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A high-energy pulsed vacuum ultraviolet (VUV) solid-state laser at 177 nm with high peak power by the sixth harmonic of a neodymium-doped yttrium aluminum garnet (Nd:YAG) amplifier in a KBe2BO3F2 prism-coupled device was demonstrated. The ultraviolet (UV) pump laser is a 352 ps pulsed, spatial top-hat super-Gaussian beam at 355 nm. A high energy of a 7.12 mJ VUV laser at 177 nm is obtained with a pulse width of 255 ps, indicating a peak power of 28 MW, and the conversion efficiency is 9.42% from 355 to 177 nm. The measured results fitted well with the theoretical prediction. It is the highest pulse energy and highest peak power ever reported in the VUV range for any solid-state lasers. The high-energy, high-peak-power, and high-spatial-uniformity VUV laser is of great interest for ultra-fine machining and particle-size measurements using UV in-line Fraunhofer holography diagnostics.
Head-up tilt test (HUTT) is an important tool in the diagnosis of pediatric vasovagal syncope. This research will explore the relationship between syncopal symptoms and HUTT modes in pediatric vasovagal syncope.
Methods:
A retrospective analysis was performed on the clinical data of 2513 children aged 3–18 years, who were diagnosed with vasovagal syncope, from Jan. 2001 to Dec. 2021 due to unexplained syncope or pre-syncope. The average age was 11.76 ± 2.83 years, including 1124 males and 1389 females. The patients were divided into the basic head-up tilt test (BHUT) group (596 patients) and the sublingual nitroglycerine head-up tilt test (SNHUT) group (1917 patients) according to the mode of positive HUTT at the time of confirmed pediatric vasovagal syncope.
Results:
(1) Baseline characteristics: Age, height, weight, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), and composition ratio of syncope at baseline status were higher in the BHUT group than in the SNHUT group (all P < 0.05). (2) Univariate analysis: Age, height, weight, HR, SBP, DBP, and syncope were potential risk factors for BHUT positive (all P < 0.05). (3) Multivariate analysis: syncope was an independent risk factor for BHUT positive, with a probability increase of 121% compared to pre-syncope (P<0.001).
Conclusion:
The probability of BHUT positivity was significantly higher than SNHUT in pediatric vasovagal syncope with previous syncopal episodes.
Seven accelerator mass spectrometry radiocarbon (AMS 14C) dates (7260±106∼7607±95 BP averaged 7444±103 BP) on a giant oyster shell, collected from an ancient shore of the Taipei Basin, are similar to the LSC (liquid scintillation counting) 14C age (7260±46 BP) of a grass sample inside the shell. The calibrated 14C ages of the C. gigas by Marine20 are 7490±240∼7805±230 cal BP (average 7660±96 cal BP), generally agreed with the calibrated LSC 14C ages of the grass and the oyster shell. Combined with other 14C ages of shoreline samples in the Taipei Basin, it is evident that sea level rose from 8600 to 7600 cal BP and reached a stand higher than modern sea level. During this marine transgression, the sedimentation rate along the shoreline was very high because 14C dating was not able to detect age differences for 4–5 m thick sediment sequences. Sixty-nine analyses of δ18O and δ13C from the oldest part of the shell exhibit clear seasonal cycles, with a 4-year period of growth in the 5.5-cm section. According to the δ18O values, the ancient oyster grew in a warmer-than-present shoreline environment, suggesting that the current absence of the giant oyster in Taiwan is not due to warming conditions.
