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Xiang Li,1,2,* Shu-Jie An,3,* Xiao-Ling Liu,1,* Ai-Ling Ji,4 Yi Cao,5 Ying Xiang,1 Xiang-Yu Ma,1 Qin Hu,1 Zhi-Quan Yuan,1 Ya-Fei Li,1 Yuan-Gang Lu,2 Tong-Jian Cai1 1Department of Epidemiology, College of Preventive Medicine, Army Medical University (Third Military Medical University), Chongqing, People’s Republic of China; 2Department of Plastic & Cosmetic Surgery, Daping Hospital, Army Medical University (Third Military Medical University), Chongqing, People’s Republic of China; 3Medical Department, Xijing Hospital, Air Force Medical University (Fourth Military Medical University), Xi’an, People’s Republic of China; 4Department of Preventive Medicine & Chongqing Engineering Research Center of Pharmaceutical Sciences, Chongqing Medical and Pharmaceutical College, Chongqing, People’s Republic of China; 5Department of Health Economics Management, Xijing Hospital, Air Force Medical University (Fourth Military Medical University), Xi’an, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yuan-Gang LuDepartment of Plastic & Cosmetic Surgery, Daping Hospital, Army Medical University, 10 Changjiang Branch Road, Daping, Chongqing, 400042, People’s Republic of ChinaTel +86-23-68757597Fax +86-23-68757596Email skin515@163.comTong-Jian Cai Email ctjcsl@fmmu.edu.cnBackground: Post-adolescent acne is a common skin disease faced by adults. However, whether air pollution (AP) serves as a risk factor for post-adolescent acne remains elusive.Aim: To determine the relationship between short-term AP exposure (within 7 days) and outpatient visits for post-adolescent acne.Methods: Daily outpatient visit data for post-adolescent acne and routinely AP data between 2010 and 2013 were collected from Xi’an, China. A generalized additive regression model was used to analyze the relationship between outpatient visits for post-adolescent acne and short-term ambient AP exposure. The gender-specific analyses were conducted as well.Results: Totally, 27,190 outpatient visits for post-adolescent acne were included. The results revealed that a 10 μg/m3 increase in PM10, SO2, and NO2 at lag 0– 7 day was associated with the increase of outpatient visits for post-adolescent acne at 0.84% (95% CI: 0.53%, 1.16%), 1.61% (95% CI: 0.12%, 3.10%), and 3.50% (95% CI: 1.60%, 5.40%), respectively. The significant positive associations of PM10, SO2, and NO2 were found at both single-lag models and moving average models. The gender-specific analyses showed that the effect estimates of PM10 was stronger for females than for males, while there was no observed gender difference in the effects of SO2 and NO2.Conclusion: Short-term exposure to AP was associated with increased outpatient visits for post-adolescent acne, especially for females in the effects of PM10.Keywords: short-term, air pollution, post-adolescent acne, adult acne, time-series analysis

Jun-Yi Wu,1,* Zhong-Xia Wang,1,* Guang Zhang,1 Xian Lu,1 Guang-Hui Qiang,2 Wei Hu,2 An-Lai Ji,3 Jun-Hua Wu,4 Chun-Ping Jiang1 1Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China; 2Department of Hepatobiliary Surgery, Drum Tower Clinical College of Nanjing Medical University, Nanjing, Jiangsu, China; 3Department of General Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China; 4Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, Jiangsu, China *These authors contributed equally to this work Purpose: FTY720, known as fingolimod, is a new immunosuppressive agent with effective anticancer properties. Although it was recently confirmed that FTY720 inhibits cancer cell proliferation, FTY720 can also induce protective autophagy and reduce cytotoxicity. Blocking autophagy with Beclin 1 siRNA after treatment with FTY720 promotes apoptosis. The objective of this study was to enhance the anticancer effect of FTY720 in hepatocellular carcinoma (HCC) by targeted co-delivery of FTY720 and Beclin 1 siRNA using calcium phosphate (CaP) nanoparticles (NPs).Materials and methods: First, the siRNA was encapsulated within the CaP core. To form an asymmetric lipid bilayer structure, we then used an anionic lipid for the inner leaflet and a cationic lipid for the outer leaflet; after removing chloroform by rotary evaporation, these lipids were dispersed in a saline solution with FTY720. The NPs were analyzed by transmission electron microscopy, dynamic light scattering and ultraviolet–visible spectrophotometry. Cancer cell viability and cell death were analyzed by MTT assays, fluorescence-activated cell sorting analysis and Western blotting. In addition, the in vivo effects of the NPs were investigated using an athymic nude mouse subcutaneous transplantation tumor model.Results: When the CaP NPs, called LCP-II NPs, were loaded with FTY720 and siRNA, they exhibited the expected size and were internalized by cells. These NPs were stable in systemic circulation. Furthermore, co-delivery of FTY720 and Beclin 1 siRNA significantly increased cytotoxicity in vitro and in vivo compared with that caused by treatment with the free drug alone.Conclusion: The CaP NP system can be further developed for co-delivery of FTY720 and Beclin 1 siRNA to treat HCC, enhancing the anticancer efficacy of FTY720. Our findings provide a new insight into HCC treatment with co-delivered small molecules and siRNA, and these results can be readily translated into cancer clinical trials. Keywords: LCP-II NPs, autophagy, FTY720, Beclin 1, co-delivery

Carbon fiber reinforced carbon and silicon carbide matrix composites for nozzle inner of solid propellant ramjet were prepared by using the hybrid process of "chemical vapor infiltration + precursor impregnation pyrolysis (CVI+PIP)". The microstructure, flexural and anti-ablation properties of the C/C-SiC composites and hydraulic test and rocket motor hot firing test for nozzle inner of solid propellant ramjet were comprehensively investigated. The results show that when the flexural strength of the composite reachs 197 MPa, the fracture damage behavior of the composites presents typical toughness mode.Also the composites has excellent anti-ablative property, i.e., linear ablation rate is only 0.0063 mm·s-1 after 200 s ablation. The C/C-SiC component have excellent integral bearing performance with the hydraulic bursting pressure of 6.5 MPa, and the high temperature combination property of the C/C-SiC composite nozzle inner is verified through motor hot firing of solid propellant ramjet.

Sarcoidosis is an inflammatory disease characterized by immune cell-rich granulomas that form in multiple organs. In this issue of the JCI, Sati and colleagues used scRNA-seq and spatial transcriptomics of skin samples from patients with sarcoidosis and non-sarcoidosis granulomatous disease to identify upregulation of a stromal-immune CXCL12/CXCR4 axis and accumulation of type 1 innate lymphoid cells (ILC1s) in sarcoidosis. The accumulation of ILC1s in skin and blood was specific to patients with sarcoidosis and not observed in other granulomatous diseases. The authors used a mouse model of lung granuloma to show that ILCs contribute to granuloma formation and that blockade of CXCR4 reduced the formation of granulomas, providing a proof of concept that sarcoidosis may be treated by CXCR4 blockade to prevent the progression of disease in patients. These results suggest ILC1s could serve as a diagnostic biomarker in sarcoidosis and a potential therapeutic target.

