Peroxydisulfate-Driven Reductive Dechlorination as Affected by Soil Constituents: Free Radical Formation and Conversion.

We report a previously unrecognized but efficient reductive degradation pathway in peroxydisulfate (PDS)-driven soil remediation. With supplements of naturally occurring low-molecular-weight organic acids (LMWOAs) in anaerobic biochar-activated PDS systems, degradation rates of 12 γ-hexachlorocyclohexanes (HCH)-spiked soils boosted from 40% without LMWOAs to a maximum of 99% with 1 mM malic acid. Structural analysis revealed that an increase in α-hydroxyl groups and a diminution in pKa1 values of LMWOAs facilitated the formation of reductive carboxyl anion radicals (COO•-) via electrophilic attack by SO4•-/•OH. Furthermore, degradation kinetics were strongly correlated with soil organic matter (SOM) contents than iron minerals. Combining a newly developed in situ fluorescence detector of reductive radicals with quenching experiments, we showed that for soils with high, medium, and low SOM contents, dominant reactive species switched from singlet oxygen/semiquinone radicals to SO4•-/•OH and then to COO•- (contribution increased from 30.8 to 66.7%), yielding superior HCH degradation. Validation experiments using SOM model compounds highlighted critical roles of redox-active moieties, such as phenolic - OH and quinones, in radical formation and conversion. Our study provides insights into environmental behaviors related to radical activation of persulfate in a broader soil horizon and inspiration for more advanced reduction technologies.

Enrichment of cadmium and selenium in soil-crop system and associated probabilistic health risks in black shale areas.

Selenium (Se) is the essential component of selenoenzymes and contributes to antioxidant defenses. The capability of Se to antagonize the toxicity of heavy metals makes it an essential trace element for human and plant health. Soils derived from black shales are naturally enriched with Se; however, these soils often contain high geological cadmium (Cd), due to the weathering of black shales rich in Cd and Se. Cadmium, as a known Group I carcinogen, could induce damage to various organs. This therefore poses a major challenge for safe cultivation of Se-rich land resources. In this study, a total of 247 paired soil-crop samples were collected from a typical farmland derived from black shales. The concentrations of Cd and Se in the samples were analyzed by inductively coupled plasma mass spectroscopy and atomic fluorescence spectrometry. Monte Carlo simulation was applied to evaluate potential health risks associated with Cd exposure. Cadmium was the critical pollutant in the study area, with the average value of 1.53 mg/kg. Moreover, both children and adults living in the area had a significant non-carcinogenic health risk. Additional health risk assessments revealed that diet was the main contributor for both children and adults among the four pathways (diet > soil ingestion > soil dermal adsorption > soil inhalation). Furthermore, our results revealed that leguminous vegetables and maize were ideal for this site due to their high Se and low Cd accumulation abilities. These findings provide support for adjusting planting structure by variety screening to mitigate the health risk induced by Cd.

Lowered oral bioaccessibility of cadmium and selenium and associated health risk by co-digestion of rice and vegetables.

Since foods are not ingested individually, co-digestion, in accordance with human daily diet conditions, should be stressed when assessing elements bioaccessibility and associated health risks. The oral bioaccessibility of cadmium (Cd) and selenium (Se) in 11 types of crops (rice, maize, pakchoi, eggplant, red pepper, towel gourd, kidney bean, soybean, cowpea, sweet potato, and taro) were determined, and the effects of co-digestion of 7 types of rice and vegetables on the bioaccessibility of Cd and Se were evaluated and validated with in vitro PBET method. The underlying mechanism was revealed by observing the surface morphological characteristics of digested substrates, and the exposure risk of Cd and Se were assessed. The results showed that the average bioaccessibility of Cd and Se in 11 types of crops varied from 58.7 % to 39.1 % and 48.4 % to 62.6 % from the gastric phase (GP) to the intestinal phase (IP). Interestingly, co-digestion of rice and vegetables reduced the bioaccessibility of Cd and Se to varying degrees compared to theoretical values. Great reduction in the bioaccessibility of Cd and Se in the GP (16.9-36.4 % and 9.9-23.2 %) than that in the IP (0.2-6.62 % and 0.23-12.3 %) were detected, which was attributed to the rice-vegetable aggregates formed during co-digestion. Rice-vegetable aggregates inhibited the release of Cd and Se, which was more pronounced in the GP than in the IP. Consequently, co-digestion of rice and vegetables reduced the oral exposure to Cd by 35.8 % and to Se by 19.6 %. The areas with higher non-carcinogenic risk of Cd and Se in the study region were reduced by 17 % and 10 %, respectively. Therefore, the role of co-digestion in assessing Cd and Se bioaccessibility and associated health risk cannot be neglected. This study has significant implications for investigating elements bioaccessibility and optimizing associated health risk assessment from a novel perspective.