The role of Mn oxide in the abiotic formation of humic substances has been well demonstrated. However, information on the effect of crystal structure and surface-chemical characteristics of Mn oxide on this process is limited. In the present study, hexagonal and triclinic birnessites, synthesized in acidic and alkali media, were used to study the influence of the crystal-structure properties of birnessites on the oxidative polymerization of hydroquinone and to elucidate the catalytic mechanism of birnessites in the abiotic formation of humic-like polymers in hydroquinone-birnessite systems. The intermediate and final products formed in solution and solid-residue phases were identified by UV/Visible spectroscopy, atomic absorption spectrometry, Fourier-transform infrared spectroscopy, X-ray diffraction, solid-phase microextraction-gaschromatography-mas ss pectrometry, ion chromatography, and ultrafiltration. The degree of oxidative polymerization of hydroquinone wasenhanced with increase in the interlayer hydrated H+, the average oxidation state (AOS), and the specific surface area of birnessites. The nature of the functional groups of the humic-like polymers formed was, however, almost identical when hydroquinone was catalyzed by hexagonal and triclinic birnessites with similar AOS of Mn. The results indicated that crystal structure and surface-chemistry characteristics have significant influence on the oxidative activity of birnessites and the degree of polymerization of hydroquinone, but have little effect on the abiotic formation mechanism of humic-like polymers. The proposed oxidative polymerization pathway for hydroquinone isthat, asit approachesthe birnessite, it formsp recursor surface complexes. Asa strong oxidant, birnessite accepts an electron from hydroquinone, which is oxidized to 1,4-benzoquinone. The coupling, cleavage, polymerization, and decarboxylation reactionsaccompany the generation of 1,4-benzoquinone, lead to the release of CO2 and carboxylic acid fragments, the generation of rhodochrosite, and the ultimate formation of humic-like polymers. These findings are of fundamental significance in understanding the catalytic role of birnessite and the mechanism for the abiotic formation of humic substances in nature.
Retropharyngeal lymphadenectomy is challenging. This study investigated a minimally invasive approach to salvage retropharyngeal lymphadenectomy in patients with nasopharyngeal carcinoma.
Methods
An anatomical study of four fresh cadaveric heads was conducted to demonstrate the relevant details of retropharyngeal lymphadenectomy using the endoscopic transoral medial pterygomandibular fold approach. Six patients with nasopharyngeal cancer with retropharyngeal lymph node recurrence, who underwent retropharyngeal lymphadenectomy with the endoscopic transoral medial pterygomandibular fold technique at the Eye and ENT Hospital of Fudan University from July to December 2021, were included in this study.
Results
The anatomical study demonstrated that the endoscopic transoral medial pterygomandibular fold approach offers a short path and minimally invasive approach to the retropharyngeal space. The surgical procedure was well tolerated by all patients, with no significant post-operative complications.
Conclusion
The endoscopic transoral medial pterygomandibular fold approach is safe and efficient for retropharyngeal lymphadenectomy.
High-speed water entry is a transient hydrodynamic process that is accompanied by strongly compressible flow, free surface splash, cavity evolution and other nonlinear hydrodynamic phenomena. To address these problems, a novel fluid–structure interaction (FSI) scheme based on the immersed boundary method is proposed which is suitable for strongly compressible multiphase flows. In this scheme, considering the multiphase interfaces at the immersed boundary, an improved immersed boundary method for effectively suppressing the non-physical force oscillation is proposed. Additionally, a quaternion-based six degrees of freedom motion system is used to describe rigid body motion, and the multiphase flow Eulerian finite element method is applied as the fluid solver. Using analytical solutions, experimental data and literature data, the accuracy and robustness of the FSI scheme are validated. Finally, the high-speed water entry of the slender body with different noses is investigated, and the hydrodynamic loads including the axial and normal drag forces and the bending moment are extensively discussed. The hydrodynamic load and motion trajectory are determined by the nose configuration. The tail slamming phenomenon is the primary focus, and it is revealed that its formation is primarily related to the pitch moment formed at the stage of crossing the free surface. Tail slamming also causes violent impact loads, especially bending moments, which may cause slender projectiles to break off. Finally, to combine the features of the flat and hemispherical noses, the water entry of the projectile with a truncated hemispherical nose is simulated and discussed.
In vitro rearing of honey bee larvae is ideal for bioassay studies; no honey bee stable cell lines are available. Inconsistency of internal development staging of reared larvae and a susceptibility to contamination are common problems encountered. Standardized protocols on rearing larvae in vitro to make the larvae growth and development more similar to that of natural colonies are necessary to ensure the accuracy of experimental results and promote honey bee research as a model organism. Here, we concluded that when larval fasting weight was >160 mg, the time point of gut emptying can be defined as the critical point separating the larval and prepupal stages. In this way, we can conduct precise studies on the prepupal stage, such as organ remodeling during metamorphosis. Simultaneously, we further verified that recombinant AccApidaecin in genetic engineered bacteria added to the larval diet upregulated antibacterial peptide gene expression, and did not stimulate the stress response in larvae, nor did it affect the pupation rate or eclosion rate. This demonstrated that feeding recombinant AccApidaecin can enhance the individual antibacterial ability at the molecular level.
