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Porcine epidemic diarrhea virus (PEDV) is an acute enteric coronavirus, inducing watery diarrhea and high mortality in piglets, leading to huge economic losses in global pig industry. Ivermectin (IVM), an FDA-approved antiparasitic agent, is characterized by high efficacy and wide applicability. However, the poor bioavailability limits its application. Since the virus is parasitized inside the host cells, increasing the intracellular drug uptake can improve antiviral efficacy. Hence, we aimed to develop nanostructured lipid carriers (NLCs) to enhance the antiviral efficacy of IVM. The findings first revealed the capacity of IVM to inhibit the infectivity of PEDV by reducing viral replication with a certain direct inactivation effect. The as-prepared IVM-NLCs possessed hydrodynamic diameter of 153.5 nm with a zeta potential of −31.5 mV and high encapsulation efficiency (95.72%) and drug loading (11.17%). IVM interacted with lipids and was enveloped in lipid carriers with an amorphous state. Furthermore, its encapsulation in NLCs could enhance drug internalization. Meanwhile, IVM-NLCs inhibited PEDV proliferation by up to three orders of magnitude in terms of viral RNA copies, impeding the accumulation of reactive oxygen species and mitigating the mitochondrial dysfunction caused by PEDV infection. Moreover, IVM-NLCs markedly decreased the apoptosis rate of PEDV-induced Vero cells. Hence, IVM-NLCs showed superior inhibitory effect against PEDV compared to free IVM. Together, these results implied that NLCs is an efficient delivery system for IVM to improve its antiviral efficacy against PEDV via enhanced intracellular uptake. [ABSTRACT FROM AUTHOR]

This study aimed to understand Bangladeshi users' satisfaction with their assistive devices, including (a) device characteristics, e.g., size, weight, safety, ease of use, comfort, and effectiveness, and (b) availability of parts and repair services. We also described how frequently individuals with disabilities living in the community used assistive devices in their daily activities and how the use of assistive devices promoted individuals' wellbeing. We conducted a cross-sectional survey with assistive device users or their guardians (if under 18) in Bangladesh about their experience and satisfaction with their assistive device 6 months after receiving it. The research team developed a survey questionnaire consisting of both closed and open-ended questions. All data were collected via telephone interviews. We employed descriptive statistics to analyse quantitative data and inductive analysis for the qualitative data. We found that out of the 376 participants, nearly 95% used assistive devices on a regular basis, and their satisfaction with the devices was high. Participants reported that assistive devices improved mobility, independence, and wellbeing of persons with disabilities. A few participants (6.4%) reported that their devices were damaged. Some participants identified concerns with their assistive devices, including (i) inappropriate size of ankle-foot orthoses, manual self-propelled wheelchairs, and prostheses, (ii) back slabs (a type of brace) being too short, and (iii) walking frames being too large. Several participants noted pain and discomfort when they used their assistive device. Additionally, some participants stated that environmental factors (e.g., muddy roads) contributed to the disrepair of their assistive devices. Finally, participants recounted that repair services were limited in rural areas of Bangladesh. These findings indicate that the provision of assistive devices requires accommodating individuals' needs and ensuring appropriate environments in which to function. The results support the need for follow-up services after distributing assistive devices. Further research could explore the impact of assistive devices on the family quality of life of persons with disabilities. It is essential for rehabilitation professionals to conduct follow-up services after distributing assistive devices among persons with disabilities. There is a need for the government of Bangladesh to revisit the Rights and Protection of Persons with Disability Act of 2013 and provide further clarity about their commitment to the provision of assistive devices and associated services (e.g., repair services) and its subsequent implementation. Policymakers in Bangladesh must be proactive to translate policy commitments into practice, as it relates to building an accessible environment for people using assistive devices. Further, government efforts are needed to educate policy implementers in all relevant ministries so that all responsible bodies are fully familiar with their national and international commitments regarding the rights of persons with disabilities. Future research could (i) include user's satisfaction with the service delivery process and (ii) measure the impact of assistive devices on family quality of life of persons with disabilities. [ABSTRACT FROM AUTHOR]

Antibacterial coordination compounds have attracted tremendous attention ascribed to their excellent designability. However, how the morphological evolution of these complexes influences their antibacterial and physicochemical properties has never been investigated based on proposed mechanisms. Thus, a series of Co–HOAT coordination compounds synthesized from inorganic to organic cobalt sources were prepared. We propose that with the same HOAT ligand, inorganic Co–HOAT nanosheets possess higher sterilization rates compared with organic Co–HOAT nanoparticles. This is explained by the different steric hindrance of cobalt sources. Relatively small steric hindrance could lead to ample active positions for inorganic cobalt ions to coordinate with both N and O atoms in HOAT. Meanwhile, organic Co2+ ions could only unite with N atoms in HOAT. Furthermore, by theoretical calculation, cobalt ions with adequate coordination sites are beneficial for developing nanosheet morphologies. Meanwhile, the Co–HOAT complexes with a lower density of electron clouds present higher sterilization rates due to the anchoring effect of electrostatic attraction. The proposed mechanism is that Co2+ released from compounds could cause multiple toxic effects to bacteria anchored by Co–HOATs. Finally, Co–HOATs' behaviors have excellent antimicrobial properties without environmental limitations. In conclusion, the Co–HOATs appear to be a potential antibacterial catalyst in the antimicrobial field. [ABSTRACT FROM AUTHOR]

Melanoma is a potentially lethal form of skin cancer resulting from the unlimited proliferation of melanocytes. Melanocytic lineage appears to have a greater rate of reactive oxygen species (ROS) production, possibly as a result of exposure to ultraviolet (UV) light and the production of melanin. It has been established that nuclear factor erythroid 2‐related factor 2 (Nrf2) serves as a master regulator of the cellular response to oxidative stresses. Recent research has shown that the Nrf2 and its critical negative regulator Kelch‐like ECH‐associated protein 1 (Keap1) are misregulated in melanoma, and the Keap1‐Nrf2 pathway has emerged as a promising new target for treating and preventing melanoma. In melanoma, Nrf2 may either limit tumor growth or promote its development. This review covers a wide range of topics, including the dual functions played by the Keap1‐Nrf2 signaling pathway in melanoma and the most recent targeting techniques of the Nrf2. [ABSTRACT FROM AUTHOR]

Simple Summary: Tree trunk damage can be influenced by multiple factors, among which trunk-boring insect infestation plays a significant role. Early external detection of such damage poses challenges. Manual observation remains the prevailing method for controlling tree trunk pests, but it demands a substantial workforce and yields limited outcomes. To address these limitations, acoustic technology has gained popularity, using vibration probes embedded in tree trunks to capture vibrations produced by insect larvae feeding, thereby facilitating the detection of pest larvae. However, traditional methods primarily rely on single-channel vibration signal acquisition, often assuming the proximity of the vibration probe to the sound source. Nevertheless, when the probe's position exceeds a certain distance from the original, capturing effective drilling vibration signals becomes difficult due to noise interference and other factors. To overcome this constraint, we have developed a novel multi-channel drilling vibration signal acquisition board that enables the distribution of multiple vibration probes at different locations on the tree trunk, allowing simultaneous collection of vibration signals from diverse probes. Additionally, we have devised a multi-channel signal separation model based on attention mechanisms, which effectively denoises and recovers clean target signals from noisy recordings. Experimental results demonstrate that this approach significantly enhances the detection efficiency of trunk-boring insects. The larvae of certain wood-boring beetles typically inhabit the interior of trees and feed on the wood, leaving almost no external traces during the early stages of infestation. Acoustic techniques are commonly employed to detect the vibrations produced by these larvae while they feed on wood, significantly increasing detection efficiency compared to traditional methods. However, this method's accuracy is greatly affected by environmental noise interference. To address the impact of environmental noise, this paper introduces a signal separation system based on a multi-channel attention mechanism. The system utilizes multiple sensors to receive wood-boring vibration signals and employs the attention mechanism to adjust the weights of relevant channels. By utilizing beamforming techniques, the system successfully removes noise from the wood-boring vibration signals and separates the clean wood-boring vibration signals from the noisy ones. The data used in this study were collected from both field and laboratory environments, ensuring the authenticity of the dataset. Experimental results demonstrate that this system can efficiently separate the wood-boring vibration signals from the mixed noisy signals. [ABSTRACT FROM AUTHOR]

Patients with chronic obstructive pulmonary disease (COPD) suffer from persistent cough and breathlessness, which can be ameliorated by the Chinese herbal medicine glycyrrhiza. Furthermore, the SRC/MAPK pathway is activated in the process of oxidative stress and inflammation, which afflict COPD progression. Thus, this research aimed at dissecting the mechanism of compound glycyrrhiza oral solution (CGOS) relieving oxidative stress and inflammation in COPD via the SRC/MAPK pathway. After a COPD rat model was established using lipopolysaccharide and cigarette smoke, rats underwent intragastric administration with CGOS and intratracheal injection with LV-NC and LV-SRC lentivirus into lungs. Then, pulmonary function-related indexes were evaluated, followed by analyses of arterial blood and inflammatory cell number in prepared bronchoalveolar lavage fluids. Meanwhile, the contents of oxidative stress-related indicators (malondialdehyde, 3NT, 8-Isoprostane, glutathione, NO, and SOD) in pulmonary tissues were measured, along with RT-qPCR and ELISA detection of the expression of inflammatory factors (TNF-α, IL-1β, IL-4, and IL-10). Moreover, western blot assay was utilized to assess p-SRC/SRC and p-p38/p38 ratios in pulmonary tissues. CGOS treatment enhanced PaO2 and reduced PaCO2 in COPD rats, accompanied by declines in the number of total cells, neutrophils, and macrophages. CGOS improved pulmonary function, decreased malondialdehyde, 3NT, 8-Isoprostane, TNF-α, and IL-1β levels, and increased GSH, NO, IL-4, and IL-10 levels and SOD activity. Mechanistically, CGOS suppressed the SRC/MAPK pathway, and SRC overexpression reversed the alleviating function of CGOS in COPD rats. In conclusion, CGOS might alleviate oxidative stress and inflammation in COPD rats by inhibiting the SRC/MAPK pathway. [ABSTRACT FROM AUTHOR]

