The associations between peripheral inflammatory and lipid parameters, white matter hyperintensity, and cognitive function in patients with non-disabling ischemic cerebrovascular events.

BACKGROUND: The global prevalence of VCI has increased steadily in recent years, but diagnostic biomarkers for VCI in patients with non-disabling ischemic cerebrovascular incidents (NICE) remain indefinite. The primary objective of this research was to investigate the relationship between peripheral serological markers, white matter damage, and cognitive function in individuals with NICE. METHODS: We collected clinical data, demographic information, and medical history from 257 patients with NICE. Using the MoCA upon admission, patients were categorized into either normal cognitive function (NCF) or VCI groups. Furthermore, they were classified as having mild white matter hyperintensity (mWMH) or severe WMH based on Fazekas scores. We then compared the levels of serological markers between the cognitive function groups and the WMH groups. RESULTS: Among 257 patients with NICE, 165 were male and 92 were female. Lymphocyte count (OR = 0.448, P < 0.001) and LDL-C/HDL-C (OR = 0.725, P = 0.028) were protective factors for cognitive function in patients with NICE. The sWMH group had a higher age and inflammation markers but a lower MoCA score, and lymphocyte count than the mWMH group. In the mWMH group, lymphocyte count (AUC = 0.765, P < 0.001) and LDL-C/HDL-C (AUC = 0.740, P < 0.001) had an acceptable diagnostic value for the diagnosis of VCI. In the sWMH group, no significant differences were found in serological markers between the NCF and VCI groups. CONCLUSION: Lymphocyte count, LDL-C/HDL-C were independent protective factors for cognitive function in patients with NICE; they can be used as potential biological markers to distinguish VCI in patients with NICE and are applicable to subgroups of patients with mWMH.

Association of neutrophil to lymphocyte ratio and D-dimer with functional outcome in patients with cerebral venous sinus thrombosis.

BACKGROUND: Investigations on the risk factors for the prognosis of cerebral venous sinus thrombosis (CVST) are limited. This study aimed to explore whether specific inflammatory factors and coagulation indictors are associated with functional outcome in patients treated for CVST. METHODS: This retrospective study included 137 patients admitted to our hospital between January 2010 and October 2021. The functional outcome was assessed with the modified Rankin Scale (mRS) score at discharge. Patients were divided into two groups, 102 patients with favorable outcomes (mRS 0-1) and 35 patients with poor outcomes (mRS 2-6). The clinical indexes were compared between two groups. Multivariable logistic regression was performed to identify the independent influencing factors for poor outcomes of CVST patients. The prognostic indicators were analyzed using the receiver operating characteristic (ROC) curve. RESULTS: Compared with the favorable outcome group, the incidence of impaired consciousness and brain lesion, the levels of D-dimer, RDW, neutrophil count, neutrophil to lymphocyte ratio (NLR) and red blood cell distribution width to platelet ratio (%) on admission were significantly higher in the poor outcome group, while the level of lymphocyte count was significantly lower. After multivariable logistic regression analysis, baseline D-dimer level (odds ratio (OR), 1.180; 95% confidence interval (CI), 1.019-1.366, P = 0.027) and NLR (OR, 1.903; 95%CI, 1.232-2.938, P = 0.004) were significantly associated with unfavorable outcome at discharge. The ROC curve analysis showed that the areas under the curve of D-dimer, NLR and their combined detection for predicting worse outcome were 0.719, 0.707 and 0.786, respectively. CONCLUSIONS: Elevated D-dimer level and NLR on admission were associated with an increased risk of poor functional outcome in patients with CVST.

The Effect of Peri-Device Leaks on Ischaemic Stroke/Transient Ischaemic Attack/Systemic Embolism after Left Atrial Appendage Closure: A Systematic Review and Meta-Analysis.

