Exploration of a hypoxia-immune-related microenvironment gene signature and prediction model for hepatitis C-induced early-stage fibrosis.

BACKGROUND: Liver fibrosis contributes to significant morbidity and mortality in Western nations, primarily attributed to chronic hepatitis C virus (HCV) infection. Hypoxia and immune status have been reported to be significantly correlated with the progression of liver fibrosis. The current research aimed to investigate the gene signature related to the hypoxia-immune-related microenvironment and identify potential targets for liver fibrosis. METHOD: Sequencing data obtained from GEO were employed to assess the hypoxia and immune status of the discovery set utilizing UMAP and ESTIMATE methods. The prognostic genes were screened utilizing the LASSO model. The infiltration level of 22 types of immune cells was quantified utilizing CIBERSORT, and a prognosis-predictive model was established based on the selected genes. The model was also verified using qRT-PCR with surgical resection samples and liver failure samples RNA-sequencing data. RESULTS: Elevated hypoxia and immune status were linked to an unfavorable prognosis in HCV-induced early-stage liver fibrosis. Increased plasma and resting NK cell infiltration were identified as a risk factor for liver fibrosis progression. Additionally, CYP1A2, CBS, GSTZ1, FOXA1, WDR72 and UHMK1 were determined as hypoxia-immune-related protective genes. The combined model effectively predicted patient prognosis. Furthermore, the preliminary validation of clinical samples supported most of the conclusions drawn from this study. CONCLUSION: The prognosis-predictive model developed using six hypoxia-immune-related genes effectively predicts the prognosis and progression of liver fibrosis. The current study opens new avenues for the future prediction and treatment of liver fibrosis.

CmNAC25 targets CmMYB6 to positively regulate anthocyanin biosynthesis during the post-flowering stage in chrysanthemum.

BACKGROUND: Anthocyanin is a class of important secondary metabolites that determines colorful petals in chrysanthemum, a famous cut flower. 'Arctic Queen' is a white chrysanthemum cultivar that does not accumulate anthocyanin during the flowering stage. During the post-flowering stage, the petals of 'Arctic Queen' accumulate anthocyanin and turn red. However, the molecular mechanism underlying this flower color change remains unclear. RESULTS: In this study, by using transcriptome analysis, we identified CmNAC25 as a candidate gene promoting anthocyanin accumulation in the post-flowering stage of 'Arctic Queen'. CmNAC25 is directly bound to the promoter of CmMYB6, a core member of the MBW protein complex that promotes anthocyanin biosynthesis in chrysanthemum, to activate its expression. CmNAC25 also directly activates the promoter of CmDFR, which encodes the key enzyme in anthocyanin biosynthesis. CmNAC25 was highly expressed during the post-flowering stage, while the expression level of CmMYB#7, a known R3 MYB transcription factor interfering with the formation of the CmMYB6-CmbHLH2 complex, significantly decreased. Genetic transformation of both chrysanthemum and Nicotiana tabacum verified that CmNAC25 was a positive regulator of anthocyanin biosynthesis. Another two cultivars that turned red during the post-flowering stages also demonstrated a similar mechanism. CONCLUSIONS: Altogether, our data revealed that CmNAC25 positively regulates anthocyanin biosynthesis in chrysanthemum petals during the post-flowering stages by directly activating CmMYB6 and CmDFR. Our results thus revealed a crucial role of CmNAC25 in regulating flower color change during petal senescence and provided a target gene for molecular design breeding of flower color in chrysanthemum.

CmMYB9a activates floral coloration by positively regulating anthocyanin biosynthesis in chrysanthemum.

