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AIM: To investigate the effects of school-based comprehensive intervention on myopia development in elementary school children. METHODS: As a part of the Wenzhou Epidemiology of Refraction Error Study, there were 1524 participating elementary students (730 girls, 47.9%) in grades 1 to 3 from three campuses of one school, aged 7.3±0.9y, who were examined twice every year for a 2.5y follow up period. Comprehensive intervention and other reminders were given at school every semester for the intervention group. The control group did not receive comprehensive intervention and did not have reminders of it. RESULTS: There were 651 students in the intervention group [mean age 7.3±0.9y; 294 (45.2%) girls] and 737 students in the control group [mean age 7.2±0.9y; 346 (46.9%) girls]. Overall mean myopia progression during the 2.5y follow-up was -0.49±1.04 diopters (D) in the intervention group and -0.65±1.08 D in the control group (P=0.004). The majority that not get myopia at baseline spherical equivalent (SE≤-1.0 D). Their mean myopia progression during the 2.5y follow-up was -0.37±0.89 D in the intervention group and -0.51±0.93 D in the control group (27.5% reduction, P=0.009); Overall, mean axial length elongation was less in the intervention group (0.56±0.32 mm) than in the control group (0.61±0.38 mm, 10.5% reduction, P=0.009). The percentage of close reading distance (

From 2018, several foodborne diseases caused by the consumption of wet rice noodles contaminated with microorganisms have attracted the attention of consumers and surveillance departments. We explored the crucial risk factors for the contamination of Bacillus cereus during the various steps of the wet rice noodles production chain (from raw material to marketing phase). A total of 273 samples were collected in each corresponding production phase. The contamination level was quantitatively detected in the samples, and the corresponding temperature and time were recorded and analyzed using @Risk software. The quantitative detection results of raw material were determined as the initial contamination level in the model to predict the final contamination level and assess the key risk factors for B. cereus contamination in wet rice noodles. The model predicted that the final contamination level of B. cereus was in the range of −3.55 to 4.34 log CFU/g in 95% wet rice noodles at the marketing phase. The highest predicted contamination level was 6.28 log CFU/g, and the risk of exceeding the threshold was 0.80%. The model was verified to be valid for R2 > 0.96, and the predicted results could be used for reference. Moreover, the sensitivity analysis revealed that in addition to raw material, the key control factors were buffering temperature in the packaging delivery phase, transporting temperature and time from factory to marketing phase; their correlation coefficients (r) were 0.18, 0.16, and 0.15, respectively. Therefore, manufacturers need to adjust the current predelivery buffering and transporting mode. It is recommended to reduce the predelivery buffering temperature, and refrigerated trucks are preferred to control the proliferation of B. cereus in transported food, thus reducing the occurrence of foodborne diseases and improving the safety of food.

Primary extraskeletal Ewing sarcoma (EES) is a rare small round cell malignancy that accounts for less than 1% of all sarcomas. It is found most commonly in the trunk and lower limbs and very rarely in the pleura and can be easily misdiagnosed in clinical practice. This study presents the case of an 11-year-old boy who presented to our hospital with no apparent cause of left shoulder pain for 6 months. On physical examination, tenderness was noted in the left chest wall and shoulder joint, which had a limited range of motion. Computed tomography (CT) and magnetic resonance imaging (MRI) of the chest revealed an irregular soft tissue mass in the upper left thorax, with a wide base attached to the adjacent pleura and bone destruction of the adjacent left first rib. The patient’s bone scan showed a dense focus of increased radiotracer accumulation in the left first rib. A subsequent CT-guided aspiration biopsy of the left pleural mass with histomorphology and immunohistochemical phenotyping led to a diagnosis of extraskeletal Ewing sarcoma. To inhibit tumor growth, alternating systemic chemotherapy cycles of vincristine, doxorubicin, and cyclophosphamide (VDC) and isocyclophosphamide and etoposide (IE) were administered at 3-week intervals. After completing three VDC and two IE cycles, the child’s condition was well and the pain in the left shoulder joint was relieved. However, a repeat MRI of the chest showed that the mass did not shrink.

Acute kidney injury has always been considered a sword of Damocles over hospitalized patients and has received increasing attention due to its high morbidity, elevated mortality, and poor prognosis. Hence, AKI has a serious detrimental impact not only on the patients, but also on the whole society and the associated health insurance systems. Redox imbalance caused by bursts of reactive oxygen species at the renal tubules is the key cause of the structural and functional impairment of the kidney during AKI. Unfortunately, the failure of conventional antioxidant drugs complicates the clinical management of AKI, which is limited to mild supportive therapies. Nanotechnology-mediated antioxidant therapies represent a promising strategy for AKI management. In recent years, two-dimensional (2D) nanomaterials, a new subtype of nanomaterials with ultrathin layer structure, have shown significant advantages in AKI therapy owing to their ultrathin structure, large specific surface area, and unique kidney targeting. Herein, we review recent progress in the development of various 2D nanomaterials for AKI therapy, including DNA origami, germanene, and MXene; moreover, we discuss current opportunities and future challenges in the field, aiming to provide new insights and theoretical support for the development of novel 2D nanomaterials for AKI treatment.

