Hepatitis B virus X protein promotes tumor glycolysis by downregulating lncRNA OIP5-AS1/HKDC1 in HCC.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide, with Hepatitis B virus (HBV) infection being the leading cause. This study aims to investigate the role of HBV in HCC pathogenesis involving glucose metabolism. Long non-coding RNA (lncRNA) OIP5-AS1 was significantly downregulated in HBV-positive HCC patients, and its low expression indicated a poor prognosis. This lncRNA was primarily localized in the cytoplasm, acting as a tumor suppressor. HBV protein X (HBx) repressed OIP5-AS1 expression by inhibiting a ligand-activated transcriptional factor peroxisome proliferator-activated receptor α (PPARα). Furthermore, mechanistic studies revealed that OIP5-AS1 inhibited tumor growth by suppressing Hexokinase domain component 1 (HKDC1)-mediated glycolysis. The expression of HKDC1 could be enhanced by transcriptional factor sterol regulatory element-binding protein 1 (SREBP1). OIP5-AS1 facilitated the ubiquitination and degradation of SREBP1 to suppress HKDC1 transcription, which inhibited glycolysis. The results suggest that lncRNA OIP5-AS1 plays an anti-oncogenic role in HBV-positive HCC via the HBx/OIP5-AS1/HKDC1 axis, providing a promising diagnostic marker and therapeutic target for HBV-positive HCC patients.

Clinical practice guidelines for prevention and treatment of postoperative gastrointestinal disorder with Integrated Traditional Chinese and Western Medicine (2023).

Postoperative gastrointestinal disorder (POGD) was a common complication after surgery under anesthesia. Strategies in combination with Traditional Chinese Medicine and Western medicine showed some distinct effects but standardized clinical practice guidelines were not available. Thus, a multidisciplinary expert team from various professional bodies including the Perioperative and Anesthesia Professional Committees of the Chinese Association of Integrative Medicine (CAIM), jointly with Gansu Province Clinical Research Center of Integrative Anesthesiology/Anesthesia and Pain Medical Center of Gansu Provincial Hospital of Traditional Chinese Medicine and WHO Collaborating Center for Guideline Implementation and Knowledge Translation/Chinese Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) Center/Gansu Provincial Center for Medical Guideline Industry Technology/Evidence-based Medicine Center of Lanzhou University, was established to develop evidence-based guidelines. Clinical questions (7 background and 12 clinical questions) were identified through literature reviews and expert consensus meetings. Based on systematic reviews/meta-analyses, evidence quality was analyzed and the advantages and disadvantages of interventional measures were weighed with input from patients' preferences. Finally, 20 recommendations were developed through the Delphi-based consensus meetings. These recommendations included disease definitions, etiologies, pathogenesis, syndrome differentiation, diagnosis, and perioperative prevention and treatment.

Hepatitis B Virus-Mediated m6A Demethylation Increases Hepatocellular Carcinoma Stemness and Immune Escape.

Hepatitis B viral (HBV) persistent infection plays a significant role in hepatocellular carcinoma (HCC) tumorigenesis. Many studies have revealed the pivotal roles of N6-methyladenosine (m6A) in multiple cancers, while the regulatory mechanism in stemness maintenance of HBV persistent infection-related HCC remains elusive. Here, we demonstrated that the level of m6A modification was downregulated by HBV in HBV-positive HCC, through enhanced stability of ALKBH5 mRNA. More specifically, we also identified that ALKBH5 mRNA was functionally required for the stemness maintenance and self-renewal in the HBV-positive HCC, but dispensable in HBV-negative HCC. Mechanistically, ALKBH5 demethylated the m6A modification in the 3' untranslated region of the oncogenic gene SNAI2 to prevent the recognition of YTHDF2 therewith stabilize SNAI2 transcripts, contributing to cancer stem cell traits in HBV-positive HCC. Moreover, the expression of SNAI2 reversed the suppression of stemness properties by knocking down ALKBH5. In addition, ALKBH5/SNAI2 axis accelerates tumor immune evasion through activated ligand of immune checkpoint CD155. Our study unveiled that the ALKBH5 induces m6A demethylation of the SNAI2 as a key regulator in HBV-related HCC, and identifies the function of ALKBH5/SNAI2/YTHDF2 axis in promoting the stem-like cells phenotype and immune escape during HBV infection. IMPLICATIONS: HBV promotes HCC stemness maintenance through elevate m6A modification of SNAI2 in an ALKBH5-YTHDF2-dependent manner and increases the expression of the ligand of immune checkpoint CD155.

