Mechanism Analysis of Antimicrobial Peptide NoPv1 Related to Potato Late Blight through a Computer-Aided Study.

Phytophthora infestans (Mont.) de Bary, the oomycotic pathogen responsible for potato late blight, is the most devastating disease of potato production. The primary pesticides used to control oomycosis are phenyl amide fungicides, which cause environmental pollution and toxic residues harmful to both human and animal health. To address this, an antimicrobial peptide, NoPv1, has been screened to target Plasmopara viticola cellulose synthase 2 (PvCesA2) to inhibit the growth of Phytophthora infestans (P. infestans). In this study, we employed AlphaFold2 to predict the three-dimensional structure of PvCesA2 along with NoPv peptides. Subsequently, utilizing computational methods, we dissected the interaction mechanism between PvCesA2 and these peptides. Based on this analysis, we performed a saturation mutation of NoPv1 and successfully obtained the double mutants DP1 and DP2 with a higher affinity for PvCesA2. Meanwhile, dynamics simulations revealed that both DP1 and DP2 utilize a mechanism akin to the barrel-stave model for penetrating the cell membrane. Furthermore, the predicted results showed that the antimicrobial activity of DP1 was superior to that of NoPv1 without being toxic to human cells. These findings may offer insights for advancing the development of eco-friendly pesticides targeting various oomycete diseases, including late blight.

Effect of Feeding Level on Growth and Slaughter Performance, and Allometric Growth of Tissues and Organs in Female Growing Saanen Dairy Goats.

This study aimed to investigate the effect of feeding level on the growth and slaughter performance, and allometric growth of tissues and organs in female growing dairy goats. The trial included 10-20 and 20-30 kg weight stages with 48 female goat kids. The 24 goat kids in each stage were divided into 8 blocks based on weight, with 3 kids per block. Then, three kids from each block were randomly assigned to one of the three treatments, namely ad libitum (AL100), 70% of ad libitum (AL70), or 40% of ad libitum (AL40). The slaughter trial was conducted when the AL100 kids reached the target weight of 20 or 30 kg. The results showed that the ADG and feed conversion rate showed a linear decline as the feed level decreased (p < 0.05). Compared with the AL70 and AL100 groups, the AL40 group exhibited lower shrunk body weight, empty body weight, hot carcass weight, net meat rate, carcass meat rate, and visceral fat weight (p < 0.05) in both stages. Moreover, the AL40 group showed lower weights for skin and mohair, blood, rumen, small intestine, large intestine, mammary gland, and uterus than the AL70 and AL100 groups (p < 0.05) in both stages. However, feeding level did not affect organ indices in the two stages (p > 0.05). The bone, skin and mohair were isometric (b ≈ 1), but the muscle, visceral fat, and most internal organs were positive (b > 1) in both stages. In conclusion, feeding level affects the growth and development of dairy goats, which vary depending on the body weight stage and specific tissues and organs.

Enlarged tumour-draining lymph node with immune-activated profile predict favourable survival in non-metastatic colorectal cancer.

BACKGROUND: The tumour-draining lymph node (TDLN) plays a pivotal role in the suppression of malignant tumour, however, the immunological profile and prognostic differences between large TDLN (L-TDLN) and small TDLN (S-TDLN) in colorectal cancer (CRC) remain unclear. METHODS: We conducted a study using data from the Chinese National Cancer Center (CNCC) database, identifying 837 CRC patients with non-metastatic TDLN, and categorised them into L-TDLN and S-TDLN groups. The long-term survival outcomes and adjuvant therapy efficacy were compared between the two groups. Furthermore, we evaluated the differences in immune activation status and immune cell subsets between patients in L-TDLN and S-TDLN groups by RNA sequencing and immunohistochemical (IHC) staining. RESULTS: Patients with L-TDLN demonstrated better long-term outcomes compared to those with S-TDLN. Among patients with L-TDLN, there was no significant difference in long-term outcomes between those who received adjuvant chemotherapy and those who did not. The RNA sequencing data revealed a wealth of immune-activating pathways explored in L-TDLN. Furthermore, IHC analysis demonstrated higher numbers of CD3+ and CD8 + T cells in L-TDLN and the corresponding CRC lesions, as compared to patients with S-TDLN. CONCLUSION: Enlarged TDLN exhibited an activated anti-tumour immune profile and may serve as an indicator for favourable survival in non-metastatic CRC.