Scaling and root planing (SRP) removes bacterial plaque, calculus, and associated microorganisms from the surface of the tooth and the surrounding soft tissue. While complete eradication of pathogenic microbes is impossible, gross removal can lower the microbial load, which in turn reduces inflammation and contributes to positive clinical outcomes. Instrumentation in limited-access anatomic areas like furcation, grooves, deep pockets, concavities, and distal molar areas is technically demanding with traditional mechanical debridement. However, emerging advanced systems such as lasers with bactericidal and detoxification effects offer the benefit of reaching limited-access areas that traditional SRP cannot reach. A digitized search was done on PubMed, Embase, Medline, and Google Scholar using the keywords "lasers", "periodontal therapy", "scaling", and "root planing". Upon screening and reviewing, the shortlisted articles comprised narrative reviews, systematic reviews, randomized controlled trials, comparative studies, split-mouth studies, case series, and reports of non-surgical laser therapy and lasers as an adjunct to SRP. This review presents a comprehensive comparative evaluation of different laser modalities utilized in non-surgical periodontal treatment in contrast to standard SRP, rather than an exhaustive article review. It delves into the history and development of lasers, highlighting key advancements made in the realm of periodontics and dental care. This review includes an elucidation of the theory behind laser operation, along with an exploration of its intrinsic characteristics and breakdown of the various types of lasers that are currently available, and an examination of existing literature in both present and historical contexts regarding the comparison of various types of lasers with traditional periodontal treatment., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Altalhi et al.)

This longitudinal study aimed to quantify the effects of dietary supplementation of a direct-fed microbial (DFM) consisting of three lactobacilli isolates on milk yield, milk fat and protein yields, somatic cell count (SCC), and liveweight in a single dairy herd in Australia. A total of 150 dairy cows were randomly selected based on parity and days in milk and divided into two groups: control ( n = 75) and DFM treatment ( n = 75). Throughout the study, the two groups of cows were housed separately in a dry lot yard, and each group had their own feeding area. For the DFM treatment group, selected cows in mid-lactation were supplemented with 10 mL/cow/day of the DFM via top dressing of the feed for the remainder of the lactation and through the dry period, extending into subsequent lactation. The control group had no supplementation. The milk yield and liveweight were recorded daily. Milk samples were collected every two months for milk component analysis (fat, protein, and somatic cell count [SCC]). The DFM-treated cows gained more liveweight across the study (19.40 kg, 95% CI 0.44 kg; 38.30 kg, p = 0.05) compared to the control cows. In the second production year, the DFM-treated cows mobilized more liveweight (-6.06 kg, 95% CI -10.49 kg; -1.61 kg, p = 0.01) and produced more milk (0.39 L/d 95% CI 0.10; 0.89, p = 0.05). Over a full lactation, DFM cows yielded at least 258 L (95% CI 252 L; 265 L) more milk than controls. No significant differences were found in fat and protein yield or SCC. This study suggests that consistent and ongoing supplementation with a Lacticaseibacillus - and Lentilactobacillus -based DFM could have a positive effect on milk production, but further research is needed to understand the underlying mechanism.

Background: Itch is a common symptom that can greatly diminish quality of life. Histamine is a potent endogenous pruritogen, and while antihistamines are often the first-line treatment for itch, in conditions like chronic spontaneous urticaria (CSU), many patients remain symptomatic while receiving maximal doses. Mechanisms that drive resistance to antihistamines are poorly defined., Objectives: Signaling of the alarmin cytokine IL-33 in sensory neurons is postulated to drive chronic itch by inducing neuronal sensitization to pruritogens. Thus, we sought to determine if IL-33 can augment histamine-induced (histaminergic) itch., Methods: Itch behavior was assessed in response to histamine after IL-33 or saline administration. Various stimuli and conditional and global knockout mice were utilized to dissect cellular mechanisms. Multiple existing transcriptomic data sets were evaluated, including single-cell RNA sequencing of human and mouse skin, microarrays of isolated mouse mast cells at steady state and after stimulation with IL-33, and microarrays of skin biopsy samples from subjects with CSU and healthy controls., Results: IL-33 amplifies histaminergic itch independent of IL-33 signaling in sensory neurons. Mast cells are the top expressors of the IL-33 receptor in both human and mouse skin. When stimulated by IL-33, mouse mast cells significantly increase IL-13 levels. Enhancement of histaminergic itch by IL-33 relies on a mast cell- and IL-13-dependent mechanism. IL-33 receptor expression is increased in lesional skin of subjects with CSU compared to healthy controls., Conclusions: Our findings suggest that IL-33 signaling may be a key driver of histaminergic itch in mast cell-associated pruritic conditions such as CSU., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Spatial transcriptomic technologies, such as the Visium platform, measure gene expression in different regions of tissues. Here, we describe new software, STmut, to visualize somatic point mutations, allelic imbalance, and copy number alterations in Visium data. STmut is tested on fresh-frozen Visium data, formalin-fixed paraffin-embedded (FFPE) Visium data, and tumors with and without matching DNA sequencing data. Copy number is inferred on all conditions, but the chemistry of the FFPE platform does not permit analyses of single nucleotide variants. Taken together, we propose solutions to add the genetic dimension to spatial transcriptomic data and describe the limitations of different datatypes., (© 2023. The Author(s).)

Epidermal homeostasis is governed by a balance between keratinocyte proliferation and differentiation with contributions from cell-cell interactions, but conserved or divergent mechanisms governing this equilibrium across species and how an imbalance contributes to skin disease are largely undefined. To address these questions, human skin single-cell RNA sequencing and spatial transcriptomics data were integrated and compared with mouse skin data. Human skin cell-type annotation was improved using matched spatial transcriptomics data, highlighting the importance of spatial context in cell-type identity, and spatial transcriptomics refined cellular communication inference. In cross-species analyses, we identified a human spinous keratinocyte subpopulation that exhibited proliferative capacity and a heavy metal processing signature, which was absent in mouse and may account for species differences in epidermal thickness. This human subpopulation was expanded in psoriasis and zinc-deficiency dermatitis, attesting to disease relevance and suggesting a paradigm of subpopulation dysfunction as a hallmark of the disease. To assess additional potential subpopulation drivers of skin diseases, we performed cell-of-origin enrichment analysis within genodermatoses, nominating pathogenic cell subpopulations and their communication pathways, which highlighted multiple potential therapeutic targets. This integrated dataset is encompassed in a publicly available web resource to aid mechanistic and translational studies of normal and diseased skin., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

A new Schiff base, 4-((1E,2E)-3-(furan-2-yl)allylidene)amino)-N-(5-methylisoxazol-3-yl) benzene-sulfonamide (L), was synthesized by thermal condensation of 3-(2-furyl)acrolein and sulfamethoxazole (SMX), and the furan Schiff base (L) was converted to a phenol Schiff base (L') according to the Diels-Alder [4 + 2] cycloaddition reaction and studied experimentally. The structural and spectroscopic properties of the Schiff base were also corroborated by utilizing density functional theory (DFT) calculations. Furthermore, a series of lanthanide and transition metal complexes of the Schiff base were synthesized from the nitrate salts of Gd, Sm, Nd, and Zn (L 1 , L 2 , L 3 , and L 4 ), respectively. Various spectroscopic studies confirmed the chemical structures of the Schiff-base ligand and its complexes. Based on the spectral studies, a nine-coordinated geometry was assigned to the lanthanide complexes and a six-coordinated geometry to the zinc complex. The elemental analysis data confirmed the suggested structure of the metal complexes, and the TGA studies confirmed the presence of one coordinated water molecule in the lanthanide complexes and one crystalline water molecule in the zinc complex; in addition, the conductivity showed the neutral nature of the complexes. Therefore, it is suggested that the ligand acts as a bidentate through coordinates to each metal atom by the isoxazole nitrogen and oxygen atoms of the sulfur dioxide moiety of the SMX based on FTIR studies. The ligand and its complexes were tested for their anti-inflammatory, anti-hemolytic, and antioxidant activities by various colorimetric methods. These complexes were found to exhibit potential effects of the selected biological activities.

