Effects of Oxygen Therapy on Patients with a Chronic Wound: A Systematic Review and Meta-analysis.

OBJECTIVE: To synthesize the effects of oxygen-based therapy on patients with a chronic wound. DATA SOURCES: The authors searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials for relevant randomized controlled trials from database inception. Investigators measured risk of bias using the Cochrane Collaboration's Risk of Bias tool. STUDY SELECTION: The included randomized controlled trials focused on the effects (short- or long-term wound healing, amputation rate, percentage of reduction in ulcer size, and poststudy transcutaneous oxygen measurement [TcPO2]) of oxygen-based therapy (including hyperbaric oxygen therapy, topical oxygen therapy, and continuous diffusion of oxygen) on patients with a chronic wound. DATA EXTRACTION: Researchers extracted information regarding participant characteristics and primary and secondary outcomes from the included studies. DATA SYNTHESIS: Pooled effects of 31 included studies showed that patients treated with oxygen had better short-term wound healing (risk ratio [RR], 1.544; 95% CI, 1.199 to 1.987), a higher percentage reduction in the ulcer area (standardized mean difference [SMD], 0.999; 95% CI, 0.439 to 1. 599), lower amputation rates (RR, 0.529; 95% CI, 0.325 to 0.862), shorter wound healing time (SMD, -0.705; 95% CI, -0.908 to -0.501), and higher poststudy TcPO2 (SMD, 2.128; 95% CI, 0.978 to 3.278) than those in the control group. For long-term wound healing, there was no statistically significant difference (RR, 1.227; 95% CI, 0.976 to 1.542). CONCLUSIONS: Oxygen-based therapy improves short-term parameters of wound healing in patients with chronic wounds.

Effect of tea polyphenols as an antioxidant on pork for frying at different temperatures and times.

The aim of this study was to investigate the effect of frying on the antioxidant properties of tea phenols added to pork. The antioxidant capacity of tea polyphenols with different concentrations was tested using different assays including total antioxidant capacity (T-AOC) (FRAP method), thiobarbituric acid reactive substance, 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging, and 2,2-diphenyl-1-(2,4,6-trinitrophenyl) hydrazyl (DPPH) radical scavenging. Our results indicated that tea polyphenols have a great antioxidant capacity and that a high frying temperature causes fat oxidation. Our study confirmed that DPPH assay is more suited to lipophilic compounds or compounds with high lipid content. In a frying temperature of 180°C, the DPPH-free radical scavenging ability of pork was not decreased. Further experiments remain necessary to explore specific temperatures with the same results. This study provides new process parameters and new references for processing techniques of healthy and high-quality pork products.

Computer-Aided Diagnosis of Complications After Liver Transplantation Based on Transfer Learning.

Liver transplantation is one of the most effective treatments for acute liver failure, cirrhosis, and even liver cancer. The prediction of postoperative complications is of great significance for liver transplantation. However, the existing prediction methods based on traditional machine learning are often unavailable or unreliable due to the insufficient amount of real liver transplantation data. Therefore, we propose a new framework to increase the accuracy of computer-aided diagnosis of complications after liver transplantation with transfer learning, which can handle small-scale but high-dimensional data problems. Furthermore, since data samples are often high dimensional in the real world, capturing key features that influence postoperative complications can help make the correct diagnosis for patients. So, we also introduce the SHapley Additive exPlanation (SHAP) method into our framework for exploring the key features of postoperative complications. We used data obtained from 425 patients with 456 features in our experiments. Experimental results show that our approach outperforms all compared baseline methods in predicting postoperative complications. In our work, the average precision, the mean recall, and the mean F1 score reach 91.22%, 91.70%, and 91.18%, respectively.

Associations of Nut Consumption with All-Cause Mortality among Individuals with Type 2 Diabetes.

