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Our study aimed to systematically analyse the risk factors of coronavirus disease 2019 (COVID-19) patients with severe disease. An electronic search in eight databases to identify studies describing severe or critically ill COVID-19 patients from 1 January 2020 to 3 April 2020. In the end, we meta-analysed 40 studies involving 5872 COVID-19 patients. The average age was higher in severe COVID-19 patients (weighted mean difference; WMD = 10.69, 95%CI 7.83–13.54). Patients with severe disease showed significantly lower platelet count (WMD = −18.63, 95%CI −30.86 to −6.40) and lymphocyte count (WMD = −0.35, 95%CI −0.41 to −0.30) but higher C-reactive protein (CRP; WMD = 42.7, 95%CI 31.12–54.28), lactate dehydrogenase (LDH; WMD = 137.4, 95%CI 105.5–169.3), white blood cell count（WBC), procalcitonin（PCT）, D-dimer, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and creatinine（Cr）. Similarly, patients who died showed significantly higher WBC, D-dimer, ALT, AST and Cr but similar platelet count and LDH as patients who survived. These results indicate that older age, low platelet count, lymphopenia, elevated levels of LDH, ALT, AST, PCT, Cr and D-dimer are associated with severity of COVID-19 and thus could be used as early identification or even prediction of disease progression.

Among the various sources of human autologous stem cells, stem cells isolated from dental tissues exhibit excellent properties in tissue engineering and regenerative medicine. However, the distinct potential of these odontogenic cell lines remains unclear. In this study, we analyzed DNA methylation patterns to determine whether specific differences existed among three different odontogenic cell types. Using the HumanMethylation450 Beadchip, the whole genomes of human dental pulp stem cells (DPSCs), periodontal ligament stem cells (PDLSCs), and dental follicle progenitor cells (DFPCs) were compared. Then, the osteogenic potential of these cells was evaluated both in vitro and in vivo, and the methylation levels of certain genes related to bone formation differed among the three cell lines. P values less than 0.05 were considered to indicate statistical significance. The three cell types showed highly similar DNA methylation patterns, although specific differences were identified. Gene ontology analysis revealed that one of the most significantly different gene categories was related to bone formation. Thus, expression of cell surface epitopes and osteogenic-related transcription factors as well as the bone formation capacity were compared. The results showed that compared with DFPCs and DPSCs, PDLSCs had higher transcription levels of osteogenic-related factors, a higher in vitro osteogenic potential, and an increased new bone formation capacity in vivo. In conclusion, the results of this study suggested that the differential DNA methylation profiles could be related to the osteogenic potential of these human odontogenic cell populations. Additionally, the increased osteogenic potential of PDLSCs might aid researchers or clinicians in making better choices regarding tissue regeneration and clinical therapies.

The present study directly tested the hypothesis that deletion of the Na+/H+ exchanger 3 (NHE3) selectively in the proximal tubules of the kidney lowers basal blood pressure by increasing the pressure natriuresis response in mice. Adult male and female, age-matched wild-type littermates (WT) and proximal tubule-specific NHE3-knockout mice (PT-Nhe3−/−) (n=6–16 per group) were studied for 1) basal phenotypes of electrolytes and pH, blood pressure, and kidney function, 2) the pressure natriuresis response using the mesenteric, celiac and abdominal arterial occlusion technique, and 3) the natriuretic responses to acute saline expansion (0.9% NaCl, 10% body wt., i.p.) or 2-week of 2% NaCl diet. Under basal conditions, PT-Nhe3−/− mice showed significantly lower systolic, diastolic, and mean arterial blood pressure (p<0.01) than WT mice (p<0.01). PT-Nhe3−/− mice also exhibited significantly greater diuretic (p<0.01) and natriuretic responses than WT mice (p<0.01), without altering 24 h fecal Na+ excretion, plasma pH, Na+, and bicarbonate levels. In response to increased renal perfusion pressure by 30 mmHg, the pressure natriuresis response increased 5-fold in WT mice (p<0.01), but it increased 8-fold in PT-Nhe3−/− mice (p<0.01). In response to 10% acute saline expansion or 2-week 2% NaCl diet, more pronounced natriuretic responses were demonstrated in PT-Nhe3−/− than WT mice (p<0.01). Our results support the scientific premise and physiological relevance that NHE3 in the proximal tubules plays an essential role in maintaining basal blood pressure homeostasis, and genetic deletion of NHE3 selectively in the proximal tubules of the kidney lowers blood pressure by increasing the pressure natriuretic response.

The present study used a novel mouse model with proximal tubule-specific knockout of AT 1a receptors in the kidney, PT- Agtr1a −/− , to test the hypothesis that intratubular Ang II (angiotensin II) and AT 1a receptors in the proximal tubules are required for maintaining normal blood pressure and the development of Ang II–induced hypertension. Twenty-six groups (n=6–15 per group) of adult male wild-type, global Agtr1a −/− , and PT- Agtr1a −/− mice were infused with Ang II (1.5 mg/kg per day, IP), or overexpressed an intracellular Ang II fusion protein in the proximal tubules for 2 weeks. Basal telemetry blood pressure were ≈15±3 mm Hg lower in PT- Agtr1a −/− than wild-type mice and ≈13±3 mm Hg higher than Agtr1a −/− mice ( P <0.01). Basal glomerular filtration was ≈23.9% higher ( P <0.01), whereas fractional proximal tubule Na + reabsorption was lower in PT- Agtr1a −/− mice ( P <0.01). Deletion of AT 1a receptors in the proximal tubules augmented the pressure-natriuresis response ( P <0.01) and natriuretic responses to salt loading or Ang III infusion ( P <0.01). Ang II induced hypertension in wild-type, PT- Agtr1a −/− and PT- Nhe3 −/− mice, but the pressor response was ≈16±2 mm Hg lower in PT- Agtr1a −/− and PT- Nhe3 −/− mice ( P <0.01). Deletion of AT 1a receptors or NHE3 (Na + /H + exchanger 3) in the proximal tubules attenuated ≈50% of Ang II–induced hypertension in wild-type mice ( P <0.01), but blocked intracellular Ang II fusion protein-induced hypertension in PT- Agtr1a −/− mice ( P <0.01). Taken together, the results of the present study provide new insights into the critical role of intratubular Ang II/AT 1 (AT 1a )/NHE3 pathways in the proximal tubules in normal blood pressure control and the development of Ang II–induced hypertension.

