Electroacupuncture for mild-to-moderate dry eye: study protocol for a multicentre, randomised, single-blind, sham-controlled trial.

INTRODUCTION: Dry eye (DE) is a multifactorial ocular surface disease causing considerable medical, social and financial implications. Currently, there is no recognised long-term, effective treatment to alleviate DE. Clinical evidence shows that electroacupuncture (EA) can improve DE symptoms, tear secretion and tear film stability, but it remains controversial whether it is just a placebo effect. We aim to provide solid clinical evidence for the EA treatment of DE. METHODS AND ANALYSIS: This is a multicentre, randomised, sham-controlled trial. A total of 168 patients with DE will be enrolled and randomly assigned to EA or sham EA groups to receive 4-week consecutive treatments and follow-up for 24 weeks. The primary outcome is the change in the non-invasive tear break-up time (NIBUT) from baseline to week 4. The secondary outcomes include tear meniscus height, the Schirmer I test, corneal and conjunctival sensation, the ocular surface disease index, corneal fluorescein staining, the numerical rating scale and the Chinese DE-related quality of life scale. ETHICS AND DISSEMINATION: The trial protocol and informed consent were approved by the Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine (identifier: 2021-119), Shanghai Eye Disease Prevention and Treatment Center (identifier: 2022SQ003) and Eye and ENT Hospital of Fudan University (identifier: 2022014). TRIAL REGISTRATION NUMBER: NCT05552820.

Efficacy Comparison Between Toric Posterior Chamber Phakic IOL and Posterior Chamber Phakic IOL Plus Modified Steep Meridian Corneal Relaxing Incision for Moderate to High Astigmatism Corrections.

PURPOSE: To compare posterior chamber phakic intraocular lens (Implantable Collamer Lens [STAAR Surgical]) (ICL) plus modified steep meridian corneal relaxing incision (MS-CRI) to toric posterior chamber phakic intraocular lens (Toric Implantable Collamer Lens [STAAR Surgical]) (TICL) implantation for the correction of moderate to high astigmatism. METHODS: In this prospective, randomized clinical trial, patients with myopia who had moderate to high astigmatism (200 eyes) were enrolled and divided into TICL (n = 100) and MSCRI (n = 100) groups. All patients underwent examinations for uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and subjective refraction before surgery and at the 1- and 6-month follow-up visits. Vector astigmatism analysis was evaluated using the Alpins method. RESULTS: The mean UDVA and CDVA demonstrated significant improvement after surgery in both groups. During the 6-month follow-up, the MS-CRI group showed a slight regression tendency (P < .001) and the TICL group was stable for the astigmatism correction (P = .510). At 6 months postoperatively, the mean magnitudes of the surgically induced astigmatism were 1.46 ± 0.53 and 1.10 ± 0.48 diopters (P < .001). The correction index of the TICL group was closer to 1 compared to that of the MS-CRI group (0.95 vs 0.76). Approximately 99% of eyes in the TICL group had angle of error within ±15°, whereas 89% eyes in the MS-CRI group were within that range. A significant relationship between the magnitudes of target induced astigmatism and correction index was noted in the MS-CRI group (P < .001), but not in the TICL group (P = .592). CONCLUSIONS: TICL implantation could achieve better visual outcomes for correcting moderate to high astigmatism compared to ICL implantation plus MS-CRI. [J Refract Surg. 2023;39(8):539-545.].

Efficacy of acupuncture in patients with mild Alzheimer's disease and its impact on gut microbiota: Study protocol for a randomized sham-controlled trial.

Introduction: Acupuncture is used as an adjuvant therapy for Alzheimer's disease (AD), but available evidence for efficacy is limited so far. Growing studies suggest that resident gut microbiota contributes to the development and progression of AD. Meanwhile, acupuncture is reported to treat gastrointestinal and neurodegenerative disorders via the gut-brain axis. Therefore, our aim is to confirm the adjunctive therapeutic effects of acupuncture for AD, and explore the relationship between clinical efficacy and shifts of gut microbiota. Methods and analysis: This is a randomized, participant-masked, sham-controlled trial. One hundred and sixty participants with mild AD will be randomly assigned (1:1) to either active acupuncture or non-penetrating sham acupuncture (three times weekly for 14 weeks) added to donepezil treatment (5 mg per day for 28 weeks). The primary efficacy outcome is the change from baseline to week 28 in the Alzheimer's disease Assessment Scale (ADAS-cog12). Secondary efficacy outcomes include other assessments of the Mini-Mental State Examination (MMSE), the Alzheimer's disease Cooperative Study-Activities of Daily Living (ADCS-ADL), and Neuropsychiatric Inventory (NPI). Gut microbiota will be measured using 16S rRNA tag sequencing. Discussion: This rigorous trial will provide high-quality evidence on the efficacy of acupuncture as adjunctive treatment for mild AD, and identify the possible mechanisms of acupuncture from gut microbiota. Clinical Trial Registration: [https://clinicaltrials.gov/ct2/show/NCT05078944], ClinicalTrials.gov [NCT05078944]. Registered 15 October 2021.

