Expression and function of VISTA on myeloid cells.

V-domain containing Ig Suppressor of T cell Activation (VISTA) is predominantly expressed on myeloid cells and functions as a ligand/receptor/soluble molecule. In inflammatory responses and immune responses, VISTA regulates multiple functions of myeloid cells, such as chemotaxis, phagocytosis, T cell activation. Since inflammation and immune responses are critical in many diseases, VISTA is a promising therapeutic target. In this review, we will describe the expression and function of VISTA on different myeloid cells, including neutrophils, monocytes, macrophages, dendritic cells (DCs), myeloid-derived suppressor cells (MDSCs). In addition, we will discuss whether the functions of VISTA on these cells impact the disease processing.

Prediction of compressive strength of concrete based on improved artificial bee colony-multilayer perceptron algorithm.

There are many factors that affect the compressive strength of concrete. The relationship between compressive strength and these factors is a complex nonlinear problem. Empirical formulas commonly used to predict the compressive strength of concrete are based on summarizing experimental data of several different mix proportions and curing periods, and their generality is poor. This article proposes an improved artificial bee colony algorithm (IABC) and a multilayer perceptron (MLP) coupled model for predicting the compressive strength of concrete. To address the shortcomings of the basic artificial bee colony algorithm, such as easily falling into local optima and slow convergence speed, this article introduces a Gaussian mutation operator into the basic artificial bee colony algorithm to optimize the initial honey source position and designs an MLP neural network model based on the improved artificial bee colony algorithm (IABC-MLP). Compared with traditional strength prediction models, the ABC-MLP model can better capture the nonlinear relationship of the compressive strength of concrete and achieve higher prediction accuracy when considering the compound effect of multiple factors. The IABC-MLP model built in this study is compared with the ABC-MLP and particle swarm optimization (PSO) coupling algorithms. The research shows that IABC can significantly improve the training and prediction accuracy of MLP. Compared with the ABC-MLP and PSO-MLP coupling models, the training accuracy of the IABC-MLP model is increased by 1.6% and 4.5%, respectively. This model is also compared with common individual learning algorithms such as MLP, decision tree (DT), support vector machine regression (SVR), and random forest algorithms (RF). Based on the comparison of prediction results, the proposed method shows excellent performance in all indicators and demonstrates the superiority of heuristic algorithms in predicting the compressive strength of concrete.

Evaluation of Laparoscopic Colorectal Resection Among Elderly Individuals With Colorectal Malignancy: A Single-center Retrospective Analysis.

OBJECTIVE: The purpose of the current study was to statistically clarify the precise risk age in elderly patients undergoing colorectal surgery and to evaluate the safety and efficacy of laparoscopic colorectal resection in these patients. METHODS: Patients' clinical variables were extracted from the database of the Gastrointestinal Surgery Centre, Third Affiliated Hospital of Sun Yat-sen University, from 2015 to 2019. Logistic regression was conducted to identify independent risk factors of postoperative complications and ORs for each age. Curves of odds ratios (ORs) and CIs for each age were fitted by using a locally weighted scatterplot smoother, and a structural breakpoint was determined by the Chow test to identify a precise cutoff risk age for elderly patients. Comparison and subgroup analysis were conducted between surgical approach groups using the Student ttest and χ2 analysis. RESULTS: Locally weighted scatterplot smoother OR analysis manifested that patients aged 69 years old or older suffered a higher possibility of postoperative complications and should be defined as high-risk age. Comparison according to the high-risk age revealed laparoscopic colorectal surgery is better than laparotomic surgery for elderly individuals in terms of hospital stay (9.46 ± 5.96 vs 15.01 ± 6.34, P< 0.05), the incidence of intensive care unit transfer (4 vs 20, P< 0.05), and incidence of surgical site infection (15 vs 20, P< 0.05). Patients who underwent laparotomic surgery had a greater prevalence of Clavien-Dindo II/III complications (P< 0.05). These findings remained stable even after propensity matching. Furthermore, such superiority was proved especially significant for patients who underwent left-side colorectal resection. In addition, overall survival was improved in the laparoscopic surgery group, whereas no differences were observed in disease-free survival. CONCLUSION: In our study population, age 69 or older was a cutoff point age suggests a higher possibility of postoperative morbidity after colorectal surgery. Laparoscopic colorectal resection should be regarded as a superior therapeutic choice for these elderly individuals, especially for left-side colorectal surgeries.

