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A chemical investigation of the dichloromethane extract from the Xisha sponge Diacarnus sp. revealed seven undescribed norterpene cyclic peroxides, named diacarperoxides T–Z, and five unreported related norterpenes, named diacarnoids E–I, and eleven previously reported compounds. The structures of these isolated compounds, including their absolute configurations, were elucidated based on extensive spectroscopic analyses, electronic circular dichroism (ECD) calculations, Snatzke's method, [Rh 2 (OCOCF 3) 4 ]-induced ECD spectra, and modified Mosher's method. Bioassays were performed to assess the antibacterial activity against six pathogenic bacteria, cytotoxicities toward three cancer cell lines, and antimalarial activity against Plasmodium parasites. Most of the cyclic peroxides exhibited substantial antibacterial activity (MIC 1–8 μg/mL). Diacarperoxide W and nuapapuin A showed substantial antimalarial activity with IC 50 values of 0.98 and 2.83 μM. Moreover, many compounds exhibited <50% cell survival rates, and IC 50 values of 0.22–6.33 μM. The apoptosis assay showed that nuapapuin A induced cancer cell apoptosis in a dose-dependent manner. [Display omitted] • Seven undescribed norterpene cyclic peroxides, were isolated from marine sponge. • Five unreported related norterpenes, were obtained from marine sponge. • Some cyclic peroxides showed antibacterial, antimalarial and cytotoxic activities. [ABSTRACT FROM AUTHOR]

Background: Enhance recovery after surgery (ERAS) is a new and promising paradigm for spine surgery. The purpose of this study is to investigate the effectiveness and safety of a multimodal and evidence-based ERAS pathway to the patients undergoing anterior cervical discectomy and fusion (ACDF).Methods: The patients treated with the ACDF-ERAS pathway were compared with a historical cohort of patients who underwent ACDF before ERAS pathway implementation. Primary outcome was length of stay (LOS). Secondary outcomes included cost, MacNab grading, complication rates and 90-day readmission and reoperation. And perioperative factors and postoperative complications were reviewed.Results: The ERAS protocol was composed of 21 components. More patients undergoing multi-level surgery (n ≥ 3) were included in the ERAS group. The ERAS group showed a shorter LOS and a lower cost than the conventional group. The postoperative satisfaction of patients in ERAS group was better than that in conventional group. In addition, the rate of overall complications was significantly higher in the conventional group than that in the ERAS group. There were no significant differences in operative time, postoperative drainage, or 90-day readmission and reoperation.Conclusions: The ACDF-tailored ERAS pathway can reduce LOS, cost and postoperative complications, and improve patient satisfaction without increasing 90-day readmission and reoperation. [ABSTRACT FROM AUTHOR]

Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide, especially in East Asia. ESCC accounts for more than 90% of esophageal cancer. Currently, neoadjuvant therapy in combination with surgical resection is the mainstay of treatment. However, the overall survival rate of patients with locally advanced ESCC is not satisfactory even when treated following the standard treatment guidelines. With neoadjuvant chemoradiotherapy, chemotherapy, or emerging immunotherapy, continuous exploration of efficacy in relation to ESCC is expected to improve overall survival further. Here, we review and summarize current evidence for efficacy of preoperative therapy for locally advanced ESCC. [ABSTRACT FROM AUTHOR]

Background: To evaluate the performance of transvaginal sonoelastography (TVSE) for differential diagnosis between malignant and benign cervical lesions using a meta‐analysis. Methods: An independent literature search was conducted on the English medical database, including PubMed, Embase and Medline, Cochrane Library, Web of Science, and OVID. The diagnostic accuracy of TVSE was compared with that of histopathology, which is the gold reference standard for diagnosis. The accuracy of TVSE was assessed by calculating the pooled sensitivity, specificity, diagnostic odds ratio, and area under the curve (AUC). The imaging mechanisms, assessment methods, and QUADAS scores were assessed with a meta‐regression analysis. A Deeks funnel plot was performed for evaluating publication bias. Results: Six eligible studies reported a total sample of 615 cervical lesions (415 cancers, 200 benign lesions). TVSE showed a pooled diagnostic odds ratio of 21.42 (95% CI 13.65‐33.61), sensitivity of 0.87 (95% CI 0.84‐0.90), specificity of 0.79 (95% CI 0.72‐0.84), and an AUC of 0.892 (Q* = 0.822). The results of the meta‐regression analysis showed that the imaging mechanism (P =.253), the assessment method (P =.279), or QUADAS score (P =.205) did not affect the study heterogeneity. Conclusion: TVSE has a relatively high and satisfactory value for differential diagnosis between malignant and benign cervical lesions. The diagnostic performance of strain elastography and shear wave elastography were similar and good. However, to accommodate heterogeneity and publication bias, high‐quality studies are required to further comparative effectiveness analyses to verify the efficacy of ultrasound detection. [ABSTRACT FROM AUTHOR]

Purpose: Gastric cancer (GC) is the fifth most common tumor in the world, and most patients with GC have a poor prognosis. This study aimed to explore the biological influence and mechanism of LINC01272 in GC. Materials and Methods: Using bioinformatic analyses, we investigated the expression of LINC01272 in TCGA database and predicted the biological functions and mechanism of LINC01272 in GC. Then, we detected the expression of LINC01272 in GC cell lines, GC tissues, and corresponding normal tissues using real-time polymerase chain reaction (RT-PCR). Finally, we explored the migration and invasion ability of LINC01272 by wound-healing and Transwell assays and examined the expression of epithelial-mesenchymal transition (EMT)-related proteins through Western blotting. Results: We found that LINC01272 was upregulated in GC and was associated with GC staging and lymph node metastasis. The results of wound-healing and Transwell assays revealed that the LINC01272 was closely related to GC cell migration and invasion. LINC01272 knockdown inhibited the migration and invasion ability of GC cells by reducing the expression of EMT-related proteins. Overexpression of LINC01272 had the opposite effect. Conclusion: Together, our results showed that LINC01272 promoted GC metastasis ability by regulating the expression of EMT-related proteins and could serve as a potential diagnostic biomarker for GC. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop a new, easily executed hair follicle regeneration system and assay, which could be further developed for clinical or cosmetic applications. Dissociated epidermal and dermal progenitor cells, isolated either from neonatal C57BL/6 mice or human foetal scalp tissues, were suspended in (10 μL) F12 medium and pipetted into a 1 or 2 mm‐diameter punch biopsy wounds on the back skin of immunodeficient mice. At 3 weeks after transplantation, although pigmented mouse hairs could efficiently form at the injection sites with delivery of mouse cells, none hair formed on the host mouse skin at 3 months after delivery of human cells. Under the same conditions, human follicles could be regenerated when the human skin cells were delivered onto a 2 mm size punch created on a reconstituted human skin (hRSK), which previously generated on the back of an immunodeficient mouse, but the efficiency of hair formation was low. We demonstrated that both mouse and human regenerated follicles showed normal histology and differentiation markers; moreover, the cell chasing experiment confirmed that the regenerated hair follicles were formed from transplanted cells. Compared to other current hair reconstituted assays, the Punch Assay is relatively simple and generates normal hair follicles within a smaller wound. We suggest that the punch assay is a better in vivo assay of cell trichogenicity. [ABSTRACT FROM AUTHOR]

Purpose: The main aim of this study was to introduce and explore plant growth-promoting bacteria (PGPB) indigenous to ginseng, and to evaluate their ability to improve production and quality, and effect on rhizosphere niche in ginseng. Materials and methods: Endophytic bacteria were isolated from root, stem, and leaf of ginseng from different sites and genotype in China and Korea, screened based on their beneficial properties as PGPB. Nine bacterial isolates were selected according to their plant growth properties including soluble phosphate and potassium, ammonia, auxin and siderophore producing, ACC deaminase, and antagonistic pathogen as well. Changes in ginseng after PGPB inoculation were evaluated with respect to the non-inoculated control. Results and Conclusions: The PGPB isolates were identified as genera Bacillus, Lysinibacillus, Rhizobium, Stenotrophomonas, Erwinia, Ochrobactrum, Enterobacter and Pantoea based on 16S rRNA sequences. Inoculation of G209 and G119 increased not only plant height, root length, fresh weight, and dry weight, but also root activity and the amount of ginsenosides significantly. In particular, using the Illumina Miseq platform, the native bacterial community of rhizospheric soil maintained high community diversity and increased abundance of specific bacteria. Therefore, they may be play a crucial role in sustainable ginseng cultivating in farmland. [ABSTRACT FROM AUTHOR]

