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The frequency and intensity of extreme weather events, including rapid temperature fluctuations, are increasing because of climate change. Long-term fertilization practices have been observed to alter microbial physiology and community structure, thereby affecting soil carbon sequestration. However, the effects of warming on the carbon sequestration potential of soil microbes adapted to long-term fertilization remain poorly understood. In this study, we utilized 18O isotope labeling to assess microbial carbon use efficiency (CUE) and employed stable isotope probing (SIP) with 18O-H2O to identify growing taxa in response to temperature changes (5–35 °C). Organic amendment with manure or straw residue significantly increased microbial CUE by 86–181 % compared to unfertilized soils. The microorganisms inhabiting organic amended soils displayed greater resistance of microbial CUE to high temperatures (25–35 °C) compared to those inhabiting soils fertilized only with minerals. Microbial growth patterns determined by the classification of taxa into incorporators or non-incorporators based on 18O incorporation into DNA exhibited limited phylogenetic conservation in response to temperature changes. Microbial clusters were identified by grouping taxa with similar growth patterns across different temperatures. Organic amendments enriched microbial clusters associated with increased CUE, whereas clusters in unfertilized or mineral-only fertilized soils were linked to decreased CUE. Specifically, shifts in the composition of growing bacteria were correlated with enhanced microbial CUE, whereas modifications in the composition of growing fungi were associated with diminished CUE. Notably, the responses of microbial CUE to temperature fluctuations were primarily driven by changes in the bacterial composition. Overall, our findings demonstrate that organic amendments enhance soil microbial CUE and promote the enrichment of specific microbial clusters that are better equipped to cope with temperature changes. This study establishes a theoretical foundation for manipulating soil microbes to enhance carbon sequestration under global climate scenarios.

Abstract Due to its decade‐long progression, colorectal cancer (CRC) is most suitable for population screening to achieve a significant reduction in its incidence and mortality. DNA methylation has emerged as a potential marker for the early detection of CRC. However, the current mainstream methylation detection method represented by bisulfite conversion has issues such as tedious operation, DNA damage, and unsatisfactory sensitivity. Herein, a new high‐performance CRC screening tool based on the promising specific terminal‐mediated polymerase chain reaction (STEM‐PCR) strategy is developed. CRC‐related methylation‐specific candidate CpG sites are first prescreened through The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases using self‐developed bioinformatics. Next, 9 homebrew colorectal cancer DNA methylated STEM‒PCR assays (ColoC‐mSTEM) with high sensitivity (0.1%) and high specificity are established to identify candidate sites. The clinical diagnostic performance of these selected methylation sites is confirmed and validated by a case‐control study. The optimized diagnostic model has an overall sensitivity of 94.8% and a specificity of 95.0% for detecting early‐stage CRC. Taken together, ColoC‐mSTEM, based on a single methylation‐specific site, is a promising diagnostic approach for the early detection of CRC which is perfectly suitable for the screening needs of CRC in primary healthcare institutions.

Abstract Background Plasma cell-free DNA (cfDNA) fragmentomics has demonstrated significant differentiation power between cancer patients and healthy individuals, but little is known in pancreatic and biliary tract cancers. The aim of this study is to characterize the cfDNA fragmentomics in biliopancreatic cancers and develop an accurate method for cancer detection. Methods One hundred forty-seven patients with biliopancreatic cancers and 71 non-cancer volunteers were enrolled, including 55 patients with cholangiocarcinoma, 30 with gallbladder cancer, and 62 with pancreatic cancer. Low-coverage whole-genome sequencing (median coverage: 2.9 ×) was performed on plasma cfDNA. Three cfDNA fragmentomic features, including fragment size, end motif and nucleosome footprint, were subjected to construct a stacked machine learning model for cancer detection. Integration of carbohydrate antigen 19–9 (CA19-9) was explored to improve model performance. Results The stacked model presented robust performance for cancer detection (area under curve (AUC) of 0.978 in the training cohort, and AUC of 0.941 in the validation cohort), and remained consistent even when using extremely low-coverage sequencing depth of 0.5 × (AUC: 0.905). Besides, our method could also help differentiate biliopancreatic cancer subtypes. By integrating the stacked model and CA19-9 to generate the final detection model, a high accuracy in distinguishing biliopancreatic cancers from non-cancer samples with an AUC of 0.995 was achieved. Conclusions Our model demonstrated ultrasensitivity of plasma cfDNA fragementomics in detecting biliopancreatic cancers, fulfilling the unmet accuracy of widely-used serum biomarker CA19-9, and provided an affordable way for accurate noninvasive biliopancreatic cancer screening in clinical practice.

Abstract Cinnamomum chago is a tree species endemic to Yunnan province, China, with potential economic value, phylogenetic importance, and conservation priority. We assembled the genome of C. chago using multiple sequencing technologies, resulting in a high-quality, chromosomal-level genome with annotation information. The assembled genome size is approximately 1.06 Gb, with a contig N50 length of 92.10 Mb. About 99.92% of the assembled sequences could be anchored to 12 pseudo-chromosomes, with only one gap, and 63.73% of the assembled genome consists of repeat sequences. In total, 30,497 genes were recognized according to annotation, including 28,681 protein-coding genes. This high-quality chromosome-level assembly and annotation of C. chago will assist us in the conservation and utilization of this valuable resource, while also providing crucial data for studying the evolutionary relationships within the Cinnamomum genus, offering opportunities for further research and exploration of its diverse applications.

IntroductionDrought stress usually inhibits plant growth, which may increase the difficulty of greening slopes.MethodsIn this study, we systematically investigated the effects of arbuscular mycorrhizal (AM) fungi on the growth and drought tolerance of two plant species, Festuca elata and Cassia glauca, in a vegetation concrete environment by exogenously inoculating AM fungi and setting three drought levels: well water, moderate drought and severe drought. The results showed that plant growth was significantly inhibited under drought stress; however, AM fungi inoculation significantly promoted plant height, root length, and above- and belowground biomass in these two plant species.ResultsCompared with, those in the CK treatment, the greatest increases in the net photosynthesis rate, stomatal conductance and transpiration rate in the AM treatment group were 36.72%, 210.08%, and 66.41%, respectively. Moreover, inoculation with AM fungi increased plant superoxide dismutase and catalase activities by 4.70–150.73% and 9.10–95.70%, respectively, and reduced leaf malondialdehyde content by 2.79–55.01%, which alleviated the damage caused by oxidative stress. These effects alleviated the damage caused by oxidative stress and increased the content of soluble sugars and soluble proteins in plant leaves by 1.52–65.44% and 4.67–97.54%, respectively, which further increased the drought adaptability of plants. However, inoculation with AM fungi had different effects on different plants.ConclusionIn summary, this study demonstrated that the inoculation of AM fungi in vegetation concrete environments can significantly increase plant growth and drought tolerance. The plants that formed a symbiotic structure with AM fungi had a larger root uptake area, greater water uptake capacity, and greater photosynthesis and gas exchange efficiency. In addition, AM fungi inoculation further increased the drought adaptability of the plants by increasing their antioxidant enzyme activity and regulating their metabolite content. These findings are highly important for promoting plant growth and increasing drought tolerance under drought conditions, especially for potential practical applications in areas such as slope protection, and provide useful references for future ecological engineering and sustainable development.

Abstract Objective To investigate the prognostic prediction of a new indicator, combined by tumor grade and Ki-67, in patients with resected pancreatic ductal adenocarcinoma (PDAC). Methods Data were retrospectively collected from consecutive patients who underwent primary resection of pancreas from December 2012 to December 2017. Tumor grade and Ki-67 were reviewed from routine pathological reports. G-Ki67 was classified as three categories as I (G1/2 and Ki-67

Harvesting and storing energy is a key problem in some applications. Elastic energy storage technology has the advantages of wide-sources, simple structural principle, renewability, high effectiveness and environmental-friendliness. This paper elaborates the operational principles and technical properties and summarizes the applicability of elastic energy storage technology with spiral springs. Elastic energy storage using spiral spring can realize the balance between energy supply and demand in some applications. Continuous input–spontaneous output working style can provide simple energy sources for short-time energy supply, and provide strong moment impact and rapid start, or realize the energy conservation for reciprocating movement. Uniform output working style can realize energy output with uniform speed for timekeeping and load-driving. Random input working style can harvest and store random mechanical energy or convert small torque into a large moment to drive external loads. Finally, this paper proposes new researches and developments of elastic energy storage technology on new materials and structures, mechanical properties and structural dynamics analyses, design and control for new functions.