AIM: To investigate the effects of baffle and intraocular pressure (IOP) on the aerosols generated in the noncontact tonometer (NCT) measurement and provide recommendations for the standardized use of the NCT during coronavirus disease 2019 (COVID-19). METHODS: This clinical trial included 252 subjects (312 eyes) in The Eye Hospital, Wenzhou Medical University from March 7, 2020, to March 28, 2020. Sixty subjects (120 eyes) with normal IOP were divided into two groups. One group used an NCT without a baffle, another group used an NCT with a baffle. Another 192 subjects (192 eyes) were divided into four groups: Group A1 (without a baffle+normal IOP), Group A2 (without a baffle+high IOP), Group B1 (with a baffle+normal IOP) and Group B2 (with a baffle+high IOP). Particulate matter (PM) 2.5 and PM10 generated by all subjects were quantified during the NCT measurement. The IOP values were recorded simultaneously. Effects of baffle and IOP on aerosols generated during the NCT measurement were analyzed. RESULTS: In the normal eye group with a baffle, the aerosol density decreased in a wave-like shape near the NCT with the increase in the number of people measured for IOP, demonstrating no cumulative effect. However, in the normal eye group without a baffle, there was a cumulative effect. PM2.5 and PM10 in Group A2 were higher than Group A1 (both P

Abstract With the rapid development of cloud computing technology and communication technology, cloud storage has become a tool used by people in daily life. Cloud storage service enables users to outsource data to cloud servers and retrieve desired document efficiently. Individual privacy in outsource data are very sensitive and should be prevented from any leakage. Public-key encryption with keyword search (PEKS) scheme resolves this tension, while public-key authentication encryption with keyword search (PAEKS) scheme improve its keyword guessing attacks problem potentially. Whereas, the loss of keyword privacy, the limitation of single user interaction and low efficiency make PEKS/PAEKS schemes far from enough in practical applications.In this paper, we develop a multi-recipient public key encryption scheme with keyword search without pairing (MREKS) for cloud storage under public key infrastructure. The proposed scheme has the merits of supporting multi-recipient keyword search way as well as requiring no expensively bilinear pairing operations under standard model. We present a concrete and efficient construction of MREKS, and prove its security based on discrete logarithm assumptions. Furthermore, we embed the algorithm of data plaintext encryption and decryption into the scheme, which makes the scheme more practical. We show that our scheme enjoys much more efficiency than previous PEKS/PAEKS scheme in the simulation experiment, especially the keyword encryption is optimized by 79.5%.

Pheromone-binding proteins (PBPs) play important roles in binding and transporting sex pheromones. However, the PBP genes identified in coleopteran insects and their information sensing mechanism are largely unknown. Cyrtotrachelus buqueti (Coleoptera: Curculionidae) is a major insect pest of bamboo plantations. In this study, a novel PBP gene, CbuqPBP2, from C. buqueti was functionally characterized. CbuqPBP2 was more abundantly expressed in the antennae of both sexes than other body parts, and its expression level was significantly male-biased. Fluorescence competitive binding assays showed that CbuqPBP2 exhibited the strongest binding affinity to dibutyl phthalate (Ki = 6.32 μM), followed by styrene (Ki = 11.37 μM), among twelve C. buqueti volatiles. CbuqPBP2, on the other hand, showed high binding affinity to linalool (Ki = 10.55), the main volatile of host plant Neosinocalamus affinis. Furthermore, molecular docking also demonstrated the strong binding ability of CbuqPBP2 to dibutyl phthalate, styrene, and linalool, with binding energy values of −5.7, −6.6, and −6.0 kcal/mol, respectively, and hydrophobic interactions were the prevailing forces. The knockdown of CbuqPBP2 expression via RNA interference significantly reduced the electroantennography (EAG) responses of male adults to dibutyl phthalate and styrene. In conclusion, these results will be conducive to understanding the olfactory mechanisms of C. buqueti and promoting the development of novel strategies for controlling this insect pest.

Interventional coronary reperfusion strategies are widely adopted to treat acute myocardial infarction, but morbidity and mortality of acute myocardial infarction are still high. Reperfusion injuries are inevitable due to the generation of reactive oxygen species (ROS) and apoptosis of cardiac muscle cells. However, many antioxidant and anti-inflammatory drugs are largely limited by pharmacokinetics and route of administration, such as short half-life, low stability, low bioavailability, and side effects for treatment myocardial ischemia reperfusion injury. Therefore, it is necessary to develop effective drugs and technologies to address this issue. Fortunately, nanotherapies have demonstrated great opportunities for treating myocardial ischemia reperfusion injury. Compared with traditional drugs, nanodrugs can effectively increase the therapeutic effect and reduces side effects by improving pharmacokinetic and pharmacodynamic properties due to nanodrugs’ size, shape, and material characteristics. In this review, the biology of ROS and molecular mechanisms of myocardial ischemia reperfusion injury are discussed. Furthermore, we summarized the applications of ROS-based nanoparticles, highlighting the latest achievements of nanotechnology researches for the treatment of myocardial ischemia reperfusion injury.

