Serum amyloid A for predicting prognosis in patients with newly diagnosed Crohn's disease.

OBJECTIVE: Serum amyloid A (SAA) was found to be positively correlated with the activity of Crohn's disease (CD); however, its prognostic value remains uncertain. Here, we examined its predictive ability in newly diagnosed CD and explored genetic association. METHODS: This retrospective cohort study included patients newly diagnosed as CD at the First Affiliated Hospital of Sun Yat-sen University between June 2010 and March 2022. We employed receiver operating characteristic curve, Cox proportional hazard regression models and restricted cubic splines to investigate the prognostic performance of SAA for surgery and disease progression. To assess possible causality, a two-sample Mendelian randomisation (MR) of published genome-wide association study data was conducted. RESULTS: During 2187.6 person-years (median age, 28 years, 72.4% male), 87 surgery and 153 disease progression events were documented. A 100-unit increment in SAA level generated 14% higher risk for surgery (adjusted HR (95% CI): 1.14 (1.05-1.23), p=0.001) and 12% for disease progression (1.12 (1.05-1.19), p<0.001). Baseline SAA level ≥89.2 mg/L led to significantly elevated risks for surgery (2.08 (1.31-3.28), p=0.002) and disease progression (1.72 (1.22-2.41), p=0.002). Such associations were assessed as linear. Adding SAA into a scheduled model significantly improved its predictive performances for surgery and disease progression (p for net reclassification indexes and integrated discrimination indexes <0.001). Unfortunately, no genetic causality between SAA and CD was observed in MR analysis. Sensitivity analyses showed robust results. CONCLUSION: Although causality was not found, baseline SAA level was an independent predictor of surgery and disease progression in newly diagnosed CD, and had additive benefit to existing prediction models.

Antidiarrheal properties of Ligusticum chuanxiong Hort's ethanol extract in mice and its impact on the contraction of rabbits' isolated jejunal smooth muscles.

Ligusticum chuanxiong Hort (CR) is the dried rhizome of Ligusticum belongs to the Umbelliferae family. The present study aimed to assess the antidiarrheal effects of ethanol extracts of CR (CR ext.). The mice were administered castor oil to induce diarrhea and the antidiarrheal effects of CR ext (250, 500 and 1000mg/kg) were assessed in vivo. The potential effect of CR ext (0.01-10 mg/mL) was examined on isolated rabbit jejunum smooth muscle in vitro. CR ext exhibited antidiarrheal effects at a dose ranging from 500 to 1000 mg/kg (P <0.01). CR ext (0.01-10 mg/mL) relaxed the smooth muscles in a dose-dependent manner and its median effective concentration (EC50) was 0.55 mg/mL (0.46-0.67, n = 6) (P<0.05; P <0.01). It alleviated jejunal contraction induced by ACh/K+ (60 mM) and EC50 values were 0.35 mg/mL (0.34-0.37) and 0.11 mg/mL (0.10-0.12), respectively. Similar to the effect of verapamil, CR ext shifted the concentration-response curve of CaCl2 downward to the right. The CR ext exhibits a notable antidiarrheal effect and can inhibit intestinal contraction. This mechanism of action may be based on its ability to inhibit Ca2+ channels.

Fine-Grained Recognition of Mixed Signals with Geometry Coordinate Attention.

With the advancement of technology, signal modulation types are becoming increasingly diverse and complex. The phenomenon of signal time-frequency overlap during transmission poses significant challenges for the classification and recognition of mixed signals, including poor recognition capabilities and low generality. This paper presents a recognition model for the fine-grained analysis of mixed signal characteristics, proposing a Geometry Coordinate Attention mechanism and introducing a low-rank bilinear pooling module to more effectively extract signal features for classification. The model employs a residual neural network as its backbone architecture and utilizes the Geometry Coordinate Attention mechanism for time-frequency weighted analysis based on information geometry theory. This analysis targets multiple-scale features within the architecture, producing time-frequency weighted features of the signal. These weighted features are further analyzed through a low-rank bilinear pooling module, combined with the backbone features, to achieve fine-grained feature fusion. This results in a fused feature vector for mixed signal classification. Experiments were conducted on a simulated dataset comprising 39,600 mixed-signal time-frequency plots. The model was benchmarked against a baseline using a residual neural network. The experimental outcomes demonstrated an improvement of 9% in the exact match ratio and 5% in the Hamming score. These results indicate that the proposed model significantly enhances the recognition capability and generalizability of mixed signal classification.