Anoctamin 4 channel currents activate glucose-inhibited neurons in the mouse ventromedial hypothalamus during hypoglycemia.

Glucose is the basic fuel essential for maintenance of viability and functionality of all cells. However, some neurons - namely, glucose-inhibited (GI) neurons - paradoxically increase their firing activity in low-glucose conditions and decrease that activity in high-glucose conditions. The ionic mechanisms mediating electric responses of GI neurons to glucose fluctuations remain unclear. Here, we showed that currents mediated by the anoctamin 4 (Ano4) channel are only detected in GI neurons in the ventromedial hypothalamic nucleus (VMH) and are functionally required for their activation in response to low glucose. Genetic disruption of the Ano4 gene in VMH neurons reduced blood glucose and impaired counterregulatory responses during hypoglycemia in mice. Activation of VMHAno4 neurons increased food intake and blood glucose, while chronic inhibition of VMHAno4 neurons ameliorated hyperglycemia in a type 1 diabetic mouse model. Finally, we showed that VMHAno4 neurons represent a unique orexigenic VMH population and transmit a positive valence, while stimulation of neurons that do not express Ano4 in the VMH (VMHnon-Ano4) suppress feeding and transmit a negative valence. Together, our results indicate that the Ano4 channel and VMHAno4 neurons are potential therapeutic targets for human diseases with abnormal feeding behavior or glucose imbalance.

Continental scale deciphering of microbiome networks untangles the phyllosphere homeostasis in tea plant.

INTRODUCTION: Assembly and co-occurrence of the host co-evolved microbiota are essential ecological and evolutionary processes, which is not only crucial for managing individual plant fitness but also ecological function. However, understanding of the microbiome assembly and co-occurrence in higher plants is not well understood. The tea plant was shown to contribute the forest fitness due to the microbiome assembled in the phyllosphere; the landscape of microbiome assembly in the tea plants and its potential implication on phyllosphere homestasis still remains untangled. OBJECTIVES: This study aimed to deciphering of the microbiome networks of the tea plants at a continental scale. It would provide fundamental insights into the factors driving the microbiome assembly, with an extended focus on the resilience towards the potential pathogen in the phyllosphere. METHODS: We collected 225 samples from 45 locations spanning approximately 2000-km tea growing regions across China. By integration of high-throughput sequencing data, physicochemical properties profiling and bioinformatics analyses, we investigated continental scale microbiome assembly and co-occurrence in the tea plants. Synthetic assemblages, interaction assay and RT-qPCR were further implemented to analyze the microbial interaction indexed in phyllosphere. RESULTS: A trade-off between stochastic and deterministic processes in microbiomes community assembly was highlighted. Assembly processes were dominated by deterministic processes in bulk and rhizosphere soils, and followed by stochastic processes in roots and leaves with amino acids as critical drivers for environmental selection. Sphingobacteria and Proteobacteria ascended from soils to leaves to sustain a core leaf taxa. The core taxa formed a close association with a prevalent foliar pathogen in the co-occurrence network and significantly attenuated the expression of a set of essential virulence genes in pathogen. CONCLUSION: Our study unveils the mechanism underpinning microbiome assembly in the tea plants, and a potential implication of the microbiome-mediated resilience framework on the phyllosphere homeostasis.

Nano and fine colloids suspended in the soil solution regulate phosphorus desorption and lability in organic fertiliser-amended soils.

