Gut microbiota and its therapeutic implications in tumor microenvironment interactions.

The development of cancer is not just the growth and proliferation of a single transformed cell, but its tumor microenvironment (TME) also coevolves with it, which is primarily involved in tumor initiation, development, metastasis, and therapeutic responses. Recent years, TME has been emerged as a potential target for cancer diagnosis and treatment. However, the clinical efficacy of treatments targeting the TME, especially its specific components, remains insufficient. In parallel, the gut microbiome is an essential TME component that is crucial in cancer immunotherapy. Thus, assessing and constructing frameworks between the gut microbiota and the TME can significantly enhance the exploration of effective treatment strategies for various tumors. In this review the role of the gut microbiota in human cancers, including its function and relationship with various tumors was summarized. In addition, the interaction between the gut microbiota and the TME as well as its potential applications in cancer therapeutics was described. Furthermore, it was summarized that fecal microbiota transplantation, dietary adjustments, and synthetic biology to introduce gut microbiota-based medical technologies for cancer treatment. This review provides a comprehensive summary for uncovering the mechanism underlying the effects of the gut microbiota on the TME and lays a foundation for the development of personalized medicine in further studies.

The impact of dioctyl phthalate exposure on multiple organ systems and gut microbiota in mice.

Dioctyl phthalate, commonly known as bis(2-ethylhexyl) phthalate (DEHP), is a widely used plasticizer in various industries and has been shown to directly or indirectly impact human health. However, there is a lack of comprehensive studies evaluating the potential health risks associated with DEHP accumulation in different organs across various age groups. This study aimed to assess the effects of low (50 mg/kg·bw) and high (500 mg/kg·bw) doses of DEHP on five different organs in mice at young (4-week-old) and aged (76-week-old) life stages. Our findings revealed that both low and high doses of DEHP exposure led to significant dose-dependent inflammation in the liver, spleen, and kidney. Furthermore, regardless of age, DEHP exposure resulted in elevated activity of alanine aminotransferase (ALT) and alkaline phosphatase (ALP) in the liver, as well as increased levels of creatinine (Cr) and urea in the kidney. Moreover, analysis of the fecal microbiota using 16S rRNA sequencing demonstrated that DEHP exposure disrupted the homeostasis of the gut microbiota, characterized by an increased abundance of pathogenic bacteria such as Desulfovibrio and Muribaculum, and a decreased abundance of beneficial bacteria like Lactobacillus. This study provides compelling evidence that DEHP at different concentrations can induce damage to multiple organs and disrupt gut microbiota composition. These findings lay the groundwork for further investigations into DEHP toxicity in various human organs, contributing to a better understanding of the potential health risks associated with DEHP exposure.

The evolution of SARS-CoV-2 and the COVID-19 pandemic.

Scientists have made great efforts to understand the evolution of SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) to provide crucial information to public health experts on strategies to control this viral pathogen. The pandemic of the coronavirus disease that began in 2019, COVID-19, lasted nearly three years, and nearly all countries have set different epidemic prevention policies for this virus. The continuous evolution of SARS-CoV-2 alters its pathogenicity and infectivity in human hosts, thus the policy and treatments have been continually adjusted. Based on our previous study on the dynamics of binding ability prediction between the COVID-19 spike protein and human ACE2, the present study mined over 10 million sequences and epidemiological data of SARS-CoV-2 during 2020-2022 to understand the evolutionary path of SARS-CoV-2. We analyzed and predicted the mutation rates of the whole genome and main proteins of SARS-CoV-2 from different populations to understand the adaptive relationship between humans and COVID-19. Our study identified a correlation of the mutation rates from each protein of SARS-CoV-2 and various human populations. Overall, this analysis provides a scientific basis for developing data-driven strategies to confront human pathogens.

Lowering water table reduces carbon sink strength and carbon stocks in northern peatlands.

