Human blood metabolites and risk of sepsis: A Mendelian randomization investigation.

BACKGROUND: Evidence supports the observational correlations between human blood metabolites and sepsis. However, whether these associations represent a causal relationship is unknown. In this study, we applied two-sample Mendelian randomization (MR) analyses to examine causality between genetically proxied 486 blood metabolites and sepsis risk. METHODS: We used summary data from genome-wide association studies (GWAS) on 486 metabolites involving 7824 individuals as exposure and a sepsis GWAS including 11,643 cases and 474,841 controls as the outcome. The inverse-variance weighted (IVW) was the primary method to estimate the causal relationship between exposure and outcome, with MR-Egger and weighted median serving as supplements. Sensitivity analyses were implemented with Cochrane's Q test, MR-Egger intercept, MR-PRESSO and leave-one-out analysis. In addition, we performed replication MR, meta-analysis, Steiger test, linkage disequilibrium score (LDSC) regression and multivariable MR (MVMR) to thoroughly verify the causation. RESULTS: We identified that genetically determined high levels of 1-oleoylglycerophosphoethanolamine (odds ratio (OR) = .52, 95% confidence interval (CI): .31-.87, p = .0122), alpha-glutamyltyrosine (OR = .75, 95% CI: .60-.93, p = .0102), heptanoate (7:0) (OR = .51, 95% CI: .33-.81, p = .0041) and saccharin (OR = .84, 95% CI: .74-.94, p = .0036) were causally associated with a lower risk of sepsis. MVMR analysis demonstrated the independent causal effect of these metabolites on sepsis. CONCLUSIONS: These findings indicated that four blood metabolites have a protective impact on sepsis, thus providing novel perspectives into the metabolite-mediated development mechanism of sepsis by combining genomics and metabolomics.

Timing of infant formula introduction in relation to BMI and overweight at ages 1 and 3 years: the Born in Guangzhou Cohort Study (BIGCS).

Mounting evidence suggests that the first few months of life are critical for the development of obesity. The relationships between the timing of solid food introduction and the risk of childhood obesity have been examined previously; however, evidence for the association of timing of infant formula introduction remains scarce. This study aimed to examine whether the timing of infant formula introduction is associated with growth z-scores and overweight at ages 1 and 3 years. This study included 5733 full-term (≥ 37 gestational weeks) and normal birth weight (≥ 2500 and < 4000 g) children in the Born in Guangzhou Cohort Study, a prospective cohort study with data collected at 6 weeks, 6, 12 and 36 months. Compared with infant formula introduction at 0-3 months, introduction at 4-6 months was associated with the lower BMI, weight-for-age and weight-for-length z-scores at 1 and 3 years old. Also, introduction at 4-6 months was associated with the lower odds of at-risk of overweight at age 1 (adjusted OR 0·72, 95 % CI 0·55, 0·94) and 3 years (adjusted OR 0·50, 95 % CI 0·30, 0·85). Introduction at 4-6 months also decreased the odds of overweight at age 1 year (adjusted OR 0·42, 95 % CI 0·21, 0·84) but not at age 3 years. Based on our findings, compared with introduction within the first 3 months, introduction at 4-6 months has a reduction on later high BMI risk and at-risk of overweight. However, these results need to be replicated in other well-designed studies before more firm recommendations can be made.

Role of adjuvant chemotherapy after concurrent chemoradiotherapy in patients with locally advanced cervical cancer.

Aims: With the use of concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC), survival outcomes are still not optimal. This study was designed to evaluate the efficacy and safety of adjuvant chemotherapy (ACT) for patients with LACC after treatment with CCRT. Methods: Patients diagnosed with stage IIA-IIIB LACC, were retrospectively analyzed. All patients received cisplatin-based CCRT and were divided into two groups: ACT after CCRT (CCRT + ACT group) and observation after CCRT (CCRT group). Overall survival (OS), progression-free survival (PFS) and adverse effects were recorded and analyzed. Results: In total, 375 patients were included; 262 patients accepted ACT after CCRT while the remaining 113 patients chose observation. With a median follow-up of 40 months, no significant differences were found in the OS rates for patients in the CCRT + ACT and CCRT groups at 1 year, 3 years and the end of follow-up. There was also no significant discrepancy in PFS between groups. Subgroup analysis showed the International Federation of Gynecology and Obstetrics (FIGO) stage and age had negligible influence on both OS and PFS. Acute adverse events (grades 3-4) happened more frequently in CCRT + ACT group than in the CCRT group, with significant differences in neutropenia, anemia and creatinine. Conclusion: ACT after CCRT did not show benefit in survival but did induce some adverse effects. Therefore, this regimen is not recommended unless further large-scale randomized controlled trials are executed.

