High Sensitivity and High Throughput Magnetic Flow CMOS Cytometers with 2D Oscillator Array and Inter-Sensor Spectrogram Cross-correlation.

In the paper, we present an integrated flow cytometer with a 2D array of magnetic sensors based on dual-frequency oscillators in a 65-nm CMOS process, with the chip packaged with microfluidic controls. The sensor architecture and the presented array signal processing allows uninhibited flow of the sample for high throughput without the need for hydrodynamic focusing to a single sensor. To overcome the challenge of sensitivity and specificity that comes as a trade off with high throughout, we perform two levels of signal processing. First, utilizing the fact that a magnetically tagged cell is expected to excite sequentially an array of sensors in a time-delayed fashion, we perform inter-site cross-correlation of the sensor spectrograms that allows us to suppress the probability of false detection drastically, allowing theoretical sensitivity reaching towards sub-ppM levels that is needed for rare cell or circulating tumor cell detection. In addition, we implement two distinct methods to suppress correlated low frequency drifts of singular sensors-one with an on-chip sensor reference and one that utilizes the frequency dependence of the susceptibility of super-paramagnetic magnetic beads that we deploy as tags. We demonstrate these techniques on a 7×7 sensor array in 65 nm CMOS technology packaged with microfluidics with magnetically tagged dielectric particles and cultu lymphoma cancer cells.

Effect of cornstalk biochar on phytoremediation of Pb-contaminated soil by females and males of Populus deltoides (Salicaceae).

Soil pollution with lead (Pb) has become a serious global concern, adversely affecting the forest ecosystem. This study was conducted to investigate the effects of corn straw on the remediation efficiency of Pb-contaminated soil using Populus deltoides. Female and male P. deltoides cuttings were subjected to soil spiked with 900 mg kg-1 Pb and amended with 5% (v/v) corn straw biochar for 90 days. Under Pb stress, the addition of biochar significantly increased the total biomass accumulation by 29% in females and 26% in males. However, without the addition of biochar, the biomass accumulation was significantly reduced by 11% in females and 3% in males under Pb stress. Females showed a higher uptake and accumulation of Pb in roots and leaves, while males accumulated more Pb in roots and stems and exhibited an increased anti-oxidative capacity. Biochar addition alleviated Pb toxicity in both male and female P. deltoides by immobilizing Pb ion in the soil, reducing Pb uptake and translocation, promoting nutrient uptake, and improving the diversity and stability of the soil bacteria community. Under Pb stress, the relative abundances of metal-resistance bacteria significantly increased, such as the abundance of Bacteroidetes in females and the abundances of Actinobacteria, Firmicutes, and Planctomycetes in males. In brief, the males under biochar addition exhibited promising potential as candidates for phytoremediation of Pb-contaminated soil. This study provides new insights into mechanisms underlying sexually differential responses to Pb stress in the presence of biochar amendment.

Tandem Ene/[4 + 2] Cycloaddition Reaction for the Synthesis of 9-Benzylphenanthrenes from Arynes and α-(Bromomethyl)styrenes.

A tandem reaction for the synthesis of phenanthrenes from arynes and α-(bromomethyl)styrenes is reported. The transformation proceeds via an ene reaction of α-(bromomethyl)styrenes with arynes, followed by a [4 + 2] cycloaddition reaction. The reaction generates 9-benzylphenanthrene derivatives in moderate to excellent yields.

Diversity and co-occurrence networks of bacterial and fungal communities on two typical debris-covered glaciers, southeastern Tibetan Plateau.

Debris-covered glaciers (DCGs) are globally distributed and thought to contain greater microbial diversity than clean surface continental glaciers, but the ecological characteristics of microbial communities on the surface of DCGs have remained underexplored. Here, we investigated bacterial and fungal diversity and co-occurrence networks on the supraglacial debris habitat of two DCGs (Hailuogou and Dagongba Glaciers) in the southeastern Tibetan Plateau. We found that the supraglacial debris harbored abundant microbes with Proteobacteria occupying more than half (51.5%) of the total bacteria operational taxonomic units. The composition, diversity, and co-occurrence networks of both bacterial and fungal communities in the debris were significantly different between Hailuogou Glacier and Dagongba Glacier even though the glaciers are geographically adjacent within the same mountain range. Bacteria were more diverse in the debris of the Dagongba Glacier, where a lower surface velocity and thicker debris layer allowed the supraglacial debris to continuously weather and accumulate nutrients. Fungi were more diverse in the debris of the Hailuogou Glacier, which experiences a wetter monsoonal climate, is richer in calcium, has greater debris instability, and greater ice velocity than the Dagongba Glacier. These factors may provide ideal conditions for the dispersal and propagation of fungi spores on the Hailuogou Glacier. In addition, we found an obvious gradient of bacterial diversity along the supraglacial debris transect on the Hailuogou Glacier. Bacterial diversity was lower where debris cover was thin and scattered and became more diverse near the glacial terminus in thick, slow-moving debris. No such increasing bacterial pattern was detected on the Dagongba Glacier, which implies a positive relationship of debris age, thickness, and weathering on bacterial diversity. Additionally, a highly connected bacterial co-occurrence network with low modularity was found in the debris of the Hailuogou Glacier. In contrast, debris from the Dagongba Glacier exhibited less connected but more modularized co-occurrence networks of both bacterial and fungal communities. These findings indicate that less disturbed supraglacial debris conditions are crucial for microbes to form stable communities on DCGs.

