Pervaporation Dehydration Mechanism and Performance of High-Aluminum ZSM-5 Zeolite Membranes for Organic Solvents.

Membrane-based pervaporation (PV) for organic solvent dehydration is of great significance in the chemical and petrochemical industries. In this work, high-aluminum ZSM-5 zeolite membranes were synthesized by a fluoride-assisted secondary growth on α-alumina tubular supports using mordenite framework inverted (MFI) nanoseeds (~110 nm) and a template-free synthesis solution with a low Si/Al ratio of 10. Characterization by XRD, EDX, and SEM revealed that the prepared membrane was a pure-phase ZSM-5 zeolite membrane with a Si/Al ratio of 3.8 and a thickness of 2.8 µm. Subsequently, two categories of PV performance parameters (i.e., flux versus separation factor and permeance versus selectivity) were used to systematically examine the effects of operating conditions on the PV dehydration performance of different organic solvents (methanol, ethanol, n-propanol, and isopropanol), and their PV mechanisms were explored. Employing permeance and selectivity effectively disentangles the influence of operating conditions on PV performance, thereby elucidating the inherent contribution of membranes to separation performance. The results show that the mass transfer during PV dehydration of organic solvents was mainly dominated by the adsorption-diffusion mechanism. Furthermore, the diffusion of highly polar water and methanol molecules within membrane pores had a strong mutual slowing-down effect, resulting in significantly lower permeance than other binary systems. However, the mass transfer process for water/low-polar organic solvent (ethanol, n-propanol, and isopropanol) mixtures was mainly controlled by competitive adsorption caused by affinity differences. In addition, the high-aluminum ZSM-5 zeolite membrane exhibited superior PV dehydration performance for water/isopropanol mixtures.

Pro-Inflammatory Cytokine TNF-α Attenuates BMP9-Induced Osteo/ Odontoblastic Differentiation of the Stem Cells of Dental Apical Papilla (SCAPs).

BACKGROUND/AIMS: Periapical periodontitis is a common oral disease caused by bacterial invasion of the tooth pulp, which usually leads to local release of pro-inflammatory cytokines and osteolytic lesion. This study is intended to examine the effect of TNF-α on BMP9-induced osteogenic differentiation of the stem cells of dental apical papilla (SCAPs). METHODS: Rat model of periapical periodontitis was established. TNF-α expression was assessed. Osteogenic markers and ectopic bone formation in iSCAPs were analyzed upon BMP9 and TNF-α treatment. RESULTS: Periapical periodontitis was successfully established in rat immature permanent teeth with periapical lesions, in which TNF-α was shown to release during the inflammatory phase. BMP9-induced alkaline phosphatase activity, the expression of osteocalcin and osteopontin, and matrix mineralization in iSCAPs were inhibited by TNF-α in a dose-dependent fashion, although increased AdBMP9 partially overcame TNF-α inhibition. Furthermore, high concentration of TNF-α effectively inhibited BMP9-induced ectopic bone formation in vivo. CONCLUSION: TNF-α plays an important role in periapical bone defect during the inflammatory phase and inhibits BMP9-induced osteoblastic differentiation of iSCAPs, which can be partially reversed by high levels of BMP9. Therefore, BMP9 may be further explored as a potent osteogenic factor to improve osteo/odontogenic differentiation in tooth regeneration in chronic inflammation conditions.

Light-Switchable Self-Healing Hydrogel Based on Host-Guest Macro-Crosslinking.

A self-healing hydrogel is prepared by crosslinking acrylamide with a host-guest macro-crosslinker assembled from poly(ß-cyclodextrin) nanogel and azobenzeneacrylamide. The photoisomerizable azobenzene moiety can change its binding affinity with ß-cyclodextrin, therefore the crosslinking density and rheology property of the hydrogel can be tuned with light stimulus. The hydrogel can repair its wound autonomously through the dynamic host-guest interaction. In addition, the wounded hydrogel will lose its ability of self-healing when exposed to ultraviolet light, and the self-healing behavior can be recovered upon the irradiation of visible light. The utilizing of host-guest macro-crosslinking approach manifests the as-prepared hydrogel reversible and light-switchable self-healing property, which would broaden the potential applications of self-healing polymers.

[Optimization and in vitro characterization of resveratrol-loaded poloxamer 403/407 mixed micelles].