BACKGROUND: Nuts are energy-dense, high-fat foods, and whether nut consumption influences mortality risk among individuals with type 2 diabetes (T2D) remains unclear. OBJECTIVES: This study aimed to investigate the associations of nut consumption with all-cause mortality among adults with T2D and to further explore the potential mediation effects of cardiometabolic biomarkers. METHODS: The current analysis included 5090 US participants with T2D from the National Health and Nutrition Examination Survey (1999-2014). Cox proportional hazards models were conducted to estimate hazard ratio (HR) and 95% confidence interval (CI). RESULTS: After 35,632 person-y of follow-up, 1174 deaths were documented. Higher nut consumption was significantly associated with a lower risk of all-cause mortality among individuals with T2D. After multivariable adjustment including lifestyles and dietary factors, diabetes duration, and glycated hemoglobin, compared with participants who did not consume nuts, the HR (95% CI) for those who consumed nuts over 3.5 ounce equivalent (oz.eq)/wk was 0.64 (0.50, 0.82; P-trend < 0.001) for all-cause mortality. A linear dose-response relationship was observed between nut consumption and all-cause mortality among individuals with T2D (Poverall=0.004, Pnonlinearity=0.35). In substitution analyses, replacing one serving of red and processed meat, refined grains, eggs, and dairy foods with one serving of nuts was associated with a 18% to 22% lower risk of all-cause mortality. In addition, mediation analysis suggested that C-reactive protein and γ-glutamine transaminase explained 6.7% and 9.1% of the relationship between nut consumption with all-cause mortality, respectively. CONCLUSIONS: Higher nut consumption was significantly associated with lower all-cause mortality among individuals with T2D. These findings indicate a potential benefit of nut consumption in the prevention of premature death among individuals with T2D.

Proteolytic rewiring of mitochondria by LONP1 directs cell identity switching of adipocytes.

Mitochondrial proteases are emerging as key regulators of mitochondrial plasticity and acting as both protein quality surveillance and regulatory enzymes by performing highly regulated proteolytic reactions. However, it remains unclear whether the regulated mitochondrial proteolysis is mechanistically linked to cell identity switching. Here we report that cold-responsive mitochondrial proteolysis is a prerequisite for white-to-beige adipocyte cell fate programming during adipocyte thermogenic remodelling. Thermogenic stimulation selectively promotes mitochondrial proteostasis in mature white adipocytes via the mitochondrial protease LONP1. Disruption of LONP1-dependent proteolysis substantially impairs cold- or ß3 adrenergic agonist-induced white-to-beige identity switching of mature adipocytes. Mechanistically, LONP1 selectively degrades succinate dehydrogenase complex iron sulfur subunit B and ensures adequate intracellular succinate levels. This alters the histone methylation status on thermogenic genes and thereby enables adipocyte cell fate programming. Finally, augmented LONP1 expression raises succinate levels and corrects ageing-related impairments in white-to-beige adipocyte conversion and adipocyte thermogenic capacity. Together, these findings reveal that LONP1 links proteolytic surveillance to mitochondrial metabolic rewiring and directs cell identity conversion during adipocyte thermogenic remodelling.

Amlodipine and Atropine for Hypoxia During One-Lung Ventilation: A Case Report.

Anesthetists are concerned about the causes and management of hypoxia during one-lung ventilation (OLV). Here, we report a hypoxic case during OLV and video-assisted thoracic surgery (VATS) for pulmonary lobectomy. The preoperative management of hypertension with amlodipine was considered to be responsible for the hypoxia. As a calcium channel blocker, amlodipine may inhibit hypoxic pulmonary vasoconstriction (HPV) and contribute to the reduction of the ventilation/perfusion ratio (or V/Q ratio). The hypoxia efficiently was treated by atropine, where both tracheal effects and the enhancement of HPV through muscarinic receptor blocking may work. For patients undertaking OLV, the effects of calcium channel blockers as a potential cause for hypoxemia should be paid attention to, where atropine administration may be of clinical benefit. One-lung ventilation (OLV) generally is used during anesthesia for thoracic surgeries. For OLV, a double-lumen tracheal tube (DLT) is used to realize lung separation in the airway. This technique is essential because it facilitates the surgical performance as well as isolates a healthy lung from the pathologic one. However, there are some concerns for OLV during anesthesia, where hypoxemia is commonly seen. There are many causes for hypoxemia during OLV. These include, for example, reduced oxygen stores due to the collapse of the non-ventilation lung, ventilation-perfusion mismatch induced by both lateral positions, and decrease in elastic recoil leading to more atelectasis. Accordingly, management of hypoxemia during OLV generally have been applied. Increase fraction of inspiration O2 (Fi O2) to 1, double checking the position of DLT, applying positive end expiratory pressure (PEEP), optimizing cardiac output (CO) all have been proven to be effective. Here, we report an efficiently treated hypoxemia case using atropine during video-assisted thoracic surgery (VATS) for pulmonary lobectomy. Preoperative medication of amlodipine may contribute to the hypoxemia through attenuating HPV during OLV, which may be antagonized by possible HPV augmentation of atropine. Further investigation is therefore suggested.