Background: Panax ginseng Meyer (P. ginseng), a herb distributed in Korea, China and Japan, exerts benefits on diverse inflammatory conditions. However, the underlying mechanism and active ingredients remains largely unclear. Herein, we aimed to explore the active ingredients of P. ginseng against inflammation and elucidate underlying mechanisms. Methods: Inflammation model was constructed by lipopolysaccharide (LPS) in C57BL/6 mice and RAW264.7 macrophages. Molecular docking, molecular dynamics, surface plasmon resonance imaging (SPRi) and immunofluorescence were utilized to predict active component. Results: P. ginseng significantly inhibited LPS-induced lung injury and the expression of pro-inflammatory factors, including TNF-α, IL-6 and IL-1β. Additionally, P. ginseng blocked fluorescence-labeled LPS (LPS488) binding to the membranes of RAW264.7 macrophages, the phosphorylation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs). Furthermore, molecular docking demonstrated that ginsenoside Ro (GRo) docked into the LPS binding site of toll like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD2) complex. Molecular dynamic simulations showed that the MD2-GRo binding conformation was stable. SPRi demonstrated an excellent interaction between TLR4/MD2 complex and GRo (KD value of 1.16 × 10−9 M). GRo significantly inhibited LPS488 binding to cell membranes. Further studies showed that GRo markedly suppressed LPS-triggered lung injury, the transcription and secretion levels of TNF-α, IL-6 and IL-1β. Moreover, the phosphorylation of NF-κB and MAPKs as well as the p65 subunit nuclear translocation were inhibited by GRo dose-dependently. Conclusion: Our results suggest that GRo exerts anti-inflammation actions by direct inhibition of TLR4 signaling pathway.

Abstract Background Methotrexate (MTX) has a protective effect against cardiovascular diseases (CVD), but the mechanism is unclear. Objective To investigate the effect of MTX on lipid profiles and the difference between psoriasis without arthritis (PsO) and psoriatic arthritis (PsA). Methods In this prospective study, we recruited 288 psoriatic patients (136 PsA and 152 PsO) who completed 12 weeks of MTX treatment. Total cholesterol (TC), triglycerides (TG), lipoprotein A [LP(a)], high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL), apolipoprotein A1 (ApoA1), and ApoB were measured. Results Compared with sex- and age-matched healthy controls, psoriatic patients had significantly (p < 0.0001) higher levels of proatherogenic lipids and lower levels of anti-atherogenic lipids. PsA patients had a higher ApoB/ApoA1 ratio than PsO patients (p < 0.05). Stepwise regression analysis found a positive correlation between the inflammatory marker hCRP and the Psoriasis Area Severity Index (PASI), ApoB/ApoA1 ratio, BMI, and smoking. ApoB was positively associated with concomitant arthritis, diabetes, and hypertension. MTX decreased the levels of pro-atherogenic and anti-atherogenic lipids. However, a significant reduction of the ApoB/ApoA1 ratio by MTX was only observed in male patients. Conclusion PsA patients had a significantly higher percentage of concomitant disease than PsO. The decrease of MTX on CVD might be related with sex. Trial registration ChiCTR2000036192

ABSTRACT Infection by fungal pathogens is the main factor leading to postharvest rot and quality deterioration of fruit and vegetables. Rotting caused by Alternaria alternata is a concerning disease for numerous crops in both production and postharvest stages, especially tomato black spots. In this study, the double Petri dish assay showed that the VOCs of Ceratocystis fimbriata WJSK-1 and Mby inhibited the mycelial growth of fungal pathogen A. alternata, with a percentage inhibition of 52.2% and 42.9%. Then, HS-SPME-GC-MS technology was used to analyze the volatiles produced by two strains of C. fimbriata (WJSK-1, Mby), a total of 42 volatile single components were obtained, the main volatiles compounds identified include nine esters, 10 ketones, five alcohols, four aldehydes, three aromatic hydrocarbons, three heterocycles, four alkenes, three alkanes, and one acid. After that, the antifungal activity of a single volatile component was evaluated both in vitro and in vivo, four single components with antifungal effects were screened out, namely, benzaldehyde, nonanal, 2-Phenylethanol and isoamyl acetate, with IC50 values show the smallest values for benzaldehyde and nonanal at 0.11 μL mL−1, 0.04 μL mL−1. A. alternata exposed to VOCs had abnormal morphology for hyphae, delayed sporulation, and inhibited spore germination. In vivo experiment shows that the four volatile components can effectively suppress disease incidence on fungal-inoculated fruit; the two aldehydes (benzaldehyde and nonanal) have more prominent effect on delaying fruit onset of disease. The results showed that VOCs produced by C. fimbriata have potential as a fumigant for controlling black rot in cherry tomatoes. IMPORTANCE In this research, the volatile organic compounds (VOCs) produced based on C. fimbriata exhibited strong antifungal activity against the fungal pathogen A. alternata. Our aim is to explore their bacteriostatic components. HS-SPME-GC-MS technology was used to analyze the volatiles produced by the C. fimbriata strain (WJSK-1, Mby). Postharvest cherry tomato fruit black rot caused by A. alternata was treated both in vitro and in vivo, with pure individual components produced by C. fimbriata. The benzaldehyde, nonanal, 2-Phenylethanol, and isoamyl acetate from C. fimbriata can effectively inhibit growth of A. alternata, and delay disease. It has the potential to be developed as a new type of fumigant, a potential replacement for fungicides in the future.