Aleutian mink disease is the most important disease in the mink-farming industry worldwide. So far, few large-scale molecular epidemiological studies of AMDV, based on the NS1 and VP2 genes, have been conducted in China. Here, eight new Chinese isolates of AMDV from three provinces in north-east China were analyzed to clarify the molecular epidemiology of AMDV. The seroprevalence of AMDV in north-east China was 41.8% according to counterimmuno-electrophoresis. Genetic variation analysis of the eight isolates showed significant non-synonymous substitutions in the NS1 and VP2 genes, especially in the NS1 gene. All eight isolates included the caspase-recognition sequence NS1:285 (DQTD↓S), but not the caspase recognition sequence NS1:227 (INTD↓S). The LN1 and LN2 strains had a new 10-amino-acid deletion in-between amino acids 28-37, while the JL3 strain had a one-amino-acid deletion at position 28 in the VP2 protein, compared with the AMDV-G strain. Phylogenetic analysis based on most of NS1 (1755 bp) and complete VP2 showed that the AMDV genotypes did not cluster according to their pathogenicity or geographic origin. Local and imported ADMV species are all prevalent in mink-farming populations in the north-east of China. This is the first study to report the molecular epidemiology of AMDV in north-east China based on most of NS1 and the complete VP2, and further provides information about polyG deletions and new variations in the amino acid sequences of NS1 and VP2 proteins. This report is a good foundation for further study of AMDV in China. [ABSTRACT FROM AUTHOR]

• JMJD3 had histone demethylase activity and catalyzed H3K27me3 demethylation. • GSK-J1 inhibited JMJD3 expression and regulated the growth of specific immune cells. • H3K27me3 played a key role in regulating T cell differentiation in UC. • JMJD3 relieved DSS-induced acute UC by improving mucosal immune dysfunction. • UC might be affected by epigenetic modification of JMJD3/H3K27me3. Ulcerative colitis (UC) is a chronic nonspecific inflammatory bowel disease characterized by chronic inflammation and ulceration of the colonic mucosa, frequent relapse, and cancerization that is difficult to cure. In recent years, the incidence of UC has increased. However, its etiology and pathogenesis are still not completely clear. In this study, dextran sodium sulfate (DSS) was used to induce the model, and GSK-J1 and dexamethasone were administered to the mice. A variety of molecular biology and immunological techniques, such as immunofluorescence, PCR and chromatin immunoprecipitation (ChIP), were used to examine JMJD3/H3K27me3-mediated regulation of Th17/Treg cell differentiation in UC by targeting histone modification. This study will provide an important theoretical basis for understanding the pathogenesis and potential therapeutic targets of UC. [ABSTRACT FROM AUTHOR]

Oxygen evolution reaction has attracted extensive attention in energy conversion and storage technology (e. g. water splitting and rechargeable metal-air batteries). Its sluggish kinetics demands effective electrocatalysts to minimize the reaction barrier. Transition metal (oxy)hydroxides with a layered structure are one of the most active non-noble electrocatalysts. In this study, we compared the oxygen evolution performance of α-Co(OH)2, β-Co(OH)2 and β-CoOOH. Our results showed that α-type hydroxide is more active than β-type with 60 mV lower overpotential at 10 mA/cm2 and three times higher current density at 450 mV overpotential. The plausible reason of this superior oxygen evolution activity is likely relevant to the large interlayer space in α-type hydroxide. © 2016 Curtin University of Technology and John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Evaluation and prediction methods for heat exchangers have significantly developed over the years where the equal flow Reynolds number, equal flow velocity, and Wilson plot techniques are commonly used. However, equal flow Re and equal flow velocity techniques impose restrictions on the flow conditions and the flow passage configuration. Similarly, Wilson plot technique is applicable under a known exponent of Re . Using these techniques, it is difficult to obtain generalized correlations even for single passage because many unknowns are needed to be solved. Therefore, a simplified and handy method to develop heat transfer correlation is required to design new equipment or predict their performance. A general variance minimization method is presented to avoid the need for determination of various coefficients and exponents used in regression process. This method is validated by comparing its results with the experimental data. [ABSTRACT FROM AUTHOR]

Electroactive graphene oxide (GO) interlayers between cathode and separator are examined in a lithium–sulfur cell. The GO interlayer is bifunctional and capable for lithium storage and polysulfide trapping depending on the specific surface properties. The corresponding electrochemical behaviors were evaluated by using galvanostatic charge–discharge, cyclic voltammetry and electrochemical impedance spectroscopy. A series of GO with different oxidation degrees were synthesized by tuning modified Hummer’s method. The results revealed that hydroxyl was formed at insufficient oxidation while epoxide appeared at strong oxidation. The residual graphitic structures in weakly oxidized GO can donate electrons to improve polysulfide utilization while the enriched oxygen functional groups can react with lithium ion giving rise to higher cathode capacity. [ABSTRACT FROM AUTHOR]

The flow fields and heat transfer characteristics in a parallel-plate channel with a transversely placed spiral coil insert were investigated by three-dimensional numerical simulation. The structure of multi-longitudinal-vortices (MLVs) induced by the spiral coil and the effects of MLVs on velocity and temperature fields were studied. The three-dimensional spiral coil induces a series of longitudinal vortices in the channel including leading longitudinal vortex, mainstream longitudinal vortices, near-wall longitudinal vortices, and rear central longitudinal vortex. Transport by the longitudinal vortices can increase the mass exchange between the boundary layer and the mainstream, which speeds up the heat migration from the channel walls and enhances the heat diffusion in the mainstream. [ABSTRACT FROM AUTHOR]

Highlights: [•] LDH activity and apoptosis in TPEN-incubated neurons were markedly increased. [•] We confirmed that TPEN induces apoptosis of hippocampal neurons through inhibition of ERK pathway. [•] We show for the first time that activation of caspase-3 induced by TPEN in was mediated by ERK pathway. [ABSTRACT FROM AUTHOR]

Abstract: Valveless piezoelectric pump has low-cost and easy miniaturization characteristics, and its important development trend is multi-function integration. The current paper reports a new phenomenon that the flow in a spiral tube element is sensitive to the element attitude caused by the Coriolis force, and that a valveless piezoelectric pump is designed by applying this phenomenon. The valveless piezoelectric pump has both the actuator function of fluid transfer and the sensor function, which can obtain the angular velocity variation when its attitude changes. First, the present paper analyzes the principle of the pump and the flow characteristics in the tube. The calculation formula for the pump flow is also obtained. Second, the relationship between pump attitude and flow is identified, which theoretically verifies the gyroscopic effect of the pump. Finally, a pump is fabricated for experimental testing of the relationship between pump attitude and flow. Experimental results show that when Archimedes spiral is selected for the tube design, the pump is most efficient, and the pressure differential between pump inlet and outlet is 29mm H2O, which achieves a one-way mean flow. On the other hand, when the rotation speed of the plate is 70r/min, the pressure differential is 9mm H2O, which is 1.5 times that of 0rpm rotation speed. The spiral tube valveless piezoelectric pump can turn the element attitude into a form of pressure output, which is important for the multi-function integration of the valveless piezoelectric pump and for the development of civil gyroscope in the future. [Copyright &y& Elsevier]

