Development and Validation of a Carbohydrate Metabolism-Related Model for Predicting Prognosis and Immune Landscape in Hepatocellular Carcinoma Patients.

OBJECTIVE: The activities and products of carbohydrate metabolism are involved in key processes of cancer. However, its relationship with hepatocellular carcinoma (HCC) is unclear. METHODS: The cancer genome atlas (TCGA)-HCC and ICGC-LIRI-JP datasets were acquired via public databases. Differentially expressed genes (DEGs) between HCC and control samples in the TCGA-HCC dataset were identified and overlapped with 355 carbohydrate metabolism-related genes (CRGs) to obtain differentially expressed CRGs (DE-CRGs). Then, univariate Cox and least absolute shrinkage and selection operator (LASSO) analyses were applied to identify risk model genes, and HCC samples were divided into high/low-risk groups according to the median risk score. Next, gene set enrichment analysis (GSEA) was performed on the risk model genes. The sensitivity of the risk model to immunotherapy and chemotherapy was also explored. RESULTS: A total of 8 risk model genes, namely, G6PD, PFKFB4, ACAT1, ALDH2, ACYP1, OGDHL, ACADS, and TKTL1, were identified. Moreover, the risk score, cancer status, age, and pathologic T stage were strongly associated with the prognosis of HCC patients. Both the stromal score and immune score had significant negative/positive correlations with the risk score, reflecting the important role of the risk model in immunotherapy sensitivity. Furthermore, the stromal and immune scores had significant negative/positive correlations with risk scores, reflecting the important role of the risk model in immunotherapy sensitivity. Eventually, we found that high-/low-risk patients were more sensitive to 102 drugs, suggesting that the risk model exhibited sensitivity to chemotherapy drugs. The results of the experiments in HCC tissue samples validated the expression of the risk model genes. CONCLUSION: Through bioinformatic analysis, we constructed a carbohydrate metabolism-related risk model for HCC, contributing to the prognosis prediction and treatment of HCC patients.

High nitrogen application in maize enhances insecticide tolerance of the polyphagous herbivore Spodoptera litura by induction of detoxification enzymes and intensification of cuticle.

Nitrogen (N) is one of the most intensively used fertilizers in cropping system and could exert a variety of bottom-up effects on the ecological fitness of herbivores. However, the effects of increased N inputs on insect pesticide tolerance have not been comprehensively understood. Bioassays showed that high N (HN) applied to maize plants significantly increased larval tolerance of Spodoptera litura to multiple insecticides. Activities of detoxification enzymes were significantly higher in the larvae fed on maize plants supplied with HN. RNA-seq analysis showed that numerous GST and cuticle-related genes were induced in the larvae fed on HN maize. RT-qPCR analysis further confirmed four GST genes and larval-specific cuticle gene LCP167. Furthermore, when injected with dsRNA specific to GSTe1, GSTs5, and LCP167, the mortality of larvae treated with methomyl was about 3-fold higher than that of dsGFP-injected larvae. Electron microscope observation showed that cuticle of the larvae fed on HN maize was thicker than the medium level of N. These findings suggest that increased application of N fertilizer enhances insecticide tolerance of lepidopteran pests via induction of detoxification enzymes and intensification of cuticle. Thus, overuse of N fertilizer may increase pest insecticide tolerance and usage of chemical insecticides.

Comparative study of the gut microbial community structure of Spodoptera frugiperda and Spodoptera literal (Lepidoptera).