KEY MESSAGE: An R2R3-MYB transcription factor, CmMYB9a, activates floral coloration in chrysanthemum by positively regulating CmCHS, CmDFR and CmFNS, but inhibiting the expression of CmFLS. Chrysanthemum is one of the most popular ornamental plants worldwide. Flavonoids, such as anthocyanins, flavones, and flavonols, are important secondary metabolites for coloration and are involved in many biological processes in plants, like petunia, snapdragon, Gerbera hybrida, as well as chrysanthemum. However, the metabolic regulation of flavonoids contributing to chrysanthemum floral coloration remains largely unexplored. Here, an R2R3-MYB transcription factor, CmMYB9a, was found to be involved in flavonoid biosynthesis. Phylogenetic analysis and amino acid sequence analysis suggested that CmMYB9a belonged to subgroup 7. Transient overexpression of CmMYB9a in flowers of chrysanthemum cultivar 'Anastasia Pink' upregulated the anthocyanin-related and flavone-related genes and downregulated CmFLS, which led to the accumulation of anthocyanins and flavones. We further demonstrated that CmMYB9a independently activates the expression of CmCHS, CmDFR and CmFNS, but inhibits the expression of CmFLS. Overexpression of CmMYB9a in tobacco resulted in increased anthocyanins and decreased flavonols in the petals by upregulating NtDFR and downregulating NtFLS. These results suggest that CmMYB9a facilitates metabolic flux into anthocyanin and flavone biosynthesis. Taken together, this study functionally characterizes the role of CmMYB9a in regulating the branched pathways of flavonoids in chrysanthemum flowers.

Effects of glutamine on the IKK/IκB/NF-кB system in the enterocytes of turbot Scophthalmus maximus L. stimulated with soya-saponins.

Soya-saponins represent key anti-nutritional factors that contribute to soybean meal-induced enteritis, and glutamine is an effective fish intestine protectant that combats the negative effects of soya-saponins. Nuclear transcription factor-kappa B (NF-кB) systems are involved in the interactions between soya-saponins and glutamine, and the goal of the present work was to clarify the related molecular mechanisms used by the NF-кB kinase (IKK)/inhibitor of NF-κB (IκB)/NF-кB system. Primary cultured turbot (Scophthalmus maximus L.) intestinal epithelial cells were concurrently administrated with 1 mg/mL of soya-saponins and several levels of glutamine (0, 0.5, 1.0 and 2.0 mM) for 12 h and then subjected to real-time PCR and Western blot assays. Compared with cells treated with soya-saponins alone, glutamine significantly decreased the expression of interleukin-1 beta, interleukin 8 and tumor necrosis factor α genes, significantly reduced nuclear and cytosolic NF-κB p65 abundance levels in a dose-dependent manner, increased the IκBα protein level but decreased its phosphorylation, and down-regulated the IKKα/ß and phosphorylated IKKα/ß levels. In conclusion, this in vitro work confirmed that glutamine attenuated soya-saponin-induced inflammatory responses in turbot intestines. Moreover, it identified molecular pathways in which glutamine first decreased the p65 level and then prevented its nuclear translocation. In addition, glutamine reduced IκBα phosphorylation and maintained its level. Finally, glutamine decreased IKK expression and phosphorylation.

Hsa_circRNA_0059655 plays a role in salivary adenoid cystic carcinoma by functioning as a sponge of miR-338-3p.

Circular RNAs(circRNA) are recently demonstrated to have a close relationship with tumors.To investigate the role of circular RNA in the pathogenesis of salivary adenoid cystic carcinoma(SACC), ten SACC tissues and paired normal submandibular gland(SMG) tissues were collected as the tumor group and the control group. Total RNA was extracted and then measured using ceRNA microarray (including mRNA, lncRNA, and circRNA) and miRNA microarray. Gene Ontology(GO) analysis and Kyoto Encyclopedia of Gene and Genomes (KEGG) pathway analysis were performed in order to investigate the function of the differential expressing genes. The ceRNA regulatory network was constructed to find the core circRNAs. Then the role of circRNA on proliferation was examined in the SACC cell line SACC-83 using CCK-8,qRT-PCR and western blotting, and its roles on migration and invasion were examined using wound healing assay and transwell assay. The results of the microarrays showed that 3792 mRNAs, 7649 lncRNAs, 11553 circRNAs, and 132 miRNAs expressed differentially. The ceRNA regulatory network analysis showed that hsa_circ_0059655 and other 14circRNAs derived from PYGB target on several similar genes by miR-338-3p.Among the 15 circRNAs derived from PYGB, hsa_circ_0059655has the most relationships in the ceRNA network. Furthermore, after hsa_circ_0059655 was knocked down in SACC-83 cells, the expression of hsa-miR-338-3p was up-regulated while CCND1was down-regulated. The proliferation, migration, and invasion of SACC-83 cells also decreased after hsa_circ_0059655 knock-downed.Taken together, the circRNAs derived from PYGB may regulate the tumorigenesis and development of SACC through competing with miR-338-3p.

