A viable remedy for overcoming resistance to anti-PD-1 immunotherapy: Fecal microbiota transplantation.

Anti-PD-1 immunotherapy is a cancer therapy that focuses explicitly on the PD-1 receptor found on the surface of immune cells. This targeted therapeutic strategy is specifically designed to amplify the immune system's innate capacity to detect and subsequently eliminate cells that have become cancerous. Nevertheless, it should be noted that not all patients exhibit a favourable response to this particular therapeutic modality, necessitating the exploration of novel strategies to augment the effectiveness of immunotherapy. Previous studies have shown that fecal microbiota transplantation (FMT) can enhance the efficacy of anti-PD-1 immunotherapy in advanced melanoma patients. To investigate this intriguing possibility further, we turned to PubMed and conducted a comprehensive search for studies that analyzed the interplay between FMT and anti-PD-1 therapy in the context of tumor treatment. Our search criteria were centred around two key phrases: "fecal microbiota transplantation" and "anti-PD-1 therapy." The studies we uncovered all echo a similar sentiment. They pointed towards the potential of FMT to improve the effectiveness of immunotherapy. FMT may enhance the effectiveness of immunotherapy by altering the gut microbiota and boosting the patient's immunological response. Although promising, additional investigation is needed to improve the efficacy of FMT in the context of cancer therapy and attain a comprehensive understanding of the possible advantages and drawbacks associated with this therapeutic strategy.

Take the bull by the horns and tackle the potential downsides of the ketogenic diet.

The ketogenic diet (KD) is a distinctive dietary regimen known for its low-carbohydrate and high-fat composition. Recently, it has garnered considerable interest from the scientific community and the general population because of its claimed efficacy in facilitating weight reduction, improving the management of glucose levels, and raising overall energy levels. The core principle of the KD is the substantial decrease in carbohydrate consumption, which is subsequently substituted by ingesting nourishing fats. While the KD has promising advantages and is gaining popularity, it must be acknowledged that this dietary method may not be appropriate for all individuals. The dietary regimen may give rise to adverse effects, including constipation, halitosis, and imbalances in electrolyte levels, which may pose a potential risk if not adequately supervised. Hence, thorough and meticulous inquiry is needed to better comprehend the possible hazards and advantages linked to the KD over prolonged durations. By obtaining a more comprehensive perspective, we can enhance our ability to make well-informed judgments and suggestions as to implementation of this specific dietary regimen.

Plant-derived nanovesicles offer a promising avenue for anti-aging interventions.

Over the past few years, the study of plant-derived nanovesicles (PDNVs) has emerged as a hot topic of discussion and research in the scientific community. This remarkable interest stems from their potential role in facilitating intercellular communication and their unique ability to deliver biologically active components, including proteins, lipids, and miRNAs, to recipient cells. This fascinating ability to act as a molecular courier has opened up an entirely new dimension in our understanding of plant biology. The field of research focusing on the potential applications of PDNVs is still in its nascent stages. However, it has already started gaining traction due to the growing interest in its possible use in various branches of biotechnology and medicine. Their unique properties and versatile applications offer promising future research and development prospects in these fields. Despite the significant progress in our understanding, many unanswered questions and mysteries surround the mechanisms by which PDNVs function and their potential applications. There is a dire need for further extensive research to elucidate these mechanisms and explore the full potential of these fascinating vesicles. As the technology at our disposal advances and our understanding of PDNVs deepens, it is beyond doubt that PDNVs will continue to be a subject of intense research in anti-aging therapeutics. This comprehensive review is designed to delve into the fascinating and multifaceted world of PDNV-based research, particularly focusing on how these nanovesicles can be applied to anti-aging therapeutics.

Vaginal microbiota transplantation is a truly opulent and promising edge: fully grasp its potential.

