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Luculia yunnanensis is a vulnerable species endemic to Yunnan Province, Southwestern China, which has high ornamental value. Its wild population has not been fully protected and utilized for a long time, which is not conducive to the long-term stable development of this species. Genetic diversity assessment is the basis and prerequisite for the conservation of rare species. In this study, 21 phenotypic traits and 17 highly polymorphic EST-SSR markers were used to analyze the genetic diversity and genetic structure of 164 individuals from six L. yunnanensis populations. The coefficient of variation of 21 phenotypic traits ranged from 11.76% to 52.58% (mean=21.72%), and the coefficient of variation of 18 traits was less than 30%. The average values of Ne, I, Ho and He were 1.710, 0.619, 0.384, and 0.352, respectively. The genetic diversity of LLO (Ho = 0.476 and He = 0.426) and LCM (Ho = 0.424 and He = 0.381) populations in Lushui County was highest. The GDX populations (Ho = 0.335 and He = 0.269) isolated by Gaoligong Mountain had the lowest genetic diversity. The AMOVA results showed that 13.04% of the genetic variation was among populations and 86.96% was within populations. The average phenotypic differentiation coefficient of phenotypic traits among populations was 18.69%. The results of phenotypic and genetic variation analysis were consistent, indicating that the most of variation exists within population. Genetic structure, UPGMA clustering and PCA analysis results showed that the populations of L. yunnanensis had obvious geographical divisions, and the populations distributed in the southern region and distributed in the northern region of the Nujiang River clustered into one group respectively. Combining the results of phenotypic and molecular markers, we recommend that give priority to the protection of LLO, LCM and GDX population, in order to ensure the sustainable utilization of L. yunnanensis germplasm resources.

IntroductionSeagrass-associated microbial communities play a crucial role in the growth and health of seagrasses. However, like seagrass meadows, seagrass-associated microbial communities are often affected by eutrophication. It remains unclear how eutrophication influences the composition and function of microbial communities associated with different parts of seagrass.MethodsWe employed prokaryotic 16S rRNA gene high-throughput sequencing combining microbial community structure analysis and co-occurrence network analysis to investigate variances in microbial community compositions, potential functions and complexities across sediment, seagrass leaves, and seawater within different eutrophic areas of two adjacent seagrass meadows on Hainan Island, China.ResultsOur results indicated that microbial diversity on seagrass leaves was significantly lower than in sediment but significantly higher than in seawater. Both sediment and phyllosphere microbial diversity showed no significant difference between the highly eutrophic and less eutrophic sites in each lagoon. However, sediment microbial diversity was higher in the more eutrophic lagoon, while phyllosphere microbial diversity was higher in the less eutrophic lagoon. Heavy eutrophication increased the relative abundance of phyllosphere microorganisms potentially involved in anaerobic metabolic processes, while reducing those responsible for beneficial functions like denitrification. The main factor affecting microbial diversity was organic carbon in seawater and sediment, with high organic carbon levels leading to decreased microbial diversity. The co-occurrence network analysis revealed that heavy eutrophication notably reduced the complexity and internal connections of the phyllosphere microbial community in comparison to the sediment and seawater microbial communities. Furthermore, ternary analysis demonstrated that heavy eutrophication diminished the external connections of the phyllosphere microbial community with the sediment and seawater microbial communities.ConclusionThe pronounced decrease in biodiversity and complexity of the phyllosphere microbial community under eutrophic conditions can lead to greater microbial functional loss, exacerbating seagrass decline. This study emphasizes the significance of phyllosphere microbial communities compared to sediment microbial communities in the conservation and restoration of seagrass meadows under eutrophic conditions.

AimTo explore the association of Hemoglobin-to-Red Cell Distribution Width Ratio (HRR) with the risk of three-month unfavorable outcomes in acute ischemic stroke (AIS).MethodsA secondary analysis was conducted based on a prospective cohort study. A total of 1,889 patients with AIS treated in South Korea from January 2010 to December 2016 were enrolled. Multivariable logistic regression was conducted to investigated the independent relationship between HRR and risk of three-month unfavorable outcomes in AIS. Fitted smoothing curves were used to determine non-linear correlations. The recursive method was employed to explore the turning point and build a two-piece linear regression model. In addition, a set of subgroup analyses were carried out to evaluate the relationship between HRR and risk of three-month unfavorable outcomes.ResultsMultivariate analysis in which potential confounders were adjusted for indicated that the risk of unfavorable outcomes was reduced by 10% for each unit increased of HRR [OR = 0.90, 95% CI: 0.84–0.96, p = 0.0024]. In addition, a non-linear relationship was observed between HRR and risk of three-month unfavorable outcomes, which had an inflection point of HRR was 10.57. The effect sizes and the confidence intervals on the left side of the inflection point were 0.83 (0.75, 0.91), p = 0.0001. On the right side of the inflection point, no association was found between HRR and the risk of three-month unfavorable outcomes.ConclusionThis study demonstrates a negative association between HRR and risk of three-month unfavorable outcomes. The relationship between HRR and risk of three-month unfavorable outcomes is non-linear. The correlation is negative for HRR values less than 10.57. For, HRR higher than 10.57, HRR is not associated with the risk of three-month unfavorable outcomes.

Background Unhealthy eating habits, such as low vegetable and fruit intake, are associated with many health problems. 24-h movement behaviors have been reported to be positively associated with numerous health-related outcomes. Despite the importance of these two modifiable lifestyle behaviors in building healthy habits in university students, there is a paucity of relevant research in this population. Therefore, this study aims to examine the correlation between compliance with 24-h movement guideline (24-h MG) and intake of fruits and vegetables (IFV) in Chinese university students. Methods This study investigated the relationship between the compliance with 24-h MG and IFV in 1,793 Chinese university students using a convenience sampling method online. Physical activity (PA) and sedentary behavior (SB) were assessed by the International Physical Activity Questionnaire-Short Form, while sleep was measured using the Pittsburgh Sleep Quality Index. The Chinese version of the Health Promoting Lifestyle Profile II was used to measure IFV. Generalized linear models were applied to examine the correlation between compliance with the 24-h MG and eating habits. Results The proportion of participants who routinely consumed vegetables and fruits was 24.6% and 43.1%, respectively, while the proportion of meeting the three 24-h MG and a combination of any two guidelines was 27.8% and 40.1%, respectively. Meeting all three guidelines was associated with a greater IFV intake compared to not meeting either guideline. Meeting all three guidelines (OR = 2.42 [1.63, 3.58]) and the combination of moderate to vigorous PA (MVPA) and sleep (OR = 2.06 [1.37, 3.10]) were positively associated with the frequency of vegetable consumption (p < 0.05). As well, meeting all three guidelines (OR = 2.06 [1.37, 3.10]), the combination of MVPA and sleep (OR = 1.72 [1.04, 2.84]), and sleep only (OR = 1.88 [1.21, 2.92]) were positively associated with fruits consumption (p < 0.05). Conclusion Almost a third of the university students met the three 24-h MG, and compliance with all three guidelines was associated with a higher frequency of IFV. Furthermore, meeting the sleep guideline alone or in conjunction with the PA, and meeting the entire 24-h MG was associated with greater consumption of fruits.

Summary: The immune evasion of emerging SARS-CoV-2 variants significantly undermines current vaccination efforts, calling for an updated vaccine composition. To identify optimal booster candidates against circulating JN.1, a panel of variant spikes were characterized. The omicron spikes exhibited reduced plasma membrane expression, accompanied by lower cell-cell fusion but increased viral entry. Regimens with DNA prime-DNA boost or DNA prime-adenoviral vectored vaccine boost by intramuscular immunization elicited neutralizing antibody (NAbs) and T cell responses against all variants except BA.2.86 and JN.1. Intranasal immunization induced high IgA and NAb titers in bronchoalveolar lavage against all variants except BA.2.86 and JN.1. T cell responses were generally comparable for all immunogens tested. JN.1 completely escaped NAbs in one immunized cohort, and breakthrough infections marginally boosted antibody titers. Overall, this study indicates intrinsic difficulty in eliciting NAbs against the JN.1 strain, whereas vaccines based on XBB and EG.5.1 are relatively superior in generating cross-reactive NAbs.

