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BACKGROUND: Anemia associated with heart failure is frequent and can exacerbate the symptoms of heart failure. Dapagliflozin is the first SGLT-2 inhibitor with significant cardiovascular protection. However, the effect of dapagliflozin on anemia in elderly patients with heart failure is unknown. OBJECTIVE: We aimed to study the effect of dapagliflozin on anemia in elderly patients with heart failure by bioinformatics analysis. METHODS: The target genes were determined, followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. The protein-protein interaction (PPI) network and modules were constructed. The dapagliflozin-targets network in anemia and heart failure was constructed. Molecular docking experiments between dapagliflozin and its key target AKT1 were performed. RESULTS: We found 1 dapagliflozin related target gene and 2 disease related genes. Totally, 134 target genes of dapagliflozin on anemia in elderly patients with heart failure were determined. The pathways may involve lipid and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, hepatitis B, insulin signaling pathway, fluid shear stress and atherosclerosis, neurotrophin signaling pathway, insulin resistance, toxoplasmosis, colorectal cancer, and EGFR tyrosine kinase inhibitor resistance. The hub genes in network were AKT1, TP53, GAPDH, TNF, CASP3, EGFR, and MAPK3. The structure of dapagliflozin and AKT1 molecular docking was exhibited. CONCLUSIONS: The hub genes in network were AKT1, TP53, GAPDH, TNF, CASP3, EGFR, and MAPK3. The structure of dapagliflozin and AKT1 molecular docking was exhibited. [ABSTRACT FROM AUTHOR]

This study aims to examine group trends and individual variability of descriptive Grammatical Complexity (GC) in writing development. A longitudinal sample of 41 high school EFL learners is followed for an academic year (12 waves of data collection), resulting in a corpus of 492 texts, coded for eight descriptive GC features of academic writing. Our analysis reveals different sets of descriptive GC features relevant to capturing group trends and individual variability in writing development. At the group level, two phrasal-level GC features could capture significant changes in group means over time; at the individual level, four types of clausal and phrasal GC features showed significant associations between individual variability over time (measured by Standard Deviation of differences) and gains (as measured by the increase of usage frequency). Findings are discussed with regard to modeling both inter-individual and intra-individual trajectories in writing development and pedagogical implications attuned to both group and individual needs. [ABSTRACT FROM AUTHOR]

The bootstrapping procedure has become the main bottleneck affecting the efficiency of all known fully homomorphic encryption (FHE) schemes. The state-of-the-art scheme for efficient bootstrapping, which is called fully homomorphic encryption over the torus (TFHE), accelerates polynomial multiplication by leveraging number theoretic transform (NTT) and implementing NTT in parallel on a GPU. Unfortunately, almost none of the recent advancements in NTT take full advantage of a GPU, leading to the need for more time. With this in mind, in this work, a novel faster number theoretic transform based on a GPU is proposed, in which matrix multiplication is used to implement a decomposed small-point NTT. When implementing matrix multiplication, we introduce a merging preprocessing method to merge multiple inputs of the small-point NTT, aiming to effectively minimize the count of modulo operations. Subsequently, when the merged result is multiplied by rotation factors, we use logical left shift rather than arithmetic multiplication to improve the computational efficiency. Our scheme can easily be used to realize a 1024-point NTT and the results of the experiments show that the speedup ratio of our method over the butterfly algorithm is about 2.49. [ABSTRACT FROM AUTHOR]

Spinocerebellar ataxia 3 (SCA3) is an incurable, neurodegenerative genetic disorder that leads to progressive cerebellar ataxia and other parkinsonian‐like pathologies because of loss of cerebellar neurons. The role of an expanded polyglutamine aggregate on neural progenitor cells is unknown. Here, we show that SCA3 patient‐specific induced neural progenitor cells (iNPCs) exhibit proliferative defects. Moreover, SCA3 iNPCs have reduced autophagic expression compared to control. Furthermore, although SCA3 iNPCs continue to proliferate, they do not survive subsequent passages compared to control iNPCs, indicating the likelihood that SCA3 iNPCs undergo rapid senescence. Exposure to interleukin‐4 (IL‐4), a type 2 cytokine produced by immune cells, resulted in an observed increase in expression of autophagic programs and a reduction in the proliferation defect observed in SCA3 iNPCs. Our results indicate a previously unobserved role of SCA3 disease ontology on the neural stem cell pool and a potential therapeutic strategy using IL‐4 to ameliorate or delay disease pathology in the SCA3 neural progenitor cell population. [ABSTRACT FROM AUTHOR]

Introduction: High serum phosphorus level has been reported to be a risk factor for disease progression in patients with chronic kidney disease, whereas, its role in IgA nephropathy (IgAN) still remains uncertain. This study aimed to investigate the association between serum phosphorus and progression of IgAN. Methods: A total of 247 patients diagnosed with IgAN from 2016.11 to 2019.12 at the First Affiliated Hospital of Xi'an Jiaotong University were retrospectively enrolled in this study. The association between serum phosphorus and kidney disease progression events, defined as 30% estimated glomerular filtration rate (eGFR) decline or kidney failure, was evaluated using Cox models. Results: Serum phosphorus was an independent risk factor for poor renal outcome after adjusting for age, gender, urine protein, MAP, eGFR, hemoglobin, Oxford S and T scores (HR, 2.586; 95% CI, 1.238–5.400, p = 0.011). The addition of serum phosphorus to the reference model containing clinical and pathological variables significantly improved the risk prediction of IgAN progression (C statistic, 0.836; 95% CI, 0.783–0.889) as compared with the reference model (C statistic, 0.821; 95% CI, 0.756–0.886). The ability of serum phosphorus level to predict progression was much stronger in IgAN patients without use of immunosuppression (HR 5.173; 95% CI, 1.791–14.944; p = 0.002). Conclusion: Higher serum phosphorus levels were independently associated with kidney disease progression in patients with IgAN, especially in those without immunosuppression. The addition of serum phosphorus to clinical and pathological data at the time of biopsy significantly improved risk prediction of IgAN progression. [ABSTRACT FROM AUTHOR]

Customers' concerns regarding product quality (CPQs), as expressed in online reviews, provide future customers with information that may influence their own purchase decisions. Recent research attaches considerable importance to consumers' emotions embedded in their language style, based on function words, but rarely touches on their CPQs, which are also embedded in their language style. Therefore, this study aims to examine the CPQs of Chinese women's clothes buyers. We build a corpus of 32,667 words from the online reviews of women's clothes buyers on the Chinese website Taobao. A novel language inquiry word count dictionary for topic types related to product quality is built, which is then imported into a language style matching algorithm which assesses the synchrony of the language style. Our results show that buyers' CPQs are diverse and concentrated in scope; consumers' different expressions in online reviews are dependent on the sequence and impact factor of CPQs embedded in their language style. This study's findings offer companies valuable insights to identify customers' CPQs based on their language style, which may allow them to devise more effective promotion strategies and product designs. [ABSTRACT FROM AUTHOR]