Cu4Ti2O/TiO2/diatomite with double interface Cu4Ti2O/TiO2 and rutile/anatase heterojunction were fabricated, which demonstrated good antibacterial activity (100%) against Acinetobacter baumannii. Cu/TiO2/diatomite prepared under optimum preparation conditions (added diatomite, 0.005 g; Cu, 0.005 g; reaction temperature, 180 °C; reaction time, 8 h) exhibited high antibacterial activity (100%) against A. baumannii. For the Cu/TiO2/diatomite powders, their structural, compositional, optical and morphological traits were characterized by XRD, SEM, TEM, XPS, BET, FTIR, Mapping, and DRS. It was shown that Cu/TiO2/diatomite under optimum conditions consisted of the double interface Cu4Ti2O/TiO2 and rutile/anatase heterojunction with the narrowest band gap and largest BET surface area, pore size, and pore volume. Then, it could exhibit the best photocatalytic activity. [ABSTRACT FROM AUTHOR]

Recently, cross-dataset facial expression recognition (FER) has obtained wide attention from researchers. Thanks to the emergence of large-scale facial expression datasets, cross-dataset FER has made great progress. Nevertheless, facial images in large-scale datasets with low quality, subjective annotation, severe occlusion, and rare subject identity can lead to the existence of outlier samples in facial expression datasets. These outlier samples are usually far from the clustering center of the dataset in the feature space, thus resulting in considerable differences in feature distribution, which severely restricts the performance of most cross-dataset facial expression recognition methods. To eliminate the influence of outlier samples on cross-dataset FER, we propose the enhanced sample self-revised network (ESSRN) with a novel outlier-handling mechanism, whose aim is first to seek these outlier samples and then suppress them in dealing with cross-dataset FER. To evaluate the proposed ESSRN, we conduct extensive cross-dataset experiments across RAF-DB, JAFFE, CK+, and FER2013 datasets. Experimental results demonstrate that the proposed outlier-handling mechanism can reduce the negative impact of outlier samples on cross-dataset FER effectively and our ESSRN outperforms classic deep unsupervised domain adaptation (UDA) methods and the recent state-of-the-art cross-dataset FER results. [ABSTRACT FROM AUTHOR]

Chemoresistance is often a cause of the failure of chemotherapy in cancer treatment. Sorcin (SRI) is a soluble resistance-related calcium-binding protein involved in chemoresistant processes and is overexpressed in many chemoresistant cancer cells, including paclitaxel (PTX)-resistant ovarian cancer. Increased SRI can reduce the concentration of calcium ions in the cytosol and mitochondria and the decrease of calcium ion concentration prevents the occurrence of apoptosis. Here we examined the SRI expression in multiple cancers using a human TissueArray and found that SRI expression was significantly higher in malignant tumor tissues. Furthermore, SRI was overexpressed, while intracellular calcium concentration was decreased, in chemoresistant cancer cells. To restore intracellular calcium homeostasis and overcome chemoresistance, we developed lipid-coated albumin-PTX nanoparticles loaded with SRI-siRNA (LANP-PTX-siSRI) for PTX and SRI-siRNA co-delivery. LANP-PTX-siSRI had dual-target roles in the regulation of SRI and the delivery of PTX into chemoresistant cells. The LANP-PTX-siSRI inhibited the expression of SRI and enhanced intracellular calcium, leading to the induction of apoptosis and the inhibition of the growth of PTX-resistant cancer cells in vitro and in vivo. In addition, the mechanism study revealed that the overexpression of SRI was associated with an impaired TGF-β signaling pathway. The administration of TGF-β1 inhibited two calcium-binding proteins SRI and S100A14. In conclusion, our data unveil that restoring intracellular calcium ion homeostasis via reducing SRI expression can reverse chemoresistance. Thus, the fabricated LANP-PTX-siSRI has a potentially therapeutical application. [ABSTRACT FROM AUTHOR]

[Display omitted] • Short-term use of glucocorticoids can also harm multiple organs. • Genetic factors have the potential to impact variations in adverse drug reactions. • It is important to evaluate how allele mutations impact drug effectiveness and safety. • ABCB1 and CYP3A5 are commonly found in Chinese children. Glucocorticoid (GC) administration has been associated with adverse drug reactions (ADRs) affecting multiple organ systems. While long-term use is widely recognized as a significant independent predictor of ADRs, it is important to note that even short-term use can lead to serious ADRs. The considerable inter-individual variability in ADRs occurrence may be influenced by genetic factors. This study, we present a case of a child who experienced significant weight gain and osteoporosis, following a brief administration of GC. To comprehensively investigate the underlying mechanisms, we conducted a genomic analysis utilizing the whole exome sequencing (WES) technique. This analysis encompassed the examination of phase I and phase II metabolism, influx transport, efflux transport, and drug targeting. Additionally, a comprehensive analysis was conducted on a cohort of 52,119 children to determine their ABCB1 rs1045642 genotype, and an additional 37,884 children were tested for their CYP3A5 rs776746 genotype. The pharmacogenetic analysis unveiled the presence of a high-risk variant in ABCB1 rs1045642 and a slow metabolism variant in CYP3A5 rs776746, both of which have the potential to substantially contribute to ADRs. The findings of this study indicate that the prevalence of ABCB1 rs1045642 CT type among patients was 47.58%, with TT type accounting for 15.69 % and CC type accounting for 36.73 %. Furthermore, the distribution of CYP3A5 rs776746 CC genotype was observed in 50.54 % of individuals, while CT and TT genotypes were present in 41.15 % and 8.31 % of the population respectively. The distribution of ABCB1 and CYP3A5 genotypes among the pediatric population in China displays notable features. Specifically, for the ABCB1 rs1045642 genotype, less than 50 % of children exhibit intermediate metabotypes. Conversely, among children with the CYP3A5 rs776746 genotype, the predominant cause for enzyme activity is the slow metabolic type, accounting for up to 90 % of cases. Consequently, it is imperative to thoroughly evaluate the impact of allele mutation on the effectiveness and safety of glucocorticoid drugs or other medications metabolized by the ABCB1 and CYP3A5, particularly in the context of Chinese pediatric patients. [ABSTRACT FROM AUTHOR]

Bacterial vaginosis (BV) is a genital infection that frequently presents in women infected with human papillomavirus (HPV), but the correlation between BV, HPV and cervical intraepithelial neoplasia (CIN) development is still elusive. We organized a cross-sectional analysis which enrolled 624 participants and obtained 423 samples of vaginal secretions from them, including 193 HPV-negative samples and 230 HR-HPV-positive samples. We used 16S rRNA sequencing to measure the vaginal microbiota diversity in women with different BV, HPV and CIN status, and then calculated risk factors for CIN by logistic regression. We found that the diversity of vaginal microbiota was significantly increased after BV, HPV and BV-infected CIN group. The Observed species and Chao1 index of H.C group showed little difference with normal group, while its Shannon index was considerable higher than normal group. L. iners enriched in HPV infection group compared with others significantly. BV (OR = 0.358; 95% CI = 0.195–0.656; P <.05) and HR-HPV infection (OR = 0.016; 95% CI = 0.004–0.072; P <.001) were risk factors for CIN. In conclusion, we consider BV as a risk factor for CIN. The enrichment of L. iners under HPV infection state may contribute to maintenance of vaginal dysbiosis, and BV infection could facilitate the disturb. [ABSTRACT FROM AUTHOR]

Objective. Ultrasound-targeted microbubble destruction (UTMD) technique has recently been developed as a nonviral delivery of gene therapy. This study aimed at investigating the survival and apoptosis of ovarian cancer cell line OVCA-433 by inhibiting Livin expression through ultrasound-targeted microbubble destruction. Methods. We synthesized a targeted microbubble agent for UTMD-mediated shRNA against Livin gene in human ovarian cancer OVCA-433 cells. Lipid microbubbles were conjugated with a luteinizing hormone-releasing hormone analog (LHRHa) by an avidin-biotin linkage to target the ovarian cancer OVCA-433 cells expressing LHRH receptors. The microbubbles were mixed with the recombinant plasmid harboring shRNA-Livin. shRNA-Livin was transfected into OVCA-433 cells upon exposure to 1 MHz pulsed ultrasound beam (0.5 W/cm2) for 8 s. Cell survival was measured by the MTT assay, cell apoptosis by flow cytometry using annexin V/PI double staining, and cell ultrastructure by using the transmission electron microscope. The mRNA and protein expression levels of caspase-3 and caspase-8 were detected by RT-qPCR and western blotting. Results. UTMD-mediated delivery of shRNA-Livin remarkably reduced the survival of OVCA-433 cells but promoted the apoptosis compared with shRNA-Livin alone, shRNA-Livin plus nontargeted microbubbles, and shRNA-Livin plus LHRHa-conjugated microbubbles containing shRNA-Livin with or without exposure to ultrasound pulses. It was also found that UTMD-mediated delivery of shRNA-Livin notably declined the mRNA and protein expression levels of caspase-3 and caspase-8 in OVCA-433 cells compared with shRNA-Livin alone, shRNA-Livin plus nontargeted microbubbles, and shRNA-Livin plus LHRHa-conjugated microbubbles containing shRNA-Livin with or without exposure to ultrasound pulses. Conclusion. Our experiment verifies the hypothesis that ultrasound mediation of targeted microbubbles can enhance the transfection efficiency of shRNA-Livin in ovarian cancer cells. [ABSTRACT FROM AUTHOR]