With the high intensification of poultry breeding, a series of diseases caused by pathogenic bacteria threaten the health of poultry and human. Among them, poultry diseases induced by Escherichia coli cause significant economic loss every year. The aim of this study was to investigate the effects of dietary supplementation with Artemisia annua L. polysaccharide (AAP) on the growth performance and intestinal barrier function of broilers with Escherichia coli (E. coli) challenge. A total of 256 one-day-old chicks were randomly assigned to four treatment groups: control group (fed basal diet), AAP group (fed basal diet supplemented with AAP), E. coli group (fed basal diet and orally administered E. coli), AAP + E. coli group (fed basal diet supplemented with AAP and orally administered E. coli). Dietary AAP supplementation elevated the BW, ADG and ADFI in non-challenged broilers. AAP also increased the apparent metabolic rate of EE and Ca in E. coli-challenged broilers. Moreover, AAP not only enhanced the serum IgA content but also decreased the serum and jejunum content of IL-6, as well as the jejunum level of IL-1β in non-challenged broilers. AAP also down-regulates the mRNA level of inflammatory factors (IL-1β, IL-6, and TNF-α) by inhibiting the mRNA expression of TLR4 and MyD88 in intestinal NF-κB signaling pathway of E. coli-challenged broilers. Meanwhile, AAP up-regulates the activity and mRNA level CAT by down-regulating the mRNA level of Keap1 in intestinal Nrf2 signaling pathway of E. coli-challenged broilers, and decreased serum MDA concentration. AAP significantly elevated the mRNA level of CAT, SOD and Nrf2 in jejunal of non-challenged broilers. Interestingly, AAP can improve intestinal physical barrier by down-regulating serum ET content, increasing the jejunal villus height/crypt depth (VH/CD) and ZO-1 mRNA level in broilers challenged by E. coli. AAP also elevated the VH/CD and the mRNA level of Occludin, ZO-1, Mucin-2 in non-challenged broilers. Importantly, AAP reshaped the balance of jejunum microbiota in E. coli-challenged broilers by altering α diversity and community composition. In summary, AAP ameliorated the loss of growth performance in broilers challenged with E. coli, probably by regulating the intestinal permeability and mucosa morphology, immune function, antioxidant ability, and microbiota.

ABSTRACT Microbial carbon use efficiency (CUE) is a critical parameter that controls carbon storage in soil, but many uncertainties remain concerning adaptations of microbial communities to long-term fertilization that impact CUE. Based on H218O quantitative stable isotope probing coupled with metagenomic sequencing, we disentangled the roles of active microbial population dynamics and life strategies for CUE in soils after a long-term (35 years) mineral or organic fertilization. We found that the soils rich in organic matter supported high microbial CUE, indicating a more efficient microbial biomass formation and a greater carbon sequestration potential. Organic fertilizers supported active microbial communities characterized by high diversity and a relative increase in net growth rate, as well as an anabolic-biased carbon cycling, which likely explains the observed enhanced CUE. Overall, these results highlight the role of population dynamics and life strategies in understanding and predicting microbial CUE and sequestration in soil.IMPORTANCEMicrobial CUE is a major determinant of global soil organic carbon storage. Understanding the microbial processes underlying CUE can help to maintain soil sustainable productivity and mitigate climate change. Our findings indicated that active microbial communities, adapted to long-term organic fertilization, exhibited a relative increase in net growth rate and a preference for anabolic carbon cycling when compared to those subjected to chemical fertilization. These shifts in population dynamics and life strategies led the active microbes to allocate more carbon to biomass production rather than cellular respiration. Consequently, the more fertile soils may harbor a greater microbially mediated carbon sequestration potential. This finding is of great importance for manipulating microorganisms to increase soil C sequestration.

ABSTRACT The soil-root interface harbors complex fungal communities that play vital roles in the fitness of host plants. However, little is known about the assembly rules and potential functions of rhizospheric and endospheric mycobiota. A greenhouse experiment was conducted to explore the fungal communities inhabiting the rhizosphere and roots of 87 rice cultivars at the tillering stage via amplicon sequencing of the fungal internal transcribed spacer 1 region. The potential relationships between these communities and host plant functional traits were also investigated using Procrustes analysis, generalized additive model fitting, and correlation analysis. The fungal microbiota exhibited greater richness, higher diversity, and lower structural variability in the rhizosphere than in the root endosphere. Compared with the root endosphere, the rhizosphere supported a larger coabundance network, with greater connectivity and stronger cohesion. Null model-based analyses revealed that dispersal limitation was primarily responsible for rhizosphere fungal community assembly, while ecological drift was the dominant process in the root endosphere. The community composition of fungi in the rhizosphere was shown to be more related to plant functional traits, such as the root/whole plant biomass, root:shoot biomass ratio, root/shoot nitrogen (N) content, and root/shoot/whole plant N accumulation, than to that in the root endosphere. Overall, at the early stage of rice growth, diverse and complex rhizospheric fungal communities are shaped by stochastic-based processes and exhibit stronger associations with plant functional traits.IMPORTANCEThe assembly processes and functions of root-associated mycobiota are among the most fascinating yet elusive topics in microbial ecology. Our results revealed that stochastic forces (dispersal limitation or ecological drift) act on fungal community assembly in both the rice rhizosphere and root endosphere at the early stage of plant growth. In addition, high covariations between the rhizosphere fungal community compositions and plant functional trait profiles were clearly demonstrated in the present study. This work provides empirical evidence of the root-associated fungal assembly principles and ecological relationships of plant functional traits with rhizospheric and root endospheric mycobiota, thereby potentially providing novel perspectives for enhancing plant performance.

Objective:. To evaluate the survival outcomes of patients who underwent conversion surgery for metastatic pancreatic ductal adenocarcinoma (mPDAC) after neoadjuvant therapy (NAT) and to identify potential candidates that may benefit from this treatment strategy. Background:. The role and eligibility population of conversion surgery for mPDAC remains controversial in the era of NAT. Methods:. A consecutive cohort of patients diagnosed with mPDAC and treated with NAT followed by conversion surgery between 2019 and 2021 were confirmed from a prospective database maintained by the Department of Pancreatic Hepatobiliary Surgery of Changhai Hospital. In accordance with residual metastases and technical resectability after NAT, patients were classified as the complete pathological response of metastases (ypM0) resection group, residual metastases (ypM1) resection group, and exploration group. Median overall survival (mOS) was calculated using the Kaplan-Meier method, uni- and multivariable cox regression was performed to identify clinicopathological predictors of OS. Results:. A total of 244 patients with mPDAC were identified from the prospective database, with 19 (7.8%) patients who underwent ypM0 resection, 22 (9.0%) underwent ypM1 resection, and 23 (9.4%) underwent explorative laparotomy. The mOS was 32.6 months for ypM0 resected patients, 15.1 months for ypM1 resected patients, and 13.4 months for those who underwent explorative laparotomy (P < .001). Univariable and multivariable Cox regression analyses confirmed that ypM0 resection, normalization of preoperative CA19-9 levels, and continued adjuvant therapy were independent prognostic factors of conversion surgery for mPDAC after NAT. Subgroup analyses revealed that oligometastases and continued adjuvant therapy were associated with improved prognosis in the ypM1 resection group. Conclusion:. In patients with mPDAC who underwent NAT followed by conversion surgery, the complete pathological response of metastases, normalization of preoperative CA19-9 levels, and continued adjuvant therapy were independent risk factors for prognosis. Patients with residual oligometastases after treatment were expected to prolong survival through resection. These patients may benefit from conversion surgery and should be potential candidates for this treatment strategy.

Fluorescence flow cytometry is a powerful instrument to distinguish cells or particles labelled with high-specificity fluorophores. However, traditional flow cytometry is complex, bulky, and inconvenient for users to adjust fluorescence channels. In this paper, we present a modular fluorescence flow cytometry (M-FCM) system in which fluorescence channels can be flexibly arranged. Modules for particle focusing and fluorescence detection were developed. After hydrodynamical focusing, the cells were measured in the detection modules, which were integrated with in situ illumination and fluorescence detection. The signal-to-noise ratio of the detection reached to 33.2 dB. The crosstalk among the fluorescence channels was eliminated. The M-FCM system was applied to evaluate cell viability in drug screening, agreeing well with the commercial cytometry. The modular cytometry presents several outstanding features: flexibility in setting fluorescence channels, cost efficiency, compact construction, ease of operation, and the potential to upgrade for multifunctional measurements. The modular cytometry provides a multifunctional platform for various biophysical measurements, e.g., electrical impedance and refractive-index detection. The proposed work paves an innovative avenue for the multivariate analysis of cellular characteristics.

