The clinical efficacy and safety of different biliary drainage in malignant obstructive jaundice: a meta-analysis.

Background: Currently, percutaneous transhepatic cholangial drainage (PTCD) and endoscopic retrograde cholangiopancreatography (ERCP) are commonly employed in clinical practice to alleviate malignant obstructive jaundice (MOJ). Nevertheless, there lacks a consensus regarding the superiority of either method in terms of efficacy and safety. Aim: To conduct a systematic evaluation of the effectiveness and safety of PTCD and ERCP in treating MOJ, and to compare the therapeutic outcomes and safety profiles of these two procedures. Methods: CNKI, VIP, Wanfang, CBM, PubMed, Web of Science, Embase, The Cochrane Library, and other databases were searched for randomized controlled trials (RCTs) on the use of PTCD or ERCP for MOJ. The search period was from the establishment of the databases to July 2023. After quality assessment and data extraction from the included studies, Meta-analysis was performed using RevMan5.3 software. Results: A total of 21 RCTs involving 1,693 patients were included. Meta-analysis revealed that there was no significant difference in the surgical success rate between the two groups for patients with low biliary obstruction (P=0.81). For patients with high biliary obstruction, the surgical success rate of the PTCD group was higher than that of the ERCP group (P < 0.0001), and the overall surgical success rate of the PTCD group was also higher than that of the ERCP group (P = 0.008). For patients with low biliary obstruction, the rate of jaundice relief (P < 0.00001) and the clinical efficacy (P = 0.0005) were better in the ERCP group, while for patients with high biliary obstruction, the rate of jaundice relief (P < 0.00001) and the clinical efficacy (P = 0.003) were better in the PTCD group. There was no significant difference in the overall jaundice remission rate and clinical efficacy between the two groups (P = 0.77, 0.53). There was no significant difference in the reduction of ALT, TBIL, and DBIL before and after surgery and the incidence of postoperative complications between the two groups (P > 0.05). Conclusion: Both PTCD and ERCP can efficiently alleviate biliary obstruction and enhance liver function. ERCP is effective in treating low biliary obstruction, while PTCD is more advantageous in treating high biliary obstruction.

Transcriptomic and Metabolomic Analyses Reveal the Role of Phenylalanine Metabolism in the Maize Response to Stalk Rot Caused by Fusarium proliferatum.

Stalk rot is a prevalent disease of maize (Zea mays L.) that severely affects maize yield and quality worldwide. The ascomycete fungus Fusarium spp. is the most common pathogen of maize stalk rot. At present, the molecular mechanism of Fusarium proliferation during the maize stalk infection that causes maize stalk rot has rarely been reported. In this study, we investigated the response of maize to F. proliferatum infestation by analyzing the phenotypic, transcriptomic, and metabolomic data of inbred lines ZC17 (resistant) and CH72 (susceptible) with different levels of resistance to stalk rot. Physiological and phenotypic results showed that the infection CH72 was significantly more severe than ZC17 after inoculation. Transcriptome analysis showed that after inoculation, the number of differentially expressed genes (DEGs) was higher in CH72 than in ZC17. Nearly half of these DEGs showed the same expression trend in the two inbred lines. Functional annotation and enrichment analyses indicated that the major pathways enriched for DEGs and DEMs included the biosynthesis of plant secondary metabolites, phenylalanine metabolism, biosynthesis of plant hormones, and plant-pathogen interactions. The comprehensive analysis of transcriptome and metabolome data indicated that phenylalanine metabolism and the phenylalanine, tyrosine, and tryptophan biosynthesis pathways played a crucial role in maize resistance to F. proliferatum infection. In addition, a transcription factor (TF) analysis of the DEGs showed that several TF families, including MYB, bHLH, NAC, and WRKY, were significantly activated after inoculation, suggesting that these TFs play important roles in the molecular regulatory network of maize disease resistance. The findings of this study provide valuable insights into the molecular basis of the response of maize to Fusarium proliferatum infection and highlight the importance of combining multiple approaches, such as phenotyping, transcriptomics, and metabolomics, to gain a comprehensive understanding of plant-pathogen interactions.