Purpose: To compare the impact of different statins therapies on the reduction of carotid intima-media thickness (CIMT) may reflect their cardiovascular benefits which is useful in clinical decision. Methods: PubMed, EMBASE, Cochrane Library, and Web of Science were searched, and 3539 articles published from 1992 to 2020 were retrieved. CIMT in randomized controlled trials for statins therapies were included for traditional and network meta-analyses analyzed by Stata 16. The quality of included studies was assessed by the Cochrane Collaboration's tool. Results: Thirty-three randomized controlled trials (n=8762) were eligible for network meta-analysis, of which 18 randomized controlled trials (n=5252) were included for comparison between statins and no statins and 11 randomized controlled trials (n=1338) were included for comparison between high-intensity statins or combination with niacin/ezetimibe and moderate/low-intensity statins in 2 traditional meta-analyses. In the traditional meta-analyses, the statins groups significantly reduce CIMT compared to no statins (standard mean difference=−0.207, 95% confidence interval: −0.291 to −0.123, p<0.001), while high-intensity statins or combination with niacin/ezetimibe performed significant CIMT reduction compared to moderate/low-intensity statins (standard mean difference=−0.287, 95% confidence interval: −0.460 to −0.114, p=0.001). In the network meta-analysis, a relative rank for the ability to reduce CIMT was given as follows: combination therapy with niacin (mean rank: 1.7), high-intensity statins, combination therapy with ezetimibe, and moderate/low-intensity statins. Conclusion: Statins combined with niacin performed a greater CIMT reduction compared to high-intensity statins alone and combination therapies with ezetimibe. The advantage of niacin-combined statins therapies to improve cardiovascular endpoint needs further validation through randomized controlled trials. Clinical trial registration: PROSPERO, CRD42020175972 [ABSTRACT FROM AUTHOR]

Background: Previous reports confirmed early spinal fusion may compromise pulmonary function and thoracic development in skeletal immature patients with scoliosis. However, the different effects in patients with various Risser signs remain unknown. This study aimed to compare the influence of early thoracic fusion on pulmonary function and thoracic growth in patients with idiopathic scoliosis (IS) with closed triangular cartilage (TRC) and different Risser signs. Methods: Thirty-six patients with IS and a closed TRC were retrospectively selected and divided into the low Risser (LR, Risser sign ≤2, 22 patients) and high Risser (HR, 280% before and after surgery. The T1-T12 and anteroposterior thoracic diameter significantly increased after surgery in both groups, while the maximum inner chest diameter only increased in the LR group at the final follow-up. However, there were no significant differences in respiratory function and thoracic data between both groups. Conclusion: For patients with IS, early fusion did not deteriorate pulmonary function or thoracic development in TRC-closed patients whose Risser sign was ≤2 compared with those with a Risser sign >2. [ABSTRACT FROM AUTHOR]

Objective: This meta-analysis aimed to systematically evaluate the effectiveness and safety of galcanezumab in the prophylactic treatment of adult migraine. Methods: A systematic literature search was performed to identity randomized-controlled trials (RCTs). The primary outcome was the decline in the number of monthly migraine days (MMDs). Secondary outcomes included the reduction of monthly acute migraine‑specific medication days (MSMDs), the number of participants showing a reduction in MMDs from baseline of ≥ 50%, ≥ 75%, and 100%, the incidence of adverse events (AEs), and the number of participants developing anti-drug antibodies (ADAs) to galcanezumab. We calculated the mean difference (MD), relative risk (RR), and 95% confidence intervals (CIs) for these outcomes. Results: Among the five included trials, galcanezumab given at doses of 120, 150, 240, and 300 mg was superior to placebo for both MMDs and secondary outcomes. The degree of AEs in all group was mild. Notably, no significant differences were found in the occurrence of AEs and ADAs between the galcanezumab and placebo groups. Conclusion: Galcanezumab is a safe and effective treatment for adult patients with episodic and chronic migraine. [ABSTRACT FROM AUTHOR]

In the present study, we explored the clinical effect of midazolam as an adjuvant analgesic and tranquilizer after brachial plexus block anesthesia with the aid of imaging guidance. We selected 106 patients who had undergone elective unilateral upper extremity surgery from January 2017 to December 2019 and randomly divided them into groups A and B, with 53 cases in each group. All the patients had undergone brachial plexus block anesthesia. Group A received imidazole-assisted sedation, and group B received fentanyl plus midazolam-assisted sedation. Under ultrasound-guided intermuscular sulcus brachial plexus block, we observed and recorded the ultrasound anatomical images before injection, including the distance from the lower edge of the upper, middle, and lower trunk of the forearm brachial plexus to the skin. We also recorded the anesthesia and operation times, effects of the anesthetic block, and incidence of adverse reactions. The distance from the lower edge of each nerve trunk to the skin averaged 1.002 cm for the upper stem, 1.598 cm for the middle stem, and 2.26 cm for the lower stem. The average anesthesia procedure time was 3 minutes, 56 seconds and was within 3–5 minutes for 92% of the procedures. The anesthesia effect was excellent, good, and poor in 81%, 11%, and 6%, respectively, and ineffective for 2% and effective for 92%. The ultrasound-guided inferior intermuscular sulcus approach for brachial plexus block is suitable for unilateral upper extremity radial hand surgery. For surgery involving the upper extremity ulnar hand side, a larger dose (concentration) of local anesthetic should be used within a safe range and/or an additional ulnar nerve block might be necessary. Midazolam adjuvant medication can have a good sedative and amnestic effect in brachial plexus block anesthesia, helping to reduce pain and inhibit the increase in stress levels. [ABSTRACT FROM AUTHOR]

Chlorella vulgaris XJW (C. vulgaris XJW), one temperature tolerable microalgae with biodiesel production potential, was selected from Ulungur Lake in Xinjiang. In this research, optimal semi-continuous cultivation conditions were obtained by employing uniform design method. The total biomass and lipid productivity of C. vulgaris XJW cultured with semi-continuous mode in Column photobioreactor were affected by renewal rate, renewal period, nitrogen concentration and phosphorus concentration. According to the regression equation, the optimal semi-continuous cultivation conditions for the total biomass of C. vulgaris XJW was renewal rate of 33%, renewal period of 4 days, NaNO3 concentration of 0.69 g·L−1 and K2HPO4 concentration of 0.02 g·L−1. In the optimal conditions, the maximum total biomass of C. vulgaris XJW was 3.682 g·L−1, which was 20.1% higher than the highest value in unoptimized semi-continuous cultivation conditions, and 2.6 times higher than that in batch cultivation. Meanwhile, the optimal semi-continuous cultivation conditions for lipid productivity of C. vulgaris XJW was renewal rate of 27%, renewal period of 3 days, NaNO3 concentration of 1.03 g·L−1 and K2HPO4 concentration of 0.02 g·L−1. In the optimal conditions, the maximum lipid productivity of C. vulgaris XJW was 110.43 mg·L−1d−1, which was 16.8% higher than the highest value in unoptimized semi-continuous cultivation conditions, and 2.7 times higher than that in batch cultivation. Results were consistent with the predicted values obtained by model equations, which confirmed the reliability of model equations. The models achieved in this work could accurately predict the semi-continuous cultivation conditions of C. vulgaris XJW with total biomass and lipid productivity as indicators. Good cultivation model would make the large-scale cultivation of this kind of microalgae possible, providing enough materials for the biodiesel production. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to evaluate the clinical features of adenoma of the retinal pigment epithelium (RPE) and eye-sparing treatment for it. Methods: The patients underwent measurement of visual acuity and intraocular pressure, slit-lamp examination, ophthalmoscopy, fluorescein fundus angiography (FFA), indocyanine green angiography (ICGA), color Doppler imaging (CDI), and magnetic resonance imaging (MRI). The tumors were endoresected and studied histopathologically. Results: Of the 16 Asian patients, 15 had RPE adenoma and 1 had RPE adenocarcinoma. Visual acuity decreased in three cases, mainly due to the macular detachment. All tumors were solitary and unilateral and measured from 1.7 × 3.2 × 2.4 to 9.3 × 8.0 × 6.6 mm3. The tumor was located in the macular area in 2 patients, in the juxtapapillary area in 1 patient, and in the peripheral fundus in 13 patients. The tumors were yellow-pink in 3 patients and brown in 13 patients. The tumors showed hypofluorescence in early stage and mottled hyperfluorescence with prominent leakage in late stage on fluorescein angiography. CDI demonstrated arterial blood signals within tumor, and MRI demonstrated hyperintensity and hypointensity in the T1- and T2-weighted images, respectively. The tumors were positive for S-100, neuron-specific enolase (NSE), CK, epithelial membrane antigen (EMA), and vimentin; occasionally positive for melanin-A; and usually negative for melanoma-specific antigen HMB45 and synaptophysin (Syn). The endoresection surgery was performed in all 16 patients by the microinvasive vitrectomy for the excision of intraocular tumors and reconstruction of the eyeball. The follow-up time was 1.5–13 years (mean, 5 years). No tumor recurrence occurred, and the retina remained attached in 16 eyes. Conclusions: RPE-derived adenomas are rare and difficult to diagnose clinically. Local resection by the mircoinvasive vitrectomy is a feasible alternative treatment for RPE adenoma. [ABSTRACT FROM AUTHOR]