ABSTRACT: Within the poultry industry, hens' reproductive performance is of great economic significance. The development and growth of follicles is a key aspect of hen egg production, and ovarian follicle growth and development are closely associated with granulosa cells (GCs) proliferation and the synthesis of steroid hormones. It has been confirmed by numerous studies that microRNAs (miRNAs) play important roles in the steroid hormone synthesis and proliferation of GCs. In this study, we examined the main miRNAs influencing hens' ability to reproduce, identified the miR-223 that is mainly expressed in atretic follicles based on sequencing, and investigated its role in GCs. Then, we used miR-223 mimic and inhibitor to knockdown or overexpress miR-223 expression. The result showed that miR-223 significantly inhibits both the steroid hormone synthesis and the proliferation of GCs. Subsequently, the results of the dual luciferase reporter experiment and bioinformatics prediction demonstrated that cysteine rich transmembrane BMP regulator 1 (CRIM1) was a downstream target gene of miR-223, and overexpression of miR-223 prevented CRIM1 expression. The function of CRIM1 was further investigated, and we observed a significant reduction in the synthesis of steroid hormones and the proliferation of GCs after transfection with CRIM1 siRNA. The opposite function of miR-223 was observed for CRIM1 in our study. Additionally, we demonstrated the involvement of the miR-223/CRIM1 axis in GCs through modulation of the AKT signaling pathway. Our data demonstrate the pivotal role of the miR-223 in the proliferation and steroid hormone synthesis of chicken GCs, which helps to explain how non-coding RNA (ncRNA) affects chicken reproductive function.

Abstract Impaired brain glucose metabolism is an early indicator of Alzheimer’s disease (AD); however, the fundamental mechanism is unknown. In this study, we found a substantial decline in isocitrate dehydrogenase 3β (IDH3β) levels, a critical tricarboxylic acid cycle enzyme, in AD patients and AD-transgenic mice’s brains. Further investigations demonstrated that the knockdown of IDH3β induced oxidation-phosphorylation uncoupling, leading to reduced energy metabolism and lactate accumulation. The resulting increased lactate, a source of lactyl, was found to promote histone lactylation, thereby enhancing the expression of paired-box gene 6 (PAX6). As an inhibitory transcription factor of IDH3β, the elevated PAX6 in turn inhibited the expression of IDH3β, leading to tau hyperphosphorylation, synapse impairment, and learning and memory deficits resembling those seen in AD. In AD-transgenic mice, upregulating IDH3β and downregulating PAX6 were found to improve cognitive functioning and reverse AD-like pathologies. Collectively, our data suggest that impaired oxidative phosphorylation accelerates AD progression via a positive feedback inhibition loop of IDH3β-lactate-PAX6-IDH3β. Breaking this loop by upregulating IDH3β or downregulating PAX6 attenuates AD neurodegeneration and cognitive impairments.

Accurate evaluation of terrestrial carbon balance is essential for designing climate change mitigation policies, and capabilities of remote sensing techniques in monitoring carbon fluxes are widely recognized for their great contributions to regional and global carbon budget accounting. In this review, we synthesized satellite-based data and methodologies to estimate the main flux components of terrestrial carbon balance and their uncertainties over the past two decades. The global gross primary production (GPP) during the period 2001–2022 is 134 ± 14 PgC yr−1, and nearly half of them occurs in tropical forest regions such as South America and Africa. Less than 2% of global GPP is converted into a net carbon sink of 2.28 ± 1.12 PgC yr−1 using satellite-based atmospheric inversion during 2015–2020, and this sink is comparable to the stock change-based estimate (2.49 PgC yr−1) but twice as large as model-based estimate (1.08 ± 0.78 PgC yr−1). By decomposing satellite-derived net carbon balance into different terms including satellite-derived carbon emissions from land-use change and wildfires (3.55 PgC yr−1), we inferred that ~ 43% of global GPP would be respired through soil microbes (57.1 PgC yr−1), but which is higher than the previous bottom-up estimate (39–46 PgC yr−1). We then propose that an accurate remote sensing of terrestrial carbon balance requires to enhance representations of photosynthetic responses to rising CO2 and disturbances, develop satellite-constrained belowground carbon dynamics and separate natural fluxes from anthropogenic CO2 emissions, by integrating multi-source satellite sensors in orbit, revolutionized remote sensing capabilities with focused field campaigns in data-scarce regions.

Abstract Background The surgical resection of very highly migrated lumbar disc herniation (VHM-LDH) is technically challenging owing to the absence of technical guidelines. Hence, in the present study, we introduced the transforaminal endoscopic lumbar discectomy (TELD) with two-segment foraminoplasty to manage VHM-LDH and evaluated its radiographic and midterm clinical outcomes. Materials and methods The present study is a retrospective analysis of 33 consecutive patients with VHM-LDH who underwent TELD with two-segment foraminoplasty. The foraminoplasty was performed on two adjacent vertebrae on the basis of the migration direction of disc fragments to fully expose the disc fragments and completely decompress the impinged nerve root. The operation duration, blood loss, intra- and postoperative complications, and recurrences were recorded. Additionally, imageological observations were evaluated immediately after the procedure via magnetic resonance image and computerized tomography. Clinical outcomes were evaluated by calculating the visual analog scale (VAS) score and Oswestry Disability Index (ODI). The MacNab criterion was reviewed to assess the patients’ opinions on treatment satisfaction. The resection rate of bony structures were quantitatively evaluated on postoperative image. The segmental stability was radiologically evaluated at least a year after the surgery. Additionally, surgery-related and postoperative complications were evaluated. Results The average age of the patients was 56.87 ± 7.77 years, with a mean follow-up of 20.95 ± 2.09 months. The pain was relieved in all patients immediately after the surgery. The VAS score and ODI decreased significantly at each postoperative follow-up compared with those observed before the surgery (P

Abstract Periodontitis is an inflammatory disease induced by the complex interactions between the host immune system and the microbiota of dental plaque. Oxidative stress and the inflammatory microenvironment resulting from periodontitis are among the primary factors contributing to the progression of the disease. Additionally, the presence of dental plaque microbiota plays a significant role in affecting the condition. Consequently, treatment strategies for periodontitis should be multi-faceted. In this study, a reactive oxygen species (ROS)-responsive drug delivery system was developed by structurally modifying hyaluronic acid (HA) with phenylboronic acid pinacol ester (PBAP). Curcumin (CUR) was encapsulated in this drug delivery system to form curcumin-loaded nanoparticles (HA@CUR NPs). The release results indicate that CUR can be rapidly released in a ROS environment to reach the concentration required for treatment. In terms of uptake, HA can effectively enhance cellular uptake of NPs because it specifically recognizes CD44 expressed by normal cells. Moreover, HA@CUR NPs not only retained the antimicrobial efficacy of CUR, but also exhibited more pronounced anti-inflammatory and anti-oxidative stress functions both in vivo and in vitro. This provides a good potential drug delivery system for the treatment of periodontitis, and could offer valuable insights for dental therapeutics targeting periodontal diseases.