Integrative single-cell and bulk transcriptomes analyses reveals heterogeneity of serine-glycine-one-carbon metabolism with distinct prognoses and therapeutic vulnerabilities in HNSCC.

Metabolic heterogeneity plays a central role in sustaining uncontrolled cancer cell proliferation and shaping the tumor microenvironment (TME), which significantly compromises the clinical outcomes and responses to therapy in head and neck squamous cell carcinoma (HNSCC) patients. This highlights the urgent need to delineate the intrinsic heterogeneity and biological roles of metabolic vulnerabilities to advance precision oncology. The metabolic heterogeneity of malignant cells was identified using single-cell RNA sequencing (scRNA-seq) profiles and validated through bulk transcriptomes. Serine-glycine-one-carbon (SGOC) metabolism was screened out to be responsible for the aggressive malignant properties and poor prognosis in HNSCC patients. A 4-SGOC gene prognostic signature, constructed by LASSO-COX regression analysis, demonstrated good predictive performance for overall survival and therapeutic responses. Patients in the low-risk group exhibited greater infiltration of exhausted CD8+ T cells, and demonstrated better clinical outcomes after receiving immunotherapy and chemotherapy. Conversely, high-risk patients exhibited characteristics of cold tumors, with enhanced IMPDH1-mediated purine biosynthesis, resulting in poor responses to current therapies. IMPDH1 emerged as a potential therapeutic metabolic target. Treatment with IMPDH inhibitors effectively suppressed HNSCC cell proliferation and metastasis and induced apoptosis in vitro and in vivo by triggering GTP-exhaustion nucleolar stress. Our findings underscore the metabolic vulnerabilities of HNSCC in facilitating accurate patient stratification and individualized precise metabolic-targeted treatment.

FOXA2 plays a critical role in hepatocellular carcinoma progression and lenvatinib-associated drug resistance.

Hepatic forkhead box protein A2 (FOXA2) is a crucial transcription factor for liver development and metabolic homeostasis. However, its role in hepatocellular carcinoma (HCC) progression and lenvatinib-related drug resistance remains unknown. In this study, the level of FOXA2 expression was found to be lower in HCC tissues than in paired adjacent tumor tissues. A low level of FOXA2 expression was associated with aggressive tumor characteristics (vascular invasion and poor differentiation). A low level of FOXA2 expression was found to be an independent risk factor for tumor recurrence (hazard ratio (HR): 1.899, P < 0.001) and long-term survival (HR: 2.011, P = 0.003) in HCC patients after hepatectomy. In xenograft animal models, FOXA2 overexpression significantly inhibited tumor growth. Moreover, FOXA2 overexpression was found to enhance the inhibitory effect of lenvatinib on HCC cells by upregulating the adenosine monophosphate-activated protein kinase-mechanistic target of rapamycin (AMPK-mTOR) pathway. Conversely, inhibition of adenosine monophosphate-activated protein kinase (AMPK) or stimulation of mechanistic target of rapamycin (mTOR) attenuated the sensitization of cells overexpressing FOXA2 to lenvatinib. Similarly, FOXA2 overexpression augmented the antitumor effect of lenvatinib in animal models with xenograft tumors. FOXA2 overexpression increased autophagy in HCC cells treated with lenvatinib. Lenvatinib treatment activated the platelet-derived growth factor receptor-extracellular regulated protein kinase (PDGFR-ERK) pathway in HCC. FOXA2 overexpression further downregulated the PDGFR-ERK pathway through the activation of the AMPK-mTOR axis. In conclusion, FOXA2 was identified as an independent risk factor for HCC after hepatectomy. FOXA2 was found to be closely associated with the biological progression of HCC. By modulating the AMPK-mTOR-autophagy signaling pathway, FOX2 significantly augmented antitumor effect of lenvatinib in HCC.