BACKGROUND: Left atrial appendage closure (LAAC) is a safe and effective method for preventing embolic events in patients with non-valvular atrial fibrillation. However, peri-device leaks (PDLs) are sometimes unavoidable. Controversy exists regarding whether PDLs lead to embolic events. OBJECTIVES: This study aimed to explore the association between PDLs and embolic events, including ischaemic stroke, transient ischaemic attacks (TIAs), and systemic embolism (SE). METHODS: We conducted a systematic search of the PubMed, Web of Science, MEDLINE, and Cochrane Library databases for studies published up to September 25, 2022, to compare the rate of ischaemic stroke/TIA/SE between the PDL group and the non-PDL group after LAAC. RESULTS: Thirteen studies comprising 54,405 patients were included in the meta-analysis. The PDL group detected by transoesophageal echocardiography (TEE) had a significantly higher rate of ischaemic stroke/TIA/SE than the non-PDL group (OR: 1.20, 95% CI: 1.08-1.33, p = 0.0009). However, no difference in ischaemic stroke/TIA/SE was found between the PDL and non-PDL subgroups of the cardiac computed tomography angiography (CCTA) group (OR: 1.12, 95% CI: 0.51-2.50, p = 0.77). CCTA and TEE showed different rates of PDL detection, with the CCTA group having a higher rate of PDL detection (p < 0.0001), especially for trivial leaks. CONCLUSIONS: PDL detected by TEE increases the risk of embolic events after LAAC. However, no association was found between PDL and ischaemic stroke/TIA/SE in the CCTA group, which showed a higher rate of PDL detection than TEE, particularly for trivial leaks. In the future, CCTA may be used to explore the relationship between PDL size and ischaemic stroke/TIA/SE.

Lower 25-hydroxyvitamin D is associated with severer white matter hyperintensity and cognitive function in patients with non-disabling ischemic cerebrovascular events.

OBJECTIVES: This study aimed to investigate the potential correlations among serum 25-hydroxyvitamin D [25(OH)D] levels, white matter hyperintensity (WMH) and cognitive function in patients with non-disabling ischemic cerebrovascular events (NICE). METHODS: This was a prospective investigation of 160 NICE patients with age of 40 years or older. Cognitive function was evaluated by the Montreal Cognitive Assessment (MoCA). White matter lesions were evaluated by WMH using Fazekas scores. Spearman correlation analysis and linear regression models were used to identify the associations between serum 25(OH)D levels and cognitive function. Binary logistic regression analysis models were used to evaluate the predictable value of serum 25(OH)D levels and WMH for cognitive impairment. RESULTS: Patients with inadequate 25(OH)D levels had lower MoCA score (P=0.008), and a higher proportion of severe WMH (P=0.043). Spearman correlation analysis demonstrated that serum 25(OH)D concentrations were positively associated with MoCA score (rs=0.185, P=0.019) while negatively related to the proportion of severe WMH (sWMH) (rs=-0.166, P=0.036).The association between 25(OH)D concentrations and MoCA score remained significant in linear regression (adjusted ß=0.012, 95%CI:0.001-0.203).Adjusted binary logistic regression analysis showed that the odds ratio of cognitive impairment with insufficient 25(OH)D concentration was 5.038 (95%CI:1.154-21.988) compared with the sufficient group and the sWMH (OR=2.728, 95%CI:1.230-6.051) was identified as an independent risk factor for cognitive decline in NICE patients. CONCLUSION: Serum 25(OH)D levels and white matter lesions were independently and significantly associated with cognitive impairment in NICE patients.

A Underwater Sequence Image Dataset for Sharpness and Color Analysis.

The complex underwater environment usually leads to the problem of quality degradation in underwater images, and the distortion of sharpness and color are the main factors to the quality of underwater images. The paper discloses an underwater sequence image dataset called TankImage-I with gradually changing sharpness and color distortion collected in a pool. TankImage-I contains two plane targets, a total of 78 images. It includes two lighting conditions and three different water transparency. The imaging distance is also changed during the photographing process. The paper introduces the relevant details of the photographing process, and provides the measurement results of the sharpness and color distortion of the sequence images. In addition, we verify the performance of 14 image quality assessment methods on TankImage-I, and analyze the results of 14 image quality assessment methods from the aspects of sharpness and color, which provides a reference for the design and improvement of underwater image quality assessment algorithm and underwater imaging system design.

