(5R)-5-hydroxytriptolide for HIV immunological non-responders receiving ART: a randomized, double-blinded, placebo-controlled phase II study.

Background: Therapeutic approaches to HIV-suppressed immunological non-responders (INRs) remain unsettled. We previously reported efficacy of Chinese herbal Tripterygium wilfordii Hook F in INRs. Its derivative (5R)-5-hydroxytriptolide (LLDT-8) on CD4 T cell recovery was assessed. Methods: The phase II, double-blind, randomized, placebo-controlled trial was conducted in adults patients with long-term suppressed HIV infection and suboptimal CD4 recovery, at nine hospitals in China. The patients were 1:1:1 assigned to receive oral LLDT-8 0.5 mg or 1 mg daily, or placebo combined with antiretroviral therapy for 48 weeks. All study staff and participants were masked. The primary endpoints include change of CD4 T cell counts and inflammatory markers at week 48. This study is registered on ClinicalTrials.gov (NCT04084444) and Chinese Clinical Trial Register (CTR20191397). Findings: A total of 149 patients were enrolled from Aug 30, 2019 and randomly allocated to receiving LLDT-8 0.5 mg daily (LT8, n = 51), 1 mg daily (HT8, n = 46), or placebo (PL, n = 52). The median baseline CD4 count was 248 cells/mm3, comparable among three groups. LLDT-8 was well-tolerated in all participants. At 48 weeks, change of CD4 counts was 49 cells/mm3 in LT8 group (95% confidence interval [CI]: 30, 68), 63 cells/mm3 in HT8 group (95% CI: 41, 85), compared to 32 cells/mm3 in placebo group (95% CI: 13, 51). LLDT-8 1 mg daily significantly increased CD4 count compared to placebo (p = 0.036), especially in participants over 45 years. The mean change of serum interferon-γ-induced protein 10 was -72.1 mg/L (95% CI -97.7, -46.5) in HT8 group at 48 weeks, markedly decreased compared to -22.8 mg/L (95% CI -47.1, 1.5, p = 0.007) in placebo group. Treatment-emergent adverse events (TEAEs) were reported in 41 of 46 (89.1%) participants in HT8 group, 43 of 51 (84.3%) in LT8, and 42 of 52 (80.7%) in PL group. No drug-related SAEs were reported. Interpretation: LLDT-8 enhanced CD4 recovery and alleviated inflammation in long-term suppressed INRs, providing them a potential therapeutic option. Fundings: Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, Shanghai Pharmaceuticals Holding Co., Ltd., and the National key technologies R&D program for the 13th five-year plan.

Wild vs. Cultivated Zingiber striolatum Diels: Nutritional and Biological Activity Differences.

Compositional, functional, and nutritional properties are important for the use-value assessments of wild and cultivated edible plants. The aim of this study was to compare the nutritional composition, bioactive compounds, volatile compounds, and potential biological activities of cultivated and wild Zingiber striolatum. Various substances, such as soluble sugars, mineral elements, vitamins, total phenolics, total flavonoids, and volatiles, were measured and analyzed using UV spectrophotometry, ICP-OES, HPLC, and GC-MS methods. The antioxidant capacity of a methanol extract of Z. striolatum, as well as the hypoglycemic abilities of its ethanol and water extracts, were tested. The results showed that the contents of soluble sugar, soluble protein, and total saponin in the cultivated samples were higher, while the wild samples contained higher amounts of K, Na, Se, vitamin C, and total amino acids. The cultivated Z. striolatum also showed a higher antioxidant potential, while the wild Z. striolatum exhibited a better hypoglycemic activity. Thirty-three volatile compounds were identified using GC-MS in two plants, with esters and hydrocarbons being the main volatile compounds. This study demonstrated that both cultivated and wild Z. striolatum have a good nutritional value and biological activity, and can be used as a source of nutritional supplementation or even in medication.

Long-term nitrogen deposition inhibits soil priming effects by enhancing phosphorus limitation in a subtropical forest.

