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Plant regeneration is important for vegetative propagation, detoxification and the obtain of transgenic plant. We found that duckweed regeneration could be enhanced by regenerating callus. However, very little is known about the molecular mechanism and the release of volatile organic compounds (VOCs). To gain a global view of genes differently expression profiles in callus and regenerating callus, genetic transcript regulation has been studied. Auxin related genes have been significantly down-regulated in regenerating callus. Cytokinin signal pathway genes have been up-regulated in regenerating callus. This result suggests the modify of auxin and cytokinin balance determines the regenerating callus. Volatile organic compounds release has been analysised by gas chromatography/ mass spectrum during the stage of plant regeneration, and 11 kinds of unique volatile organic compounds in the regenerating callus were increased. Cyclohexane treatment enhanced duckweed regeneration by initiating root. Moreover, Auxin signal pathway genes were down-regulated in callus treated by cyclohexane. All together, these results indicated that cyclohexane released by regenerating callus promoted duckweed regeneration. Our results provide novel mechanistic insights into how regenerating callus promotes regeneration.

Diabetes mellitus causes an increased incidence of congenital heart malformations. However, the pathogenesis and potential epigenetic mechanism involved in this process are unclear. In this study, we used MethylRAD sequencing to compare changes in methylation levels in the genomic landscapes in the fetal heart in a rat model of hyperglycemia. Our results showed that methylation of CCGG/CCNGG sites were mostly enriched in intergenic regions, followed by intron, exon, upstream and the 5′ and 3′ untranslated regions. qRT-PCR results confirmed the MethylRAD sequencing findings, suggesting that abnormal CCGG/CCNGG methylation in the upstream region regulated gene expression. The differential methylation genes (DMGs) based on the CCGG and CCNGG sites in the upstream region were examined by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Gene Ontology indicated that the CCGG-based DMGs involved in biological process and function were mainly related to transcription and co-SMAD binding. The CCNGG-based DMGs were mainly related to transcription and cytokine-mediated signaling pathways. Kyoto Encyclopedia of Genes and Genomes analysis indicated that CCGG-based DMGs were mainly involved in the Wnt signaling and TGF-β signaling pathways. CCNGG-based DMGs were involved in the TNF signaling and apoptosis pathways. These genes may play dominant roles in cardiomyocyte apoptosis and heart disease and require further study. These genes may also serve as potential molecular targets or diagnostic biomarkers for heart malformations under hyperglycemia.

OBJECTIVE:This study is aimed at determining the preoperative nutritional status of patients with hepatic alveolar echinococcosis (HAE), and subsequently establish a concise and reasonable nutritional evaluation indicator. The established evaluation method could be used for clinical preoperative risk assessment and prediction of post-operation recovery. METHODS:The basic patient information on height, body weight, BMI and hepatic encephalopathy of 93 HAE patients were examined. Subsequently, abdominal ultrasonography, blood coagulation and liver function tests were done on the patients. Liver function was assessed using the Child-Pugh improved grading method while nutritional status was evaluated using the European Nutrition Risk Screening 2002 (NRS 2002) method. Additional parameters including hospitalization time, the hemoglobin (HGB) level on the 3rd day after the operation, and the number of postoperative complications of HAE patients were also recorded. RESULTS:The NRS 2002 score was negatively correlated with body weight, body mass index (BMI)and albumin (ALB) (P

To reduce the cost of production and the pollution of the environment that is due to the overapplication of herbicide in paddy fields, the location information of rice seedlings and weeds must be detected in site-specific weed management (SSWM). With the development of deep learning, a semantic segmentation method with the SegNet that is based on fully convolutional network (FCN) was proposed. In this paper, RGB color images of seedling rice were captured in paddy field, and ground truth (GT) images were obtained by manually labeled the pixels in the RGB images with three separate categories, namely, rice seedlings, background, and weeds. The class weight coefficients were calculated to solve the problem of the unbalance of the number of the classification category. GT images and RGB images were used for data training and data testing. Eighty percent of the samples were randomly selected as the training dataset and 20% of samples were used as the test dataset. The proposed method was compared with a classical semantic segmentation model, namely, FCN, and U-Net models. The average accuracy rate of the SegNet method was 92.7%, whereas the average accuracy rates of the FCN and U-Net methods were 89.5% and 70.8%, respectively. The proposed SegNet method realized higher classification accuracy and could effectively classify the pixels of rice seedlings, background, and weeds in the paddy field images and acquire the positions of their regions.

Seagrass meadows (Zostera marina) are important coastal ecosystems with high levels of productivity and biodiversity. They often have high biomass turnover and are susceptible to dislodgment, leading to export of biomass from seagrass beds. In September 2016, two cruises covering a total area of 52 km x 15 km (38°57'1.14"-39° 0'41.28" N, 118°45'23.22"-118°47'6.96" E) found floating Z. marina aggregations along 13 km of the transect in the northernmost area of Bohai Bay, in the Bohai Sea, China. This floating seagrass was 6.3-13.4 km northeast (offshore) of the Caofeidian seagrass bed, which is a large (10 km2) seagrass bed discovered in 2015 in the Bohai Sea, China. The modal length of floating intact shoots (from meristem to longest leaf tip) matched samples from the Caofeidian seagrass bed. The dominant individuals lengths were 40-50 cm, with less than 5% of the total number of individuals found in larger size categories (80-90 and 90-100 cm). We concluded that they originated from the nearby Caofeidian seagrass meadows.

BackgroundMolecular size determination of circulating free fetal DNA in maternal plasma is an important detection method for noninvasive prenatal testing (NIPT). The fetal DNA molecule is the primary factor determining the overall performance of NIPT and its clinical interpretation. The proportion of cell-free fetal DNA molecules is expressed as the fetal DNA fraction in the plasma of pregnant women.MethodsWe proposed an effective method to deduce fetal chromosomal aneuploidy based on the proportion of a certain range of DNA fragment lengths from maternal plasma. We gradually narrowed the range of the upper and lower boundary via a traversing algorithm.ResultsWe explored the optimal range of the upper and lower boundary by using size-based DNA fragment length. Using this range, the accuracy of the sensitivity and specificity could be improved by up to 100% for detecting the three most common autosomal aneuploidies, namely trisomy 13, trisomy 18, trisomy 21 in the sample set.ConclusionsNumerical experiments demonstrate that our method is effective and efficient. The program is available upon request.

[This corrects the article DOI: 10.1371/journal.pone.0153314.].

Puerarin was a major isoflavonoid derived from the Chinese medical herb radix puerariae (Gegen). In present study effect of puerarin on cisplatin nephrotoxicity was evaluated. Rat model of nephrotoxicity was established by a single intraperitoneal injection of cisplatin (7mg/kg). Puerarin was administrated through caudal vein injection once per day at the dose of 10mg/kg, 30mg/kg and 50mg/kg. Biochemical assays showed that after cisplatin treatment the serum urea and creatinine increased significantly compared with control (P

BACKGROUND:Single nucleotide polymorphisms (SNPs) in the estrogen receptor gene (ESR1) play critical roles in breast cancer (BC) susceptibility. Genome-wide association studies have reported that SNPs in ESR1 are associated with BC susceptibility; however, the results of recent studies have been inconsistent. Therefore, we performed this meta-analysis to obtain more accurate and credible results. METHODS:We pooled published literature from PubMed, EMBASE, and Web of Science and calculated odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of associations using fixed effects models and random effects models. Twenty relevant case-control and cohort studies of the 3 related SNPs were identified. RESULTS:Three SNPs of the ESR1 gene, rs2077647:T>C, rs2228480:G>A and rs3798577:T>C, were not associated with increased BC risk in our overall meta-analysis. Stratified analysis by ethnicity showed that in Caucasians, the rs2228480 AA genotype was associated with a 26% decreased risk of BC compared with the GG genotype (OR = 0.740, 95% CI: 0.555-0.987). The C allele of the rs3798577:T>C variant was associated with decreased BC risk in Asians (OR = 0.828, 95% CI: 0.730-0.939), while Caucasians with this allele were found to experience significantly increased BC risk (OR = 1.551, 95% CI: 1.037-2.321). A non-significant association between rs2077647 and BC risk was identified in all of the evaluated ethnic populations. CONCLUSION:Rs3798577 was associated with an increased risk of BC in Caucasian populations but a decreased risk in Asians. Rs2228480 had a large protective effect in Caucasians, while rs2077647 was not associated with BC risk.

