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Abstract Land use is key in regulating surface temperature, yet these relationships are often obscured by long-term mean responses. Here we employed numerical multi-model results to investigate the response of the surface temperature to land use change, especially its lower tails corresponding to boreal winter. The surface temperature decrease in the lower tails can exhibit up to ten times greater than the mean response to land use change over both the historical and future periods. Downward longwave radiation has emerged as the most remarkable contributing factor in controlling surface temperature change in mid-high latitudes of the Northern Hemisphere. Land use change can modify surface energy balance through land-atmosphere firstly, thereby regulate spatial patterns of water vapor and cloud cover in the Northern Hemisphere through teleconnection. The unity of local and remote effects influences the levels of downward longwave radiation and altering surface temperature at mid-high latitudes in extreme cold seasons.

Brachial plexus injury (BPI) with motor neurons (MNs) damage still remain poor recovery in preclinical research and clinical therapy, while cell-based therapy approaches emerged as novel strategies. Previous work of rat skin precursor-derived Schwann cells (SKP–SCs) provided substantial foundation for repairing peripheral nerve injury (PNI). Given that, our present work focused on exploring the repair efficacy and possible mechanisms of SKP-SCs implantation on rat BPI combined with neurorrhaphy post-neurotomy. Results indicated the significant locomotive and sensory function recovery, with improved morphological remodeling of regenerated nerves and angiogenesis, as well as amelioration of target muscles atrophy and motor endplate degeneration. Besides, MNs could restore from oxygen-glucose-deprivation (OGD) injury upon SKP-SCs-sourced secretome treatment, implying the underlying paracrine mechanisms. Moreover, rat cytokine array assay detected 67 cytokines from SKP-SC-secretome, and bioinformatic analyses of screened 32 cytokines presented multiple functional clusters covering diverse cell types, including inflammatory cells, Schwann cells, vascular endothelial cells (VECs), neurons, and SKP-SCs themselves, relating distinct biological processes to nerve regeneration. Especially, a panel of hypoxia-responsive cytokines (HRCK), can participate into multicellular biological process regulation for permissive regeneration milieu, which underscored the benefits of SKP-SCs and sourced secretome, facilitating the chorus of nerve regenerative microenvironment. Furthermore, platelet-derived growth factor-AA (PDGF-AA) and vascular endothelial growth factor-A (VEGF-A) were outstanding cytokines involved with nerve regenerative microenvironment regulating, with significantly elevated mRNA expression level in hypoxia-responsive SKP-SCs. Altogether, through recapitulating the implanted SKP-SCs and derived secretome as niche sensor and paracrine transmitters respectively, HRCK would be further excavated as molecular underpinning of the neural recuperative mechanizations for efficient cell therapy; meanwhile, the analysis paradigm in this study validated and anticipated the actions and mechanisms of SKP-SCs on traumatic BPI repair, and was beneficial to identify promising bioactive molecule cocktail and signaling targets for cell-free therapy strategy on neural repair and regeneration.

Abstract Background B-cell maturation antigen (BCMA)-targeted chimeric antigen receptor T-cell (CAR T-cell) therapy has exhibited remarkable efficacy in refractory or relapsed multiple myeloma (R/R MM), but recurrence and rapid progression of disease are still observed within a short time after treatment. Long-term pomalidomide therapy, which potentiates T-cell functionality, might enhance the efficacy of BCMA CAR T-cell therapy. Methods We performed a single-center retrospective clinical study. Patients with relapsed or refractory multiple myeloma who received BCMA CAR T-cell infusion were enrolled in our study, and were followed by long-term pomalidomide treatment (4 mg/day) or not one month after infusion. The response and adverse events were assessed after infusion. The effect of pomalidomide on BCMA CAR T-cells was assessed in vitro. Results The objective response rate (ORR) of BCMA-CART was 100%. Three months following CAR T-cell infusion, of the 8 patients receiving pomalidomide, except for 2 patients who stopped maintenance therapy and were lost to follow-up, all patients (6/6) achieved VGPR (very good partial response) or CR (complete response), while only 5 patients (5/8) who did not receive pomalidomide treatment achieved VGPR or better. At a median follow-up of 27 months, for the 8 patients who did not receive pomalidomide administration, the median TTP (time to progression) was 5.85 (1–14) months, while the OS (overall survival) was 10.7 (1.2–16) months. Of the 8 patients who received pomalidomide therapy after CAR T-cell infusion, the median TTP was 13 (7–13) months, while the OS was not reached. Moreover, neither long-term hematological toxicity nor drug-induced liver damage was observed during the follow-up period. Mechanistically, pomalidomide promotes antimyeloma efficacy of BCMA CAR T-cells by inhibiting cell apoptosis and enhancing cytoxicity. Conclusions Our results confirmed that BCMA CAR T-cell therapy combined with long-term pomalidomide had a low recurrence rate and manageable therapy-related side effects, providing a promising option for treating R/R MM. Graphical Abstract

The True Story of Ah Q is the first complete translation of a Chinese modern literary work to be introduced to Thailand. Its dissemination in Thailand has undergone a transformation, from being considered a progressive literary classic (1952–1958) to being banned for political reasons (1958–1990), and then reclaiming its status as a literary classic (1990-present). This transformation perfectly exemplifies the symbiotic and exclusive relationship between literature and social politics. After more than 70 years of dissemination, The True Story of Ah Q has had a wide and profound impact on Thai society, politics, and literary development. It has enlightened people, inspiring Thai citizens to strive for democracy and freedom. It has also contributed to the development of critical literature in Thailand, nurturing a group of progressive intellectuals who fearlessly criticize social issues and further promote the literary movement of “art for life, art for the people” in Thailand. Furthermore, it has provided new creative techniques for Thai literary creation.

A novel series of meta-diamide compounds incorporating a pyrazole moiety (2a–2v) were designed and synthesized based on cyproflanilide. Their structures were validated through 1H NMR, 13C NMR, and HRMS analyses. These compounds were evaluated for their insecticidal activity against Plutella xylostella, Mythimna separate, Tetranychus cinnabarinus, and Nilaparvata lugens. Most of the title compounds exhibited good activity against N. lugens at 400 mg/L. Compound 2k demonstrated potential for further optimization as an insecticidal lead, thereby extending the application of meta-diamide compounds in the field of sucking mouthparts.

This study was conducted to investigate the effects and mechanisms of glutamine (Gln) on the repair of acid-induced injury in dairy cow ruminal epithelial cells (RECs) in vitro. Dairy cow RECs were cultured in a medium with pH of 5.5 for 3 h and subsequently treated with various concentrations of Gln (4, 8, 12, 32 mmol/l) for 12 h. The messenger ribonucleic acid (mRNA) expression levels of occludin (OCLN), claudin 1 (CLDN1), toll-like receptor 2 (TLR2), toll-like receptor 4 (TLR4) and genes for inflammatory factors were measured using reverse transcription-quantitative real-time PCR (RT-qPCR). The results showed that cellular activity and OCLN expression were significantly highest at 8 mmol/l Gln (P < 0.05). CLDN1 expression was significantly higher at 4 mmol/l Gln compared to the other groups (P < 0.05). The relative expression levels of tumour necrosis factor (TNF), interleukin 1B (IL1B), C-X-C motif chemokine ligand 8 (CXCL8), TLR2 and TLR4 in the acid treatment group were significantly higher than those in the control group (P < 0.05), but they were lower in the Gln-treated groups than in the acid treatment group (P < 0.05). These findings demonstrate that Gln promotes the proliferation of RECs, enhances the expression of epithelial cell junction proteins, and inhibits the expression of inflammatory factors and surface receptors. In conclusion, Gln shows a potential for repairing acid-induced injury in RECs.

