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Abstract Background and aims The impact of lipids on the overall survival (OS) of patients with malignancy has not yet been clarified. This study aimed to evaluate the effect of hyperlipidemia on the OS among Chinese patients based on Body Mass Index (BMI) stratifications and hyperlipidemia types. Method The patients in this study were derived from the Investigation of the Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) trial. Kaplan–Meier was used to draw the survival curve, and the log-rank test was used to estimate the survival rates between each group. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI). Results A total of 9054 patients were included in the final study, with a median age of 59 years, and 55.3% (5004) of them were males. Regarding types of hyperlipidemia, only low high-density lipoprotein was an independent risk factor for the prognosis of all patients (HR = 1.35, 95% CI: 1.25–1.45, P

Abstract Motivated by recent experimental observations of opposite Chern numbers in R-type twisted MoTe2 and WSe2 homobilayers, we perform large-scale density-functional-theory calculations with machine learning force fields to investigate moiré band topology across a range of twist angles in both materials. We find that the Chern numbers of the moiré frontier bands change sign as a function of twist angle, and this change is driven by the competition between moiré ferroelectricity and piezoelectricity. Our large-scale calculations, enabled by machine learning methods, reveal crucial insights into interactions across different scales in twisted bilayer systems. The interplay between atomic-level relaxation effects and moiré-scale electrostatic potential variation opens new avenues for the design of intertwined topological and correlated states, including the possibility of mimicking higher Landau level physics in the absence of magnetic field.

Abstract Background The C-reactive protein (CRP)-triglyceride-glucose (TyG) index (CTI), which is a measure representing the level of inflammation and insulin resistance (IR), is related to poor cancer prognosis; however, the CTI has not been validated in patients with cancer cachexia. Thus, this study aimed to explore the potential clinical value of the CTI in patients with cancer cachexia. Methods In this study, our prospective multicenter cohort included 1411 patients with cancer cachexia (mean age 59.45 ± 11.38, 63.3% male), which was a combined analysis of multiple cancer types. We randomly selected 30% of the patients for the internal test cohort (mean age 58.90 ± 11.22% 61.4% male). Additionally, we included 307 patients with cancer cachexia in the external validation cohort (mean age 61.16 ± 11, 58.5% male). Receiver operating characteristic (ROC) and calibration curves were performed to investigate the prognostic value of CTI. The prognostic value of the CTI was also investigated performing univariate and multivariate survival analyses. Results The survival curve indicated that the CTI showed a significant prognostic value in the total, internal, and external validation cohorts. Prognostic ROC curves and calibration curves revealed that the CTI showed good consistency in predicting the survival of patients with cancer cachexia. Multivariate survival analysis showed that an elevated CTI increased the risk of death by 22% (total cohort, 95% confidence interval [CI] = 1.13–1.33), 34% (internal test cohort, 95%CI = 1.11–1.62), and 35% (external validation cohort, 95%CI = 1.14–1.59) for each increase in the standard deviation of CTI. High CTI reliably predicted shorter survival (total cohort, hazard ratio [HR] = 1.45, 95%CI = 1.22–1.71; internal test cohort, HR = 1.62, 95%CI = 1.12–2.36; external validation cohort, HR = 1.61, 95%CI = 1.15–2.26). High CTI significantly predicted shorter survival in different tumor subgroups, such as esophageal [HR = 2.11, 95%CI = 1.05–4.21] and colorectal cancer [HR = 2.29, 95%CI = 1.42–3.71]. The mediating effects analysis found that the mediating proportions of PGSGA, ECOG PS, and EORTC QLQ-C30 on the direct effects of CTI were 21.72%, 19.63%, and 11.61%, respectively We found that there was a significant positive correlation between the CTI and 90-day [HR = 2.48, 95%CI = 1.52–4.14] and 180-day mortality [HR = 1.77,95%CI = 1.24–2.55] in patients with cancer cachexia. Conclusion The CTI can predict the short- and long-term survival of patients with cancer cachexia and provide a useful prognostic tool for clinical practice.

Abstract Background Although socioeconomic factors are important determinants of population mortality, the effect of educational level on the survival of patients with cancer in China is unclear. This study aimed to assess whether educational level is associated with the prognosis of patients with cancer and to explore the mediators of this association. Methods This multicentre cohort study included 18,251 patients diagnosed with cancer between May 2013 and December 2018. The main parameters measured were overall survival (OS) and all‐cause mortality. The relationship between educational level and all‐cause mortality was assessed using multifactor‐corrected Cox survival analysis. Logistic regression was used to analyze the association between educational level and patient‐generated subjective global assessment (PG‐SGA). Results The mean age of the 18,251 participants (men, 9939 [54.4%]) was 57.37 ± 11.66 years. Multifactorial survival analysis showed that patients survived longer with increasing education (university and above vs. elementary school and below; p = p =

Abstract Background The development and progression of cancer cachexia are connected to systemic inflammation and physical performance. However, few relevant studies have reported the survival outcomes prediction of systemic inflammation and physical performance in patients with colorectal cancer (CRC) cachexia. This study investigated the prognostic prediction value of systemic inflammation and performance status in patients with CRC cachexia. Methods This multicentre cohort study prospectively collected 905 patients with CRC (58.3% males, 59.3 ± 11.5 years old). Cancer cachexia was diagnosed according to the 2011 Fearon Cachexia Diagnostic Consensus. The prognostic value of systematic inflammatory indicators was determined using the area under the curve, concordance index, and multivariate survival analysis. Performance status was evaluated with Eastern Coopertive Oncology Group performance score (ECOG‐PS). Survival data were analysed using univariate and multivariate Cox regression analyses. Results The area under the curve, concordance index and survival analysis showed that C‐reactive protein (CRP), lymphocyte to CRP ratio (LCR) and CRP to albumin ratio (CAR) were more stable and consistent with the survival of patients with CRC, both in non‐cachexia and cachexia populations. Among patients with CRC cachexia, high inflammation [low LCR, hazard ratio (HR) 95% confidence interval (95% CI) = 3.33 (2.08–5.32); high CAR, HR (95% CI) = 2.92 (1.88–4.55); high CRP, HR (95% CI) = 3.12 (2.08–4.67)] indicated a worse prognosis, compared with non‐cachexia patients [low LCR, HR (95% CI) = 2.28 (1.65–3.16); high CAR, HR (95% CI) = 2.36 (1.71–3.25); high CRP, HR (95% CI) = 2.58 (1.85–3.60)]. Similarly, among patients with CRC cachexia, high PS [ECOG‐PS 2, HR (95% CI) = 1.61 (1.04–2.50); ECOG‐PS 3/4, HR (95% CI) = 2.91 (1.69–5.00]) indicated a worse prognosis, compared with patients with CRC without cachexia [ECOG‐PS 2, HR (95% CI) = 1.28 (0.90–1.81); ECOG‐PS 3/4, HR (95% CI) = 2.41 (1.32–4.39]). Patients with CRC cachexia with an ECOG‐PS score of 2 or 3–4 and a high inflammation had a shorter median survival time, compared with patients with an ECOG‐PS score of 0/1 and a low inflammation. Conclusions The systemic inflammatory markers LCR, CAR and CRP have stable prognostic values in patients with CRC. The ECOG‐PS may be an independent risk factor for CRC. Combined evaluation of systemic inflammation and ECOG‐PS in patients with CRC cachexia could provide a simple survival prediction.