A major concern in Pluripotent Stem Cell (PSC)-derived cell replacement therapy is the risk of teratoma formation from contaminating undifferentiated cells. Removal of undifferentiated cells from differentiated cultures is an essential step before PSC-based cell therapies can be safely deployed in a clinical setting. We report a group of novel small molecules that are cytotoxic to PSCs. Our data indicates that these molecules are specific and potent in their activity allowing rapid eradication of undifferentiated cells. Experiments utilizing mixed PSC and primary human neuronal and cardiomyocyte cultures demonstrate that up to a 6-fold enrichment for specialized cells can be obtained without adversely affecting cell viability and function. Several structural variants were synthesized to identify key functional groups and to improve specificity and efficacy. Comparative microarray analysis and ensuing RNA knockdown studies revealed involvement of the PERK/ATF4/DDIT3 ER stress pathway. Surprisingly, cell death following ER stress induction was associated with a concomitant decrease in endogenous ROS levels in PSCs. Undifferentiated cells treated with these molecules preceding transplantation fail to form teratomas in SCID mice. Furthermore, these molecules remain non-toxic and non-teratogenic to zebrafish embryos suggesting that they may be safely used in vivo.

MicroRNAs (miRNAs) are short non-coding RNAs which modulate gene expression by binding to complementary segments present in the 3'UTR of the mRNAs of protein coding genes. MiRNAs play very important roles in maintaining normal human body physiology conditions, meanwhile, abnormal miRNA expressions have been found related to many human diseases spanning from psychiatric disorders to malignant cancers. Recently, emerging reports have indicated that disturbed miRNAs expression contributed to the pathogenesis of recurrent pregnancy loss (RPL). In this study, we identified a new mutation site (+29A>G, position relative to pre-miR-125a) by scanning pri-miR-125a coding region in 389 Chinese Han RPL patients. This site was co-existed with two polymorphisms (rs12976445 and rs41275794) in patients heterogeneously and changed the predicted secondary structures of pri-miR-125a. Subsequent in vitro analysis indicated that the A>G mutation reduced mature miR-125a expression, and further led to less efficient inhibition of verified target genes. Functional analysis showed that mutant pri-mir-125a can enhance endometrial stromal cells (ESCs) invasive capacity and increase the sensitivity of ESCs cells to mifepristone. Moreover, we further analyzed the possible molecular mechanism by RIP-chip assay and found that mutant pri-mir-125a disturbed the expression of miR-125a targetome, the functions of which includes embryonic development, cell proliferation, migration and invasion. These data suggest that A>G mutation in pri-miR-125a coding region contributes to the genetic predisposition to RPL by disordering the production of miR-125a, which consequently meddled in gene regulatory network between mir-125a and mRNA.

MicroRNAs (miRNAs) are small, noncoding RNA molecules that regulate post-transcriptional gene expression by base pairing with partially complementary sequences within target messenger RNAs (mRNAs). Although the target genes and the precise biological functions of individual miRNAs remain largely unknown, miRNAs have been implicated in diverse biological processes, including both normal and pathological states. As a single stranded mRNA can be directly targeted by multiple miRNAs, and as the target sites may exist in the 3'-untranslated region (UTR), 5'-UTR, or the coding regions, it is essential to develop an effective method to identify the full-scale miRNA regulatory pattern of each particular gene. In this study, we employed a biochemical approach to identify the miRNA profiles that regulate the expression of embryonic ectoderm development (EED) protein by using anti-PABPC1 ribonucleoprotein (RNP) co-immunoprecipitation (Co-IP). The full length EED mRNA was subcloned into an expression vector and transiently transfected into a Flag-PABPC1 stable expression cell line. Subsequent to cross-linking and an anti-Flag Co-IP, the miRNAs that directly targeted EED were identified. We found that the best time point to distinguish the positive miRNAs from the background was 18 hours after the plasmid transfection. As expected, the miRNAs that directly target EED were found to interact with EED mRNA through the miRNA-induced silencing complex (miRISC). Meanwhile, the EED mRNA was bound by Flag-PABPC1. This method depends on the integrity of the miRISC complex and achieves greater efficiency when ultraviolet irradiation is used for the process of cross-linking. By using anti-PABPC1 RIP, we identified EED to be a new target gene of miR-16; a finding further confirmed using a dual-luciferase assay. In summary, our data indicate that anti-PABPC1 RIP is a validated and direct biochemical method to provide data about specific miRNA-mRNA interactions, as well as global miRNA patterns regulating the mRNAs.

CITED2 was identified as a cardiac transcription factor which is essential to the heart development. Cited2-deficient mice showed cardiac malformations, adrenal agenesis and neural crest defects. To explore the potential impact of mutations in CITED2 on congenital heart disease (CHD) in humans, we screened the coding region of CITED2 in a total of 700 Chinese people with congenital heart disease and 250 healthy individuals as controls. We found five potential disease-causing mutations, p.P140S, p.S183L, p.S196G, p.Ser161delAGC and p. Ser192_Gly193delAGCGGC. Two mammalian two-hybrid assays showed that the last four mutations significantly affected the interaction between p300CH1 and CITED2 or HIF1A. Further studies showed that four CITED2 mutations recovered the promoter activity of VEGF by decreasing its competitiveness with HIF1A for binding to p300CH1 and three mutations decreased the consociation of TFAP2C and CITED2 in the transactivation of PITX2C. Both VEGF and PITX2C play very important roles in cardiac development. In conclusion, we demonstrated that CITED2 has a potential causative impact on congenital heart disease.

As a major product of extracellular matrix (ECM), Hyaluronic acid (HA) is involved in early cardiac development and mainly synthesized by Hyaluronan synthase 2 (HAS2) during embryogenesis. Targeted deletion of HAS2 gene in mice led to obvious cardiac and vascular defects. To clarify the potential association of the mutation in HAS2 with the development of congenital heart disease (CHD), in this study, we sequenced the coding region of HAS2 and identified a novel non-synonymous variant c.A1496T (p.Glu499Val) in one of 100 non-syndromic Ventricular Septal Defect (VSD) patients. The variant was not observed in 250 controls. In addition, to determine the contribution of HAS2 variant in VSD, we compared HA content in supernatant using HA quantitative analysis and found that the mutation obviously affected the HA synthetic activity of HAS2. To our knowledge, this is the first time that the mutation in HAS2 was found in Chinese VSD patients, which suggested that HAS2 may be involved in the etiology of non-syndromic VSD and have the vital function in the development of heart septum.