Transcriptome analysis of mRNAs, lncRNAs, and miRNAs in the skeletal muscle of Tibetan chickens at different developmental stages.

Introduction: As a valuable genetic resource, native birds can contribute to the sustainable development of animal production. Tibetan chickens, known for their special flavor, are one of the important local poultry breeds in the Qinghai-Tibet Plateau. However, Tibetan chickens have a slow growth rate and poor carcass traits compared with broilers. Although most of the research on Tibetan chickens focused on their hypoxic adaptation, there were fewer studies related to skeletal muscle development. Methods: Here, we performed the transcriptional sequencing of leg muscles from Tibetan chicken embryos at E (embryonic)10, E14, and E18. Results: In total, 1,600, 4,610, and 2,166 DE (differentially expressed) mRNAs, 210, 573, and 234 DE lncRNAs (long non-coding RNAs), and 52, 137, and 33 DE miRNAs (microRNAs) were detected between E10 and E14, E10 and E18, and E14 and E18, respectively. Functional prediction showed several DE mRNAs and the target mRNAs of DE lncRNAs and DE miRNAs were significantly enriched in sarcomere organization, actin cytoskeleton organization, myofibril, muscle fiber development, and other terms and pathways related to muscle growth and development. Finally, a lncRNA-miRNA-mRNA ceRNA (competing endogenous RNA) network associated with muscle growth and development, which contained 6 DE lncRNAs, 13 DE miRNAs, and 50 DE mRNAs, was constructed based on the screened DE RNAs by Gene Ontology (GO) enrichment. These DE RNAs may play a critical regulatory role in the skeletal muscle development of chickens. Discussion: The results provide a genomic resource for mRNAs, lncRNAs, and miRNAs potentially involved in the skeletal muscle development of chickens, which lay the foundation for further studies of the molecular mechanisms underlying skeletal muscle growth and development in Tibetan chickens.

Minimally Invasive Donors Right Hepatectomy versus Open Donors Right Hepatectomy: A Meta-Analysis.

BACKGROUND: How to obtain a donor liver remains an open issue, especially in the choice of minimally invasive donors right hepatectomy versus open donors right hepatectomy (MIDRH versus ODRH). We conducted a meta-analysis to clarify this question. METHODS: A meta-analysis was performed in PubMed, Web of Science, EMBASE, Cochrane Central Register, and ClinicalTrials.gov databases. Baseline characteristics and perioperative outcomes were analyzed. RESULTS: A total of 24 retrospective studies were identified. For MIDRH vs. ODRH, the operative time was longer in the MIDRH group (mean difference [MD] = 30.77 min; p = 0.006). MIDRH resulted in significantly less intraoperative blood loss (MD = -57.86 mL; p < 0.00001), shorter length of stay (MD = -1.22 days; p < 0.00001), lower pulmonary (OR = 0.55; p = 0.002) and wound complications (OR = 0.45; p = 0.0007), lower overall complications (OR = 0.79; p = 0.02), and less self-infused morphine consumption (MD = -0.06 days; 95% CI, -1.16 to -0.05; p = 0.03). In the subgroup analysis, similar results were observed in pure laparoscopic donor right hepatectomy (PLDRH) and the propensity score matching group. In addition, there were no significant differences in post-operation liver injury, bile duct complications, Clavien-Dindo ≥ 3 III, readmission, reoperation, and postoperative transfusion between the MIDRH and ODRH groups. DISCUSSION: We concluded that MIDRH is a safe and feasible alternative to ODRH for living donators, especially in the PLDRH group.

Patent iliolumbar artery increase no risk of type II endoleaks after endovascular abdominal aortic aneurysm: a case-control study.