Abstract Background Oral cancer is the most common malignant tumor of the head and neck, and 90% of cases are oral squamous cell carcinoma (OSCC). Chemotherapy is an important component of comprehensive treatment for OSCC. However, the clinical treatment effect of chemotherapy drugs, such as doxorubicin (DOX), is limited due to the lack of tumor targeting and rapid clearance by the immune system. Thus, based on the tumor-targeting and immune evasion abilities of macrophages, macrophage membrane-encapsulated poly(methyl vinyl ether alt maleic anhydride)-phenylboronic acid-doxorubicin nanoparticles (MM@PMVEMA-PBA-DOX NPs), briefly as MM@DOX NPs, were designed to target OSCC. The boronate ester bonds between PBA and DOX responded to the low pH value in the tumor microenvironment, selectively releasing the loaded DOX. Results The results showed that MM@DOX NPs exhibited uniform particle size and typical core-shell structure. As the pH decreased from 7.4 to 5.5, drug release increased from 14 to 21%. The in vitro targeting ability, immune evasion ability, and cytotoxicity of MM@DOX NPs were verified in HN6 and SCC15 cell lines. Compared to free DOX, flow cytometry and fluorescence images demonstrated higher uptake of MM@DOX NPs by tumor cells and lower uptake by macrophages. Cell toxicity and live/dead staining experiments showed that MM@DOX NPs exhibited stronger in vitro antitumor effects than free DOX. The targeting and therapeutic effects were further confirmed in vivo. Based on in vivo biodistribution of the nanoparticles, the accumulation of MM@DOX NPs at the tumor site was increased. The pharmacokinetic results demonstrated a longer half-life of 9.26 h for MM@DOX NPs compared to 1.94 h for free DOX. Moreover, MM@DOX NPs exhibited stronger tumor suppression effects in HN6 tumor-bearing mice and good biocompatibility. Conclusions Therefore, MM@DOX NPs is a safe and efficient therapeutic platform for OSCC.

Abstract Background Clinicians traditionally aim to identify a singular explanation for the clinical presentation of a patient; however, in some cases, the diagnosis may remain elusive or fail to comprehensively explain the clinical findings. In recent years, advancements in next-generation sequencing, including whole-exome sequencing, have led to the incidental identification of dual diagnoses in patients. Herein we present the cases of five pediatric patients diagnosed with dual rare genetic diseases. Their natural history and diagnostic process were explored, and lessons learned from utilizing next-generation diagnostic technologies have been reported. Results Five pediatric cases (3 boys, 2 girls) with dual diagnoses were reported. The age at diagnosis was from 3 months to 10 years. The main clinical presentations were psychomotor retardation and increased muscular tension, some accompanied with liver dysfunction, abnormal appearance, precocious puberty, dorsiflexion restriction and varus of both feet, etc. After whole-exome sequencing, nine diseases were confirmed in these patients: Angelman syndrome and Krabbe disease in case 1, Citrin deficiency and Kabuki syndrome in case 2, Homocysteinemia type 2 and Copy number variant in case 3, Isolated methylmalonic acidemia and Niemann-Pick disease type B in case 4, Isolated methylmalonic acidemia and 21-hydroxylase deficiency in case 5. Fifteen gene mutations and 2 CNVs were identified. Four novel mutations were observed, including c.15292de1A in KMT2D, c.159_164inv and c.1427G > A in SLC25A13, and c.591 C > G in MTHFR. Conclusions Our findings underscore the importance of clinicians being vigilant about the significance of historical and physical examination. Comprehensive clinical experience is crucial for identifying atypical clinical features, particularly in cases involving dual rare genetic diseases.

Abstract Background Radiculopathy of the lower limb after acute osteoporotic vertebral fractures (OVFs) in the lower lumbar spine is uncommon in geriatric patients. Moreover, surgical intervention is generally recommended in patients who are irresponsive to conservative treatment. Determining an optimum surgical strategy is challenging considering the poor general condition of this population. Thus, herein, we established an algorithm for surgically managing this clinical scenario, hoping to provide a reference for making a surgical decision. Methods We retrospectively studied patients who suffered from new-onset radiculopathy of the lower limb after acute single-level OVFs in the lower lumbar spine and eventually underwent surgical intervention at our department. Information on the demographics, bone quality, AO spine classification of the vertebral fracture, pre-existing degenerative changes, including foraminal stenosis and lumbar disc herniation, and surgical intervention type was collected. Additionally, clinical outcomes, including preoperative and postoperative visual analog scale (VAS) scores for back and leg pain, Oswestry disability index (ODI), and MacNab criterion for response to surgery, were evaluated. Results From September 2019 to December 2021, a total of 22 patients with a mean age of 68.59 ± 9.74 years were analyzed. The most involved vertebra was L5 (54.5%), followed by L4 (27.3%) and L3 (18.2%). Among the 22 patients, 15 (68.2%) were diagnosed with the A1 type fracture of AO classification, and among them, 11 (73.3%) were characterized by the collapse of the inferior end plate (IEP). Three patients (13.6%) suffered from A2-type fractures, whereas four patients (18.2%) suffered from A3-type fractures. Pre-existing degenerative changes were observed in 12 patients (54.5%) of the patients. A total of 16 patients (72.7%) were treated by percutaneous kyphoplasty (PKP). Additionally, three patients underwent posterior instrumentation and fusion, two patients underwent a secondary endoscopic foraminoplasty, and one patient underwent a secondary radiofrequency ablation. The mean follow-up period was 17.42 ± 9.62 months. The mean VAS scores for leg and back pain and ODI decreased significantly after the surgery (P

Abstract Using (27.12 ± 0.14) × 108 ψ(3686) events collected with the BESIII detector at BEPCII, the decay of ψ(3686) → Ω − K + Ξ ¯ 0 $$ {\varOmega}^{-}{K}^{+}{\overline{\Xi}}^0 $$ + c.c. is observed for the first time. The branching fraction of this decay is measured to be B ψ 3686 → Ω − K + Ξ ¯ 0 + c . c . $$ {\mathcal{B}}_{\psi (3686)\to {\varOmega}^{-}{K}^{+}{\overline{\Xi}}^0+\textrm{c}.\textrm{c}.} $$ = (2.78 ± 0.40 ± 0.18) × 10 −6, where the first uncertainty is statistical and the second is systematic. Possible baryon excited states are searched for in this decay, but no evident intermediate state is observed with the current sample size.

Background/purpose: The relationship between Vitamin D (VD) and periodontitis in patients with metabolic syndrome (MetS) was unclear. This study was to investigate the relationship between VD and periodontitis in MetS patients. Materials and methods: This cross-sectional study collected the data of 2165 MetS patients from the National Health and Nutrition Examination Survey (NHANES). The weighted univariate and multivariable Logistic regression models were applied to identify covariates and evaluate the association between 25-hydroxy vitamin D (25(OH)D) [25(OH)D]2 + 25(OH)D3 and periodontitis in patients. Odds ratio (OR) [95% confidence interval (CI)] was effect size. Subgroup analysis was performed in people with or without diabetes, dyslipidemia, hypertension, cardiovascular disease (CVD) and central obesity groups. Results: In the unadjusted model, compared with patients with 25(OH)D2 + 25(OH)D3

Abstract The development of renewable energy will increase the demand for flexible resources in power systems due to the strong uncertainties. To allocate resources and cope with these uncertainties, it is beneficial to apply robust coordinated energy storage and transmission expansion planning (ES&TEP). The large candidate line set can significantly increase the computational complexity of robust optimization models. However, there is currently no suitable network search space reduction (NSSR) method to address this problem. This paper designs a NSSR method based on redundancy constraint identification that only requires information on component power ranges rather than fixed power curves, which can be well adapted to robust optimization. Additionally, this method requires only basic numerical calculations and ensures convergence within a finite number of iterations. The classical stochastic robust ES&TEP model and the column and constraint generation (C&CG) algorithm are used to validate the effectiveness of the NSSR method. In the case studies, the numerical results confirm the rationality and effectiveness of the approach proposed in this paper. By selecting appropriate parameters, the candidate line set can be reduced by over 70% and the computational efficiency can be improved by an order of magnitude.

Metasurfaces are one of the most promising devices to break through the limitations of bulky optical components. By offering a new method of light manipulation based on the light-matter interaction in subwavelength nanostructures, metasurfaces enable the efficient manipulation of the amplitude, phase, polarization, and frequency of light and derive a series of possibilities for important applications. However, one key challenge for the realization of applications for meta-devices is how to fabricate large-scale, uniform nanostructures with high resolution. In this review, we review the state-of-the-art nanofabrication techniques compatible with the manufacture of meta-devices. Maskless lithography, masked lithography, and other nanofabrication techniques are highlighted in detail. We also delve into the constraints and limitations of the current fabrication methods while providing some insights on solutions to overcome these challenges for advanced nanophotonic applications.