It is widely accepted that phosphorus (P) limits microbial metabolic processes and thus soil organic carbon (SOC) decomposition in tropical forests. Global change factors like elevated atmospheric nitrogen (N) deposition can enhance P limitation, raising concerns about the fate of SOC. However, how elevated N deposition affects the soil priming effect (PE) (i.e., fresh C inputs induced changes in SOC decomposition) in tropical forests remains unclear. We incubated soils exposed to 9 years of experimental N deposition in a subtropical evergreen broadleaved forest with two types of 13 C-labeled substrates of contrasting bioavailability (glucose and cellulose) with and without P amendments. We found that N deposition decreased soil total P and microbial biomass P, suggesting enhanced P limitation. In P unamended soils, N deposition significantly inhibited the PE. In contrast, adding P significantly increased the PE under N deposition and by a larger extent for the PE of cellulose (PEcellu ) than the PE of glucose (PEglu ). Relative to adding glucose or cellulose solely, adding P with glucose alleviated the suppression of soil microbial biomass and C-acquiring enzymes induced by N deposition, whereas adding P with cellulose attenuated the stimulation of acid phosphatase (AP) induced by N deposition. Across treatments, the PEglu increased as C-acquiring enzyme activity increased, whereas the PEcellu increased as AP activity decreased. This suggests that P limitation, enhanced by N deposition, inhibits the soil PE through varying mechanisms depending on substrate bioavailability; that is, P limitation regulates the PEglu by affecting soil microbial growth and investment in C acquisition, whereas regulates the PEcellu by affecting microbial investment in P acquisition. These findings provide new insights for tropical forests impacted by N loading, suggesting that expected changes in C quality and P limitation can affect the long-term regulation of the soil PE.

Ecosystem-dependent responses of soil carbon storage to phosphorus enrichment.

Phosphorus deposition can stimulate both plant carbon inputs and microbial carbon outputs. However, how P enrichment affects soil organic carbon (SOC) storage and the underlying mechanisms remain unclear. We conducted a meta-analysis of 642 SOC observations from 213 field P addition experiments world-wide and explored the regulations of plant inputs, microbial outputs, plant characteristics, and environmental and experimental factors on SOC responses. We found that, globally, P addition stimulated SOC by 4.0% (95% CI: 2.0-6.0%), but the stimulation only occurred in forest and cropland rather than in grassland. Across sites, the response of SOC correlated with that of plant aboveground rather than belowground biomass, suggesting that the change in plant inputs from aboveground was more important than that from belowground in regulating SOC changes due to P addition. Among multiple factors, plant N fixation status and mean annual temperature were the best predictors for SOC responses to P addition, with SOC stimulation being higher in ecosystems dominated by symbiotic nitrogen fixers and ecosystems in high-temperature regions like tropical forests. Our findings highlight the differential and ecosystem-dependent responses of SOC to P enrichment and can contribute to accurate predictions of soil carbon dynamics in a P-enriched world.

Nutritional Composition and Antioxidant Activity of Gonostegia hirta: An Underexploited, Potentially Edible, Wild Plant.

Wild, edible plants have received increasing attention as an important complement to cultivate vegetables, as they represent an easily accessible source of nutrients, mineral elements, and antioxidants. In this study, the tender stems and leaves of Gonostegia hirta, an edible species for which only scarce data are available in the literature, are thoroughly evaluated for their nutritional profile, chemical characterization, and antioxidant activity. Being considered as an underexploited, potentially edible plant, the nutritional composition of Gonostegia hirta was identified, and several beneficial compounds were highlighted: sugars, potassium, calcium, organic acids, fatty acids, phenolics, and flavonoids. A total of 418 compounds were identified by metabolomic analysis, including phenolic acids, flavonoids, amino acids, lipids, organic acids, terpenoids, alkaloids, nucleotides, tannins, lignans, and coumarin. The plant sample was found to have good antioxidant capacities, presented by DPPH, FRAP, ABTS+, hydroxyl radical scavenging capacity, and its resistance to the superoxide anion radical test. In general, Gonostegia hirta has a good nutritional and phytochemical composition. The health benefits of Gonostegia hirta as a vegetable and herbal medicine is important for both a modern diet and use in medication.

