Impact and potential value of immunosenescence on solid gastrointestinal tumors.

Solid gastrointestinal tumors often respond poorly to immunotherapy for the complex tumor microenvironment (TME), which is exacerbated by immune system alterations. Immunosenescence is the process of increased diversification of immune genes due to aging and other factors, leading to a decrease in the recognition function of the immune system. This process involves immune organs, immune cells, and the senescence-associated secretory phenotype (SASP). The most fundamental change is DNA damage, resulting in TME remodeling. The main manifestations are worsening inflammation, increased immunosuppressive SASP production, decreased immune cell antitumor activity, and the accumulation of tumor-associated fibroblasts and myeloid-derived suppressor cells, making antitumor therapy less effective. Senotherapy strategies to remove senescent cells and block key senescence processes can have synergistic effects with other treatments. This review focuses on immunoenescence and its impact on the solid TME. We characterize the immunosenescent TME and discuss future directions for antitumor therapies targeting senescence.

Neoadjuvant chemoradiation therapy combined with immunotherapy for microsatellite stable ultra-low rectal cancer (CHOICE II): study protocol of a multicentre prospective randomised clinical trial.

INTRODUCTION: Neoadjuvant chemoradiotherapy (nCRT) could bring tumour shrinking and downstaging and increase the probability of organ preservation for patients with low rectal cancer. But for ultra-low rectal cancer, there is little possibility for organ preservation. Immunotherapy has been shown to have significant survival benefits in microsatellite instability-high patients but poor response in microsatellite stable (MSS) patients. Studies have demonstrated that radiotherapy and immunotherapy have synergistic effects in cancer treatment. There is no existing evidence about the clinical efficacy of immunotherapy combined with nCRT for patients with MSS ultra-low rectal cancer. METHOD AND ANALYSIS: This trial is an open-labelled multicentre prospective randomised controlled trial (NCT05215379) with two parallel groups and allocation ratio 1:1 (nCRT+immunotherapy vs nCRT group). Eligible participants will be aged 18-75 years, with a desire for anus preservation, confirmed cT1-3aN0-1M0 rectal adenocarcinoma, confirmed MSS type, inferior margin of ≤5 cm from the anal verge. The primary endpoint of this trial is complete clinical response (cCR) rate. Immunotherapy is added after 1 week of chemoradiotherapy for two cycles, and then the patients will be administered two cycles of immunotherapy and CAPOX. The evaluations will be carried out after the completion of the whole neoadjuvant therapy. We expect the programme to improve the cCR rate and the quality of life for patients with ultra-low rectal cancer. ETHICS AND DISSEMINATION: This trial was approved by the Ethics committee of Changhai Hospital and other medical centres (Grant number:CHEC2022-118). The results of this study will provide further insight into the clinical efficacy of immunotherapy in combination with nCRT in patients with MSS ultra-low rectal cancer. TRIAL REGISTRATION NUMBER: NCT05215379.

Object-level complete coverage path planning for excavators in earthwork construction.

Autonomous excavators are gradually gaining attention because they can reduce the waste of human resources and improve the efficiency. This study proposed a complete coverage path planning algorithm for autonomous excavators based on the Rotating Calipers Path Planning (RCPP) algorithm, which called the Excavator-Rotating Calipers Path Planning (E-RCPP) algorithm. This study uses boustrophedon cellular decomposition (BCD) to decompose the construction area to obtain the convex and non-convex sub-areas without obstacles, and describes a non-decomposition principle to determine whether to decompose non-convex areas that are difficult to plan. To obtain the optimal path, an adaptive spacing adjustment model which is used to adjust the spacing between parallel paths is designed. To improve the coverage rate at the corner, this study proposed a novel boundary corner turning method. The algorithm's cost function considers the path length, the number of turns, the coverage rate and the overlap rate. The Digital Orthophoto Map (DOM) of the construction area is created by Unmanned Aerial Vehicle (UAV) and cropped into three polygonal areas, the 2D top-views of the them are used for simulation experiments to verify the performance of E-RCPP algorithm, the results show that the E-RCPP algorithm has better performance when applied to the complete coverage path planning for excavator compared with the traditional RCPP algorithm.