Deep Learning of Multimodal Ultrasound: Stratifying the Response to Neoadjuvant Chemotherapy in Breast Cancer Before Treatment.

BACKGROUND: Not only should resistance to neoadjuvant chemotherapy (NAC) be considered in patients with breast cancer but also the possibility of achieving a pathologic complete response (PCR) after NAC. Our study aims to develop 2 multimodal ultrasound deep learning (DL) models to noninvasively predict resistance and PCR to NAC before treatment. METHODS: From January 2017 to July 2022, a total of 170 patients with breast cancer were prospectively enrolled. All patients underwent multimodal ultrasound examination (grayscale 2D ultrasound and ultrasound elastography) before NAC. We combined clinicopathological information to develop 2 DL models, DL_Clinical_resistance and DL_Clinical_PCR, for predicting resistance and PCR to NAC, respectively. In addition, these 2 models were combined to stratify the prediction of response to NAC. RESULTS: In the test cohort, DL_Clinical_resistance had an AUC of 0.911 (95%CI, 0.814-0.979) with a sensitivity of 0.905 (95%CI, 0.765-1.000) and an NPV of 0.882 (95%CI, 0.708-1.000). Meanwhile, DL_Clinical_PCR achieved an AUC of 0.880 (95%CI, 0.751-0.973) and sensitivity and NPV of 0.875 (95%CI, 0.688-1.000) and 0.895 (95%CI, 0.739-1.000), respectively. By combining DL_Clinical_resistance and DL_Clinical_PCR, 37.1% of patients with resistance and 25.7% of patients with PCR were successfully identified by the combined model, suggesting that these patients could benefit by an early change of treatment strategy or by implementing an organ preservation strategy after NAC. CONCLUSIONS: The proposed DL_Clinical_resistance and DL_Clinical_PCR models and combined strategy have the potential to predict resistance and PCR to NAC before treatment and allow stratified prediction of NAC response.

Exercise training and vascular heterogeneity in db/db mice: evidence for regional- and duration-dependent effects.

Exercise training (ET) has several health benefits; however, our understanding of regional adaptations to ET is limited. We examined the functional and molecular adaptations to short- and long-term ET in elastic and muscular conduit arteries of db/db mice in relation to changes in cardiovascular risk factors. Diabetic mice and their controls were exercised at moderate intensity for 4 or 8 weeks. The vasodilatory and contractile responses of thoracic aortae and femoral arteries isolated from the same animals were examined. Blood and aortic samples were used to measure hyperglycemia, oxidative stress, inflammation, dyslipidemia, protein expression of SOD isoforms, COX, eNOS, and Akt. Short-term ET improved nitric oxide (NO) mediated vasorelaxation in the aortae and femoral arteries of db/db mice in parallel with increased SOD2 and SOD3 expression, reduced oxidative stress and triglycerides, and independent of weight loss, glycemia, or inflammation. Long-term ET reduced body weight in parallel with reduced systemic inflammation and improved insulin sensitivity along with increased SOD1, Akt, and eNOS expression and improved NO vasorelaxation. Exercise did not restore NOS- and COX-independent vasodilatation in femoral arteries, nor did it mitigate the hypercontractility in the aortae of db/db mice; rather ET transiently increased contractility in association with upregulated COX-2. Long-term ET differentially affected the aortae and femoral arteries contractile responses. ET improved NO-mediated vasodilation in both arteries likely due to collective systemic effects. ET did not mitigate all diabetes-induced vasculopathies. Optimization of the ET regimen can help develop comprehensive management of type 2 diabetes.

Combination therapy of irreversible electroporation and cytokine-induced killer cells for treating mice bearing panc02 pancreatic-cancer xenografts.