Thermal modification could act as pretreatment for promoting silica sol impregnation in wood. It could create extra available channels and spaces for silica transportation and deposition owing to the presence of micro-cracks and enlarged pore size. The significant improvements on anti-hygroscopicity, hydrophobicity, and dimensional stability of treated wood were attributed to the degradation of cell wall polymer (hemicellulose, cellulose, and lignin) and filling effect of silica in wood. The synergistic effect contained the reduction on –OH concentration owing to thermal degradation, and consumption of –OH groups via the interaction (Si–O–Si cross linked networks and Si–O–C covalent bonds) between silica and wood matrix. Furthermore, the degradation of cell wall polymers resulted in the increase of crystallinity in wood. However, the crystallinity turned to decrease due to the amorphous silica impregnation. The silica impregnation could compensate the mass loss caused by thermal degradation, leading to various weight percentage gains (WPGs) that depended on treatment temperature. Moreover, owing to the coverage and penetration of mineral silica in wood, acting as a thermal barrier, the thermal stability and surface hardness of treated wood improved prominently. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Type 2 diabetes mellitus has been a leading cause of chronic kidney disease (CKD), with a heterogeneous distribution worldwide. Optimal healthcare planning requires an understanding of how the burden of CKD as a result of type 2 diabetes mellitus has changed over time and geographic location, as well as the potential roles of sociodemographic, clinical and behavioral factors in these changes. Materials and Methods: We used the Global Burden of Disease data from 1990 to 2017 at the global, regional and national levels to investigate changes in the incidence, death and disability‐adjusted life years of CKD as a result of type 2 diabetes mellitus, incorporating both epidemiological research and risk factor monitoring. Results: The incident cases of CKD as a result of type 2 diabetes mellitus worldwide in 2017 had increased by 74% compared with 1990; total disability‐adjusted life years had increased by 113%, mainly attributable to population expansion and demographic transition. The Sociodemographic Index was significantly and negatively correlated with overall CKD as a result of type 2 diabetes mellitus burden. However, in 82 countries and territories, the burden was not alleviated in parallel with socioeconomic development. Conclusions: CKD as a result of type 2 diabetes mellitus has been the main contributor to the increasing burden of CKD over the past several decades. We suggest a more pragmatic approach focusing on early diagnosis, primary care and adequate follow up to reduce mortality and the long‐term burden in low‐to‐middle Sociodemographic Index regions. Interventions should address high systolic blood pressure, as well as overweight and obesity problems, especially in high‐income regions. [ABSTRACT FROM AUTHOR]

Acute toxicity of antimony pentavalent to neonatal Daphnia magna and the influence of water quality parameters were investigated, and enzymatic activities of organisms at environmentally relevant levels of antimony were determined. EC 50 values of antimony to neonatal D. magna were 90.3 and 63.8 mg/L at 24 and 48 h of exposure, respectively. Dissolved organic matter (FA and HA) and cation (Ca2+, Mg2+ or Na+) had significant protective effects on D. magna against antimony toxicity. With increasing pH in the range from 7.4 to 8.5, increase of EC 50 were observed due to the competition of OH- on biotic ligands. Based on the biotic ligand model (BLM) concept, stability constants for the binding of Sb(OH) 6 - and OH- to the biotic ligand were estimated, and the Log K XSb (OH) 6 - and Log K XOH - were 3.137 and 2.859, respectively. Moreover, antimony exposure in low concentrations significantly increased MDA levels and maybe exert oxidative stress to the organisms. Antimony can also induce toxicity in D. magna by affecting oxidative stress and neurotransmitter systems. The relatively comprehensive toxicological data can contribute to the toxicity prediction and ecological risk assessments of antimony. [Display omitted] • FA and HA weaken Sb toxicity to Daphnia magna. • Ca2+, Mg2+ and Na+ have significant protective effects against Sb toxicity. • Low levels of Sb exhibit oxidative stress and neurotoxicity on Daphnia magna. • Constants for the binding of Sb(OH) 6 - with the competition of OH- was calculated. [ABSTRACT FROM AUTHOR]

The phosphorus content in eel aquaculture wastewater exceeds the discharge standard, and the amount of wastewater discharged is substantial. Therefore, there is an urgent need to explore an economical and efficient method of treating aquaculture wastewater. This study explored the use of Desmodesmus sp. PW1, a type of microalgae, to treat eel aquaculture wastewater. By optimizing the conditions, Desmodesmus sp. PW1 achieved a total phosphorus (TP) removal efficiency of 92.3%, as well as total nitrogen (TN) and ammonia nitrogen (NH 4 +-N) removal efficiency of 99%, using a photoperiod of 24:0, a temperature of 25 °C, and an inoculation amount of 15%. Furthermore, Desmodesmus sp. PW1 demonstrated a high self-flocculating efficiency (>90%) within 100 min of settling, which facilitated biomass recovery. Subsequently, a semi-continuous treatment process mode was established with a sewage renewal rate of 90%. The results showed that after four rounds of sewage renewal operations, the microalgae biomass in the sewage treatment system could be maintained between 160.0 and 220.0 mg/L, and the average removal rate of TP was 0.13 mg/(L * h). The lipid content of algae cells collected in the semi-continuous treatment system for eel aquaculture wastewater was as high as 36.5%, and the biodiesel properties met the biodiesel standards authorized by Europe and the United States. Overall, this study provides an economical and effective strategy for converting wastewater into high-value microalgae products. [Display omitted] • Desmodesmus sp. PW1 demonstrated high removal efficiencies of 92.3% for TP and 99% for TN in treating eel aquaculture wastewater • Desmodesmus sp. PW1 demonstrated a self-flocculating efficiency of over 90% within a settling time of 100 min. • A semi-continuous model with a renewal rate of 90% for treating eel aquaculture wastewater was constructed. • Desmodesmus sp. PW1 contained 36.5% lipid that can be utilized for preparing biodiesel. [ABSTRACT FROM AUTHOR]

It has been reported that variceal pressure can predict the occurrence of variceal bleeding. However, the majority of methods presently used to measure variceal pressure are either invasive or inconvenient. In the present study, a fiber-optic pressure sensor was constructed to detect variceal pressure. The prospective study focused on the in vitro accuracy of a fiber-optic pressure sensor and investigated the clinical reliability and feasibility of this method. The fiber-optic pressure sensor covered a pressure-sensitive probe containing a fiber-optic pressure sensor and a workstation to record the pressure tracing. It was hypothesized that the endoscopic fiber-optic pressure sensor can effectively predict the risk of variceal bleeding. To test this hypothesis, 80 patients who suffered from cirrhosis and who had a history of variceal bleeding were included in the present study. The fiber-optic pressure sensor was guided through the biopsy channel using an endoscope in the patient cohort. Transjugular intrahepatic stent-shunt (TIPS) was subsequently performed within 24 h after measuring variceal pressure. A comparison of the results of the 80 patients was made between variceal pressure measured by the endoscopic fiber-optic pressure sensor and the portal pressure gradient (PPG) measured by a TIPS. The variceal pressure measurements with the fiber-optic pressure sensor were technically satisfactory in 78 patients. The results indicated that there was a linear correlation between the variceal pressure measured by the endoscopic fiber-optic pressure sensor and the PPG (r=0.940, P<0.001). These observations suggest that the fiber-optic pressure sensor is an accurate and feasible measurement technique. Therefore, the results of the present study indicate that the endoscopic fiber-optic pressure sensor is effective in predicting the risk of variceal bleeding. [ABSTRACT FROM AUTHOR]

Background: Peritoneal dialysis (PD) is a kind of renal replacement therapy (RRT), which can be employed to treat pediatric acute kidney injury (AKI) as it is safe, simple, and cost-effective. The studies of PD treatment in pediatric AKI in China have rarely been reported in English literature. Objective: To investigate the efficacy and the outcome of PD in pediatric patients with AKI. Methods: We performed a retrospective study of children who received PD as RRT for AKI in a teaching hospital in northwest China from 2003 to 2013. Demographic characteristics and laboratory data were collected, and the prognostic factors of renal recovery were identified. Results: There were 24 children (62.5% male) identified, with the mean age of 22.4 ± 18.7 months (3 months to 5 years old). The most common causes of AKI were drug induced (25.0%), glomerulonephritis (20.9%), and obstructive nephropathy (16.7%). The mean duration of PD was 11.3 ± 7.8 days (2–39 days). PD treatment was highly effective in attenuation of toxics, improvement of fluid overload, and correction of electrolyte disturbances (p < 0.001). One catheter outflow obstruction was noted, and no major complication was identified. In total, 18 children (75.0%) recovered and had the catheter successfully removed, 2 (8.3%) needed further PD treatment, and 4 (16.7%) died. The albumin level was significantly higher in patients who recovered with PD treatment (33.7 ± 6.2 vs. 21.5 ± 4.8 g/L, p = 0.002). Conclusions: PD can be performed safely and efficiently for the treatment of pediatric AKI. Low albumin level may be associated with poor prognosis of pediatric AKI. [ABSTRACT FROM AUTHOR]