A recurrence-predictive model based on eight genes and tumor mutational burden/microsatellite instability status in Stage II/III colorectal cancer.

BACKGROUND: Although adjuvant chemotherapy (ACT) is widely used to treat patients with Stage II/III colorectal cancer (CRC), administering ACT to specific patients remains a challenge. The decision to ACT requires an accurate assessment of recurrence risk and absolute treatment benefit. However, the traditional TNM staging system does not accurately assess a patient's individual risk of recurrence. METHODS: To identify recurrence risk-related genetic factors for Stage II/III CRC patients after radical surgery, we conducted an analysis of whole-exome sequencing of 47 patients with Stage II/III CRC who underwent radical surgery at five institutions. Patients were grouped into non-recurrence group (NR, n = 24, recurrence-free survival [RFS] > 5 years) and recurrence group (R, n = 23, RFS <2 years). The TCGA-COAD/READ cohort was employed as the validation dataset. RESULTS: A recurrence-predictive model (G8plus score) based on eight gene (CUL9, PCDHA12, HECTD3, DCX, SMARCA2, FAM193A, AATK, and SORCS2) mutations and tumor mutation burden/microsatellite instability (TMB/MSI) status was constructed, with 97.87% accuracy in our data and 100% negative predictive value in the TCGA-COAD/READ cohort. For the TCGA-COAD/READ cohort, the G8plus-high group had better RFS (HR = 0.22, p = 0.024); the G8plus-high tumors had significantly more infiltrated immune cell types, higher tertiary lymphoid structure signature scores, and higher immunological signature scores. The G8plus score was also a predict biomarker for immunotherapeutic in advanced CRC in the PUCH cohort. CONCLUSIONS: In conclusion, the G8plus score is a powerful biomarker for predicting the risk of recurrence in patients with stage II/III CRC. It can be used to stratify patients who benefit from ACT and immunotherapy.

Effects of microcystin on protein profile in hepatopancreas of Litopenaeus vannamei.

For intensive aquaculture in freshwater ponds, microcystin (MC-LR) generated from cyanobacterial blooms is one of the bottlenecks for the healthy and sustainable development of shrimp aquaculture industry. In this study, we measured the MC-LR content in the hepatopancreas and muscles of Litopenaeus vannamei stressed by MC-LR, and analyzed protein expression in the hepatopancreas using DIA high-throughput proteomics technology. The results showed that MC-LR content in the hepatopancreas and muscles reached the highest at 1 h after MC-LR injection, which was (6.12±0.45) µg·kg-1 and (5.00±0.19) µg·kg-1, respectively. Then, it decreased gra-dually, with that in the hepatopancreas being significantly higher than in muscles. We identified 820 differential expressed proteins, including 586 up-regulated and 234 down-regulated ones. Results of bioinformatics analysis showed that MC-LR stress significantly affected immune-related pathways such as lysosome, RIG-Ⅰ receptor signals and interleukin-2. It also altered energy metabolisms including citrate cycle, metabolism of starch and sucrose, and interconversion of pentose and glucoronate, which in turn led to the disorder of carbohydrate metabolism. In addition, MC-LR significantly upregulated 19 cytoskeleton-related blood shadow proteins and damaged the hepatopancreas cytoskeleton. It was concluded that MC-LR mainly affected the physiological processes associated with immunity, energy metabolism, and cytoskeleton in the hepatopancreas of L. vannamei.

Perineal defect reconstruction after surgery for advanced or locally recurrent rectal cancer involving organ resection: Multiple flaps combined with lining repair.

AIM: The aim of this study was to investigate the efficacy of multiple perineal perforator flaps in repairing deep perineal defects after pelvic exenteration for locally advanced or recurrent rectal cancer. METHOD: We investigated the outcomes of eight patients whose repairs involved a novel method of using an internal pudendal artery perforator (IPAP) flap combined with an inferior gluteal artery perforator (IGAP) flap. RESULTS: There were four male and four female patients with a mean age of 56 years (36-72 years). Bilateral IPAP flaps combined with bilateral IGAP flaps were used in five patients, unilateral IPAP flaps combined with bilateral IGAP flaps were used in two patients and bilateral IPAP flaps were used in one patient. There were no functional limitations in daily activities during the 6-month follow-up period. CONCLUSION: Our study showed that using multiple perineal perforator flaps combined with lining repair is feasible for repairing deep perineal defects in patients who have undergone rectal cancer surgery that includes pelvic exenteration.

