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C-type lectin (CTL) plays a vital role in parasite adhesion, invading host's cells and immune escape. The objective of this research was to explore whether recombinant T. spiralis CTL (rTsCTL) binding with syndecan-1 damages intestine epithelial integrity and mediates T. spiralis intrusion in mice. The results showed that rTsCTL interacted with syndecan-1 and activated STAT3 pathway in gut epithelium, decreased tight junctions (TJs) expressions and damaged gut epithelium integrity, promoted T. spiralis intrusion, and increased expression level of inflammatory cytokine and mucin. The syndecan-1 inhibitor (β-xyloside) and STAT3 phosphorylation inhibitor (Stattic) significantly suppressed syndecan-1 expression and STAT3 pathway activation, reduced the expression levels of TJs, pro-inflammatory cytokines (TNF-α and IL-1β), Muc2 and Muc5ac, and declined intestinal permeability in T. spiralis-infected mice. These results revealed that the inhibitors suppressed T. spiralis invasion and development in gut mucosa, decreased intestinal adult burdens and relieved gut inflammation. These findings further testified that the in vivo binding of TsCTL with syndecan-1 destroyed enteral mucosal epithelial integrity and promoted T. spiralis intrusion of gut mucosa via activating STAT3 pathway and decreasing TJs expression. TsCTL could be deemed as a promising vaccine target to interrupt T. spiralis infection., Competing Interests: Declaration of competing interest The authors declare that they have no competing financial interests or personal relationships that influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Long-chain fatty acid transport protein 1 (FATP1) is a member of the fatty acid transporter family. It facilitates transmembrane transport of fatty acids and participates in lipid metabolism. Lipids are essential components of the cell and organelle membranes of Trichinella spiralis. The nematode has lost the capacity to synthesise the necessary lipids de novo and has instead evolved to obtain fatty acids and their derivatives from its host. This study aims to ascertain the primary biological characteristics and roles of T. spiralis FATP1 (TsFATP1) in lipid metabolism, larval moulting, and the development of this nematode. The results show that TsFATP1 is highly expressed at enteral T. spiralis stages, mainly localised at the cuticle, the stichosome and the intrauterine embryos of the parasite. The silencing of the TsFATP1 gene by TsFATP1-specific dsRNA significantly decreases the expression levels of TsFATP1 in the worm. It reduces the contents of ATP, triglycerides, total cholesterol, and phospholipids both in vitro and in vivo. RNAi inhibits lipid metabolism, moulting, and the growth of this nematode. The results demonstrate that TsFATP1 plays an essential role in lipid metabolism, moulting, and the development of T. spiralis. It could also be a target candidate for the anti-Trichinella vaccine and drugs., (© 2024. The Author(s).)

Background: The pollution of organophosphate flame retardants (OPFRs) is of global concern, but the site-specific data of OPFR concentrations in drinking water are scarce for many areas of the world outside of Europe and the US. This study aimed to investigate the occurrence and profiles of OPFRs in the tap water treatment and delivery process in Shanghai., Methods: In total, 106 samples were analyzed for 10 OPFRs, which were collected periodically from monitoring points of drinking water treatment plants and piped water between November 2021 and July 2023. The average daily doses of OPFRs through the ingestion of tap water were calculated by multiplying nominal volumes of water ingestion rates with the measured concentrations of OPFRs. Hazard quotients, the hazard index, and the carcinogenic risks of OPFRs via drinking water were used to estimate the health risks., Results: Tributyl phosphate (TBP), tris(2-chloroethyl) phosphate (TCEP), and tris (1-chloro-2-propyl) phosphate (TCIPP) were found in >90% of the tap water samples, whereas triethyl phosphate (TEP) and tris (2,3-dibromopropyl) phosphate (TDBPP) were not found in any samples. The concentrations of Σ 10 OPFRs were found at part-per-trillion ranges, with average concentrations that ranged from 86.0 ng/L in February 2023 (dry season) to 218 ng/L in July 2022 (wet season). TCIPP was the most abundant compound among the investigated OPFRs. The average daily dose of Σ 10 OPFRs via the ingestion of tap water was up to 20.4 ng/kg body weight/day. The hazard quotients of OPFRs through drinking water were in the range of 10 -5 -10 -4 , indicating low risk levels. Moreover, the hazard index of OPFRs indicated that the risk for children (2 × 10 -4 ) was higher than adults (7 × 10 -5 )., Conclusion: Tap water intake may be an important source of OPFRs exposure. But the risk of OPFRs for local residents is at a low level through drinking water.