The objectives of this study are to prepare resveratrol loaded mixed micelles composed of poloxamer 403 and poloxamer 407, and optimize the formulation in order to achieve higher drug solubility and sustained drug release. Firstly, a thin-film hydration method was utilized to prepare the micelles. By using drug-loading, encapsulation yield and particle size of the micelles as criteria, influence of three variables, namely poloxamer 407 mass fraction, amount of water and feeding of resveratrol, on the quality of the micelles was optimized with a central composite design method. Steady fluorescence measurement was carried out to evaluate the critical micelle concentration of the carriers. Micelle stability upon dilution with simulated gastric fluid and simulated intestinal fluid was investigated. The in vitro release of resveratrol from the mixed micelles was monitored by dialysis method. It was observed that the particle size of the optimized micelle formulation was 24 nm, with drug-loading 11.78%, and encapsulation yield 82.51%. The mixed micelles increased the solubility of resveratrol for about 197 times. Moreover, the mixed micelles had a low critical micelle concentration of 0.05 mg · mL(-1) in water and no apparent changes in particle size and drug content were observed upon micelles dilution, indicating improved kinetic stability. Resveratrol was released from the micelles in a controlled manner for over 20 h, and the release process can be well described by Higuchi equation. Therefore, resveratrol-loaded poloxamer 403/407 mixed micelles could improve the solubility of resveratrol significantly and sustained drug release behavior can be achieved.

Preparation of the new peptide drug ACTY116-loaded in situ forming implants and evaluation of its efficacy in pulmonary arterial hypertension and right ventricular hypertrophy induced by SU5416/hypoxia in mice.

There is a lack of effective therapeutic drugs for pulmonary arterial hypertension. Previous studies have demonstrated the positive cardiovascular system protective effects of the new peptide ACTY116. However, its stability in ordinary aqueous solution injections is poor and its half-life in the body is short, which has hindered the development of preparations. This study aimed to prepare in situ forming implants (ISFIs) of the peptide ACTY116 and investigate its impact on pulmonary arterial hypertension. We prepared ISFIs using NMP/TA as a solvent and PLGA as a polymer. These ISFIs exhibited low viscosity, low toxicity and sustained release properties. In a mouse model of pulmonary hypertension induced by SU5416/hypoxia, both ISFIs and ACTY116 peptides effectively reduced pulmonary hypertension, cardiac hypertrophy and pulmonary blood vessel wall thickness. In conclusion, this study highlights the potential of ACTY116 as a treatment for pulmonary arterial hypertension and suggests that incorporating it into an in-situ gel implant could be a promising option.

Association between inequalities in human resources for health and all cause and cause specific mortality in 172 countries and territories, 1990-2019: observational study.

OBJECTIVE: To explore inequalities in human resources for health (HRH) in relation to all cause and cause specific mortality globally in 1990-2019. DESIGN: Observational study. SETTING: 172 countries and territories. DATA SOURCES: Databases of the Global Burden of Disease Study 2019, United Nations Statistics, and Our World in Data. MAIN OUTCOME MEASURES: The main outcome was age standardized all cause mortality per 100 000 population in relation to HRH density per 10 000 population, and secondary outcome was age standardized cause specific mortality. The Lorenz curve and the concentration index (CCI) were used to assess trends and inequalities in HRH. RESULTS: Globally, the total HRH density per 10 000 population increased, from 56.0 in 1990 to 142.5 in 2019, whereas age standardized all cause mortality per 100 000 population decreased, from 995.5 in 1990 to 743.8 in 2019. The Lorenz curve lay below the equality line and CCI was 0.43 (P<0.05), indicating that the health workforce was more concentrated among countries and territories ranked high on the human development index. The CCI for HRH was stable, at about 0.42-0.43 between 1990 and 2001 and continued to decline (narrowed inequality), from 0.43 in 2001 to 0.38 in 2019 (P<0.001). In the multivariable generalized estimating equation model, a negative association was found between total HRH level and all cause mortality, with the highest levels of HRH as reference (low: incidence risk ratio 1.15, 95% confidence interval 1.00 to 1.32; middle: 1.14, 1.01 to 1.29; high: 1.18, 1.08 to 1.28). A negative association between total HRH density and mortality rate was more pronounced for some types of cause specific mortality, including neglected tropical diseases and malaria, enteric infections, maternal and neonatal disorders, and diabetes and kidney diseases. The risk of death was more likely to be higher in people from countries and territories with a lower density of doctors, dentistry staff, pharmaceutical staff, aides and emergency medical workers, optometrists, psychologists, personal care workers, physiotherapists, and radiographers. CONCLUSIONS: Inequalities in HRH have been decreasing over the past 30 years globally but persist. All cause mortality and most types of cause specific mortality were relatively higher in countries and territories with a limited health workforce, especially for several specific HRH types among priority diseases. The findings highlight the importance of strengthening political commitment to develop equity oriented health workforce policies, expanding health financing, and implementing targeted measures to reduce deaths related to inadequate HRH to achieve universal health coverage by 2030.