The current study aimed to investigate the antitumor effects and potent mechanism of cytokine-induced killer (CIK) cells combined with irreversible electroporation (IRE) via Panc02 cell-bearing mouse model in vivo. CIK cells were isolated from the spleens of Panc02 pancreatic-cancer (PC) subcutaneous-xenograft model and the proportion of different lymphocytes was also determined. The antitumor effect of the combination of IRE and CIK cells in a PC subcutaneous-xenograft model was also investigated. The proportion of cells that were positive for CD3+CD8+ and the proportion of CD3+CD56+ cells were both significantly increased after 21 days of in vitro culture. Combined treatment of IRE and CIK cell significantly inhibited tumor growth and increased the survival rate of Panc02 cell-bearing mice. Furthermore, infiltration of lymphocytes into tumor tissue was significantly increased by this combination therapy compared with the untreated group or monotherapy group. In addition, IRE significantly enhanced the expression of chemokine receptors elicited by CIK cells. In conclusion, IRE combined with CIK cells showed superior antitumor efficacy in a PC xenograft model, which we attributed to the promotion of lymphocytic infiltration, as well as to upregulation of chemokine receptor expression and the regulators of CIK cell proliferation.

Biological functions and molecular subtypes regulated by miR-142-3p in colon cancer.

MicroRNA-142-3p (miR-142-3p) has been reported to be implicated in colon cancer; however, the possible regulatory mechanisms and molecular subtypes regulated by miR-142-3p have not been fully elucidated. This study aimed to investigate the biological functions and regulatory mechanism of miR-142-3p in colon cancer. The expression level of miR-142-3p in colon cancer was analyzed based on the mRNA and miRNA expression datasets of colon cancer retrieved from The Cancer Genome Atlas. Target genes of miR-142-3p were also predicted. Based on these target genes, the functions and subtypes of miR-142-3p were investigated. The metabolic and tumor-related pathways, immune microenvironment, and target gene expression between the 2 subtypes were analyzed. MiR-142-3p was upregulated in tumor tissues, and its high expression indicated a poor prognosis. A total of 39 target genes were predicted, which were significantly involved in autophagy- and metabolism-related functions and pathways. Based on these target genes, the colon cancer samples were clustered into 2 subtypes. There were 35 metabolism-related pathways that were significantly different between the 2 clusters. The immune and stromal scores in cluster 2 were higher than those in cluster 1, whereas the tumor purity of cluster 2 was significantly lower than that of cluster 1. TP53INP2 expression in cluster 2 was higher than that in cluster 1. MiR-142-3p may promote colon cancer progression via autophagy- and metabolism-related pathways. MiR-142-3p may be served as a candidate target for the treatment of colon cancer.

Comprehensive workplace intervention for cancer prevention in China (WECAN): protocol for a stepped-wedge, cluster-randomised controlled trial.

INTRODUCTION: Cancer is the second leading cause of death across the globe with the majority of deaths occurring in low-income and middle-income countries. Evidence has shown that the cancer burden can be substantially reduced by avoiding behavioural risk factors through comprehensive intervention strategies, including workplace health promotion, which has shown to be cost-effective in developed countries while rarely conducted in developing countries. This study aims to explore a feasible and sustainable approach to the prevention and control of cancer in China by developing an evidence-based comprehensive workplace health model equipped with a smartphone application for implementation. METHODS AND ANALYSIS: This study is designed as a stepped-wedge, cluster-randomised controlled trial. We will recruit 15 workplaces from three cities in China. A total of 750 employees will be randomly selected for evaluation that includes five rounds of survey conducted every 6 months. After the second evaluation, workplaces will be randomly allocated to start the intervention sequentially every 6 months in three steps with five workplaces per step. A mobile application 'Healthy Workplace' will be developed to support the intervention. On-line and off-line health-related activities will be carried out among employees. Employers will provide supportive policies, environment and benefits to facilitate the adoption of healthy behaviours. The primary outcome is the change of Healthy Lifestyle Index Score, which consists of five components including smoking, alcohol drinking, physical activity, diet and body mass index. ETHICS AND DISSEMINATION: The study has been approved by Queen Mary University of London Ethics of Research Committee (QMERC22.257) and Chinese Centre for Disease Control and Prevention Institutional Review Board (202210). Written informed consent is required from all participants. Results will be disseminated through presentations, publications and social media. TRIAL REGISTRATION NUMBER: ChiCTR2200058680.

Prospective assessment of pancreatic ductal adenocarcinoma diagnosis from endoscopic ultrasonography images with the assistance of deep learning.