Binary ruthenium dioxide (RuO 2 ) has gradually attracted much attention in condensed matter physics and material sciences due to its various intriguing physical properties, such as strain-induced superconductivity, anomalous Hall effect, collinear anti-ferromagnetism, etc. However, its complex emergent electronic states and the corresponding phase diagram over a wide temperature range remain unexplored, which is critically important to understanding the underlying physics and exploring its final physical properties and functionalities. Here, through optimizing the growth conditions by using versatile pulsed laser deposition, high-quality epitaxial RuO 2 thin films with clear lattice structure are obtained, upon which the electronic transport is investigated, and emergent electronic states and the relevant physical properties are unveiled. Firstly, at a high-temperature range, it is the Bloch-Grüneisen state, instead of the common Fermi liquid metallic state, that dominates the electrical transport behavior. Moreover, the recently reported anomalous Hall effect is also revealed, which confirms the presence of the Berry phase in the energy band structure. More excitingly, we find that above the superconductivity transition temperature, a new positive magnetic resistance quantum coherent state with an unusual dip as well as an angel-dependent critical magnetic field emerges, which can be attributed to the weak antilocalization effect. Lastly, the complex phase diagram with multiple intriguing emergent electronic states over a wide temperature range is mapped. The results greatly promote the fundamental physics understanding of the binary oxide RuO 2 and provide guidelines for its practical applications and functionalities., (© 2023 IOP Publishing Ltd.)

The development of multiomic profiling tools has rapidly expanded in recent years, along with their use in profiling skin tissues in various contexts, including dermatologic diseases. Among these tools, single-cell RNA-sequencing (scRNA-seq) and spatial transcriptomics (ST) have emerged as widely adopted and powerful assays for elucidating key cellular components and their spatial arrangement within skin disease. In this paper, we review the recent biological insights gained from the use of scRNA-seq and ST and the advantages of combining both for profiling skin diseases, including aberrant wound healing, inflammatory skin diseases, and cancer. We discuss the role of scRNA-seq and ST in improving skin disease treatments and moving toward the goal of achieving precision medicine in dermatology, whereby patients can be optimally matched to treatments that maximize therapeutic response., (© 2023 The Authors.)

Evidence of the short-term effects of ambient sulfur dioxide (SO 2 ) exposure on the economic burden of ischemic stroke is limited. This study aimed to explore the association between short-term ambient SO 2 exposure and hospitalization costs for ischemic stroke in Chongqing, the most populous city in China. The hospital-based study included 7271 ischemic stroke inpatients. Multiple linear regression models were used to estimate the association between SO 2 concentration and hospitalization costs. Propensity score matching was used to compare the patients' characteristics when exposed to SO 2 concentrations above and below 20 μg/m 3 . It is found that short-term SO 2 exposure was positively correlated with the hospitalization costs of ischemic stroke. The association was more evident in males, people younger than 65, and people hospitalized in the cool seasons. Besides, among the components of hospitalization costs, medicine costs were most significantly associated with SO 2 . More interesting, the lower concentration of SO 2 , the higher costs associated with 1 μg/m 3 SO 2 change. Above all, SO 2 was positively associated with hospitalization costs of ischemic stroke, even at its low levels. The measures to reduce the level of SO 2 can help reduce the burden of ischemic stroke., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Previous researches have reported the association between air pollution and various diseases. However, few researches have investigated whether air pollutants are associated with the economic loss resulting from patients' hospitalization, especially the economic loss of hospitalization due to acute cardiovascular events. The purpose of our research was to explore the association between the levels of carbon monoxide (CO), taken as an index of pollution, and the hospitalization costs of myocardial infarction (MI), and the potential effect modification by the ABO blood group. A total of 3237 MI inpatients were included in this study. A multiple linear regression model was used to evaluate the association between ambient CO levels and hospitalization costs of MI patients. Moreover, we performed stratified analyses by age, gender, body mass index (BMI), season, hypertension, and ABO blood types. There was a positive association between the levels of CO in the air and the costs of hospitalization caused by MI. Furthermore, such association was stronger in males, BMI ≥25, <65 years, with hypertension, and non-O blood group. Interestingly, we found the association was particularly significant in patients with blood group B. Overall, our study first found that ambient CO levels could have an impact on the hospitalization costs for MI patients, and those with blood group B can be more sensitive., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: There are many reasons that could lead to finger joint arthroplasty, and the most familiar reason is osteoarthritis. Silicone finger joint are the most commonly used implants. However, these implants might fracture with time and cause wear which will lead to chronic inflammation and synovitis for the patient and then implant failure., Objective: The aim of this study is to improve the design of the silicone finger joint and simulate the different designs using finite element analysis (FEA) simulation., Method: Three different designs were drawn and FEA has been used in this study using Solidworks software. The first design is the silicone finger joint design without any modification, the second one is modified design with added ribs to the junction of distal stem and hinge and the third design was added filler material inside the body of the artificial joint. An axial force with 625 N that was applied on the upper part of the distal stem which is nearly represents the maximum value of the grip strength for normal males., Results: The results showed improvement on the design in which the concentrated stress at the junction of the distal stem and hinge of the design was distributed. In addition, the Von Mises stress was stable for the modified design with added ribs and the added filler material designs after 15°., Conclusion: The design modification could improve the stress distribution and stability of the artificial finger joint and increase the lifetime expectancy of these implants.

