Search

Soybean yield is affected by soil, terrain, biology, and other factors. However, few studies have considered the main and secondary influencing factors of soybean yield and the interaction mechanisms among these factors within a catchment area in the black soil region. This study aims to explore the main influencing factors and the coupling mechanisms affecting soybean yield in China’s northeast black soil region. Using 46 samples from Heshan Farm, Nenjiang City, a driving factor model for soybean yield was developed using PLS-SEM, incorporating latent variables such as soybean yield, topographic characteristics, soil physical properties, soil chemical properties, and biological factors. The main factors, secondary factors, and their interactions affecting soybean yield were discussed. Topographic factors, soil physical properties, and soil chemical properties had positive total effects on soybean yield, while biological factors had a direct negative impact on soybean yield, with the total effects ranging from soil physical properties > biological factors > topographic factors > soil chemical properties. In terms of soil physical properties, the load value of soil bulk density was the largest (−0.917). This was followed by saturated water content (0.886), total porosity (0.855), capillary water holding capacity (0.837), field water holding capacity (0.763), black soil thickness (0.695), sand particle size (−0.664), clay particle size (0.450), and gravel ratio (−0.439). These findings demonstrate soil physical properties are the key factors affecting soybean yield. Thus, soil improvement in small catchment, by reducing bulk density, increasing porosity, and improving soil water retention capacity are key to improving soybean yield.

PurposeThe aim of this study was to improve the intratumoral accumulation of an antibody–drug conjugate (ADC) and minimize its off-target toxicity, SKB264, a novel anti-trophoblast antigen 2 (TROP2) ADC that was developed using 2-methylsulfonyl pyrimidine as the linker to conjugate its payload (KL610023), a belotecan-derivative topoisomerase I inhibitor. The preclinical pharmacologic profiles of SKB264 were assessed in this study.MethodsThe in vitro and in vivo pharmacologic profiles of SKB264, including efficacy, pharmacokinetics–pharmacodynamics (PK-PD), safety, and tissue distribution, were investigated using TROP2-positive cell lines, cell-derived xenograft (CDX), patient-derived xenograft (PDX) models, and cynomolgus monkeys. Moreover, some profiles were compared with IMMU-132.ResultsIn vitro, SKB264 and SKB264 monoclonal antibody (mAb) had similar internalization abilities and binding affinities to TROP2. After cellular internalization, KL610023 was released and inhibited tumor cell survival. In vivo, SKB264 significantly inhibited tumor growth in a dose-dependent manner in both CDX and PDX models. After SKB264 administration, the serum or plasma concentration/exposure of SKB264 (conjugated ADC, number of payload units ≥1), total antibody (Tab, unconjugated and conjugated mAb regardless of the number of the payload units), and KL610023 in cynomolgus monkeys increased proportionally with increasing dosage from 1 to 10 mg/kg. The linker stability of SKB264 was significantly enhanced as shown by prolonged payload half-life in vivo (SKB264 vs. IMMU-132, 56.3 h vs. 15.5 h). At the same dose, SKB264’s exposure in tumor tissue was 4.6-fold higher than that of IMMU-132.ConclusionsCompared with IMMU-132, the longer half-life of SKB264 had a stronger targeting effect and better antitumor activity, suggesting the better therapeutic potential of SKB264 for treating TROP2-positive tumors.

Isatis indigotica is a popular herbal medicine with its noticeable antiviral properties, which are primarily due to its lignan glycosides such as lariciresinol-4-O-β-D-glucoside and lariciresinol-4,4′-bis-O-β-D-glucosides (also called clemastanin B). UDP-glucose-dependent glycosyltransferases are the key enzymes involved in the biosynthesis of these antiviral metabolites. In this study, we systematically characterized the UGT72 family gene IiUGT1 and two UGT71B family genes, IiUGT4 and IiUGT71B5a, with similar enzymatic functions. Kinetic analysis showed that IiUGT4 was more efficient than IiUGT1 or IiUGT71B5a for the glycosylation of lariciresinol. Further knock-down and overexpression of these IiUGTs in I. indigotica’s hairy roots indicates that they play different roles in planta: IiUGT71B5a primarily participates in the biosynthesis of coniferin not pinoresinol diglucoside, and IiUGT1 primarily participates in the biosynthesis of pinoresinol diglucoside, while IiUGT4 is responsible for the glycosylation of lariciresinol and plays a dominant role in the biosynthesis of lariciresinol glycosides in I. indigotica. Analysis of the molecular docking and site-mutagenesis of IiUGT4 have found that key residues for its catalytic activity are H373, W376, E397, and that F151 could be associated with substrate preference. This study elucidates the biosynthetic route of anti-viral lignan glycosides in I. indigotica, and provides the foundation for the production of anti-viral lignan glycosides via synthetic biology under the heterologous model.