Mental health and academic performance of college students: Knowledge in the field of mental health, self-control, and learning in college.

The aim of this research is to analyze the impact of mental health on the academic performance of junior and senior students studying in a university setting during the 2022-2023 academic year, in the post-COVID period. The study was conducted in Beijing, China, with the participation of 600 students, including 300 first-year students and 300 fifth-year students. DASS (Depression, Anxiety, and Stress Scale) and PHQ-9 (Patient Health Questionnaire-9) questionnaires were employed to measure mental health. The DASS assesses symptoms of depression, anxiety, and stress, while the PHQ-9 specifically evaluates depression severity. Academic performance was evaluated using a 12-point scale, which incorporated various criteria such as exam scores, coursework performance, and participation in extracurricular activities. The research was conducted across five faculties of the university from 2022 to 2023. In the study, fifth-year students demonstrated a higher level of mental health compared to first-year students, with an average DASS score of 27.1 and 24.2, respectively. Interestingly, despite this, first-year students achieved higher academic performance indicators, with an average score of 8.2 compared to 9.8 in fifth-year students. Correlation analysis revealed significant associations between stress, depression, and anxiety levels with academic performance (stress: r = -0.25, p < 0.001; depression: r = -0.20, p = 0.003; anxiety: r = -0.18, p = 0.008). These findings highlight the critical importance of addressing students' mental well-being, particularly in later academic years. Recommendations include implementing support programs and developing online resources for students.

Longitudinal albuminuria patterns predict coronary artery calcification progression: Findings from the Coronary Artery Risk Development in Young Adults study.

BACKGROUND AND AIMS: Albuminuria is an established risk factor for adverse cardiovascular outcomes. However, few studies have characterized longitudinal albuminuria patterns based on long-term measurement of urine albumin-to-creatinine ratio (UACR) levels. We aimed to evaluate the association between longitudinal albuminuria patterns in midlife adults and subsequent CAC progression. METHODS: We included 1919 participants with CAC assessment by computed tomography from CARDIA (Coronary Artery Risk Development in Young Adults) study. CAC progression was determined for each individual as the difference of logarithmic CAC scores at follow-up and baseline. Albuminuria patterns across a 10-year span were estimated by longitudinal UACR levels. Multivariable general linear models were used to evaluate the association of long-term albuminuria patterns with CAC progression. RESULTS: Of the 1919 included participants, 583 (30.4 %) participants experienced CAC progression, and the mean (SD) age was 50.4 (3.5) years at year 25. A total of four dynamic albuminuria patterns were identified. After multivariable adjustment, there were significant differences in CAC progression by albuminuria patterns as demonstrated as percent change in CAC with 36.0 % (SE, 1.5) progression for mid- and late-life normoalbuminuria group, 46.0 % (SE, 7.6) for midlife normoalbuminuria and late-life high albuminuria group, 52.4 % (SE, 7.1) for midlife high albuminuria and late-life normoalbuminuria group, and 54.5 % (SE, 8.7) for mid- and late-life high albuminuria group (p = 0.019). Similar findings were also observed in CAC volume score changes. CONCLUSIONS: Longitudinal albuminuria patterns across a 10-year span were associated with worse CAC progression independent of baseline CAC level and albuminuria changes, suggesting that it may provide early identification of high-risk individuals with dynamic rises in albuminuria who may benefit from aggressive risk factor modification.

Baicalin-peptide supramolecular self-assembled nanofibers effectively inhibit ferroptosis and attenuate doxorubicin-induced cardiotoxicity.