Influence of social and environmental drivers on nutrient concentrations and ratios in lakes: A comparison between China and Europe.

Global anthropogenic flows of nitrogen (N) and phosphorus (P) have exceeded planetary boundaries with significant implications for pollution of the freshwater resources in the world. Understanding the global patterns and drivers of N and P concentrations and their ratios in the lakes could help design more effective management and remediation strategies to mitigate the impacts of eutrophication. While a suite of drivers are associated with the sources of nutrients, their transport and internal processes that control concentrations of N and P in the lakes, much less is known about the relative importance of different drivers in explaining spatial variations of lake nutrients and ratios. In this study, we compared N and P concentrations and their ratios in the lakes across China and Europe and examined the differences of dominant environmental and social drivers on lake nutrients. Our comparison showed that total nitrogen (TN) and total phosphorus (TP) concentrations were much higher in the lakes in China compared to those in Europe (i.e., TN: 1.13 mg/L in China vs. 0.64 mg/L in Europe; TP: 35.83 µg/L in China vs. 19.38 µg/L in Europe, the median value). However, lake N/P ratios for both regions were not statistically different. Concentrations of TN and TP showed decoupling in both regions, with the majority of lakes having high N/P mass ratios when evaluated by the commonly accepted threshold of 23 (i.e., 61% in China and 68% in Europe), indicating that phytoplankton are more P limited relative to N. Agricultural activity in the lake catchment is an important predictor for both nutrient concentrations and their ratio in Europe. This reflects successful investments in infrastructure and policy prescriptions in addressing point sources of pollution. In comparison, lake depth and water residence time are important in the decoupling of N and P concentrations in China. The regional difference between the dominant drivers can provide important insights into development of effective water pollution control measures. It is necessary for policy makers and water resource managers to be aware of large-scale imbalance of nutrients in lake due to the potential environmental consequences. A set of spatially flexible policies for water quality controls would be beneficial for sustaining the ecological integrity and future health of lakes.

LncRNA-miRNA-mRNA Network Analysis Reveals the Potential Biomarkers in Crohn's Disease Rats Treated with Herb-Partitioned Moxibustion.

Background: Long noncoding RNA (lncRNA) is receiving growing attention in Crohn's disease (CD). However, the mechanism by which herb-partitioned moxibustion (HPM) regulates the expression and functions of lncRNAs in CD rats is still unclear. The aim of our study is to identify lncRNA-miRNA-mRNA network potential biological functions in CD. Methods: RNA sequencing and microRNA (miRNA) sequencing were carried out to analyze lncRNA, miRNA and mRNA expression profiles among the CD rats, normal control rats, and CD rats after HPM treatment and constructed the potential related lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) networks. Then, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, protein-protein interaction (PPI) analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were performed to explore potentially important genes in ceRNA networks. Results: A total of 189 lncRNAs, 32 miRNAs and 463 mRNAs were determined as differentially expressed (DE) genes in CD rats compared to normal control rats, and 161 lncRNAs, 12 miRNAs and 130 mRNAs were identified as remarkably DE genes in CD rats after HPM treatment compared to CD rats. GO analysis indicated that the target genes were most enriched in cAMP and in KEGG pathway analysis the main pathways included adipocytokine, PPAR, AMPK, FoxO and PI3K-Akt signaling pathway. Finally, qRT-PCR results confirmed that lncRNA LOC102550026 sponged miRNA-34c-5p to regulate the intestinal immune inflammatory response by targeting Pck1. Conclusion: By constructing a ceRNA network with lncRNA-miRNA-mRNA, PCR verification, and KEGG analysis, we revealed that LOC102550026/miRNA-34c-5p/Pck1 axis and adipocytokine, PPAR, AMPK, FoxO, and PI3K-Akt signaling pathways might regulate the intestinal immune-inflammatory response, and HPM may regulate the lncRNA LOC102550026/miR-34c-5p/Pck1 axis and adipocytokine, PPAR, AMPK, FoxO, and PI3K-Akt signaling pathways, thus improving intestinal inflammation in CD. These findings may be novel potential targets in CD.