As a remote and non-contact stimulus, light offers the potential for manipulating the polarization of ferroelectric materials without physical contact. However, in current research, the non-contact write-read (erase) process lacks direct observation through the stable current as output signal. To address this limitation, we investigated the photoinduced polarization switching capabilities of the cyanide-bridged compound [Fe 2 Co] using visible light, leading to the achievement of rewritable polarization. By subjecting [Fe 2 Co] crystals to alternating irradiation with 785 nm and 532 nm light, the polarization changes exhibited a distinct square wave pattern, confirming the reliability of the writing and erasing processes. Initialization involved exposing specific crystal units to 532 nm light for storing "1" or "0" information, while reading was accomplished by scanning the units with 785 nm light, resulting in brief current pulses for "1" states and no current signal for "0" states. This research unveils new possibilities for optical storage systems, paving the way for efficient and rewritable data storage and retrieval technologies, such as the next-generation memories., (© 2024 Wiley-VCH GmbH.)

Antibody (Ab)-based drugs have been widely used in targeted therapies and immunotherapies, leading to significant improvements in tumor therapy. However, the failure of Ab therapy due to the loss of target antigens or Ab modifications that affect its function limits its application. In this study, we expanded the application of antibodies (Abs) by constructing a fusion protein as a versatile tool for Ab-based target cell detection, delivery, and therapy. We first constructed a SpaC Catcher (SpaCC for short) fusion protein that included the C domains of Staphylococcal protein A (SpaC) and the SpyCatcher. SpaCC conjugated with SpyTag-X (S-X) to form the SpaCC-S-X complex, which binds non-covalently to an Ab to form the Ab-SpaCC-S-X protein complex. The "X" can be a variety of small molecules such as fluoresceins, cell-penetrating peptide TAT, Monomethyl auristatin E (MMAE), and DNA. We found that Ab-SpaCC-S-FITC(-TAT) could be used for target cell detection and delivery. Besides, we synthesized the Ab-SpaCC-SN3-MMAE complex by linking Ab with MMAE by SpaCC, which improved the cytotoxicity of small molecule toxins. Moreover, we constructed an Ab-DNA complex by conjugating SpaCC with the aptamer (Ap) and found that Ab-SpaCC-SN3-Ap boosted the tumor-killing function of T-cells by retargeting tumor cells. Thus, we developed a multifunctional tool that could be used for targeted therapies and immunotherapies, providing a cheap and convenient novel drug development strategy., (© 2024 The Protein Society.)

Vonoprazan, a novel acid suppressant and the first potassium-competitive acid blocker, has the potential to enhance the eradication rate of Helicobacter pylori due to its robust acid-suppressing capacity. This study aimed to compare the efficacy of vonoprazan-based dual therapy (vonoprazan-amoxicillin, VA) with vonoprazan-based bismuth quadruple therapy (VBQT) as a first-line treatment for H pylori infection. This retrospective single-center non-inferiority study was conducted in China. Treatment-naive H pylori-positive patients aged 18 to 80 received one of the 2 treatment regimens at our center. The VA group received vonoprazan 20 mg twice daily and amoxicillin 1000 mg 3 times daily for 14 days, whereas the VBQT group received vonoprazan 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth potassium citrate 220 mg twice daily for 14 days. The eradication rate was evaluated 4 to 6 weeks after treatment using the carbon-13/14 urea breath test. Propensity score matching was used to analyze eradication rates, adverse events (AEs), and patient compliance between the 2 groups. Initially, 501 patients were included, and after propensity score analysis, 156 patients were selected for the study. Intention-to-treat analysis showed eradication rates of 87.2% (95% CI, 79.8-94.6%) for the VA group and 79.5% (95% CI, 70.5-88.4%) for the VBQT group (P = .195). Per-protocol analysis demonstrated rates of 94.4% (95% CI, 89.2-99.7%) for the VA group and 96.8% (95% CI, 92.4-100%) for the VBQT group (P = .507). Non-inferiority was confirmed between the 2 groups, with P values < .025. The VA group showed a lower rate of AEs (10.3% vs 17.9%, P = .250) compared to the VBQT group. There were no significant differences in patient compliance between the 2 groups. In treatment-naive patients with H pylori infection, both the 14-day VA and VBQT regimens demonstrated comparable efficacy, with excellent eradication rates. Moreover, due to reduced antibiotic