The progression of breast cancer is closely related to obstructive sleep apnea-hypopnea syndrome (OSAHS). Low concentrations of cannabinoids promote tumor proliferation. However, the role of cannabinoid receptors (CBs) in chronic intermittent hypoxia (CIH)-induced breast cancer has not been reported. The migration and invasion of breast cancer cell lines (MCF-7 and T47D) were measured by scratch assay and transwell assay. Gene and protein expressions were analyzed by qPCR and western blotting. Tumor xenograft mice model were established to evaluate the function of CBs. We observed that chronic hypoxia (CH) and CIH increased CBs expression and promoted migration and invasion in breast cancer. Mice grafted with MCF-7 exhibited obvious tumor growth, angiogenesis, and lung metastasis in CIH compared with CH and control. In addition, CIH induced CBs expression, which subsequently activated insulin-like growth factor-1 receptor (IGF-1R)/AKT/glycogen synthase kinase-3β (GSK-3β) axis. Knockdown of CBs alleviated CIH-induced migration and invasion of breast cancer in vitro. Furthermore, CIH exaggerated the malignancy of breast cancer and silencing of CBs suppressed tumor growth and metastasis in vivo. Our study contributed to understanding the role of CIH in breast cancer development modulation.

Molybdenum is a trace dietary element necessary for the survival of humans. Some molybdenum-bearing enzymes are involved in key metabolic activities in the human body (such as xanthine oxidase, aldehyde oxidase and sulfite oxidase). Many molybdenum-based compounds have been widely used in biomedical research. Especially, MoS2-nanomaterials have attracted more attention in cancer diagnosis and treatment recently because of their unique physical and chemical properties. MoS2 can adsorb various biomolecules and drug molecules via covalent or non-covalent interactions because it is easy to modify and possess a high specific surface area, improving its tumor targeting and colloidal stability, as well as accuracy and sensitivity for detecting specific biomarkers. At the same time, in the near-infrared (NIR) window, MoS2 has excellent optical absorption and prominent photothermal conversion efficiency, which can achieve NIR-based phototherapy and NIR-responsive controlled drug-release. Significantly, the modified MoS2-nanocomposite can specifically respond to the tumor microenvironment, leading to drug accumulation in the tumor site increased, reducing its side effects on non-cancerous tissues, and improved therapeutic effect. In this review, we introduced the latest developments of MoS2-nanocomposites in cancer diagnosis and therapy, mainly focusing on biosensors, bioimaging, chemotherapy, phototherapy, microwave hyperthermia, and combination therapy. Furthermore, we also discuss the current challenges and prospects of MoS2-nanocomposites in cancer treatment.

Microorganism-produced volatile organic compounds (VOCs) are considered promising environmental-safety fumigants in food preservation. In this study, the VOCs from fungal Ceratocystis fimbriata strains (WSJK-1, Mby) were tested against postharvest fungi Monilinia laxa, Fusarium oxysporum, Monilinia fructicola, Botrytis cinerea, Alternaria solani, and Aspergillus flavus in vitro. The mycelial growth was significantly inhibited, in particular M. fructicola and B. cinerea (76.95, 76.00%), respectively. VOCs were identified by headspace solid-phase microextraction coupled with Gas Chromatography–Mass Spectrometry (HS-SPME-GC–MS); 40 compounds were identified. The antifungal activity of 21 compounds was tested by the minimum inhibitory concentrations (MIC) value. Benzaldehyde, 2-Phenylethanol, and 1-Octen-3-ol showed strong antifungal activity with the MIC in vitro ranging from 0.094 to 0.284 ml L−1 depending on the pathogen tested. The optical microscope showed serious morphological damage, including cell deformation, curling, collapse, and deficiency in mycelial or conidia cell structures treated with C. fimbriata VOCs and pure compounds. In vivo tests, C. fimbriata VOCs decreased brown rot severity in peaches, and compounds Benzaldehyde and 2-Phenylethanol could reduce peach brown rot in peaches at 60 μl L−1. The VOCs produced by C. fimbriata strain have good antifungal effects; low concentration fumigation could control peach brown rot. Its fragrance is fresh, safe, and harmless, and it is possible to replace chemical fumigants. It could be used as a potential biofumigant to control fruit postharvest transportation, storage, and food preservation. To the best of our knowledge, this is the first report on the antifungal activity and biocontrol mechanism of VOCs produced by C. fimbriata.