BACKGROUND: Ganglionated plexi (GP) ablation has been become an adjunct to pulmonary vein isolation (PVI). This study describes the long-term results of minimally invasive surgical PVI, ablation of GPs, and exclusion of the left atrial appendage for atrial fibrillation (AF). METHODS: Long-term follow-up of 55 months was performed in 139 consecutive patients (age 58.3±20.8 years) with symptomatic, drug-refractory lone AF who underwent minimally invasive surgical PVI, GPs ablation, and exclusion of the left atrial appendage. Success was defined as freedom from AF, atrial flutter, or atrial tachycardia off antiarrhythmic drugs. RESULTS: AF was paroxysmal in 77.7%, persistent in 12.2% and long-standing persistent in 10.1%. Single-procedure success rate was 71.7%, 59.4% and 46.6% at 12, 24 and 60 months respectively. Single-procedure success rate was 72.9%, 62.6% and 51.8% for paroxysmal AF, 64.7%, 35.3%, and 28.2% for persistent AF, 71.4%, 64.3% and 28.6% for long-standing persistent AF at 12, 24 and 60 months respectively. Duration of AF>24 months (hazard ratio [HR]: 3.09, 95% confidence interval [CI]: 1.51 to 6.32; p = 0.002), left atrial diameter≥40 mm (HR: 4.03, 95% CI: 1.88 to 8.65; p

Congenital cataract is a clinically and genetically heterogeneous group of eye disorders that causes visual impairment and childhood blindness. The purpose of this study was to identify the genetic defect associated with autosomal dominant congenital perinuclear cataract in a Chinese family. A detailed family history and clinical data of the family were recorded, and candidate gene sequencing was performed to screen for mutation-causing disease in our study. Direct sequencing revealed a c.601G>A (p.E201K) transversion in exon 2 of GJA8. This mutation co-segregated with all affected individuals in the family and was not found in unaffected family members or 100 unrelated controls. The function and mechanism of novel GJA8 point mutation E201K in Chinese patients were then investigated in this study. We found E201K aberrantly located in cytoplasm and prevented its location in the plasma membrane. Induction of E201K expression led to a decrease in cell growth and viability by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Our study provides important evidence that GJA8 is a disease-causing gene for congenital cataract and that mutation of GJA8 has a potential causative effect.

BACKGROUND: We evaluated retrospectively the early and midterm results of using veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support in patients undergoing valvular surgery. METHODS: A total of 87 patients undergoing valvular surgery received VA-ECMO due to refractory postcardiotomy cardiogenic shock (PCS), who were eligible for inclusion were enrolled in this study. Preoperative, perioperative, and postoperative variables were assessed and analyzed for possible associations with mortality in hospital and after discharge. RESULTS: The mean age, additive EuroSCORE, and left ventricular ejection fraction (LVEF) for all patients was 65 ± 7 years, 6.1 ± 1.9 points, and 46% ± 12%, respectively. The mean duration of VA-ECMO support was 61 ± 37 hours. Intra-aortic balloon pumps (IABP) were implanted in 47.1% of patients. Weaning from VA-ECMO was successful in 59% of patients, and 49% were discharged. Multivariate analysis revealed that being >65 years old (odds ratio [OR], 2.75), receiving postoperative renal replacement treatment (OR, 2.47), having a peak lactate level ≥ 12 mmol L(-1) (OR, 2.18), and receiving VA-ECMO for >60 hours (OR, 3.2) were independent predictors of in-hospital mortality. IABP support (OR, 0.46) was protective. In addition, persistent heart failure with an LVEF

BACKGROUND: MicroRNA-101 (miR-101) expression is negatively associated with tumor growth and blood vessel formation in several solid epithelial cancers. However, the role of miR-101 in human breast cancer remains elusive. RESULTS: MiR-101 was significantly decreased in different subtypes of human breast cancer tissues compared with that in adjacent normal breast tissues (P

BACKGROUND: Glucose transporter 9 (GLUT9) is a high-capacity/low-affinity urate transporter. To date, several recent genome-wide association studies (GWAS) and follow-up studies have identified genetic variants of SLC2A9 associated with urate concentrations and susceptibility to gout. We therefore investigated associations between gout and polymorphisms and haplotypes in the presumptive promoter region of GLUT9 in Chinese males. METHODOLOGY/PRINCIPAL FINDINGS: The approximately 2000 bp presumptive promoter region upstream of the start site of exon 1 of GLUT9 was sequenced and subjected to genetic analysis. A genotype-phenotype correlation was performed and polymorphisms-induced changes in transcription factor binding sites were predicted. Of 21 SNPs identified in GLUT9, five had not been previously reported. Two of the SNPs (rs13124007 and rs6850166) were associated with susceptibility to gout (p = 0.009 and p = 0.042, respectively). The C allele of rs13124007 appeared to be the risk allele for predisposition to gout (p = 0.006, OR 1.709 [95% CI 1.162-2.514]). For rs6850166, an increased risk of gout was associated with the A allele (p = 0.029, OR 1.645 [95% CI 1.050-2.577]). After Bonferroni correction, there was statistically difference in rs13124007 allele frequencies between gout cases and controls (P = 0.042). Haplotype analyses showed that haplotype GG was a protective haplotype (p = 0.0053) and haplotype CA was associated with increased risk of gout (p = 0.0326). Genotype-phenotype analysis among gout patients revealed an association of rs13124007 with serum triglycerides levels (P = 0.001). The C to G substitution in polymorphism rs13124007 resulted in a loss of a binding site for transcription factor interferon regulatory factor 1 (IRF-1). CONCLUSIONS/SIGNIFICANCE: Polymorphisms rs13124007 and rs6850166 are associated with susceptibility to gout in Chinese males.

Since their arrival in the Tibetan Plateau during the Neolithic Age, Tibetans have been well-adapted to extreme environmental conditions and possess genetic variation that reflect their living environment and migratory history. To investigate the origin of Tibetans and the genetic basis of adaptation in a rigorous environment, we genotyped 30 Tibetan individuals with more than one million SNP markers. Our findings suggested that Tibetans, together with the Yi people, were descendants of Tibeto-Burmans who diverged from ancient settlers of East Asia. The valleys of the Hengduan Mountain range may be a major migration route. We also identified a set of positively-selected genes that belong to functional classes of the embryonic, female gonad, and blood vessel developments, as well as response to hypoxia. Most of these genes were highly correlated with population-specific and beneficial phenotypes, such as high infant survival rate and the absence of chronic mountain sickness.

γD-crystallin is one of the major structural proteins in human eye lens. The solubility and stability of γD-crystallin play a crucial role in maintaining the optical properties of the lens during the life span of an individual. Previous study has shown that the inherited mutation G61C results in autosomal dominant congenital cataract. In this research, we studied the effects of the G61C mutation on γD-crystallin structure, stability and aggregation via biophysical methods. CD, intrinsic and extrinsic fluorescence spectroscopy indicated that the G61C mutation did not affect the native structure of γD-crystallin. The stability of γD-crystallin against heat- or GdnHCl-induced denaturation was significantly decreased by the mutation, while no influence was observed on the acid-induced unfolding. The mutation mainly affected the transition from the native state to the intermediate but not that from the intermediate to the unfolded or aggregated states. At high temperatures, both proteins were able to form aggregates, and the aggregation of the mutant was much more serious than the wild type protein at the same temperature. At body temperature and acidic conditions, the mutant was more prone to form amyloid-like fibrils. The aggregation-prone property of the mutant was not altered by the addition of reductive reagent. These results suggested that the decrease in protein stability followed by aggregation-prone property might be the major cause in the hereditary cataract induced by the G61C mutation.