Abstract Elimination of cancer stem cells (CSCs) and reinvigoration of antitumor immunity remain unmet challenges for cancer therapy. Tumor-associated macrophages (TAMs) constitute the prominant population of immune cells in tumor tissues, contributing to the formation of CSC niches and a suppressive immune microenvironment. Here, we report that high expression of inhibitor of differentiation 1 (ID1) in TAMs correlates with poor outcome in patients with colorectal cancer (CRC). ID1 expressing macrophages maintain cancer stemness and impede CD8+ T cell infiltration. Mechanistically, ID1 interacts with STAT1 to induce its cytoplasmic distribution and inhibits STAT1-mediated SerpinB2 and CCL4 transcription, two secretory factors responsible for cancer stemness inhibition and CD8+ T cell recruitment. Reducing ID1 expression ameliorates CRC progression and enhances tumor sensitivity to immunotherapy and chemotherapy. Collectively, our study highlights the pivotal role of ID1 in controlling the protumor phenotype of TAMs and paves the way for therapeutic targeting of ID1 in CRC.

Chinese cabbage is an economically important Brassica vegetable worldwide, and clubroot, which is caused by the soil-borne protist plant pathogen Plasmodiophora brassicae is regarded as a destructive disease to Brassica crops. Previous studies on the gene transcripts related to Chinese cabbage resistance to clubroot mainly employed RNA-seq technology, although it cannot provide accurate transcript assembly and structural information. In this study, PacBio RS II SMRT sequencing was used to generate full-length transcriptomes of mixed roots at 0, 2, 5, 8, 13, and 22 days after P. brassicae infection in the clubroot-resistant line DH40R. Overall, 39 376 high-quality isoforms and 26 270 open reading frames (ORFs) were identified from the SMRT sequencing data. Additionally, 426 annotated long noncoding RNAs (lncRNAs), 56 transcription factor (TF) families, 1 883 genes with poly(A) sites and 1 691 alternative splicing (AS) events were identified. Furthermore, 1 201 of the genes had at least one AS event in DH40R. A comparison with RNA-seq data revealed six differentially expressed AS genes (one for disease resistance and five for defensive response) that are potentially involved in P. brassicae resistance. The results of this study provide valuable resources for basic research on clubroot resistance in Chinese cabbage.

Abstract The widespread application of antiandrogen therapies has aroused a significant increase in the incidence of NEPC, a lethal form of the disease lacking efficient clinical treatments. Here we identified a cell surface receptor neurokinin-1 (NK1R) as a clinically relevant driver of treatment-related NEPC (tNEPC). NK1R expression increased in prostate cancer patients, particularly higher in metastatic prostate cancer and treatment-related NEPC, implying a relation with the progression from primary luminal adenocarcinoma toward NEPC. High NK1R level was clinically correlated with accelerated tumor recurrence and poor survival. Mechanical studies identified a regulatory element in the NK1R gene transcription ending region that was recognized by AR. AR inhibition enhanced the expression of NK1R, which mediated the PKCα-AURKA/N-Myc pathway in prostate cancer cells. Functional assays demonstrated that activation of NK1R promoted the NE transdifferentiation, cell proliferation, invasion, and enzalutamide resistance in prostate cancer cells. Targeting NK1R abrogated the NE transdifferentiation process and tumorigenicity in vitro and in vivo. These findings collectively characterized the role of NK1R in tNEPC progression and suggested NK1R as a potential therapeutic target.

Abstract Background Changes in body composition and systemic inflammation are important characteristics of cancer cachexia. This multi‐centre retrospective study aimed to explore the prognostic value of the combination of body composition and systemic inflammation in patients with cancer cachexia. Methods The modified advanced lung cancer inflammation index (mALI), which combines body composition and systemic inflammation, was defined as appendicular skeletal muscle index (ASMI) × serum albumin/neutrophil‐lymphocyte ratio. The ASMI was estimated according to a previously validated anthropometric equation. Restricted cubic splines were used to evaluate the relationship between mALI and all‐cause mortality in patients with cancer cachexia. Kaplan–Meier analysis and Cox proportional hazard regression analysis were used to evaluate the prognostic value of mALI in cancer cachexia. A receiver operator characteristic curve was used to compare the effectiveness of mALI and nutritional inflammatory indicators in predicting all‐cause mortality in patients with cancer cachexia. Results A total of 2438 patients with cancer cachexia were enrolled, including 1431 males and 1007 females. The sex‐specific optimal cut‐off values of mALI for males and females were 7.12 and 6.52, respectively. There was a non‐linear relationship between mALI and all‐cause mortality in patients with cancer cachexia. Low mALI was significantly associated with poor nutritional status, high tumour burden, and high inflammation. Patients with low mALI had significantly lower overall survival (OS) than those with high mALI (39.5% vs. 65.5%, P

Abstract Background Aging is accompanied by muscle loss. In older adults with cancer sarcopenia (OACS), systemic inflammation, reduced food intake, and reduced physical activity led to a poor prognosis. This study was to investigate the prognostic ability of the inflammatory Geriatric Nutritional Risk Index (GNRI), which combines patient's inflammation, diet status, and physical activity status to predict overall survival of OACS. Methods This prospective multi‐center study enrolled 637 OACS, with an average age of 72.78 ± 5.98 years, of which 408 (64.1%) were males. We constructed the Inflammatory Functional Prognostic Index (IFPI) of OACS based on inflammatory GNRI scores, reduced food intake, and reduced physical activity. According to the IFPI, OACS was divided into high‐, moderate‐, and low‐risk groups. Univariate and multivariate survival analyses analyzed the prognostic ability of the clinical parameters. Results Compared with OACS with a high GNRI score, the 1‐, 3‐, and 5‐year hazard ratios (95% confidence interval) of OACS with a low GNRI score was 1.816 (1.076–3.063), 1.678 (1.118–2.518), and 1.627 (1.101–2.407), respectively. This result was consistent with that of the calibration curve. The subgroup analysis showed that the low GNRI score had a significant positive relation with patients with gastrointestinal cancer (Pinteraction

Abstract To investigate the prognostic value of systemic inflammation and insulin resistance in women with breast cancer with different body mass index (BMI). This multicenter, prospective study included 514 women with breast cancer. Multivariate survival analysis showed that patients with high C-reactive protein (CRP), high CRP to albumin ratio (CAR), high lymphocyte to CRP ratio (LCR), high low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (LHR), and high triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-c) were significantly associated with worse prognosis. The mortality rate of patients with both high CAR and high LHR or both low LCR and high LHR were 3.91-fold or 3.89-fold higher than patients with both low CAR and low LHR or both high LCR and low LHR, respectively. Furthermore, the combination of LCR and LHR significantly predicted survival in patients within the high BMI group. The CRP, CAR, LCR, LHR, and TG/HDL-c were associated with poor survival in women with breast cancer. The combination of CAR and LHR or LCR and LHR could better predict the prognostic outcomes of women with breast cancer, while the combination of LCR and LHR could better predict the prognosis of those patients with overweight or obese patients.

Abstract Background Precisely predicting the short- and long-term survival of patients with cancer is important. The tumor-node-metastasis (TNM) stage can accurately predict the long-term, but not short-term, survival of cancer. Nutritional status can affect the individual status and short-term outcomes of patients with cancer. Our hypothesis was that incorporating TNM stage and nutrition-related factors into one nomogram improves the survival prediction for patients with colorectal cancer (CRC). Method This multicenter prospective primary cohort included 1373 patients with CRC, and the internal validation cohort enrolled 409 patients with CRC. Least absolute shrinkage and selection operator regression analyses were used to select prognostic indicators and develop a nomogram. The concordance (C)-index, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to assess the prognostic discriminative ability of the nomogram, TNM stage, Patient-Generated Subjective Global Assessment (PGSGA), and TNM stage + PGSGA models. The overall survival (OS) curve of risk group stratification was calculated based on the nomogram risk score. Results TNM stage, radical resection, reduced food intake, activities and function declined, and albumin were selected to develop the nomogram. The C-index and calibration plots of the nomogram showed good discrimination and consistency for CRC. Additionally, the ROC curves and DCA of the nomogram showed better survival prediction abilities in CRC than the other models. The stratification curves of the different risk groups of the different TNM categories were significantly different. Conclusion The novel nomogram showed good short- and long-term outcomes of OS in patients with CRC. This model provides a personalized and convenient prognostic prediction tool for clinical applications.