Objective: The aims of the present study were to explore the risk factors for type 2 endoleaks (T2ELs) after endovascular aneurysm repair (EVAR) and the association between T2ELs and the iliolumbar artery. Materials and methods: A single-center, retrospective case-control study in West China Hospital was conducted among patients with infrarenal abdominal aortic aneurysm (AAA) who underwent EVAR between June 2010 and June 2019. The associations of patient characteristics, anatomical factors, internal iliac artery embolization, and ILA with the primary outcome were analyzed. The secondary objective was to analyze survival and reintervention between the T2EL group and the non-T2EL group. Kaplan-Meier survival, propensity matching analysis and multivariate logistic regression analysis were used. Results: A total of 603 patients were included. The median follow-up was 51 months (range 5.0-106.0). There was a significant difference in the diameter of the lumbar artery (LA), middle sacral artery (MSA) and inferior mesentery artery (IMA), proportion of thrombus and LA numbers. The univariate analysis showed that T2ELs were more likely to develop more thrombus in aneurysm cavity (OR = 0.294, p = 0.012), larger MSA (OR = 1.284, p = 0.04), LA (OR = 1.520, p = 0.015), IMA (OR = 1.056, p < 0.001) and more LAs (OR = 1.390, p = 0.019). The multivariate analysis showed that the number of LAs (HR: 1.349, 95% CI: 1.140-1.595, p < .001) and the diameter of the IMA (HR: 1.328, 95% CI: 1.078-1.636, p = 0.008) were significantly associated with T2ELs. There were no new findings from the propensity score matching. The reintervention-free survival rates were significantly different between the two groups (p = 0.048). Overall survival and AAA-related death rates were not different between the two group. This was consistent with the PSM analysis. Conclusion: The iliolumbar artery and the different internal iliac artery interventions may not increase the incidence of T2ELs. But the numbers of LAs and IMA diameter were independent risk factors for T2Els. T2ELs was associated with the reintervention but did not affect long-term survival or increase aneurysm-related mortality after EVAR.

Analyses of a chromosome-scale genome assembly reveal the origin and evolution of cultivated chrysanthemum.

Chrysanthemum (Chrysanthemum morifolium Ramat.) is a globally important ornamental plant with great economic, cultural, and symbolic value. However, research on chrysanthemum is challenging due to its complex genetic background. Here, we report a near-complete assembly and annotation for C. morifolium comprising 27 pseudochromosomes (8.15 Gb; scaffold N50 of 303.69 Mb). Comparative and evolutionary analyses reveal a whole-genome triplication (WGT) event shared by Chrysanthemum species approximately 6 million years ago (Mya) and the possible lineage-specific polyploidization of C. morifolium approximately 3 Mya. Multilevel evidence suggests that C. morifolium is likely a segmental allopolyploid. Furthermore, a combination of genomics and transcriptomics approaches demonstrate the C. morifolium genome can be used to identify genes underlying key ornamental traits. Phylogenetic analysis of CmCCD4a traces the flower colour breeding history of cultivated chrysanthemum. Genomic resources generated from this study could help to accelerate chrysanthemum genetic improvement.

Sustained injection of miR-499-5p alters the gastrocnemius muscle metabolome in broiler chickens.

To investigate the effects of miR-499-5p on muscle metabolism in broiler chickens, eight broiler chicks were assigned to the control group and eight to the treatment group, and then we monitored the effects using metabolomics. Chicks were fed basal diets without or with miR-499-5p delivery. Gastrocnemius muscle samples were collected and analyzed by ultrahigh-performance liquid chromatography-tandem mass spectrometry. The results showed that miR-499-5p injection altered the concentrations of a variety of metabolites in the gastrocnemius muscle. Thereby, a total of 46 metabolites were identified at higher ( P < 0.05 ) concentrations and 30 metabolites were identified at lower ( P < 0.05 ) concentrations in the treatment group compared with the control group. These metabolites were primarily involved with the regulation of lipid and carbohydrate metabolism. Further metabolic pathway analysis revealed that fructose and mannose metabolism, galactose metabolism, inositol phosphate metabolism, and terpenoid backbone biosynthesis were the most critical pathway which may partially interpret the effects of miR-499-5p. To our knowledge, this research is the first report of metabolic signatures and related metabolic pathways in the skeletal muscle for miR-499-5p injection and provides new insight into the effect of miRNA on growth performance.

Season impacts on estimating plant's particulate retention: Field experiments and meta-analysis.