OBJECTIVE: To assess the efficacy of video-assisted minimally invasive surgical vs. catheter ablation for the long-standing persistent AF. METHODS: We performed a retrospective comparative analysis in a series of 166 long-standing persistent AF patients treated between 2006 and 2009 with either video-assisted minimally invasive ablation (83 patients), or catheter ablations (83 patients). The catheter group was screened using a 'pair-matched case-control' methodology in order to select appropriate statistical comparison candidates out of 169 long-standing persistent AF patients which were potentially suitable for surgery, but have been treated with catheter approaches in order to balance major prognostic factors between the two groups. Follow-up for all patients ranged from 1 to 3.6 years. RESULTS: No patient died postoperatively. One patient suffered from stroke in the surgical group but recovered before discharge. Freedom from AF was obtained in 59.0% and 74.7% during follow-up in the catheter group and the surgical group respectively (P = 0.047). Patients in the catheter group had a significantly higher rate of recurrent arrhythmia (P = 0.011, hazard ratio: 0.555, 95% CI: 0.354 to 0.872) compared with the surgically treated group. The freedom from antiarrhythmic drugs was 44.6% in the catheter group and 61.4% in the surgical group (P = 0.043). CONCLUSIONS: The video-assisted minimally invasive ablation was safe and effective, and had an optimistic success rate for patients with long-standing persistent AF in our retrospective comparative study. Thus, further randomized studies addressing this issue seem to be justified.

BACKGROUND: Chemokine (C-C motif) ligand 2 CCL2/MCP-1 is among the key signaling molecules of innate immunity; in particular, it is involved in recruitment of mononuclear and other cells in response to infection, including tuberculosis (TB) and is essential for granuloma formation. METHODOLOGY/PRINCIPAL FINDINGS: We identified a tag SNP for the CCL2/MCP-1 gene (rs4586 C/T). In order to understand whether this SNP may serve to evaluate the contribution of the CCL2 gene to the expression of TB disease, we further analysed distribution of its alleles and genotypes in 301 TB cases versus 338 non-infected controls (all BCG vaccinated) representing a high-risk pediatric population of North China. In the male TB subgroup, the C allele was identified in a higher rate (P = 0.045), and, acting dominantly, was found to be a risk factor for clinical TB (P = 0.029). Homozygous TT genotype was significantly associated with lower CSF mononuclear leukocyte (ML) counts in patients with tuberculous meningitis (TBM) (P = 0.001). CONCLUSIONS/SIGNIFICANCE: The present study found an association of the CCL2 tag SNP rs4586 C allele and pediatric TB disease in males, suggesting that gender may affect the susceptibility to TB even in children. The association of homozygous TT genotype with decreased CSF mononuclear leukocyte (ML) count not only suggests a clinical significance of this SNP, but indicates its potential to assist in the clinical assessment of suspected TBM, where delay is critical and diagnosis is difficult.

BACKGROUND: Cardiac cell death and generation of oxidative stress contribute to doxorubicin (DOX)-induced cardiac dysfunction. E3 ligase Nrdp1 plays a critical role in the regulation of cell apoptosis, inflammation and production of reactive oxygen species (ROS), which may contribute to heart failure. However, the role of Nrdp1 in DOX-induced cardiac injury remains to be determined. METHODS AND RESULTS: We examined the effect of Nrdp1 overexpression with DOX treatment in rat neonatal cardiomyocytes and mouse heart tissue. Cardiomyocytes were infected with adenovirus containing GFP (Ad-GFP), Nrdp1 wild-type (Ad-Nrdp1) or the dominant-negative form of Nrdp1 (Ad-Dn-Nrdp1), then treated with DOX for 24 hr. DOX treatment increased cell death and apoptosis, with Ad-Nrdp1 infection enhancing these actions but Ad-Dn-Nrdp1 infection attenuating these effects. Furthermore, 5 days after a single injection of DOX (20 mg/kg, intraperitoneally), Nrdp1 transgenic mice (TG) showed decreased cardiac function and increased apoptosis, autophagy and oxidative stress as compared with wild-type (WT) mice (P