The poultry red mite (PRM), Dermanyssus gallinae , is a hematophagous ectoparasite considered as the major pest in the egg-laying industry. Vaccination is feasible strategy for controlling the haematophagous PRMs. Cathepsin D (CatD), cathepsin L (CatL) and legumain (Lgm) are three endopeptidases participating in digestion of hemoglobin in ticks. The in vitro test and the on-hen feeding device have been used to evaluate the efficacy of vaccines against D. gallinae , however they lacked some of the natural feeding cues for mites, resulting in unreliable results. In the present study, a reliable in vivo rearing system which was nearly close to the natural infestation status of mites was applied to evaluate the efficacy of vaccines against D. gallinae. After vaccinations with rDg-CatD-1, rDg-CatL-1 or rDg-Lgm, chicks developed the antigen-specific IgY immune response to each antigen. The survival rates of D. gallinae in three groups decreased significantly after they fed on the immunized birds. And the oviposition rate and fecundity were significantly reduced by 13.18% and 49.90% in the rDg-CatD-1 immunized group, 5.49% and 38.55% in the rDg-CatL-1 immunized group, respectively. Moreover, immunization with rDg-CatD-1 or rDg-CatL-1 significantly decreased the blood digestion rate of D. gallinae. However, no statistically significant effects on reproduction performance and blood digestion rate of mite were observed in group immunized with rDg-Lgm. Our results demonstrated that immunization with rDg-CatD-1 or rDg-CatL-1 could prevent and control D. gallinae by reducing the survival, reproductive capacity and blood digestion of mite. Importantly, the evaluation system based on the in vivo rearing system was reliable and practical, and it can accurately evaluate the effects of immunization on D. gallinae for pre-screening of potential novel antigens. [ABSTRACT FROM AUTHOR]

In this paper, we propose a novel paper currency defect detection algorithm using quaternion uniform strength. We first build paper currency image preprocessing integration framework which includes intensity balancing, paper currency location, and geometric correction. We then propose a global–local paper currency image registration algorithm by moving key areas within certain range which can eliminate the false difference effectively. Finally, the quaternion uniform strength is calculated by using quaternion convolution edge detector. The defect degree of paper currency is determined by using the quaternion uniform color difference. The proposed algorithm is tested using different datasets from five countries: CNY, USD, EUR, VND, and RUB. The experimental results demonstrate that the proposed algorithm yields better results than the existing state-of-the-art paper currency defect detection techniques. The demo of the proposed paper currency defect detection algorithm will be publicly available. [ABSTRACT FROM AUTHOR]

Products such as cattles and pigs can be processed into several types of products (parts) targeting different segments of customers, which belong to the so called coproducts. Mismatch risk is a significant issue in such coproduct supply chains. Under the Stackelberg game setting, we consider a coproduct supply chain consisting of one producer acting as the leader and one retailer being the follower and establish a stylized model to study how the mismatch risk should be allocated. Two supply chain modes are considered, i.e., the P-chain mode under which the producer is responsible for the processing activity and hence holds the mismatch risk, and the R-chain under which the retailer is responsible for the processing activity. We use the unbalanced ratio to reflect the degree of mismatch between supply and demand among different parts of the coproduct and study how the tradeoff between the bargaining power and the mismatch cost, by different mismatch risk allocations, influences the optimal decisions and the performances of the two parties as well as the whole supply chain. Our main findings include: (1) P-chain dominates R-chain from the perspective of the chain performance; and (2) the upstream producer is not always better off in the P-chain under which he bears more mismatch risk. Numerical study shows the robustness of our main results and further studies the effect of demand uncertainty and the processing cost on the performance of P-chain as compared to R-chain. [ABSTRACT FROM AUTHOR]

• Coronoviruses not only affect the respiratory system, but also have deleterious effects on the central nervous system. • Most neurological diseases could be caused by coronoviruses invasion. • Coronoviruses cause nerve damage via diverse pathways. Viral infections have detrimental impacts on neurological functions, and even to cause severe neurological damage. Very recently, coronaviruses (CoV), especially severe acute respiratory syndrome CoV 2 (SARS-CoV-2), exhibit neurotropic properties and may also cause neurological diseases. It is reported that CoV can be found in the brain or cerebrospinal fluid. The pathobiology of these neuroinvasive viruses is still incompletely known, and it is therefore important to explore the impact of CoV infections on the nervous system. Here, we review the research into neurological complications in CoV infections and the possible mechanisms of damage to the nervous system. [ABSTRACT FROM AUTHOR]

To evaluate the perceptual interactions among key aroma compounds found in milk fan, propanoic acid, butanoic acid, octanoic acid, octanal, nonanal, 2-nonanone, and ethyl hexanoate were analyzed by threshold values, aroma addition experiments (subthreshold), Feller's additive model (threshold), and σ-τ diagrams (threshold and superthreshold) at various concentrations. Aroma addition experiments highlighted that 7 key aroma compounds had significant effects on the aroma intensity of the sensory attributes of milk fan at the concentrations measured in a milk fan sample, and they might have synergistic effects with other compounds. The components of the 7 aroma compounds in binary mixtures showed synergistic effects from 21 binary mixtures by Feller's additive model. The components of 9 mixtures showed synergistic effects in the superadditive region (σ > 1.05), and 3 mixtures showed additive effects in the additive region (0.95 < σ < 1.05) of the σ-τ diagrams for all 168 binary mixtures. The results showed that perceptual interactions among the key aroma compounds in milk fan vary with different concentrations and threshold ratios. These results are helpful for further understanding the aroma of milk fan and improving the quality of its aroma. [ABSTRACT FROM AUTHOR]

While the risk factors for infertility are well-established, research on factors associated with voluntary childlessness is limited and mainly focused on adulthood factors. Thus, we examined the associations between factors in childhood and young adulthood and different types of childlessness. The analysis included 4653 women from the Australian Longitudinal Study on Women's Health from 1996 to 2021. Childlessness was categorised as: voluntary, due to infertility issues, or due to other reasons. The associations between factors in childhood and young adulthood and childlessness were assessed using multinomial logistic regression models. In their 40s, 4.8 % of women were voluntarily childless, 6.7 % were childless due to infertility issues, and 7.8 % were childless due to other reasons. Regardless of types of childlessness, being childless was associated with poorer self-rated health during childhood and having been unpartnered and obese in young adulthood. Ex-smokers in young adulthood had lower odds of childlessness. Childhood physical abuse was associated with childlessness due to infertility issues and other reasons. Voluntary childlessness and childlessness due to infertility issues were associated with having identified as non-exclusively heterosexual in early adulthood. Lower social support in early adulthood was associated with voluntary childlessness and childlessness due to other reasons. The direction of the associations could not be determined and using self-reported data may introduce recall bias. Factors in childhood and young adulthood were associated with different types of childlessness, highlighting the importance of adopting a life course perspective when studying childlessness. • Longitudinal data were used to examine factors associated with childlessness. • Several factors in childhood and young adulthood were associated with different types of childlessness. • Our results highlighted the importance of adopting a life course perspective when studying childlessness. [ABSTRACT FROM AUTHOR]

Two new indolizidine alkaloids crepidatumines A (1) and B (2) together with the stereoisomer of dendrocrepidine B (3) and known analog dendrocrepine (4) were isolated from D. crepidatum. Their structures were determined by HR-ESI-MS, NMR, and Electronic Circular Dichroism (ECD) experiments together with comparison of analogues. Compound (1) possess a (5/6/6/5) tetra-hetero-cyclic ring, whereas compound (2) contains a tricyclic system with an unusual bridged ring, which are the first report in Nature. The biological evaluation revealed that dendrocrepine (4) displayed a potent hypoglycemic effect in vitro. [ABSTRACT FROM AUTHOR]