E2F3 accelerates the stemness of colon cancer cells by activating the STAT3 pathway.

Introduction: Colon cancer is one of the most prevalent malignancies and causes of cancer-related deaths worldwide. Thus, further research is required to explicate the latent molecular mechanisms and look for novel biomarkers. E2F3 has been confirmed to be an oncogene in a variety of cancers. However, the particular regulation of E2F3 in colon cancer needs further investigation. Methods: The self-renewal ability was detected through a sphere formation assay. The tumorigenic ability was measured through nude mice in vivo assay. The protein expression of genes was examined through a Western blot. The expression of E2F3 in tumor tissues was detected through an IHC assay. The resistance to cisplatin was assessed through the CCK-8 assay. The cell migration and invasion abilities were measured after upregulating or suppressing E2F3 through the Transwell assay. Results: Results uncovered that E2F3 was upregulated in spheroid cells. In addition, E2F3 facilitates stemness in colon cancer. Moreover, E2F3 facilitated colon cancer cell migration and invasion. Finally, it was revealed that E2F3 affected the STAT3 pathway to modulate stemness in colon cancer. E2F3 served as a promoter regulator in colon cancer, aggravating tumorigenesis and stemness in colon cancer progression through the STAT3 pathway. Conclusion: E2F3 may be a useful biomarker for anticancer treatment in colon cancer.

Rectal cancer-derived exosomes activate the nuclear factor kappa B pathway and lung fibroblasts by delivering integrin beta-1.

Numerous studies have revealed the importance of tumor-derived exosomes in rectal cancer (RC). This study aims to explore the influence of tumor-derived exosomal integrin beta-1 (ITGB1) on lung fibroblasts in RC along with underlying mechanisms. Exosome morphology was observed using a transmission electron microscope. Protein levels of CD63, CD9, ITGB1, p-p65 and p65 were detected using Western blot. To determine ITGB1's mRNA expression, quantitative real-time polymerase chain reaction was used. Moreover, levels of interleukin (IL)-8, IL-1ß, and IL-6 in cell culture supernatant were measured via commercial ELISA kits. ITGB1 expression was increased in exosomes from RC cells. The ratio of p-p65/p65 as well as levels of interleukins in lung fibroblasts was raised by exosomes derived from RC cells, while was reduced after down-regulation of exosomal ITGB1. The increased ratio of p-p65/p65 as well as levels of pro-inflammatory cytokines caused by exosomes from RC cells was reversed by the addition of nuclear factor kappa B (NF-κB) inhibitor. We concluded that the knockdown of RC cells-derived exosomal ITGB1 repressed activation of lung fibroblasts and the NF-κB pathway in vitro.

Breviscapine regulates the proliferation, migration, invasion, and apoptosis of colorectal cancer cells via the PI3K/AKT pathway.

Colorectal cancer (CRC) is ranked as one of the most common malignancies with a high death rate. It has been discovered that breviscapine can alter the progression and development of various cancers. Nevertheless, the function and mechanisms of breviscapine in CRC progression have not yet been described. The cell proliferation capacity of HCT116 and SW480 cells was assessed using the CCK-8 and EdU assays. Cell apoptosis was tested through flow cytometry, and cell migration and invasion were examined using the transwell assay. Moreover, protein expression was examined through a western blot. Tumor weight and volume were assessed using the nude mice in vivo assay, and the Ki-67 protein expression was verified through the IHC assay. This study discovered that an increased dose of breviscapine (0, 12.5, 25, 50, 100, 200, and 400 µM) gradually reduced cell proliferation and increased apoptosis in CRC. Additionally, breviscapine restricted the migration and invasion CRC cells. Moreover, it was revealed that breviscapine inactivated the PI3K/AKT pathway and inhibited CRC progression. Finally, an in vivo assay demonstrated that breviscapine restrained tumor growth in vivo. It affected the CRC cells' proliferation, migration, invasion, and apoptosis through the PI3K/AKT pathway. This discovery may offer new insights into CRC treatment.