Accurately understanding the critical threshold of leaf magnesium (Mg) concentration is crucial for rapid diagnosis of crop Mg status; however, little information is available on critical Mg concentration for different physiological processes in dicots and monocots. Here, we investigated the sensitivity of biomass, chlorophyll (Chl) at different leaf positions/ages, leaf area (LA), and photosynthesis (Pn) to Mg deficiency between rice (Oryza sativa L.) and cucumber (Cucumis sativus L.). Plants were grown hydroponically under twelve Mg concentration gradients. Results showed reducing the external Mg supply to a certain level resulted in significant decline in biomass, Chl, LA, and Pn in both plants. A leaf Mg threshold of 0.97 mg g−1 DM (dry matter) for total biomass was found in rice, which was not identified in cucumber. Critical Mg thresholds for Chl a, b, and carotenoids (Car) showed a decreasing trend with leaf age, suggesting Chl in upper young leaves are more sensitive to Mg deficiency; however, visible Mg-deficiency symptoms were predominantly in mid-aged leaves with a higher rate of Mg remobilization, especially in cucumber. Leaf critical Mg concentrations for Chl a+b, Pn, and LA were 1.22, 1.05, and 1.00 mg g−1 DM in rice, respectively, which were lower than those of cucumber, 4.23, 4.09, and 3.55 mg g−1 DM, implying that cucumber was more susceptible to low Mg stress; Chl a+b was the most sensitive indicator of Mg deficiency. Overall, Chl a+b of upper young mature leaves can be used as an early diagnostic index of Mg nutrition in crops, especially Mg-insensitive crops.

Abstract Objective To improve prediction, the AJCC staging system was revised to be consistent with upfront surgery (UFS) and neoadjuvant therapy (NAT) for PDAC. Background The AJCC staging system was designed for patients who have had UFS for PDAC, and it has limited predictive power for patients receiving NAT. Methods We examined 146 PDAC patients who had resection after NAT and 1771 who had UFS at Changhai Hospital between 2012 and 2021. The clinicopathological factors were identified using Cox proportional regression analysis, and the Neoadjuvant Therapy Compatible Prognostic (NATCP) staging was developed based on these variables. Validation was carried out in the prospective NAT cohort and the SEER database. The staging approach was compared to the AJCC staging system regarding predictive accuracy. Results The NAT cohort’s multivariate analysis showed that tumor differentiation and the number of positive lymph nodes independently predicted OS. The NATCP staging simplified the AJCC stages, added tumor differentiation, and restaged the disease based on the Kaplan-Meier curve survival differences. The median OS for NATCP stages IA, IB, II, and III was 31.7 months, 25.0 months, and 15.8 months in the NAT cohort and 30.1 months, 22.8 months, 18.3 months, and 14.1 months in the UFS cohort. Compared to the AJCC staging method, the NATCP staging system performed better and was verified in the validation cohort. Conclusions Regardless of the use of NAT, NATCP staging demonstrated greater predictive abilities than the existing AJCC staging approach for resected PDAC and may facilitate clinical decision-making based on accurate prediction of patients’ OS.

Abstract To meet the demands for the data combination with multiple space geodetic techniques at the observation level, we developed a new software platform with high extensibility and computation efficiency, named space Geodetic SpatioTemporal data Analysis and Research software (GSTAR). Most of the modules in the GSTAR are coded in C++ with object-oriented programming. The layered modular theory is adopted for the design of the software, and the antenna-based data architecture is proposed for users to construct personalized geodetic application scenarios easily. The initial performance of the GSTAR software is evaluated by processing the Global Navigation Satellite System (GNSS) data collected from 315 globally distributed stations over two and a half years. The accuracy of GNSS-based geodetic products is evaluated by comparing them with those released by International GNSS Service (IGS) Analysis Centers (AC). Taking the products released by European Space Agency (ESA) as reference, the Three-Dimension (3D) Root-Mean-Squares (RMS) of the orbit differences are 2.7/6.7/3.3/7.7/21.0 cm and the STandard Deviations (STD) of the clock differences are 19/48/16/32/25 ps for Global Positioning System (GPS), GLObal NAvigation Satellite System (GLONASS), Galileo navigation satellite system (Galileo), BeiDou Navigation Satellite System (BDS), Medium Earth Orbit (MEO), and BDS Inclined Geo-Synchronous Orbit (IGSO) satellites, respectively. The mean values of the $$X$$ X and $$Y$$ Y components of the polar coordinate and the Length of Day (LOD) with respect to the International Earth Rotation and Reference Systems Service (IERS) 14 C04 products are -17.6 microarc-second (µas), 9.2 µas, and 14.0 µs/d. Compared to the IGS daily solution, the RMSs of the site position differences in the north/east/up direction are 1.6/1.5/3.9, 3.8/2.4/7.6, 2.5/2.4/7.9 and 2.7/2.3/7.4 mm for GPS-only, GLONASS-only, Galileo-only, and BDS-only solution, respectively. The RMSs of the differences of the tropospheric Zenith Path Delay (ZPD), the north gradients, and the east gradients are 5.8, 0.9, and 0.9 mm with respect to the IGS products. The $$X$$ X and $$Y$$ Y components of the geocenter motion estimated from GPS-only, Galileo-only, and BDS-only observations well agree with IGS products, while the $$Z$$ Z component values are much nosier where anomalous harmonics in GNSS draconitic year can be found. The accuracies of the above products calculated by the GSTAR are comparable with those from different IGS ACs. Compared to the precise scientific orbit products, the 3D RMS of the orbit differences for the two Gravity Recovery and Climate Experiment Follow-on (GRACE-FO) satellites is below 1.5 cm by conducting Precise Point Positioning with Ambiguity Resolution (PPP-AR). In addition, a series of rapid data processing algorithms are developed, and the operation speed of the GSTAR software is 5.6 times faster than that of the Positioning and Navigation Data Analyst (PANDA) software for the quad-system precise orbit determination procedure.

This paper proposes a finite time containment control scheme to achieve distributed control of a weak grid which is integrated with photovoltaic (PV), wind turbine (WT) and battery energy storage system (BESS). Taking advantage of the containment control in multi-dimensional control, we proposed a multi-objective control scheme of the WT-PV-BESS system in a weak grid, wherein four control objectives are specified, namely, bus voltage regulation, grid frequency control, peak load shaving and economic benefits optimization for the system operator. Firstly, the sizing approach of BESSs to fulfill the operation mission requirements is proposed; meanwhile, the general coordination strategy for the PV, WT and BESS to achieve the demand–supply balance is proposed. Subsequently, the predefined four control objectives are modeled and transferred into the long/short time frame operational constraints of the BESSs. Afterwards, the finite time containment control algorithm is proposed to force the BESSs into achieving containment status within prescribed time. Simulation case studies are conducted on a modified IEEE 9-bus system to show the effectiveness and performance of the proposed scheme.

Summary: Here, we present a protocol for exploring the effects of PPP1R15A inhibitor, Sephin1, on antitumor immunity of B16F1 subcutaneous tumor in mice. We describe steps for constructing single-cell transcriptome and TCR libraries, sequencing, and using sequencing data for the integration of expression and TCR data. We then detail procedures for gene differentiation, regulon and cell-cell communication analysis, and validation of single-cell analysis results.For complete details on the use and execution of this protocol, please refer to Wang et al.1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Abstract Background B-cell lymphoma 6 (BCL6) is a transcription repressor that plays a tumor suppressor or promoting role in various tumors. However, its function and molecular mechanism in gastric cancer (GC) remain unclear. Ferroptosis, a novel programmed cell death, is closely related to tumor development. In this research, we aimed to explore the role and mechanism of BCL6 in malignant progression and ferroptosis of gastric cancer. Methods Firstly, BCL6 was identified as an important biomarker that attenuated the proliferation and metastasis of GC through tumor microarrays and confirmed in GC cell lines. RNA sequence was performed to explore the downstream genes of BCL6. The underlying mechanisms were further investigated by ChIP, dual luciferase reporter assays and rescue experiments. Cell death, lipid peroxidation, MDA and Fe2+ level were detected to determine the effect of BCL6 on ferroptosis and the mechanism was revealed. CHX, MG132 treatment and rescue experiments were used to explore the upstream regulatory mechanism of BCL6. Results Here we showed that BCL6 expression was significantly decreased in GC tissues, and patients with low BCL6 expression showed more malignant clinical features and poor prognosis. The upregulation of BCL6 may significantly inhibited the proliferation and metastasis of GC cells in vitro and in vivo. In addition, we found that BCL6 directly binds and transcriptionally represses Wnt receptor Frizzled 7 (FZD7) to inhibit the proliferation, metastasis of GC cells. We also found that BCL6 promoted lipid peroxidation, MDA and Fe2+ level to facilitate ferroptosis of GC cells by FZD7/β-catenin/TP63/GPX4 pathway. Furthermore, the expression and function of BCL6 in GC were regulated by the ring finger protein 180 (RNF180)/ras homolog gene family member C (RhoC) pathway, which had been elucidated to be involved in significantly mediating the proliferation and metastasis of GC cells. Conclusions In summary, BCL6 should be considered a potential intermediate tumor suppressor to inhibit the malignant progression and induce ferroptosis, which might be a promising molecular biomarker for further mechanistic investigation of GC.