Abstract Ran (Ras-related nuclear protein) plays several important roles in nucleo-cytoplasmic transport, mitotic spindle formation, nuclear envelope/nuclear pore complex assembly, and other functions in the cytoplasm, as well as in cellular transformation when switched on. Unlike other members of the GTPase superfamily, Ran binds more tightly to GDP than to GTP due to the presence of an auto-inhibitory C-terminal tail. Multiple missense mutations in the C-terminus of Ran occur in cancers, but their biological significance remains unclear. Here, the quantitative GDP/GTP binding preference of four engineered mutations with unstable C-termini was analyzed using a devised mant-GDP dissociation assay. The results showed that the impact of different C-terminal mutations depends on multiple factors. Although these mutants were more GTP-loaded in human cells, they were shown to be more cytoplasmic, and to support nuclear transport with minimally or partially reduced efficiency. Further, several Ran cancer mutants were compromised in autoinhibition, slightly more GTP-bound, more cytoplasmic, and enhanced the proliferation of A549 and HeLa cells in vitro. Thus, our work reveals a new route of Ran activation independent of guanine nucleotide exchange factor (GEF), which may account for the hyper-proliferation induced by Ran cancer mutations.

Objective: To investigate the pyroptosis-inducing effects of celastrol on tumor cells and to explore the potential mechanisms involved, specifically focusing on the role of the caspase-3/gasdermin E (GSDME) signaling pathway and the impact of endoplasmic reticulum (ER) stress and autophagy. Methods: Necrostatin-1 (Nec-1), lactate dehydrogenase release (LDH) assay, and Hoechst/propidium iodide (PI) double staining were employed to validate the mode of cell death. Western blot was used to detect the cleavage of GSDME and the expression of light chain 3 (LC3) and BIP. Results: Celastrol induced cell swelling with large bubbles, which is consistent with the pyroptotic phenotype. Moreover, treatment with celastrol induced GSDME cleavage, indicating the activation of GSDME-mediated pyroptosis. GSDME knockout via CRISPR/Cas9 blocked the pyroptotic morphology of celastrol in HeLa cells. In addition, cleavage of GSDME was attenuated by a specific caspase-3 inhibitor in celastrol-treated cells, suggesting that GSDME activation was induced by caspase-3. Mechanistically, celastrol induced endoplasmic reticulum (ER) stress and autophagy in HeLa cells, and other ER stress inducers produced effects consistent with those of celastrol. Conclusion: These findings suggest that celastrol triggers caspase-3/GSDME-dependent pyroptosis via activation of ER stress, which may shed light on the potential antitumor clinical applications of celastrol.

The influence of gut microbiota on transient receptor potential (TRP) channels has been identified as an important element in the development of gastrointestinal conditions, yet its involvement in cancer progression is not as thoroughly understood. This review explores the multifaceted roles of TRP channels in oncogenesis and emphasizes their significance in cancer progression and therapeutic outcomes. Critical focus was placed on the influence of traditional medicines, such as traditional Chinese medicine (TCM) related aromatic medicines, on TRP channel functions. Moreover, we explored the interplay between the gut microbiota and TRP channels in cancer signaling, highlighting the therapeutic potential of targeting this axis in cancer treatment. The impact of current therapies on TRP channel function was examined, demonstrating the need for a comprehensive understanding of how different modalities affect TRP channels in cancer. Technological advancements, including artificial intelligence (AI) tools and computer-aided drug development (CADD), have been discussed in the context of leveraging TRP channels for innovative cancer therapies. Future directions emphasize the potential applications of TRP channel research in advancing cancer treatment and enhancing patients' well-being.