Visible-Light-Induced Copper-Catalyzed Intermolecular Three-Component Difluoroalkyl Thiocyanidation of Alkenes.

In this report, we develop a new strategy for visible-light-induced, copper-catalyzed three-component difluoroalkyl thiocyanidation of alkenes to construct a series of important difluorothiocyanate compounds. The new approach can also be applied to perfluorothiocyanate compounds, even target molecules containing drug/natural product skeletons. Mechanistic studies provide that the copper complex plays a dual role, as both the photoredox catalyst for electron transfer and the cross-coupling catalyst for C-SCN bond formation.

Copper-catalyzed radical-mediated intermolecular cyanomonofluoroalkylation of alkenes and alkynes.

A novel copper-catalyzed three-component reaction of monofluoroalkylation agents, alkenes and TMSCN is described. In addition, alkynes could also be compatible with the reaction system to obtain three-component products for the first time with moderate yield and excellent E/Z stereoselectivity. This reaction provides a facile method for the synthesis of cyanomonofluoroalkyl compounds, which may serve as potentially useful organic intermediates for further transformations. Preliminary mechanistic investigation indicated that monofluoroalkyl free radicals were involved in the cyanomonofluoroalkylation process.

Examining the Effects of Socioeconomic Development on Fine Particulate Matter (PM2.5) in China's Cities Based on Spatial Autocorrelation Analysis and MGWR Model.

Understanding the characteristics of PM2.5 and its socioeconomic factors is crucial for managing air pollution. Research on the socioeconomic influences of PM2.5 has yielded several results. However, the spatial heterogeneity of the effect of various socioeconomic factors on PM2.5 at different scales has yet to be studied. This paper collated PM2.5 data for 359 cities in China from 2005 to 2020, as well as socioeconomic data: GDP per capita (GDPP), secondary industry proportion (SIP), number of industrial enterprise units above the scale (NOIE), general public budget revenue as a proportion of GDP (PBR), and population density (PD). The spatial autocorrelation and multiscale geographically weighted regression (MGWR) model was used to analyze the spatiotemporal heterogeneity of PM2.5 and explore the impact of different scales of economic factors. Results show that the overall economic level was developing well, with a spatial distribution trend of high in the east and low in the west. With a large positive spatial correlation and a highly concentrated clustering pattern, the PM2.5 concentration declined in 2020. Secondly, the OLS model's statistical results were skewed and unable to shed light on the association between economic factors and PM2.5. Predictions from the GWR and MGWR models may be more precise than those from the OLS model. The scales of the effect were produced by the MGWR model's variable bandwidth and regression coefficient. In particular, the MGWR model's regression coefficient and variable bandwidth allowed it to account for the scale influence of economic factors; it had the highest adjusted R2 values, smallest AICc values, and residual sums of squares. Lastly, the PBR had a clear negative impact on PM2.5, whereas the negative impact of GDPP was weak and positively correlated in some western regions, such as Gansu and Qinghai provinces. The SIP, NOIE, and PD were positively correlated with PM2.5 in most regions. Our findings can serve as a theoretical foundation for researching the associations between PM2.5 and socioeconomic variables, and for encouraging the coequal growth of the economy and the environment.

Electroreductively Induced Radicals for Organic Synthesis.

Organic electrochemistry has attracted tremendous interest within the novel sustainable methodologies that have not only reduced the undesired byproducts, but also utilized cleaner and renewable energy sources. Particularly, oxidative electrochemistry has gained major attention. On the contrary, reductive electrolysis remains an underexplored research direction. In this context, we discuss advances in transition-metal-free cathodically generated radicals for selective organic transformations since 2016. We highlight the electroreductive reaction of alkyl radicals, aryl radicals, acyl radicals, silyl radicals, fluorosulfonyl radicals and trifluoromethoxyl radicals.

Development and validation of postoperative circulating tumor DNA combined with clinicopathological risk factors for recurrence prediction in patients with stage I-III colorectal cancer.