Summary: Objective: Positive resection margin indicates worse prognosis. The present study identified the independent risk factors of R1 resection in pancreaticoduodenectomy (PD) and distal pancreatosplenectomy (DP) for patients with pancreatic ductal adenocarcinoma (PDAC). Method: Consecutive patients who were operated from 1st December 2017 to 30th December 2018 were analyzed retrospectively. A standardized pathological examination with digital whole-mount slide images (DWMSIs) was utilized for evaluation of resection margin status. R1 was defined as microscopic tumor infiltration within 1 mm to the resection margin. The potential risk factors of R1 resection for PD and DP were analyzed separately by univariate and multivariate logistic regression analyses. Results: For the 192 patients who underwent PD, and the 87 patients who underwent DP, the R1 resection rates were 31.8% and 35.6%, respectively. Univariate analysis on risk factors of R1 resection for PD were tumor location, lymphovascular invasion, N staging, and TNM staging; while those for DP were T staging and TNM staging. Multivariate logistic regression analysis showed the location of tumor in the neck and uncinate process, and N1/2 staging were independent risk factors of R1 resection for PD; while those for DP were T3 staging. Conclusions: The clarification of the risk factors of R1 resection might clearly make surgeons take reasonable decisions on surgical strategies for different surgical procedures in patients with PDAC, so as to obtain the first attempt of R0 resection.

Artemisia annua L. is a natural herb with a variety of bioactive substances, which can play a variety of biological functions such as anti-inflammatory, antioxidant, antibacterial and antiviral, and can be used as a potential feed additive. The purpose of this study was to investigate the effects of different doses of Artemisia annua L. water extract (AAWE) on growth performance and intestinal related indicators in broilers. A total of 200 one-day-old Arbor Acre broilers were selected and randomly divided into five treatment groups, with five replicates in each group and eight birds per replicate. The control group was fed a basal diet, whereas the other groups were fed a basal diet supplemented with 0.5, 1.0, 1.5, or 2.0 g/kg AAWE. On d 21, with the increase in AAWE dose, final body weight and feed efficiency showed a quadratic increase effect, whereas feed intake showed a linear reduction effect; however, the apparent metabolic rate of dry matter, crude protein, and ether extract increased quadratically on d 42. In addition, the activity of duodenal chymotrypsin and trypsin, and of jejunal lipase quadratically increased, whereas the intestine crypt depth linearly decreased on d 42. The number of total anaerobic bacteria increased quadratically, whereas the number of Escherichia coli decreased quadratically. The number of Lactobacillus increased linearly, whereas H2S emission linearly decreased on d 21; moreover, NH3 emission (24 h) quadratically decreased on d 42. In conclusion, AAWE promoted the growth performance and intestinal related indicators of broilers.

Microbial ecological strategies are expected to be phylogenetically conserved, but plasticity and acclimation to environmental change may complicate the picture. Here, the authors show that shifts in soil bacterial ecological strategies deviate from phylogenetic-based predictions after acclimation to long-term warming and CO2 enrichment.

This research aims to study the effects of rare earth-chitosan chelates (RECC) on growth performance, immunity and antioxidant function in broilers. A total of 192 one-day-old mixed-sex Arbour Acres (AA) broilers were allotted into 4 treatment groups with 6 replicates per treatment and 8 broilers per pen. Broilers were fed the basal diet supplemented with, respectively, 0 (control group), 150, 200 and 250 mg/kg RECC for 42 d. The results showed that dietary RECC improved average daily gain and decreased feed/gain (p

In this study, the effects of Artemisia argyi polysaccharide (AAP) on broilers’ immune and antioxidative functions and the underlying regulatory mechanism were investigated. In this experiment, 288 one-day-old Arbor Acres plus broilers were randomly allocated into 6 treatments with 6 replicates where each treatment group contained 6 replicate groups and there were 8 broilers in each replicate group. The control group was fed the basal diet, and the experimental groups were fed the basal diet supplemented with 250, 500, 750 or 1000 mg/kg AAP in comparison with 50 mg/kg chlortetracycline for 42 d. The result demonstrated that the best amount of AAP addition was 1000 mg/kg for growth. It could promote the contents of cytokines, immunoglobulin as well as the activity of the antioxidant enzyme (GPx), and reduce the malondialdehyde (MDA) content in the serum of broilers on 42 d. The same dose of AAP could regulate the immune and antioxidant functions in the liver of broilers, and activate the TLR/NF-κB signal pathway in broilers. The growth-promoting effect of AAP was comparable to that of chlorotetracycline.

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) has the lowest overall survival rate primarily due to the late onset of symptoms and rapid progression. Reliable and accurate tests for early detection are lacking. We aimed to develop a noninvasive test for early PDAC detection by capturing the circulating tumour DNA (ctDNA) methylation signature in blood. Methods Genome-wide methylation profiles were generated from PDAC and nonmalignant tissues and plasma. Methylation haplotype blocks (MHBs) were examined to discover de novo PDAC markers. They were combined with multiple cancer markers and screened for PDAC classification accuracy. The most accurate markers were used to develop PDACatch, a targeted methylation sequencing assay. PDACatch was applied to additional PDAC and healthy plasma cohorts to train, validate and independently test a PDAC-discriminating classifier. Finally, the classifier was compared and integrated with carbohydrate antigen 19-9 (CA19-9) to evaluate and maximize its accuracy and utility. Results In total, 90 tissues and 546 plasma samples were collected from 232 PDAC patients, 25 chronic pancreatitis (CP) patients and 323 healthy controls. Among 223 PDAC cases with known stage information, 43/119/38/23 cases were of Stage I/II/III/IV. A total of 171 de novo PDAC-specific markers and 595 multicancer markers were screened for PDAC classification accuracy. The top 185 markers were included in PDACatch, from which a 56-marker classifier for PDAC plasma was trained, validated and independently tested. It achieved an area under the curve (AUC) of 0.91 in both the validation (31 PDAC, 26 healthy; sensitivity = 84%, specificity = 89%) and independent tests (74 PDAC, 65 healthy; sensitivity = 82%, specificity = 88%). Importantly, the PDACatch classifier detected CA19-9-negative PDAC plasma at sensitivities of 75 and 100% during the validation and independent tests, respectively. It was more sensitive than CA19-9 in detecting Stage I (sensitivity = 80 and 68%, respectively) and early-stage (Stage I-IIa) PDAC (sensitivity = 76 and 70%, respectively). A combinatorial classifier integrating PDACatch and CA19-9 outperformed (AUC=0.94) either PDACatch (0.91) or CA19-9 (0.89) alone (p < 0.001). Conclusions The PDACatch assay demonstrated high sensitivity for early PDAC plasma, providing potential utility for noninvasive detection of early PDAC and indicating the effectiveness of methylation haplotype analyses in discovering robust cancer markers. Graphic Abstract

Introduction: Microbial generalists and specialists are thought to have distinct impacts on community dynamics, while there have been limited efforts to estimate their contribution to microbial diversity. Objectives: We aimed to resolve this research gap in microbial ecology to strengthen our understanding of the biogeography of microbial diversity, with implications for global-scale biodiversity mapping. Methods: Herein, we identified the ecological characteristics of microbial generalists and specialists across over 3,000 farmland soil samples from eleven countries that encompassed seven climate types. Results: Considering the distinct distributions of generalists and specialists in degree of connexions, betweenness and as key species in network topology, both generalists and specialists contributed to species interactions, though through different modalities. A stronger signature of deterministic processes in specialists indicated their lower tolerance to environment fluctuations. Generalists, in contrast, were more characterized by stochastic processes with higher diversification and transition rates that suggested more important roles in maintaining community stability when exposed to environmental disturbances. The relationship between latitude and diversity combining with distance-decay effects showed that generalists dampened microbial biogeographical patterns, with contrasting impacts by specialists. Conclusion: By demonstrating the ecological characteristics of microbial generalists and specialists, this study deepens our understanding of microbial diversity and highlights the need to impart systematic distinctions among different categories of species when modelling and predicting the fate of ecosystems in the face of global climate change, rather than assuming that species are functionally equivalent.