Bupleurum, belonging to the Apiaceae, is widely distributed across the Eurasian continent. The origin and species diversification of Bupleurum in East Asia, remain incompletely resolved due to the limited samples in previous studies. To address these issues, we have reconstructed a robust phylogenetic framework for Bupleurum in East Asia based on the ITS and three plastid genes. Our phylogenetic analysis confirms the monophyly of Bupleurum with strong support. Both ITS and chloroplast dataset divided the Bupleurum in East Asia into East Asia Group I and East Asia Group II in this study. The divergence time and ancestral area reconstruction of ITS dataset indicated that the Bupleurum originated in the Mediterranean basin and its adjacent areas around 50.33 Ma. subg. Penninervia and subg. Bupleurum diverged at about 44.35 Ma, which may be related to the collision of India with the Eurasian continent. Both East Asia Group I and East Asia Group II originated from a common ancestor in the Mediterranean, East Asia Group I divergence around 12.95 Ma; East Asia Group II divergence around 13.32 Ma. The character reconstruction showed that the morphological characters and altitude distribution analyzed in this study exhibit a scattered distribution in East Asian Group I and East Asian Group II. Additionally, diversification rate analysis shows that the East Asian Group I and East Asian Group II exhibited no significant shifts in diversification rates in the evolutionary history according to ITS and combined dataset. Both molecular and morphological data supports that East Asian Bupleurum is a museum taxon, meaning that the species diversity of East Asian Bupleurum has gradually accumulated over time.

The orchid Calanthe discolor, which has high ornamental and medicinal value, is mainly distributed in Zhejiang, Jiangsu, and southeast Hubei Provinces of China, as well as in Japan and the southern Korean peninsula. In this study, the whole chloroplast genome sequence of C. discolor was first assembled using high-throughput Illumina paired-end technology, providing data to evaluate the evolution of this species. The C. discolor chloroplast genome was158,286 bp long, including a large single-copy region of 87,095 bp, a small single-copy region of 18,407 bp, and two copies of a repeat region (26,392-bp each). The overall G + C content was 41.2%. A total of 133 genes were predicted from the genome, including 87 protein-coding genes, eight ribosomal RNAs, 38 transfer RNAs. Phylogenetic analysis indicated a close relationship between C. discolor and C. bicolor.

Abstract The production of double P-wave heavy quarkonia is studied systematically within the framework of non-relativistic quantum chromodynamics at the exclusive process of the electron–positron collision annihilation at the CM energy $$\sqrt{s}=91.1876$$ s = 91.1876 GeV of the $$Z^0$$ Z 0 pole, i.e., double P-wave charmonia, double P-wave $$B_c$$ B c mesons, and double P-wave bottomonia in $$e^+e^-\rightarrow \gamma ^*/Z^0 \rightarrow |(Q\bar{Q'})[n]\rangle +|(Q'\bar{Q})[n^\prime ]\rangle $$ e + e - → γ ∗ / Z 0 → | ( Q Q ′ ¯ ) [ n ] ⟩ + | ( Q ′ Q ¯ ) [ n ′ ] ⟩ ( $$Q/Q'=c$$ Q / Q ′ = c - or b-quarks) at a future super Z factory, where [n] or $$[n^\prime ]$$ [ n ′ ] stands for the color-singlet $$[^1P_1]$$ [ 1 P 1 ] and $$[^3P_J]$$ [ 3 P J ] ( $$J=0,1,2$$ J = 0 , 1 , 2 ) Fock states. As an improved trace technology is useful for calculating the complicated double P-wave channels, the analytical result can be obtained at the amplitude level. According to our study, the generation rates for the double P-wave heavy quarkonia at the future super Z factory are considerable. The values obtained for the total cross sections of the double P-wave charmonium for $$\sigma {(|(c\bar{c})[1]\rangle +|(c\bar{c})[1]\rangle )}=4.191^{+0.489}_{-0.498}\times 10^{-3}~fb$$ σ ( | ( c c ¯ ) [ 1 ] ⟩ + | ( c c ¯ ) [ 1 ] ⟩ ) = 4 . 191 - 0.498 + 0.489 × 10 - 3 f b , the total cross sections of the double P-wave $$B_c$$ B c mesons for $$\sigma {(|(c\bar{b})[1]\rangle +|(b\bar{c})[1]\rangle )}=0.2045^{+0.0084}_{-0.0080}~fb$$ σ ( | ( c b ¯ ) [ 1 ] ⟩ + | ( b c ¯ ) [ 1 ] ⟩ ) = 0 . 2045 - 0.0080 + 0.0084 f b , and the total cross sections of the double P-wave bottomonium for $$\sigma {(|(b\bar{b})[1]\rangle +|(b\bar{b})[1]\rangle )}=5.244^{+0.134}_{-0.136}\times 10^{-3}~fb$$ σ ( | ( b b ¯ ) [ 1 ] ⟩ + | ( b b ¯ ) [ 1 ] ⟩ ) = 5 . 244 - 0.136 + 0.134 × 10 - 3 f b . The main uncertainties come from the mass of heavy quarkonia and the corresponding first-derivative radial wave functions at the origin under the Buchmüller–Tye (BT) potential. The number of events in the production of double P-wave charmonium, $$B_c$$ B c -meson, and bottomonium states via $$e^-e^+\rightarrow \gamma ^*/Z^0 \rightarrow |(Q\bar{Q}')[n]\rangle + |(Q'\bar{Q})[n^\prime ]\rangle $$ e - e + → γ ∗ / Z 0 → | ( Q Q ¯ ′ ) [ n ] ⟩ + | ( Q ′ Q ¯ ) [ n ′ ] ⟩ at the integrated luminosity $$\mathcal{L}\approx 10^{34}cm^{-2}s^{-1}$$ L ≈ 10 34 c m - 2 s - 1 at the super Z factory is almost unobservable.

Abstract Nutrition support is an important care component for patients on hemodialysis. Also, patient self-management is important to maintaining proper nutritional intake during hemodialysis. This cross-sectional study investigated the knowledge, attitude, and practice (KAP) towards nutrition support and management among hemodialysis patients treated at the West China Hospital of Sichuan University between January and March 2023. Among 445 (95.91%) valid questionnaires, 58.43% were filled out by male patients. The knowledge, attitude, and practice scores were 11.44 ± 1.80 (possible range: 0–13), 30.29 ± 3.22 (possible range: 8–40), and 31.27 ± 5.67 (possible range: 8–40), respectively. Age > 60 years (OR = 0.487, 95%CI: 0.260–0.913, P = 0.025) and junior college or undergraduate or above (OR = 2.606, 95%CI: 1.621–4.189, P

Abstract Background Associations of dietary sodium and potassium intake with fracture risk are inconsistent and the effects of salt substitute on fracture incidence are unknown. We assessed the effect of salt substitute compared to regular salt intake on fracture incidence using data from the Salt Substitute and Stroke Study (SSaSS). Methods SSaSS was a cluster-randomized controlled trial conducted in 600 villages in northern China. Villages were randomly allocated into intervention and control groups in a 1:1 ratio. Salt substitute was provided to intervention villages and control villages continued regular salt use for 5 years. The primary outcome for this secondary analysis was the incidence of all fractures. Secondary outcomes included incidence of vertebral fracture, non-vertebral fracture, and fracture of unknown or non-specific location. Results 20,995 participants were included in this study, and 821 fractures occurred during follow-up. Intention-to-treat analyses showed no differences between the salt substitute and regular salt groups in the incidence of all fractures (rate ratio (RR) 0.96; 95% CI 0.81 to 1.14), vertebral fracture (RR 0.82; 95% CI 0.53 to 1.26), non-vertebral fracture (RR 1.05; 95% CI 0.86 to 1.29), or fracture of unknown or non-specific location (RR 0.80; 95% CI 0.54 to 1.18). Conclusions Use of salt substitute compared to regular salt had no detectable effect on the incidence of fracture in a population at high risk of cardiovascular disease and fracture. Trial registration ClinicalTrials.gov, NCT02092090. Registered on March 12, 2014.

