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Geological characteristics, genetic model, and exploration implications in the Daduhe gold belt are studied. Three categories of gold deposits have been distinguished: “gold deposits in the basement (GDB),” “gold deposits in the cover layer (GDC),” and “gold deposits at the interface (GDI).” Among them, quartz vein type and quartz vein altered rock type are the main types of mineral deposits. The following features have been obtained: (1) inclusions of gold particles exist in pyrite, pyrrhotite, quartz, sellaite, and other sulfides; in fractures; or along cracks and grain margins. (2) The distribution curve of rare earth elements in pyrite and quartz indicates strong mineralization intensity in the GDB, (La/Sm)N fractionation characteristics, suggesting that pyrite may be more influenced by crustal materials and quartz by mantle materials. (3) The H–O and He–Ar isotopes manifested the ore-forming fluids derived from the mixing between crust and mantle. (4) The ranges of δ 34 S values of pyrite (−5.0 to 7.6‰) are consistent with those of metasomatized mantle lithosphere. (5) The homogenization temperatures and salinity of all quartz inclusions are concentrated from 150 to 210°C and 2.1–8.7 wt%, indicating a medium-low-temperature, low-salinity hydrothermal fluid. (6) The Daduhe orogenic gold deposits can be defined as epizonal subtypes. (7) The Daduhe gold deposits are medium-low temperature, low-salinity, and epizonal orogenic gold deposits, and fluid comes from a mixture of crust and mantle. In the future, efforts should be made to increase the exploration of deep gold deposits.

Abstract Epithelial ovarian cancer (EOC) presents considerable difficulties in prognostication and treatment strategy development. Bevacizumab, an anti-angiogenic medication, has demonstrated potential in enhancing progression-free survival (PFS) in EOC patients. Nevertheless, the identification of individuals at elevated risk of disease progression following treatment remains a challenging task. This study was to develop and validate a deep learning (DL) model using retrospectively collected computed tomography (CT) plain scans of inoperable and recurrent EOC patients receiving bevacizumab treatment diagnosed between January 2013 and January 2024. A total of 525 patients from three different institutions were retrospectively included in the study and divided into training set (N = 400), internal test set (N = 97) and external test set (N = 28). The model’s performance was evaluated using Harrell’s C-index. Patients were categorized into high-risk and low-risk group based on a predetermined cutoff in the training set. Additionally, a multimodal model was evaluated, incorporating the risk score generated by the DL model and the pretreatment level of carbohydrate antigen 125 as input variables. The Net Reclassification Improvement (NRI) metric quantified the reclassification performance of our optimal model in comparison to the International Federation of Gynecology and Obstetrics (FIGO) staging model. The results indicated that DL model achieved a PFS predictive C-index of 0.73 in the internal test set and a C-index of 0.61 in the external test set, along with hazard ratios of 34.24 in the training set (95% CI: 21.7, 54.1; P

As a kind of pressurized combustion, pulse detonation combustion brings many possibilities for the improvement of aero-engine performance.In this paper, energy and exergy analyses of pulse detonation combustor (PDC) and pulse detonation turbine engine (PDTE) cycles based on unsteady analysisare conducted. A simplified exergy flow model is proposed to describe the exergy flow of PDC under different inlet conditions, and based on this, the exergy efficiency of PDC is compared with that of an isobaric combustion chamber. In addition, the energy and exergy flows of ideal and real PDTE cycles are analyzed, and the cycle thermal and exergy efficiencies under different inlet conditions are obtained. The results show that the exergy efficiency of PDC is higher than that of an isobaric combustion chamber from an inlet pressure ratio of 3–45, but the efficiency improvement decreases from 13.2 % to 7.2 %. The thermal efficiency of the ideal PDTE cycle is higher than that of the Brayton cycle, but the efficiency improvement decreases from 78.2 % to 4.7 %. The irreversible losses in the real process will lead to energy loss during compression and expansion processes in the PDTE cycle, thus reducing its exergy efficiency and thermal efficiency.

Abstract Numerous studies have suggested a strong association between paternal adverse environmental exposure and increased disease susceptibility in offspring. However, the impact of paternal pre‐pregnant caffeine exposure (PPCE) on offspring health remains unexplored. This study elucidates the sperm reprogramming mechanism and potential intervention targets for PPCE‐induced non‐alcoholic steatohepatitis (NASH) in offspring. Here, male rats are administrated caffeine (15–60 mg kg−1/d) by gavage for 8 weeks and then mated with females to produce offspring. This study finds that NASH with transgenerational inheritance occurred in PPCE adult offspring. Mechanistically, a reduction of miR‐142‐3p is implicated in the occurrence of NASH, characterized by hepatic lipid metabolism dysfunction and chronic inflammation through an increase in ACSL4. Conversely, overexpression of miR‐142‐3p mitigated these manifestations. The origin of reduced miR‐142‐3p levels is traced to hypermethylation in the miR‐142‐3p promoter region of parental sperm, induced by elevated corticosterone levels rather than by caffeine per se. Similar outcomes are confirmed in offspring conceived via in vitro fertilization using miR‐142‐3pKO sperm. Overall, this study provides the first evidence of transgenerational inheritance of NASH in PPCE offspring and identifies miR‐142‐3p as a potential therapeutic target for NASH induced by paternal environmental adversities.

IntroductionPorcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent 13 of porcine reproductive and respiratory syndrome (PRRS), which is one of the most economically 14 devastating viruses in the Vietnamese swine industry.MethodsWith a view toward determining the 15 genetic variation among PRRSV strains in Vietnam, we examined 271 PRRSV GP5 protein 16 sequences obtained from strains isolated in Vietnam from 2007 to 2023, for which we constructed 17 phylogenetic trees. Additionally, a collection of 52 PRRSV-1 strains and 80 PRRSV-2 strains 18 isolated in different years were specifically selected for nucleotide and amino acid homology analysis 19 and amino acid sequence alignment.ResultsThe results revealed 76.1%–100.0% nucleotide and 20 75.2%–100.0% amino acid homologies for the PRRSV-1 GP5 gene, and 81.8%–100.0% nucleotide 21 and 81.1%–100.0% amino acid homologies for the PRRSV-2 GP5 gene. Amino acid mutation sites 22 in PRRSV-2 were found to be primarily distributed in the signal peptide region, antigenic sites, two 23 T-cell antigen regions, two highly variable regions (HVRs), and in the vicinity of the neutralizing 24 epitope, with a deletion mutation occurring in the neutralizing epitope, whereas amino acid mutations 25 in the PRRSV-1 sequences were found to occur predominantly in two T-cell epitopes. Genetic 26 analysis revealed that PRRSV-1 strains in Vietnam are of subtype 1 (Global), whereas PRRSV-2 27 strains are categorized into sublineages L1A, L5A, and L8E, with L8E being the predominantly 28 prevalent strain at present. Recombination analyses indicated that no significant recombination 29 events have occurred in any of the assessed 271 Vietnamese PRRSV strains.DiscussionOur 30 analyses of 271 Vietnamese PRRSV strains have yielded valuable insights regarding the 31 epidemiological trends and genetic dynamics of PRRSV in Vietnam, and will provide a theoretical 32 basis for formulating prevention and control measures for PRRS and the development of PRRS 33 vaccines.

Objectives: SPARCL1 is a matricellular protein that mediates the cell–matrix interactions and participates in physiological processes such as cell adhesion, differentiation and proliferation. However, its role in chondrocyte and osteoarthritis (OA) progression has not been fully characterized. We aimed to evaluate the effects of SPARCL1 on OA through in vitro and in vivo experiments. Methods: Expression of SPARCL1 was examined in 55 paired human OA samples. Effects of Sparcl1 on chondrocytes were identified in vitro. Intra-articular injection was performed in an anterior cruciate ligament transection (ACLT) mouse model. Alterations of SPARCL1-mediated signaling pathway were identified by RNA-seq analysis. qPCR and western-blot were used to demonstrate the potential signaling pathway. Results: SPARCL1 expression in the OA cartilage was increased compared with undamaged cartilage. Recombinant Sparcl1 protein induced extracellular matrix degradation in chondrocytes. Furthermore, intra-articular injection of recombinant Sparcl1 protein in ACLT mice could promote OA pathogenesis. Mechanistically, Sparcl1 activated TNF/NF-κB pathway and consequently led to increased transcription of inflammatory factors and catabolism genes of cartilage, which could be reversed by NF-κB inhibitor BAY 11–7082. Conclusion: SPARCL1 could promote extracellular matrix degradation and inflammatory response to accelerate OA progression via TNF/NF-κB pathway. The translational potential of this article: The current research could help to gain further insights into the underlying molecular mechanism in OA development, and provides a biological rationale for the use of SPARCL1 as a potential therapeutic target of OA.