Background: Spodoptera frugiperda, the fall armyworm is a destructive invasive pest, and S. litura the tobacco cutworm, is a native species closely related to S. frugiperda. The gut microbiota plays a vital role in insect growth, development, metabolism and immune system. Research on the competition between invasive species and closely related native species has focused on differences in the adaptability of insects to the environment. Little is known about gut symbiotic microbe composition and its role in influencing competitive differences between these two insects. Methods: We used a culture-independent approach targeting the 16S rRNA gene of gut bacteria of 5th instar larvae of S. frugiperda and S. litura. Larvae were reared continuously on maize leaves for five generations. We analyzed the composition, abundance, diversity, and metabolic function of gut microbiomes of S. frugiperda and S. litura larvae. Results: Firmicutes, Proteobacteria, and Bacteroidetes were the dominant bacterial phyla in both species. Enterococcus, ZOR0006, Escherichia, Bacteroides, and Lactobacillus were the genera with the highest abundance in S. frugiperda. Enterococcus, Erysipelatoclostridium, ZOR0006, Enterobacter, and Bacteroides had the highest abundance in S. litura. According to α-diversity analysis, the gut bacterial diversity of S. frugiperda was significantly higher than that of S. litura. KEGG analysis showed 15 significant differences in metabolic pathways between S. frugiperda and S. litura gut bacteria, including transcription, cell growth and death, excretory system and circulatory system pathways. Conclusion: In the same habitat, the larvae of S. frugiperda and S. litura showed significant differences in gut bacterial diversity and community composition. Regarding the composition and function of gut bacteria, the invasive species S. frugiperda may have a competitive advantage over S. litura. This study provides a foundation for developing control strategies for S. frugiperda and S. litura.

Comprehensive Pan-Cancer Analysis of Connexin 43 as a Potential Biomarker and Therapeutic Target in Human Kidney Renal Clear Cell Carcinoma (KIRC).

Background and Objectives: Connexin 43 (Cx43) is involved in the transfer of small signaling molecules between neighboring cells, thereby exerting a major influence on the initiation and progression of tumorigenesis. However, there is a lack of systematic research on Cx43 expression and its predictive role in clinical diagnosis and prognosis in pan-cancer. Materials and Methods: Several biological databases were used to evaluate the expression levels of GJA1 (encoding Cx43) and its diagnostic and prognostic significance in pan-cancer. We targeted kidney renal clear cell carcinoma (KIRC) and investigated the relationship between GJA1 expression and different clinical features of KIRC patients. Then, we performed cell-based experiments to partially confirm our results and predicted several proteins that were functionally related to Cx43. Results: The expression of GJA1 has a high level of accuracy in predicting KIRC. High GJA1 expression was remarkably correlated with a favorable prognosis, and this expression was reduced in groups with poor clinical features in KIRC. Cell experiments confirmed the inhibitory effects of increased GJA1 expression on the migratory capacity of human renal cancer (RCC) cell lines, and protein-protein interaction (PPI) analysis predicted that CDH1 and CTNNB1 were closely related to Cx43. Conclusions: GJA1 could be a promising independent favorable prognostic factor for KIRC, and upregulation of GJA1 expression could inhibit the migratory capacity of renal cancer cells.

Impact of Anti-angiogenic Drugs on Severity of COVID-19 in Patients with Non-Small Cell Lung Cancer.

Introduction: The 2019 coronavirus disease (COVID-19) pandemic has reshaped oncology practice, but the impact of anti-angiogenic drugs on the severity of COVID-19 in patients with non-small cell lung cancer (NSCLC) remains unclear. Patients and Methods: We carried out a retrospective study involving 166 consecutive patients with NSCLC who were positive for COVID-19, aiming to determine the effects of anti-angiogenic drugs on disease severity, as defined by severe/critical symptoms, intensive care unit (ICU) admission/intubation, and mortality outcomes. Risk factors were identified using univariate and multivariate logistic regression models. Results: Of the participants, 73 had been administered anti-angiogenic drugs (termed the anti-angiogenic therapy (AT) group), while 93 had not (non-AT group). Comparative analyses showed no significant disparity in the rates of severe/critical symptoms (21.9% vs 35.5%, P = 0.057), ICU admission/intubation (6.8% vs 7.5%, P = 0.867), or death (11.0% vs 9.7%, P = 0.787) between these two groups. However, elevated risk factors for worse outcomes included age ≥ 60 (odds ratio (OR): 2.52, 95% confidence interval (CI): 1.07-5.92), Eastern Cooperative Oncology Group performance status of 2 or higher (OR: 21.29, 95% CI: 4.98-91.01), chronic obstructive pulmonary disease (OR: 7.25, 95% CI: 1.65-31.81), hypertension (OR: 2.98, 95% CI: 1.20-7.39), and use of immunoglobulin (OR: 5.26, 95% CI: 1.06-26.25). Conclusion: Our data suggests that the use of anti-angiogenic drugs may not exacerbate COVID-19 severity in NSCLC patients, indicating their potential safe application even during the pandemic period.

