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Abstract Mitochondrial calcium overload plays an important role in the neurological insults in seizure. The Rab7 GTPase-activating protein, Tre-2/Bub2/Cdc16 domain family member 15 (TBC1D15), is involved in the regulation of mitochondrial calcium dynamics by mediating mitochondria–lysosome membrane contact. However, whether TBC1D15-regulated mitochondria–lysosome membrane contact and mitochondrial calcium participate in neuronal injury in seizure is unclear. We aimed to investigate the effect of TBC1D15-regulated mitochondria–lysosome membrane contact on epileptiform discharge-induced neuronal damage and further explore the underlying mechanism. Lentiviral vectors (Lv) infection and stereotaxic adeno-associated virus (AAV) injection were used to regulate TBC1D15 expression before establishing in vitro epileptiform discharge and in vivo status epilepticus (SE) models. TBC1D15’s effect on inter-organellar interactions, mitochondrial calcium levels and neuronal injury in seizure was evaluated. The results showed that abnormalities in mitochondria–lysosome membrane contact, mitochondrial calcium overload, mitochondrial dysfunction, increased levels of reactive oxygen species, and prominent neuronal damage were partly relieved by TBC1D15 overexpression, whereas TBC1D15 knockdown markedly deteriorated these phenomena. Further examination revealed that epileptiform discharge-induced mitochondrial calcium overload in primary hippocampal neurons was closely associated with abnormal mitochondria–lysosome membrane contact. This study highlights the crucial role played by TBC1D15-regulated mitochondria–lysosome membrane contact in epileptiform discharge-induced neuronal injury by alleviating mitochondrial calcium overload.

ABSTRACT Importance Nutrition is associated with neurodevelopment. Infants at high risk of cerebral palsy (CP) usually suffer from undernutrition, yet the relationship between nutritional status and neurodevelopmental levels is unclear. Objective To describe the nutritional status characteristics of infants at high risk of CP, and to explore the relationship between neurodevelopmental levels and nutritional status. Methods This single‐center cross‐sectional study enrolled infants at high risk of CP, with corrected age from 0 days to 12 months. Weight and height were measured and calculated into z‐scores, which were used to classify the nutritional status based on the World Health Organization growth charts and American Society for Parenteral and Enteral Nutrition standards. The Bayley Scales of Infant and Toddler Development were used to evaluate the developmental levels of gross motor, fine motor, cognition, receptive communication, and expressive communication. Results A total of 479 infants at high risk of CP were recruited, with 43.4% classified as undernutrition. Compared to those with normal neurodevelopment, the odds of moderate and severe undernutrition were about 1.8 and 3.9 times higher in gross motor delay, 2.2 and 3.1 times higher in fine motor delay, 2.5 and 9.4 times higher in cognition delay, 2.2 and 3.9 times higher in receptive communication delay, and 3.0 and 5.6 times higher in expressive communication delay. There were significant positive correlations between nutritional status and neurodevelopmental levels (P < 0.001). Interpretation Undernutrition and neurodevelopmental delays are prevalent among infants at high risk of CP. Worse nutritional status was correlated with lower neurodevelopmental levels.

Abstract Reliable estimates of saturated hydraulic conductivity (Ks) are usually difficult to obtain, as Ks is regulated by a variety of soil processes acting at different spatial scales that may obscure each other's impacts. We hypothesized that these scale‐specific relationships could be well characterized with the aid of the noise‐assisted multivariate empirical mode decomposition (NA‐MEMD), thereby serving as a solid foundation for an accurate Ks prediction. The objective was to evaluate whether the incorporation of NA‐MEMD could improve the estimation of Ks based on the multiscale associations it unraveled. On a typical slope transect of 860 m in the black soil region of northeast China, Ks, mollic epipedon thickness, bulk density, soil organic carbon content, total (ϕ) and effective porosities (ϕe), and particle size distribution were investigated at every 20 m. Prior to NA‐MEMD, Ks was most strongly correlated with ϕe, and the linear regression models based on ϕe solely were satisfactory for Ks estimation at the scale of investigation. Adding other predictors significantly improved Ks prediction in calibration, but impaired it in validation. Upon decomposition by NA‐MEMD, Ks was found to be significantly associated with each attribute at two scales of oscillation at least. Summing up the estimates of each Ks component derived from the properties at the equivalent oscillation scales, the results outperformed the traditional multiple linear regressions made at the investigation scale, when the same sets of predictors were used. The application of NA‐MEMD, moreover, could save the tedious measurements of ϕe and ϕ. Excluding these two porosity‐related properties, Ks estimates obtained by incorporating NA‐MEMD were statistically similar or even better than those involving them before NA‐MEMD. These findings demonstrate the great potential of NA‐MEMD in untangling scale‐dependent relationships of Ks with various processes and hold important implications for future estimations of Ks and other hydraulic properties in the black soil region of northeast China and similar regions.

Skin and soft-tissue infections require significant consideration because of their prolonged treatment duration and propensity to rapidly progress, resulting in severe complications. The primary challenge in their treatment stems from the involvement of drug-resistant microorganisms that can form impermeable biofilms, as well as the possibility of infection extending deep into tissues, thereby complicating drug delivery. Dissolving microneedle patches are an innovative transdermal drug-delivery system that effectively enhances drug penetration through the stratum corneum barrier, thereby increasing drug concentration at the site of infection. They offer highly efficient, safe, and patient-friendly alternatives to conventional topical formulations. This comprehensive review focuses on recent advances and emerging trends in dissolving-microneedle technology for antimicrobial skin-infection therapy. Conventional antibiotic microneedles are compared with those based on emerging antimicrobial agents, such as quorum-sensing inhibitors, antimicrobial peptides, and antimicrobial-matrix materials. The review also highlights the potential of innovative microneedles incorporating chemodynamic, nanoenzyme antimicrobial, photodynamic, and photothermal antibacterial therapies. This review explores the advantages of various antimicrobial therapies and emphasizes the potential of their combined application to improve the efficacy of microneedles. Finally, this review analyzes the druggability of different antimicrobial microneedles and discusses possible future developments.