BACKGROUND: Circulating tumor DNA (ctDNA) detection following curative-intent surgery could directly reflect the presence of minimal residual disease, the ultimate cause of clinical recurrence. However, ctDNA is not postoperatively detected in ≥ 50% of patients with stage I-III colorectal cancer (CRC) who ultimately recur. Herein we sought to improve recurrence risk prediction by combining ctDNA with clinicopathological risk factors in stage I-III CRC. METHODS: Two independent cohorts, both consisting of early-stage CRC patients who underwent curative surgery, were included: (i) the discovery cohort (N = 124) with tumor tissues and postoperative plasmas for ctDNA determination; and (ii) the external validation cohort (N = 125) with available ctDNA results. In the discovery cohort, somatic variations in tumor tissues and plasmas were determined via a 733-gene and 127-gene next-generation sequencing panel, respectively. RESULTS: In the discovery cohort, 17 of 108 (15.7%) patients had detectable ctDNA. ctDNA-positive patients had a significantly high recurrence rate (76.5% vs. 16.5%, P < 0.001) and short recurrence-free survival (RFS; P < 0.001) versus ctDNA-negative patients. In addition to ctDNA status, the univariate Cox model identified pathologic stage, lymphovascular invasion, nerve invasion, and preoperative carcinoembryonic antigen level associated with RFS. We combined the ctDNA and clinicopathological risk factors (CTCP) to construct a model for recurrence prediction. A significantly higher recurrence rate (64.7% vs. 8.1%, P < 0.001) and worse RFS (P < 0.001) were seen in the high-risk patients classified by the CTCP model versus those in the low-risk patients. Receiver operating characteristic analysis demonstrated that the CTCP model outperformed ctDNA alone at recurrence prediction, which increased the sensitivity of 2 year RFS from 49.6% by ctDNA alone to 87.5%. Harrell's concordance index, calibration curve, and decision curve analysis also suggested that the CTCP model had good discrimination, consistency, and clinical utility. These results were reproduced in the validation cohort. CONCLUSION: Combining postoperative ctDNA and clinical risk may better predict recurrence than ctDNA alone for developing a personalized postoperative management strategy for CRC.

Development of the maize 5.5K loci panel for genomic prediction through genotyping by target sequencing.

Genotyping platforms are important for genetic research and molecular breeding. In this study, a low-density genotyping platform containing 5.5K SNP markers was successfully developed in maize using genotyping by target sequencing (GBTS) technology with capture-in-solution. Two maize populations (Pop1 and Pop2) were used to validate the GBTS panel for genetic and molecular breeding studies. Pop1 comprised 942 hybrids derived from 250 inbred lines and four testers, and Pop2 contained 540 hybrids which were generated from 123 new-developed inbred lines and eight testers. The genetic analyses showed that the average polymorphic information content and genetic diversity values ranged from 0.27 to 0.38 in both populations using all filtered genotyping data. The mean missing rate was 1.23% across populations. The Structure and UPGMA tree analyses revealed similar genetic divergences (76-89%) in both populations. Genomic prediction analyses showed that the prediction accuracy of reproducing kernel Hilbert space (RKHS) was slightly lower than that of genomic best linear unbiased prediction (GBLUP) and three Bayesian methods for general combining ability of grain yield per plant and three yield-related traits in both populations, whereas RKHS with additive effects showed superior advantages over the other four methods in Pop1. In Pop1, the GBLUP and three Bayesian methods with additive-dominance model improved the prediction accuracies by 4.89-134.52% for the four traits in comparison to the additive model. In Pop2, the inclusion of dominance did not improve the accuracy in most cases. In general, low accuracies (0.33-0.43) were achieved for general combing ability of the four traits in Pop1, whereas moderate-to-high accuracies (0.52-0.65) were observed in Pop2. For hybrid performance prediction, the accuracies were moderate to high (0.51-0.75) for the four traits in both populations using the additive-dominance model. This study suggests a reliable genotyping platform that can be implemented in genomic selection-assisted breeding to accelerate maize new cultivar development and improvement.