BACKGROUND: Endosonographers are highly dependent on the diagnosis of pancreatic ductal adenocarcinoma (PDAC). The objectives of this study were to develop a deep-learning radiomics (DLR) model based on endoscopic ultrasonography (EUS) images for identifying PDAC and to explore its true clinical benefit. METHODS: A retrospective data set of EUS images that included PDAC and benign lesions was used as a training cohort (N = 368 patients) to develop the DLR model, and a prospective data set was used as a test cohort (N = 123 patients) to validate the effectiveness of the DLR model. In addition, seven endosonographers performed two rounds of reader studies on the test cohort with or without DLR assistance to further assess the clinical applicability and true benefits of the DLR model. RESULTS: In the prospective test cohort, DLR exhibited an area under the receiver operating characteristic curves of 0.936 (95% confidence interval [CI], 0.889-0.976) with a sensitivity of 0.831 (95% CI, 0.746-0.913) and 0.904 (95% CI, 0.820-0.980), respectively. With DLR assistance, the overall diagnostic performance of the seven endosonographers improved: one endosonographer achieved a significant expansion of specificity (p = .035,) and another achieved a significant increase in sensitivity (p = .038). In the junior endosonographer group, the diagnostic performance with the help of the DLR was higher than or comparable to that of the senior endosonographer group without DLR assistance. CONCLUSIONS: A prospective test cohort validated that the DLR model based on EUS images effectively identified PDAC. With the assistance of this model, the gap between endosonographers at different levels of experience narrowed, and the accuracy of endosonographers expanded.

Berberine Alleviates the Damage, Oxidative Stress and Mitochondrial Dysfunction of PC12 Cells Induced by High Glucose by Activating the KEAP1/Nrf2/ARE Pathway.

Diabetic encephalopathy (DE) is one of the major chronic complications of diabetes mellitus. This study aims to investigate the inhibitory effect of berberine (BBR) on the damage of PC12 cells induced by high glucose (HG). Differentiated PC12 cells were treated with different concentrations of glucose/BBR. The cell morphology, cell viability, lactate dehydrogenase (LDH) activity, apoptosis, oxidative stress (OS), mitochondrial structure, mitochondrial membrane potential (MMP), mitochondrial complex I-V activity, and adenosine triphosphate (ATP) levels were evaluated. The mRNA and protein levels of the Keap1/Nrf2/ARE pathway-related genes were assessed by RT-qPCR and Western blot. High-dose BBR and HG jointly treated-PC12 cells were treated with Nrf2-specific inhibitor ML385 to further verify whether Nrf2 was the target of BBR. The results showed that BBR inhibited cell damage, OS, and mitochondrial dysfunction induced by HG. The inhibitory effect of high BBR was more significant. The Keap1/Nrf2/ARE pathway was inhibited in PC12 cells induced by HG. BBR could activate the Keap1/Nrf2/ARE pathway, thus up-regulating the expression levels of antioxidant enzymes. ML385 antagonized the ameliorating effect of BBR on OS and mitochondrial dysfunction. The conclusion is that BBR can activate the Keap1/Nrf2/ARE pathway, upregulate the expression patterns of antioxidant enzymes, and reduce cell damage, OS, and mitochondrial dysfunction of PC12 cells induced by HG.

Gestational trophoblastic neoplasia with primary lung cancer and mesenchymal tumor of sigmoid colon: a case report and literature review.

BACKGROUND: Gestational trophoblastic neoplasia (GTN) is rare, and it is even rarer for GTN to merge with primary malignant tumors in other organs. Herein is described a rare clinical case of GTN combined with primary lung cancer and mesenchymal tumor of the sigmoid colon, followed with literature review. CASE PRESENTATION: The patient was hospitalized due to diagnosis of GTN with primary lung cancer. Firstly, two cycles of chemotherapy including 5-fluorouracil (5-FU) and actinomycin-D(Act-D) was given. Laparoscopic total hysterectomy and right salpingo-oophorectomy was performed during the third chemotherapy. During the operation, a 3*2 cm nodule was removed which was protruded from the serous surface of the sigmoid colon, and the nodule was confirmed mesenchymal tumor pathologically, in accord with gastrointestinal stromal tumor. During the treatment of GTN, Icotinib tablets were taken orally to control the progression of lung cancer. After 2 cycles of consolidation chemotherapy of GTN, she received thoracoscopic lower lobe of right lung lobectomy and the mediastinum lymph nodes removal. She undertook gastroscopy and colonoscopy and the tubular adenoma of the descending colon was removed. At present, the regular follow-up is taken and she remains free of tumors. CONCLUSIONS: GTN combined with primary malignant tumors in other organs are extremely rare in clinical practice. When imaging examination reveals a mass in other organs, clinicians should be aware of the possibility of a second primary tumor. It will increase the difficulty of GTN staging and treatment. We emphasis the importance of the collaboration of multidisciplinary teams. Clinicians should choose a reasonable treatment plan according to the priorities of different tumors.