Plants can effectively remove atmospheric particles, which contribute to air pollution. However, few studies have focused on seasonal variability of plant dust retention, an essential factor to estimate annual dust removal from the atmosphere. This study conducted a field experiment to explore the seasonal variability of particulate retention on evergreen leaved urban greening shrub plants. We performed a meta-analysis to synthesize the available literature on the subject to discuss our findings further. Results showed that particulate matter deposited on leaf surfaces (sPM) in autumn and winter was significantly higher than in spring and summer. In comparison, the particulate matter trapped in epicuticular waxes (wPM) in summer was significantly higher than in the other three seasons. The seasonal differences also existed in both sPM and wPM among particle sizes. The total dust retention of Rhododendron × pulchrum Sweet, Osmanthus fragrans Lour, and Photinia × fraseri Dress were estimated as 360.89 t, 586.66 t, and 448.84 t per year, respectively. They were significantly different from model estimates if only one season was chosen as an estimator. Furthermore, the meta-analysis revealed significant differences among seasons, particle sizes, and different leaf habits (evergreen or deciduous). In contrast, no significant differences were observed between life forms or between growth forms. Our findings both from field experiment and met-analysis highlights that seasonal variation can significantly affect the dust retention capacity of plants, which should be taken into account into particle matter retention capacity evaluations.

Primary Functioning Hepatic Paraganglioma Treated by Laparoscopy: A Case Report.

Paragangliomas are highly vascularised and often heritable tumors derived from the paraganglia. They are typically discovered in the retroperitoneal space as well as the head and neck region but are rarely encountered in the liver parenchyma. We report a case of a primary functioning hepatic paraganglioma and provide an up-to-date literature review of patients with such tumors. We present a case of functioning paraganglioma in a 34-year-old female patient who suffered a solitary lesion in her left lateral lobe with symptoms of hypertension since pregnancy. She did not have any family history and her pre-pregnancy examination was negative. An abdominal CT imaging revealed a 6.5 × 5.7 cm liver lesion in segments II and III. Laboratory investigations identified elevation in plasma-free catecholamines. With sufficient preoperative preparation, the patient underwent laparoscopic left hemihepatectomy. Immunohistochemical staining revealed Syn (+) tumor cell nests surrounded by S-100 sustentacular cells (+), providing a definitive diagnosis of paraganglioma. The patient recovered uneventfully without signs of recurrence during a 1-year follow-up period. Our case demonstrates that primary refractory hypertension in pregnancy should be screened for paraganglioma through abdominal ultrasound and plasma free catecholamines. On the other hand, laparoscopic surgery is technically safe and feasible for the treatment of patients with hepatic paragangliomas in favorable locations.

Is robotic distal pancreatectomy better than laparoscopic distal pancreatectomy after the learning curve? A systematic review and meta-analysis.

Aim: The aim of this study was to compare the safety and overall effect of robotic distal pancreatectomy (RDP) to laparoscopic distal pancreatectomy (LDP) after the learning curve, especially in perioperative outcome and short-term oncological outcome. Methods: A literature search was performed by two authors independently using PubMed, Embase, and Web of Science to identify any studies comparing the results of RDP versus LDP published until 5 January 2022. Only the studies where RDP was performed in more than 35 cases were included in this study. We performed a meta-analysis of operative time, blood loss, reoperation, readmission, hospital stay, overall complications, major complications, postoperative pancreatic fistula (POPF), blood transfusion, conversion to open surgery, spleen preservation, tumor size, R0 resection, and lymph node dissection. Results: Our search identified 15 eligible studies, totaling 4,062 patients (1,413 RDP). It seems that the RDP group had a higher rate of smaller tumor size than the LDP group (MD: -0.15; 95% CI: -0.20 to -0.09; p < 0.00001). Furthermore, compared with LPD, RDP was associated with a higher spleen preservation rate (OR: 2.19; 95% CI: 1.36-3.54; p = 0.001) and lower rate of conversion to open surgery (OR: 0.43; 95% CI: 0.33-0.55; p < 0.00001). Our study revealed that there were no significant differences in operative time, overall complications, major complications, blood loss, blood transfusion, reoperation, readmission, POPF, and lymph node dissection between RDP and LDP. Conclusions: RDP is safe and feasible for distal pancreatectomy compared with LDP, and it can reduce the rate of conversion to open surgery and increase the rate of spleen preservation, which needs to be further confirmed by quality comparative studies with large samples. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails.

