Transarterial Chemoembolization Plus Lenvatinib and PD-1 Inhibitors for Hepatocellular Carcinoma with Main Trunk Portal Vein Tumor Thrombus: A Multicenter Retrospective Study.

Purpose: In recent years, immune checkpoint inhibitors have been used in combination with tyrosine kinase inhibitors and local therapies, creating a new era in treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). However, the benefits of this triple therapy remain unclear. Thus, this study evaluated whether the combination of transarterial chemoembolization (TACE), lenvatinib, and programmed death-1 (PD-1) inhibitors (triple therapy) was effective and safe for unresectable HCC with main trunk portal vein tumor thrombus (Vp4). Patients and Methods: This study enrolled patients receiving triple therapy at four institutions between August 2018 and April 2022. Patient characteristics and course of treatment were extracted from patient records. Tumors and tumor thrombus response were evaluated using an HCC-specific modified RECIST. Kaplan-Meier curve analysis demonstrated overall survival (OS) and progression-free survival (PFS). Adverse events (AEs) were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Results: Median follow-up duration was 18 (4.0-26.3) months. Overall, 41 patients with HCC and Vp4 receiving first-line triple therapy were enrolled. The intrahepatic tumor objective response rate was 68.3%. The median OS was 21.7 (range, 2.8-30.5) months, whereas the median PFS was 14.5 (range, 1.3-27.6) months. Twelve patients received sequential resections. Resection was independently associated with favorable OS and PFS. Fever (31.7%), hypertension (26.8%), fatigue (24.4%), abnormal liver function (63.4%) and decreased appetite (21.9%) were the AEs frequently associated with treatment. No treatment-related mortality occurred. Conclusion: TACE plus lenvatinib and PD-1 inhibition was effective and tolerable for treating unresectable HCC with Vp4, with a high tumor response rate and favorable prognosis.

Robust electrical impedance tomography for biological application: A mini review.

Electrical impedance tomography (EIT) has been used by researchers across several areas because of its low-cost and no-radiation properties. Researchers use complex conductivity in bioimpedance experiments to evaluate changes in various indicators within the image target. The diverse volumes and edges of biological tissues and the large impedance range impose dedicated demands on hardware design. The EIT hardware with a high signal-to-noise ratio (SNR), fast scanning and suitable for the impedance range of the image target is a fundamental foundation that EIT research needs to be equipped with. Understanding the characteristics of this technique and state-of-the-art design will accelerate the development of the robust system and provide a guidance for the superior performance of next-generation EIT. This review explores the hardware strategies for EIT proposed in the literature.

All-solid-state potentiometric salicylic acid sensor for in-situ measurement of plant.

Using PEDOT as the conductive polymer, an innovative small-scale sensor for directly measuring salicylate ions in plants was developed, which avoided the complicated sample pretreatment of traditional analytical methods and realized the rapid detection of salicylic acid. The results demonstrate that this all-solid-state potentiometric salicylic acid sensor is easy to miniaturize, has a longer lifetime (≥1 month), is more robust, and can be directly used for the detection of salicylate ions in real samples without any additional pretreatment. The developed sensor has a good Nernst slope (63.6 ± 0.7 mV/decade), the linear range is 10-2 ~ 10-6 M, and the detection limit can reach (2.8 × 10-7 M). The selectivity, reproducibility, and stability of the sensor were evaluated. The sensor can perform stable, sensitive, and accurate in situ measurement of salicylic acid in plants, and it is an excellent tool for determining salicylic acid ions in plants in vivo.

Prediction of Re-positivity for Coronavirus Nucleic Acid Among COVID-19 Patients in the Recovery Phase.

Background and Objectives: Although the pathogenesis and treatment of coronavirus disease 2019 (COVID-19) have been gradually revealed, the risk for re-emergence of coronavirus nucleic acids in recovered patients remains poorly understood. Hence, this study evaluated the risk predictors associated with re-positivity for virus nucleic acid. Methods: Between February 1 and March 20, 2020, we retrospectively reviewed the clinical epidemiological data of 129 COVID-19 patients who were treated at Zhongxiang People's Hospital of Hubei Province in China. Subsequently, a risk prediction model for the re-positivity of virus nucleic acid was developed, and a receiver operating characteristic (ROC) curve was drawn for further validation. Results: In this study, the rate of re-positivity for virus nucleic acid was 17.8% (23/129) where all re-positivity cases were asymptomatic. The median time interval from discharge to nucleic acid re-positivity to discharge after being cured again was 11.5 days (range: 7-23 days). Multivariate logistic regression analysis showed that leukocytopenia [odds ratio (OR) 7.316, 95% confidence interval (CI) 2.319-23.080, p = 0.001], prealbumin < 150 mg/L (OR 4.199, 95% CI 1.461-12.071, p = 0.008), and hyperpyrexia (body temperature >39°C, OR 4.643, 95% CI 1.426-15.117, p = 0.011) were independent risk factors associated with re-positivity. The area under the ROC curve was 0.815 (95% CI, 0.729-0.902). Conclusion: COVID-19 patients with leukocytopenia, low prealbumin level, and hyperpyrexia are more likely to test positive for virus nucleic acid after discharge. Timely and effective treatment and appropriate extension of hospital stays and quarantine periods may be feasible strategies for managing such patients.

