An Fgr kinase inhibitor attenuates sepsis-associated encephalopathy by ameliorating mitochondrial dysfunction, oxidative stress, and neuroinflammation via the SIRT1/PGC-1α signaling pathway.

BACKGROUND: Sepsis-associated encephalopathy (SAE) is characterized by diffuse brain dysfunction, long-term cognitive impairment, and increased morbidity and mortality. The current treatment for SAE is mainly symptomatic; the lack of specific treatment options and a poor understanding of the underlying mechanism of disease are responsible for poor patient outcomes. Fgr is a member of the Src family of tyrosine kinases and is involved in the innate immune response, hematologic cancer, diet-induced obesity, and hemorrhage-induced thalamic pain. This study investigated the protection provided by an Fgr kinase inhibitor in SAE and the underlying mechanism(s) of action. METHODS: A cecal ligation and puncture (CLP)-induced mouse sepsis model was established. Mice were treated with or without an Fgr inhibitor and a PGC-1α inhibitor/activator. An open field test, a novel object recognition test, and an elevated plus maze were used to assess neurobehavioral changes in the mice. Western blotting and immunofluorescence were used to measure protein expression, and mRNA levels were measured using quantitative PCR (qPCR). An enzyme-linked immunosorbent assay was performed to quantify inflammatory cytokines. Mitochondrial membrane potential and morphology were measured by JC-1, electron microscopy, and the MitoTracker Deep Red probe. Oxidative stress and mitochondrial dysfunction were analyzed. In addition, the regulatory effect of Fgr on sirtuin 1 (SIRT1) was assessed. RESULTS: CLP-induced sepsis increased the expression of Fgr in the hippocampal neurons. Pharmacological inhibition of Fgr attenuated CLP-induced neuroinflammation, the survival rate, cognitive and emotional dysfunction, oxidative stress, and mitochondrial dysfunction. Moreover, Fgr interacted with SIRT1 and reduced its activity and expression. In addition, activation of SIRT1/PGC-1α promoted the protective effects of the Fgr inhibitor on CLP-induced brain dysfunction, while inactivation of SIRT1/PGC-1α counteracted the benefits of the Fgr inhibitor. CONCLUSIONS: To our knowledge, this is the first report of Fgr kinase inhibition markedly ameliorating SAE through activation of the SIRT1/PGC-1α pathway, and this may be a promising therapeutic target for SAE.

Reversibly reconfigurable GSST metasurface for broadband beam steering and achromatic focusing in the long-wave infrared.

Active optical metasurfaces promise compact, lightweight, and energy-efficient optical systems with unprecedented performance. Chalcogenide phase-change material Ge2Sb2Se4Te1 (GSST) has shown tremendous advantages in the design of mid-infrared active metasurfaces. However, most of the GSST-based active metasurfaces can only work efficiently within a narrow frequency range. Furthermore, their design flexibility and reversible switching capability are severely restricted by the melting of GSST during re-amorphization. Here, we propose broadband, reversibly tunable, GSST-based transmissive metasurfaces operating in the long-wave infrared spectrum, where the GSST micro-rods are cladded by refractory materials. To accurately evaluate the performance of the proposed metasurfaces, two figures of merits are defined: FOMΦ for the evaluation of wavefront matching, and FOMop for the assessment of the overall performance incorporating both wavefront modulation efficiency and switching contrast ratio. For the proof of concept, two meta-devices are numerically presented: a multifunctional deflector that offers continuous beam steering and long-wave pass filtering simultaneously, and a large-area (1 cm × 1 cm) broadband (11-14 µm) varifocal metalens with the ability of achromatic imaging (12.5-13.5 µm). In particular, the metalens features high FOMop values over 16 dB in the achromatic band, with the average focusing efficiency approximating 70% (60%) in amorphous (crystalline) state and a spectral switching contrast ratio surpassing 25 dB. Our design scheme provides an additional degree of freedom for dynamic modulation and offers a novel approach for achieving high-efficiency mid-infrared compact optical devices.