Metagenomic insights into the toxicity of carbamazepine to functional microorganisms in sludge anaerobic digestion.

Contaminants of emerging concern (CECs) contained in sludge, such as carbamazepine, may be toxic to microorganisms and affect the biogenesis of methane during anaerobic digestion. In this study, different scales of anaerobic digesters were constructed to investigate the inhibitory effect of carbamazepine. Results showed that carbamazepine reduced methane production by 11.3 % and 62.1 % at concentrations of 0.4 and 2 mg/g TS, respectively. Carbamazepine hindered the dissolution of organic matter and the degradation of protein. Carbamazepine inhibited some fermentative bacteria, especially uncultured Aminicenantales, whose abundance decreased by 9.5-93.4 % under carbamazepine stress. It is worth noting that most prior studies investigated the effects of CECs only based on well-known microorganisms, ignoring the metabolisms of uncultured microorganisms. Genome-predicted metabolic potential suggested that 54 uncultured metagenome-assembled genomes (MAGs) associated with acidogenesis or acetogenesis. Therein, uncultured Aminicenantales related MAGs were proved to be acetogenic fermenters, their significant reduction may be an important reason for the decrease of methane production under carbamazepine stress. The toxicity of carbamazepine to microorganisms was mainly related to the overproduction of reactive oxygen species. This study elucidates the inhibition mechanism of carbamazepine and emphasizes the indispensable role of uncultured microorganisms in anaerobic digestion.

A near-infrared fluorescent probe for detecting hydrazine metabolized from isoniazid in living cells.

Isoniazid is a drug for treating tuberculosis, but hydrazine (N2 H4 ), the major metabolite of isoniazid, can cause hepatotoxicity. Therefore, monitoring the content of N2 H4 in time is of great significance for studying the hepatotoxicity induced by isoniazid. In this study, a near-infrared fluorescent probe (BC-N) was designed and synthesized based on the specific reaction of acetyl ester with N2 H4 . BC-N exhibits excellent selectivity, sensitivity, and biocompatibility. In addition, BC-N is applied in the visualization of N2 H4 produced from isoniazid in living cells and is a potential tool for monitoring hepatotoxicity induced by isoniazid.

Dysfunction of DMT1 and miR-135b in the gut-testis axis in high-fat diet male mice.

BACKGROUND: Obese patients have been found to be susceptible to iron deficiency, and malabsorption of dietary iron is the cause of obesity-related iron deficiency (ORID). Divalent metal transporter 1 (DMT1) and ferroportin (FPN), are two transmembrane transporter proteins expressed in the duodenum that are closely associated with iron absorption. However, there have been few studies on the association between these two proteins and the increased susceptibility to iron deficiency in obese patients. Chronic inflammation is also thought to be a cause of obesity-related iron deficiency, and both conditions can have an impact on spermatogenesis and impair male reproductive function. Based on previous studies, transgenerational epigenetic inheritance through gametes was observed in obesity. RESULTS: Our results  showed that obese mice had decreased blood iron levels (p < 0.01), lower protein and mRNA expression for duodenal DMT1 (p < 0.05), but no statistically significant variation in mRNA expression for duodenal FPN (p > 0.05); there was an increase in sperm miR-135b expression (p < 0.05). Bioinformatics revealed ninety overlapping genes and further analysis showed that they were primarily responsible for epithelial cilium movement, fatty acid beta-oxidation, protein dephosphorylation, fertilization, and glutamine transport, which are closely related to spermatogenesis, sperm development, and sperm viability in mice. CONCLUSIONS: In obese mice, we observed downregulation of DMT1 in the duodenum and upregulation of miR-135b in the spermatozoa.

Paternal high-fat diet altered H3K36me3 pattern of pre-implantation embryos.