Peatlands at high latitudes have accumulated >400 Pg carbon (C) because saturated soil and cold temperatures suppress C decomposition. This substantial amount of C in Arctic and Boreal peatlands is potentially subject to increased decomposition if the water table (WT) decreases due to climate change, including permafrost thaw-related drying. Here, we optimize a version of the Organizing Carbon and Hydrology In Dynamic Ecosystems model (ORCHIDEE-PCH4) using site-specific observations to investigate changes in CO2 and CH4 fluxes as well as C stock responses to an experimentally manipulated decrease of WT at six northern peatlands. The unmanipulated control peatlands, with the WT <20 cm on average (seasonal max up to 45 cm) below the surface, currently act as C sinks in most years (58 ± 34 g C m-2  year-1 ; including 6 ± 7 g C-CH4 m-2  year-1 emission). We found, however, that lowering the WT by 10 cm reduced the CO2 sink by 13 ± 15 g C m-2  year-1 and decreased CH4 emission by 4 ± 4 g CH4 m-2  year-1 , thus accumulating less C over 100 years (0.2 ± 0.2 kg C m-2 ). Yet, the reduced emission of CH4 , which has a larger greenhouse warming potential, resulted in a net decrease in greenhouse gas balance by 310 ± 360 g CO2-eq  m-2  year-1 . Peatlands with the initial WT close to the soil surface were more vulnerable to C loss: Non-permafrost peatlands lost >2 kg C m-2 over 100 years when WT is lowered by 50 cm, while permafrost peatlands temporally switched from C sinks to sources. These results highlight that reductions in C storage capacity in response to drying of northern peatlands are offset in part by reduced CH4 emissions, thus slightly reducing the positive carbon climate feedbacks of peatlands under a warmer and drier future climate scenario.

Empirical estimates of regional carbon budgets imply reduced global soil heterotrophic respiration.

Resolving regional carbon budgets is critical for informing land-based mitigation policy. For nine regions covering nearly the whole globe, we collected inventory estimates of carbon-stock changes complemented by satellite estimates of biomass changes where inventory data are missing. The net land-atmospheric carbon exchange (NEE) was calculated by taking the sum of the carbon-stock change and lateral carbon fluxes from crop and wood trade, and riverine-carbon export to the ocean. Summing up NEE from all regions, we obtained a global 'bottom-up' NEE for net land anthropogenic CO2 uptake of -2.2 ± 0.6 PgC yr-1 consistent with the independent top-down NEE from the global atmospheric carbon budget during 2000-2009. This estimate is so far the most comprehensive global bottom-up carbon budget accounting, which set up an important milestone for global carbon-cycle studies. By decomposing NEE into component fluxes, we found that global soil heterotrophic respiration amounts to a source of CO2 of 39 PgC yr-1 with an interquartile of 33-46 PgC yr-1-a much smaller portion of net primary productivity than previously reported.

Large historical carbon emissions from cultivated northern peatlands.

When a peatland is drained and cultivated, it behaves as a notable source of CO2 However, we lack temporally and spatially explicit estimates of carbon losses from cultivated peatlands. Using a process-based land surface model that explicitly includes representation of peatland processes, we estimate that northern peatlands converted to croplands emitted 72 Pg C over 850-2010, with 45% of this source having occurred before 1750. This source surpassed the carbon accumulation by high-latitude undisturbed peatlands (36 to 47 Pg C). Carbon losses from the cultivation of northern peatlands are omitted in previous land-use emission assessments. Adding this ignored historical land-use emission implies an 18% larger terrestrial carbon storage since 1750 to close the historical global carbon budget. We also show that carbon emission per unit area decrease with time since drainage, suggesting that time since drainage should be accounted for in inventories to refine land-use emissions from cultivated peatlands.

Climate warming from managed grasslands cancels the cooling effect of carbon sinks in sparsely grazed and natural grasslands.

Grasslands absorb and release carbon dioxide (CO2), emit methane (CH4) from grazing livestock, and emit nitrous oxide (N2O) from soils. Little is known about how the fluxes of these three greenhouse gases, from managed and natural grasslands worldwide, have contributed to past climate change, or the roles of managed pastures versus natural grasslands. Here, global trends and regional patterns of the full greenhouse gas balance of grasslands are estimated for the period 1750 to 2012. A new spatially explicit land surface model is applied, to separate the direct effects of human activities from land management and the indirect effects from climate change, increasing CO2 and regional changes in nitrogen deposition. Direct human management activities are simulated to have caused grasslands to switch from a sink to a source of greenhouse gas, because of increased livestock numbers and accelerated conversion of natural lands to pasture. However, climate change drivers contributed a net carbon sink in soil organic matter, mainly from the increased productivity of grasslands due to increased CO2 and nitrogen deposition. The net radiative forcing of all grasslands is currently close to neutral, but has been increasing since the 1960s. Here, we show that the net global climate warming caused by managed grassland cancels the net climate cooling from carbon sinks in sparsely grazed and natural grasslands. In the face of future climate change and increased demand for livestock products, these findings highlight the need to use sustainable management to preserve and enhance soil carbon storage in grasslands and to reduce greenhouse gas emissions from managed grasslands.