The continuous process of urbanization and climate change has led to severe urban heat island (UHI) effects. Constructing parks with cooling capabilities is considered an effective measure to alleviate UHI effects. However, most studies only quantify the cooling effect from a maximum value perspective, lacking a measure of temperature diffusion in space. This study combines the perspectives of maximum value and accumulation to define a cold island index, quantifying the cooling effect of 40 urban parks in the main urban area of Xi'an city. The results show that, on average, urban parks can reduce the surrounding environment by approximately 2.3℃, with a cooling range of about 127.1ha, which is three times the park area. Different factors drive the measurement of the cooling effect using different cold island indexes, but all indexes are highly correlated with green space area. There are significant differences in the cooling effect among different types of parks, and overall, ecological parks have the best cooling effect. The directional spread of internal cold islands in parks is most related to park shape, while external spread is related to surrounding green spaces. The research results have practical value in the construction of parks with cooling effects and the sustainable development of cities in urban planning processes..

Abstract Clinical deployment of oligonucleotides requires delivery technologies that improve stability, target tissue accumulation and cellular internalization. Exosomes show potential as ideal delivery vehicles. However, an affordable generalizable system for efficient loading of oligonucleotides on exosomes remain lacking. Here, we identified an Exosomal Anchor DNA Aptamer (EAA) via SELEX against exosomes immobilized with our proprietary CP05 peptides. EAA shows high binding affinity to different exosomes and enables efficient loading of nucleic acid drugs on exosomes. Serum stability of thrombin inhibitor NU172 was prolonged by exosome-loading, resulting in increased blood flow after injury in vivo. Importantly, Duchenne Muscular Dystrophy PMO can be readily loaded on exosomes via EAA (EXOEAA-PMO). EXOEAA-PMO elicited significantly greater muscle cell uptake, tissue accumulation and dystrophin expression than PMO in vitro and in vivo. Systemic administration of EXOEAA-PMO elicited therapeutic levels of dystrophin restoration and functional improvements in mdx mice. Altogether, our study demonstrates that EAA enables efficient loading of different nucleic acid drugs on exosomes, thus providing an easy and generalizable strategy for loading nucleic acid therapeutics on exosomes.

Abstract Background Cervicovaginal microbiome plays an important role in the persistence of HPV infection and subsequent disease development. However, cervicovaginal microbiota varied cross populations with different habits and regions. Identification of population-specific biomarkers from cervicovaginal microbiota and host metabolome axis may support early detection or surveillance of HPV-induced cervical disease at all sites. Therefore, in the present study, to identify HPV-specific biomarkers, cervicovaginal secretion and serum samples from HPV-infected patients (HPV group, n = 25) and normal controls (normal group, n = 17) in Xichang, China were collected for microbiome (16S rRNA gene sequencing) and metabolome (UHPLC-MS/MS) analysis, respectively. Results The results showed that key altered metabolites of 9,10-DiHOME, α-linolenic acid, ethylparaben, glycocholic acid, pipecolic acid, and 9,12,13-trihydroxy-10(E),15(Z)-octadecadienoic acid, correlating with Sneathia (Sneathia_amnii), Lactobacillus (Lactobacillus_iners), Atopobium, Mycoplasma, and Gardnerella, may be potential biomarkers of HPV infection. Conclusion The results of current study would help to reveal the association of changes in cervicovaginal microbiota and serum metabolome with HPV infections.

The juvenile-to-adult phase change with first flowering as the indicator plays a crucial role in the lifecycle of fruit trees. However, the molecular mechanisms underlying phase change in fruit trees remain largely unknown. Shikimic acid (ShA) pathway is a main metabolic pathway closely related to the synthesis of hormones and many important secondary metabolites participating in plant phase change. So, whether ShA regulates phase change in plants is worth clarifying. Here, the distinct morphological characteristics and the underlying mechanisms of phase change in jujube (Ziziphus jujuba Mill.), an important fruit tree native to China with nutritious fruit and outstanding tolerance abiotic stresses, were clarified. A combined transcriptome and metabolome analysis found that ShA is positively involved in jujube (‘Yuhong’ × ‘Xing 16’) phase change. The genes in the upstream of ShA synthesis pathway (ZjDAHPS, ZjDHQS and ZjSDH), the contents of ShA and the downstream secondary metabolites like phenols were significantly upregulated in the phase change period. Further, the treatment of spraying exogenous ShA verified that ShA at a very low concentration (60 mg · L−1) can substantially speed up the phase change and flowering of jujube and other tested plants including Arabidopsis, tomato and wheat. The exogenous ShA (60 mg · L−1) treatment in jujube seedlings could increase the accumulation of endogenous ShA, enhance leaf photosynthesis and the synthesis of phenols especially flavonoids and phenolic acids, and promote the expression of genes (ZjCOs, ZjNFYs and ZjPHYs) involved in flowering pathway. Basing on above results, we put forward a propose for the underlying mechanism of ShA regulating phase change, and a hypothesis that ShA could be considered a phytohormone-like substance because it is endogenous, ubiquitous, movable and highly efficient at very low concentrations. This study highlights the critical role of ShA in plant phase change and its phytohormone-like properties.

Abstract Background Peritoneal dialysis (PD) remains underutilised in Germany, prompting the initiation of the Sustainable Intensification of Peritoneal Dialysis in Schleswig–Holstein (SKIP-SH) project. The SKIP-SH cohort study aims to demonstrate the presumed benefits of PD, including enhanced quality of life and reduced healthcare personnel requirements, and to generate data to strengthen the use of PD. Methods The prospective SKIP-SH cohort study recruits patients with advanced chronic kidney disease (CKD) and their caregivers. Comprehensive data, including demographic information, medical history, clinical course, laboratory data, and quality-of-life assessments, are collected. Additionally, biomaterials will be obtained. Primary study objectives are documenting the clinical course and complications, time on therapy for new dialysis patients, reasons influencing treatment modality choices, circumstances at the initiation of dialysis, and quality of life for patients with CKD and their caregivers. The collected biomaterials will serve as a basis for further translational research. Secondary objectives include identifying factors impacting disease-related quality of life, clinical complications, and therapy dropout, estimating ecological footprints, and evaluating healthcare costs and labour time for initiating and sustaining PD treatment. Discussion PD is notably underutilised in Germany. The current therapy approach for advanced CKD often lacks emphasis on patient-focused care and quality-of-life considerations. Furthermore, adequate explorative research programs to improve our knowledge of mechanisms leading to disease progression and therapy failure in PD patients are scarce. The overarching goal of the SKIP-SH cohort study is to address the notably low PD prevalence in Germany whilst advocating for a shift towards patient-focused care, quality-of-life considerations, and robust translational research. Trial registration This study was registered with the German trial registry (Deutsches Register klinischer Studien) on November 7, 2023, under trial number DRKS00032983.

