Reducing cadmium and arsenic accumulation in rice grains: The coupled effect of sulfur's biomass dilution and soil immobilization analyzed using meta-analysis and machine learning.

The biogeochemical cycling of sulfur (S) in paddy soil influences cadmium (Cd) and arsenic (As) migration. However, the impact of S application on Cd and As within the soil-rice system has not been fully explored. This study aimed to examine the effect of S application on Cd/As soil-rice system dynamics by conducting an extensive meta-analysis of 322 sets of observational data from 46 publications, which were published between 2004 and 2023. Furthermore, a machine learning model was only used to forecast the potential influence of S on Cd within the soil-rice system rather than the influence of As due to the limited data samples. The results indicated that the basal application of S mainly reduced the accumulation of Cd and As in the grains [Cd: 29.00 % (28.48 % to 29.52 %); As: 38.31 % (37.79 % to 38.85 %)] by the coupling effect of promoting rice growth 40.87 % (40.61 %-41.14 %) and reducing the soil bioavailable Cd/As by 18.20 % (18.05 % to 18.36 %)/19.59 % (19.44 % to 19.75 %). However, the efficacy of actual field farmland remediation is often suboptimal because the actual soil physical and chemical properties frequently do not meet the ideal conditions [pH: 6.5-7.5, Total S: < 200 mg/kg, soil organic matter (SOM): 30-40 g/kg, Total Fe: 20-30 g/kg] that are required to mitigate Cd and As accumulation in rice grains. Notably, the random forest machine learning model achieved an acceptable level of accuracy when compared to the excessive linear regression simulation. The model suggested that the decrease in the Cd/As accumulation in the rice was due to the soil available S content, which was primarily influenced by S application. This study provides novel insights for managers and researchers for the amelioration of Cd/As-contaminated farmland soil.

Photon number adaptive single-photon detection with time-walk passive compensation.

In long-distance laser time transfer, such as satellite-to-satellite and satellite-to-ground, the accuracy of flight time measurement for photon pulses is significantly compromised by the time walk phenomenon, stemming from variations of the incident photon numbers. In this paper, we propose a single-photon detection method, which is adaptive to the photon number, and passively compensates for the time walk effect. This method utilizes a fiber ring to divide an incident photon pulse into a series of photon pulse trains, with each pulse in the train separated by equal time intervals and subject to equal attenuation. The last detected photon pulse in the pulse train can always be attenuated to a single-photon level sufficient to render the time walk effect negligible. The experimental results demonstrate that the proposed method effectively mitigates the time walk effect across a range of average photon numbers, spanning from 1 to 100. It provides high-precision single-photon detection for laser time transfer in complex and variable environments.

Deciphering Cadmium Accumulation in Peanut Kernels through Growth Stages and Source Organs: A Multi-Stable Isotope Labeling Study.

The mechanisms of cadmium (Cd) uptake and redistribution throughout the peanut lifecycle remain unclear. This study employed multi-isotope labeling techniques in hydroponic and soil-foliar systems, revealing that Cd uptake during podding (Cdp) constituted 73.7% of kernel Cd content, whereas contributions from the flowering (Cdf) and seedling (Cds) stages were 22.2 and 4.1%, respectively. Stem-stored Cd (Cdstem) contributes 53.2% to kernel Cd accumulation, while leaf-stored Cd (Cdleaf) contributes 46.8%. Prestored Cdf in shoots demonstrated the most efficient transport to pods, approximately twice that of Cds and Cdp. Cds and Cdf were predominantly stored in leaves (51.0%), while Cdp mainly in stems (46.3%), 2.8 times its presence in leaves (16.5%), indicating distinct root-stem-kernel translocation. In the transfer of shoot Cd from stems to pods, 29.3% of Cdleaf and 25.0% of Cdstem were exported. This study provides novel insights into Cd dynamics in peanuts, establishing a foundation for future Cd regulation strategies.

Combinatorial transcription factor binding encodes cis-regulatory wiring of mouse forebrain GABAergic neurogenesis.