The wheat aphid Sitobion miscanthi (CWA) is an important harmful pest in wheat fields. Insecticide application is the main method to effectively control wheat aphids. However, CWA has developed resistance to some insecticides due to its extensive application, and understanding resistance mechanisms is crucial for the management of CWA. In our study, a new P450 gene, CYP4CJ6, was identified from CWA and showed a positive response to imidacloprid and thiamethoxam. Transcription of CYP4CJ6 was significantly induced by both imidacloprid and thiamethoxam, and overexpression of CYP4CJ6 in the imidacloprid-resistant strain was also observed. The sensitivity of CWA to these two insecticides was increased after the knockdown of CYP4CJ6. These results indicated that CYP4CJ6 could be associated with CWA resistance to imidacloprid and thiamethoxam. Subsequently, the posttranscriptional regulatory mechanism was assessed, and miR-316 was confirmed to participate in the posttranscriptional regulation of CYP4CJ6. These results are crucial for clarifying the roles of P450 in the resistance of CWA to insecticides.
Seasonal climate variability is an important component of Earth's climate system, and has a significant impact on ecosystems and social systems. However, the temporal resolution of most proxy-based paleoclimate records is limiting to fully understand the past seasonal changes. Here, we used high-precision monthly resolution Sr/Ca records of three Tridacna squamosa specimens from the northern South China Sea (SCS) to reconstruct the sea surface temperature (SST) seasonality during three time periods from the middle Holocene. The results suggested that SST seasonality in the northern SCS during the middle Holocene (3.21 ± 0.98°C) was smaller than that for recent decades (AD 1994–2004, 4.32 ± 0.59°C). Analysis of modern instrumental data showed that the SST seasonality in the northern SCS was dominated by the winter SST, which was deeply influenced by the intensity of East Asian winter monsoon (EAWM). A strong EAWM usually resulted in cooler winter SST and a larger SST seasonality in the northern SCS. The reconstructed Holocene EAWM records showed that the EAWM strengthened from the middle to late Holocene, which was seen in our reconstruction of less SST seasonality changes during the middle Holocene in the northern SCS. This study highlighted that the Sr/Ca ratios from Tridacna shells can be used as a potential high-resolution indicator of past seasonal climate changes.
This experiment was designed to investigate the effect of supplementing conjugated linoleic acid (CLA) in breeder hens diet on development and hepatic lipid metabolism of chick offspring. Hy-Line Brown breeder hens were allocated into two groups, supplemented with 0 (control (CT)) or 0·5 % CLA for 8 weeks. Offspring chicks were grouped according to the mother generation and fed for 7 d. CLA treatment had no significant influence on development, egg quality and fertility of breeder hens but darkened the egg yolks in shade and increased yolk sac mass compared with the CT group. Addition of CLA resulted in increased body mass and liver mass and decreased deposition of subcutaneous adipose tissue in chick offspring. The serum TAG and total cholesterol levels of chick offspring were decreased in CLA group. CLA treatment increased the incorporation of both CLA isomers (c9t11 and t10c12) in the liver of chick offspring, accompanied by the decreased hepatic TAG levels, related to the significant reduction of fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) enzyme activities and the increased carnitine palmitoyltransferase-1 (CPT1) enzyme activity. Meanwhile, CLA treatment reduced the mRNA expression of genes related to fatty acid biosynthesis (FAS, ACC and sterol regulatory element-binding protein-1c) and induced the expression of genes related to β-oxidative (CPT1, AMP-activated protein kinase and PPARα) in chick offspring liver. In summary, the addition of CLA in breeder hens diet significantly increased the incorporation of CLA in the liver of chick offspring, which further regulate hepatic lipid metabolism.