usage, lower rate of AEs, and lower costs, VA dual therapy should be prioritized., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Chimeric antigen receptor (CAR)-positive cell therapy, specifically with anti-CD19 CAR-T (CAR19-T) cells, achieves a high complete response during tumor treatment for hematological malignancies. Large-scale production and application of CAR-T therapy can be achieved by developing efficient and low-cost enrichment methods for CAR-T cells, expansion monitoring in vivo, and overcoming tumor escape. Here, novel CAR-specific binding aptamers (CAR-ap) to traceless sort CAR-positive cells and obtain a high positive rate of CAR19-T cells is identified. Additionally, CAR-ap-enriched CAR19-T cells exhibit similar antitumor capacity as CAR-ab (anti-CAR antibody)-enriched CAR-T cells. Moreover, CAR-ap accurately monitors the expansion of CAR19-T cells in vivo and predicts the prognosis of CAR-T treatment. Essentially, a novel class of stable CAR-ap-based bispecific circular aptamers (CAR-bc-ap) is constructed by linking CAR-ap with a tumor surface antigen (TSA): protein tyrosine kinase 7 (PTK7) binding aptamer Sgc8. These CAR-bc-aps significantly enhance antitumor cytotoxicity with a loss of target antigens by retargeting CAR-T cells to the tumor in vitro and in vivo. Overall, novel CAR-aptamers are screened for traceless enrichment, monitoring of CAR-positive cells, and overcoming tumor cell immune escape. This provides a low-cost and high-throughput approach for CAR-positive cell-based immunotherapy., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Light-induced polarization switchable molecular materials have attracted attention for decades owing to their potential remote manipulation and ultrafast responsiveness. Here we report a valence tautomeric (VT) complex with an enantiopure chiral ligand. By a suitable choice of counter anions, a significant improvement in photoconversion has been demonstrated, leading to novel photo-responsive polarization switching materials.

Background: The excretory/secretory (ES) antigen of Trichinella spiralis muscle larvae (ML) is currently the most widely used diagnostic antigen to detect T. spiralis infection. However, this antigen has certain drawbacks, such as a complicated ES antigen preparation process and lower sensitivity during the early phase of infection. The aim of this study was to investigate the features of a novel T. spiralis trypsin (TsTryp) and evaluate its potential diagnostic value for trichinellosis., Methods: The TsTryp gene was cloned and recombinant TsTryp (rTsTryp) expressed. Western blotting and an enzyme-linked immunosorbent assay (ELISA) were performed to confirm the antigenicity of rTsTryp. The expression pattern and distribution signature of TsTryp at various life-cycle stages of T. spiralis were analyzed by quantitative PCR, western blotting and the immunofluorescence test. An ELISA with rTsTryp and ML ES antigens was used to detect immunoglobulins G and M (IgG, IgM) in serum samples of infected mice, swine and humans. The seropositive results were further confirmed by western blot with rTsTryp and ML ES antigens., Results: TsTryp expression was observed in diverse T. spiralis life-cycle phases, with particularly high expression in the early developmental phase (intestinal infectious larvae and adults), with distribution observed mainly at the nematode outer cuticle and stichosome. rTsTryp was identified by T. spiralis-infected mouse sera and anti-rTsTryp sera. Natural TsTryp protease was detected in somatic soluble and ES antigens of the nematode. In mice infected with 200 T. spiralis ML, serum-specific IgG was first detected by rTsTryp-ELISA at 8 days post-infection (dpi), reaching 100% positivity at 12 dpi, and first detected by ES-ELISA at 10 dpi, reaching 100% positivity at 14 dpi. Specific IgG was detected by rTsTryp 2 days earlier than by ES antigens. When specific IgG was determined in serum samples from trichinellosis patients, the sensitivity of rTsTryp-ELISA and ES antigens-ELISA was 98.1% (51/52 samples) and 94.2% (49/52 samples), respectively (P = 0.308), but the specificity of rTsTryp was significantly higher than that of ES antigens (98.7% vs. 95.4%; P = 0.030). Additionally, rTsTryp conferred a lower cross-reaction, with only three serum samples in total testing positive from 11 clonorchiasis, 20 cysticercosis and 24 echinococcosis patients (1 sample from each patient group)., Conclusions: TsTryp was shown to be an early and highly expressed antigen at intestinal T. spiralis stages, indicating that rTsTryp represents a valuable diagnostic antigen for the serodiagnosis of early Trichinella infection., (© 2023. The Author(s).)