Single-cell sequencing technology in colorectal cancer: a new technology to disclose the tumor heterogeneity and target precise treatment.

Colorectal Cancer (CRC) is one of the most common gastrointestinal tumors, and its high tumor heterogeneity makes traditional sequencing methods incapable of obtaining information about the heterogeneity of individual cancer cells in CRC. Therefore, single-cell sequencing technology can be applied to better analyze the differences in genetic and protein information between cells, to obtain genomic sequence information of single cells, and to more thoroughly analyze the cellular characteristics and interactions in the CRC microenvironment. This will provide a more comprehensive understanding of colorectal cancer development and metastasis and indicate the treatment plan and prognosis. In this study, we review the application of single-cell sequencing to analyze the tumor microenvironment of CRC, explore the mechanisms involved in CRC metastasis and progression, and provide a reference for potential treatment options.

Deep Neural Networks Based on Span Association Prediction for Emotion-Cause Pair Extraction.

The emotion-cause pair extraction task is a fine-grained task in text sentiment analysis, which aims to extract all emotions and their underlying causes in a document. Recent studies have addressed the emotion-cause pair extraction task in a step-by-step manner, i.e., the two subtasks of emotion extraction and cause extraction are completed first, followed by the pairing task of emotion-cause pairs. However, this fail to deal well with the potential relationship between the two subtasks and the extraction task of emotion-cause pairs. At the same time, the grammatical information contained in the document itself is ignored. To address the above issues, we propose a deep neural network based on span association prediction for the task of emotion-cause pair extraction, exploiting general grammatical conventions to span-encode sentences. We use the span association pairing method to obtain candidate emotion-cause pairs, and establish a multi-dimensional information interaction mechanism to screen candidate emotion-cause pairs. Experimental results on a quasi-baseline corpus show that our model can accurately extract potential emotion-cause pairs and outperform existing baselines.

Distribution and diversity of filamentous bacteria in wastewater treatment plants exhibiting foaming of Taihu Lake Basin, China.

Foaming caused by filamentous bacteria in activated sludge (AS) is a common phenomenon in municipal wastewater treatment plants (WWTPs) in Taihu Lake Basin of South China. In this study, total bacterial and filamentous bacterial communities were comprehensively characterized in AS and foams from eight municipal WWTPs by high-throughput sequencing technology. Results showed that alpha diversities of total bacterial communities in foams were obviously lower than those in AS samples. The bacterial community structures were significantly different between WWTPs rather than sample types (AS vs. foam). For most WWTPs, the Actinobacteria phylum was highly enriched in foams and the most abundant genera in foams were common mycolata. Sixteen filamentous bacteria were identified against the improved bulking and foaming bacteria (BFB) database. Abundance and composition of BFB in different WWTPs and different sample types were significantly different. 'Nostocoida limicola' I Trichococcus and Microthrix were generally dominant in AS samples. The dominant BFB in foams were associated with Microthrix, Skermania, Gordonia, and Mycobacterium. A new Defluviicoccus spp. in cluster III was identified in severe and continuous foams. Moreover, dominant BFB in stable and continuous foams with light level in one typical WWTP were diverse, even, and dynamic. Bacterial co-occurrence network analysis implied that the bacterial community of AS was more sensitive to disturbance than that of foam.

Contrasting distribution of antibiotic resistance genes and microbial communities in suspended activated sludge versus attached biofilms in an integrated fixed film activated sludge (IFAS) system.