ObjectivePatient education is an important part of ankylosing spondylitis (AS) management. Effective patient education should be targeted at specific priorities and needs of the patients. However, the educational needs of patients with AS in China have not been systematically explored. The purpose of this study was to assess the level of educational needs and analyze associated factors in patients with AS in China.MethodsThis multicenter cross-sectional study was conducted at five hospitals in China. The Chinese version of the Educational Needs Assessment Tool (ENAT) was used to measure educational needs. Disease activity and physical function were assessed using the Bath Ankylosing Spondylitis Functional Index (BASFI) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Multiple linear regression analysis was used to identify the predictors of educational needs.ResultsThis study included 163 patients with AS. The mean ENAT score was 86.25 (31.64). Patients wanted to know more about the arthritis process, self-help measures, and treatments. Multiple linear regression analysis indicated that younger age, being female, higher disease activity, and no family history of AS (p

NQO1 is a FAD containing NAD(P)H-dependent oxidoreductase that catalyzes the reduction of quinones and related substrates, which plays an important role in the treatment of non-small cell lung cancer (NSCLC). Based on the indolequinone structure from 5-methoxy-2-methylindole, the indolequinone of NQO1 agonists was first coupled with amino-evodiamine derivatives by esterification reaction, and sixteen new compounds targeting NQO1 were developed. Among them, compounds 11b and 12d (IC50 = 2.72 or 3.66 µM, respectively) were showed better activity by cytotoxicity assay than the reference drug EVO (IC50 = 19.65 µM). Furthermore, the results of flow cytometry analysis showed that compounds 11b and 12d promoted apoptosis in A549 cells, blocked the cell cycle to the G2/M stage and caused a burst of reactive oxygen species. Western blotting experiments revealed that compounds 11b and 12d, after 24 h of treatment in A549 cells, downregulate the expression of Keap1 while upregulating the expression of Nrf2, NQO1, and HO-1. This suggests that compounds 11b and 12d increase cellular antioxidant capacity by regulating the Keap1/Nrf2/NQO1 antioxidant pathway. In vivo anti-tumor experiments showed that the reference drugs EVO (TGI = 15.94 %) and 5-Fu (TGI = 27.54 %) inhibited the proliferation of tumor tissue, while compound 11b could better inhibit the proliferation of tumor tissue (TGI = 39.13 %). In conclusion, our research results suggest that compounds 11b and 12d are potent agonism of the NQO1 signaling pathway and provide a potential opportunity to improve the treatment of NSCLC.

Hepatitis C virus (HCV) can cause a range of kidney diseases. HCV is the primary cause of mixed cryoglobulinaemia, which leads to cryoglobulinaemic vasculitis and cryoglobulinaemic glomerulonephritis (GN). Patients with acute cryoglobulinaemic vasculitis often exhibit acute kidney disease due to HCV infection, which typically progresses to acute kidney injury (AKI). HCV also increases the risk of chronic kidney disease (CKD) and the likelihood of developing end-stage renal disease (ESRD). Currently, direct-acting antiviral agents (DAAs) can be used to treat kidney disease at different stages. This review focuses on key findings regarding HCV and kidney disease, discusses the impact of DAAs, and highlights the need for further research and treatment.

Introduction: Human topoisomerase 1 (TOP1) is an important target of various anticancer compounds. The design and discovery of inhibitors targeting TOP1 are of great significance for the development of anticancer drugs. Evodiamine and thieno [2,3-d] pyridine hybrids show potential antitumor activity. Herein, the anti-gastric cancer activities of these hybrids were investigated.Methods: The inhibitory effects of different concentrations of ten evodiamine derivatives on the gastric cancer cell line SGC-7901 were assessed using a methyl thiazolyl tetrazolium assay. Compounds EVO-1 and EVO-6 strongly inhibited gastric cancer cell proliferation, with inhibition rates of 81.17% ± 5.08% and 80.92% ± 2.75%, respectively. To discover the relationship between the structure and activity of these two derivatives, density functional theory was used to investigate their optimized geometries, natural population charges, frontier molecular orbitals, and molecular electrostatic potentials. To clarify their anti-gastric cancer mechanisms, molecular docking, molecular dynamics simulations, and binding free energy calculations were performed against TOP1.Results: The results demonstrated that these compounds could intercalate into the cleaved DNA-binding site to form a TOP1–DNA–ligand ternary complex, and the ligand remained secure at the cleaved DNA-binding site to form a stable ternary complex. As the binding free energy of compound EVO-1 with TOP1 (−38.33 kcal·mol−1) was lower than that of compound EVO-6 (−33.25 kcal·mol−1), compound EVO-1 could be a more potent anti-gastric cancer agent than compound EVO-6.Discussion: Thus, compound EVO-1 could be a promising anti-gastric cancer drug candidate. This study may facilitate the design and development of novel TOP1 inhibitors.