Summary: Background: Studies from the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2021 can guide screening and prevention strategies for tracheal, bronchus, and lung (TBL) cancer. We aim to provide global, regional, and national estimates of the TBL cancer burden and its attributable risk from 1990 to 2021, including during the coronavirus disease 2019 (COVID-19) pandemic. Methods: Incidence, age-standardised incidence rate (ASIR), deaths, age-standardised mortality rate (ASMR), disability-adjusted life years (DALYs), age-standardised rate of DALYs (ASDR), and the burden due to risk factors associated with TBL cancer were analysed from 1990 to 2021. Trends in ASIR, ASMR, and ASDR of TBL cancer during the COVID-19 pandemic (2019–2021) were also determined. All statistical analyses were performed using Join-point software (version 4.9.1.0). Findings: Between 1990 and 2021, the global incidence, deaths, and DALYs of TBL cancer to varying degrees. However, the ASIR (Average Annual Percent Change [AAPC], −0.3 [−0.4 to −0.2]), ASMR (AAPC, −0.5 [−0.7 to −0.4]), and ASDR (AAPC, −0.9 [−1.0 to −0.7]) all showed a decreasing trend. However, the ASIR, ASMR, and ASDR of TBL cancer in males all showed a decreasing trend from 1990 to 2021. In contrast, the ASIR and ASMR of TBL cancer in females showed an increasing trend, while the ASDR showed a relatively stable trend. During the COVID-19 pandemic, the trends for ASIR, ASMR, and ASDR remained stable across both sexes combined, females, males, five socio-demographic index (SDI) quintiles, and the 21 GBD regions. In 2021, smoking was a major risk factor for TBL cancer DALYs, but the attributable ASDR for smoking decreased from 1990 to 2021 in both sexes combined, as well as individually for males and females. Conversely, the attributable ASDR for secondhand smoke, high fasting plasma glucose and occupational exposure factors increased primarily among females. Furthermore, the attributable ASDR for ambient particulate matter pollution, household air pollution from solid fuels, and low–fruit diets increased primarily in regions with lower SDI quintiles from 1990 to 2021. Interpretation: The burden attributable to TBL cancer has increased in some populations from 1990 to 2021, highlighting the importance of implementing targeted measures to mitigate this trend. No significant change in the burden of TBL cancer was observed during the COVID-19 pandemic; however, post-COVID-19 rates still require further observation. Funding: This study was supported by National Key Research and Development Program of China (2023YFC3503300, 2023YFC3503305), and High Level Chinese Medical Hospital Promotion Project (HLCMHPP2023085, HLCMHPP2023001, HLCMHPP2023097).

Locally advanced breast cancer (LABC) remains a significant clinical challenge, particularly in developing countries. While neoadjuvant systemic therapy (NST) has improved the pathological complete response (pCR) rates, particularly in HER2-positive and triple-negative breast cancer patients, surgical management post-NST continues to evolve. The feasibility of omitting surgery and the increasing consideration of breast-conserving surgery, immediate reconstruction in LABC patients are important areas of exploration. Accurate assessment of tumor response to NST through advanced imaging and minimally invasive biopsies remains pivotal, though challenges persist in reliably predicting pCR. Additionally, axillary lymph node management continues to evolve, with emerging strategies aiming to minimize the extent of surgery in patients who achieve nodal downstaging post-NST. Minimizing axillary lymph node dissection in favor of less invasive approaches is gaining attention, though further evidence is needed to establish its oncological safety. The potential for personalized treatment approaches, reducing surgical morbidity, and improving quality of life are key goals in managing LABC, while maintaining the priority of achieving favorable long-term outcomes.

Porcine reproductive and respiratory syndrome virus (PRRSV) has become widespread in China particularly the highly pathogenic porcine reproductive and respiratory syndromes (HP-PRRSV), NADC30, and NADC34 strains, and has posed a threat to the swine industry for over 20 years. To monitor genetic variation in PRRSV-2 GP3 strains in China, we analyzed 618 strains isolated between 1996 to 2023 and constructed phylogenetic trees. Additionally, 60 selected strains were used to analyze nucleotide and amino acid homology. PRRSV GP3 gene exhibited nucleotide identity ranging from 78.2% to 100.0% and amino acid similarity ranging from 74.9% to 99.6%. The GP3 gene in the 60 selected strains consisted of 254 amino acids, and amino acid mutations in the strains primarily occurred in B-cell epitopes, T-cell epitopes, and highly variable regions. The glycosylation sites of the strains used for amino acid sequence comparisons remained unaltered, except for the N29 site in the GD20220303-2022 strain. PRRSV-2 strains in China belong to lineages 1, 3, 5, and 8. Recombination analysis detected two recombination events, involving lineages 1 and 8. In conclusion, this study investigated multiple strains of the PRRSV-2 GP3 gene to explore the prevalence and genetic diversity of the GP3 gene in China from a gene family perspective. The results of the analyses provide a basis for clinical prevention strategies and vaccine development.

IntroductionPorcine reproductive and respiratory syndrome (PRRS) is a significant threat to the global swine industry, and its prevalence in Thailand spans over two decades.MethodsTo understand the genetic variation and recombination of the PRRS virus (PRRSV) GP5 gene in Thailand, we retrieved 726 GP5 gene sequences from the NCBI database. Phylogenetic trees were constructed using the neighbor-joining (NJ) and maximum likelihood (ML) methods, and recombination analysis was performed.ResultsHomology analysis was conducted on 83 PRRSV-1 and 83 PRRSV-2 strains. Phylogenetic analysis revealed the prevalence of both PRRSV-1 and PRRSV-2 strains in Thailand, with the latter exhibiting wider distribution. PRRSV-1 strains clustered into clades A, D, and H, while PRRSV-2 strains grouped into lineages 1, 5, and sublineage 8.7, further divided into 8.7/HP and 8.7/NA sublineages. Sublineage 8.7/NA strains accounted for a significant proportion of circulating PRRSV-2 strains. Homology analysis showed nucleotide and amino acid similarities ranging from 75.4 to 100.0% and 41.3 to 100.0% for PRRSV-1, and 78.6 to 100.0% and 70.8 to 100.0% for PRRSV-2 strains. Amino acid sequence alignments revealed mutations, insertions, and deletions in PRRSV-1 GP5, and key residue mutations in PRRSV-2 GP5 associated with biological functions. Recombination analysis identified two recombination events within PRRSV-2 sublineage 8.7 strains.DiscussionThese findings confirm the variability of the GP5 protein. This study enhances our understanding of PRRSV prevalence and genetic variation in Thailand, contributing valuable insights for PRRS prevention and control.

Pyrethrum (Tanacetum cinerariifolium), a perennial herb within the Tanacetum genus, stands as a crucial source of natural insecticides pyrethrins which have been utilized for centuries. This study delves into the historical utilization of pyrethrum and elucidates the biosynthetic pathways of pyrethrum, uncovering the majority of genes responsible for pyrethrin production. Moreover, pyrethrum flowers and stems are rich in sesquiterpene lactones, known for their antifungal attributes, and they release (E)-β-farnesene, an aphid alarm pheromone that lures predators such as ladybirds. These discoveries emphasize pyrethrum's multifaceted chemical defense against various biotic adversaries and its viability as a companion plant in agricultural settings. Farmers have recognized and begun utilizing pyrethrum in this capacity. The paper underscores the need for further research to thoroughly comprehend and exploit pyrethrum defense strategies for sustainable farming practices, underscoring its potential in ecological and agricultural spheres.