Abstract: A live-attenuated highly pathogenic porcine reproductive and respiratory syndrome (HP-PRRS) virus (HP-PRRSV) TJM vaccine strain was derived from the HP-PRRSV TJ strain by passage 92 times in the African green monkey kidney epithelial cell line Marc-145. We found that the virulence of the TJ strain to piglets was decreased greatly from passage 19. To identify mutations associated with attenuation of the TJM vaccine strain, we determined the nucleotide changes that arose during Marc-145 passage of the HP-PRRSV TJ virus. The TJM strain contains a 360 nucleotide (120 amino acids) deletion and a 118 nucleotide mutation that resulted in 48 amino acid changes. Analysis of the complete nucleotide sequences of intermediate passage-level viruses F19, F46 and F78 showed that 31 (64.6%) of the 48 amino acid mutations occurred in F19, 7 (14.6%) occurred in F46, 7 (14.6%) occurred in F78 and 3 (6.3%) occurred in F92. The 120 amino acid deletion occurred from F19 to TJM. Therefore, we hypothesized that the 31 amino acid mutations distributed in nsp1β, nsp2–nsp5, nsp7, nsp9, nsp10, GP4 and GP5 and the continuous 120 amino acid deletion in the nsp2 region from F19 provide a strong potential molecular basis for the observed attenuated phenotype. [Copyright &y& Elsevier]

Abstract: Emerging evidence suggests that a high level of circulating heat shock protein 70 (HSP70) correlates with a lower risk of vascular disease; however, the biological significance of this inverse relationship has not been explored. Herein, we report that oxidative low density lipoprotein (Ox-LDL) and homocysteine (Hcy) induce HSP70 release from endothelial cells. In rat endothelial cells, Ox-LDL and Hcy induced robust release of HSP70, independent of the classical route of endoplasmic reticulum/Golgi protein trafficking or the formation of lipid rafts. In contrast, Ox-LDL and Hcy significantly enhanced the exosomal secretory rate and increased the HSP70 content of exosomes. Exogenous HSP70 had no impact on LPS-, Ox-LDL- and Hcy-induced activation of endothelial cells, whereas HSP70 did activate monocytes alone, resulting in monocyte adhesion to endothelial cells. These results indicate that exosome-dependent secretion of HSP70 from endothelial cells provides a novel paracrine mechanism to regulate vascular endothelial functional integrity. [Copyright &y& Elsevier]

Background: Minimally invasive esophagectomy is the first-line approach for esophageal cancer; however, there has recently been a paradigm shift toward robotic esophagectomy (RE). We investigated the clinical outcomes of patients who underwent RE compared with those of patients who underwent conventional minimally invasive thoracoscopic esophagectomy (TE) for locally advanced cT3 or cT4 esophageal cancer using a propensity-matched analysis. Methods: Overall, 342 patients with locally advanced cT3 or cT4 esophageal cancer underwent transthoracic esophagectomy with total mediastinal lymph node dissection between 2018 and 2022. The propensity-matched analysis was performed to assign the patients to either RE or TE by covariates of histological type, tumor location, and clinical N factor. Results: Overall, 87 patients were recruited in each of the RE and TE groups according to the propensity-matched analysis. The total complication rate and the rates of the three major complications (recurrent laryngeal nerve paralysis, anastomotic leakage, and pneumonia) were not significantly different between the RE and TE groups. However, the peak C-reactive protein concentration on postoperative day 3, rate of surgical site infection, and intensive care unit length of stay after surgery were significantly shorter in the RE group than in the TE group. No significant differences were observed in the harvested total and mediastinal lymph nodes. The total operation time was significantly longer in the RE group, while the thoracic operation time was shorter in the RE group than in the TE group. There was no significant difference between the two groups in the recurrence rate of oncological outcomes after surgery. Conclusion: RE may facilitate early recovery after esophagectomy with total mediastinal lymph node dissection and has the same technical feasibility and oncological outcomes as TE. [ABSTRACT FROM AUTHOR]

Objective: Tubular microdiskectomy (tMD) is one of the most commonly used for treating lumbar disk herniation. However, there still patients still complain of persistent postoperative residual low back pain (rLBP) postoperatively. This study attempts to develop a nomogram to predict the risk of rLBP after tMD. Methods: The patients were divided into non-rLBP (LBP VAS score < 2) and rLBP (LBP VAS score ≥ 2) group. The correlation between rLBP and these factors were analyzed by multivariate logistic analysis. Then, a nomogram prediction model of rLBP was developed based on the risk factors screened by multivariate analysis. The samples in the model are randomly divided into training and validation sets in a 7:3 ratio. The Receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the diskrimination, calibration and clinical value of the model, respectively. Results: A total of 14.3% (47/329) of patients have persistent rLBP. The multivariate analysis suggests that higher preoperative LBP visual analog scale (VAS) score, lower facet orientation (FO), grade 2–3 facet joint degeneration (FJD) and moderate-severe multifidus fat atrophy (MFA) are risk factors for postoperative rLBP. In the training and validation sets, the ROC curves, calibration curves, and DCAs suggested the good diskrimination, predictive accuracy between the predicted probability and actual probability, and clinical value of the model, respectively. Conclusion: This nomogram including preoperative LBP VAS score, FO, FJD and MFA can serve a promising prediction model, which will provide a reference for clinicians to predict the rLBP after tMD. [ABSTRACT FROM AUTHOR]

Ascorbate peroxidase (APX) is a member of class I of the heme-containing peroxidase family. The enzyme plays important roles in scavenging reactive oxygen species for protection against oxidative damage and maintaining normal plant growth and development, as well as in biotic stress responses. In this study, we identified 11 APX genes in the Populus trichocarpa genome using bioinformatic methods. Phylogenetic analysis revealed that the PtrAPX proteins were classifiable into three clades and the members of each clade shared similar gene structures and motifs. The PtrAPX genes were distributed on six chromosomes and four segmental-duplicated gene pairs were identified. Promoter cis-elements analysis showed that the majority of PtrAPX genes contained a variety of phytohormone- and abiotic stress-related cis-elements. Tissue-specific expression profiles indicated that the PtrAPX genes primarily function in roots and leaves. Real-time quantitative PCR (RT-qPCR) analysis indicated that PtrAPX transcription was induced in response to drought, salinity, high ammonium concentration, and exogenous abscisic acid treatment. These results provide important information on the phylogenetic relationships and functions of the APX gene family in P. trichocarpa. [ABSTRACT FROM AUTHOR]

Octenyl succinic anhydride modified waxy maize starch after heat-moisture treatment (HT-OSAS) is a heat-stable slowly digestible starch (SDS), but the mechanism is poorly understood. Tea polyphenols (TP), as a probe with hydrophobic moiety, were employed to study the structural basis for its slow digestion. The content of RS (8.91%) in the HT-OSAS was significantly increased by TP in a dose-dependent manner (19.06% at TP of 15%) while there is a slight decrease of SDS content (34.85–30.63%). However, after retrogradation for one week, TP significantly reduced the SDS content (29.79%–15.67%). Additionally, TP increased the hydrodynamic radius of HT-OSAS (60–102 nm), but reduced its emulsifying activity (−35%), gelatinization enthalpy (−45%), and viscosity (−66%), demonstrating an inhibitory effect of TP on the association of HT-OSAS molecules, and a compact physical structure of HT-OSAS formed through OSA-mediated hydrophobic interaction is likely the basis to its slow digestion property. Novel strategies to densify the physical structure of starch could improve the nutritional quality of starch with a slow digestion property. Rigid and compact structure of HOSA starch. Image 1 • Slowly digestible starch (SDS) is beneficial to health. • The heat-moisture treated OSA starch (HT-OSAS) is slowly digestible. • Tea polyphenol can disrupt the structure of the HT-OSAS. • HT-OSAS has a rigid and compact physical structure. [ABSTRACT FROM AUTHOR]

Purpose: Surgery for esophageal squamous cell carcinoma (ESCC) is characterized by a poor prognosis and high complication rate, resulting in a heavy symptom burden and poor health-related quality of life (QOL). We evaluated longitudinal patient-reported outcomes (PROs) to analyze the correlations between symptoms and QOL and their changing characteristics during postoperative rehabilitation. Methods: We investigated patients with ESCC who underwent minimally invasive McKeown esophagectomy at Sichuan Cancer Hospital between April 2019 and December 2019. Longitudinal data of the clinical characteristics and PROs were collected. The MD Anderson Symptom Inventory and European Organization for Research and Treatment of Cancer (EORTC) QOL questionnaires were used to assess symptoms and QOL and compare the trajectories of PROs during the investigation. Results: A total of 244 patients with ESCC were enrolled in this study. Regarding QOL, role and emotional functions returned to baseline at 1 month after surgery, and cognitive and social functions returned to baseline at 3 months after surgery. However, physical function and global QOL did not return to baseline at 1 year after surgery. At 7 days and 1, 3, 6, and 12 months after surgery, the main symptoms of the patients were negatively correlated with physical, role, emotional, cognitive, and social functions and the overall health status (P < 0.05). Conclusion: Patients with ESCC experience reduced health-related QOL and persisting symptoms after minimally invasive McKeown esophagectomy, but a recovery trend was observed within 1 month. The long-term QOL after esophagectomy is acceptable. [ABSTRACT FROM AUTHOR]

Background: Hybridization capture-based targeted next generation sequencing (NGS) is gaining importance in routine cancer clinical practice. DNA library preparation is a fundamental step to produce high-quality sequencing data. Numerous unexpected, low variant allele frequency calls were observed in libraries using sonication fragmentation and enzymatic fragmentation. In this study, we investigated the characteristics of the artifact reads induced by sonication and enzymatic fragmentation. We also developed a bioinformatic algorithm to filter these sequencing errors. Results: We used pairwise comparisons of somatic single nucleotide variants (SNVs) and insertions and deletions (indels) of the same tumor DNA samples prepared using both ultrasonic and enzymatic fragmentation protocols. Our analysis revealed that the number of artifact variants was significantly greater in the samples generated using enzymatic fragmentation than using sonication. Most of the artifacts derived from the sonication-treated libraries were chimeric artifact reads containing both cis- and trans-inverted repeat sequences of the genomic DNA. In contrast, chimeric artifact reads of endonuclease-treated libraries contained palindromic sequences with mismatched bases. Based on these distinctive features, we proposed a mechanistic hypothesis model, PDSM (pairing of partial single strands derived from a similar molecule), by which these sequencing errors derive from ultrasonication and enzymatic fragmentation library preparation. We developed a bioinformatic algorithm to generate a custom mutation "blacklist" in the BED region to reduce errors in downstream analyses. Conclusions: We first proposed a mechanistic hypothesis model (PDSM) of sequencing errors caused by specific structures of inverted repeat sequences and palindromic sequences in the natural genome. This new hypothesis predicts the existence of chimeric reads that could not be explained by previous models, and provides a new direction for further improving NGS analysis accuracy. A bioinformatic algorithm, ArtifactsFinder, was developed and used to reduce the sequencing errors in libraries produced using sonication and enzymatic fragmentation. [ABSTRACT FROM AUTHOR]

Objective: Presently, no study has compared the clinical outcomes of minimally invasive transforaminal lumbar interbody fusion (Mis-TLIF) with bilateral decompression via the unilateral approach (BDUA) and Open-TLIF with bilateral decompression for degenerative lumbar diseases (DLD). We aimed to compare the clinical outcomes of through Mis-TLIF combined with BDUA and Open-TLIF with bilateral decompression for the treatment of DLD, and reported the learning curve of the procedure of MIS-TLIF with BDUA. Methods: We retrospectively analyzed the prospectively collected data of consecutive DLD patients in the two groups from January 2016 to January 2020. Results: The operative time (OT) was significantly longer in the Mis-TLIF group (n = 113) than in the Open-TLIF group (n = 135). The postoperative drainage volume (PDV) and length of stay (LOS) were significantly higher in the Open-TLIF group than in the Mis-TLIF group. Additionally, the complication rate was significantly higher in the Open-TLIF group than in the Mis-TLIF group (14.8% vs. 6.2%, P = 0.030), while there was no significant difference in the reoperation and adjacent segment disease rates between the two groups. There were no significant differences in back pain and leg pain Numerical Rating Scale (NRS) scores and Oswestry Disability Index (ODI) between the two groups preoperatively, at discharge, and 2 years postoperatively. Patients in both groups showed significant improvements in NRS scores and ODI scores after surgery. OT was negatively correlated with the number of surgeries performed (P < 0.001, r = −0.43). The learning curve of Mis-TLIF with BDUA was steep, with OT tapered to steady state in 43 cases. Conclusion: Compared with Open-TLIF with bilateral decompression, Mis-TLIF with BDUA can achieve equivalent clinical outcomes, lower PDV and LOS, and lower complication rates. Although this procedure took longer, it could be a viable alternative for the treatment of DLD after a steep learning curve. [ABSTRACT FROM AUTHOR]

Background: The blood-brain barrier (BBB) strongly restricts the entry of anti-glioma drugs into tumor tissues and thus decreases chemotherapy efficacy. Malignant gliomas are highly invasive tumours that use the perivascular space for invasion and co-opt existing vessels as satellite tumor form. Because regulation of the effect of noncoding RNA on BBB function is attracting growing attention, we investigated the effects of noncoding RNA on the permeability of glioma conditioned normal BBB and the mechanism involved using PIWI-associated RNA piR-DQ590027 as a starting point. Methods: The mRNA levels of MIR17HG, miR-153, miR-377, ZO-1, occludin, and claudin-5 were determined using real-time PCR. Transient cell transfection was performed using Lipofectamine 3000 reagent. TEER and HRP flux were applied to measure the permeability of glioma conditioned normal BBB. Western blotting and immunofluorescence assays were used to measure ZO-1, occludin, and claudin-5 levels. Reporter vector construction and a luciferase reporter assay were performed to detect the binding sites of MIR17HG and piR-DQ590027, MIR17HG and miR-153 (miR-377), and FOXR2 and miR-153 (miR-377). RNA immunoprecipitation was used to test the interaction between miR-153 (miR-377) and its target proteins. Chromatin immunoprecipitation was performed to detect the interaction between the transcription factor FOXR2 and ZO-1, occludin, and claudin-5. Results: piR-DQ590027 was expressed at low levels in glioma-conditioned ECs (GECs) of the in vitro glioma conditioned normal BBB model. Overexpression of piR-DQ590027 down-regulated the expressions of ZO-1, occludin, and claudin-5 and increased the permeability of glioma conditioned normal BBB. MIR17HG had high expression in GECs but miR-153 and miR-377 had low expression. piR-DQ590027 bound to and negatively regulated MIR17HG. FOXR2 was a downstream target of miR-153 and miR-377; MIR17HG bound separately to miR-153 and miR-377 and negatively regulated their ability to mediate FOXR2 expression. FOXR2 associated with the promoter regions of ZO-1, occludin, and claudin-5 in GECs to promote their transcription. Conclusion: The piR-DQ590027/MIR17HG/miR-153 (miR-377)/FOXR2 pathway plays an important role in regulating glioma conditioned normal BBB permeability and provides a new target for the comprehensive treatment of glioma. [ABSTRACT FROM AUTHOR]

Background Esophageal cancer treatment is largely determined by tumor stage. Despite improvements made in the treatment of different types of this malignant disease, staging has still in continuous renewal. The role of perineural invasion (PNI) in staging remains debated. We have assessed the relation of PNI with metastatic pattern to evaluate whether PNI might add significant new information to staging. Methods We performed a systematic literature search that was focused on the PNI in esophageal cancer published up to February 2018. Studies with neoadjuvant-treated patients were excluded. Data on T stage, N stage and other characteristics were extracted. Data were analyzed for the relevance of the presence of PNI, lymph node metastases, and the tumor invasion on the depth of esophageal structure and outcomes. Results A total of 9 cohorts were retrieved, covering 2207 patients. PNIs are invariably associated with poor outcome. Moreover, a total analysis of 2207 patients showed improved PNI in T3 + T4 (OR = 0.25, 95% CI: 0.15–0.44, and P  < 0.00001), 674 of 2204 patients showed PNI more favored in N positive (OR = 0.61, 95% CI: 0.38–0.96, and P = 0.03), and 461 of 1788 patients showed improved PNI in G3 + G4 (OR = 0.70, 95% CI: 0.54–0.92, and P = 0.010) compared with T1 + T2, N − , and G1 + G2 patients, respectively. Conclusion PNI is an adverse prognostic factor in esophageal cancer. We have shown that PNIs have valuable prognostic information in advanced T, N stage and poor cell differentiation. Therefore, we propose that PNI may provide a vital clue to esophageal cancer staging in the future. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]

Although lumbar disc herniation (LDH) patients' sciatic symptoms such as leg pain can be improved by decompressive surgery, some patients report postoperative aggravated low back pain (LBP). However, the exact reason for this phenomenon remained unknown. We retrospectively analyzed the prospectively collected LDH data of patients who underwent tubular microdiscectomy between December 2015 and December 2020. The patients were divided into aggravated and non-aggravated group according to whether the postoperative LBP visual analogue scale (VAS) score was higher than the preoperative score. We analyzed the relationship of the clinical and radiologic parameters with aggravated LBP. Postoperative aggravated LBP cases accounted for 14.1% (57 of 404) of this series. Of the 57 patients, 88% (50 of 57) had mild postoperative LBP aggravation (1–2), and 12% (7 of 57) had severe LBP aggravation (>2). The preoperative LBP VAS score of the aggravated group was significantly lower than that of the non-aggravated group (P < 0.001), while the LBP VAS score and Oswestry Disability Index at final follow-up was significantly higher in the aggravated group (P < 0.05). Additionally, the proportion of preoperative moderate-to-severe multifidus fatty atrophy (MFA) and lumbar facet joint degeneration (LFJD) was significantly higher in the aggravated group. A multiple stepwise logistic regression analysis indicated that the preoperative LBP VAS score (P < 0.001, odds ratio 0.266, 95% CI 0.161–0.439) and MFA (P < 0.001, odds ratio 4.491, 95% CI 2.092-9.640) were the risk factors for postoperative aggravated LBP. A preoperative lower LBP VAS score and moderate-to-severe MFA were associated with postoperative aggravated LBP. This will provide important guidance for patient's preoperative assessment and education. [ABSTRACT FROM AUTHOR]

Introduction: Although the anatomy and pathology of lumbar disc herniation (LDH) have been clearly defined and classified in many studies, its imaging definition and classification still needs further clarification. This study intends to propose a novel classification and individualized surgical strategy for LDH based on preoperative magnetic resonance imaging (MRI). Materials and methods: According to MRI features, LDH types were identified, and the corresponding surgical strategies were formulated to accurately remove the herniated discs while minimizing the disturbance to the normal disc. We retrospectively analyzed prospectively collected data of LDH patients who underwent surgery guided by this classification system. Results: This study included 357 patients with LDH who underwent tubular microdiscectomy. LDH was classified into four types based on MRI features. The inter- and intra-observer agreement using this classification was good. The follow-up results showed that surgery improved visual analog scale scores for low-back and leg pain and the Oswestry disability index in patients with different LDH types. The average recurrence rate at 1–5 years postoperatively was 5.62%. There was no significant difference in recurrence rates among the four LDH types (3.7–6.2%). MRI showed no significant differences in the Pfirrmann grade and disc height index of the operated segment between before surgery and 1–3 years after surgery. The operated segments did not show faster disc degeneration rates compared to adjacent proximal segments. Conclusions: We proposed a novel classification system and an individualized surgical strategy for LDH based on preoperative MRI. Further, the surgical suitable interventions guided by this system achieved good clinical outcomes and mild recurrence rates. [ABSTRACT FROM AUTHOR]

This paper introduces a new calibration method for the mapping camera called Precise Grouped Approach Method (PGAM). The conventional calibration method for the mapping camera is the exact measuring angle method. The accuracy of this method can be reduced by theoretical uncertainties and the number and distribution of observation points. PGAM is able to overcome these disadvantages and improve the accuracy. Firstly, we reduce the theoretical uncertainties by means of a grouped approach method, which rectifies the high-precision rotation stage to zero position. Secondly, a weighted theory is applied to eliminate the effect of the number and distribution of observation points. Finally, the accuracy of PGAM is analyzed. The experiment result shows that the calibration accuracy is significantly improved when using the proposed PGAM algorithm, compared to the conventional one under the identical experimental condition. [ABSTRACT FROM AUTHOR]

The precise diagnosis and treatment of spinal infections (SI) remains challenging for spine surgeons. Identifying the pathogens of SI through metagenomic next-generation sequencing (mNGS) may be a key approach to addressing this challenge. To evaluate the accuracy and applicability of mNGS in determining the etiology of SI. Diagnostic test study. Twenty-five patients who had a clinical suspicion of SI and underwent mNGS testing. The specificity, sensitivity, and time cost of mNGS and bacterial culture were compared. Clinical outcomes were assessed using the numeric rating scale (NRS) score, Oswestry Disability Index (ODI), and the Japanese Orthopedic Association (JOA) score. Demographic data and laboratory results (blood cell count (WBC), erythrocyte sedimentation rate (ESR), neutrophil percentage (NEUT%), and C-reactive protein level (CRP) were also evaluated. In this retrospective study, samples were obtained from 25 eligible patients via surgery or CT-guided puncture and subjected to histopathological examination, bacterial culture, and mNGS. The sensitivity and specificity of the bacterial cultures and mNGS were calculated with respect to the histopathological results as a reference. Postoperative antibiotics or antituberculosis drugs were administered on the basis of mNGS results, combined with clinical manifestations, imaging examination, and histopathology. The changes of clinical outcomes and laboratory results after treatment were observed. Of the 25 patients, 21 had a positive pathology, of which 10 showed a tuberculous pathology, and the remaining 11 showed a nontuberculous inflammatory pathology. The sensitivity of mNGS was higher than that of the bacterial culture. However, the difference in specificity between bacterial culture and mNGS was not significant. Moreover, the time needed to perform mNGS was significantly lower than that of bacterial culture and pathology. All patients were followed up for more than three months, and CRP and NEUT% significantly decreased by three months after treatment. There was no significant difference in WBC and ESR. The ODI, NRS and JOA scores were significantly improved after treatment. Metagenomic next-generation sequencing technology can play an important role in the detection of pathogens in SI and should be further investigated and applied in future studies. [ABSTRACT FROM AUTHOR]

Small molecule covalent drugs have proved to be desirable therapies especially on drug resistance related to point mutations. Secondary mutations of FLT3 have become the main mechanism of FLT3 inhibitors resistance which further causes the failure of treatment. Herein, a series of 4‐(4‐aminophenyl)‐6‐phenylisoxazolo[3,4‐b]pyridine‐3‐amine covalent derivatives were synthesized and optimized to overcome the common secondary resistance mutations of FLT3. Among these derivatives, compound F15 displayed potent inhibition activities against FLT3 (IC50 = 123 nM) and FLT3‐internal tandem duplication (ITD) by 80% and 26.06%, respectively, at the concentration of 1 μM. Besides, F15 exhibited potent activity against FLT3‐dependent human acute myeloid leukemia (AML) cell lines MOLM‐13 (IC50 = 253 nM) and MV4‐11 (IC50 = 91 nM), as well as BaF3 cells with variety of secondary mutations. Furthermore, cellular mechanism assays indicated that F15 inhibited phosphorylation of FLT3 and its downstream signaling factors. Notably, F15 could be considered for further development as potential drug candidate to treat AML. [ABSTRACT FROM AUTHOR]

Intervertebral release (IVR) in the apical region is critical for full release of a rigid spine. Previous studies have mainly reported IVR techniques using an anterior approach or posterior apical convex IVR. We first report the surgical procedure of posterior multisegment apical convex plus concave IVR combined with posterior column osteotomy (PCO) for treating rigid thoracic/thoracolumbar scoliosis. This study retrospectively analyzed clinical, radiologic outcomes and technique notes of 18 patients with rigid scoliosis treated with posterior multisegment convex plus concave IVR combined with PCO. The preoperative, postoperative, and final follow-up mean sagittal Cobb angles of the main curve were 75.2° (58.7°–110.2°), 18.4° (9°–35.1°), and 19.0° (8.2°–36.3°), respectively. The mean correction rate was 75.3% (66.7%–86.7%). In cases of thoracolumbar kyphosis, the preoperative, postoperative, and final follow-up mean sagittal Cobb angles were 45.7° (40.5°–52.6°), 18.8° (10.2°–27.5°), and 19.8° (11.1°–29°), respectively. The mean correction rate was 57% (42.1%–72.6%). The mean axial vertebral rotation (AVR) in the IVR region was 24.4° (14.3°–46.3°) preoperatively and was corrected to 10.9° (10.9°–26.6°) postoperatively. The mean correction rate for AVR was 55.9% (41.1%–78.6%). The coronal and sagittal Cobb angles and AVR postoperatively were significantly lower than those preoperatively (P < 0.001). This case series reported 2 cases of pleural effusion and 1 case of wound infection. Single posterior multilevel apical convex plus concave IVR combined with PCO is a safe and effective surgical method for treating rigid thoracic/thoracolumbar scoliosis that does not need 3-column osteotomy. [ABSTRACT FROM AUTHOR]

Several biological processes as well as infectious agents, physiological or environmental stress, and perturbed antioxidant response can promote oxidative stress. Oxidative stress usually happens when cells are exposed to more electrically charged reactive oxygen species (ROS) such as HO or O . ROS are well known for being both beneficial and deleterious. Recent studies have indicated that ROS are deleterious to cells, leading to programmed cell death (PCD) at high concentrations. At low concentrations, however, ROS can act as signaling molecules in a variety of cellular processes. In this review, we present an update of our current understanding of the role and regulation of reactive oxygen species in various viral infections, cellular signaling pathways and immune responses. We then discuss how the antioxidant defense system acts as an antiviral effector to limit cell damage. [ABSTRACT FROM AUTHOR]

An effective procedure for synthesis of amides from alkenes and PhI NTs via Pd and Fe catalysts under mild conditions is described. A series of benzamides containing various functional groups can be obtained in reasonable yield and the possible reaction pathway is proposed in this Letter. [ABSTRACT FROM AUTHOR]

Background and Aim: Programmed death‐ligand 1 (PD‐L1) was involved in regulating Th17/Treg cell balance in ulcerative colitis (UC). Extracellular vesicles (EVs) from genetically modified bone marrow mesenchymal stem cells (BMSCs) can serve as a stable delivery system to overexpress PD‐L1. The study was designed to evaluate the therapeutic mechanism of BMSC‐EVs overexpressing PD‐L1 (PD‐L1‐EVs) on ulcerative colitis. Methods: Experimental model of UC was established in rats by drinking 5% dextran sulfate sodium (DSS). Apoptosis‐related proteins, inflammatory response‐related factors and oxidative stress related mediators were detected. Westernblot was used to detecte key proteins in the PI3K/AKT signaling pathway and its downstream effectors. The CD4+Foxp3+Treg cells and CD4+IL‐17A+Th17 cells in spleen and mesenteric lymph nodes (MLNs) was detected by flow cytometry. Results: PD‐L1‐EVs significantly alleviated the manifestations and pathological damage of UC rats by inhibiting the expression of IFN‐γ, IL‐1β, IL‐8, IL‐6, IL‐2, BAX, NF‐κB, TNF‐α, MPO, and MDA, and up‐regulating the expression of IL‐4, BCL‐2, SOD, and GSH. Furthermore, the proportions of Th17 cells were decreased and that of Treg cells were upregulated by PD‐L1‐EVs treatment. PTEN inhibitors (bpv) partially abolished the inhibitory effect of PD‐L1‐EVs on PI3K‐AKT signaling and impaired the therapeutic efficacy of PD‐L1‐EVs. Conclusions: PD‐L1‐EVs mitigated colonal inflammation, apoptosis and oxidative stress through blocking the activation of PI3K/Akt/mTOR pathway and regulating the balance of Th17/Treg cells. [ABSTRACT FROM AUTHOR]

[Display omitted] • A series of 4-(4-aminophenyl)-6-methylisoxazolo[3,4-b] pyridin-3-amine derivatives as FLT3 covalent inhibitors were designed and synthesized. • Compound C14 was potent to inhibit FLT3 (IC 50 = 256 nM) and had strong inhibitory activity against the human AML cell lines MOLM-13 (IC 50 = 507 nM) as well as MV4-11 (IC 50 = 325 nM). • The mechanism of C14 against FLT3 was explored. • Compound C14 could be a promising agent for further developing therapeutic remedy for AML. Fms-like tyrosine kinase 3 (FLT3) mutation has been strongly associated with increased risk of relapse, and the irreversible covalent FLT3 inhibitors had the potential to overcome the drug-resistance. In this study, a series of simplified 4-(4-aminophenyl)-6-methylisoxazolo[3,4-b] pyridin-3-amine derivatives containing two types of Michael acceptors (vinyl sulfonamide, acrylamide) were conveniently synthesized to target FLT3 and its internal tandem duplications (ITD) mutants irreversibly. The kinase inhibitory activities showed that compound C14 displayed potent inhibition activities against FLT3 (IC 50 = 256 nM) and FLT3-ITD by 73 % and 25.34 % respectively, at the concentration of 1 μM. The antitumor activities indicated that C14 had strong inhibitory activity against the human acute myeloid leukemia (AML) cell lines MOLM-13 (IC 50 = 507 nM) harboring FLT3-ITD mutant, as well as MV4-11 (IC 50 = 325 nM) bearing FLT3-ITD mutation. The biochemical analyses showed that these effects were related to the ability of C14 to inhibit FLT3 signal pathways, and C14 could induce apoptosis in MV4-11 cell as demonstrated by flow cytometry. Fortunately, C14 showed very weak potency against FLT3-independent human cervical cancer cell line HL-60 (IC 50 > 10 μM), indicating that it might have no off-target toxic effects. In light of these data, compound C14 represents a novel covalent FLT3 kinase inhibitor for targeted therapy of AML. [ABSTRACT FROM AUTHOR]

Infectious respiratory disease is one of the most common diseases in dogs worldwide. Several bacterial and viral pathogens can serve as causative agents of canine infectious respiratory disease (CIRD), including Mycoplasma cynos , Mycoplasma canis , Bordetella bronchiseptica , canine adenovirus type 2 (CAdV-2), canine herpesvirus 1 (CHV-1), canine parainfluenza virus (CPIV), canine distemper virus (CDV), canine influenza virus (CIA) and canine respiratory coronavirus (CRCoV). Since these organisms cause similar clinical symptoms, disease diagnosis based on symptoms alone can be difficult. Therefore, a quick and accurate test is necessary to rapidly identify the presence and relative concentrations of causative CIRD agents. In this study, a multiplex real-time PCR panel assay was developed and composed of three subpanels for detection of the aforementioned pathogens. Correlation coefficients (R2) were >0.993 for all singleplex and multiplex real-time PCR assays with the exception of one that was 0.988; PCR amplification efficiencies (E) were between 92.1% and 107.8% for plasmid DNA, and 90.6–103.9% for RNA templates. In comparing singular and multiplex PCR assays, the three multiplex reactions generated similar R2 and E values to those by corresponding singular reactions, suggesting that multiplexing did not interfere with the detection sensitivities. The limit of detection (LOD) of the multiplex real-time PCR for DNA templates was 5, 2, 3, 1, 1, 1, 4, 24 and 10 copies per microliter for M. cynos, M. canis, B. brochiseptica , CAdV-2, CHV-1, CPIV, CDV, CIA and CRCoV, respectively; and 3, 2, 6, 17, 4 and 8 copies per microliter for CAdV-2, CHV-1, CPIV, CDV, CIA and CRCoV, respectively, when RNA templates were used for the four RNA viruses. No cross-detection was observed among the nine pathogens. For the 740 clinical samples tested, the newly designed PCR assay showed higher diagnostic sensitivity compared to an older panel assay; pathogen identities from selected samples positive by the new assay but undetected by the older assay were confirmed by Sanger sequencing. Our data showed that the new assay has higher diagnostic sensitivity while maintaining the assay's specificity, as compared to the older version of the panel assay. • A real-time PCR assay was developed for nine canine respiratory pathogen detections; • Multiplexed reactions generated similar sensitivity as of singular reactions; • No cross reaction among the nine pathogens was observed; • PCR amplification efficiencies were between 90.6% and 107.8% with R2 > 0.99; • Limit of detections were between 5 and 120 copies per PCR reaction. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM), a cancer of plasma cells, is the second most common hematological malignancy which is characterized by aberrant plasma cells infiltration in the bone marrow and complex heterogeneous cytogenetic abnormalities. Over the past two decades, novel treatment strategies such as proteasome inhibitors, immunomodulators, and monoclonal antibodies have significantly improved the relative survival rate of MM patients. However, the development of drug resistance results in the majority of MM patients suffering from relapse, limited treatment options and uncontrolled disease progression after relapse. There are urgent needs to develop and explore novel MM treatment strategies to overcome drug resistance and improve efficacy. Here, we review the recent small molecule therapeutic strategies for MM, and introduce potential new targets and corresponding modulators in detail. In addition, this paper also summarizes the progress of multi-target inhibitor therapy and protein degradation technology in the treatment of MM. [Display omitted] • The current challenges and urgency of drug resistance in multiple myeloma (MM). • Emerging potential targets and innovative therapeutic strategies to overcome drug resistance in MM. • Mechanisms of action, structure-activity relationships, binding-modes to targets and efficacy of novel anti-MM drugs. [ABSTRACT FROM AUTHOR]

V-doped TiO 2 /diatomite composite photocatalysts with different vanadium concentrations were synthesized by a modified sol–gel method. The diatomite was responsible for the well dispersion of TiO 2 nanoparticles on the matrix and consequently inhibited the agglomeration. V-TiO 2 /diatomite hybrids showed red shift in TiO 2 absorption edge with enhanced absorption intensity. Most importantly, the dopant energy levels were formed in the TiO 2 bandgap due to V 4+ ions substituted to Ti 4+ sites. The 0.5% V-TiO 2 /diatomite photocatalyst displayed narrower bandgap (2.95 eV) compared to undoped sample (3.13 eV) and other doped samples (3.05 eV) with higher doping concentration. The photocatalytic activities of V doped TiO 2 /diatomite samples for the degradation of Rhodamine B under stimulated solar light illumination were significantly improved compared with the undoped sample. In our case, V 4+ ions incorporated in TiO 2 lattice were responsible for increased visible-light absorption and electron transfer to oxygen molecules adsorbed on the surface of TiO 2 to produce superoxide radicals O 2 – , while V 5+ species presented on the surface of TiO 2 particles in the form of V 2 O 5 contributed to e – –h + separation. In addition, due to the combination of diatomite as support, this hybrid photocatalyst could be separated from solution quickly by natural settlement and exhibited good reusability. [ABSTRACT FROM AUTHOR]

Here, we report a model for studying wound repair based on skin regenerated from human tissue culture-expanded cells. The reconstituted skin (hRSK) responds to injury similar to that of intact human skin, and its constituent cells contribute to the healing process. As we have demonstrated that hRSK composed of GFP-labelled cells also heals 'normally,' we believe this model will be useful in analysing the wound repair process using genetically modified human cells. [ABSTRACT FROM AUTHOR]

[Display omitted] Acute myeloid leukemia (AML) is the most common type of blood cancer and has been strongly correlated with the overexpression of Fms-like tyrosine kinase 3 (FLT3), a member of the class III receptor tyrosine kinase family. With the emergence of FLT3 internal tandem duplication alteration (ITD) and tyrosine kinase domain (TKD) mutations, the development of FLT3 small molecule inhibitors has become an effective medicinal chemistry strategy for AML. Herein, we have designed and synthesized two series of 1 H -pyrrolo[2,3- b ]pyridine derivatives CM1 – CM24 , as FLT3 inhibitors based on F14 , which we previously reported, that can target the hydrophobic FLT3 back pocket. Among these derivates, CM5 showed significant inhibition of FLT3 and FLT3-ITD, with inhibitory percentages of 57.72 % and 53.77 % respectively at the concentration of 1 μΜ. Furthermore, CM5 demonstrated potent inhibition against FLT3-dependent human AML cell lines MOLM-13 and MV4-11 (both harboring FLT3 - ITD mutant), with IC 50 values of 0.75 μM and 0.64 μM respectively. In our cellular mechanistic studies, CM5 also effectively induces apoptosis by arresting cell cycle progression in the G0/G1 phase. In addition, the amide and urea linker function were discussed in detail based on computational simulations studies. CM5 will serve as a novel lead compound for further structural modification and development of FLT3 inhibitors specifically targeting AML with FLT3 - ITD mutations. [ABSTRACT FROM AUTHOR]

Disruption of intervertebral disc (IVD) homeostasis caused by oxidative stress and nucleus pulposus cell (NPC) senescence is a main cause of intervertebral disc degeneration (IDD). The sonic hedgehog (Shh) pathway plays an important role in IVD development, but its roles in IDD are unknown. This study aimed to investigate the effects of the Shh pathway on the alleviation of IDD and the related mechanisms. In vivo, the effect of the Shh pathway on IVD homeostasis was studied by intraperitoneal injection of recombinant Shh (rShh) and GANT61 based on puncture-induced IDD. GANT61, lentivirus-coated sh-Gli1 and rShh were used to investigate the role and mechanism of the Shh pathway in NPCs based on senescence induced by Braco19 and oxidative stress induced by TBHP. Shh pathway expression decreased, and senescence and oxidative stress increased with age. Intraperitoneal injection of rShh activated the Shh pathway to suppress oxidative stress and NPC senescence and consequently alleviated needle puncture-induced IDD. In vitro, the Shh pathway upregulated glutathione peroxidase 4 (GPX4) expression to suppress oxidative stress and senescence in NPCs. Moreover, GPX4 suppression in NPCs by si-GPX4 significantly reduced the protective effect of the Shh pathway on oxidative stress and senescence in NPCs. Our results demonstrate for the first time that the Shh pathway plays a key role in the alleviation of IDD by suppressing oxidative stress and cell senescence in NP tissues. This study provides a new potential target for the prevention and reversal of IDD. [Display omitted] • Shh pathway contributes to IVD homeostasis maintenance. • Shh pathway alleviates the oxidative stress in NP effectively. • GPX4 mediates the anti-senescence and antioxidative effects of Shh pathway on NP cells. • Shh pathway reduces the oxidative stress of NPCs by GPX4 to suppress NPC senescence and alleviates IDD. [ABSTRACT FROM AUTHOR]

Background: Swine coccidiosis, a protozoan disease caused by coccidia, can result in diarrhoea and weight loss in piglets and even economic losses in the pig industry. Here, we report the first systematic review and meta-analysis of the prevalence of coccidia (including Eimeria spp. and Cystoisospora suis) in pigs in China. Methods: Five databases (PubMed, ScienceDirect, Chinese Web of Knowledge, Wanfang, and Chongqing VIP) were searched and 50 studies (46,926 domestic pigs, 22 provinces) ultimately identified pertaining to the prevalence of coccidia infection from 1980 to 2019. We incorporated the effect size using the random-effects model in the "meta" package in R software and conducted univariate and multivariate meta-regression analyses using a mixed-effects model. Results: The pooled prevalence rate of coccidia in pigs was 21.9%, including the C. suis infection rate of 9.1%. The highest prevalence of coccidia (39.6%) was found in northwest China, and this region also presented the lowest prevalence of C. suis (4.7%). In the subgroup analysis based on sampling year, the highest prevalence of coccidia was detected in 2001 or earlier (32.6%), whereas the lowest rate was found in 2012 or later (14.3%). An opposite trend was observed for C. suis (5.5% in 2000 or earlier vs 14.4% in 2000 or later). The prevalence of coccidia in extensive farming systems (29.5%) was higher than that in intensive farming systems (17.3%). In contrast, the point estimate of C. suis prevalence was lower in the extensive farming systems (5.1%) than in the intensive farming systems (10.0%), but the difference was not significant (P > 0.05). Among the four age categories, the highest total coccidia prevalence (26.2%) was found in finishing pigs, followed by suckling piglets (19.9%), whereas the highest prevalence of C. suis (14.9%) was observed in suckling piglets. Conclusions: Our findings suggest that coccidia infection in Chinese pigs is common, although the prevalence of C. suis in pigs does not receive sufficient attention. We recommend the rational use of anticoccidial drugs to avoid drug resistance and the development of preventive and control measures for C. suis to reduce the incidence of swine coccidiosis. [ABSTRACT FROM AUTHOR]

The Qinshui Basin in China is a major area for exploration and development of high rank coalbed methane. Due to the high rank coal and complicated pore system, no substantial breakthrough in the exploration and development of coalbed methane has been made until now. Many systematic tests show that a pore system of coal reservoir has some features as follows: the porosity is relatively low; the pore system is dominated by micropores and transition pores; mesopores take the second place, and macropores are nearly absent, which is exceedingly adverse for production of coal-bed methane. However, testing data also revealed the differential development for the pore of high rank coal reservoirs in the Qinshui Basin, which necessarily led to the different physical properties of desorption, diffusion and permeability. This paper classifies the testing data using cluster analysis method and selects the typical samples to establish four pore system models, analyzes the differences of reservoir physical property, and provides a guidance for the exploration and development of coalbed methane in the Qinshui Basin. [ABSTRACT FROM AUTHOR]

Chlamydia is a small gram-negative (G−) microorganism that can be dangerous to human and animals. In this study, we conducted a systematic review and meta-analysis of Chlamydia infection in swine in China. From PubMed, ScienceDirect, Chinese Web of knowledge (CNKI), VIP Chinese journal database, and Wanfang database, we collected a total of 72 publications reported in 1985–2020. The prevalence of Chlamydia was 22.48% in China. In the sampling year subgroup, the prevalence after 2011 was the highest (26.14%). In southern China, the prevalence was 30.97%. By contrast, the prevalence in northern China was only 10.79%. Also the difference was significant (p < 0.05). In the provincial level, Hubei had the highest rate of 36.23%. Boars had a higher prevalence (29.47%). The prevalence of Chlamydia detection in pigs with reproductive disorders (21.86%) was higher than that without reproductive disorders. Among the three age groups, finishing pigs (21.43%) had the highest prevalence. The prevalence in large-scale farmed pigs (28.58%) was the highest in the subgroup of feeding methods. The prevalence in farms was 24.29%, which was the highest in the survey areas. The prevalence in spring was the highest with 40.51%. Other methods had the highest prevalence (39.61%) than enzyme-linked immunosorbent assay (ELISA) and indirect hemagglutination assay. The prevalence of Chlamydia psittaci 18.41% was lower than the prevalence of Chlamydia abortus (41.35%). We also analyzed the impact of different climate factor subgroups (rainfall, temperature, and humidity) on the probability of pigs suffering from the disease. The results showed that Chlamydia was widespread in pigs in China. We suggest that we should strengthen the detection of Chlamydia in the semen of breeding pigs and pigs with reproductive disorders, and reasonably control the environment of large-scale pig farms, so as to reduce further infection of Chlamydia in pigs. [ABSTRACT FROM AUTHOR]

Background: Swine coccidiosis, a protozoan disease caused by coccidia, can result in diarrhoea and weight loss in piglets and even economic losses in the pig industry. Here, we report the first systematic review and meta-analysis of the prevalence of coccidia (including Eimeria spp. and Cystoisospora suis) in pigs in China. Methods: Five databases (PubMed, ScienceDirect, Chinese Web of Knowledge, Wanfang, and Chongqing VIP) were searched and 50 studies (46,926 domestic pigs, 22 provinces) ultimately identified pertaining to the prevalence of coccidia infection from 1980 to 2019. We incorporated the effect size using the random-effects model in the "meta" package in R software and conducted univariate and multivariate meta-regression analyses using a mixed-effects model. Results: The pooled prevalence rate of coccidia in pigs was 21.9%, including the C. suis infection rate of 9.1%. The highest prevalence of coccidia (39.6%) was found in northwest China, and this region also presented the lowest prevalence of C. suis (4.7%). In the subgroup analysis based on sampling year, the highest prevalence of coccidia was detected in 2001 or earlier (32.6%), whereas the lowest rate was found in 2012 or later (14.3%). An opposite trend was observed for C. suis (5.5% in 2000 or earlier vs 14.4% in 2000 or later). The prevalence of coccidia in extensive farming systems (29.5%) was higher than that in intensive farming systems (17.3%). In contrast, the point estimate of C. suis prevalence was lower in the extensive farming systems (5.1%) than in the intensive farming systems (10.0%), but the difference was not significant (P > 0.05). Among the four age categories, the highest total coccidia prevalence (26.2%) was found in finishing pigs, followed by suckling piglets (19.9%), whereas the highest prevalence of C. suis (14.9%) was observed in suckling piglets. Conclusions: Our findings suggest that coccidia infection in Chinese pigs is common, although the prevalence of C. suis in pigs does not receive sufficient attention. We recommend the rational use of anticoccidial drugs to avoid drug resistance and the development of preventive and control measures for C. suis to reduce the incidence of swine coccidiosis. [ABSTRACT FROM AUTHOR]

Background: Echinococcosis (canine Echinococcus disease) is a neglected tropical disease that causes serious public harm. Dogs, as a terminal host of Echinococcus spp., are a key part of the Echinococcus epidemic. Echinococcosis spreads easily in humans and animals in some areas of China and it is therefore necessary to fully understand the prevalence of Echinococcus spp. in dogs. Methodology/Principal findings: PubMed, ScienceDirect, Chongqing VIP, China National Knowledge Infrastructure (CNKI), and WanFang databases were searched for relevant articles published in the past 10 years. A final total of 108 studies were included. The overall prevalence of Echinococcus spp. in dogs in China was 7.3%, with the highest point estimate found in sampling year 2015 (8.2%) and publication year 2015 (16.5%). Northwestern China (7.9%) had the highest infection rate in China. Qinghai Province (13.5%) showed the highest prevalence among the 11 provinces we included. We also found that geographical and climatic factors are related to the incidence of canine echinococcosis. We further investigated the source of heterogeneity by analysis of subgroups (sampling district, detection method, dog type, season, parasite species, medication, and study quality level). Conclusions/Significance: Our research indicated that Echinococcus spp. were still prevalent in some areas in China. More localized prevention and control policies should be formulated, including improving drinking water hygiene and strengthening hygiene promotion. We recommend the rational use of anti-Echinococcus drugs. In addition, treatment of livestock offal and feces and improving the welfare of stray dogs may play an important role in reducing canine Echinococcus infections. Author summary: Echinococcosis is a neglected zoonotic disease caused by the larval form of Echinococcus spp. tapeworms. It is prevalent in parts of China although unevenly distributed. The dog is one of the terminal hosts of Echinococcus spp., which is key in controlling the epidemic of canine echinococcosis. We constructed the first meta-analysis to assess the epidemic of Echinococcus in dogs in China over the past 10 years, and analyzed potential risk factors. We analyzed 108 studies of Echinococcus in dogs in China and evaluated the infection status and potential risk factors. The influential factors included province, geographical and climatic factors, publication year, sampling district category, detection methods, dog classification, medication, and the quality level of included studies. These important findings explain the differences in prevalence of canine echinococcosis in parts of China, and help to prevent the disease and reduce the risk to the public. [ABSTRACT FROM AUTHOR]

The therapeutic benefits of available FLT3 inhibitors for AML are limited by drug resistance, which is related to mutations, as well toxicity caused by off-target effects. In this study, we introduce a new small molecule FLT3 inhibitor called danatinib, which was designed to overcome the limitations of currently approved agents. Danatinib demonstrated greater potency and selectivity, resulting in cytotoxic activity specific to FLT3-ITD and/or FLT3-TKD mutated models. It also showed a superior kinome inhibition profile compared to several currently approved FLT3 inhibitors. In diverse FLT3-TKD models, danatinib exhibited substantially improved activity at clinically relevant doses, outperforming approved FLT3 inhibitors. In vivo safety evaluations performed on the granulopoiesis of transgenic myeloperoxidase (MPO) zebrafish and mice models proved danatinib to have an acceptable safety profile. Danatinib holds promise as a new and improved FLT3 inhibitor for the treatment of AML, offering long-lasting remissions and improved overall survival rates. [Display omitted] • Danatinib displayed increased potency and selectivity. • Danatinib showed a superior kinome inhibition profile. • Danatinib significantly enhanced activity at clinically relevant doses. • Danatinib had an acceptable safety profile. [ABSTRACT FROM AUTHOR]