Doxorubicin, an anthracycline chemotherapeutic agent, elicits a deleterious cardiotoxicity known as doxorubicin-induced cardiomyopathy (DIC) that circumscribes its chemotherapy utility for malignancies. Recent empirical evidence implicates ferroptosis, an iron-dependent form of regulated cell death, as playing a pivotal role in the pathogenesis of DIC. We postulated that anti-ferroptosis agents may constitute a novel therapeutic strategy for mitigating DIC. To test this hypothesis, we engineered baicalin-peptide supramolecular self-assembled nanofibers designed to selectively target the angiotensin II type I receptor (AT1R), which is upregulated in doxorubicin-damaged cardiomyocytes. This enabled targeted delivery of baicalin, a natural antioxidant compound, to inhibit ferroptosis in the afflicted myocardium. In vitro, the nanofibers ameliorated cardiomyocyte death by attenuating peroxide accumulation and suppressing ferroptosis. In a murine model of DIC, AT1R-targeted baicalin delivery resulted in efficacious cardiac accumulation and superior therapeutic effects compared to systemic administration. This investigation delineates a promising framework for developing targeted therapies that alleviate doxorubicin-induced cardiotoxicity by inhibiting the ferroptosis pathway in cardiomyocytes.

Biomimetic Grapefruit-Derived Extracellular Vesicles for Safe and Targeted Delivery of Sodium Thiosulfate against Vascular Calcification.

As the prevalence of vascular calcification (VC), a strong contributor to cardiovascular morbidity and mortality, continues to increase, the need for pharmacologic therapies becomes urgent. Sodium thiosulfate (STS) is a clinically approved drug for therapy against VC; however, its efficacy is hampered by poor bioavailability and severe adverse effects. Plant-derived extracellular vesicles have provided options for VC treatment since they can be used as biomimetic drug carriers with higher biosafety and targeting abilities than artificial carriers. Inspired by natural grapefruit-derived extracellular vesicles (EVs), we fabricated a biomimetic nanocarrier comprising EVs loaded with STS and further modified with hydroxyapatite crystal binding peptide (ESTP) for VC-targeted delivery of STS. In vitro, the ESTP nanodrug exhibited excellent cellular uptake capacity by calcified vascular smooth muscle cells (VSMCs) and subsequently inhibited VSMCs calcification. In the VC mice model, the ESTP nanodrug showed preferentially the highest accumulation in the calcified arteries compared to other treatment groups. Mechanistically, the ESTP nanodrug significantly prevented VC via driving M2 macrophage polarization, reducing inflammation, and suppressing bone-vascular axis as demonstrated by inhibiting osteogenic phenotype trans-differentiation of VSMCs while enhancing bone quality. In addition, the ESTP nanodrug did not induce hemolysis or cause any damage to other organs. These results suggest that the ESTP nanodrug can prove to be a promising agent against VC without the concern of systemic toxicity.

Lonicera japonica Thunb extract ameliorates lipopolysaccharide-induced acute lung injury associated with luteolin-mediated suppression of NF-κB signaling pathway.