The brushless DC motor is generally used in small satellite flywheel systems due to its good control performance and structure robustness. However, its driving inverter still suffers from hard-switching that leads to higher loss and larger heatsink requirement. The resulting low power density and EMI problems have been a great challenge for the space satellite applications. This paper describes a novel auxiliary resonant commutated pole inverter (ARCPI) for driving the brushless DC motor. An inserted inductor is controlled to resonant with the buffer capacitor of the inverter’s lower arm switches; a resonant capacitor is paralleled with the inductor branch as well. Zero-current switching and zero-voltage switching conditions are therefore realized for the switches of the entire circuit. The reverse recovery problem of diodes are also avoided by zero current turning-off. The working states of the proposed novel ARCPI inverter are analyzed and the mathematical model for every state is established. Furthermore, the parameter design is discussed to provide soft-switching conditions. Finally, the proposed ARCPI inverter is applied for driving a brushless DC motor. A voltage/current double closed control loop is designed for the motor controller and the system simulation setup is built. The simulation results prove that soft-switching operation is realized for all of the switches; the proposed inverter is effective for driving brushless DC motors. Besides, the motor current fluctuation decreases by 45.7%. The motor torque and the motor speed present with good control performance as well.

Abstract Background Systemic inflammation is currently regarded as a hallmark of cancer. This study aimed to accurately clarify the prognostic value of various inflammatory markers in patients with stage IV cancer. Methods This study assessed 2,424 patients with cancer diagnosed with cancer in tumor, node, metastasis (TNM) stage IV. After evaluating the predictive value of 13 inflammatory indicators for patient prognosis using the C index, the lymphocyte C-reactive protein ratio (LCR) was selected to elucidate the prognostic and predictive values in patients with stage IV cancer. Kaplan–Meier and Cox proportional hazards regression models were used to analyze long-term survival. Results A total of 1,457 men (60.1%) and 967 women (39.9%) diagnosed with TNM stage IV cancer were enrolled. A ratio of 2,814 was defined as the optimal cut-off value for the LCR. The LCR was the most accurate prognosis predictor for patients with stage IV cancer among the 13 inflammatory nutritional markers evaluated. The multivariate-adjusted restricted cubic spline plot suggested that LCR had an L-shaped dose–response association with all-cause mortality risk. Patients with lower LCR levels tended to present with worse prognoses. Kaplan–Meier curves and log-rank test results showed that the high LCR groups (LCR ≥ 2,814) exhibited a better prognosis, whereas patients with stage IV cancer of different sex and tumor types (for example, gastrointestinal tumor, non-gastrointestinal tumor, and lung cancer) had a worse survival time. Conclusion The LCR score can be regarded as a stable and useful biomarker to predict prognosis in patients with TNM stage IV compared to other evaluated inflammation indicators.

Habitats of large herbivores have shrunk owing to the expansion of human activities. Consequently, wild herbivores frequently venture into adjacent farmlands to forage for crops. As a result, farmers use fences to prevent these herbivores from foraging. A dynamic game exists between whether farmers choose to set up fences and whether herbivores choose to venture into farmlands. This study established an evolutionary game model between farmers and herbivorous species. The effects of different factors on the game process were studied using model simulations to provide theoretical guidance for the conservation and management of herbivore species. Model simulations showed that food resources in herbivore habitats are key to protecting their populations. Therefore, management needs to restore and protect herbivore habitats, and in cases of extreme food shortages, herbivores should be artificially fed. Simultaneously, herbivores need to obtain certain food supplements from outside their habitats when food resources are scarce. Therefore, subsidies should be provided to farmers close to herbivore habitats to encourage them to use fences that allow a certain number of herbivores to pass through. In addition, increasing the buffer zone between herbivore habitats and farmland has positive implications for the conservation of large herbivore populations.

Aberrant mitophagy has been identified as a driver for energy metabolism disorder in most cardiac pathological processes. However, finding effective targeted agents and uncovering their precise modulatory mechanisms remain unconquered. Fuzi, the lateral roots of Aconitum carmichaelii, shows unique efficacy in reviving Yang for resuscitation, which has been widely used in clinics. As a main cardiotonic component of Fuzi, mesaconine has been proven effective in various cardiomyopathy models. Here, we aimed to define a previously unrevealed cardioprotective mechanism of mesaconine-mediated restoration of obstructive mitophagy. The functional implications of mesaconine were evaluated in doxorubicin (DOX)-induced heart failure models. DOX-treated mice showed characteristic cardiac dysfunction, ectopic myocardial energy disorder, and impaired mitophagy in cardiomyocytes, which could be remarkably reversed by mesaconine. The cardioprotective effect of mesaconine was primarily attributed to its ability to promote the restoration of mitophagy in cardiomyocytes, as evidenced by elevated expression of PINK1, a key mediator of mitophagy induction. Silencing PINK1 or deactivating mitophagy could completely abolish the protective effects of mesaconine. Together, our findings suggest that the cardioprotective effects of mesaconine appear to be dependent on the activation of PINK1-induced mitophagy and that mesaconine may constitute a promising therapeutic agent for the treatment of heart failure.

Abstract Background Systemic inflammation and insulin resistance (IR) are often associated with poor prognosis in cancer. This study aimed to investigate the prognostic value of surrogate systemic inflammation and IR indices in patients with cancer. Methods This multicenter prospective study included 5,221 patients with cancer, with a mean age of 59.41±11.15 years, of whom 3,061 (58.6%) were male. The surrogate IR indices included low-density lipoprotein cholesterol to high-density lipoprotein cholesterol (LHR) ratio, total cholesterol to high-density lipoprotein cholesterol (TC/ HDL-c) ratio, triglyceride to high-density lipoprotein cholesterol (TG/HDL-c) ratio, and fasting triglyceride glucose (TyG). Prognostic receiver operator characteristic (ROC) curves and C-indices were used to select a better surrogate IR index in patients with cancer. The prognostic value of the indicators was evaluated using univariate and multivariate survival analyses. Results In this study, the median survival time of patients was 44.5 (40.5–51.4) months, and the overall mortality in the 12-month period was 1,115 (53.7%), with 196 mortality events per 1,000 patient-years of patients’ follow-up. The prognostic ROC curve and C-index suggested that the prognostic value of LHR was better than that of the other IR indices. The multivariate-adjusted hazard ratios (HRs) for overall survival (OS) were higher in patients with high C-reactive protein (CRP) (HR, 1.51; 95% confidence interval [CI]: 1.38–1.65) and high LHR (HR, 1.20; 95% CI: 1.06–1.37), respectively. The mortality rate of patients with both high CRP and LHR was 1.75-fold higher than that of patients with both low CRP and LHR. Conclusion Both CRP and LHR showed good survival predictions in patients with cancer. CRP combined with LHR can improve the predictive power of patients with cancer.