Laparoscopic vs. open colectomy for T4 colon cancer: A meta-analysis and trial sequential analysis of prospective observational studies.

Background: To evaluate short- and long-term outcomes of laparoscopic colectomy (LC) vs. open colectomy (OC) in patients with T4 colon cancer. Methods: Three authors independently searched PubMed, Web of Science, Embase, Cochrane Library, and Clinicaltrials.gov for articles before June 3, 2022 to compare the clinical outcomes of T4 colon cancer patients undergoing LC or OC. Results: This meta-analysis included 7 articles with 1,635 cases. Compared with OC, LC had lesser blood loss, lesser perioperative transfusion, lesser complications, lesser wound infection, and shorter length of hospital stay. Moreover, there was no significant difference between the two groups in terms of 5-year overall survival (5y OS), and 5-year disease-free survival (5y DFS), R0 resection rate, positive resection margin, lymph nodes harvested ≥12, and recurrence. Trial Sequential Analysis (TSA) results suggested that the potential advantages of LC on perioperative transfusion and the comparable oncological outcomes in terms of 5y OS, 5y DFS, lymph nodes harvested ≥12, and R0 resection rate was reliable and no need of further study. Conclusions: Laparoscopic surgery is safe and feasible in T4 colon cancer in terms of short- and long-term outcomes. TSA results suggested that future studies were not required to evaluate the 5y OS, 5y DFS, R0 resection rate, positive resection margin status, lymph nodes harvested ≥12 and perioperative transfusion differences between LC and OC.Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022297792.

Design of Reflective Polarization Rotator in Silicon Waveguide.

In this work, we investigate theoretically the reflective polarization rotator in a silicon waveguide formed by periodically arranged rectangular air holes. The etched air holes generate the large birefringence for the waveguide. The effective refractive index of the non-etched waveguide is isotropic. The structure can be regarded as a stack of alternating birefringent waveplates and isotropic material similar to the folded Solc filter. The band structure of the stack of birefringent waveplates with isotropic background is calculated to confirm the fact that high reflection peaks in the reflection spectra of the waveguide result from the photonic bandgap. The polarization extinction ratio for the reflected light is 15.8 dB. The highest reflectivity of the device is 93.1%, and the device length is 9.21 µm. An ultra-wide operation bandwidth from 1450.3 to 1621.8 nm can be achieved.

Carboxylesterase 2 induces mitochondrial dysfunction via disrupting lipid homeostasis in oral squamous cell carcinoma.

OBJECTIVE: Oral squamous cell carcinoma (OSCC) is characterized by high recurrence and metastasis and places a heavy burden on societies worldwide. Cancer cells thrive in a changing microenvironment by reprogramming lipidomic metabolic processes to provide nutrients and energy, activate oncogenic signaling pathways, and manage redox homeostasis to avoid lipotoxicity. The mechanism by which OSCC cells maintain lipid homeostasis during malignant progression is unclear. METHODS: The altered expression of fatty acid (FA) metabolism genes in OSCC, compared with that in normal tissues, and in OSCC patients with or without recurrence or metastasis were determined using public data from the TCGA and GEO databases. Immunohistochemistry was performed to examine the carboxylesterase 2 (CES2) protein level in our own cohort. CCK-8 and Transwell assays and an in vivo xenograft model were used to evaluate the biological functions of CES2. Mass spectrometry and RNA sequencing were performed to determine the lipidome and transcriptome alterations induced by CES2. Mitochondrial mass, mtDNA content, mitochondrial membrane potential, ROS levels, and oxygen consumption and apoptosis rates were evaluated to determine the effects of CES2 on mitochondrial function in OSCC. RESULTS: CES2 was downregulated in OSCC patients, especially those with recurrence or metastasis. CES2high OSCC patients showed better overall survival than CES2low OSCC patients. Restoring CES2 expression reduced OSCC cell viability and suppressed their migration and invasion in vitro, and it inhibited OSCC tumor growth in vivo. CES2 reprogrammed lipid metabolism in OSCC cells by hydrolyzing neutral lipid diacylglycerols (DGs) to release free fatty acids and reduce the membrane structure lipid phospholipids (PLs) synthesis. Free FAs were converted to acyl-carnitines (CARs) and transferred to mitochondria for oxidation, which induced reactive oxygen species (ROS) accumulation, mitochondrial damage, and apoptosis activation. Furthermore, the reduction in signaling lipids, e.g., DGs, PLs and substrates, suppressed PI3K/AKT/MYC signaling pathways. Restoring MYC rescued the diminished cell viability, suppressed migratory and invasive abilities, damaged mitochondria and reduced apoptosis rate induced by CES2. CONCLUSIONS: We demonstrated that CES2 downregulation plays an important role in OSCC by maintaining lipid homeostasis and reducing lipotoxicity during tumor progression and may provide a potential therapeutic target for OSCC.