Background: Proteases secreted by Trichinella spiralis intestinal infective larvae (IIL) play an important role in larval invasion and pathogenesis. However, the mechanism through which proteases mediate larval invasion of intestinal epithelial cells (IECs) remains unclear. A novel T. spiralis trypsin (TsTryp) was identified in IIL excretory/secretory (ES) proteins. It was an early and highly expressed protease at IIL stage, and had the potential as an early diagnostic antigen. The aim of this study was to investigate the biological characteristics of this novel TsTryp, its role in larval invasion of gut epithelium, and the mechanisms involved., Methodology/principal Finding: TsTryp with C-terminal domain was cloned and expressed in Escherichia coli BL21 (DE3), and the rTsTryp had the enzymatic activity of natural trypsin, but it could not directly degrade gut tight junctions (TJs) proteins. qPCR and western blotting showed that TsTryp was highly expressed at the invasive IIL stage. Immunofluorescence assay (IFA), ELISA and Far Western blotting revealed that rTsTryp specifically bound to IECs, and confocal microscopy showed that the binding of rTsTryp with IECs was mainly localized in the cytomembrane. Co-immunoprecipitation (Co-IP) confirmed that rTsTryp bound to protease activated receptors 2 (PAR2) in Caco-2 cells. rTsTryp binding to PAR2 resulted in decreased expression levels of ZO-1 and occludin and increased paracellular permeability in Caco-2 monolayers by activating the extracellular regulated protein kinases 1/2 (ERK1/2) pathway. rTsTryp decreased TJs expression and increased epithelial permeability, which could be abrogated by the PAR2 antagonist AZ3451 and ERK1/2 inhibitor PD98059. rTsTryp facilitated larval invasion of IECs, and anti-rTsTryp antibodies inhibited invasion. Both inhibitors impeded larval invasion and alleviated intestinal inflammation in vitro and in vivo., Conclusions: TsTryp binding to PAR2 activated the ERK1/2 pathway, decreased the expression of gut TJs proteins, disrupted epithelial integrity and barrier function, and consequently mediated larval invasion of the gut mucosa. Therefore, rTsTryp could be regarded as a potential vaccine target for blocking T. spiralis invasion and infection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Han et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Previous studies have shown that recombinant Trichinella spiralis galectin (rTsgal) is characterized by a carbohydrate recognition domain sequence motif binding to beta-galactoside, and that rTsgal promotes larval invasion of intestinal epithelial cells. Galactomannan is an immunostimulatory polysaccharide composed of a mannan backbone with galactose residues. The aim of this study was to investigate whether galactomannan inhibits larval intrusion of intestinal epithelial cells and enhances antibody-dependent cellular cytotoxicity (ADCC), killing newborn larvae by polarizing macrophages to the M1 phenotype. The results showed that galactomannan specially binds to rTsgal, and abrogated rTsgal facilitation of larval invasion of intestinal epithelial cells. The results of qPCR, Western blotting, and flow cytometry showed that galactomannan and rTsgal activated macrophage M1 polarization, as demonstrated by high expression of iNOS (M1 marker) and M1 related genes (IL-1β, IL-6, and TNF-α), and increased CD86 + macrophages. Galactomannan and rTsgal also increased NO production. The killing ability of macrophage-mediated ADCC on larvae was also significantly enhanced in galactomannan- and rTsgal-treated macrophages. The results demonstrated that Tsgal may be considered a potential vaccine target molecule against T. spiralis invasion, and galactomannan may be a novel adjuvant therapeutic agent and potential vaccine adjuvant against T. spiralis infection., (© R. Zhang et al., published by EDP Sciences, 2024.)