Foliar phosphorus allocation and photosynthesis reveal plants' adaptative strategies to phosphorus limitation in tropical forests at different successional stages.

High atmospheric nitrogen (N) deposition and low soil phosphorus (P) availability occur simultaneously in tropical areas, and thus tropical plants need to adapt nutrient-use strategies to maintain growth and survival. Therefore, identifying the adaptative strategies of tropical plants at different successional stages under low soil P availability is indispensable. Here, we separately investigated foliar traits, photosynthetic characteristics, and P fractions of 8 species in the primary and secondary tropical forests after 10 years of N and P fertilization. P addition increased foliar P concentrations and deceased N:P ratio in the primary forest and secondary forest. The foliar photosynthetic rates did not significantly respond to nutrient additions, and the foliar photosynthetic P-use efficiency (PPUE) reduced under the P addition in the primary forest. In contrast, the foliar photosynthetic rates and photosynthetic nitrogen (N)-use efficiency (PNUE) were enhanced with nutrient additions in the secondary forest. The allocations of foliar nucleic acid P and residual P were reduced by P addition in the primary forest, whereas the allocation of metabolic P was enhanced and the allocation of residual P was reduced by P addition in the secondary forest. Additionally, a higher proportion of structural P was found in the primary forest, and a higher proportion of metabolic P was observed in the secondary forest. Interesting, structural equation model analysis revealed that the plants decreased the allocation of foliar nucleic acid P and increased the allocation of structural P in the primary forest, thereby reducing photosynthetic rates. Whereas the plants enhanced photosynthetic rates by promoting PPUE and the allocation of foliar metabolic P in the secondary forest. Our findings highlighted tropical plants at different successional stages can reasonably allocate foliar P to regulate photosynthetic rates and acclimate to low P environments.

Phosphorus addition decreases plant lignin but increases microbial necromass contribution to soil organic carbon in a subalpine forest.

Increasing phosphorus (P) inputs induced by anthropogenic activities have increased P availability in soils considerably, with dramatic effects on carbon (C) cycling and storage. However, the underlying mechanisms via which P drives plant and microbial regulation of soil organic C (SOC) formation and stabilization remain unclear, hampering the accurate projection of soil C sequestration under future global change scenarios. Taking the advantage of an 8-year field experiment with increasing P addition levels in a subalpine forest on the eastern Tibetan Plateau, we explored plant C inputs, soil microbial communities, plant and microbial biomarkers, as well as SOC physical and chemical fractions. We found that continuous P addition reduced fine root biomass, but did not affect total SOC content. P addition decreased plant lignin contribution to SOC, primarily from declined vanillyl-type phenols, which was coincided with a reduction in methoxyl/N-alkyl C by 2.1%-5.5%. Despite a decline in lignin decomposition due to suppressed oxidase activity by P addition, the content of lignin-derived compounds decreased because of low C input from fine roots. In contrast, P addition increased microbial (mainly fungal) necromass and its contribution to SOC due to the slower necromass decomposition under reduced N-acquisition enzyme activity. The larger microbial necromass contribution to SOC corresponded with a 9.1%-12.4% increase in carbonyl C abundance. Moreover, P addition had no influence on the slow-cycing mineral-associated organic C pool, and SOC chemical stability indicated by aliphaticity and recalcitrance indices. Overall, P addition in the subalpine forest over 8 years influenced SOC composition through divergent alterations of plant- and microbial-derived C contributions, but did not shape SOC physical and chemical stability. Such findings may aid in accurately forecasting SOC dynamics and their potential feedbacks to climate change with future scenarios of increasing soil P availability in Earth system models.

Effects of nitrogen and phosphorus enrichment on soil N2O emission from natural ecosystems: A global meta-analysis.