Transcription factors (TFs) bind combinatorially to cis-regulatory elements, orchestrating transcriptional programs. Although studies of chromatin state and chromosomal interactions have demonstrated dynamic neurodevelopmental cis-regulatory landscapes, parallel understanding of TF interactions lags. To elucidate combinatorial TF binding driving mouse basal ganglia development, we integrated chromatin immunoprecipitation sequencing (ChIP-seq) for twelve TFs, H3K4me3-associated enhancer-promoter interactions, chromatin and gene expression data, and functional enhancer assays. We identified sets of putative regulatory elements with shared TF binding (TF-pRE modules) that orchestrate distinct processes of GABAergic neurogenesis and suppress other cell fates. The majority of pREs were bound by one or two TFs; however, a small proportion were extensively bound. These sequences had exceptional evolutionary conservation and motif density, complex chromosomal interactions, and activity as in vivo enhancers. Our results provide insights into the combinatorial TF-pRE interactions that activate and repress expression programs during telencephalon neurogenesis and demonstrate the value of TF binding toward modeling developmental transcriptional wiring.

Oxytocin Protects Nigrostriatal Dopamine Signal via Activating GABAergic Circuit in the MPTP-Induced Parkinson's Disease Model.

The most pronounced neuropathological feature of Parkinson's disease (PD) is the loss of dopamine (DA) neurons in the substantia nigra compacta (SNc), which depletes striatal DA. Hypothalamic oxytocin is found to be reduced in PD patients and closely interacts with the DA system, but the role of oxytocin in PD remains unclear. Here, the disturbances of endogenous oxytocin level and the substantia nigra (SN) oxytocin receptor expression in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD mouse model is observed, correlated with the striatal tyrosine hydroxylase (TH) expression reduction. Killing/silencing hypothalamic oxytocin neurons aggravates the vulnerability of nigrostriatal DA signal to MPTP, whereas elevating oxytocin level by intranasal delivery or microinjecting into the SN promotes the resistance. In addition, knocking out SN oxytocin receptors induces the time-dependent reductions of SNc DA neurons, striatal TH expression, and striatal DA level by increasing neuronal excitotoxicity. These results further uncover that oxytocin dampens the excitatory synaptic inputs onto DA neurons via activating oxytocin receptor-expressed SN GABA neurons, which target GABA(B) receptors expressed in SNc DA neuron-projecting glutamatergic axons, to reduce excitotoxicity. Thus, besides the well-known prosocial effect, oxytocin acts as a key endogenous factor in protecting the nigrostriatal DA system.

Spatial heterogeneity of soil moisture caused by drainage and its effects on cadmium variation in rice grain within individual fields.

Paddy drainage is the critical period for rice grain to accumulate cadmium (Cd), however, its roles on spatial heterogeneity of grain Cd within individual fields are still unknown. Herein, field plot experiments were conducted to study the spatial variations of rice Cd under continuous and intermittent (drainage at the tillering or grain-filling or both stages) flooding conditions. The spatial heterogeneity of soil moisture and key factors involved in Cd mobilization during drainages were further investigated to explain grain Cd variation. Rice grain Cd levels under continuous flooding ranged from 0.16 to 0.22 mg kg-1 among nine sampling sites within an individual field. Tillering drainage slightly increased grain Cd levels (0.19-0.31 mg kg-1) with little change in spatial variation. However, grain-filling drainage greatly increased grain Cd range to 0.33-0.95 mg kg-1, with a huge spatial variation observed among replicated sites. During two drainage periods, soil moisture decreased variously in different monitoring sites; greater variation (mean values ranged from 0.14 to 0.27 m3 m-3) was observed during grain-filling drainage. Accordingly, 2.9-3.3-fold variation in soil Eh and 0.55-0.67-unit variation in soil pH were observed among those sites. In the soil with low moisture, ferrous fractions such as ferrous sulfide (FeS) were prone to be oxidized to ferric fractions; meanwhile, the followed generation of hydroxyl radicals involved in Cd remobilization was enhanced. Consequently, soil dissolved Cd changed from 2.97 to 8.92 µg L-1 among different sampling sites during grain-filling drainage; thus, large variation was observed in grain Cd levels. The findings suggest that grain-filling drainage is the main process controlling spatial variation of grain Cd, which should be paid more attention in paddy Cd evaluation.

gem-Difluoroalkylation of Cyclic Ethers Enabled by Cobalt-Catalyzed C(sp3)-H Oxidation under Mild Conditions.

