Search

Abstract We measured the Born cross sections for the process e + e − → ωη′ at 22 center-of-mass energies from 2.000 to 3.080 GeV with the BESIII detector at the BEPCII collider. We observed a resonant structure with a statistical significance of 9.6σ. A Breit-Wigner fit determines its mass to be M R = (2153 ± 30 ± 31) MeV/c 2 and its width to be Γ R = (167 ± 77 ± 7) MeV, where the first uncertainties are statistical and the second are systematic.

Abstract Fully targeted mRNA therapeutics necessitate simultaneous organ-specific accumulation and effective translation. Despite some progress, delivery systems are still unable to fully achieve this. Here, we reformulate lipid nanoparticles (LNPs) through adjustments in lipid material structures and compositions to systematically achieve the pulmonary and hepatic (respectively) targeted mRNA distribution and expression. A combinatorial library of degradable-core based ionizable cationic lipids is designed, following by optimisation of LNP compositions. Contrary to current LNP paradigms, our findings demonstrate that cholesterol and phospholipid are dispensable for LNP functionality. Specifically, cholesterol-removal addresses the persistent challenge of preventing nanoparticle accumulation in hepatic tissues. By modulating and simplifying intrinsic LNP components, concurrent mRNA accumulation and translation is achieved in the lung and liver, respectively. This targeting strategy is applicable to existing LNP systems with potential to expand the progress of precise mRNA therapy for diverse diseases.

The cam tappet friction pair is one of the three major friction pairs in an internal combustion engine, and the surface of the tappet undergoes severe wear during operation. To improve the wear resistance of the cam tappet friction pair during operation, in this study, crescent-shaped micro-textures were prepared on the surface of the tappet material of GCr15 steel by laser machining technique, and the effects of the orientation and depth of the texture on the friction properties of GCr15 steel were studied. The processed test samples were tested and characterized by friction and wear tests, scanning electron microscopy (SEM), 3D morphometry, and EDS. The flow field simulation model of micro-texture was established by using Fluent finite element software. The simulation and experimental results show that the crescent-shaped microtexture prepared on the surface of GCr15 steel can play a certain role in reducing friction and wear resistance, meanwhile orientation and depth of the texture affect the friction performance. In the fluid simulation, the positively oriented texture can produce higher oil film pressure than the opposite texture. When the texture depth is 20 μm, it has a better friction and wear reduction effect, and the friction coefficient decreases by 65.81% compared with that of the untextured surface, and the amount of wear decreases by 74.19%. This is mainly due to the existence of texture in the friction process to reduce the contact area and the shallower depth of texture can produce a larger oil film pressure in the oil lubrication state, so it has better tribological performance. The research data provide a certain reference for the design and optimization of the cam tappet friction pair.

With the development of industrial activities, global warming has accelerated due to excessive emission of CO2. Enhanced Geothermal System (EGS) utilizes deep geothermal heat for power generation. Although porous medium theory is commonly employed to model geothermal reservoirs in EGS, Hot Dry Rock (HDR) presents a challenge as it consists of impermeable granite with zero porosity, potentially distorting the physical interpretation. To address this, the Lattice Boltzmann Method (LBM) is employed to simulate CO2 flow within geothermal reservoirs and the Finite Volume Method (FVM) to solve the energy conservation equation for temperature distribution. This combined method of LBM and FVM is implemented using MATLAB. The results showed that the Reynolds numbers (Re) of 3,000 and 8,000 lead to higher heat extraction rates from geothermal reservoirs. However, higher Re values may accelerate thermal breakthrough, posing challenges to EGS operation. Meanwhile, non-equilibrium of density in fractures becomes more pronounced during the system's life cycle, with non-Darcy's law becoming significant at Re values of 3,000 and 8,000. Density stratification due to buoyancy effects significantly impacts temperature distribution within geothermal reservoirs, with buoyancy effects at Re=100 under gravitational influence being noteworthy. Larger Re values (3,000 and 8,000) induce stronger forced convection, leading to more uniform density distribution. The addition of proppant negatively affects heat transfer performance in geothermal reservoirs, especially in single fractures. Practical engineering considerations should determine the quantity of proppant through detailed numerical simulations.