Study Question: Is age at natural menopause (ANM) associated with the development of multiple chronic conditions (multimorbidity) in postmenopausal life?Summary Answer: Women with premature menopause experience increased odds of developing individual chronic conditions and multimorbidity.What Is Known Already: ANM is considered as a marker of age-related morbidity and mortality in postmenopausal life. Multimorbidity affects more than 60% of older women and has been recognized as the most common 'chronic condition'. Few studies have examined the association between ANM and the development of multimorbidity.Study Design, Size, Duration: A prospective national cohort study of 11 258 Australian women, aged 45-50 years in 1996. Women were followed from 1996 to 2016.Participants/materials, Setting, Methods: Information about ANM and 11 chronic conditions (diabetes, hypertension, heart disease, stroke, arthritis, osteoporosis, asthma, chronic obstructive pulmonary disease, depression, anxiety and breast cancer) were estimated approximately every 3 years. Multimorbidity is defined as 2 or more of these 11 conditions. Generalized estimating equations were used to link the categorical ANM with individual chronic conditions and multimorbidity.Main Results and the Role Of Chance: Among 5107 women reporting ANM, 2.3% experienced premature menopause (≤40 years) and 55.1% developed multimorbidity. Compared with women who experienced menopause at age 50-51 years, women with premature menopause had twice the odds of experiencing multimorbidity by age 60 (OR = 1.98, 95% CI 1.31 to 2.98) and three times the odds of developing multimorbidity in their 60s (OR = 3.03, 95% CI 1.62 to 5.64). Women with premature menopause also experienced higher incidence of most individual chronic conditions.Limitations, Reasons For Caution: The main limitation of this study was the use of self-reported data, but with repeated assessments from prospective study design and the validity of most of the chronic conditions from hospital data, the potential for non-differential misclassification is minimized.Wide Implications Of the Findings: To our knowledge, this is the first study to assess the association of premature menopause and development of multimorbidity in a larger national cohort of mid-aged women. Health professionals should consider comprehensive screening and assessment of risk factors for multimorbidity when treating women who experienced premature menopause.Study Funding/competing Interest(s): The Australian Longitudinal Study on Women's Health was supported by the Australian Government Department of Health. X.X. is funded by an International Postgraduate Research Scholarship from the Australian government and a UQ Centennial Scholarship from The University of Queensland. G.D.M. is supported by the National Health and Medical Research Council Principal Research Fellowship (APP1121844). None of the authors has any conflicts of interest to declare. [ABSTRACT FROM AUTHOR]

Background: Although public medical insurance covers over 95% of the population in China, disparities in health service use and out-of-pocket (OOP) health expenditure across income groups are still widely observed. This study aims to investigate the socio-economic disparities in perceived healthcare needs, informal care, formal care and payment for healthcare and explore their equity implication.Methods: We assessed healthcare needs, service use and payment in 400 households in rural and urban areas in Jiangsu, China, and included only the adult sample (N = 925). One baseline survey and 10 follow-up surveys were conducted during the 7-month monitoring period, and the Affordability Ladder Program (ALP) framework was adopted for data analysis. Negative binomial/zero-inflated negative binomial and logit regression models were used to explore factors associated with perceived needs of care and with the use of self-treatment, outpatient and inpatient care respectively. Two-part model and logit regression modeling were conducted to explore factors associated with OOP health expenditure and with the likelihood of incurring catastrophic health expenditure (CHE).Results: After adjusting for covariates, rural residence was significantly associated with more perceived healthcare needs, more self-treatment, higher probability of using outpatient and inpatient service, more OOP health expenditure and higher likelihood of incurring catastrophic expenditure (P < 0.05). Compared to the Urban Employee Basic Medical Insurance (UEBMI), enrollment in the New Rural Cooperative Medical Scheme (NRCMS) or in the Urban Resident Basic Medical Insurance (URBMI) was correlated with lower probability of ever using outpatient services, but with more outpatient visits when people were at risk of using outpatient service (P < 0.05). NRCMS/URBMI enrollment was also associated with higher likelihood of incurring CHE compared to UEBMI enrollment (OR = 2.02, P < 0.05); in stratified analysis of the rural and urban sample this effect was only significant for the rural population.Conclusions: The rural population in Jiangsu perceived more healthcare needs, had a higher probability of using both informal and formal healthcare services, and had more OOP health expenditure and a higher likelihood of incurring CHE. The inequity mainly exists in health care financing, and may be partially addressed through improving the benefit packages of NRCMS/URBMI. [ABSTRACT FROM AUTHOR]

To determine the key aroma compounds in Chinese milk fan cheese, samples from 6 of the most popular handmade milk fan workshops in Yunnan province of China were analyzed by gas chromatography-mass spectrometry (GC-MS), gas chromatography-olfactometry (GC-O), sensory evaluation, aroma recombination and omission experiments. Seventy-one aroma compounds were identified by GC-MS, and 31 odor-active compounds were detected by GC-O. The relationships between the 31 odor-active compounds and 10 sensory evaluation properties were explored by partial least squares discriminant analysis. The results identified 23 initial key aroma compounds, which were used to simulate the aroma profile of milk fan in aroma recombination experiments. Aroma omission experiments identified propanoic acid, butanoic acid, octanoic acid, octanal, nonanal, 2-nonanone, and ethyl hexanoate as the key aroma compounds. Propanoic acid and butanoic acid contributed to cheese and rancid aromas, octanal and nonanal to the fat aroma, octanoic acid and 2-nonanone to the cheese aroma, and ethyl hexanoate to the fruity aroma of milk fan. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective analysis of collected data and operative experiment on human cadavers.Objective: To describe a novel technique of the anterior atlantooccipital (AC) transarticular screw fixation, and to analyze the pertinent anatomy with cadaveric and radiographic assessment of the feasibility, safety, and general applicability of this technique.Summary Of Background Data: In some situations, the posterior AC fixation techniques may not be possible, or may require supplemental fixation, which include the congenital hypoplasia, absence of the bony elements, and even revision surgery. However, an anterior screw fixation technique may add stability to further attempts at obtaining an arthrodesis.Methods: A detailed description of the surgical technique was presented. Three-dimensional (3D) CT reconstruction of the cranioverteral region of 30 patients were performed to determine screw entry points, target points, and proposed screw trajectories. Following screw insertion in eight fresh frozen human cadaver spine specimens, dissection verified screw location relative to structures at risk.Results: The ideal entry point is located caudal to the C1 superior facet joint in line with the medial third of the C1 superior facet. The ideal screw is directed 41.7° posteriorly in the sagittal plane and 11.6° laterally in the coronal plane with a length around 30.4 mm. The feasibility of anterior AC screw fixation was 92% (35/38 cases). There is a risk of injury to the vertebral artery and the hypoglossal nerve.Conclusion: Anterior AC transarticular screw fixation is feasible and can be considered as a salvage technique or an alternative for the posterior AC fixation, as well as the supplement to the anterior occipitocervical fixation.Level Of Evidence: 3. [ABSTRACT FROM AUTHOR]

In situations in which posterior atlanto-occipital fixation might not be possible or might require supplemental fixation, anterior fixation might add stability in obtaining arthrodesis. The present study aimed to provide a radiographic evaluation of the safety and feasibility in the anterior approach. The bilateral craniocervical computed tomography slices of 60 patients were examined. The anterior screw entry point was the lowest point at the middle anterior aspect of C1 (atlas) lateral mass. To avoid hypoglossal canal and craniocerebral injury, the height of the hypoglossal canal and occipital condyle and occipital condyle width were obtained. The mandible occlusion angle (MOA), anterior screw trajectory above, under, and distal to the hypoglossal canal (AHA, UHA, and DHA) relative to the tangent line of C1 front border were measured, together with the maximum screw length under each angle (AHL, UHL and DHL). An independent samples t test was used for statistical analysis. The height of the hypoglossal canal and occipital condyle and occipital condyle width were all larger in the men than in the women. The MOA, AHA, UHA, and DHA were 55.0°, 18.7°, 41.0°, and 55.0°, respectively, and were similar between genders. The AHL, UHL, and DHL were 34.5, 30.9, and 31.3 mm, with the measurements for the men generally longer than those for the women by 3–4 mm. A total of 10 of 120 bilateral measurements showed the possibility of mandible occlusion, and the potential success rate of the anterior approach could reach 91.7%. The ideal entry angle for anterior atlanto-occipital fixation ranges from 41.0° to 55.0°, with a safe screw length from 30.9 to 31.3 mm. The potential success rate could reach >90%. [ABSTRACT FROM AUTHOR]

Background: Screening for type 2 diabetes mellitus (T2DM) targets people aged 35+ years and those with overweight/obesity. With mounting evidence on young‐onset T2DM and T2DM patients with lean phenotypes, it is worth revising the screening criteria to include younger and leaner adults. We quantified the mean age and body mass index (BMI; kg/m2) at T2DM diagnosis in 56 countries. Methods: Descriptive cross‐sectional analysis of WHO STEPS surveys. We analysed adults (25–69 years) with new T2DM diagnosis (not necessarily T2DM onset) as per fasting plasma glucose ≥126 mg/dL measured during the survey. For people with new T2DM diagnosis, we summarized the mean age and the proportion of each five‐year age group; also, we summarized the mean BMI and the proportion of mutually exclusive BMI categories. Results: There were 8695 new T2DM patients. Overall, the mean age at T2DM diagnosis was 45.1 years in men and 45.0 years in women; and the mean BMI at T2DM diagnosis was 25.2 in men and 26.9 in women. Overall, in men, 10.3% were 25–29 years and 8.5% were 30–34 years old; in women, 8.6% and 12.5% were 25–29 years and 30–34 years old, respectively. 48.5% of men and 37.3% of women were in the normal BMI category. Conclusions: A non‐negligible proportion of new T2DM patients were younger than 35 years. Many new T2DM patients were in the normal weight range. Guidelines for T2DM screening may consider revising the age and BMI criteria to incorporate young and lean adults. [ABSTRACT FROM AUTHOR]