Circulating microRNAs (miRNAs) are potential biomarkers for cardiovascular diseases. Our study aimed to determine whether miR-22-5p, miR-132-5p, and miR-150-3p represent novel biomarkers for acute myocardial infarction (AMI). Plasma samples were isolated from 35 AMI patients and 55 matched controls. Total RNA was extracted, and quantitative real-time PCR and ELISA were performed to investigate the expressions of miRNAs and cardiac troponin I (cTnI), respectively. We found that plasma levels of miR-22-5p and miR-150-3p were significantly higher during the early stage of AMI and their expression levels peaked earlier than cTnI. Conversely, circulating miR-132-5p was sustained at a low level during the early phase of AMI. All three circulating miRNAs were correlated with plasma cTnI levels. A receiver operating characteristic (ROC) analysis suggested that each single miRNA had considerable diagnostic efficacy for AMI. Moreover, combining the three miRNAs improved their diagnostic efficacy. Furthermore, neither heparin nor medications for coronary heart disease (CHD) affected plasma levels of miR-22-5p and miR-132-5p, but circulating miR-150-3p was downregulated by medications for CHD. We concluded that plasma miR-22-5p, miR-132-5p, and miR-150-3p may serve as candidate diagnostic biomarkers for early diagnosis of AMI. Moreover, a panel consisting of these three miRNAs may achieve a higher diagnostic value. [ABSTRACT FROM AUTHOR]

Necrotic enteritis (NE) is an enterotoxigenic disease caused by Clostridium perfringens that results in substantial economic losses to the global poultry industry. Here, we investigated the effects of dietary microencapsulated sodium butyrate (MSB) on the growth performance and intestinal barrier function of broiler chickens co-infected with Eimeria spp. and C. perfringens . Chickens were fed, from hatch, either a diet supplemented with MSB, or with a non-supplemented control diet, and were either left uninfected or orally infected with mixed strains of Eimeria species at 12 d of age, followed by an oral inoculation with C. perfringens at 16, 17, and 18 d of age. NE-infected chickens fed MSB-supplemented diets had greater body weight (BW), improved average daily gains (ADG), and higher feed conversion ratios (FCR) than NE-infected birds fed unsupplemented diets. Increased jejunal villus height, reduced duodenal lesion scores, reduced cecal Escherichia coli and C. perfringens counts, and reduced liver C. perfringens load were also observed in the NE-infected, MSB-supplemented chickens as compared to the NE-infected, unsupplemented birds. NE infection downregulated claudin-4, ZO-1, occludin, LEAP-2, and mucin-2 in the jejunum. However, MSB-fed birds infected with NE had significantly upregulated claudin-1, claudin-4, ZO-1, occludin, LEAP-2, and mucin-2 levels in the jejunum as compared with infected birds fed the non-supplemented diet. We have thus demonstrated that the administration of MSB alleviates intestinal mucosal barrier injury of broiler chickens infected with NE. [ABSTRACT FROM AUTHOR]

Porokeratotic eccrine ostial and dermal duct nevus (PEODDN) is a rare benign skin disease. Widespread involvement of PEODDN is more uncommon and its association with squamous cell carcinoma (SCC) is also rare. In this case report, we present the case of a 50-year-old woman with serious widespread PEODDN along Blaschko's lines and concomitant invasive SCC with lymph node metastasis. This was the first reported case of metastatic SCC arising from PEODDN. [ABSTRACT FROM AUTHOR]

Certificateless multi-receiver signcryption scheme provides an efficient solution for one-to-many communication applications and avoids the key escrow problem in the existing identity-based multi-receiver signcryption schemes. Many certificateless multi-receiver signcryption schemes have been proposed with various secure properties, such as receiver anonymity and sender anonymity. However, among the existing certificateless multi-receiver signcryption schemes with sender anonymity, there is no scheme considers the sender tracing functionality. Sender anonymity is vulnerable and contradicts with non-repudiation. The anonymous sender may disavow the illegal message he has sent, which compromises the non-repudiation, so there is a high desirability to provide a sender tracing functionality which can be execute under certain conditions to balance the sender anonymity and non-repudiation. Motivated by these concerns, a new certificateless multi-receiver signcryption scheme is proposed, which achieves completely anonymity and provides the sender tracing functionality. In the proposed scheme, the key generation center can cooperate with any authorized receiver to trace the anonymous sender, but neither of them can do it alone. In this case, sender anonymity and non-repudiation reach a certain degree of balance. [ABSTRACT FROM AUTHOR]

Ciphertext-Policy Attribute-Based Proxy Reencryption (CP-ABPRE) has found many practical applications in the real world, because it extends the traditional Proxy Reencryption (PRE) and allows a semitrusted proxy to transform a ciphertext under an access policy to the one with the same plaintext under another access policy. The existing CP-ABPRE schemes were proven secure only in the selective security model, a limited model, which is an unnatural constraint on the attacker. The scheme proved in this model can only be called selectively secure one. However, from a security perspective, the adaptively secure CP-ABPRE scheme is more desirable. In this paper, an adaptively secure CP-ABPRE scheme is proposed, which is based on Waters’ dual system encryption technology. The proposed scheme is constructed in composite order bilinear groups and proven secure under the complexity assumptions of the subgroup decision problem for 3 primes (3P-SDP). Analyses show that our proposal provides higher computational efficiency compared with the existing schemes. [ABSTRACT FROM AUTHOR]

[Display omitted] • 2-MIB exists in several forms, such as intra-, extracellular, free and bound forms. • Powdered activated carbon (PAC) is of special use in removing free form 2-MIB. • Uncontrolled preoxidation causes serious cell lysis and intracellular 2-MIB release. • The combination of 2-MIB with other organic materials enhances its removal by NF. • The combination of PAC, CSF, and NF removes 98% of 2-MIB in raw water. 2-Methylisoborneol (2-MIB) is a typical and common off-flavor pollutant in drinking water, which is produced by cyanobacteria and other microorganisms. 2-MIB exists in several forms, such as intracellular, extracellular; and a fraction of 2-MIB is in free form, while the remaining fraction is combined with coexisting organic matters, which complicates the study of 2-MIB removal mechanisms in drinking water production. This research used raw water containing 2-MIB to investigate the effect of combination processes on the removal of 2-MIB (in different forms) and the coexisting organic substances. With conventional processes alone (coagulation, sedimentation and filtration (CSF)), the removal ratio of 2-MIB was 49.4%, which was due to the removal of intracellular 2-MIB. The removal ratio after CSF increased to 80.0–89.4% when powdered activated carbon (PAC) pretreatment (doses of 10, 20, and 50 mg/L) was applied. The fraction of 2-MIB adsorbed by PAC was in the extracellular free form. For preoxidation, the combination of KMnO 4 and CSF (KMnO 4 -CSF) was more effective than H 2 O 2 -CSF and NaClO-CSF but less effective in removing dissolved organic carbon (DOC) than the other two methods. H 2 O 2 exhibited the best overall removal of 2-MIB and DOC after CSF. NaClO caused the release of a large amount of intracellular 2-MIB. The removal ratio of 2-MIB by nanofiltration (NF, ∼300 Da) alone was ∼ 87%, and the total removal ratio with PAC, CSF, and NF was as high as 98%. The findings are of particular significance for selecting the combined drinking treatment processes (e.g. PAC-CSF-NF) when odorous compounds are present in high concentrations. [ABSTRACT FROM AUTHOR]

Indolosesquiterpenexiamycin A features a pentacyclic core structure.The chemical synthesis of two key precursors, 3-farnesylindole and3-(epoxyfarnesyl)-indole, allowed elucidation of the enzymatic cascadesforming the pentacyclic ring system of xiamycin A by XiaO-catalyzedepoxidation and the membrane protein XiaH-catalyzed terpene cyclization.The substrate flexibility of XiaI, an indole oxygenase for assemblyof the central ring, was also demonstrated. [ABSTRACT FROM AUTHOR]