Background and Objective: Rhegmatogenous retinal detachment (RRD) is the most common ophthalmic emergency threatening vision, with an incidence ranging from 6.3 to 17.9 per 100,000 people per year. However, optimal surgical management of RRD remains controversial. This network meta-analysis compared the efficacy and safety of different surgical options in patients with RRD., Methods: We systematically searched PubMed, Embase, Cochrane Library and Web of science for randomized controlled trials (RCT) from inception to 24th September 2023. Frequentist network meta-analyses with the random-effects model was used to synthesize data. The risk of bias for the included RCTs was evaluated using the Cochrane tool for assessing risk of bias, and the certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation approach. And we performed the network meta-analysis utilizing R 4.1.3 software and Stata 16SE., Results: A total of 19 RCTs enrolled 2589 eyes were included. With high-to-very low certainty of evidence, compared with pneumatic retinopexy (PR), scleral buckling (SB) (odd ratio (OR) = 0.52, 95% confidence interval (CI) [0.30; 0.91]), pars plana vitrectomy (PPV) (OR = 2.35, 95% CI [1.32; 4.20]), PPV+SB (OR = 2.59, 95% CI [1.32; 5.09]) and PPV combined with phacomulsification (PCV) (OR = 7.72, 95% CI [1.07; 55.87]) were more effect in improving primary reattachment rate; for postoperative 6-month vision, SB was superior to PPV+SB (mean difference (MD) = 0.14, 95% CI [0.01; 0.27]). When compared with SB, PPV (OR = 5.27, 95% CI [3.13; 8.86]) and PPV+SB (OR = 10.12, 95% CI [4.31; 23.77]) shows a higher incidence of postoperative cataract progression. Compared to PR, the same is true for PPV (OR = 7.51, 95% CI [3.33; 16.91]) and PPV+SB (OR = 14.43, 95% CI [4.97; 41.93])., Conclusions: PR appears to be associated with a lower rate of primary reattachment rate and postoperative cataract progression. In view of the small sample sizes of the included studies and the low certainty of evidence, these findings must be interpreted with caution. A large number of high-quality trials should be conducted to verify the effects of different surgical techniques in the future., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Yan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The slewing crane is easily affected by the wind and the manipulation level of the operator when it is working, which in turn impacts its swing angle, affects the working efficiency and safety of the crane., Objective: Toimprove the operation safety andreduce the swing angle, this study design and research the anti-swing control system for the slewing crane., Methods: Firstly, based on the Lagrange equation, the dynamic model of the crane hoisting system is established. Then, the mechanical anti-swing mechanism driven by a four-motor rope is established. Finally, based on fuzzy PID control, an anti-swing platform is established, and the performance of anti-swing control is verified., Results: Compared to no anti-swing control, the in-plane swing angle θ1 and out-of-plane swing angle θ2 of the lifting arm are reduced by 88% and 75% respectively., Conclusion: The results show that the four-motor rope-driven anti-swing mechanism can achieve better anti-swing effect, which provides an effective swing suppression method for the slewing crane in the actual operation., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Tilianin (TIL), a bioactive component derived from Dracocephalum Moldavica L., has been recognized for its anti-inflammatory properties. However, its effects on the Nlrp3 inflammasome within endothelial progenitor cells (EPCs) during myocardial ischemia-reperfusion injury (MIRI) remain unexplored. This study aimed to elucidate the role of TIL in modulating Nlrp3 inflammasome activation under MIRI conditions. A mouse model of MIRI was established to assess the therapeutic potential of TIL. EPCs treated with TIL at concentrations of 5, 10, and 20 μM were administered into the myocardium before reperfusion. Additionally, the cardioprotective effects of TIL were further examined by pre-treating EPCs with the compound before exposing them to hypoxia/reoxygenation (H/R) using cardiomyocyte supernatants. The impact on Nlrp3 inflammasome was assessed through western blotting, immunofluorescence, and ELISA. Our results showed that TIL concentration-dependently inhibited Nlrp3 inflammasome-related protein levels,and inhibited Asc oligomerization and Asc-Speck complex formation in EPCs, resulting in improved the migratory capacity and vascular structure formation of EPCs. In addition, TIL-treated EPCs significantly attenuated I/R injury and improved cardiac function. These results suggest that TIL ameliorates the inflammatory response in EPCs by suppressing Nlrp3 inflammasome activation, thereby facilitating neovascularization in the myocardium and conferring protection against MIRI. The study provides valuable insights into the potential of TIL as a therapeutic agent for cardiovascular diseases linked to ischemia-reperfusion injury., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Majority of macrozooplankton have a wider dietary niche breadth and utilize small invertebrates, microzooplankton and mesozooplankton, so effect on primary production might be through trophic cascading effect. To better understand the ecosystem structure of benthic oyster-macroalgae reefs, we analyzed zooplankton community structure before (July 2016) and after (from September 2016 to October 2017) the construction of benthic reefs in the 2 km2 sea ranch area in Xiangyun Cove, Tangshan, China. We identified 57 zooplankton species, including the 12 cnidarian (e.g., Clytia hemisphaerica Linnaeus and Eirene ceylonensis Browne), 1 ctenopharyngodon (Pleurobrachia globosa Moser), 24 crustacean (e.g., Calanus sinicus Brodsky, Paracalanus parvus Claus, Labibocera euchaeta Glesbrecht, Labibocera bipinnata Tanaka, Calanopia thompsoni Scott, and Centropages dorsispinatus Thompson), 1 chaetognath (Sagitta crassa Tokioka), 1 urochordate species (Oikopleura dioica Fol), and 18 species of planktonic polychaete and gastropod larvae. The zooplankton density and biomass values before reef construction were 266.14 ind/m3 and 2.72 mg/m3, respectively, and those after reef construction were 138.06 ind/m3 and 32.91 mg/m3, respectively. The biomass trend was as follow: October 2017 (89.08 mg/m3) > August 2017 (70.97) > September 2016 (3.17) > July 2016 (2.72) > June 2017 (0.86) > May 2017 (0.44). The common dominant organisms were crustaceans and chaetognaths. According to the RDA ranking results, water temperature was positively correlated with the Shannon-Wiener diversity index and Margalef's richness indexes. With the increasement of Margalef's richness index, the value of dissolved oxygen content showed a significant negative correlation with zooplankton abundance. The results of this study are applicable to sustainable development and management strategies of coastal reef ecosystems and provide a basis for further surveys of secondary productivity in the sea ranch area., Competing Interests: NO authors have competing interests., (Copyright: © 2024 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In this paper, we introduce the mixed-frequency data model (MIDAS) to China's insurance demand forecasting. We select the monthly indicators Consumer Confidence Index (CCI), China Economic Policy Uncertainty Index (EPU), Consumer Price Index (PPI), and quarterly indicator Depth of Insurance (TID) to construct a Mixed Data Sampling (MIDAS) regression model, which is used to study the impact and forecasting effect of CCI, EPU, and PPI on China's insurance demand. To ensure forecasting accuracy, we investigate the forecasting effects of the MIDAS models with different weighting functions, forecasting windows, and a combination of forecasting methods, and use the selected optimal MIDAS models to forecast the short-term insurance demand in China. The experimental results show that the MIDAS model has good forecasting performance, especially in short-term forecasting. Rolling window and recursive identification prediction can improve the prediction accuracy, and the combination prediction makes the results more robust. Consumer confidence is the main factor influencing the demand for insurance during the COVID-19 period, and the demand for insurance is most sensitive to changes in consumer confidence. Shortly, China's insurance demand is expected to return to the pre-COVID-19 level by 2023Q2, showing positive development. The findings of the study provide new ideas for China's insurance policymaking., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Promoting the social integration of rural migrants is key to improving the mechanism of rural-urban integration and development. This study utilizes the 2017 China Migrants Dynamic Survey and matched urban macro data to systematically explore the impact of homesteads on the social integration of rural migrants. Research has shown that social integration of rural migrants will be inhibited if they own homesteads. Simultaneously, the degree of inhibition varies according to the individual characteristics of rural migrants, the region to which they belong, and other factors. Specifically, when rural migrants aged 18 to 50 own homesteads, their degree of social integration into the cities they move into will be low. At the same time, for rural migrants in the central region, homestead ownership will not affect their degree of social integration. In addition, the mechanism analysis shows that increased housing expenditure inhibits rural migrants' willingness to integrate. Meanwhile, owning contracted land and owning a house in the city also affect the degree of social integration of rural migrants to a certain extent. The findings of this study can broaden research on the effects of land on the free movement of population factors. In the meantime, it provides theoretical references for improving the level of social integration of migrants, enhancing people's well-being, and improving the mechanism of urban-rural integration and development., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: The genotype distribution of human papillomavirus (HPV) infection varies greatly in different regions. This study aims to determine the prevalence and type-specific distribution of HPV among females from Chengdu and Aba in Sichuan Province, which differ in geographical location, economic status, and living habits. These can serve as evidence of epidemic patterns for future design and implementation of vaccination and screening programs., Methods: A retrospective cross-sectional study was conducted on 144 113 women who underwent cervical screening at Chengdu Women's and Children's Central Hospital from January 2015 to September 2020. Meanwhile, 1799 samples from February 2018 to December 2021 were collected from Aba Maternal and Child Health Hospital. HPV DNA genotype testing was performed using real-time PCR. The overall prevalence, annual trend, age-specific prevalence, and type distribution were analyzed., Results: The overall HPV prevalence was 22.51% in Chengdu. During 2015-2020, the highest prevalence rate was observed in 2018. Age-specific HPV distribution displayed a bimodal distribution among women aged ≤25 or ≥46 years old. The top three prevalent genotypes were HPV52, -16, and -58. Although the total prevalence of HPV in Aba was 14.23%, there was an upward trend from 2018 to 2021. However, no significant differences were identified in HPV infection rate across all age groups. HPV52, -53, and -16 were the major genotypes. Furthermore, single-type HPV infections and high-risk HPV infections were identified as the most common infection types in both regions., Conclusion: Our findings demonstrate the overall prevalence of HPV was still high in Chengdu and Aba. The age-specific prevalence distribution demonstrated different patterns. Non-vaccine-covered HR-HPV53, -51and LR-HPV81, -CP8304 were frequently detected, which was worth significant clinical attention. In summary, regional HPV screening provides valuable clinical guidance for cervical cancer prevention and vaccine selection in Western China., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Peptide receptor radionucleotide therapy (PRRT) with 177Lu-dotatate is widely used for the treatment of patients with neuroendocrine tumors (NETs). We analyzed data from 104 patients with NETs treated with 177Lu -dotatate at a US academic center between December 2017 and October 2020 to better understand patterns of long-term efficacy, safety, and toxicity in the real-world setting. 177Lu-dotatate (200 mCi) was administered every eight weeks for four doses. The most common sites of primary disease were small intestine NETs (n = 49, 47%), pancreatic NETs (n = 32, 31%), and lung NETs (n = 7, 7%). Twenty-seven percent had Ki-67 <3%, 49% had Ki-67 between 3-20%, and 13.5% had Ki-67 >20%. The cohort had been pretreated with a median of two prior lines of treatment. Forty percent had received prior liver-directed treatment. Seventy-four percent of patients completed all four doses of treatment. The objective response rate was 18%. The median time-to-treatment failure/death was significantly longer for small-bowel NETs when compared to pancreatic NETs (37.3 months vs. 13.2 months, p = 0.001). In a multivariate model, Ki-67, primary site, and liver tumor burden ≥50% were found to independently predict time-to-treatment failure/death. Around 40% of patients experienced adverse events of ≥grade 3 severity. Treatment-related adverse events leading to discontinuation of therapy happened in 10% of patients. Preexisting mesenteric/peritoneal disease was present in 33 patients; seven of these patients developed bowel-related toxicities including two grade 5 events. We also report two cases of delayed-onset minimal change nephrotic syndrome, which occurred 14 and 27 months after the last dose of PRRT. Lastly, we describe six patients who developed rapid tumor progression in the liver leading to terminal liver failure within 7.3 months from the start of PRRT, and identify potential risk factors associated with this occurrence, which will need further study., Competing Interests: The authors have read the journal’s policy and have the following competing interests: Vineeth Sukrithan has received clinical research, on behalf of Ohio State University, funding from Eli Lilly and Company and Crinetics Pharmaceuticals, as well as consulting fees from GE Oncology, Exelixis, and Lantheus. Bhavana Konda has received grant funding, on behalf of Ohio State University, from Xencor, Merck, and Eisai., (Copyright: © 2024 Sukrithan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