OBJECTIVE: Lonicera japonica Thunb (LJT) is a commonly used herbal soup to treat inflammation-related diseases. However, the effect of LJT on ALI is unknown. The present study was aimed at investigating the protective effects of LJT extract (LTE) and its active ingredient luteolin (Lut) on lipopolysaccharide (LPS)-stimulated ALI and investigate its potential mechanism. MATERIALS AND METHODS: The effects of LTE and Lut were explored in an ALI mouse model induced by intraperitoneal injection of lipopolysaccharide (LPS). Besides, the LPS-induced inflammation model in BEAS-2B cells was used to clarify the underlying mechanisms. The ALI pathological changes in lung tissues were tested through Haematoxylin and eosin (HE) staining. The apoptosis of cells in lung tissue and the cell model in vitro was evaluated by TUNEL assays, respectively. Meanwhile, the viability of cells in vitro was evaluated by Cell Counting Kit-8 (CCK-8) assay. The levels/concentrations of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1ß and IL-10 in BALF were detected by enzyme-linked immunosorbent assay (ELISA). Besides, through quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting, the expression of the above-mentioned inflammatory factors and key factors in the NF-κB signaling pathway was examined. The distribution of inflammatory factors in tissue was observed through immunohistochemistry (IHC) assays . RESULTS: In relative to LPS-stimulated group, the in vivo study showed that LTE and different concentrations of Lut dramatically alleviated LPS-evoked lung pathological injury and lung edema based on the changes in total protein levels and lung wet/dry (W/D) ratio in the bronchoalveolar lavage fluid (BALF) from ALI mice. LTE and different concentrations of Lut also suppressed the inflammatory response, as reflected by the variations of neutrophil accumulation and the production of proinflammatory and anti-inflammatory cytokines in the lung tissues and BALF of ALI mice. The in vitro research also demonstrated that LTE and Lut visibly facilitated cell viability and restrained the apoptosis of BEAS-2B cells stimulated by LPS. Lut hindered LPS-inducible activation of NF-κB pathway in BEAS-2B cells. CONCLUSION: The present study proved that LTE might suppress LPS-induced acute injury and inflammation in mice and BEAS-2B cells through the Lut-caused suppression of NF-κB signal path (Figure 1).

Effect of Phosphoric Acid on the Preparation of α-Hemihydrate Gypsum Using Hydrothermal Method.

The effects of phosphoric acid (H3PO4) in pressurized aqueous solution on the dehydration of CaSO4·2H2O to form α-hemihydrate gypsum (α-HH) phase and the regulation of crystal shape were studied in this paper in order to provide guidance for the low-cost and high-value utilization of phosphogypsum. The results showed that H3PO4 can significantly accelerate the formation rate of the α-HH phase and that it did not participate in the formation of the α-HH phase in the form of eutectic phosphorus during crystalline phase transformation. In terms of crystal shape regulation, H3PO4 can impact the effect of a citric acid crystal regulator on α-HH crystal shape regulation. The more H3PO4 added, the greater the aspect ratio of α-HH. Accordingly, the water consumption and 2 h dry compressive strength of α-HH products were gradually increased and decreased with an increase in H3PO4 content, respectively. Despite this, the compressive strength of α-HH can still meet the requirements of the α20 grade in JC/T 2038-2010 "α High Strength Gypsum" in China when the H3PO4 content was limited to less than 0.4%.

Analyzing environmental impact assessment of income inequality, globalization, and growth in sub-Saharan African countries.

Despite the growing literature on the inequality-emissions nexus, this area of empirical interest is still inconclusive, particularly in the era of globalization. Hence, this empirical work investigates the effect of income inequality on carbon dioxide (CO2) emissions controlling the model for globalization. Considering the unique characteristics of various proxies of inequality, different proxies have been employed to develop an in-depth understanding of the inequality-emission nexus. The Driscoll-Kraay and generalized least square regression approaches are used for 38 sub-Saharan African countries from 1990 to 2016. Empirical results infer that higher income inequality promotes carbon reduction in the sample countries of the study. Further, findings suggest that globalization is beneficial for the environment by contributing to carbon emission mitigation. Several additional variables are used to validate the findings. The study offers some important policy implications in the end.

Ethanol Extract of Glycyrrhiza uralensis Fisch: Antidiarrheal Activity in Mice and Contraction Effect in Isolated Rabbit Jejunum.