Vaginal microbiota transplantation (VMT) is a cutting-edge treatment modality that has the potential to revolutionize the management of vaginal disorders. The human vagina is a complex and dynamic ecosystem home to a diverse community of microorganisms. These microorganisms play a crucial role in maintaining the health and well-being of the female reproductive system. However, when the balance of this ecosystem is disrupted, it can lead to the development of various vaginal disorders. Conventional treatments, such as antibiotics and antifungal medications, can temporarily relieve the symptoms of vaginal disorders. However, they often fail to address the underlying cause of the problem, which is the disruption of the vaginal microbiota. In recent years, VMT has emerged as a promising therapeutic approach that aims to restore the balance of the vaginal ecosystem. Several studies have demonstrated the safety and efficacy of VMT in treating bacterial vaginosis, recurrent yeast infections, and other vaginal conditions. The procedure has also shown promising results in reducing the risk of sexually transmitted infections and preterm birth in pregnant women. However, more research is needed to establish optimal donor selection, preparation, and screening protocols, as well as long-term safety and efficacy. VMT offers a safe, effective, and minimally invasive treatment option for women with persistent vaginal problems. It could improve the quality of life for millions of women worldwide and become a standard treatment option shortly. With further research and development, it could potentially treat a wide range of other health problems beyond the scope of vaginal disorders.

High resolution spatiotemporal modeling of long term anthropogenic nutrient discharge in China.

High-resolution integration of large-scale and long-term anthropogenic nutrient discharge data is crucial for understanding the spatiotemporal evolution of pollution and identifying intervention points for pollution mitigation. Here, we establish the MEANS-ST1.0 dataset, which has a high spatiotemporal resolution and encompasses anthropogenic nutrient discharge data collected in China from 1980 to 2020. The dataset includes five components, namely, urban residential, rural residential, industrial, crop farming, and livestock farming, with a spatial resolution of 1 km and a temporal resolution of monthly. The data are available in three formats, namely, GeoTIFF, NetCDF and Excel, catering to GIS users, researchers and policymakers in various application scenarios, such as visualization and modelling. Additionally, rigorous quality control was performed on the dataset, and its reliability was confirmed through cross-scale validation and literature comparisons at the national and regional levels. These data offer valuable insights for further modelling the interactions between humans and the environment and the construction of a digital Earth.

Harnessing the power of goat milk-derived extracellular vesicles for medical breakthroughs: A review.

Research into goat milk-derived extracellular vesicles (GMVs) has grown in popularity in recent years owing to their potential uses in several sectors, including medicine. GMVs are tiny, lipid-bound structures that cells secrete and use to transport bioactive substances like proteins, lipids, and nucleic acids. They may be extracted from different body fluids, including blood, urine, and milk, and have been found to play crucial roles in cell-to-cell communication. GMVs are a promising field of study with applications in preventing and treating various disorders. Their immune-modulating properties, for instance, have been investigated, and they have shown promise in treating autoimmune illnesses and cancer. They may be loaded with therapeutic compounds and directed to particular cells or tissues, but they have also been studied for their potential use as drug-delivery vehicles. Goat milk extracellular vesicles are an intriguing study topic with many possible benefits. Although more study is required to thoroughly understand their functioning and prospective applications, they provide a promising path for creating novel medical treatments and technology.

Decoding China's anthropogenic typical pollutant discharge patterns: Long-term dynamics and hotspot transitions driven by population, diet, and sanitation.

Human activities have led to an alarming increase in pollution, resulting in widespread water contamination. A comprehensive understanding of the quantitative relationship between anthropogenic pollutant discharges and the escalating anthropogenic disturbances and environmental efforts is crucial for effective water quality management. Here we establish a Model for Estimating Anthropogenic pollutaNts diScharges (MEANS) and simulate the long-term dynamics of various types of anthropogenic discharges in China based on an unprecedented spatio-temporal dynamic parameter dataset. Our findings reveal that from 1980 to 2020, anthropogenic discharges exhibited an overall trend of initially increasing and subsequently decreasing, with the peak occurring around 2005. During this period, the dominant pollution sources in China shifted from urban to rural areas, thereby driving the transition of hotspot pollutants from nitrogen to phosphorus in the eastern regions. The most significant drivers of anthropogenic pollutant discharges gradually shifted from population size and dietary structure to wastewater treatment and agricultural factors. Furthermore, we observed that a significant portion of China's regions still exceed the safety thresholds for pollutant discharges, with excessive levels of total phosphorus (TP) being particularly severe. These findings highlight the need for flexible management strategies in the future to address specific pollution levels and hotspots in different regions. Our study underscores the importance of considering the complex interplay between anthropogenic disturbances, environmental efforts, and long-term anthropogenic pollutant discharges for effective water pollution control.