Periodontal disease (PD) is a local inflammatory disease with high morbidity, manifesting tissue destruction results from inflammation of the host immune response to bacterial antigens and irritants. The supportive function of connective tissue and skeletal tissue can be jeopardized without prompt and effective intervention, representing the major cause of tooth loss. However, traditional treatments exhibited great limitations, such as low efficacies, causing serious side effects and recurrent inflammatory episodes. As a major defense mechanism, reactive oxygen species (ROS) play important roles in the pathological progression of PD. Antioxidant therapy is widely believed to be an effective strategy for ROS-triggered diseases, including oxidative stress-induced PD. Most antioxidants can only scavenge one or a few limited kinds of ROS and cannot handle all kinds. In addition, current antioxidant nanomaterials present limitations associated with toxicity, low stability, and poor biocompatibility. To this end, we develop ultra-small molybdenum-based nanodots (MoNDs) with strong ROS in oxidative stress-induced PD. To the best of our knowledge, this is the first time that MoNDs have been used for PD. In the present study, MoNDs have shown extremely good therapeutic effects as ROS scavengers. Spectroscopic and in vitro experiments provided strong evidence for the roles of MoNDs in eliminating multiple ROS and inhibiting ROS-induced inflammatory responses. In addition, the mouse model of PD was established and demonstrated the feasibility of MoNDs as powerful antioxidants. It can alleviate periodontal inflammation by scavenging multiple ROS without obvious side effects and exhibit good biocompatibility. Thus, this newly developed nanomedicine is effective in scavenging ROS and inhibiting M1 phenotypic polarization, which provides promising candidates for the treatment of PD.

Drug-induced liver injury (DILI) is a serious clinical disease associated with reactive oxygen species (ROS) burst and subsequent inflammatory responses. However, traditional treatments were limited by low efficacy and serious side effects due to the special liver structure. Here, we developed a molybdenum (Mo)-based nanoparticles, EGM NPs, after overall consideration of the pathophysiology of DILI and the advantages of nanodrugs. It demonstrated that EGM NPs treated acetaminophen (APAP)-induced DILI by scavenging ROS and inhibiting inflammation. EGM NPs effectively scavenged various ROS and reduced cell apoptosis at the cellular level. More importantly, EGM NPs can treat APAP-induced DILI in vivo, reducing the levels of liver function indicators in mice with liver injury, scaling down the area of hepatocyte necrosis and successfully inhibiting endoplasmic reticulum (ER) stress in the liver. EGM NPs also showed a certain anti-inflammatory effect by reducing infiltration of macrophages, decreasing pro-inflammatory factors and inhibiting the expression levels of inducible nitric oxide synthase (NOS2) and myeloperoxidase (MPO). Collectively, our findings suggest that EGM NPs-based nanotherapeutic is a novel strategy for the treatment of DILI.

Abstract Immunotherapy has revolutionized cancer treatment, dramatically improving survival rates of melanoma and lung cancer patients. Nevertheless, immunotherapy is almost ineffective against ovarian cancer (OC) due to its cold tumor immune microenvironment (TIM). Many traditional medications aimed at remodeling TIM are often associated with severe systemic toxicity, require frequent dosing, and show only modest clinical efficacy. In recent years, emerging nanomedicines have demonstrated extraordinary immunotherapeutic effects for OC by reversing the TIM because the physical and biochemical features of nanomedicines can all be harnessed to obtain optimal and expected tissue distribution and cellular uptake. However, nanomedicines are far from being widely explored in the field of OC immunotherapy due to the lack of appreciation for the professional barriers of nanomedicine and pathology, limiting the horizons of biomedical researchers and materials scientists. Herein, a typical cold tumor‐OC is adopted as a paradigm to introduce the classification of TIM, the TIM characteristics of OC, and the advantages of nanomedicines for immunotherapy. Subsequently, current nanomedicines are comprehensively summarized through five general strategies to substantially enhance the efficacy of immunotherapy by heating the cold OC. Finally, the challenges and perspectives of this expanding field for improved development of clinical applications are also discussed.

Sepsis-associated encephalopathy (SAE) is an intricated complication of sepsis that brings abnormal emotional and memory dysfunction and increases patients’ mortality. Patients’ alterations and abnormal function seen in SAE occur in the hippocampus, the primary brain region responsible for memory and emotional control, but the underlying pathophysiological mechanisms remain unclear. In the current study, we employed an integrative analysis combining the RNA-seq-based transcriptomics and liquid chromatography/mass spectrometry (LC-MS)-based metabolomics to comprehensively obtain the enriched genes and metabolites and their core network pathways in the endotoxin (LPS)-injected SAE mice model. As a result, SAE mice exhibited behavioral changes, and their hippocampus showed upregulated inflammatory cytokines and morphological alterations. The omics analysis identified 81 differentially expressed metabolites (variable importance in projection [VIP] > 1 and p < 0.05) and 1747 differentially expressed genes (Foldchange >2 and p < 0.05) were detected in SAE-grouped hippocampus. Moreover, 31 compounds and 100 potential target genes were employed for the Kyoto Encyclopedia of Genes and Genomes (KEGG) Markup Language (KGML) network analysis to explore the core signaling pathways for the progression of SAE. The integrative pathway analysis showed that various dysregulated metabolism pathways, including lipids metabolism, amino acids, glucose and nucleotides, inflammation-related pathways, and deregulated synapses, were tightly associated with hippocampus dysfunction at early SAE. These findings provide a landscape for understanding the pathophysiological mechanisms of the hippocampus in the progression of SAE and pave the way to identify therapeutic targets in future studies.

