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Natural polymer hydrogels have good mechanical properties and biocompatibility. This study designed hydroxyapatite-enhanced photo-oxidized double-crosslinked hydrogels. Hyaluronic acid (HA) and gelatin (Gel) were modified with methacrylate anhydride. The catechin group was further introduced into the HA chain inspired by the adhesion chemistry of marine mussels. Hence, the double-crosslinked hydrogel (HG) was formed by the photo-crosslinking of double bonds and the oxidative-crosslinking of catechins. Moreover, hydroxyapatite was introduced into HG to form hydroxyapatite-enhanced hydrogels (HGH). The results indicate that, with an increase in crosslinking network density, the stiffness of hydrogels became higher; these hydrogels have more of a compact pore structure, their anti-degradation property is improved, and swelling property is reduced. The introduction of hydroxyapatite greatly improved the mechanical properties of hydrogels, but there is no change in the stability and crosslinking network structure of hydrogels. These inorganic phase-enhanced hydrogels were expected to be applied to tissue engineering scaffolds.

The detection of all glands during total parathyroidectomy (TPTX) in secondary hyperparathyroidism (SHPT) patients is often difficult due to their variability in number and location. The objective of this study was to evaluate the feasibility of near-infrared fluorescence (NIRF) imaging using indocyanine green (ICG) for intraoperative parathyroid gland (PTG) localization in SHPT patients. Twenty-nine patients with SHPT were divided into two groups with or without intraoperative NIRF imaging. ICG was administered in patients undergoing intraoperative imaging, and the fluorescence of PTGs was assessed. Clinical and histopathologic variables were analyzed to determine factors associated with ICG uptake. Comparisons between NIRF and preoperative imaging, as well as differences between groups with or without NIRF imaging, were carried out to evaluate the efficacy of this technique. Most PTGs could be clearly identified, including one ectopic gland. The sensitivity of NIRF imaging is 91.1% in contrast to 81.82% for ultrasonography (US), 62.34% for 99m Tc-MIBI and 85.71% for computed tomography (CT). In addition, intraoperative NIRF imaging can reduce the operation time and improve the complete resection rate compared with the group not using it. Intraoperative NIRF imaging using ICG during TPTX is technically feasible and reliable for assisting surgeons in detecting and confirming PTGs.

The outbreak of coronavirus disease 2019 (COVID-19) that occurred in Wuhan, China, has become a global public health threat. It is necessary to identify indicators that can be used as optimal predictors for clinical outcomes of COVID-19 patients. The clinical information from 126 patients diagnosed with COVID-19 were collected from Wuhan Fourth Hospital. Specific clinical characteristics, laboratory findings, treatments and clinical outcomes were analyzed from patients hospitalized for treatment from 1 February to 15 March 2020, and subsequently died or were discharged. A random forest (RF) algorithm was used to predict the prognoses of COVID-19 patients and identify the optimal diagnostic predictors for patients' clinical prognoses. Seven of the 126 patients were excluded for losing endpoints, 103 of the remaining 119 patients were discharged (alive) and 16 died in the hospital. A synthetic minority over-sampling technique (SMOTE) was used to correct the imbalanced distribution of clinical patients. Recursive feature elimination (RFE) was used to select the optimal subset for analysis. Eleven clinical parameters, Myo, CD8, age, LDH, LMR, CD45, Th/Ts, dyspnea, NLR, D-Dimer and CK were chosen with AUC approximately 0.9905. The RF algorithm was built to predict the prognoses of COVID-19 patients based on the best subset, and the area under the ROC curve (AUC) of the test data was 100%. Moreover, two optimal clinical risk predictors, lactate dehydrogenase (LDH) and Myoglobin (Myo), were selected based on the Gini index. The univariable logistic analysis revealed a substantial increase in the risk for in-hospital mortality when Myo was higher than 80 ng/ml (OR = 7.54, 95% CI [3.42-16.63]) and LDH was higher than 500 U/L (OR = 4.90, 95% CI [2.13-11.25]). We applied an RF algorithm to predict the mortality of COVID-19 patients with high accuracy and identified LDH higher than 500 U/L and Myo higher than 80 ng/ml to be potential risk factors for the prognoses of COVID-19 patients in the early stage of the disease.

Otitis media is a middle ear disease common in children under three years old. Otitis media can occur in normal individuals with no other symptoms or syndromes, but it is often seen in individuals clinically diagnosed with genetic diseases such as CHARGE syndrome, a complex genetic disease caused by mutation in the Chd7 gene and characterized by multiple birth defects. Although otitis media is common in human CHARGE syndrome patients, it has not been reported in mouse models of CHARGE syndrome. In this study, we report a mouse model with a spontaneous deletion mutation in the Chd7 gene and with chronic otitis media of early onset age accompanied by hearing loss. These mice also exhibit morphological alteration in the Eustachian tubes, dysregulation of epithelial proliferation, and decreased density of middle ear cilia. Gene expression profiling revealed up-regulation of Muc5ac, Muc5b and Tgf-β1 transcripts, the products of which are involved in mucin production and TGF pathway regulation. This is the first mouse model of CHARGE syndrome reported to show otitis media with effusion and it will be valuable for studying the etiology of otitis media and other symptoms in CHARGE syndrome.