Abstract Reactive capture of carbon dioxide (CO2) offers an electrified pathway to produce renewable carbon monoxide (CO), which can then be upgraded into long-chain hydrocarbons and fuels. Previous reactive capture systems relied on hydroxide- or amine-based capture solutions. However, selectivity for CO remains low (

Abstract Background Scutellaria, a sub-cosmopolitan genus, stands as one of the Lamiaceae family’s largest genera, encompassing approximately 500 species found in both temperate and tropical montane regions. Recognized for its significant medicinal properties, this genus has garnered attention as a research focus, showcasing anti-cancer, anti-inflammatory, antioxidant, and hepatoprotective qualities. Additionally, it finds application in agriculture and horticulture. Comprehending Scutellaria’s taxonomy is pivotal for its effective utilization and conservation. However, the current taxonomic frameworks, primarily based on morphological characteristics, are inadequate. Despite several phylogenetic studies, the species relationships and delimitations remain ambiguous, leaving the genus without a stable and reliable classification system. Results This study analyzed 234 complete chloroplast genomes, comprising 220 new and 14 previously published sequences across 206 species, subspecies, and varieties worldwide. Phylogenetic analysis was conducted using six data matrices through Maximum Likelihood and Bayesian Inference, resulting in a robustly supported phylogenetic framework for Scutellaria. We propose three subgenera, recommending the elevation of Section Anaspis to subgeneric rank and the merging of Sections Lupulinaria and Apeltanthus. The circumscription of Subgenus Apeltanthus and Section Perilomia needs to be reconsidered. Comparative analysis of chloroplast genomes highlighted the IR/SC boundary feature as a significant taxonomic indicator. We identified a total of 758 SSRs, 558 longer repetitive sequences, and ten highly variable regions, including trnK–rps16, trnC–petN, petN–psbM, accD–psaI, petA–psbJ, rpl32–trnL, ccsA–ndhD, rps15–ycf1, ndhF, and ycf1. These findings serve as valuable references for future research on species identification, phylogeny, and population genetics. Conclusions The phylogeny of Scutellaria, based on the most comprehensive sample collection to date and complete chloroplast genome analysis, has significantly enhanced our understanding of its infrageneric relationships. The extensive examination of chloroplast genome characteristics establishes a solid foundation for the future development and utilization of Scutellaria, an important medicinal plant globally.

Abstract. Background:. Accurately and efficiently extracting microbial genomic sequences from complex metagenomic data is crucial for advancing our understanding in fields such as clinical diagnostics, environmental microbiology, and biodiversity. As sequencing technologies evolve, this task becomes increasingly challenging due to the intricate nature of microbial communities and the vast amount of data generated. Especially in intensive care units (ICUs), infections caused by antibiotic-resistant bacteria are increasingly prevalent among critically ill patients, significantly impacting the effectiveness of treatments and patient prognoses. Therefore, obtaining timely and accurate information about infectious pathogens is of paramount importance for the treatment of patients with severe infections, which enables precisely targeted anti-infection therapies, and a tool that can extract microbial genomic sequences from metagenomic dataset would be of help. Methods:. We developed MetaGeneMiner to help with retrieving specific microbial genomic sequences from metagenomes using a k-mer-based approach. It facilitates the rapid and accurate identification and analysis of pathogens. The tool is designed to be user-friendly and efficient on standard personal computers, allowing its use across a wide variety of settings. We validated MetaGeneMiner using eight metagenomic samples from ICU patients, which demonstrated its efficiency and accuracy. Results:. The software extensively retrieved coding sequences of pathogens Acinetobacter baumannii and herpes simplex virus type 1 and detected a variety of resistance genes. All documentation and source codes for MetaGeneMiner are freely available at https://gitee.com/sculab/MetaGeneMiner. Conclusions:. It is foreseeable that MetaGeneMiner possesses the potential for applications across multiple domains, including clinical diagnostics, environmental microbiology, gut microbiome research, as well as biodiversity and conservation biology. Particularly in ICU settings, MetaGeneMiner introduces a novel, rapid, and precise method for diagnosing and treating infections in critically ill patients. This tool is capable of efficiently identifying infectious pathogens, guiding personalized and precise treatment strategies, and monitoring the development of antibiotic resistance, significantly impacting the diagnosis and treatment of severe infections.

Abstract Introduction The COVID-19 pandemic in the past few years led to major adjustments in the provision of healthcare. This study aimed to investigate trainees’ perception of impact of the pandemic on specialty training in Obstetrics & Gynaecology (O&G) in Hong Kong. Methods A cross-sectional questionnaire survey was performed on all the O&G trainees and the young fellows of the Hong Kong College of Obstetricians and Gynaecologists (HKCOG). The questionnaires included 5 parts: demographic data, impact on clinical activities, redeployment, educational activities and career progression. Results A total of 104 questionnaires (92.9%) were received for final analysis. The majority of the participants had reductions in elective and emergency operations, as well as exposure to in-patient admissions and out-patient clinics in both obstetrics and gynaecology. The reduction was most significant in elective gynaecology operations. One-third (34.6%) of the participants had been redeployed to other departments, and educational activities were reduced during the pandemic. Around 58% of the trainees were concerned with the reduction in clinical exposure, and 78% worried they would not be able to log sufficient number of surgical procedures. Basic trainees were significantly more worried than higher trainees. Around half of the trainees had doubts or regrets about choosing to undergo O&G specialty training. Conclusion The O&G trainees in Hong Kong perceived that the COVID-19 pandemic had significant negative impacts on their training. Many trainees were worried they would not be able to attain the required level of competence when they complete their specialist training.

Abstract Background As a common disabling disease, irreversible neuronal death due to spinal cord injury (SCI) is the root cause of functional impairment; however, the capacity for neuronal regeneration in the developing spinal cord tissue is limited. Therefore, there is an urgent need to investigate how defective neurons can be replenished and functionally integrated by neural regeneration; the reprogramming of intrinsic cells into functional neurons may represent an ideal solution. Methods A mouse model of transection SCI was prepared by forceps clamping, and an adeno-associated virus (AAV) carrying the transcription factors NeuroD1 and Neurogenin-2(Ngn2) was injected in situ into the spinal cord to specifically overexpress these transcription factors in astrocytes close to the injury site. 5-bromo-2´-deoxyuridine (BrdU) was subsequently injected intraperitoneally to continuously track cell regeneration, neuroblasts and immature neurons marker expression, neuronal regeneration, and glial scar regeneration. In addition, immunoprotein blotting was used to measure the levels of transforming growth factor-β (TGF-β) pathway-related protein expression. We also evaluated motor function, sensory function, and the integrity of the blood-spinal cord barrier(BSCB). Results The in situ overexpression of NeuroD1 and Ngn2 in the spinal cord was achieved by specific AAV vectors. This intervention led to a significant increase in cell regeneration and the proportion of cells with neuroblasts and immature neurons cell properties at the injury site(p 0.05), although the treated mice had more sensory sensitivity and greater voluntary motor ability in open field than the non-intervention mice. We observed significant repair of the BSCB at the center of the injury site (p

【Objective】The use of artificial inoculation to ferment cigar tobacco leaves is an inevitable trend in the industrial production of cigar tobacco leaves, and the neutral aroma components are the important quality components of cigar tobacco leaves. The study aims to investigate the effect of Bacillus safensis GL2 on the neutral aroma components of cigar tobacco leaves.【Method】GL2 was screened from Cuban cigar Cohiba Robert and used to ferment cigar leaves. The neutral aroma components in tobacco leaves were determined by distillation extraction-gas chromatography-mass spectrometry, and multivariate statistical methods were used for analysis and statistics.【Result】The total aroma and the contents of most neutral aroma components in cigar tobacco leaves were significantly increased after GL2 fermentation (P < 0.05), and the increased aroma substances mainly included olefins, ketones and alcohols. A total of 13 differentially neutral aroma components were selected by VIP > 1 and P < 0.05, and 9 of them were significantly up-regulated and positively correlated with tobacco leaf aroma. There were 7 species with significant positive correlation (P < 0.05), which were the key differential aroma components of 2, 6, 6-trimethyl-2-cyclohexene-1, 4-dione, 2, 6, 6-trimethyl-1, 4-cyclohexanedione, geraniyl acetone, acanthyl acetone, neophydiene, solanone and phytoalcohol. In addition, 4 different aroma components were significantly decreased and negatively correlated with tobacco leaf aroma, among which 2, 4-di-tert-butyl-6-nitrophenol was significantly negatively correlated with cigar tobacco aroma (P < 0.05). 2, 6, 6-trimethyl-2-cyclohexene-1, 4-dione, geranyl acetone, solanone and phytol contributed significantly to the aroma of fermented cigar tobacco leaves, resulting in a stronger overall dry and floral fragrances. As a result, they enriched the aroma and improved the sensory quality of cigar tobacco leaves.【Conclusion】Inoculation of B. safensis during cigar tobacco fermentation is beneficial for improving the quality of cigar tobacco leaves, which provide theoretical support for improving the fermentation quality of cigar tobacco leaves with biotechnology.