Abstract Background Body water measured by bioelectrical impedance analysis (BIA) predicts the outcomes of many diseases. This study aimed to evaluate the relationship between body water and the prognosis of cancer patients with sarcopenia. Methods This study employed 287 cancer patients with sarcopenia underwent BIA from a prospective multicenter study of patients with cancer in China from 2013 to 2020. The primary outcome of interest was all-cause mortality presented as the longest time to follow-up available. Eight indicators of body water [total body water, extracellular water, intracellular water, free fat mass, active cell mass, extracellular water/intracellular water, extracellular water/total body water (ECW/TBW), and intracellular water/total body water] were included in the research. Neutrophil–lymphocyte ratio (NLR) = neutrophil (× 109)/lymphocyte (× 109). The discriminatory ability and prediction accuracy of each factor were assessed using the C-index. The hazard ratios (HR) and 95% confidence intervals (CI) were calculated using the Cox proportional hazard model. Results The median age was 65 years old, and 138 (48%) patients were men. During a mean follow-up of 46 months, 140 deaths were recorded, resulting in a rate of 204.6 events per 1000 patient-years. ECW/TBW showed the best predictive accuracy (C-index = 0.619) compared to the other indicators [p = 0.004, adjusted HR (95% CI) 1.70 (1.18,2.44)]. In the middle tertile (0.385–0.405), ECW/TBW had a strong independent negative association with patient survival [adjusted HR (95% CI) 2.88 (1.39–5.97), p = 0.004]. Patients who had a high ECW/TBW (ECW/TBW ≥ 0.395) combined with a high NLR had 3.84-fold risk of mortality (p

Abstract Background There is no consensus on whether triplet regimen is better than doublet regimen in the first‐line treatment of advanced gastric cancer (AGC). We aimed to compare the efficacy and safety of oxaliplatin plus capecitabine (XELOX) and epirubicin, oxaliplatin, plus capecitabine (EOX) regimens in treating AGC. Methods This phase III trial enrolled previously untreated patients with AGC who were randomly assigned to receive the XELOX or EOX regimen. The primary endpoint was non‐inferiority in progression‐free survival (PFS) for XELOX as compared with EOX on an intention‐to‐treat basis. Results Between April 10, 2015 and August 20, 2020, 448 AGC patients were randomized to receive XELOX (n = 222) or EOX (n = 226). The median PFS (mPFS) was 5.0 months (95% confidence interval [CI] = 4.5‐6.0 months) in the XELOX arm and 5.5 months (95% CI = 5.0‐6.0 months) in the EOX arm (hazard ratio [HR] = 0.989, 95% CI = 0.812‐1.203; Pnon‐inferiority = 0.003). There was no significant difference in median overall survival (mOS) (12.0 vs. 12.0 months, P = 0.384) or objective response rate (37.4% vs. 45.1%, P = 0.291) between the two groups. In patients with poorly differentiated adenocarcinoma and liver metastasis, the EOX arm had a significantly longer mOS (P = 0.021) and a trend of longer mPFS (P = 0.073) than the XELOX arm. The rate of grade 3/4 adverse events (AEs) was 42.2% (90/213) in the XELOX arm and 72.5% (156/215) in the EOX arm (P = 0.001). The global health‐related quality of life (QoL) score was significantly higher in the XELOX arm than in the EOX arm during chemotherapy. Conclusions This non‐inferiority trial demonstrated that the doublet regimen was as effective as the triplet regimen and had a better safety profile and QoL as a first‐line treatment for AGC patients. However, the triplet regimen might have a survival advantage in patients with poorly differentiated adenocarcinoma and liver metastasis.

BackgroundColorectal cancer (CRC) is among the most common malignant cancers worldwide, and its development is influenced by inflammation, nutrition, and the immune status. Therefore, we combined C-reactive protein (CRP), albumin, and lymphocyte, which could reflect above status, to be the CRP-albumin-lymphocyte (CALLY) index, and evaluated its association with overall survival (OS) in patients with CRC.MethodsThe clinicopathological and laboratory characteristics of 1260 patients with CRC were collected from the Investigation on Nutrition Status and Clinical Outcome of Common Cancers (INSCOC) study. Cox regression analysis was performed to assess the association between the CALLY index and OS. A nomogram including sex, age, the CALLY index and TNM stage was constructed. The Concordance Index (C-index) was utilized to evaluate the prognostic value of the CALLY index and classical CRC prognostic factors, such as modified Glasgow prognostic score (mGPS), neutrocyte to lymphocyte ratio (NLR), systemic immune inflammation index (SII), and platelet to lymphocyte ratio (PLR), as well as to assess the prognostic value of the nomogram and TNM stage.ResultsMultivariate Cox regression analyses demonstrated that the CALLY index was independently associated with OS in patients with CRC [Hazard ratio (HR) = 0.91, 95% confidence interval (CI) = 0.87-0.95, P

PurposePrevious studies have shown that both hand grip strength (HGS) and the modified Glasgow Prognostic Score (mGPS) are associated with poor clinical outcomes in patients with liver cancer. In spite of this, no relevant studies have been conducted to determine whether the combination of HGS and mGPS can predict the prognosis of patients with liver cancer. Accordingly, this study sought to explore this possibility.MethodsThis was a multicenter study of patients with liver cancer. Based on the optimal HGS cutoff value for each sex, we determined the HGS cutoff values. The patients were divided into high and low HGS groups based on their HGS scores. An mGPS of 0 was defined as low mGPS, whereas scores higher than 0 were defined as high mGPS. The patients were combined into HGS-mGPS groups for the prediction of survival. Survival analysis was performed using Kaplan–Meier curves. A Cox regression model was designed and adjusted for confounders. To evaluate the nomogram model, receiver operating characteristic curves and calibration curves were used.ResultsA total of 504 patients were enrolled in this study. Of these, 386 (76.6%) were men (mean [SD] age, 56.63 [12.06] years). Multivariate analysis revealed that patients with low HGS and high mGPS had a higher risk of death than those with neither low HGS nor high mGPS (hazard ratio [HR],1.50; 95% confidence interval [CI],1.14–1.98; p = 0.001 and HR, 1.55; 95% CI, 1.14–2.12, p = 0.001 respectively). Patients with both low HGS and high mGPS had 2.35-fold increased risk of death (HR, 2.35; 95% CI, 1.52–3.63; p

There is no well-established procedure for the management of small penis syndrome (SPS), especially when psychological interventions fail. This study aimed at systematically evaluating the physical and psychological benefits of penile augmentation (PA) using injectable hyaluronic acid (HA) gel. Thirty-eight patients receiving PA with HA gel from January 2017 to March 2020 were included and followed up for 1 year. Penile size, erectile function, and psychological burden measured by the Index of Male Genital Image (IMGI), Index of International Erectile Function (IIEF), and Beliefs about Penis Size (BPAS), respectively, were assessed at the beginning and at 1, 3, 6, and 12 months postinjection. The volume of HA gel injected was 21.5 ± 3.7 ml. Compared to baseline data, flaccid penile girth and length significantly increased by 3.41 ± 0.95 cm (P < 0.01) and 2.55 ± 0.55 cm (P < 0.01) at the 1st month postinjection, respectively. At the endpoint, despite attenuations, statistically significant improvements in flaccid penis size were still obtained, namely 2.44 ± 1.14 cm in girth (P < 0.01) and 1.65 ± 0.59 cm in length (P < 0.01). Similarly, erectile penile girth statistically increased by 1.32 ± 1.02 cm (P < 0.01) at the 1st month but were only 0.80 ± 0.54 cm bigger than baseline (P < 0.01) at the endpoint. At the 1st month, the average score of IMGI and the mean score of IIEF statistically increased by 46.2 ± 10.5 (P < 0.01) and 7.6 ± 6.2 (P < 0.01), respectively; the score of BAPS significantly decreased by 18.3 ± 4.5 (P < 0.01). These alterations remained steady during follow-up. Considering the significant penile size improvement, lasting psychological benefit, and low complication rate, PA with HA might serve as an appropriate alternative for patients with SPS.