Atoh1 is a transcription factor that regulates neural development in multiple tissues and is conserved among species. Prior mouse models of Atoh1, though effective and important in the evolution of our understanding of the gene, have been limited by perinatal lethality. Here we describe a novel point mutation of Atoh1 (designated Atoh1(trhl) ) underlying a phenotype of trembling gait and hearing loss. Histology revealed inner ear hair cell loss and cerebellar atrophy. Auditory Brainstem Response (ABR) and Distortion Product Otoacoustic Emission (DPOAE) showed functional abnormalities in the ear. Normal lifespan and fecundity of Atoh1(trhl) mice provide a complementary model to facilitate elucidation of ATOH1 function in hearing,central nervous system and cancer biology.

Craniofacial defects that occur through gene mutation during development increase vulnerability to eustachian tube dysfunction. These defects can lead to an increased incidence of otitis media. We examined the effects of a mutation in the Sh3pxd2b gene (Sh3pxd2b(nee)) on the progression of otitis media and hearing impairment at various developmental stages. We found that all mice that had the Sh3pxd2b(nee) mutation went on to develop craniofacial dysmorphologies and subsequently otitis media, by as early as 11 days of age. We found noteworthy changes in cilia and goblet cells of the middle ear mucosa in Sh3pxd2b(nee) mutant mice using scanning electronic microscopy. By measuring craniofacial dimensions, we determined for the first time in an animal model that this mouse has altered eustachian tube morphology consistent with a more horizontal position of the eustachian tube. All mutants were found to have hearing impairment. Expression of TNF-α and TLR2, which correlates with inflammation in otitis media, was up-regulated in the ears of mutant mice when examined by immunohistochemistry and semi-quantitative RT-PCR. The mouse model with a mutation in the Sh3pxd2b gene (Sh3pxd2b(nee)) mirrors craniofacial dysmorphology and otitis media in humans.

Genetic susceptibility underlying otitis media (OM) remains to be understood. We show in this study that mutation in Phex gene predisposes the BALB/c-Phex(Hyp-Duk)/Y (abbreviated Hyp-Duk/Y) mice to OM, which occurs at post-natal day 21 (P21) with an average penetrance of 73%. The OM was identified by effusion in the middle ear cavity and/or thickening of middle ear mucosae, and was characterised by increase in goblet cells, deformity of epithelial cilia and higher expression of proliferating cell nuclear antigen (PCNA) in cells of the middle ear mucosae. Moreover, the transcription levels of Tlr2, Tlr4, Nfkb1, Ccl4, Il1b and Tnfα in the ears of the Hyp-Duk/Y mice at P35 were significantly upregulated, compared to those of the controls. Higher expression levels of TLR2, TLR4, NF-κB and TNF-α in the middle ears were demonstrated by immunohistochemistry (IHC). However, the OM in the mice was not prevented by azithromycin administration from gestational day 18 to P35. Further study showed that, in contrast to the low mRNA levels of Phex gene in the ears of the Hyp-Duk/Y mice, the mRNA level of Fgf23 was significantly elevated at P9, P14, P21 and P35. Meanwhile, mRNA levels of EP2 (PGE2 receptor), which expressed in the middle ear epithelia as demonstrated by IHC, were already increased at P14 even before the occurrence of OM, indicating that PGE2, an inflammatory mediator, is involved in the OM development in the mutants. Taking together, Phex mutation primarily up-regulates gene expression levels in FGF23 mediated pathways in the middle ears, resulting in cell proliferation and defence impairment at the mucosae and subsequently bacterial infection. The Hyp-Duk/Y mouse is a new genetic mouse model of OM.

Hearing loss is one of the most common sensory impairments in humans. Mouse mutant models helped us to better understand the mechanisms of hearing loss. Recently, we have discovered that the erlong (erl) mutation of the cadherin23 ( Cdh 23) gene leads to hearing loss due to hair cell apoptosis. In this study, we aimed to reveal the molecular pathways upstream to apoptosis in hair cells to exploit more effective therapeutics than an anti-apoptosis strategy. Our results suggest that endoplasmic reticulum (ER) stress is the earliest molecular event leading to the apoptosis of hair cells and hearing loss in erl mice. We also report that the ER stress inhibitor, Salubrinal (Sal), could delay the progression of hearing loss and preserve hair cells. Our results provide evidence that therapies targeting signaling pathways in ER stress development prevent hair cell apoptosis at an early stage and lead to better outcomes than those targeting downstream factors, such as tip-link degeneration and apoptosis.

Color is an important indicator for evaluating the quality of natural rubber (NR). Light-colored standard rubbers are widely used in high-grade products and have high economic value. This paper first introduces the history and test standards of the standard light-colored rubber. The origin of color deepening in NR processing, color substances, and its biosynthetic pathway are reviewed. Then, the discoloration mechanism of NR is studied from the perspectives of enzymatic browning (caused by polyphenol oxidase and polyphenols) and non-enzymatic browning (including Maillard reaction and lipid oxidation). Finally, the strategies to control the discoloration of NR will be described.

In 1904, China encouraged the business community to set up chambers of commerce in an effort to bridge the gulf between government officials and businessmen. They encouraged businesses to engage in industry and commerce, and to boost competitiveness with foreign capital investors. Over 45 years, spanning 1904 to 1949, Chinese chambers of commerce flourished and matured, and they played a key role in the structural and economic creation of modern China. This book documents the historical role of China's chambers of commerce.