Bacterial pathogens destroy the structural integrity of functional organs in fish, leading to severe challenges in the aquaculture industry. Vitamin D3 (VD3) prevents bacterial infections and strengthens immune system function via vitamin D receptor (VDR). However, the correlation between VD3/VDR and the structural integrity of functional organs remains unclarified. This study aimed to investigate the influence of VD3 supplementation on histological characteristics, apoptosis, and tight junction characteristics in fish intestine during pathogen infection. A total of 540 healthy grass carp (257.24 ± 0.63 g) were fed different levels of VD3 (15.2, 364.3, 782.5, 1,167.9, 1,573.8, and 1,980.1 IU/kg) for 70 d. Subsequently, fish were challenged with Aeromonas hydrophila, a pathogen that causes intestinal inflammation. Our present study demonstrated that optimal supplementation with VD3 (1) alleviated intestinal structural damage, and inhibited oxidative damage by reducing levels of oxidative stress biomarkers; (2) attenuated excessive apoptosis-related death receptor and mitochondrial pathway processes in relation to p38 mitogen-activated protein kinase signaling (P

Abstract Background Glymphatic dysfunction is a crucial pathway for dementia. Alzheimer’s disease (AD) pathologies co-existing with cerebral small vessel disease (CSVD) is the most common pathogenesis for dementia. We hypothesize that AD pathologies and CSVD could be associated with glymphatic dysfunction, contributing to cognitive impairment. Method Participants completed with amyloid PET, diffusion tensor imaging (DTI), and T2 fluid-attenuated inversion-recovery (FLAIR) sequences were included from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). White matter hyperintensities (WMH), the most common CSVD marker, was evaluated from T2FLAIR images and represented the burden of CSVD. Amyloid PET was used to assess Aβ aggregation in the brain. We used diffusion tensor image analysis along the perivascular space (DTI-ALPS) index, the burden of enlarged perivascular spaces (PVS), and choroid plexus volume to reflect glymphatic function. The relationships between WMH burden/Aβ aggregation and these glymphatic markers as well as the correlations between glymphatic markers and cognitive function were investigated. Furthermore, we conducted mediation analyses to explore the potential mediating effects of glymphatic markers in the relationship between WMH burden/Aβ aggregation and cognition. Results One hundred and thirty-three participants along the AD continuum were included, consisting of 40 CN − , 48 CN + , 26 MCI + , and 19 AD + participants. Our findings revealed that there were negative associations between whole-brain Aβ aggregation (r = − 0.249, p = 0.022) and WMH burden (r = − 0.458, p

Abstract B- and T-lymphocyte attenuator (BTLA) levels are increased in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). This condition is characterized by susceptibility to infection and T-cell immune exhaustion. However, whether BTLA can induce T-cell immune exhaustion and increase the risk of infection remains unclear. Here, we report that BTLA levels are significantly increased in the circulating and intrahepatic CD4+ T cells from patients with HBV-ACLF, and are positively correlated with disease severity, prognosis, and infection complications. BTLA levels were upregulated by the IL-6 and TNF signaling pathways. Antibody crosslinking of BTLA activated the PI3K-Akt pathway to inhibit the activation, proliferation, and cytokine production of CD4+ T cells while promoting their apoptosis. In contrast, BTLA knockdown promoted their activation and proliferation. BTLA-/- ACLF mice exhibited increased cytokine secretion, and reduced mortality and bacterial burden. The administration of a neutralizing anti-BTLA antibody reduced Klebsiella pneumoniae load and mortality in mice with ACLF. These data may help elucidate HBV-ACLF pathogenesis and aid in identifying novel drug targets.

Abstract The heavy fermion physics is dictated by subtle competing exchange interactions, posing a challenge to their understanding. One-dimensional (1D) Kondo lattice model has attracted special attention in theory, because of its exact solvability and expected unusual quantum criticality. However, such experimental material systems are extremely rare. Here, we demonstrate the realization of quasi-1D Kondo lattice behavior in a monolayer van der Waals crystal NbSe2, that is driven into a stripe phase via Se-deficient line defects. Spectroscopic imaging scanning tunneling microscopy measurements and first-principles calculations indicate that the stripe-phase NbSe2 undergoes a novel charge-density wave transition, creating a matrix of local magnetic moments. The Kondo lattice behavior is manifested as a Fano resonance at the Fermi energy that prevails the entire film with a high Kondo temperature. Importantly, coherent Kondo screening occurs only in the direction of the stripes. Upon approaching defects, the Fano resonance exhibits prominent spatial 1D oscillations along the stripe direction, reminiscent of Kondo holes in a quasi-1D Kondo lattice. Our findings provide a platform for exploring anisotropic Kondo lattice behavior in the monolayer limit.

Abstract Efficient upconversion electroluminescence is highly desirable for a broad range of optoelectronic applications, yet to date, it has been reported only for ensemble systems, while the upconversion electroluminescence efficiency remains very low for single-molecule emitters. Here we report on the observation of anomalously bright single-molecule upconversion electroluminescence, with emission efficiencies improved by more than one order of magnitude over previous studies, and even stronger than normal-bias electroluminescence. Intuitively, the improvement is achieved via engineering the energy-level alignments at the molecule−substrate interface so as to activate an efficient spin-triplet mediated upconversion electroluminescence mechanism that only involves pure carrier injection steps. We further validate the intuitive picture with the construction of delicate electroluminescence diagrams for the excitation of single-molecule electroluminescence, allowing to readily identify the prerequisite conditions for producing efficient upconversion electroluminescence. These findings provide deep insights into the microscopic mechanism of single-molecule upconversion electroluminescence and organic electroluminescence in general.

Abstract Background Tubulointerstitial fibrosis plays an important role in the progression of diabetic kidney disease (DKD). Sacubitril/valsartan (Sac/Val) exerts a robust beneficial effect in DKD. However, the potential functional effect of Sac/Val on tubulointerstitial fibrosis in DKD is still largely unclear. Methods Streptozotocin-induced diabetic mice were given Sac/Val or Val by intragastric administration once a day for 12 weeks. The renal function, the pathological changes of tubule injury and tubulointerstitial fibrosis, as well as mitochondrial morphology of renal tubules in mice, were evaluated. Genome-wide gene expression analysis was performed to identify the potential mechanisms. Meanwhile, human tubular epithelial cells (HK-2) were cultured in high glucose condition containing LBQ657/valsartan (LBQ/Val). Further, mitochondrial functions and Sirt1/PGC1α pathway of tubular epithelial cells were assessed by Western blot, Real-time-PCR, JC-1, MitoSOX or MitoTracker. Finally, the Sirt1 specific inhibitor, EX527, was used to explore the potential effects of Sirt1 signaling in vivo and in vitro. Results We found that Sac/Val significantly ameliorated the decline of renal function and tubulointerstitial fibrosis in DKD mice. The enrichment analysis of gene expression indicated metabolism as an important modulator in DKD mice with Sac/Val administration, in which mitochondrial homeostasis plays a pivotal role. Then, the decreased expression of Tfam and Cox IV;, as well as changes of mitochondrial function and morphology, demonstrated the disruption of mitochondrial homeostasis under DKD conditions. Interestingly, Sac/Val administration was found to restore mitochondrial homeostasis in DKD mice and in vitro model of HK-2 cells. Further, we demonstrated that Sirt1/PGC1α, a crucial pathway in mitochondrial homeostasis, was activated by Sac/Val both in vivo and in vitro. Finally, the beneficial effects of Sac/Val on mitochondrial homeostasis and tubulointerstitial fibrosis was partially abolished in the presence of Sirt1 specific inhibitor. Conclusions Taken together, we demonstrate that Sac/Val ameliorates tubulointerstitial fibrosis by restoring Sirt1/PGC1α pathway-mediated mitochondrial homeostasis in DKD, providing a theoretical basis for delaying the progression of DKD in clinical practice.

Abstract Maintaining energy balance and economical operation is significant for energy hub (EH) which serves as the central component. Implementing real‐time regulation for heating and cooling equipment within the EH is challenging due to their slow response time in response to the stochastic fluctuation in renewable energy sources and demands while the opposite is true for electric energy storage equipment (EST), a conventional single timescale energy management strategy is no longer sufficient to take into account the operating characteristics of all equipment. With this motivation, this study proposes a deep reinforcement learning based two‐timescale energy management strategy for EH, which controls heating & cooling equipment on a long timescale of 1 h, and EST on a short timescale of 15 min. The actions of the EST are modelled as discrete to reduce the action spaces, and the discrete‐continuous hybrid action sequential TD3 model is proposed to address the problem of handling both discrete and continuous actions in long timescale policy. A joint training approach based on the centralized training framework is proposed to learn multiple levels of policies in parallel. The case studies demonstrate that the proposed strategy reduces the economic cost and carbon emissions by 1%, and 0.5% compared to the single time‐scale strategy respectively.