Mobile colloids impact phosphorus (P) binding and transport in agroecosystems. However, their relationship to P-lability and their relative importance to P-bioavailability is unclear. In soils amended with organic fertilisers, we investigated the effects of nano (NC; 1-20 nm), fine (FC; 20-220 nm), and medium (MC; 220-450 nm) colloids suspended in soil solution on soil P-desorption and lability. The underlying hypothesis is that mobile colloids of different sizes, i.e., NC, FC, and MC, may contribute differently to P-lability in soils enriched with organic fertiliser. NC- and FC-bound Pcoll were positively correlated with P-lability parameters from diffusive gradient in thin films (DGTA-labile P concentration, r ≥ 0.88; and DGTA-effective P concentration, r ≥ 0.87). The corresponding relations with MC-bound Pcoll are weaker (r values of 0.50 and 0.51). NC- and FC-bound Pcoll were also strongly correlated with soil P-resupply (r ≥ 0.64) and desorption (r ≥ 0.79) parameters during DGTA deployment, and the mobility of these colloids was corroborated by electron microscopy of DGTA gels. MC-bound Pcoll was negatively correlated with the solid-to-solution distribution coefficient (r = -0.42), indicating this fraction is unlikely to be the source of P-release from the solid phase after P-depletion from the soil solution. We conclude that NC and FC mainly contribute to regulating soil desorbable-P supply to the soil solution in the DGTA depletion zone (in vitro proxy for plant rhizosphere), and consequently may act as critical conditioners of P-bioavailability, whereas MC tends to form complexes that lead to P-occlusion rather than lability.

Systemic Therapy for Hepatocellular Carcinoma: Chinese Consensus-Based Interdisciplinary Expert Statements.

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and causes many cancer-related deaths worldwide; in China, it is the second most prevalent cause of cancer deaths. Most patients are diagnosed clinically with advanced stage disease. Summary: For more than a decade, sorafenib, a small-molecular-weight tyrosine kinase inhibitor (SMW-TKI) was the only molecular targeted drug available with a survival benefit for the treatment of advanced HCC. With the development of novel TKIs and immune checkpoint inhibitors for advanced HCC, the management of patients has been greatly improved. However, though angiogenic-based targeted therapy remains the backbone for the systemic treatment of HCC, to date, no Chinese guidelines for novel molecular targeted therapies to treat advanced HCC have been established. Our interdisciplinary panel on the treatment of advanced HCC comprising hepatologists, hepatobiliary surgeons, oncologists, radiologists, pathologists, orthopedic surgeons, traditional Chinese medicine physicians, and interventional radiologists has reviewed the literature in order to develop updated treatment regimens. Key Messages: Panel consensus statements for the appropriate use of new molecular -targeted drugs including doses, combination therapies, adverse reaction management as well as efficacy evaluation, and predictions for treatment of advanced HCC with evidence levels based on published data are presented, thereby providing an overview of molecular targeted therapies for healthcare professionals.

Host genetic determinants drive compartment-specific assembly of tea plant microbiomes.

Diverse host factors drive microbial variation in plant-associated environments, whereas their genetic mechanisms remain largely unexplored. To address this, we coupled the analyses of plant genetics and microbiomes in this study. Using 100 tea plant (Camellia sinensis) cultivars, the microbiomes of rhizosphere, root endosphere and phyllosphere showed clear compartment-specific assembly, whereas the subpopulation differentiation of tea cultivars exhibited small effects on microbial variation in each compartment. Through microbiome genome-wide association studies, we examined the interactions between tea genetic loci and microbial variation. Notably, genes related to the cell wall and carbon catabolism were heavily linked to root endosphere microbial composition, whereas genes related to the metabolism of metal ions and small organic molecules were overrepresented in association with rhizosphere microbial composition. Moreover, a set of tea genetic variants, including the cytoskeleton-related formin homology interacting protein 1 gene, were strongly associated with the ß-diversity of phyllosphere microbiomes, implying their interactions with the overall structure of microbial communities. Our results create a catalogue of tea genetic determinants interacting with microbiomes and reveal the compartment-specific microbiome assembly driven by host genetics.

Hypothalamic steroid receptor coactivator-2 regulates adaptations to fasting and overnutrition.