OBJECTIVE: To evaluate the antidiarrheal effect of ethanol extract of Glycyrrhiza uralensis Fisch root (GFR) in vivo and jejunal contraction in vitro. METHODS: In vivo, 50 mice were divided into negative control, positive control (verapamil), low-, medium- and high-dose GFR (250, 500, 1,000 mg/kg) groups by a random number table, 10 mice in each group. The antidiarrheal activity was evaluated in castor oil-induced diarrhea mice model by evacuation index (EI). In vitro, the effects of GFR (0.01, 0.03, 0.1, 0.3, 1, 3, and 10 g/L) on the spontaneous contraction of isolated smooth muscle of rabbit jejunum and contraction of pretreated by Acetylcholine (ACh, 10 µmol/L) and KCl (60 mmol/L) were observed for 200 s. In addition, CaCl2 was accumulated to further study its mechanism after pretreating jejunal smooth muscle with GFR (1 and 3 g/L) or verapamil (0.03 and 0.1 µmol/L) in a Ca2+-free-high-K+ solution containing ethylene diamine tetraacetic acid (EDTA). RESULTS: GFR (500 and 1,000 mg/kg) significantly reduced EI in castor oil-induced diarrhea model mice (P<0.01). Meanwhile, GFR (0.01, 0.03, 0.1, 0.3, 1, 3, and 10 g/L) inhibited the spontaneous contraction of rabbit jejunum (P<0.05 or P<0.01). Contraction of jejunums samples pretreated by ACh and KCl with 50% effective concentration (EC50) values was 1.05 (0.71-1.24), 0.34 (0.29-0.41) and 0.15 (0.11-0.20) g/L, respectively. In addition, GFR moved the concentration-effect curve of CaCl2 down to the right, showing a similar effect to verapamil. CONCLUSIONS: GFR can effectively against diarrhea and inhibit intestinal contraction, and these antidiarrheal effects may be based on blocking L-type Ca2+ channels and muscarinic receptors.

Antidiarrheal effect of the ethanol extract from Scutellaria barbata and its effect on the contraction of jejunum smooth muscles.

Scutellaria barbata (S. barbata), a traditional herbal medicine used in southern China, possesses anti-inflammatory, antitumor, spasmolytic and expectorant effects. However, there are not many recent studies on its gastrointestinal effects. This study aimed to evaluate the antidiarrheal effect of the ethanol extract of S. barbata (SBE) and its effect on the isolated jejunum smooth muscle. METHODS: The antidiarrheal effect of SBE (doses: 125, 250 and 500 mg/kg) on castor oil-induced diarrhea was investigated in vivo. The effect of SBE (0.01-10 mg/mL) on spontaneous or acetylcholine chloride (ACh, 10µM)/KCl (60mM)-induced contraction of isolated rabbit jejunum smooth muscle was examined in vitro. The possible spasmolytic mechanism of SBE (1 and 3mg/mL) was analyzed by accumulating CaCl2 in a Ca2+-free high-K+ (60mM) solution. RESULTS: SBE (125, 250 and 500mg/kg) could delay the initial semi-solid onset time of mice and also reduce the diarrhea index in vivo. Furthermore, SBE (0.01-10mg/mL) could alleviate the spontaneous or ACh/KCl-induced contraction in vitro. SBE (1 and 3mg/mL) also inhibited the contraction induced by CaCl2, and the concentration-response curves of CaCl2 moved downward and to the right, similar to those of verapamil (0.01 and 0.1µM). CONCLUSIONS: SBE exerts antidiarrheal and spasmolytic effects, which provides a pharmacological basis for its use in functional gastrointestinal disorders.

Antidiarrheal effect of ethanol extract from Lophatheri Herba and its effect on isolated jejunal smooth muscle in rabbits.

Lophatheri Herba is a traditional Chinese medicine, which is commonly used in the treatment of fever, stomatitis, urodynia. The aim of the study is to evaluate the antidiarrheal activity of the ethanol extract of Lophatheri Herba (Gramineae, ELH) and observe its effect on isolated jejunum smooth muscle in rabbits, so that we can provide a possible pharmacological basis for its clinical use. Methods: In vivo, the antidiarrheal activity of ELH (250, 500 and 1000 mg/kg; orally) in castor oil-induced Kun Ming mice was evaluated. In vitro, the effect of ELH (0.01-10 mg/mL) on the spontaneous and ACh (10µM)/K+ (60mM)-induced contraction of isolated rabbit jejunum smooth muscle was studied. The possible mechanism of spasmolytic effect of ELH (1, 3mg/mL) was explored by pretreatment of intestinal tract with CaCl2. Results: ELH (500 and 1000mg/kg) exhibited antidiarrheal effect and it (0.01-10 mg/mL) inhibited the spontaneous and ACh/K+-induced contraction with an EC50 value of 1.27 (0.89-1.34), 0.76 (0.54-1.02) and 0.34 (0.27-0.53), it also shifted the concentration-response curves of CaCl2 to right with decreased in max, similar to verapamil. ELH has significant antidiarrheal and spasmolytic effect, this provides the pharmacological basis for use in gastrointestinal disorders.