Viral pathogens among elderly people with acute respiratory infections in Shanghai, China: Preliminary results from a laboratory-based surveillance, 2012-2015.

Acute respiratory infections (ARIs), with viral pathogens as the major contributors, are the most common illnesses worldwide, and increase the morbidity and mortality among the elderly population. The clinical and pathological features of elderly people with ARIs need to be identified for disease intervention. From January 1, 2012 through December 31, 2015, respiratory specimens from patients above 60 years old with ARIs were collected from the outpatient and inpatient settings of six sentinel hospitals in Pudong New Area. Each specimen was tested via multiplex polymerase chain reaction (PCR) for eight target viral etiologies including influenza, human rhinovirus (HRV), human para-influenza virus (PIV), adenovirus (ADV), respiratory syncytial virus (RSV), human metapneumovirus (hMPV), human coronavirus (hCoVs), and human bocavirus (hBoV). A total of 967 elderly patients with ARIs were enrolled, including 589 (60.91%) males, and the median age was 73 years old. 306 (31.64%) patients were tested positive for any one of the eight viruses, including 276 single infections and 30 co-infections. Influenza was the predominant virus (14.17%, 137/967), detected from 21.35% (76/356) of the outpatients and 9.98% (61/611) of the inpatients. Influenza infections presented two annual seasonal peaks during winter and summer. Compared with non-influenza patients, those with influenza were more likely to have fever, cough, sore throat, and fatigue. This study identified influenza as the leading viral pathogen among elderly with ARIs, and two seasonal epidemic peaks were observed in Shanghai. An influenza vaccination strategy needs to be advocated for the elderly population.

An outbreak of acute norovirus gastroenteritis in a boarding school in Shanghai: a retrospective cohort study.

BACKGROUND: More than 200 students and teachers at a boarding school in Shanghai developed acute gastroenteritis in December, 2012. The transmission mode remained largely unknown. An immediate epidemiological investigation was conducted to identify it. METHODS: Using a retrospective cohort design, we investigated demographic characteristics, school environment, and previous contacts with people who had diarrhea and/or vomiting, drinking water conditions, recalls of food consumption in the school cafeteria, hand-washing habits and eating habits. Rectal swabs of the new cases and food handlers as well as water and food samples were collected to test potential bacteria and viruses. Norovirus was detected by real-time reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: A total of 278 cases developed gastrointestinal symptoms in this outbreak, and the overall attack rate was 13.9%. The main symptoms included vomiting (50.0%), abdominal cramps (40.3%), nausea (27.0%), diarrhea (6.8%) and fever (6.8%). Twenty rectal swab samples were detected as Norovirus-positive, including 11 from student cases and 9 from asymptomatic food handlers (non-cases). Among environmental surface samples from the kitchen, 8 samples were also detected as Norovirus-positive. The genotypes of viral strains were the same (GII) in patients, asymptomatic food handlers and environmental surfaces. Other samples, including rectal swabs, water samples and food samples were negative for any bacteria and other tested viruses. Asymptomatic food handlers may have contaminated the cooked food during the food preparation. CONCLUSION: The study detected that the outbreak was caused by Norovirus and should be controlled by thorough disinfection and excluding asymptomatic food handlers from food preparation. Early identification of the predominant mode of transmission in this outbreak was necessary to prevent new cases. Furthermore, good hygiene practices such as regular hand washing and efficient daily disinfection should be promoted to prevent such infection and outbreaks.

Swimming short fibrous nasal drops achieving intraventricular administration.