The neuroendocrine system coordinates metabolic and behavioral adaptations to fasting, including reducing energy expenditure, promoting counterregulation, and suppressing satiation and anxiety to engage refeeding. Here, we show that steroid receptor coactivator-2 (SRC-2) in pro-opiomelanocortin (POMC) neurons is a key regulator of all these responses to fasting. POMC-specific deletion of SRC-2 enhances the basal excitability of POMC neurons; mutant mice fail to efficiently suppress energy expenditure during food deprivation. SRC-2 deficiency blunts electric responses of POMC neurons to glucose fluctuations, causing impaired counterregulation. When food becomes available, these mutant mice show insufficient refeeding associated with enhanced satiation and discoordination of anxiety and food-seeking behavior. SRC-2 coactivates Forkhead box protein O1 (FoxO1) to suppress POMC gene expression. POMC-specific deletion of SRC-2 protects mice from weight gain induced by an obesogenic diet feeding and/or FoxO1 overexpression. Collectively, we identify SRC-2 as a key molecule that coordinates multifaceted adaptive responses to food shortage.

Contrasting effects of carbon source recalcitrance on soil phosphorus availability and communities of phosphorus solubilizing microorganisms.

Carbon (C) additions to soil interact through chemical and microbiological processes to cause changes in soil phosphorus (P) availability. However, the response of soil P transformations and relevant microbial communities to C additions having different degrees of recalcitrance remains uncertain. We studied the effects of glucose, hemicellulose and lignin addition on soil P availability, P transformation processes and relevant microbial activity and communities in a P-deficient flooded soil. Lignin significantly increased soil available P concentrations, which was attributed to chemical release of inorganic P and increased alkaline phosphatase activity. Glucose and hemicellulose additions stimulated microbial metabolism of C thereby enhancing microbial demand for P, with increased soil P availability especially in the early incubation period. Glucose or hemicellulose addition changed soil microbial diversity and community composition, leading to enhanced growth and interactions of P solubilizing microorganisms such as Desulfitobacterium, Bacillus and Desulfosporosinus. Our results infer the importance of pH alteration and competitive sorption between PO4 and functional groups of recalcitrant C (e.g., lignin) with Fe/Al (hydr) oxides in regulating soil P availability. Further, the microbial response to labile C additions led to increased P availability in the P-deficient soil. This study provides important mechanistic information to guide microbially-regulated soil P management in agricultural ecosystems.

Sintilimab plus a bevacizumab biosimilar (IBI305) versus sorafenib in unresectable hepatocellular carcinoma (ORIENT-32): a randomised, open-label, phase 2-3 study.