Abstract Neurofibromatosis Type II (NFII) is a genetic condition caused by loss of the NF2 gene, resulting in activation of the YAP/TAZ pathway and recurrent Schwann cell tumors, as well as meningiomas and ependymomas. Unfortunately, few pharmacological options are available for NFII. Here, we undertake a genome-wide CRISPR/Cas9 screen to search for synthetic-lethal genes that, when inhibited, cause death of NF2 mutant Schwann cells but not NF2 wildtype cells. We identify ACSL3 and G6PD as two synthetic-lethal partners for NF2, both involved in lipid biogenesis and cellular redox. We find that NF2 mutant Schwann cells are more oxidized than control cells, in part due to reduced expression of genes involved in NADPH generation such as ME1. Since G6PD and ME1 redundantly generate cytosolic NADPH, lack of either one is compatible with cell viability, but not down-regulation of both. Since genetic deficiency for G6PD is tolerated in the human population, G6PD could be a good pharmacological target for NFII.

Abstract Background and aims To investigate the clinical features, ALDH5A1 gene variations, treatment, and prognosis of patients with succinic semialdehyde dehydrogenase (SSADH) deficiency. Materials and methods This retrospective study evaluated the findings in 13 Chinese patients with SSADH deficiency admitted to the Pediatric Department of Peking University First Hospital from September 2013 to September 2023. Results Thirteen patients (seven male and six female patients; two sibling sisters) had the symptoms aged from 1 month to 1 year. Their urine 4-hydroxybutyrate acid levels were elevated and were accompanied by mildly increased serum lactate levels. Brain magnetic resonance imaging (MRI) showed symmetric abnormal signals in both sides of the globus pallidus and other areas. All 13 patients had psychomotor retardation, with seven showing epileptic seizures. Among the 18 variants of the ALDH5A1 gene identified in these 13 patients, six were previously reported, while 12 were novel variants. Among the 12 novel variants, three (c.85_116del, c.206_222dup, c.762C > G) were pathogenic variants; five (c.427delA, c.515G > A, c.637C > T, c.755G > T, c.1274T > C) were likely pathogenic; and the remaining four (c.454G > C, c.479C > T, c.1480G > A, c.1501G > C) were variants of uncertain significance. The patients received drugs such as L-carnitine, vigabatrin, and taurine, along with symptomatic treatment. Their urine 4-hydroxybutyric acid levels showed variable degrees of reduction. Conclusions A cohort of 13 cases with early-onset SSADH deficiency was analyzed. Onset of symptoms occurred from 1 month to 1 year of age. Twelve novel variants of the ALDH5A1 gene were identified.

Abstract Using e + e − collision data collected at the BESIII detector at center-of-mass energies between 4.128 and 4.226 GeV, corresponding to an integrated luminosity of 7.33 fb −1, we determine the absolute branching fractions of fifteen hadronic D s + $$ {D}_s^{+} $$ decays with a double-tag technique. In particular, we make precise measurements of the branching fractions B D s + → K + K − π + = 5.49 ± 0.04 ± 0.07 % $$ \mathcal{B}\left({D}_s^{+}\to {K}^{+}{K}^{-}{\pi}^{+}\right)=\left(5.49\pm 0.04\pm 0.07\right)\% $$ , B D s + → K S 0 K + = 1.50 ± 0.01 ± 0.01 % $$ \mathcal{B}\left({D}_s^{+}\to {K}_S^0{K}^{+}\right)=\left(1.50\pm 0.01\pm 0.01\right)\% $$ and B D s + → K + K − π + π 0 = 5.50 ± 0.05 ± 0.11 % $$ \mathcal{B}\left({D}_s^{+}\to {K}^{+}{K}^{-}{\pi}^{+}{\pi}^0\right)=\left(5.50\pm 0.05\pm 0.11\right)\% $$ , where the first uncertainties are statistical and the second ones are systematic. The CP asymmetries in these decays are also measured and all are found to be compatible with zero.