Herb-partitioned moxibustion alleviates colonic inflammation in Crohn's disease rats by inhibiting hyperactivation of the NLRP3 inflammasome via regulation of the P2X7R-Pannexin-1 signaling pathway.

Crohn's disease is a chronic inflammatory bowel disease and the NLRP3 inflammasome plays an important role in Crohn's disease. Previous studies have shown that Herb-partitioned moxibustion treating (at Qihai (CV 6) and Tianshu (ST 25)) prevented the excessive activation of the NLRP3 inflammasome and repaired damaged colonic mucosa in Crohn's disease. However, the mechanism by which Herb-partitioned moxibustion (at CV 6 and ST 25) regulates NLRP3 remains unclear. In this study, we treated Crohn's disease rats with herb-partitioned moxibustion (at CV 6 and ST 25) to investigate the mechanism by which Herb-partitioned moxibustion regulates the colonic NLRP3 inflammasome by observing colon length, the colon macroscopic damage indexes, and the expression of ATP, P2X7R, Pannexin-1, NF-κBp65, NLRP3, ASC, caspase-1, IL-1ß and IL-18 in the colon in Crohn's disease. Here, this study shows that herb-partitioned moxibustion (at CV 6 and ST 25) can reduce colon macroscopic damage indexes and colon histopathological scores, alleviate colon shortening and block the abnormal activation of the NLRP3 inflammasome by inhibiting the ATP content and the expression of P2X7R, Pannexin-1 and NF-κBp65, thereby reducing the release of the downstream inflammatory cytokine IL-1ß and ultimately suppressing colonic inflammation in Crohn's disease rats. This study for the first time identifies the mechanism by which herb-partitioned moxibustion (at CV 6 and ST 25) may inhibit the abnormal activation of the NLRP3 inflammasome by inhibiting the P2X7R-Pannexin-1 signaling pathway in Crohn's disease rats.

Human Methylmercury Exposure and Potential Impacts in Central Tibet: Food and Traditional Tibetan Medicine.

Methylmercury presents potent neurotoxicity to humans. Fish consumption is the leading source of human exposure to methylmercury worldwide. However, the exposure source in Tibet remains poorly understood because of the scarcity of observational data on most Tibetan foods, although high mercury levels were recently detected in some traditional Tibetan medicines. Here, the results of field investigations show that the joint consumption of traditional Tibetan medicines (TTMs), fish, and rice constitutes a primary exposure pathway to methylmercury in Tibetans and that the probable daily intake of methylmercury is close to that for many coastal regions. People who are young and high-income may have higher methylmercury exposure levels mainly because of economic development and cultural exchanges among regions. Our analysis indicates that a large proportion of the Tibetan population are likely to face a high methylmercury exposure risk and that mercury-susceptible populations in Tibet should be attentive to consuming TTMs with fish.

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: An evidence-based clinical practice guideline (updated version).

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: an evidence-based clinical practice guideline (updated version)

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)"; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID19 patients

Improvement in municipal wastewater treatment alters lake nitrogen to phosphorus ratios in populated regions.

Large-scale and rapid improvement in wastewater treatment is common practice in developing countries, yet this influence on nutrient regimes in receiving waterbodies is rarely examined at broad spatial and temporal scales. Here, we present a study linking decadal nutrient monitoring data in lakes with the corresponding estimates of five major anthropogenic nutrient discharges in their surrounding watersheds over time. Within a continuous monitoring dataset covering the period 2008 to 2017, we find that due to different rates of change in TN and TP concentrations, 24 of 46 lakes, mostly located in China's populated regions, showed increasing TN/TP mass ratios; only 3 lakes showed a decrease. Quantitative relationships between in-lake nutrient concentrations (and their ratios) and anthropogenic nutrient discharges in the surrounding watersheds indicate that increase of lake TN/TP ratios is associated with the rapid improvement in municipal wastewater treatment. Due to the higher removal efficiency of TP compared with TN, TN/TP mass ratios in total municipal wastewater discharge have continued to increase from a median of 10.7 (95% confidence interval, 7.6 to 15.1) in 2008 to 17.7 (95% confidence interval, 13.2 to 27.2) in 2017. Improving municipal wastewater collection and treatment worldwide is an important target within the 17 sustainable development goals set by the United Nations. Given potential ecological impacts on biodiversity and ecosystem function of altered nutrient ratios in wastewater discharge, our results suggest that long-term strategies for domestic wastewater management should not merely focus on total reductions of nutrient discharges but also consider their stoichiometric balance.