Luteoloside Prevents Sevoflurane-induced Cognitive Dysfunction in Aged Rats via Maintaining Mitochondrial Function and Dynamics in Hippocampal Neurons.

Postoperative cognitive dysfunction (POCD) is characterized by impaired cognitive function, such as decreased learning and memory after anesthesia and surgery. This study aimed to explore the effect of luteoloside, a flavonoid extracted from natural herbs, on sevoflurane-induced cognitive dysfunction. Aged Sprague-Dawley male rats (20 months old) were treated with luteoloside for 7 days prior to sevoflurane exposure. After evaluation using an open field, novel object recognition, and Y-maze tests, it was determined that luteoloside effectively prevented sevoflurane-induced cognitive dysfunction. Sevoflurane exposure led to hippocampal neuron apoptosis in vivo (n = 6) and in vitro (n = 3), while this injury was prevented by luteoloside in a dose-dependent manner. Mechanistically, luteoloside maintained mitochondrial function and dynamics, as evidenced by the restored adenosine triphosphate (ATP) production and mitochondrial membrane potential as well as the upregulated levels of mitochondrial fission (optic atrophy protein 1 (Opa1) and mitofusin1 (Mfn1)) and downregulated mitochondrial fusion (mitochondrial fission 1 (Fisl) and dynamin-related protein 1 (Drp1)) factors. Notably, silencing Opa1 blocked the protective effect of luteoloside on hippocampal neurons and mitochondrial function. In summary, luteoloside prevented sevoflurane-induced cognitive dysfunction in aged rats, which may be achieved by regulating mitochondrial dynamics. Our study reveals the potential of luteoloside in preventing POCD in aged patients.

Associations of healthy dietary patterns with mortality among people with prediabetes.

PURPOSE: To examine the associations of healthy dietary patterns with cardiometabolic biomarkers and all-cause mortality among individuals with prediabetes. METHODS: This cohort study included 8363 adults with prediabetes from the National Health and Nutrition Examination Survey 1999-2014. Healthy dietary patterns including Alternate Healthy Eating Index-2010 (AHEI-2010), Alternate Mediterranean Diet score (AMED), Dietary Approaches to Stop Hypertension score (DASH), and Healthy Eating Index-2015 (HEI-2015) were calculated based on 24-h dietary recall data. Mortality status was obtained by linkage to National Death Index records. Cardiometabolic biomarkers, including blood glucose, insulin, HbA1c, C-reactive protein (CRP), and lipids, were measured at recruitment. RESULTS: During 61,991 person-years of follow-up, 991 deaths occurred. Comparing the extreme quartiles, the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality were 0.65 (0.49, 0.85) for AHEI-2010 (P-trend = 0.002), 0.68 (0.50, 0.92) for AMED (P-trend = 0.004), 0.72 (0.53, 0.98) for DASH (P-trend = 0.03), and 0.78 (0.58, 1.05) for HEI-2015 (P-trend = 0.08). Besides, the HRs (95% CIs) for all-cause mortality per 20-percentile increment in scores were 0.78 (0.67, 0.90) for AHEI-2010 (P = 0.001), 0.73 (0.62, 0.86) for AMED (P < 0.001), 0.84 (0.69, 1.02) for DASH (P = 0.08), and 0.86 (0.74, 1.00) for HEI-2015 (P = 0.04). In addition, higher dietary scores were associated with favorable blood glucose, insulin, HOMA-IR, blood lipids, and CRP (all P-trend < 0.05). The high-density lipoprotein cholesterol and CRP explained 1.53-9.21% of the associations between dietary patterns and all-cause mortality (P < 0.05). CONCLUSIONS: Diets with higher AHEI-2010, AMED, DASH, and HEI-2015 were associated with improved cardiometabolic factors and lower all-cause mortality among individuals with prediabetes. These findings suggest that multiple healthy dietary patterns instead of a one-size-fits-all diet plan might be beneficial and acceptable for individuals with prediabetes.