Abstract Cancer immunotherapies have achieved unprecedented success in clinic, but they remain largely ineffective in some major types of cancer, such as colorectal cancer with microsatellite stability (MSS CRC). It is therefore important to study tumor microenvironment of resistant cancers for developing new intervention strategies. In this study, we identify a metabolic cue that determines the unique immune landscape of MSS CRC. Through secretion of distal cholesterol precursors, which directly activate RORγt, MSS CRC cells can polarize T cells toward Th17 cells that have well-characterized pro-tumor functions in colorectal cancer. Analysis of large human cancer cohorts revealed an asynchronous pattern of the cholesterol biosynthesis in MSS CRC, which is responsible for the abnormal accumulation of distal cholesterol precursors. Inhibiting the cholesterol biosynthesis enzyme Cyp51, by pharmacological or genetic interventions, reduced the levels of intratumoral distal cholesterol precursors and suppressed tumor progression through a Th17-modulation mechanism in preclinical MSS CRC models. Our study therefore reveals a novel mechanism of cancer–immune interaction and an intervention strategy for the difficult-to-treat MSS CRC.

Shrimp (Penaeus vannamei) proteins have been shown an allergenic potential; however, little information is available on the sensitizing and eliciting capacity of shrimp protein digestion products. In this study, a BALB/c mice model was used to explore the allergenicity of shrimp protein sample (SPS) and their gastric and gastrointestinal digestion products (GDS/GIDS). As compared with the SPS groups, the GDS/GIDS groups caused lower specific immunoglobulins (IgE/IgG1) levels (P < 0.05), but higher than the control groups, indicating that the digestion products sensitized the mice. Meanwhile, spleen index, mouse mast cell protease-1 (mMCP-1) concentration and proportion of degranulated mast cells were significantly reduced in the GDS/GIDS groups (P < 0.05); simultaneously, allergic symptoms, vascular permeability and histopathological changes of tissues were alleviated. Nevertheless, the allergenicity of digestion products cannot be eliminated and still cause systemic allergic reactions in mice. The study showed that the digestion products of shrimp still had high sensitizing and eliciting capacity.

Volatile compounds are important determinants affecting fruit flavor. Previous study has identified a bud mutant of ‘Ehime 38’ (Citrus reticulata) with different volatile profile. However, the volatile changes between WT and MT during fruit development and underlying mechanism remain elusive. In this study, a total of 35 volatile compounds were identified in the pulps of WT and MT at five developmental stages. Both varieties accumulated similar and the highest levels of volatiles at stage S1, and showed a downward trend as the fruit develops. However, the total volatile contents in the pulps of MT were 1.4–2.5 folds higher than those in WT at stages S2-S5, which was mainly due to the increase in the content of d-limonene. Transcriptomic and RT-qPCR analysis revealed that most genes in MEP pathway were positively correlated with the volatile contents, of which DXS1 might mainly contribute to the elevated volatiles accumulation in MT by increasing the flux into the MEP pathway. Moreover, temporal expression analysis indicated that these MEP pathway genes functioned at different developmental stages. This study provided comprehensive volatile metabolomics and transcriptomics characterizations of a citrus mutant during fruit development, which is valuable for fruit flavor improvement in citrus.

ABSTRACT: The objective of this study was to investigate the protective effects and mechanisms of dietary administration of sodium humate (HNa) and its zinc and selenium chelate (Zn/Se-HNa) in mitigating Salmonella Typhimurium (S. Typhi) induced intestinal injury in broiler chickens. Following the gavage of 109 CFU S. Typhi to 240 broilers from 21-d to 23-d aged, various growth performance parameters such as body weight (BW), average daily gain (ADG), average daily feed intake (ADFI), and feed ratio (FCR) were measured before and after infection. Intestinal morphology was assessed to determine the villus height, crypt depth, and chorionic cryptologic ratio. To evaluate intestinal barrier integrity, levels of serum diamine oxidase (DAO), D-lactic acid, tight junction proteins, and the related genes were measured in each group of broilers. An analysis was conducted on inflammatory-related cytokines, oxidase activity, and Nuclear Factor Kappa B (NF-κB) and Nuclear factor erythroid2-related factor 2 (Nrf2) pathway-related proteins and mRNA expression. The results revealed a significant decrease in BW, ADG, and FCR in S. typhi-infected broilers. HNa tended to increase FCR (P = 0.056) while the supplementation of Zn/Se-HNa significantly restored BW and ADG (P < 0.05). HNa and Zn/Se-HNa exhibit favorable and comparable effects in enhancing the levels of serum DAO, D-lactate, and mRNA and protein expression of jejunum and ileal tight junction. In comparison to HNa, Zn/Se-HNa demonstrates a greater reduction in S. Typhi shedding in feces, as well as superior efficacy in enhancing the intestinal morphology, increasing serum catalase (CAT) activity, inhibiting pro-inflammatory cytokines, and suppressing the activation of the NF-κB pathway. Collectively, Zn/Se-HNa was a more effective treatment than HNa to alleviate adverse impact of S. Typhi infection in broiler chickens.

Abstract BackgroundRemovable partial denture (RPD) design is crucial to long-term success in dental treatment, but shortcomings in RPD design training and competency acquisition among dental students have persisted for decades. Digital production is increasing in prevalence in stomatology, and a digital RPD (D-RPD) module, under the framework of the certified Objective Manipulative Skill Examination of Dental Technicians (OMEDT) system reported in our previous work, may improve on existing RPD training models for students. ObjectiveWe aimed to determine the efficacy of a virtual 3D simulation–based progressive digital training module for RPD design compared to traditional training. MethodsWe developed a prospective cohort study including dental technology students at the Stomatology College of Chongqing Medical University. Cohort 1 received traditional RPD design training (7 wk). Cohort 2 received D-RPD module training based on text and 2D sketches (7 wk). Cohort 3 received D-RPD module pilot training based on text and 2D sketches (4 wk) and continued to receive training based on 3D virtual casts of real patients (3 wk). RPD design tests based on virtual casts were conducted at 1 month and 1 year after training. We collected RPD design scores and the time spent to perform each assessment. ResultsWe collected the RPD design scores and the time spent to perform each assessment at 1 month and 1 year after training. The study recruited 109 students, including 58 (53.2%) female and 51 male (56.8%) students. Cohort 1 scored the lowest and cohort 3 scored the highest in both tests (cohorts 1-3 at 1 mo: mean score 65.8, SD 21.5; mean score 81.9, SD 6.88; and mean score 85.3, SD 8.55, respectively; PPPPPPP ConclusionsCohort 3 obtained the highest score at both time points with retention of competency at 1 year, indicating that progressive D-RPD training including virtual 3D simulation facilitated improved competency in RPD design. The adoption of D-RPD training may benefit learning outcomes.

Ginsenoside Rc, a dammarane-type tetracyclic triterpenoid saponin primarily derived from Panax ginseng, has garnered significant attention due to its diverse pharmacological properties. This review outlined the sources, putative biosynthetic pathways, extraction, and quantification techniques, as well as the pharmacokinetic properties of ginsenoside Rc. Furthermore, this study explored the pharmacological effects of ginsenoside Rc against metabolic syndrome (MetS) across various phenotypes including obesity, diabetes, atherosclerosis, non-alcoholic fatty liver disease, and osteoarthritis. It also highlighted the impact of ginsenoside Rc on multiple associated signaling molecules. In conclusion, the anti-MetS effect of ginsenoside Rc is characterized by its influence on multiple organs, multiple targets, and multiple ways. Although clinical investigations regarding the effects of ginsenoside Rc on MetS are limited, its proven safety and tolerability suggest its potential as an effective treatment option.

Soil visible and near–infrared reflectance spectroscopy is an effective tool for the rapid estimation of soil organic carbon (SOC). The development of spectroscopic technology has increased the application of spectral libraries for SOC research. However, the direct application of spectral libraries for SOC prediction remains challenging due to the high variability in soil types and soil–forming factors. This study aims to address this challenge by improving SOC prediction accuracy through spectral classification. We utilized the European Land Use and Cover Area frame Survey (LUCAS) large–scale spectral library and employed a geographically weighted principal component analysis (GWPCA) combined with a fuzzy c–means (FCM) clustering algorithm to classify the spectra. Subsequently, we used partial least squares regression (PLSR) and the Cubist model for SOC prediction. Additionally, we classified the soil data by land cover types and compared the classification prediction results with those obtained from spectral classification. The results showed that (1) the GWPCA–FCM–Cubist model yielded the best predictions, with an average accuracy of R2 = 0.83 and RPIQ = 2.95, representing improvements of 10.33% and 18.00% in R2 and RPIQ, respectively, compared to unclassified full sample modeling. (2) The accuracy of spectral classification modeling based on GWPCA–FCM was significantly superior to that of land cover type classification modeling. Specifically, there was a 7.64% and 14.22% improvement in R2 and RPIQ, respectively, under PLSR, and a 13.36% and 29.10% improvement in R2 and RPIQ, respectively, under Cubist. (3) Overall, the prediction accuracy of Cubist models was better than that of PLSR models. These findings indicate that the application of GWPCA and FCM clustering in conjunction with the Cubist modeling technique can significantly enhance the prediction accuracy of SOC from large–scale spectral libraries.

The formation of learning and memory is regulated by synaptic plasticity in hippocampal neurons. Here we explored how gestational exposure to dexamethasone, a synthetic glucocorticoid commonly used in clinical practice, has lasting effects on offspring's learning and memory. Adult offspring rats of prenatal dexamethasone exposure (PDE) displayed significant impairments in novelty recognition and spatial learning memory, with some phenotypes maintained transgenerationally. PDE impaired synaptic transmission of hippocampal excitatory neurons in offspring of F1 to F3 generations, and abnormalities of neurotransmitters and receptors would impair synaptic plasticity and lead to impaired learning and memory, but these changes failed to carry over to offspring of F5 and F7 generations. Mechanistically, altered hippocampal miR-133a-3p-SIRT1-CDK5-NR2B signaling axis in PDE multigeneration caused inhibition of excitatory synaptic transmission, which might be related to oocyte-specific high expression and transmission of miR-133a-3p. Together, PDE affects hippocampal excitatory synaptic transmission, with lasting consequences across generations, and CDK5 in offspring's peripheral blood might be used as an early-warning marker for fetal-originated learning and memory impairment.

Abstract Adjustment difficulties of school students are common and their school adjustment has gained wide concern in recent years. Negative life events (NLEs) hope, and gratitude have been associated with school adjustment. However, the potential effect of NLEs on hope and gratitude and whether hope and gratitude mediate the association between NLEs and school adjustment among high students have not been studied. Thus, this study aims to investigate the association between NLEs, hope and gratitude, and school adjustment in high school students in China. Additionally, the study aims to examine the mediating role of hope and gratitude in the association between NLEs and school adjustment. A total of 700 junior high school students in Guangxi Province (336 boys, 364 girls, M age = 15 years) completed the questionnaire. The results indicated significant mediating effects of hope and gratitude in the sequential positive association between NLEs and school adjustment. Furthermore, this study unraveled the complexity of the link between NLEs and school adjustment with the combination of hope and gratitude. The findings emphasized the importance of fostering hope and gratitude in left-behind adolescents to combat the negative consequences of NLEs. The study is also one of the first to investigate a serial mediation model to determine which NLEs influence Chinese left-behind adolescents’ school adjustment.

Sugar is a primary determinant of citrus fruit flavour, but undergoes varied accumulation processes across different citrus varieties owing to high genetic variability. Sucrose phosphate synthase (SPS), a key enzyme in glucose metabolism, plays a crucial role in this context. Despite its significance, there is limited research on sugar component quality and the expression and regulatory prediction of SPS genes during citrus fruit development. Therefore, we analysed the sugar quality formation process in ‘Kiyomi’ and ‘Succosa’, two citrus varieties, and performed a comprehensive genome-wide analysis of citrus CsSPSs. We observed that the accumulation of sugar components significantly differs between the two varieties, with the identification of four CsSPSs in citrus. CsSPS sequences were highly conserved, featuring typical SPS protein domains. Expression analysis revealed a positive correlation between CsSPS expression and sugar accumulation in citrus fruits. However, CsSPS expression displays specificity to different citrus tissues and varieties. Transcriptome co-expression network analysis suggests the involvement of multiple transcription factors in shaping citrus fruit sugar quality through the regulation of CsSPSs. Notably, the expression levels of four CsWRKYs (CsWRKY2, CsWRKY20, CsWRKY28, CsWRKY32), were significantly positively correlated with CsSPSs and CsWRKY20 might can activate sugar accumulation in citrus fruit through CsSPS2. Collectively, we further emphasize the potential importance of CsWRKYs in citrus sugar metabolism, our findings serve as a reference for understanding sugar component formation and predicting CsSPS expression and regulation during citrus fruit development.

‘Fengtang‘ plums soften quickly and lose flavor after harvest. This study comprehensively evaluated the effect of exogenous melatonin on the fruit quality of ‘Fengtang’ plums. According to our findings, exogenous melatonin prevented plum fruit from losing water, delayed the decline in firmness, and preserved a high TSS/TA level. Additionally, exogenous melatonin also enhanced the activity of antioxidant enzymes and increased the non-enzymatic antioxidants, thereby further increasing the antioxidant capacity of plum fruit. Notably, exogenous melatonin delayed the degradation of covalent soluble pectin (CSP), cellulose, and hemicellulose, as well as the rise in water-soluble pectin (WSP) concentration and the activity of cell wall degrading enzymes. Further investigation using atomic force microscopy (AFM) revealed that the chain-like structure of ionic-soluble pectin (ISP) and the self-assembly network structures of CSP were depolymerized, and melatonin treatment retarded the depolymerization of pectin structures. Our results showed that exogenous melatonin preserved the postharvest quality of plum fruits by controlling fruit softness and antioxidant capacity during storage.

Accurate prediction of bus arrival time is essential to achieve efficient bus dispatch and improve bus trip sharing rate. This article proposes using the improved whale optimization algorithm–long short-term memory (IWOA–LSTM) model to predict bus arrival times and improving the whale algorithm by optimizing the hyperparameters of the LSTM model, so that the advantages and disadvantages of the whale algorithm and the LSTM model can complement each other, thus enhancing the robustness of the model. Initially, the bus arrival process and its associated influencing factors are analyzed, with certain factors being quantified to serve as input features for the prediction model. After processing the GPS data of the No. 220 bus in Nanchang, Jiangxi, China, the proposed prediction model is analyzed and validated using an example and compared with other prediction models. The results show that the IWOA–LSTM prediction model has the best-fitting effect between the predicted values and actual values in all time periods. Its MAPE, RMSE, and MAE have been reduced by at least 9.47%, 12.77%, and 8.93%, respectively, and the overall R2 has been improved by at least 10.65%. These results indicate that the model has the best predictive performance.

The excessive accumulation of antibiotic residue in animal-derived foods pose a threat to our heath. Therefore, it is necessary to establish a rapid, simple, effective, safe and highly sensitive lincomycin (LIN) residues detection method by high-performance liquid chromatography equipped with ultraviolet. Here, due to the weak UV absorption of LIN, the p-Toluenesulfonyl isocyanate (PTSI, has a strong UV absorption) was binded to the hydroxyl group of LINs by using pre-column derivatization method, improving the UV absorption of LIN. This 9-min-run analytical method detects and quantifies LIN residues with acceptable validation performance parameters in terms of sensitivity, selectivity, linearity, the limit of quantification, accuracy, and precision.Our result showed that the limits of detection and quantification for LIN in samples were 25–40 μg/kg and 40–60 μg/kg, respectively, under the optimized conditions. Furthermore, the LIN recoveries ranged from 72.4 % to 96.7 %; the determination coefficients were 0.9912–0.9996, and the relative standard deviations were 5.6 %-12.7 %. Therefore, the HPLC-UVD method for detecting LIN residues in animal-derived food products has been established.

Currently, complex scene classification strategies are limited to high-definition image scene sets, and low-quality scene sets are overlooked. Although a few studies have focused on artificially noisy images or specific image sets, none have involved actual low-resolution scene images. Therefore, designing classification models around practicality is of paramount importance. To solve the above problems, this paper proposes a two-stage classification optimization algorithm model based on MPSO, thus achieving high-precision classification of low-quality scene images. Firstly, to verify the rationality of the proposed model, three groups of internationally recognized scene datasets were used to conduct comparative experiments with the proposed model and 21 existing methods. It was found that the proposed model performs better, especially in the 15-scene dataset, with 1.54% higher accuracy than the best existing method ResNet-ELM. Secondly, to prove the necessity of the pre-reconstruction stage of the proposed model, the same classification architecture was used to conduct comparative experiments between the proposed reconstruction method and six existing preprocessing methods on the seven self-built low-quality news scene frames. The results show that the proposed model has a higher improvement rate for outdoor scenes. Finally, to test the application potential of the proposed model in outdoor environments, an adaptive test experiment was conducted on the two self-built scene sets affected by lighting and weather. The results indicate that the proposed model is suitable for weather-affected scene classification, with an average accuracy improvement of 1.42%.

Although MALDI-TOF mass spectrometry (MS) is widely known as a rapid and cost-effective reference method for identifying microorganisms, its commercial databases face limitations in accurately distinguishing specific subspecies of Bifidobacterium. This study aimed to explore the potential of MALDI-TOF MS protein profiles, coupled with prediction methods, to differentiate between Bifidobacterium longum subsp. infantis (B. infantis) and Bifidobacterium longum subsp. longum (B. longum). The investigation involved the analysis of mass spectra of 59 B. longum strains and 41 B. infantis strains, leading to the identification of five distinct biomarker peaks, specifically at m/z 2,929, 4,408, 5,381, 5,394, and 8,817, using Recurrent Feature Elimination (RFE). To facilate classification between B. longum and B. infantis based on the mass spectra, machine learning models were developed, employing algorithms such as logistic regression (LR), random forest (RF), and support vector machine (SVM). The evaluation of the mass spectrometry data showed that the RF model exhibited the highest performace, boasting an impressive AUC of 0.984. This model outperformed other algorithms in terms of accuracy and sensitivity. Furthermore, when employing a voting mechanism on multi-mass spectrometry data for strain identificaton, the RF model achieved the highest accuracy of 96.67%. The outcomes of this research hold the significant potential for commercial applications, enabling the rapid and precise discrimination of B. longum and B. infantis using MALDI-TOF MS in conjunction with machine learning. Additionally, the approach proposed in this study carries substantial implications across various industries, such as probiotics and pharmaceuticals, where the precise differentiation of specific subspecies is essential for product development and quality control.

Abstract Chemo‐immunotherapy has made significant progress in cancer treatment. However, the cancer cell self‐defense mechanisms, including cell cycle checkpoint and programmed cell death‐ligand 1 (PD‐L1) upregulation, have greatly hindered the therapeutic efficacy. Herein, norcantharidin (NCTD)‐platinum (Pt) codelivery nanoparticles (NC‐NP) with tumor‐sensitive release profiles are designed to overcome the self‐defense mechanisms via synergistic chemo‐immunotherapy. NC‐NP remains stable under normal physiological conditions but quickly releases 1,2‐diaminocyclohexane‐platinum(II) (DACHPt, a parent drug of oxaliplatin) and NCTD in response to the tumor acidity. NCTD inhibits protein phosphatase 2A (PP2A) activity to relieve cell cycle arrest and downregulates the tumor PD‐L1 expression to disrupt the programmed cell death‐1 (PD‐1)/PD‐L1 interaction, synergistically enhancing Pt‐based chemotherapy and immunogenic cell death‐induced immunotherapy. As a result, NC‐NP exhibits potent synergistic cytotoxicity and promotes T cell recruitment to generate robust antitumor immune responses. The dual synergism exhibits potent antitumor activity against orthotopic 4T1 tumors, providing a promising chemo‐immunotherapy paradigm for cancer treatment.

Coxsackievirus A10 (CVA10) has recently emerged as one of the major causative agents of hand, foot, and mouth disease. CVA10 may also cause a variety of complications. No approved vaccine or drug is currently available for CVA10. The residues of CVA10 critical for viral attachment, infectivity and in vivo pathogenicity have not been identified by experiment. Here, we report the identification of CVA10 residues important for binding to cellular receptor KREMEN1. We identified VP2 N142 as a key receptor-binding residue by screening of CVA10 mutants resistant to neutralization by soluble KREMEN1 protein. The receptor-binding residue N142 is exposed on the canyon rim but highly conserved in all naturally occurring CVA10 strains, which provides a counterexample to the canyon hypothesis. Residue N142 when mutated drastically reduced receptor-binding activity, resulting in decreased viral attachment and infection in cell culture. More importantly, residue N142 when mutated reduced viral replication in limb muscle and spinal cord of infected mice, leading to lower mortality and less severe clinical symptoms. Additionally, residue N142 when mutated could decrease viral binding affinity to anti-CVA10 polyclonal antibodies and a neutralizing monoclonal antibody and render CVA10 resistant to neutralization by the anti-CVA10 antibodies. Overall, our study highlights the essential role of VP2 residue N142 of CVA10 in the interactions with KREMEN1 receptor and neutralizing antibodies and viral virulence in mice, facilitating the understanding of the molecular mechanisms of CVA10 infection and immunity. Our study also provides important information for rational development of antibody-based treatment and vaccines against CVA10 infection.

Twisted tri-lobed tubes have garnered attention due to their exceptional heat transfer efficiency and straightforward fabrication. Existing literature lacks comprehensive assessments of the overall heat transfer performance of twisted tri-lobed tubes from the perspective of energy loss and irreversibility. This research aims to investigate entropy generation during turbulent water flow within twisted tri-lobed tubes, examining the influence of geometric parameters on local and average entropy production. Findings indicate that larger small circle radius (r) and straight lengths (l), coupled with smaller transition circle radius (R) and twist pitch lengths (p), result in diminished local and average heat transfer entropy production while enhancing local and average frictional entropy production, with heat transfer entropy generation dominating the overall entropy production. Additionally, with increasing Reynolds numbers, all twisted tubes demonstrate an increasing trend in average frictional entropy production, except for some cases (Case 1-Case 4) that exhibit an initial rise followed by a decline in average heat transfer entropy generation. Among the examined Reynolds range, Case 4 displays lower overall irreversibility compared to a plain tube. Following the second law of thermodynamics, Case 4 is preferred. The findings and methodology contribute to enhancing the thermodynamic evaluation of convective heat transfer in twisted tri-lobed tubes.

Medication during pregnancy is widespread, but there are few reports on its fetal safety. Recent studies suggest that medication during pregnancy can affect fetal morphological and functional development through multiple pathways, multiple organs, and multiple targets. Its mechanisms involve direct ways such as oxidative stress, epigenetic modification, and metabolic activation, and it may also be indirectly caused by placental dysfunction. Further studies have found that medication during pregnancy may also indirectly lead to multi-organ developmental programming, functional homeostasis changes, and susceptibility to related diseases in offspring by inducing fetal intrauterine exposure to too high or too low levels of maternal-derived glucocorticoids. The organ developmental toxicity and programming alterations caused by medication during pregnancy may also have gender differences and multi-generational genetic effects mediated by abnormal epigenetic modification. Combined with the latest research results of our laboratory, this paper reviews the latest research progress on the developmental toxicity and functional programming alterations of multiple organs in offspring induced by medication during pregnancy, which can provide a theoretical and experimental basis for rational medication during pregnancy and effective prevention and treatment of drug-related multiple fetal-originated diseases.