Aim: To evaluate the efficacy of retinal laser photocoagulation and intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) for hemorrhagic retinal arterial macroaneurysm (RAM)., Methods: This was a retrospective clinical study. Patients with hemorrhagic RAM were divided into 4 groups defined by different treatments: a retinal laser photocoagulation therapy monotherapy group, an anti-VEGF intravitreal injection monotherapy group, a laser and anti-VEGF combination therapy group, and an observation group. Visual acuity (VA), central macular thickness (CMT), and retinal hemorrhage area (RHA) were collected., Results: Forty-seven eyes of 47 patients were enrolled. VA improved and had a significant difference between baseline and final in each treatment group (logMAR; laser group: 1.90±0.53 vs 1.05±0.63, P <0.001; anti-VEGF group: 1.75±0.63 vs 1.12±0.54, P =0.009; combination group: 1.76±0.38 vs 1.01±0.52, P <0.001); however, VA decreased and had no significant difference in observation group (1.63±0.51 vs 1.76±0.61, P =0.660). CMT decreased and had a significant difference between baseline and final in each group (laser group: 815.16±310.83 vs 252.05±83.90 µm, P <0.001; anti-VEGF group: 725.00±290.79 vs 203.56±69.89 µm, P =0.001; combination group: 595.50±186.51 vs 253.13±55.06 µm, P =0.001; observation group: 758.88±195.65 vs 267.00±120.90 µm, P =0.001). RHA were 28.99±28.15, 25.94±11.58, 19.64±8.97, and 27.45±13.76 mm 2 in laser group, anti-VEGF group, combination group and observation group, respectively. RHA was statistically correlated with final VA ( P =0.032) in the observation group., Conclusion: Both laser and anti-VEGF treatments are effective for hemorrhagic RAM. Combination therapy reduces the number of injections of anti-VEGF. RHA is a visual prognosis predictor in the natural history of hemorrhagic RAM., (International Journal of Ophthalmology Press.)

Aim: To describe the optical coherence tomography angiography (OCTA) characteristics of exudative and non-exudative treatment-naïve pachychoroid neovasculopathy (PNV)., Methods: Thirty-five patients with exudative treatment-naïve PNV and 13 with non-exudative treatment-naïve PNV between March 2020 and December 2021 were included. All patients underwent ophthalmologic examination, including fluorescein angiography (FA), indocyanine green angiography (ICGA), spectral-domain OCT, and OCTA. The clinical data of the patients were retrospectively analyzed., Results: The study included 51 eyes from 46 patients, of whom 33 (71.7%) were male. The central macular thickness (CMT) in the exudative PNV group was significantly higher than that in the non-exudative PNV group (383.97±132.16 µm vs 213.13±51.63 µm; P <0.001). The maximum height of flat irregular pigment epithelial detachments (FIPED) was 45.40±11.86 µm in the non-exudative PNV group, significantly lower than the 71.58±20.91 µm ( P <0.001) in the exudative PNV group. The area of PNV of the non-exudative PNV group was, significantly larger than that of the exudative PNV group (1.06±0.84 mm 2 vs 0.63±0.80 mm 2 , P =0.016). There was a significant difference in PNV morphology between the two groups ( P <0.001). Multivariate logistic regression analysis found that the maximum height of FIPED (OR=1.156, 95%CI: 1.019-1.312; P =0.024) and microvascular branches (OR=69.412, 95%CI: 3.538-1361.844; P =0.005) were independent predictors of PNV activity., Conclusion: The OCTA imaging finds that there are significant differences in CMT, maximum height of FIPED, PNV area, and morphology of exudative PNV and non-exudative PNV groups. OCTA can accurately identify the clinical and imaging features of exudative and non-exudative treatment-naïve PNV, and distinguish PNV activity., (International Journal of Ophthalmology Press.)