IntroductionIn achieving food security and sustainable agricultural development, improving and maintaining soil health is considered as a key driving factor. The improvement based on different forms of nitrogen fertilization has aroused great public interest in improving and restoring monocropping obstacles for specific soil problems.MethodsFor this, a short-term cucumber cropping field experiment was conducted in the subtropical region of China under four fertilization treatments: ammonium (AN), nitrate (NN), ammonium with dicyandiamide (AN+DCD), nitrate with dicyandiamide (NN+DCD). In this study, we measured the effects of nitrogen forms addition on plant productivity and soil health in a monocropping system over seven seasons. ResultsTo systematically evaluate soil health, a wide range of soil environmental factors were measured and incorporated into the soil health index (SHI) by entropy method. Compared with ammonium treatment (SHIAN = 0.059, SHIAN+DCD = 0.081), the positive effect of nitrate was mainly reflected in improving soil health (SHINN = 0.097, SHINN+DCD = 0.094), which was positively correlated with the increase in plant productivity of cucumber after seven seasons of monocropping. The most critical factor affecting SHI is soil ammonium nitrogen content, which was negatively correlated with plant productivity. DiscussionNitrate promotes soil health and plant productivity by optimizing soil environmental factors. The study thus emphasized the necessity of nitrate input for the sustenance of soil-crop ecosystems, with the consequent possibility of application of the results in planning monoculture obstacle prevention and management measures.

Background: Neoadjuvant therapy has been the standard care for borderline resectable or locally advanced pancreatic ductal carcinoma (BR/LA PDAC). The textbook outcome (TO) for curative resection after neoadjuvant therapy (NAT) remains understudied. Method: Patients underwent curative resection for PDAC between 2019 and 2020 were confirmed from the multidisciplinary team (MDT) database prospectively maintained by the Department of Pancreatic Hepatobiliary Surgery of Changhai hospital. TO of patients received NAT was compared to those received upfront surgery (UFS), and multivariate analysis of clinicopathological parameters was performed to explore predictors for TO. Results: Of 435 patients, 329(76%) patients received UFS whereas 106(24%) patients received NAT. The TO was 82.1% for the NAT cohort, 77.8% for pancreaticoduodenectomy (PD) and 86.8% for distal pancreatectomy (DP). In the UFS cohort, the TO was 73.3% overall, 70.6% for PD and 77.3% for DP. Patients in the NAT cohort had longer time of operation, more intra-operative blood loss and more vascular resection. However, TO of the NAT cohort were not statistically different compared to that in the UFS cohort (p ​= ​0.27 for PD and p ​= ​0.20 for DP). On multivariable analysis, only diabetes-free was predictive for a better TO rate after PD in the UFS cohort(p ​= ​0.003). There were no factors associated with TO after DP in the UFS cohort, nor after PD or DP in the NAT cohort. Conclusion: As a composite indicator of desired surgical outcome, TO for curative resection after neoadjuvant therapy is similar to that in upfront surgery. All patients with stable or regressed tumors after NAT should be candidates for curative resection in an MDT setting.

To establish an analytical method for the determination of total polyphenols and catechins and rutin in tea by electrochemical sensors. The nanogold/carboxylated carbon nanotube-modified polyphenol electrochemical sensors were prepared by modifying carboxylated carbon nanotubes (SWNTs-COOH) on glassy carbon electrodes by drop coating method and then depositing nanogold (AuNPs) on their surfaces by electrodeposition, and the morphological observations and performance tests were performed by scanning electron microscopy (SEM) and electrochemical impedance spectroscopy (EIS). Electrochemical characterization of gallic acid (GA), epigallocatechin gallate (EGCG), rutin and other standard substances in tea leaves as well as mixed systems simulating tea leaves was carried out with the constructed polyphenol sensors. SEM observation confirmed that the nanogold/carboxylated multi-carbon nanotubes were successfully modified on the surface of the glassy carbon electrode, and the impedance of the modified electrode was 78.2% lower than that of the bare electrode, and the peak current response value of the electrode was 253.5% of that of the bare electrode, which significantly improved the sensitivity of the modified electrode. The redox characterization of GA, EGCG and other standards revealed that the Peak I peak potentials of GA, EGCG, quercetin and epicatechin were all 0.50±0.05 V, and the corresponding peak currents Ip were linearly correlated with the concentration of substance c, which can be used as a common landmark oxidation peak for total phenol detection. While EGCG besides Peak I also has an oxidation peak Peak III with a peak potential of 0.42±0.05 V, and the rutin oxidation peak Peak I with a potential of 0.56 V. These two distinct peaks potentials can be quantified separately for EGCG and rutin along with the determination of total phenols. In the tea simulation system containing mixed polyphenols, the peak current of the sensor and the concentration of total polyphenols showed a good linear relationship in the range of 5.0×10-6~6.0×10-5 mol/L, and the correlation coefficient R2 was 0.982. The detection limit was 3.1×10-7 mol/L (S/N=3), and the recovery rate of standard addition was 96.60%~101.17%. This method is characterized with simple operation, short detection time, and no complicated sample pretreatment, which could be a new method for rapid detection of polyphenols.

Magnesium is an essential macronutrient for plant photosynthesis, and in response to Mg deficiency, dicots appear more sensitive than monocots. Under Mg deficiency, we investigated the causes of differing photosynthetic sensitivities in a dicot and a monocot species. Rice (Oryza sativa L.) and cucumber (Cucumis sativus L.) were grown in hydroponic culture to explore their physiological responses to Mg deficiency stress. Both Mg-deficient rice and cucumber plants exhibited lower biomass, leaf area, Mg concentration, and chlorophyll content (Chl) compared with Mg-sufficient plants. However, a more marked decline in Chl and carotenoid content (Car) occurred in cucumber. A lower CO2 concentration in chloroplasts (Cc) was accompanied by a decrease in the maximum rate of electron transport (Jmax) and the maximum rate of ribulose 1,5-bisphosphate carboxylation (Vcmax), restricting CO2 utilization in Mg-deficient plants. Rice and cucumber photorespiration rate (Pr) increased under Mg deficiency. Additionally, for cucumber, Car and non-photochemical quenching (NPQ) were reduced under lower Mg supply. Meanwhile, cucumber Mg deficiency significantly increased the fraction of absorbed light energy dissipated by an additional quenching mechanism (Φf,D). Under Mg deficiency, suppressed photosynthesis was attributed to comprehensive restrictions of mesophyll conductance (gm), Jmax, and Vcmax. Cucumber was more sensitive to Mg deficiency than rice due to lower NPQ, higher rates of electron transport to alternative pathways, and subsequently, photooxidation damage.

The chromatin accessibility landscape and gene regulatory network of pancreatic cancer has not been fully characterised. Here, the authors perform multi-omics analysis of 84 pancreatic cancer organoid lines and reveal gene regulatory networks and distinct molecular subtypes.

Abstract Purpose To develop and validate a radiomics nomogram for the preoperative prediction of lymph node (LN) metastasis in pancreatic ductal adenocarcinoma (PDAC). Materials and methods In this retrospective study, 225 patients with surgically resected, pathologically confirmed PDAC underwent multislice computed tomography (MSCT) between January 2014 and January 2017. Radiomics features were extracted from arterial CT scans. The least absolute shrinkage and selection operator method was used to select the features. Multivariable logistic regression analysis was used to develop the predictive model, and a radiomics nomogram was built and internally validated in 45 consecutive patients with PDAC between February 2017 and December 2017. The performance of the nomogram was assessed in the training and validation cohort. Finally, the clinical usefulness of the nomogram was estimated using decision curve analysis (DCA). Results The radiomics signature, which consisted of 13 selected features of the arterial phase, was significantly associated with LN status (p

IntroductionRNA editing, a wide-acknowledged post-transcriptional mechanism, has been reported to be involved in the occurrence and development of cancer, especially the abnormal alteration of adenosine to inosine. However, fewer studies focus on pancreaticcancer. Therefore, we aimed to explore the possible linkages between altered RNA editing events and the development of PDAC.MethodWe characterized the global A-to-I RNA editing spectrum from RNA and matched whole-genome sequencing data of 41 primary PDAC and adjacent normal tissues. The following analyses were performed: different editing level and RNA expression analysis,pathway analysis, motif analysis, RNA secondary structure analysis, alternative splicing events analysis, and survival analysis.The RNA editing of single-cell RNA public sequencing data was also characterized.ResultA large number of adaptive RNA editing events with significant differences in editing levels were identified, which are mainly regulated by ADAR1. Moreover, RNA editing in tumors has a higher editing level and more abundant editing sites in general. 140genes were screened out since they were identified with significantly different RNA editing events and were significantly different in expression level between tumor and matched normal samples. Further analysis showed a preference that in the tumor-specific group, they are mainly enriched in cancer-related signal pathways, while in the normal tissue-specific group, they are mainly enriched in pancreatic secretion. At the same time, we also found positively selected differentially edited sites in a series of cancer immune genes, including EGF, IGF1R, and PIK3CD. RNA editing might participate in pathogenisis of PDAC through regulating the alternative splicing and RNA secondary structure of important genesto further regulate gene expression and protein synthesis, including RAB27B and CERS4. Furthermore, single cell sequencing results showed that type2 ductal cells contributed the most to RNA editing events in tumors.ConclusionRNA editing is an epigenetic mechanism involved in the occurrence and development of pancreatic cancer, which has the potential to diagnose of PDAC and is closely related to the prognosis.