Abstract Background The majority of HBeAg-positive mothers with chronic hepatitis B have high levels of viremia and inactive disease with normal alanine aminotransferase (ALT) during pregnancy. In addition, postpartum disease activation and ALT flare have been reported in the range of 15 − 35%. However, the current International Association Guidelines have not provided clear recommendations and a risk-stratified monitoring schedule. Furthermore, data are lacking on the definition of normal ALT in the postpartum period in mothers with chronic hepatitis B. The clinical features and ALT flare patterns in HBeAg-positive mothers versus HBeAg-negative mothers are not fully explored. Thus, we design a cohort study to investigate the aforementioned area and generate data to assist healthcare providers in better managing mothers with hepatitis B. We aim to assess the frequency of postpartum ALT flares and predictors for such events. Method This study is a single-center and prospective cohort study (n = 360) that consists of two groups of patients including HBsAg-positive mothers (n = 120) and healthy mothers without HBV infection (n = 240). In HBeAg-positive mothers, antiviral therapy during late pregnancy is permitted to prevent Mother-to-child transmission (MTCT) but discontinued at delivery if there is no further indication for the treatment. Mothers are enrolled at the gestational weeks of 12–24. After delivery, both mothers and their infants will be followed up until postpartum week 24. Clinical and laboratory data are collected every 4 weeks during the study except there are no follow-up visits at the postpartum weeks 16 and 20. The primary objective is the proportion of patients with postpartum ALT flares. The secondary objectives are independent risk factors during pregnancy for predicting postpartum ALT flares and the normal range of postpartum ALT levels in healthy mothers. Discussion The current study focuses on the incidence of postpartum ALT flares in mothers with chronic hepatitis B including subgroup analysis based on HBeAg status. The data will have several clinical implications, such as providing evidence for an appropriate monitoring schedule in CHB mothers after delivery. Further analyses on predictors of such events may assist clinicians in identifying mothers who might develop severe postpartum ALT flares. The data generated from healthy mothers have the potential to identify the patterns of ALT changes during pregnancy and postpartum, so we can gain a better understanding of the normal range of ALT in this subpopulation. Trial Registration Number at the Chinese Clinical Trial Registry ChiCTR2200061130.

Microneedles (MNs) can be used for the topical treatment of skin disorders as they directly deliver therapeutics to the site of skin lesions, resulting in increased therapeutic efficacy while having minimum side effects. MNs are used to deliver different kinds of therapeutics (e.g., small molecules, macromolecules, nanomedicines, living cells, bacteria, and exosomes) for treating various skin disorders, including superficial tumors, wounds, skin infections, inflammatory skin diseases, and abnormal skin appearance. The therapeutic efficacy of MNs can be improved by integrating the advantages of multiple therapeutics to perform combination therapy. Through careful designing, MNs can be further modified with biomimetic structures for the responsive drug release from internal and external stimuli and to enhance the transdermal delivery efficiency for robust therapeutic outcomes. Some studies have proposed the use of drug-free MNs as a promising mechanotherapeutic strategy to promote wound healing, scar removal, and hair regeneration via a mechanical communication pathway. Although MNs have several advantages, the practical application of MNs suffers from problems related to industrial manufacture and clinical evaluation, making it difficult for clinical translation. In this study, we summarized the various applications, emerging challenges, and developmental prospects of MNs in skin disorders to provide information on ways to advance clinical translation.

Glioblastoma multiforme (GBM), a potential public health issue, is a huge challenge for the advanced scientific realm to solve. Chemodynamic therapy (CDT) based on the Fenton reaction emerged as a state-of-the-art therapeutic modality to treat GBM. However, crossing the blood–brain barrier (BBB) to reach the GBM is another endless marathon. In this review, the physiology of the BBB has been elaborated to understand the mechanism of crossing these potential barriers to treat GBM. Moreover, the designing of Fenton-based nanomaterials has been discussed for the production of reactive oxygen species in the tumor area to eradicate the cancer cells. For effective tumor targeting, biological nanomaterials that can cross the BBB via neurovascular transport channels have also been explored. To overcome the neurotoxicity caused by inorganic nanomaterials, the use of smart nanoagents having both enhanced biocompatibility and effective tumor targeting ability to enhance the efficiency of CDT are systematically summarized. Finally, the advancements in intelligent Fenton-based nanosystems for a multimodal therapeutic approach in addition to CDT are demonstrated. Hopefully, this systematic review will provide a better understanding of Fenton-based CDT and insight into GBM treatment.

Regulatory T cells (Tregs) can eliminate autoreactive lymphocytes, induce self-tolerance, and suppress the inflammatory response. Mitochondria, as the energy factories of cells, are essential for regulating the survival, differentiation, and function of Tregs. Studies have shown that patients with autoimmune diseases of the central nervous system, such as multiple sclerosis, neuromyelitis optica spectrum disorder, and autoimmune encephalitis, have aberrant Tregs and mitochondrial damage. However, the role of mitochondrial-regulated Tregs in autoimmune diseases of the central nervous system remains inconclusive. Therefore, this study reviews the mitochondrial regulation of Tregs in autoimmune diseases of the central nervous system and investigates the possible mitochondrial therapeutic targets.

Abstract Background Migraine is a complex disorder characterized by debilitating headaches. Despite its prevalence, its pathophysiology remains unknown, with subsequent gaps in diagnosis and treatment. We combined machine learning with connectivity analysis and applied a whole-brain network approach to identify potential targets for migraine diagnosis and treatment. Methods Baseline anatomical T1 magnetic resonance imaging (MRI), resting-state functional MRI(rfMRI), and diffusion weighted scans were obtained from 31 patients with migraine, and 17 controls. A recently developed machine learning technique, Hollow Tree Super (HoTS) was used to classify subjects into diagnostic groups based on functional connectivity (FC) and derive networks and parcels contributing to the model. PageRank centrality analysis was also performed on the structural connectome to identify changes in hubness. Results Our model attained an area under the receiver operating characteristic curve (AUC-ROC) of 0.68, which rose to 0.86 following hyperparameter tuning. FC of the language network was most predictive of the model’s classification, though patients with migraine also demonstrated differences in the accessory language, visual and medial temporal regions. Several analogous regions in the right hemisphere demonstrated changes in PageRank centrality, suggesting possible compensation. Conclusions Although our small sample size demands caution, our preliminary findings demonstrate the utility of our method in providing a network-based perspective to diagnosis and treatment of migraine.

Abstract This study analyzes the change characteristics of compound extreme events (CEEs) of temperature and precipitation (including warm‐wet, warm‐dry, cold‐wet and cold‐dry) in China on interannual and interdecadal scales between 1901 and 2019. The results demonstrate a long‐term increasing trend and interdecadal oscillations in CEEs total frequency. However, the frequency of each type of CEEs changes in a different manner compared with total CEEs frequency. There are fewer CEEs but increasing warm‐dry during 1901–1950. The period 1951–1995 are characterized by frequent cold CEEs (cold‐wet and cold‐dry), cold‐wet are largely distributed in most areas except for northeast and coastal areas of China, while cold‐dry are distributed in most areas except for the northwest regions of China. There are frequent warm CEEs (warm‐wet and warm‐dry) and fewer cold CEEs during 1996–2019. Warm‐wet frequently occurs in the Tibetan Plateau and northwest China, and warm‐dry mainly concentrates in southwest and northern China during this period. The frequency of warm‐dry and cold‐wet were higher than that of warm‐wet and cold‐dry over the past 119 years, whereas warm‐wet increased fastest in the northwest region after 1996, consistent with the warming and wetting characteristics in the northwest region of China. Further study show that long‐term change and low frequency oscillations have the greatest impact on CEEs among different time scale factors. Furthermore, the temperature rise caused by climate change affects the interdecadal characteristics of CEEs in China through the changes of circulation fields such as East Asian trough and subtropical high and the configuration between them.