Mycorrhizal symbioses in the Andean paramo.

The Andean paramo, hereafter "paramo", is a Neotropical high-mountain region between the treeline and permanent snowline (3500-4800 m) and is considered the world's coolest biodiversity hotspot. Because of paramo's high humidity, solar radiation and temperature variation, mycorrhizal symbiosis is expected to be essential for plants. Existing theory suggests that replacement of arbuscular mycorrhizal (AM) by ectomycorrhizal (ECM) and then ericoid mycorrhizal plants (ERM) can be expected with increasing elevation. Previous findings also suggest that non-(NM) and facultatively mycorrhizal (FM) species predominate over obligatory mycorrhizal (OM) species at high elevations. However, these expectations have never been tested outside of the northern temperate zone. We addressed the distribution and environmental drivers of plant mycorrhizal types (AM, ECM and ERM) and statuses (NM, FM and OM) along the paramo's elevational gradient. We used vegetation plots from the VegParamo database, climatic and edaphic data from online repositories, and up-to-date observation information about plant mycorrhizal traits at species and genus level, the latter being proposed as hypotheses. AM plants were dominant along the entire gradient, and ERM plants were most abundant at the lowest elevations (2500-3000 m). The share of FM plants increased and that of OM plants decreased with elevation, while NM plants increased above 4000 m. Temperature and soil pH were positively related to the abundance of AM plants and negatively to ERM plants. Our results reveal patterns that contrast with those observed in temperate northern-hemisphere ecosystems.

Estimating Yangtze River basin's riverine N2O emissions through hybrid modeling of land-river-atmosphere nitrogen flows.

Riverine ecosystems are a significant source of nitrous oxide (N2O) worldwide, but how they respond to human and natural changes remains unknown. In this study, we developed a compound model chain that integrates mechanism-based modeling and machine learning to understand N2O transfer patterns within land, rivers, and the atmosphere. The findings reveal a decrease in N2O emissions in the Yangtze River basin from 4.7 Gg yr-1 in 2000 to 2.8 Gg yr-1 in 2019, with riverine emissions accounting for 0.28% of anthropogenic nitrogen discharges from land. This unexpected reduction is primarily attributed to improved water quality from human-driven nitrogen control, while natural factors contributed to a 0.23 Gg yr-1 increase. Notably, urban rivers exhibited a more rapid N2O efflux ( [Formula: see text] ), with upstream levels nearly 3.1 times higher than rural areas. We also observed nonlinear increases in [Formula: see text] with nitrogen discharge intensity, with urban areas showing a gradual and broader range of increase compared to rural areas, which exhibited a sharper but narrower increase. These nonlinearities imply that nitrogen control measures in urban areas lead to stable reductions in N2O emissions, while rural areas require innovative nitrogen source management solutions for greater benefits. Our assessment offers fresh insights into interpreting riverine N2O emissions and the potential for driving regionally differentiated emission reductions.

Methionine enkephalin inhibited cervical cancer migration as well as invasion and activated CD11b+ NCR1+ NKs of tumor microenvironment.

This study was to study the role of methionine enkephalin (menk) in cell invasion and migration as well as NK cells activation of tumor microenvironment in cervical cancer. The results showed that menk inhibited cervical cancer migration and invasion. In addition, we found menk affected epithelial to mesenchymal transition (EMT) related indicators, with increasing E-cadherin level, decreasing N-cadherin and vimentin level. Through in vivo mouse model, we found that menk IFNγ and NKP46 expression was upregulated in tumor tissues by menk compared with controls, while LAG3 expression was inhibited by menk, besides, there was an upregulation of CD11b+ NCR1+ NKs of tumor microenvironment in cervical cancer. Therefore, we concluded that menk inhibited cancer migration and invasion via affecting EMT related indicators and activated CD11b+ NCR1+ NKs of tumor microenvironment in cervical cancer, laying a theoretical foundation for the further clinical treatment of menk.

Environmental modulation of plant mycorrhizal traits in the global flora.