For expedited transportation, vehicular tunnels are often designed as two adjacent tunnels, which frequently experience dynamic stress waves from various orientations during blasting excavation. To analyze the impact of dynamic loading orientation on the stability of the twin-tunnel, a split Hopkinson pressure bar (SHPB) apparatus was used to conduct a dynamic test on the twin-tunnel specimens. The two tunnels were rotated around the specimen’s center to consider the effect of dynamic loading orientation. LS-DYNA software was used for numerical simulation to reveal the failure properties and stress wave propagation law of the twin-tunnel specimens. The findings indicate that, for a twin-tunnel exposed to a dynamic load from different orientations, the crack initiation position appears most often at the tunnel corner, tunnel spandrel, and tunnel floor. As the impact direction is created by a certain angle (30°, 45°, 60°, 120°, 135°, and 150°), the fractures are produced in the middle of the line between the left tunnel corner and the right tunnel spandrel. As the impact loading angle (α) is 90°, the tunnel sustains minimal damage, and only tensile fractures form in the surrounding rocks. The orientation of the impact load could change the stress distribution in the twin-tunnel, and major fractures are more likely to form in areas where the tensile stress is concentrated.

This study conducted experimental research on the strength and micro–expansion properties of mortar with varying dosages of steel slag powder (SSP) and fly ash (FA) to enhance the application of SSP as a mineral admixture in concrete cementitious material systems. Scanning electron microscopy and X-ray diffractometry were employed to analyze the microscopic morphology and structure of the specimens before and after hydration. This study discussed the impact of the water–to–binder ratio (w/b), curing age, SSP, and FA dosage on the mechanical properties and volume stability of mortar. Then models for predicting the strength and expansion deformation prediction through correlation analyses were proposed. The results indicated that the mechanical strength of the mortar decreased with increasing substitution of the composite admixture, while reducing w/b and increasing SSP dosage improved the resistance to shrinkage that was positively correlated with SSP dosage under the same w/b. Furthermore, correlation analyses revealed that the cement and SSP dosage significantly affected the 28-day strength and 90-day expansion deformation of mortar, and the established models could well describe the strength and expansion deformation of composite mortar incorporating SSP, providing valuable insights for the engineering application of SSP.

Adhere to the concept of low-carbon environmental protection and turning waste into treasure, polysaccharides from Flammulina velutipes residue polysaccharide (FVRP) has been developed and possesses diverse bioactivities, comprising antioxidant, hypoglycemic, and relieving heavy metal damage, which still has the disadvantages of high molecular weight and low bioavailability. The current work is the first to prepare a degraded polysaccharide (FVRPV) from FVRP by ultrasonic assisted H2O2-Vc technique in order to reduce its molecular weight, thereby improving its activity and bioavailability. Our results found that the molecular weight and average particle size were declined, but the monosaccharide composition and characteristic functional group types of FVRPV had no impact. The structural changes of polysaccharides analyzed by XRD, Congo Red test, I2-KI, SEM, and methylation analysis indicated that the surface morphology and glycosidic bond composition of FVRPV possessed longer side chains and a greater number of branches with an amorphous crystal structure devoid of a triple helix configuration, and had experienced notable alterations after ultrasonic assisted H2O2-Vc treatment. Meanwhile, the in vitro antioxidant capacity of FVRPV had significantly increased compared to FVRP, implying ultrasonic assisted H2O2-Vc technique maybe a effective method to enhance the bioactivity of polysaccharides. In addition, the content of polysaccharide, reducing sugar, and uronic acid in FVRPV was significantly decreased, but antioxidant capacity of fermentation broth was stronger by in vitro human fecal fermentation. The 16S rDNA sequencing data displayed that FVRPV can enrich probiotics and reduce the abundance of pathogenic bacteria through different metabolic pathways mediated by gut microbiota, thereby exerting its potential probiotic effects. The interesting work provides a novel degraded polysaccharide by ultrasonic assisted H2O2-Vc technique, laying a foundation for developing FVRPV as a new antioxidant and prebiotic.

Compound flash drought and heatwave (FDHW) events have garnered increasing amounts of attention due to their substantial impacts on agriculture, water resources, and public health. However, studies on their intensity and classification in China are limited. In this study, we classified FDHW events in China from 1980 to 2022 using a classification framework designed to address regional patterns and explore their characteristics further. The results showed that FDHW events in northern China mostly occurred in early to mid-summer, whereas in southern China, excluding the Southwest River Basin, they occurred predominantly in mid to late summer. Furthermore, the spatial coverage of FDHW events across China significantly expanded. From 1980 to 2022, FDHW events in China evolved toward higher intensities and longer durations. This trend was especially notable in the Jiang-Huai River Basin, the main grain-producing region and a densely populated area of China. From the perspective of land‒atmosphere coupling, the amplifying effect of flash droughts and high temperatures increased with their intensity. When high temperatures reached the extreme level, the amplification effect on flash droughts was evident: 35.76% from the water deficit perspective and 38.82% from the soil moisture perspective. During extreme flash droughts, the amplification effect on high temperatures intensified: 41.51% from the water deficit perspective and 45.06% from the soil moisture perspective. The Southwest River Basin became a hotspot for the interaction between flash droughts and high temperatures. This study has implications for developing science-based policies to tackle risks in the water, energy and food sectors in China.

Microparticle sorting is a crucial technique with diverse applications spanning biomedical research, microfluidics, and beyond. Conventional methods often face limitations in throughput, precision, and sample integrity. Here we present an optofluidic approach for size-based directional sorting of microparticles using optical manipulation with Airy beams. By harnessing the non-diffracting properties and transverse gradient force of Airy beams, we achieve a non-invasive, high-precision sorting method capable of sorting and selectively clearing microparticles based on their sizes. We also demonstrate more complex operations involving wavefront modulation and microfluidic devices. The proposed method offers effective and versatile microparticle sorting, providing a powerful optofluidic tool for applications requiring precise and efficient sorting of microparticles while maintaining sample integrity.

Heat treatment free aluminum alloys have been developed for wire arc directed energy deposition (DED) large thin-walled components, but their further performance enhancement methods remain unexplored. In this study, laser shock peening (LSP) treatment was performed on wire arc DED Al-6Mg-0.3Sc components. The results show that LSP creates a gradient microstructure with submicro-grains near the surface. The effects of LSP on defects were quantified by quasi-in-situ CT, demonstrating a reduction in porosity by over 68% together with decreased size. Simultaneously, tensile strength increases by 39.5% to 295.8 ± 6.4 MPa with only a marginal loss of elongation, as compared to the as-deposited (AD) state. This was due to the accumulation of dislocations and continuous dynamic recrystallization lead to grain refinement, as well as the appearance of a triple heterogeneous microstructure. Therefore, this study offers a novel solution for manufacturing of high-performance heat treatment free large thin-walled components.

ABSTRACTImmune checkpoint inhibitors (ICIs) have emerged as a promising therapeutic option for large cell neuroendocrine carcinoma (LCNEC). However, various studies have suggested a potential risk of hyperprogressive disease (HPD) in patients receiving ICI, which might be associated with gene alterations. Here, this is the first report on an unknown primary LCNEC patient who had achieved a long-term response from ICI treatment (atezolizumab), but developed HPD after tumor progression due to receiving another ICI agent (serplulimab). The mutation region of FAT4, SMARCA4, CYLD, CTNNB1, and KIT was altered prior to serplulimab treatment compared to before atezolizumab treatment. This case suggested a potential association between these mutated genes and HPD. Patients with the aforementioned genes should caution when selecting ICI treatment. These findings required further confirmation in a larger study cohort.

ABSTRACT: Fatty liver disease in laying hens, characterized by excessive lipid accumulation in hepatocytes, poses significant challenges to poultry health and production efficiency. In this study, we investigated the therapeutic potential of epigallocatechin gallate (EGCG), a bioactive compound found in green tea, in mitigating oleic acid (OA)-induced hepatic steatosis in primary chicken hepatocytes. Treatment with EGCG effectively attenuated lipid deposition by downregulating lipid synthesis-related genes. Moreover, EGCG mitigated oxidative stress, inflammation, DNA damage, and apoptosis induced by OA, thereby preserving hepatocyte viability. Mechanistically, EGCG exerted its protective effects by modulating the p38 MAPK signaling pathway. Our findings suggest that EGCG holds promise as a therapeutic agent for managing fatty liver disease in poultry, offering insights into novel strategies for improving poultry health and production outcomes.