Adequate drug delivery across the blood-brain barrier (BBB) is a critical factor in treating central nervous system (CNS) disorders. Inspired by swimming fish and the microstructure of the nasal cavity, this study is the first to develop swimming short fibrous nasal drops that can directly target the nasal mucosa and swim in the nasal cavity, which can effectively deliver drugs to the brain. Briefly, swimming short fibrous nasal drops with charged controlled drug release were fabricated by electrospinning, homogenization, the π-π conjugation between indole group of fibers, the benzene ring of leucine-rich repeat kinase 2 (LRRK2) inhibitor along with charge-dipole interaction between positively charged poly-lysine (PLL) and negatively charged surface of fibers; this enabled these fibers to stick to nasal mucosa, prolonged the residence time on mucosa, and prevented rapid mucociliary clearance. In vitro, swimming short fibrous nasal drops were biocompatible and inhibited microglial activation by releasing an LRRK2 inhibitor. In vivo, luciferase-labelled swimming short fibrous nasal drops delivered an LRRK2 inhibitor to the brain through the nasal mucosa, alleviating cognitive dysfunction caused by sepsis-associated encephalopathy by inhibiting microglial inflammation and improving synaptic plasticity. Thus, swimming short fibrous nasal drops is a promising strategy for the treatment of CNS diseases.

Corrigendum to "Cilengitide inhibits osteoclast adhesion through blocking the αvß3-mediated FAK/Src signaling pathway" [Heliyon 9(7) (July 2023) e17841].

[This corrects the article DOI: 10.1016/j.heliyon.2023.e17841.].

Cancer incidence and patient survival rates among the residents in the Pudong New Area of Shanghai between 2002 and 2006.

With the growing threat of malignancy to health, it is necessary to analyze cancer incidence and patient survival rates among the residents in Pudong New Area of Shanghai to formulate better cancer prevention strategies. A total of 43,613 cancer patients diagnosed between 2002 and 2006 were recruited from the Pudong New Area Cancer Registry. The incidence, observed survival rate, and relative survival rate of patients grouped by sex, age, geographic area, and TNM stage were calculated using the Kaplan-Meier, life table, and Ederer II methods, respectively. Between 2002 and 2006, cancer incidence in Pudong New Area was 349.99 per 100,000 person-years, and the 10 most frequently diseased sites were the lung, stomach, colon and rectum, liver, breast, esophagus, pancreas, brain and central nervous system, thyroid, and bladder. For patients with cancers of the colon and rectum, breast, thyroid, brain and central nervous system, and bladder, the 5-year relative survival rate was greater than 40%, whereas patients with cancers of the liver and pancreas had a 5-year relative survival rate of less than 10%. The 1-year to 5-year survival rates for patients grouped by sex, age, geographic area, and TNM stage differed significantly (all P < 0.001). Our results indicate that cancer incidence and patient survival in Pudong New Area vary by tumor type, sex, age, geographic area, and TNM stage.

Gene Screening for Non-Syndromic Deafness in Hainanese Patients.

BACKGROUND: Hainan Province is the southernmost island in China, far from the mainland, and the resident population changes little. In order to understand the mutation spectrum in Hainan and provide effective genetic counseling for deaf people, we carried out genetic analysis on the non-comprehensive hearing impairment in this population. Therefore, in this study, 183 children with moderate sensorineural deafness in the northeast of Hainan were analyzed with susceptibility gene carrying and gene mutation, providing some reference for hainan to guide the prevention and treatment of deafness. METHODS: Complete clinical evaluations were performed on 183 unrelated patients with a non-syndromic hearing impairment from Hainan Province. Each subject was screened for common mutations using the matrix-assisted laser desorption ionization-time of flight mass spectrometry, including GJB2 c.35delG,c.235delC,c.299_300del AT,c.176_191del16,c.167delT; GJB3 c.538 C>T,c.547G >A;SLC26A4 IVS7-2 A>G,c.2168 A>G,c.1174A>T,c.1229 C>T,c.1226G>A,c.1975G>C,c.2027T>A,c.2162C>T,c.281C>T,c.589G>A,IVS15+5G>A; and mtRNA 1494 C>T,1555 A>G. RESULTS: Genetic analysis showed that GJB2, SLC26A4, and mitochondrial M. 1555A > G mutations accounted for 7.10%, 8.74%, and 0.55% of the etiology of non-syndromic hearing impairment, respectively. Common mutations include GJB2 C. 235delC, SLC26A4 c.I vs7-2a →G, C. 2168A→G, and mitochondrial M. 1555A > G. The total mutation rate in Hainan was 16.39%. CONCLUSION: Our study is the first one to carry out genetic analysis on non-syndromic hearing impairment in Hainan. The results show that in the cases of non-syndromic hearing impairment in these areas, there is a clear genetic cause accounted for 16.39%, and the mutation hot spots are mainly GJB2 and SLC26A4, and SLC26A4 is the most common mutation site. This study provides useful and targeted information for genetic counseling of deafness in people with non-syndromic hearing impairment in Hainan.