Insights into direct reduction iron using bamboo biomass as a green and renewable reducer: Reduction behavior study and kinetics analysis.

Biochar is a renewable, carbon-neutral energy source that can replace traditional fossil fuels for iron and steel production, so it is of great significance to reduce carbon emissions and reduce pollution. In this paper, the reaction characteristics and kinetics between biomass (bamboo powder) pyrolysis gas, biochar, and iron ore powder are studied by a thermogravimetric analyzer (TG). Comparing the samples with four different C/O ratios (C/O = 0.375, 0.5, 1, 3), it is found that the sample with C/O = 1 can completely reduce hematite. The mass loss process is divided into the following four stages: de-crystal water, hematite to magnetite, magnetite to wustite, and wustite to metallic iron. Among them, the latter three stages are following the kinetic model of random nucleation (n = 1, 2) and three-dimensional diffusion, and the activation energy of the three stages increases and then decreases. Through scanning electron microscopy (SEM), the surface of hematite particles changed from relatively flat to porous and finally the reduced metal iron aggregated, and connected into large pieces. By using online Thermogravimetry-Fourier Transform Infrared Reflection (TG-FTIR), when the reduction temperature is lower than 700 °C, biochar plays a leading role. On the contrary, the CO produced by biochar gasification plays a leading role.

AN0025, a novel antagonist of PGE2-receptor E-type 4 (EP4), in combination with total neoadjuvant treatment of advanced rectal cancer.

PURPOSE: To assess the safety and efficacy of AN0025 in combination with preoperative radiotherapy and chemotherapy in either short course (SCRT) or long course radiotherapy (LCRT) settings for those with locally advanced rectal cancer. PATIENTS AND METHODS: Twenty-eight subjects with locally advanced rectal cancer participated in this multicenter, open-label, Phase Ib trial. Enrolled subjects received either 250 mg or 500 mg of AN0025 once daily for 10 weeks with either LCRT or SCRT with chemotherapy (7 subjects/group). Participants were assessed for safety/efficacy starting from the first dose of study drug administration and were followed for 2 years. RESULTS: No treatment-emergent adverse or serious adverse events meeting dose-limiting criteria were observed, with only 3 subjects discontinuing AN0025 treatment due to adverse events. Twenty-five of 28 subjects completed 10 weeks of AN0025 and adjuvant therapy and were evaluated for efficacy. Overall, 36.0% of subjects (9/25 subjects) achieved a pathological complete response or a complete clinical response, including 26.7% of subjects (4/15 subjects who underwent surgery) who achieved a pathological complete response. A total of 65.4% of subjects had magnetic resonance imaging-confirmed down-staging ≤ stage 3 following completion of treatment. With a median follow-up of 30 months. The 12-month disease-free survival and overall survival were 77.5% (95% confidence interval [CI]: 56.6, 89.2) and 96.3% (95% CI: 76.5, 99.5), respectively. CONCLUSIONS: Treatment with AN0025 administered for 10 weeks along with preoperative SCRT or LCRT did not appear to worsen the toxicity in subjects with locally advanced rectal cancer, was well-tolerated and showed promise in inducing both a pathological and complete clinical response. These findings suggest its activity deserves further investigation in larger clinical trials.

Responses of soil bacterial communities to precipitation change in the semi-arid alpine grassland of Northern Tibet.