Circularly Polarized Antenna Array with Decoupled Quad Vortex Beams.

Achieving multiple vortex beams with different modes in a planar microstrip array is pivotal, yet still extremely challenging. Here, a hybrid method combining both Pancharatnam−Berry (PB) phase that is induced by the rotation phase and excitation phase of a feeding line has been proposed for decoupling two orthogonal circularly polarized vortex beams. Theoretical analysis is derived for array design to generate quad vortex beams with different directions and an arbitrary number of topological charges. On this basis, two 8 × 8 planar arrays were theoretically designed in an X band, which are with topological charges of l1 = −1, l2 = 1, l3 = −1, and l4 = 1 in Case I and topological charges of l1 = −1, l2 = 1, l3 = −1, and l4 = 1 in Case II. To further verify the above theory, the planar array in Case I is fabricated and analyzed experimentally. Dual-LP beams are realized by using rectangular patch elements with two orthogonally distributed feeding networks on different layers based on two types of feeding: proximity coupling and aperture coupling. Both the numerical simulation and experimental measurement results are in good agreement and showcase the corresponding quad-vortex-beam characteristics within 8~12 GHz. The array achieves a measured S11 < −10 dB and S22 < −10 dB bandwidth of more than 33.4% and 29.2%, respectively. In addition, the isolation between two ports is better than −28 dB. Our strategy provides a promising way to achieve large capacity and high integration, which is of great benefit to wireless and radar communication systems.

Transcriptomic Variations and Network Hubs Controlling Seed Size and Weight During Maize Seed Development.

To elucidate the mechanisms underlying seed development in maize, comprehensive RNA-seq analyses were conducted on Zhengdan1002 (ZD1002), Zhengdan958 (ZD958), and their parental lines during seven seed developmental stages. We found that gene expression levels were largely nonadditive in hybrids and that cis-only or trans × cis pattern played a large role in hybrid gene regulation during seed developmental stage. Weighted gene co-expression network (WGCNA) analysis showed that 36 modules were highly correlated (r = -0.90-0.92, p < 0.05) with kernel weight, length, and width during seed development. Forty-five transcription factors and 38 ribosomal protein genes were identified as major hub genes determining seed size/weight. We also described a network hub, Auxin Response Factor 12 of maize (ZmARF12), a member of a family of transcription factor that mediate gene expression in response to auxin, potentially links auxin signal pathways, cell division, and the size of the seeds. The ZmARF12 mutant exhibited larger seed size and higher grain weight. ZmARF12 transcription was negatively associated with cell division during seed development, which was confirmed by evaluating the yield of protoplasts that isolated from the kernels of the mutant and other inbred lines. Transient knock-down of ZmARF12 in maize plants facilitated cell expansion and division, whereas transient silencing of its potential interactor ZmIAA8 impaired cell division. ZmIAA8 expression was repressed in the ZmARF12 over-expressed protoplasts. The mutant phenotype and the genetics studies presented here illustrated evidence that ZmARF12 is a cell division repressor, and potentially determines the final seed size.

Adaptable Invisibility Management Using Kirigami-Inspired Transformable Metamaterials.

Many real-world applications, including adaptive radar scanning and smart stealth, require reconfigurable multifunctional devices to simultaneously manipulate multiple degrees of freedom of electromagnetic (EM) waves in an on-demand manner. Recently, kirigami technique, affording versatile and unconventional structural transformation, has been introduced to endow metamaterials with the capability of controlling EM waves in a reconfigurable manner. Here, we report for a kirigami-inspired sparse meta-architecture, with structural density of 1.5% in terms of the occupation space, for adaptive invisibility based on independent operations of frequency, bandwidth, and amplitude. Based on the general principle of dipolar management via structural reconstruction of kirigami-inspired meta-architectures, we demonstrate reconfigurable invisibility management with abundant EM functions and a wide tuning range using three enantiomers (A, B, and C) of different geometries characterized by the folding angle ß. Our strategy circumvents issues of limited abilities, narrow tuning range, extreme condition, and high cost raised by available reconfigurable metamaterials, providing a new avenue toward multifunctional smart devices.