During the radio-frequency identification authentication process, it is of great significance to quickly find out the target tag from all tags stored in the database, because it affects the authentication performance to a great extent. Most of the existing schemes use the Hash or pseudorandom number generator operation to locate the target tag, but if the number of tags is extremely large, vast Hash or pseudorandom number generator operations may take much time and lower the authentication efficiency. To locate the target tag quickly, the RAP and LADP protocols adopt the simple value comparison method, and the back-end server can easily find the target tag by directly comparing the received index-pseudonym value with those stored in the database. This method does improve the authentication performance, but it results that these schemes suffer from the tag tracking attack. Motivated by these concerns, we propose a novel tag indexing method called the two-layer tag indexing mechanism, and at the same time, we give a lightweight radio-frequency identification authentication protocol based on it. Analyses show that our scheme can effectively resist the tag tracking attack and is almost as efficient as the RAP and LADP protocols in indexing tags. [ABSTRACT FROM AUTHOR]

Long-running applications are often subject to failures. Once failures occur, it will lead to unacceptable system overheads. The checkpoint technology is used to reduce the losses in the event of a failure. For the two-level checkpoint recovery scheme used in the long-running tasks, it is unavoidable for the system to periodically transfer huge memory context to a remote stable storage. Therefore, the overheads of setting checkpoints and the re-computing time become a critical issue which directly impacts the system total overheads. Motivated by these concerns, this paper presents a new model by introducing i-checkpoints into the existing two-level checkpoint recovery scheme to deal with the more probable failures with the smaller cost and the faster speed. The proposed scheme is independent of the specific failure distribution type and can be applied to different failure distribution types. We respectively make analyses between the two-level incremental and two-level checkpoint recovery schemes with the Weibull distribution and exponential distribution, both of which fit with the actual failure distribution best. The comparison results show that the total overheads of setting checkpoints, the total re-computing time and the system total overheads in the two-level incremental checkpoint recovery scheme are all significantly smaller than those in the two-level checkpoint recovery scheme. At last, limitations of our study are discussed, and at the same time, open questions and possible future work are given. [ABSTRACT FROM AUTHOR]

The existing certificateless signcryption schemes were designed mainly based on the traditional public key cryptography, whose security relies on the hard problems, such as factor decomposition, and discrete logarithm. However, these problems will be easily solved by the quantum computing. So the existing certificateless signcryption schemes are vulnerable to quantum attacks. Multivariate public key cryptography (MPKC), which can resist the quantum attack, is one of the alternatives to guarantee the security of communication in the post-quantum age. Motivated by these concerns, we proposed a new construction of the certificateless multi-receiver signcryption scheme (CLMSC) based on MPKC. The new scheme inherits the security of MPKC, that is, it can withdraw quantum attacks. Multivariate quadratic polynomial operations, which need lower computation than pairing operations, are employed in signcrypting a message for any number of receivers in our scheme. We proved its semantic security under the hardness of Multivariate Quadratic (MQ) problem and its unforgeability under the Isomorphism of Polynomials (IP) assumption in the random oracle model, respectively. The results of analyses show that our scheme also has the security properties of non-repudiation, perfect forward secrecy, perfect backward secrecy and publicly verifiability. Compared with the existing schemes in terms of the computational complexity and the ciphertext size, our scheme is more efficient, and thus it is suitable for terminals with lower computation capacity like smart cards. [ABSTRACT FROM AUTHOR]

Most of the existing multi-recipient signcryption schemes do not take the anonymity of recipients into consideration because the list of the identities of all recipients must be included in the ciphertext as a necessary element for decryption. Although the signer’s anonymity has been taken into account in several alternative schemes, these schemes often suffer from the cross-comparison attack and joint conspiracy attack. That is to say, there are few schemes that can achieve complete anonymity for both the signer and the recipient. However, in many practical applications, such as network conference, both the signer’s and the recipient’s anonymity should be considered carefully. Motivated by these concerns, we propose a novel multi-recipient signcryption scheme with complete anonymity. The new scheme can achieve both the signer’s and the recipient’s anonymity at the same time. Each recipient can easily judge whether the received ciphertext is from an authorized source, but cannot determine the real identity of the sender, and at the same time, each participant can easily check decryption permission, but cannot determine the identity of any other recipient. The scheme also provides a public verification method which enables anyone to publicly verify the validity of the ciphertext. Analyses show that the proposed scheme is more efficient in terms of computation complexity and ciphertext length and possesses more advantages than existing schemes, which makes it suitable for practical applications. The proposed scheme could be used for network conferences, paid-TV or DVD broadcasting applications to solve the secure communication problem without violating the privacy of each participant. Key words: Multi-recipient signcryption; Signcryption; Complete Anonymity; Public verification. [ABSTRACT FROM AUTHOR]

The P450 enzyme XiaM was identified as a candidate to form the C-24 carboxyl group in xiamycin A (1). Alteration of medium composition led to the discovery of four new compounds from the ΔxiaMand the ΔxiaK(encoding an aromatic ring hydroxylase) mutants. Biotransformation experiments revealed that XiaM was capable of converting a methyl group to a carboxyl group through diol and aldehyde intermediates. [ABSTRACT FROM AUTHOR]

A putative methionine γ-lyase (MGL) gene was identified from a deep-sea sediment metagenomic library. The gene ( mgl_deepsea), consisting of 1,281 nucleotides, shares a high degree of sequence identity (67%) with the mgl gene from genus Idiomarina. The mgl gene was cloned and overexpressed in Escherichia coli. The expressed product of the gene has a molecular mass of 46 kDa as determined by SDS-PAGE. The recombinant enzyme (rMGL) was able to catalyse the lysis of l-methionine and DL-homocysteine, but not l-cysteine and l-cystine. The optimal temperature of the rMGL was 60°C and pH was 9.5. This is the first report to identify and characterize the mgl gene from a deep-sea metagenomic library. [ABSTRACT FROM AUTHOR]

Pain assessment is crucial for in-labour pain management. Even though women's self-rated pain intensity is the standard for pain relief or analgesic administration, multiparas appear to receive worse in-labour pain management than primiparas do. The discrepancy in pain perception between primiparas and multiparas remains unclear. Healthcare providers tend to think that multiparas endure the pain and report less pain because they have experienced childbirth. To retrospectively analyse the intensity of in-labour pain during first and second vaginal childbirth within the same group of women and explore whether parity may be an influential factor in labour pain intensity. Retrospective cohort study. Labour and delivery in a large academic specialized hospital in Guangzhou, China. Women were included if they had two consecutive vaginal childbirths with singleton cephalic presentations and cervical dilation ≤ 3 cm for the first childbirth and ≤ 2 cm for the second childbirth. The final study sample consisted of 417 women. All childbirth case records between January 2015 and August 2018 were scanned using a structured electronic medical system. Maternal and neonatal demographics as well as obstetric and neonatal outcomes were extracted. The in-labour pain for each childbirth was compared between first and second births. Paired t -tests, McNemar's c hi -square tests and mixed-effects modelling were applied to compare the differences in labour pain intensity between the two vaginal childbirths and explore the factors that influenced maximum labour pain scores during the second childbirth. Four hundred seventeen women were included, with an average birth interval of 1.7 years. The average maximum labour pain score during the latent phase was 6 (5,6) for the first childbirth and 5 (4,6) for the second childbirth (paired t =-6.13, P <0.001). Pain scores decreased in 28.1% (117/417) of women and increased in 13.7% (57/417) of women from the first to the second childbirth. More than half of the women in our study experienced the same maximum labour pain score during the first and second labour. Mixed-effects modelling revealed that parity, education and pregnancy complications were independently associated with maximum labour pain scores. From a clinical point of view, in-labour pain is not clinically different for women when comparing their first and second labours. Health care professionals may underestimate in-labour pain in primiparas when comparing them with nulliparas. More studies are warranted to explore options for achieving better pain management for women with more childbirths. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction (AMI) is characterized by myocardial tissue necrosis and activation of inflammatory response. This study aims to elucidate the potential mechanism underlying the protective effects of long non-coding RNA (lncRNA) highly up-regulated in liver cancer (HULC) against myocardial ischemia/reperfusion (I/R) injury in rat models and apoptosis of cardiomyocytes. We firstly established rat models of myocardial I/R injury and rat cardiomyocyte (H9c2 cells) models of hypoxia/reoxygenation (H/R) injury. Sprague-Dawley (SD) neonatal rats were randomized into four groups: sham, I/R, I/R+ microRNA (miR) −377-5p mimic, and I/R+ miR-377-5p antagomir, respectively. Then, histopathological examination was applied. Apoptosis was evaluated by transferase-mediated dUTP nick end labeling (TUNEL) staining. Cell vitality was measured using MTT assay. The concentrations of creatine kinase MB (CK-MB), cardiac troponin I (cTnI), interleukin (IL) −6 (IL-6), and tumor necrosis factor-α (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA). The expression of Cleaved-Caspase-3, Caspase-3, NOD-like receptor P3 (NLRP3), Caspase-1, and IL-1β was analyzed by immunohistochemical (IHC) or Western blot analysis. We found that HULC was downregulated and miR-377-5p was upregulated in IR-injured myocardial tissue and the H/R-induced H9c2 cell. Overexpression of miR-377-5p increased myocardial dysfunction and apoptosis and activated formation and secretion of IL-6 and TNF-α. The preprocessing of miR-377-5p silencing emerged opposite results. Strikingly, dual luciferase reporter assay showed that HULC was a sponge of miR-377-5p. Subsequently, mechanism experiments revealed that NLRP3/Caspase‑1/IL‑1β was a target axis of miR-377-5p. In vitro, the protective effect of HULC overexpression on H9c2 cell viability and inflammation was offset by miR-377-5p silencing. Finally, rescue assay suggested that HULC-miR-377-5p -NLRP3/Caspase‑1/IL‑1β axis regulated the apoptosis and inflammation of H/R-induced H9c2 cells. Overall, these results indicate that the protective effect of HULC against myocardial I/R injury and H/R cardiomyocyte apoptosis partially relies on the inhibition of NLRP3/Caspase‑1/IL‑1β signaling pathway. [ABSTRACT FROM AUTHOR]