Abstract Background Bacterial nanocellulose (BNC), a natural polymer material, gained significant popularity among researchers and industry. It has great potential in areas, such as textile manufacturing, fiber-based paper, and packaging products, food industry, biomedical materials, and advanced functional bionanocomposites. The main current fermentation methods for BNC involved static culture, as the agitated culture methods had lower raw material conversion rates and resulted in non-uniform product formation. Currently, studies have shown that the production of BNC can be enhanced by incorporating specific additives into the culture medium. These additives included organic acids or polysaccharides. γ-Polyglutamic acid (γ-PGA), known for its high polymerization, excellent biodegradability, and environmental friendliness, has found extensive application in various industries including daily chemicals, medicine, food, and agriculture. Results In this particular study, 0.15 g/L of γ-PGA was incorporated as a medium additive to cultivate BNC under agitated culture conditions of 120 rpm and 30 ℃. The BNC production increased remarkably by 209% in the medium with 0.15 g/L γ-PGA and initial pH of 5.0 compared to that in the standard medium, and BNC production increased by 7.3% in the medium with 0.06 g/L γ-PGA. The addition of γ-PGA as a medium additive resulted in significant improvements in BNC production. Similarly, at initial pH levels of 4.0 and 6.0, the BNC production also increased by 39.3% and 102.3%, respectively. To assess the characteristics of the BNC products, scanning electron microscopy, Fourier transform infrared spectroscopy, and thermogravimetric analysis were used. The average diameter of BNC fibers, which was prepared from the medium adding 0.15 g/L γ-PGA, was twice thicker than that of BNC fibers prepared from the control culture medium. That might be because that polyglutamic acid relieved the BNC synthesis from the shear stress from the agitation. Conclusions This experiment held great significance as it explored the use of a novel medium additive, γ-PGA, to improve the production and the glucose conversion rate in BNC fermentation. And the BNC fibers became thicker, with better thermal stability, higher crystallinity, and higher degree of polymerization (DPv). These findings lay a solid foundation for future large-scale fermentation production of BNC using bioreactors.

Abstract Ferroelectric materials, whose electrical polarization can be switched under external stimuli, have been widely used in sensors, data storage, and energy conversion. Molecular orbital breaking can result in switchable structural and physical bistability in ferroelectric materials as traditional spatial symmetry breaking does. Differently, molecular orbital breaking interprets the phase transition mechanism from the perspective of electronics and sheds new light on manipulating the physical properties of ferroelectrics. Here, we synthesize a pair of organosilicon Schiff base ferroelectric crystals, (R)- and (S)-N-(3,5-di-tert-butylbenzylidene)-1-((triphenylsilyl)oxy)ethanamine, which show optically controlled phase transition accompanying the molecular orbital breaking. The molecular orbital breaking is manifested as the breaking and reformation of covalent bonds during the phase transition process, that is, the conversion between C = N and C–O in the enol form and C–N and C = O in the keto form. This process brings about photo-mediated bistability with multiple physical channels such as dielectric, second-harmonic generation, and ferroelectric polarization. This work further explores this newly developed mechanism of ferroelectric phase transition and highlights the significance of photo-mediated ferroelectric materials for photo-controlled smart devices and bio-sensors.

Abstract Metal-hydrogen systems have attracted intense interest for diverse energy-related applications. However, metals usually reduce their ductility after hydrogenation. Here, we show that hydrogen can take the form of nano-sized ordered hydrides (NOH) homogeneously dispersed in a stable glassy shell, leading to remarkable enhancement in both strength and ductility. The yield strength is enhanced by 44% and the plastic strain is substantially improved from almost zero to over 70%, which is attributed to the created NOH and their interplay with the glassy shell. Moreover, the hydride-glass composite GdCoAlH possesses a giant magnetic entropy change (−ΔS M) of 18.7 J kg−1K−1 under a field change of 5 T, which is 105.5% larger than the hydrogen-free sample and is the largest value among amorphous alloys and related composites. The prominent ΔS M-ductility combination overcomes the bottlenecks of amorphous alloys as magnetic refrigerants. These results provide a promising strategy for property breakthrough of structural-functional alloys.

Abstract Background Protein posttranslational modifications (PTMs) are fast and early responses to environmental changes, including pathogen infection. Jujube witches’ broom (JWB) is a phytoplasma disease causing great economic loss in jujube production. After phytoplasma infection, the transcriptional, translational, and metabolic levels in jujube were activated, enabling it to survive during phytoplasma invasion. However, no study has yet reported on PTMs in jujube. Lysine crotonylation (Kcr) and lysine succinylation (Ksu) have been popular studies in recent years and their function in plant phytoplasma-stress responses remains unclear. Results Here, 1656 crotonylated and 282 succinylated jujube proteins were first identified under phytoplasma-stress, of which 198 were simultaneously crotonylated and succinylated. Comparative analysis revealed that 656 proteins, 137 crotonylated and 43 succinylated proteins in jujube were regulated by phytoplasma infection, suggesting that Kcr was more universal than Ksu. Kcr differentially expressed proteins (DEPs) were related to ribosomes, photosynthetic and carbon metabolism, while Ksu DEPs were mainly involved in carbon metabolism, the TCA cycle and secondary metabolite biosynthesis. The crosstalk network among proteome, crotonylome and succinylome showed that DEPs related to ribosomal, peroxidases and glutathione redox were enriched. Among them, ZjPOD51 and ZjPHGPX2 significantly increased at the protein and Kcr level under phytoplasma-stress. Notably, 7 Kcr sites were identified in ZjPHGPX2, a unique antioxidant enzyme. After inhibitor nicotinamide (NAM) treatment, GPX enzyme activity in jujube seedlings was reduced. Further, site-directed mutagenesis of key Kcr modification sites K130 and/or K135 in ZjPHGPX2 significantly reduced its activity. Conclusions This study firstly provided large-scale datasets of Kcr and Ksu in phytoplasma-infected jujube and revealed that Kcr modification in ZjPHGPX2 positively regulates its activity.