Integrated analysis of multiple transcriptomic data identifies ST8SIA6­AS1 and LINC01093 as potential biomarkers in HBV­associated liver cancer.

The mechanisms of long-non-coding RNAs (lncRNAs) in hepatitis B virus (HBV) infection-associated liver cancer remain largely unclear. Therefore, the aim of the present study was to investigate the regulatory mechanisms of lncRNAs in this disease. HBV-liver cancer related transcriptome expression profile data (GSE121248 and GSE55092) from the Gene Expression Omnibus database and survival prognosis information from The Cancer Genome Atlas (TCGA) database were obtained for analysis. The limma package was used to identify the overlapped differentially expressed RNAs (DERs), including DElncRNAs and DEmRNAs, in the GSE121248 and GSE55092 datasets. The screened optimized lncRNA signatures were used to develop a nomogram model based on the GSE121248 dataset, which was validated using the GSE55092 and TCGA datasets. A competitive endogenous RNA (ceRNA) network was constructed based on the screened prognosis-associated lncRNA signatures from TCGA dataset. In addition, the levels of specific lncRNAs were evaluated in HBV-infected human liver cancer tissues and cells, and Cell Counting Kit-8, ELISA and Transwell assays were performed to evaluate the effects of the lncRNAs in HBV-expressing liver cancer cells. A total of 535 overlapped DERs, including 30 DElncRNAs and 505 DEmRNAs, were identified in the GSE121248 and GSE55092 datasets. An optimized DElncRNA signature comprising 10 lncRNAs was used to establish a nomogram. ST8SIA6-AS1 and LINC01093 were identified as lncRNAs associated with HBV-liver cancer prognosis in TCGA dataset, and were applied to construct a ceRNA network. Reverse transcription-quantitative PCR analysis showed that ST8SIA6-AS1 was upregulated and LINC01093 was downregulated in HBV-infected human liver cancer tissues and HBV-expressing liver cancer cells compared with non-HBV-infected controls. ST8SIA6-AS1 knockdown and LINC01093 overexpression independently reduced the number of copies of HBV DNA, the levels of hepatitis B surface antigen and hepatitis B e antigen, as well as cell proliferation, migration and invasion. In summary, the present study identified ST8SIA6-AS1 and LINC01093 as two potential biomarkers that may be effective therapeutic targets for HBV-associated liver cancer.

Acid-sensing ion channel 1a modulation of apoptosis in acidosis-related diseases: implications for therapeutic intervention.

Acid-sensing ion channel 1a (ASIC1a), a prominent member of the acid-sensing ion channel (ASIC) superfamily activated by extracellular protons, is ubiquitously expressed throughout the human body, including the nervous system and peripheral tissues. Excessive accumulation of Ca2+ ions via ASIC1a activation may occur in the acidified microenvironment of blood or local tissues. ASIC1a-mediated Ca2+­induced apoptosis has been implicated in numerous pathologies, including neurological disorders, cancer, and rheumatoid arthritis. This review summarizes the role of ASIC1a in the modulation of apoptosis via various signaling pathways across different disease states to provide insights for future studies on the underlying mechanisms and development of therapeutic strategies.

Cerium Oxide Nanoparticles Conjugated with Tannic Acid Prevent UVB-Induced Oxidative Stress in Fibroblasts: Evidence of a Promising Anti-Photodamage Agent.