Differences in adsorption, transmembrane transport and degradation of pyrene and benzo[a]pyrene by Bacillus sp. strain M1.

In a previous study our group identified Bacillus sp. strain M1 as an efficient decomposer of high molecular weight-polycyclic aromatic hydrocarbons (HMW-PAHs). Interestingly, its removal efficiency for benzo[a]pyrene (BaP) was nearly double that of pyrene (Pyr), which was the reverse of what is reported for most other species. Here we compared the differential steps of biosorption, transmembrane transport and biodegradation of Pyr and BaP by strain M1 in order to assist in targeted selection of dominant strains and their degradation efficiency in the remediation of these two HMW-PAHs. The overall biosorption efficiency for BaP was 19% higher than that for Pyr, and the time needed to reach BaP peak adsorption efficiency was 4 days shorter than for Pyr. Transmembrane transport of the PAHs was compared in presence of sodium azide which inhibits ATP synthesis and metabolism. This indicated that both Pyr and BaP entered the cells by the same means of passive transport. Biodegradation of Pyr and BaP did not differ in the early stage of culture, but around days 5-7, the biodegradation efficiency of BaP was significantly (30-61%) higher than that of Pyr. Key enzymes involved in these processes were identified and their activity differed, with intracellular gentisate 1,2-dioxygenase and extracellular polyphenol oxidase as likely candidates to be involved in BaP degradation, while intracellular catechol-1,2- dioxygenase and salicylate hydroxylase are more likely involved in Pyr degradation. These results provide new insights for sustainable environmental remediation of pyrene and benzo(a)pyrene by these bacteria.

Study on the Predictive Value of Thromboelastography in Early Neurological Deterioration in Patients with Primary Acute Cerebral Infarction.

Objective: To investigate the predictive value of thromboelastography for the occurrence of early neurological deterioration (END) in patients with primary acute cerebral infarction (ACI). Methods: 150 patients who were hospitalized in the department of neurology of our hospital from September 2020 to September 2021 and were clearly diagnosed with primary ACI by head CT and head magnetic resonance imaging (MRI) were selected and divided into END and non-END groups according to the change in National Institute of Health Stroke Scale (NIHSS) score within 72 h of admission. The general baseline data and laboratory indexes of the first examination at admission were compared between the two groups, and the factors that may affect the occurrence of END were determined by univariate analysis and multivariate logistic regression analysis, and the predictive value of thromboelastography on the occurrence of END after ACI was analyzed by applying the receiver operating characteristic (ROC) curve. Results: Time to onset, baseline NIHSS score, percentage of diabetes, white blood cell (WBC) levels, C-reactive protein (CRP), and apolipoprotein B (Apo B) levels were higher in the END group than in the non-END group (P < 0.05); coagulation reaction time (RT) (3.97 ± 1.16 vs. 5.49 ± 1.03) and kinetic time (KT) (1.32 ± 0.67 vs. 1.82 ± 0.58) were lower in the END group than in the non-END group (P < 0.05). Inthe END group (P < 0.05) diabetes, baseline NHISS score, CRP level, Apo B level, and RT were independent risk factors for the development of END in patients with ACI (P < 0.05). The AUC of RT to predict the occurrence of END in patients with ACI was 0.855 (95% CI: 0784 to 0925, P = 0.001), with a sensitivity of 81.70% and specificity of 78.00% when the optimal cut-off value was 0.597. Conclusion: NIHSS score at admission, CRP, apolipoprotein B, RT shortening, and diabetes mellitus were independent risk factors for the development of END in ACI patients; RT shortening in TEG was predictive of END in ACI patients.