Introduction: A large proportion of patients initiated hemodialysis with a central vein catheter rather than a permanent vascular access which was recommended by guidelines. One major barrier was the paucity of evidence regarding the optimal timing of vascular access creation in predialysis patients. Methods: Our study prospectively enrolled 300 patients undergoing predialysis arteriovenous fistula (AVF) creation in our center from 2015 to 2018. Cox proportional hazard regression was performed to identify which demographic and clinical factors were associated with the initiation of hemodialysis after AVF surgery. A receiver operating characteristic area under the curve (AUC) was used to assess the predictive power of preoperative factors for the likelihood of hemodialysis initiation. Results: Overall, 163 (54.3%), 214 (71.3%), and 275 (91.7%) patients initiated hemodialysis within 3 months, 6 months, and 1 year, respectively, after AVF creation. The median time between AVF creation and hemodialysis start was 71.5 days. Using multivariate Cox regression analysis, three factors were associated with hemodialysis initiation within 1 year: serum phosphorus (HR = 1.407, p = 0.021), diabetic kidney disease (DKD) (HR = 1.429, p = 0.039), and cystatin C (HR = 1.179, p = 0.009). Cystatin C alone had a moderate predictive value for dialysis initiation (AUC = 0.746; p < 0.001), whereas the full model had a higher predictive value (AUC = 0.800; p < 0.001). Conclusion: DKD, serum cystatin C, and phosphorus at access surgery were associated with hemodialysis initiation within 1 year of the predialysis AVF creation. Our findings provide a basis for a more customized approach to planning AVF placement in patients with chronic kidney disease. [ABSTRACT FROM AUTHOR]

Background: Multiple rib fractures can lead to flail chest with up to 35% mortality rate due to severe pulmonary complications. Current treatments of flail chest remain controversial. Studies have shown that surgical treatments can improve outcomes and reduce mortality, comparing to non-operative treatments. Current surgical fixation methods focus on stabilization of ribs on the outward facing side, and they require division of intercostal muscles. Damages to surrounding nerves and vessels may lead to chronic pain. This study tests a novel interior fixation method that minimizes neurovascular injuries. Methods: Twelve healthy canines were divided in two surgical operation groups for exterior and interior fixation using titanium metal plates. Osteotomy with oblique fractures was prepared under general anesthesia. Exterior fixation was performed in open surgery. Interior fixation was minimally invasive using custom made tools including a flexible shaft extension screwdriver, solid plate stand, guiding wire loop and metal plates with threaded holes. Results: Respiratory and cardiovascular functions (RR, PO2, PCO2, SpO2, and HR) together with body temperature were measured before anesthesia and within 48 h after surgery. The difference in measurements was not statistically significant between the two groups before surgery with P values greater than 0.05. However, the interior group canines had better RR and PO2 values starting from the 24th hour, and better PCO2, SpO2, and HR values starting from the 48th hour. It took longer operation time to complete the minimally invasive interior fixation surgery (P value less than 0.001), but the total blood loss was less than the exterior fixation group (P value less than 0.001). Results also showed that interior group canines suffered less pain, and they had quicker recovery in gastrointestinal and physical mobility. Conclusions: The investigative interior fixation method was safe and effective in rib stabilization on a canine rib fracture model, comparing to the exterior fixation method. The interior fixation was minimally invasive, with less damages to tissues and nerves surrounding the ribs, leading to better postoperative outcomes. Highlights: Current metal prosthesis surgical fixation requires division of intercostal muscles, which may lead to neurovascular injuries and chronic pain. Metal plate stabilization from the inward facing side of the rib avoids muscle division, and only needs a cut through a thin layer of periosteum to expose the bones. A flexible soft shaft extension screwdriver can be bent, twisted, rotated, and turned into narrow space and dead end. It can be used with VATS in surgical rib fixation. [ABSTRACT FROM AUTHOR]

To investigate the clinical characteristics, pathological features, and outcomes of patients with antineutrophil cytoplasmic antibody (ANCA)-positive systemic lupus erythematosus (SLE) in northwest China. This retrospective study included 491 patients with SLE tested for ANCA antibodies and 171 patients with ANCA-associated vasculitis (AAV) as controls. Subgroup analysis limited to those with renal involvement, and by ANCA antibody subtype (PR3 vs MPO). To compare the proteinuria remission rates between ANCA-positive and ANCA-negative lupus nephritis (LN) groups, a logistic regression model was used for propensity score matching based on age, hemoglobin, and baseline estimated glomerular filtration rate (eGFR). Compared to ANCA-negative SLE (n = 442), ANCA-positive SLE (n = 46) occur in older patients; however, these patients were younger than those with AAV (n = 167). The eGFR of patients with ANCA-positive LN (n = 25) was higher than that of patients having AAV with renal involvement (n = 56) but lower than that of patients with ANCA-negative LN (n = 163). Patients with SLE who had MPO-ANCA (n = 16) had higher levels of serum creatinine compared to those with PR3-ANCA (n = 30) (156.5 µmol/L vs. 45.5 µmol/L, p = 0.005). During the follow-up period, the remission rate of proteinuria in patients with ANCA-positive LN was lower than that of patients with ANCA-negative LN (50% vs. 75%, p = 0.008). Patients with ANCA-positive LN may have worse baseline renal function and lower protein remission rates compared to patients with ANCA-negative LN. ANCA titers should be regularly monitored throughout the follow-up period in patients with SLE, especially in cases of renal involvement. [ABSTRACT FROM AUTHOR]

This paper derives a control solution for mitigation of Parametrically excited vibration of taut cable in cable-truss couple system, which ensures safe and stable regulation for cable towards the desired patterns. The dynamic characteristics with periodic perturbation and the parametrically excited instability of cable are both analyzed; the physical factors of damping influence on the cable are investigated and demonstrated. Based on the linear quadratic regulator principle (LQR), the optimal control algorithms are presented, which play an effective role in suppressing the the vibration distribution and improving significantly the transverse stability of the inclined cable system. The simulation results demonstrate the validity and effectiveness of the presented control method. [ABSTRACT FROM AUTHOR]