Introduction: The coronavirus (COVID-19) became a global pandemic in March 2020 and impacted nations worldwide not only because of the disease but also because the containment measures-imposed created ripple effects for the populations in each country. The COVID-19 pandemic disproportionately affected vulnerable groups, such as persons with disabilities. This study aimed to understand the impact of COVID-19 on the function of Community-Based Rehabilitation (CBR)/Community-Based Inclusive Development (CBID) across nations and for their target communities—persons with disabilities. The current article also described some measures CBR/CBID programs took in light of service closure to facilitate access to needed services for persons with disabilities. Methods: We conducted a secondary analysis of qualitative data to understand the impact of COVID-19 on the functioning of CBR/CBID programs and their target communities. The original qualitative data were collected through online dialogues among CBR/CBID partners across five regions of the world, facilitated for understanding of their practices on five other topics. Findings: COVID-19 significantly impacted the function of CBR/CBID programs across the world. Many services were halted due to public health measures, such as maintaining social distancing or lockdowns. The COVID-19 pandemic also had a negative impact on access to health, education and livelihood support for persons with disabilities. Additionally, many people with disabilities did not have access to COVID-19 related information and services like vaccines. However, we found that technology played a significant role in revitalizing CBR/CBID programs during COVID-19. CBR/CBID service providers across five regions used online platforms to disseminate information about COVID-19. Professionals also used technology to provide rehabilitation and educational services to people with disabilities through online platforms. Conclusion: Our findings suggest that technology can play a vital role in continuing many services (e.g., CBR/CBID) that cannot be offered in person during crises like COVID-19. However, it is important to remember that technology may not be accessible to many individuals with disabilities, specifically those who reside in rural areas and who experience adverse situations like financial constraints. Additionally, many persons with disabilities may not have the necessary knowledge and skills to use technology. CBR personnel must consider that before adopting technology to provide services under CBR programs. [ABSTRACT FROM AUTHOR]

Activated carbon is one of the most widely used electrode materials for supercapacitors owing to its excellent porosity, large specific surface area and long cycle life. However, its utilization in electrode fabrication necessitates the incorporation of insulating binders to facilitate shaping due to its powdery nature. This may obstruct the pores and increase the internal resistance of the electrode, resulting in poor flexibility and electrochemical performance. To address this problem, an innovative and universal packaging strategy is proposed, in which composite films are prepared by double vacuum filtration, coated with gel electrolyte and then patterned by selective laser carving based on the principle of "Selective Optical Transmittance", to achieve the fabrication of binder-free and substrate-free all-carbon-based micro-supercapacitors. The areal capacitance of obtained Activated Carbon/Super P-Reduced Graphene Oxide Micro-supercapacitors (AC/SP-rGO MSCs) without binder are three times higher than those with binder. The prepared AC/SP-rGO MSCs exhibit remarkable areal capacitance of 177.32 mF cm−2, volumetric capacitance of 52.15 F cm−3 and high energy density of 4.44 mWh cm−3. Meanwhile, they also exhibit excellent flexibility with no capacitance degradation after 5000 bending cycles. Specifically, the energy provided by four AC/SP-rGO MSCs connected in series can light up to 46 red LEDs or provide a thermo-hygrometer with a long endurance of over 45 min. This packaging method has proven to be an effective strategy for the fabrication of powdery materials into binder-free electrodes, presenting a unique idea for the fabrication of electrodes within the realm of flexible electronics. [Display omitted] • Vacuum filtration complemented with selective laser carving is used to fabricate binder-free and substrate-free all-carbon-based micro-supercapacitors (MSCs). • The MSC exhibits remarkable capacitance of 177.32 mF cm−2 (52.15 F cm−3) and high energy density of 4.44 mWh cm−3. • The MSC shows excellent flexibility with no capacitance degradation after 5000 bending cycles. • Four MSCs connected in series can provide a thermo-hygrometer with a long endurance of over 45 min. [ABSTRACT FROM AUTHOR]

A ketogenic diet (KD) is composed of low-carbohydrate, high-fat and adequate levels of protein. It has been used for decades as a method to treat pediatric refractory epilepsy. However, recently, its side effects on the bones have received increasing attention. In order to comprehensively evaluate the effect of KD on the microstructures and mechanical properties of the skeleton, 14 male Sprague-Dawley rats were equally divided into two groups and fed with a KD (ratio of fat to carbohydrate and protein, 3:1) or a standard diet for 12 weeks. Body weight, as well as blood ketone and glucose levels, were monitored during the experiment. Bone morphometric analyses via micro-computerized tomography were performed on cortical and trabecular bone at the middle L4 vertebral body, the proximal humerus and tibia. The compressive stiffness and strength of scanned skeletal areas were calculated using micro-finite element analysis. The KD led to higher ketone levels and lower glucose levels, with reduced body weight and total bone mineral density (TBMD). After 12 weeks, the diet reduced the bone volume fraction, the trabecular number of cancellous bone, cortical thickness, total cross-sectional area inside the periosteal envelope and the bone area of cortical bone in the tibia and humerus, while increasing trabecular separation. However, KD may not affect the L4 vertebral body. The serum calcium or phosphate concentrations in the blood remained unchanged. In addition, bone stiffness and strength were clearly decreased by the KD, and significantly correlated with the BMD and bone area at all scanned sites. In conclusion, KD led to significant bone loss and reduced biomechanical function in appendicular bones, with a lesser impact on axial bones. [ABSTRACT FROM AUTHOR]

Background: Mental health symptoms are highly prevalent and dynamic among young people. Little is known about the trajectories of these symptoms and subsequent development of chronic conditions. This study examines whether (1) mental health trajectories can predict the onset of chronic conditions in young women and (2) trajectories are stronger predictors of the incidence of these conditions than mental health status measured at single time point.Methods: 6013 young Australian women were followed every 3-year for 20 years. The mental health trajectories in their 20s and mental health status 3-year before the onset of chronic conditions were used to predict the incidence of six chronic conditions in their 30s. Mental health trajectories were identified using latent mixture modelling of five-item Mental Health Index.Results: Five mental health trajectories were identified: maintaining a high score (high-stable); starting low then steadily increasing (improving); moderately high score, declining, then increasing (declining-improving); starting high then steadily decreasing (declining), and maintaining a low score (low-stable). In their 30s, 1015 (16.9%) women developed one or more conditions. The low-stable and declining groups were associated with increased odds of developing one or more conditions by 45% (odds ratio [OR] 1.45, 95% confidence interval [CI] 1.09-1.94) and 48% (OR 1.48, 95% CI 1.10-1.98), respectively, compared with the high-stable group. These are not so clearly distinguished by only considering mental health status at single time.Limitation: Self-reported chronic conditions.Conclusion: Mental health symptom trajectories in women's 20s are associated with the onset of chronic physical conditions in their 30s. [ABSTRACT FROM AUTHOR]

Metformin (Met), an anti-diabetes drug, has also shown therapeutic effects for ovariectomy-induced (OVX) osteoporosis. However, similar effects against bone loss induced by a ketogenic diet (KD) have not been tested. This study was aimed to evaluate the microarchitectures and biomechanics of KD-induced osteoporosis with and without administration of Met, and compare the effect of Met on bone loss induced by KD with OVX. Forty female C57BL/6J mice were randomly divided into Sham, OVX, OVX + Met (100 mg/kg/day), KD (3:1 ratio of fat to carbohydrate and protein), and KD + Met (100 mg/kg/day) groups. After 12 weeks, the bone mass and biomechanics were measured in distal cancellous bone and in mid-shaft cortical bone of the femur. The activities of serum alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP), together with immunohistochemistry staining of osteocalcin (OCN) and TRAP, were evaluated. Both OVX and KD induced significant bone loss and compromised biomechanical properties in the cancellous bone, but no effect was found in cortical bone. The administration of Met increased the cancellous bone volume fraction (BV/TV) from 3.78 to 5.23% following the OVX and from 4.04 to 6.33% following the KD, it also enhanced the compressive stiffness from 47 to 160 N/mm following the OVX and from 35 to 340 N/mm with the KD. Met effectively increased serum ALP in the KD group while decreased serum TRAP in the OVX group, but up-regulated expression of OCN and down-regulated expression of TRAP in both OVX and KD groups. The present study demonstrated that Met effectively attenuated the cancellous bone loss induced by KD and maintained the biomechanical properties of long bones, providing evidence for Met as a treatment of by KD-induced osteoporosis in teenage skeleton. [ABSTRACT FROM AUTHOR]

Abstract Objective Recent studies reported that hydrogen sulfide (H 2 S) is an effective agent for the prevention and treatment of acute lung injury (ALI). But the underlying mechanisms have not been understood clearly. In this study, we explored the possible mechanism from the perspective of autophagy regulation. Methods A mouse model of ALI and alveolar type II epithelial cells (MLE-12 cells) injury was induced using lipopolysaccharide (LPS). Expression of Beclin 1 and the conversion of LC3I to LC3II were detected to evaluate the activity of autophagy. Lung histopathological changes, wet/dry (W/D) ratio, pro-inflammatory cytokines TNF-α, IL-1β and protein content in bronchoalveolar lavage fluid (BALF), cell viability and lactic dehydrogenase (LDH) in the culture medium were determined to evaluate the severity of ALI. The activity of PI3K/Akt/mTOR pathway was detected to explore the possible mechanisms involved in the regulation of autophagy by H 2 S. Results The expression of Beclin 1 and the conversion of LC3I to LC3II were significantly increased after LPS treatment and reversed by H 2 S both in vivo and in vitro. Lung histopathological changes, W/D ratio, TNF-α, IL-1β and protein content in BALF induced by LPS were effectively ameliorated by H 2 S and autophagy inhibitor 3-methyladenine. The in vitro results showed that H 2 S and 3-methyladenine also attenuated LPS-induced cell viability decrease and LDH release. Furthermore, H 2 S effectively reversed LPS-induced PI3K/Akt/mTOR signaling pathway inhibition. Conclusion Autophagy inhibition through PI3K/Akt/mTOR pathway was involved in H 2 S prevention of LPS-induced ALI in mice. Highlights • Autophagy activation is an important pathogenesis of LPS-induced ALI in mouse. • H 2 S can inhibit the activation of autophagy in ALI induced by LPS. • H 2 S and 3-MA ameliorated LPS-induced ALI both in vivo and in vitro. • H 2 S inhibit the activation of autophagy through PI3K/Akt/mTOR pathway. [ABSTRACT FROM AUTHOR]