Anlotinib plus tislelizumab for recurrent metastatic pancreas ductal adenocarcinoma with germline BRCA2 mutation: A case report.

While combined immunotherapy and anti-angiogenic therapy have demonstrated efficacy in renal cell carcinoma, non-small cell lung cancer and hepatocellular carcinoma, the efficacy of first-line treatment for pancreatic ductal adenocarcinoma (PDAC) with germline BRCA2 mutation remains unproven. We described a BRCA2-mutated patient with PDAC who presented with posterior cardiac metastasis 8 months after surgery. After receiving four cycles of anlotinib combined with tislelizumab, abdominal CT scans indicated a complete response. The patient sustained this response for over 14 months on the combination regimen, with no reported adverse events. In conclusion, the combination of tislelizumab and anlotinib may offer a viable therapeutic option for recurrent metastatic BRCA2-mutated PDAC.

Red blood cell-derived materials for cancer therapy: Construction, distribution, and applications.

Cancer has become an increasingly important public health issue owing to its high morbidity and mortality rates. Although traditional treatment methods are relatively effective, they have limitations such as highly toxic side effects, easy drug resistance, and high individual variability. Meanwhile, emerging therapies remain limited, and their actual anti-tumor effects need to be improved. Nanotechnology has received considerable attention for its development and application. In particular, artificial nanocarriers have emerged as a crucial approach for tumor therapy. However, certain deficiencies persist, including immunogenicity, permeability, targeting, and biocompatibility. The application of erythrocyte-derived materials will help overcome the above problems and enhance therapeutic effects. Erythrocyte-derived materials can be acquired via the application of physical and chemical techniques from natural erythrocyte membranes, or through the integration of these membranes with synthetic inner core materials using cell membrane biomimetic technology. Their natural properties such as biocompatibility and long circulation time make them an ideal choice for drug delivery or nanoparticle biocoating. Thus, red blood cell-derived materials are widely used in the field of biomedicine. However, further studies are required to evaluate their efficacy, in vivo metabolism, preparation, design, and clinical translation. Based on the latest research reports, this review summarizes the biology, synthesis, characteristics, and distribution of red blood cell-derived materials. Furthermore, we provide a reference for further research and clinical transformation by comprehensively discussing the applications and technical challenges faced by red blood cell-derived materials in the treatment of malignant tumors.

Malate-Based Biodegradable Scaffolds Activate Cellular Energetic Metabolism for Accelerated Wound Healing.

The latest advancements in cellular bioenergetics have revealed the potential of transferring chemical energy to biological energy for therapeutic applications. Despite efforts, a three-dimensional (3D) scaffold that can induce long-term bioenergetic effects and facilitate tissue regeneration remains a big challenge. Herein, the cellular energetic metabolism promotion ability of l-malate, an important intermediate of the tricarboxylic acid (TCA) cycle, was proved, and a series of bioenergetic porous scaffolds were fabricated by synthesizing poly(diol l-malate) (PDoM) prepolymers via a facial one-pot polycondensation of l-malic acid and aliphatic diols, followed by scaffold fabrication and thermal-cross-linking. The degradation products of the developed PDoM scaffolds can regulate the metabolic microenvironment by entering mitochondria and participating in the TCA cycle to elevate intracellular adenosine triphosphate (ATP) levels, thus promoting the cellular biosynthesis, including the production of collagen type I (Col1a1), fibronectin 1 (Fn1), and actin alpha 2 (Acta2/α-Sma). The porous PDoM scaffold was demonstrated to support the growth of the cocultured mesenchymal stem cells (MSCs) and promote their secretion of bioactive molecules [such as vascular endothelial growth factor (VEGF), transforming growth factor-ß1 (TGF-ß1), and basic fibroblast growth factor (bFGF)], and this stem cells-laden scaffold architecture was proved to accelerate wound healing in a critical full-thickness skin defect model on rats.

Serum Insulin-Like Growth Factor-Binding Protein 7 Deriving from Spleen and Lung Could Be Used for Early Recognition of Cardiac Surgery-Associated Acute Kidney Injury.

INTRODUCTION: The utility of arithmetic product of urinary tissue metalloproteinase inhibitor 2 (TIMP2) and insulin-like growth factor-binding protein 7 (IGFBP7) concentrations has been widely accepted on early diagnosis of acute kidney injury (AKI). However, which organ is the main source of those two factors and how the concentration of IGFBP7 and TIMP2 changed in serum during AKI still remain to be defined. METHODS: In mice, gene transcription and protein levels of IGFBP7/TIMP2 in the heart, liver, spleen, lung, and kidney were measured in both ischemia-reperfusion injury (IRI)- and cisplatin-induced AKI models. Serum IGFBP7 and TIMP2 levels were measured and compared in patients before cardiac surgery and at inclusion (0 h), 2 h, 6 h, and 12 h after intensive care unit (ICU) admission, and compared with serum creatinine (SCr), blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), and serum uric acid (UA). RESULTS: In mouse IRI-AKI model, compared with the sham group, the expression levels of IGFBP7 and TIMP2 did not change in the kidney, but significantly upregulated in the spleen and lung. Compared with patients who did not develop AKI, the concentration of serum IGFBP7 at as early as 2 h after ICU admission (sIGFBP7-2 h) was significantly higher in patients who developed AKI. The relationships between sIGFBP7-2 h in AKI patients and log2 (SCr), log2 (BUN), log2 (eGFR), and log2 (UA) were statistically significant. The diagnostic performance of sIGFBP7-2 h measured by the macro-averaged area under the receiver operating characteristic curve was 0.948 (95% CI, 0.853-1.000; p < 0.001). CONCLUSION: The spleen and lung might be the main source of serum IGFBP7 and TIMP2 during AKI. The serum IGFBP7 value demonstrated good predictive accuracy for AKI following cardiac surgery within 2 h after ICU admission.

Immunotherapy combined with rh-endostatin improved clinical outcomes over immunotherapy plus chemotherapy for second-line treatment of advanced NSCLC.

Background: Despite the fact that numerous clinical and preclinical studies have demonstrated the synergistic effects of combining antiangiogenic or chemotherapy with immunotherapy, no data have been found to indicate that combination therapy is more effective and safer as second-line therapy. Methods: We retrospectively compared the effectiveness and safety of ICIs plus rh-endostatin to ICIs plus chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). The evaluation indicators of this study were progression-free survival (PFS), safety profile, objective response rate (ORR), disease control rate (DCR), and 1-year overall survival (OS). Results: The median PFS with immunotherapy plus rh-endostatin (IE) was 7.10 months (95% CI, 4.64 to 9.56) versus 5.13 months (95% CI, 4.29 to 5.97) with immunotherapy plus chemotherapy (IC) (HR, 0.56; 95%CI, 0.33 to 0.95). Treatment-related adverse events of grade 3 or 4 occurred in 7.5% of the IE group versus 25.0% of the IC group. The ORR in the IE group was 35.0% versus 20.8% in the IC group (P = 0.137), and the DCR in the IE group was 92.5% versus 77.1% in the IC group (P = 0.049). The 1-year OS rate for the IE group was 69.4%, which was higher than the 61.4% of the IC group. Conclusion: Our study showed that ICI therapy combined with endostatin therapy exhibits high efficacy and safety, suggesting that such a combination might be a viable treatment option for patients with pre-treated NSCLC in the future.

Osteoporotic-like vertebral fracture with less than 20% height loss is associated with increased further vertebral fracture risk in older women: the MrOS and MsOS (Hong Kong) year-18 follow-up radiograph results.

Background: For osteoporotic fractures in men (MrOS) and in women (MsOS) (Hong Kong) baseline (BL) study, Chinese men and women ≥65 years were recruited during 2001 to 2003. This study presents the year-18 follow-up (FU) results. We were particularly interested in whether women with 'minimal' grade osteoporotic-like vertebral fracture (OLVF) of <20% height loss have an increased vertebral fracture (VF) risk than those without BL OLVF. Methods: At year-18 FU, spine radiography was performed on 144 males (mean: 87.4±3.1 years) and 156 females (mean: 87.0±3.2 years). OLVF classification included no OLVF (grade 0), and OLVFs with <20%, ≥20-25%, ≥25%-1/3, ≥1/3-40%, ≥40%-2/3, ≥2/3 height loss (grades 1-6). With an existing OLVF, a further height loss of ≥15% was an OLVF progression. A new incident OLVF was a change from grade 0 to ≥ grade 2 or to grade 1 with the appearance of endplate and/or cortex fracture (ECF) during FU. Both OLVF progression and incident OLVF were considered incident VF. Acquired short vertebra (aSV) was defined as with decreased vertebral anterior and middle heights, while without anterior wedging and bi-concave changes, and only those with at least two adjacent aSVs were recorded as aSV cases. Results: For subjects without BL OLVF, 12.5% of the males and 27.1% of the females had incident VF. For subjects with BL OLVF of ≥20% height loss, males' and females' incident VF rate were 20% and 66.7% respectively. Females subjects with BL minimal OLVF, while all without radiographic ECF, had an incident VF rate of 59.3% during the FU. For males with and without aSV, 11.8% and 15% have incident fracture of other vertebrae. For females with and without aSV, 35.3% and 34.5% have incident fracture of other vertebrae. Recovery from minimal or mild grades OLVF to normal shape was observed in a number of cases. Conclusions: OLVF with less than 20% height loss is associated with increased VF risk in older females, but not in older males. Acquired short vertebra (SV) is not associated with increased incident fracture risk for other vertebrae, both for females and males. OLVF among older subjects can repair and heal.

Efficacy and safety of immune checkpoint inhibitors combined with recombinant human endostatin and chemotherapy as the first-line treatment of advanced non-small-cell lung cancer.

Aim: To assess the efficacy and safety of combination of PD-1 inhibitors, recombinant human endostatin (Rh-endostatin) and chemotherapy as first-line treatment for advanced non-small-cell lung cancer (NSCLC). Methods: A total of 100 patients with advanced NSCLC were retrospectively reviewed and analyzed (58 in the group receiving PD-1 inhibitors plus Rh-endostatin and chemotherapy; 42 in the group receiving Rh-endostatin and chemotherapy). The primary end point was progression-free survival. Results: Patients in the group receiving PD-1 inhibitors plus Rh-endostatin and chemotherapy had significantly improved progression-free survival (10.2 vs 6.5 months; p < 0.001) and objective response rate (67.2 vs 42.9%; p = 0.015), with acceptable toxicity. Conclusion: Our study showed the superiority of combination therapy of PD-1 inhibitors and Rh-endostatin as first-line treatment for advanced NSCLC.

This study retrospectively analyzed the effectiveness and safety of PD-1 inhibitors combined with recombinant human endostatin (Rh-endostatin) and chemotherapy as first-line treatment for advanced non-small-cell lung cancer. Among them, 58 patients received a PD-1 inhibitor combined with Rh-endostatin and chemotherapy (treatment group), and 42 patients received Rh-endostatin combined with chemotherapy (control group). Patients in the treatment group had a significantly improved objective response rate (67.2 vs 42.9%; p = 0.015) and prolonged survival without their disease getting worse (10.2 vs 6.5 months; p < 0.001). No significant differences were found in the adverse events between the two groups.

Predictive role of cardiac valvular calcification in all-cause mortality of Chinese initial haemodialysis patients: a follow-up study of 4 years.

BACKGROUND: Cardiac valvular calcification (CVC) is prevalent in haemodialysis (HD) patients. Its association with mortality in Chinese incident haemodialysis (IHD) patients remains unknown. METHODS: A total of 224 IHD patients who had just begun HD therapy at Zhongshan Hospital, Fudan University, were enrolled and divided into two groups according to the detection of cardiac valvular calcification (CVC) by echocardiography. The patients were followed for a median of 4 years for all-cause mortality and cardiovascular mortality. RESULTS: During follow-up, 56 (25.0%) patients died, including 29 (51.8%) of cardiovascular disease. The adjusted HR related to all-cause mortality was 2.14 (95% CI, 1.05-4.39) for patients with cardiac valvular calcification. However, CVC was not an independent risk factor for cardiovascular mortality in patients who had just begun HD therapy. CONCLUSION: CVC at baseline is an independent risk factor for all-cause mortality in HD patients and makes an independent contribution to the prediction of all-cause mortality. These findings support the use of echocardiography at the beginning of HD.

Effect of a fall prevention strategy for the older patients: A quasi-experimental study.

AIM: To explore the effect of a fall prevention strategy on older patients based on the Patient Engagement Framework. DESIGN: A longitudinal quasi-experimental quantitative design. METHODS: Older patients who met the inclusion criteria were recruited from geriatric, oncology, neurology and cardiology departments of a teaching general hospital in China. Development of a fall prevention intervention strategy for older patients was based on the Patient Engagement Framework. Patients in the intervention group were given this fall prevention strategy (N = 58), and those in the control group were given conventional measures (N = 58). The following indicators were compared between the two groups after intervention: (a) number of falls; (b) Knowledge-Attitude-Practice (KAP) score; (c) Modified Fall Efficacy Scale score. RESULTS: After the implementation of an intervention strategy in older patients, the number of falls decreased from 3 to 0; the score of KAP and Modified Fall Efficacy Scale was promoted (p < .05).

Efficacy and safety analyses of epidermal growth factor receptor tyrosine kinase inhibitors combined with chemotherapy in the treatment of advanced non-small-cell lung cancer with an EGFR/TP53 co-mutation.

PURPOSE: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) combined with cytotoxic chemotherapy are highly effective in the treatment of advanced non-small-cell lung cancer (NSCLC) with EGFR mutations. The purpose of this study is to evaluate the efficacy and safety of this combination in advanced NSCLC patients with an EGFR/TP53 co-mutation. METHODS: Ninety-five advanced NSCLC patients with an EGFR/TP53 co-mutation were enrolled in this study. Treatments with either EGFR-TKI monotherapy (T group, n = 61) or EGFR-TKI combined with chemotherapy (TC group, n = 34) were evaluated in relation to objective response rate (ORR), disease control rate (DCR), median time to progression (TTP), and median overall survival (OS). RESULTS: There were no statistically significant differences in DCR between the treatment groups. The ORR was significantly improved in the TC group versus the T group (55.9% vs. 34.4%, P = 0.042). A higher median TTP was noted in TC group compared with T group (16.1 vs. 11.1 months, P = 0.002). Patients without brain metastases in TC group had a longer median OS than in T group (48.4 vs. 28.8 months, P = 0.003). However, there was a non-significant trend towards longer OS in TC group in the entire cohort (36.9 vs. 28.2 months, P = 0.078). Cox multivariate regression analysis showed that clinical stage, brain metastases, EGFR21 L858R mutation, and T790M status at first progression were independent risk factors for OS. However, the incidence of grade 3 or higher adverse events were higher in the TC group than in the T group (32.4% vs. 13.1%, P = 0.025). CONCLUSION: Our study indicates that EGFR-TKIs combined with chemotherapy could significantly improve the ORR and TTP of advanced NSCLC patients with an EGFR/TP53 co-mutation. Combination therapy may be a promising treatment for advanced NSCLC patients with an EGFR/TP53 co-mutation without brain metastases.

Effects of Elevated CO2 Concentration on Host Adaptability and Chlorantraniliprole Susceptibility in Spodoptera frugiperda.

Elevated atmospheric carbon dioxide concentrations (eCO2) can affect both herbivorous insects and their host plants. The fall armyworm (FAW), Spodoptera frugiperda, is a highly polyphagous agricultural pest that may attack more than 350 host plant species and has developed resistance to both conventional and novel-action insecticides. However, the effects of eCO2 on host adaptability and insecticide resistance of FAW are unclear. We hypothesized that eCO2 might affect insecticide resistance of FAW by affecting its host plants. To test this hypothesis, we investigated the effect of eCO2 on (1) FAW's susceptibility to chlorantraniliprole after feeding on wheat, (2) FAW's population performance traits (including the growth and reproduction), and (3) changes in gene expression in the FAW by transcriptome sequencing. The toxicity of chlorantraniliprole against the FAW under eCO2 (800 µL/L) stress showed that the LC50 values were 2.40, 2.06, and 1.46 times the values at the ambient CO2 concentration (400 µL/L, aCO2) for the three generations, respectively. Under eCO2, the life span of pupae and adults and the total number of generations were significantly shorter than the FAW under aCO2. Compared to the aCO2 treatment, the weights of the 3rd and 4th instar larvae and pupae of FAW under eCO2 were significantly heavier. Transcriptome sequencing results showed that more than 79 detoxification enzyme genes in FAW were upregulated under eCO2 treatment, including 40 P450, 5 CarE, 17 ABC, and 7 UGT genes. Our results showed that eCO2 increased the population performance of FAW on wheat and reduced its susceptibility to chlorantraniliprole by inducing the expression of detoxification enzyme genes. This study has important implications for assessing the damage of FAW in the future under the environment of increasing atmospheric CO2 concentration.

BMI1 induces ubiquitination and protein degradation of Nod-like receptor family CARD domain containing 5 and suppresses human leukocyte antigen class I expression to induce immune escape in non-small cell lung cancer.

The Nod-like receptor (NLR) family CARD domain containing 5 (NLRC5) has been reported as an activator of human leukocyte antigen (HLA) class I that is responsible for immune activity in cancer treatment. This work focuses on the role of BMI1 proto-oncogene (BMI1) in the NLRC5-HLA class I axis and in immune escape in non-small cell lung cancer (NSCLC). First, immunoblot analysis and/or reverse transcription-quantitative polymerase chain reaction were performed, which identified decreased NLRC5 and HLA class I levels in NSCLC tissues and cell lines. NSCLCs were co-cultured with activated CD8+ T cells. Overexpression of NLRC5 in NSCLC cells elevated the expression of HLA class I and increased the activity of T cells and IL-2 production, and it reduced the PD-1/PD-L1 levels. The ubiquitination and immunoprecipitation assays confirmed that BMI1 bound to NLRC5 to induce is ubiquitination and protein degradation. Downregulation of BMI1 in NSCLC cells elevated NLRC5 and HLA class I levels, and consequently promoted T cell activation and decreased PD-1/PD-L1 levels in the co-culture system. However, overexpression of BMI1 in cells led to inverse trends. In summary, this study demonstrates that BMI1 induces ubiquitination and protein degradation of NLRC5 and suppresses HLA class I expression, which potentially helps immune escape in NSCLC.