IntroductionArtemisinin (ART) is very common as a diet additive due to its immunoregulatory activities. Nonetheless, the immunoregulatory mechanism of ART in marine fish remains unknown. This study comprehensively examined the effects and explored the potential mechanism of ART ameliorating intestinal immune disease (IID) in fat greenlings (Hexagrammos otakii).Methods and resultsThe targets of ART were screened using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Here, eight putative targets of ART were collected and identified with the Uniprot database, and 1419 IID-associated target proteins were filtered through the Drugbank, Genecards, OMIM, and PHARMGKB Databases. The results of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways point out that ART may have immunoprotective effects by regulating cellular responses to stress, hypoxia, inflammation, and vascular endothelial growth factor stimulus through the hypoxia-inducible factor 1 (HIF-1) signaling pathway. The findings of molecular docking indicated that ART contains one active ingredient and three cross-targets, which showed a kind combination with hypoxia-inducible factor 1-alpha (HIF1-a), transcription factor p65 (RELA), and vascular endothelial growth factor A (VEGF-A), respectively. Furthermore, an ART feeding model was established to assess the ART’s immunoprotect effect on the intestine of H.otakii in vivo. The D48 group showed smaller intestinal structural changes after being challenged by Edwardsiella tarda. The supplementation of ART to the diet improved total superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) and reduced the malondialdehyde (MDA) in intestine of H. otakii. The expression of transcription factor p65, HIF1-α, VEGF-A, cyclin D1, matrix metalloprotease 9 (MMP9), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) was decreased after dietary ART in the intestinal of H. otakii.DiscussionThe present results demonstrated that dietary ART improved antioxidants and immunity, optimized the intestinal structure, and increased resistance to E. tarda through the SOD2/nuclear-factor-kappa- B (NFkB)/HIF1-a/VEGF-A pathway in the intestinal tract of H.otakii. This study integrated pharmacological analysis and experimental validation and revealed the mechanism of ART on IID, which provides insight into the improvement of IID in H. otakii.

Abstract Reading speed in intermittent exotropia (IXT) children has been minimally examined. This study assessed reading speed in school-age children with IXT and determined clinical characteristics of IXT that impacted their reading ability. We compared the reading speed of 63 school-age (10–14 years) children with IXT to 44 age-matched normal counterparts. In addition, the correlation between reading speed and clinical characteristics of IXT were evaluated. The reading speed in children with IXT was 231 ± 51 CPM, while reading speed in normal counterparts was 257 ± 33 CPM. Age, gender were found to be factors associated with reading speed in children with IXT. After adjusting for the age and gender, we found a significant correlation between the LogTNO and reading speed in IXT group based on a generalized linear model (p = 0.014). These data show that reading speed was slower in school-age children with IXT assessed with the International Reading Speed Texts. When age and gender were adjusted, poor stereo function at near was found to be related with a slower reading speed.

Aiming at the problem that current schemes mostly let the latter signer to verify the multiple signatures of the previous signer, and the message is signed and then passed to the next signer, leading to the efficiency problem of long overall signature time.A sequential aggregate signature scheme based on bilinear pairs was proposed.The aggregate signatures of documents were generated by multiple users in a certain order, and only the final signature was needed to be verified to confirm the correct order of signatures and the legitimacy of multiple user signatures.The complexity of verifying the multi-user sequential signature was effectively reduced and the offline verification of the authenticity of signature was realized when the user was offline or in a delay-tolerant network with limited node caching capacity and network resources.It is shown that the proposed scheme is existential unforgeability against chosen-message attacks under adversary adaptive selection messages in the random oracle model.

Background: Nutritional problems are common in children with cerebral palsy (CP), yet the relationship between nutritional status and the severity of CP is unclear. Objective: To describe the nutritional status and characteristics of children with CP, and to explore the relationship between severity of CP and nutritional status in children. Methods: This multicentre cross-sectional study included children with CP in China. Weight and height were measured and converted to z-scores. Gross Motor Function Classification System (GMFCS), Eating and Drinking Ability Classification System (EDACS), Subjective Global Nutritional Assessment (SGNA), social life ability, and blood indicators were tested. Results: All 1,151 participants were given oral-feeding and 50.8% of them demonstrated undernutrition. Compared with those in GMFCS or EDACS levels I–III, the odds of moderate and severe undernutrition were 2.6 and 8.9 times higher in GMFCS levels IV and V, and 4.3 and 12.6 times higher in EDACS levels IV and V, respectively. Except for serum 25-hydroxyvitamin D, no significant differences were found in blood indicators among normal, undernourished and overnourished groups. Conclusion: Degrees of undernutrition in children with CP are correlated with the severity of eating and drinking dysfunction and with gross motor impairment. Blood indicators may not reflect nutritional status in children with CP. LAY ABSTRACT Cerebral palsy is the most common physical disability in children in the world. Children with cerebral palsy may have a high risk of having malnutrition as a result of the high energy consumption and/or low energy intake. The former is mainly caused by the abnormal muscular tone, and the latter may emerge from the dysphagia and gastrointestinal problems. As for the optimization of nutritional status is integral to the overall health and clinical management of children with cerebral palsy, the nutritional status stands out for its clinical importance in this group. Children with cerebral palsy are affected by different degrees of motor dysfunction, and may also be faced with eating and drinking problems or limited daily life ability, it is not clear whether nutritional status and function are interrelated. What's more, it is believed that the blood tests may indicate the nutritional status, but it is not well understood. In this project we will look at the nutritional status of children with cerebral palsy in China and investigate the relationship between nutritional status and function and blood indicators. This will then allow clinicians and caregivers to formulate future policies to improve nutritional status for this group of children.

PurposeTo describe a new technique for repairing wide iridodialysis (>180°) with a double-armed flanged polypropylene suture.SettingPrivate practice, Wuhan, China.DesignCase report.MethodsAdjacent to the iridodialysis side, the sclera was punctured 2 mm exterior to the corneal limbus into the anterior chamber with a 30-G needle, then the root of the de-inserted iris was punctured. A 7-0 polypropylene thread was placed into the anterior chamber through a corneal incision on the opposite side and inserted into the needle. The needle was withdrawn, leaving one side of the suture out of the eye. Then, the sclera was punctured by a new needle 2 mm from the first puncture site and passed through the iris root 2 mm from the original iris puncture point. The other end of the thread was inserted into the needle and taken out of the eye. The suture was tightened to make the iris root adhere to the corneal limbus. Finally, the suture is was cut, and the ends were cauterized and left inside the sclera. This procedure can be repeated until the iridodialysis is solved.ResultsThe abovementioned technique was applied in four cases. At the end of the operations, the pupils of all patients were nearly round, with a diameter of about 3 mm. No patient suffered from intraoperative and postoperative complications.ConclusionsThe double-armed flanged polypropylene suture is a simple and safe operation method that can be applied to repair wide iridodialysis.