Maternal dietary patterns during pregnancy and preterm delivery: a large prospective cohort study in China.

BACKGROUND: Evidence about the associations between maternal dietary patterns and preterm delivery is scarce in Eastern countries. The purpose of this study was to examine the associations between maternal dietary patterns during pregnancy and preterm delivery in a Chinese population. METHODS: A total of 7352 mothers were included in the Born in Guangzhou Cohort Study, a prospective study in China. A validated self-administered food frequency questionnaire (FFQ) was used to assess maternal diet at 24-27 weeks of gestation. Dietary patterns were identified by cluster analysis. Gestational age was obtained from routine medical records. Preterm delivery was defined as delivery before 37 completed weeks of gestation, and was further classified into spontaneous and iatrogenic preterm delivery, and also early/moderate and late preterm delivery. Associations between dietary patterns and preterm delivery outcomes were assessed using logistic regression analyses. RESULTS: Six dietary patterns were identified, including 'Milk', 'Cereals, eggs, and Cantonese soups', 'Meats', 'Fruits, nuts, and Cantonese desserts', 'Vegetables', and 'Varied'. There were 351 (4.8%) preterm deliveries in this study population. Among those of preterm delivery, 16.2 and 83.8% were early/moderate and late preterm delivery, respectively. Compared with women of 'Vegetables' pattern, those of 'Milk' pattern had greater odds of overall preterm delivery (adjusted odds ratio [OR] 1.59, 95% confidence interval [CI] 1.11, 2.29, p < 0.05), spontaneous preterm delivery (adjusted OR 1.73, 95% CI 1.14, 2.62, p < 0.05) and late preterm delivery (adjusted OR 1.73, 95% CI 1.08, 2.62, p < 0.05); those of 'Cereals, eggs, and Cantonese soups' and 'Fruits, nuts, and Cantonese desserts' patterns had greater odds of late preterm delivery (adjusted OR 1.54, 95% CI 1.01, 2.35 for 'Cereals, eggs, and Cantonese soups', adjusted OR 1.61, 95% CI 1.04, 2.50 for 'Fruits, nuts, and Cantonese desserts', respectively). CONCLUSION: Maternal diet with frequent consumption of milk and less frequent consumption of vegetables during pregnancy might be associated with increased odds of preterm delivery. Future interventions should investigate whether increasing vegetable intake reduces preterm deliveries.

Early life vitamin D status and asthma and wheeze: a systematic review and meta-analysis.

BACKGROUND: Vitamin D deficiency has been linked to an increased risk of asthma. This study aimed to quantify the effect of early life vitamin D status on asthma and wheeze later in life. METHODS: PubMed, Embase, CINAHL, and CNKI databases, the Cochrane Central Register of Controlled Trials, and Google Scholar were searched up to July 2017. We included randomized controlled trials (RCTs) and cohort studies with vitamin D level in blood (maternal or cord or infant) or intake (maternal intake during pregnancy or infant intake) and asthma and/or wheeze. Two reviewers independently extracted data. Fixed- and random-effects models were used to summarize the risk estimates of comparisons between highest vs. lowest vitamin D categories. RESULTS: Of the 1485 studies identified, three RCTs and 33 cohort studies were included. We did not include the RCTs (1619 participants) in the meta-analysis as the comparators and outcome definitions were heterogenous. Three RCTs reported a non-statistically significant effect of vitamin D supplementation during pregnancy on offspring wheeze/asthma at 3 years of age. Pooled estimates of cohort studies suggest no association between antenatal blood vitamin D levels or vitamin D intake and offspring asthma assessed either > 5 years or ≤ 5 years. The estimate for blood vitamin D remained unchanged when two studies assessing asthma in adulthood were excluded, but a significant inverse association emerged between vitamin D intake and childhood asthma. We found no association between antenatal vitamin D level and wheeze. On the other hand, vitamin D intake during pregnancy may have a protective effect against wheeze. CONCLUSIONS: The pooled estimates from cohort studies show no association between antenatal blood vitamin D level and asthma/wheeze in later life. Whereas, the pooled estimates from cohort studies suggest that antenatal vitamin D intake may have an effect on childhood asthma > 5 years or childhood wheeze. The inconsistent results from studies assessing vitamin D either in blood or intake may be explained by previously reported non-linear association between blood vitamin D3 and childhood asthma. Further trials with enough power and longer follow-up time should be conducted to confirm the results.