Plant electrical signals: A multidisciplinary challenge.

Plant electrical signals, an early event in the plant-stimulus interaction, rapidly transmit information generated by the stimulus to other organs, and even the whole plant, to promote the corresponding response and trigger a regulatory cascade. In recent years, many promising state-of-the-art technologies applicable to study plant electrophysiology have emerged. Research focused on expression of genes associated with electrical signals has also proliferated. We propose that it is appropriate for plant electrical signals to be considered in the form of a "plant electrophysiological phenotype". This review synthesizes research on plant electrical signals from a novel, interdisciplinary perspective, which is needed to improve the efficient aggregation and use of plant electrical signal data and to expedite interpretation of plant electrical signals.

Composition and Genetic Diversity of the Nicotiana tabacum Microbiome in Different Topographic Areas and Growth Periods.

Fungal endophytes are the most ubiquitous plant symbionts on earth and are phylogenetically diverse. Studies on the fungal endophytes in tobacco have shown that they are widely distributed in the leaves, stems, and roots, and play important roles in the composition of the microbial ecosystem of tobacco. Herein, we analyzed and quantified the endophytic fungi of healthy tobacco leaves at the seedling stage (SS), resettling growth stage (RGS), fast-growing stage (FGS), and maturing stage (MS) at three altitudes (600, 1000, and 1300 m). We sequenced the internal transcribed spacer (ITS) region of fungal samples to delimit operational taxonomic units (OTUs) and phylogenetically characterize the communities. The results showed that the numbers of clustering OTUs at SS, RGS, FGS, and MS were 516, 709, 469, and 428, respectively. At the phylum level, species in Ascomycota and Basidiomycota had absolute predominance, representing 97.8% and 2.0% of the total number of species, respectively. We also found the number of fungi at the RGS and FGS stages was higher than those at the other two stages. Additionally, OTU richness was determined by calculating the Observed Species, Shannon, Simpson, Chao1, abundance-based coverage estimator (ACE), Good's coverage and phylogenetic distance (PD)_whole_tree indices based on the total number of species. Our results showed RGS samples had the highest diversity indices. Furthermore, we found that the diversity of fungal communities tended to decrease with increasing altitude. The results from this study indicated that tobacco harbors an abundant and diverse endophytic fungal community, which provides new opportunities for exploring their potential utilization.

Decreased expression of long noncoding RNA GAS5 indicates a poor prognosis and promotes cell proliferation in gastric cancer.

BACKGROUND: Gastric cancer is the second leading cause of cancer death and remains a major clinical challenge due to poor prognosis and limited treatment options. Long noncoding RNAs (lncRNAs) have emerged recently as major players in tumor biology and may be used for cancer diagnosis, prognosis, and potential therapeutic targets. Although downregulation of lncRNA GAS5 (Growth Arrest-Specific Transcript) in several cancers has been studied, its role in gastric cancer remains unknown. Our studies were designed to investigate the expression, biological role and clinical significance of GAS5 in gastric cancer. METHODS: Expression of GAS5 was analyzed in 89 gastric cancer tissues and five gastric cancer cell lines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Over-expression and RNA interference (RNAi) approaches were used to investigate the biological functions of GAS5. The effect of GAS5 on proliferation was evaluated by MTT and colony formation assays, and cell apoptosis was evaluated by hochest stainning. Gastric cancer cells transfected with pCDNA3.1 -GAS5 were injected into nude mice to study the effect of GAS5 on tumorigenesis in vivo. Protein levels of GAS5 targets were determined by western blot analysis. Differences between groups were tested for significance using Student's t-test (two-tailed). RESULTS: We found that GAS5 expression was markedly downregulated in gastric cancer tissues, and associated with larger tumor size and advanced pathologic stage. Patients with low GAS5 expression level had poorer disease-free survival (DFS; P = 0.001) and overall survival (OS; P < 0.001) than those with high GAS5 expression. Further multivariable Cox regression analysis suggested that decreased GAS5 was an independent prognostic indicator for this disease (P = 0.006, HR = 0.412; 95%CI = 2.218-0.766). Moreover, ectopic expression of GAS5 was demonstrated to decrease gastric cancer cell proliferation and induce apoptosis in vitro and in vivo, while downregulation of endogenous GAS5 could promote cell proliferation. Finally, we found that GAS5 could influence gastric cancer cells proliferation, partly via regulating E2F1 and P21 expression. CONCLUSION: Our study presents that GAS5 is significantly downregulated in gastric cancer tissues and may represent a new marker of poor prognosis and a potential therapeutic target for gastric cancer intervention.