Fluorinated rings have emerged as privileged structural modules in the fields of drug discovery and materials research. The incorporation of fluorine atoms into aromatic rings or heterocycles can lead to significant improvements in the physicochemical and biological properties of small molecules, making them valuable components in the design of new drugs and functional materials. Herein, we presented a cobalt-catalyzed C-H oxidation/gem-difluorination cascade reaction of readily available cyclic ethers with difluoroenoxysilanes, affording a series of gem-difluorinated analogues with moderate to high yields. The obtained products as versatile fluoroalkyl building blocks were showcased through divergent-oriented transformations.

Comparative analysis of bacterial community structure and physicochemical quality in high-temperature Daqu of different colors in Qingzhou production area.

To compare the effects of differences in Daqu making technology and production regions on the bacterial composition and physicochemical properties of high-temperature Daqu (HTD), this study analyzed the bacterial community structure of three colors of HTD in the Qingzhou production area and measured their physicochemical quality. At the same time, a comparative analysis was conducted on the bacterial composition of Qingzhou and Xiangyang regions. The results revealed that the HTD in the Qingzhou area exhibited a diverse bacterial community dominated by Lentibacillus, Scopulibacillus, and Staphylococcus. The black HTD displayed the lowest bacterial richness (P < 0.05) and a relatively unique microbial structure. Significant variations were observed in the physicochemical qualities of the three colors of HTD. Notably, white HTD demonstrated higher moisture and ash content, saccharification and liquor-producing power. Yellow HTD exhibited higher amino nitrogen and protein content, and black HTD displayed higher water activity, acidity, and starch content. The variation in Bacillus, Limosilactobacillus, and Weissella distributions across different colors of HTD primarily contributed to these findings. From the HTD samples in the Qingzhou area, Bacillus (61.90 %) and lactic acid bacteria (17.46 %) being the predominant cultivable communities. Cluster analysis identified significant differences in bacterial communities among HTD samples from various production areas. It can enhance the understanding of HTD quality in the Qingzhou area and offer insights for optimizing HTD and Maotai-flavor Baijiu quality.

Sappanone A ameliorated imiquimod-induced psoriasis-like dermatitis in BALB/c mice via suppressing Mmp8 expression and IL-17 signaling pathway.

Psoriasis is a prevalent immune-mediated inflammatory skin disease characterized by excessive abnormal proliferation of keratinocytes and infiltration of immune cells, which have significant impact on the life quality of individuals. Although biological agents and small molecule targeted drugs have brought significant clinical benefits to psoriasis patients, adverse reactions and high prices remains key issues in clinical medication of psoriasis, while natural product monomers possess high efficiency, low toxicity, anti-inflammatory and immunomodulatory properties, and bring new hope for the clinical treatment of psoriasis. Sappanone A (SA), a small molecule compound isolated from Caesalpinia sappan L, exhibits significant anti-inflammatory properties in various models, such as kidney inflammation and LPS-induced mice inflammation. Among these effects, the anti-inflammatory property of SA has received significant attention. In our study, we found that SA exhibited anti-proliferation and anti-inflammatory effects in HaCaT cells, and significantly alleviated imiquimod-induced psoriasis-like skin lesions via the inhibition of the excessive proliferation of keratinocytes and the infiltration of lymphocytes. Furthermore, the combinational analysis of network pharmacology and transcriptome sequencing revealed that SA exerted anti-psoriasis effects by inhibiting the matrix metalloproteinase 8 (Mmp8) expression and IL-17 pathway activation. In summary, we have first demonstrated that SA can be used as a novel anti-psoriasis drug, which may provide a novel strategy for the clinical treatment of psoriasis.

Correlation between newborn weight and serum BCAAs in pregnant women with diabetes.