• A novel polysaccharide named as Ge-1 was extracted by cold water and purified from Pueraria lobate (Willd.) Ohwi root. • Ge-1 was an alpha glucan that mainly consisted of 1,3,6-α-D-Glc p and 1,3,6-α-D-Glc p. • Ge-1 had remarkable immunomodulatory activity in RAW264.7 cells. • The membrane receptors of Ge-1 were GR, SR and TLR4 mainly. A novel polysaccharide with a molecular weight of 12.3 kDa, was isolated from the root of Pueraria lobata (Willd.) Ohwi using cold water extraction method. Methylation analysis, Periodate oxidation, Smith degradation, and nuclear magnetic resonance analysis showed that 1,4-α-D-Glc p and 1,3,6-α-D-Glc p were the main linkage types of this polysaccharide. It exhibited immunomodulatory activity by enhancing the pinocytic and phagocytic capacities and promoting the secretion of nitric oxide, interleukin (IL)-6, and tumor necrosis factor alpha by RAW 264.7 cells. The beta glucan receptor, scavenger receptor I, and toll-like receptor 4 were identified as the main receptors of the polysaccharide on the membrane of RAW 264.7 cells. These results suggested that this polysaccharide is a candidate functional food supplement for hypoimmune populations. [ABSTRACT FROM AUTHOR]

This retrospective study aimed to derive the clinical phenotypes of ventilated ICU patients to predict the outcomes on the first day of ventilation. Clinical phenotypes were derived from the eICU Collaborative Research Database (eICU) cohort via cluster analysis and were validated in the Medical Information Mart for Intensive Care (MIMIC-IV) cohort. Four clinical phenotypes were identified and compared in the eICU cohort (n = 15,256). Phenotype A (n = 3112) was associated with respiratory disease, had the lowest 28-day mortality (16%), and had a high extubation success rate (~80%). Phenotype B (n = 3335) was correlated with cardiovascular disease, had the second-highest 28-day mortality (28%), and had the lowest extubation success rate (69%). Phenotype C (n = 3868) was correlated with renal dysfunction, had the highest 28-day mortality (28%), and had the second-lowest extubation success rate (74%). Phenotype D (n = 4941) was associated with neurological and traumatic diseases, had the second-lowest 28-day mortality (22%), and had the highest extubation success rate (>80%). These findings were validated in the validation cohort (n = 10,813). Additionally, these phenotypes responded differently to ventilation strategies in terms of duration of treatment, but had no difference in mortality. The four clinical phenotypes unveiled the heterogeneity of ICU patients and helped to predict the 28-day mortality and the extubation success rate. [ABSTRACT FROM AUTHOR]

Study Objective: The pharmacokinetics and pharmacodynamics of tacrolimus (TAC) vary greatly among individuals, hindering its precise utilization. Moreover, effective models for the early prediction of TAC efficacy in patients with nephrotic syndrome (NS) are lacking. We aimed to identify key factors affecting TAC efficacy and develop efficacy prediction models for childhood NS using machine learning algorithms. Design: This was an observational cohort study of patients with pediatric refractory NS. Setting: Guangzhou Women and Children's Medical Center between June 2013 and December 2018. Patients 203 patients with pediatric refractory NS were used for model generation and 35 patients were used for model validation. Intervention: All patients regularly received double immunosuppressive therapy comprising TAC and low‐dose prednisone or methylprednisolone. In this observational cohort study of 203 pediatric patients with refractory NS, clinical and genetic variables, including single‐nucleotide polymorphism (SNPs), were identified. TAC efficacy was evaluated 3 months after administration according to two different evaluation criteria: response or non‐response (Group 1) and complete remission, partial remission, or non‐remission (Group 2). Measurements Logistic regression, extremely random trees, gradient boosting decision trees, random forest, and extreme gradient boosting algorithms were used to develop and validate the models. Prediction models were validated among a cohort of 35 patients with NS. Main Results The random forest models performed best in both groups, and the area under the receiver operating characteristics curve of these two models was 80.7% (Group 1) and 80.3% (Group 2). These prediction models included urine erythrocyte count before administration, steroid types, and eight SNPs (ITGB4 rs2290460, TRPC6 rs3824934, CTGF rs9399005, IL13 rs20541, NFKBIA rs8904, NFKBIA rs8016947, MAP3K11 rs7946115, and SMARCAL1 rs11886806). Conclusions: Two pre‐administration models with good predictive performance for TAC response of patients with NS were developed and validated using machine learning algorithms. These accurate models could assist clinicians in predicting TAC efficacy in pediatric patients with NS before utilization to avoid treatment failure or adverse effects. [ABSTRACT FROM AUTHOR]

Objective. To observe the efficacy and safety of dopamine plus furosemide in treating patients with heart failure. Methods. This research included 150 patients with heart failure who were diagnosed and treated at our hospital between March 2018 and November 2020. The patients were randomly assigned to a study group or a reference group according to the data of admission (the cut-off date was June 2019). Patients in the reference group were given furosemide, whereas those in the study group were given dopamine plus furosemide intravenous pumping. Outcome measures included clinical effectiveness, heart function changes, and adverse responses. Results. Dopamine plus furosemide resulted in higher treatment efficiency (96.00%) versus furosemide (74.67%) study group (P < 0.05). Before therapy, there was no significant change in the scores of cardiac function indices between the two groups (P > 0.05). The cardiac function of the two groups of patients was improved after treatment, and the left ventricular ejection fraction (LVEF) of the study group (44.85 ± 4.12) was higher than that of the reference group (38.45 ± 4.36), and the left ventricular end-systolic diameter (LVESD), left ventricular end-diastolic diameter (LVESD), and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) (43.17 ± 3.98, 51.32 ± 4.25, 3045.56 ± 365.48) were lower than the reference group (47.56 ± 4.65, 56.28 ± 4.85, 4856.48 ± 395.46) (P < 0.05). There was no significant difference in the total incidence of adverse reactions between the two groups (P > 0.05). Conclusion. Dopamine plus intravenous furosemide infusion treatment has an obvious therapeutic benefit in treating patients with heart failure and dramatically enhances cardiac function without noteworthy adverse responses. It demonstrated great potential for clinical promotion. [ABSTRACT FROM AUTHOR]

One of the purposes is to reduce the sample bias that may be caused by data imputation by controlling the number of missing variables and their missing rates. The machine learning algorithm is used to balanced samples to build a model, each variable can have at least 10 observations according to the common guideline.[1] Similarly, the same is true for the model construction in Group 2, and there are only 5 independent variables. [Extracted from the article]

The black hole candidate MAXI J1348-630 was discovered in 2019 January 26, with the Gas Slit Camera (GSC) on-board MAXI. We report a detailed spectral analysis of this source by using the archived data of NuSTAR. A total of nine observations covered the complete outburst evolution of MAXI J1348-630 from the hard state to the soft state and finally back to the hard state. Additionally, the intermediate state is found in the transition from the hard state to the soft state. We use the state-of-the-art reflection model relxill family to fit all the nine spectra, and the spectra from two focal plane module detectors of NuSTAR are jointly fitted for each observation. In particular, we concentrate on the results of the black hole spin parameter and the inclination of the accretion disc. Based on the analysis of the inner radius of the accretion disc, we obtain the spin parameter |$a_* =0.78_{-0.04}^{+0.04}$|⁠ , and the inclination angle of the inner disc |$i = 29.2_{-0.5}^{+0.3}$| °. Furthermore, we also find that when the black hole is in the hard state, the accretion disc would show a significant truncation. The high iron abundance and ionization of the accretion disc obtained in the fitting results can be possibly explained by the high density of the accretion disc. [ABSTRACT FROM AUTHOR]