The optimal interval before receiving SARS-COV-2 vaccination for patients who have received anti-CD 20 monoclonal antibodies remains unclear. We considered original studies up to 29 October 2022 and conducted searches in Embase,Medrxiv, PubMed, and SSRN. We excluded search results that did not match our research question’s subject. Human immune response outcomes were analysed inpatients who had previously received anti-CD20 antibody therapy. We analyzed the collected results using sensitivity curves and forest plots. Twenty-eight studies with a total of 1455 subjects receiving anti-CD20 monoclonal antibodies were included in the present analysis. The humoral immune response rates to the time between the last anti-CD20 treatment and vaccination for 3–6 months, 6 months,6–9 months, and 9–12 months were 0.23 (95% CI 0.14 to 0.36), 0.36 (95% CI 0.19 to 0.58), 0.49 (95% CI 0.35 to 0.64) and 0.64 (95% CI 0.48 to 0.77),respectively. The humoral immune response rates were.16 (95% CI 0.03 to 0.57) when B cell was 0/ul, and 0.49 (95% CI 0.38 to 0.61)when B cells were more than 5/ul. The humoral immune response rate for multiple sclerosis was 0.39 (95% CI 0.22 to 0.60) and 0.48 (95% CI 0.29 to 0.68) for B-cell non-Hodgkin lymphoma. The area underneath the curve(AUC) was 0.69 with a cut-off value of 5.5 months. The present results suggested that the optimal interval for SARS-COV-2 vaccination after the final dose of anti-CD20 monoclonal antibody was 5.5 months.

Abstract Industrial robots are widely used in various industrial fields, such as handling and welding, due to their good repeat positioning accuracy. The motion error determines the absolute accuracy. For robot design, dimensional parameter errors and drive parameter errors, a mathematical model of a kinematic exponential product with error screws was proposed. The influence of different rod lengths and transmission errors on the accuracy of the end motion was analysed. A composite analysis method based on screw theory and vector method is proposed for the spatial deflection error of robot rotating joints with clearance. By using screw theory, a mathematical error model of the axial movement and spatial deflection of the joint gap was established. A mathematical model of joint space radial movement was established by using the three-dimensional vector method. Through numerical simulation, the position distribution law of the random error of the robot terminal in the workspace and the distribution of the plane projection density were obtained. By solving the attitude matrix, the distribution of each Euler angle error was obtained. A simulation test was carried out to verify the model's correctness. The calculation showed that the method is simple and correct, and the obtained error distribution characteristics are of great significance to improving robotic kinematic calibration accuracy and optimising the spatial position error distribution.

Sugars and organic acids are the main factors determining the flavor of citrus fruit. The WRKY transcription factor family plays a vital role in plant growth and development. However, there are still few studies about the regulation of citrus WRKY transcription factors (CsWRKYs) on sugars and organic acids in citrus fruit. In this work, a genome-wide analysis of CsWRKYs was carried out in the citrus genome, and a total of 81 CsWRKYs were identified, which contained conserved WRKY motifs. Cis-regulatory element analysis revealed that most of the CsWRKY promoters contained several kinds of hormone-responsive and abiotic-responsive cis-elements. Furthermore, gene expression analysis and fruit quality determination showed that multiple CsWRKYs were closely linked to fruit sugars and organic acids with the development of citrus fruit. Notably, transcriptome co-expression network analysis further indicated that three CsWRKYs, namely, CsWRKY3, CsWRKY47, and CsWRKY46, co-expressed with multiple genes involved in various pathways, such as Pyruvate metabolism and Citrate cycle. These CsWRKYs may participate in the metabolism of fruit sugars and organic acids by regulating carbohydrate metabolism genes in citrus fruit. These findings provide comprehensive knowledge of the CsWRKY family on the regulation of fruit quality.

During their journey of developing, resource-based cities gradually deplete the resources on which they rely for survival. Scientific and reasonable research on the industrial and ecological aspects of resource-based cities is conducive to the coordinated development of cities. In order to further analyze the industrial structure of resource-based cities systematically and analyze the comprehensive level of resource-based cities from multi-dimensional perspective. This paper took 8 resource-based cities in Sichuan Province as the research object, and constructed the index system from two systems: industrial structure and ecological environment, then the shift-share analysis, entropy weight method and capacity coupling coefficient model were used to analyze their level of industrial structure, ecological environment and the coupling relationship respectively. According to the results of the study, it can be concluded that the main influencing factor in the development of industrial structure is the industrialmix effect, while the ecological level presents a decreasing level due to the lack of control of total industrial solid waste and energy consumption. The coupling degree between industrial structure and ecological environment in resource-based cities in Sichuan Province is relatively stable, and the coupling coordination degree also gradually tends to a stable state. In the subsequent development, the focus should be on the coal mining and dressing industry and the power, heat production and supply industry. Starting with the actual industrial structure of resource-based cities and specific indicators that affected the ecological environment, this paper hereby analyzed the development momentum and unified and coordinated development status of resource-based cities. The main purpose of this paper is providing some technical support for resource-based cities to improve their coordinated urban development, and giving policy suggestions for the coordinated development of resource-based cities.

Saffron (Crocus sativus L.) is one of the most expensive spices in the world, boasting rich medicinal and edible value. However, the effective development of active natural substances in saffron is still limited. Currently, there is a lack of comprehensive studies on the saffron stigma protein, and the main effect peptides have not been identified. In this study, the total protein composition of saffron stigmas was analyzed, and two main antioxidant peptides (DGGSDYLGK and VDPYFNK) were identified, which showed high antioxidant activity. Then, the stability of two peptides was further evaluated. Furthermore, our results suggested that these two peptides may protect HepG2 cells from H2O2-induced oxidative damage by significantly improving the activity of endogenous antioxidant enzymes and reducing the malondialdehyde (MDA) content. Collectively, we identified two peptides screened from the saffron protein possessing good antioxidant activity and stability, making them promising candidates for use as functional foods, etc., for health promotion. Our findings indicated that proteomic analysis together with peptide identification is a good method for exploitation and utilization of spice plants.

In conventional point-line visual–inertial odometry systems in indoor environments, consideration of spatial position recovery and line feature classification can improve localization accuracy. In this paper, a monocular visual–inertial odometry based on structured and unstructured line features of vanishing points is proposed. First, the degeneracy phenomenon caused by a special geometric relationship between epipoles and line features is analyzed in the process of triangulation, and a degeneracy detection strategy is designed to determine the location of the epipoles. Then, considering that the vanishing point and the epipole coincide at infinity, the vanishing point feature is introduced to solve the degeneracy and direction vector optimization problem of line features. Finally, threshold constraints are used to categorize straight lines into structural and non-structural features under the Manhattan world assumption, and the vanishing point measurement model is added to the sliding window for joint optimization. Comparative tests on the EuRoC and TUM-VI public datasets validated the effectiveness of the proposed method.

Abstract Determination of malignancy in thyroid nodules remains a major diagnostic challenge. Here we report the feasibility and clinical utility of developing an AI-defined protein-based biomarker panel for diagnostic classification of thyroid nodules: based initially on formalin-fixed paraffin-embedded (FFPE), and further refined for fine-needle aspiration (FNA) tissue specimens of minute amounts which pose technical challenges for other methods. We first developed a neural network model of 19 protein biomarkers based on the proteomes of 1724 FFPE thyroid tissue samples from a retrospective cohort. This classifier achieved over 91% accuracy in the discovery set for classifying malignant thyroid nodules. The classifier was externally validated by blinded analyses in a retrospective cohort of 288 nodules (89% accuracy; FFPE) and a prospective cohort of 294 FNA biopsies (85% accuracy) from twelve independent clinical centers. This study shows that integrating high-throughput proteomics and AI technology in multi-center retrospective and prospective clinical cohorts facilitates precise disease diagnosis which is otherwise difficult to achieve by other methods.