Type 2 diabetes (T2DM) as a non-communicable disease imposes heavy disease burdens on society. Limited studies have been conducted to assess the effects of short-term air pollution exposure on T2DM, especially in Asian regions. Our research aimed to determine the association between short-term exposure to ambient nitrogen dioxide (NO 2 ) and outpatient visits for T2DM in Chongqing, the largest city in western China, based on the data collected from November 28, 2013 to December 31, 2019. A generalized additive model (GAM) was applied, and stratified analyses were performed to investigate the potential modifying effects by age, gender, and season. Meanwhile, the disease burden was revealed from attributable risk. Positive associations between short-term NO 2 and daily T2DM outpatient visits were observed. The strongest association was observed at lag 04, with per 10 μg/m 3 increase of NO 2 corresponded to increased T2DM outpatient visits at 1.57% [95% confidence interval (CI): 0.48%, 2.65%]. Stronger associations were presented in middle-aged group (35-64 years old), male group, and cool seasons (October to March). Moreover, there were 1.553% (8664.535 cases) of T2DM outpatient visits attributable to NO 2 . Middle-aged adults, males, and patients who visited in cool seasons suffered heavier burdens. Conclusively, short-term exposure to NO 2 was associated with increased outpatient visits for T2DM. Attention should be paid to the impact of NO 2 on the burden of T2DM, especially for those vulnerable groups., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Atrial fibrillation (AF) is the most common sustained heart rhythm disorder associated with high mortality and morbidity. Limited studies have been conducted to assess the relationship between short-term exposure to ambient air pollution and AF attacks. This study aimed to explore the association between short-term ambient nitrogen dioxide (NO 2 ) exposure and outpatient visits for AF in Xi'an, China. Data on daily AF outpatient visits and air pollutants from 2013 to 2019 (2555 days) were obtained. A time-series approach using over-dispersed Poisson generalized additive model (GAM) was employed, and stratified analyses were performed to investigate the potential modifying effects by season, age, and gender. A total of 8307 outpatient visits for AF were recorded. Increased levels of NO 2 were associated with increased AF outpatient visits, and the most significant effect estimates were observed at lag 03: A 10 μg/m 3 increase of NO 2 at lag 03 was related to an elevation of 5.59% (95% CI: 2.67%, 8.51%) in daily outpatient visits for AF. Stratified analyses showed that there were no gender and age difference in the effect of NO 2 , while more obvious association was observed in cool seasons (October to March) than in warm seasons (April to September). In summary, short-term ambient NO 2 exposure can be positively associated with daily outpatient visits for AF, especially in cool seasons. This work provided novel data that the association between air pollutants and AF can vary by seasons, further supporting that the prevention of cardiovascular health effects should be strengthened in winter., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Sleep disorders attract increasing concerns. However, the evidence of the association between ambient air pollution and sleep disorders is limited. Therefore, our aim was to determine the association between short-term air pollution exposure and outpatient visits for sleep disorders in Xi'an, the largest city in Northwest China. Baseline outpatient data of daily sleep disorders between 2011 and 2013 were collected. Quasi-Poisson distribution was applied by adjusting the day of the week and weather conditions. A total of 49,282 sleep disorder outpatient visits were recorded. The most significant association between air pollutants and outpatient visits was observed on concurrent day: per 10 μg/m 3 increase of NO 2 , SO 2 , and PM 10 at lag 0 corresponded to increased outpatient sleep disorder visits at 0.22% (95% CI: 0.03%, 0.42%), 1.53% (95% CI: 0.53, 2.53%), and 2.57% (95% CI: 1.33%, 3.82%), respectively. As for gender-specific analysis, there was no statistically significant difference between males and females. The result of season-specific analysis showed no statistically significant difference between warm seasons and cool seasons, either. As for age-specific analysis, obvious associations were observed in 20-40 age group (NO 2 ) and > 40 age group (PM 10 and SO 2 ), while no evident association was found for the young age group (< 20 years old). Conclusively, short-term exposure to air pollutants, especially gaseous air pollutants, might increase the risk of sleep disorders, and such association appears to be more obvious in elder people. We provide novel data that there may be age differences in the relationship between short-term air pollution exposure and sleep disorders., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In recent years, the development of biomedical monitoring systems, including respiration monitoring systems, has been accelerated. Wearable and implantable medical devices are becoming increasingly important in the diagnosis and management of disease and illness. Respiration can be monitored using a variety of biosensors and systems. Auto-charged sensors have a number of advantages, including low cost, ease of preparation, design flexibility, and a wide range of applications. It is possible to use the auto-charged sensors to directly convert mechanical energy from the airflow into electricity. The ability to monitor and diagnose one's own health is a major goal of auto-charged sensors and systems. Respiratory disease model output signals have not been thoroughly investigated and clearly understood. As a result, figuring out their exact interrelationship is a difficult and important research question. This review summarized recent developments in auto-charged respiratory sensors and systems in terms of their device principle, output property, detecting index, and so on. Researchers with an interest in auto-charged sensors can use the information presented here to better understand the difficulties and opportunities that lie ahead., Competing Interests: The authors declare that they have no conflicts of interest to report regarding the present work., (Copyright © 2022 Hamza Abu Owida et al.)

Defining the transition from benign to malignant tissue is fundamental to improving early diagnosis of cancer 1 . Here we use a systematic approach to study spatial genome integrity in situ and describe previously unidentified clonal relationships. We used spatially resolved transcriptomics 2 to infer spatial copy number variations in >120,000 regions across multiple organs, in benign and malignant tissues. We demonstrate that genome-wide copy number variation reveals distinct clonal patterns within tumours and in nearby benign tissue using an organ-wide approach focused on the prostate. Our results suggest a model for how genomic instability arises in histologically benign tissue that may represent early events in cancer evolution. We highlight the power of capturing the molecular and spatial continuums in a tissue context and challenge the rationale for treatment paradigms, including focal therapy., (© 2022. The Author(s).)

Ambient carbon monoxide (CO) is associated with bronchitis morbidity, but there is no evidence concerning its correlation with hospitalization costs for bronchitis patients. This study aimed to investigate the relationship between short-term ambient CO exposure and hospitalization costs for bronchitis patients in Chongqing, China. Baseline data for 3162 hospitalized bronchitis patients from November 2013 to December 2019 were collected. Multiple linear regression analysis was used to determine the association, delayed and cumulative, between short-term CO exposure and hospitalization costs. Additionally, subgroup analyses were performed by gender, age, season, and comorbidity. Positive association between CO and hospitalization costs for bronchitis patients was observed. The strongest association was observed at lag 015 days, with per 1 mg/m 3 increase of CO concentrations corresponded to 5834.40 Chinese Yuan (CNY) (95% CI: 2318.71, 9350.08; P < 0.001) (845.97 US dollars) increment in hospitalization costs. Stratified analysis results showed that the association was more obvious among those males, elderly, with comorbidities, and in warm seasons. More importantly, there was strongest correlation between CO and bronchitis patients with coronary heart disease. In summary, short-term exposure to ambient CO, even lower than Chinese and WHO standards, can be associated with increased hospitalization costs for bronchitis. Controlling CO exposure can be helpful to reduce medical burden associated with bronchitis patients. The results also suggest that when setting air quality standards and formulating preventive measures, susceptible subpopulations ought to be considered., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Trans fatty acids (TFAs) are not synthesized in the human body but are generally ingested in substantial amounts. The widespread view that TFAs, particularly those of industrial origin, are unhealthy and contribute to obesity, cardiovascular diseases and diabetes is based mostly on in vivo studies, and the underlying molecular mechanisms remain to be elucidated. Here, we used a hepatoma model of palmitate-induced lipotoxicity to compare the metabolism and effects of the representative industrial and ruminant TFAs, elaidate and vaccenate, respectively, with those of cis-oleate. Cellular FAs, triacylglycerols, diacylglycerols and ceramides were quantitated using chromatography, markers of stress and apoptosis were assessed at mRNA and protein levels, ultrastructural changes were examined by electron microscopy and viability was evaluated by MTT assay. While TFAs were just slightly more damaging than oleate when applied alone, they were remarkably less protective against palmitate toxicity in cotreatments. These differences correlated with their diverse incorporation into the accumulating diacylglycerols and ceramides. Our results provide in vitro evidence for the unfavorable metabolic features and potent stress-inducing character of TFAs in comparison with oleate. These findings strengthen the reasoning against dietary trans fat intake, and they can also help us better understand the molecular mechanisms of lipotoxicity.

Electrospinning enables simple and cost-effective production of polymer nanofibers from different polymer materials. Drug delivery systems are capable of achieving maximum drug treatment benefits by significantly reducing adverse complications. Electrospun nanofibers have recently attracted considerable attention owing to their distinctive properties, including flexibility and biocompatibility. The implementation of functional constituents within nanostructure fibers blends is an effective technique for the administration of a variety of drugs in animal research, broadening the nanofiber capability and reliability. The nanofibrous mesh and its various application purposes are discussed in terms of a summary of recent research, emphasizing the ease of streaming and a large number of combinations of this approach, which could lead to a breakthrough in targeted therapy., Competing Interests: The authors declare that they have no conflicts of interest to report regarding this work., (Copyright © 2022 Hamza Abu Owida et al.)