Background: This study explores whether the differences in cognitive performance among individuals with permanent atrial fibrillation (AF) are attributable to the duration of AF and anticoagulant therapy and explores the possible inflammatory mechanism of cognitive dysfunction related to AF. Methods: A total of 260 patients aged 50–75 years without previous cerebrovascular events were enrolled in this study. These 260 patients had been divided into the AF group (140 patients) and sinus rhythm group (120 patients). In the AF group, we divided participants into cognitive impairment (CI) group (90 patients) and cognitive normal (CN) group (50 patients). In the sinus rhythm group, we also divided participants into CI group (61 patients) and CN group (59 patients). The Mini‐Mental State Examination (MMSE) was used to assess the cognitive function of all participants. Neuronal‐derived exosomes were enriched in peripheral blood by immunoprecipitation and were confirmed by a transmission electron microscope, nanoparticle tracking analysis, and western blot. Alzheimer's disease‐pathogenic exosomal proteins and inflammatory cytokines were quantified. The association between AF and cognitive function was estimated by logistic regression analysis. ANOVA or Welch's t‐test compared the difference in protein concentrations between groups. Results: Non‐anticoagulant therapy in patients with AF was significantly associated with CI (OR = 13.99, 95% CI: 2.67–73.36, p <.01). The incidence of dementia in patients with AF > 3 years was significantly higher than in patients with AF ≤ 3 years, but there was no significant difference in total cognitive dysfunction (mild cognitive impairment [MCI] + dementia) (p =.126). The adjusted exosome concentrations of T‐tau and amyloid-β protein 42 (Aβ42) in the CI group were significantly higher than in the CN group (p <.001). The serum concentrations of IL‐6 and matrix metalloproteinase‐9 (MMP‐9) in patients with AF were higher than those in patients with sinus rhythm (p <.001). Conclusion: Aβ42 and T‐tau in peripheral blood neuronal‐derived exosomes maybe be associated with the early diagnosis of CI in patients with permanent AF. However, the value of Aβ42 and T‐tau for CI in patients with permanent AF still needs to be confirmed in future randomized control trials. [ABSTRACT FROM AUTHOR]

• GPR139 activation in the brain ameliorated Aβ 1-42 -induced cognitive impairment. • GPR139 activation alleviated Aβ 1-42 -induced apoptosis and synaptotoxicity in the basal forebrain. • GPR139 overexpression in the MS ameliorated cognitive impairment in APP/PS1 mice. • GPR139 overexpression in the MS alleviated apoptosis and synaptotoxicity in APP/PS1 mice. G-protein coupled receptors (GPCRs) constitute the largest class of cell surface receptors and present prominent drug targets. GPR139 is an orphan GPCR detected in the septum of the brain. However, its roles in cognition are still unclear. Here we first established a mouse model of cognitive impairment by a single intracerebroventricular injection of aggregated amyloid-beta peptide 1–42 (Aβ 1-42). RNA-sequencing data analysis showed that Aβ 1-42 induced a significant decrease of GPR139 mRNA in the basal forebrain. Using GPR139 agonist JNJ-63533054 and behavioral tests, we found that GPR139 activation in the brain ameliorated Aβ 1-42 -induced cognitive impairment. Using western blot, TUNEL apoptosis and Golgi staining assays, we showed that GPR139 activation alleviated Aβ 1-42 -induced apoptosis and synaptotoxicity in the basal forebrain rather than prefrontal cortex and hippocampus. The further study identified that GPR139 was widely expressed in cholinergic neurons of the medial septum (MS). Using the overexpression virus and transgenic animal model, we showed that up-regulation of GPR139 in MS cholinergic neurons ameliorated cognitive impairment, apoptosis and synaptotoxicity in APP/PS1 transgenic mice. These findings reveal that GPR139 of MS cholinergic neurons could be a critical node in cognition and potentially provides insight into the pathogenesis of Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. Tyrosine kinase inhibitors (TKIs) are currently the most effective chemotherapy for NSCLC. However, most cancer patients develop TKI resistance at tumor relapse stage. We firstly measured the expression change of miR-519d-3p in TKI resistance NSCLC cells. We then ectopically expressed miR-519-3p in TKI resistant cells to study its functional impact on cell proliferation, migration, invasion and cell sensitivity to gefitinib. The downstream target of miR-519-3p was identified by bioinformatics and validated in luciferase reporter assay and western blotting analysis. We also studied the reversing effect of the candidate target in NSCLC cells expressing miR-519d-3p. Lastly, we compared the miR-519d-3p level in NSCLC patients with good or poor response to gefitinib. miR-519d-3p level was downregulated in TKI resistant NSCLC cells. The restoration of miR-519d-3p in these NSCLC cells inhibited cell proliferation, invasion and migration; enhanced cell sensitivity to gefitinib. EPAS1 was identified and validated as downstream target of miR-519d-3p. Co-expressing EPAS1 antagonized the inhibitory effect of miR-519d-3p on NSCLC cells. MiR-519d-3p was downregulated in NSCLC patients with poor response to gefitinib. Targeting miR-519d-3p/EPAS1 axis may provide alternative treatment for TKI-resistant NSCLC. [ABSTRACT FROM AUTHOR]

Antimony (Sb) persists in environmental media and can be toxic to aquatic organisms and humans. Although China is the primary Sb-producing country, the levels of Sb contamination and their potential risk to water resources remain unclear. This study provides an overview of Sb contamination in surface water and centralized drinking water sources across China and assesses its potential ecological and human health risks. Species sensitivity distribution was used to derive acute and chronic aquatic life criteria for Sb, which were 511.7 μg/L and 148.3 μg/L, respectively. Zooplankton were determined to be the most sensitive species, and fish were the least sensitive. Sb contamination in China is more serious than other countries. Risk quotients were used to assess the ecological risks of Sb. Chronic ecological risk quotients of 0.0013–27.39 were identified for surface water located near Sb mines. The highest values indicate high risk, particularly for zooplankton species. Exposure characteristics for the Chinese population across age group, sex, season, and region were used to assess the non-carcinogenic risk of Sb in centralized drinking water sources in China. Hazard quotients of 0.001–0.99 were found for these centralized drinking water sources. The non-carcinogenic risk posed by Sb was acceptable in the majority of locations, except in Hunan Province, which had the highest hazard quotient (approximately 1). This province contains the main Sb mining area in China, which poses a relatively large threat to human health. The Sb health risk for children was significantly higher than adults, but there was no significant difference in risk between men and women. The Sb drinking water guidance value to protect human health was calculated to be 19.65 μg/L for Chinese population. The results of this ecological and human health risk assessment highlight the importance of clean Sb production to reduce the negative effects of Sb contamination in China. [Display omitted] • Antimony (Sb) constitutes an ecological risk in surface water near mines in China. • Sb poses a high health risk to residents in Southern China. • The acute and chronic Sb criteria for native Chinese freshwater organisms are 511.7 and 148.3 μg/L, respectively. • The Sb drinking water guidance value to protect human health is recommended to be 19.65 μg/L for the Chinese population. [ABSTRACT FROM AUTHOR]

The change of water quality can reflect the important indicators of ecological environment measurement. Sewage discharge is an important factor causing environmental pollution. Establishing an effective water ecological prediction model can detect changes in the ecological environment system quickly and effectively. In order to detect high error rate and poor convergence of the water ecological chemical oxygen demand (COD) prediction model, combining the limit learning machine (ELM) model and whale optimization algorithm, CAWOA is improved by the sin chaos search strategy, while the ELM optimizes the parameters of the algorithm to improve convergence speed, thus improving the generalization performance of the ELM. In the CAWOA, the global optimization results of the WOA are promoted by introducing a sin chaotic search strategy and adaptive inertia weights. On this basis, the COD prediction model of CAWOA-ELM is established and compared with similar algorithms by using the optimized ELM to predict the water ecological COD in a region. Finally, from the experimental results of the CAWOA-ELM algorithm, it has excellent prediction effect and practical application value. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN), a common cardiovascular disease, has been a global health threat. MicroRNAs (miRNAs) have been proposed to frequently participate in the occurrence and development of DN, however, the role of miR‐325‐3p in DN remains uncharacterized. Our research aimed to explore the function and mechanism of miR‐325‐3p in DN. Bioinformatics analysis (Targetscan, http://www.targetscan.org) and a wide range of experiments including RT‐qPCR, CCK‐8 assay, western blot, luciferase reporter assay, RNA immunoprecipitation (RIP) assays, urine protein and blood glucose assays, histology analysis and morphometric analysis were used to explore the function and mechanism of miR‐325‐3p and C‐C motif chemokine ligand 19 (CCL19). CCL19 could facilitate the progression of DN by inhibiting cell viability and promoting inflammation and fibrosis in HK‐2 and HMC cells. In addition, CCL19 was confirmed to be targeted and negatively regulated by miR‐325‐3p. Rescue assays validated that the impacts of miR‐325‐3p mimics on the viability, inflammation and fibrosis of HK‐2 and HMC cells were recovered by CCL19 overexpression. To sum up, miR‐325‐3p inhibits renal inflammation and fibrosis by targeting CCL19 in a DN cell model and mice model, implying miR‐325‐3p as a possible therapeutic target for DN treatment. [ABSTRACT FROM AUTHOR]