BACKGROUND: Branched-chain amino acids (BCAAs), including leucine, isoleucine, and valine, are essential amino acids for mammals. Maternal BCAAs during pregnancy have been associated with newborn development. Meanwhile, BCAAs have been tightly linked with insulin resistance and diabetes in recent years. Diabetes in pregnancy is a common metabolic disorder. The current study aims to assess the circulating BCAA levels in pregnant women with diabetes and their relationship with neonatal development. METHODS: The serum concentrations of BCAAs and their corresponding branched-chain α-keto acids (BCKAs) catabolites in 33 pregnant women with normal glucose tolerance, 16 pregnant women with type 2 diabetes before pregnancy (PDGM), and 15 pregnant women with gestational diabetes mellitus (GDM) were determined using a liquid chromatography system coupled to a mass spectrometer. The data were tested for normal distribution and homogeneity of variance before statistical analysis. Correlations were computed with the Pearson correlation coefficient. RESULTS: The maternal serum BCAAs and BCKAs levels during late pregnancy were higher in women with PGDM than those in healthy women. Meanwhile, the circulating BCAAs and BCKAs showed no significant changes in women with GDM compared with those in healthy pregnant women. Furthermore, the circulating BCAA and BCKA levels in women with PGDM were positively correlated with the weight of the newborn. The circulating leucine level in women with GDM was positively correlated with the weight of the newborn. BCAA and BCKA levels in healthy pregnant women showed no correlation with newborn weight. CONCLUSIONS: The serum BCAAs in pregnant women with diabetes, which was elevated in PGDM but not GDM, were positively correlated with newborn weight. These findings highlight potential approaches for early identification of high-risk individuals and interventions to reduce the risk of adverse pregnancy outcomes.

Identifying novel clinical phenotypes of acute respiratory distress syndrome using trajectories of daily fluid balance: a secondary analysis of randomized controlled trials.

BACKGROUND: Previously identified phenotypes of acute respiratory distress syndrome (ARDS) could not reveal the dynamic change of phenotypes over time. We aimed to identify novel clinical phenotypes in ARDS using trajectories of fluid balance, to test whether phenotypes respond differently to different treatment, and to develop a simplified model for phenotype identification. METHODS: FACTT (conservative vs liberal fluid management) trial was classified as a development cohort, joint latent class mixed models (JLCMMs) were employed to identify trajectories of fluid balance. Heterogeneity of treatment effect (HTE) for fluid management strategy across phenotypes was investigated. We also constructed a parsimonious probabilistic model using baseline data to predict the fluid trajectories in the development cohort. The trajectory groups and the probabilistic model were externally validated in EDEN (initial trophic vs full enteral feeding) trial. RESULTS: Using JLCMM, we identified two trajectory groups in the development cohort: Class 1 (n = 758, 76.4% of the cohort) had an early positive fluid balance, but achieved negative fluid balance rapidly, and Class 2 (n = 234, 24.6% of the cohort) was characterized by persistent positive fluid balance. Compared to Class 1 patients, patients in Class 2 had significantly higher 60-day mortality (53.5% vs. 17.8%, p < 0.001), and fewer ventilator-free days (0 vs. 20, p < 0.001). A significant HTE between phenotypes and fluid management strategies was observed in the FACTT. An 8-variables model was derived for phenotype assignment. CONCLUSIONS: We identified and validated two novel clinical trajectories for ARDS patients, with both prognostic and predictive enrichment. The trajectories of ARDS can be identified with simple classifier models.

Selective and efficient immobilization of cadmium in soil by layered double hydroxides intercalated with the mercaptosuccinic acid.

Cadmium (Cd) contamination in cropland poses a significant threat to the quality of agricultural products, but even though in-situ remediation has been extensively applied, non-selective immobilization remains an issue. In order to develop a material that specifically immobilizes Cd in soil, a layered double hydroxide, intercalated with mercaptosuccinic acid (MSA-CFA), was synthesized through co-precipitation. In this case, the MSA-CFA's maximum adsorption capacity was increased from the 513.8 mg·g-1 for unintercalated hydrotalcite CFA to 692.6 mg·g-1. Besides, MSA-CFA efficiently removed 99.25 % of Cd from soil water-extract solution and immobilized up to 70.03 % of bio-available Cd. However, interestingly, its immobilization effects on beneficial metal elements Fe, Mn and Zn were milder, being equivalent to 2/7, 5/7 and 1/2 that of lime, respectively. Moreover, XRD and XPS techniques revealed isomorphous substitution with calcium and sulfhydryl complexation during the Cd adsorption by MSA-CFA. Compared with CFA, the increased adsorption capacity of MSA-CFA for Cd was due to intercalated MSA acting as a new adsorption site, while the enhanced selectivity was contributed by sulfhydryl's affinity for Cd. Altogether, MSA-CFA showed great promise as a competitive and highly efficient candidate amendment in Cd-contaminated soil remediation.