Exposure to ultraviolet radiation induces photodamage towards cellular macromolecules that can progress to photoaging and photocarcinogenesis. The topical administration of compounds that maintain the redox balance in cells presents an alternative approach to combat skin oxidative damage. Cerium oxide nanoparticles (CNPs) can act as antioxidants due to their enzyme-like activity. In addition, a recent study from our group has demonstrated the photoprotective potential of tannic acid (TA). Therefore, this work aimed to synthesize CNPs associated with TA (CNP-TA) and investigate its photoprotective activity in L929 fibroblasts exposed to UVB radiation. CNP conjugation with TA was confirmed by UV-Vis spectra and X-ray photoelectron spectroscopy. Bare CNPs and CNP-TA exhibited particle sizes of ~5 and ~10 nm, superoxide dismutase activity of 3724 and 2021 unit/mg, and a zeta potential of 23 and -19 mV, respectively. CNP-TA showed lower cytotoxicity than free TA and the capacity to reduce the oxidative stress caused by UVB; supported by the scavenging of reactive oxygen species, the prevention of endogenous antioxidant system depletion, and the reduction in oxidative damage in lipids and DNA. Additionally, CNP-TA improved cell proliferation and decreased TGF-ß, metalloproteinase-1, and cyclooxygenase-2. Based on these results, CNP-TA shows therapeutic potential for protection against photodamage, decreasing molecular markers of photoaging and UVB-induced inflammation.

An osteogenic magnesium alloy with improved corrosion resistance, antibacterial, and mechanical properties for orthopedic applications.

The aim of this study was to develop a novel biodegradable magnesium (Mg) alloy for bone implant applications. We used scandium (Sc; 2 wt %) and strontium (Sr; 2 wt %) as alloying elements due to their high biocompatibility, antibacterial efficacy, osteogenesis, and protective effects against corrosion. In the present work, we also examined the effect of a heat treatment process on the properties of the Mg-Sc-Sr alloy. Alloys were manufactured using a metal casting process followed by heat treatment. The microstructure, corrosion, mechanical properties, antibacterial activity, and osteogenic activity of the alloy were assessed in vitro. The results showed that the incorporation of Sc and Sr elements controlled the corrosion, reduced the hydrogen generation, and enhanced mechanical properties. Furthermore, alloying with Sc and Sr demonstrated a significantly enhanced antibacterial activity and decreased biofilm formation compared to control Mg. Also, culturing Mg-Sc-Sr alloy with human bone marrow-derived mesenchymal stromal cells showed a high degree of biocompatibility (>90% live cells) and a significant increase in osteoblastic differentiation in vitro shown by Alizarin red staining and alkaline phosphatase activity. Based on these results, the Mg-Sc-Sr alloy heat-treated at 400°C displayed optimal mechanical properties, corrosion rate, antibacterial efficacy, and osteoinductivity. These characteristics make the Mg-Sc-Sr alloy a promising candidate for biodegradable orthopedic implants in the fixation of bone fractures such as bone plate-screws or intramedullary nails.

Cilengitide inhibits osteoclast adhesion through blocking the αvß3-mediated FAK/Src signaling pathway.

The remodeling of actin cytoskeleton of osteoclasts on the bone matrix is essential for osteoclastic resorption activity. A specific regulator of the osteoclast cytoskeleton, integrin αvß3, is known to provide a key role in the degradation of mineralized bone matrixes. Cilengitide is a potent inhibitor of integrins and is capable of affecting αvß3 receptors, and has anti-tumor and anti-angiogenic and apoptosis-inducing effects. However, its function on osteoclasts is not fully understood. Here, the cilengitide role on nuclear factor κB ligand-receptor activator (RANKL)-induced osteoclasts was explored. Cells were cultured with varying concentrations of cilengitide (0,0.002,0.2 and 20 µM) for 7 days, followed by detected via Cell Counting Kit-8, staining for tartrate resistant acid phosphatase (TRAP), F-actin ring formation, bone resorption assays, adhesion assays, immunoblotting assays, and real-time fluorescent quantitative PCR. Results demonstrated that cilengitide effectively restrained the functionality and formation of osteoclasts in a concentration-dependent manner, without causing any cytotoxic effects. Mechanistically, cilengitide inhibited osteoclast-relevant genes expression; meanwhile, cilengitide downregulated the expression of key signaling molecules associated with the osteoclast cytoskeleton, including focal adhesion kinase (FAK), integrin αvß3 and c-Src. Therefore, this results have confirmed that cilengitide regulates osteoclast activity by blocking the integrin αvß3 signal pathway resulting in diminished adhesion and bone resorption of osteoclasts.