Development and validation of an artificial intelligence prediction model and a survival risk stratification for lung metastasis in colorectal cancer from highly imbalanced data: A multicenter retrospective study.

BACKGROUND: To assist clinicians with diagnosis and optimal treatment decision-making, we attempted to develop and validate an artificial intelligence prediction model for lung metastasis (LM) in colorectal cancer (CRC) patients. METHODS: The clinicopathological characteristics of 46037 CRC patients from the Surveillance, Epidemiology, and End Results (SEER) database and 2779 CRC patients from a multi-center external validation set were collected retrospectively. After feature selection by univariate and multivariate analyses, six machine learning (ML) models, including logistic regression, K-nearest neighbor, support vector machine, decision tree, random forest, and balanced random forest (BRF), were developed and validated for the LM prediction. In addition, stratified LM patients by risk score were utilized for survival analysis. RESULTS: Extremely low rates of LM with 2.59% and 4.50% were present in the development and validation set. As the imbalanced learning strategy, the BRF model with an Area under the receiver operating characteristic curve (AUC) of 0.874 and an average precision (AP) of 0.184 performed best compares with other models and clinical predictor. Patients with LM in the high-risk group had significantly poorer survival (P＜0.001) and failed to benefit from resection (P = 0.125). CONCLUSIONS: In summary, we have utilized the BRF algorithm to develop an effective, non-invasive, and practical model for predicting LM in CRC patients based on highly imbalanced datasets. In addition, we have implemented a novel approach to stratify the survival risk of CRC patients with LM based the output of the model.

Optimal examined lymph node number for accurate staging and long-term survival in rectal cancer: a population-based study.

BACKGROUND: Although the recommended minimal examined lymph node (ELN) number in rectal cancer (RC) is 12, this standard remains controversial because of insufficient evidence. We aimed to refine this definition by quantifying the relationship between ELN number, stage migration and long-term survival in RC. METHODS: Data from a Chinese multi-institutional registry (2009-2018) and the Surveillance, Epidemiology, and End Results (SEER) database (2008-2017) on stages I-III resected RC were analysed to determine the relationship between ELN count, stage migration, and overall survival (OS) using multivariable models. The series of odds ratios (ORs) for negative-to-positive node stage migration and hazard ratios (HRs) for survival with more ELNs were fitted using a Locally Weighted Scatterplot Smoothing (LOWESS) smoother, and structural breakpoints were determined using the Chow test. The relationship between ELN and survival was evaluated on a continuous scale using restricted cubic splines (RCS). RESULTS: The distribution of ELN count between the Chinese registry ( n =7694) and SEER database ( n =21 332) was similar. With increasing ELN count, both cohorts exhibited significant proportional increases from node-negative to node-positive disease (SEER, OR, 1.012, P <0.001; Chinese registry, OR, 1.016, P =0.014) and serial improvements in OS (SEER: HR, 0.982; Chinese registry: HR, 0.975; both P <0.001) after controlling for confounders. Cut-point analysis showed an optimal threshold ELN count of 15, which was validated in the two cohorts, with the ability to properly discriminate probabilities of survival. CONCLUSIONS: A higher ELN count is associated with more precise nodal staging and better survival. Our results robustly conclude that 15 ELNs are the optimal cut-off point for evaluating the quality of lymph node examination and stratification of prognosis.

The tumor characteristics, treatment strategy, and prognosis in colorectal cancer patients with synchronous liver metastasis in China and the USA.