Deep learning radiomics of ultrasonography for comprehensively predicting tumor and axillary lymph node status after neoadjuvant chemotherapy in breast cancer patients: A multicenter study.

BACKGROUND: Neoadjuvant chemotherapy (NAC) can downstage tumors and axillary lymph nodes in breast cancer (BC) patients. However, tumors and axillary response to NAC are not parallel and vary among patients. This study aims to explore the feasibility of deep learning radiomics nomogram (DLRN) for independently predicting the status of tumors and lymph node metastasis (LNM) after NAC. METHODS: In total, 484 BC patients who completed NAC from two hospitals (H1: 297 patients in the training cohort and 99 patients in the validation cohort; H2: 88 patients in the test cohort) were retrospectively enrolled. The authors developed two deep learning radiomics (DLR) models for personalized prediction of the tumor pathologic complete response (PCR) to NAC (DLR-PCR) and the LNM status (DLR-LNM) after NAC based on pre-NAC and after-NAC ultrasonography images. Furthermore, they proposed two DLRNs (DLRN-PCR and DLRN-LNM) for two different tasks based on the clinical characteristics and DLR scores, which were generated from both DLR-PCR and DLR-LNM. RESULTS: In the validation and test cohorts, DLRN-PCR exhibited areas under the receiver operating characteristic curves (AUCs) of 0.903 and 0.896 with sensitivities of 91.2% and 75.0%, respectively. DLRN-LNM achieved AUCs of 0.853 and 0.863, specificities of 82.0% and 81.8%, and negative predictive values of 81.3% and 87.2% in the validation and test cohorts, respectively. The two DLRN models achieved satisfactory predictive performance based on different BC subtypes. CONCLUSIONS: The proposed DLRN models have the potential to accurately predict the tumor PCR and LNM status after NAC. PLAIN LANGUAGE SUMMARY: In this study, we proposed two deep learning radiomics nomogram models based on pre-neoadjuvant chemotherapy (NAC) and preoperative ultrasonography images for independently predicting the status of tumor and axillary lymph node (ALN) after NAC. A more comprehensive assessment of the patient's condition after NAC can be achieved by predicting the status of the tumor and ALN separately. Our model can potentially provide a noninvasive and personalized method to offer decision support for organ preservation and avoidance of excessive surgery.

Contrast-enhanced ultrasonography for early prediction of response of neoadjuvant chemotherapy in breast cancer.

Neoadjuvant chemotherapy (NAC) is widely accepted as a primary treatment for inoperable or locally advanced breast cancer before definitive surgery. However, not all advanced breast cancers are sensitive to NAC. Contrast-enhanced ultrasonography (CEUS) has been considered to assess tumor response to NAC as it can effectively reflect the condition of blood perfusion and lesion size. Therefore, this study aimed to evaluate the diagnostic performance of CEUS to predict early response in different regions of interest in breast tumors under NAC treatment. This prospective study included 82 patients with advanced breast cancer. Parameters of TIC (time-intensive curve) between baseline and after the first cycle of NAC were calculated for the rate of relative change (Δ), including Δpeak, ΔTTP (time to peak), ΔRBV (regional blood volume), ΔRBF (regional blood flow) and ΔMTT (mean transit time). The responders and non-responders were distinguished by the Miller-Payne Grading (MPG) system and parameters from different regions of tumors were compared in these two groups. For ROI 1(the greatest enhancement area in the central region of the tumor), there were significant differences in Δpeak1, ΔRBV1 and ΔRBF1 between responders and non-responders. For ROI 2 (the greatest enhancement area on edge of the tumor), there were significant differences in Δpeak2 and ΔRBF2 between the groups. The Δpeak1 and ΔRBF2 showed good prediction (AUC 0.798-0.820, p ≤ 0.02) after the first cycle of NAC. When the cut-off value was 0.115, the ΔRBF2 had the highest diagnostic accuracy and the maximum NPV. Quantitative TIC parameters could be effectively used to evaluate early response to NAC in advanced breast cancer.

Phylogenetic analysis and stress response of the plant U2 small nuclear ribonucleoprotein B″ gene family.