A change in precipitation can profoundly change the structure of soil microbial communities, especially in arid and semi-arid areas which are limited by moisture conditions. Therefore, it is crucial to explore how soil bacterial community composition and diversity will respond to variation in precipitation. Here we conducted a precipitation control experiment to simulate precipitation change by reducing and increasing rainfall by 25%, 50%, and 75% in the alpine grasslands of northern Tibet. The composition, diversity, and species interaction network of soil microbial community were studied by high-throughput sequencing, and the relationship between microbial community species and soil environmental factors was analyzed. Our results showed that Proteobacteria (45%-52%) and Actinobacteria (37%-45%) were the dominant bacteria in the soil. The alpha diversity index based on Shannon, Chao1, and Simpson indices revealed that precipitation change had no significant effect on richness and evenness of soil microbial communities. Non-metric multidimensional scaling (NMDS) and analysis of similarities (ANOSIM) showed that a clear separation of soil microbial communities between D2(-50%),D3(-75%) and W2(+50%), W3(+75%) treatments. The microbial interaction network indicated that the water-increasing treatment group had closer connections, and Proteobacteria and Actinomycetes were the core species. Furthermore, there was a stronger positive correlation between species in the water-reducing treatment group, the contribution of Proteobacteria decreased significantly, the role of connecting hub decreased, and Actinomycetes became the most important core microbial species. In addition, soil water content (SWC) and available phosphorus (AP) were closely related to the variations in soil microbial compositions. The findings of this study provide a theoretical basis for the driving mechanism of global climate change on soil microbial community and grassland ecosystem in alpine grassland.

Rhizosphere soil microbial community and its response to different utilization patterns in the semi-arid alpine grassland of northern Tibet.

As the link between plants and soils, rhizosphere soil microorganisms play an important role in the element cycle. This study aimed to understand the response of the rhizosphere soil microbial community structure and interaction network to grassland utilization in the alpine steppe of the northern Tibet Plateau. High-throughput sequencing was employed to study the composition, diversity, and species interaction network of rhizosphere soil microbial communities under grazing, mowing, and enclosing treatments. Proteobacteria (47.19%) and Actinobacteria (42.20%) were the dominant bacteria in the rhizosphere soil. There was no significant difference in relative abundance among rhizosphere soil microorganisms at phylum and genus levels, but differences were found in Chlorobi, Ignavibacteriae, and Micromonospora. The alpha diversity index based on Shannon, Chao1, and Simpson indices revealed that except for a significant difference in the Shannon index of the Artemisia nanschanica group, the richness and evenness of rhizosphere soil microbial communities among all groups were similar. Non-metric multidimensional scaling (NMDS) and multi-response permutation procedure (MRPP) analyses showed that the inter-group differences of three plants (Stipa purpurea, Carex moorcroftii, and Artemisia nanschanica) were greater than the differences within the groups; however, only the inter-group difference with the Stipa purpurea group was significant. The microbial interaction network showed that the network complexity of the Artemisia nanschanica group and the enclosing treatment, which were not easily influenced by external factors, were higher than those of the other groups and treatments; this again demonstrated that Proteobacteria and Actinobacteria were the network core microbial species in alpine steppe of the northern Tibet Plateau and were crucial for maintaining stability of the microbial communities. Findings from this study provide a theoretical basis for the restoration of degraded alpine grassland and the development of microbial functions.

Origami Microwave Imaging Array: Metasurface Tiles on a Shape-Morphing Surface for Reconfigurable Computational Imaging.

Origami is the art of paper folding that allows a single flat piece of paper to assume different 3D shapes depending on the fold patterns and the sequence of folding. Using the principles of origami along with computation imaging technique the authors demonstrate a versatile shape-morphing microwave imaging array with reconfigurable field-of-view and scene-adaptive imaging capability. Microwave/millimeter-wave based array imaging systems are expected to be the workhorse for sensory perception of future autonomous intelligent systems. The imaging capability of a planar array-based systems operating in complex scattering conditions have limited field-of-view and lack the ability to adaptively reconfigure resolution. To overcome this, here, deviations from planarity and isometry are allowed, and a shape-morphing computational imaging system is demonstrated. Implemented on a reconfigurable Waterbomb origami surface with 22 active metasurface panels that radiate near-orthogonal modes across 17-27 GHz, capability to image complex 3D objects in full details minimizing the effects of specular reflections in diffraction-limited sparse imaging with scene adaptability, reconfigurable cross-range resolution, and field-of-view is demonstrated. Such electromagnetic origami surfaces, through simultaneous surface shape-morphing ability (potentially with shape-shifting electronic materials) and electromagnetic field programmability, opens up new avenues for intelligent and robust sensing and imaging systems for a wide range of applications.