The global transition towards diets high in calories has contributed to 2.1 billion people becoming overweight, or obese, which damages male reproduction and harms offspring. Recently, more and more studies have shown that paternal exposure to stress closely affects the health of offspring in an intergenerational and transgenerational way. SET Domain Containing 2 (SETD2), a key epigenetic gene, is highly conserved among species, is a crucial methyltransferase for converting histone 3 lysine 36 dimethylation (H3K36me2) into histone 3 lysine 36 trimethylation (H3K36me3), and plays an important regulator in the response to stress. In this study, we compared patterns of SETD2 expression and the H3K36me3 pattern in pre-implantation embryos derived from normal or obese mice induced by high diet. The results showed that SETD2 mRNA was significantly higher in the high-fat diet (HFD) group than the control diet (CD) group at the 2-cell, 4-cell, 8-cell, and 16-cell stages, and at the morula and blastocyst stages. The relative levels of H3K36me3 in the HFD group at the 2-cell, 4-cell, 8-cell, 16-cell, morula stage, and blastocyst stage were significantly higher than in the CD group. These results indicated that dietary changes in parental generation (F0) male mice fed a HFD were traceable in SETD2/H3K36me3 in embryos, and that a paternal high-fat diet brings about adverse effects for offspring that might be related to SETD2/H3K36me3, which throws new light on the effect of paternal obesity on offspring from an epigenetic perspective.

Overexpression of Corin Ameliorates Kidney Fibrosis through Inhibition of Wnt/ß-Catenin Signaling in Mice.

The Wnt/ß-catenin pathway represents a promising therapeutic target for mitigating kidney fibrosis. Corin possesses the homologous ligand binding site [Frizzled-cysteine-rich domain (Fz-CRD)] similar to Frizzled proteins, which act as receptors for Wnt. The Fz-CRD has been found in eight different proteins, all of which, except for corin, are known to bind Wnt and regulate its signal transmission. We hypothesized that corin may inhibit the Wnt/ß-catenin signaling pathway and thereby reduce fibrogenesis. Reduced expression of corin along with the increased activity of Wnt/ß-catenin signaling was found in unilateral ureteral obstruction (UUO) and ureteral ischemia/reperfusion injury (UIRI) models. In vitro, corin bound to the Wnt1 through its Fz-CRDs and inhibit the Wnt1 function responsible for activating ß-catenin. Transforming growth factor-ß1 inhibited corin expression, accompanied by activation of ß-catenin; conversely, overexpression of corin attenuated the fibrotic effects of transforming growth factor-ß1. In vivo, adenovirus-mediated overexpression of corin attenuated the progression of fibrosis, which was potentially associated with the inhibition of Wnt/ß-catenin signaling and the down-regulation of its target genes after UUO and UIRI. These results suggest that corin acts as an antagonist that protects the kidney from pathogenic Wnt/ß-catenin signaling and from fibrosis following UUO and UIRI.

The synergistic regulation of sewage sludge biodrying and greenhouse gas reduction by additives.

As a dewatering method of high moisture solid waste sludge, biodrying still faces environmental problems such as material loss and greenhouse gas emission in the process of treatment. In this study, biochar and magnesium chloride were used to explore the synergistic effect of enhancing sludge biodrying and reducing greenhouse gas emissions. The highest temperature of biodrying was raised to 68.2 °C within 3 days, extending the longest high-temperature period to 5 days, which reduced the water content to 28.8 % in the single addition of biochar treatment. The complex addition increased the NH4+-N content of materials by 57.49 % and decreased the NO3--N content of materials by 40.62 %. The use of additives significantly reduced the emissions of CO2, CH4, and N2O compared to the no-addition treatment. The increase in dominant Actinomycetes and Chloroflexibacter was the main reason for the reduction in gas emissions.

Osteogenic effect of magnesium oxychloride cement modified with phytic acid and loaded with strontium ranelate.