Recent advances in natural therapeutic approaches for the treatment of cancer.

Plants and natural compounds have been widely recognized to have potential for the prevention of cancer progression and as complementary or standalone treatments for cancer patients. The major benefits of natural compounds are their reduced toxicity compared to more aggressive and widely utilized cancer treatment approaches. Preclinical studies have led to the discovery of a number of natural anticancer compounds, including preparations of Vitex negundo L., green tea, mandarin peel oil, ursolic acid, curcumin and resveratrol. Although the in vitro data highlights the potential of these natural alternatives, their benefits in clinical cancer treatment remain less conclusive. In this review, we will discuss some of the recent advances in natural anticancer treatment discovery for the four most prominent global cancers, namely, breast, lung, prostate and skin metastases. As the exploration of natural therapeutics continues to expand, these substances have the potential to be utilized as preventative strategies and complimentary therapeutics. In some cases, they may have sufficient anti-tumor and anti-carcinogenic properties to function as standalone cancer treatments.

Seasonal Pattern of Nutrient Limitation in a Eutrophic Lake and Quantitative Analysis of the Impacts from Internal Nutrient Cycling.

Nutrient dynamics in lakes are determined by the external anthropogenic discharges and unobserved internal cycling processes. In this work, a decadal nutrient data set from the eutrophic Lake Taihu, China, revealed a strong seasonal pattern of nutrient concentration and limitation. A nutrient-driven dynamic eutrophication model based on a Bayesian hierarchical framework was established to quantify the relative contributions to temporal variations from external discharges and internal processes. Results showed that after years of efforts on nutrient reduction, external discharges were relatively small and fluctuated less between seasons compared to the internal processes. A quantitative relationship between monthly nutrient concentration and corresponding internal loading was observed. Lake sediment could transform from a source of phosphorus in overlying water in summer and autumn to a sink in winter and spring. Together with temporal variations in nitrification and denitrification, seasonal transformation from the limitation of phosphorus induced colimitation of nitrogen and phosphorus. Understanding the potential impact of internal nutrient cycling on a seasonal pattern of nutrient concentration and limitation, the growth of phytoplankton, and, possibly, phytoplankton community composition should be emphasized, given the change in the relative importance of external discharges and internal loading in the process of lake restoration.

Antagonistic Effect of Cuscuta chinensis on a Rat Model with Unilateral Cryptorchidism.

BACKGROUND The aim of this study was to investigate the effect of Cuscuta chinensis Lam. on germ cell apoptosis in a rat model of unilateral cryptorchidism. MATERIAL AND METHODS Thirty male SD rats were randomly and equally divided into a control group, a model group, and a Cuscuta group (5.0 g/kg/d) (n=10). The rat model of unilateral cryptorchidism in the model and Cuscuta groups was established by removal of the right gubernaculum, while rats in the control group received no treatment. After modeling, rats in the Cuscuta chinensis group were intragastrically administered Cuscuta chinensis extract (5.0 g/kg/d), while rats in the control group and model group were administered an equal volume of normal saline. After 90 days, all the rats were sacrificed and the testicles were separated and weighed, followed by TUNEL staining to detect germ cell apoptosis, flow cytometry to measure JC-1, ROS, and MDA, and Western blot analysis to evaluate the expression of Bax, Bcl-2, and cleaved caspase3. RESULTS Ninety days after the operation, Cuscuta chinensis Lam significantly minimized the damage caused by modeling by increasing weight of testis, reducing the germ cell apoptosis, and enhancing the mitochondrial membrane potential of testicles, as shown by levels of JC-1, ROS, and MDA, as well as elevating the level of Bcl-2/Bax and reducing the level of cleaved caspase3 (P<0.05). CONCLUSIONS Treatment with Cuscuta chinensis Lam reduced the germ cell apoptosis in rats with unilateral cryptorchidism, which provides new insight for the development of cryptorchidism therapy in the future.

Metabolite Cross-Feeding between Rhodococcus ruber YYL and Bacillus cereus MLY1 in the Biodegradation of Tetrahydrofuran under pH Stress.