PurposeThis study aimed to investigate the clinical presentation of acute primary angle closure (APAC) during the COVID-19 epidemic lockdown in Wuhan.MethodsConsecutive patients seeking APAC treatment at the Wuhan Aier Eye Hospital during the 76 days (January 23–April 8, 2020) when the lockdown policy was implemented due to the COVID-19 pandemic were compared to those during the same period the following year (January 23–April 8, 2021), when the lockdown policy was not implemented. The cohorts were compared to assess demographic variables and clinical presentations.ResultsA total of 54 patients (64 eyes) were included in the 2020, compared with 46 patients (51 eyes) in the 2021. Demographic factors were similar between the groups. Significantly more patients developed blindness in the 2020 cohort (21.87%) than in the 2021 cohort (7.84%). Patients in the 2020 showed a longer time from symptom to treatment (241.84 ± 211.95 h in 2020 vs. 121.53 ± 96.12 h in 2021; P = 0.001), higher intraocular pressure at presentation (52.63 ± 12.45 mmHg in 2020 vs. 45.16 ± 9.79 mmHg in 2021; P = 0.001), larger pupil diameter (5.47 ± 1.62 mm in 2020 vs. 4.33 ± 1.27 mm in 2021; P = 0.001), and more glaucomatous optic neuropathy diagnoses [20/64 eyes (31.25%) in 2020 vs. 7/51 eyes (13.73%) in 2021; P = 0.03].ConclusionThe time between the onset of APAC symptoms and its treatment during the COVID-19 epidemic lockdown was significantly prolonged, which increased the blindness rate of APAC patients.

Nanoparticles (NPs) have shown potential in cancer therapy, while a single administration conferring a satisfactory outcome is still unavailable. To address this issue, the dissolving microneedles (DMNs) were developed to locally deliver functionalized NPs with combined chemotherapy and photothermal therapy (PTT). α-Tocopheryl polyethylene glycol succinate (TPGS)/hyaluronic acid (HA) dual-functionalized PLGA NPs (HD10 NPs) were fabricated to co-load paclitaxel and indocyanine green. HD10 NPs significantly enhanced the cytotoxicity of low-dose paclitaxel because of active and mitochondrial targeting by HA and TPGS, respectively. PTT could further sensitize tumor cells toward chemotherapy by promoting apoptosis into the advanced period, highly activating caspase 3 enzyme, and significantly reducing the expression of survivin and MMP-9 proteins. Further, the anti-tumor effects of HD10 NPs delivered through different administration routes were conducted on the 4T1 tumor-bearing mice. After a single administration, HD10 NPs delivered with DMNs showed the best anti-tumor effect when giving chemotherapy alone. As expected, the anti-tumor effect was profoundly enhanced after combined therapy, and complete tumor ablation was achieved in the mice treated with DMNs and intra-tumor injection. Moreover, DMNs showed better safety due to moderate hyperthermia. Therefore, the DMNs along with combined chemo-photothermal therapy provide a viable treatment option for superficial tumors.

AimTo investigate the efficacy and safety of high-calorie formula vs. Chinese daily food on the nutritional status and motor function of undernourished children with cerebral palsy (CP).MethodsIn this prospective, assessor-blind, and randomized controlled trial, we recruited children (1–10 years) with CP and undernutrition based on the WHO and the American Society for Parenteral and Enteral Nutrition criteria from the National Children's Medical Center. Participants were randomly allocated (1:1) to a high-calorie formula group or a Chinese daily food diet group (control group) for 6 months. Indirect calorimetry was used to estimate energy requirements. We compared the nutritional status and gross motor function of participants in both groups based on weight, height, z-scores (weight-for-age, height-for-age, weight-for-height, and BMI-for-age), and the Gross Motor Function Measure (GMFM), respectively, at baseline, 3-, and 6-months follow-up. In addition, the effective rate of nutritional intervention, and adverse events were simultaneously assessed.ResultsFrom July 2020 to December 2021, a total of 119 participants were enrolled and randomized, and 110 participants completed the study (with 54 children in the high-calorie formula group and 56 children in the control group). After 6 months of treatment, the weight, height, z-scores (weight-for-height, weight-for-age, and BMI-for-age), and GMFM of both groups were significantly improved (p < 0.05). There were significant differences in changes in weight, weight-for-age z-scores, and GMFM between the two groups (p < 0.05). During the study period, 16 children experienced at least one mild adverse event [9 (16.7%) in the formula group and 7 (12.5%) in the control group].ConclusionNutritional intervention with a high-calorie formula may be an effective and safe option in children with CP for improving undernutrition and gross motor dysfunction.Clinical trial registrationwww.chictr.org.cn, identifier: ChiCTR2000033878.

Superparamagnetic iron oxide (SPIO) nanocrystals have been extensively studied as theranostic nanoparticles to increase transverse (T2) relaxivity and enhance contrast in magnetic resonance imaging (MRI). To improve the blood circulation time and enhance the diagnostic sensitivity of MRI contrast agents, we developed an amphiphilic copolymer, PCPZL, to effectively encapsulate SPIO nanocrystals. PCPZL was synthesized by crosslinking a polyethylene glycol (PEG)-based homobifunctional linker with a hydrophobic star-like poly(ε-benzyloxycarbonyl-L-lysine) segment. Consequently, it could self-assemble into shell-crosslinked micelles with enhanced colloidal stability in bloodstream circulation. Notably, PCPZL could effectively load SPIO nanocrystals with a high loading capacity of 66.0 ± 0.9%, forming SPIO nanoclusters with a diameter of approximately 100 nm, a high cluster density, and an impressive T2 relaxivity value 5.5 times higher than that of Resovist®. In vivo MRI measurements highlighted the rapid accumulation and contrast effects of SPIO-loaded PCPZL micelles in the livers of both healthy mice and nude mice with an orthotopic hepatocellular carcinoma tumor model. Moreover, the magnetic micelles remarkably enhanced the relative MRI signal difference between the tumor and normal liver tissues. Overall, our findings demonstrate that PCPZL significantly improves the stability and magnetic properties of SPIO nanocrystals, making SPIO-loaded PCPZL micelles promising MRI contrast agents for diagnosing liver diseases and cancers.

Idiopathic pulmonary fibrosis (IPF) refers to chronic progressive fibrotic interstitial pneumonia. It is called a “tumor-like disease” and cannot be cured using existing clinical drugs. Therefore, new treatment options are urgently needed. Studies have proven that ferroptosis is closely related to the development of IPF, and ferroptosis inhibitors can slow down the occurrence of IPF by chelating iron or reducing lipid peroxidation. For example, the ferroptosis inhibitor deferoxamine (DFO) was used to treat a mouse model of pulmonary fibrosis, and DFO successfully reversed the IPF phenotype and increased the survival rate of mice from 50% to 90%. Given this, we perceive that the treatment of IPF by delivering ferroptosis inhibitors is a promising option. However, the delivery of ferroptosis inhibitors faces two bottlenecks: low solubility and targeting. For one thing, we consider preparing ferroptosis inhibitors into nanomedicines to improve solubility. For another thing, we propose to deliver nanomedicines through pulmonary drug-delivery system (PDDS) to improve targeting. Compared with oral or injection administration, PDDS can achieve better delivery and accumulation in the lung, while reducing the systemic exposure of the drug, and is an efficient and safe drug-delivery method. In this paper, three possible nanomedicines for PDDS and the preparation methods thereof are proposed to deliver ferroptosis inhibitors for the treatment of IPF. Proper administration devices and challenges in future applications are also discussed. In general, this perspective proposes a promising strategy for the treatment of IPF based on inhalable nanomedicines carrying ferroptosis inhibitors, which can inspire new ideas in the field of drug development and therapy of IPF.