Abstract Natural answer generation is in a very clear practical significance and strong application background, which can be widely used in the field of knowledge services such as community question answering and intelligent customer service. Traditional knowledge question answering is to provide precise answer entities and neglect the defects; namely, users hope to receive a complete natural answer. In this research, we propose a novel attention-based recurrent neural network for natural answer generation, which is enhanced with multi-level copying mechanisms and question-aware loss. To generate natural answers that conform to grammar, we leverage multi-level copying mechanisms and the prediction mechanism which can copy semantic units and predict common words. Moreover, considering the problem that the generated natural answer does not match the user question, question-aware loss is introduced to make the generated target answer sequences correspond to the question. Experiments on three response generation tasks show our model to be superior in quality while being more parallelizable and requiring significantly less time to train. Our model achieves 0.727 BLEU on the SimpleQuestions response generation task, improving over the existing best results by over 0.007 BLEU. Our model has scored a significant enhancement on naturalness with up to 0.05 more than best performing baseline. The simulation results show that our method can generate grammatical and contextual natural answers according to user needs.

Abstract A dose-escalation and expansion, phase 1/2 study (ClinicalTrials.gov, NCT04818333) was conducted to assess the novel antibody-drug conjugate SHR-A1811 in pretreated HER2-altered advanced non-small cell lung cancer (NSCLC). Here, we report results from the phase 1 portion. Patients who had previously failed or were intolerant to platinum-based chemotherapy were enrolled and received SHR-A1811 intravenously at doses of 3.2 to 8.0 mg/kg every 3 weeks. Dose escalation followed a Bayesian logistic regression model that included overdose control, with subsequent selection of tolerable levels for dose expansion. Overall, 63 patients were enrolled, including 43 receiving a recommended dose for expansion of 4.8 mg/kg. All patients had HER2-mutant disease. Dose-limiting toxicity occurred in one patient in the 8.0 mg/kg dose cohort. Grade ≥ 3 treatment-related adverse events occurred in 29 (46.0%) patients. One patient in the 6.4 mg/kg cohort died due to interstitial lung disease. As of April 11, 2023, the 4.8 mg/kg cohort showed an objective response rate of 41.9% (95% CI 27.0–57.9), and a disease control rate of 95.3% (95% CI 84.2–99.4). The median duration of response was 13.7 months, with 13 of 18 responses ongoing. The median progression-free survival was 8.4 months (95% CI 7.1–15.0). SHR-A1811 demonstrated favourable safety and clinically meaningful efficacy in pretreated advanced HER2-mutant NSCLC.

Abstract Rock mass deformation and failure are macroscopic manifestations of crack initiation, propagation, and coalescence. However, simulating the transition of rocks from continuous to discontinuous media under cyclic dynamic loading remains challenging. This study proposes a hybrid finite-discrete element method (HFDEM) to model crack propagation, incorporating a frequency-dependent cohesive-zone model. The mechanical properties of standard sandy mudstone under quasi-static and cyclic dynamic loading were simulated using HFDEM, and the method's reliability was verified through experimental comparison. The comparative analysis demonstrates that HFDEM successfully captures crack interaction mechanisms and accurately simulates the overall failure behavior of specimens. Additionally, the effects of pre-existing flaw inclination angle and dynamic loading frequency on rock failure mechanisms were investigated. The numerical results reveal that rock samples exhibit significantly higher compressive strength under dynamic loading compared to quasi-static loading, with compressive strength increasing with higher cyclic dynamic load frequencies. Furthermore, by analyzing the strength characteristics, crack propagation, and failure modes of the samples, insights into the failure mechanisms of rocks under different frequency loads were obtained. This study provides valuable insights into crack development and failure of rocks under seismic loads, offering guidance for engineering practices.

In the increasingly competitive global market, emerging market companies, represented by China, have shown mixed performance during their development process. Many companies grow rapidly in the early stages of development but cannot maintain long-term growth. How to achieve sustainable development has become a major challenge for emerging market companies, and green innovation is considered an effective way to address this issue. Based on the resource-based view, this paper conducts a longitudinal case study on Angel Yeast as the research subject, dividing the development process of Angel Yeast into three stages: the start-up period (1986-2000), the growth period (2000-2010), and the maturity period (2010-present), discussing how Angel Yeast has grown from a small start-up company to a world-class manufacturer. The study finds that Angel Yeast has utilized its unique resources at different stages of development for green technology innovation, green product innovation, green management innovation, green marketing innovation, green supply chain management, and green organizational culture construction, enabling Angel Yeast to gain a sustained competitive advantage and grow into a global leader in the yeast industry. This paper expands the research on the evolution of emerging market companies under the resource-based view theory and enriches the understanding of the role of green innovation in the growth process of enterprises.

BackgroundThe mechanisms underlying the resistance of the genus Providencia to aminoglycosides are complex, which poses a challenge for the efficient treatment of infectious diseases caused by these pathogens. To help clinicians treat infections more effectively, a more comprehensive understanding of antibiotic resistance mechanisms is urgently needed.MethodsPlates were streaked to isolate bacteria from the intestinal contents of fish. The standard agar dilution method was used to determine the minimum inhibitory concentrations (MICs) of the antimicrobial agents. Molecular cloning was carried out to study the function of the novel antibiotic inactivation gene ant(9)-Id. The kinetic parameters of ANT(9)-Id were measured by a SpectraMax multifunctional microplate reader. Whole-genome sequencing and bioinformatic analysis were conducted to elucidate the sequence structure and evolutionary relationships of similar genes.ResultsThe novel aminoglycoside O-nucleotidyltransferase gene ant(9)-Id was encoded on the chromosome of a species-unclassified isolate designated Providencia sp. TYF-12, which was isolated from the intestine of a marine fish. Among the 11 aminoglycosides tested, ant(9)-Id was resistant to only spectinomycin. The MIC of spectinomycin for the recombinant strain carrying ant(9)-Id (pUCP20-ant(9)-Id/DH5α) increased 64-fold compared with that of the control strain (pUCP20/DH5ɑ). ANT(9)-Id shares the highest amino acid (aa) identity of 46.70% with the known drug resistance enzyme ANT(9)-Ic. Consistent with the MIC results, ANT(9)-Id showed high affinity and catalytic efficiency for spectinomycin, with a Km of 8.94 ± 2.50 μM and a kcat/Km of 26.15 μM−1·s−1. This novel resistance gene and its close homologs are conserved in Providencia strains from various sources, including some of clinical significance. No mobile genetic elements (MGEs) surrounding the ant(9)-Id(−like) genes were identified.ConclusionThis work revealed and characterized a novel spectinomycin resistance gene, ant(9)-Id, along with its biological features. Identifying novel resistance genes in pathogens can assist in rational medication use and the identification of additional antimicrobial resistance mechanisms in microbial populations.

BackgroundThis study aimed to determine the associations between different intensities of moderate to vigorous physical activity (MVPA) and the incidence of chronic diseases, and to assess the risk levels associated with these activities over time.MethodsA prospective cohort study (UK Biobank Activity Project) with data collected between June 2013 and December 2015 included 59,896 adults (mean age = 59.68; male = 38.03%) free from chronic diseases. Participants were categorized into tertiles based on their weekly MVPA: lowest (

Abstract Little is known about if and how circular RNAs (circRNAs) are involved in skeletal muscle atrophy. Here a conserved circular RNA Damage‐specific DNA binding protein 1 (circDdb1), derived from the host gene encoding Damage‐specific DNA binding protein 1 (DDB1), as a mechanism of muscle atrophy is identified. circDdb1 expression is markedly increased in a variety of muscle atrophy types in vivo and in vitro, and human aging muscle. Both in vivo and in vitro, ectopic expression of circDdb1 causes muscle atrophy. In contrast, multiple forms of muscle atrophy caused by dexamethasone, tumor necrosis factor‐alpha (TNF‐α), or angiotensin II (Ang II) in myotube cells, as well as by denervation, angiotensin II, and immobility in mice, are prevented by circDdb1 inhibition. Eukaryotic initiation factor 4A3 (EIF4A3) is identified as a regulator of circDdb1 expression in muscle atrophy, whereas circDdb1 encodes a novel protein, circDdb1‐867aa. circDdb1‐867aa binds with and increases the phosphorylation level of eukaryotic elongation factor 2 (eEF2) at Thr56 to reduce protein translation and promote muscle atrophy. In summary, these findings establish circDdb1 as a shared regulator of muscle atrophy across multiple diseases and a potential therapeutic target.