Bacterial consortia are among the most basic units in the biodegradation of environmental pollutants. Pollutant-degrading strains frequently encounter different types of environmental stresses and must be able to survive with other bacteria present in the polluted environments. In this study, we proposed a noncontact interaction mode between a tetrahydrofuran (THF)-degrading strain, Rhodococcus ruber YYL, and a non-THF-degrading strain, Bacillus cereus MLY1. The metabolic interaction mechanism between strains YYL and MLY1 was explored through physiological and molecular studies and was further supported by the metabolic response profile of strain YYL, both monocultured and cocultured with strain MLY1 at the optimal pH (pH 8.3) and under pH stress (pH 7.0), through a liquid chromatography-mass spectrometry-based metabolomic analysis. The results suggested that the coculture system resists pH stress in three ways: (i) strain MLY1 utilized acid metabolites and impacted the proportion of glutamine, resulting in an elevated intracellular pH of the system; (ii) strain MLY1 had the ability to degrade intermediates, thus alleviating the product inhibition of strain YYL; and (iii) strain MLY1 produced some essential micronutrients for strain YYL to aid the growth of this strain under pH stress, while strain YYL produced THF degradation intermediates for strain MLY1 as major nutrients. In addition, a metabolite cross-feeding interaction with respect to pollutant biodegradation is discussed.IMPORTANCERhodococcus species have been discovered in diverse environmental niches and can degrade numerous recalcitrant toxic pollutants. However, the pollutant degradation efficiency of these strains is severely reduced due to the complexity of environmental conditions and limitations in the growth of the pollutant-degrading microorganism. In our study, Bacillus cereus strain MLY1 exhibited strong stress resistance to adapt to various environments and improved the THF degradation efficiency of Rhodococcus ruber YYL by a metabolic cross-feeding interaction style to relieve the pH stress. These findings suggest that metabolite cross-feeding occurred in a complementary manner, allowing a pollutant-degrading strain to collaborate with a nondegrading strain in the biodegradation of various recalcitrant compounds. The study of metabolic exchanges is crucial to elucidate mechanisms by which degrading and symbiotic bacteria interact to survive environmental stress.

Construction of artificial micro-aerobic metabolism for energy- and carbon-efficient synthesis of medium chain fatty acids in Escherichia coli.

Medium-chain (C6-C10) chemicals are important components of fuels, commodities and fine chemicals. Numerous exciting achievements have proven reversed ß-oxidation cycle as a promising platform to synthesize these chemicals. However, under native central carbon metabolism, energetic and redox constraints limit the efficient operation of reversed ß-oxidation cycle. Current fermentative platform has to use different chemically and energetically inefficient ways for acetyl-CoA and NADH biosynthesis, respectively. The characteristics such as supplementation of additional acetate and formate or high ATP requirement makes this platform incompatible with large-scale production. Here, an artificial micro-aerobic metabolism for energy and carbon-efficient conversion of glycerol to MCFAs was constructed to present solutions towards these barriers. After evaluating numerous bacteria pathways under micro-aerobic conditions, one synthetic metabolic step enabling biosynthesis of acetyl-CoA and NADH simultaneously, without any energy cost and additional carbon requirement, and reducing loss of carbon to carbon dioxide-emitting reactions, was conceived and successfully constructed. The pyruvate dehydrogenase from Enterococcus faecalis was identified and biochemically characterized, demonstrating the most suitable characteristics. Furthermore, the carbon and energy metabolism in Escherichia coli was rewired by the clustered regularly interspaced short palindromic repeats interference system, inhibiting native fermentation pathways outcompeting this synthetic step. The present engineered strain exhibited a 15.7-fold increase in MCFA titer compared with that of the initial strain, and produced 15.67 g/L MCFAs from the biodiesel byproduct glycerol in 3-L bioreactor without exogenous feed of acetate or formate, representing the highest MCFA titer reported to date. This work demonstrates this artificial micro-aerobic metabolism has the potential to enable the cost-effective, large-scale production of fatty acids and other value-added reduced chemicals.

Traditional Tibetan Medicine Induced High Methylmercury Exposure Level and Environmental Mercury Burden in Tibet, China.

Highly elevated concentrations of total mercury (THg) and methylmercury (MeHg) were found in the municipal sewage in Tibet. Material flow analysis supports the hypothesis that these elevated concentrations are related to regular ingestion of Hg-containing Traditional Tibetan Medicine (TTM). In Tibet in 2015, a total of 3600 kg of THg was released from human body into the terrestrial environment as a result of TTM ingestion, amounting to 45% of the total THg release into the terrestrial environment in Tibet, hence substantially enhancing the environmental Hg burden. Regular ingestion of TTM leads to chronic exposure of Tibetans to inorganic Hg (IHg) and MeHg, which is 34 to 3000-fold and 0-12-fold higher than from any other known dietary sources, respectively. Application of a human physiology model demonstrated that ingestion of TTM can induce high blood IHg and MeHg levels in the human body. Moreover, 180 days would be required for the MeHg to be cleared out of the human body and return to the initial concentration i.e. prior to the ingestion of 1 TTM pill. Our analysis suggests that high Hg level contained in TTM could be harmful to human health and elevate the environmental Hg burden in Tibet.