BACKGROUND: Magnesium oxychloride cement has good mechanical properties, but poor water resistance. METHODS: Phytic acid, which can form chelate with Mg2+, was used to modify magnesium oxychloride cement, and the effects of phytic acid on the strength, in vitro degradation and biological activity of magnesium oxychloride cement were studied. Based on the preparation of phytic acid modified magnesium oxychloride cement with good water resistance and biological activity, osteoporosis treatment strontium ranelate was loaded on phytic acid- magnesium oxychloride cement, strontium ranelate/phytic acid-magnesium oxychloride cement was prepared. RESULTS: It was found that the compressive strength of 1.25 wt% phytic acid-magnesium oxychloride cement after soaking in SBF for 28 d could reach 40.5 ± 2.0 MPa, 13.33% higher than that of the control group (when phytic acid was 0 wt%), and the mass loss rate of all ages was lower than that of the control group. The water resistance of magnesium oxychloride cement was effectively improved by phytic acid. After loading with strontium ranelate, the water resistance of 1.25 wt% phytic acid-magnesium oxychloride cement was improved. Cell experiments showed that strontium ranelate could effectively promote cell proliferation and improve the expression of osteoblast-related proteins. When strontium ranelate/phytic acid-magnesium oxychloride cement samples were implanted subcutaneously in rats for 4 w, no obvious inflammatory response was observed, and the material was tightly bound to the surrounding tissues. When bone cement was implanted into rat femur for 4 w, the bone cement was gradually wrapped and absorbed by new bone tissue, which grew from the outside to the inside, indicating that the bone cement containing strontium ranelate/phytic acid-magnesium oxychloride cement had excellent bone-forming ability. CONCLUSIONS: In conclusion, the results indicated that strontium ranelate/phytic acid-magnesium oxychloride cement composite bone cement had a potential application prospect in clinical bone repair.

Effects of resveratrol on DLD and NDUFB9 decrease in frozen semen of Mongolian sheep.

Mongolian sheep are a breed of sheep in China known for their excellent cold and drought resistance. Sperm from Mongolian sheep are often cryopreserved to improve breeding outcomes. However, cryopreservation of sperm often results in issues such as reduced vitality and altered morphology. Therefore, the objective of this study was to investigate the impact of the cryoprotectant resveratrol on frozen sperm from Mongolian sheep, specifically examining its effects on key proteins during cryopreservation. In this study, sperm samples were obtained from three adult Mongolian rams and processed through semen centrifugation. The sperm motility parameters of Fresh Sperm Group (FR), Resveratrol added before freezing group (FF-Res), Resveratrol-free frozen sperm group (FT), and Resveratrol added after freeze-thawing group (FA-Res) were determined. The tandem mass tags (TMT) peptide labeling combined with LC-MS/MS was used for proteomic analysis of the total proteins in FR and FT groups. A total of 2651 proteins were identified, among which 41 proteins were upregulated and 48 proteins were downregulated after freezing. In-depth bioinformatics analysis of differentially abundant proteins (DAPs) revealed their close association with the tricarboxylic acid cycle (TCA) and oxidative phosphorylation pathway. The energy-related protein dihydrolipoamide dehydrogenase (DLD) and the reactive oxygen species (ROS)-related protein NADH dehydrogenase 1 beta subcomplex subunit 9 (NDUFB9) exhibited significant decreases, indicating their potential role as key proteins contributing to reduced sperm vitality. The study demonstrated that the addition of resveratrol (RES) to semen could elevate the expression levels of DLD and NDUFB9 proteins. This study represents the pioneering proteomic analysis of Mongolian ram sperm before and after cryopreservation, establishing the significance of DLD and NDUFB9 as key proteins influencing the decline in vitality following cryopreservation of Mongolian ram sperm. These findings clarify that resveratrol can enhance the levels of DLD and NDUFB9 proteins in cryopreserved Mongolian ram sperm, consequently enhancing their vitality.

Efficient removal of per- and polyfluoroalkyl substances from biochar composites: Cyclic adsorption and spent regenerant degradation.