Abstract Despite the great advances in target therapy, lung cancer remains the top cause of cancer-related death worldwide. G protein-coupled receptor neurokinin-1 (NK1R) is shown to play multiple roles in various cancers; however, the pathological roles and clinical implication in lung cancer are unclarified. Here we identified NK1R as a significantly upregulated GPCR in the transcriptome and tissue array of human lung cancer samples, associated with advanced clinical stages and poor prognosis. Notably, NK1R is co-expressed with epidermal growth factor receptor (EGFR) in NSCLC patients’ tissues and co-localized in the tumor cells. NK1R can crosstalk with EGFR by interacting with EGFR, transactivating EGFR phosphorylation and regulating the intracellular signaling of ERK1/2 and Akt. Activation of NK1R promotes the proliferation, colony formation, EMT, MMP2/14 expression, and migration of lung cancer cells. The inhibition of NK1R by selective antagonist aprepitant repressed cell proliferation and migration in vitro. Knockdown of NK1R significantly slowed down the tumor growth in nude mice. The sensitivity of lung cancer cells to gefitinib/osimertinib is highly increased in the presence of the selective NK1R antagonist aprepitant. Our data suggest that NK1R plays an important role in lung cancer development through EGFR signaling and the crosstalk between NK1R and EGFR may provide a potential therapeutic target for lung cancer treatment.

Objective To investigate the biomechanical and elution properties of meropenem‐loaded bone cement. Methods Bone cement (Palacos LV) with 5% (2 g/4 0g), 10% (4 g/40 g), and 15% (6 g/40 g) meropenem; 5% (2 g/40 g) and 10% (4 g/40 g) vancomycin; and blank bone cement were prepared in a total of six groups named A2, A4, A6, B2, B4, and A0 (antibiotic‐free). 36 cylinder specimens (6‐mm diameter and 12‐mm height) of all six groups were molded for a compression test. After the compression test, because of mechanical properties below the ISO standard requirements, groups B2, B4 were not subjected to a bending test. So a total of 24 rectangular strip specimens (10‐mm width, 75‐mm length, and 3.3‐mm thickness) for groups A2, A4, A6 and A0 were molded for the bending test. Between‐group differences of compressive strength, bending strength and bending modulus were analyzed. The meropenem standard was prepared as a series of standard solutions to calculate the standard curve. At a constant temperature of 37 °C, separately, meropenem‐loaded bone cement cylinder specimens (12 mm in diameter and 17 mm in length) of A2, A4 and A6 were serially immersed in saline solution without stirring. The eluent drug concentration at 24, 48, 72 h and 6, 12, 24 days was measured and the drug concentration‐time curve of meropenem was constructed. Results With the exception of groups B2 and B4, all cements compressive strength values were well above the minimum requirement of the ISO 5833 standard (70 MPa). The compressive strength and bending strength values of group A4 were higher than those of group A0 (P 0.05). There were no intergroup differences of bending modulus between the A0, A2, A4 and A6 groups (P > 0.05). A standard curve of meropenem was obtained and a regression equation was constructed: Y = 15.0265 X + 13.5218, r = 1.00. At 37 °C, the release of meropenem was rapid during the first 48 h for all A2, A4, A6 samples, and subsequent release continued to decrease. Conclusion When adding up to 15% (6 g/40 g) meropenem to the bone cement, the biomechanical properties were not reduced, and bone cement with 10% (4 g/40 g) meropenem had the best performance. At a constant temperature of 37°C, meropenem can be released from bone cement for up to 24 days.

Abstract Background Although systemic inflammation is an important feature of the cancer cachexia, studies on the association between systemic inflammation and prognostic of cancer cachexia are limited. The objective of this study is to evaluate whether the neutrophil‐to‐lymphocyte ratio (NLR) is associated with outcome and quality of life for patients with cancer cachexia and investigated any interaction between NLR and the clinical parameters. Methods This is a multicentre cohort study of 2612 cancer patients suffering from cachexia diagnosed between June 2012 and December 2019. The main parameters measured were overall survival (OS) time and all‐cause mortality. The association between NLR and all‐cause mortality was evaluated using hazard ratios (HRs) and the restricted cubic spline model with a two‐sided P‐value. Optimal stratification was used to solve threshold points. We also evaluated the cross‐classification of NLR for each variable of survival. Results Of the 2612 participants diagnosed with cancer cachexia, 1533 (58.7%) were male, and the mean (SD) age was 58.7 (11.7) years. Over a median follow‐up of 4.5 years, we observed 1189 deaths. The overall mortality rate for patients with cancer cachexia during the first 12 months was 30.2% (95%CI: 28.4%–32.0%), resulting in a rate of 226.07 events per 1000 patient‐years. An increase in NLR had an inverted L‐shaped dose–response association with all‐cause mortality. The optimal cut‐off point for NLR as a predictor of mortality in cancer patients with cachexia was 3.5. An NLR of 3.5 or greater could independently predict OS (HR, 1.51, 95%CI: 1.33–1.71). These associations were consistent across subtypes of cancer. Several potential effect modifiers were identified including gender, BMI, tumour type, KPS score and albumin in content. Increasing NLRs were independently associated with a worsening in the majority of EORTC QLQ‐C30 domains. Elevated baseline NLR was associated with low response and poor survival in patients treated with immunotherapy. Conclusions The baseline NLR status was found to be a significant negative prognostic biomarker for patients with cachexia; this effect was independent of other known prognostic factors.

Abstract Background Systemic inflammation and cachexia are associated with adverse clinical outcomes in elderly patients with cancer. The Geriatric Nutritional Risk Index (GNRI) is a simple and useful tool to assess these conditions, but its predictive ability for elderly patients with cancer cachexia (EPCC) is unknown. Methods This multicentre cohort study included 746 EPCC with an average age of 72.00 ± 5.24 years, of whom 489 (65.5%) were male. The patients were divided into two groups (high GNRI group ≥91.959 vs. low GNRI group

BackgroundElderly patients with cancer face the challenge of systemic inflammation, which can lead to a poor prognosis. Existing inflammatory indices cannot fully reflect the immune-inflammatory status of patients. This study aimed to develop a new scoring system to predict the survival of elderly patients with cancer using inflammatory indices, namely, the systemic inflammation prognostic score (SIPS).Materials and MethodsThis prospective multicenter study included a total of 1,767 patients with cancer, with a mean age of 70.97 ± 5.49 years, of whom 1,170 (66.2%) were men. We performed the least absolute shrinkage and selection operator (LASSO) regression to screen inflammatory indicators to include in constructing SIPS. Prognostic analysis of SIPS was performed using univariate and multivariate survival analyzes. The prognostic value of SIPS and its components were compared using the prognostic receiver operating characteristic curve and concordance index. The population was divided into the training cohort and the validation cohort in a 7:3 ratio and a SIPS prognostic analysis was performed.ResultsThe LASSO regression selected C-reactive protein (CRP) (≤ 9.81, “0”; > 9.81, “1”), geriatric nutritional risk index (GNRI) (≤ 93.85, “1”; 93.85, “0”), advanced lung cancer inflammation index (ALI) (≤ 23.49, “1”; > 23.49, “0”), and lymphocyte to C-reactive protein ratio (LCR) (≤ 2523.81, “1”; > 2523.81, “0”) to develop SIPS. Patients were divided into the three groups based on the total SIPS: low-risk (0), moderate-risk (1–2), and high-risk (3–4). On the multivariate survival analysis, patients in the moderate-risk [P < 0.001, hazard ratio (HR) = 1.79, 95% CI: 1.47–2.17] and high-risk groups (P < 0.001, HR = 2.40, 95% CI: 1.98–2.92) showed a worse prognosis than those in the low-risk group. The total cohort, training cohort, and validation cohort all showed that SIPS had better survival prediction than CRP, GNRI, ALI, and LCR. The HRs were 2.81 times higher in patients in the high-risk group with malnutrition than in patients in the low-risk group without malnutrition.ConclusionSIPS was an independent prognostic indicator in elderly patients with cancer. Malnutrition in the high-risk group increased the mortality risk.