The incidence and mortality of lung cancer are on the rise worldwide. However, the benefit of clinical treatment in lung cancer is limited. Owning to important sources of drug development, natural products have received constant attention around the world. Main ingredient polysaccharides in natural products have been found to have various activities in pharmacological research. In recent years, more and more scientists are looking for the effects and mechanisms of different natural product polysaccharides on lung cancer. In this review, we focus on the following aspects: First, natural product polysaccharides have been discovered to directly suppress the growth of lung cancer cells, which can be effective in limiting tumor progression. Additionally, polysaccharides have been considered to enhance immune function, which can play a pivotal role in fighting lung cancer. Lastly, polysaccharides can improve the efficacy of drugs in lung cancer treatment by regulating the gut microbiota. Overall, the research of natural product polysaccharides in the treatment of lung cancer is a promising area that has the potential to lead to new clinical treatments. With better understanding, natural product polysaccharides have the potential to become important components of future lung cancer treatments.

Background: Toxic Euphorbia kansui (EK) is employed to treat malignant ascites effusion (MAE). EK stir-fried with vinegar (VEK) has been demonstrated to reduce toxicity due to its preserved water-expelling effect. This was demonstrated to be correlated with gut microbiota. Therein, bile acids (BAs) have a bidirectional relationship with the gut microbiota. Therefore, the aim of this study is to explore whether BA-mediated gut microbiota influences the water-expelling effect of VEK against MAE.Methods: The MAE rat model was established by intraperitoneal injection of Walker-256 tumor cells. A reliable simultaneous method for the determination of 15 bile acids in rat feces using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established and applied to analyze the fecal BAs in rats treated with VEK. The screened BA was then administered to VEK-treated MAE rats. The water-expelling effect was evaluated using histopathological analysis, biochemical examination, inflammatory factors in ascites, urine volume, ascites amount, and intestinal aquaporin expression. The microbial composition was determined using 16S rRNA sequencing, and the contents of bile acids were finally measured.Results: VEK decreased the content of fecal deoxycholic acid (DCA), lithocholic acid (LCA), and taurocholic acid (TCA) while increasing the content of ursodeoxycholic acid (UDCA). VEK alleviated liver, stomach, and intestinal injuries; oxidative damage; and inflammation, which were further ameliorated with UDCA intervention. VEK alleviated MAE by increasing the fecal water content, urine volume, and AQP3 protein expression and decreasing the urine levels of Na+, K+, and Cl−. This was retained with the intervention of UDCA. UDCA and VEK regulated the BA metabolism disorder to a certain extent. Analysis of gut microbiota showed that VEK increased the abundance of Lactobacillus and decreased that of Prevotella_9 in MAE rats. The combined administration of UDCA and VEK showed a better modulation of the microbiota structure than that of VEK alone, and the effect of this administration reached closer to the reference state.Conclusion: The water-expelling effect of VEK did not directly depend on the BA-mediated gut microbiota. However, VEK and BAs had a synergistic effect on malignant ascites effusion through the regulation of the gut microbiota. These results provided a scientific basis for the reasonable usage of VEK and the novel combination treatment strategy of VEK and UDCA.