Objectives: The incidence and prevalence of inflammatory bowel disease (IBD), mainly including ulcerative colitis (UC) and Crohn's disease (CD), are increasing globally. We aimed to evaluate the potential association between IBD and nephrolithiasis, tubulointerstitial nephritis, and chronic kidney disease (CKD)., Methods: Data of hospitalized adults ≥20 years of age were extracted from the U.S. National Inpatient Sample (NIS) during 2016-2018. Patients with UC, CD, or CKD were identified through the International Classification of Diseases, Tenth Revision (ICD-10) codes. Propensity score matching (PSM) analysis (1:1) was conducted to balance the characteristics between groups. Logistic regression analyses were performed to determine the relationships between UC or CD and kidney conditions., Results: Three cohorts were included for analysis after PSM analysis. Cohorts 1, 2 and 3 contained 235 262 subjects (117 631 with CD or without IBD), 140 856 subjects (70 428 with UC or without IBD), and 139 098 subjects (69 549 with CD or UC), respectively. Multivariate analysis revealed that compared to non-IBD individuals, CD patients were significantly associated with greater odds for nephrolithiasis (adjusted odds ratio [aOR] 2.25, 95% confidence interval [CI] 2.08-2.43), tubulointerstitial nephritis (aOR 1.31, 95% CI 1.24-1.38), CKD at any stage (aOR 1.28, 95% CI 1.24-1.32), and moderate-to-severe CKD (aOR 1.22, 95% CI 1.17-1.26), while UC was associated with a higher rate of nephrolithiasis. Compared to UC, CD was associated with higher odds for all such kidney conditions., Conclusions: Patients with CD are more likely to have nephrolithiasis, tubulointerstitial nephritis, CKD at any stage, and moderate-to-severe CKD compared to non-IBD individuals., (© 2023 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Antibody drugs have been widely used to treat many diseases and are the fastest-growing drug class. IgG1 is the most common type of antibody because of its good serum stability; however, effective methods for the rapid detection of IgG1-type antibodies are lacking. In this study, we designed two aptamer molecules derived from the reported aptamer probe that has been proven to bind to the Fc fragment of the IgG1 antibody. The results showed that Fc-1S could specifically bind to the human IgG1 Fc proteins. In addition, we modified the structure of Fc-1S and constructed three aptamer molecular beacons that could quantitatively detect IgG1-type antibodies within a short time. Furthermore, we unveiled that the Fc-1S37R beacon has the highest sensitivity for IgG1-type antibodies with a detection limit of 48.82813 ng/mL and can accurately detect serum antibody concentrations in vivo with consistent results to ELISA. Therefore, Fc-1S37R is an efficient method for the production monitoring and quality control of IgG1-type antibodies to enable the large-scale production and application of antibody drugs., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

CD19 CAR-T (chimeric antigen receptor-T) cell immunotherapy achieves a remission rate of approximately 70% in recurrent and refractory lymphoma treatment. However, the loss or reduction of CD19 antigen on the surface of lymphoma cells results in the escape of tumor cells from the immune killing of CD19 CAR-T cells (CAR19-T). Therefore, novel therapeutic strategies are urgently required. In this study, an anti-CD79b/CD3 bispecific antibody (BV28-OKT3) was constructed and combined with CAR19-T cells for B-cell lymphoma treatment. When the CD19 antigen was lost or reduced, BV28-OKT3 redirected CAR19-T cells to CD79b + CD19 - lymphoma cells; therefore, BV28-OKT3 overcomes the escape of CD79b + CD19 - lymphoma cells by the killing action of CAR19-T cells in vitro and in vivo. Furthermore, BV28-OKT3 triggered the antitumor function of CAR - T cells in the infusion product and boosted the antitumor immune response of bystander T cells, markedly improving the cytotoxicity of CAR19-T cells to lymphoma cells in vitro and in vivo. In addition, BV28-OKT3 elicited the cytotoxicity of donor-derived T cells toward lymphoma cells in vitro, which depended on the presence of tumor cells. Therefore, our findings provide a new clinical treatment strategy for recurrent and refractory B-cell lymphoma by combining CD79b/CD3 BsAb with CAR19-T cells., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Screening novel aptamers for recombinant protein detection is of great significance in industrial mass production of antibody drugs. In addition, construction of structurally stable bispecific circular aptamers (bc-apts) may provide a tumor-targeted treatment strategy by simultaneously binding two different cell types. In this study, we obtained a high-affinity hexahistidine tag (His-tag)-binding aptamer 20S and explored its application in recombinant protein detection and T cell-based immunotherapy. We developed a new molecular beacon (MB) 20S-MB to detect His-tagged