Transcriptome profiling of tissues and single cells facilitates interrogation of gene expression changes within diverse biological contexts. However, spatial information is often lost during tissue homogenization or dissociation. Recent advances in transcriptome profiling preserve the in situ spatial contexts of RNA molecules and together comprise a group of techniques known as spatial transcriptomics (ST), enabling localization of cell types and their associated gene expression within intact tissues. In this paper, we review ST methods; summarize data analysis approaches, including integration with single-cell transcriptomics data; and discuss their applications in dermatologic research. These tools offer a promising avenue toward improving our understanding of niche patterning and cell‒cell interactions within heterogeneous tissues that encompass skin homeostasis and disease., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Current methods for spatial transcriptomics are limited by low spatial resolution. Here we introduce a method that integrates spatial gene expression data with histological image data from the same tissue section to infer higher-resolution expression maps. Using a deep generative model, our method characterizes the transcriptome of micrometer-scale anatomical features and can predict spatial gene expression from histology images alone., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Tissue engineering is a relatively new area of research that combines medical, biological, and engineering fundamentals to create tissue-engineered constructs that regenerate, preserve, or slightly increase the functions of tissues. To create mature tissue, the extracellular matrix should be imitated by engineered structures, allow for oxygen and nutrient transmission, and release toxins during tissue repair. Numerous recent studies have been devoted to developing three-dimensional nanostructures for tissue engineering. One of the most effective of these methods is electrospinning. Numerous nanofibrous scaffolds have been constructed over the last few decades for tissue repair and restoration. The current review gives an overview of attempts to construct nanofibrous meshes as tissue-engineered scaffolds for various tissues such as bone, cartilage, cardiovascular, and skin tissues. Also, the current article addresses the recent improvements and difficulties in tissue regeneration using electrospinning., Competing Interests: The authors declare that they have no conflicts of interest to report regarding the present work., (Copyright © 2022 Hamza Abu Owida et al.)

Implantable devices have successfully proven their reliability and efficiency in the medical field due to their immense support in a variety of aspects concerning the monitoring of patients and treatment in many ways. Moreover, they assist the medical field in disease diagnosis and prevention. However, the devices' power sources rely on batteries, and with this reliance, comes certain complications. For example, their depletion may lead to surgical interference or leakage into the human body. Implicit studies have found ways to reduce the battery size or in some cases to eliminate its use entirely; these studies suggest the use of biocompatible harvesters that can support the device consumption by generating power. Harvesting mechanisms can be executed using a variety of biocompatible materials, namely, piezoelectric and triboelectric nanogenerators, biofuel cells, and environmental sources. As with all methods for implementing biocompatible harvesters, some of them are low in terms of power consumption and some are dependent on the device and the place of implantation. In this review, we discuss the application of harvesters into implantable devices and evaluate the different materials and methods and examine how new and improved circuits will help in assisting the generators to sustain the function of medical devices., Competing Interests: The authors declare that they have no conflicts of interest to report regarding the present work., (Copyright © 2021 Hamza Abu Owida et al.)

Single-cell RNA sequencing (scRNA-seq) identifies cell subpopulations within tissue but does not capture their spatial distribution nor reveal local networks of intercellular communication acting in situ. A suite of recently developed techniques that localize RNA within tissue, including multiplexed in situ hybridization and in situ sequencing (here defined as high-plex RNA imaging) and spatial barcoding, can help address this issue. However, no method currently provides as complete a scope of the transcriptome as does scRNA-seq, underscoring the need for approaches to integrate single-cell and spatial data. Here, we review efforts to integrate scRNA-seq with spatial transcriptomics, including emerging integrative computational methods, and propose ways to effectively combine current methodologies., (© 2021. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

There are increasing concerns with regard to spontaneous abortion (SAB), the loss of pregnancy without external intervention before 20 weeks of gestation, among reproductive-aged women. To date, limited evidence is available concerning the association between SAB and air pollutants, especially in developing countries. Daily baseline outpatient data for SAB from January 1, 2014, to December 31, 2018 (1826 days) were obtained in Chongqing, a metropolis of southwest China. The over-dispersed Poisson generalized additive model with control of meteorological conditions and day of week was used to estimate the short-term effects of ambient air pollution on the daily number of SAB outpatients. A total of 42,334 SAB outpatient visits for SAB were recorded. No statistically significant association was observed between SAB and CO, PM 2.5 , PM 10 , O 3 , and SO 2 . The positive association only appeared for NO 2 : positive associations between SAB and NO 2 were observed in both single-day models (lag 0, lag 1, lag 3, and lag 4) and cumulative exposure models (lag 01, lag 03, and lag 05) and the most significant effects were observed at lag 05 (3.289%; 95% CI: 1.568%, 5.011%). Moreover, the women with higher ages (30-39 and > 39) were more sensitive than those with lower ages (18-29), and the effect estimates were more evident in cool seasons. Collectively, our results suggested that short-term NO 2 exposure was associated with higher risk of SAB, especially in elder women and cool seasons, which may contribute to further understand the role of air pollution on SAB and other adverse obstetric outcomes., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Anxiety, a common and devastating mental disorder, has raised widespread interests. The impacts of air pollution on physical health are well known, whereas few studies have explored the association of atmospheric pollution, especially short-term air pollution exposure, with the risk of anxiety disorders. In addition, there are increasing concerns in emerging evidence supporting a possible etiological link. Therefore, our aim was to evaluate the relationship between short-term exposure to atmospheric pollutants and anxiety outpatient visits in Xi'an, a city of northwestern China and a metropolis with relatively heavy air pollution. We collected the data of both daily outpatient visits and daily air pollution (SO 2 , NO 2 , and PM 10 ) between January 1, 2010 and January 31, 2016 (2222 days). To clarify the association between short-term ambient atmospheric pollution exposure and anxiety outpatient visits, an over-dispersed Poisson generalized additive model was applied by adjusting the day of the week and weather conditions (including temperature, humidity, sunlight hours, and rainfalls). Positive association between gaseous air pollutants (SO 2 and NO 2 ) and anxiety daily outpatient visits was observed. Moreover, the largest estimated values of both SO 2 and NO 2 were evidence at lag 03 (4-day moving average lag), with 10 μg/m 3 increase corresponded to the increase of outpatient anxiety visits at 4.11% (95% CI: 2.15%, 6.06%) for SO 2 and 3.97% (95% CI: 1.90%, 6.06%) for NO 2 . However, there was no differences in susceptibility to air pollutants between different genders as well as different ages. Taken together, short-term exposure to ambient air pollutants, especially gaseous air pollutants (NO 2 and SO 2 ), can be related to higher risk of anxiety outpatient visits., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Depression is known to be one of the most common mental disorders raising global concerns. However, evidence regarding the association between short-term air pollution exposure and risk of development of depression is limited. The aim of this was to assess the relationship between short-term ambient air pollution exposure and depression in outpatient visits in Xi'an, a northwestern Chinese metropolis. Data for air pollutants including particulate matter (PM 10 ), sulfur dioxide (SO 2 ), and nitrogen dioxide (NO 2 ) levels from October 1, 2010 to December 31, 2013 and number of daily depression outpatient visits (92,387 in total) were collected. A time-series quasi-Poisson regression model was adopted to determine the association between short-term air pollutant concentrations and frequency of outpatient visits for depression with different lag models. Consequently, 10 μg/m 3 increase of SO 2 and NO 2 levels corresponded to significant elevation in number of outpatient-visits for depression on concurrent days (lag 0), and this relationship appeared stronger in cool seasons (October to March). However, the association of PM 10 was only significant in males aged 30-50 at lag 0. Evidence indicated that short-term exposure to ambient air pollutants especially in cool seasons might be associated with increased risk of outpatient visits for depression.