Shaofuzhuyu Decoction (SFZYD) is a classical formula for treating endometriosis of cold coagulation and blood stasis (ECB). The clinical efficacy is definite, but the potential mechanisms require further exploration. The study aimed to reveal the metabolic mechanisms of SFZYD for treating ECB using mass spectrum oriented metabolomics. Firstly, the study has used metabolomics data to identify biomarkers and to investigate metabolic pathways. Then, the targets of SFZYD for treating ECB were dug by building and analyzing a biological network of biomarkers. Finally, the obtained targets were validated by molecular docking. This study found that SFZYD could significantly improve the biochemical indicators and metabolic abnormalities of ECB. A total of 18 ECB-related biomarkers in 7 pathways were identified. SFZYD was able to regulate the levels of 14 biomarkers that were involved in 5 metabolic pathways. Furthermore, the study yielded 119 SFZYD active ingredients, 1119 target proteins associated with endometriosis, 610 targets associated with biomarkers, 727 GO functions, and 159 KEGG pathways. Biological network analysis constructed a network diagram of herbs-ingredients-targets-biomarkers, and found 6 key active ingredients and 9 core targets. Molecular docking showed high affinities between key ingredients and core targets. This study elucidated that SFZYD plays a role in treating ECB through multi-component, multi-target, and multi-pathway.

BackgroundOsteosarcoma primarily affects children and adolescents, with current clinical treatments often resulting in poor prognosis. There has been growing evidence linking programmed cell death (PCD) to the occurrence and progression of tumors. This study aims to enhance the accuracy of OS prognosis assessment by identifying PCD-related prognostic risk genes, constructing a PCD-based OS prognostic risk model, and characterizing the function of genes within this model.MethodWe retrieved osteosarcoma patient samples from TARGET and GEO databases, and manually curated literature to summarize 15 forms of programmed cell death. We collated 1621 PCD genes from literature sources as well as databases such as KEGG and GSEA. To construct our model, we integrated ten machine learning methods including Enet, Ridge, RSF, CoxBoost, plsRcox, survivalSVM, Lasso, SuperPC, StepCox, and GBM. The optimal model was chosen based on the average C-index, and named Osteosarcoma Programmed Cell Death Score (OS-PCDS). To validate the predictive performance of our model across different datasets, we employed three independent GEO validation sets. Moreover, we assessed mRNA and protein expression levels of the genes included in our model, and investigated their impact on proliferation, migration, and apoptosis of osteosarcoma cells by gene knockdown experiments.ResultIn our extensive analysis, we identified 30 prognostic risk genes associated with programmed cell death (PCD) in osteosarcoma (OS). To assess the predictive power of these genes, we computed the C-index for various combinations. The model that employed the random survival forest (RSF) algorithm demonstrated superior predictive performance, significantly outperforming traditional approaches. This optimal model included five key genes: MTM1, MLH1, CLTCL1, EDIL3, and SQLE. To validate the relevance of these genes, we analyzed their mRNA and protein expression levels, revealing significant disparities between osteosarcoma cells and normal tissue cells. Specifically, the expression levels of these genes were markedly altered in OS cells, suggesting their critical role in tumor progression. Further functional validation was performed through gene knockdown experiments in U2OS cells. Knockdown of three of these genes—CLTCL1, EDIL3, and SQLE—resulted in substantial changes in proliferation rate, migration capacity, and apoptosis rate of osteosarcoma cells. These findings underscore the pivotal roles of these genes in the pathophysiology of osteosarcoma and highlight their potential as therapeutic targets.ConclusionThe five genes constituting the OS-PCDS model—CLTCL1, MTM1, MLH1, EDIL3, and SQLE—were found to significantly impact the proliferation, migration, and apoptosis of osteosarcoma cells, highlighting their potential as key prognostic markers and therapeutic targets. OS-PCDS enables accurate evaluation of the prognosis in patients with osteosarcoma.

Tiller number serves as a crucial indicator of total yield in agriculture. Accurately monitoring tiller numbers is essential for guiding variable fertilization to optimize inputs and enhance final yields. Currently, most of the existing winter wheat tillering sensing monitoring methods cannot meet the three requirements of fast, accurate and efficient at the same time. In order to improve the monitoring accuracy and efficiency, this paper proposes a fast UAV remote sensing method for winter wheat tiller number estimation, combined with self-adaptive segmentation framework and multi-feature selection method. The self-adaptive segmentation framework is designed from the perspective of amplifying the difference of spectral information of ground objects. This framework fully considers the influence of complex environment, especially vegetation coverage, on parameter setting while using mathematical function means and polarization ideas. It aims to solve the problem of insufficient applicability of traditional segmentation methods under different environmental conditions. Subsequently, an optimized grey wolf search algorithm CMI-IGWO with multi-strategy fusion is proposed. Its novel evaluation criteria and iterative mechanism provide important algorithm support for the determination of the best inversion feature combination. The search algorithm combines statistics and information theory, comprehensively considers the linear and nonlinear relationships between variables, and guides the gray wolf to select the optimal features. Experiments show that the mixed features covering spectral, texture, color and shape information can make the final tiller number prediction model work best, achieving an R2 value exceeding 0.75. It affirms the efficacy and robustness of the proposed method in estimating winter wheat tiller numbers, providing valuable guidance for precise topdressing. This study provides a new feasible solution for predicting crop tiller number with high accuracy and efficiency using UAV remote sensing technology.

ABSTRACT: Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs that have been implicated in mediating granulosa cell (GC) proliferation and apoptosis. CircRAB11A was found to have a significantly higher expression in normal follicles compared to atrophic follicles. In this study, we determined that the knockdown of circRAB11A resulted in the inhibition of proliferation and promotion of apoptosis in GCs of chicken. Moreover, circRAB11A was found to act as a sponge for miR-24-5p, both member RAS oncogene family (RAB11A) and epidermal growth factor receptor (EGFR) were revealed to be targets of miR-24-5p through a dual-luciferase reporter assay. RAB11A or EGFR promoted proliferation and suppressed apoptosis in GCs through the phosphatidylinositol-kinase (PI3K)/AKT or extracellular signal-regulated kinase (ERK)1/2 pathway. These findings suggest that circRAB11A may function as a competing endogenous RNA (ceRNA) by targeting the miR-24-5p/RAB11A and miR-24-5p/EGFR axes and activating the ERK1/2 and PI3K/AKT pathways, offering a potential avenue for exploring the mechanism of follicle development.

Abstract Multiple lines of evidence confirm a widespread increase in vegetation growth across China over the past few decades. The relationship between vegetation growth and water availability is thought to be becoming stronger under climate change, that is, water constraints on vegetation growth have been increasing. However, our understanding of how water constraints have influenced these vegetation greening trends, especially those climate change‐driven ones, remains limited. Here, we conduct a comprehensive evaluation of recent water constraints and their implications for vegetation growth in China between 1982 and 2015. By analyzing the spatiotemporal patterns of the relationship between vegetation growth and water availability, we reveal recent water constraints and their changes hidden within an overall greening trend in China. Further analysis demonstrates that two climate change‐related categories, defined broadly as “climate” (e.g., air temperature, precipitation, and so on) and “CO2” (i.e., atmospheric carbon dioxide), have exerted varying levels of importance in regulating vegetation growth across different water constraints. With increasing water constraints, the proportion of the climate‐dominated area has significantly risen, while that of the CO2‐dominated area has sharply declined. Our findings highlight that water constraints can mediate the dominance of climate and atmospheric CO2 on vegetation growth. This has the great potential to exacerbate the uncertainty surrounding current and future sustainable vegetation greening trends.