In order to solve the problem of efficient desorption of per- and polyfluoroalkyl substances (PFAS) and regeneration of adsorbents, a novel biochar composite was prepared based on the quaternary ammonium groups and hydrophobicity of sulfobetaine polymer, which can be used for the efficient removal of various PFASs and has great regeneration ability. Through adsorption, regeneration and degradation experiment, the comprehensive effect of the novel biochar composite on the whole process of removal of PFAS was systematically investigated. The results showed that the maximum adsorption capacity of PFOS, PFOA, PFBS, and PFBA reached 634 mg/g, 536 mg/g, 301 mg/g and 264 mg/g, respectively. The adsorption process involved hydrophobicity, electrostatic, pore diffusion and complexation. The NaI + NaOH solution was used at 50 °C to achieve efficient regeneration of the adsorbent, which can be recycled more than 4 times. When the vacuum-ultraviolet (VUV)/sulfite reduction system was used for deep degradation of the regenerated solution, the effect of hydrated electrons on PFAS was enhanced due to the inclusion of NaI and NaOH in the regeneration reagent, resulting in an increase in the degradation efficiency (89.1%-99.9%) and defluorination efficiency (63.3%-84.1%). Based on the performance of BC-P(SB-co-AM) and the treatment efficiency of PFAS, the design idea of the whole process treatment technology of PFAS proposed in this work is expected to hold great promise in environmental applications. This work provides a novel idea and system for the efficient adsorption removal and desorption of PFAS, and subsequent deep degradation.

Ultrasound Treatment Improves Fruit Quality of Postharvest Blood Oranges (Citrus sinensis L. Osbeck): Anthocyanin Enrichment and Its Biosynthesis.

This study was to investigate the effects of different nonthermal treatments on quality attributes, anthocyanin profiles, and gene expressions related to anthocyanin biosynthesis during low-temperature storage, including pulsed light (PL), magnetic energy (ME), and ultrasound (US). Among these treatments, 1 min US treatment was the most effective method for improving fruit quality and increasing total anthocyanin contents (by 29.89 ± 3.32%) as well as individual anthocyanins during low-temperature storage of 28 days. This treatment resulted in high color intensity, intact cellular architectures, and positive sensory evaluation. In contrast, PL and ME treatments displayed negative effects on quality improvement, leading to the destruction of cell architectures and inhibiting anthocyanin levels. Furthermore, qPCR analysis revealed that the structural genes (C4H, CHS1, CHS2, CHI, F3H, ANS, and GST) related to anthocyanin biosynthesis and transport were the target genes and upregulated in response to the cavitation effect of US treatment.

Variation Pattern of the Elastic Modulus of Concrete under Combined Humidity and Heat Conditions.

The coupling effect of moisture content and temperature on the elastic modulus of concrete is experimentally investigated. The elastic modulus of dry concrete exhibits a clear temperature-weakening effect, while the elastic modulus of wet concrete exhibits a water-strengthening effect at room temperature. Under humidity-heat conditions, the elastic modulus of wet concrete declines with the temperature rise. When the temperature is 20 °C, 200 °C, 400 °C, 520 °C, and 620 °C, the humidity-heat coupling factors of the elastic modulus change rate DI˙F with moisture content are 0.08, 0.07, 0.04, 0.01, and -0.03, respectively, and the declining rate increases with the rise of moisture content. The relation between the humidity-heat coupling factor DIF, moisture content, and temperature was established; The equivalent relation between the water-strengthening effect and the temperature-weakening effect of the elastic modulus was obtained. The temperature range of the strengthening effect and "apparent weakening effect" of water stored inside concrete before heating on elastic modulus was determined; The evolutionary mechanism of the competition between the microcrack expansion and healing of concrete under combined humidity and heat conditions was revealed.

Single-cell RNA sequencing identifies critical transcription factors of tumor cell invasion induced by hypoxia microenvironment in glioblastoma.

Rationale: Glioblastoma (GBM) is an aggressive malignant primary brain cancer with poor survival. Hypoxia is a hallmark of GBM, which promotes tumor cells spreading (invasion) into the healthy brain tissue. Methods: To better elucidate the influence of hypoxia on GBM invasion, we proposed a data-driven modeling framework for predicting cellular hypoxia (CHPF) by integrating single cell transcriptome profiling and hypoxia gene signatures. Results: We characterized the hypoxia status landscape of GBM cells and observed that hypoxic cells were only present in the tumor core. Then, by investigating the cell-cell communication between immune cells and tumor cells, we discovered significant interaction between macrophages and tumor cells in hypoxic microenvironment. Notably, we dissected the functional heterogeneity of tumor cells and identified a hypoxic subpopulation that had highly invasive potential. By constructing cell status specific gene regulatory networks, we further identified 14 critical regulators of tumor invasion induced by hypoxic microenvironment. Finally, we confirmed that knocking down two critical regulators CEBPD and FOSL1 could reduce the invasive ability of GBM under hypoxic conditions. Additionally, we revealed the therapeutic effect of Axitinib and Entinostat through the mice model. Conclusion: Our work revealed the critical regulators in hypoxic subpopulation with high invasive potential in GBM, which may have practical implications for clinical targeted-hypoxia cancer drug therapy.