BackgroundExercise is one of the effective ways to improve cognition. Different forms of exercises, such as aerobic exercise, resistance exercise, and coordination exercise, have different effects on the improvement of cognitive impairment. In recent years, exergames based on Non-Immersive Virtual Reality (NIVR-Exergames) have been widely used in entertainment and have gradually been applied to clinical rehabilitation. However, the mechanism of NIVR-Exergames on improving motor cognition has not been clarified. Therefore, the aim of this study is to find whether NIVR-Exergames result in a better neural response mechanism to improve the area of the cerebral cortex related to motor cognition under functional near-infrared spectroscopy (fNIRS) dynamic monitoring in comparison with resistance exercise (resistance band stretching).MethodsA cross-over study design was adopted in this study, and 15 healthy young subjects (18–24 years old) were randomly divided into group A (n = 8) and group B (n = 7) according to a computerized digital table method. Task 1 was an NIVR-Exergame task, and Task 2 was resistance band stretching. Group A first performed Task 1, rested for 30 min (i.e., a washout period), and then performed Task 2. Group B had the reverse order. The fNIRS test was synchronized in real time during exercise tasks, and heart rate measurements, blood pressure measurements, and 2-back task synchronization fNIRS tests were performed at baseline, Post-task 1, and Post-task 2. The primary outcomes were beta values from the general linear model (GLM) in different regions of interest (ROIs), and the secondary outcomes were heart rate, blood pressure, reaction time of 2-back, and accuracy rate of 2-back.ResultsThe activation differences of Task 1 and Task 2 in the right premotor cortex (PMC) (P = 0.025) and the left PMC (P = 0.011) were statistically significant. There were statistically significant differences in the activation of the right supplementary motor area (SMA) (P = 0.007), left dorsolateral prefrontal cortex (DLPFC) (P = 0.031), left and right PMC (P = 0.005; P = 0.002) between baseline and Post-task 1. The differences in systolic pressure (SBP) between the two groups at three time points among women were statistically significant (P1 = 0.009, P2 < 0.001, P3 = 0.044).ConclusionIn this study, we found that NIVR-Exergames combined with motor and challenging cognitive tasks can promote the activation of SMA, PMC and DLPFC in healthy young people compared with resistance exercise alone, providing compelling preliminary evidence of the power for the rehabilitation of motor and cognitive function in patients with central nervous system diseases.

Dissolving microneedles (MNs) have emerged as a promising transdermal delivery system, as they integrate the advantages of both injection and transdermal preparations. However, the low drug-loading and limited transdermal delivery efficiency of MNs severely hinder their clinical applications. Microparticle-embedded gas-propelled MNs were developed to simultaneously improve drug-loading and transdermal delivery efficiency. The effects of mold production technologies, micromolding technologies, and formulation parameters on the quality of gas-propelled MNs were systematically studied. Three-dimensional printing technology was found to prepare male mold with the highest accuracy, while female mold made from the silica gel with smaller Shore hardness could obtain a higher demolding needle percentage (DNP). Vacuum micromolding with optimized pressure was superior to centrifugation micromolding in preparing gas-propelled MNs with significantly improved DNP and morphology. Moreover, the gas-propelled MNs could achieve the highest DNP and intact needles by selecting polyvinylpyrrolidone K30 (PVP K30), polyvinyl alcohol (PVA), and potassium carbonate (K2CO3): citric acid (CA) = 0.15:0.15 (w/w) as the needle skeleton material, drug particle carrier, and pneumatic initiators, respectively. Moreover, the gas-propelled MNs showed a 1.35-fold drug loading of the free drug-loaded MNs and 1.19-fold cumulative transdermal permeability of the passive MNs. Therefore, this study provides detailed guidance for preparing MNs with high productivity, drug loading, and delivery efficiency.

Constraint-induced movement therapy (CIMT) combined with repetitive transcranial magnetic stimulation (rTMS) have shown great potential in improving function in schoolchildren with unilateral cerebral palsy attributed to perinatal stroke. However, the prospect of application in preschool children with unilateral cerebral palsy (UCP) attributed to various brain disorders remains unclear. In this prospective, assessor-blinded, randomized controlled study, 40 preschool children with UCP (aged 2.5–6 years) were randomized to receive 10 days of CIMT combined with active or sham rTMS. Assessments were performed at baseline, 2 weeks, and 6 months post-intervention to investigate upper limb extremity, social life ability, and perceived changes by parents and motor-evoked potentials. Overall, 35 participants completed the trial. The CIMT plus active stimulation group had greater gains in the affected hand function (range of motion, accuracy, and fluency) than the CIMT plus sham stimulation group (P < 0.05), but there was no significant difference in muscular tone, social life ability, and perceived changes by parents between the two groups (P > 0.05). In addition, there was no significant difference in hand function between children with and without motor-evoked potential (P > 0.05). No participants reported severe adverse events during the study session. In short, the treatment of CIMT combined with rTMS is safe and feasible for preschool children with UCP attributed to various brain disorders. Randomized controlled studies with large samples and long-term effects are warranted.

BackgroundThe motor imagery brain computer interface (MI-BCI) is now available in a commercial product for clinical rehabilitation. However, MI-BCI is still a relatively new technology for commercial rehabilitation application and there is limited prior work on the frequency effect. The MI-BCI has become a commercial product for clinical neurological rehabilitation, such as rehabilitation for upper limb motor dysfunction after stroke. However, the formulation of clinical rehabilitation programs for MI-BCI is lack of scientific and standardized guidance, especially limited prior work on the frequency effect. Therefore, this study aims at clarifying how frequency effects on MI-BCI training for the plasticity of the central nervous system.MethodsSixteen young healthy subjects (aged 22.94 ± 3.86 years) were enrolled in this randomized clinical trial study. Subjects were randomly assigned to a high frequency group (HF group) and low frequency group (LF group). The HF group performed MI-BCI training once per day while the LF group performed once every other day. All subjects performed 10 sessions of MI-BCI training. functional near-infrared spectroscopy (fNIRS) measurement, Wolf Motor Function Test (WMFT) and brain computer interface (BCI) performance were assessed at baseline, mid-assessment (after completion of five BCI training sessions), and post-assessment (after completion of 10 BCI training sessions).ResultsThe results from the two-way ANOVA of beta values indicated that GROUP, TIME, and GROUP × TIME interaction of the right primary sensorimotor cortex had significant main effects [GROUP: F(1,14) = 7.251, P = 0.010; TIME: F(2,13) = 3.317, P = 0.046; GROUP × TIME: F(2,13) = 5.676, P = 0.007]. The degree of activation was affected by training frequency, evaluation time point and interaction. The activation of left primary sensory motor cortex was also affected by group (frequency) (P = 0.003). Moreover, the TIME variable was only significantly different in the HF group, in which the beta value of the mid-assessment was higher than that of both the baseline assessment (P = 0.027) and post-assessment (P = 0.001), respectively. Nevertheless, there was no significant difference in the results of WMFT between HF group and LF group.ConclusionThe major results showed that more cortical activation and better BCI performance were found in the HF group relative to the LF group. Moreover, the within-group results also showed more cortical activation after five sessions of BCI training and better BCI performance after 10 sessions in the HF group, but no similar effects were found in the LF group. This pilot study provided an essential reference for the formulation of clinical programs for MI-BCI training in improvement for upper limb dysfunction.