Lnc RNA HOTAIR functions as a competing endogenous RNA to regulate HER2 expression by sponging miR-331-3p in gastric cancer.

BACKGROUND: Accumulating evidence indicates that the long non-coding RNA HOTAIR plays a critical role in cancer progression and metastasis. However, the overall biological role and clinical significance of HOTAIR in gastric carcinogenesis remains largely unknown. METHODS: HOTAIR expression was measured in 78 paired cancerous and noncancerous tissue samples by real-time PCR. The effects of HOTAIR on gastric cancer cells were studied by overexpression and RNA interference approaches in vitro and in vivo. Insights of the mechanism of competitive endogenous RNAs (ceRNAs) were gained from bioinformatic analysis, luciferase assays and RNA binding protein immunoprecipitation (RIP). The positive HOTAIR/HER2 interaction was identified and verified by immunohistochemistry assay and bivariate correlation analysis. RESULTS: HOTAIR upregulation was associated with larger tumor size, advanced pathological stage and extensive metastasis, and also correlated with shorter overall survival of gastric cancer patients. Furthermore, HOTAIR overexpression promoted the proliferation, migration and invasion of gastric carcinoma cells, while HOTAIR depletion inhibited both cell invasion and cell viability, and induced growth arrest in vitro and in vivo. In particular, HOTAIR may act as a ceRNA, effectively becoming a sink for miR-331-3p, thereby modulating the derepression of HER2 and imposing an additional level of post-transcriptional regulation. Finally, the positive HOTAIR/HER2 correlation was significantly associated with advanced gastric cancers. CONCLUSIONS: HOTAIR overexpression represents a biomarker of poor prognosis in gastric cancer, and may confer malignant phenotype to tumor cells. The ceRNA regulatory network involving HOTAIR and the positive interaction between HOTAIR and HER2 may contribute to a better understanding of gastric cancer pathogenesis and facilitate the development of lncRNA-directed diagnostics and therapeutics against this disease.

MiR-196a is upregulated in gastric cancer and promotes cell proliferation by downregulating p27(kip1).

Aberrant expression of miR-196a has been frequently reported in cancer studies. However, the expression and mechanism of its function in gastric cancer remains unclear. Quantitative real-time PCR was carried out to detect the relative expression of miR-196a in gastric cancer cell lines and tissues. SGC7901 cells were treated with miR-196a inhibitors, mimics, or pCDNA/miR-196a to investigate the role of miR-196a in cell proliferation. Higher expression of miR-196a in gastric cancer tissues was associated with tumor size, a higher clinical stage, and was also correlated with shorter overall survival of patients with gastric cancer. Exogenous downregulation of miR-196a expression significantly suppressed the in vitro cell-cycle progression, proliferation, and colony formation of gastric cancer cells, and ectopic miR-196a expression significantly enhanced the development of tumors in nude mice. Luciferase assays revealed that miR-196a inhibited p27(kip1) expression by targeting one binding site in the 3'-untranslated region (3'-UTR) of p27(kip1) mRNA. qPCR and Western blot assays verified that miR-196a reduced p27(kip1) expression at both mRNA and protein levels. The p27(kip1)-mediated repression in cell proliferation was reverted by exogenous miR-196a expression. A reverse correlation between miR-196a and p27(kip1) expression was noted in gastric cancer tissues. Our study shows that aberrant overexpression of miR-196a and consequent downregulation of p27(kip1) could contribute to gastric carcinogenesis and would be targets for gastric cancer therapies and further developed as potential prognostic factors.

[Design of dynamic simulation system for carbon cycle in forest ecosystem].

Modeling techniques are indispensable for the researches on the carbon cycle of forest ecosystem. In this paper, a new general simulation system FORCASS (FORest CArbon Simulation System) was designed and developed under Simulink environment, with the objectives of modeling the carbon cycle dynamics of forest ecosystems. A comprehensive analysis on the framework, design solution, and development process showed that the FORCASS was feasible. This simulation system had the characteristics of 1) it divided the carbon storage in forest ecosystem into four compartments, i.e., vegetation, litter, soil, and animal, and took into account the carbon flows between the compartments, possessing high mechanism and easily to be comprehended, 2) it was a process-based system, taking the Richards growth function of vegetation component biomass carbon storage as the input to solve difference equations, and was easily to export the outputs such as net primary productivity (NPP) and net ecosystem productivity (NEP) at different stand ages, and 3) it had the explicit expansibility because it was developed based on a general framework for carbon cycle patterns.