proteins in vitro and in vivo with high sensitivity and specificity, and the results showed high consistency with the enzyme-linked immunosorbent assay (ELISA). Moreover, we constructed two kinds of bc-apts by cyclizing 20S or another His-tag-binding aptamer, 6H5-MU, with Sgc8, which specifically recognizes protein tyrosine kinase 7 (PTK7) on tumor cells. After forming a complex with His-tagged OKT3, an anti-CD3 antibody for T cell activation, we utilized these aptamer-antibody complexes (ap-ab complex) to enhance cytotoxicity of T cells by linking T cells and target cells together, and 20S-sgc8 exhibited antitumor efficacy superior to that of 6H5-sgc8. In conclusion, we screened a novel His-tag-binding aptamer and used it to construct a new type of MB for rapid detection of recombinant proteins, as well as establish a feasible approach for T cell-based immunotherapy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Cai-Wen Duan reports financial support was provided by National Natural Science Foundation of China. Cai-Wen Duan reports financial support was provided by Guangxi Natural Science Foundation. Cai-Wen Duan reports financial support was provided by Science and Technology Commission of Shanghai Municipality. Kai-Ming Chen reports financial support was provided by Science and Technology Commission of Shanghai Municipality. Kai-Ming Chen reports financial support was provided by Science and Technology Commission of Pudong New Area., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Polysaccharides are one of the most abundant and active components of Lysimachia christinae (L. christinae), which is widely adopted for attenuating abnormal cholesterol metabolism; however, its mechanism of action remains unclear. Therefore, we fed a natural polysaccharide (NP) purified from L. christinae to high-fat diet mice. These mice showed an altered gut microbiota and bile acid pool, which was characterized by significantly increased Lactobacillus murinus and unconjugated bile acids in the ileum. Oral administration of the NP reduced cholesterol and triglyceride levels and enhanced bile acid synthesis via cholesterol 7α-hydroxylase. Additionally, the effects of NP are microbiota-dependent, which was reconfirmed by fecal microbiota transplantation (FMT). Altered gut microbiota reshaped bile acid metabolism by modulating bile salt hydrolase (BSH) activity. Therefore, bsh genes were genetically engineered into Brevibacillus choshinensis, which was gavaged into mice to verify BSH function in vivo. Finally, adeno-associated-virus-2-mediated overexpression or inhibition of fibroblast growth factor 15 (FGF15) was used to explore the farnesoid X receptor-fibroblast growth factor 15 pathway in hyperlipidemic mice. We identified that the NP relieves hyperlipidemia by altering the gut microbiota, which is accompanied by the active conversion of cholesterol to bile acids., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Appraisal of cancer survival is essential for cancer control, but studies related to gynecological cancer are scarce. Using cancer registration data, we conducted an in-depth survival analysis of cervical, uterine corpus, and ovarian cancers in an urban district of Shanghai during 2002-2013., Materials and Methods: The follow-up data of gynecological cancer from the Changning District of Shanghai, China, were used to estimate the 1-5-year observed survival rate (OSR) and relative survival rate (RSR) by time periods and age groups during 2002-2013. Age-standardized relative survival rates estimated by the international cancer survival standards were calculated during 2002-2013 to describe the prognosis of cervical, uterine corpus, and ovarian cancers among women in the district., Results: In total, 1307 gynecological cancer cases were included in the survival analysis in the district during 2002-2013. Among gynecological cancers, the 5-year OSRs and RSRs of uterine corpus cancer were highest (5-year OSR 84.40%, 5-year RSR 87.67%), followed by those of cervical cancer (5-year OSR 73.58%, 5-year RSR 75.91%), and those of ovarian cancer (5-year OSR 53.89%, 5-year RSR 55.90%). After age adjustment, the 5-year relative survival rates of three gynecological cancers were 71.23%, 80.11%, and 43.27%, respectively., Conclusion: The 5-year relative survival rate did not show a systematic temporal trend in cervical cancer, uterine cancer, or ovarian cancer. The prognosis in elderly patients was not optimistic, and this needs a more advanced strategy for early diagnosis and treatment. The age structure of gynecological cancer patients in the district tended to be younger than the standardized age, which implies that more attention to the guidance and health education for the younger generation is needed., Competing Interests: Competing interests The authors declare that they have no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: This study aimed to investigate the correlation between