BACKGROUND: Alternative splicing (AS) is an important channel for gene expression regulation and protein diversification, in addition to a major reason for the considerable differences in the number of genes and proteins in eukaryotes. In plants, U2 small nuclear ribonucleoprotein B″ (U2B″), a component of splicing complex U2 snRNP, plays an important role in AS. Currently, few studies have investigated plant U2B″, and its mechanism remains unclear. RESULT: Phylogenetic analysis, including gene and protein structures, revealed that U2B″ is highly conserved in plants and typically contains two RNA recognition motifs. Subcellular localisation showed that OsU2B″ is located in the nucleus and cytoplasm, indicating that it has broad functions throughout the cell. Elemental analysis of the promoter region showed that it responded to numerous external stimuli, including hormones, stress, and light. Subsequent qPCR experiments examining response to stress (cold, salt, drought, and heavy metal cadmium) corroborated the findings. The prediction results of protein-protein interactions showed that its function is largely through a single pathway, mainly through interaction with snRNP proteins. CONCLUSION: U2B″ is highly conserved in the plant kingdom, functions in the nucleus and cytoplasm, and participates in a wide range of processes in plant growth and development.

Genome-wide chromatin accessibility analysis unveils open chromatin convergent evolution during polyploidization in cotton.

Allopolyploidization, resulting in divergent genomes in the same cell, is believed to trigger a "genome shock", leading to broad genetic and epigenetic changes. However, little is understood about chromatin and gene-expression dynamics as underlying driving forces during allopolyploidization. Here, we examined the genome-wide DNase I-hypersensitive site (DHS) and its variations in domesticated allotetraploid cotton (Gossypium hirsutum and Gossypium barbadense, AADD) and its extant AA (Gossypium arboreum) and DD (Gossypium raimondii) progenitors. We observed distinct DHS distributions between G. arboreum and G. raimondii. In contrast, the DHSs of the two subgenomes of G. hirsutum and G. barbadense showed a convergent distribution. This convergent distribution of DHS was also present in the wild allotetraploids Gossypium darwinii and G. hirsutum var. yucatanense, but absent from a resynthesized hybrid of G. arboreum and G. raimondii, suggesting that it may be a common feature in polyploids, and not a consequence of domestication after polyploidization. We revealed that putative cis-regulatory elements (CREs) derived from polyploidization-related DHSs were dominated by several families, including Dof, ERF48, and BPC1. Strikingly, 56.6% of polyploidization-related DHSs were derived from transposable elements (TEs). Moreover, we observed positive correlations between DHS accessibility and the histone marks H3K4me3, H3K27me3, H3K36me3, H3K27ac, and H3K9ac, indicating that coordinated interplay among histone modifications, TEs, and CREs drives the DHS landscape dynamics under polyploidization. Collectively, these findings advance our understanding of the regulatory architecture in plants and underscore the complexity of regulome evolution during polyploidization.

Genome-wide identification and analysis of ACP gene family in Sorghum bicolor (L.) Moench.

BACKGROUND: Acyl carrier proteins (ACP) constitute a very conserved carrier protein family. Previous studies have found that ACP not only takes part in the fatty acid synthesis process of almost all organisms, but also participates in the regulation of plant growth, development, and metabolism, and makes plants adaptable to stresses. However, this gene family has not been systematically studied in sorghum. RESULTS: Nine ACP family members were identified in the sorghum genome, which were located on chromosomes 1, 2, 5, 7, 8 and 9, respectively. Evolutionary analysis among different species divided the ACP family into four subfamilies, showing that the SbACPs were more closely related to maize. The prediction results of subcellular localization showed that SbACPs were mainly distributed in chloroplasts and mitochondria, while fluorescence localization showed that SbACPs were mainly localized in chloroplasts in tobacco leaf. The analysis of gene structure revealed a relatively simple genetic structure, that there were 1-3 introns in the sorghum ACP family, and the gene structure within the same subfamily had high similarity. The amplification method of SbACPs was mainly large fragment replication, and SbACPs were more closely related to ACPs in maize and rice. In addition, three-dimensional structure analysis showed that all ACP genes in sorghum contained four α helices, and the second helix structure was more conserved, implying a key role in function. Cis-acting element analysis indicated that the SbACPs might be involved in light response, plant growth and development regulation, biotic and abiotic stress response, plant hormone regulation, and other physiological processes. What's more, qRT-PCR analysis uncovered that some of SbACPs might be involved in the adaptive regulation of drought and salt stresses, indicating the close relationship between fatty acids and the resistance to abiotic stresses in sorghum. CONCLUSIONS: In summary, these results showed a comprehensive overview of the SbACPs and provided a theoretical basis for further studies on the biological functions of SbACPs in sorghum growth, development and abiotic stress responses.