Hypertension represents one of the most common pre-existing conditions and comorbidities in Coronavirus disease 2019 (COVID-19) patients. To explore whether hypertension serves as a risk factor for disease severity, a multi-centre, retrospective study was conducted in COVID-19 patients. A total of 498 consecutively hospitalised patients with lab-confirmed COVID-19 in China were enrolled in this cohort. Using logistic regression, we assessed the association between hypertension and the likelihood of severe illness with adjustment for confounders. We observed that more than 16% of the enrolled patients exhibited pre-existing hypertension on admission. More severe COVID-19 cases occurred in individuals with hypertension than those without hypertension (21% vs. 10%, P = 0.007). Hypertension associated with the increased risk of severe illness, which was not modified by other demographic factors, such as age, sex, hospital geological location and blood pressure levels on admission. More attention and treatment should be offered to patients with underlying hypertension, who usually are older, have more comorbidities and more susceptible to cardiac complications.
The impact of diet on the metabolic syndrome (MetS) and CVD has been investigated widely, but few studies have investigated the association between dietary patterns (DP) and the predicted CVD, derived from reduced rank regression (RRR). The objectives of this study were to derive DP using RRR and principal component analysis (PCA) and investigate their associations with the MetS and estimated 10-year atherosclerotic CVD (ASCVD). We used the baseline dataset from the Xinjiang multi-ethnic cohort study in China, collected from June 2018 to May 2019. A total of 14 982 subjects aged 35–74 years from Urumqi, Huo Cheng and Mo Yu were included in the analysis. The 10-year ASCVD risk was estimated using the Chinese ASCVD risk equations. The associations of DP with the MetS and 10-year ASCVD were determined using multivariable logistic regression models. In Urumqi and Mo Yu, the increased RRR DP score was associated with a higher OR of having the MetS and with a higher OR of elevated 10-year ASCVD risk. However, only the first DP determined by PCA in Urumqi was inversely associated with the MetS and elevated 10-year ASCVD risk. The prevalence of the MetS and elevated ASCVD risk in urban population is higher than that in rural areas. Our results may help nutritionists develop more targeted dietary strategies to prevent the MetS and ASCVD in different regions in China.
The FNDC5 gene encodes the fibronectin type III domain-containing protein 5 that is a membrane protein mainly expressed in skeletal muscle, and the FNDC5 rs3480 polymorphism may be associated with liver disease severity in non-alcoholic fatty liver disease (NAFLD). We investigated the influence of the FNDC5 rs3480 polymorphism on the relationship between sarcopenia and the histological severity of NAFLD. A total of 370 adult individuals with biopsy-proven NAFLD were studied. The association between the key exposure sarcopenia and the outcome liver histological severity was investigated by binary logistic regression. Stratified analyses were undertaken to examine the impact of FNDC5 rs3480 polymorphism on the association between sarcopenia and the severity of NAFLD histology. Patients with sarcopenia had more severe histological grades of steatosis and a higher prevalence of significant fibrosis and definite non-alcoholic steatohepatitis than those without sarcopenia. There was a significant association between sarcopenia and significant fibrosis (adjusted OR 2·79, 95 % CI 1·31, 5·95, P = 0·008), independent of established risk factors and potential confounders. Among patients with sarcopenia, significant fibrosis occurred more frequently in the rs3480 AA genotype carriers than in those carrying the FNDC5 rs3480 G genotype (43·8 v. 17·2 %, P = 0·031). In the association between sarcopenia and liver fibrosis, there was a significant interaction between the FNDC5 genotype and sarcopenia status (P value for interaction = 0·006). Sarcopenia is independently associated with significant liver fibrosis, and the FNDC5 rs3480 G variant influences the association between sarcopenia and liver fibrosis in patients with biopsy-proven NAFLD.
Parakmeria omeiensis is a Critically Endangered tree species in the family Magnoliaceae, endemic to south-west China. The tree is functionally dioecious, but little is known about the species’ status in the wild. We investigated the range, population size, age structure, habitat characteristics and threats to P. omeiensis. We located a total of 74 individuals in two populations on the steep slopes of Mount Emei, Sichuan province, growing under the canopy of evergreen broadleaved forest in well-drained gravel soil. A male-biased sex ratio, lack of effective pollinating insects, and habitat destruction result in low seed set and poor seedling survival in the wild. We have adopted an integrated conservation approach, including strengthening in situ conservation, cultivation of saplings, ex situ conservation and reintroduction, to protect this species. The successful conservation of P. omeiensis has important implications for the conservation of the genus Parakmeria and the family Magnoliaceae.