Multiscale Characterization and Biomimetic Design of Porcupine Quills for Enhanced Mechanical Performance.

The mechanical properties of porcupine quills have attracted the interest of researchers due to their unique structure and composition. However, there is still a knowledge gap in understanding how these properties can be utilized to design biomimetic structures with enhanced performance. This study delves into the nanomechanical and macro-mechanical properties of porcupine quills, unveiling varied elastic moduli across different regions and cross sections. The results indicated that the elastic moduli of the upper and lower epidermis were higher at 8.13 ± 0.05 GPa and 7.71 ± 0.14 GPa, respectively, compared to other regions. In contrast, the elastic modulus of the mid-dermis of the quill mid-section was measured to be 7.16 ± 0.10 GPa. Based on the micro- and macro-structural analysis of porcupine quills, which revealed distinct variations in elastic moduli across different regions and cross sections, various biomimetic porous structures (BPSs) were designed. These BPSs were inspired by the unique properties of the quills and aimed to replicate and enhance their mechanical characteristics in engineering applications. Compression, torsion, and impact tests illustrated the efficacy of structures with filled hexagons and circles in improving performance. This study showed enhancements in maximum torsional load and crashworthiness with an increase in filled structures. Particularly noteworthy was the biomimetic porous circular structure 3 (BPCS_3), which displayed exceptional achievements in average energy absorption (28.37 J) and specific energy absorption (919.82 J/kg). Finally, a response surface-based optimization method is proposed to enhance the design of the structure under combined compression-torsion loads, with the goal of reducing mass and deformation. This research contributes to the field of biomimetics by exploring the potential applications of porcupine quill-inspired structures in fields such as robotics, drive shafts, and aerospace engineering.

Structural clarification of mannoglucan GSBP-2 from Ganoderma sinense and its effects on triple-negative breast cancer migration and invasion.

Ganoderma sinense, known as Lingzhi in China, is a medicinal fungus with anti-tumor properties. Herein, crude polysaccharides (GSB) extracted from G. sinense fruiting bodies were used to selectively inhibit triple-negative breast cancer (TNBC) cells. GSBP-2 was purified from GSB, with a molecular weight of 11.5 kDa and a composition of α-l-Fucp-(1→, ß-d-Glcp-(1→, ß-d-GlcpA-(1→, →3)-ß-d-Glcp-(1→, →3)-ß-d-GlcpA-(1→, →4)-α-d-Galp-(1→,→6)-ß-d-Manp-(1→, and →3,6)-ß-d-Glcp-(1→ at a ratio of 1.0:6.3:1.7:5.5:1.5:4.3:8.0:7.9. The anti-MDA-MB-231 cell activity of GSBP-2 was determined by methyl thiazolyl tetrazolium, colony formation, scratch wound healing, and transwell migration assays. The results showed that GSBP-2 could selectively inhibit the proliferation, migration, and invasion of MDA-MB-231 cells through the regulation of genes targeting epithelial-mesenchymal transition (i.e., Snail1, ZEB1, VIM, CDH1, CDH2, and MMP9) in the MDA-MB-231 cells. Furthermore, Western blotting results indicated that GSBP-2 could restrict epithelial-mesenchymal transition by increasing E-cadherin and decreasing N-cadherin expression through the PI3K/Akt pathway. GSBP-2 also suppressed the angiogenesis of human umbilical vein endothelial cells. In conclusion, GSBP-2 could inhibit the proliferation, migration, and invasion of MDA-MB-231 cells and showed significant anti-angiogenic ability. These findings indicate that GSBP-2 is a promising therapeutic adjuvant for TNBC.