Dynamics of particle retention and physiology in Euonymus japonicus Thunb. var. aurea-marginatus Hort. with severe exhaust exposure under continuous drought.

Frequent drought events and particulate matter pollution from vehicular exhaust seriously affect urban plant growth and provisioning of ecological services. Yet, how plants respond physiologically and morphologically to these two combined stressors remains unknown. Here, we assessed particle retention dynamics and plant morphology and physiology of Euonymus japonicus Thunb. var. aurea-marginatus Hort. under continuous drought with severe exhaust exposure. Our results showed that continuous drought insignificantly lowered particle retention in each of three size fractions by 1.02 µg·cm-2 on average in the first 28 days, but significantly lowered total particle retention by 35.75 µg·cm-2 on the 35th day. We observed evident changes in morphology, leaf mass per area (LMA), pigments, gas exchange in all stressed plants. Compared with single stress, combined drought and pollution caused earlier yellowing and shedding of old leaves, significantly lowered LMA by 1.21 mg·cm-2, caused a greater decline in pigments and net photosynthetic rate (Pn). Large particles may mainly explain pigment reduction, lower weekly LMA increases, and stomatal restriction, while coarse particles may be the main drivers of the decline in Pn. Continuous drought mediated the influence of all three particle sizes on some parameters, such as weakening the impact of total particles on LMA, strengthening the impact of fine particles on photosynthesis. Our findings suggest that drought accelerates the physiological responses of plants to exhaust pollution. Under controlled severe exhaust pollution conditions, the optimal time to maintain high particle retention during continuous drought without decline in physiological conditions for E. japonicus var. aurea-marginatus was 14 days. Some additional interventions after 14 days (it could be postponed appropriately under field conditions) may help ensure healthy growth of plants and retention of particulate matter.

A novel transcription factor CmMYB012 inhibits flavone and anthocyanin biosynthesis in response to high temperatures in chrysanthemum.

Flavones are among the major colorless pigments synthesized through branches of the flavonoid pathway in plants. However, due to the absence of a gene encoding flavone synthase (FNS) in the model plant Arabidopsis thaliana species, the regulatory mechanism of FNS-catalyzed flavone biosynthesis has rarely been studied in plants. Here, it was found that flavones play a predominant role in the elimination of excess reactive oxygen species (ROS) at high temperatures in colorless plant organs. A novel atypical subgroup 7 (SG7) R2R3-MYB transcription factor, CmMYB012, was found to be induced in response to prolonged high temperatures and to inhibit flavone biosynthesis by directly regulating CmFNS. Moreover, CmMYB012 was also found to inhibit anthocyanin biosynthesis by suppressing the expression of CmCHS, CmDFR, CmANS, and CmUFGT. CmMYB012 overexpression exerted a negative influence on plant fitness and pink flower color formation, while CmMYB012 suppression had the opposite effect in response to high temperatures. Our findings provide new insights into the mechanisms by which high temperatures regulate the metabolism of flavones and anthocyanins to affect plant fitness and flower color formation.