Quantitative criteria to identify proteins as RNA-binding proteins (RBPs) are presently lacking, as are criteria to define RBP target RNAs. Here, we develop an ultraviolet (UV) cross-linking immunoprecipitation (CLIP)-sequencing method, easyCLIP. easyCLIP provides absolute cross-link rates, as well as increased simplicity, efficiency, and capacity to visualize RNA libraries during sequencing library preparation. Measurement of >200 independent cross-link experiments across >35 proteins identifies an RNA cross-link rate threshold that distinguishes RBPs from non-RBPs and defines target RNAs as those with a complex frequency unlikely for a random protein. We apply easyCLIP to the 33 most recurrent cancer mutations across 28 RBPs, finding increased RNA binding per RBP molecule for KHDRBS2 R168C, A1CF E34K and PCBP1 L100P/Q cancer mutations. Quantitating RBP-RNA interactions can thus nominate proteins as RBPs and define the impact of specific disease-associated RBP mutations on RNA association.

Human papillomavirus (HPV) infections are common sexually-transmitted diseases among reproductive-aged women with increasing concern. Until now, there are no prior study about the association between HPV infections and ambient air pollution. This study aimed to explore the relationship between short-term exposure to ambient pollutants and daily outpatient visits for HPV infections in China. Data of daily outpatient visits for HPV infections were obtained from January 1, 2014 to December 31, 2018 (1826 days). Over-dispersed Poisson generalized additive models were applied by adjusting weather conditions and day of the week. We identified a total of 39,746 cases for HPV infections. A 10 μg/m 3 increase of PM 10 , PM 2.5 , SO 2 , and NO 2 or a 0.1 mg/m 3 rise of CO in concurrent day (lag 0) concentrations was related to an elevation of 0.822% (95% Cl: 0.282%, 1.36%), 1.05% (95% Cl: 0.280%, 1.81%), 5.72% (95% Cl: 1.79%, 9.65%), 5.02% (95% Cl: 3.45%, 6.60%), and 2.40% (95% Cl: 1.43%, 3.37%) in daily outpatient-visits for HPV infections, respectively. The association was more significant in those women aged 41 or over. As for 10 μg/m 3 increase of O 3 , a -1.33% (95% Cl: -2.13%, -0.530%) change was observed on the lag 03 and such effects appeared to be more obvious in the aged 18-40 group. Our results provided the first evidence that short-term exposure to ambient pollutants was related to, which may be indirectly, the increased risk of HPV infections while O 3 may act as a "protective" factor., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Carbon monoxide (CO) is a well-known "toxic gas". It represents a toxic inhalation hazard at high concentration and is commonly found in polluted air. However, a series of recent studies have suggested that low concentration of CO can also produce protective functions. This study was performed to investigate the association between ambient CO exposure and vaginitis outpatient visits. Daily baseline outpatient data of vaginitis from January 1, 2013 to December 31, 2015 were obtained from Xi'an, a heavily-polluted metropolis in China. The over-dispersed Poisson generalized additive model was applied to discover the relations between short-term ambient CO exposure and the number of vaginitis outpatient visits by adjusting day of the week and weather conditions. A total of 16,825 outpatient hospital visits for vaginitis were recorded. The mean daily concentration of carbon monoxide (CO) was well below Chinese and WHO guidelines. During the study period, increased levels of ambient CO was associated with reduced outpatient-visits through concurrent to lag 5 days, and the most significant association was evidenced at lag 05. A 0.1 mg/m 3 increase in daily average CO at lag 05 corresponded to -1.25% (95%CI: -1.85%, -0.65%) change in outpatient-visits for vaginitis. Moreover, the association was more significant in those women aged 20-29 years. After adjustment for PM 10 , PM 2.5 , SO 2 , and NO 2 , and O 3 , the negative associations of CO with vaginitis kept significant, suggesting relative stability of effect estimates. In summary, this is the first evidence that increased ambient CO exposure can be related to reduced daily outpatient visits for vaginitis. The results of our study may not only help to establish more comprehensive understanding of the health effects of ambient air on vaginitis and other gynecological diseases, but also provide a clue to new potential interventions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Menstrual disorders are common diseases among reproductive-aged women with increasing concerns. Until now, there have been limited studies about the association between menstrual disorders and air pollution. This study aimed to investigate the association between short-term (concurrent day and within 1 week prior) ambient air pollution exposure and menstrual disorder outpatient visits in Xi'an, a metropolis in northwestern China. Daily baseline outpatient data of menstrual disorders from January 1, 2010 to February 18, 2016 (2239 days) were obtained. An over-dispersed Poisson generalized additive model was applied to discover the relationship between short-term air pollution exposure and the number of menstrual disorder outpatient visits by adjusting the day of the week and weather conditions. A total of 51,893 outpatient visits for menstrual disorders were recorded. A 10 μg/m 3 increase of PM 10 and NO 2 concentrations corresponded to 0.236% (95% Cl: 0.075%, 0.397%) and 2.173% (95% Cl: 0.990%, 3.357%) elevations in outpatient-visits for menstrual disorders at lag 7 and lag 01 (concurrent day and previous 1 day), respectively. The association was more significant in young females (18-29 years) and there was no obvious association observed between SO 2 and menstrual disorder outpatient visits. This is the first evidence that short-term exposure to ambient air pollution can be associated with an increased risk of menstrual disorder attacks. The results of our study may help to establish more comprehensive understanding of the health effects of ambient air pollution on menstrual disorders and other reproductive diseases., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Hepatic ischemia/reperfusion (I/R) injury remains a significant problem in clinical practice. Sphingosine kinase 1 (SphK1) phosphorylates sphingosine to sphingosine-1-phosphate (S1P) which participates in multiple bioactive processes. However, little is known about the role of SphK1 in hepatic I/R injury. This study aimed to investigate the effect of SphK1 knockout on liver I/R injury and to explore underlying mechanisms., Methods: SphK1 knockout and wild type mice were subjected to 70% partial hepatic I/R. Serum alanine aminotransferase was determined to indicate the degree of liver damage. Hematoxylin-eosin staining and TUNEL assay were used to assess histological changes and hepatocellular apoptosis, respectively. Immunohistochemistry was performed to detect the expression and translocation of phosphorylated p65 and signal transducer and activator of transcription 3 (STAT3). Western blotting was used to determine the expression of S1P receptor 1 (S1PR1), phosphorylated p65 and STAT3. Real-time PCR was used to demonstrate the changes of proinflammatory cytokines. Oxidative stress markers were also determined through biochemical assays., Results: SphK1 knockout significantly ameliorated I/R-induced liver damage, mitigated liver tissue necrosis and apoptosis compared with wild type control. I/R associated inflammation was alleviated in SphK1 knockout mice as demonstrated by attenuated expression of S1PR1 and reduced phosphorylation of nuclear factor kappa B p65 and STAT3. The proinflammatory cytokines interleukin-1β, interleukin-6 and tumor necrosis factor-α were also inhibited by SphK1 genetic deletion. The oxidative stress markers were lower in SphK1 knockout mice after I/R injury than wild type mice., Conclusions: Knockout of SphK1 significantly alleviated damage after hepatic I/R injury, possibly through inhibiting inflammation and oxidative stress. SphK1 may be a novel and potent target in clinical practice in I/R-related liver injury., (Copyright © 2019 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Purpose: Incidence rate of registered blindness and low vision (IR) among the Kuwaitis from 2005 to 2014 and longitudinal changes since 2000., Methods: Data of newly certified Kuwaitis with best-corrected visual acuity 0.1 or less or visual field constriction to 20 ° or less in their better eye, aggregated in intervals from 2005 to 2009 and 2010 to 2014 and presented as IR per 100 000 person years of observation by age, gender, severity and leading cause., Results: Delayed certification resulted in rise of IR from 2005. IR of males declined since 2010, whereas among the females it continued rising at a slower rate. After 2010 IR of patients from 40 to 59 years expanded significantly and declined in the group over 60 years. Retinitis pigmentosa was the leading cause driven by high prevalence of consanguineous marriages; the large difference between the males and females is due mainly to cultural factors. Diabetic complications escalated from 2005 affecting patients over 40 years. Glaucoma became the leading cause in the age over 60 years after 2005 and while the male patients decreased after 2010 by 18%, disabled females grew by further 35%., Conclusions: Demographic, social and behavioral factors had impact on the structure and time trends of registered blindness among the Kuwaitis. High prevalence of diabetes and aging of the population resulted in rise of certification from diabetic complications and glaucoma in the last 10 years.