Characterization and correlation analysis of microbial flora and flavor profile of stinky acid, a Chinese traditional fermented condiment.

To explore the microbial diversity and flavor profiles of stinky acid, we utilized high-throughput sequencing, culture-based techniques, and bionic E-sensory technologies. The results revealed a significant correlation between the acidity levels of stinky acid and the richness of its microbial community. Ten core bacterial genera and three core fungal genera exhibited ubiquity across all stinky acid samples. Through E-nose analysis, it was found that sulfides constituted the principal odor compounds responsible for stinky acid's distinct aroma. Further insights arose from the correlation analysis, indicating the potential contribution of Debaryomyces yeast to the sour taste profile. Meanwhile, three genera-Rhizopus and Thermoascus and Companilactobacillus-were identified as contributors to aromatic constituents. Interestingly, the findings indicated that Rhizopus and Thermoascus could reduce the intensity of the pungent odor of stinky acid. In summary, this investigation's outcomes offer new insights into the complex bacterial diversity of stinky acid.

Microbial communities, functional, and flavor differences among three different-colored high-temperature Daqu: A comprehensive metagenomic, physicochemical, and electronic sensory analysis.

High-temperature Daqu (HTD) is the starter for producing sauce-flavor Baijiu, with different-colored Daqu (white, yellow, and black) reflecting variations in fermentation chamber conditions, chemical reactions, and associated microbiota. Understanding the relationship between Daqu characteristics and flavor/taste is challenging yet vital for improving Baijiu fermentation. This study utilized metagenomic sequencing, physicochemical analysis, and electronic sensory evaluation to compare three different-colored HTD and their roles in fermentation. Fungi and bacteria dominated the HTD-associated microbiota, with fungi increasing as the fermentation temperature rose. The major fungal genera were Aspergillus (40.17%) and Kroppenstedtia (21.16%), with Aspergillus chevalieri (25.65%) and Kroppenstedtia eburnean (21.07%) as prevalent species. Microbial communities, functionality, and physicochemical properties, particularly taste and flavor, were color-specific in HTD. Interestingly, the microbial communities in different-colored HTDs demonstrated robust functional complementarity. White Daqu exhibited non-significantly higher α-diversity compared to the other two Daqu. It played a crucial role in breaking down substrates such as starch, proteins, hyaluronic acid, and glucan, contributing to flavor precursor synthesis. Yellow Daqu, which experienced intermediate temperature and humidity, demonstrated good esterification capacity and a milder taste profile. Black Daqu efficiently broke down raw materials, especially complex polysaccharides, but had inferior flavor and taste. Notably, large within-group variations in physicochemical quality and microbial composition were observed, highlighting limitations in color-based HTD quality assessment. Water content in HTD was associated with Daqu flavor, implicating its crucial role. This study revealed the complementary roles of the three HTD types in sauce-flavor Baijiu fermentation, providing valuable insights for product enhancement.

The Design and Experimentation of a Corn Moisture Detection Device Based on Double Capacitors.

Detecting the moisture content of grain accurately and rapidly has important significance for harvesting, transport, storage, processing, and precision agriculture. There are some problems with the slow detection speeds, unstable detection, and low detection accuracy of moisture contents in corn harvesters. In that case, an online moisture detection device was designed, which is based on double capacitors. A new method of capacitance complementation and integration was proposed to eliminate the limitation of single data. The device is composed of a sampling mechanism and a double-capacitor sensor consisting of a flatbed capacitor and a cylindrical capacitor. The optimum structure size of the capacitor plates was determined by simulation optimization. In addition to this, the detection system with software and hardware was developed to estimate the moisture content. Indoor dynamic measurement tests were carried out to analyze the influence of temperature and porosity. Based on the influencing factors and capacitance, a model was established to estimate the moisture content. Finally, the support vector machine (SVM) regressions between the capacitance and moisture content were built up so that the R2 values were more than 0.91. In the stability test, the standard deviation of the stability test was 1.09%, and the maximum relative error of the measurement accuracy test was 1.22%. In the dynamic verification test, the maximum error of the measurement was 4.62%, less than 5%. It provides a measurement method for the accurate, rapid, and stable detection of the moisture content of corn and other grains.

