A novel surgical scheme for hepatectomy in hepatocellular carcinoma patients with clinically significant portal hypertension.

OBJECTIVE: Clinically significant portal hypertension (CSPH) seriously affects the feasibility and safety of surgical treatment for hepatocellular carcinoma (HCC) patients. The aim of this study was to establish a new surgical scheme defining risk classification of post-hepatectomy liver failure (PHLF) to facilitate the surgical decision-making and identify suitable candidates for individual hepatectomy among HCC patients with CSPH. BACKGROUNDS: Hepatectomy is the preferred treatment for HCC. Surgeons must maintain a balance between the expected oncological outcomes of HCC removal and short-term risks of severe PHLF and morbidity. CSPH aggravates liver decompensation and increases the risk of severe PHLF thus complicating hepatectomy for HCC. METHODS: Multivariate logistic regression and stochastic forest algorithm were performed, then the independent risk factors of severe PHLF were included in a nomogram to determine the risk of severe PHLF. Further, a conditional inference tree (CTREE) through recursive partitioning analysis validated supplement the misdiagnostic threshold of the nomogram. RESULTS: This study included 924 patients, of whom 137 patients (14.8%) suffered from mild-CSPH and 66 patients suffered from (7.1%) with severe-CSPH confirmed preoperatively. Our data showed that preoperative prolonged prothrombin time, total bilirubin, indocyanine green retention rate at 15 min, CSPH grade, and standard future liver remnant volume were independent predictors of severe PHLF. By incorporating these factors, the nomogram achieved good prediction performance in assessing severe PHLF risk, and its concordance statistic was 0.891, 0.850 and 0.872 in the training cohort, internal validation cohort and external validation cohort, respectively, and good calibration curves were obtained. Moreover, the calculations of total points of diagnostic errors with 95% CI were concentrated in 110.5 (range 76.9-178.5). It showed a low risk of severe PHLF (2.3%), indicating hepatectomy is feasible when the points fall below 76.9, while the risk of severe PHLF is extremely high (93.8%) and hepatectomy should be rigorously restricted at scores over 178.5. Patients with points within the misdiagnosis threshold were further examined using CTREE according to a hierarchic order of factors represented by the presence of CSPH grade, ICG-R15, and sFLR. CONCLUSION: This new surgical scheme established in our study is practical to stratify risk classification in assessing severe PHLF, thereby facilitating surgical decision-making and identifying suitable candidates for individual hepatectomy.

Temporal-spatial variability of grazing behaviors of yaks and the drivers of their intake on the eastern Qinghai-Tibetan Plateau.

Introduction: Grassland-livestock balance is an important principle of sustainable development of grassland livestock production and grassland ecosystem health. Grassland degradation becomes more serious at global scales and especially at the area that is sensitive to climate change and human activities. Decreases in pasture biomass and shifts in plant community composition in degraded grasslands can largely affect grazing behaviors of livestock. Up to date, however, it is unclear that whether livestock behaviors change across spatial and temporal scales and what key factors are to shape observed behavioral patterns of livestock. Methods: Here, yak behaviors including grazing, rumination and walking on the eastern Qinghai-Tibetan Plateau (QTP) were monitored by a continuous visual observation, to investigate temporal and spatial variations of grazing behavior of yaks (Bos grunniens); based on the data from public database in the past 18 years, a meta-analysis was conducted to examine the main factors that affect grazing behaviors and intake of yaks. Results: We showed that grazing behaviors of yaks differed significantly within hours, among hours of each day and among days as well as across different observation sites. Intake rate of yaks was higher in the morning than in the afternoon, but walking speed showed an inverse trend compared with intake rate. Resting, altitude, the mean annual precipitation (MAP), the mean annual temperature (MAT), forage ash, yak age and season were the main predictors for yak intake, and forage and yak individual characteristics had direct effects on grazing behaviors and intake of yaks. Discussion: The findings confirm that grazing behaviors of yaks can vary even at small temporal scales and regional scales, which is closely related to the shift in forage quality and biomass caused by environmental changes. The study suggests that multiple factors can be responsible for the variation in livestock behaviors and shifts in behavioral patterns may consequently lead to positive or negative feedback to grassland ecosystems through plant-animal interactions.

