintaining temporal and spatial consistency with actual drought conditions. Notably, strong consistency was observed between the simulated SPEI-3 and the 3-month Standardized Soil Moisture Index (SSMI-3) (CC=0.42, p

In this study, phase-transited lysozyme (PTL) induced Ca10(PO4)6(OH)2 (PTL-HA) coating was applied to the 3D-printed titanium surface for improving bioactivity. The morphology and phase of the coating were analyzed by EDS, SEM, XRD, and XPS, while biocompatibility was investigated in vitro. The observation from SEM showed that a uniform coating with the presence of spheric-like and plate-shaped crystals was covered on the titanium. The main composition of the coating was Ca10(PO4)6(OH)2. More importantly, the in vitro results showed the PTL-HA coating could upregulate the expression of osteogenic-related genes. Therefore, it is considered that the phase-transited lysozyme-induced hydroxyapatite film was a promising, rapid, low-cost, and green route to improve the bioactivity of a bone implant.

Rain-on-snow (ROS) events can cause rapid snowmelt, leading to flooding and avalanches in the pan-Arctic and can also lead to starvation and the death of massive ungulates. Reanalysis products (e.g., ERA-I, ERA5-land, JRA55, MERRA2) are the primary source data for the research about ROS events in the large-scale region. However, the accuracy and reliability of reanalyses have never been evaluated with respect to the determination of terrestrial ROS events. The present study aims to statistically evaluate the performance of reanalysis datasets in identifying ROS events with different criteria based on in-situ rainfall data and MODIS snow cover product. The results show that all reanalysis datasets exhibit poor performance (Recall ≤ 0.16, Kappa coefficient ≤ 0.26, F-score ≤ 0.42, MCC ≤ 0.33) in all criteria in the pan-Arctic, mainly due to the low accuracy of rainfall data (r ≤ 0.56). Nevertheless, the spatial distribution pattern and hot spots of ROS from all reanalysis datasets are essentially close. The hot spots of ROS are mainly located on the coast of Alaska, Norway, and Greenland. All reanalyses demonstrate an increase in rainy days, but there is little overall change in ROS events due to the reduction in snow cover days. This work suggests that none of the current reanalyses are reliable in the determination of ROS events due to the poor representation of the rainfall parameterization scheme. The development of alternative strategies that can investigate ROS events at large-scale is urgently needed in a changing Arctic under rapid warming.

Abstract The genomic components of multipartite viruses are encapsidated in separate virus particles, and the frequencies of genomic components represent one of the key genetic features. Many begomoviruses of economic significance are bipartite, and the details of the association between their genomic components remain largely unexplored. We first analyzed the temporal dynamics of the quantities of DNA-A and DNA-B and the B/A ratio of the squash leaf curl China virus (SLCCNV) in plants and found that while the quantities of DNA-A and DNA-B varied significantly during infection, the B/A ratio remained constant. We then found that changes in the B/A ratio in agrobacteria inoculum may significantly alter the B/A ratio in plants at 6 days post inoculation, but the differences disappeared shortly thereafter. We next showed that while the quantities of DNA-A and DNA-B among plants infected by agrobacteria, sap transmission and whitefly-mediated transmission differed significantly, the B/A ratios were similar. Further analysis of gene expression revealed that the ratio of the expression of genes encoded by DNA-A and DNA-B varied significantly during infection. Finally, we monitored the temporal dynamics of the quantities of DNA-A and DNA-B and the B/A ratio of another bipartite begomovirus, and a constant B/A ratio was similarly observed. Our findings highlight the maintenance of a constant ratio between the two genomic components of bipartite begomoviruses during infection and transmission, and provide new insights into the biology of begomoviruses.

Multiscale virtual environments (MSVEs) allow the integration of elements and environments at different scale levels into a unified space, which facilitates researchers’ perception, understanding, and experimental research of complex geospatial spaces. Although there have been several methods for achieving multiscale effects in virtual environments (VEs), they cannot assist users in constructing more complete spatial cognitive maps and presenting multiscale information efficiently. This study proposes a hierarchical-structure-based MSVE construction method, which can effectively integrate multiscale information and ensure that the richness of details of information is gradually enhanced with the progression of the hierarchical structure. In addition, a spatial navigation study is conducted, considering the relationship between users’ perspective changes and spatial cognition, and the effects of users’ perspective changes on their spatial cognition in an MSVE are explored. A multiscale virtual wetland environment covering four levels is constructed to conduct a case study of a virtual environment of a wetland of Poyang Lake. The research results show that the proposed method is feasible. Moreover, the spatial navigation based on the change in the hierarchical perspective is in line with the spatial cognitive habits of users, which can satisfy the cognitive needs of users from the macro-region to specific wetland landscapes.

Metabolic syndrome (MetS) significantly predisposes individuals to diabetes and is a prognostic factor for the progression of diabetic nephropathy (DN). This study aimed to evaluate the efficacy of (-)–gallocatechin gallate (GCG) in alleviating signs of MetS-associated DN in db/db mice. We administered GCG and monitored its effects on several metabolic parameters, including food and water intake, urinary output, blood glucose levels, glucose and insulin homeostasis, lipid profiles, blood pressure, and renal function biomarkers. The main findings indicated that GCG intervention led to marked improvements in these metabolic indicators and renal function, signifying its potential in managing MetS and DN. Furthermore, transcriptome analysis revealed substantial modifications in gene expression, notably the downregulation of pro-inflammatory genes such as S100a8, S100a9, Cd44, Socs3, Mmp3, Mmp9, Nlrp3, IL–1β, Osm, Ptgs2, and Lcn2 and the upregulation of the anti-oxidative gene Gstm3. These genetic alterations suggest significant effects on pathways related to inflammation and oxidative stress. In conclusion, GCG demonstrates therapeutic efficacy for MetS–associated DN, mitigating metabolic disturbances and enhancing renal health by modulating inflammatory and oxidative responses.

Hydrogen production technology has triggered a research boom in order to alleviate the problems of environmental pollution and the pressure on non-renewable energy sources. The key factor of this technology is the use of an efficient photocatalyst. g-C3N4 is a typical semiconductor photocatalytic material that is non-toxic and environmentally friendly and does not cause any serious harm to human beings. Therefore, it can be applied to drug degradation and the photocatalytic production of H2. Combined with ZnIn2S4, this semiconductor photocatalytic material, with a typical lamellar structure, has become one of the most promising catalysts for research due to its suitable bandgap structure and excellent photoelectric properties. In this study, 10% g-C3N4/ZnIn2S4 nano-heterojunction composite photocatalytic materials were successfully prepared by compounding ZnIn2S4 and g-C3N4 semiconductor materials with good visible-light-trapping ability. Under visible light irradiation, the photocatalytic activity of the composites was significantly better than that of pure g-C3N4 and ZnIn2S4. This is attributed to the formation of a heterojunction structure, which effectively inhibited the recombination of photogenerated carriers through the interfacial contact between the two semiconducting materials, and then improved the separation efficiency of the photogenerated electron–hole pairs, thus enhancing the catalytic activity. In this study, pure g-C3N4 and ZnIn2S4 were prepared using calcination and hydrothermal methods, and then, the composites were synthesized using ultrasonic and hydrothermal means. The differences in the structure, morphology, and hydrogen production performance of the materials before and after recombination were analyzed in detail using XRD, SEM, and FTIR characterization, which further verified that the 10% g-C3N4/ZnIn2S4 nano-heterojunction composites possessed excellent photocatalytic activity and stability, providing new possibilities for the optimization and application of photocatalytic hydrogen production technology.