The Born in Guangzhou Cohort Study (BIGCS).

The Born in Guangzhou Cohort Study (BIGCS) is a large-scale prospective observational study investigating the role of social, biological and environmental influences on pregnancy and child health and development in an urban setting in southern China. Pregnant women who reside in Guangzhou and who attend Guangzhou Women and Children's Medical Center (GWCMC) for antenatal care in early pregnancy (<20 weeks' gestation) are eligible for inclusion. Study recruitment commenced in February 2012, with an overall participation rate of 76.3%. Study recruitment will continue until December 2018 to achieve the target sample size of 30,000 mother-child pairs. At 30 April 2016, a total of 75,422 questionnaires have been collected, while 14,696 live births have occurred with planned follow-up of cohort children until age 18 years. During the same period a total of 1,053,000 biological samples have been collected from participants, including maternal, paternal and infant blood, cord blood, placenta, umbilical cord, and maternal and infant stool samples. The dataset has been enhanced by record linkage to routine health and administrative records. We plan future record linkage to school enrolment and national examination records.

Does tea consumption during early pregnancy have an adverse effect on birth outcomes?

BACKGROUND: Tea, a common beverage, has been suggested to exhibit a number of health benefits. However, one of its active ingredients, caffeine, has been associated with preterm birth and low birthweight. We investigated whether tea consumption during early pregnancy is associated with an increased risk of preterm birth and abnormal fetal growth. METHODS: A total of 8775 pregnant women were included from the Born in Guangzhou Cohort Study. Tea consumption (type, frequency, and strength) during their first trimester and social and demographic factors were obtained by way of questionnaires administered during pregnancy. Information on birth outcomes and complications during pregnancy was obtained from hospital medical records. RESULTS: Overall habitual tea drinking (≥1 serving/week) prevalence among pregnant women was low, at 16%. After adjustment for potential confounding factors (eg, maternal age, educational level, monthly income) tea drinking during early pregnancy was not associated with an increased risk of preterm birth or abnormal fetal growth (small or large for gestational age) (P>.05). CONCLUSIONS: We did not identify a consistent association between frequency of tea consumption or tea strength and adverse birth outcomes among Chinese pregnant women with low tea consumption. Our findings suggest that occasional tea drinking during pregnancy is not associated with increased risk of preterm birth or abnormal fetal growth. Given the high overall number of annual births in China, our findings have important public health significance.

[Induction and analysis for NIR features of frequently-used mineral traditional Chinese medicines].

In order to provide theoretical basis for the rapid identification of mineral traditional Chinese medicines(TCM) with near infrared (NIR)diffuse reflectance spectroscopy, Characteristic NIR spectra of 51 kinds of mineral TCMs were generalized and compared on the basis of the previous research, and the characteristic spectral bands were determined and analyzed by referring to mineralogical and geological literatures. It turned out that the NIR features of mineral TCMs were mainly at 8 000-4 000 cm ⁻¹ wavebands, which can be assigned as the absorption of water, -OH and[CO3 ²â»] and so on. Absorption peaks of water has regularity as follows, the structure water and -OH had a combined peak which was strong and keen-edged around 7 000 cm ⁻¹, the crystal water had two strong peak around 7 000 cm ⁻¹ and 5 100 cm ⁻¹, and water only has a broad peak around 5 100 cm ⁻¹. Due to the differences in the crystal form and the contents of water in mineral TCMs, NIR features of water in mineral TCMs which could be used for identification were different. Mineral TCMs containing sulfate are rich in crystal water, mineral TCMs containing silicate generally had structure water, and mineral TCMs containing carbonate merely had a little of water, so it was reasonable for the use of NIR spectroscopy to classify mineral TCMs with anionic type. In addition, because of the differences in cationic type, impurities, crystal form and crystallinity, mineral TCMs have exclusive NIR features at 4 600-4 000 cm ⁻¹, which can be assigned as Al-OH, Mg-OH, Fe-OH, Si-OH,[CO3 ²â»] and so on. Calcined mineral TCMs are often associated with water and main composition changes, also changes of the NIR features, which could be used for the monitoring of the processing, and to provide references for the quality control of mineral TCMs. The adaptability and limitation of NIR analysis for mineral TCMs were also discussed:the majority of mineral TCMs had noteworthy NIR features which could be used for the NIR analysis. And the NIR features of a few mineral TCMs were inapparent, such as Fluoritum, Realgar and Cinnabar, for which the Raman spectroscopy can be adopted alternatively.