ABSTRACT Salmonella is a foodborne pathogen that is one of the main causes of gastroenteric disease in humans and animals. As a natural organic substance, sodium humate (HNa) possesses antibacterial, antidiarrheal, and anti-inflammatory properties. However, it is unclear whether the HNa and HNa-derived microbiota exert alleviative effects on Salmonella enterica serovar Typhimurium-induced enteritis. We found that treatment with HNa disrupted the cell wall of S. Typhimurium and decreased the virulence gene expression. Next, we explored the effect of HNa presupplementation on S. Typhimurium-induced murine enteritis. The results revealed that HNa ameliorated intestinal pathological damage. In addition, we observed that presupplementation with HNa enhanced intestinal barrier function via modulating gut microbiota, downregulating toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) and NOD-like receptor protein 3 (NLRP3) signaling pathways, regulating intestinal mucosal immunity, and enhancing tight junction protein expression. To further validate the effect of HNa-derived microbiota on S. Typhimurium-induced enteritis, we performed fecal microbiota transplantation and found that HNa-derived microbiota also alleviated S. Typhimurium-induced intestinal damage. It is noteworthy that both HNa and HNa-derived microbiota improved the liver injury caused by S. Typhimurium infection. Collectively, this is the first study to confirm that HNa could alleviate S. Typhimurium-induced enteritis in a gut microbiota-dependent manner. This study provides a new perspective on HNa as a potential drug to prevent and treat salmonellosis. IMPORTANCE Salmonella Typhimurium is an important zoonotic pathogen, widely distributed in nature. S. Typhimurium is one of the leading causes of foodborne illnesses worldwide, and more than 350,000 people died from Salmonella infection each year, which poses a substantial risk to public health and causes a considerable economic loss. Here, we found that the S. Typhimurium infection caused severe intestinal and liver damage. In addition, we first found that sodium humate (HNa) and HNa-derived gut microbiota can alleviate S. Typhimurium infection-induced intestinal damage. These findings extend the knowledge about the public health risk and pathogenic mechanisms of S. Typhimurium.

Abstract Chemoresistance is the main obstacle in osteosarcoma (OS) treatment; however, the underlying mechanism remains unclear. In this study, it is discovered that DDRGK domain‐containing protein 1 (DDRGK1) plays a fundamental role in chemoresistance induced in OS. Bioinformatic and tissue analyses indicate that higher expression of DDRGK1 correlates with advanced tumor stage and poor clinical prognosis of OS. Quantitative proteomic analyses suggest that DDRGK1 plays a critical role in mitochondrial oxidative phosphorylation. DDRGK1 knockout trigger the accumulation of reactive oxygen species (ROS) and attenuate the stability of nuclear factor erythroid‐2‐related factor 2 (NRF2), a major antioxidant response element. Furthermore, DDRGK1 inhibits ubiquitin‐proteasome‐mediated degradation of NRF2 via competitive binding to the Kelch‐like ECH‐associated protein 1 (KEAP1) protein, which recruits NRF2 to CULLIN(CUL3). DDRGK1 knockout attenuates NRF2 stability, contributing to ROS accumulation, which promotes apoptosis and enhanced chemosensitivity to doxorubicin (DOX) and etoposide in cancer cells. Indeed, DDRGK1 knockout significantly enhances osteosarcoma chemosensitivity to DOX in vivo. The combination of DDRGK1 knockdown and DOX treatment provides a promising new avenue for the effective treatment of OS.

AimsImmune stress in broiler chickens is characterized by the development of persistent pro-inflammatory responses that contribute to degradation of production performance. However, the underlying mechanisms that cause growth inhibition of broilers with immune stress are not well defined.MethodsA total of 252 1-day-old Arbor Acres(AA) broilers were randomly allocated to three groups with six replicates per group and 14 broilers per replicate. The three groups comprised a saline control group, an Lipopolysaccharide (LPS) (immune stress) group, and an LPS and celecoxib group corresponding to an immune stress group treated with a selective COX-2 inhibitor. Birds in LPS group and saline group were intraperitoneally injected with the same amount of LPS or saline from 14d of age for 3 consecutive days. And birds in the LPS and celecoxib group were given a single intraperitoneal injection of celecoxib 15 min prior to LPS injection at 14 d of age.ResultsThe feed intake and body weight gain of broilers were suppressed in response to immune stress induced by LPS which is an intrinsic component of the outer membrane of Gram-negative bacteria. Cyclooxygenase-2 (COX-2), a key enzyme that mediates prostaglandin synthesis, was up-regulated through MAPK-NF-κB pathways in activated microglia cells in broilers exposed to LPS. Subsequently, the binding of prostaglandin E2 (PGE2) to the EP4 receptor maintained the activation of microglia and promoted the secretion of cytokines interleukin-1β and interleukin-8, and chemokines CX3CL1 and CCL4. In addition, the expression of appetite suppressor proopiomelanocortin protein was increased and the levels of growth hormone-releasing hormone were reduced in the hypothalamus. These effects resulted in decreased expression of insulin-like growth factor in the serum of stressed broilers. In contrast, inhibition of COX-2 normalized pro-inflammatory cytokine levels and promoted the expression of Neuropeptide Y and growth hormone-releasing hormone in the hypothalamus which improved the growth performance of stressed broilers. Transcriptomic analysis of the hypothalamus of stressed broilers showed that inhibition of COX-2 activity significantly down-regulated the expression of the TLR1B, IRF7, LY96, MAP3K8, CX3CL1, and CCL4 genes in the MAPK-NF-κB signaling pathway.ConclusionThis study provides new evidence that immune stress mediates growth suppression in broilers by activating the COX-2-PGE2-EP4 signaling axis. Moreover, growth inhibition is reversed by inhibiting the activity of COX-2 under stressed conditions. These observations suggest new approaches for promoting the health of broiler chickens reared in intensive conditions.

ABSTRACT: Immune stress exerts detrimental effects on growth performance and intestinal barrier function during intensive animal production with ensuing serious economic consequences. Chlorogenic acid (CGA) is used widely as a feed additive to improve the growth performance and intestinal health of poultry. However, the effects of dietary CGA supplementation on amelioration of the intestinal barrier impairment caused by immune stress in broilers are unknown. This study investigated the effects of CGA on growth performance, intestinal barrier function, and the inflammatory response in lipopolysaccharide (LPS) mediated immune-stressed broilers. Three hundred and twelve 1-day-old male Arbor Acres broilers were divided randomly into 4 groups with 6 replicates of thirteen broilers. The treatments included: i) saline group: broilers injected with saline and fed with basal diet; ii) LPS group: broilers injected with LPS and fed with basal diet; iii) CGA group: broilers injected with saline and feed supplemented with CGA; and iv) LPS+CGA group: broilers injected with LPS and feed supplemented with CGA. Animals in the LPS and LPS+CGA groups were injected intraperitoneally with an LPS solution prepared with saline from 14 d of age for 7 consecutive days, whereas broilers in the other groups were injected only with saline. LPS induced a decrease in feed intake of broilers during the stress period, but CGA effectively alleviated this decrease. Moreover, CGA inhibited the reduction of villus height and improved the ratio of villus height to crypt depth in the duodenum of broilers 24 and 72 h after LPS injection. In addition, dietary CGA supplementation significantly restored the expression of cation-selective and channel-forming Claudin2 protein 2 h after LPS injection in the ileum. LPS enhanced the expression of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in the small intestine, but this enhancement was blocked by CGA supplementation. The expression of interleukin-10 (IL-10) increased with LPS injection and CGA promoted the production of IL-10. CGA addition downregulated the expression of intestinal interleukin-6 (IL-6) of broilers under normal rearing conditions. However, CGA supplementation upregulated the expression of IL-6 of broilers 72 h after LPS injection. The data demonstrate that dietary supplementation with CGA alleviates intestinal barrier damage and intestinal inflammation induced by LPS injection during immune stress thereby improving growth performance of broilers.