Background: Intestinal ischemia reperfusion (I/R) injury is a serious but common pathophysiological process of many diseases, resulting in a high mortality rate in clinical practice. Ubiquitin-specific protease 22 (USP22) acts as regulator of cell cycle progression, proliferation, and tumor invasion. Depleted USP22 expression has been reported to contribute to arrested cell cycle and disrupted generation of differentiated cell types in crypts and villi. However, the role of USP22 in intestinal damage recovery has not been investigated. Therefore, elucidation of the underlying mechanism of USP22 in intestinal I/R injury may help to improve the tissue repair and patient prognosis in clinical practice., Aim: To investigate the role of USP22 in intestinal cell proliferation and regeneration after intestinal I/R injury., Methods: An animal model of intestinal I/R injury was generated in male Sprague-Dawley rats by occlusion of the superior mesenteric artery followed by reperfusion. Chiu's scoring system was used to grade the damage to the intestinal mucosa. An in vitro model was developed by incubating rat intestinal epithelial IEC-6 cells in hypoxia/reoxygenation conditions in order to simulate I/R in vivo . siRNA and overexpression plasmid were used to regulate the expression of USP22. USP22, Cyclin D1, and proliferating cell nuclear antigen (PCNA) expression levels were measured by Western blot analysis and immunohistochemistry staining. Cell survival (viability) and cell cycle were evaluated using the Cell Counting Kit-8 and flow cytometry, respectively., Results: USP22 expression was positively correlated with the expression levels of PCNA and Cyclin D1 both in vivo and in vitro , which confirmed that USP22 was involved in cell proliferation and intestinal regeneration after intestinal I/R injury. Decreased levels of Cyclin D1 and cell cycle arrest were observed in the USP22 knockdown group ( P < 0.05), while opposite results were observed in the USP22 overexpression group ( P < 0.05). In addition, increased expression of USP22 was related to improved intestinal pathology or IEC-6 cell viability after I/R or hypoxia/reoxygenation. These results suggested that USP22 may exert a protective effect on intestinal I/R injury by regulating cell proliferation and facilitating tissue regeneration., Conclusion: USP22 is correlated with promoting intestinal cell proliferation and accelerating intestinal tissue regeneration after intestinal I/R injury and may serve as a potential target for therapeutic development for tissue repair during intestinal I/R injury., Competing Interests: Conflict-of-interest statement: All the authors have no conflict of interest related to the manuscript.

Here, we present Perturb-ATAC, a method that combines multiplexed CRISPR interference or knockout with genome-wide chromatin accessibility profiling in single cells based on the simultaneous detection of CRISPR guide RNAs and open chromatin sites by assay of transposase-accessible chromatin with sequencing (ATAC-seq). We applied Perturb-ATAC to transcription factors (TFs), chromatin-modifying factors, and noncoding RNAs (ncRNAs) in ∼4,300 single cells, encompassing more than 63 genotype-phenotype relationships. Perturb-ATAC in human B lymphocytes uncovered regulators of chromatin accessibility, TF occupancy, and nucleosome positioning and identified a hierarchy of TFs that govern B cell state, variation, and disease-associated cis-regulatory elements. Perturb-ATAC in primary human epidermal cells revealed three sequential modules of cis-elements that specify keratinocyte fate. Combinatorial deletion of all pairs of these TFs uncovered their epistatic relationships and highlighted genomic co-localization as a basis for synergistic interactions. Thus, Perturb-ATAC is a powerful strategy to dissect gene regulatory networks in development and disease., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Reports of fractures in racehorses have predominantly focused on catastrophic injuries, and there are limited data identifying the location and incidence of fractures that did not result in a fatal outcome., Objective: To describe the nature and the incidence of noncatastrophic and catastrophic fractures in Thoroughbreds racing at the Hong Kong Jockey Club (HKJC) over seven racing seasons., Study Design: Retrospective cohort study., Methods: Data of fractures sustained in horses while racing and of race characteristics were extracted from the HKJC Veterinary Management Information System (VMIS) and Racing Information System (RIS), respectively. The fracture event was determined from the first clinical entry for each specific injury. The incidence rates of noncatastrophic and catastrophic fractures were calculated per 1000 racing starts for racetrack, age, racing season, sex and trainer., Results: One hundred and seventy-nine first fracture events occurred in 64,807 racing starts. The incidence rate of noncatastrophic fractures was 2.2 per 1000 racing starts and of catastrophic fractures was 0.6 per 1000 racing starts. Fractures of the proximal sesamoid bones represented 55% of all catastrophic fractures, while the most common noncatastrophic fractures involved the carpus and the first phalanx. Significant associations were detected between the incidence of noncatastrophic fractures and sex, trainer and racing season., Main Limitations: The first fracture event was used to calculate the incidence rate in this study and may have resulted in underestimation of the true incidence rate of fractures in this population. However, given the low number of recorded fracture events compared with the size of the study population, this underestimation is likely to be small., Conclusions: There were 3.6 times as many noncatastrophic fractures as catastrophic fractures in Thoroughbreds racing in Hong Kong between 2004 and 2011. Noncatastrophic fractures interfere with race training schedules and may predispose to catastrophic fracture. Future analytical studies on noncatastrophic racing fractures should be a priority for the racing industry., (© 2018 EVJ Ltd.)