Suspended activated sludge (AS) and carrier-attached biofilms simultaneously exist in an integrated fixed film activated sludge (IFAS) system. However, the differentiation of antibiotic resistance genes (ARGs) and microbial communities in different types of biofilms is rarely reported. In this study, successions of ARGs and microbial communities of AS and two types of suspended carrier-attached biofilms over seasons were investigated in the IFAS system of one municipal wastewater treatment plant. Results showed that substantial differences were found in the distribution pattern of ARGs, bacterial communities, and predicted microbial function between AS and attached biofilms. The relative abundances of all detected ARGs in AS were significantly higher than those in attached biofilms. ARGs with higher relative abundances generally existed in K3 carrier (surface area ≥ 800 m2/m3) attached biofilms than those in K1 carrier (surface area ≥ 450 m2/m3) biofilms. The relative abundances of ARGs were negatively correlated with temperature and biochemical oxygen demand (BOD5) and positively correlated with ammonium nitrogen contents for AS but not for attached biofilms. No significant relationship was found between the extracellular polymeric substance (EPS) content and ARG abundance for all samples. Temperature, BOD5, and ammonium nitrogen contents were closely connected to microbial communities. The Bray-Curtis distance of bacterial communities between two adjacent sampling seasons for AS was larger than those of two attached biofilms. Network analysis indicated that the AS network had more positive links and intense connections than the attached biofilm networks, potentially facilitating the dissemination of ARGs. The differential distribution of ARGs among the three types of samples was significantly correlated with the microbial co-occurrence network topological properties. Bray-Curtis distance and network analysis suggest that microbial community is more robust in attached biofilms than in suspended AS. This work provides a more in-depth understanding of ARGs and microbial community distributions in wastewater biofilms.

[Estimating glomerular filtration rate based on serum cystatin C].

OBJECTIVE: To develop an estimating formula for glomerular filtration Rate (GFR) based on serum cystatin C in patients with chronic kidney disease (CKD). METHODS: Clinical characteristics of 242 CKD patients were collected. The patients were randomly divided into modeling group and model validation group. The rGFR obtained from 99mTc-DTPA clearance rate was used as a reference value of GFR. s-cystatin C was detected by latex enhanced immunoturbidimetric method. Preliminary linear regression analysis followed by multiple linear regression were performed to investigate the association between s-cystatin C and rGFR. The validity of the estimation formula was tested in the model validation group in comparison with Hoek formula and Orebro formula. RESULTS: With standardised countdown conversion, s-cystatin showed linear correlation with rGFR, with a correlation coefficient of 0.773. The multiple correlation coefficient, determination coefficient, adjusted R square and std. error of the estimation model were 0.863, 0.745, 0.742, and 0.207, respectively. The residuals P-P probability plot analysis showed that the model residuals fitted into normal distribution with homogeneity of variance. Theeformula was: eGFR = 67/s-cystatin C +3. No significant difference was found between the distribution of eGFR and rGFR. Our formula had an accuracy of 30% and 50%, which were no less than those obtained from Hoek formula and Orebro formula. The new formula also had acceptable bias and high precision. The Bland-Altman analysis and ROC curve analysis showed good applicability of the new formula. CONCLUSION: The GFR prediction formula we established has a good prediction performance as comparised with other formulae, which could be used in measuring GFR in CKD patients.

[Source of variations of serum urea levels and consideration of reference interval in urban Chengdu].

OBJECTIVE: To determine the serum Urea levels in healthy adults living in urban Chengdu and to identify factors that influence the serum urea levels for the purpose of establishing reference interval. METHODS: Serum urea levels were determined in 17 787 healthy adults in urban Chengdu who underwent physical examinations. The characteristics of distribution of serum urea levels in the population and its relationships with liver function, renal function, serum glucose, and serum lipid were analyzed. RESULTS: Increased Crea, Uric, Glu, and HDL-C levels and decreased Glb level were associated with increased serum urea levels, which was independent of the impact of sex and age. The association between serum urea and Crea, Glu, and HDL-C existed in normal healthy adults. Men had higher urea levels than women. Regardless of gender, serum urea increased with age (with a cut off point at 30, 50, 60 and 70 years). CONCLUSION: Serum urea levels in healthy adults living in urban Chengdu vary in different gender and age groups. Serum urea levels are associated with serum Crea, Glu, the HDL-C levels. It is necessary to establish gender and age-specific reference intervals for serum urea.

[Bacterial conversion of sulfur-and phosphorous-compounds and microbial diversity in sediments from a near-shore marine-cultural region].