BACKGROUND: China has a high burden of hepatocellular carcinoma, and hepatitis B virus (HBV) infection is the main causative factor. Patients with hepatocellular carcinoma have a poor prognosis and a substantial unmet clinical need. The phase 2-3 ORIENT-32 study aimed to assess sintilimab (a PD-1 inhibitor) plus IBI305, a bevacizumab biosimilar, versus sorafenib as a first-line treatment for unresectable HBV-associated hepatocellular carcinoma. METHODS: This randomised, open-label, phase 2-3 study was done at 50 clinical sites in China. Patients aged 18 years or older with histologically or cytologically diagnosed or clinically confirmed unresectable or metastatic hepatocellular carcinoma, no previous systemic treatment, and a baseline Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 were eligible for inclusion. In the phase 2 part of the study, patients received intravenous sintilimab (200 mg every 3 weeks) plus intravenous IBI305 (15 mg/kg every 3 weeks). In the phase 3 part, patients were randomly assigned (2:1) to receive either sintilimab plus IBI305 (sintilimab-bevacizumab biosimilar group) or sorafenib (400 mg orally twice daily; sorafenib group), until disease progression or unacceptable toxicity. Randomisation was done using permuted block randomisation, with a block size of six, via an interactive web response system, and stratified by macrovascular invasion or extrahepatic metastasis, baseline α-fetoprotein, and ECOG performance status. The primary endpoint of the phase 2 part of the study was safety, assessed in all patients who received at least one dose of study drug. The co-primary endpoints of the phase 3 part of the study were overall survival and independent radiological review committee (IRRC)-assessed progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 in the intention-to-treat population. The study is registered with ClinicalTrials.gov, NCT03794440. The study is closed to new participants and follow-up is ongoing for long-term outcomes. FINDINGS: Between Feb 11, 2019 and Jan 15, 2020, we enrolled 595 patients: 24 were enrolled directly into the phase 2 safety run-in and 571 were randomly assigned to sintilimab-bevacizumab biosimilar (n=380) or sorafenib (n=191). In the phase 2 part of the trial, 24 patients received at least one dose of the study drug, with an objective response rate of 25·0% (95% CI 9·8-46·7). Based on the preliminary safety and activity data of the phase 2 part, in which grade 3 or worse treatment-related adverse events occurred in seven (29%) of 24 patients, the randomised phase 3 part was started. At data cutoff (Aug 15, 2020), the median follow-up was 10·0 months (IQR 8·5-11·7) in the sintilimab-bevacizumab biosimilar group and 10·0 months (8·4-11·7) in the sorafenib group. Patients in the sintilimab-bevacizumab biosimilar group had a significantly longer IRRC-assessed median progression-free survival (4·6 months [95% CI 4·1-5·7]) than did patients in the sorafenib group (2·8 months [2·7-3·2]; stratified hazard ratio [HR] 0·56, 95% CI 0·46-0·70; p<0·0001). In the first interim analysis of overall survival, sintilimab-bevacizumab biosimilar showed a significantly longer overall survival than did sorafenib (median not reached [95% CI not reached-not reached] vs 10·4 months [8·5-not reached]; HR 0·57, 95% CI 0·43-0·75; p<0·0001). The most common grade 3-4 treatment-emergent adverse events were hypertension (55 [14%] of 380 patients in the sintilimab-bevacizumab biosimilar group vs 11 [6%] of 185 patients in the sorafenib group) and palmar-plantar erythrodysaesthesia syndrome (none vs 22 [12%]). 123 (32%) patients in the sintilimab-bevacizumab biosimilar group and 36 (19%) patients in the sorafenib group had serious adverse events. Treatment-related adverse events that led to death occurred in six (2%) patients in the sintilimab-bevacizumab biosimilar group (one patient with abnormal liver function, one patient with both hepatic failure and gastrointestinal haemorrhage, one patient with interstitial lung disease, one patient with both hepatic faliure and hyperkalemia, one patient with upper gastrointestinal haemorrhage, and one patient with intestinal volvulus) and two (1%) patients in the sorafenib group (one patient with gastrointestinal haemorrhage and one patient with death of unknown cause). INTERPRETATION: Sintilimab plus IBI305 showed a significant overall survival and progression-free survival benefit versus sorafenib in the first-line setting for Chinese patients with unresectable, HBV-associated hepatocellular carcinoma, with an acceptable safety profile. This combination regimen could provide a novel treatment option for such patients. FUNDING: Innovent Biologics. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Methane-associated micro-ecological processes crucially improve the self-purification of lindane-polluted paddy soil.

Reductive dechlorination, an efficient pathway for complete removal of organic chlorinated pollutants (OCPs), is commonly reported to be coupled to oxidation of methane (CH4) or methanogenesis in anaerobic environments. However, the relationship between dechlorination and CH4-associated bioprocesses is unclear. Based on the hypothesis that CH4 supplementation could facilitate OCP dechlorination, we investigated the role of CH4-associated bioprocesses in the self-purification of flooded lindane-spiked paddy soils. Four treatments were conducted for up to 28 days: sterilized soil (S), sterilized soil + CH4 (SC), non-sterilized soil (NS), and non-sterilized soil + CH4 (NSC). Results indicated that both sterilization and addition of CH4 promoted lindane degradation and CH4 emissions in the flooded paddy soils. In the NS treatment, lindane had the lowest degradation rate when CH4 emissions were barely detected; while in the SC treatment, lindane had the highest degradation rate when CH4 achieved its highest emissions from anaerobic soil. Also, sterilization led to microbial diversity loss and functional recession, but increased ferrous ion [Fe(II)] concentrations compared to non-sterilized soils. Methanogenic communities and mcrA gene recovered faster than the majority of microorganisms (e.g., Fe bacteria, Bdellovibrionaceae, Rhizobiaceae, Dehalogenimonas) or functional genes (e.g., Dhc, Geo, narG, nirS). Collectively, we assume the enhanced removal of lindane may partly be due to both abiotic dechlorination promoted by chemical Fe redox processes and methanogenesis-derived biotic dechlorination. Revealing the coupling between dechlorination and CH4-associated bioprocesses is helpful to resolve both pollution remediation and mitigation of CH4 emissions in anaerobic contaminated sites.

Gain in carbon: Deciphering the abiotic and biotic mechanisms of biochar-induced negative priming effects in contrasting soils.