Chlorinated Paraffins in Two Snake Species from the Yangtze River Delta: Tissue Distribution and Biomagnification.

Very-short, short-, medium-, and long-chain chlorinated paraffins (vSCCPs, SCCPs, MCCPs, and LCCPs, respectively) were analyzed in different tissues of the terrestrial short-tailed mamushi (Gloydius brevicaudus) and the semi-aquatic red-backed rat snake (Elaphe rufodorsata) from the Yangtze River Delta, China. The total CP concentrations in liver, muscle, and adipose tissues in the two snake species were in the range of 2500-24 000, 4900-48 000, and 12-630 ng/g lw, respectively. Tissue burdens indicated that vSCCPs (C6-9) and SCCPs (C10-13) preferentially distributed to snake liver, while adipose was an important storage site and sink of MCCPs (C14-17) and LCCPs (C>18). On a lipid weight basis, vSCCPs and SCCPs were found in highest concentrations in red-backed rat snake liver and MCCPs and LCCPs in muscle, whereas for short-tailed mamushi, all CP groups were predominant in muscle, probably reflecting ecosystem/food web differences. Moreover, vSCCPs, SCCPs, MCCPs, and LCCPs were found to be biomagnified from black-spotted frogs to red-backed rat snakes with mean (maximum) biomagnification factors of 2.2 (3.4), 1.9 (3.7), 1.8 (2.8), and 1.7 (4.5), respectively. This is the first field study of biomagnification potential involving vSCCPs and LCCPs and highlights the need to include all CPs in studies.

Chlorinated Paraffins in Human Milk from Urban Sites in China, Sweden, and Norway.

Short-, medium-, and long-chain chlorinated paraffins (SCCPs, MCCPs, and LCCPs) were analyzed in human milk from the Yangtze River Delta (YRD) and Scandinavia. Individual samples were collected from Shanghai, Jiaxing, and Shaoxing (China), Stockholm (Sweden), and Bodø (Norway) between 2010 and 2016. Mean concentrations (range) of SCCPs, MCCPs, and LCCPs in samples from the YRD were 124 [

Tissue-Specific Accumulation, Sexual Difference, and Maternal Transfer of Chlorinated Paraffins in Black-Spotted Frogs.

The restriction on usage of short-chain chlorinated paraffins (SCCPs) under Stockholm Convention may promote the production and application of medium chain chlorinated paraffins (MCCPs) and long chain chlorinated paraffins (LCCPs) as substitutes. This study focused on the tissue-specific exposure to SCCPs, MCCPs, and LCCPs in black-spotted frog, a prevalent amphibian species in the Yangtze River Delta, China. The total CP concentrations in frog liver, muscle, and egg samples ranged of 35-1200, 6.3-97, and 6.8-300 ng/g wet weight (ww), respectively. Livers and eggs contained primary SCCPs (on average 78%) while MCCPs (43%) together with SCCPs (41%) were dominant in muscles. A significantly negative correlation was observed between hepatosomatic index and CPs concentration in liver ( p < 0.01), indicating that CP exposure may lower survival rates of frogs by suppressing the energy storage in liver. Additionally, maternal transfer, an important uptake pathway for CPs, was evaluated for the first time by calculating the ratios of CP levels in eggs to those in their paired liver tissues. The ratio of egg to liver for CP congener groups raised with the increasing of log Kow values, indicating mother to egg transport of CPs was related to the lipophilicity of the chemicals.

Method development for analyzing ultratrace polyhalogenated carbazoles in soil and sediment.