ObjectiveTo systematically evaluate the efficacy and safety of PD-1 inhibitors in neoadjuvant therapy for locally advanced colorectal cancer (LACRC).MethodRetrieved from PubMed, Embase, and the Cochrane Library, all relevant studies about PD-1 inhibitors for neoadjuvant treatment of LACRC were collected from inception to 31 December 2023. The efficacy was assessed by the rate of pathological complete response (PCR), clinical complete response (CCR), and major pathological response (MPR), and the safety was evaluated by the incidence of all adverse effects (TRAEs). Subgroup analysis was conducted by experimental design, types of PD-1 inhibitors, and disease types.ResultA total of 803 patients were included in 21 studies. The results of the meta-analysis showed that the PCR rate of PD-1 inhibitors in the treatment of LACRC was 54% (95% CI: 43%–65%, P

The reproductive age is a crucial stage for women to bear offspring. However, reproductive-aged women are simultaneously exposed to various phthalates, which may pose a threat to their reproductive health. This study employed generalized linear regression and weighted quantile sum (WQS) regression to explore the associations between monoesters of phthalates (MPAEs) and sex hormones in 913 reproductive-aged women in the National Health and Nutrition Examination Survey. Key risk factors driving hormone disruption were identified based on the weights of the WQS models. Interaction models were used to unravel the synergistic or antagonistic effects between MPAEs. The potential toxicological targets of MPAEs interfering with sex hormone-binding globulin (SHBG) levels were revealed based on prior knowledge and molecular docking of hepatocyte nuclear factor 4α (HNF4α). Compared with the first quartile, mono-benzyl phthalate (MBZP) in the second quartile exhibited a decrease in total testosterone (TT) and TT/E2 (estradiol) ratio. Mono-2-ethyl-5-carboxypentyl phthalate (MECPP) in the fourth quartile showed a decrease in SHBG and TT/E2. Additionally, mono-(carboxyoctyl) phthalate and mono-(carboxynonyl) phthalate (MCNP) were negatively associated with SHBG. Each unit increase in the WQS index of MPAE mixtures was associated with 6.73 % lower SHBG levels (95 %CI: −12.80 %, −0.24 %) with mono-(3-carboxypropyl) phthalate, MCNP, MBZP, and MECPP identified as major risk factors. Interaction analyses revealed that the effects of high-risk MPAEs on SHBG were predominantly antagonistic. Molecular docking suggested that MPAEs might compete to bind tryptophan residues of HNF4α. This study provides key information to help develop the most effective phthalate interventions and improve the reproductive health of reproductive-aged women.

Introduction/backgroundVibrio cholerae is the causative agent of the human intestinal infectious disease cholera, which includes a variety of serogroups. However, there have been very few cases of hepatic space-occupying lesions associated with this infection. Currently, there are various methods for detecting this pathogen, including metagenomic sequencing, which enables quicker and more accurate identification. In this study, metagenomic sequencing is employed to accurately identify non-O1/O139 Vibrio cholerae infections by analyzing the genetic material present in clinical samples.Presentation of caseA 75-year-old man presented with diarrhea and fever after consuming crabs. The initial treatment improved the diarrhea, but a liver abscess developed later. Magnetic resonance imaging (MRI) of the liver revealed a hepatic space-occupying lesion. Upon further investigation, a Gram-negative, rod-shaped bacterium was cultured from the patient’s liver puncture fluid, and Vibrio cholerae was detected in the same fluid using metagenomic next-generation sequencing (mNGS). The pathogen was confirmed to be non-O1/non-O139 Vibrio cholerae (NOVC) using polymerase chain reaction (PCR). Following treatment with piperacillin/tazobactam sodium and moxifloxacin, the patient’s body temperature returned to normal, the liver abscess improved significantly, and he was subsequently discharged from the hospital.DiscussionThis case study describes an elderly male patient with a hepatic space-occupying lesion. Multiple cultures of specimens failed to identify the underlying cause; however, advanced techniques such as mNGS and PCR confirmed an NOVC infection. This indicates that mNGS can serve as a valuable tool in diagnosing cases of unexplained liver infections.ConclusionThe use of mNGS is significant for detecting and clinically diagnosing infectious pathogens in patients with unexplained space-occupying lesions.

Metallic sodium (Na) serving as anode for sodium-based batteries (SBBs) has caught much attention, owning to its low electrode potential and high theoretical capacity. However, the notorious Na dendrites severely restrict its practical application in Na metal batteries (SMBs). Herein, the hybrid artificial layer (Na/VN-S) composed of sodium sulfide, vanadium nitride and metal vanadium are constructed on Na anode via pretreatment metallic Na with vanadium nitride and vanadium sulfide powders. The obtained Na/VN-S electrode presents superior electrolyte wettability, high sodiophilicity, low activation energy barrier and high Young’s modulus, leading to homogeneous distribution of Na ions and even Na deposition, so that the Na dendrite growth can be suppressed. Owing to these virtues, the Na/VN-S symmetrical cells present a long cycle life of 1400 h at 0.5 mA cm−2 with 1 mAh cm−2, and can stably cycle at a higher current density of 4 mA cm−2. Moreover, when the commercial Na3V2(PO4)3 (NVP) cathodes are coupled with the Na/VN-S anodes, the Na/VN-S||NVP full cells display a prolonged life of 1900 cycles at 5 C with an outstanding capacity retention of 84.2%. This work contributes to the advancement of Na metal anode in high performance SBBs.

The blowing process in converter steelmaking at the blowing stage mainly includes oxygen supply, slag discharge, and bottom blowing. The stability of the blowing process directly affects the quality of the molten steel at the end. The traditional static control method derived from the blowing process model based on material and heat balances ignores the strong coupling relationship between raw materials and process parameters, resulting in its low reliability. Furthermore, data types for raw materials and process parameters are scalar and time series, respectively. Therefore, to extract the features of the abovementioned complex mixed data, this paper proposes a process model extraction method for converter steelmaking based on an improved autoencoder (IAE). The IAE method is based on an autoencoder that includes fully connected modules, long short-term memory network, one-dimensional convolution, and batch K-means module. In the encoder, fully connected modules, long short-term memory networks, and one-dimensional convolutional modules extract nonlinear features of scalar data, long-term dependent features of time series, and local features of time series, respectively. Hence, the hidden vector is obtained by mapping the original high-dimensional data to a low-dimensional feature space using the encoder. To update the cluster center and calculate the clustering loss, the hidden vector is input to the batch K-Means module. Thus, the decoder reconstructs the hidden vector back to the original space to yield reconstructed data, which is then used to calculate the reconstruction loss. The IAE model is trained jointly with clustering and reconstruction losses. Finally, the cluster center of the original data and cluster category of each sample are obtained. The closer the sample is to the cluster center, the better the process parameters are controlled. Additionally, samples within the same cluster category are closer during the process operation. Therefore, the oxygen supply, slagging, and bottom-blowing processes of the closest samples are considered the process models for this type of sample. The effectiveness of the IAE model is evaluated using the endpoint quality index of real data from converter steelmaking. The average hit rate for the endpoint carbon mass fraction within the error range of ±0.02% is 95.06%, the average hit rate for the endpoint temperature within the error range of ±20 ℃ is 91.48%, and the average double hit rate within the error range of ±0.02% carbon mass fraction and ±20 ℃ temperature is 90.80%. Therefore, the results show that the process model extraction method improves the endpoint hit rate.