Maternal dietary patterns and gestational diabetes mellitus: a large prospective cohort study in China.

Few studies have explored the relationship between dietary patterns and the risk of gestational diabetes mellitus (GDM). Evidence from non-Western areas is particularly lacking. In the present study, we aimed to examine the associations between dietary patterns and the risk of GDM in a Chinese population. A total of 3063 pregnant Chinese women from an ongoing prospective cohort study were included. Data on dietary intake were collected using a FFQ at 24-27 weeks of gestation. GDM was diagnosed using a 75 g, 2 h oral glucose tolerance test. Dietary patterns were determined by principal components factor analysis. A log-binomial regression model was used to examine the associations between dietary pattern and the risk of GDM. The analysis identified four dietary patterns: vegetable pattern; protein-rich pattern; prudent pattern; sweets and seafood pattern. Multivariate analysis showed that the highest tertile of the vegetable pattern was associated with a decreased risk of GDM (relative risk (RR) 0·79, 95% CI 0·64, 0·97), compared with the lowest tertile, whereas the highest tertile of the sweets and seafood pattern was associated with an increased risk of GDM (RR 1·23, 95% CI 1·02, 1·49). No significant association was found for either the protein-rich or the prudent pattern. The protective effect of a high vegetable pattern score was more evident among women who had a family history of diabetes (P for interaction=0·022). These findings suggest that the vegetable pattern was associated with a decreased risk of GDM, while the sweets and seafood pattern was associated with an increased risk of GDM. These findings may be useful in dietary counselling during pregnancy.

[Study on identification of traditional Chinese medicine Yangqishi and Yinqishi by X-ray diffraction].

The aim of this paper is to clarify the mineral origin of traditional Chinese medicine (TCM) Yangqishi and Yinqishi and guide identification of the both, by X-ray diffraction (XRD) Fourier patterns. Morphological identification and conventional physical and chemical analysis wee used to identify 22 batches of Yangqishi and Yinqishi. It used XRD Fourier patterns which has been collected from sample powders to analyze phase composition. It has been found experimentally that the mineral origin of Yinqishi is Talc schist and the mineral origin of Yangqishi is tremolite and actinolite. The results also showed that the method using XRD can get not only an accurate but also rapid identification of Yangqishi and Yinqishi. There are many differences in medicinal properties, efficacy, indications and composition of Yangqishi and Yinqishi, so be careful not to mix them up.

[Quantitative models of Raman spectroscopy for five kinds of traditional Chinese medicine containing CaCO3 based on an improved siPLS].

The aim of this paper is to apply Raman spectroscopy technique to develop rapid quantitative models for five kinds of Traditional Chinese Medicine containing CaCO3. In the experiment, Raman spectras of 67 batch of sample including Otolithum Sciaenae, Galaxeae Os, Ophicalcitum, Calcite, Stalactite and their mixture which had different content of CaCO3 were collected, and the quantitative models were established by using an improved siPLS to optimize the characteristic spectral bands and using the CaCO3 contents which were measured by EDTA titration method as references. Compared with the results by EDTA titration, the established quantitative model for CaCO, content showed a prediction result that the average relative deviation of the prediction results is 2. 71% and the average recovery rate was 100.46%, when the content is between 0.465 4-0.999 7, and when the characteristic spectral bands of 1 290-1 280, 730-714, 700-690, 660-650, 465-460, 455-445, 405-385 cm(-1) had been optimized. The result also showed that the model using Raman spectroscopy and based on an improved siPLS can get a rapid determination for contents of 5 kinds of Traditional Chinese Medicine containing CaCO3.

[A NIR qualitative and quantitative model of 8 kinds of carbonate-containing mineral Chinese medicines].