Evodiamine (EVO) is a quinazoline carboline alkaloid isolated from the fruits of the traditional Chinese herb Evodiae fructus. In the present study, we synthesized thirty EVO derivatives (9–38) with various benzenesulfonyl groups by sulfonylation of the amino group of 3-NH-EVO and thirty benzenesulfonyl chloride substituents. The results of the MTT assay showed that most of the compounds had good antitumor activity on H460, PC9, PC9/GR, H1299 and SW620 cancer cells as well as on normal LO2 cells. Among them, compounds 9, 18 and 28 were more potent than other compounds on H460 cell lines with an IC50 value of 9.1 M, 10.5 M and 9.5 M, respectively, even more potent than the positive PGMI-004A with one IC50 of 31.1 M. The enzymatic activity of representative compounds was further evaluated against phosphoglycerate mutase 1 (PGAM1). The results showed that compound 11 with an IC50 of 0.062 μM and compound 34 with an IC50 of 0.059 μM were similar to the positive drug’s IC50 of 0.052 μM. These results indicated that these compounds could be developed into potential PGAM1 inhibitors. In addition, compounds 9, 18, and 28 could induce apoptosis, block the cell cycle at the G2/M stage, lead to bursting of reactive oxygen species, and induce mitochondrial dysfunction. Overall, the present work showed that the benzenesulfonyl chloride-substituted evodiamine derivatives have good antitumor activity against tumor cells and show promise as anticancer agents.

Abstract To investigate the outcomes of the modified radial tongue-shaped flap following stepwise surgery release for treating Benson type I camptodactyly of the 5th digit. A retrospective analysis involving patients with Benson type I camptodactyly of the 5th digit was performed. A total of 8 patients with 12 affected digits were included. Extent of surgical release depended on the degree of soft tissue contracture. Skin release, subcutaneous fascial release, and flexor digitorum superficialis tenotomy were performed in all 12 digits, sliding volar plate release in 2 digits, and intrinsic tendon transfer in 1 digit. The mean total passive motion of proximal interphalangeal joint significantly increased from 32.5° ± 16° to 86.3° ± 20.4°, while mean total active motion significantly increased from 22° ± 10.5° to 73.8° ± 27.5° (P

Abstract Hypertension is a global public health problem which affects the physical and mental health of individuals. The management of hypertension is a long‐term process that requires the cooperation of both doctors and patients, and the blood pressure variability is closely related to the clinical prognosis. In recent years, the development of telemedicine has promoted better blood pressure monitoring and management for patients, as well as better medical intervention and health education for patients by medical staff. This article provides a review of remote blood pressure monitoring and management.

Mutant isocitrate dehydrogenase 1 (mIDH1) is a common driving factor in acute myeloid leukemia (AML), with the R132 mutation accounting for a high proportion. The U.S. Food and Drug Administration (FDA) approved Ivosidenib, a molecular entity that targets IDH1 with R132 mutations, as a promising therapeutic option for AML with mIDH1 in 2018. It was of concern that the occurrence of disease resistance or recurrence, attributed to the IDH1 R132C/S280F second site mutation, was observed in certain patients treated with Ivosidenib within the same year. Furthermore, it should be noted that most mIDH1 inhibitors demonstrated limited efficacy against mutations at this specific site. Therefore, there is an urgent need to investigate novel inhibitors targeting mIDH1 for combating resistance caused by IDH1 R132C/S280F mutations in AML. This study aimed to identify novel mIDH1 R132C/S280F inhibitors through an integrated strategy of combining virtual screening and dynamics simulations. First, 2000 hits were obtained through structure-based virtual screening of the COCONUT database, and hits with better scores than −10.67 kcal/mol were obtained through molecular docking. A total of 12 potential small molecule inhibitors were identified through pharmacophore modeling screening and Prime MM-GBSA. Dynamics simulations were used to study the binding modes between the positive drug and the first three hits and IDH1 carrying the R132C/S280F mutation. RMSD showed that the four dynamics simulation systems remained stable, and RMSF and Rg showed that the screened molecules have similar local flexibility and tightness to the positive drug. Finally, the lowest energy conformation, hydrogen bond analysis, and free energy decomposition results indicate that in the entire system the key residues LEU120, TRP124, TRP267, and VAL281 mainly contribute van der Waals forces to the interaction, while the key residues VAL276 and CYS379 mainly contribute electrostatic forces.