Objective: To observe the characteristics of brain fMRI during olfactory stimulation in patients with neuromyelitis optica spectrum disease (NMOSD) and multiple sclerosis (MS), compare the differences of brain functional activation areas between patients with NMOSD and MS, and explore the characteristics of olfactory-related brain networks of NMOSD and MS.Methods: Nineteen patients with NMOSD and 16 patients with MS who met the diagnostic criteria were recruited, and 19 healthy controls matched by sex and age were recruited. The olfactory function of all participants was assessed using the visual analog scale (VAS). Olfactory stimulation was alternately performed using a volatile body (lavender and rose solution) and the difference in brain activation was evaluated by task-taste fMRI scanning simultaneously.Results: Activation intensity was weaker in the NMOSD group than in the healthy controls, including the left rectus, right superior temporal gyrus, and left cuneus. The activation intensity was stronger for the NMOSD than the controls in the left insula and left middle frontal gyrus (P < 0.05). Activation intensity was weaker in the MS group than the healthy controls in the bilateral hippocampus, right parahippocampal gyrus, right insula, left rectus gyrus, and right precentral gyrus, and stronger in the left paracentral lobule among the MS than the controls (P < 0.05). Compared with the MS group, activation intensity in the NMOSD group was weaker in the right superior temporal gyrus and left paracentral lobule, while it was stronger among the NMOSD group in the bilateral insula, bilateral hippocampus, bilateral parahippocampal gyrus, left inferior orbital gyrus, left superior temporal gyrus, left putamen, and left middle frontal gyrus (P < 0.05).Conclusion: Olfactory-related brain networks are altered in both patients, and there are differences between their olfactory-related brain networks. It may provide a new reference index for the clinical differentiation and disease evaluation of NMOSD and MS. Moreover, further studies are needed.

PurposeTo study the longitudinal rehabilitation of binocular visual function in adolescent intermittent exotropia (IXT) after successful surgery and compare the results with those of a normal population. The role of binocular function in ocular alignment stability was also evaluated postoperatively.MethodsIn this prospective study, 30 adolescents with IXT successfully corrected after 1 month were followed for 12 months, and 30 children with normal vision were enrolled as controls. Stereopsis, the fusional vergence amplitude, sensory fusion, and accommodative flexibility were measured to assess binocular function at baseline and 6 and 12 months postoperatively. The controls were tested once when they were enrolled in the study.ResultsThe deviation was −32.00 ± 8.60 prism diopters (PD) at distance fixation and −36.0 ± 9.10 PD at near fixation preoperatively with an average correction of 28.53 ± 3.79 PD and 30.67 ± 1.34 PD at 1 month postoperatively. Distance stereoacuity and near stereoacuity improved from 1 to 12 months postoperatively (p = 0.025 and p = 0.041, respectively). Compared with the controls, the fusional convergence reserve at distance (p = 0.025) and near (p = 0.033) fixations and fusion reserve ratio at distance (p = 0.000) and near (p = 0.000) fixations remained subnormal, whereas sensory fusion (p = 0.237), distance stereopsis (p = 0.120), and the fusional divergence amplitude at a distance (p = 0.168) were normal. However, no significant correlations were found between binocular functions at 1 month postoperatively and the postoperative drift.ConclusionBinocular function significantly improved from before to after successful corrective surgery and continued to improve from 1 to 12 months postoperatively in adolescents with IXT. No significant correlations were found between binocular functions at 1 month postoperatively and ocular alignment stability.

Introduction: DBS is a widely used therapy for PD. There is now a choice between fixed-life implantable pulse generators (IPGs) and rechargeable IPGs, each having advantages and disadvantages. This study aimed to evaluate the preference and satisfaction of Chinese patients with Parkinson's disease (PD) who were treated with deep brain stimulation (DBS).Materials and Methods: Two hundred and twenty PD patients were treated with DBS and completed a self-reported questionnaire to assess their long-term satisfaction and experience with the type of battery they had chosen and the key factors affecting these choices. The survey was performed online and double-checked for completeness and accuracy.Results: The median value of the postoperative duration was 18 months. The most popular way for patients to learn about DBS surgery was through media (79/220, 35.9%) including the Internet and television programs. In total, 87.3% of the DBS used rechargeable IPGs (r-IPG). The choice between rechargeable and non-rechargeable IPGs was significantly associated with affordability (χ(1)2 = 19.13, p < 0.001). Interestingly, the feature of remote programming significantly affected patients' choices between domestic and imported brands (χ(1)2 = 16.81, p < 0.001). 87.7% of the patients were satisfied with the stimulating effects as well as the implanted device itself. 40.6% of the patients with r-IPGs felt confident handling devices within 1 week after discharge. More than half of the patients checked their batteries every week. The mean interval for battery recharge was 4.3 days. 57.8% of the patients spent around 1 h recharging, and 71.4% of them recharged the battery independently.Conclusions: Most patients were satisfied with their choice of IPGs. The patients' economic status and the remote programming function of the device were the two most critical factors in their decision. The skill of recharging the IPG was easy to master for most patients.

Glaucoma is a chronic eye disease that causes loss of vision and it is irreversible. Accurate segmentation of optic disc and optic cup is a basic step in screening glaucoma. The most existing deep convolutional neural network (DCNN) methods have insufficient feature information extraction, and hence they are susceptible to pathological regions and low-quality images, with have poor ability to restore context information. Finally, the accuracy of the model segmentation is low. In this paper, we propose GL-Net, a multi-label DCNN model that combines the generative adversarial networks. GL-Net consists of two network structures including a Generator and a Discriminator. In the Generator, we use skip connection to promote the fusion of low-level feature information and high-level feature information, which alleviates the difficulty of restoring detailed feature information during upsampling, and reduces the downsampling factor, effectively alleviating excessive feature information loss. In the loss function, we add the L1 distance function and the cross-entropy function to prevent the mode collapse when the model is trained, which makes the segmentation result more accurate. We use transfer learning and data augmentation to alleviate the problem of insufficient data and over-fitting of the model during training. Finally, GL-Net was verified on DRISHTI-GS1 dataset. The experimental results show that GL-Net outperforms some state-of-the-art method, such as M-Net, Stack-U-Net, RACE-net, and BCRF in terms of F1 and boundary distance localization error (BLE). Particularly, in the optic cup segmentation, GL-Net outperforms RACE-net by 3.5% and 4.16 pixels in terms of F1 and BLE, respectively.