In the past few years, polyhalogenated carbazoles (PHCZs) have been of increasing concern because their structure is similar to that of legacy POPs. In the present study, an analytical method, including intensive cleanup and fractionation procedures in combination with instrumental parameters, was developed to determine ultratrace polyhalogenated carbazoles (PHCZs) in soil and sediment. The eluting sorbents, volume and packing of the column were optimized. Our results showed that 5 g of florisil and 4 g of silica gel under 150 mL of hexane/DCM = 3:1 presented good performance in terms of recovery and repeatability. GC-HRMS, GC-MS/MS (EI-MRM) and GC-MS (EI-SIM) were applied to compare the performance of PHCZ analysis. For sensitivity, EI-MRM presents method detection limits comparable to those of GC-HRMS and much lower than those of EI-SIM. Regarding selectivity, GC-HRMS performed better than the other two techniques since GC-HRMS can reduce interference from perfluorokerosene (PFK) and DDX (DDT, DDE, and DDD) due to its high resolution. GC-HRMS was then further optimized by shortening the run time and modifying the SIM ion. The final method was successfully applied to determine PHCZs in soil and sediment, and the target compounds had almost 100% detection frequency in the samples. The ubiquitous presence of PHCZ in soil and sediment calls for a further investigation of its source, distribution and degradation in the environment.

Short-, Medium-, and Long-Chain Chlorinated Paraffins in Wildlife from Paddy Fields in the Yangtze River Delta.

Short-chain chlorinated paraffins (SCCPs) were added to Annex A of the Stockholm Convention on Persistent Organic Pollutants in April, 2017. As a consequence of this regulation, increasing production and usage of alternatives, such as medium- and long-chain chlorinated paraffins (MCCPs and LCCPs, respectively), is expected. Little is known about the environmental fate and behavior of MCCPs and LCCPs. In the present study, SCCPs, MCCPs, and LCCPs were analyzed in nine wildlife species from paddy fields in the Yangtze River Delta, China, using atmospheric pressure chemical ionization-quadrupole time-of-flight mass spectrometry. SCCPs, MCCPs, and LCCPs were detected in all samples at concentrations ranging from <91-43 000, 96-33 000, and 14-10 000 ng/g lipid, respectively. Most species contained primarily MCCPs (on average 44%), with the exception of collared scops owl and common cuckoo, in which SCCPs (43%) accumulated to a significantly (i.e., p < 0.05) greater extent than MCCPs (40%). Cl6 groups were dominant in most species except for yellow weasel and short-tailed mamushi, which contained primarily Cl7 groups. Principal components analysis, together with CP concentrations and carbon stable isotope analysis showed that habitat and feeding habits were key factors driving CP accumulation and congener group patterns in wildlife. This is the first report of LCCP exposure in wildlife and highlights the need for data on risks associated with CP usage.

Food Insecurity Is Associated with Subsequent Cognitive Decline in the Boston Puerto Rican Health Study.

BACKGROUND: Living with hunger and fear of not having enough food is a growing worldwide concern. In our previous cross-sectional study, we found that food insecurity was associated with poor cognitive function, but the direction of this relation remains unclear. OBJECTIVE: We investigated whether food insecurity is associated with subsequent cognitive decline. METHODS: This was a longitudinal study of 597 participants aged 40-75 y from the Boston Puerto Rican Health Study cohort, with a Mini-Mental State Examination score of ≥24 at baseline. Food security was assessed at baseline with the US Household Food Security Scale. Participants completed cognitive batteries, which included 7 cognitive tests, twice-at baseline and again at a 2-y follow-up. The primary outcome was the change in global cognitive function over 2 y. Multiple linear regression was used to obtain adjusted mean differences and 95% CIs in cognitive decline across baseline food security status. RESULTS: Food insecurity at baseline was associated with a 2-y decline in global cognitive function (P-trend = 0.03) after adjusting for relevant potential confounders, including age, sex, baseline cognitive score, body mass index, education, poverty, acculturation score, depression score, smoking status, use of alcohol, physical activity score, presence of diabetes and hypertension, apolipoprotein E status, plasma homocysteine, healthy eating index, and time between baseline and follow-up measures. Compared with the food-secure group, the decline in the very low food security group was greater [mean difference: -0.26 (95% CI: -0.41, -0.10)]. Baseline food insecurity was significantly associated with a faster decline in executive function (P-trend = 0.02) but not memory function (P-trend = 0.66). CONCLUSIONS: Food insecurity was associated with faster cognitive decline in this cohort of Puerto Rican adults. Our study emphasizes the importance of developing interventions for food insecurity that take into account the impact of food insecurity on cognition.