Abstract As a hepatotropic virus, hepatitis B virus (HBV) can establish a persistent chronic infection in the liver, termed, chronic hepatitis B (CHB), which causes a series of liver-related complications, including fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). HCC with HBV infection has a significantly increased morbidity and mortality, whereas it could be preventable. The current goal of antiviral therapy for HBV infection is to decrease CHB-related morbidity and mortality, and achieve sustained suppression of virus replication, which is known as a functional or immunological cure. The natural history of chronic HBV infection includes four immune phases: the immune-tolerant phase, immune-active phase, inactive phase, and reactivation phase. However, many CHB patients do not fit into any of these defined phases and are regarded as indeterminate. A large proportion of indeterminate patients are only treated with dynamic monitoring rather than recommended antiviral therapy, mainly due to the lack of definite guidelines. However, many of these patients may gradually have significant liver histopathological changes during disease progression. Recent studies have focused on the prevalence, progression, and carcinogenicity of indeterminate CHB, and more attention has been given to the prevention, detection, and treatment for these patients. Herein, we discuss the latest understanding of the epidemiology, clinical characteristics, and therapeutic strategies of indeterminate CHB, to provide avenues for the management of these patients.

Abstract Cell membrane-camouflaged nanoparticles possess inherent advantages derived from their membrane structure and surface antigens, including prolonged circulation in the bloodstream, specific cell recognition and targeting capabilities, and potential for immunotherapy. Herein, we introduce a cell membrane biomimetic nanodrug platform termed MPB-3BP@CM NPs. Comprising microporous Prussian blue nanoparticles (MPB NPs) serving as both a photothermal sensitizer and carrier for 3-bromopyruvate (3BP), these nanoparticles are cloaked in a genetically programmable cell membrane displaying variants of signal regulatory protein α (SIRPα) with enhanced affinity to CD47. As a result, MPB-3BP@CM NPs inherit the characteristics of the original cell membrane, exhibiting an extended circulation time in the bloodstream and effectively targeting CD47 on the cytomembrane of colorectal cancer (CRC) cells. Notably, blocking CD47 with MPB-3BP@CM NPs enhances the phagocytosis of CRC cells by macrophages. Additionally, 3BP, an inhibitor of hexokinase II (HK2), suppresses glycolysis, leading to a reduction in adenosine triphosphate (ATP) levels and lactate production. Besides, it promotes the polarization of tumor-associated macrophages (TAMs) towards an anti-tumor M1 phenotype. Furthermore, integration with MPB NPs-mediated photothermal therapy (PTT) enhances the therapeutic efficacy against tumors. These advantages make MPB-3BP@CM NPs an attractive platform for the future development of innovative therapeutic approaches for CRC. Concurrently, it introduces a universal approach for engineering disease-tailored cell membranes for tumor therapy.

Objectives It is now understood that pedicle screw loosening at the implant‐bone interface can lead to poor screw–bone interface purchase and decreased fixation stability. Previous biomechanical tests used cadaveric vertebrae and pull‐out or torque loads to assess the effect of the insertional direction of pedicle screws on screw loosening. However, these tests faced challenges in matching biomechanical differences among specimens and simulating in vivo loads applied on pedicle screws. This study aimed to evaluate the effect of the insertional direction of pedicle screws on screw loosening using tension‐compression‐bending loads and synthetic bone vertebrae. Methods Polyaxial pedicle screws were inserted into nine synthetic bone vertebrae in three directions (three samples per group): cranial, parallel, and caudad (−10°, 0°, +10° of the pedicle screw rod to the upper plane of the vertebra, respectively). Pedicle screws in the vertebrae were loaded using a polyethylene block connected to a material testing machine. Tension‐compression‐bending loads (100N–250N) with 30,000 cycles were applied to the pedicle screws, and displacements were recorded and then cycle‐displacement curve was drawn based on cycle number. Micro‐CT scans were performed on the vertebrae after removing the pedicle screws to obtain images of the screw hole, and the screw hole volume was measured using imaging analysis software. Direct comparison of displacements was conducted via cycle‐displacement curve. Screw hole volume was analyzed using analysis of variance. The correlation between the displacement, screw hole volume and the direction of pedicle screw was assessed by Spearman correlation analysis. Results The smallest displacements were observed in the caudad group, followed by the parallel and cranial groups. The caudad group had the smallest screw hole volume (p

Objective With the steady advancement of technology and China's dual carbon process, the application of hydrogen energy in urban transportation is increasing. To reduce the overall energy consumption of fuel cell/supercapacitor hybrid power system for virtual-rail trams, an energy management method based on optimal power consumption is proposed. Method Based on the power distribution of virtual-rail trams in different operating states, an instantaneous power consumption function for the hybrid power system is jointly constructed by fitting approximation and combining the power consumption models of fuel cell systems and supercapacitor systems. By optimizing and solving the power consumption function, the optimal output power of the fuel cell system is obtained. The online control capability of the proposed method is verified using a semi-physical simulation platform and actual operational data of the virtual-rail tram. Result & Conclusion Experimental results show that under the control of the proposed method, the fuel cell system maintains a stable output power under complex conditions, with an average electricity-to-hydrogen conversion efficiency of 54.84%. This can effectively reduce the operation and maintenance costs of virtual-rail trams.

Objective Equivalent hydrogen consumption, as a method for optimizing fuel economy, performs poorly in following the state of charge of energy storage systems. Therefore, it is necessary to improve it to achieve dynamic balance of interval state of charge. Method Based on the conventional equivalent hydrogen consumption algorithm, the hydrogen consumption function of the system is optimized. By adding a voltage balance coefficient, it ensures that the supercapacitor will not be overcharged or over-discharged during vehicle operation. Then, through minimization solution, real-time allocation of power to the system is achieved. Result & Conclusion Based on the operational data of virtual-rail trams, the proposed method is validated on a semi-physical simulation platform. Experimental results show that the improved equivalent hydrogen consumption algorithm can achieve energy distribution of hybrid power systems under complex working conditions. The added voltage balance coefficient ensures that the voltage of the supercapacitor at the end of the vehicle interval remains within a reasonable range.

This study aimed to optimize the composition of a liquid medium for Mycoplasma gallisepticum growth rate and density through statistical approach. The growth concentration of M. gallisepticum was determined by plotting a standard curve using Real-Time Quantitative PCR. The one-factor-at-a-time method and the Plakett-Burman design were initially applied to identify the factors that influenced the biomass of M. gallisepticum. The steepest ascent experiment and response surface methodology (RSM) with Box-Behnken design was employed to simultaneously assess the effects of multiple factors. Finally, optimization of the initial pH and validation of the model were done. The optimum concentrations of the critical components were obtained as follows: 203.96 mL/L of horse serum, 9.64 g/L of glucose, and 9.49 g/L of PPLO broth. The nucleic acid copy number of M. gallisepticum reached 1010.5147 copies/mL and the viable cell count reached a maximum of 109.8451 CCU/mL. This medium reduced the incubation time by approximately 6 h, and M. gallisepticum nucleic acid concentration and viable cell count were higher than those in the modified Frey medium (9.99 and 7 times, respectively). The new liquid medium is likely to improve productivity and reduce the production costs for vaccine-manufacturing companies in the future by reducing incubation times and increasing the growth rate and concentration of M. gallisepticum.

ObjectiveThis study aimed to assess and visually depict the clinical evidence landscape of traditional Chinese exercises and identify any research gaps and future research needs.MethodsWe comprehensively searched seven Chinese and English databases to identify randomized controlled trials (RCTs) and systematic reviews (SRs) evaluating the effects of traditional Chinese exercises from their inception until May 2023. The quality of evidence was assessed via the GRADE approach, and the research topics, intervention effects, and strength of evidence were graphically displayed.ResultsThis evidence map includes 2,017 studies, comprising 1,822 RCTs and 195 SRs. These studies were conducted globally in various countries. Among the traditional Chinese exercises, Tai Chi and Baduanjin have received the most research attention, with a growing number of publications. When traditional Chinese exercises were compared with the control groups, 88.2% of the included SRs reported significantly positive effects, 4.1% reported unclear effects, and 7.7% reported no significant differences. The findings suggested that traditional Chinese exercises could benefit patients with osteoarthritis, osteoporosis, hypertension, coronary heart disease, diabetes, chronic obstructive pulmonary disease, stroke, Parkinson’s disease, anxiety, and depression. However, the overall quality of the evidence was suboptimal, with 11.3% rated as moderate, 45.6% as low, and 43.1% as critically low.ConclusionThis evidence map visually represents valuable information on traditional Chinese exercises. While most studies have reported significant benefits, the overall quality of evidence is low.