The aim of this paper is to apply near infrared spectroscopy techniques to construct a rapid identification method for 8 kinds of mineral Chinese Medicines containing carbonates. The qualitative model using clustering analysis method in OPUS software can identify accurately 8 kinds of carbonate-containing mineral Chinese medicines. The near-infrared quantitative model was established by using partial least squares method (PLS) for 7 mineral Chinese Medicines in which main component is calcium carbonate. Compared with the results by EDTA titration, the established quantitative analysis model for calcium carbonate content showed a good prediction result that when the content is between 47.61% -99.17%, the average relative deviation of the prediction result is 0.24% and the average recovery rate was 100.3%. The results also showed that the model using near infrared spectroscopy can get not only a rapid identification of the 8 mineral Chinese medicines containing carbonates, but also an accurate and reliabe content determination of calcium carbonate for the 7 mineral Chinese medicines which contain the component.

Causal association between brain structure and obstructive sleep apnea: A mendelian randomization study.

OBJECTIVE: Previous studies have reported contradictory findings regarding the relationship between obstructive sleep apnea (OSA) and abnormal brain morphology. Furthermore, the causal relationship between OSA and brain morphology has not been clearly established. The aim of this study was to utilize Mendelian randomization (MR) analysis to investigate the impact of obstructive sleep apnea (OSA) on brain morphology and determine its potential causal relationship. METHODS: Firstly, the inverse-variance weighted (IVW) method was employed to assess the causal effects of OSA on cortical surface area and brain structure volume. Additionally, two additional MR methods, namely weighted median and MR-Egger, were used to supplement the results from IVW. Subsequently, a reverse MR analysis was conducted to determine the direction of causality. Furthermore, sensitivity analyses were performed including Cochrane's Q test, MR-Egger intercept test, MR-PRESSO global test, and leave-one-out analysis. RESULTS: The results of the study showed that OSA patients had a tendency towards decreased cortical surface area and hippocampal volume in the precuneus region compared to individuals without OSA, while the superior temporal cortical surface area showed an increase. The results from the weighted median and MR-Egger analyses were consistent with those from the IVW analysis. Sensitivity tests confirmed the reliability of the causal estimates. CONCLUSIONS: This study provides preliminary evidence of an association between OSA and brain structure using large-scale genome-wide association data. The results demonstrate that OSA is associated with changes in brain structure. Therefore, individuals with OSA should be vigilant about the risks of related diseases due to alterations in brain tissue.

CO2-Controlled Water Injection in Carbonate Gas Reservoirs: An Effective Approach to Improve Production.

In the development of edgewater-type carbonate gas reservoirs, the challenge posed by water flooding in production wells is a significant concern. This study investigates the potential of CO2 injection as a solution for water control. Experiments were conducted to understand the gas-water flow dynamics during CO2-controlled water injection in a series-connected core. Emphasis was placed on the effects of varying the CO2 injection pressure on water flow and gas cumulative production rate. The mechanisms influencing water control and production efficiency across different injection pressures in multiwell production were elucidated. The results showed that the gas production rate of the core increased by 27.2% over the depletion production rate after the CO2 injection pressure was increased from 8 to 13 MPa. The gas production rate increases during the second development cycle from 20% to 55% after switching to CO2 injection, which pushes the edge water further back, slowing down side water flow in the core in the form of segmental plugs, and prolonging the time before water breakthrough. The production time and water breakthrough time for the second development cycle increased with increasing CO2 injection, while the degree of water flow on the core side decreased. These insights are crucial for optimizing the recovery efficiency of edgewater-type gas reservoirs and provide guidance on the application of CO2 injection for water control and CO2 sequestration in carbonate gas reservoirs.

Application and Properties of Polyglycolic Acid as a Degradation Agent in MPU/HNBR Degradable Elastomer Composites for Dissolvable Frac Plugs.

In this research, fully degradable elastomeric sealing materials were developed to enhance the environmental sustainability of oil and gas extraction. The modification of millable polyurethane rubber (MPU) with polyglycolic acid/hydrogenated nitrile butadiene rubber (PGA/HNBR) led to the synthesis of PGA@MPU/HNBR composite materials. The impact of varying monomer quantities on the mechanical properties, degradation behavior, degradation mechanisms, and thermal stability of these materials was investigated. Our findings illustrate that an increasing proportion of HNBR in the PGA@MPU/HNBR composite materials resulted in a decreased degradation rate. Simultaneously, higher HNBR content improved the thermal stability of the materials, while the inclusion of PGA reduced material hardness, rendering the composites more susceptible to swelling. At an HNBR content of 40 phr, MPU at 60 phr, and PGA at 6 phr, the composite material demonstrated the highest retention of mechanical properties at 31.3% following 168 h of hydrolysis at 100 °C. The degradation of the composite materials in 100 °C water primarily resulted from the hydrolysis of MPU's ester groups, with HNBR remaining unaffected.