Apiculture has been greatly developed in recent years in China. Beekeeping cooperatives and honey manufacturing enterprises have increased rapidly. As a result, a variety of honey products have entered the market, adding vitality to the food economy; however, the adulteration of honey products is on the rise in China. Previous attempts to control the adulteration of honey products mostly relied on technical, product-specific measures, and there was a lack of modeling research to guide the supervision of the honey product industry. In order to help local governments to better control the adulteration of honey products from a management perspective, this paper establishes an evolutionary game model composed of beekeeping cooperatives, honey product enterprises, and local governments. Through stability analysis and model simulation, we found that local government subsidies to cooperatives have little impact on the game system. Local government penalties to cooperatives and price adjustments of unadulterated raw honey by cooperatives are effective management tools to reduce the adulteration behavior of cooperatives. Local government penalties for enterprises are an effective management tool to reduce the adulteration behavior of enterprises. This research provides useful information for government agencies to design appropriate policies/business modes so as to promote sustainability and the healthy development of the honey product industry in China.

BackgroundSystemic inflammation and insulin resistance (IR) are closely related in patients with cancer. However, there is no relevant indicator that combines inflammation and IR to predict patient prognosis. Therefore, this study aimed to develop and validate a novel inflammation- and IR-related marker in patients with cancer.MethodsThe total cohort of this study included 5221 patients with cancer, and the training and validation cohorts were randomized in a 7:3 ratio. C-reactive protein (CRP) and fasting triglyceride glucose (TyG) were used to reflect patients’ inflammation and IR status, respectively. The CRP-TyG index (CTI) was composed of CRP and TyG. The concordance (C)-index, receiver operator characteristic (ROC) curve, and calibration curve reflected the prognostic predictive power of CTI. Univariate and multivariate survival analyses predicted the prognostic value of CTI in patients with cancer.ResultsThe C-indices of CTI in patients with cancer were 0.636, 0.617, and 0.631 in the total, training, and validation cohorts, respectively. The 1-, 3-, and 5-year ROC and calibration curves showed that CTI had a good predictive ability of survival in patients with cancer. Meanwhile, patients with high CTI had a worse prognosis compared to patients with low CTI (total cohort: hazard ratio [HR] = 1.46, 95% confidence interval [95% CI] = 1.33–1.59; training cohort: HR = 1.36, 95% CI = 1.22–1.52; validation cohort: HR = 1.73, 95% CI = 1.47–2.04].ConclusionThe CTI is a useful prognostic indicator of poor prognosis and a promising tool for treatment strategy decision-making in patients with cancer.

BackgroundNon-small cell lung cancer (NSCLC) is among the most prevalent malignancies worldwide. Previous studies have shown that the status of inflammation, nutrition and immune are closely related to overall survival (OS) of patients with NSCLC, but little is known about their interactive and combined roles. Hence, we chose glucose to lymphocyte ratio (GLR) and modified Glasgow Prognosis Score (mGPS) as prognostic factors and assessed the prognostic values of them for patients with NSCLC.MethodsBaseline clinicopathologic and laboratory characteristics of 862 patients with NSCLC were obtained from a multicenter prospective cohort. The Cox proportional hazard regression models were used to determine prognostic values of the clinical factors. A nomogram was also constructed integrating the clinical factors with clinical significance or independent prognostic values. Concordance index (C-index) was utilized to evaluate the prediction accuracy of the TNM stage and the nomogram.ResultsMultivariate analyses demonstrated that GLR [Hazard ratio (HR) = 1.029, 95% confidence interval (CI) = 1.004–1.056, P = 0.023] and mGPS (score of 1: HR = 1.404, 95% CI = 1.143–1.726, P = 0.001; score of 2: HR = 1.515, 95% CI = 1.159–1.980, P = 0.002) were independent prognostic factors for patients with NSCLC. The C-indexes of the TNM stage and the nomogram were 0.642 (95% CI = 0.620–0.663) and 0.694 (95% CI = 0.671–0.717), respectively.ConclusionGLR and mGPS were independent prognostic factors for patients with NSCLC. Moreover, our constructed nomogram might be superior in predicting prognosis of patients with NSCLC compared with the TNM stage.

Atractylodes macrocephala rhizome (called Bái-zhú in China) has a long history as a functional food and herbal medicine in East Asia, especially China. Sesquiterpenoids are one of the main active compounds of Atractylodes macrocephala rhizome. This study aimed to explore the unknown sesquiterpenoids of A. macrocephala rhizome using a molecular networking strategy. Two new nitrogen-containing sesquiterpenoids, atractylenolactam A (1) and atractylenolactam B (2), and 2 new sesquiterpene lactones, 8-methoxy-atractylenolide V (6) and 15-acetoxyl atractylenolide III (7), along with 12 known analogs (3-5 and 8-16) were discovered and isolated. All the structures were assigned based on detailed spectroscopic analyses. The absolute configurations of 1, 2, 6, and 7 were established by time-dependent density functional theory ECD (TDDFT-ECD) calculations. All these compounds had different degrees of concentration-dependent activating effects on nuclear-factor-E2-related factor-2 (Nrf2).

Carbon dots have attracted much attention for biomedical applications but potential degradation and associated toxicity are still poorly understood. Here, the authors report on a study into the photo-degradation of carbon dots, the products produced and associated cytotoxicity.

Hyaluronic acid injection is becoming a popular way for penile augmentation. However, only few studies and follow-ups have investigated the various complications of hyaluronic acid injection and their corresponding management. In this study, a total of 230 patients who had penile augmentation with hyaluronic acid injection from January 2018 to December 2019 were examined on follow-up for penile girth, complications, and their corresponding management. At 1-month, 3-month, and 6-month postoperative follow-ups, the penile circumference had increased by 2.66 ± 1.24 cm, 2.28 ± 1.02 cm, and 1.80 ± 0.83 cm, respectively. During the entire 6-month follow-up, 4.3% had complications such as subcutaneous bleeding, subcutaneous nodules, and infection. There were no systemic or local allergic reactions among all the patients. All complications were treated accordingly, and no further deterioration or severe sequelae were observed. Although complications of hyaluronic acid injections are mild and rare, these may affect the patient's satisfaction postoperatively. Preoperative redundant prepuce may increase the incidence of penile edema or postoperative gel migration. Standardization of the surgery protocol and elucidation of the effects of other injection parameters are still lacking. Nevertheless, it still highlights the importance of preoperative preparation and surgical technique.