Genome-Wide Identification and Expression Analysis Elucidates the Potential Role of PFK Gene Family in Drought Stress Tolerance and Sugar Metabolism in Cotton.

Drought has been identified as a major threat for global crop production worldwide. Phosphofructokinase (PFK) is vital for sugar metabolism. During phosphorylation, plants have two enzymes: ATP-dependent phosphofructokinase (PFK) and pyrophosphate-dependent fructose-6-phosphate phosphotransferase (PFP). Genome-wide identification led to the identification of 80 PFK genes, 26 genes in G. hirsutum and G. barbadense, and 14 genes in G. arboreum and G. raimondii. Phylogenetic, gene structure, and motif analyses showed that PFK genes were grouped into two main categories, namely, PFK and PFP, with 18 and 8 genes in the allotetraploid species and 10 PFK and 4 PFP genes in the diploid species, respectively. Using the RNA-seq expressions of 26 genes from GhPFK, a co-expression network analysis was performed to identify the hub genes. GhPFK04, GhPFK05, GhPFK09, GhPFK11, GhPFK13, GhPFK14, and GhPFK17 in leaves and GhPFK02, GhPFK09, GhPFK11, GhPFK15, GhPFK16, and GhPFK17 in root tissues were found as hub genes. RT-qPCR analysis validated the expressions of identified hub genes. Interestingly, GhPFK11 and GhPFK17 were identified as common hub genes, and these might be the true candidate genes involved in the drought stress tolerance. In the KEGG enrichment analysis, amino acids such as L-valine, L-histidine, L-glutamine, L-serine, L-homoserine, L-methionine, L-cysteine, and gluconic acid were significantly upregulated, whereas sugars, mainly fructose-1-phosphate, D-mannitol, D-sorbitol, dulcitol, and lactose, were significantly downregulated during drought stress. Genome-wide analysis paves the way for a deeper understanding of the PFK genes and establishes the groundwork for future research into PFK's role in enhancing drought stress tolerance and sugar metabolism in cotton.

[Analysis on liver cancer mortality and cause eliminated life expectancy in key areas of 4 provinces, China, 2008-2018].

Objective: To explore the changes of liver cancer mortality and the effect of liver cancer on life expectancy in key areas of four provinces in China from 2008 to 2018 and provide the basis for the evaluation of comprehensive prevention and control of cancer and promotion of the rational allocation of health resources. Methods: Based on the national cause-of-death surveillance in key areas of the 4 provinces from 2008 to 2018, we analyzed the mortality of liver cancer, cause eliminated life expectancy (CELE) and potential gains in life expectancy (PGLEs). Software Joinpoint 4.9.0.0 was used to calculate the average annual percentage change (AAPC). Arriaga's decomposition method was used to estimate the contribution of the changes of liver cancer mortality in each age group to life expectancy. Results: The standardized mortality of liver cancer in key areas of the 4 provinces showed a downward trend from 2008 to 2018 (AAPC=-4.37%, P<0.001). The changes of liver cancer mortality had a positive effect on the increase of life expectancy, with a contribution value of 0.240 years and a contribution degree of 5.62%. The positive effect was greatest in age group 45-49 years (0.041 years, 0.96%), and the negative effect was greatest in age group 50-54 years (-0.015 years, -0.35%). Compared with 2008, the life expectancy increased by 4.27 years (AAPC=0.59%, P<0.001), the liver cancer CELE increased by 4.20 years (AAPC=0.58%, P<0.001), the PGLEs decreased by 0.07 years (AAPC=-0.62%,P<0.001), and life loss rate decreased by 0.13% (AAPC=-1.18%, P=0.001). The liver cancer PGLEs increased in Yongqiao district, Anhui province (0.09 years), and decreased in other districts (counties), with the largest decline was in Fugou county, Henan province (-0.21 years). Conclusions: From 2008 to 2018, the standardized mortality rate of liver cancer in key areas of the 4 provinces decreased gradually, contributing to the growth of life expectancy. The life loss caused by liver cancer decreased gradually, but the PGLEs varied with districts (counties).