Mycorrhizal symbioses are known to strongly influence plant performance, structure plant communities and shape ecosystem dynamics. Plant mycorrhizal traits, such as those characterising mycorrhizal type (arbuscular (AM), ecto-, ericoid or orchid mycorrhiza) and status (obligately (OM), facultatively (FM) or non-mycorrhizal) offer valuable insight into plant belowground functionality. Here, we compile available plant mycorrhizal trait information and global occurrence data ( ∼ 100 million records) for 11,770 vascular plant species. Using a plant phylogenetic mega-tree and high-resolution climatic and edaphic data layers, we assess phylogenetic and environmental correlates of plant mycorrhizal traits. We find that plant mycorrhizal type is more phylogenetically conserved than plant mycorrhizal status, while environmental variables (both climatic and edaphic; notably soil texture) explain more variation in mycorrhizal status, especially FM. The previously underestimated role of environmental conditions has far-reaching implications for our understanding of ecosystem functioning under changing climatic and soil conditions.

Sparganosis of a thoracic vertebra misdiagnosed as bone metastasis from lung cancer.

Sparganosis is a rare parasitic infection caused by plerocercoid tapeworm larvae. We described a case of a 27-year-old man presenting with numbness in both legs and masses in the right lung and spine, initially thought to have spinal metastasis from lung cancer. However, after pathological and parasitological examinations, the patient was found to have spinal sparganosis, likely due to a history of consuming raw frogs. The patient was successfully treated with praziquantel, resulting in the recovery of muscle strength in his legs. This case highlights the importance of considering spinal sparganosis as a differential diagnosis in patients with spinal masses, especially those with a history of consuming raw or undercooked frogs. Accurate diagnosis and early treatment are crucial for managing this infection.

Characterizing legacy nitrogen-induced time lags in riverine nitrogen reduction for the Songhuajiang River Basin: Source analysis, spatio-seasonal patterns, and impacts on future water quality improvement.

Legacy nitrogen (N) originating from net N inputs (NNI) may pose ongoing threats to riverine water quality worldwide and even cause serious time-lags between water quality restoration and NNI declines. A better understanding of legacy N effects on riverine N pollutions in different seasons is essential to improve riverine water quality. Here, we investigated contributions of legacy N on riverine dissolved inorganic N (DIN) changes in different seasons and quantified spatio-seasonal time-lags in the Songhuajiang River basin (SRB), a hotspot of NNI with four distinct seasons, by exploring long-term (1978-2020) NNI-DIN relationships. Results firstly showed a significant seasonal difference in NNI, with the highest value observed in spring (average, 2184.1 kg/km2), 1.2, 5.0, and 4.6 times higher than that in summer, autumn, and winter, respectively. Cumulative legacy N had dominated riverine DIN changes, with a relative contribution of approximately 64% in 2011-2020, causing time-lags of 11-29 years across the SRB. The longest seasonal lags existed in spring (average, 23 years) owing to greater impacts of legacy N to riverine DIN changes in this season. Mulch film application, soil organic matter accumulation, N inputs, and snow cover were identified as the key factors that strengthened seasonal time-lags by collaboratively enhancing legacy N retentions in soils. Furthermore, a machine learning-based model system suggested that timescales for water quality improvement (DIN, ≤1.5 mg/L) varied considerably (from 0 to >29 years, Improved N Management-Combined scenario) across the SRB, with greater lag effects contributing to slower recovery. These findings can provide a more comprehensive insight into sustainable basin N management in the future.

Distinctive roles of L-type calcium channels subtypes within the dorsal hippocampus in formation of morphine withdrawal-induced aversion in rats.

Although the negative effects coming along with opiate withdrawal are in part modulated by L-type calcium channels (LTCCs), the distinctive physiological properties and functions of LTCCs subtypes suggest differential roles of subtypes during withdrawal. The present study aimed to examine the contributions of LTCC subtypes, Cav1.2 and Cav1.3, within the dorsal hippocampus (DH) in naloxone-precipitated morphine withdrawal using the conditioned place aversion (CPA) paradigm. Firstly, we injected the non-specific LTCCs antagonist verapamil into the DH of morphine-dependent rats before conditioning an environment with naloxone-precipitated withdrawal. Our results showed that verapamil blocked the acquisition of CPA. Then, to explore the molecular mechanisms of LTCCs subtypes during withdrawal, we measured the protein expression of Cav1.2 and Cav1.3 in morphine-dependent rats under different conditions. In morphine-dependent rats, conditioning with withdrawal increased Cav1.2 expression in the membrane, while only acute naloxone injection increased the membrane expression of Cav1.3. To further determine the causal roles of LTCCs subtypes in the withdrawal process, we used Cav1.2 siRNA or Cav1.3 shRNA to knock down the expression of subtypes and detected the effects on CPA and somatic withdrawal signs in morphine-dependent rats. Cav1.2 siRNA, but not Cav1.3 shRNA, inhibited the acquirement of CPA and relieved somatic withdrawal symptoms. Together, our findings reveal that Cav1.2, but not Cav1.3 plays an important role in mediating morphine withdrawal, suggesting this subtype may serve as a potential therapeutic target for the treatment of negative effects in opiate dependence.