The Oral Microbiome as Mediator between Oral Hygiene and Its Impact on Nasopharyngeal Carcinoma.

Oral hygiene and the alteration of the oral microbiome have been linked to nasopharyngeal carcinoma (NPC). This study aimed to investigate whether the oral microbiome plays a mediating role in the relationship between oral hygiene and NPC, and identify differential microbial taxonomies that potentially mediated this association. We conducted a case-control study that involved 218 NPC patients and 192 healthy controls. The 16S rRNA gene sequencing of the V4 region was performed to evaluate the composition of the oral microbiome. Mediation analysis was applied to explore the relationship among oral hygiene, the oral microbiome and NPC. We found that dental fillings and poor oral hygiene score were associated with increased risks of NPC (OR = 2.51 (1.52-4.25) and OR = 1.54 (1.02-2.33)). Mediation analysis indicated that dental fillings increased the risk of NPC by altering the abundance of Erysipelotrichales, Erysipelotrichaceae, Solobacterium and Leptotrichia wadei. In addition, Leptotrichia wadei also mediated the association between oral hygiene score and the risk of NPC. Our study confirmed that poor oral hygiene increased the risk of NPC, which was partly mediated by the oral microbiome. These findings might help us to understand the potential mechanism of oral hygiene influencing the risk of NPC via the microbiome.

Effect and Blood Flow Parameters of Biomaterials-Based Endovascular Interventional Embolization and Craniotomy Clipping in the Treatment of Cerebral Aneurysms.

Objective: The effects of interventional embolization and craniotomy clipping on the treatment of intracranial aneurysms were investigated in this study, as well as their influence on the hemodynamics of postoperative patients. Methods: 102 patients with intracranial aneurysms were selected as the research objects, and they were rolled into an experimental (group A) and a control group (group B) according to the random number table method, with 51 cases in each group. The group A was treated with intravascular interventional embolization, and the group B received craniotomy clipping. Besides, a biodegradable magnesium titanium alloy biological stent was independently developed in this study, which was applied to endovascular interventional embolization in the group A. The hemodynamic model was established by using three-dimensional (3D) computer hemodynamic numerical simulation technology. Besides, the effects of all the patients before and after treatment were evaluated, in terms of blood pressure (BP), average wall shear stress (WSS) (AWSS), AWSS gradient (AWSSG), oscillatory shear index (OSI), aneurysm formation index (AFI), gradient oscillation number (GON), and intraoperative complication rate. Results: After 3 days of treatment, the BP, AWSS, and AWSSG of patients from the two groups were higher than those before treatment. The index values of the group A were greater markedly than the values of the group B (P < 0.05); the BP of the group A and the group B at the 0th day, 1st day, 3rd day, 5th day, and 7th day after treatment was 21±5.1 Versus 20.1±4.7, 22±4.8 Versus 21.1± 5.17, 26±6.2 Versus 22.31±5.21, 27±5.77 Versus 24.02±5.11, and 30±6.09 Versus 24.99±5.03, respectively; AWSSG values were 120±10.11 Versus 120.1±10.98, 130.1±10.36 Versus 123.3±11.06, 162.5±9.92 Versus 131.31±10.97, 171±8.13 Versus 155.02±8.36, and 200.1±7.22 Versus 180.01±8.98 in turn. GON and OSI were both decreased, and the values of various indexes in the group A were sharply lower than those of the group B (P < 0.05); the values of GON at the 0th day, 1st day, 3rd day, 5th day, and 7th day after treatment in the group A and the group B were 0.077±0.01 Versus 0.08±0.011, 0.07±0.012 Versus 0.073 ± 0.01, 0.051 ± 0.02 Versus 0.071 ± 0.011, 0.045 ± 0.01 Versus 0.069 ± 0.011, and 0.042 ± 0.012 Versus 0.063±0.013, respectively; OSI values were 4.8±0.51 Versus 4.9±0.52, 3.6±0.52 Versus 3.62±0.51, 2.82±0.51 Versus 3.1 ± 0.57, 1.9 ± 0.512 Versus 2.91 ± 0.51, and 0.5 ± 0.51 Versus 1.8 ± 0.501 in turn. By comparing the intraoperative complications and postoperative mortality risk score (MRS) of patients in the two groups, it was found that the incidence of intraoperative complications and postoperative MRS scores in the group A were lower steeply than those of the group B, suggesting that endovascular interventional embolization had a better effect on the treatment of intracranial aneurysms. Conclusion: Endovascular interventional embolization based on biodegradable magnesium alloy coated scaffold could better improve the distribution of shear stress on the vascular wall, stabilize vascular blood flow, and achieve better therapeutic effect for patients.