Due to the advantages such as low multi-solution, high signal-to-noise ratio, low environmental impact, high efficiency and low cost, microbial prospection for oil and gas has been accepted for petroleum exploreration. With the rapid development of high-throughput sequencing, molecular biology and bioinformatics, describing the changes of specific oil and gas indicator micro-organisms from the perspective of microbial community as a whole has become an valuable progress of microbial exploration method for the future. In this paper, soil sampling, DNA extraction and analysis, discriminant model development and favorable area prediction are introduced, and soil DNA extraction as well as oil/gas indicator micro-organism detection are emphasized. With the study of industrial-grade DNA extraction technology, Griffth method has been considered as the best effect for the extraction and purification of soil microbial DNA. For projects with a large sample number, high-throughput pipetting workstations and commercial multi-well plate DNA extraction kits can greatly improve working efficiency. Integrated stable isotope probes and the molecular detection of high-throughput sequencing showed that the main hydrocarbon indicator microorganism strains typically imply the expected distribution. High frequency oil indicator bacteria (AMNR) are Arthrobacter, Mycobacterium, Nocardia, and Rhodospirillum, while high frequency gas indicator bacteria include Methylococcus, Methylobacterium, and Methylocystis. The preliminary application in the Hangjinqi area shows that the microbial molecular exploration technology can significantly improve the oil and gas identification accuracy in loess tableland regions, and has a good effect on the evaluation of oil and gas bearing property, which provides a reference for the selection of favorable tight gas regions in the northern part of Ordos Basin.

BackgroundThe impact of using invasive coronary angiography (ICA) or coronary computed tomography angiography (CCTA) as an initial examination on the incidence of major adverse cardiovascular events (MACEs) in patients with stable coronary artery disease and the occurrence of major operation-related complications is uncertain.ObjectiveThis study aimed to explore the effects of ICA vs. CCTA on MACEs, all-cause death, and major operation-related complications.MethodsA systematic search of electronic databases (PubMed and Embase) was conducted for randomized controlled trials and observational studies comparing MACEs between ICA and CCTA from January 2012 to May 2022. The primary outcome measure was analyzed using a random-effects model as a pooled odds ratio (OR). The main observations were MACEs, all-cause death, and major operation-related complications.ResultsA total of six studies, comprising 26,548 patients, met the inclusion criteria (ICA n = 8,472; CCTA n = 18,076). There were statistically significant differences between ICA and CCTA for MACE [OR 1.37; 95% confidence interval (CI), 1.06–1.77; p = 0.02], all-cause death (OR 1.56; 95% CI, 1.38–1.78; p

Abstract Background Functional exercises is very essential to the recovery of patients with fracture. We aimed to evaluate the compliance of functional exercises in school-age children with limb fracture, to provide evidence to the clinical management and nursing care of children with limb fracture. Methods School-age children with limb fractures treated in our hospital from January 1, 2020 to June 30, 2021 were selected. The characteristics and postoperative functional exercise compliance of included children were analyzed. Pearson correlation and Logistic regression analysis were conducted to analyze the influencing factors of compliance to functional exercises. Results A total of 328 children with limb fracture were included, the incidence of compliance to functional exercise was only 35.98%. Pearson correlation analysis showed that age(r = 0.707), only child of family(r = 0.537), guardians(r = 0.642) and type of temperament(r = 0.635) were correlated with compliance to functional exercises in school-age children with limb fractures (all p

Isocitrate dehydrogenase (IDH) is the key metabolic enzyme that catalyzes the conversion of isocitrate to α-ketoglutarate (α-KG). Two main types of IDH1 and IDH2 are present in humans. In recent years, mutations in IDH have been observed in several tumors, including glioma, acute myeloid leukemia, and chondrosarcoma. Among them, the frequency of IDH1 mutations is higher than IDH2. IDH1 mutations have been shown to increase the conversion of α-KG to 2-hydroxyglutarate (2-HG). IDH1 mutation-mediated accumulation of 2-HG leads to epigenetic dysregulation, altering gene expression, and impairing cell differentiation. A rapidly emerging therapeutic approach is through the development of small molecule inhibitors targeting mutant IDH1 (mIDH1), as evidenced by the recently approved of the first selective IDH1 mutant inhibitor AG-120 (ivosidenib) for the treatment of IDH1-mutated AML. This review will focus on mIDH1 as a therapeutic target and provide an update on IDH1 mutant inhibitors in development and clinical trials.