Schizophrenia is a devastating neuropsychiatric disorder with increasing concern. Limited studies have been conducted to assess the relationship between short-term exposure to ambient air pollution and schizophrenia attacks. This study aimed to investigate the associations between short-term air pollution exposure and schizophrenia outpatient visits based on a time-series study performed in China. Daily data of schizophrenia outpatient admissions and air pollution from 1 October 2010 to 31 December 2013 were collected in Xi'an, a heavily-polluted city in China. We utilized a time-series Poisson regression model to examine the associations between short-term air pollution and schizophrenia outpatient visits with different lag days. A total of 34,865 outpatient-visits for schizophrenia were identified. A 10 μg/m 3 increase of PM 10 , SO 2 , and NO 2 concentrations corresponded to 0.289% (95% Cl: 0.118%, 0.460%), 1.374% (95% Cl: 0.723%, 2.025%), and 1.881% (95% Cl: 0.957%, 2.805%) elevation in outpatient-visits for schizophrenia at lag 0, and the associations appeared to be stronger, although not statistically significantly, in females and in middle and older age adults (40 and over). The most significant associations were observed on the concurrent day in different lag models. In conclusion, short-term exposure to ambient air pollution (PM 10 , SO 2 , and NO 2 ) can be associated with increased risk of daily outpatient visits for schizophrenia, which may contribute to the further understanding of the potential adverse effects of air pollution in schizophrenia and other neuropsychiatric disorders., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

The liver has great regenerative capacity after functional mass loss caused by injury or disease. Many studies have shown that primary hepatocyte-derived exosomes, which can deliver biological information between cells, promote the regenerative process of the liver. However, the yield of exosomes is very limited. Recent studies have demonstrated that exosome-mimetic nanovesicles (NVs) can be prepared from cells with almost 100 times the production yield compared with exosomes. Thus, this study investigated the therapeutic capacity of exosome-mimetic NVs from primary hepatocytes in liver regeneration. Exosome-mimetic NVs were prepared by serial extrusions of cells through polycarbonate membranes, and the yield of these NVs was more than 100 times that of exosomes. The data indicated that the NVs could promote hepatocyte proliferation and liver regeneration by significantly enhancing the content of sphingosine kinase 2 in recipient cells. To the best of our knowledge, this is the first time that exosome-mimetic NVs from primary hepatocytes have been prepared, and these NVs have components similar to exosomes from primary hepatocytes and, in some respects, biofunctions similar to exosomes. Strategies inspired by this study may lead to substitution of exosomes with exosome-mimetic NVs for biofunctional purposes, including utilization in tissue repair and regeneration.

Air pollution is a risk factor for type 2 diabetes (T2D), exerting heavy economic burden on both individuals and societies. However, there is no apparent report regarding the influence of air pollutants such as particulate matter (PM 2.5 and PM 10 ), sulfur dioxide (SO 2 ), carbon monoxide (CO), nitrogen dioxide (NO 2 ), and ozone (O 3 ) on financial burden to individuals and societies suffering from T2D. This study aimed to determine whether short-term (no more than 16 d) air pollution exposure was associated with T2D-related length of stay (LOS) and hospitalization expenses incurred by patients. This investigation examined 2840 T2D patients hospitalized from December 17, 2013 to May 31, 2016 in China. Multiple linear regression analysis was applied to determine the association between short-term (no more than 16 d) ambient air pollution, LOS, and hospitalization expenses, controlling for age, gender, ethnicity, marital status, and weather conditions. Sulfur dioxide (SO 2 ) and carbon monoxide (CO) were significantly positively while nitrogen dioxide (NO 2 ) was negatively associated with presence of T2D, LOS, and expenses. A 10-μg/m 3 rise in 16-d (lag 0-15) average concentrations of SO 2 and CO prior to hospitalization was correlated with a significant elevation in LOS and elevation in expenses in T2D patients. However, a 10-μg/m 3 rise in 16-d average NO 2 was associated with marked negative alterations in LOS and hospital costs in T2D patients. Taken together, data demonstrate that exposure to air pollutants impacts differently on LOS and hospitalization costs for T2D patients. This is the first apparent report regarding the correlation between air pollution exposure and clinical costs of T2D in China. It is of interest that air pollutants affected T2D patients differently as evidenced by LOS and clinical expenses where SO 2 and CO exhibited a positive adverse relationship in contrast to NO 2 .

Recent genetic discoveries have dramatically changed our understanding of two major neurodegenerative conditions. Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are common, devastating diseases of the brain. For decades, ALS and FTD were classified as movement and cognitive disorders, respectively, due to their distinct clinical phenotypes. The recent identification of chromosome 9 open reading frame 72 ( C9orf72 ) as the major gene causative of familial forms of ALS and FTD uncovered a new reality of a continuous FTD/ALS spectrum. The finding that up to 50% of all patients present some degree of ALS and FTD phenotypes supports this ALS/FTD continuum. Now >100 genes are known to contribute to ALS/FTD, with a few major contributors that are reviewed below. The low penetrance of C9orf72 mutations, its contribution to sporadic cases, and its combination with other genes support an oligogenic model where two or more genes contribute to disease risk, onset, progression and phenotype: from 'pure' ALS or FTD to combined ALS/FTD. These advances in the genetics of ALS/FTD will soon lead to a better mechanistic understanding of the pathobiology of the disease, which should result in the development of effective therapies in the near future., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

The neutrophil is the major phagocyte and the final effector cell of the innate immunity, with a primary role in the clearance of extracellular pathogens. Using the broad array of cytokines, extracellular traps, and effector molecules as the humoral arm, neutrophils play a crucial role in the host defense against pathogen infections. On the other hand, the pathogen has the capacity to overcome neutrophil-mediated host defense to establish infection causing human disease. Pathogens, such as S. aureus , have the potential to thwart neutrophil chemotaxis and phagocytosis and thereby succeed in evading killing by neutrophils. Furthermore, S. aureus surviving within neutrophils promotes neutrophil cytolysis, resulting in the release of host-derived molecules that promote local inflammation. Here, we provide a detailed overview of the mechanisms by which neutrophils kill the extracellular pathogens and how pathogens evade neutrophils degradation. This review will provide insights that might be useful for the development of novel therapies against infections caused by antibiotic resistant pathogens., Competing Interests: The authors declare that they have no competing interests.

Objective: We investigated the effects of oral administration of enteric coated aspirin (ASA) on blood pressure and blood pressure variability of hypertension patients before sleep., Patients and Methods: We observed 150 hypertension cases, classified as Grade 1-2, from September 2006 to March 2008. They are divided into a control group with 30 cases, ASA I group with 60 cases and ASA II group with 60 cases randomly. Subjects in the control group had proper diets, were losing weight, exercising and maintaining a healthy mentality and were taking 30 mg Adalat orally once a day. Based on the treatment of control group, patients in ASA I group were administered 0.1 g Bayaspirin (produced by Bayer Company) at drought in the morning. Also, based on the treatment of control group, patients in ASA II group were administered 0.1 g Bayaspirin at draught before sleep., Results: The course of treatment is 3 months and then after the treatment, decreasing blood pressure and blood pressure variability conditions in three groups will be compared. Through the comparison of ASA II group with the control group, they have differences in terms of systolic blood pressure (SBP), diastolic blood pressure (DBP), decreasing range of blood pressure and blood pressure variability (p < 0.05)., Conclusions: The oral administration of ASA before sleep has synergistic effects on decreasing blood pressure of hypertension patients and improving blood pressure variability.