Nitrogen (N) and phosphorous (P) enrichment play an important role in regulating soil N2O emission, but their interactive effect remains elusive (i.e. whether the effect of P or N enrichment on soil N2O emission varies between ambient and elevated soil N or P conditions). Here, we conducted a Bayesian meta-analysis across the global natural ecosystems to determine this effect. Our results showed that P enrichment significantly decreased soil N2O emission by 13.9% at ambient soil N condition. This N2O mitigation is likely due to the decreased soil NO3--N content (-17.6%) derived by the enhanced plant uptake when the P limitation was alleviated by P enrichment. However, this P-induced N2O (and NO3--N) mitigation was not found at elevated soil N condition. Additionally, N enrichment significantly increased soil N2O emission by 101.4%, which was associated with the increased soil NH4+-N (+41.0%) and NO3--N (+82.3%). However, the effect of N enrichment on soil N2O emission did not differ between ambient and elevated soil P subgroups, indicating that the P-derived N2O mitigation could be masked by N enrichment. Further analysis showed that manipulated N rate, soil texture, soil dissolved organic nitrogen, soil total nitrogen, soil organic carbon, soil pH, aboveground plant biomass, belowground plant biomass, and plant biomass nitrogen were the main factors affecting soil N2O emission under N enrichment. Taken together, our study provides evidence that P enrichment has the potential to reduce soil N2O emission from natural ecosystems, but this mitigation effect could be masked by N enrichment.

Changes in soil total, microbial and enzymatic C-N-P contents and stoichiometry with depth and latitude in forest ecosystems.

Soil microorganisms and their extracellular enzymes are key factors determining the biogeochemical cycles of carbon (C), nitrogen (N) and phosphorus (P). Relevant studies mainly focus on surface soils (0-20 cm), while deep soils (>20 cm) are often neglected, let alone comparing multiple ecosystems simultaneously. In this study, we studied the latitudinal (19-48°N) and vertical (0-100 cm) patterns of soil total, microbial and enzymatic C-N-P contents and ratios (stoichiometry) in eight temperate, subtropical and tropical forest ecosystems in eastern China. We found that the C-N-P contents and their stoichiometry in soil, microbial biomass and extracellular enzymes all varied significantly with depth and latitude. Soil total C, N and P declined with depth, as did microbial biomass and enzyme activity, while microbial and enzymatic C:N ratios showed increasing or no trend with increasing soil depth. Moreover, soil total and microbial C-N-P contents in surface soils (0-20 cm) showed positive correlations with increasing latitude, and such correlations tended to be weaker or disappeared in deep soils (>20 cm). Overall, changes in total, microbial and enzymatic C-N-P contents and ratios among latitudes suggested a shift from relative N limitation in the north to relative P limitation in the south.

Loss of soil microbial residue carbon by converting a tropical forest to tea plantation.

Land-use change can lead to profound changes in the storage of soil organic carbon (SOC) in the tropics. Soil microbial residues make up the majority of persistent SOC pools, yet the impact of land-use change on microbial residue C accumulation in the tropics is not well understood. Here, we investigated how the conversion of tropical primary montane rainforest to secondary forest and the conversions of secondary forest to Prunus salicina plantation and tea plantation, influence the accumulation of soil microbial residue C (indicated by amino sugars). Our results showed that the secondary forest had a higher SOC than that of the primary forest (+63%), while they had no difference in microbial residue C concentration, indicating a relatively slow microbial-derived C accrual during secondary succession. Moreover, the P. salicina plantation and tea plantation had lower SOC than the secondary forest (-53% and -57%, respectively). A decrease in fungal biomass (-51%) resulted in less fungal and total residue C concentrations in the tea plantation than in the secondary forest (-38% and -35%, respectively), indicating microbial-derived C loss following the forest conversion. The change in microbial residue C depended on litter standing crop rather than soil nutrient and root biomass. Litter standing crop affected microbial residue C concentration by regulating fungal biomass and hydrolytic enzyme activities. Taken together, our results highlight that litter-microbe interactions drive microbial residue C accumulation following forest conversions in the tropics.

Successful treatment with tumor necrosis factor-α blockers for poison-induced liver injury: case report and literature review.