Tyrosinase (TYR) inhibitors are in great demand in the food, cosmetic and medical industrials due to their important roles. Therefore, the discovery of high-quality TYR inhibitors is always pursued. Natural products as one of the most important sources of bioactive compounds discovery have been increasingly used for TYR inhibitors screening. However, due to their complex compositions, it is still a great challenge to rapid screening and identification of biologically active components from them. In recent years, with the help of separation technologies and the affinity and intrinsic activity of target enzymes, two advanced approaches including affinity screening and inhibition profiling showed great promises for a successful screening of bioactive compounds from natural sources. This review summarises the recent progress of separation-based methods for TYR inhibitors screening, with an emphasis on the principle, application, advantage, and drawback of each method along with perspectives in the future development of these screening techniques and screened hit compounds.

c-MYC is often deregulated in human cancers including lymphomas. Here, the authors show that a member of the pseudokinase family, tribbles homologue 3 (TRIB3), interacts with c-MYC to suppress c-MYC ubiquitination and degradation, leading to increased proliferation and self-renewal of lymphoma cells.

ObjectiveSystemic inflammation and malnutrition are correlated with cancer sarcopenia and have deleterious effects on oncological outcomes. However, the combined effect of inflammation and malnutrition in patients with cancer sarcopenia remains unclear.MethodsWe prospectively collected information on 1,204 patients diagnosed with cancer sarcopenia. the mean (SD) age was 64.5 (11.4%) years, and 705 (58.60%) of the patients were male. The patients were categorized into the high advanced lung cancer inflammation index (ALI) group (≥18.39) and the low ALI group (

Flower color is an important trait in Brassica species. However, genes responsible for the dark yellow flower trait in Chinese cabbage have not been reported. In this study, we identified a dark-yellow-flowered Chinese cabbage line SD369. Genetic analysis indicated that the dark yellow flower trait in SD369 was controlled by a single recessive locus, Br-dyp1 (dark yellow petal color 1 in Brassica rapa). Using bulked segregant RNA sequencing and kompetitive allele-specific PCR assays, Br-dyp1 was fine-mapped to an interval of 53.6 kb on chromosome A09. Functional annotation analysis, expression analysis, and sequence variation analysis revealed that Bra037130 (BraA09.ZEP), which encodes a zeaxanthin epoxidase, was the most likely candidate gene for Br-dyp1. Carotenoid profile analysis suggested that Bra037130 (BraA09.ZEP) might participate in the epoxidation from zeaxanthin to violaxanthin. The 679 bp insertion in dark yellow petal caused premature stop codon, thus caused the loss-of-function of the enzyme zeaxanthin epoxidase (ZEP), which disturbed the carotenoid metabolism, and caused the increased accumulation of total carotenoid, and finally converted the flower color from yellow to dark yellow. Comparative transcriptome analysis also showed that the “carotenoid biosynthesis” pathway was significantly enriched, and genes involved in carotenoid degradation and abscisic acid biosynthesis and metabolism were significantly downregulated. Furthermore, we developed and validated the functional marker Br-dyp1-InDel for Br-dyp1. Overall, these results provide insight into the molecular basis of carotenoid-based flower coloration in B. rapa and reveal valuable information for marker-assisted selection breeding in Chinese cabbage.

Hypertension induces both structural and functional changes in blood vessels, thereby increasing endothelial dysfunction, which in turn, contributes to an increase in blood pressure. A popular and widely used noninvasive tool, flow-mediated dilation (FMD), is used to examine peripheral artery endothelium-dependent dilation. This study aimed to compare the efficacies of different classes of antihypertensive agents based on their effects on FMD. PubMed, Embase, and Cochrane Library were queried till November 1, 2020. Comparative studies on the efficacies of two or more antihypertensive agents or placebos for hypertensive patients were included. The outcomes were variations in mean systolic and diastolic blood pressure. Two reviewers independently reviewed and filtered the literature and extracted the data; the Cochrane “risk of bias” method was used to evaluate the methodological quality of the randomized controlled trials. A network meta-analysis was performed using Stata 15.0 software with a total of 49 studies. Subgroup analysis based on age and duration of treatments was performed. As compared to the placebo group, patients receiving the antihypertensive drugs exhibited significantly enhanced FMD (ARB + CCB: 4.01%, 95% CI, 0.92–7.11%, p

Depletion of tribbles pseudokinase 3 (TRIB3) is known to suppress the expression of several tumor-promoting factors, including EGFR. Here, the authors show that TRIB3 interacts with EGFR and regulates its stability and activity, and perturbing EGFR-TRIB3 interaction attenuates NSCLC progression by accelerating EGFR degradation.

Cancer stem cells contribute to breast cancer metastasis and recurrence. Here the authors show that TRIB3 enhances breast cancer stemness through interaction with AKT to promote FOXO1 stability, which then increases SOX2 activity.

BackgroundColorectal cancer (CRC) is one of the most common malignancies throughout the world, with high rates of morbidity and mortality. Previous studies reported that serum creatinine (Scr) concentrations were associated with overall survival (OS) in cancer patients, but little is known about the association between Scr and OS in patients with CRC. This study investigated the relationship between Scr concentrations and OS in patients with CRC and examined possible effect modifiers.MethodsA retrospective cohort, including 1,733 patients with CRC, was established from a multi-center clinical study. Patients were divided into low (104 μmol/L in men or >85 μmol/L in women) Scr groups. Cox regression analysis was used to examine association between Scr concentrations and OS. Stratified (subgroup) analyses were used to examine men and women separately. Interaction tests were used to evaluate associations between each variable and OS, as well as possible interactions of these variables with Scr levels. Cross-classified analyses were used only in men.ResultsPatients with low [hazard ratio (HR) = 1.43, 95% confidence interval (CI) = 1.19-1.72; P < 0.001] or high (HR = 1.89, 95% CI = 1.36-2.63; P < 0.001) Scr level had a significantly lower OS than patients with normal Scr levels. Significant interactions with Scr concentrations were observed for body mass index (P for interaction = 0.019) in men.ConclusionLow or high Scr concentration is associated with significantly lower OS in patients with CRC. Future study is warranted to investigate the underlying mechanism.

Dandelion is an edible plant with a variety of bioactive components. This paper mainly reports the antitumor activity of dandelion polysaccharide DLP120 on H22 tumor-bearing mice. DLP120 is an acidic polysaccharide composed of pectin and arabinogalactan. The results indicate that DLP120 markedly inhibited tumor growth in a dose-dependent manner and attenuated and regulated negative effects on organs. In addition, DLP120 not only increased the viability of spleen lymphocytes and natural killer (NK) cells, but also increased the proportion of lymphocyte subsets in peripheral blood. Furthermore, Hematoxylin-Eosin (HE) staining showed that tumor tissues and cells exhibited typical pathology features. Annexin V FITC/PI staining and cell cycle distribution results further confirmed apoptosis and cell cycle arrest in S and G2 phases. Notably, there was a significant accumulation of reactive oxygen species. Western blotting results demonstrated that the expression of p53 was up-regulated in the DLP120 group. Moreover, the pro-apoptotic protein Bax was up-regulated while the inhibitory-apoptotic protein Bcl-2 was down-regulated. In addition, the expression of Fas and FasL, associated with the death receptor pathway, were also up-regulated. Overall, administration of DLP120 in H22 tumor-bearing mice can not only enhance immunity but also directly induce tumor cell apoptosis.