Fasting-induced miR-7a-5p in AgRP neurons regulates food intake.

OBJECTIVE: The molecular control of feeding after fasting is essential for maintaining energy homeostasis, while overfeeding usually leads to obesity. Identifying non-coding microRNAs (miRNAs) that control food intake could reveal new oligonucleotide-based therapeutic targets for treating obesity and its associated diseases. This study aims to identify a miRNA modulating food intake and its mechanism in neuronal regulation of food intake and energy homeostasis. METHODS: A comprehensive genome-wide miRNA screening in the arcuate nucleus of the hypothalamus (ARC) of fasted mice and ad libitum mice was performed. Through stereotactic virus injections, intracerebroventricular injections, and miRNA sponge technology, miR-7a-5p was inhibited specifically in AgRP neurons and the central nervous system, and metabolic phenotypes were monitored. Quantitative real-time PCR, Western blotting, immunofluorescence, whole-cell patch-clamp recording, and luciferase reporter assay were used to investigate the mechanisms underlying miR-7a-5p's regulation of food intake. RESULTS: We found a significant increase in miR-7a-5p levels after fasting. miR-7a-5p was highly expressed in the ARC, and inhibition of miR-7a-5p specifically in AgRP neurons reduced food intake and body weight gain. miR-7a-5p inhibited S6K1 gene expression by binding to its 3'-UTR. Furthermore, the knockdown of ribosomal S6 kinase 1 (S6K1) in AgRP neurons can partially reverse the effects caused by miR-7a-5p inhibition. Importantly, intracerebroventricular administration of the miR-7a-5p inhibitor could also reduce food intake and body weight gain. CONCLUSION: Our findings suggest that miR-7a-5p responds to energy deficit and regulates food intake by fine-tuning mTOR1/S6K1 signaling in the AgRP neurons, which could be a promising oligonucleotide-based therapeutic target for treating obesity and its associated diseases.

Quantifying irregular pulsation of intracranial aneurysms using 4D-CTA.

Recent studies have suggested that irregular pulsation of intracranial aneurysm during the cardiac cycle may be potentially associated with aneurysm rupture risk. However, there is a lack of quantification method for irregular pulsations. This study aims to quantify irregular pulsations by the displacement and strain distribution of the intracranial aneurysm surface during the cardiac cycle using four-dimensional CT angiographic image data. Four-dimensional CT angiography was performed in 8 patients. The image data of a cardiac cycle was divided into approximately 20 phases, and irregular pulsations were detected in four intracranial aneurysms by visual observation, and then the displacement and strain of the intracranial aneurysm was quantified using coherent point drift and finite element method. The displacement and strain were compared between aneurysms with irregular and normal pulsations in two different ways (total and stepwise). The stepwise first principal strain was significantly higher in aneurysms with irregular than normal pulsations (0.20±0.01 vs 0.16±0.02, p=0.033). It was found that the irregular pulsations in intracranial aneurysms usually occur during the consecutive ascending or descending phase of volume changes during the cardiac cycle. In addition, no statistically significant difference was found in the aneurysm volume changes over the cardiac cycle between the two groups. Our method can successfully quantify the displacement and strain changes in the intracranial aneurysm during the cardiac cycle, which may be proven to be a useful tool to quantify intracranial aneurysm deformability and aid in aneurysm rupture risk assessment.

Bacteroides methylmalonyl-CoA mutase produces propionate that promotes intestinal goblet cell differentiation and homeostasis.

Propionate is a short-chain fatty acid that is generated upon microbiome-mediated fiber fermentation in the intestine. By modulating immune and metabolic pathways, propionate exerts many health benefits. Key bacterial species, such as Bacteroides thetaiotaomicron, generate propionate, but the biochemical pathways and specific functions remain undetermined. We identified a gene operon-encoding methylmalonyl-CoA mutase (MCM) that contributes to propionate biosynthesis in B. thetaiotaomicron. Colonization of germ-free mice with wild-type or MCM-deficient strains as well as in vitro examination demonstrated that MCM-mediated propionate production promotes goblet cell differentiation and mucus-related gene expression. Intestinal organoids lacking the propionate receptor, GPR41, showed reduced goblet cell differentiation upon MCM-mediated propionate production. Furthermore, although wild-type B. thetaiotaomicron alleviated DSS-induced intestinal inflammation, this effect was abolished in mice receiving the MCM-deficient strain but restored upon propionate supplementation. These data emphasize the critical role of MCM-mediated propionate biosynthesis in goblet cell differentiation, offering potential pathways to ameliorate colitis.