The H2S-producing bacteria and the phosphorous-cycling bacteria in sediments from near-shore marine-cultural region were investigated. Results indicate that the bacterial H2S production in aerobic condition is the dominating process to produce H2S in the sediment of cultural pond. The total counts of H2S-producing bacteria utilizing cysteine and Na2S2O3 were 1.6 x 10(6) and 4.35 x 10(3) cells g(-1) respectively. The counts of sulfate-reducing bacteria in the sediments were very little, only 2.5 x 10(1) g(-1). Further results show that the bacterial counts of decomposing lecithin and secreting phosphatase were 2.17 x 10(5) and 1.21 x 10(6) g(-1) respectively, bacterial counts of dissolving Ca3PO4 were 6.96 x 10(3) g(-1). Traditional taxonomy and partial 16S rRNA gene sequencing on the H2S-producing and phosphate-cycling bacteria indicate that most isolates could be classified as members of the following Genera: Bacillus, Halobacillus, Microbacterium, etc.

[Comparison of hepatic protein synthesis function between Banna Minipig Inbred Line and human].

OBJECTIVE: This is a research aimed at comparing the hepatic protein synthesis function of Banna Minipig Inbred Line (BMI) with that of human so as to evaluate the possibility of porcine liver replacement of human counterpart. METHODS: The venous blood samples from BMI and volunteer participants were collected. The albumin and total protein in the separated sera were tested using Beckman delta CX7 autoanalyzer, and serum protein electrophoresis was performed. RESULTS: No significant differences in albumin and in the percentage and concentration of globulins synthesized in liver (alpha1-, alpha2- and beta-globulin) between BMI and human were observed. The percentage and concentration of gamma-globulin synthesized in the lymphocytes of BMI were significantly higher than those of human. CONCLUSION: The above findings suggested the similarity between BMI liver and human liver in respect to albumin and alpha, beta-globulin synthesis.

[A study on the protective efficacy of yisheng injection against IRI in pig renal-transplant model and the mechanism therein involved].

OBJECTIVE: To inquire into the mechanism of the protective efficacy of Yisheng injection against ischemia/reperfusion injury(IRI) in pig renal-transplant model. METHODS: A total of 24 Chinese Sichuan White Pigs (SWPs) (2-3 months old, 17.5 +/- 4.6 kg, with clear family background) were used. 6 pairs of SWPs with better results of tissue typing were allocated to the group of renal allotransplantation. The other SWPs were subjected to renal autotransplantation. Yisheng injection was added into the preservative fluid and injected intravenously after transplantation in the test groups against IRI. We detected the SWPs' liver and kidney functions and serum superoxide dismutase(SOD) and malondialdehyde(MDA) concentrations after transplantation. RESULTS: Serum creatinine and urea levels increased in 2 days after operation and then returned to normal in both groups except the pigs suffering from acute tubular necrosis or acute rejection. The concentrations of serum MDA, SOD began to increase 2 days after operation (P < 0.05). Less increase of serum MDA, less decrease of NO and more increase of SOD in test groups were detected, compared with those in control groups (P < 0.05). CONCLUSION: Yisheng injection has protective efficacy against IRI and hence may have an application foreground.

[The lipid peroxidation mechanism initiated by ischemia-reperfusion injury during renal transplantation].

OBJECTIVE: To explore the mechanism of acute ischemia-reperfusion injury (IRI) to renal-transplant METHODS: A total of 12 Chinese Sichuan White Pigs (SWPs) (2-3 months old, 17.5 +/- 4.6 kg, with clear family background) were used. 3 pairs of them with better tissue typing were subjected to renal allotransplantation. The other SWPs were allocated to renal autotransplantation. We assessed the SWPs' kidney function, serum superoxide dismutase (SOD) and malonaldehyde (MDA) after transplantation so as to shed light on the possible mechanism of IRI and to find out good detecting methods which could monitor IRI. RESULTS: Serum creatinine and urea increased in 2 days of postoperation and then returned to normal in both groups except the pigs that suffered from acute tubular necrosis or acute rejection. The concentrations of serum MDA and SOD began to increase 2 days after operation (P < 0.05). More increase of serum MDA and less increase of SOD were detected in renal allotransplant groups than in renal autotransplant groups (P < 0.05). The concentration of serum SOD and MDA were correlated (r = 0.961). CONCLUSION: IRI could initiate lipid peroxidation. IRI could be a single factor or be synergistic with immunologic factors to injure the transplanted organs.