Hopf Bifurcations of Moore-Greitzer PDE Model with Additive Noise.

The Moore-Greitzer partial differential equation (PDE) is a commonly used mathematical model for capturing flow and pressure changes in axial-flow jet engine compressors. Determined by compressor geometry, the deterministic model is characterized by three types of Hopf bifurcations as the throttle coefficient decreases, namely surge (mean flow oscillations), stall (inlet flow disturbances) or a combination of both. Instabilities place fundamental limits on jet-engine operating range and thus limit the design space. In contrast to the deterministic PDEs, the Hopf bifurcation in stochastic PDEs is not well understood. The goal of this particular work is to rigorously develop low-dimensional approximations using a multiscale analysis approach near the deterministic stall bifurcation points in the presence of additive noise acting on the fast modes. We also show that the reduced-dimensional approximations (SDEs) contain multiplicative noise. Instability margins in the presence of uncertainties can be thus approximated, which will eventually lead to lighter and more efficient jet engine design.

Fecal microbiota transplantation holds the secret to youth.

Aging shows itself not just at the cellular level, with shortened telomeres and cell cycle arrest, but also at the organ and organismal level, with diminished brainpower, dry eyes, intestinal inflammation, muscular atrophy, wrinkles, etc. When the gut microbiota, often called the "virtual organ of the host," fails to function normally, it can lead to a cascade of health problems including, but not limited to, inflammatory bowel disease, obesity, metabolic liver disease, type II diabetes, cardiovascular disease, cancer, and even neurological disorders. An effective strategy for restoring healthy gut bacteria is fecal microbiota transplantation (FMT). It can reverse the effects of aging on the digestive system, the brain, and the vision by transplanting the functional bacteria found in the excrement of healthy individuals into the gut tracts of patients. This paves the way for future research into using the microbiome as a therapeutic target for disorders associated with aging.

Unexpected worsening of doxorubicin cardiotoxicity upon intermittent fasting.

Recently in Cell Metabolism, Ozcan et al. used preclinical and clinical data to suggest that alternate-day fasting may exacerbate the cardiotoxic effects of doxorubicin through the TFEB/GDF15 pathway, leading to myocardial atrophy and impaired cardiac function. The link between caloric intake, chemotherapy-induced cachexia, and cardiotoxicity warrants more clinical attention.

Bacteria associated with glioma: a next wave in cancer treatment.

Malignant gliomas occur more often in adults and may affect any part of the central nervous system (CNS). Although their results could be better, surgical excision, postoperative radiation and chemotherapy, and electric field therapy are today's mainstays of glioma care. However, bacteria can also exert anti-tumor effects via mechanisms such as immune regulation and bacterial toxins to promote apoptosis, inhibit angiogenesis, and rely on their natural characteristics to target the tumor microenvironment of hypoxia, low pH, high permeability, and immunosuppression. Tumor-targeted bacteria expressing anticancer medications will go to the cancer site, colonize the tumor, and then produce the therapeutic chemicals that kill the cancer cells. Targeting bacteria in cancer treatment has promising prospects. Rapid advances have been made in the study of bacterial treatment of tumors, including using bacterial outer membrane vesicles to load chemotherapy drugs or combine with nanomaterials to fight tumors, as well as the emergence of bacteria combined with chemotherapy, radiotherapy, and photothermal/photodynamic therapy. In this study, we look back at the previous years of research on bacteria-mediated glioma treatment and move forward to where we think it is headed.