Study Design: A retrospective analysis of collected data.Objective: Our study aims to present the morphology of cranial-cervical spinal canal in basilar invagination (BI) patients.Summary Of Background Data: BI is characterized by protrusion of the odontoid process into the foramen magnum (C0), leading to compression of the cervicomedullary junction. However, no study has ever clarified the anatomical diameters of spinal canal in patients with BI.Methods: The study retrospectively examined computed tomography (CT)-based anatomical characteristics in a cohort of 84 patients with and without BI. We measured the anteroposterior diameter (APD) and transversal diameter (TVD) of spinal canal from C0 to C4, together with the area of vertebral canal (Area). Independent samples t test was used for statistical analysis.Results: The APD in the BI group was shorter than the control group from C0 to C2 (C0: 27.98 vs. 35.11 mm, P < 0.001; C1: 11.87 vs. 16.91 mm, P < 0.001; C2: 12.91 vs. 14.84 mm, P < 0.001), but it became longer from C3 to C4. The TVD of the BI group was significantly wider from C0 to C3 (C0: 30.59 vs. 28.54 mm, P < 0.001; C1: 31.31 vs. 25.98 mm, P < 0.001; C2: 21.56 vs. 20.40 mm, P = 0.01; C3: 22.45 vs. 21.23 mm, P = 0.013), and it had no significance at C4. The Area showed no difference between the two groups from C1 to C2, but it turned larger at C3 and C4 in BI patients.Conclusion: BI patients may have shorter APD from C0 to C2, which could be the leading cause of neurological compression, necessitating decompression on sagittal plane. Below the pathological levels, BI patients have larger spinal canal than general population.Level Of Evidence: 3. [ABSTRACT FROM AUTHOR]

To achieve efficient ultrasonography-guided photodynamic therapy (PDT), two major obstacles need to be overcome. On the one hand, O 2 -dependent PDT produces limited effects on hypoxic solid tumors. On the other hand, small particles facilitate tumor accumulation whereas large ones strengthen ultrasound (US) imaging, which makes the development of an ultrasonographic probe showing effective tumor accumulation and high US sensitivity an intractable challenge. Therefore, an intelligent perfluorohexane (PFH)-based nanodroplet, PFH@Ce6@O 2 , was fabricated in order to simultaneously solve the above problems. The nanoscale PFH@Ce6@O 2 particles were firstly delivered to elevate the local O 2 level of tumors, which is critical for achieving excellent PDT effect under laser irradiation. Then, a spontaneous “small-to-large” growth of droplet at tumor acidic microenvironment resulted in an echo-contrast enhancement for high-performance US imaging of tumor. The in vitro and in vivo results manifested the advantage of PFH@Ce6@O 2 in alleviating hypoxic status to inhibit tumor growth. Overall, PFH@Ce6@O 2 integrating US/FL bimodal imaging and PDT effect appears to be a promising nanoplatform for ultrasonography-guided PDT of solid tumors. [ABSTRACT FROM AUTHOR]

The aim of this study was to analyze the features of non-mass breast lesions (NMLs) on B-mode ultrasound (US), color Doppler US, strain elastography (SE) and contrast-enhanced ultrasound (CEUS) and to develop a multimode ultrasonic method for NML differentiation. Seventy-one NMLs were included in this retrospective study. Binary logistic regression was used to identify the independent risk factors. Pathology results were used as the standard criterion. Microcalcification on US, high stiffness on SE and hyper-enhanced intensity on CEUS were identified as features correlated with malignancy. A multimode method to evaluate NMLs based on the logistic regression was developed. The sensitivity and specificity for US, US + Doppler, US + SE, US + CEUS and the multimode method were 100% and 29%, 92.5% and 41.9%, 97.5% and 58.1%, 90.0% and 58.1% and 95.0% and 77.4%, respectively. The accuracy of these methods was 69.0%, 70.4%, 80.2%, 76.1% and 87.3%, respectively. The multimode ultrasonic method is simple and exhibited high diagnostic performance, which might be helpful for predicting the potential malignancy of NMLs. [ABSTRACT FROM AUTHOR]

• Developing a hybrid model reproducing daily variation of pan evaporation. • Using the hybrid model assimilates different pan evaporation into a consistent series. • Constructing a homogeneous pan evaporation dataset for 2000 stations over China. • Estimating the long-term trend of pan evaporation in China from 1961 to 2018. • Inhomogeneities exaggerated the downward trend of pan evaporation before the 1990s. Global warming is expected to increase the atmospheric evaporative demand and make more surface water for evapotranspiration, aggerating water sources' social and ecological shortage. Pan evaporation, as a routine observation worldwide, is an excellent metric to indicate the response of terrestrial evaporation to global warming. However, several non-climatic effects, such as instrument upgrades, have destroyed the homogenization of pan evaporation and limited its applications. In China, 2400s meteorological stations have observed daily pan evaporation since 1951. The observed records became discontinuous and inconsistent due to the instrument upgrade from micro-pan D20 to large-pan E601. Here, combining the Penpan model (PM) and random forest model (RFM), we developed a hybrid model to assimilate different types of pan evaporation into a consistent dataset. Based on the cross-validation test, on a daily scale, the hybrid model has a lower bias (RMSE=0.41 mm day−1) and better stability (NSE=0.94) than the two sub-models and the conversion coefficient method. Finally, we produced a homogenized daily dataset of E601 across China from 1961 to 2018. Based on this dataset, we analyzed the long-term trend of pan evaporation. Pan evaporation showed a -1.23±0.57 mm a−2 downward trend from 1961-1993, primarily caused by decreased pan evaporation in warm seasons over North China. After 1993, the pan evaporation in South China increased significantly, resulting in a 1.83±0.87 mm a−2 upward trend across China. With better homogeneity and higher temporal resolution, the new dataset is expected to promote drought monitoring, hydrological modeling, and water resources management. Free access to the dataset can be found at https://figshare.com/s/0cdbd6b1dbf1e22d757e. [ABSTRACT FROM AUTHOR]

Poly(ADP-ribose) polymerase-1 (PARP-1) is a highly conserved nuclear enzyme, which binds tightly to damaged DNA and plays a key role in DNA repair, recombination, proliferation, and genomic stability. However, due to the poor electrochemical and optical activity of PARP-1 and its product PAR, only a few studies on its activity detection method have been reported. Herein, we report a simple and sensitive colorimetric strategy to monitor PARP-1 activity based on enzyme-initiated auto-PARylation-controlled aggregation of hemin-graphene nanocomposites (H-GNs). PARP, activated by dsDNA, catalyzed its substrate nicotinamide adenine dinucleotide (NAD+) to polymerize as a poly(ADP-ribose) polymer (PAR). PAR possesses several negative charges, and its charge density is twice that of a single-stranded DNA, which greatly impacts the dispersibility of H-GNs; due to their peroxidase-like catalytic activities, H-GNs can catalyze the chromogenic reaction of TMB and H2O2. As a result, in the presence of different PARP-1 activities, the supernatant of the corresponding solution contained different amounts of dispersed H-GNs and showed different colors after the chromogenic reaction that could be discerned easily by the absorbance or the color changes of the solution. The method was simple, sensitive, and reliable. The proposed method displays a linear range from 0.05 to 1 U with a detection limit of 0.03 U. In addition, this new method has been successfully applied to detect PARP-1 activity in human serum and different cancer cells and evaluate PARP-1 inhibitors. [ABSTRACT FROM AUTHOR]

Background: The prevalence of diabetes, heart disease, and stroke multimorbidity (co-occurrence of two or three of these conditions) has increased rapidly. Little is known about how the three conditions progress from one to another sequentially through the life course. We aimed to delineate this progression in middle-aged women and to determine the roles of common risk factors in the accumulation of diabetes, heart disease, and stroke multimorbidity.Methods and Findings: We used data from 13,714 women aged 45-50 years without a history of any of the three conditions. They were participants in the Australian Longitudinal Study on Women's Health (ALSWH), enrolled in 1996, and surveyed approximately every 3 years to 2016. We characterized the longitudinal progression of the three conditions and multimorbidity. We estimated the accumulation of multimorbidity over 20 years of follow-up and investigated their association with both baseline and time-varying predictors (sociodemographic factors, lifestyle factors, and other chronic conditions). Over 20 years, 2,511 (18.3%) of the women progressed to at least one condition, of whom 1,420 (56.6%) had diabetes, 1,277 (50.9%) had heart disease, and 308 (12.3%) had stroke; 423 (16.8%) had two or three of these conditions. Over a 3-year period, the age-adjusted odds of two or more conditions was approximately twice that of developing one new condition compared to women who did not develop any new conditions. For example, the odds for developing one new condition between Surveys 7 and 8 were 2.29 (95% confidence interval [CI], 1.93-2.72), whereas the odds for developing two or more conditions was 6.51 (95% CI, 3.95-10.75). The onset of stroke was more strongly associated with the progression to the other conditions (i.e., 23.4% [95% CI, 16.3%-32.2%] of women after first onset of stroke progressed to other conditions, whereas the percentages for diabetes and heart disease were 9.9% [95% CI, 7.9%-12.4%] and 11.4% [95% CI, 9.1%-14.4%], respectively). Being separated, divorced, or widowed; being born outside Australia; having difficulty managing on their available income; being overweight or obese; having hypertension; being physically inactive; being a current smoker; and having prior chronic conditions (i.e., mental disorders, asthma, cancer, osteoporosis, and arthritis) were significantly associated with increased odds of accumulation of diabetes, heart disease, and stroke multimorbidity. The main limitations of this study were the use of self-reported data and the low number of events.Conclusions: Stroke was associated with increased risk of progression to diabetes or heart disease. Social inequality, obesity, hypertension, physical inactivity, smoking, or having other chronic conditions were also significantly associated with increased odds of accumulating multimorbidity. Our findings highlight the importance of awareness of the role of diabetes, heart disease, and stroke multimorbidity among middle-aged women for clinicians and health-promotion agencies. [ABSTRACT FROM AUTHOR]