Performance of a Mid-Infrared Sensor for Simultaneous Trace Detection of Atmospheric CO and N2O Based on PSO-KELM.

In this article, a field deployable sensor was developed using a self-developed 4.58-µm continuous wave quantum cascade laser (CW-QCL) for the simultaneous detection of carbon monoxide (CO) and nitrous oxide (N2O), both of which have strong fundamental absorption bands in this waveband. The sensor is based on tunable diode laser absorption spectroscopy (TDLAS) technology, which combined a multi-pass gas cell (MPGC) with a 41 m optical path length to achieve high-precision detection. Meanwhile, the particle swarm optimization-kernel extreme learning machine (PSO-KELM) algorithm was applied for CO and N2O concentration prediction. In addition, the self-designed board-level QCL driver circuit and harmonic signal demodulation circuit reduce the sensor cost and size. A series of validation experiments were conducted to verify the sensor performance, and experiments showed that the concentration prediction results of the PSO-KELM algorithm are better than those of the commonly used back propagation (BP) neural networks and partial least regression (PLS), with the smallest root mean square error (RMSE) and linear correlation coefficient closest to 1, which improves the detection precision of the sensor. The limit of detection (LoD) was assessed to be 0.25 parts per billion (ppb) for CO and 0.27 ppb for N2O at the averaging time of 24 and 38 s. Field deployment of the sensor was reported for simultaneous detection of CO and N2O in the air.

Optimization of Ultrasound-Assisted Extraction of Polyphenols from Ilex latifolia Using Response Surface Methodology and Evaluation of Their Antioxidant Activity.

The polyphenolic extract of Ilex latifolia (PEIL) exhibits a variety of biological activities. An evaluation of the parameters influencing the ultrasonic extraction process and the assessment of PEIL antioxidant activity are presented herein. Response surface methodology (RSM) was used to optimize the experimental conditions for the polyphenols ultrasonic-assisted extraction (UAE) from the leaves of Ilex latifolia. We identified the following optimal conditions of PEIL: ethanol concentration of 53%, extraction temperature of 60 °C, extraction time of 26 min and liquid−solid ratio of 60 mL/g. Using these parameters, the UAE had a yield of 35.77 ± 0.26 mg GAE/g, similar to the value we predicted using RSM (35.864 mg GAE/g). The antioxidant activity of PEIL was assessed in vitro, using various assays, as well as in vivo. We tested the effects of various doses of PEIL on D-galactose induced aging. Vitamin C (Vc) was used as positive control. After 21 days of administration, we measured superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, malondialdehyde (MDA) levels in mouse serum and liver tissue. The results demonstrated that the PEIL exhibits potent radical scavenging activity against 1,1-diphenyl-2-picrythydrazyl (DPPH∙), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS+), and hydroxyl (∙OH) radicals. The serum concentrations of SOD and GSH-Px were higher, and MDA levels were lower, in the medium- and high-dose PEIL-treated groups than those in the aging group (p < 0.01), and the activity of MDA was lower than those of the model group (p < 0.01). The liver concentrations of SOD and GSH-Px were higher (p < 0.05), and MDA levels were lower, in the medium- and high-dose PEIL-treated groups than those in the aging control group (p < 0.01). These results suggest that optimizing the conditions of UAE using RSM could significantly increase the yield of PEIL extraction. PEIL possesses strong antioxidant activity and use as a medicine or functional food could be further investigated.

Utility of Serum Growth Arrest-Specific Protein 6 as a Biomarker of Severity and Prognosis After Severe Traumatic Brain Injury: A Prospective Observational Study.