BackgroundRecently, albumin–globulin ratio (AGR), a serological indicator that reflects nutritional status and systemic inflammatory, has been reported to be associated with the prognosis of various cancers. However, there is currently no research report on its relationship with cancer cachexia.ObjectivesThis study aimed to explore the prognostic value of AGR in patients with cancer cachexia through a multicenter retrospective analysis.MethodsWe recruited 2,364 patients with cancer cachexia and randomly divided the patients into training and validation cohorts at a ratio of 7:3. The optimal stratification method was used to determine the optimal cutoff value of AGR. The survival curve was evaluated by the Kaplan–Meier method. Cox regression proportional-hazards model was used to determine independent prognostic factors in patients with cancer cachexia. The time-dependent receiver operating characteristic curve was used to compare the prognostic performance of different malnutrition evaluation tools.ResultsThe optimal cutoff value of AGR is 1.24 in patients with cancer cachexia. Increasing AGR was associated with survival in a dose–response manner with a forward L-shape. Compared with the high AGR group, the low AGR group had a shorter overall survival; and there was consistency in training and validation cohorts. In the stratified analysis of TNM stage, AGR has good prognostic distinguishing ability for advanced patients. Multivariate survival analysis determined that low AGR was an independent risk factor affecting all-cause mortality in patients with cancer cachexia. In addition, compared with other malnutrition evaluation tools, AGR could effectively stratify the prognosis of patients with cancer cachexia.ConclusionAGR was an independent prognostic factor affecting patients with cancer cachexia, especially in advanced patients. Compared with other malnutrition evaluation tools, AGR can effectively stratify the prognosis of patients with cancer cachexia.

Background: Fat-free mass (FFM) depletion can be masked by a stable body weight or weight gain in the presence of a normal or high body mass index (BMI). This study investigated the prognostic value of low fat-free mass index (FFMI) in cancer patients with normal or high BMI.Methods: This multicenter retrospective cohort study included 1,602 cancer patients with normal/high BMI. The association of FFMI with patients' overall survival (OS) was analyzed by the Kaplan-Meier method and a Cox model.Results: In this analysis, there were 974 (60.8%) females and 628 (39.2%) males. Low FFMI was associated with worse OS when compared with those patients with normal FFMI. After multivariate adjustment, low FFMI was demonstrated to be an independent unfavorable prognostic factor (HR: 1.69; 95% CI: 1.28, 2.23; P < 0.001) in cancer patients with normal/high BMI. For specific tumor type, low FFMI was found to be associated with worse prognosis in patients with lung cancer, breast cancer and upper gastrointestinal cancer. In subgroup analysis, the association of low FFMI with worse survival was significantly modified by weight loss (P for interaction = 0.012), and those patients with concurrent low FFMI and weight loss showed the worst prognosis (HR: 3.53; 95% CI: 2.04, 6.11; P < 0.001).Conclusion: Low FFMI was associated with worse prognosis in cancer patients with normal/high BMI. This study highlights the usefulness of FFMI for prognostic estimation in these patients.

Salicylic acid (SA) has been proven to be a multifunctional signaling molecule that participates in the response of plants to abiotic stresses. In this study, we used cold-sensitive cucumber and cold-tolerant pumpkin as experimental materials to examine the roles of SA in root–shoot communication responses to aerial or/and root-zone chilling stress in own-root and hetero-root grafted cucumber and pumpkin plants. The results showed that pumpkin (Cm) rootstock enhanced the chilling tolerance of grafted cucumber, as evidenced by the observed lower levels of electrolyte leakage (EL), malondialdehyde (MDA), and higher photosynthetic rate (Pn) and gene expression of Rubisco activase (RCA). However, cucumber (Cs) rootstock decreased the chilling tolerance of grafted pumpkins. Cs/Cm plants showed an increase in the mRNA expression of C-repeat-binding factor (CBF1), an inducer of CBF expression (ICE1), and cold-responsive (COR47) genes and CBF1 protein levels in leaves under 5/25 and 5/5°C stresses, or in roots under 25/5 and 5/5°C stresses, respectively, compared with the Cs/Cs. Chilling stress increased the endogenous SA content and the activity of phenylalanine ammonia-lyase (PAL), and the increase in SA content and activity of PAL in Cs/Cm plants was much higher than in Cs/Cs plants. Transcription profiling analysis revealed the key genes of SA biosynthesis, PAL, ICS, and SABP2 were upregulated, while SAMT, the key gene of SA degradation, was downregulated in Cs/Cm leaves, compared with Cs/Cs leaves under chilling stress. The accumulation of SA in the Cs/Cm leaves was mainly attributed to an increase in SA biosynthesis in leaves and that in transport from roots under aerial and root-zone chilling stress, respectively. In addition, exogenous SA significantly upregulated the expression level of cold-responsive (COR) genes, enhanced actual photochemical efficiency (ΦPSII), maximum photochemical efficiency (Fv/Fm), and Pn, while decreased EL, MDA, and CI in grafted cucumber. These results suggest that SA is involved in rootstock–scion communication and grafting-induced chilling tolerance by upregulating the expression of COR genes in cucumber plants under chilling stress.

Flower color is an important trait in plants. However, genes responsible for the white flower trait in Chinese cabbage are rarely reported. In this study, we constructed an F2 population derived from the Y640-288 (white flower) and Y641-87 (yellow flower) lines for the fine mapping of the white flower gene BrWF3 in Chinese cabbage. Genetic analysis indicated that BrWF3 was controlled by a single recessive gene. Using BSA-seq and KASP assays, BrWF3 was fine-mapped to an interval of 105.6 kb. Functional annotation, expression profiling, and sequence variation analyses confirmed that the AtPES2 homolog, Bra032957, was the most likely candidate gene for BrWF3. Carotenoid profiles and transmission electron microscopy analysis suggested that BrWF3 might participate in the production of xanthophyll esters (particularly violaxanthin esters), which in turn disrupt chromoplast development and the formation of plastoglobules (PGs). A SNP deletion in the third exon of BrWF3 caused the loss of protein function, and interfered with the normal assembly of PGs, which was associated with reduced expression levels of genes involved in carotenoid metabolism. Furthermore, we developed and validated the functional marker TXBH83 for BrWF3. Our results provide insight into the molecular mechanism underlying flower color pigmentation and reveal valuable information for marker-assisted selection (MAS) breeding in Chinese cabbage.

Objective To investigate the effect of psychological intervention on the prognosis of patients with C4 dislocation and spinal cord injury. Methods We investigated target patients admitted between 2010 and 2018. Patients’ mental state, quality of life and neurological function at different time points were evaluated to examine the relationship between psychological intervention and recovery and prognosis of acute and critical spinal cord injury. Results All patients showed improvements in clinical symptoms, neurological function and quality of life. Psychological intervention significantly improved Zung Self-Rating Anxiety Scale score, Zung Self-Rating Depression Scale score and SF-36 Mental Component Summary score within 3 months. Japanese Orthopaedic Association neurological function score and SF-36 Physical Component Summary score were significantly improved after 1-year follow-up. Psychological intervention did not improve 2-year survival. Conclusion Timely and professional psychological intervention can eliminate the psychological disorders of C4 dislocation patients with spinal cord injury. This has a positive effect on their quality of life and prognosis.

Surface adsorption of N2 molecules is a critical factor to limit the reduction of secondary electron (SE) yield (SEY) in many fields of applied physics. On the basis of the Polanyi potential theory, we describe a multi-layer N2 physical adsorption model to arrange the distribution of N2 molecules adsorbed on a Cu (110) surface. Considering six scattering types, we used a Monte Carlo method to develop a three-dimensional numerical model that simulated the scattering processes between electrons and adsorbed molecules. Thus, the SEY of a surface covered by an adsorbed layer could be obtained by statistical analysis of the final SE states. We found that the maximum of total SEY decreased exponentially with increasing N2 pressure between 0 and 0.1 Torr and decreased linearly with increased adsorbed layer thickness between 0 and 10 nm. The reduction in SEY was due mainly to the elastic scattering of large scattering angle and ionization of energy consumption in the scattering processes of electrons and adsorbed molecules. Accordingly, our model and results provide a powerful tool to fully understand the microcosmic mechanism of the SE emission of a metal surface with adsorbed layer.