Multiple neurotrophic factors, including vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF)-2, nerve growth factor (NGF) and insulin-like growth factor(IGF)-1, have been shown to play important roles in the pathophysiology of mood disorders. However, insufficient clinical data supporting the importance of these neurotrophic factors in mood disorders, especially manic episode, have made inconclusive to make a connection between these factors and the disorder.
Objectives:
This study intended to investigate possible peripheral biomarkers in serum of manic episode of bipolar disorder.
Aims:
We aimed to investigate whether or not serum levels of VEGF, FGF-2, NGF and IGF-1 varied in manic state.
Methods:
Serum levels of VEGF, FGF-2, NGF and IGF-1 were examined in 70 drug-naïve patients with manic episode of bipolar disorder (BM) as well as 50 healthy controls, using an ELISA method.
Results:
The mean serum levels of VEGF, FGF-2, NGF and IGF-1 were 168.13±225.61pg/ml, 279.09±378.62pg/ml, 61.38±171.67pg/ml and 162.01±72.00ng/ml in BM patients, and 140.80±143.71pg/ml, 275.46±235.29pg/ml, 36.34±15.14pg/ml and 138.90±80.11ng/ml in healthy controls, respectively. Serum levels of FGF-2, NGF and IGF-1 in patients were significantly higher than those in healthy controls (Z=−2.896, P=0.004; Z=− 2.050, P=0.040; Z=−2.188, P=0.029; respectively), although there was no statistical difference in the serum levels of VEGF between two groups (Z=-0.468, P=0.639). Moreover, serum levels of NGF in patients correlated with the duration of disorder (rs=−0.241, P=0.044).
Conclusions:
The increase in serum levels of FGF-2, NGF and IGF-1 in manic state may reflect a neuroprotective role for these factors, and these factors may be considered biological markers for manic episode.
Varicella is an acute respiratory infectious diseases, with high transmissibility and quick dissemination. In this study, an SEIR (susceptible-exposed-infected-recovered) dynamic model was established to explore the optimal prevention and control measures according to the epidemiological characteristics about varicella outbreak in a school in a central city of China. Berkeley Madonna 8.3.18 and Microsoft Office Excel 2010 software were employed for the model simulation and data management, respectively. The result showed that the simulated result of SEIR model agreed well with the reported data when β (infected rate) equal to 0.067. Models showed that the cumulative number of cases was only 13 when isolation adopted when the infected individuals were identified (assuming isolation rate was up to 100%); the cumulative number of cases was only two and the TAR (total attack rate) was 0.56% when the vaccination coefficient reached 50%. The cumulative number of cases did not change significantly with the change of efficiency of ventilation and disinfection, but the peak time was delayed; when δ (vaccination coefficient) = 0.1, m (ventilation efficiency) = 0.7 or δ = 0.2, m = 0.5 or δ = 0.3, m = 0.1 or δ = 0.4 and above, the cumulative number of cases would reduce to one case and TAR would reduce to 0.28% with combined interventions. Varicella outbreak in school could be controlled through strict isolation or vaccination singly; combined interventions have been adopted when the vaccination coefficient was low.
We previously reported four heterozygous missense mutations of MYH7, KCNQ1, MYLK2, and TMEM70 in a single three-generation Chinese family with dual Long QT and hypertrophic cardiomyopathy phenotypes for the first time. However, the clinical course among the family members was various, and the potential myocardial dysfunction has not been investigated.
Objectives
The objective of this study was to investigate the echocardiographic and electrocardiographic characteristics in a genetic positive Chinese family with hypertrophic cardiomyopathy and further to explore the association between myocardial dysfunction and electric activity, and the identified mutations.
Methods
A comprehensive echocardiogram – standard two-dimensional Doppler echocardiography and three-dimensional speckle tracking echocardiography – and electrocardiogram were obtained for members in this family.
Results
As previously reported, four missense mutations – MYH7-H1717Q, KCNQ1-R190W, MYLK2-K324E, and TMEM70-I147T – were identified in this family. The MYH7-H1717Q mutation carriers had significantly increased left ventricular mass indices, elevated E/e’ ratio, deteriorated global longitudinal stain, but enhanced global circumferential and radial strain compared with those in non-mutation patients (all p<0.05). The KCNQ1-R190W carriers showed significantly prolonged QTc intervals, and the MYLK2-K324E mutation carriers showed inverted T-waves (both p<0.05). However, the TMEM70-I147T mutation carriers had similar echocardiography and electrocardiographic data as non-mutation patients.