Association of glucose-lowering drug target and risk of gastrointestinal cancer: a mendelian randomization study.

BACKGROUND & AIMS: Glucose-lowering drug is associated with various cancers, but the causality with gastrointestinal cancer risk is rarely reported. We aimed to explore the causality between them in this Mendelian randomization (MR) study. METHODS: Two-sample MR, summary-data-based (SMR), mediation MR, and colocalization analyses was employed. Ten glucose-lowering drug targets (PPARG, DPP4, GLP1R, INSR, SLC5A2, ABCC8, KCNJ11, ETFDH, GPD2, PRKAB1) and seven types of gastrointestinal cancer (anal carcinoma, cardia cancer, gastric cancer, hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), pancreatic cancer, rectum cancer) were included. Patients with gastrointestinal cancers from six different large GWAS databases, including the UK Biobank and Finnish cohorts were incorporated, for discovery and external validation. Meta-analysis was employed to integrate the results from both discovery and validation cohorts, thereby ensuring the reliability of findings. RESULTS: ABCC8/KCNJ11 were associated with pancreatic cancer risk in both two-sample MR (odds ratio (OR): 15.058, per standard deviation unit (SD) change of glucose-lowering durg target perturbation equivalent to 1 SD unit of HbA1c lowering; 95% confidence interval (95% CI): 3.824-59.295; P-value = 0.0001) and SMR (OR: 1.142; 95% CI: 1.013-1.287; P-value = 0.030) analyses. The mediation effect of body mass index (OR: 0.938; 95% CI: 0.884-0.995; proportion of mediation effect: 3.001%; P-value = 0.033) on ABCC8/KCNJ11 and pancreatic cancer was uncovered. Strong connections of DPP4 with anal carcinoma (OR: 0.123; 95% CI: 0.020-0.745; P-value = 0.023) and ICC (OR: 7.733; 95% CI: 1.743-34.310; P-value = 0.007) were detected. PPARG was associated with anal carcinoma (OR: 12.909; 95% CI: 3.217-51.795; P-value = 0.0003), HCC (OR: 36.507; 95% CI: 8.929-149.259; P-value < 0.0001), and pancreatic cancer (OR: 0.110; 95% CI: 0.071-0.172; P-value < 0.0001). SLC5A2 was connected with pancreatic cancer (OR: 8.096; 95% CI: 3.476-18.857; P-value < 0.0001). Weak evidence indicated the connections of GLP1R, GPD2, and PRKAB1 with anal carcinoma, cardia cancer, ICC, and rectum cancer. In addition, the corresponding results were consistently validated in both the validation cohorts and the integrated outcomes. CONCLUSIONS: Some glucose-lowering drugs were associated with gastrointestinal cancer risk, which might provide new ideas for gastrointestinal cancer treatment.

Enhancement of yellow pigments production via high CaCl2 stress fermentation of Monascus purpureus.

Monascus pigments (MPs) are a kind of natural ingredient fermented by Monascus spp., which contains three types of pigments: red, orange, and yellow ones. Monascus yellow pigments have a restricted yield and cannot meet industrial application. The method and mechanism of CaCl2 improving yellow pigments production by liquid fermentation of Monascus purpureus M8 were studied in order to overcome the low yield of yellow pigments produced by liquid fermentation. Changes in physiological and biochemical indicators explained the effects of CaCl2 on the production of Monascus yellow pigments from solid fermentation. The intracellular yellow pigments, orange pigments, and red pigments increased by 156.08%, 43.76%, and 42.73%, respectively, with 60 g/l CaCl2 addition to culture medium. The amount of red and orange pigments reduced, while the proportion of yellow pigments increased and the relative peak area of intracellular yellow pigments accounted for a dominant 98.2%, according to thin layer chromatography and high performance liquid chromatography analyses. Furthermore, the influence of CaCl2 extended to the modulation of pigments synthesis-related gene expression in M8 strain. This modulation led to a pronounced upregulation in the expression of the yellow pigments synthesis-related gene, mppE, signifying a pivotal role played by CaCl2 in orchestrating the intricate machinery behind yellow pigments biosynthesis.