Abstract Background Klebsiella pneumoniae is widely distributed in water and plays a major role in both human and poultry infections. Many K. pneumoniae strains form biofilms on various surfaces, enhancing their pathogenicity and resistance to antibiotics. The water supply pipeline of chicken farms has become a hotbed for the growth of K pneumoniae biofilm because of its humid environment, and because the chicken drinking water pipeline is thin, it is easily blocked by the biofilm, and the diffused cells can cause repeated and persistent infections. Iron is vital to the growth of microorganisms and the formation of biofilms. Therefore, the aim of this study was to examine the effects of iron on K. pneumoniae biofilm formation and any associated metabolic changes to provide a rationale for reducing the formation of biofilms. Results Biofilm formation was enhanced to the greatest extent by the presence of 0.16 mM FeCl2, producing a denser structure under electron microscopy. The number of biofilm-forming and planktonic bacteria did not change, but protein and polysaccharide concentrations in the bacterial extracellular polymeric substances (EPS) were significantly increased by iron supplementation. To clarify this mechanism, intracellular metabolomic analysis was carried out, showing that the differential, down-regulated metabolites included succinic acid. The addition of 1.7 mM succinic acid counteracted the biofilm-forming effect of iron, with no bactericidal side effects. Conclusion This study demonstrates the importance of succinic acid and iron in K. pneumoniae biofilms, and provides insight into the formation of K. pneumoniae biofilms and direction for the development of new antibacterial agents.

The first millennium BC saw the expansion of the Western Zhou dynasty in its northwestern frontier, alongside the rise and development of the Qin State in the Longshan Mountain region of northern China. Exploring the subsistence practices of these communities is crucial to gaining a better understanding of the social, cultural, and political landscape in this region at the time. While much of the research to date has focused on the Qin people, the subsistence practices of the Zhou people remain poorly understood. In this study, we analyzed animal remains from Yucun, a large settlement site associated with the Zhou people, located to the east of the Longshan Mountain. These animal remains were recovered in the excavation seasons of 2018–2020. Our results show that pigs, dogs, cattle, caprines, and horses, which were the major domestic animals at Yucun, accounted for over 90.8% of the animal remains examined in terms of the number of identified specimens (NISP) and 72.8% in terms of the minimum number of individuals (MNI), with cattle and caprines playing dominant roles. In terms of the taxonomic composition and the mortality profiles of pigs, caprines, and cattle, Yucun shared similarities with Maojiaping and Xishan, two contemporaneous Qin cultural sites located to the west of the Longshan Mountain, and differ from other farming societies in the middle and lower reaches of the Yellow River valley. Considering the cultural attributes and topographic conditions of these various sites, these findings imply that environmental conditions may have played a more significant role than cultural factors in shaping the animal-related subsistence practices in northern China during the first millennium BC.

The late second and first millennium BC witnessed extensive economic, cultural, and political exchanges between pastoralists and sedentary farming states in East Asia. Decades of archaeological fieldwork across northern China have revealed a large number of burial sites associated with pastoralists during the first millennium BC. These sites were characterized by the inhumation of specific animal parts in burials, predominantly the skulls and hooves of sheep, goats, cattle, and horses. However, the selection preference for these animals and how they were integrated into the mortuary contexts of these pastoral societies remain poorly investigated. Here, we report a preliminary analysis of caprine remains from 70 burials at the site of Dunping in the southern Gansu region of northwestern China, dated to approximately the seventh to fourth centuries BC. Based on an examination of species composition, post-depositional effects, traces of human alteration, skeletal element representation, and age at death, we discussed the selection, slaughtering, and inhumation of caprines concerning the mortuary practices at the site. Comparisons between Dunping and several other contemporaneous burial sites in neighboring regions, specifically in terms of the mortality profiles, further highlight distinct patterns in the selection of caprines for mortuary purposes among pastoral societies. These differences suggest varying degrees of emphasis placed on the economic and social significance attributed to caprines. Our findings provide new insights into the roles that caprines played in both ritual performances and subsistence practices among pastoralists in East Asia during the first millennium BC.

Abstract Background Accurate posterior column reduction remains a challenging and controversial topic in the management of complex pilon fractures (AO/OTA C3). We aim to report the outcomes of surgical treatment for 22 AO/OTA C3 pilon fracture cases between January 2015 and May 2017 and highlight some traps and tips. Methods Three patients underwent two-stage early plating on the posterior column through a posterolateral approach. The remaining 19 patients were treated with two-stage delayed plating on the posterior column: 11 patients were treated with a posterolateral approach, five patients with a modified posteromedial approach, and three patients with a single anterior approach. The reduction of the posterior column was evaluated according to the Burwell-Charnley’s radiographic criteria, and functional outcomes were assessed using the American Orthopedic Foot and Ankle Society (AOFAS) scores. Results Posterior column malreduction occurred in five cases, including in one case that was re-adjusted immediately and in another case that was re-adjusted during a two-staged delayed operation. According to Burwell-Charnley’s criteria, the satisfactory rate of fracture reduction was 81.8%. After 1 year, the mean AOFAS score was 81.9 (81.9 ± 9.9); the outcome was excellent in three (20.0%), good in nine (60.0%), and fair in three (20.0%). Excellent or good outcomes were noted in 12 patients (80.0%). Conclusions The combined anterior and posterior approach is suggested in the second stage of plating so that the posterior column fragments can be re-adjusted intraoperatively, if necessary. Following these procedures, satisfactory reduction and recovery of good ankle function can be anticipated.

Osteonecrosis of the femoral head (ONFH) is a recalcitrant ischemic disorder, which could be classified into two major categories: traumatic and nontraumatic. Regardless of different risk factors, it has been testified that ONFH results from primitive vascular problems, leading to temporary or permanent loss of blood supply to bone tissue. Histopathological and microarchitectural alterations ensues, which is a gradual evolutionary process involving bone marrow and osteocyte necrosis, progressive destruction of subchondral bone, unsuccessful reparative process, and eventual articular collapse and degenerative arthritis. Based on the imaging features of ONFH, different classification systems have been developed to evaluate the severity and prognosis of the disease, which is pivotal for implementation of treatment strategy, especially the joint-preserving surgery. However, patients classified with the same severity stage, especially in the peri-collapse stage, sometimes responded differently after similar joint-preserving surgery. The unusual phenomenon may be attributed to the limitation of the current imaging classification systems, which might underestimate the disease severity, especially when referring to the early stages. In this review, we briefly summarize the etiology and pathogenesis of ONFH. The imaging features and staging classification systems of ONFH are also described. More importantly, we focus on histopathological and microstructural alterations of the femoral head, and provide an overview of their essential contribution to ONFH progression. Given the observation of discordance between imaging characteristics and histopathological alterations, a substantial amount of research on the relationship between imaging and histopathological features is required to further modify and revise the current wide-accepted classification systems.

In this paper, a reconfigurable metal rim antenna with a small clearance and compact structure for 4G/5G smartphones is proposed. It consists of the system ground plane and a metal rim with two slits, in which a U-shaped slot of 1 mm (the smallest) clearance is realized between the system ground and metal rim. The theory of characteristic modes is applied to analyze the eigenmodes of the antenna so as to aid the optimum design. The characteristic modes (CMs) in the band of interest are studied, and an inductive coupling exciter is identified as the best since three CMs can therefore be generated in the lower frequency band (0.69-0.96 GHz), and an SP4T switch can be utilized to increase the bandwidth of the whole lower band. A prototype antenna of the optimized design was fabricated. A good agreement was obtained between the measured and simulated results. The 6-dB frequency bands are the lower band (0.69-0.96 GHz), the middle band (1.7- 2.7 GHz), and the higher 5G band (3.4- 3.6 GHz), respectively, and the total efficiencies are over 50% in all these frequency bands. They indicate that the antenna is a very good candidate for smartphone applications.

Photocathode plays an important role in generating high brightness and low emittance electron beam and K-Cs-Sb photocathode is preferred in SRF injectors for its high quantum efficiency, long lifetime, and low thermal emittance. To predict the QE change of K-Cs-Sb at cryogenic temperature more correctly, we have modified the QE formula of Spicer’s photoemission model considering the temperature dependence of work function and mean free path of photocathode material, which is obtained by fitting experimental data. The calculated QE drop of about 90.1% at 36.4 K fits well with the measured QE change in DC-SRF photoinjector at Peking University. This improved formula could provide a method to evaluate the QE performance of semiconductor photocathodes at cryogenic temperature.