Citric acid-modified pH-sensitive bone-targeted delivery of estrogen for the treatment of postmenopausal osteoporosis.

Bone targeted delivery of estrogen offers great promise for the clinical application of estrogen in the treatment of postmenopausal osteoporosis (PMOP). However, the current bone-targeted drug delivery system still has several issues that need to be solved, such as the side effects of bone-targeted modifier molecules and the failure of the delivery system to release rapidly in the bone tissue. It is important to aggressively search for new bone-targeted modifier molecules and bone microenvironment-responsive delivery vehicles. Inspired by the distribution of citric acid (CA) mainly in bone tissue and the acidic bone resorption microenvironment, we constructed a CA-modified diblock copolymer poly(2-ethyl-2-oxazoline)-poly(ε-caprolactone) (CA-PEOz) drug delivery system. In our study, we found that the CA modification significantly increased the bone targeting of this drug delivery system, and the delivery system was able to achieve rapid drug release under bone acidic conditions. The delivery system significantly reduced bone loss in postmenopausal osteoporotic mice with a significant reduction in estrogenic side effects on the uterus. In summary, our study shows that CA can act as an effective bone targeting modifier molecule and provides a new option for bone targeting modifications. Our study also provides a new approach for bone-targeted delivery of estrogen for the treatment of PMOP.

A novel approach for the prevention of ionizing radiation-induced bone loss using a designer multifunctional cerium oxide nanozyme.

The disability, mortality and costs due to ionizing radiation (IR)-induced osteoporotic bone fractures are substantial and no effective therapy exists. Ionizing radiation increases cellular oxidative damage, causing an imbalance in bone turnover that is primarily driven via heightened activity of the bone-resorbing osteoclast. We demonstrate that rats exposed to sublethal levels of IR develop fragile, osteoporotic bone. At reactive surface sites, cerium ions have the ability to easily undergo redox cycling: drastically adjusting their electronic configurations and versatile catalytic activities. These properties make cerium oxide nanomaterials fascinating. We show that an engineered artificial nanozyme composed of cerium oxide, and designed to possess a higher fraction of trivalent (Ce3+) surface sites, mitigates the IR-induced loss in bone area, bone architecture, and strength. These investigations also demonstrate that our nanozyme furnishes several mechanistic avenues of protection and selectively targets highly damaging reactive oxygen species, protecting the rats against IR-induced DNA damage, cellular senescence, and elevated osteoclastic activity in vitro and in vivo. Further, we reveal that our nanozyme is a previously unreported key regulator of osteoclast formation derived from macrophages while also directly targeting bone progenitor cells, favoring new bone formation despite its exposure to harmful levels of IR in vitro. These findings open a new approach for the specific prevention of IR-induced bone loss using synthesis-mediated designer multifunctional nanomaterials.

Study on the mechanism of public attention to a major event: The outbreak of COVID-19 in China.