PURPOSE: This study performed an analysis of clinicopathological characteristics, surgical treatment strategy, and survival for CRC patients with LM between China and the USA. METHODS: The CRC patients with simultaneous LM were identified from the Surveillance, Epidemiology, and End Results (SEER) registry and the Chinese National Cancer Center (CNCC) database from 2010 to 2017. We assessed 3-year cancer-specific survival (CSS) according to surgical treatment strategy and time period. RESULTS: Differences in patient age, gender, primary tumor location, tumor grade, tumor histology, and tumor stage were observed between the USA and China. Compared to the USA, a larger proportion of patients in China underwent both primary site resection (PSR) and hepatic resection (HR) (35.1% vs 15.6%, P < 0.001), and fewer patients underwent only PSR in China (29.1% vs 45.1%, P < 0.001). From 2010 to 2017, the proportion of patient who underwent both PSR and HR has increased from 13.9% to 17.4% in the USA and from 25.4% to 39.4% in China. The 3-year CSS were increasing over time in both the USA and China. The 3-year CSS of patients receiving HR and PSR were significantly higher than those receiving only PSR and patients treated with no surgery in the USA and China. There were no significant differences of 3-year CSS between the USA and China after adjustment (P = 0.237). CONCLUSIONS: Despite the distinctions of tumor characteristics and surgical strategy in patients with LM between the USA and China, increased adoption of HR has contributed to the profound improvements of survival during recent decade.

Prognostic impact of increased lymph node yield in colorectal cancer patients with synchronous liver metastasis: a population-based retrospective study of the US database and a Chinese registry.

BACKGROUND: The National Quality Forum has endorsed at least 12 lymph node yield (LNY) as a surgical quality indicator in colorectal cancer (CRC), but the prognostic value of adequate lymphadenectomy has rarely been investigated for CRC patients with distant metastatic disease. METHODS: A total of 4575 CRC patients with synchronous liver metastasis who underwent primary tumor resection were identified from a Chinese registry and the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2017. The Kaplan-Meier methods and Cox regression models were performed to assess the correlations between LNY and 3-year cancer-specific survival (CSS). Propensity score matching were used to confirmed the survival comparison between patients with less than 12 and of at least 12 LNY. RESULTS: The retrieval of at least 12 LNY was identified in most CRC patients (SEER database, 3380/3899, 86.7%; Chinese cohort, 565/676, 83.6%). In both the SEER database and the Chinese cohort, the patients with LNY ≥12 was significantly associated with better CSS compared with patients with LNY <12 before and after propensity score matching, with all P -value less than 0.05. After controlling for the confounders, multivariate analysis demonstrated that LNY was also an independent prognostic factor for patients with distant metastasis in both cohorts. In subgroup analysis, the CSS benefit for patients with LNY ≥12 was observed across most of the subgroups. CONCLUSIONS: Clinical feasibility of the 12-node threshold as a guideline quality metric of cancer care for CRC patients is necessary, and an oncologically adequate lymphadenectomy is still a critical component of high-quality surgical standard in CRC patients with distant metastases.

An easy-to-use artificial intelligence preoperative lymph node metastasis predictor (LN-MASTER) in rectal cancer based on a privacy-preserving computing platform: multicenter retrospective cohort study.

BACKGROUND: Although the surgical treatment strategy for rectal cancer (RC) is usually based on the preoperative diagnosis of lymph node metastasis (LNM), the accurate diagnosis of LNM has been a clinical challenge. In this study, we developed machine learning (ML) models to predict the LNM status before surgery based on a privacy-preserving computing platform (PPCP) and created a web tool to help clinicians with treatment-based decision-making in RC patients. PATIENTS AND METHODS: A total of 6578 RC patients were enrolled in this study. ML models, including logistic regression, support vector machine, extreme gradient boosting (XGB), and random forest, were used to establish the prediction models. The areas under the receiver operating characteristic curves (AUCs) were calculated to compare the accuracy of the ML models with the US guidelines and clinical diagnosis of LNM. Last, model establishment and validation were performed in the PPCP without the exchange of raw data among different institutions. RESULTS: LNM was detected in 1006 (35.3%), 252 (35.3%), 581 (32.9%), and 342 (27.4%) RC patients in the training, test, and external validation sets 1 and 2, respectively. The XGB model identified the optimal model with an AUC of 0.84 [95% confidence interval (CI), 0.83-0.86] compared with the logistic regression model (AUC, 0.76; 95% CI, 0.74-0.78), random forest model (AUC, 0.82; 95% CI, 0.81-0.84), and support vector machine model (AUC, 0.79; 95% CI, 0.78-0.81). Furthermore, the XGB model showed higher accuracy than the predictive factors of the US guidelines and clinical diagnosis. The predictive XGB model was embedded in a web tool (named LN-MASTER) to predict the LNM status for RC. CONCLUSION: The proposed easy-to-use model showed good performance for LNM prediction, and the web tool can help clinicians make treatment-based decisions for patients with RC. Furthermore, PPCP enables state-of-the-art model development despite the limited local data availability.

Dietary medium-chain fatty acid and Bacillus in combination alleviate weaning stress of piglets by regulating intestinal microbiota and barrier function.

The present study evaluated the effects of dietary medium-chain fatty acid (MCFA) and Bacillus on growth performance, nutrient digestibility, antioxidant capacity, colonic fermentation, and microbiota of weaning piglets. A total of 400 weaned piglets were randomly divided into 4 treatments, with 10 replicates per treatment and 10 pigs per replicate. The treatment included: basal diet (control, CON), basal diet with 0.588 g/kg MCFA (MCF), basal diet with 1.3 × 109 CFU/kg Bacillus (BAC), and basal diet with 0.588 g/kg MCFA and 1.3 × 109 CFU/kg Bacillus (SYN). Compared with CON group, the average daily gain of MCF and SYN in the early (1 to 9 d) and whole stage (1 to 36 d) of trail were improved (P < 0.05), the feed to gain ratio of MCF in later (10 to 36 d) and whole stage of trial were decreased (P < 0.05), and the diarrhea rate of SYN in the early stage (1 to 9 d) of trial decreased (P < 0.05). The digestibility of dry matter, ether extract, acid detergent fiber digestibility of MCF were decreased (P < 0.05) compared with CON. The serum d-lactic acid in MCF, BAC, and SYN were lower (P < 0.05) compared with CON group. Compared with CON group, the contents of total antioxidant capacity, superoxide dismutase, and glutathione peroxidase were greater (P < 0.05), whereas the content of malondialdehyde and the contents of colonic isobutyrate and isovalerate were lower (P < 0.05) in MCF. The microbial Shannon and Simpson diversity was lower in MCF (P < 0.05) than that in BAC and SYN. The relative abundance of Prevotella was greater (P < 0.05), whereas the Treponema and Oscillibacter were lower (P < 0.05) in MCF than that in BAC and SYN. In addition, the metabolic pathways of bacteria such as pentose phosphate pathway, adenosine nucleotides degradation II were enhanced (P < 0.05), whereas the pathways such as incomplete reductive TCA cycle, and TCA cycle IV (2-oxoglutarate decarboxylase) were decreased (P < 0.05) in MCF compared with BAC. The results indicated that dietary MCFA and Bacillus in combination improved the intestinal barrier function of piglets by changing the intestinal microbiota and its metabolic function, and finally alleviated the diarrhea rate in early weaning stage and improved growth performance in whole trial period. In addition, MCFA was effective in improving feed efficiency and antioxidant capacity of piglets.

Weaning is the most stressful stage in the growth of piglets. Weaning stress can reduce the feed intake of piglets, cause diarrhea and even death of piglets, and finally result in economic losses to livestock production. To alleviate the weaning stress of piglets after the prohibition of antibiotics in feed, this study evaluated the effect and mechanism of medium-chain fatty acid (MCFA) and Bacillus in combination on regulating the intestinal microbiota balance and health status of weaned piglets. It was found that dietary MCFA and Bacillus in combination improved the intestinal barrier function of piglets by changing the intestinal microbial community and metabolic pathway encoded by bacteria, and finally alleviated the diarrhea rate in the early weaning stage and improved the growth performance in whole trial period. In addition, MCFA was effective in improving feed efficiency and antioxidant capacity of piglets.

Long-term oncologic outcomes of natural orifice specimen extraction surgery versus conventional laparoscopic-assisted resection in the treatment of rectal cancer: a propensity-score matching study.

BACKGROUND: Natural orifice specimen extraction surgery (NOSES) has been increasingly applied in radical surgery of abdominal and pelvic organs, but it is still in the exploratory stage. There is insufficient evidence to prove its efficacy. METHODS: From January 2013 to June 2017, a total of 351 patients diagnosed with rectal cancer were eventually included in this study. Patients who underwent NOSES were assigned to the NOSES group, while patients undergoing conventional laparoscopic assisted resection were assigned as to the LAP group. Propensity score matching was used to align clinicopathological features between the two groups. RESULTS: From the perioperative data and postoperative follow-up results of both groups, patients in the NOSES group had less intraoperative bleeding (47.0 ± 60.4 ml vs 87.1 ± 101.2 ml, P = 0.011), shorter postoperative gastrointestinal recovery (50.7 ± 27.3 h vs 58.6 ± 28.5 h, P = 0.040), less postoperative analgesic use (36.8% vs 52.8%, P = 0.019), lower postoperative pain scores (P < 0.001), lower rate of postoperative complications (5.7% vs 15.5%, P = 0.020), more satisfaction with body image (P = 0.001) and cosmesis (P < 0.001) postoperatively. The NOSES group had a higher quality of life. Moreover, there was no significant difference in overall survival (OS) and disease-free survival (DFS) between the two groups. CONCLUSION: NOSES could be a safe and reliable technique for radical resection of rectal cancer, with better short-term outcomes than conventional laparoscopy, while long-term survival is not significantly different from that of conventional laparoscopic surgery.

The effect of tillage systems on phosphorus distribution and forms in rhizosphere and non-rhizosphere soil under maize (Zea mays L.) in Northeast China.

An appropriate tillage method must be implemented by maize growers to improve phosphorus dynamics in the soil in order to increase phosphorus uptake by plant. The objective of this study was to investigate the effects of tillage systems on phosphorus and its fractions in rhizosphere and non-rhizosphere soils under maize. An experimental field was established, with phosphate fertilizers applied to four treatment plots: continuous rotary tillage (CR), continuous no-tillage (CN), plowing-rotary tillage (PR), and plowing-no tillage (PN). Under the different tillage methods, the available P was increased in the non-rhizosphere region. However, the concentration of available P was reduced in the rhizosphere soil region. The soil available P decreased with the age of the crop until the maize reached physiological maturity. The non-rhizosphere region had 132.9%, 82.5%, 259.8%, and 148.4% more available P than the rhizosphere region under the CR, PR, CN, and PN treatments, respectively. The continuous no-tillage method (CN) improved the uptake of soil phosphate by maize. The concentrations of Ca2-P, Ca8-P, Fe-P, Al-P and O-P at the maturity stage were significantly lower than other seedling stages. However, there was no significant relationship between total P and the P fractions. Therefore, a continuous no-tillage method (CN) can be used by farmers to improve phosphorus availability for spring maize. Soil management practices minimizing soil disturbance can be used to impove phosphorus availability for maize roots, increase alkaline phosphatase activity in the rhizosphere soil and increase the abundance of different phosphorus fractions.

Research progress on the pathogenesis of microvascular neuropathy in diabetic retinopathy / 国际眼科杂志(Guoji Yanke Zazhi)

Diabetic retinopathy is one of the common and serious microvascular complications of diabetes. In foreign countries, DR is the leading cause of blindness in the working age group (20 - 64 years). In China, the incidence of DR and the rate of blindness increase year by year, which seriously affects the patients' quality of life. Previous studies on the pathogenesis and treatment of diabetic retinopathy were mainly focused on the microvascular; in recent years, with the deepening of researches, more and more scholars believe that DR is no longer simply a kind of microangiopathy, but is also accompanied by retinal neurodegeneration. However, studies on the pathogenesis of microvascular disease and neurodegenerative changes of diabetic retinopathy in the literature domestic and abroad are mostly single. This article reviews the relationship between microvascular disease and neurodegenerative changes in diabetic retinopathy.

Effect of intravitreal injection of conbercept on diabetic diffuse macular edema / 眼科新进展

Objective To investigate the effects of intravitreal injection of conbercept on diffuse macular edema (DME) of diabetes mellitus.Methods Together 51 diabetic patients (51 eyes) with diffuse macular edema were collected between July 2016 to July 2017,and randomly divided into three groups (n =17):group A,in which patients received solely intravitreal injection of 0.5 mg conbercept,group B,those who was intravitreally injected with 0.5 mg of conbercept and modified macular grating photocoagulation,and group C,patients undergoing modified grid photocoagulation (GPG).Then,before treatment and 1 week,1 month,3 months and 6 months after treatment,all patients were examined by optical coherence tomography for determining central macular thickness (CMT),followed by fundus fluorescein angiography (FFA),the best corrected visual acuity (BCVA),slit lamp,intraocular pressure for compare the efficacy and safety of the three procedures.Results All the three treatments improved BCVA,CMT,retinal neovascularization (RNV) leakage in diffuse DME patients,but group A and B were better than group C (both P ＜ 0.05),while there was no significant difference in BCVA improvement between A and B group (P ＞ 0.05),whereas the improvement in CMT of group B patients was better than that of group A [(197.47 ±45.26) μm vs.(205.59 ± 47.33) μm] (P ＜ 0.001),and this was true of RNV leakage [(9.91 ±3.18)mm vs.(13.24 ±4.87) rnm] (P＜0.001),without related complications.Conclusion Combination of modified macular grid photocoagulation and intravitreal injection of conbercept can quickly relieve diabetic macular edema and alleviate neovascularization,thus improving the patients' vision acuity,of which the efficacy is superior to the pure modified macular grid photocoagulation and conbercept injection.

Mechanisms of Cd and Cr removal and tolerance by macrofungus Pleurotus ostreatus HAU-2.

Fungi bioaccumulation is a novel and highly promising approach to remediate polluted soil. The present study revealed a high ability to tolerate Cd and Cr in the fungus Pleurotus ostreatus HAU-2. However, high concentrations of Cd and Cr can suppress fungal growth and result in a variation of hypha micromorphology. Batch experiments were performed to investigate Cd and Cr stress effects on the amount of active oxygen in fungi, activity of antioxidant enzyme, as well as the removal efficiency of Cd and Cr. The results revealed that Cd and Cr caused increasing active oxygen and malonaldehyde (MDA) concentrations. Antioxidant enzymes play a central role in removing active oxygen, while glutathione (GSH) aids the Cd detoxification within cells. In fluid culture, fungal removal rates of Cd and Cr ranged from 44.85% to 80.36% and 14.49% to 45.55%, respectively. Intracellular accumulation and extracellular adsorption were the major removal approaches. Bag cultivation testing indicated that the fungus absorbed Cd and Cr contained within soil. In particular, the accumulation ability of Cd (15.6mgkg-1) was higher compared to that of Cr (8.9mgkg-1). These results successfully establish P. ostreatus HAU-2 as promising candidate for the remediation of heavy-metal polluted soils.