Objective: Growth arrest-specific protein 6 (Gas6) may harbor protective effects in acute brain injury. This study was designed to determine the relation of serum Gas6 levels to severity and prognosis after traumatic brain injury (TBI). Methods: In this prospective cohort study of 114 controls and 114 patients with severe TBI, multivariate analysis was used to assess relationships between serum Gas6 levels, Glasgow coma scale (GCS) score, Rotterdam computed tomography (CT) score, postinjury 180-day mortality, overall survival and poor prognosis (Extended Glasgow outcome scale score 1-4). Results: Significantly increased serum Gas6 levels of patients (median, 10.3 ng/mL versus 32.5 ng/mL; P < 0.001), as compared with controls, were independently correlated with Rotterdam CT score (t = 3.629, P < 0.001) and GCS score (t=-3.393, P = 0.001), and independently predicted 180-day mortality (odds ratio, 1.078; 95% confidence interval (CI), 1.007-1.154), overall survival (hazard ratio, 1.074; 95% CI, 1.012-1.139) and poor prognosis (odds ratio, 1.129; 95% CI, 1.059-1.205). Areas under receiver operating characteristic curve (AUCs) of serum Gas6 levels for discriminating risks of 180-day mortality and poor prognosis were 0.785 (95% CI, 0.699-0.857) and 0.793 (95% CI, 0.707-0.863), respectively; and serum Gas6 levels above 30.9 ng/mL and 28.3 ng/mL predicted 180-day mortality and poor prognosis with maximum Youden indices of 0.451 and 0.468, respectively. The predictive ability of serum Gas6 levels for mortality was similar to those of GCS score (AUC, 0.833; 95% CI, 0.751-0.896; P = 0.286) and Rotterdam CT score (AUC, 0.823; 95% CI, 0.740-0.888; P = 0.432). The discriminatory capability of serum Gas6 levels for the risk of poor prognosis was in the range of GCS score (AUC, 0.846; 95% CI, 0.766-0.906; P = 0.178) and Rotterdam CT score (AUC, 0.831; 95% CI, 0.750-0.895; P = 0.368). Conclusion: Serum Gas6 may appear as a promising biochemical parameter for aiding in the assessment of trauma severity and prediction of prognosis among patients with severe TBI.

MYPT1 reduction is a pathogenic factor of erectile dysfunction.

Erectile dysfunction (ED) is closely associated with smooth muscle dysfunction, but its underlying mechanisms remains incompletely understood. We here reported that the reduced expression of myosin phosphatase target subunit 1 (MYPT1), the main regulatory unit of myosin light chain phosphatase, was critical for the development of vasculogenic ED. Male MYPT1 knockout mice had reduced fertility and the penises displayed impaired erections as evidenced by reduced intracavernous pressure (ICP). The penile smooth muscles of the knockout mice displayed enhanced response to G-Protein Couple Receptor agonism and depolarization contractility and resistant relaxation. We further identified a natural compound lotusine that increased the MYPT1 expression by inhibiting SIAH1/2 E3 ligases-mediated protein degradation. This compound sufficiently restored the ICP and improved histological characters of the penile artery of Mypt1 haploinsufficiency mice. In diabetic ED mice (db/db), the decreased expression of MYPT1 was measured, and ICP was improved by lotusine treatment. We conclude that the reduction of MYPT1 is the major pathogenic factor of vasculogenic ED. The restoration of MYPT1 by lotusine improved the function of injured penile smooth muscles, and could be a novel strategy for ED therapy.

Associations of exposure to lead and cadmium with risk of all-cause and cardiovascular disease mortality among patients with type 2 diabetes.

The aim of this paper is to investigate the associations of lead and cadmium exposure with all-cause and cardiovascular disease (CVD) mortality among adults with type 2 diabetes (T2D). The prospective cohort study included participants with T2D (n = 7420 for blood lead; n = 5113 for blood cadmium) from the National Health and Nutrition Examination Survey (NHANES) III and NHANES 1999-2014. Death outcomes were ascertained through linkage with the National Death Index records. The geometric mean (interquartile range) concentrations of blood lead and cadmium were 19.6 (11.8, 35.0) µg/L and 0.39 (0.21, 0.60) µg/L, respectively. During 72,279 and 37,017 person-years of followup, 2818 all-cause deaths (including 832 CVD deaths) for blood lead and 1237 all-cause deaths (including 319 CVD deaths) for blood cadmium were documented, respectively. Comparing extreme quartiles, the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of all-cause mortality were 1.51 (1.25, 1.82) for blood lead (Ptrend < 0.001) and 1.58 (1.22, 2.03) for blood cadmium (Ptrend < 0.001); and the HRs (95% CIs) of CVD mortality were 2.27 (1.54, 3.34) for blood lead (Ptrend < 0.001) and 1.78 (1.04, 3.03) for blood cadmium (Ptrend = 0.07). In the joint analysis, compared with participants in the lowest tertiles of blood lead and cadmium, participants in the highest tertiles had a HR (95% CI) of 2.09 (1.35, 3.24) for all-cause mortality. Exposure to lead and cadmium alone or in combination was significantly associated with higher risk of mortality among patients with T2D. These findings imply that minimizing exposure to lead and cadmium may aid in the prevention of premature death among individuals with diabetes.