Bacillus spore germination: mechanisms, identification, and antibacterial strategies.

Bacterial spores are metabolically inactive and highly resistant to harsh environmental conditions in nature and during decontamination processes in food and related industries. However, inducing germination using specific germinants in dormant spores can convert them into vegetative cells which are metabolically active and fragile. The potential utility of a "germinate to eradicate" strategy, also known as germination-inactivation, has been validated in foods. Meanwhile, the strategy has sparked much interest in triggering and maximizing spore germination. Although many details of the spore germination process have been identified over the past decades, there remain many uncertainties, including some signal transduction mechanisms involved in germination. In addition, the successful implementation of the germination-inactivation strategy relies on the sensitive detection of germinative biomarkers within minutes of germination initiation and the optimal timing for the subsequent inactivation step. Meanwhile, the emergence of biomarkers has renewed attention to the practical application of the spore germination process. Here, this review presents the current knowledge of the germination mechanisms of Bacillus spore, influencing factors, and germination biomarkers. It also covers a detailed discussion on the development of germination-inactivation as a spore eradication strategy.

Triptolide enhances carboplatin-induced apoptosis by inhibiting nucleotide excision repair (NER) activity in melanoma.

Introduction: Carboplatin (CBP) is a DNA damaging drug used to treat various cancers, including advanced melanoma. Yet we still face low response rates and short survival due to resistance. Triptolide (TPL) is considered to have multifunctional antitumor effects and has been confirmed to enhance the cytotoxic effects of chemotherapeutic drugs. Herein, we aimed to investigate the knowledge about the effects and mechanisms for the combined application of TPL and CBP against melanoma. Methods: Melanoma cell lines and xenograft mouse model were used to uncover the antitumor effects and the underlying molecular mechanisms of the alone or combined treatment of TPL and CBP in melanoma. Cell viability, migration, invasion, apoptosis, and DNA damage were detected by conventional methods. The rate-limiting proteins of the NER pathway were quantitated using PCR and Western blot. Fluorescent reporter plasmids were used to test the NER repair capacity. Results: Our results showed that the presence of TPL in CBP treatment could selectively inhibit NER pathway activity, and TPL exerts a synergistic effect with CBP to inhibit viability, migration, invasion, and induce apoptosis of A375 and B16 cells. Moreover, combined treatment with TPL and CBP significantly inhibited tumor progression in nude mice by suppressing cell proliferation and inducing apoptosis. Discussion: This study reveals the NER inhibitor TPL which has great potential in treating melanoma, either alone or in combination with CBP.

Triglyceride-Glucose Index is Significantly Associated with the Risk of Hyperuricemia in Patients with Nonalcoholic Fatty Liver Disease.