LGR4: A New Receptor Member in Endocrine and Metabolic Diseases.

Classic hormone membrane receptors, such as leucine-rich repeat-containing G protein-coupled receptor (LGR) 1 (follicle-stimulating hormone receptor), LGR2 (luteinizing hormone receptor), and LGR3 (thyrotropin receptor), are crucial in endocrinology and metabolism, and the identification of new receptors can advance this field. LGR4 is a new member of this G protein-coupled receptor family and shows ways of expression and function similar to those of LGR1/2/3. Several recent studies have reported that, unlike LGR5/6, LGR4 plays essential roles in endocrine and metabolic diseases, including hypothalamic-gonadal axis defects, mammary gland dysplasia, osteoporosis, cardiometabolic diseases, and obesity. An inactivating mutation p.R126X in LGR4 leads to osteoporosis, electrolyte disturbance, abnormal sex hormone levels, and weight loss, whereas an activating mutation p.A750T is associated with bone mineral density, insulin resistance, and adiposity. Though several paracrine ligands are known to act on LGR4, the endocrine ligands of LGR4 remain poorly defined. In this review, we highlight LGR4 dysfunction in clinical diseases, animal models, and pathophysiological changes, discuss their known ligands and downstream signaling pathways, and identify unresolved questions and future perspectives of this new receptor.

Effect of Graphene Oxide-Modified CaAl-Layered Double Hydroxides on the Carbon Dioxide Permeation Properties of Fluoroelastomers.

This work aimed to investigate the CO2 gas barrier and mechanical properties of fluorine rubber nanocomposites filled with Ca/Al layered hydroxide (graphene oxide [GO]/LDH-Ca2Al) modified by GO. GO/LDH-Ca2Al nanocomposite fillers were prepared by depositing Ca/Al layered hydroxide (LDH-Ca2Al) into the surface of alkalized GO (Al-GO). The prepared GO/LDH-Ca2Al nanocomposite fillers and complexes were characterized by Fourier infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) for structural and micromorphological characterization. The results showed that GO/LDH-Ca2Al was successfully prepared with strong interactions between Al-GO and LDH, and the compatibility of GO/LDH-Ca2Al nanocomposite fillers with the polymer was significantly improved compared with that of LDH-Ca2Al. Consequently, both the fracture strength (σb) and strain (εb) of GO/LDH-Ca2Al nanocomplexes remarkably increased, and they exhibited excellent mechanical properties. Differential scanning calorimetry and thermogravimetric analysis were used to characterize the thermal stability of GO/LDH-Ca2Al nanocomposite fillers, and GO/LDH-Ca2Al nanocomposite fillers have better thermal stability than LDH-Ca2Al. The reaction products (S-LDH-Ca2Al and S-GO-Ca2Al) of LDH-Ca2Al and GO/LDH-Ca2Al with CO2 were characterized using XRD and TGA, respectively, and the results show that LDH-Ca2Al reacts readily and chemically with CO2, resulting in a lower diffusion coefficient of CO2 in the LDH-Ca2Al nanocomplexes than that of the GO/LDH-Ca2Al nanocomplexes and leading to the destruction of the laminar structure of LDH-Ca2Al, while GO/LDH-Ca2Al has better CO2 resistance stability. GO/LDH-Ca2Al nanocomplexes exhibited a reduced content of hydroxyl groups with pro-CO2 nature exposed on the surface of LDH-Ca2Al, improving the interfacial interaction between the nanofillers and the rubber matrix and enhancing the dispersion of GO/LDH-Ca2Al in the polymers. Moreover, CO2 in the soluble GO/LDH-Ca2Al nanocomposites was significantly reduced, while the diffusion properties demonstrated weak temperature dependence on solubility. The mechanism of the CO2 gas barrier of polymers filled with GO/LDH-Ca2Al was proposed on the basis of the Arrhenius equation.