This study focuses on public attention to major events, which has become an important topic in the context of the COVID-19 pandemic. In the background of the global transmission of COVID-19, this study discusses the relationship between information shock and sustainable development, which is rarely mentioned before. By developing an appropriate theoretical model, we discuss how the level of public attention changes over time and with the severity of events. Then we use data on the daily clicks on a popular Chinese medical website to indicate public attention to the pandemic. Our analysis shows that, in the first half of 2020, the level of public attention is closely related to the scale of domestic transmission. The marginal effect of the domestic cases in the first wave is 1% to 0.217%. After the pandemic was largely under control in China, people still followed the latest news, but the scale of public attention to regional transmission diminished. And when the pandemic quickly and severely worsened in other countries, people in China were very attentive, that is, public attention increased. The time interval of social reaction we calculate is fairly stable, with a value of between 0 and 5 most of the time. The average time interval from January 2020 to May 2021 ranges from 1.76 days to 1.94 days, depending on the choice of models and parameters. This study suggests that raising public participation in dealing with the crisis over the long term would be enhanced in China by media encouragement to pay more attention to small-scale regional transmission and the course of the pandemic in other countries. The goal of sustainable development requires dealing with health and economic crises much better in the long term. Thus, the model and method used in the paper serve to enhance general interest.

[Correlation of temporal bone HRCT, SLC26A4 gene and hearing loss in enlarged vestibular aqueduct].

Objective:To explore the correlation between high-resolution computed tomography（HRCT） of temporal bones, SLC26A4 gene mutation and hearing loss in patients with enlarged vestibular aqueduct（EVA）. Methods:The medical records of 257 subjects hospitalized for moderate to severe sensorineural hearing loss in the Department of Otolaryngology Head and Neck Surgery, Hainan General Hospital between May 2018 to 2021 were retrospectively reviewed. All included cases received audiological examination, HRCT scanning of temporal bones and SLC26A4 gene sequencing. According to the Valvassori standard, cases with the diameter from the common peduncle of the semicircular canal to the midpoint of the outer orifice of the vestibular aqueduct（MP） over 1.5 mm, or the diameter of the outer orifice of the vestibular aqueduct（OP） more than 2.0 mm were diagnosed as EVA. There were 22 cases（44 ears） of EVA in the study, aged between 6 months to 17 years old. Based on the hearing changes at birth and during growth, 18 ears of which were classified into the stable hearing group, while the other 26 ears in the unstable group. Moreover, all involved cases were grouped by MP（1.5 to <3.0 mm and ≥3.0 mm） and OP（2.0 to <4.0 mm and ≥4.0 mm）. SPSS 25.0 software was applied in the study. The correlation between hearing loss and MP and OP was analyzed. The results of HRCT of temporal bones and SLC26A4 gene sequencing were compared as well. Results:Though the size of MP and OP was not statistically different between the stable and hearing groups in EVA ears（P>0.05）, it was significantly correlated with the severity of hearing loss（P<0.05）. Of the 22 EVA patients diagnosed by HRCT, 21 were positive for SLC26A4 gene mutation. The positive rate of EVA by SLC26A4 gene sequencing was highly consistent with HRCT（Kappa=0.975）. Conclusion:The size of MP and OP in EVA patients was related to the degree of hearing loss, but not to the stable nature of hearing loss. Temporal bone HRCT scanning and SLC26A4 gene sequencing are highly consistent in the diagnosis of EVA. The latter has no radiation and can be combined with hearing screening for early diagnosis of EVA.

Antiviral nanopharmaceuticals: Engineered surface interactions and virus-selective activity.

The COVID-19 pandemic has inspired large research investments from the global scientific community in the study of viral properties and antiviral technologies (e.g., self-cleaning surfaces, virucides, antiviral drugs, and vaccines). Emerging viruses are a constant threat due to the substantial variation in viral structures, limiting the potential for expanded broad-spectrum antiviral agent development, and the complexity of targeting multiple and diverse viral species with unique characteristics involving their virulence. Multiple, more infectious variants of SARS-CoV2 (e.g., Delta, Omicron) have already appeared, necessitating research into versatile, robust control strategies in response to the looming threat of future viruses. Nanotechnology and nanomaterials have played a vital role in addressing current viral threats, from mRNA-based vaccines to nanoparticle-based drugs and nanotechnology enhanced disinfection methods. Rapid progress in the field has prompted a review of the current literature primarily focused on nanotechnology-based virucides and antivirals. In this review, a brief description of antiviral drugs is provided first as background with most of the discussion focused on key design considerations for high-efficacy antiviral nanomaterials (e.g., nanopharmaceuticals) as determined from published studies as well as related modes of biological activity. Insights into potential future research directions are also provided with a section devoted specifically to the SARS-CoV2 virus. This article is categorized under: Toxicology and Regulatory Issues in Nanomediciney > Toxicology of Nanomaterials Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease Therapeutic Approaches and Drug Discovery > Nanomedicine for Respiratory Disease.