Soil fungal community structure and function response to rhizoma perennial peanut cultivars.

BACKGROUND: Crop-associated microorganisms play a crucial role in soil nutrient cycling, and crop growth, and health. Fine-scale patterns in soil microbial community diversity and composition are commonly regulated by plant species or genotype. Despite extensive reports in different crop or its cultivar effects on the microbial community, it is uncertain how rhizoma peanut (RP, Arachis glabrata Benth.), a perennial warm-season legume forage that is well-adapted in the southern USA, affects soil microbial community across different cultivars. RESULTS: This study explored the influence of seven different RP cultivars on the taxonomic composition, diversity, and functional groups of soil fungal communities through a field trial in Marianna, Florida, Southern USA, using next-generation sequencing technique. Our results showed that the taxonomic diversity and composition of the fungal community differed significantly across RP cultivars. Alpha diversity (Shannon, Simpson, and Pielou's evenness) was significantly higher in Ecoturf but lower in UF_Peace and Florigraze compared to other cultivars (p < 0.001). Phylogenetic diversity (Faith's PD) was lowest in Latitude compared to other cultivars (p < 0.0001). The dominant phyla were Ascomycota (13.34%), Mortierellomycota (3.82%), and Basidiomycota (2.99%), which were significantly greater in Florigraze, UF_Peace, and Ecoturf, respectively. The relative abundance of Neocosmospora was markedly high (21.45%) in UF_Tito and showed large variations across cultivars. The relative abundance of the dominant genera was significantly greater in Arbrook than in other cultivars. There were also significant differences in the co-occurrence network, showing different keystone taxa and more positive correlations than the negative correlations across cultivars. FUNGuild analysis showed that the relative abundance of functional guilds including pathogenic, saprotrophic, endophytic, mycorrhizal and parasitic fungi significantly differed among cultivars. Ecoturf had the greatest relative abundance of mycorrhizal fungal group (5.10 ± 0.44), whereas UF_Peace had the greatest relative abundance of endophytic (4.52 ± 0.56) and parasitic fungi (1.67 ± 0.30) compared to other cultivars. CONCLUSIONS: Our findings provide evidence of crop cultivar's effect in shaping fine-scale fungal community patterns in legume-based forage systems.

Chloramphenicol alleviates 5-fluorouracil-induced cellular senescence through activation of autophagy.

5-Fluorouracil (5-FU) is a first-line treatment for colorectal cancer, but side effects such as severe diarrhea are common in clinical use and have been linked to its induction of normal cell senescence. Chloramphenicol (CAP) is an antibiotic commonly used to treat typhoid or anaerobic infections, but its senescence-related aspects have not been thoroughly investigated. Here, we used 5-FU to induce senescence in human umbilical vein endothelial cells (HUVECs) and investigated the relationship between CAP and cellular senescence at the cellular level. In a model of cellular senescence induced by 5-FU treatment, we discovered that CAP treatment reversed the rise in the percentage of senescence-associated galactosidase (SA-ß-gal)-positive cells and decreased the expression of senescence-associated proteins (p16), senescence-associated genes (p21), and senescence-associated secretory phenotypes (SASPs: IL-6, TNF-α). In addition, CAP subsequently restored the autophagic process inhibited by 5-FU and upregulated the levels of autophagy-related proteins. Mechanistically, we found that CAP restored autophagic flux by inhibiting the mTOR pathway, which in turn alleviated FU-induced cellular senescence. Our findings suggest that CAP may help prevent cellular senescence and restore autophagy, opening up new possibilities and approaches for the clinical management of colorectal cancer.

Tedizolid phosphate alleviates DSS-induced ulcerative colitis by inhibiting senescence of cell and colon tissue through activating AMPK signaling pathway.

Ulcerative colitis (UC) is a subtype of inflammatory bowel disease. Previous studies have suggested a link between senescence process and the body's inflammatory reaction, indicating that senescence may exacerbate UC, yet the relation between UC and senescence remains unclear. Tedizolid Phosphate (TED), a novel oxazolidinone antimicrobial, is indicated in acute bacterial skin infections, its impact on senescence is not known. Our research revealed that the UC inducer dextran sulfate sodium (DSS) triggers senescence in both colon epithelial NCM460 cells and colon tissues, and TED that screened from a compound library demonstrated a strong anti-senescence effect on DSS treated NCM460 cells. As an anti-senescence medication identified in this research, TED efficiently alleviated UC and colonic senescence in mice caused by DSS. By proteomic analysis and experimental validation, we found that DSS significantly inhibits the AMPK signaling pathway, while TED counteracts senescence by restoring AMPK activity. This research verified that the development of UC is accompanied with colon tissue senescence, and TED, an anti-senescence medication, can effectively treat UC caused by DSS and alleviate colon senescence. Our work suggests anti-senescence strategy is an effective approach for UC treatment.

An effective strategy for assembling the sex-limited chromosome.

BACKGROUND: Most currently available reference genomes lack the sequence map of sex-limited (such as Y and W) chromosomes, which results in incomplete assemblies that hinder further research on sex chromosomes. Recent advancements in long-read sequencing and population sequencing have provided the opportunity to assemble sex-limited chromosomes without the traditional complicated experimental efforts. FINDINGS: We introduce the first computational method, Sorting long Reads of Y or other sex-limited chromosome (SRY), which achieves improved assembly results compared to flow sorting. Specifically, SRY outperforms in the heterochromatic region and demonstrates comparable performance in other regions. Furthermore, SRY enhances the capabilities of the hybrid assembly software, resulting in improved continuity and accuracy. CONCLUSIONS: Our method enables true complete genome assembly and facilitates downstream research of sex-limited chromosomes.

A general pattern of plant traits and their relationships with environmental factors and microbial life-history strategies.

The trait-based unidimensional plant economics spectrum provides a valuable framework for understanding plant adaptation strategies to the environment. However, it is still uncertain whether there is a general multidimensionality of how variation of both leaf and fine root traits are influenced by environmental factors, and how these relate to microbial resource strategies. Here, we examined the coordination patterns of four pairs of similar leaf and fine root traits of herbaceous plants in an alpine meadow at the community-level, and their environmental driving patterns. We then assessed their correlation with microbial life-history strategies, as these exhibit analogous resource strategies with plants in terms of growth and resource utilization efficiency. Results exhibited an analogous multidimensionality of the economics spectrum for leaf and fine root traits: the first dimension, collaboration gradient, primarily represented a tradeoff between lifespan and resource foraging efficiency; the second dimension, conservation gradient, primarily represented a tradeoff between conservation and acquisition in resource uptake. Climate variables had a stronger impact on both dimensions for leaf and fine root traits than soil variables did; whereas, the primary drivers were more complex for fine root traits than for leaf traits. The collaboration gradient of leaf and fine root traits exhibited consistent relationships with soil microbial life-history strategies, both showed negative and positive correlation with bacterial and fungal strategies, respectively. Our findings suggest that both leaves and fine roots have general multidimensional strategies for adapting to new environments and provide a solid basis for further understanding the relationships between the adaptive strategies of plants and microbes.

Radiotherapy is superior to transarterial chemoembolization as adjuvant therapy after narrow-margin hepatectomy in patients with hepatocellular carcinoma: A single-center prospective randomized study.

BACKGROUND: This study was recruited to compare the efficacy and safety of radiotherapy (RT) and transarterial chemoembolization (TACE) as postoperative adjuvant therapy after narrow-margin hepatectomy in hepatocellular carcinoma (HCC) patients. METHODS: This single-center prospective randomized study was conducted in the Cancer Hospital, Guang Xi Medical University, Nanning. A total of 72 patients who received treatment in this hospital between August 2017 and July 2019 were included and randomly allocated to TACE group (n = 48) and RT group (n = 24). Next, overall survival (OS) and progression-free survival (PFS) rates, recurrence patterns, financial burden, and safety were evaluated. RESULTS: The difference between the RT and TACE groups was not significant in one-, three-, and five-year OS (87.5%, 79.0%, and 62.5% vs. 93.8%, 75.9%, and 63.4%, respectively, P = 0.071) and PFS rates (79.0%, 54.2%, and 22.6% vs. 75.0%, 47.9%, and 32.6%, respectively, P = 0.071). Compared to the TACE group, the RT group had significantly lower intrahepatic recurrence rate (20.8% vs. 52.1%, P = 0.011), higher extrahepatic recurrence rate (37.5% vs. 14.6%, P = 0.034), and no marginal and diffuse recurrences (0% vs. 16.7%, P < 0.05). The mean overall treatment cost was higher (¥62,550.59 ± 4397.27 vs. ¥40,732.56 ± 9210.54, P < 0.01), the hospital stay (15.1 ± 3.7 vs. 11.8 ± 4.1 days, P < 0.01) was longer, and the overall treatment stay (13.3 ± 5.3 vs. 41.29 ± 12.4 days, P < 0.01) was shorter in the TACE group than in the RT group. Besides, both groups did not exhibit significant differences in the frequency and severity of adverse events. CONCLUSION: Both adjuvant TACE and RT can better the OS and PFS of patients with HCC. However, RT has a significantly better performance than TACE in terms of improving intrahepatic recurrence rate, treatment cost and hospital stay.

[Characteristics of Municipal Solid Waste in Some Urban Agglomeration in the Past Five Years].

The treatment and disposal of municipal solid waste has increasingly become a common concern around the world, and the characteristics of municipal solid waste(MSW) are an important basis for the selection of terminal treatment methods. In this study, more than 400 MSW samples from over 30 cities across China were collected, and the basic physical and chemical properties, such as the physical composition, pollutant content, and calorific value, were analyzed. Shenzhen was taken as an example to analyze the influence of time and waste sorting measures on the physical and chemical characteristics of MSW. The correlation model between MSW composition and calorific value was established using partial least squares(PLS) regression, and the model was verified. The results showed that with per capita GDP increasing by 10,000 yuan, per capita MSW production and the low calorific value of MSW increased by 0.1 kg·(person·d)-1 and 373.8 kJ·kg-1, respectively. However, when per capita GDP was less than 60,000 yuan, the correlation between per capita GDP and per capita MSW production was relatively poor. Kitchen waste was still the most abundant component of MSW, and the content of most samples was between 40% and 60%. The combustible content of rubber/plastic and paper was relatively high, between 20%-30% and 10%-20%, respectively. The inorganic content did not usually exceed 5%, and the moisture content of the MSW was between 50% and 60%. After the implementation of waste classification in 2019, the content of kitchen waste in MSW had been significantly reduced, the content of rubber/plastic had increased, and other components had not changed much. Additionally, the calorific value of waste had been improved to a certain extent. The pollution element contents in MSW, S Cl, and N were all below 1%, and the average value was:N>Cl>S. The contents of Hg, As, Cr, Cd, and Pb in MSW samples did not change significantly with the composition and sampling time, and the content of Pb and Cr in MSW was affected by the environmental background value. The model analysis revealed that rubber/plastics and moisture content were the main variables that affected the calorific value of MSW. The deviation between the measured value and the predicted value was less than 20% for 85.96% of the samples. The model established in this study can meet the needs of the prediction of the calorific value of MSW.

Plant growth promoting rhizobacteria induced metal and salt stress tolerance in Brassica juncea through ion homeostasis.

Soil heavy metal contamination and salinity constitute a major environmental problem worldwide. The affected area and impact of these problems are increasing day by day; therefore, it is imperative to restore their potential using environmentally friendly technology. Plant growth-promoting rhizobacteria (PGPR) provides a better option in this context. Thirty-seven bacteria were isolated from the rhizosphere of maize cultivated in metal- and salt-affected soils. Some selected bacterial strains grew well under a wide range of pH (4-10), salt (5-50 g/L), and Cd (50-1000 mg/L) stress. Three bacterial strains, Exiguobacterium aestuarii (UM1), Bacillus cereus (UM8), and Bacillus megaterium (UM35), were selected because of their robust growth and high tolerance to both stress conditions. The bacterial strains UM1, UM8, and UM35 showed P-solubilization, whereas UM8 and UM35 exhibited 1-aminocyclopropane-1-carboxylate deaminase activity and indole acetic acid (IAA) production, respectively. The bacterial strains were inoculated on Brassica juncea plants cultivated in Cd and salt-affected soils due to the above PGP activities and stress tolerance. Plants inoculated with the bacterial strains B. cereus and B. megaterium significantly (p < 0.05) increased shoot fresh weight (17 ± 1.17-29 ± 0.88 g/plant), shoot dry weight (2.50 ± 0.03-4.40 ± 0.32 g/plant), root fresh weight (7.30 ± 0.58-13.30 ± 0.58 g/plant), root dry weight (0.80 ± 0.04-2.00 ± 0.01 g/plant), and shoot K contents (62.76 ± 1.80-105.40 ± 1.15 mg/kg dwt) in normal and stressful conditions. The bacterial strain B. megaterium significantly (p < 0.05) decreased shoot Na+ and Cd++ uptake in single and dual stress conditions. Both bacterial strains, E. aestuarii and B. cereus, efficiently reduced Cd++ translocation and bioaccumulation in the shoot. Bacterial inoculation improved the uptake of K+ and Ca++, while restricted Na+ and Cd++ in B. juncea shoots indicated their potential to mitigate the dual stresses of salt and Cd in B. juncea through ion homeostasis.

Soil and vegetation characteristics during the formation of typical Ligularia virgaurea degraded grassland.

To understand the formation process of typical poisonous plant degraded grassland, we studied the cha-racteristics of vegetation and soil during the gradual expansion of Ligularia virgaurea into the native grassland of Qinghai-Tibet Plateau. The results showed that population density, plant height, coverage, and biomass of L. virgaurea increased during the formation of L. virgaurea degraded grassland. In comparison with native grassland, the degraded grassland had higher total aboveground biomass (113.9%), soil total nitrogen concentration (61.0%), NH4+-N (77.9%), organic carbon concentration (45.3%), available phosphorus concentration (78.8%) as well as soil microbial biomass carbon (42.1%) and nitrogen (47.4%), but lower NO3--N (40.1%) and species richness (28.5%) and aboveground biomass (45.7%) of other species beyond L. virgaurea. The extremely strong abilities of interspecific inhibition and morphological plasticity of L. virgaurea, as well as efficient nutrient accumulation and utilization were the keys to its successful expansion, which facilitated the formation of typical L. virgaurea degraded grassland.

Neuroprotective effect and possible mechanism of edaravone in rat models of spinal cord injury: a protocol for a systematic review and meta-analysis.

BACKGROUND: Spinal cord injury (SCI) is one of the most disabling neurological conditions, afflicting thousands of human beings. Edaravone, a well-known reactive oxygen species scavenger, is expanding its new scope in field of SCI. The objective of this systematic review is to determine the neuroprotective effects and discuss the underlying mechanism of edaravone in management of SCI. METHODS: The systematic review will include the controlled studies evaluating the neurological roles of edaravone on experiment rat models following SCI. The primary outcome will be the 21-point Basso, Beattie, and Bresnahan locomotor rating scale. The secondary outcomes will include the preservation of white matter areas and malondialdehyde levels. Two researchers will independently search PubMed, Embase, Web of Science, Scopus and Cochrane Library from their inception date. Following study selection, data extraction, and assessment of methodological quality in included studies using the SYRCLE's RoB tool, data from eligible studies will be pooled and analyzed using random-effects models with RevMan 5.3 software. In case of sufficient data, subgroup analyses with respect to species, age, gender, injury characteristics, or administration details will be carried out to explore the factors modifying efficacy of edaravone. For exploring the appropriate dose of edaravone, a network meta-analysis approach will be conducted based on the Bayesian method. Importantly, the proposed mechanisms and changes of related molecules will be also extracted from included studies for comprehensively investigating the mechanisms underlying the neuroprotective effects of edaravone. DISCUSSION: In this study, we aim to quantitatively analyze the role of edaravone in locomotor recovery and tissue damage in SCI rat model. The efficacy of edaravone in distinct scenarios will be investigated by subgroup analyses, and we expect to predict the candidate dose that offers a superior treatment effect using network meta-analyses. Moreover, a comprehensive framework regarding the neuroprotective mechanisms behind edaravone will be constructed via a combination of systematic and traditional review. This study will bring implications for future preclinical studies and clinical applications of SCI. Nonetheless, in light of the anticipated limitations in animal experimental design and methodological quality, the results in this review should be interpreted with caution.

Peficitinib ameliorates 5-fluorouracil-induced intestinal damage by inhibiting aging, inflammatory factors and oxidative stress.

5-Fluorouracil (5-FU) is a conventional and effective drug for colorectal cancer patients, and it is an important part of combined chemotherapy and adjuvant chemotherapy. Chemotherapy intestinal mucositis (CIM) is a severe side effect caused by 5-FU that, induces cancer treatment failure and affects patients' quality of life. The mechanism of 5-FU-induced CIM is related to normal cell senescence induced by 5-FU. Peficitinib, a Janus Kinase (JAK) inhibitor, treats inflammatory disorders, including rheumatoid arthritis, psoriasis, and inflammatory bowel disease. However, the therapeutic role and underlying mechanism of peficitinib in CIM remain unclear. The main objective of our research was to investigate the effects of peficitinib on 5-FU-induced senescence and intestinal damage in human umbilical vein endothelial (HUVEC) cells, human intestinal epithelial (HIEC) cells and BABL/C mice. The results showed that 5-FU caused intestinal damage by inducing aging and increasing inflammation and oxidative stress. Peficitinib alleviated aging by reducing senescence-beta-galactosidase (SA-ß-gal) activity and the protein levels of aging indicators (p53, p21, p16). Moreover, peficitinib reversed the changes in senescence-associated secretory phenotype (SASP) expression caused by 5-FU. Besides, 5-FU induced release of inflammatory factors and oxidative stress indicators was reversed by peficitinib. Additionally, the combination of peficitinib and 5-FU reinforced the anticancer curative intent of 5-FU in two colorectal cancer cell lines (HCT116 cells and SW620 cells). In conclusion, peficitinib alleviates mucositis by alleviating aging, reducing inflammatory accumulation and oxidative stress and enhancing the antitumor activity of 5-FU.

Serum Soluble Vascular Endothelial Growth Factor Receptor 1 as a Potential Biomarker of Hepatopulmonary Syndrome.

Background and Aims: The results of basic research implicate the vascular endothelial growth factor (VEGF) family as a potential target of hepatopulmonary syndrome (HPS). However, the negative results of anti-angiogenetic therapy in clinical studies have highlighted the need for markers for HPS. Therefore, we aimed to determine whether VEGF family members and their receptors can be potential biomarkers for HPS through clinical and experimental studies. Methods: Clinically, patients with chronic liver disease from two medical centers were enrolled and examined for HPS. Patients were divided into HPS, intrapulmonary vascular dilation [positive contrast-enhanced echocardiography (CEE) and normal oxygenation] and CEE-negative groups. Baseline information and perioperative clinical data were compared between HPS and non-HPS patients. Serum levels of VEGF family members and their receptors were measured. In parallel, HPS rats were established by common bile duct ligation. Liver, lung and serum samples were collected for the evaluation of pathophysiologic changes, as well as the expression levels of the above factors. Results: In HPS rats, all VEGF family members and their receptors underwent significant changes; however, only soluble VEGFR1 (sFlt-1) and the sFlt-1/ placental growth factor (PLGF) ratio were changed in almost the same manner as those in HPS patients. Furthermore, through feature selection and internal and external validation, sFlt-1 and the sFlt-1/PLGF ratio were identified as the most important variables to distinguish HPS from non-HPS patients. Conclusions: Our results from animal and human studies indicate that sFlt-1 and the sFlt-1/PLGF ratio in serum are potential markers for HPS.

Peficitinib ameliorates doxorubicin-induced cardiotoxicity by suppressing cellular senescence and enhances its antitumor activity.

Irreversible cardiotoxicity limits the clinical applications of doxorubicin (DOX). Cardiotoxicity can be detected early using clinical assessment; however, effective preventive measures are still lacking. Peficitinib (ASP015K), a JAK (Janus kinase) inhibitor, is a potent anti-inflammatory agent in autoimmune diseases. Nevertheless, little research has been conducted on anti-ageing and anti-tumour therapies. In this study, we investigated whether ASP015K could attenuate DOX-induced cardiotoxicity through its anti-ageing effects and whether it would affect the tumour treatment effect of DOX by establishing senescence, acute heart injury, and xenograft models. We observed that ASP015K could antagonise the senescence induced by various factors, including hydrogen peroxide and DOX. In addition, ASP015K treatment significantly alleviated cardiac function damage, histopathological deterioration, myocardial fibrosis, and oxidative damage in acute injury mouse models. ASP015K enhanced the sensitivity of tumour cells to DOX therapy and significantly slowed down the tumour growth rate and tumour volume in the xenograft mouse model. Therefore, ASP015K is expected to be developed as a potential cardioprotective agent to prevent or reduce the cardiotoxic side effects of anthracyclines in chemotherapy.

Soil Bacterial Communities Across Seven Rhizoma Peanut Cultivars (Arachis glabrata Benth.) Respond to Seasonal Variation.

Soil microorganisms play key roles in soil nutrient transformations and have a notable effect on plant growth and health. Different plant genotypes can shape soil microbial patterns via the secretion of root exudates and volatiles, but it is uncertain how a difference in soil microorganisms induced by crop cultivars will respond to short-term seasonal variations. A field experiment was conducted to assess the changes in soil bacterial communities of seven rhizoma peanut (Arachis glabrata Benth, RP) cultivars across two growing seasons, April (Spring season) and October (Fall season). Soils' bacterial communities were targeted using 16S rRNA gene amplicon sequencing. Bacterial community diversity and taxonomic composition among rhizoma peanut cultivars were significantly affected by seasons, cultivars, and their interactions (p < 0.05). Alpha diversity, as estimated by the OTU richness and Simpson index, was around onefold decrease in October than in April across most of the RP cultivars, while the soils from Arblick and Latitude had around one time higher alpha diversity in both seasons compared with other cultivars. Beta diversity differed significantly in April (R = 0.073, p < 0.01) and October (R = 0.084, p < 0.01) across seven cultivars. Bacterial dominant taxa (at phylum and genus level) were strongly affected by seasons and varied towards more dominant groups that have functional potentials involved in nutrient cycling from April to October. A large shift in water availability induced by season variations in addition to host cultivar's effects can explain the observed patterns in diversity, composition, and co-occurrence of bacterial taxa. Overall, our results demonstrate an overriding effect of short-term seasonal variations on soil bacterial communities associated with different crop cultivars. The findings suggest that season-induced shifts in environmental conditions could exert stronger impacts on soil microorganisms than the finer-scale rhizosphere effect from crop cultivars, and consequently influence largely microbe-mediated soil processes and crop health in agricultural ecosystems.

A national, multicenter, retrospective study of Castleman disease in China implementing CDCN criteria.

Background: Castleman disease (CD) is a group of rare and heterogenous lymphoproliferative disorders including unicentric CD (UCD), human herpesvirus-8(HHV-8)-associated multicentric CD (HHV8-MCD), and HHV-8-negative/idiopathic multicentric CD (iMCD). Knowledge of CD mainly comes from case series or retrospective studies, but the inclusion criteria of these studies vary because the Castleman Disease Collaborative Network (CDCN) diagnostic criteria for iMCD and UCD were not available until 2017 and 2020, respectively. Further, these criteria and guidelines have not been systematically evaluated. Methods: In this national, multicenter, retrospective study implementing CDCN criteria, we enrolled 1634 CD patients (UCD, n = 903; MCD, n = 731) from 2000 to 2021 at 40 Chinese institutions to depict clinical features, treatment options, and prognostic factors of CD. Findings: Among UCD, there were 162 (17.9%) patients with an MCD-like inflammatory state. Among MCD, there were 12 HHV8-MCD patients and 719 HHV-8-negative MCD patients, which included 139 asymptomatic MCD (aMCD) and 580 iMCD meeting clinical criteria. Of 580 iMCD patients, 41 (7.1%) met iMCD-TAFRO criteria, the others were iMCD-NOS. iMCD-NOS were further divided into iMCD-IPL (n = 97) and iMCD-NOS without IPL (n = 442). Among iMCD patients with first-line treatment data, a trend from pulse combination chemotherapy toward continuous treatment was observed. Survival analysis revealed significant differences between subtypes and severe iMCD (HR = 3.747; 95% CI: 2.112-6.649, p < 0.001) had worse outcome. Interpretation: This study depicts a broad picture of CD, treatment options and survival information in China and validates the association between the CDCN's definition of severe iMCD and worse outcomes, requiring more intensive treatment. Fundings: Beijing Municipal Commission of Science and Technology, CAMS Innovation Fund and National High Level Hospital Clinical Research Funding.

Bis(benzonitrile) dichloroplatinum (II) interrupts PD-1/PD-L1 interaction by binding to PD-1.

Checkpoint inhibitors such as PD-1/PD-L1 antibody therapeutics are a promising option for the treatment of multiple cancers. Due to the inherent limitations of antibodies, great efforts have been devoted to developing small-molecule PD-1/PD-L1 signaling pathway inhibitors. In this study we established a high-throughput AlphaLISA assay to discover small molecules with new skeletons that could block PD-1/PD-L1 interaction. We screened a small-molecule library of 4169 compounds including natural products, FDA approved drugs and other synthetic compounds. Among the 8 potential hits, we found that cisplatin, a first-line chemotherapeutic drug, reduced AlphaLISA signal with an EC50 of 8.3 ± 2.2 µM. Furthermore, we showed that cisplatin-DMSO adduct, but not semplice cisplatin, inhibited PD-1/PD-L1 interaction. Thus, we assessed several commercial platinum (II) compounds, and found that bis(benzonitrile) dichloroplatinum (II) disturbed PD-1/PD-L1 interaction (EC50 = 13.2 ± 3.5 µM). Its inhibitory activity on PD-1/PD-L1 interaction was confirmed in co-immunoprecipitation and PD-1/PD-L1 signaling pathway blockade bioassays. Surface plasmon resonance assay revealed that bis(benzonitrile) dichloroplatinum (II) bound to PD-1 (KD = 2.08 µM) but not PD-L1. In immune-competent wild-type mice but not in immunodeficient nude mice, bis(benzonitrile) dichloroplatinum (II) (7.5 mg/kg, i.p., every 3 days) significantly suppressed the growth of MC38 colorectal cancer xenografts with increasing tumor-infiltrating T cells. These data highlight that platinum compounds are potential immune checkpoint inhibitors for the treatment of cancers.

Circular RNA hsa_circ_0005218 promotes the early recurrence of hepatocellular carcinoma by targeting the miR-31-5p/CDK1 pathway.

Increasing evidence has manifested that circular RNAs (circRNAs) exhibited critical function in regulating various signaling pathways related to hepatocellular carcinoma (HCC) recurrence. However, the role and mechanism of the circRNAs in the HCC early recurrence remain elusive. In this study, high-throughput RNA-sequencing (RNA-seq) analysis was conducted to identify the expression profile of circRNAs in HCC tissues and circ_0005218 was identified as one circRNA that significantly up-regulated in early recurrent HCC tissues. And patients with high expression of circ_0005218 showed worsen overall survival (OS) and disease-free survival (DFS). Moreover, the promotion effects of circ_0005218 on HCC cells in term of proliferation, invasion and metastasis were confirmed both in vitro and vivo by gain- and loss-of function assays. In addition, dual-luciferase reporter assays showed that circ_0005218 could competitively bind to micro-RNA (miR)-31-5p. Furthermore, we showed that suppression of CDK1 by miR-31-5p could be partially rescued by up-regulating circ_0005218. Taken together, the present study indicates that circ_0005218 absorbed miR-31-5p as a sponge to weaken its suppression on CDK1 expression, and thus boost HCC cell invasion and migration, which would act as a potential biomarker to predict the HCC early recurrence and as a new therapeutic target for treatment of HCC.