Acute poisoning could result in hepatic dysfunction which is potentially life threatening. We reviewed three cases of poison-induced liver injury with gastrointestinal disorder on admission. Two cases were poisoned by mushroom α-Amanitin while the other was poisoned by acetaminophen (APAP). They were cured under the close monitor of laboratory examinations and other supportive therapies, as well as the off-label medication of etanercept, a kind of tumor necrosis factor-α (TNF-α) blockers with written informed consent. Among them, case1 was given the first dose doubling of TNF-α blockers for higher liver enzyme levels. There is a lack of effective and safe treatments for poison-induced liver injury. TNF-α has been proved to play an important role in the aggravation of liver injury and the start-up of inflammatory cascade reaction. Therapy with TNF-α blockers shown potential therapeutic efficacy in hepatic dysfunction by some researches. Anyway, no strong recommendation could be drawn from these small sample size studies. On the other side, TNF-α could also mediate an opposing effect for hepatocytes since the hepatic toxicity of TNF-α blockers has generated attentions. The safety for the off-label medication of TNF-α blockers in liver injury, however, still lacks strong evidences. More experimental and clinical researches are needed to focus on potential mechanisms.

Complementarity in nutrient foraging strategies of absorptive fine roots and arbuscular mycorrhizal fungi across 14 coexisting subtropical tree species.

In most cases, both roots and mycorrhizal fungi are needed for plant nutrient foraging. Frequently, the colonization of roots by arbuscular mycorrhizal (AM) fungi seems to be greater in species with thick and sparsely branched roots than in species with thin and densely branched roots. Yet, whether a complementarity exists between roots and mycorrhizal fungi across these two types of root system remains unclear. We measured traits related to nutrient foraging (root morphology, architecture and proliferation, AM colonization and extramatrical hyphal length) across 14 coexisting AM subtropical tree species following root pruning and nutrient addition treatments. After root pruning, species with thinner roots showed more root growth, but lower mycorrhizal colonization, than species with thicker roots. Under multi-nutrient (NPK) addition, root growth increased, but mycorrhizal colonization decreased significantly, whereas no significant changes were found under nitrogen or phosphate additions. Moreover, root length proliferation was mainly achieved by altering root architecture, but not root morphology. Thin-root species seem to forage nutrients mainly via roots, whereas thick-root species rely more on mycorrhizal fungi. In addition, the reliance on mycorrhizal fungi was reduced by nutrient additions across all species. These findings highlight complementary strategies for nutrient foraging across coexisting species with contrasting root traits.

Effect of intestinal microbiota alteration on hepatic damage in rats with acute rejection after liver transplantation.

The previous studies all focus on the effect of probiotics and antibiotics on infection after liver transplantation. Here, we focus on the effect of gut microbiota alteration caused by probiotics and antibiotics on hepatic damage after allograft liver transplantation. Brown-Norway rats received saline, probiotics, or antibiotics via daily gavage for 3 weeks. Orthotopic liver transplantation (OLT) was carried out after 1 week of gavage. Alteration of the intestinal microbiota, liver function and histopathology, serum and liver cytokines, and T cells in peripheral blood and Peyer's patch were evaluated. Distinct segregation of fecal bacterial diversity was observed in the probiotic group and antibiotic group when compared with the allograft group. As for diversity of intestinal mucosal microbiota and pathology of intestine at 2 weeks after OLT, antibiotics and probiotics had a significant effect on ileum and colon. The population of Lactobacillus and Bifidobacterium in the probiotic group was significantly greater than the antibiotic group and the allograft group. The liver injury was significantly reduced in the antibiotic group and the probiotic group compared with the allograft group. The CD4/CD8 and Treg cells in Peyer's patch were decreased in the antibiotic group. The intestinal Treg cell and serum and liver TGF-ß were increased markedly while CD4/CD8 ratio was significantly decreased in the probiotic group. It suggested that probiotics mediate their beneficial effects through increase of Treg cells and TGF-ß and deduction of CD4/CD8 in rats with acute rejection (AR) after OLT.