Conclusions
Three of the identified four mutations had potential pathogenic effects in this family: MYH7-H1717Q was associated with increased left ventricular thickness, elevated left ventricular filling pressure, and altered myocardial deformation; KCNQ1-R190W and MYLK2-K324E mutations were correlated with electrocardiographic abnormalities reflected in long QT phenotype and inverted T-waves, respectively.
The present study aims to evaluate the antiparasitic activity of active components from Cynanchum paniculatum against Ichthyophthirius multifiliis. The antiparasitic activities of two bioassay-guided fractionationated compounds from C. paniculatum identified as Cynatratoside-A and Cynanversicoside C, by comparing spectral data (NMR and ESI-MS) with literature values, were evaluated by in vitro assay. These showed that both could kill theronts of I. multifiliis at a concentration of 10·0 mg L−1, with the median effective concentration (EC50) values of 4·6 mg L−1 and 5·2 mg L−1 for Cynatratoside-A and Cynanversicoside C, respectively. Encysted tomonts were killed at concentrations of 8·0 mg L−1 with both compounds. In vivo experiments demonstrated that fish treated with both compounds at 15·0 mg L−1 carried significantly fewer parasites than controls (P < 0·05). There were no mortalities among treated fish group compared with 75% mortality of untreated fish. Cynatratoside-A and Cynanversicoside C are therefore potential candidate drugs for use against I. multifiliis.
To determine dynamic changes in clinical characteristics by examining an outbreak of adenovirus infection that occurred from December 20, 2012, to February 25, 2013, in Tianjin, China.
Methods
Active surveillance for febrile respiratory illnesses was conducted, and medical records of patients were collected. Real-time quantitative polymerase chain reaction and sequencing were used for pathogen identification and viral genome study, respectively. Student’s t-test was used to compare the mean values of normally distributed continuous variables. Mann-Whitney U or Kruskal-Wallis tests were used if continuous variables were not normally distributed. Pearson’s chi-square test or Fisher’s exact test was used to compare categorical variables.
Results
The outbreak was sourced from the index case diagnosed as the common cold on December 20, 2012; a total of 856 cases were reported in the following 66 days. The pathogen was identified as human adenovirus (HAdV) 55. The symptoms manifested differently in severe and mild cases. Routine blood examinations, liver function indexes, and heart function indexes showed different dynamic patterns over time in hospitalized patients.
Conclusions
Clinical characteristics and laboratory examinations may reveal unique patterns over the course of HAdV-55 infection. (Disaster Med Public Health Preparedness. 2018;12:464–469)
To examine the vitamin D status, SNP of the vitamin D receptor gene (VDR) and the effects of vitamin D supplementation on parathyroid hormone and insulin secretion in adult males with obesity or normal weight in a subtropical Chinese city.
Design
An intervention trial.
Setting
Shenzhen City, Guangdong Province, China.
Subjects
From a cross-sectional survey conducted from June to July, eighty-two normal-weight and ninety-nine obese males (18–69 years) were screened to analyse their vitamin D status and for five SNP of VDR. From these individuals, in the same season of a different year, obese and normal-weight male volunteers (twenty-one per group) were included for an intervention trial with oral vitamin D supplementation at 1250 µg/week for 8 weeks.
Results
For the survey, there was no significant difference (P>0·05) in baseline circulating 25-hydroxyvitamin D concentrations or in the percentages of participants in different categories of vitamin D status between the two groups. The VDR SNP, rs3782905, was significantly associated with obesity (P=0·043), but none of the examined SNP were correlated with serum 25-hydroxyvitamin D when adjusted for age, BMI and study group. After vitamin D supplementation, serum 25-hydroxyvitamin D concentration, hypersecretions of parathyroid hormone and insulin, and insulin resistance in the obese were changed beneficially (P<0·05); however, the increase in serum 25-hydroxyvitamin D was less than that of the normal-weight men.
Conclusions
For obese and normal-weight men of subtropical China, the summer baseline vitamin D status was similar. However, oral vitamin D supplementation revealed a decreased bioavailability of vitamin D in obese men and ameliorated their hypersecretion of parathyroid hormone and insulin resistance.