The biochar-induced priming effects (PEs) were investigated by applying maize straw (C4) derived biochar to eight C3 soils, with a gradient of pH and a sub-gradient of soil organic carbon (SOC). To decipher the physicochemical and microbial mechanisms, we adopted C-isotopic analysis, high-throughput sequencing and multivariate statistical analyses such as random forest (RF) and structure equation modeling (SEM). Negative and neutral PEs were observed up to -48.5% of relative PEs during 28 days of incubation. All the acidic soils exhibited negative PEs, so as the neutral Alfisol and alkaline Aridisol, which had a suppression effect on SOC mineralization accounted for -29.4 and -32.0% of relative PEs. Among all abiotic factors, soil silt-clay fraction and the initial pH values play the most important roles in PEs determination through directly inhibiting PEs by protection SOC and indirectly shaping bacterial communities respectively. On the whole community level, biochar treatments defined much less microbiome (0.6% and 1.2% for variance of bacterial and fungal community) than soil types (93.5% and 83.3% respectively) across soils. Thus, the initial community (i.e., bacteria alpha-diversity and copiotrophic bacteria as revealed by SEM) of different soils might be more critical for PE prediction. Furthermore, co-occurrence network analysis indicated out-competition of fungi by bacteria with increase of mutual exclusion and decrease of fungal occupancy. This could exacerbate negative PEs in soils with lower bacterial alpha-diversity and dominance by copiotrophys due to less functional complementary for recalcitrant SOC decomposition.

Long-term nutrient inputs shift soil microbial functional profiles of phosphorus cycling in diverse agroecosystems.

Microorganisms play an important role in soil phosphorus (P) cycling and regulation of P availability in agroecosystems. However, the responses of the functional and ecological traits of P-transformation microorganisms to long-term nutrient inputs are largely unknown. This study used metagenomics to investigate changes in the relative abundance of microbial P-transformation genes at four long-term experimental sites that received various inputs of N and P nutrients (up to 39 years). Long-term P input increased microbial P immobilization by decreasing the relative abundance of the P-starvation response gene (phoR) and increasing that of the low-affinity inorganic phosphate transporter gene (pit). This contrasts with previous findings that low-P conditions facilitate P immobilization in culturable microorganisms in short-term studies. In comparison, long-term nitrogen (N) input significantly decreased soil pH, and consequently decreased the relative abundances of total microbial P-solubilizing genes and the abundances of Actinobacteria, Gammaproteobacteria, and Alphaproteobacteria containing genes coding for alkaline phosphatase, and weakened the connection of relevant key genes. This challenges the concept that microbial P-solubilization capacity is mainly regulated by N:P stoichiometry. It is concluded that long-term N inputs decreased microbial P-solubilizing and mineralizing capacity while P inputs favored microbial immobilization via altering the microbial functional profiles, providing a novel insight into the regulation of P cycling in sustainable agroecosystems from a microbial perspective.

Steroid receptor coactivator-1 modulates the function of Pomc neurons and energy homeostasis.

Hypothalamic neurons expressing the anorectic peptide Pro-opiomelanocortin (Pomc) regulate food intake and body weight. Here, we show that Steroid Receptor Coactivator-1 (SRC-1) interacts with a target of leptin receptor activation, phosphorylated STAT3, to potentiate Pomc transcription. Deletion of SRC-1 in Pomc neurons in mice attenuates their depolarization by leptin, decreases Pomc expression and increases food intake leading to high-fat diet-induced obesity. In humans, fifteen rare heterozygous variants in SRC-1 found in severely obese individuals impair leptin-mediated Pomc reporter activity in cells, whilst four variants found in non-obese controls do not. In a knock-in mouse model of a loss of function human variant (SRC-1L1376P), leptin-induced depolarization of Pomc neurons and Pomc expression are significantly reduced, and food intake and body weight are increased. In summary, we demonstrate that SRC-1 modulates the function of hypothalamic Pomc neurons, and suggest that targeting SRC-1 may represent a useful therapeutic strategy for weight loss.

Quantitative Analysis of CT Images in Patients with Pyrrolizidine Alkaloid-Induced Sinusoidal Obstruction Syndrome.