3-Hydroxyacyl-CoA dehydratase 2 deficiency confers resistance to diet-induced obesity and glucose intolerance.

Obesity and associated complications are becoming a pandemic. Inhibiting fatty acid synthesis and elongation is an important intervention for the treatment of obesity. Despite intensive investigations, many potential therapeutic targets have yet to be discovered. In this study, decreased expression of Hacd2 (a newly found enzyme in fatty acid elongation) was found in HFD induced mice and loss of Hacd2 expression in the liver protected mice against HFD induced obesity as well as associated fatty liver disease and diabetes. Additionally, further study indicated that hepatic HACD2 deficiency increased energy expenditure by upregulating the transcription of thermogenic programming genes. Our results suggest that HACD2 may be a promising therapeutic target for the management of obesity and associated metabolic diseases.

Response of net reduction rate in vegetation carbon uptake to climate change across a unique gradient zone on the Tibetan Plateau.

The Tibetan Plateau (TP) has a variety of vegetation types that range from alpine tundra to tropic evergreen forest, which play an important role in the global carbon (C) cycle and is extremely vulnerable to climate change. The vegetation C uptake is crucial to the ecosystem C sequestration. Moreover, net reduction in vegetation C uptake (NRVCU) will strongly affect the C balance of terrestrial ecosystem. Until now, there is limited knowledge on the recovery process of vegetation net C uptake and the spatial-temporal patterns of NRVCU after the disturbance that caused by climate change and human activities. Here, we used the MODIS-derived net primary production to characterize the spatial-temporal patterns of NRVCU. We further explored the influence factors of the net reduction rate in vegetation C uptake (NRRVCU) and recovery processes of vegetation net C uptake across a unique gradient zone on the TP. Results showed that the total net reduction amount of vegetation C uptake gradually decreased from 2000 to 2015 on the TP (Slope = -0.002, P < 0.05). Specifically, an increasing gradient zone of multi-year average of net reduction rate in vegetation carbon uptake (MYANRRVCU) from east to west was observed. In addition, we found that the recovery of vegetation net C uptake after the disturbance caused by climate change and anthropogenic disturbance in the gradient zone were primarily dominated by precipitation and temperature. The findings revealed that the effects of climate change on MYANRRVCU and vegetation net C uptake recovery differed significantly across geographical space and vegetation types. Our results highlight that the biogeographic characteristics of the TP should be considered for combating future climate change.

Distinguishing Stoichiometric Homeostasis of Soil Microbial Biomass in Alpine Grassland Ecosystems: Evidence From 5,000 km Belt Transect Across Qinghai-Tibet Plateau.

The biogeographic characteristics of soil microbial biomass stoichiometry homeostasis and also its mechanisms are commonly thought to be key factors for the survival strategies and resource utilization of soil microbes under extreme habitat. In this work, we conducted a 5,000-km transect filed survey in alpine grassland across Qinghai-Tibet Plateau in 2015 to measure soil microbial biomass carbon (MBC) and nitrogen (MBN) across alpine steppe and meadow. Based on the differences of climate and soil conditions between alpine steppe and meadow, the variation coefficient was calculated to investigate the homeostatic degree of MBC to MBN. Furthermore, the "trade-off" model was utilized to deeply distinguish the homeostasis degree of MBC/MBN between alpine steppe and meadow, and the regression analysis was used to explore the variability of trade-off in response to environmental factors in the alpine grassland. The results showed that the coefficient of variation (CV) of MBC/MBN in alpine meadow (CV = 0.4) was lower than alpine steppe (CV = 0.7). According to the trade-off model, microbial turnover activity of soil N relative to soil C increased rapidly and then decreased slightly with soil organic carbon (SOC), soil total nitrogen (STN), and soil water content across alpine meadow. Nevertheless, in alpine steppe, SOC/STN had a positive effect on microbial turnover of soil N. These results suggested that water, heat, and soil nutrients availability were the key factors affecting the C:N stoichiometry homeostasis of soil microbial biomass in Qinghai-Tibet Plateau (QTP)'s alpine grassland. Since the difference of survival strategy of the trade-off demands between soil C and N resulting in different patterns and mechanism, the stoichiometry homeostasis of soil microbial biomass was more stable in alpine meadow than in alpine steppe.

Plants and Microbes Mediate the Shift in Ecosystem Multifunctionality From Low to High Patterns Across Alpine Grasslands on the Tibetan Plateau.