Seasonal variation in the mating system of a selfing annual with large floral displays.

BACKGROUND AND AIMS: Flowering plants display considerable variation in mating system, specifically the relative frequency of cross- and self-fertilization. The majority of estimates of outcrossing rate do not account for temporal variation, particularly during the flowering season. Here, we investigated seasonal variation in mating and fertility in Incarvillea sinensis (Bignoniaceae), an annual with showy, insect-pollinated, 'one-day' flowers capable of delayed selfing. We examined the influence of several biotic and abiotic environmental factors on day-to-day variation in fruit set, seed set and patterns of mating. METHODS: We recorded daily flower number and pollinator abundance in nine 3 × 3-m patches in a population at Mu Us Sand land, Inner Mongolia, China. From marked flowers we collected data on daily fruit and seed set and estimated outcrossing rate and biparental inbreeding using six microsatellite loci and 172 open-pollinated families throughout the flowering period. KEY RESULTS: Flower density increased significantly over most of the 50-d flowering season, but was associated with a decline in levels of pollinator service by bees, particularly on windy days. Fruit and seed set declined over time, especially during the latter third of the flowering period. Multilocus estimates of outcrossing rate were obtained using two methods (the programs MLTR and BORICE) and both indicated high selfing rates of ∼80 %. There was evidence for a significant increase in levels of selfing as the flowering season progressed and pollinator visitation declined. Biparental inbreeding also declined significantly as the flowering season progressed. CONCLUSIONS: Temporal variation in outcrossing rates may be a common feature of the mating biology of annual, insect-pollinated plants of harsh environments but our study is the first to examine seasonal mating-system dynamics in this context. Despite having large flowers and showy floral displays, I. sinensis attracted relatively few pollinators. Delayed selfing by corolla dragging largely explains the occurrence of mixed mating in I. sinensis, and this mode of self-fertilization probably functions to promote reproductive assurance when pollinator service is limited by windy environmental conditions and competition from co-occurring flowering plants.

B7-H3 promotes aggression and invasion of hepatocellular carcinoma by targeting epithelial-to-mesenchymal transition via JAK2/STAT3/Slug signaling pathway.

BACKGROUND: B7-homologue 3 (B7-H3), a recently identified immunoregulatory protein, has been shown to be overexpressed in human hepatocellular carcinoma (HCC). However, whether the dynamic expression pattern of B7-H3 contributes to early invasion of HCC is largely unknown. In addition, the biological roles of B7-H3 in HCC are still unclear. Herein, we are going to examine B7-H3 expression profile and its clinicopathological significance in primary and metastatic HCC, and further determine whether B7-H3 knockdown simulates different pathological states of HCC progression and metastasis. METHODS: Using immunohistochemistry, B7-H3 expression was studied on 116 HCC containing primary and metastatic HCCs. Survival curves and log-rank tests were used to test the association of B7-H3 expression with survival. HCC cells with B7-H3 depletion were established by RNA interference to investigate the effect of B7-H3 on cell proliferation, apoptosis, migration and invasion in vitro. RESULTS: Statistical analysis of clinical cases revealed that B7-H3 high expression group had inclinations towards late TNM stage, the presence of vascular invasion, lymph metastasis, and the formation of microsatellite tumors. Increased intensity of tumor B7-H3 staining was detected more significantly in metastatic HCC tumors. Consistently in experiments performed in vitro, B7-H3 was able to stimulate the wound healing, metastasis and invasion of hepatoma cells by targeting epithelial-to-mesenchymal transition (EMT) via JAK2/Stat3/Slug signaling pathway, while no obvious influence on cell growth and apoptosis. CONCLUSION: B7-H3 in the regulation of the metastatic capacity of HCC cells makes itself a promising therapeutic target for anti-metastasis therapy.

Characteristics of the HIV/AIDS Epidemic in Women Aged 15-49 Years from 2005 to 2012 in China.