It is significant to systematically quantify the propagation thresholds of meteorological drought to different levels of agricultural drought in karst areas, and revealit's the propagation driving mechanisms. This can guide early warning and fine management of agricultural drought. In this study,we selected Guizhou Province as an example. The standardized precipitation evapotranspiration index (SPEI) and standardized soil moisture index (SSI) were used to characterize meteorological and agricultural drought. The run theory was used to identify, merge and eliminate drought events. The maximum correlation coefficient was used to capture the propagation time of meteorological-agricultural drought. The regression models were used to quantify the propagation intensity threshold from meteorological drought to different levels of agricultural drought. Finally, the propagation threshold driving mechanism was explored using geographical detectors. The results show that: (1) in terms of temporal variations during the past 21 years, regional meteorological drought had a shorter duration and a higher intensity than agricultural drought, Particularly, 2011 was a year of severe drought, and agricultural drought was significantly alleviated after 2014. (2) In terms of spatial variations, the "long duration area" of meteorological drought duration showed an "S" shaped distribution in the northeast, and the "short duration area" showed a point-like distribution. The overall duration of agricultural drought showed a spatial distribution of northeast to "medium-high in the northeast and low in the southwest. (3) The drought propagation time showed an alternating distribution of "valley-peak-valley-peak" from southeast to northwest. In terms of propagation intensity thresholds, light drought showed an overall spatial distribution of high in the east and low in the west. Moderate, severe, and extreme droughts showed a spatial distribution of low in the center north of southern Guizhou) and high in the borders. (4) There was a strong spatial coupling relationship between karst development intensity, altitude and meteorological-agricultural drought propagation thresholds. The interaction of different factors exhibited a two-factor enhancement and nonlinear enhancement on the propagation threshold. This indicates that synergistic effects of different factors on the propagation threshold were larger than single-factor effects., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: This study aimed to assess the difference in prognosis of patients with early-stage liver cancer after surgery or external radiation., Methods: Between 2010 and 2015, 2155 patients with AJCC 7th stage I liver cancer were enrolled in the SEER database. Among these, 1972 patients had undergone surgery and 183 had undergone external beam radiation. The main research endpoints were overall survival (OS) and disease-specific survival (DSS). The competitive risk model was used to calculate the risk ratio of liver cancer-specific deaths when there was a competitive risk. Propensity Score Matching (PSM) method using a 1:1 ratio was used to match confounders such as sex, age, and treatment method. Conditional survival was dynamically assessed for patient survival after surgery or external radiation., Results: Multivariate analysis of the competitive risk model showed that age, disease diagnosis time, grade, and treatment [surgery and external beam radiation therapy (EBRT)] were independent prognostic factors for patients with hepatocellular carcinoma. Surgery had a higher survival improvement rate than that of EBRT. As the survival of patients with liver cancer increased, the survival curve of surgery declined more slowly than that of radiotherapy patients and stabilized around 3 years after surgery. The survival curve of radiotherapy patients significantly dropped within 4 years and then stabilized., Conclusion: Surgery was better than EBRT for patients with stage I liver cancer. Close follow-up was required for 3 years after surgery or 4 years after external radiation. This study can help clinicians make better informed clinical decisions., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The Yangtze River Delta urban agglomeration (YRDUA) is China's most representative region with remarkable economic development vitality. The purpose of this study is to provide valuable data analysis to actively respond to the population aging in China. We mainly focus on the spatial and temporal evolution of population aging in YRDUA from 2000 to 2020 using city-level population data. This study constructs a multi-dimensional index system to measure population aging including population aging degree, speed, and density. It finds out: (1) the elderly population rate (EPR), the elder-child ratio (ECR), and the elderly dependency ratio (EDR) in the YRDUA area are gradually increasing from 2000 to 2020. In addition, the trends of these indicators in various cities and regions are relatively consistent. All 27 cities in YRDUA entered an aging society, from the primary to the moderate aging stage from 2000 to 2010 and from the moderate to the hyper aging stage from 2010 to 2020. (2) the absolute and relative growth rate of EPR is increasing from 2000 to 2020. However, the absolute and relative growth rate of ECR is increasing from 2000 to 2010 and then decreasing from 2010 to 2020. These results indicate that the two-child policy adopted by the Chinese government plays a positive role. (3) the density level of the elderly population in the YRDUA evolved from low in 2000 to middle in 2010 and then to high in 2020. (4) There are remarkable differences in the process of population aging among three provinces and one city. The contribution of this study is mainly reflected in two aspects: firstly, it constructs a multi-dimensional index system to measure population aging; secondly, using this multi-dimensional index system, it systematically observes the spatial and temporal evolution of population aging from 2000 to 2020 in the Yangtze River Delta Urban Agglomeration., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The cancer hazard associated with lifetime exposure to radiofrequency radiation (RFR) was examined in Sprague Dawley (SD) rats at the Ramazzini Institute (RI), Italy. There were increased incidences of gliomas and cardiac schwannomas. The translational relevance of these rare rat tumors for human disease is poorly understood. We examined the genetic alterations in RFR-derived rat tumors through molecular characterization of important cancer genes relevant for human gliomagenesis. A targeted next-generation sequencing (NGS) panel was designed for rats based on the top 23 orthologous human glioma-related genes. Single-nucleotide variants (SNVs) and small insertion and deletions (indels) were characterized in the rat gliomas and cardiac schwannomas. Translational relevance of these genetic alterations in rat tumors to human disease was determined through comparison with the Catalogue of Somatic Mutations in Cancer (COSMIC) database. These data suggest that rat gliomas resulting from life-time exposure to RFR histologically resemble low grade human gliomas but surprisingly no mutations were detected in rat gliomas that had homology to the human IDH1 p.R132 or IDH2 p.R172 suggesting that rat gliomas are primarily wild-type for IDH hotspot mutations implicated in human gliomas. The rat gliomas appear to share some genetic alterations with IDH1 wildtype human gliomas and rat cardiac schwannomas also harbor mutations in some of the queried cancer genes. These data demonstrate that targeted NGS panels based on tumor specific orthologous human cancer driver genes are an important tool to examine the translational relevance of rodent tumors resulting from chronic/life-time rodent bioassays., Competing Interests: The authors have declared that no competing interests exist., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Objectives: To compare the clinical curative effects, survival and complications of recombinant human adenovirus-p53 (rAd-p53) combined with transcatheter arterial chemoembolization (TACE) versus TACE for the treatment of liver cancer., Methods: We searched all the eligible studies of rAd-p53 plus TACE versus control group had only TACE in the treatment of liver cancer, which were retrieved from CNKI, Wanfang database, CBM, VIP, PubMed, EMBase, The Chrance of Library, Web of Science from its inception to august 2022., Results: A total of 17 studies were included, which involved 1045 patients. The results of the meta analysis indicated that the the rAd-p53combined with TACE markedly improved the patients' complete remission(OR = 2.19, 95% CI:1.13-4.22, P = 0.02), partial remission (OR = 2.22, 95% CI:1.67-2.94, P<0.00001), objective tumor response rate (OR = 2.58, 95% CI:1.95-3.41, P<0.00001) and disease control rate(OR = 2.39, 95% CI:1.65-3.47, P<0.00001) compared with TACE alone. And our results showed that rAd-p53combined with TACE had better survival benefit [6-month OS (OR = 3.41, 95% CI: 1.62-7.14, p = 0.001); 1-year OS (OR = 1.95, 95% CI: 1.28-2.96, p = 0.002)] and better quality of life(MD = 5.84, 95% CI:2.09-9.60, P = 0.002). In addition, the immunity of the patients was enhanced by the combination therapy, as demonstrated by the increase in the ratio of CD4+ to CD4+/CD8+. In adverse effects, except for fever in the TACE combined with rAd-p53 group, which was higher than that in the TACE group(OR = 2.62, 95% CI:2.02-3.49, P<0.00001), all other adverse effects were lower in the TACE combined with rAd-p53 group than in the TACE group., Conclusion: RAd-p53 combined with TACE for liver cancer showed significant advantages in terms of clinical efficacy, survival rate, and safety compared to the TACE alone, and effectively improved patient quality of life and immune function., Systematic Review Registration: https://inplasy.com/inplasy-2022-9-0127/., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Guo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The burden of type 2 diabetes (T2DM) in China is significant and growing, and this is reflected in high rates of T2DM in the city of Ningbo, China. Consequent impacts on morbidity, mortality, healthcare expenditure, and health-related quality of life, make this a problem of the utmost importance to address. One way to improve T2DM outcomes is to address lifestyle behaviours that may affect prognosis and complications, such as physical activity levels, dietary habits, smoking status, and alcohol intake. A cross-sectional survey was undertaken to describe the prevalence of being physically active, having a healthy diet, currently smoking, and currently drinking alcohol among people living with T2DM attending a diabetes clinic in Ningbo, China. Regression analysis was used to determine the factors associated with these lifestyle behaviours. We found a high prevalence of a healthy diet (97.8%, 95% CI 96.5-98.7%). Prevalence of being physically active (83.4%, 95% CI 80.6-85.9%), smoking (21.6%, 95% CI 18.8-24.6%), and alcohol drinking (32.9%. 95% CI 29.6-36.2%) appeared in keeping with those of the general population. Marked associations were demonstrated between male sex and smoking (OR 41.1, 95% CI 16.2-139.0), and male sex and alcohol drinking (OR 4.00, 95% CI 2.62-6.20). Correlation between lifestyle factors was demonstrated including between alcohol drinking and smoking, and between physical activity and reduced smoking. General diabetes self-management education programmes that address multiple lifestyle risk factors simultaneously may be beneficial in this population. Specific interventions targeting smoking cessation and reduction in alcohol drinking may be of benefit to men living with T2DM attending a diabetes clinic in Ningbo., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Carter et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The ability to model human neurological tissues in vitro has been a major hurdle to effective drug development for neurological disorders. iPSC-derived brain organoids have emerged as a compelling solution to this problem as they have the potential to relevantly model the protein expression pattern and physiology of specific brain regions. Although many protocols now exist for the production of brain organoids, few attempts have been made to do an in-depth kinetic evaluation of expression of mature regiospecific markers of brain organoids. To address this, we differentiated midbrain-specific brain organoids from iPSC-lines derived from three apparently healthy individuals using a matrix-free, bioreactor method. We monitored the expression of midbrain-specific neuronal markers from 7 to 90-days using immunofluorescence and immunohistology. The organoids were further characterized using electron microscopy and RNA-seq. In addition to serving as a potential benchmark for the future evaluation of other differentiation protocols, the markers observed in this study can be useful as control parameters to identify and evaluate the disease phenotypes in midbrain organoid derived from patient iPSC-lines with genetic neurological disorders., Competing Interests: Author HNN was employed by 3Dnamics Inc. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