This study evaluated hepatic lesion volumes on contrast-enhanced computed tomography (CT) images in patients with pyrrolizidine alkaloid-induced sinusoidal obstruction syndrome (PA-SOS) and the association of lesion volume with the clinical severity and prognosis of the disease. Twenty-five patients with PA-SOS were included in this study, and all patients were subjected to a complete CT imaging series. The imaging results were quantitatively analyzed by a threshold-based region growing algorithm. The liver volumes and hepatic lesion volumes of the patients were estimated. Based on clinical presentations, PA-SOS was classified into three categories: mild, moderate and severe. The associations of hepatic lesion volumes with liver function test parameters and the clinical severity and prognosis of the disease were analyzed. Based on estimations using the threshold-based region growing algorithm, hepatic lesion volumes in patients with mild PA-SOS were significantly lower than those in patients with moderate and severe PA-SOS (P < 0.05). The ratio of hepatic lesion volume to liver volume (Ratio) varied based on alanine aminotransferase (ALT), aspartate aminotransferase (AST) and serum total bilirubine levels; clinical severity; and disease prognosis, and the differences were statistically significant (P < 0.05). In conclusion, the threshold-based region growing algorithm can be employed to quantitatively analyze enhanced CT images of PA-SOS patients. And the ratio of hepatic lesion volume to liver volume in patients with PA-SOS is associated with a more serious clinical course and a poorer outcome.

Incidence and Etiology of Drug-Induced Liver Injury in Mainland China.

BACKGROUND & AIMS: We performed a nationwide, retrospective study to determine the incidence and causes of drug-induced liver injury (DILI) in mainland China. METHODS: We collected data on a total of 25,927 confirmed DILI cases, hospitalized from 2012 through 2014 at 308 medical centers in mainland China. We collected demographic, medical history, treatment, laboratory, disease severity, and mortality data from all patients. Investigators at each site were asked to complete causality assessments for each case whose diagnosis at discharge was DILI (n = 29,478) according to the Roussel Uclaf Causality Assessment Method. RESULTS: Most cases of DILI presented with hepatocellular injury (51.39%; 95% confidence interval [CI] 50.76-52.03), followed by mixed injury (28.30%; 95% CI 27.73-28.87) and cholestatic injury (20.31%; 95% CI 19.80-20.82). The leading single classes of implicated drugs were traditional Chinese medicines or herbal and dietary supplements (26.81%) and antituberculosis medications (21.99%). Chronic DILI occurred in 13.00% of the cases and, although 44.40% of the hepatocellular DILI cases fulfilled Hy's Law criteria, only 280 cases (1.08%) progressed to hepatic failure, 2 cases underwent liver transplantation (0.01%), and 102 patients died (0.39%). Among deaths, DILI was judged to have a primary role in 72 (70.59%), a contributory role in 21 (20.59%), and no role in 9 (8.82%). Assuming the proportion of DILI in the entire hospitalized population of China was represented by that observed in the 66 centers where DILI capture was complete, we estimated the annual incidence in the general population to be 23.80 per 100,000 persons (95% CI 20.86-26.74). Only hospitalized patients were included in this analysis, so the true incidence is likely to be higher. CONCLUSIONS: In a retrospective study to determine the incidence and causes of DILI in mainland China, the annual incidence in the general population was estimated to be 23.80 per 100,000 persons; higher than that reported from Western countries. Traditional Chinese medicines, herbal and dietary supplements, and antituberculosis drugs were the leading causes of DILI in mainland China.

The efficacy of oral Zhizhu Kuanzhong, a traditional Chinese medicine, in patients with postprandial distress syndrome.

BACKGROUND AND AIM: The treatment of patients with functional dyspepsia (FD) remains unsatisfactory. We assessed the efficacy of Zhizhu Kuanzhong (ZZKZ) capsule, a traditional Chinese medicine formula, in patients with postprandial distress syndrome (PDS) of FD. METHODS: The study was designed as a multicenter, randomized, double-blinded, controlled clinical trial. Three-hundred ninety-two patients with PDS defined by Rome III criteria from 16 centers in China were randomly assigned to receive either ZZKZ or placebo. The proportion of the responders at 4 weeks after randomization was considered primary endpoint. Secondary endpoint was the symptom score reduction of each dyspeptic symptom relative to the baseline at 4 weeks after randomization in all subjects. RESULTS: In terms of the primary endpoint, the proportion of the responders concerning the composite PDS symptom score was 38.8% and 54.7% in placebo group and ZZKZ group, respectively (P = 0.003), in per protocol analysis at 4 weeks after randomization. Concerning the individual evaluated upper gastrointestinal symptoms, only postprandial fullness and early satiety showed significant difference in symptom score reduction at 4 weeks after randomization between placebo and ZZKZ groups. CONCLUSIONS: Zhizhu Kuanzhong is superior to placebo in the treatment of PDS with FD. The exact mechanisms by which ZZKZ improves symptoms remain to be established (http://www.chictr.org.cn/ChinCTR-TRC-14004714).