Objective: The goal of this study was to analyze perioperative risk factors to predict one- year mortality after operation for acute type A aortic dissection (AAD).Methods: A total of 121 consecutive patients undergoing Stanford type A AAD surgery in Beijing Anzhen Hospital were enrolled. Preoperative clinical and laboratory data from patients were collected.Results: Multivariable Cox regression analysis showed that significant factors associated with increased one-year mortality were elder age (year) (hazard ratio (HR) 1.0985; 95% confidence interval (CI) 1.0334-1.1677), intraoperative blood transfusion ≥2000 mL (HR 8.8081; 95% CI 2.3319-33.2709), a higher level of serum creatinine (μmol/L) at postoperative one day (HR 1.0122; 95% CI 1.0035-1.0190) and oxygenation index (OI) < 200 (mmHg) at the end of surgery (HR 5.7575; 95% CI 1.1695-28.3458).Conclusion: In this study, perioperative risk factors to predict one-year prognosis are age, intraoperative blood transfusion ≥2000 mL, postoperative OI < 200 mmHg and level of postoperative serum creatinine. The results aid in the comprehension of surgical outcomes and assist in the optimization of treatment strategies for those with perioperative risk factors to decrease one-year mortality. [ABSTRACT FROM AUTHOR]

Obesity is strongly linked to male infertility. Testicular spermatogenic cell apoptosis plays an important role in obesity‐related male infertility. Pituitary adenylate cyclase‐activating peptide (PACAP) has been recently shown to exhibit antiapoptotic and antidiabetic effects. However, the effects of PACAP on obesity‐related male infertility remain unknown. The purpose of the current study is to explore the role of PACAP in obesity‐related male infertility. Here, C57BL/6 male mice were fed with a high‐fat diet to induce obesity and then treated with PACAP. PACAP treatment ameliorated obesity characteristics, including body weight, epididymal adipose weight, testes/body weight, serum lipids levels, and reproductive hormone levels in vivo. Additionally, PACAP was shown to improve the reproductive function of the obese mice, which was characterized by improved testis morphology, sperm parameters, acrosome reaction, and embryo quality after in vitro fertilization via silent information regulator 1 (Sirt1) activation and p53 deacetylation. These beneficial effects of PACAP were abolished in obese mice with testis‐specific knockdown of Sirt1. The mechanism studies showed that PACAP selectively binds to the PAC1 receptor to attenuate palmitic acid‐induced mouse spermatogenic cell (GC‐1) apoptosis via the PKA/CREB/Sirt1/p53 pathway. However, this mechanism was inhibited in GC‐1 cells lacking Sirt1. Finally, human semen studies showed that the decline in sperm quality in obese infertile men was partly due to Sirt1 downregulation and p53 acetylation. Our data suggest that PACAP could ameliorate fertility in obese male mice and may be a promising candidate drug for obesity‐induced male infertility. [ABSTRACT FROM AUTHOR]

In the current study, we report the high-quality draft genome sequence of Neonectria sp. DH2, an endophytic fungus isolated from Meconopsis grandis Prain in Tibet. The whole genome is about 45.8 Mbp, with a GC content of 53%. A total of 14,163 genes are predicted to encode proteins, and 557 of them are considered as unique, as no matches are found in five gene databases. A neighbor-joining phylogenetic tree based on internal transcribed spacer (ITS) region sequences shows that Neonectria sp. DH2 was most closely related to Neonectria ramulariae. 47 biosynthetic gene clusters (BGC) were identified in Neonectria sp. DH2 genome, and only 5 BGCs shows significant similarities to previously reported BGCs. The presence of 42 unique BGCs in Neonectria sp. DH2 suggests that it has great potential to produce novel secondary metabolites. [ABSTRACT FROM AUTHOR]

Background: Peritoneal protein clearance has been suggested to be a marker of peritoneal inflammation and systemic endothelial dysfunction. Methods: We enrolled 711 consecutive incident PD patients. Baseline peritoneal protein clearance and other clinical information were reviewed. All patients were followed for at least 1 year for all-cause and cardiovascular mortality. Results: The average PD effluent protein loss was 6.41 ± 2.16 g/day; peritoneal protein clearance was 97.15 ± 41.55 mL/day. The average duration of follow-up was 50.8 ± 36.2 months. Multivariate linear regression analysis showed that serum albumin, C-reactive protein, and mass transfer area coefficients of creatinine were independently associated with peritoneal protein clearance. By multivariate Cox regression analysis, age, Charlson comorbidity score, volume of overhydration and peritoneal protein clearance were independent predictors of all-cause mortality. Every 10 mL/day increase in peritoneal protein clearance confers 10.4% increase in risk of all-cause mortality (95% confidence interval 2.6–18.7%, p = 0.008). Peritoneal protein clearance was also associated with cardiovascular mortality by univariate analysis, but the association became insignificant after adjusting for confounding factors Cox regression analysis. Conclusions: Baseline peritoneal protein clearance is an independent predictor of all-cause mortality in incident PD patients. Routine measurement of peritoneal protein clearance may facilitate patient risk stratification. [ABSTRACT FROM AUTHOR]

Abstract Aim We investigated the potential role of pescadillo ribosomal biogenesis factor 1 (PES1) in the development of hepatocellular carcinoma (HCC). Material and methods One hundred and thirty-four patients with hepatocellular carcinoma were chosen to evaluate the association between the expression of PES1 and survival, clinical characteristics of these patients. Western blotting, real-time PCR, immunohistochemistry, CCK-8 assay, colony formation and subcutaneous tumors in nude mice were conducted. Key findings We found that PES1 was commonly upregulated in HCC tissues and cells. Immunohistochemical analysis of 134 paraffin-embedded archived HCC tissues showed that the protein expression level of PES1 was positively correlated with clinical characteristics and reduced the survival time of HCC patients. Univariate and multivariate analysis revealed that PES1 expression may be an independent prognostic indicator of poorer overall survival in HCC patients. Furthermore, silencing of endogenous PES1 significantly inhibited the proliferation and tumorigenicity of SMMC 7721 and HepG2 cells in vitro as well as in vivo in nude mice. Finally, we found that PES1 affected cell proliferation by regulating the PI3K/AKT/GSK3β/cyclinD1 signaling pathway. Significance Our data suggest that PES1 may promote proliferation and tumorigenicity, and potentially representing a novel prognostic marker for overall survival in HCC. Core tip We report that pescadillo ribosomal biogenesis factor 1 (PES1) plays an oncogenic role in hepatocellular carcinoma, which was commonly upregulated in hepatocellular carcinoma tissues and cells. Immunostaining analysis found that the protein expression level of PES1 was positively correlated with clinical characteristics and reduced survival time of hepatocellular carcinoma patients. Multivariate analysis revealed that PES1 expression might be an independent prognostic indicator of survival in hepatocellular carcinoma patients. Furthermore, PES1 knockdown inhibited the proliferation and tumorigenesis in hepatocellular carcinoma cell lines. Additionally, we found that PES1 is involved in the cell proliferation by regulating the AKT/GSK3β/cyclinD1 signaling pathway. [ABSTRACT FROM AUTHOR]