The present study directly tested the hypothesis that the NHE3 (Na + /H + exchanger 3) in the proximal tubules of the kidney is required for the development of Ang II (angiotensin II)-induced hypertension using PT- Nhe3 −/− (proximal tubule-specific NHE3 knockout) mice. Specifically, PT- Nhe3 −/− mice were generated using the SGLT2-Cre / Nhe3 loxlox approach, whereas Ang II-induced hypertension was studied in 12 groups (n=5–12 per group) of adult male and female wild-type (WT) and PT- Nhe3 −/− mice. Under basal conditions, systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure were significantly lower in male and female PT- Nhe3 −/− than WT mice ( P <0.01). A high pressor, 1.5 mg/kg per day, intraperitoneal or a slow pressor dose of Ang II, 0.5 mg/kg per day, intraperitoneal for 2 weeks significantly increased systolic blood pressure, diastolic blood pressure, and mean arterial blood pressure in male and female WT mice ( P <0.01), but the hypertensive response to Ang II was markedly attenuated in male and female PT- Nhe3 −/− mice ( P <0.01). Ang II impaired the pressure-natriuresis response in WT mice, whereas proximal tubule-specific deletion of NHE3 improved the pressure-natriuresis response in Ang II-infused PT- Nhe3 −/− mice ( P <0.01). AT 1 receptor blocker losartan completely blocked Ang II-induced hypertension in both WT and PT- Nhe3 −/− mice ( P <0.01). However, inhibition of nitric oxide synthase with L-N G -Nitroarginine methyl ester had no effect on Ang II-induced hypertension in WT or PT- Nhe3 −/− mice (not significant). Furthermore, Ang II-induced hypertension was significantly attenuated by an orally absorbable NHE3 inhibitor AVE0657. In conclusion, NHE3 in the proximal tubules of the kidney may be a therapeutical target in hypertension induced by Ang II or with increased NHE3 expression in the proximal tubules.

Inflammatory bowel disease (IBD) is an intestinal immune-dysfunctional disease worldwide whose prevalence increasing in Asia including China. It is a chronic disease of the gastrointestinal tract with unknown cause. Exosomes are small vesicles in various body fluids. They have diameters of 40–120 nm, and one of their functions is long-distance transfer of various substances. In this study, we investigated the contents of salivary exosomes in patients with IBD and in healthy controls to explore a new biomarker in patients with IBD. In this study, whole saliva was obtained from patients with IBD (ulcerative colitis (UC), n = 37; Crohn’s disease (CD), n = 11) and apparently healthy individuals (HC, n = 10). Salivary exosomes were extracted from samples, and the proteins within the exosomes were identified by liquid chromatograph-mass spectrometer (LC-MS/MS). The results showed that more than 2000 proteins were detected in salivary exosomes from patients with IBD. Through gene ontology analysis, we found that proteasome subunit alpha type 7 (PSMA7) showed especially marked differences between patients with IBD and the healthy controls, in that its expression level was much higher in the CD and UC groups. This exosomal protein is related to proteasome activity and inflammatory responses. So we conclude that in this research, salivary exosomal PSMA7 was present at high levels in salivary exosomes from subjects with IBD. It can be a very promising biomarker to release the patients from the pain of colonoscopy.Electronic supplementary materialThe online version of this article (doi:10.1007/s13238-017-0413-7) contains supplementary material, which is available to authorized users.

Shape memory polymers (SMPs) change shapes as-designed through altering the chain segment movement by external stimuli, promising wide uses in actuators, sensors, drug delivery, and deployable devices. However, the recovery speed of SMPs is still far slower than the benchmark shape memory alloys (SMAs), originating from their intrinsic poor heat transport and retarded viscoelasticity of polymer chains. In this work, monolithic nanocomposite aerogels composed of bicontinuous graphene and SMP networks are designed to promote the recovery time of SMP composites to a record value of 50 ms, comparable to the SMA case. The integration of a stretchable graphene framework as a fast energy transformation grid with ultrathin polycaprolactone nanofilms (tunable at 2.5−60 nm) enables the rapid phase transition of SMPs under electrical stimulation. The graphene−SMP nanocomposite aerogels, with a density of ∼10 mg cm −3 , exhibit a fast response (175 ± 40 mm s −1 ), large deformation (∼100%), and a wide response bandwidth (0.1−20 Hz). The ultrafast response of SMP nanocomposite aerogels confers extensive uses in sensitive fuses, micro-oscillators, artificial muscles, actuators, and soft robotics. The design of bicontinuous ultralight aerogels can be extended to fabricate multifunctional and multiresponsive hybrid materials and devices.