Abstract Background Biomarkers for distinguishing psoriatic arthritis (PsA) from psoriasis without arthritis (PsO) are still lacking. Methods We applied isobaric tags for relative and absolute quantification (iTRAQ) and LC–MS/MS to analyze the proteome profile of peripheral blood mononuclear cells (PBMCs) collected from patients with PsO, patients with PsA, and healthy controls. Bioinformatics analysis and western blotting were performed to identify and validate differentially expressed proteins. Results We identified 389, 199, 291, and 60 significantly differentially expressed proteins (adj.p

This study explored the effects of combined urea and 3,4-dimethylpyrazole phosphate (DMPP) on several components critical to the soil system: net nitrification rates; communities of targeted ammonia oxidizers [ammonia-oxidizing archaea (AOA) and bacteria (AOB) and complete ammonia-oxidizing bacteria (comammox)]; non-targeted nitrite-oxidizing bacteria (NOB) and bacteria. We conducted the study in two contrasting soils (acidic and neutral) over the course of 28 days. Our results indicated that DMPP had higher inhibitory efficacy in the acidic soil (30.7%) compared to the neutral soil (12.1%). The abundance of AOB and Nitrospira-like NOB were positively associated with nitrate content in acidic soil. In neutral soil, these communities were joined by the abundance of AOA and Nitrobacter-like NOB in being positively associated with nitrate content. By blocking the growth of AOB in acidic soil—and the growth of both AOB and comammox in neutral soil—DMPP supported higher rates of AOA growth. Amplicon sequencing of the 16S rRNA gene revealed that urea and urea + DMPP treatments significantly increased the diversity indices of bacteria, including Chao 1, ACE, Shannon, and Simpson in the acidic soil but did not do so in the neutral soil. However, both urea and urea + DMPP treatments obviously altered the community structure of bacteria in both soils relative to the control treatment. This experiment comprehensively analyzed the effects of urea and nitrification inhibitor on functional guilds involved in the nitrification process and non-targeted bacteria, not just focus on targeted ammonia oxidizers.

Cancer is one of the leading causes of death worldwide due to high morbidity and mortality. Many attempts and efforts have been devoted to fighting cancer. Owing to the significant role of the endoplasmic reticulum (ER) in cell function, inducing ER stress can be promising for cancer treatment. However, the sustained activation of cytoprotective unfolded protein response (UPR) presents a tremendous obstacle for drugs in inducing unsolved ER stress in tumor cells, especially small-molecule drugs with poor bioavailability. Therefore, many emerging nanodrugs inducing and amplifying ER stress have been developed for efficient cancer treatment. More importantly, the novel discovery of ER stress in immunogenic cell death (ICD) makes it possible to repurpose antitumor drugs for immunotherapy through nanodrug-based strategies amplifying ER stress. Therefore, this mini-review aims to provide a comprehensive summary of the latest developments of the strategies underlying nanodrugs in the treatment of cancer via manipulating ER stress. Meanwhile, the prospects of ER stress–inducing nanodrugs for cancer treatment are systematically discussed, which provide a sound platform for novel therapeutic insights and inspiration for the design of nanodrugs in treating cancer.

Abstract Dysregulations in transcription factors (TFs) and their genetic products play important roles in tumorigenesis, tumor progression and metastasis. However, prognostic value of the transcriptional regulatory networks in different cancers has not been investigated in depth. The purpose of our study was to identify and validate a potential predictive signature that combines TFs and their regulatory products in eight solid tumors. We used bioinformatics analysis to identify MET Transcriptional Regulator (MACC1) and Serine Peptidase Inhibitor Kunitz Type 1 (SPINT1) as candidate TFs with the respective downstream regulatory proteins for patient prognosis in pan‐cancer. Subsequent molecular analysis of clinical gastric cancer tissue samples further verified the negative correlation between MACC1 and SPINT1. Further, we showed that mechanistically, MACC1/SPINT1 mediated the pro‐HGF proteolysis and c‐Met phosphorylation in HGF/c‐MET signaling pathway. Kaplan‐Meier plots and receiver operating characteristics analysis revealed that the two‐gene signature combining MACC1 with SPINT1 was effective in predicting survival in all eight cancer cohorts tested. In conclusion, our study clarified the regulatory relationship between MACC1 and SPINT1 in the context of the HGF/c‐MET signaling pathway and determined MACC1/SPINT1 panel as a valuable signature for the prediction of prognosis in patients for multiple solid cancer types.