Noroviruses are a group of non-enveloped single-stranded positive-sense RNA virus belonging to Caliciviridae family. They can be transmitted by the fecal-oral route from contaminated food and water and cause mainly acute gastroenteritis. Outbreaks of norovirus infections could be difficult to detect and investigate. In this study, we developed a simple threshold detection approach based on variations of the P2 domain of the capsid protein. We obtained sequences from the norovirus hypervariable P2 region using Sanger sequencing, including 582 pairs of epidemiologically-related strains from 35 norovirus outbreaks and 6402 pairs of epidemiologically-unrelated strains during the four epidemic seasons. Genetic distances were calculated and a threshold was performed by adopting ROC (Receiver Operating Characteristic) curve which identified transmission clusters in all tested outbreaks with 80 % sensitivity. In average, nucleotide diversity between outbreaks was 67.5 times greater than the diversity within outbreaks. Simple and accurate thresholds for detecting norovirus transmissions of three genotypes obtained here streamlines molecular investigation of norovirus outbreaks, thus enabling rapid and efficient responses for the control of norovirus.

RNA-binding motif protein 10 (RBM10) has a tumor suppressor role in multiple cancers. Combining Oncomine database results with tissue samples, Western blot analysis showed that RBM10 was significantly lower in lung adenocarcinoma (LUAD) than in adjacent normal tissues. Moreover, KM analysis revealed that the group with higher RBM10 expression in LUAD correlated with better overall survival (OS). Luciferase reporter assay revealed that an important tumor-promotive miRNA, miR-224-5p, was directly bound to the 3′UTR of RBM10, resulting in inhibition of RBM10 expression, and promoted LUAD progression both in vitro and in vivo. Mechanistically, we found that miR-224-5p directly targeted RBM10 to inhibit p53 expression during LUAD progression. Meanwhile, p53 affected RBM10 expression through p53/miR-224-5p axis. Our study identified RBM10 as a key tumor suppressor in the proliferation and metastasis of LUAD. The findings provide a novel mechanism involving a feedback loop of miR-224-5p/RBM10/p53 regulated tumor progression in LUAD, which may help with the design of more effective LUAD treatments.

Summary: Ovarian cancer (OC) remains the most lethal gynecological malignant tumor. PARP inhibitors (PARPi) have significantly improved survival, particularly in patients with OC with BRCA1/2 mutations. However, the majority of patients eventually develop resistance to PARPi. Cancer stem cells (CSCs) are considered the source of drug resistance in cancer. Our study found that the synergistic effect of astragalus polysaccharides (APSs) and PARPi was observed in ovarian cancer stem cells (OCSCs) by decreasing cell viability and self-renewal potential while inducing apoptosis. The present study also demonstrated that OCSCs had increased mitophagy. Furthermore, it was observed that APS in combination with PARPi inhibits mitophagy and downregulates the PINK1 protein level in OCSCs. The overexpression of PINK1 via the pEGFP(+)-PINK1 plasmid resulted in a partial reversal of the increased susceptibility of OCSCs when PARPi were administrated concurrently with APS. In conclusion, APS increases OCSC sensitivity to PARPi by inhibiting mitophagy via the PINK1/Parkin pathway regulation.

Background: Brain metastasis (BM) is a prevalent form of metastasis in lung adenocarcinoma (LUAD), necessitating investigations into the underlying mechanisms. Interleukin 34 (IL-34) and its receptors, macrophage colony-stimulating factor-1 receptor (CSF-IR), Syndecan-1 (SDC-1), and protein-tyrosine phosphatase zeta receptor (PTPRZ1), are known to play pivotal roles in the metastasis of malignant tumors, thereby holding promise as potential biomarkers for studying BM in LUAD. Methods: We performed immunohistochemistry to analyze the expression of IL-34, CSF-1R, SDC-1, and PTPRZ1 in 10 pairs of LUAD primary tissues and BMs, along with 96 unpaired primary tissues and 68 unpaired BMs. Subsequently, we evaluated the association between protein expression and the occurrence of BM. Furthermore, Kaplan-Meier survival curve analysis was conducted on both network and clinical data to explore the association between protein expression and patient prognosis and survival. Results: At the protein level, the expression of IL-34 and its receptors showed significant variation between paired primary tumors and BMs in 10 LUAD patients. The levels of IL-34, CSF-1R, and SDC-1 expression are typically elevated in brain metastatic lesions of LUAD compared to primary LUAD tumors. Furthermore, patients with high CSF-1R expression in primary LUAD are at a greater risk of developing brain metastases. High expression of IL-34 and CSF-1R in primary LUAD lesions indicated poor disease-free survival (DFS) and overall survival (OS), while high expression of SDC-1 indicated poor OS. Cox multivariate analysis further revealed that CSF-1R and IL-34+CSF-1R positivity independently affected LUAD OS. These findings were further substantiated in unpaired samples. Conclusions: Our results indicate significant alterations in the expression of IL-34 and its receptors, CSF-1R and SDC-1, between LUAD primary lesions and BMs, with increased expression observed in BMs. LUAD patients with positive CSF-1R expression in primary lesions exhibited a higher likelihood of developing BM, and high expression of IL-34, CSF-1R, and SDC-1 correlated with poor prognosis. These findings contribute novel insights towards identifying potential treatment or diagnostic targets for metastatic LUAD.

Abstract Background/Aim With the pharmaceutical innovation and clinical knowledge updating, the continuing education and on-the-job training are extremely important for improving community pharmacists’ professional competence. Previous training often adopted traditional lecture-based teaching, and the efficacy was limited. The aim of this study is to develop a new strategy for community pharmacist training. Methods Based on the BOPPPS (Bridge-in, Objective, Pre-assessment, Participatory Learning, Post-assessment and Summary) teaching model and workshop method, a continuing on-the-job training program was constructed. Participates were randomly and evenly divided into two groups by random number table method. Twenty-four community pharmacists in total completed all training contents and evaluation components in this study. Twelve pharmacists in experimental group were trained via this new BOPPPS-based workshop, while others still adopted traditional didactic lecture-based approaches. Results After training, quantitative examination combined with clinical pharmacy practice tests were carried out to evaluate the effectiveness and outcomes of two training groups. For written exam, the total scores from the BOPPPS-based workshop group (82.67 ± 4.70) was higher than that of traditional lectured-base group (73.75 ± 6.15) (P

Abstract Electrical stimulation is a fundamental tool in studying neural circuits, treating neurological diseases, and advancing regenerative medicine. Injectable, free-standing piezoelectric particle systems have emerged as non-genetic and wireless alternatives for electrode-based tethered stimulation systems. However, achieving cell-specific and high-frequency piezoelectric neural stimulation remains challenging due to high-intensity thresholds, non-specific diffusion, and internalization of particles. Here, we develop cell-sized 20 μm-diameter silica-based piezoelectric magnetic Janus microparticles (PEMPs), enabling clinically-relevant high-frequency neural stimulation of primary neurons under low-intensity focused ultrasound. Owing to its functionally anisotropic design, half of the PEMP acts as a piezoelectric electrode via conjugated barium titanate nanoparticles to induce electrical stimulation, while the nickel-gold nanofilm-coated magnetic half provides spatial and orientational control on neural stimulation via external uniform rotating magnetic fields. Furthermore, surface functionalization with targeting antibodies enables cell-specific binding/targeting and stimulation of dopaminergic neurons. Taking advantage of such functionalities, the PEMP design offers unique features towards wireless neural stimulation for minimally invasive treatment of neurological diseases.