Enhancing photosynthetic capacity is widely accepted as critical to advancing crop yield. Therefore, identifying photosynthetic parameters positively related to biomass accumulation in elite cultivars is the major focus of current rice research. In this work, we assessed leaf photosynthetic performance, canopy photosynthesis, and yield attributes of super hybrid rice cultivars Y-liangyou 3218 (YLY3218) and Y-liangyou 5867 (YLY5867) at tillering stage and flowering stage, using inbred super rice cultivars Zhendao11(ZD11) and Nanjing 9108 (NJ9108) as control. A diurnal canopy photosynthesis model was applied to estimate the influence of key environmental factors, canopy attributes, and canopy nitrogen status on daily aboveground biomass increment (AMDAY). Results showed that primarily the light-saturated photosynthetic rate at tillering stage contributed to the advancing yield and biomass of super hybrid rice in comparison to inbred super rice, and the light-saturated photosynthetic rate between them was similar at flowering stage. At tillering stage, the higher CO2 diffusion capacity, together with higher biochemical capacity (i.e., maximum carboxylation rate of Rubisco, maximum electron transport rate (Jmax), and triose phosphate utilization rate) favored leaf photosynthesis of super hybrid rice. Similarly, AMDAY in super hybrid rice was higher than inbred super rice at tillering stage, and comparable at flowering stage partially due to increased canopy nitrogen concentration (SLNave) of inbred super rice. At tillering stage, model simulation revealed that replacement of Jmax and gm in inbred super rice by super hybrid rice always had a positive effect on AMDAY, and the averaged AMDAY increment was 5.7% and 3.4%, respectively. Simultaneously, the 20% enhancement of total canopy nitrogen concentration through the improvement of SLNave (TNC-SLNave) resulted in the highest AMDAY across cultivars, with an average increase of 11.2%. In conclusion, the advancing yield performance of YLY3218 and YLY5867 was due to the higher Jmax and gm at tillering stage, and TCN-SLNave is a promising target for future super rice breeding programs.

Summary: Protein phosphatase 1 regulatory subunit 15A (PPP1R15A) is an important factor in the integrated stress response (ISR) in mammals and may play a crucial role in tumorigenesis. In our studies, we found an inhibitor of PPP1R15A, Sephin1, plays a protumorigenic role in mouse tumor models. By analyzing the single-cell transcriptome data of the mouse tumor models, we found that in C57BL/6 mice, Sephin1 treatment could lead to higher levels of ISR activity and lower levels of antitumor immune activities. Specifically, Sephin1 treatment caused reductions in antitumor immune cell types and lower expression levels of cytotoxicity-related genes. In addition, T cell receptor (TCR) repertoire analysis demonstrated that the clonal expansion of tumor-specific T cells was inhibited by Sephin1. A special TCR + macrophage subtype in tumor was identified to be significantly depleted upon Sephin1 treatment, implying its key antitumor role. These results suggest that PPP1R15A has the potential to be an effective target for tumor therapy.

Nanoparticle shape has been acknowledged as an important design parameter due to its influence on nanoparticle interaction with biological systems. However, there is lacking of simple and scalable preparation technique for drug loaded non-spherical polymeric nanoparticles for a long time, thus hindering the potential applications. Although our previous research has modified the traditional emulsion solvent evaporation technique by adding guest molecules to prepare non-spherical poly (lactic-co-glycolic acid) (PLGA) particles, it is difficult to obtain nano-sized rods with minor axis less than 200 nm, which may have great potential in cancer therapy. Herein, in present research, the two-step ESE method was used and optimized to prepare poly (lactic-co-glycolic acid) nanorods for paclitaxel delivery. Firstly, the single-factor experiment was used to screen the influence of multi-factors including type of guest molecules, concentration of guest molecules, emulsification method, surfactant concentration, oil volume, poly (lactic-co-glycolic acid) concentration on the size and shape to determine the range of variables; based on the above range, a multi-factor and multi-level orthogonal experiment was designed. The formula is evaluated by the rod fabrication yield and the aspect ratio of major axis to minor axis. The results showed that the yield of nanorods in the optimal formula was 99% and the aspect ratio was 5.35 ± 2.05 with the minor axis of 135.49 ± 72.66 nm, and major axis of 657.77 ± 307.63 nm. In addition, the anti-cancer drug paclitaxel was successfully encapsulated in PLGA nanorods by the same technique. Our results not only enrich the ESE technique for preparing small sized poly (lactic-co-glycolic acid) nanorods, but also envision the potential application of nanorods for targeted cancer therapy with the delivery of paclitaxel.

Artemisia ordosica has been applied as a traditional Chinese/Mongolian medicine for treating csertain inflammatory ailments. This study was conducted to investigate the effect of Artemisia ordosica alcohol extract (AOAE) supplemented in diets on growth performance, immune, and inflammatory response in lipopolysaccharide (LPS)-challenged broilers. A total of 240 one-day-old Arbor Acre male broilers were randomly allotted into 5 groups with 6 replicates (n = 8), which were basal diet group (CON), LPS-challenge and basal diet group (LPS), LPS-challenge and the basal diet added with low (500 mg/kg), middle (750 mg/kg), and high (1,000 mg/kg) dose of AOAE groups (AOAE-L, AOAE-M, and AOAE-H), respectively. On d 16, 18, 20, 22, 24, 26, and 28, all broilers were injected intra-abdominally either with LPS or an equivalent amount of saline. Results showed that dietary AOAE alleviated the LPS-induced decrease in average daily gain and average daily feed intake in the broilers (P < 0.05). Dietary AOAE supplementation reversed the increased spleen index and the decreased bursa index in LPS-challenged broilers (P < 0.05). Moreover, feeding AOAE could mitigate the elevation of IL-1β in serum, liver, and spleen, IL-2 in serum and liver, IL-6 in serum and spleen, and the decrease of IgG in spleen, IgM in serum, liver, and spleen, and IL-4 in serum of the LPS-challenged broilers (P < 0.05). This study also showed that AOAE supplementation alleviated the increase of mRNA expression of TLR4, MyD88, TRAF6, NF-κB p65, NF-κB p50, IL-1β, and IL-6, and the decrease of gene expression of IκBα and PPARγ in liver and/or spleen of broilers challenged by LPS (P < 0.05). We speculated that AOAE administration could effectively alleviate LPS-induced inflammation via decreasing over-production of proinflammatory cytokines, ultimately relieving the growth inhibition of broilers caused by LPS. In conclusion, 1,000 mg/kg AOAE has a strong capacity to enhance immunity and inhibit inflammation, and can be used as a potential novel feed additive with applications in treating inflammation-related diseases and bacterial infection in broilers.

Guo, Zhang, Guo et al. investigate microbiome alterations in different molecular subtypes of PDAC and report that distinct signatures exist in basal-like tumours, characterized by an increase in certain bacteria, such as Acinetobacter, Pseudomonas and Sphingopyxis. The authors associate increases in these bacteria with increased inflammation and carcinogenic potential, as suggested by pathway analyses.