Traumatic brain injury (TBI) is a leading cause of disability and mortality worldwide, whose symptoms ranging from mild to severe, even life-threatening. However, specific cell types and key regulators involved in traumatic brain injury have not been well elucidated. In this study, utilizing single-cell RNA-seq (scRNA-seq) data from mice with TBI, we have successfully identified and characterized 13 cell populations including astrocytes, oligodendrocyte, newly formed oligodendrocytes, microglia, two types of endothelial cells, five types of excitatory and two types of inhibitory neurons. Differential expression analysis and gene set enrichment analysis (GSEA) revealed the upregulation of microglia and endothelial markers, along with the downregulation of markers of excitatory neurons in TBI. The cell-cell communication analysis revealed that microglia and endothelial cell might interact through the interaction of Icam1-Il2rg and C1qa-Cd93, and microglia might also communicate with each other via Icam1-Itagm. The autocrine ligand-receptor in microglia might result in activation of TYROBP causal network via Icam1-Itgam. The cell-cell contact between microglia and endothelial cell might activate integrin signaling pathways. Moreover, we also found that genes involved in microglia activation were highly downregulated in Tyrobp/Dap12-deficient microglia, indicating that the upregulation of Tyrobp and TYROBP causal network in microglia might be a candidate therapeutic target in TBI. In contrast, the excitatory neurons were involved in maintaining normal brain function, and their inactivation might cause dysfunction of nervous system in TBI patients. In conclusion, the present study has discerned major cell types such as microglia, endothelial cells and excitatory neurons, and revealed key regulator such as TYROBP, C1QA, and CD93 in TBI, which shall improve our understanding of the pathogenesis of TBI.

Objective To investigate the contamination levels and critical control point of Bacillus cereus in wet rice products and starch products and propose control measures. Methods Enterprises and workshops that produce wet rice products and starch products in Guangzhou were selected to collect food samples in production and sale. Raw materials including rice and starch were also collected. Quantitative detection of Bacillus cereus was carried out. Results A total of 32 production samples, 139 sales samples, 32 rice samples and 8 starch samples were collected. The detection rates of Bacillus cereus were 50.00%(16/32), 43.17%(60/139), 93.75%(30/32), 40.00%(2/5) and 66.67%(2/3), the exceeding standard rate of Bacillus cereus in wet rice products and starch products was 3.60%, while Bacillus cereus counts were 10-4.97×104, 10-2.10×106, 10-1.22×103, 10-30 and 10 CFU/g respectively. There was no significant difference in the positive rates of sales products in four quarters, which were 45.28%, 42.50%, 31.03% and 58.82% respectively. Conclusion The contamination of Bacillus cereus in wet rice products and starch products in Guangzhou was serious. Microbiological control measures should focus on material rinsing, equipment cleaning, whole-process cold chain transportation and storage, storage time control and formation of good eating habits.

A ring signature (RS) scheme enables a group member to sign messages on behalf of its group without revealing the definite signer identify, but this also leads to the abuse of anonymity by malicious signers, which can be prevented by traceable ring signatures (TRS). Up until that point, traceable ring signatures have been secure based on the difficult problem of number-theoretic (discrete logarithms or RSA), but since the advent of quantum computers, traditional traceable ring signatures may no longer be secure. Thus Feng proposed a lattice based TRS, which are resistant to attacks by quantum computers. However, that works did not tackle the certificate management problem. To close this gap, a quantum-resistant certificateless TRS scheme was proposed in the study. To the best of our knowledge, this is the first lattice based certificateless TRS. In detail, a specific TRS scheme was combined with the lattice-based certificateless signature technology to solve the certificate management problem while avoid key escrow problem. Additionally, a better zero-knowledge protocol is used to improve the computational efficiency of the scheme, and by reducing the soundness error of the zero-knowledge protocol, the number of runs of the zero-knowledge protocol is reduced, so that the communication overhead of the scheme is reduced. Under random oracle model, the proposed scheme satisfies tag-linkability, anonymity, exculpability and is secure based on the SIS problem and the DLWE problem. In conclusion, the proposed scheme is more practical and promising in e-voting.

Objectives: We aimed to estimate the time-varying transmission dynamics of COVID-19 in China, Wuhan City, and Guangdong province, and compare to that of severe acute respiratory syndrome (SARS). Methods: Data on COVID-19 cases in China up to 20 March 2020 was collected from epidemiological investigations or official websites. Data on SARS cases in Guangdong Province, Beijing, and Hong Kong during 2002–3 was also obtained. We estimated the doubling time, basic reproduction number (R0), and time-varying reproduction number (Rt) of COVID-19 and SARS. Results: As of 20 March 2020, 80,739 locally acquired COVID-19 cases were identified in mainland China, with most cases reported between 20 January and 29 February 2020. The R0 value of COVID-19 in China and Wuhan was 5.0 and 4.8, respectively, which was greater than the R0 value of SARS in Guangdong (R0 = 2.3), Hong Kong (R0 = 2.3), and Beijing (R0 = 2.6). At the start of the COVID-19 epidemic, the Rt value in China peaked at 8.4 and then declined quickly to below 1.0 in one month. With SARS, the Rt curve saw fluctuations with more than one peak, the highest peak was lower than that for COVID-19. Conclusions: COVID-19 has much higher transmissibility than SARS, however, a series of prevention and control interventions to suppress the outbreak were effective. Sustained efforts are needed to prevent the rebound of the epidemic in the context of the global pandemic.