Aims: Thermal ablation can evoke an immune response, which may have effects on the prognosis of patients with hepatocellular carcinoma (HCC). Our aim is to investigate the changes of circulating T-cell subsets after microwave ablation (MWA) and to explore the risk factors of tumor recurrence in patients with hepatitis B virus (HBV)-related HCC.Methods: Thirty patients with HBV-related HCC were enrolled in this study. The blood samples were collected both before and after MWA (24 h, 72 h, and 1 month after MWA). The distributions of Th17 cells, regulatory Treg-cells, CD4+ T-cells, CD8+ T-cells, and CD3+ T-cells were determined by flow cytometer. The potential-related factors of tumor recurrence were analyzed by logistic regression.Results: The levels of circulating T-cell subsets, except for Th17 cells, were relatively stable after MWA. The frequency of Th17 cells increased from 3.98% ± 2.40% before treatment to 5.53% ±3.27% 24 h after treatment. Eight of 30 patients had a tumor recurrence. The results of logistic regression suggested that among 11 candidates, only the level of Th17 cells was the risk factor of tumor recurrence. To remove the interference from other factors, seven patients with tumor(s) >3 cm or alpha-fetoprotein >400 ng/mL were excluded in another parallel logistic regression. The results of such regression clearly demonstrated that circulating Th17 cells is indeed a related factor of tumor recurrence.Conclusions: Thermal ablation may evoke a transitional immune response by increasing the frequency of Th17 cells. Patients with high levels of baseline circulating Th17 cells, instead of the transient elevation of Th17 cells induced by MWA, are at the risk of tumor recurrence. [ABSTRACT FROM AUTHOR]

In this paper, novel copper/titanium dioxide (Cu/TiO 2 ) composites were facilely prepared by simple sol-gel hydrothermal method. The crystalline phases, surface morphology and antibacterial activity of Cu/TiO 2 were investigated systematically. Interestingly, the as-prepared Cu/TiO 2 materials were made up with three different crystalline phases, including cuprite Cu 2 Cl(OH) 3 , Cu 2+1 O, and anatase TiO 2 . Next, the ‘zone of inhibition’ experiment was performed against E. coli using Cu/TiO 2 catalysts with different Cu doping concentration as the antibacterial agents. Our results show that the Cu/TiO 2 -3.00 catalyst possesses optimal antibacterial ability against E. coli , which may be connected with the strong oxidizing reactive oxygen species (ROS) destroying the bacteria and photogenerated charge separation and recombination. [ABSTRACT FROM AUTHOR]

The increasing challenge of multiple chronic diseases (multimorbidity) requires more evidence-based knowledge and effective practice. In order to better understand the existing evidence on multimorbidity, we performed a systematic review of systematic reviews on multimorbidity with pre-established search strategies and exclusion criteria by searching multiple databases and grey literature. Of 8006 articles found, 53 systematic reviews (including meta-analysis and qualitative research synthesis performed in some reviews) that stated multimorbidity as the main focus were included, with 79% published during 2013–2016. Existing evidence on definition, measurement, prevalence, risk factors, health outcomes, clinical practice and medication (polypharmacy), and intervention and management were identified and synthesised. There were three major definitions from three perspectives. Seven studies on prevalence reported a range from 3.5% to 100%. As six studies showed, depression, hypertension, diabetes, arthritis, asthma, and osteoarthritis were prone to be comorbid with other conditions. Four groups of risk factors and eight multimorbidity associated outcomes were explored by five and six studies, respectively. Nine studies evaluated interventions, which could be categorized into either organizational or patient-oriented, the effects of these interventions were varied. Self-management process, priority setting and decision making in multimorbidity were synthesised by evidence from 4 qualitative systematic reviews. We were unable to draw solid conclusions from this overview due to the heterogeneity in methodology and inconsistent findings among included reviews. As suggested by all included studies, there is a need for prospective research, especially longitudinal cohort studies and randomized control trials, to provide more definitive evidence on multimorbidity. [ABSTRACT FROM AUTHOR]

Purpose: Eyelid sebaceous gland carcinoma (SGC) is a malignancy with fatal risk, high recurrence rate, and pagetoid spread. Thus, recurrence risk prediction and prompt treatment are extremely important. This study aimed to develop a nomogram to predict SGC recurrence based on potential risk factors. Methods: We conducted a retrospective study to train and test a nomogram based on the clinical data of 391 patients across our hospital (304) and other grass‐roots hospitals (87). After Cox regression, predictors included in the nomogram were selected, and sensitivity, specificity, concordance index (C‐index), etc., were calculated to test their discrimination ability. Results: After a median follow‐up period of 4.12 years, SGC recurred in 52 (17.11%) patients. The 1‐, 2‐, and 5‐year recurrence‐free survival rates were 88.3%, 85.4%, and 81.6%, respectively. We examined five risk factors, such as lymph node metastasis at initial diagnosis (hazard ratio [HR], 2.260; 95% confidence interval [CI], 1.021–5.007), Ki67 (HR, 1.036; 95% CI, 1.020–1.052), histology differentiation degree (HR, 2.274; 95% CI, 1.063–4.865), conjunctival pagetoid infiltration (HR, 2.100; 95% CI, 1.0058–4.167), and orbital involvement (HR, 4.764; 95% CI, 1.436–15.803). The model had good discrimination in both internal and external test sets. The model had good discrimination in both internal and external test sets. The sensitivity of the internal test and external test set were 0.722 and 0.806, respectively, and specificity of the internal test and external test set were 0.886 and 0.893, respectively. Conclusion: We examined the potential risk factors for eyelid SGC recurrence and constructed a nomogram, which complements the TNM system in terms of prediction, indicating that our nomogram has the potential to reach clinical significance. This nomogram has the potential to assist healthcare practitioners in promptly detecting patients who are at an elevated risk and in tailoring clinical interventions to meet their individualized needs. [ABSTRACT FROM AUTHOR]

A nanocomposite consisting of polyaniline and multiwalled carbon nanotubes was tethered with a thiolated thrombin-specific aptamer and placed on a glassy carbon electrode (GCE) to obtain a biosensor for thrombin that has a limit of detection of 80 fM. Tethering was accomplished via a thiol-ene reaction between thiolated thrombin aptamer (TTA) and oxidized polyaniline (PANI) that was chemically synthesized in the presence of solution-dispersed multiwalled carbon nanotubes (MWCNTs). The modified GCE exhibits a pair of well-defined redox peaks (at 50/−25 mV) of self-doped PANI in neutral solution, and the tethered TTA-thrombin interaction gives a decreased electrochemical signal. Cyclic voltammetry, scanning electron microscopy and ultraviolet visible spectroscopy were used to characterize the film properties. This amperometric aptasensor is sensitive, selective and reproducible. It was applied to the determination of thrombin in spiked human serum (0.2 to 4 nM) and gave recoveries that ranged from 95 to 102%. [ABSTRACT FROM AUTHOR]

Telomerase, a widely accepted cancer biomarker for early cancer diagnostics, is considered as an important therapeutic target. To now, it is still a challenging subject to develop a simple and sensitive strategy for telomerase activity detection. Herein, we reported a simple colorimetric strategy for label-free quantification of human telomerase activity in urine by using hemin-graphene nanomaterial (H-GNs). H-GNs possessed tailored dispersibility in the high salt concentration and highly active biomimetic oxidation catalyst property. In this strategy, H-GNs were adjusted to coagulate to appropriate degree by carefully selecting the contained NaCl amount in the presence of original TS primer. The supernatant of the solution contained few H-GNs and showed light blue color. Under the action of telomerase, TS primer was elongated with repeating sequences of (TTAGGG) n . These negatively charged DNA enhanced individual H-GNs electrostatic repulsion and resisted salt-induced H-GNs coagulation. As a result, the supernate of the corresponding solution containing more dispersed H-GNs and showed dark blue color after chromogenic reaction. Thus, telomerase activity could be quasi-quantified by naked eye and precise quantified by UV spectrometer. The proposed method has the linear range from 100 to 2300 HeLa cells/mL and the detection limit was 60 cells/mL. It has been successfully applied to detect telomerase activity in real urine samples. Obtained results were in good agreement with the clinical diagnosis. Therefore, this colorimetric approach affords simplicity, sensitivity and reliability in telomerase activity detection. [ABSTRACT FROM AUTHOR]