OBJECTIVE: To describe the characteristics of the HIV/AIDS epidemic in women aged 15-49 years in China. METHODS: HIV/AIDS cases from 2005 to 2012 that fulfilled the inclusion and exclusion criteria were identified on the Chinese HIV/AIDS case reporting system. Descriptive and spatial analyses were performed. RESULTS: A total of 103,559 female HIV/AIDS cases were included in our study. Based on the descriptive analysis, between 2005 and 2012, the proportion of heterosexually acquired HIV infection among women (15-49 years) increased rapidly from 35.8% to 87.4%. Approximately 60% of these cases were infected through non-marital heterosexual contact. Among older women (40-49 years), a slightly increasing trend was identified. The spatial analysis detected 'hot spots' in the Xinjiang, Yunnan, Sichuan, Guangxi, and Chongqing provinces. The epidemic trends in these areas were predominately driven by heterosexual transmission. CONCLUSION: Non-marital heterosexual contact is a very important factor in the HIV/AIDS epidemic in women aged 15-49 years, and the HIV infection rate in older women is increasing. Several epidemic hot spots were detected in northwestern and southwestern China. Efficient interventions are needed to control the spread of HIV/AIDS among women living in these areas.

The HIV, syphilis, and HCV epidemics among female sex workers in china: results from a serial cross-sectional study between 2008 and 2012.

BACKGROUND: Studies on the transmission of human immunodeficiency virus (HIV) and sexually transmitted diseases in female sex workers (FSWs) have been limited primarily to inferences drawn by focusing on defined geographical areas. METHODS AND FINDINGS: This serial cross-sectional study was conducted in mainland China from 2008 through 2012. Data for 827 079 participants was analyzed. We classified venues such as karaoke bars and hotels as high tier and venues such as hair salons and barbershops, massage parlors, and other public outdoor venues as low tier based on the participants' socioeconomic status. FSWs who worked at the venues and those who were present on the days of the survey were recruited. The prevalence of HIV decreased from 0.6% in 2008 to 0.3% in 2012, the syphilis prevalence ranged from 2.4% to 3.2% between 2008 and 2012, and hepatitis C virus (HCV) prevalence decreased from 0.9% in 2008 to 0.8% in 2012. Further, we found that HIV, syphilis, and HCV prevalence proportions were high in FSWs from low tiers. CONCLUSIONS: HIV, syphilis, and HCV prevalence among FSWs in our study decreased during the study period. Comprehensive intervention strategies, particularly those that focus on low-tier and older FSWs, are needed in order to decrease the disease burden in this population.

HIV/AIDS epidemic among older adults in China during 2005-2012: results from trend and spatial analysis.

BACKGROUND: Recent studies have indicated an increasing burden of human immunodeficiency virus (HIV)/AIDS among older adults. METHODS: All identified people living with HIV/AIDS (PLWHA) recorded through the Chinese HIV/AIDS CRS during 2005-2012 were included in the study, except for the cases that lacked specific spatial information. Trend tests and spatial analyses were conducted. RESULTS: Information about 73,521 PLWHA (aged ≥50 years) was collected during 2005-2012. Three provinces-Guangxi, Henan, and Yunnan-accounted for 54.4% of the identified cases during the study period. Compared with 2005, the ratio between residents and migrants among the study population decreased to 40.1% in 2012. The ratio of HIV-infected patients to AIDS patients and the ratio of males to females increased gradually among older infected adults. Results of spatial analysis indicate a clustered distribution of HIV/AIDS among older adults throughout the country. Hot spots were observed in 4 provinces (Guangxi, Henan, Yunnan, and Sichuan) and 1 municipality (Chongqing). A trend from central provinces toward southern provinces was also identified. CONCLUSIONS: The number and proportion of HIV/AIDS among older adults have increased in recent years. The hot spots showed movement from central to southern China. A focused intervention strategy targeting the older PLWHA is urgently required in China.

Epidemiologic studies of particulate matter and lung cancer.