Multifunctional Graphene Oxide Nanodelivery Platform for Breast Cancer Treatment.

Background: Breast cancer (BC) has the highest global prevalence among all malignancies in women and the second highest prevalence in the overall population. Paclitaxel (PTX), a tricyclic diterpenoid, is effective against BC. However, its poor solubility in water and the allergenicity of its dissolution medium limited its clinical application. Methods: In this work, we established a multifunctional graphene oxide (GO) tumor-targeting drug delivery system using nanosized graphene oxide (nGO) modified with D-tocopherol polyethylene glycol succinate (TPGS) and arginine-glycine-aspartic acid (RGD) for PTX loading. Results: The obtained RGD-TPGS-nGO-PTX was 310.20±19.86 nm in size; the polydispersity index (PDI) and zeta potential were 0.21±0.020 and -23.42 mV, respectively. The mean drug loading capacity of RGD-TPGS-nGO-PTX was 48.78%. RGD-TPGS-nGO-PTX showed satisfactory biocompatibility and biosafety and had no significant toxic effects on zebrafish embryos. Importantly, it exerted excellent cytotoxicity against MDA-MB-231 cells, reversed multi-drug resistance (MDR) in MCF-7/ADR cells, and showed significant anti-tumor efficacy in tumor-bearing nude mice. Conclusion: These findings strongly suggested that the multifunctional GO tumor-targeting drug delivery system RGD-TPGS-nGO-PTX could be used in clinical settings to improve PTX delivery, reverse MDR and increase the therapeutic efficacy of BC treatment.

Periodontal Diseases and the Risk of Metabolic Syndrome: An Updated Systematic Review and Meta-Analysis.

Background: Periodontitis and metabolic syndrome (MetS) are two major global health problems that are widely prevalent in the world, although the former is a common infection in developing countries and the latter is a non-infectious but prevalent disease in developed countries. This study aims to provide an updated review on the existence and magnitude of the relationship between periodontal disease and the risk of MetS. Methods: We searched the PubMed, Web of Science, ScienceDirect, Chinese National Knowledge Infrastructure, and Wanfang databases for original studies assessing the association between periodontitis and MetS published before August 2019. We calculated the pooled crude and adjusted odds ratios (ORs) together with the 95% confidence intervals (95% CIs) to estimate the strength of this association. Subgroup analysis was performed by considering the diagnostic method or the country where the studies were performed. Results: We identified 43 potentially eligible articles for this systematic review, including 32 cross-sectional studies, eight case-control studies, and three cohort studies. Among them, 39 articles presented enough information to be included in the meta-analysis. The pooled crude and adjusted ORs were 1.99 (95% CI: 1.75-2.25) and 1.46 (95% CI: 1.31-1.61), respectively. Subgroup analysis showed a consistent relation stratified by either the diagnostic method or the country where the studies were performed. The pooled OR was 1.68 (95% CI: 1.41-2.00) for Japan, 1.75 (95% CI: 1.31-2.34) for the USA, 1.81 (95% CI: 1.35-2.42) for Korea, and 2.29 (95% CI: 1.53-3.41) for China. Conclusion: Our results provide compelling evidence for the association between periodontitis and MetS. Patients with periodontal disease are a critical screening population for MetS. We also recommend that people exhibiting components of MetS should receive a periodontal check-up and pay attention to their oral health.

[Three-dimensional morphological analysis of the palate of mouth-breathing children in mixed dentition].

OBJECTIVE: To study the effects of mouth-breathing on maxillary arch development by comparing the palatal morphology of mouth- and nose-breathing children in mixed dentition. METHODS: Children in mixed dentition were enrolled and categorized into mouth-breathing (test group) and nose-breathing groups (control group) according to their breathing patterns. Children's plaster models were scanned with 3D laser scanner, and the 3D data were reconstructed and measured using Minics 15.0 and Geomagic 12.0 software. Measurement data (inter-molar width, palatal height, palatal volume, and palatal surface area) of the two groups were compared, and the correlation among the four measurement items was analyzed. RESULTS: The participants were 73 children (37 in test group and 36 in control group) with a mean age of (8.63±0.78) years old. The test group had significantly smaller inter-molar width, palatal volume, and palatal surface area but significantly higher palatal height than the control group (P<0.05). Inter-molar width and palatal volume were positively correlated with the palatal surface area in the test group (P<0.05). Inter-molar width and palatal height were positively correlated with the palatal surface area in the control group (P<0.01). CONCLUSIONS: Mouth-breathing children have significantly reduced inter-molar width, palatal volume, and surface, and substantially increased palatal height, leading to different developmental patterns of the palatal morphology.