Abstract Using 24.1 fb −1 of e + e − collision data collected with the BESIII detector at the BEPCII collider, the Born cross sections and effective form factors of the e + e − → Σ + Σ ¯ − $$ {e}^{+}{e}^{-}\to {\Sigma}^{+}{\overline{\Sigma}}^{-} $$ reaction are measured. The measurements are performed at center-of-mass energies ranging from 3.510 to 4.951 GeV. No significant evidence for the decay of the charmonium(-like) states, ψ(3770), ψ(4040), ψ(4160), Y(4230), Y(4360), ψ(4415), and Y(4660), into a Σ + Σ ¯ − $$ {\Sigma}^{+}{\overline{\Sigma}}^{-} $$ final state is observed. Consequently, upper limits for the products of the branching fractions and the electronic partial widths at the 90% confidence level are reported for these decays.

Abstract Background Neoadjuvant chemoimmunotherapy (NCIT) for locally advanced esophageal squamous cell carcinoma (ESCC) is supported by increasing data, but the sample size is limited, and the findings are not completely consistent. We conducted a real‐world study and a meta‐analysis to evaluate the efficacy and safety of NCIT in locally advanced ESCC. Methods We retrospectively assessed the outcomes of patients with locally advanced ESCC who completed NICT and subsequent esophagectomy at our hospital between January 2019 and December 2022, including pathological complete response (pCR) rate, major pathological response (MPR) rate, 1‐, 2‐, and 3‐year overall survival (OS) rates, disease control rate (DCR), objective response rate (ORR), 1‐year recurrence rate, R0 resection rate and adverse events. Moreover, a meta‐analysis of 27 published literatures was also conducted for comparison. Results In the analysis, 128 patients were studied, with 25% achieving pCR, 46.1% MPR, and 99.2% R0 resection. The 1‐, 2‐, and 3‐year OS rates were 91.41% (95% CI: 85.15%–95.63%), 75.00% (95% CI: 66.58%–82.23%) and 64.84% (95% CI: 55.91%–73.07%).ORR and DCR were 31.2% (95% CI: 23.31–39.99) and 64.1% (95% CI: 55.15%–72.38%), and the 1‐year recurrence rate was 26.7% (95% CI: 22.5%–38.1%). Treatment‐related events occurred in 96.1% but were acceptable. In a meta‐analysis of 27 studies with 1734 patients, pooled rates for pCR, MPR, ORR, DCR, and R0 resection were 29%, 52%, 71%, 97%, and 98%, respectively, with a 1‐year recurrence rate of 12%. Conclusion NCIT is safe and provides potential survival benefits for patients with locally advanced ESCC. However, randomized phase 3 trial data is still needed.

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.

ABSTRACTAccurate 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.

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.

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.

Despite an increasing number of manufacturing companies innovating their business models in the digital economy, how innovative business models are formed has remained an under-researched area, especially in the manufacturing industry. This study addresses the particular research gap by analyzing the business model innovation process and identifies and explores five conditions that influence the business model innovation process: creative ideas, value proposition optimization, transaction structure reconstruction, profit model exploration, and dynamic potential accumulation. Then, based on the data of 238 respondents in Chinese manufacturing companies, the fuzzy-set approach is employed by conducting Qualitative Comparative Analysis (fsQCA) to explore the configurations of the innovative business model formation process. The results show that high levels of business model innovation can be achieved through different configurations: (1) creative ideas, value proposition optimization, and transaction structure reconstruction combined with dynamic potential accumulation, (2) creative ideas, value proposition optimization, and profit model exploration combined with dynamic potential accumulation, (3) value proposition optimization, and profit model exploration combined with transaction structure reconstruction, and (4) transaction structure reconstruction combined with dynamic potential accumulation. This study contributes to the theoretical literature on business model innovation and provides practical information for manufacturing companies looking to innovate their business models.

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.