Both plant communities and soil microbes have been reported to be correlated with ecosystem multifunctionality (EMF) in terrestrial ecosystems. However, the process and mechanism of aboveground and belowground communities on different EMF patterns are not clear. In order to explore different response patterns and mechanisms of EMF, we divided EMF into low (<0) and high patterns (>0). We found that there were contrasting patterns of low and high EMF in the alpine grassland ecosystem on the Tibetan Plateau. Specifically, compared with low EMF, environmental factors showed higher sensitivity to high EMF. Soil properties are critical factors that mediate the impact of community functions on low EMF based on the change of partial correlation coefficients from 0 to 0.24. In addition, plant community functions and microbial biomass may mediate the shift of EMF from low to high patterns through the driving role of climate across the alpine grassland ecosystem. Our findings will be vital to clarify the mechanism for the stability properties of grassland communities and ecosystems under ongoing and future climate change.

Cholesteryl Ester Promotes Mammary Tumor Growth in MMTV-PyMT Mice and Activates Akt-mTOR Pathway in Tumor Cells.

The association between intratumoral cholesteryl ester (CE) and tumor progression has been reported previously. The objective of our study was to investigate a causal effect of CE on mammary tumor progression. Using MMTV-PyMT (MMTV-polyoma virus middle T) transgenic mice and breast tumor cell MCF-7, we show that both exogenous and endogenous CE can increase mammary tumor growth, that CE upregulates the AKT/mTOR pathway, and that CE synthesis blockade suppresses this signaling pathway. Our data suggest that SOAT1, a sterol O-acyltransferase, may be a potential target for the treatment of breast cancer.

Five-year study on the effects of warming and plant litter quality on litter decomposition rate in a Tibetan alpine grassland.

The decomposition of plant litter is a key link in global C budgets and provides strong feedback to changes in climate and biogeochemical cycles. However, the combined effects of global warming and plant litter quality on the rate of plant litter decomposition and nutrient dynamics in alpine ecosystems are still poorly understood. We conducted a warming experiment to investigate the effects of litter quality and temperature on decomposition rates and variations in nutrients of four common herbaceous plants (low-quality litter species Stipa purpurea and Carex moorcroftii and high-quality litter species Astragalus confertus and Leontopodium nanum) during 2011-2016. During the initial stages of decomposition, warming had no significant effect on the mass loss of plant litter for low-quality litter species, but in the later stages of decomposition, it had a negative effect on the mass loss across all species (P < 0.05). Litter quality was the best predictor of N and P release/immobilisation during the decomposition of aboveground plant litter. Low-quality litter had the highest immobilisation of N at about 80% of the initial remaining mass; nutrients were then released in the following stages of decomposition. However, the fraction of initial P decreased with the mass remaining during the initial and later phases of decomposition, but a short period of P immobilisation occurred in the middle phase of decomposition. For high-quality litter, the fraction of initial N and P decreased with the mass remaining during the whole decomposition process. Warming had a marginal influence on the N and P dynamics throughout the decomposition process. Our study showed that the decay of plant litter was strongly suppressed by warming climate and that the N and P dynamics on the investigated Tibetan grassland were mainly regulated by litter quality, providing valuable insights into the biogeochemical cycles of nutrients in alpine ecosystems.

Breast cancer induces systemic immune changes on cytokine signaling in peripheral blood monocytes and lymphocytes.

BACKGROUND: It is increasingly recognized that cancer progression induces systemic immune changes in the host. Alterations in number and function of immune cells have been identified in cancer patients' peripheral blood and lymphoid organs. Recently, we found dysregulated cytokine signaling in peripheral blood T cells from breast cancer (BC) patients, even those with localized disease. METHODS: We used phosphoflow cytometry to determine the clinical significance of cytokine signaling responsiveness in peripheral blood monocytes from non-metastatic BC patients at diagnosis. We also examined the correlation between cytokine signaling in peripheral monocytes and the number of tumor-infiltrating macrophages in paired breast tumors. FINDINGS: Our results show that cytokine (IFNγ) signaling may also be dysregulated in peripheral blood monocytes at diagnosis, specifically in BC patients who later relapsed. Some patients exhibited concurrent cytokine signaling defects in monocytes and lymphocytes at diagnosis, which predict the risk of future relapse in two independent cohorts of BC patients. Moreover, IFNγ signaling negatively correlates with expression of CSF1R on monocytes, thus modulating their ability to infiltrate into tumors. INTERPRETATION: Our results demonstrate that tumor-induced systemic immune changes are evident in peripheral blood immune cells for both myeloid and lymphoid lineages, and point to cytokine signaling responsiveness as important biomarkers to evaluate the overall immune status of BC patients. FUNDING: This study was supported by the Department of Defense Breast Cancer Research Program (BCRP), The V Foundation, Stand Up to Cancer (SU2C), and Breast Cancer Research Foundation (BCRF).