Regioselective Fluoroalkylphosphorylation of Unactivated Alkenes by Radical-Mediated Alkoxyphosphine Rearrangement.

A novel distal radical rearrangement of alkoxyphosphine is developed for the first time and applied to the regioselective radical fluoroalkylphosphorylation of unactivated olefins. By employing a one-pot two-step reaction of (bis)homoallylic alcohols, organophosphine chlorides, and fluoroalkyl iodides under CFL (compact fluorescence light) irradiation, a series of fluoroalkylphosphorylated alkyl iodides and alcohols are easily synthesized by regiospecific installing a phosphonyl onto the inner carbon of terminal olefins and further iodination/hydroxylation. Mechanism studies reveal that the migration undergoes a distinctive radical cyclization/ß-scission on the lone electron pair of phosphorus, resulting in C-P bond formation and C-O bond cleavage.

Saikosaponin A Inhibits Growth of Human Bladder Carcinoma T24 and 5637 Cells Both in Vitro and in Vivo.

Saikosaponin A (SSA)-a natural compound extracted from Radix bupleuri-possesses antitumor properties in several types of carcinomas. However, the role of SSA on bladder cancer and the mechanisms remain unclear. In this study, we have described the effect of SSA on human bladder cancer cell lines T24 and 5637 in the context of the regulation of mitochondrial pathways of apoptosis. In vitro, the Cell Counting Kit-8 (CCK-8) assay and cell wound healing assays were used to determine the proliferative effect of SSA treatment. Flow cytometry and Western blotting were performed to evaluate the apoptosis and related mechanisms. To further confirm that apoptosis is mediated through Caspase activation, Hoechst 33258 fluorescence staining assay was done after cells were treated with SSA and caspase inhibitor-Z-VAD-FMK. In vivo, an orthotopic xenograft mice model was adopted to evaluate the effect of SSA. The tumors were analyzed by hematoxylin-eosin (H&E) staining, immunohistochemical analysis, and Western blotting. In vitro, the results with CCK-8 assay showed obvious SSA-induced suppression in cell growth in a dose- and time-dependent manner. Flow cytometry analysis, Hoechst 33258 fluorescence staining assay and the assessment of the changes in the B-cell lymphoma 2 (Bcl-2) family protein expression level revealed that SSA could significantly induce cell apoptosis, which was associated with apoptosis via the mitochondrial pathways. In vivo, the results revealed a reduction in cell proliferation. In conclusion, our data suggest that SSA inhibits the growth of bladder cancer cells by activating the mitochondrial apoptosis pathway and inducing cell apoptosis.

Sequential Catalytic Annulations: Divergent Synthesis of Heterocycles through a Radical [1,4]-Oxygen Shift.

A radical [1,4]-oxygen-atom transfer has been realized by the reaction of linear alkyne-tethered ketoximes and ethynylbenziodoxolones (EBX) under sequential catalytic conditions. Mechanism studies indicate that the O atom transfer experiences a cascade O atom radical cyclization/alkynylation/N-O bond photocleavage and subsequent N,O-diradical rearrangement. By the diversification of catalytic sequences, a series of structurally important 3H-pyrrol-3-ones and chlorinated furo[3,2-b]pyrroles are divergently synthesized along with an O atom shift under the catalysis of Cu/Ir photosensitization and Cu/Ir photosensitization/AlCl3, respectively.