Molecular mechanism of atractylon in the invasion and migration of hepatic cancer cells based on high­throughput sequencing.

The aim of the present study was to investigate the molecular mechanisms of atractylon in the inhibition of invasion and migration of hepatic cancer cells. High­throughput sequencing was used to compare the expression of long non­coding (lnc)RNAs between hepatic carcinoma and healthy controls. A competing endogenous RNA network was constructed. The top significantly differentially expressed lncRNAs were screened and verified by reverse transcription­quantitative PCR in vitro and in vivo. Small interfering (si)RNA against thymopoietin­antisense 1 (TMPO­AS1) or coiled­coil domain­containing 183­antisense 1 (CCDC183­AS1) overexpression (oe) vectors were transfected into cells following atractylon treatment. Wound healing and Matrigel assays were used to determine the effects of migration and invasion, respectively. Western blot analysis was used to detect the expression levels of invasion­ and migration­related proteins, including N­cadherin, E­cadherin and MMP­2. Flow cytometry analysis was used to detect apoptosis. Based on transcriptome sequencing and analysis, the top seven upregulated [(FAM201A, RP11­640M9.2, AL589743.1, TMEM51­AS1, clathrin heavy chain­like 1 (CLTCL1), TMPO­AS1 and LINC00652] and top six downregulated lncRNAs (RP11­465B22.5, CCDC183­AS1, TCONS_00072529, RP11­401F2.3, RP11­290F20.1 and TCONS_00070568) were identified. Only TMPO­AS1 and CCDC183­AS1 were differently regulated by atractylon in vivo. The proliferative ability of HepG2 liver cancer cells decreased, whereas the apoptotic rate improved after atractylon treatment. Notably, the invasive and migratory ability of HepG2 cells significantly declined. In addition, siTMPO­AS1 and oeCCDC183­AS1 reduced the effect of atractylon in vitro. Atractylon was demonstrated to regulate the expression of TMPO­AS1 and CCDC183­AS1 and inhibited the invasion and migration of liver cancer cells. Thus, TMPO­AS1 and CCDC183­AS1 may be potential targets for diagnosis and treatment of hepatic carcinoma.

Nanoparticle mediated RNA delivery for wound healing.

Wound healing is a complicated physiological process that comprises various steps, including hemostasis, inflammation, proliferation, and remodeling. The wound healing process is significantly affected by coexisting disease states such as diabetes, immunosuppression, or vascular disease. It can also be impacted by age, repeated injury, or hypertrophic scarring. These comorbidities can affect the rate of wound closure, the quality of wound closure, and tissues' function at the affected sites. There are limited options to improve the rate or quality of wound healing, creating a significant unmet need. Advances in nucleic acid research and the human genome project have developed potential novel approaches to address these outstanding requirements. In particular, the use of microRNA, short hairpin RNA, and silencing RNA is unique in their abilities as key regulators within the physiologic machinery of the cell. Although this innovative therapeutic approach using ribonucleic acid (RNA) is an attractive approach, the application as a therapeutic remains a challenge due to site-specific delivery, off-target effects, and RNA degradation obstacles. An ideal delivery system is essential for successful gene delivery. An ideal delivery system should result in high bioactivity, inhibit rapid dilution, controlled release, allow specific activation timings facilitating physiological stability, and minimize multiple dosages. Currently, these goals can be achieved by inorganic nanoparticle (NP) (e.g., cerium oxide, gold, silica, etc.) based delivery systems. This review focuses on providing insight into the preeminent research carried out on various RNAs and their delivery through NPs for effective wound healing. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures.