Yi-Zhi-Fang-Dai formula (YZFDF) is an experiential prescription used to cure dementia cases like Alzheimer's disease (AD). In this study, the main effective compounds of YZFDF have been identified from this formula, and the neuroprotective effect against Aβ1-42 oligomer of YZFDF has been tested in SH-SY5Y cells. Our results showed that YZFDF could increase cell viability and could attenuate endothelial reticula- (ER-) mediated apoptosis. Evidence indicated that protein folding and endothelial reticula stress (ERS) played an important role in the AD pathological mechanism. We further explored the expression of Hsp70, an important molecular chaperon facilitating the folding of other proteins, and Grp78, the marker protein of ERS in SH-SY5Y cells. Data told us that YZFDF pretreatment could influence the mRNA and protein expression of these two proteins. At last, we also found that YZFDF pretreatment could activate Akt in SH-SY5Y cells. All these above indicate that YZFDF could be a potent therapeutic candidate for AD treatment.

Low-level laser therapy (LLLT) may have an effect on the pain associated with orthodontic treatment. The aim of this study was to evaluate the effect of LLLT on pain and somatosensory sensitization induced by orthodontic treatment. Forty individuals (12-33 years old; mean ± standard deviations: 20.8 ± 5.9 years) scheduled to receive orthodontic treatment were randomly divided into a laser group (LG) or a placebo group (PG) (1:1). The LG received LLLT (810-nm gallium-aluminium-arsenic diode laser in continuous mode with the power set at 400 mW, 2 J·cm-2) at 0 h, 2 h, 24 h, 4 d, and 7 d after treatment, and the PG received inactive treatment at the same time points. In both groups, the non-treated side served as a control. A numerical rating scale (NRS) of pain, pressure pain thresholds (PPTs), cold detection thresholds (CDTs), warmth detection thresholds (WDTs), cold pain thresholds (CPTs), and heat pain thresholds (HPTs) were tested on both sides at the gingiva and canine tooth and on the hand. The data were analysed by a repeated measures analysis of variance (ANOVA). The NRS pain scores were significantly lower in the LG group (P = 0.01). The CDTs, CPTs, WDTs, HPTs, and PPTs at the gingiva and the PPTs at the canine tooth were significantly less sensitive on the treatment side of the LG compared with that of the PG (P < 0.033). The parameters tested also showed significantly less sensitivity on the non-treatment side of the LG compared to that of the PG (P < 0.043). There were no differences between the groups for any quantitative sensory testing (QST) measures of the hand. The application of LLLT appears to reduce the pain and sensitivity of the tooth and gingiva associated with orthodontic treatment and may have contralateral effects within the trigeminal system but no generalized QST effects. Thus, the present study indicated a significant analgesia effect of LLLT application during orthodontic treatment. Further clinical applications are suggested.

Dynamic contrast-enhanced computed tomography (CECT) has been used previously to evaluate severe acute pancreatitis (SAP)-associated complications. However, optimal time points of CECT have not yet been established. The present study aimed to determine optimal timings for CECT to be undertaken for patients with SAP. The results of CECT from 309 patients with SAP, who were classified into either infected or non-infected SAP groups, were retrospectively analyzed. The severity and alterations in the periods within 72 h to >4 weeks of SAP onset were also assessed. In the analysis of the disease severity and changes, acute peripancreatic fluid collection was detected, where the number of areas increased within 1 week of SAP onset but decreased within 4 weeks and longer. However, no significant differences were observed between the infected and non-infected groups. The acute necrotic collection (ANC) areas were ≤30% of the area of the pancreas, with significantly more ANC areas and pancreatic necrosis in the infected SAP group compared with the non-infected SAP group at a time interval of >4 weeks. The exudation of pleural effusion (PE) was elevated within 1 week, but decreased within 2 weeks and longer. The difference in the alteration of the exudation of PE was not statistically different between the two groups. In conclusion, the results suggest that the period between 72 h and 1 week of SAP onset is optimal timing of CECT to assess SAP-associated complications, particularly for infected SAP patients.

During the past several years, the rapid development of neuroimaging techniques has contributed greatly in the noninvasive imaging studies of tinnitus. The aim of the present study was to explore the brain anatomical alterations in patients with right-sided unilateral pulsatile tinnitus (PT) in the early stage of PT symptom using voxel-based morphometry (VBM) analysis. Twenty-four patients with right-sided pulsatile tinnitus and 24 age- and gender-matched normal controls were recruited to this study. Structural image data preprocessing was performed using VBM8 toolbox. Tinnitus Handicap Inventory (THI) score was acquired in the tinnitus group to assess the severity of tinnitus and tinnitus-related distress. Two-sample t-test and Pearson's correlation analysis were used in statistical analysis. Patients with unilateral pulsatile tinnitus had significantly increased gray matter (GM) volume in bilateral superior temporal gyrus compared with the normal controls. However, the left cerebellum posterior lobe, left frontal superior orbital lobe (gyrus rectus), right middle occipital gyrus (MOG), and bilateral putamen showed significantly decreased brain volumes. This was the first study which demonstrated the features of neuroanatomical changes in patients with unilateral PT during their early stages of the symptom.

Simultaneous deep brain stimulation (DBS) and functional magnetic resonance imaging (fMRI) constitutes a powerful tool for elucidating brain functional connectivity, and exploring neuromodulatory mechanisms of DBS therapies. Previous DBS-fMRI studies could not provide full activation pattern maps due to poor MRI compatibility of the DBS electrodes, which caused obstruction of large brain areas on MRI scans. Here, we fabricate graphene fiber (GF) electrodes with high charge-injection-capacity and little-to-no MRI artifact at 9.4T. DBS-fMRI with GF electrodes at the subthalamic nucleus (STN) in Parkinsonian rats reveal robust blood-oxygenation-level-dependent responses along the basal ganglia-thalamocortical network in a frequency-dependent manner, with responses from some regions not previously detectable. This full map indicates that STN-DBS modulates both motor and non-motor pathways, possibly through orthodromic and antidromic signal propagation. With the capability for full, unbiased activation pattern mapping, DBS-fMRI using GF electrodes can provide important insights into DBS therapeutic mechanisms in various neurological disorders.

Purpose: Eupatilin is a pharmacologically active flavonoid extracted from Asteraceae argyi that has been identified as having antitumor effects. Gliomas are the most common intracranial malignant tumors and are associated with high mortality and a poor postoperative prognosis. There are few studies on the therapeutic effects of eupatilin on glioma. Therefore, we explored the efficacy and the underlying molecular mechanism of eupatilin on glioma. Methods: The effect of eupatilin on cell proliferation and viability was detected using Cell Counting Kit-8 assays. Cell migration was analyzed with a scratch wound healing assay and invasion was analyzed using transwell assays. Results: We found that eupatilin significantly inhibits the viability and proliferation of glioma cells by arresting the cell cycle at the G1/S phase. In addition, eupatilin disrupts the structure of the cytoskeleton and affects F-actin depolymerization via the "P-LIMK"/cofilin pathway, thereby inhibiting the migration of glioma. We also found that eupatilin inhibits the invasion of gliomas. The underlying mechanism may be related to the destruction of epithelial-mesenchymal transition, with eupatilin also affecting the RECK/matrix metalloproteinase pathway. However, we did not observe the proapoptotic effect of eupatilin on glioma, which is inconsistent with other studies. Finally, we observed a significant inhibitory effect of eupatilin on U87MG glioma in xenograft nude mice. Conclusion: Eupatilin inhibits the viability and proliferation of glioma cells, attenuates the migration and invasion, and inhibits tumor growth in vivo, but does not promote apoptosis. Therefore, due to the poor clinical efficacy of drug treatment of glioma and high drug resistance, the emergence of eupatilin brings a new dawn for glioma patients.

To overcome the easy loss of microorganism, the mass production of sludge and the consumption of aeration energy during biological treatment of anaerobically digested swine wastewater, this study used chitosan-sodium alginate composite carrier to prepare immobilized bacteria pellets. The heterotrophic bacteria tolerant to high concentrations of ammonia nitrogen were isolated and the conditions for immobilizing bacteria were optimized. The performance of immobilized bacteria pellets to remove ammonia nitrogen from ADSW was determined and the corresponding mechanism was investigated. Results showed that the isolated bacteria were Bacillus subtilis, and the optimal conditions to prepare the immobilized bacteria pellets by response surface methodology tests were sodium alginate of 0.84% (m/V), chitosan of 0.22% (m/V), embedding time of 32 min and embedding amount of 15% (V/V). In ADSW treatment, at pH 6, 20 g/L of the immobilized bacteria pellets removed 96.5% of ammonia nitrogen. Both adsorption and microbial action contributed to ammonia nitrogen removal, and their contributions were 54.3% and 42.2%, respectively. Compared with the immobilized bacteria pellets using chitosan-sodium alginate as carrier, the one using mono alginate as carrier had a weaker ability to remove ammonia nitrogen, with a removal efficiency of 67.4%. The main mechanism was the formation of polyelectrolyte membrane by the connection between amino groups of chitosan and carboxyl groups of sodium alginate, which stabilized the immobilized bacteria pellets and prolonged their service life. To sum up, the immobilized bacteria pellets using chitosan-sodium alginate as an embedding agent have a promising prospect in ammonia nitrogen removal from wastewater.

Currently, there are shortcomings in diagnosing gastric cancer with or without serous invasion, making it difficult for patients to receive appropriate treatment. Therefore, we aimed to develop a radiomic nomogram for preoperative identification of serosal invasion.

The present study investigated the function of sinigrin in angiotensin II (Ang II)‑induced renal damage. The results demonstrated that systolic blood pressure (SBP) and diastolic blood pressure (DBP) were increased in Ang II‑challenged rats, and sinigrin treatment inhibited their increase. The levels of blood urea nitrogen (BUN) and serum creatinine (SCR) were increased by Ang II in the rats, and these were reversed by sinigrin in a dose‑dependent manner. In addition, the Ang II‑induced elevation of urinary protein levels was inhibited by sinigrin treatment. Glomerular basement membrane thickness and ECM degradation markers, such as collagen I, collagen IV and fibronectin, were suppressed by sinigrin in the Ang II‑challenged rats. Moreover, the levels of inflammatory regulators, including tumor necrosis factor‑α (TNF‑α), interleukin‑6 (IL‑6) and monocyte chemoattractant protein‑1 (MCP‑1), were reduced following sinigrin treatment of the Ang II‑challenged rats and in Ang II‑exposed proximal tubule epithelial cells. Furthermore, the superoxide dismutase (SOD) and catalase (CAT) levels were downregulated, whereas the malondialdehyde (MDA) levels were upregulated by Ang II; these effects were reversed by sinigrin treatment in vivo and in vitro. Mechanistically, sinigrin inhibited the Ang II‑induced phosphorylation of ERK, p65 and IκBα. Thus, sinigrin attenuated Ang II‑induced renal injury by inactivating ERK and NF‑κB signaling. Sinigrin may thus prove to be a potential candidate for the treatment of hypertension‑induced kidney damage.

Plant height is an important architecture trait which is a fundamental yield-determining trait in crops. Variety with dwarf or semi-dwarf phenotype is a major objective in the breeding because dwarfing architecture can help to increase harvest index, increase planting density, enhance lodging resistance, and thus be suitable for mechanization harvest. Although some germplasm or genes associated with dwarfing plant type have been carried out. The molecular mechanisms underlying dwarfism in oilseed rape (Brassica napus L.) are poorly understood, restricting the progress of breeding dwarf varieties in this species. Here, we report a new dwarf mutant Bndwarf2 from our B. napus germplasm. We studied its inheritance and mapped the dwarf locus BnDWARF2.

Gastric cancer (GC) is an aggressive malignant tumor and causes a significant number of deaths every year. With the coming of the age of cancer immunotherapy, search for a new target in gastric cancer may benefit more advanced patients. Melanoma-associated antigen-A3 (MAGEA3), one of the members of the cancer-testis antigen (CTA) family, was considered an important part of cancer immunotherapy. We evaluate the potential role of MAGEA3 in GC through the TCGA database. The result revealed that MAGEA3 is upregulated in GC and linked to poor OS and lymph node metastasis. MAGEA3 was also correlated with immune checkpoints, TMB, and affected the tumor immune microenvironment and the prognosis of GC through CIBERSORT, TIMER, and Kaplan-Meier plotter database analysis. In addition, GSEA-identified MAGEA3 is involved in the immune regulation of GC. Moreover, the protein-protein interaction (PPI) networks of MAGEA3 were constructed through STRING database and MAGEA3-correlated miRNAs were screened based on the joint analysis of multiple databases. In terms of experimental verification, we constructed pET21a (+)/MAGEA3 restructuring plasmids and transformed to Escherichia coli Rosetta. MAGEA3 protein was used as an antigen after being expressed and purified and can effectively detect the specific IgG in 93 GC patients' serum specimens with 44.08% sensitivity and 92.54% specificity. Through further analysis, the positive rate of MAGEA3 was related to the stage and transfer number of lymph nodes. These results indicated that MAGEA3 is a novel biomarker and correlated with lymph node metastasis and immune infiltrates in GC, which could be a new target for immunotherapy.

Although cisplatin is the most effective first-line drug in the management of advanced non-small cell lung cancer (NSCLC), drug resistance remains a major clinical challenge. There is increasing evidence that icariside II (IS) exhibits antitumour activity in a variety of cancers. In the current study, we investigated the anticancer effects of icariside II combined with cisplatin and elucidated the underlying mechanism in NSCLC. Here, we showed that cotreatment with IS and cisplatin inhibited cell proliferation and induced cellular apoptosis. Using mRNA sequencing (mRNA-seq), we identified differentially expressed genes (DEGs) in which there was an enrichment in PERK-mediated unfolded protein response (UPR) signalling. The western blot results revealed that IS activated endoplasmic reticulum (ER) stress, including three branches of UPR signalling, PERK, IRE1 and ATF6, and the downstream PERK-eIF2α-ATF4-CHOP pathway, thus potentiating the apoptosis induced by cisplatin. In addition, the combination of IS with cisplatin significantly reduced xenograft tumour growth in C57BL/6 and BALB/c nude mice in vivo. Notably, the combination therapy displayed no evident toxicity. Taken together, IS enhances cisplatin-induced apoptosis partially by promoting ER stress signalling in NSCLC, suggesting that combination treatment with IS and cisplatin is a novel potential therapeutic strategy for NSCLC.

Cleidocranial dysplasia (CCD) is mainly attributable to a variant of runt-related transcription factor 2 (RUNX2) on chromosome 6p21. CCD is an autosomal dominant skeletal disorder characterized by open/delayed closure of fontanels, clavicular hypoplasia, retention of deciduous teeth, and supernumerary permanent teeth. The aim of this study was to investigate potentially pathogenic mutations in 2 Chinese families. Genomic DNA was obtained from peripheral blood lymphocytes, and whole exome sequencing and Sanger sequencing were performed to detect gene variants. Real-time quantitative PCR was performed to determine the mRNA expression level of RUNX2 in the proband of family 1. Silico algorithms and conservation analyses were used to evaluate the functional impact. We identified a novel initiation codon mutation (c.2T>C) and a previously reported mutation (c.569G>A). Familial co-segregation verified an autosomal-dominant inheritance pattern. Our findings demonstrated that the novel mutation c.2T>C causes CCD. Quantitative real-time PCR suggested that downregulated RUNX2 levels and haploinsufficiency in RUNX2 lead to CCD. These results extend the spectrum of RUNX2 mutations in CCD patients and can be used for genetic consultation and prenatal diagnosis.

The worldwide contagion, human cytomegalovirus (HCMV), may cause a series of disorders in infected individuals. The aim of the present study was to investigate whether HCMV infection is associated with the development of gastric cancer. In this study, the positive expression of unique long (UL)133-UL138 and immediate-early (IE)1 genes, which are associated with viral latency and replication, respectively, were detected using nested polymerase chain reaction. A χ2 test and logistic regression analysis were performed to further investigate the preliminary data. The data indicated that the positive rate of UL133, UL135 and UL136 expression in cancer tissues was higher than that in paired normal tissues (P=0.01, 0.027 and 0.013, respectively). However, no significant differences were identified in the UL133-138 locus and IE1 gene when associated with clinicopathological features. Furthermore, seven infection patterns were identified, with the UL133 + UL138 infection pattern representing the largest proportion in the cancer (60.34%) and normal tissues (42.11%). In conclusion, it is possible that the UL133-UL138 locus is important in the occurrence of gastric cancer. The mechanism by which UL133-UL138 locus expression differs in human gastric cancer requires further investigation.

Irisin is secreted by muscle, increases with exercise, and mediates certain favorable effects of physical activity. In particular, irisin has been shown to have beneficial effects in adipose tissues, brain, and bone. However, the skeletal response to exercise is less clear, and the receptor for irisin has not been identified. Here we show that irisin binds to proteins of the αV class of integrins, and biophysical studies identify interacting surfaces between irisin and αV/β5 integrin. Chemical inhibition of the αV integrins blocks signaling and function by irisin in osteocytes and fat cells. Irisin increases both osteocytic survival and production of sclerostin, a local modulator of bone remodeling. Genetic ablation of FNDC5 (or irisin) completely blocks osteocytic osteolysis induced by ovariectomy, preventing bone loss and supporting an important role of irisin in skeletal remodeling. Identification of the irisin receptor should greatly facilitate our understanding of irisin's function in exercise and human health.

The partial nitrification (PN) performance and the microbial community variations were evaluated in a sequencing batch reactor (SBR) for 172 days, with the stepwise elevation of ammonium concentration. Free ammonia (FA) and low dissolved oxygen inhibition of nitrite-oxidized bacteria (NOB) were used to achieve nitritation in the SBR. During the 172 days operation, the nitrogen loading rate of the SBR was finally raised to 3.6 kg N/m3/d corresponding the influent ammonium of 1500 mg/L, with the ammonium removal efficiency and nitrite accumulation rate were 94.12% and 83.54%, respectively, indicating that the syntrophic inhibition of FA and low dissolved oxygen contributed substantially to the stable nitrite accumulation. The results of the 16S rRNA high-throughput sequencing revealed that Nitrospira, the only nitrite-oxidizing bacteria in the system, were successively inhibited and eliminated, and the SBR reactor was dominated finally by Nitrosomonas, the ammonium-oxidizing bacteria, which had a relative abundance of 83%, indicating that the Nitrosomonas played the primary roles on the establishment and maintaining of nitritation. Followed by Nitrosomonas, Anaerolineae (7.02%) and Saprospira (1.86%) were the other mainly genera in the biomass.

The prevalence of antimicrobial resistance in zoonotic Salmonella is a significant ongoing concern over the world. Several reports have investigated the prevalence of Salmonella infections in the farm animals in China; however, there is only limited knowledge about the Salmonella cross-contamination in the slaughterhouses. Moreover, the application of genomic approaches for understanding the cross-contamination in the food-animal slaughterhouses is still in its infancy in China. In the present study, we have isolated 105 Salmonella strains from pig carcasses and environment samples collected from four independent slaughterhouses in Jiangsu, China. All the Salmonella isolates were subjected to whole genome sequencing, bioinformatics analysis for serovar predictions, multi-locus sequence types, antimicrobial resistance genes, and plasmid types by using the in-house Galaxy platform. The antimicrobial resistance of Salmonella isolates was determined using a minimal inhibitory concentration assay with 14 antimicrobials. We found that the predominant serovar and serogroup was S. Derby and O:4(B), with a prevalence of 41.9 and 55%, respectively. All the isolates were multidrug-resistant and the highest resistance was observed against antimicrobials tetracycline (95.4%) and trimethoprim and sulfamethoxazole (90.9%). Additionally, the colistin-resistant determinant mcr-1 gene was detected in five (4.8%) strains. Our study demonstrated the prevalence of antimicrobial resistance in Salmonella strains isolated from pig slaughterhouses in China and suggested that the genomic platform can serve as routine surveillance along with the food-chain investigation.

We aimed to investigate the accuracy of different equations in evaluating estimated glomerular filtration rate (eGFR) in a Chinese population with different BMI levels.

The recent outbreak of human infections caused by SARS-CoV-2, the third zoonotic coronavirus has raised great public health concern globally. Rapid and accurate diagnosis of this novel pathogen posts great challenges not only clinically but also technologically. Metagenomic next-generation sequencing (mNGS) and reverse-transcription PCR (RT-PCR) have been the most commonly used molecular methodologies. However, each has their own limitations. In this study, we developed an isothermal, CRISPR-based diagnostic for COVID-19 with near single-copy sensitivity. The diagnostic performances of all three technology platforms were also compared. Our study aimed to provide more insights into the molecular detection of SARS-CoV-2, and also to present a novel diagnostic option for this new emerging virus.

Background: Laparoscopic gastrectomy for gastric cancer shortens the recovery period without decreasing long-term survival. However, clinical evidence on whether laparoscopic radical gastrectomy reduces the surgical stress and improves the short- and long-term outcomes of obese patients with gastric cancer is lacking. We compared the short- and long-term outcomes of gastric cancer patients with visceral obesity (VO) who underwent laparoscopic gastrectomy (LG) or open gastrectomy (OG). Methods: We prospectively collected data from 578 patients who underwent radical gastrectomy in two centers between January 2014 and December 2016. The visceral fat area (VFA) was measured on the umbilicus level, and VFA ≥100 cm2 was defined as VO. The section bias was reduced by conducting a propensity score matching analysis. The short- and long-term outcomes were further compared between patients who underwent OG and those who underwent LG. Results: Overall, 245 patients (42.61%) were classified as having VO, of whom 102 were included for further analysis after matching. There were no significant differences in clinical characteristics between the two groups in the matched cohort. The LG group had significantly fewer overall complications (P<0.001) and shorter postoperative hospital stays (P<0.001). Subgroup analysis of postoperative complications also showed that the incidence of surgical complications was lower in the LG group (P=0.002). Further survival analysis showed the LG group had significantly better long-term overall survival (P=0.017). Conclusions: Compared with open radical gastrectomy, laparoscopy would reduce the rate of postoperative complications in patients with VO, as well as prolong their overall survival.