Qiliqiangxin Rescues Mouse Cardiac Function by Regulating AGTR1/TRPV1-Mediated Autophagy in STZ-Induced Diabetes Mellitus.

BACKGROUND/AIMS: To explore the potential role of qiliqiangxin (QLQX) A traditional Chinese medicine and the involvement of angiotensin II receptor type 1 (AGTR1) and transient receptor potential vanilloid 1 (TRPV1) in diabetic mouse cardiac function. METHODS: Intragastric QLQX was administered for 5 weeks after streptozotocin (STZ) treatment. Additionally, Intraperitoneal injections of angiotensin II (Ang II) or intragastric losartan (Los) were administered to assess the activities of AGTR1 and TRPV1. Two-dimensional echocardiography and tissue histopathology were used to assess cardiac function Western blot was used to detect the autophagic biomarkers Such as light chain 3 P62 and lysosomal-associated membrane protein 2 And transmission electron microscopy was used to count the number of autophagosomes. RESULTS: Decreased expression of TRPV1 and autophagic hallmarks and reduced numbers of autophagolysosomes as well as increased expression of angiotensin converting enzyme 1 and AGTR1 were observed in diabetic hearts. Blocking AGTR1 with Los mimicked the QLQX-mediated improvements in cardiac function Alleviated myocardial fibrosis and enabled autophagy Whereas Ang II abolished the beneficial effects of QLQX in wild type diabetic mice but not in TRPV1-/- diabetic mice. CONCLUSIONS: QLQX may improve diabetic cardiac function by regulating AGTR1/ TRPV1-mediated autophagy in STZ-induced diabetic mice.

Historical and future trends in global source-receptor relationships of mercury.

Growing concern about the risk associated with increasing environmental mercury (Hg) concentrations has resulted in a focus on the relationships between intercontinental emitted and accumulated Hg. We use a global biogeochemical Hg model with 8 continental regions and a global ocean to evaluate the legacy impacts of historical anthropogenic releases (2000BCE to 2008AD) on global source-receptor relationships of Hg. Legacy impacts of historical anthropogenic releases are confirmed to be significant on the source-receptor relationships according to our results. Historical anthropogenic releases from Asia account for 8% of total soil Hg in North America, which is smaller than the proportion (~17%) from previous studies. The largest contributors to the global oceanic Hg are historical anthropogenic releases from North America (26%), Asia (16%), Europe (14%) and South America (14%). Although anthropogenic releases from Asia have exceeded North America since the 1970s, source contributions to global Hg receptors from Asia have not exceeded North America so far. Future projections indicate that if Hg emissions are not effectively controlled, Asia will exceed North America as the largest contributor to the global ocean in 2019 and this has a long-term adverse impact on the future environment. For the Arctic Ocean, historical anthropogenic release from North America contributes most to the oceanic Hg reservoir and future projections reveal that the legacy impacts of historical releases from mid-latitudes would lead to the potential of rising Hg in the Arctic Ocean in the future decades, which calls for more effective Hg controls on mid-latitude releases.

Synergistic chemo-photothermal therapy of tumor by hollow carbon nanospheres.

Combined use of different therapies is conducive to improve the effectiveness of cancer therapy. The chemo-photothermal therapy is commonly used in one nanocarrier to provide an excellent synergistic effect for cancer therapy over photothermal therapy (PTT) or chemotherapy alone. In this study, biocompatible and monodisperse hollow carbon nanospheres (HCNs) were developed as a multifunctional platform for the delivery of paclitaxel (PTX) and PTT of cancer simultaneously. The mesoporous HCNs have large pore volume and proper channels for loading and release of PTX. Upon near-infrared (NIR) laser illumination, the photothermal mediator of HCNs could effectively convert absorbed light into heat, which triggered rapid release of chemotherapeutic drug from HCNs through dissociating the interactions between PTX and HCNs by heat energy. A large number of tumor cells were significantly destroyed when hct116 cells treated with PTX@HCNs were irradiated, which was mainly attribute to the synergistic result of HCNs-mediated photothermal damage and cytotoxicity of light-triggered PTX release.