Accurate segmentation of retinal vessels is a basic step in diabetic retinopathy (DR) detection. Most methods based on deep convolutional neural network (DCNN) have small receptive fields, and hence they are unable to capture global context information of larger regions, with difficult to identify pathological. The final segmented retina vessels contain more noise with low classification accuracy. Therefore, in this paper, we propose a DCNN structure named as D-Net. In the encoding phase, we reduced the loss of feature information by reducing the downsampling factor, which reduced the difficulty of tiny thin vessels segmentation. We use the combined dilated convolution to effectively enlarge the receptive field of the network and alleviate the “grid problem” that exists in the standard dilated convolution. In the proposed multi-scale information fusion module (MSIF), parallel convolution layers with different dilation rates are used, so that the model can obtain more dense feature information and better capture retinal vessel information of different sizes. In the decoding module, the skip layer connection is used to propagate context information to higher resolution layers, so as to prevent low-level information from passing the entire network structure. Finally, our method was verified on DRIVE, STARE, and CHASE dataset. The experimental results show that our network structure outperforms some state-of-art method, such as N4-fields, U-Net, and DRIU in terms of accuracy, sensitivity, specificity, and ${AUC_{ROC}}$ . Particularly, D-Net outperforms U-Net by 1.04 %, 1.23 %, and 2.79% in DRIVE, STARE, and CHASE dataset, respectively.

To effectively utilize a feature set to further improve fault diagnosis of a rolling bearing vibration signal, a method based on multi-fractal detrended fluctuation analysis (MF-DFA) and smooth intrinsic time-scale decomposition (SITD) was proposed. The vibration signal was decomposed into several proper rotation components by applying this new SITD method to overcome noise effects, preserve the effective signal, and improve the signal-to-noise ratio. Wavelet analysis was embedded in iteration procedures of intrinsic time-scale decomposition (ITD). For better results, an adaptive threshold function was used for signal recovery from noisy proper rotation components in the wavelet domain. Additionally, MF-DFA was used to reveal the multi-fractality present in the instantaneous amplitude of the proper rotation components. Finally, linear local tangent space alignment was applied for feature dimension reduction and to obtain fault characteristics of different types, further improving identification accuracy. The performance of the proposed method is determined to be superior to that of the ITD-MF-DFA method.

Ethyl cellulose (EC) based microparticles (MPs) could provide sustained release for Huperzine A. The drug release mechanism of MPs was exploited to achieve an ideal drug release profile. We previously found that the wettability of MPs greatly contributed to facilitating drug release, which was detailed in a research article entitled “Huperzine A loaded multiparticulate disintegrating tablet: Drug release mechanism of ethyl cellulose microparticles and pharmacokinetic study” (Peng et al., 2019) [1]. In this article, the influence of different polymers and drugs on the drug release behavior was investigated to broaden or compensate this finding. Besides, powder characterization of MPs was used to evaluate the further application of MPs for tablets. Keywords: Microparticles, Drug release profile, Powder characteristic

Purpose. To evaluate whether clinical measures of postoperative binocular functions could predict the long-term stability of postoperative ocular alignment in children with intermittent exotropia. Methods. A retrospective study was performed in thirty-nine children (median: 7 years) who have been surgically treated from intermittent exotropia without overcorrection (less than 10 prism diopters [pd] of exodeviation at 1 month postoperatively). Angles of deviation and binocular functions were measured preoperatively and at 1 month, 6 months, and the final follow-up visit (≥24 months) postoperatively. We examined the relationships between postoperative drift (change of ocular alignment) and binocular functions (sensory fusion, fusional convergence amplitude, and stereoacuity). Results. The surgical success rate (esophoria/tropia ≤5 pd to exophoria/tropia ≤10 pd) dropped to 76.9% at 6 months after surgery and to 53.8% at individuals’ last visit (mean: 37 months). The mean exodrift was 7.7 ± 9.2 pd from the postoperative month 1 to the final visit (p0.13). Conclusion. Our findings suggest that the clinical measures of sensory fusion, fusional convergence amplitude, and stereoacuity cannot serve as a robust predictor for the long-term stability of postoperative ocular alignment in patients who underwent successful surgery without overcorrection at 1 month postoperatively.

Abstract Background Daytime napping has been postulated as both a protective and a risk factor for depression in previous studies. In addition to these conflicting results, research gaps also exist with regard to controlling confounding bias between daytime napping and depression and examining the potential association within the Chinese population. To facilitate the prevention and diagnosis of depression, this study aims to provide insight into the association of daytime napping and depression in 0.5 million Chinese adults by fully controlling confounders, and further examine the modifying effects of socio-economic status (SES) and age. Methods Data were drawn from the baseline of a Chinese cohort study of 0.5 million adults. Depressive status was measured by the Composite International Diagnostic Inventory (CIDI). Logistic regression models were used to examine the association between depression and daytime napping adjusted for SES, sleep-related factors, lifestyle factors and related diseases. Further stratified analyses were conducted to identify the modifying effects of socio-economic status and age. Results The odds ratio of depression by daytime napping was 1.15 (95% CI: 1.01–1.31) in females and 1.42 (95% CI: 1.18–1.71) in males. Factors including living in a rural area (OR = 1.31, 95% CI: 1.13–1.52), receiving less education (OR = 1.42, 95% CI: 1.22–1.66), getting married (OR = 1.24, 95% CI: 1.10–1.40) and being 45–65 years old (OR = 1.29, 95% CI: 1.12–1.49) had a modifying effect on daytime napping and depression that could strengthen the association. Conclusions A significantly positive association was found between depression and daytime napping, as well as daytime dysfunction, snoring and both shorter and longer sleep duration. Lower SES and age could possibly modify the association. Further clinical or epidemiological studies are needed to investigate the mechanism and facilitate the prevention of depression.

Lanthanide-doped upconversion nanoparticles (UCNPs) are promising bioimaging nanoprobes due to their excellent photostability. As one of the most commonly used lanthanide activators, Tm3+ ions have perfect ladder-type electron configuration and can be directly excited by bio-friendly near-infrared-II (NIR-II) wavelengths. Here, the emission characteristics of Tm3+-doped nanoparticles under laser excitations of different near-infrared-II wavelengths were systematically investigated. The 1064 nm, 1150 nm, and 1208 nm lasers are proposed to be three excitation strategies with different response spectra of Tm3+ ions. In particular, we found that 1150 nm laser excitation enables intense three-photon 475 nm emission, which is nearly 100 times stronger than that excited by 1064 nm excitation. We further optimized the luminescence brightness after investigating the luminescence quenching mechanism of bare NaYF4: Tm (1.75%) core. After growing an inert shell, a ten-fold increase of emission intensity was achieved. Combining the advantages of NIR-II wavelength and the higher-order nonlinear excitation, a promising facile excitation strategy was developed for the application of thulium-doped upconversion nanoparticles in nanoparticles imaging and cancer cell microscopic imaging.