Recent Advances in the Development and Antimicrobial Applications of Metal-Phenolic Networks.

Due to the abuse of antibiotics and the emergence of multidrug resistant microorganisms, medical devices, and related biomaterials are at high risk of microbial infection during use, placing a heavy burden on patients and healthcare systems. Metal-phenolic networks (MPNs), an emerging organic-inorganic hybrid network system developed gradually in recent years, have exhibited excellent multifunctional properties such as anti-inflammatory, antioxidant, and antibacterial properties by making use of the coordination between phenolic ligands and metal ions. Further, MPNs have received widespread attention in antimicrobial infections due to their facile synthesis process, excellent biocompatibility, and excellent antimicrobial properties brought about by polyphenols and metal ions. In this review, different categories of biomaterials based on MPNs (nanoparticles, coatings, capsules, hydrogels) and their fabrication strategies are summarized, and recent research advances in their antimicrobial applications in biomedical fields (e.g., skin repair, bone regeneration, medical devices, etc.) are highlighted.

Engineering Yarrowia lipolytica to Produce Itaconic Acid From Waste Cooking Oil.

Itaconic acid (IA) is a high-value organic acid with a plethora of industrial applications. In this study, we seek to develop a microbial cell factory that could utilize waste cooking oil (WCO) as raw material for circular and cost-effective production of the abovementioned biochemical. Specifically, we expressed cis-aconitic acid decarboxylase (CAD) gene from Aspergillus terreus in either the cytosol or peroxisome of Yarrowia lipolytica and assayed for production of IA on WCO. To further improve production yield, the 10 genes involved in the production pathway of acetyl-CoA, an intermediate metabolite necessary for the synthesis of cis-aconitic acid, were individually overexpressed and investigated for their impact on IA production. To minimize off-target flux channeling, we had also knocked out genes related to competing pathways in the peroxisome. Impressively, IA titer up to 54.55 g/L was achieved in our engineered Y. lipolytica in a 5 L bioreactor using WCO as the sole carbon source.

Effects of Host Plants on Bacterial Community Structure in Larvae Midgut of Spodoptera frugiperda.

The fall armyworm (FAW), Spodoptera frugiperda, is one of the most important invasive species and causes great damage to various host crops in China. In this study, the diversity and function of gut bacteria in the 5th instar larvae of FAW fed on maize, wheat, potato and tobacco leaves were analyzed through 16S rRNA sequencing. A total of 1324.25 ± 199.73, 1313.5 ± 74.87, 1873.00 ± 190.66 and 1435.25 ± 139.87 operational taxonomic units (OTUs) from the gut of FAW fed on these four different host plants were detected, respectively. Firmicutes, Proteobacteria and Bacteroidetes were the most abundant bacterial phyla. Beta diversity analysis showed that the gut bacterial community structure of larvae fed on different host plants was significantly differentiated. At the genus level, the abundance of Enterococcus in larvae fed on wheat was significantly lower than those fed on the other three host plants. Enterobacter and ZOR0006 were dominant in FAW fed on tobacco leaves, and in low abundance in larvae fed on wheat. Interestingly, when fed on Solanaceae (tobacco and potato) leaves which contained relative higher levels of toxic secondary metabolites than Gramineae (wheat and maize), the genera Enterococcus, Enterobacter and Acinetobacter were significantly enriched. The results indicated that gut bacteria were related to the detoxification and adaptation of toxic secondary metabolites of host plants in FAW. Further analysis showed that replication, repair and nucleotide metabolism functions were enriched in the gut bacteria of larvae fed on tobacco and potato. In conclusion, the gut bacterial diversity and community composition in FAW larvae fed on different host plants showed significant differences, and the insect is likely to regulate their gut bacteria for adaptation to different host plants.