Tas2R activation relaxes airway smooth muscle by release of Gαt targeting on AChR signaling.

Both chronic obstructive pulmonary disease (COPD) and asthma are severe respiratory diseases. Bitter receptor-mediated bronchodilation is a potential therapy for asthma, but the mechanism underlying the agonistic relaxation of airway smooth muscle (ASM) is not well defined. By exploring the ASM relaxation mechanism of bitter substances, we observed that pretreatment with the bitter substances nearly abolished the methacholine (MCh)-induced increase in the ASM cell (ASMC) calcium concentration, thereby suppressing the calcium-induced contraction release. The ASM relaxation was significantly inhibited by simultaneous deletion of three Gαt proteins, suggesting an interaction between Tas2R and AChR signaling cascades in the relaxation process. Biochemically, the Gαt released by Tas2R activation complexes with AChR and blocks the Gαq cycling of AChR signal transduction. More importantly, a bitter substance, kudinoside A, not only attenuates airway constriction but also significantly inhibits pulmonary inflammation and tissue remodeling in COPD rats, indicating its modulation of additional Gαq-associated pathological processes. Thus, our results suggest that Tas2R activation may be an ideal strategy for halting multiple pathological processes of COPD.

Associations of Serum Carotenoids With Risk of Cardiovascular Mortality Among Individuals With Type 2 Diabetes: Results From NHANES.

OBJECTIVE: Although carotenoids have been suggested to exhibit antioxidant properties, some experimental studies reported that ß-carotene may show pro-oxidant effects under certain conditions. Current evidence regarding the cardiovascular effects of carotenoids among patients with type 2 diabetes (T2D) is scarce. This study aimed to prospectively examine the associations of individual serum carotenoid concentrations with cardiovascular mortality among adults with T2D. RESEARCH DESIGN AND METHODS: This analysis included 3,107 individuals with T2D from the Third National Health and Nutrition Examination Survey (NHANES III) and NHANES 2001-2006. Cardiovascular mortality was ascertained by linkage to National Death Index records through 31 December 2015. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: During an average of 14 years of follow-up, 441 cardiovascular deaths occurred. After multivariate adjustment including lifestyles, dietary factors, glucose control, and other major carotenoids, higher serum ß-carotene concentrations were significantly associated with an elevated risk of cardiovascular mortality in a dose-response manner. When extreme quartiles of ß-carotene were compared, the multivariable-adjusted HR was 2.47 (95% CI 1.62, 3.76) for cardiovascular mortality (Ptrend = 0.002); and per one-unit increment in natural log-transformed serum ß-carotene was associated with a 46% higher risk of cardiovascular mortality (P = 0.001). Other individual carotenoids (α-carotene, ß-cryptoxanthin, lycopene, and lutein/zeaxanthin) were not significantly associated with the risk of cardiovascular mortality. Consistent results were observed when stratifying by age, sex, race, BMI, smoking status, diabetes duration, and glycated hemoglobin A1c levels. CONCLUSIONS: Higher concentrations of serum ß-carotene, but not other individual carotenoids, were significantly associated with an increased risk of cardiovascular mortality among individuals with T2D. Our findings, if replicated, underscore the need to estimate the optimal serum ß-carotene concentrations in individuals with T2D.

A Shigella species variant is causally linked to intractable functional constipation.