Abstract Background Macromoleculization of nitroxides has been an effective strategy to improve low relaxivities and poor in vivo stability, however, nitroxides-based metal-free magnetic resonance imaging (MRI) macromolecular contrast agents (mCAs) are still under-performed. These mCAs do not possess a high nitroxides content sufficient for a cumulative effect. Amphiphilic nanostructures in these mCAs are not stable enough for highly efficient protection of nitroxides and do not have adequate molecular flexibility for full contact of the paramagnetic center with the peripheral water molecules. In addition, these mCAs still raise the concerns over biocompatibility and biodegradability due to the presence of macromolecules in these mCAs. Results Herein, a water-soluble biodegradable nitroxides-based mCA (Linear pDHPMA-mPEG-Ppa-PROXYL) was prepared via covalent conjugation of a nitroxides (2,2,5,5-tetramethyl-1-pyrrolidinyl-N-oxyl, PROXYL) onto an enzyme-sensitive linear di-block poly[N-(1, 3-dihydroxypropyl) methacrylamide] (pDHPMA). A high content of PROXYL up to 0.111 mmol/g in Linear pDHPMA-mPEG-Ppa-PROXYL was achieved and a stable nano-sized self-assembled aggregate in an aqueous environment (ca. 23 nm) was formed. Its longitudinal relaxivity (r 1 = 0.93 mM− 1 s− 1) was the highest compared to reported nitroxides-based mCAs. The blood retention time of PROXYL from the prepared mCA in vivo was up to ca. 8 h and great accumulation of the mCA was realized in the tumor site due to its passive targeting ability to tumors. Thus, Linear pDHPMA-mPEG-Ppa-PROXYL could provide a clearly detectable MRI enhancement at the tumor site of mice via the T1WI SE sequence conventionally used in clinical Gd3+-based contrast agents, although it cannot be compared with DTPA-Gd in the longitudinal relaxivity and the continuous enhancement time at the tumor site of mice. Additionally, it was demonstrated to have great biosafety, hemocompatibility and biocompatibility. Conclusions Therefore, Linear pDHPMA-mPEG-Ppa-PROXYL could be a potential candidate as a substitute of metal-based MRI CAs for clinical application. Graphic Abstract

Abstract Background In order to address the potential toxicity of metal-based magnetic resonance imaging (MRI) contrast agents (CAs), a concept of non-metallic MRI CAs has emerged. Currently, paramagnetic nitroxides (such as (2,2,5,5-tetramethylpyrrolidine-1-oxyl, PROXYL), (2,2,6,6-tetramethylpiperidine-1-oxide, TEMPO), etc.) are being extensively studied because their good stability and imaging mechanism are similar to metal-based contrast agents (such as Gd3+ chelate-based clinical CAs). However, a lower relaxivity and rapid in vivo metabolism of nitroxides remain to be addressed. Previous studies have demonstrated that the construction of macromolecular nitroxides contrast agents (mORCAs) is a promising solution through macromolecularization of nitroxides (i.e., use of large molecules to carry nitroxides). Macromolecular effects not only increase the stability of nitroxides by limiting their exposure to reductive substances in the body, but also improve the overall 1H water relaxation by increasing the concentration of nitroxides and slowing the molecular rotation speed. Results Branched pDHPMA-mPEG-Ppa-PROXYL with a high molecular weight (MW = 160 kDa) and a nitroxides content (0.059 mmol/g) can form a nanoscale (~ 28 nm) self-assembled aggregate in a water environment and hydrophobic PROXYL can be protected by a hydrophilic outer layer to obtain strong reduction resistance in vivo. Compared with a small molecular CA (3-Carboxy-PROXYL (3-CP)), Branched pDHPMA-mPEG-Ppa-PROXYL displays three prominent features: (1) its longitudinal relaxivity (0.50 mM− 1 s− 1) is about three times that of 3-CP (0.17 mM− 1 s− 1); (2) the blood retention time of nitroxides is significantly increased from a few minutes of 3-CP to 6 h; (3) it provides long-term and significant enhancement in MR imaging of the tumor, liver, kidney and cardiovascular system (heart and aortaventralis), and this is the first report on nitroxides-based MRI CAs for imaging the cardiovascular system. Conclusions As a safe and efficient candidate metal-free magnetic resonance contrast agent, Branched pDHPMA-mPEG-Ppa-PROXYL is expected to be used not only in imaging the tumor, liver and kidney, but also the cardiovascular system, which expands the application scope of these CAs. Graphical abstract

This study was conducted to investigate the effects of Artemisia annua L. aqueous extract (AAE) on intestinal immune and antioxidative function of broilers. A total of 200 one-day-old Arbor Acre broilers were randomly allotted into five dietary treatment groups, with five replicates per treatment and eight broilers per replicate. The five treatment diets were formulated by adding, respectively, 0 (control group), 0.5, 1.0, 1.5, and 2.0 g/kg AAE in the basal diet. The results showed that dietary inclusion of AAE quadratically decreased interleukin (IL)-1β content, linearly decreased IL-6 content in the small intestine through regulating the nuclear factor-kappa B signal pathway, and quadratically increased immunoglobulin (Ig)M and sIgA content in ileum and jejunum. Besides, there was a quadratic decrease in the gene expression of IL-1β, IL-6, and toll like receptor 4 (TLR4) in ileum on day 21, and the gene expression of IL-6 and TLR4 in duodenum on day 42, thereby improving small intestinal immune function in broilers. Additionally, dietary inclusion of AAE improves antioxidative function through the nuclear factor-erythroid 2-related factor 2 (Nrf2) signal pathway in the small intestinal mucosa of broilers, especially, quadratically increased catalase (CAT) and superoxidase dismutase activity in ileum, and total antioxidant capacity and glutathione peroxidase activity in duodenum, and quadratically decreased malondialdehyde concentration in ileum, besides, linearly increased heme oxygenase-1 and Nrf2 gene expression in jejunum and ileum on day 42, quadratically increased CAT gene expression in the small intestine. Furthermore, regression analyses of the above parameters showed that the optimal dose range of AAE in the diet of broilers was 1.12–1.38 g/kg.

Abstract Purpose The study aimed to investigate the potential benefit of more than 4 courses of S1 adjuvant chemotherapy for patients with pancreatic ductal adenocarcinoma (PDAC) after surgery. Method Data were retrospectively collected from consecutive patients who underwent S-1 adjuvant chemotherapy following curative pancreatectomy between January 2016 and December 2018. Four-courses and > 4 courses cohorts were compared for overall survival (OS) as a primary outcome, and relapse-free survival (RFS) and adverse event incidence as secondary outcomes. Results Four-courses and > 4 courses cohorts comprised 99 patients and 64 ones, respectively. TNM stage (stage II vs. I: HR, 2.125; 95% CI, 1.164–4.213; P = 0.015), duration of S-1 administration (4 vs. > 4 courses: HR, 3.113; 95% CI, 1.531–6.327; P = 0.002) and tumor grade (G3 vs. G1/2: HR, 3.887; 95% CI, 1.922–7.861; P 4 courses cohort was significantly prolonged compared with that of 4 courses cohort (4 vs. > 4 courses: HR, 2.284; 95% CI, 1.197–4.358; P = 0.012), especially for patients in TNM stageII (4 vs. > 4 courses: HR, 2.906; 95% CI, 1.275–6.623; P = 0.011).RFS and adverse events incidence did not signifcantly difer between both cohorts. Conclusion Prolonged duration of S-1 intake is beneficial to prognosis of patients with PDAC resection.

Magnesium (Mg) affects various critical physiological and biochemical processes in higher plants, and its deficiency impedes plant growth and development. Although potassium (K)-induced Mg deficiency in agricultural production is widespread, the specific relationship of K with Mg and especially its competitive nature is poorly understood. This review summarizes current knowledge on the interactions between K and Mg with respect to their root uptake, root-to-shoot translocation and distribution in plants. Their synergistic effects on certain physiological functions are also described. The antagonistic effect of K on Mg is stronger than that of Mg on K in root absorption and transport within plants, indicating that the balanced use of K and Mg fertilizers is necessary for sustaining high plant-available Mg and alleviating K-induced Mg deficiency, especially in plant species with high K demand or in high-available-K soil. The relationship between Mg and K in plant tissues may be antagonistic or synergistic depending on plant species, cell type, leaf age, source- and sink organs. There are synergistic effects of K and Mg on photosynthesis, carbohydrate transport and allocation, nitrogen metabolism, and turgor regulation. Definition of optimal K/Mg ratios for soils and plant tissues is desirable for maintaining proper nutritional status in plants, leading to a physiological state supporting crop production. Future research should concentrate on identifying the physiological and molecular mechanisms underlying the interactions between K and Mg in a given physiological function.

Improved utilisation of nitrogen and carbon could boost agricultural productivity. Here Zhang et al. show that overexpression of a single gene, encoding the plasma membrane H+ -ATPase 1 OSA1, is able to increase both carbon fixation via photosynthesis and nitrogen assimilation via ammonium uptake in rice.