Nitrate supply and sulfate-reducing suppression facilitate the removal of pentachlorophenol in a flooded mangrove soil.

An anaerobic incubation was launched with varying nitrate (1, 5, 10 and 20 mM exogenous NaNO3) and molybdate (20 mM Na2MoO4, a sulfate-reducing inhibitor) additions to investigate the characteristics of PCP dechlorination, as well as the reduction of natural co-occurring electron acceptors, including NO3-, Fe(III) and SO42-, and the responses of microbial community structures under a unique reductive mangrove soil. Regardless of exogenous addition, nitrate was rapidly eliminated in the first 12 days. The reduction process of Fe(III) was inhibited, while that of SO42- reduction depended on addition concentration as compared to the control. PCP was mainly degraded from orth-position, forming the only intermediate 2,3,4,5-TeCP by anaerobic microbes, with the highest PCP removal rate of average 21.9% achieved in 1 and 5 mM NaNO3 as well as 20 mM Na2MoO4 treatments and the lowest of 7.5% in 20 mM NaNO3 treatment. The effects of nitrate on PCP dechlorination depended on addition concentration, while molybdate promoted PCP attenuation significantly. Analyses of the Illumina sequencing data and the relative abundance of dominant microorganisms indicated that the core functional groups regulated PCP removal at genera level likely included Bacillus, Pesudomonas, Dethiobacter, Desulfoporosinus and Desulfovbrio in the nitrate treatments; while that was likely Sedimentibacter and Geosporobacter_Thermotalea in the molybdate treatment. Nitrate supplement but not over supplement, or addition of molybdate are suggested as alternative strategies for better remediation in the nitrate-deficient and sulfur-accumulated soil ecosystem contaminated by PCP, through regulating the growth of core functional groups and thereby coordinating the interaction between dechlorination and its coupled soil redox processes due to shifts of more available electrons to dechlorination. Our results broadened the knowledge regarding microbial PCP degradation and their interactions with natural soil redox processes under anaerobic soil ecosystems.

Soil available phosphorus content drives the spatial distribution of archaeal communities along elevation in acidic terrace paddy soils.

Archaea play crucial roles in geochemical cycles and influence the emission of greenhouse gases in acidic soils. However, little is known about the distribution pattern of total archaeal diversity and community composition with increasing elevation, especially in acidic agricultural ecosystems. Terraces, characterized by vertical climate changes and unique hydrological properties, are "natural experiments" to explore the spatial distribution of microorganisms along elevation in paddy soils. Here we investigated the diversity and structure of soil archaeal communities in nine increasingly elevated acidic paddy soils of the Yunhe terrace, China. Archaeal communities were dominated by Methanomicrobia of Euryarchaeota (38.5%), Group 1.1a-associated cluster (SAGSCG-1) of Thaumarchaeota (22.0%) and Subgroup-6 (previously described as crenarchaeotal group 1.3b) of Bathyarchaeota (17.8%). The archaeal phylotype richness decreased with increasing elevation. Both the species richness and phylogenetic diversity of the archaeal communities were significantly negatively correlated with soil available phosphorus (AP) content according to linear regression analyses. The archaeal communities differed greatly between soils of increasing elevation, and were roughly clustered into three groups, mostly in relation to AP contents. A variation partitioning analysis further confirmed that edaphic factors including the content of AP (17.1%), nitrate (7.83%), soil organic carbon (4.69%), dissolved organic carbon (4.22%) and soil pH (4.07%) shaped the archaeal community. The variation of soil properties were probably induced by elevation. The co-occurrence network indicated a modular structure of the archaeal community. Overall, our results emphasized that soil AP content was the best predictor of archaeal diversity and community structure, and the impacts of elevation on soil archaeal communities were not diminished by long-term rice cultivation, although minor compared with the effects of soil properties.