Cancer incidence and mortality and risk factors in member countries of the " Belt and Road " initiative.

BACKGROUND: At present, "Belt and Road" ("B&R") member states (accounting for about 61.78% of the world's population) face different types of cancer threats to varying degrees. We analyzed the incidence and mortality and risk factors of cancer in the member countries of the "B&R" to explore the basis of health and medical cooperation between countries and provide a foundation for formulating cancer prevention and control policies for building a healthy "B&R." METHODS: Data were derived from the Global Cancer Observatory and Cancer Country Profiles in 2020. Incidence and mortality were age-standardized rates (ASRs). Population attributable fractions (PAFs) was applied to measure risk factors of cancers in the "B&R" countries. The mortality-to-incidence ratio (MIR) was calculated by dividing the mortality rate by the incidence rate. RESULTS: A total of 26 cancers were included in the study. Lung, breast, colorectal, stomach, liver, prostate, cervical, esophageal, thyroid, and uterine cancers were the most common and highest in age-standardized mortality in the "B&R" countries. For men, Hungary had the highest cancer age-standardized incidence and mortality (ASR, 289.3 per 100,000 and ASR, 235.7 per 100,000, respectively), followed by Latvia (ASR, 288.6 per 100,000 and ASR, 196.5 per 100,000, respectively). In females, the highest incidence rates were estimated in Greece (ASR, 238.7 per 100,000), and the highest mortality rate was Brunei (ASR, 192.3 per 100,000). All countries were in the middle or high HDI range, with about half (46.88%) of countries achieving high HDI, mostly in Central and Eastern Europe (13 countries) and West Asia (10 countries). The United Arab Emirates had the highest MIR in male and female (1.59 vs 2.19). Tobacco products, infectious factors, and ultraviolet rays were the three main cancer risk factors in the "B&R" countries. CONCLUSION: The overall burden of cancer in the countries along the "B&R" remains substantial, while the corresponding cancer prevention and control policies need to be improved. Strengthening health cooperation among member countries will contribute to a joint response to the risks and challenges posed by cancer.

Age-period-cohort analysis of lung cancer mortality in China and Australia from 1990 to 2019.

Lung cancer (LC) is the leading cause of cancer death in China and Australia, the countries with different socioenvironmental contexts in the Western Pacific Region. Comparing the age-period-cohort effect on LC mortality (LCM) between the two countries can help plan interventions and draw lessons for countries in the region. We collected LCM estimates between 1990 and 2019 from the GBD 2019. Age-period-cohort modelling was applied to compute the net drift, local drift, cross-sectional age curve, longitudinal age curve, and the rate ratios (RRs) of period and cohort. China had a higher LC age-standardized mortality rate than Australia in 2019 (men: 58.10 [95% uncertainty interval (UI): 46.53, 70.89] vs. 30.13 [95% UI: 27.88, 32.31]/100,000 population; women: 22.86 [95% UI: 18.52, 27.52] vs. 17.80 [95% UI: 15.93, 19.34]/100,000 population). Period and cohort effects on LCM improved more markedly among Australian men (RR for period effect, from 1.47 [95% confidence interval (CI) 1.41, 1.53] to 0.79 [95% CI 0.75, 0.84]; RR for cohort effect, from 2.56 [95% CI 2.44, 2.68] to 0.36 [95% CI 0.11, 1.18]) and Chinese women (RR for period effect, from 1.06 [95% CI 1.01, 1.11] to 0.85 [95% CI 0.82, 0.89]; RR for cohort effect, from 0.71 [95% CI 0.65, 0.78] to 0.51 [95% CI 0.26, 1.03]) during the study period and birth cohort. The LCM in Chinese population aged 65 to 79 and Australian women aged 75 to 79 increased. Smoking and particulate matter (PM) contributed most to LCM in China, while smoking and occupational carcinogens contributed most in Australia. Decreasing period and cohort risks for LCM attributable to smoking and PM were more remarkable in Australia than in China. The LCM attributable to occupational carcinogens was higher in Australia than in China, particularly for those aged 60 to 79. Vigorous tobacco and PM control, which brought a substantial decline in LCM in Australia, may help reduce LCM in China. Australia should highlight LC prevention among people with occupational exposure. Chinese aged ≥ 65 and Australian women aged ≥ 75 should be the priorities for LC interventions.