Purpose: The triglyceride-glucose (TyG) index is a new index of insulin resistance (IR), and its association with hyperuricemia (HUA) is unclear. The aim of this study was to investigate whether TyG is an independent risk factor for hyperuricemia (HUA) in patients with nonalcoholic fatty liver disease (NAFLD). Patients and Methods: We retrospectively analyzed 461 patients with ultrasound-confirmed NAFLD and calculated the TyG index. Multivariate logistic regression was used to analyze the relationship between the TyG index and HUA in NAFLD patients. The correlation between the TyG index and HUA was further confirmed by a restricted cubic spline. Furthermore, the stability of the association between TyG index and HUA was examined using subgroup analysis. Receiver operating characteristic (ROC) curves were constructed to evaluate the predictive value of the TyG index on HUA. Multivariate linear regression was used to analyze the linear relationship between the TyG index and serum uric acid. Results: A total of 166 HUA patients and 295 non-HUA patients were included in the study. The results of multivariate logistic regression analysis showed that after controlling the confounding risk factors, TyG was still an independent risk factor for HUA (OR = 2.00, 95% CI: 1.38 -2.91, p < 0.001). Restricted cubic splines showed that HUA risk increased linearly with TyG across the entire TyG range. The ROC curve showed that TyG index was better than triglyceride in predicting HUA in NAFLD patients, with AUC values of 0.62 and 0.59, respectively. Multiple linear regression analysis showed that TyG index was significantly positively correlated with blood uric acid (B = 1.37, 95% CI: 0.67-2.08, p < 0.001). Conclusion: TyG index is an independent risk factor for HUA in patients with NAFLD. The increase of the TyG index level is closely related to the occurrence and development of HUA in patients with NAFLD.

New staging systems for left-sided colon cancer based on the number of retrieved and metastatic lymph nodes provide a more accurate prognosis.

Objectives: We aimed to explore reasonable lymph node classification strategies for left-sided colon cancer (LCC) patients. Methods: 48,425 LCC patients from 2010 to 2015 were identified in the US Surveillance, Epidemiology, and End Results database. We proposed an innovative revised nodal (rN) staging of the 8th American Joint Committee on Cancer (AJCC) Tumor/Node/Metastasis (TNM) classification based on the cut-off value of retrieved lymph nodes and survival analyses in patients with LCC. Log odds of positive lymph nodes (LODDS) stage is a numerical classification strategy obtained by a formula that incorporates the numbers of retrieved and positive lymph nodes. To develop the TrN or TLODDS classification, patients with similar survival rates were grouped by combining T and rN or LODDS stage. The TrN or TLODDS classification was further evaluated in a validation set of 12,436 LCC patients from 2016 to 2017 in the same database and a Chinese application set of 958 LCC patients. Results: We developed novel TrN and TLODDS classifications for LCC patients that incorporated 7 stages with reference to the AJCC staging system. In comparison to the 8th AJCC TNM and TrN classifications, TLODDS classification demonstrated significantly better discrimination (area under the receiver operating characteristic curve, 0.650 vs. 0.656 vs. 0.661, p < 0.001), better model-fitting (Akaike information criteria, 309,287 vs. 308,767 vs. 308,467), and superior net benefits. The predictive performance of the TrN and TLODDS classifications was further verified in the validation and application sets. Conclusion: Both the TrN and TLODDS classifications have better discriminatory ability, model-fitting, and net benefits than the existing TNM classification, and represent an alternative to the current TNM classification for LCC patients.

Accelerating carbon neutrality could help China's energy system align with below 1.5 °C.

To support the achievement of the Paris Agreement's 1.5 °C global warming threshold, China aims to peak CO2 emissions before 2030 and achieve carbon neutrality before 2060. However, the specific carbon neutrality pathway remains to be designed. By applying a refined Chinese version of Global Change Analysis Model, this study examines implications of four illustrative carbon neutrality scenarios for aligning China's energy system with below 1.5 °C by 2100. The results feature a trade-off between China's ambition to transform its energy system toward mid-century and its reliance on carbon dioxide removal (CDR) after carbon neutrality. From a full time perspective until 2100, accelerating carbon neutrality could help China's energy system align with below 1.5 °C. Compared to a 2060 carbon neutrality scenario, a 2050 carbon neutrality scenario reduces China's total mitigation costs between 2021 and 2100 by 1.04% of GDP, reduces reliance on CDR by 36%, and provides some additional co-benefits, such as reduced air pollutants. However, special attention needs to be paid to the fact that accelerating carbon neutrality poses greater challenges and costs to China in overcoming development inertia and restructuring its energy system over the next 30-40 years. Compared to a 2060 carbon neutrality scenario, a 2050 scenario increases China's mitigation costs by a factor of 1.13 between 2021 and 2050. This study suggests through quantitative evidence that China could accelerate emissions reductions and energy system transformation to achieve carbon neutrality, based on its national circumstances and capabilities and international support.