Dry powder inhalers (DPIs) offer distinct advantages as a means of pulmonary drug delivery and have attracted much attention in the field of pharmaceutical science. DPIs commonly contain micronized drug particles which, because of their cohesiveness and strong propensity to aggregate, have poor aerosolization performance. Thus carriers with a larger particle size are added to address this problem. However, the performance of DPIs is profoundly influenced by the physical properties of the carrier, particularly their particle size, morphology/shape and surface roughness. Because these factors are interdependent, it is difficult to completely understand how they individually influence DPI performance. The purpose of this review is to summarize and illuminate how these factors affect drug–carrier interaction and influence the performance of DPIs.

Film coating is an important unit operation to produce solid dosage forms, thereby, the monitoring of this process is helpful to find problems in time and improve the quality of coated products. Traditional methods adopted to monitor this process include measurement of coating weight gain, performance of disintegration and dissolution test, etc. However, not only do these methods cause destruction to the samples, but also consume time and energy. There have recently emerged the applications of process analytical technologies (PAT) on film coating, especially some novel spectroscopic and imaging technologies, which have the potential to real-time track the progress in film coating and optimize production efficiency. This article gives an overview on the application of such technologies for film coating, with the goal to provide a reference for the further researches.

Single Shot MultiBox Detector (SSD) has achieved good results in object detection but there are problems such as insufficient understanding of context information and loss of features in deep layers. In order to alleviate these problems, we propose a single-shot object detection network Context Perception-SSD (CP-SSD). CP-SSD promotes the network’s understanding of context information by using context information scene perception modules, so as to capture context information for objects of different scales. Deep layer feature map used semantic activation module, through self-supervised learning to adjust the context feature information and channel interdependence, and enhance useful semantic information. CP-SSD was validated on benchmark dataset PASCAL VOC 2007. The experimental results show that, compared with SSD, the mean Average Precision (mAP) of the CP-SSD detection method reaches 77.8%, which is 0.6% higher than that of SSD, and the detection effect was significantly improved in images with difficult to distinguish the object from the background.

The rapid release of poorly water-soluble drugs from amorphous solid dispersion (ASD) is often associated with the generation of supersaturated solution, which provides a strong driving force for precipitation and results in reduced absorption. Precipitation inhibitors, such as polymers and surfactants, are usually used to stabilize the supersaturated solution by blocking the way of kinetic or thermodynamic crystal growth. To evaluate the combined effect of polymers and surfactants on maintaining the supersaturated state of itraconazole (ITZ), various surfactants were integrated with enteric polymer hydroxypropyl methylcellulose acetate succinate (HPMC AS) to develop polymer–surfactant based solid dispersion. The supersaturation stability was investigated by in vitro supersaturation dissolution test and nucleation induction time measurement. Compared to the ASD prepared with HPMC AS alone, the addition of d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS) exhibited a synergistic effect on precipitation inhibition. The results indicated that the TPGS not only significantly reduced the degree of supersaturation which is the driving force for precipitation, but also provided steric hindrance to delay crystal growth by absorbing onto the surface of small particles. Subsequently, the formulations were evaluated in vivo in beagle dogs. Compared with commercial product Sporanox®, the formulation prepared with HPMC AS/TPGS exhibited a 1.8-fold increase in the AUC (0–24 h) of ITZ and a 1.43-fold increase of hydroxyitraconazole (OH-ITZ) in the plasma. Similarly, the extent of absorption was increased by more than 40% when compared to the formulation prepared with HPMC AS alone. The results of this study demonstrated that the ASD based on polymer–surfactant system could obviously inhibit drug precipitation in vitro and in vivo, which provides a new access for the development of ASD for poorly water-soluble drug.

Temperature is a predominant environmental factor affecting grass germination and distribution. Various thermal-germination models for prediction of grass seed germination have been reported, in which the relationship between temperature and germination were defined with kernel functions, such as quadratic or quintic function. However, their prediction accuracies warrant further improvements. The purpose of this study is to evaluate the relative prediction accuracies of genetic algorithm (GA) models, which are automatically parameterized with observed germination data. The seeds of five P. pratensis (Kentucky bluegrass, KB) cultivars were germinated under 36 day/night temperature regimes ranging from 5/5 to 40/40 °C with 5 °C increments. Results showed that optimal germination percentages of all five tested KB cultivars were observed under a fluctuating temperature regime of 20/25 °C. Meanwhile, the constant temperature regimes (e.g., 5/5, 10/10, 15/15 °C, etc.) suppressed the germination of all five cultivars. Furthermore, the back propagation artificial neural network (BP-ANN) algorithm was integrated to optimize temperature-germination response models from these observed germination data. It was found that integrations of GA-BP-ANN (back propagation aided genetic algorithm artificial neural network) significantly reduced the Root Mean Square Error (RMSE) values from 0.21~0.23 to 0.02~0.09. In an effort to provide a more reliable prediction of optimum sowing time for the tested KB cultivars in various regions in the country, the optimized GA-BP-ANN models were applied to map spatial and temporal germination percentages of blue grass cultivars in China. Our results demonstrate that the GA-BP-ANN model is a convenient and reliable option for constructing thermal-germination response models since it automates model parameterization and has excellent prediction accuracy.

Ternary blend films were prepared with different ratios of starch/polyvinyl alcohol (PVA)/citric acid. The films were characterized by field emission scanning electron microscopy (FE-SEM), thermogravimetric analysis, as well as Fourier transform infrared (FTIR) analysis. The influence of different ratios of starch/polyvinyl alcohol (PVA)/citric acid and different drying times on the performance properties, transparency, tensile strength (TS), water vapor permeability (WVP), water solubility (WS), color difference (ΔE), and antimicrobial activity of the ternary blends films were investigated. The starch/polyvinyl alcohol/citric acid (S/P/C1:1:0, S/P/C3:1:0.08, and S/P/C3:3:0.08) films were all highly transparent. The S/P/C3:3:0.08 had a 54.31 times water-holding capacity of its own weight and its mechanical tensile strength was 46.45 MPa. In addition, its surface had good uniformity and compactness. The S/P/C3:1:0.08 and S/P/C3:3:0.08 showed strong antimicrobial activity to Listeria monocytogenes and Escherichia coli, which were the food-borne pathogenic bacteria used. The freshness test results of fresh figs showed that all of the blends prevented the formation of condensed water on the surface of the film, and the S/P/C3:1:0.08 and S/P/C3:3:0.08 prevented the deterioration of figs during storage. The films can be used as an active food packaging system due to their strong antibacterial effect.