BackgroundThere have been numerous studies on NMDA receptors as therapeutic targets for depression. However, so far, there has been no comprehensive scientometric analysis of this field. Thus, we conducted a scientometric analysis with the aim of better elucidating the research hotspots and future trends in this field.MethodsPublications on NMDAR in Depression between 2004 and 2023 were retrieved from the Web of Science Core Collection (WoSCC) database. Then, VOSviewer, CiteSpace, Scimago Graphica, and R-bibliometrix—were used for the scientometric analysis and visualization.Results5,092 qualified documents were identified to scientometric analysis. In the past 20 years, there has been an upward trend in the number of annual publications. The United States led the world in terms of international collaborations, publications, and citations. 15 main clusters were identified from the co-cited references analysis with notable modularity (Q-value = 0.7628) and silhouette scores (S-value = 0.9171). According to the keyword and co-cited references analysis, treatment-resistant depression ketamine (an NMDAR antagonist), oxidative stress, synaptic plasticity, neuroplasticity related downstream factors like brain-derived neurotrophic factor were the research hotspots in recent years.ConclusionAs the first scientometric analysis of NMDAR in Depression, this study shed light on the development, trends, and hotspots of research about NMDAR in Depression worldwide. The application and potential mechanisms of ketamine in the treatment of major depressive disorder (MDD) are still a hot research topic at present. However, the side effects of NMDAR antagonist like ketamine have prompted research on new rapid acting antidepressants.

Abstract Citrate is a key metabolite and nutrient in humans. Its level is associated with many diseases from tumor growth to bone diseases. Detection of citrate has relied on its high negative charge, metal chelating properties and as an enzyme substrate. In this work, the capture‐selection method is used to isolate DNA aptamers for citrate. After 18 rounds of selection, a highly converged library is obtained and the first two sequences reached 99.6% of the library. Using the most abundant sequence named CA1, thioflavin T fluorescence spectroscopy and isothermal titration calorimetry show dissociation constants of 7.4 and 4.4 µm citrate, respectively. CA1 does not require sodium for binding but requires 1.0 mm magnesium. Among the tested carboxylate molecules, only citrate can bind to the aptamer. A light‐up fluorescence strand displacement biosensor is developed and it can detect citrate in simulated urine with a detection limit of 1.1 µm. This short 42‐nucleotide aptamer can be readily adapted to other types of sensing mechanisms for the detection of citrate.

Summary: Systemic neutrophil dysregulation contributes to atherosclerosis pathogenesis, and restoring neutrophil homeostasis may be beneficial for treating atherosclerosis. Herein, we report that a homeostatic resolving subset of neutrophils exists in mice and humans characterized by the low expression of TRAM, correlated with reduced expression of inflammatory mediators (leukotriene B4 [LTB4] and elastase) and elevated expression of anti-inflammatory resolving mediators (resolvin D1 [RvD1] and CD200R). TRAM-deficient neutrophils can potently improve vascular integrity and suppress atherosclerosis pathogenesis when adoptively transfused into recipient atherosclerotic animals. Mechanistically, we show that TRAM deficiency correlates with reduced expression of 5-lipoxygenase (LOX5) activating protein (LOX5AP), dislodges nuclear localization of LOX5, and switches the lipid mediator secretion from pro-inflammatory LTB4 to pro-resolving RvD1. TRAM also serves as a stress sensor of oxidized low-density lipoprotein (oxLDL) and/or free cholesterol and triggers inflammatory signaling processes that facilitate elastase release. Together, our study defines a unique neutrophil population characterized by reduced TRAM, capable of homeostatic resolution and treatment of atherosclerosis.

Uncaria rhynchophylla (Gouteng), as an evergreen woody vine belong to Rubiaceae family, is a traditional medicinal herb in China. Its terpenoid indole alkaloids (TIAs), which have good antidepressant and combined therapeutic effects on Alzheimer's disease, have attracted widespread attention. However, the content of TIAs is relatively low in U.rhynchophylla, which is unable to meet the growing market demand. The basic helix loop-helix (bHLH) transcription factor family exists in all three eukaryotic kingdoms and can participate in regulating secondary metabolite pathways. So far, there has been no comprehensive analysis of the bHLH gene in U. rhynchophylla, and their role in TIAs is almost unknown. In this study, a total of 171 UrbHLH genes (UrbHLHs) were unevenly distributed on 22 chromosomes and divided into 23 subfamilies. In addition, the physicochemical properties of UrbHLHs were analyzed. Most UrbHLHs in each subgroup had similar gene structures and conserved motifs. Intraspecific collinearity analysis showed that UrbHLH1 may be related to the biosynthesis of TIAs. Subcellular localization experiments revealed that UrbHLH1 is located in the nucleus; Dual luciferase reporter gene analysis (Dual-LUC) showed that UrbHLH1 could activate the expression of UrG10H and Ur10HGO in the TIAs synthesis pathway of U. rhynchophylla. Finally, using yeast one hybrid (Y1H) it was found that the promoter regions of these two genes both have E-box binding elements, which can be bound by UrbHLH1 and produced strong interactions. Therefore, UrbHLH1 may participate in the synthesis of TIAs pathway. In conclusion, this study provides foundation data on the role of UrbHLH transcription factors in regulating TIAs of U. rhynchophylla.

Abstract Floodplain wetlands are critical to the conservation of aquatic biodiversity and the ecological integrity of river networks. However, increasing drought severity and frequency caused by climate change can reduce floodplain wetlands' resistance and recovery capacities. Mollusks, which are common inhabitants of floodplain wetlands, are among the most vulnerable species to drought. However, the response of mollusk communities to drought has received little attention. Here, we investigated how the structure and functional traits of mollusk communities changed in response to varying hydrological conditions, including a flash drought (FD) in the Poyang Lake floodplain wetland. Our findings showed that FD strongly reduced mollusk abundance and biomass, decreased both α‐ and β‐diversity, and resulted in the extinction of bivalve taxa. A sudden shift in community trait structure was discovered due to the extinction of many species. These traits, which include deposit feeding, crawling, scraping, aerial respiration, and dormancy, help mollusks survive in FD and tolerate completely dry out of their Changhuchi habitat. Finally, we discovered that dissolved oxygen was an important controlling variable for mollusk communities during drought. Our findings provide a scientific basis for the management and conservation of floodplain wetland biodiversity in the context of increasing drought frequency and intensity.

ABSTRACT Soil microbial community composition and diversity are often affected by nutrient enrichment, which may influence soil microbes to affect nutrient cycling and plant community structure. However, the response of soil bacteria to nitrogen (N) and phosphorus (P) addition and whether it is influenced by plants remains unclear. By 16S rRNA sequencing, we investigated the response of the rhizosphere and bulk soil bacterial communities of different halophytes (salt-rejecting, salt-absorbing, and salt-secreting plant) in the Yellow River Delta to short-term N and P addition. The response of rhizosphere bacterial diversity to N and P addition was opposite in Phragmites communis and Suaeda salsa. N addition increased the rhizosphere soil bacterial α-diversity of S. salsa and Aeluropus sinensis, while P addition decreased the rhizosphere bacterial α-diversity bacteria of S. salsa. The N and P addition had a weak effect on the rhizosphere bacterial community composition and a significant effect on the bulk soil bacterial community composition of halophytes. The S. salsa and P. communis bulk soil bacterial community were mainly influenced by P addition, while it was influenced by N addition in A. sinensis. N and P addition reduced the difference in bacterial community composition between the two types of soil. N and P addition increased the eutrophic taxa (Proteobacteria and Bacteroidetes) and decreased the oligotrophic taxa (Acidobacteria). Redundancy analysis showed that soil organic matter, salt, and total N content had significant effects on the bacterial community composition. The results clarify that the response of soil bacterial communities to N and P additions is inconsistent across the three halophyte soils, and the effect of plant species on the bacterial community was stronger than short-term N and P addition.IMPORTANCEThe bulk soil bacterial community was more affected by nutrient addition. Nitrogen (N) and phosphorus (P) have different effects on bacterial community. Soil organic matter is a key factor influencing the response of bacterial community to nutrient addition. N and P influence on bacterial community changes with plants.