Abstract Functional encryption (FE) is a novel paradigm for encryption scheme which allows tremendous flexibility in accessing encrypted information. In FE, a user can learn specific function of encrypted messages by restricted functional key and reveal nothing else about the messages. Inner product encryption (IPE) is a special type of functional encryption where the decryption algorithm, given a ciphertext related to a vector x and a secret key related to a vector y, computes the inner product x·y. In this paper, we construct an efficient private-key functional encryption (FE) for inner product with simulation-based security, which is much stronger than indistinguishability-based security, under the External Decisional Linear assumption in the standard model. Compared with the existing schemes, our construction is faster in encryption and decryption, and the master secret key, secret keys and ciphertexts are shorter.

Abstract Private Set Intersection Cardinality (PSI-CA) and Private Set Union Cardinality (PSU-CA) are two cryptographic primitives whereby two or more parties are able to obtain the cardinalities of the intersection and the union of their respective private sets, and the privacy of their sets is preserved. In this paper, we propose a three-party protocol to finish these tasks by using quantum resources, where every two, as well as three, parties can obtain the cardinalities of the intersection and the union of their private sets with the help of a semi-honest third party (TP). In our protocol, GHZ states play a role in encoding private information that will be used by TP to compute the cardinalities. We show that the presented protocol is secure against well-known quantum attacks. In addition, we analyze the influence of six typical kinds of Markovian noise on our protocol.

BackgroundVisceral fat has been considered an important risk factor of elevated serum uric acid (SUA). Perirenal fat is a unique visceral fat around the kidneys that has special morphological and physiological features while its relationship with SUA remains incompletely elucidated. This study aimed to assess the association between perirenal fat volume (PrFV) and SUA.MethodsA cross-sectional study was conducted in 102 subjects aged ≥ 18 years old recruited from Nanjing,China. The clinical characteristics including age, sex, drinking behavior, history of hypertension, body mass index, waist circumference, total cholesterol, fast plasma glucose, urea, serum creatinine, C-reactive protein, and SUA were recorded. PrFV was measured by ultrasonography. Multivariate linear models and the restricted cubic spline were used to investigate the association between PrFV and SUA.ResultsThe median age of this study population was 52.5 (42.0-60.0) years and 56.9% were female. The median value of SUA was 5.73 mg/dL (4.58-6.80 mg/dL). The subjects were divided by PrFV tertiles and we found that the subjects in the highest PrFV tertile had a higher level of SUA compared to those in the lowest tertile (β=1.86, 95%CI 1.23–2.48, P for trend

DNA is always one of the most important targets for cancer therapy due to its leading role in the proliferation of cancer cells. Phototherapy kills cancer cells by generating reactive oxygen species (ROS) and local hyperthermia under light. It has attracted extensive interest in the clinical treatment of tumors because of many advantages such as non-invasiveness, high patient compliance, and low toxicity and side effects. However, the short ROS diffusion distance and limited thermal diffusion rate make it difficult for phototherapy to damage DNA deep in the nucleus. Therefore, nucleus-targeting phototherapy that can destroy DNAs via in-situ generation of ROS and high temperature can be a very effective strategy to address this bottleneck. Recently, some emerging nucleus-targeting phototherapy nanodrugs have demonstrated extremely effective anticancer effects. However, reviews in the field are still rarely reported. Here, we comprehensively summarized recent advances in nucleus-targeting phototherapy in recent years. We classified nucleus-targeting phototherapy into three categories based on the characteristics of these nucleus-targeting strategies. The first category is the passive targeting strategy, which mainly targets the nucleus by adjusting the physicochemical characteristics of phototherapy nanomedicines. The second category is to mediate the phototherapy nanodrugs into the nucleus by modifying functional groups that actively target the nucleus. The third category is to assist nanodrugs enter into the nucleus in a light-controlled way. Finally, we provided our insights and prospects for nucleus-targeting phototherapy nanodrugs. This minireview provides unique insights and valuable clues in the design of phototherapy nanodrugs and other nucleus-targeting drugs.

Cancer cell lysosomes contain various hydrolases and non-degraded substrates that are corrosive enough to destroy cancer cells. However, many traditional small molecule drugs targeting lysosomes have strong side effects because they cannot effectively differentiate between normal and cancer cells. Most lysosome-based research has focused on inducing mild lysosomal membrane permeabilization (LMP) to release anticancer drugs from lysosomal traps into the cancer cell cytoplasm. In fact, lysosomes are particularly powerful “bombs”. Achieving cancer cell-selective LMP induction may yield high-efficiency anticancer effects and extremely low side effects. Nanodrugs have diverse and combinable properties and can be specifically designed to selectively induce LMP in cancer cells by taking advantage of the differences between cancer cells and normal cells. Although nanodrugs-induced LMP has made great progress recently, related reviews remain rare. Herein, we first comprehensively summarize the advances in nanodrugs-induced LMP. Next, we describe the different nanodrugs-induced LMP strategies, namely nanoparticles aggregation-induced LMP, chemodynamic therapy (CDT)-induced LMP, and magnetic field-induced LMP. Finally, we analyze the prospect of nanodrugs-induced LMP and the challenges to overcome. We believe this review provides a unique perspective and inspiration for designing lysosome-targeting drugs.