Intractable functional constipation (IFC) is the most severe form of constipation, but its etiology has long been unknown. We hypothesized that IFC is caused by refractory infection by a pathogenic bacterium. Here, we isolated from patients with IFC a Shigella species - peristaltic contraction-inhibiting bacterium (PIB) - that significantly inhibited peristaltic contraction of the colon by production of docosapentenoic acid (DPA). PIB colonized mice for at least 6 months. Oral administration of PIB was sufficient to induce constipation, which was reversed by PIB-specific phages. A mutated PIB with reduced DPA was incapable of inhibiting colonic function and inducing constipation, suggesting that DPA produced by PIB was the key mediator of the genesis of constipation. PIBs were detected in stools of 56% (38 of 68) of the IFC patients, but not in those of non-IFC or healthy individuals (0 of 180). DPA levels in stools were elevated in 44.12% (30 of 68) of the IFC patients but none of the healthy volunteers (0 of 97). Our results suggest that Shigella sp. PIB may be the critical causative pathogen for IFC, and detection of fecal PIB plus DPA may be a reliable method for IFC diagnosis and classification.

Associations of lower-carbohydrate and lower-fat diets with mortality among people with prediabetes.

BACKGROUND: Although low-carbohydrate and low-fat diets are beneficial in short-term metabolic improvement, the associations of these dietary patterns, particularly with different food sources and quality of macronutrients, with mortality remain unclear among people with prediabetes. OBJECTIVES: We aimed to examine the associations of different types of lower-carbohydrate diets (LCDs) and lower-fat diets (LFDs) with mortality among individuals with prediabetes. METHODS: This study included 9793 adults with prediabetes from the NHANES 1999-2014. Mortality status was linked to National Death Index mortality data through 31 December, 2015. Overall, unhealthy, and healthy LCD and LFD scores were determined based on the percentages of energy from total and subtypes of carbohydrate, fat, and protein. Cox proportional hazards regression models were applied to calculate HRs and 95% CIs. RESULTS: Higher healthy LCD score was associated with favorable blood glucose, insulin, HOMA-IR, C-reactive protein (CRP), and blood lipids, whereas higher healthy LFD score was associated with lower blood glucose and CRP at baseline (all P-trend < 0.05). During 72,054 person-years of follow-up, 1352 deaths occurred. The multivariate-adjusted HRs (95% CIs) of all-cause mortality per 20-percentile increment in dietary scores were 0.88 (0.80, 0.96) for healthy LCD score (P = 0.003), 0.85 (0.78, 0.93) for healthy LFD score (P < 0.001), 1.09 (0.99, 1.21) for unhealthy LCD score (P = 0.08), and 1.11 (1.00, 1.22) for unhealthy LFD score (P = 0.05). Isocalorically replacing 3%-5% energy of low-quality carbohydrate or saturated fat with high-quality carbohydrate, plant-based protein, or unsaturated fat was associated with a 14%-37% reduced all-cause mortality. CONCLUSIONS: Healthy LCD and LFD scores were significantly associated with lower all-cause mortality, whereas unhealthy LCD and LFD scores tended to be associated with higher all-cause mortality, among people with prediabetes.

Point-of-care testing of methylamphetamine with a portable optical fiber immunosensor.

Owing to the increasing worldwide abuse of methamphetamine (MA), which may induce severe public health and social problems, rapid and sensitive method is highly in demand for forensic point-of-care testing (POCT) of MA. Herein we report a portable chemiluminescent fiber-based immunosensor (PCFS) for highly sensitive quantitative and specifically immune recognition of MA in biological sources. The PCFS combines the optical fiber sensor with competitive enzyme-linked immunoassay and biotin-streptavidin-mediated peroxidase nanocomposite for signal amplification. Equipped with a portable battery-powered photon counting detector, the PCFS is suitable for rapid and cost-effective POCT of MA with a wide linear range of 1.5-300 ng/mL and a low detection limit of 0.5 ng/mL. The method is successfully applied for determination of MA in various biological sources (human blood, urine and oral fluid) with analytical time of 10 min. The practicability and accuracy of the PCFS fulfill the requirements of forensic identification and clinical diagnosis. With the advantages of easy operation, rapid analysis, sensitive and selective detection, the proposed PCFS offers a reliable and convenient method for POCT of drug abuse in different biological sources.