[Spatial, Temporal Distribution Characteristics and Potential Risk of PPCPs in Surface Sediments from Taihu Lake].

Fourteen sediment samples from 15 river estuaries and six sediments from 6 drinking water resource were collected from Taihu Lake. Nine pharmaceutical and personal care products(PPCPs) in the sediments samples were measured by using the HPLC-MS/MS technique. The ranges of geometric mean values were 1.60-129 ng·g-1 and 1.36-22.0 ng·g-1, respectively. Caffeine was the dominant pollutant in fourteen sediments near the river estuary, the content of which covered 52% of amounts of 9 PPCPs. Lincomycin, trimethoprime, azithromycin, sulfamethoxazole and tylosin were the dominant pollutants in six sediments near the drinking water resource, the contents of which covered 79% of amounts 9 PPCPs. From the point of spatial distribution, the results of PPCPs in Zhushan bay and East of Yixing in the northwest and west of Taihu Lake showed higher concentration than those in other sample sites. From the composition, the origin of PPCPs was different. Municipal sewage, stock farming and aquaculture were the main sources of PPCPs in Taihu Lake. Pharmaceuticals of human use showed the dominant pollution in fourteen sediments near the river estuary and drugs of veterinary use showed the dominant pollution in six sediments near the water resource. The concentrations of PPCPs in fourteen sediments of river mouth showed high level. It suggested that PPCPs pollutants were discharged to Taihu Lake continuously. Further risk assessment results showed that the overall risk was not high except for some PPCPs compounds. The RQ exceeded 1 for acetaminophen, azithromycin and sulfamethoxazole in the surface sediments of 15 river estuaries and 6 water resources, which showed high risk. The RQ was between 0.01 to 0.1 for carbazepine in the surface sediments of 15 river estuaries and 6 water resources, which showed medium risk. The RQ was below 0.01 for caffeine, lincomycin, trimethoprim, diltiazem and tylosin in the sediments of 15 river estuaries and 6 water resources, which showed low risk.

[Geographic distribution and gene sequencing of Paragonimus westermani in some areas of Guangdong Province].

OBJECTIVE: To investigate the current distribution of Paragonimus westermani in Guangdong Province. METHOD: Snails and crabs collected from mountain streams in regional survey sites were dissected to detect cercarial and metacercarial infections of P. westermani. Domestic cats and dogs artificially infected with the collected metacercariae were also dissected to detect adult worms of P. westermani. The COI and ITS2 gene sequences of those adult worms were compared with those of known Paragonimus specimen deposited in the GenBank. RESULTS: All of the first intermediate hosts in five survey sites of Liangkou, Nankun, Mountain, Dadong, Muxi, Guowu, were identified as Semisulcospira libertina, whose cercariae infection rates were 0.33%, 0.15%, 0.058%, 0.10%, and 0.05%, respectively; the second intermediate hosts in above five sites were all identified as Sinopotamon denticulatum, whose metacercariae infection rates were 100%, 100%, 38.09%, 55.36%, and 65.26%, respectively. The numbers of metacercariae in the five sites were 79.4, 105.66, 9.16, 16.18, and 15.6 per positive crab, respectively, and 11.12, 7.87, 0.58, 0.69, and 0.85 per gram of crab, respectively. All the metacercariae were identical to those of P. westermani. Adult worms and eggs of P. westermani were found in both reservoir hosts of domestic cats and dogs infected artificially. By comparing the COI genes of five representative samples from each survey site with that of Paragonimus #AF219379.21, AF540958.1 from GenBank, we found out the homology to be 99%, 99%, 99%, 98%, and 99%, respectively. In addition, a comparison of the ITS2 gene sequences between the above five samples and Paragonimus #DQ836243.1, DQ351845.1, AB354217.1 from GenBank revealed 98%, 99%, 98%, 98%, and 98% gene homology, respectively. CONCLUSION: Two ultra-high and three high endemic areas of P. westermani are discovered in Guangdong Province. No obvious differences were found among the types of P. westermani in the above five endemic areas.