Due to the confidentiality, value and exclusivity of technical secrets, how to protect the technical secrets within cultural industry clusters has become a paradoxical issue and a research hotspot. Focusing on the collaborative protection of technical secrets within cultural industry clusters, this paper analyzes the strategies of collaborative protection of technical secrets between leading enterprises and following enterprises based on evolutionary game theory, and uses dynamic evolution and simulation methods to identify key factors behind the strategy choices, which further enriches the evolutionary mechanism of collaborative protection, and expands the application scenarios of the theory of evolutionary game. As the research results show, the collaborative protection strategy of technical secrets within cultural industry clusters is feasible, the cost of collaborative protection, government subsidies, and compensation for collaborative deposits are key variables that determine the trend of the game. The government subsidy coefficient, the collaborative deposits, and the difference in the number of technology secrets are strongly sensitive factors underlying the mode of protection, while the synergistic benefits between firms are weakly sensitive factors. Therefore, this paper proposes that increasing government subsidies and collaborative deposits, and reducing the differences in the number of technical secrets among game subjects can promote enterprises to eliminate suspicion and increase their willingness to cooperate in protecting technical secrets., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Xu, Hu. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The vibration signals measured in practical engineering are usually complex and noisy, which brings challenges to fault diagnosis. In addition, industrial scenarios also put forward higher requirements for the accuracy and computational efficiency of diagnostic models. Aiming at these problems, an improved multiscale branching convolutional neural network is proposed for rolling bearing fault diagnosis. The proposed method first applies the multiscale feature learning strategy to extract rich and compelling fault information from diverse and complex vibration signals. Further, the lightweight dynamic separable convolution is elaborated and coupled into the feature extractor to "slim down" the model, reduce the computational loss on the one hand, and further improve the model's adaptive learning ability for different inputs hand. Extensive experiments indicate that the proposed method is significantly improved compared with existing multi-scale neural networks., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Persistent variability observed during spirometry, even when technical and personal factors are controlled, has prompted interest in uncovering its underlying mechanisms. Notably, our prior investigations have unveiled that spirometry has the potential to trigger gastro-esophageal reflux in a susceptible population. This current study embarks on elucidating the intricate mechanisms orchestrating reflux induced by spirometry. To achieve this, we enlisted twenty-four (24) participants exhibiting reflux symptoms for esophageal assessment. These participants underwent two sets of spirometry sessions, interspersed with a 10-minute intermission, during which we closely scrutinized fluid flow dynamics and esophageal function through high-resolution impedance esophageal manometry. Our comprehensive evaluation juxtaposed baseline manometric parameters against their equivalents during the initial spirometry session, the intervening rest period, and the subsequent spirometry session. Remarkably, impedance values, serving as a metric for fluid quantity, exhibited a substantial elevation during each spirometry session and the ensuing recovery interval in the pan-esophageal and hypopharyngeal regions when compared to baseline levels. Additionally, the resting pressure of the lower esophageal sphincter experienced a noteworthy reduction subsequent to the first bout of spirometry (13.6 ± 8.8 mmHg) in comparison to the baseline pressure (22.5 ± 13.3 mmHg). Furthermore, our observations unveiled a decline in spirometric parameters-FEV1 (0.14 ± 0.24 L, P = 0.042) and PEFR (0.67 L/s, P = 0.34)-during the second spirometry session when contrasted with the first session. Collectively, our study underscores the compelling evidence that spirometry maneuvers can elicit gastro-esophageal reflux by eliciting intra-esophageal pressure differentials and inducing temporary relaxation of the lower esophageal sphincter., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study aims to reveal short-run and long-run asymmetries among human capital, educational inequality, and income inequality in China over the period 1975-2020 using a nonlinear autoregressive distributed lag (NARDL) model. The estimated long-run asymmetry parameters reflect that positive shocks to secondary education (SSE) and higher education (HE) are negatively correlated with income Gini coefficient. The adverse shocks of secondary education (SSE) and higher education (HE) stimulate the Gini coefficient of income, but the effect of secondary education (SSE) on the Gini coefficient of income is not significant, while that of higher education (HE) is significant. The results also highlight that, in the long run, there is a significant asymptotic effect of the education Gini coefficient (educational inequality) and economic growth on the income Gini coefficient (income inequality). However, physical capital stock has a significant adverse effect on income inequality in the long run. Higher education significantly promotes educational inequality, while the square of higher education significantly reduces educational inequality, thus verifying the inverted U-shaped Kuznets curve hypothesis between higher education and educational inequality. Strategically, this study suggests higher education as a powerful tool for mitigating income inequality by emphasizing educational equity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Castanopsis carlesii (Hemsl.) Hay. is a widely distributed and dominant tree species native to subtropical China with significant ecological and economic value. Due to serious human-related disturbance, its wild resources have been increasingly reduced, and whether may result in the loss of genetic diversity. However, no population genetics studies of natural C. carlesii have been reported to date. Microsatellite markers have been a useful tool in population genetics. Therefore, we developed EST-SSR markers based on the transcriptome sequencing of C. carlesii leaves. A total of 149,380,224 clean reads were obtained, and 63,012 nonredundant unigenes with a mean length of 1,034 bp were assembled and annotated based on sequence similarity searches in the Nr, Nt, KO, SwissProt, PFAM, KOG, and GO databases. The results showed that only 5,559 (8.82%) unigenes were annotated in all seven databases, but 46,338 (73.53%) could be annotated in at least one database. A total of 31,459 potential EST-SSRs were identified in 18,690 unigenes, with an average frequency of one SSR approximately 2 kb. Among the 100 EST-SSR primer pairs designed, 49 primer pairs successfully produced the expected product by amplification, with a success rate of 49%, but only 20 primer pairs showed abundant polymorphisms. Polymorphisms were verified using 25 samples from C. carlesii in Qimen, Anhui. A total of 119 alleles were detected, with a mean number of alleles (Na) of 5.95 per locus and a mean polymorphism information content (PIC) of 0.6125. All the 20 newly developed EST-SSR markers were verified in other Castanopsis species (C. sclerophylla, C. lamontii, C. fargesii, C. eyrei and C. jucunda). Sixteen primer pairs showed successful amplification in all five Castanopsis species (80%), and the transferability ratios ranged from 90% to 100%. These developed EST-SSR markers can be applied to population genetic and germplasm evaluations of C. carlesii and related species., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Zhong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: This work was aimed to analyze the effect of vitamin energy drink on muscle fatigue by surface electromyography (SEMG) and ultrasonic bioimaging (USBI)., Methods: 20 healthy men were selected to do increasing load fatigue test. Surface electromyographic signals and ultrasonic biological images were collected based on wavelet threshold function with improved thresholds. Time domain and frequency domain characteristic integrated electromyography (IEMG), root mean square amplitude (RMS), average power frequency (MPF), and surface and deep muscle morphological changes were analyzed. Hemoglobin concentration (HB), red blood cell number (RBC), mean volume of red blood cell (MCV), blood lactic acid (BLA), malondialdehyde (MDA), and phosphocreatine kinase (CK) were measured., Results: 1) the Accuracy (94.10%), Sensitivity (94.43%), Specificity (93.75%), and Precision (94.07%) of the long and short-term memory (LSTM) specificity for muscle fatigue recognition were higher than those of other models. 2) Compared with the control group, the levels of BLA, MDA, and CK in the experimental group were decreased and HB levels were increased after exercise (P < 0.05). 3) IEMG and RMS of the experimental group were higher than those of the control group, and increased with time (P < 0.05). 4) The mean amplitude of the response signal decreased with time. Compared with the control group, the surface muscle thickness, deep muscle thickness, total muscle thickness, contrast, and homogeneity (HOM) decreased in the experimental group; while the angular second moment (ASM) and contrast increased, showing great differences (P < 0.05)., Conclusion: Surface electromyographic signal and ultrasonic biological image can be used as auxiliary monitoring techniques for muscle fatigue during exercise. Drinking vitamin energy drinks before exercise can relieve physical fatigue to a certain extent and promote the maintenance of muscle microstructure., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Wang, Xu. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