During inflammation, inflammatory cells are rapidly recruited to sites of infection or injury, where they cross physiological barriers around the infected site and further infiltrate into the tissues. Other cells, such as erythrocytes, endothelial cells and stem cells, also play prominent roles in host defense and tissue repair. In recent years, nanotechnology has been exploited to deliver drugs to sites of inflammation. For example, nanoparticles camouflaged with a cell membrane are a novel drug-delivery platform that can interact with the immune system and that show great potential for treating inflammation. Encapsulating drugs inside plasma membranes derived from various cells involved in inflammatory processes can be effective against inflammation. This review describes the preparation, characterization, and properties of various types of cell membrane-camouflaged biomimetic nanoparticles. It also summarizes preclinical research into their efficacy against inflammation.

Due to a series of problems, such as drug resistance and tissue residue caused by adding antibiotics to feed, this research aimed to study the effects of Artemisia annua L. aqueous extract (AAE) as an alternative to antibiotics on growth performance and antioxidant capacity of broilers. A total of 240 one-day-old mixed-sex Arbour Acres broilers were randomly allotted into six groups with five replicates of eight birds each. These six diets were formulated by adding 0, 500, 1000, 1500, 2000 mg/kg AAE and 50 mg/kg chlortetracycline (CTC) to the basal diet, respectively. Average daily body weight gain (ADG), average daily feed intake (ADFI), and feed conversion ratio (FCR) were measured. Total antioxidant capacity (T-AOC), the activity of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and the concentrations of malondialdehyde (MDA) were determined, and the relative gene expression in tissues was measured. The polyphenol flavonoid contents and in vitro antioxidative results showed that: the total phenolic and flavonoid contents were 39.58 ± 6.01 mg GAE/g, 7.04 ± 0.55 mg RE/g, respectively. The inclusion of AAE increased ADG, the activities of T-AOC, CAT, SOD and GSH-Px, and the gene expression of antioxidant enzymes, the concentrations of MDA decreased in serum and tissues. In conclusion, AAE can be used as a feed additive due to its capability to improve growth performance, antioxidant function in broilers. Dietary inclusion of 1000–1500 mg/kg AAE can be used as an alternative for antibiotic growth promoter replacement without negative effect on broiler performance.Highlights Artemisia annua L. aqueous extract can promote growth performance and antioxidant function of Broilers. Artemisia annua L. aqueous extract is expected to become the substitute for antibiotics and promote the growth of the body. The optimal dose range of Artemisia annua L. aqueous extract in diet of broilers was 1000–1500 mg/kg.

Abstract. Objective:. To investigate the effect of long-acting octreotide as adjuvant therapy in the prevention of tumor recurrence in patients with grade 2 pancreatic neuroendocrine tumors (pNETs) after radical resection. Methods:. The postoperative follow-up data of 130 patients with resectable G2 pNET treated in the Changhai Hospital from 2008 to 2018 were retrospectively analyzed: 59 patients received long-acting octreotide as adjuvant therapy for 6 to 12 months (Oct group) and 71 patients received active follow-up (control group), both of which began after the radical resection, with the primary observation endpoint of disease-free survival (DFS) and the secondary study endpoint of overall survival. Results:. The median age of the patients in the Oct group and control group was 52 and 54 years, respectively. There were 28 male cases (47.5%) and 33 male cases (46.5%) in the 2 groups. The median maximum tumor diameter was 3.5 and 3.0 cm, respectively; lymph node metastasis was positive in 13 cases (22.0%) and 9 cases (12.7%); there was peripancreatic nerve invasion in 11 cases (18.6%) and 6 cases (8.5%). Survival analysis revealed that there were significant differences in 2-year DFS% (98.3% vs 88.7%, P = .0371) and 3-year DFS% (96.6% vs 85.9%, P = .0498) between the Oct group and control group. Long-acting octreotide treatment was found to reduce the risk of 3-year recurrence of G2 pNET after radical resection (HR = 0.2, P = .044) with the application of inverse-probability-of-treatment weighted to balance the limited data bias. Conclusion:. Using long-acting octreotide as adjuvant therapy for G2 pNET patients after radical surgery may improve the rate of 3y-DFS, but the benefit needs to be confirmed in a well-designed random control clinical trial.

A simple and efficient method for the synthesis of dialdehyde aniline in good yields (up to 83%) is explored using Cu(OTf)2 as the catalyst, Selectfluor as the radical initiator, and DMSO as both the carbon and oxygen sources. Experimental studies indicate that the reaction is achieved by the formylation of two CAr-H bonds, first at the para-position and then at the ortho-position. A possible mechanism is proposed, including the thermal homolysis of Selectfluor, the Cu(II)-facilitated formylation of the CAr-H bonds, and the hydrolysis of the amide under alkaline conditions in air atmosphere.

Abstract Background The ratio of CO2 mesophyll conductance (g m) to Ribulose-1, 5-bisphosphate carboxylase/oxygenase (Rubisco) content has been suggested to positively affect photosynthetic nitrogen use efficiency (PNUE). The anatomical basis of g m has been quantified, but information on the relationship between cell-level anatomies and PNUE is less advanced. Here, hydroponic experiments were conducted in rice plants supplied with ammonium (NH4 +) and nitrate (NO3 −) under three N levels (low, 0.71 mM; intermediate, 2.86 mM; high, 7.14 mM) to investigate the gas exchange parameters, leaf anatomical structure and PNUE. Results The results showed a lower PNUE in plants supplied with high nitrogen and NH4 +, which was positively correlated with the g m/Rubisco ratio. A one-dimensional within-leaf model revealed that the resistance to CO2 diffusion in the liquid phase (r liq) dominated the overall mesophyll resistance (r m), in which CO2 transfer resistance in the cell wall, cytoplasm and stroma were significantly affected by nitrogen supply. The chloroplast surface area exposed to intercellular space (S c) per Rubisco rather than the g m/S c ratio was positively correlated with PNUE and was thus considered a key component influencing PNUE. Conclusion In conclusion, our study emphasized that S c was the most important anatomical trait in coordinating g m and PNUE with contrasting N supply.

Abstract Background The differential diagnosis of pancreatic ductal adenocarcinoma (PDAC) from chronic pancreatitis (CP) is clinically challenging due to a lack of minimally invasive diagnosis methods. MicroRNAs (miRNAs) derived from small extracellular vesicles (EVs) in the blood have been reported as a promising diagnosis biomarker for various types of cancer. However, blood small EV miRNA signatures and their diagnostic value to differentiate between PDAC and CP remain to be determined. Methods In this study, 107 patients with PDAC or CP were recruited, and 90 patients were finally enrolled for a training cohort (n = 48) and test cohort (n = 42). Small RNA sequencing was used to assess the expression of blood small EV miRNAs in these patients. Results The linear model from the differentially expressed blood small EV miR‐95‐3p divided by miR‐26b‐5p showed an average sensitivity of 84.1% and an average specificity of 96.6% to identify PDAC from CP in the training cohort and the test cohort, respectively. When the model was combined with serum carbohydrate antigen 19‐9 (CA19‐9), the average sensitivity increased to 96.5%, and the average specificity remained at 96.4% of both cohorts, which demonstrated the best performance of all the published biomarkers for distinguishing between PDAC and CP. The causal analysis performed using the Bayesian network demonstrated that miR‐95‐3p was associated with a “consequence” of “cancer” and miR‐26b‐5p as a “cause” of “pancreatitis.” A subgroup analysis revealed that blood small EV miR‐335‐5p/miR‐340‐5p could predict metastases in both cohorts and was associated with an overall survival (p = 0.020). Conclusions This study indicated that blood small EV miR‐95‐3p/miR‐26b‐5p and its combination with serum levels of CA19‐9 could separate PDAC from CP, and miR‐335‐5p/miR‐340‐5p was identified to associate with PDAC metastasis and poor prognosis. These results suggested the potentiality of blood small EV miRNAs as differential diagnosis and metastases biomarkers of PDAC.

As natural bioactive components, plant-derived polysaccharides have many biological functions, such as anti-inflammatory, antioxidant, anticoccidial, and immunity regulation, and have been widely used in poultry production. In this review paper, firstly, the sources and structures of plant-derived polysaccharides are reviewed; secondly, the effects of plant-derived polysaccharides on the intestinal microbiome, permeability, morphology and immune function of poultry are summarized; thirdly, the potential molecular regulation mechanism of plant-derived polysaccharides on the intestinal barrier function of poultry was preliminarily analyzed. The review paper will bring a basis for the scientific utilization of plant-derived polysaccharides in the poultry industry.