Particulate matter (PM) plays an important role in air pollution, especially in China. European and American researchers conducted several cohort-based studies to examine the potential relationship between PM and lung cancer and found a positive association between PM and lung cancer mortality. In contrast, the results regarding PM and lung cancer risk remain inconsistent. Most of the previous studies had limitations such as misclassification of PM exposure and residual confounders, diminishing the impact of their findings. In addition, prospective studies on this topic are very limited in Chinese populations. This is an important problem because China has one of the highest concentrations of PM in the world and has had an increased mortality risk due to lung cancer. In this context, more prospective studies in Chinese populations are warranted to investigate the relationship between PM and lung cancer.

Effects of collagen modification on the osteogenic performance of different surface-modified titanium samples in vitro.

OBJECTIVES: The aim of this study was to evaluate the effects of collagen modification on the osteogenic performance of different surface-modified titanium, including alkaline etching, alkaline etching followed by silanization, and alkaline etching followed by dopamine modification. The proliferation, adhesion, and osteogenic differentiation abilities of MC3T3-E1 cells on the surfaces with collagen modification were analyzed and compared. METHODS: Collagen was immobilized on the surfaces of pure titanium (Ti-C), alkaline-etched titanium (Ti-Na-C), alkaline-etched and silanized titanium (Ti-A-C), and alkaline-etched and dopamine-modified titanium (Ti-D-C), with pure titanium (Ti) as the control group. The surface morphology was observed by scanning electron microscopy (SEM), and the surface elemental composition was analyzed by X-ray photoelectron spectroscopy (XPS). Contact angle measurements were conducted to evaluate the hydrophilicity of the surfaces. MC3T3-E1 cells were cultured on the surfaces, and their proliferation, adhesion, and osteogenic differentiation abilities were assessed using CCK-8 assay, laser scanning confocal microscope, alkaline phosphatase (ALP) staining, Alizarin red staining and quantitative analysis, as well as real-time quantitative polymerase chain reaction (RT-qPCR) to evaluate the mRNA expression levels of osteogenic-related genes, including ALP, typeⅠcollagen (COL-1), osteocalcin (OCN), osteopontin (OPN). RESULTS: SEM and XPS results confirmed the successful immobilization of collagen on the titanium surfaces, with the Ti-Na-C group exhibiting a higher amount of collagen modification. Contact angle measurements showed improved hydrophilicity of the surfaces after collagen modification. CCK-8 results indicated good compatibility of the materials with MC3T3-E1, with enhanced cell proliferation on the collagen-modified surfaces. Cell fluorescence staining revealed better cell spreading on the collagen-modified surfaces, and ALP and Alizarin red staining results suggested that the Ti-Na-C group exhibited the best osteogenic performance, with significantly higher absorbance values in the Alizarin red quantification analysis. RT-qPCR analysis showed that the Ti-Na-C group had the highest expression of the osteogenic-related gene OPN. CONCLUSIONS: Among the different collagen modification approaches employed in this study, collagen modification on alkaline-etched titanium surfaces showed the most conducive effects on MC3T3-E1 cell adhesion, spreading, proliferation, and osteogenic differentiation. This approach can be considered as the optimal collagen modification strategy for enhancing osteogenesis on titanium surfaces.

In Utero Gene Therapy and its Application in Genetic Hearing Loss.

For monogenic genetic diseases, in utero gene therapy (IUGT) shows the potential for early prevention against irreversible and lethal pathological changes. Moreover, animal models have also demonstrated the effectiveness of IUGT in the treatment of coagulation disorders, hemoglobinopathies, neurogenetic disorders, and metabolic and pulmonary diseases. For major alpha thalassemia and severe osteogenesis imperfecta, in utero stem cell transplantation has entered the phase I clinical trial stage. Within the realm of the inner ear, genetic hearing loss significantly hampers speech, cognitive, and intellectual development in children. Nowadays, gene therapies offer substantial promise for deafness, with the success of clinical trials in autosomal recessive deafness 9 using AAV-OTOF gene therapy. However, the majority of genetic mutations that cause deafness affect the development of cochlear structures before the birth of fetuses. Thus, gene therapy before alterations in cochlear structure leading to hearing loss has promising applications. In this review, addressing advances in various fields of IUGT, the progress, and application of IUGT in the treatment of genetic hearing loss are focused, in particular its implementation methods and unique advantages.