As information and communication technology advances rapidly, real-time live online broadcasting has emerged as a novel social media platform. In particular, live online broadcasts have gained widespread popularity among audiences. However, this process can cause environmental problems. When audiences imitate live content and perform similar field activities, it can have a negative effect on the environment. In this study, an extended theory of planned behavior (TPB) was used to explore how online live broadcasts relate to environmental damage from the perspective of human behavior. A total of 603 valid responses were collected from a questionnaire survey, and a regression analysis was conducted to verify the hypotheses. The findings showed that the TPB can be applied to account for the formation mechanism of behavioral intention of field activities caused by online live broadcasts. The mediating effect of imitation was verified using the above relationship. These findings are expected to provide a practical reference for the control of online live broadcast content and guidance on public environmental behavior., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Xiao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The fungal genus Ophiocordyceps contains a number of insect pathogens. One of the best known of these is Ophiocordyceps sinensis, which is used in Chinese medicine and its overharvesting threatens sustainability; hence, alternative species are being sought. Ophiocordyceps robertsii, found in Australia and New Zealand, has been proposed to be a close relative to O. sinensis, but little is known about this species despite being also of historical significance. Here, O. robertsii strains were isolated into culture and high coverage draft genome sequences obtained and analyzed. This species has a large genome expansion, as also occurred in O. sinensis. The mating type locus was characterized, indicating a heterothallic arrangement whereby each strain has an idiomorphic region of two (MAT1-2-1, MAT1-2-2) or three (MAT1-1-1, MAT1-1-2, MAT1-1-3) genes flanked by the conserved APN2 and SLA2 genes. These resources provide a new opportunity for understanding the evolution of the expanded genome in the homothallic species O. sinensis, as well as capabilities to explore the pharmaceutical potential in a species endemic to Australia and New Zealand., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Xu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)