Abstract The implementation of sodium metal batteries (SMBs) is known for their low cost and high energy density. However, a major concern in SMBs is the formation of dendrites on the Na metal anode, which can potentially cause short circuits and compromise safety. Herein, to address this issue, we propose a novel approach to create a protective layer by decorating Na surface with NaI particles. This protective layer exhibits a high Young’s modulus and excellent sodium ion transference ability. As a result, the lifespan of the Na/NaI||Na/NaI cell is significantly extended to 850 h at 0.5 mA cm−2/1 mAh cm−2. Furthermore, when the Na/NaI anode is combined with a Na3V2(PO4)3 (NVP) cathode, the full cell retains 83 mAh g−1 (approximately 94% of its initial capacity) even after 1500 cycles at 5 C. Overall, this work presents a simple and effective method for establishing a protective layer on the Na surface, thereby enabling the realization of long lifespan and stable SMBs.

Abstract Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide, and destruction of the cerebrovascular system is a major factor in the cascade of secondary injuries caused by TBI. Laser speckle imaging (LSCI)has high sensitivity in detecting cerebral blood flow. LSCI can visually show that transcranial focused ultrasound stimulation (tFUS) treatment stimulates angiogenesis and increases blood flow. To study the effect of tFUS on promoting angiogenesis in Controlled Cortical impact (CCI) model. tFUS was administered daily for 10 min and for 14 consecutive days after TBI. Cerebral blood flow was measured by LSCI at 1, 3, 7 and 14 days after trauma. Functional outcomes were assessed using LSCI and neurological severity score (NSS). After the last test, Nissl staining and vascular endothelial growth factor (VEGF) were used to assess neuropathology. TBI can cause the destruction of cerebrovascular system. Blood flow was significantly increased in TBI treated with tFUS. LSCI, behavioral and histological findings suggest that tFUS treatment can promote angiogenesis after TBI.

Abstract Phenotype-guided gene prioritizers have proved a highly efficient approach to identifying causal genes for Mendelian diseases. In our previous study, we preliminarily evaluated the performance of ten prioritizers. However, all the selected software was run based on default settings and singleton mode. With a large-scale family dataset from Deciphering Developmental Disorders (DDD) project (N = 305) and an in-house trio cohort (N = 152), the four optimal performers in our prior study including Exomiser, PhenIX, AMELIE, and LIRCIAL were further assessed through parameter optimization and/or the utilization of trio mode. The in-depth assessment revealed high diagnostic yields of the four prioritizers with refined preferences, each alone or together: (1) 83.3–91.8% of the causal genes were presented among the first ten candidates in the final ranking lists of the four tools; (2) Over 97.7% of the causal genes were successfully captured within the top 50 by either of the four software. Exomiser did best in directly hitting the target (ranking the causal gene at the very top) while LIRICAL displayed a predominant overall detection capability. Besides, cases affected by low-penetrance and high-frequency pathogenic variants were found misjudged during the automated prioritization process. The discovery of the limitations shed light on the specific directions of future enhancement for causal-gene ranking tools.

Changes in intracellular nicotinamide adenine dinucleotide (NAD+) levels have been observed in various disease states. A decrease in NAD+ levels has been noted following spinal cord injury (SCI). Nicotinamide riboside (NR) serves as the precursor of NAD+. Previous research has demonstrated the anti-inflammatory and apoptosis-reducing effects of NR supplements. However, it remains unclear whether NR exerts a similar role in mice after SCI. The objective of this study was to investigate the impact of NR on these changes in a mouse model of SCI. Four groups were considered: (1) non-SCI without NR (Sham), (2) non-SCI with NR (Sham +NR), (3) SCI without NR (SCI), and (4) SCI with NR (SCI + NR). Female C57BL/6J mice aged 6–8 weeks were intraperitoneally administered with 500 mg/kg/day NR for a duration of one week. The supplementation of NR resulted in a significant elevation of NAD+ levels in the spinal cord tissue of mice after SCI. In comparison to the SCI group, NR supplementation exhibited regulatory effects on the chemotaxis/recruitment of leukocytes, leading to reduced levels of inflammatory factors such as IL-1β, TNF-α, and IL-22 in the injured area. Moreover, NR supplementation notably enhanced the survival of neurons and synapses within the injured area, ultimately resulting in improved motor functions after SCI. Therefore, our research findings demonstrated that NR supplementation had inhibitory effects on leukocyte chemotaxis, anti-inflammatory effects, and could significantly improve the immune micro-environment after SCI, thereby promoting neuronal survival and ultimately enhancing the recovery of motor functions after SCI. NR supplementation showed promise as a potential clinical treatment strategy for SCI.

In hospitals and pharmacies, the demand for efficient medication management (e.g., item storage and access) is rapidly increasing, and the scale of medication management systems is gradually expanding. Intelligent medication management systems based on Internet of Things (IoT) can enhance the system efficiency and largely save labor costs through contactless medication dispensing and robotic item access. A typical medication management system that can store medicines usually includes several cabinets, each cabinet contains several drawers, and each drawer contains medicine boxes. In this paper, we propose, Flexit, a framework of flexible location encoding schemes that can encode the locations of cabinets, drawers, and boxes for efficient item access in an intelligent medication management system. Flexit includes a human/user interface, a central control unit, and a medication storage system, built upon medicine cabinets. Given storage space constraints, we propose a hybrid data compression method that combines trees and bitmaps, which is further optimized according to Huffman coding principles. Additionally, given a location code, the user/robot is capable to decode a number of locations, and Flexit employs a location-aware path planning algorithm to help access the stored items at these decoded locations at the minimal time-distance combined cost. We evaluate the performance of the data compression and path-planning algorithms through experiments over datasets, which show superior performance compared to existing methods, i.e., the compression algorithm can save 5-10 times the storage space on average, and the path-planning algorithm can reduce the system’s runtime by 20-50%.

Abstract Rapeseed (Brassica napus L.) with short or no dormancy period are easy to germinate before harvest (pre-harvest sprouting, PHS). PHS has seriously decreased seed weight and oil content in B. napus. Short-chain dehydrogenase/ reductase (SDR) genes have been found to related to seed dormancy by promoting ABA biosynthesis in rice and Arabidopsis. In order to clarify whether SDR genes are the key factor of seed dormancy in B. napus, homology sequence blast, protein physicochemical properties, conserved motif, gene structure, cis-acting element, gene expression and variation analysis were conducted in present study. Results shown that 142 BnaSDR genes, unevenly distributed on 19 chromosomes, have been identified in B. napus genome. Among them, four BnaSDR gene clusters present in chromosome A04、A05、C03、C04 were also identified. These 142 BnaSDR genes were divided into four subfamilies on phylogenetic tree. Members of the same subgroup have similar protein characters, conserved motifs, gene structure, cis-acting elements and tissue expression profiles. Specially, the expression levels of genes in subgroup A, B and C were gradually decreased, but increased in subgroup D with the development of seeds. Among seven higher expressed genes in group D, six BnaSDR genes were significantly higher expressed in weak dormancy line than that in nondormancy line. And the significant effects of BnaC01T0313900ZS and BnaC03T0300500ZS variation on seed dormancy were also demonstrated in present study. These findings provide a key information for investigating the function of BnaSDRs on seed dormancy in B. napus.

Abstract To emphasize the semantic impact of local semantic and grammatical information among adjacent words in the input text, we establish a constraint functions-based quantum-like tensor compression sentence representation model by integrating the concept of extending the pure state-based density matrix to the mixed-state projection operator in quantum mechanics. The provided model highlights the semantic significance of mixed word associations in the input text, simultaneously reducing the reliance on information derived solely from dictionary statistics. We combine the correlation coefficient with the attention mechanism to establish the correlation coefficient between words. The quantum-like sentence representation based on pure state density matrix is extended to the projection operator of mixed states. Combining the acquisition of maximum in convex optimization, a constraint functions-based quantum-like text representation pruning model is established to reduce redundant information caused by dimensional expansion of tensor operations. The experimental results on SICK-2014, STS-benchmark, and STS-companion show that the provided model is more effective than the mainstream models in mining semantic information, especially more sensitive to the negative semantics of sentences.