Association of Chronic Respiratory Symptoms With Incident Cardiovascular Disease and All-Cause Mortality: Findings From the Coronary Artery Risk Development in Young Adults Study.

BACKGROUND: Respiratory and cardiovascular diseases (CVDs) frequently coexist; however, there is limited evidence on the relationship between chronic respiratory symptoms in young adulthood and late-onset CVD. RESEARCH QUESTION: Are chronic respiratory symptoms in young adulthood associated with CVD and all-cause mortality in later life? STUDY DESIGN AND METHODS: A total of 4,621 participants from the Coronary Artery Risk Development in Young Adults Study (CARDIA) cohort study aged 18 to 30 years were included. Chronic respiratory symptoms were identified through respiratory symptom questionnaires in two consecutive examinations. Incident CVD and all-cause mortality were adjudicated over 30-year follow-up. Multivariable Cox proportional hazards models were used to explore the association of chronic respiratory symptoms with incident CVD and all-cause mortality. RESULTS: During a median follow-up of 30.9 years, 284 CVD events (6.15%) and 378 deaths (8.18%) occurred. Following multivariable adjustment for demographic characteristics, cardiovascular risk factors, smoking, and lung function, the hazard ratios (95% CIs) for CVD events were 1.51 (1.18-1.93) for any respiratory symptom, 1.57 (1.18-2.09) for cough or phlegm, 1.31 (1.01-1.68) for wheeze, 1.73 (1.25-2.41) for shortness of breath, and 1.32 (1.01-1.71) for chest illnesses. Similar findings were also observed in all-cause mortality. Comparing zero vs three to four respiratory symptoms, the hazard ratios (95% CIs) were 1.97 (1.34-2.91) for CVD and 1.75 (1.23-2.47) for all-cause mortality. Similar results were observed in various sensitivity analyses. INTERPRETATION: Chronic respiratory symptoms in young adulthood are associated with an increased risk of CVD and all-cause mortality in midlife independent of established cardiovascular risk factors, smoking, and lung function. Identifying chronic respiratory symptoms in young adulthood may help provide prognostic information regarding future cardiovascular health. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT00005130; URL: https://www. CLINICALTRIALS: gov.

Corticotropin-releasing factor receptor 1 (CRF-R1) antagonists: Promising agents to prevent visceral hypersensitivity in irritable bowel syndrome.

Corticotropin-releasing factor (CRF) is a 41-amino acid polypeptide that coordinates the endocrine system, autonomic nervous system, immune system, and physiological behavior. CRF is a signaling regulator in the neuro-endocrine-immune (NEI) network that mediates visceral hypersensitivity. Rodent models to simulate changes in intestinal motility similar to those reported in the irritable bowel syndrome (IBS), demonstrate that the CRF receptor 1 (CRF-R1) mediates intestinal hypersensitivity under many conditions. However, the translation of preclinical studies into clinical trials has not been successful possibly due to the lack of sufficient understanding of the multiple variants of CRF-R1 and CRF-R1 antagonists. Investigating the sites of action of central and peripheral CRF is critical for accelerating the translation from preclinical to clinical studies.

Research on Labor Market Institutional Environment and Labor Agglomeration-Analysis Based on Dynamic Spatial Panel Data.

The institutional environment not only has a great impact on economic development but also has a certain impact on labor agglomeration. This paper explains the phenomenon of labor agglomeration from the perspective of the labor market institutional environment. Taking the labor market institutional environment including social contract environment and labor contract environment as the premise, it is considered that a good labor institutional market can promote labor agglomeration and technological progress can stimulate the agglomeration of highly-skilled talents through theoretical analysis. Based on the provincial panel data from 2001 to 2017, the empirical analysis is conducted to verify the relevant factors through the dynamic spatial Durbin model. The paper finally puts forward some policy suggestions to maintain a good institutional environment of the labor market, including that the local government should continue to improve the labor dispute settlement system, strengthen the protection of labor rights and interests, and enhance the institutional environment of the regional labor market.