First-in-Human Phase I Study to Evaluate the Brain-Penetrant PI3K/mTOR Inhibitor GDC-0084 in Patients with Progressive or Recurrent High-Grade Glioma.

PURPOSE: GDC-0084 is an oral, brain-penetrant small-molecule inhibitor of PI3K and mTOR. A first-in-human, phase I study was conducted in patients with recurrent high-grade glioma. PATIENTS AND METHODS: GDC-0084 was administered orally, once daily, to evaluate safety, pharmacokinetics (PK), and activity. Fluorodeoxyglucose-PET (FDG-PET) was performed to measure metabolic responses. RESULTS: Forty-seven heavily pretreated patients enrolled in eight cohorts (2-65 mg). Dose-limiting toxicities included 1 case of grade 2 bradycardia and grade 3 myocardial ischemia (15 mg), grade 3 stomatitis (45 mg), and 2 cases of grade 3 mucosal inflammation (65 mg); the MTD was 45 mg/day. GDC-0084 demonstrated linear and dose-proportional PK, with a half-life (∼19 hours) supportive of once-daily dosing. At 45 mg/day, steady-state concentrations exceeded preclinical target concentrations producing antitumor activity in xenograft models. FDG-PET in 7 of 27 patients (26%) showed metabolic partial response. At doses ≥45 mg/day, a trend toward decreased median standardized uptake value in normal brain was observed, suggesting central nervous system penetration of drug. In two resection specimens, GDC-0084 was detected at similar levels in tumor and brain tissue, with a brain tissue/tumor-to-plasma ratio of >1 and >0.5 for total and free drug, respectively. Best overall response was stable disease in 19 patients (40%) and progressive disease in 26 patients (55%); 2 patients (4%) were nonevaluable. CONCLUSIONS: GDC-0084 demonstrated classic PI3K/mTOR-inhibitor related toxicities. FDG-PET and concentration data from brain tumor tissue suggest that GDC-0084 crossed the blood-brain barrier.

Reconsidering the efficiency of grazing exclusion using fences on the Tibetan Plateau.

Grazing exclusion using fences is a key policy being applied by the Chinese government to rehabilitate degraded grasslands on the Tibetan Plateau (TP) and elsewhere. However, there is a limited understanding of the effects of grazing exclusion on alpine ecosystem functions and services and its impacts on herders' livelihoods. Our meta-analyses and questionnaire-based surveys revealed that grazing exclusion with fences was effective in promoting aboveground vegetation growth for up to four years in degraded alpine meadows and for up to eight years in the alpine steppes of the TP. Longer-term fencing did not bring any ecological and economic benefits. We also found that fencing hindered wildlife movement, increased grazing pressure in unfenced areas, lowered the satisfaction of herders, and rendered substantial financial costs to both regional and national governments. We recommend that traditional free grazing should be encouraged if applicable, short-term fencing (for 4-8 years) should be adopted in severely degraded grasslands, and fencing should be avoided in key wildlife habitat areas, especially the protected large mammal species.

Metabolic Alterations Induced by Kudingcha Lead to Cancer Cell Apoptosis and Metastasis Inhibition.

Kudingcha is implicated in alleviating metabolic disorders in traditional Chinese medicine. However, the role of Kudingcha, one of the Ligustrum robustum species, in metabolic regulations and its antitumor activity in triple-negative breast cancer (TNBC) remains to be determined. Two breast cancer cell lines and immunocompetent and immunodeficient mice were used to evaluate the therapeutic effects of Kudingcha treatment. The production of reactive oxygen species (ROS) and glucose uptake were examined by flow cytometry. Metabolic shift was examined by metabonomics and western blot analysis. In this study, we found that aqueous extract of Kudingcha dose dependently inhibited cell growth and induced apoptosis in vitro and in vivo. Moreover, Kudingcha supplementation significantly reduced cancer metastasis. Kudingcha significantly inhibited glycolysis and glutamine metabolism. In addition, we demonstrated that the antitumor effects of Kudingcha were dependent on ROS production, which was increased by ß-oxidation and oxidative phosphorylation. These findings provide a novel potential benefit of Kudingcha from targeting the cancer metabolism.