sonographic features and central neck lymph node metastasis (CNLM) in solitary solid papillary thyroid microcarcinoma (PTMC) with a taller-than-wide shape. Methods: A total of 103 patients with solitary solid PTMC with a taller-than-wide shape on ultrasonography who underwent surgical histopathological examination were retrospectively selected. Based on the presence or absence of CNLM, patients with PTMC were divided into a CNLM ( n = 45) or nonmetastatic ( n = 58) group, respectively. Clinical findings and ultrasonographic features, including a suspicious thyroid capsule involvement sign (STCS, which is defined as PTMC abutment or a disrupted thyroid capsule), were compared between the two groups. Additionally, postoperative ultrasonography was performed to assess patients during the follow-up period. Results: Significant differences were observed in sex and the presence of STCS between the two groups ( p < 0.05). The specificity and accuracy of the male sex for predicting CNLM were 86.21% (50/58 patients) and 64.08% (66/103 patients), respectively. The sensitivity, specificity, positive predictive value (PPV), and accuracy of STCS for predicting CNLM were 82.22% (37/45 patients), 70.69% (41/58 patients), 68.52% (37/54 patients), and 75.73% (78/103 patients), respectively. The specificity, PPV, and accuracy of the combination of sex and STCS for predicting CNLM were 96.55% (56/58 patients), 87.50% (14/16 patients), and 67.96% (70/103 patients), respectively. A total of 89 (86.4%) patients were followed up for a median of 4.6 years, with no patient having recurrence as detected on ultrasonography and pathological examination. Conclusions : STCS is a useful ultrasonographic feature for predicting CNLM in patients with solitary solid PTMC with a taller-than-wide shape, especially in male patients. Solitary solid PTMC with a taller-than-wide shape may have a good prognosis.

Recombinant protein drugs, which are typically produced by mammalian host cells, have been approved for the treatment of a range of diseases. Accordingly, systems for selecting recombinant cell lines with efficient protein expression and for testing the content of recombinant proteins in vivo are crucial to the large-scale production and application of protein-based therapeutic drugs. In this study, we designed three aptamer beacons to detect His-tag, a common label of recombinant proteins. We found that all three beacons could specifically and quantitatively measure the His-tagged recombinant proteins with a short reaction time. Among these three beacons, the 6H5-MU beacon had the highest sensitivity for His polypeptides with a detection limit of 250 ng/mL and the shortest detection time within 1 min. Furthermore, we established a rapid and highly effective recombinant cell line construction system, which could obtain monoclonal cell lines with high yields of target proteins within 21 days, by combining 6H5-MU with pSB, a novel plasmid composed of a Sleeping Beauty transposase and a transposon. Finally, 6H5-MU also discriminately tested the serum concentration of His-tagged recombinant proteins in vivo, with consistent results compared to enzyme-linked immunosorbent assay (ELISA). We thus established a rapid and high-throughput method for generating recombinant cell lines and in vivo monitoring of recombinant protein levels, thereby providing a new platform for the development and preparation of recombinant protein drugs. KEY POINTS: • The 6H5-MU aptamer beacon rapidly and accurately binds to His-tagged recombinant proteins. • A system for rapid and high-throughput generation of recombinant cell lines is established using 6H5-MU and pSB. • 6H5-MU allows in vivo monitoring of recombinant protein levels., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Lateral neck dissection (LND) is a necessary treatment for thyroid cancer with lateral lymph node metastasis. However, the defect created during open surgery leaves a visible scar on the neck. With advancements in surgical technology, many robotic and endoscopic surgical techniques have been reported as alternatives to open surgery. In this study, we present a case series demonstrating the successful application of a novel hybrid approach for endoscopic LND and a review of different surgical approaches for "scarless" (at the neck) LND. We performed endoscopic LND via a combined chest and transoral approach in 24 patients between January 2021 and March 2022. The surgery was completed successfully in all patients with an average operation time of 298.1 ± 72.9 min. The numbers of positive/retrieved lymph nodes at levels II, III-IV, and VI were 0.7 ± 0.9/8.4 ± 4.1, 3.6 ± 2.7/19.5 ± 6.8, and 4.9 ± 3.9/10.3 ± 4.5, respectively. Complications included transient hypoparathyroidism in 10 patients, transient recurrent laryngeal nerve injury in 1 patient, internal jugular vein (IJN) injury in 1 patient, IJN sacrifice due to cancer invasion in 1 patient, and chyle leak in 1 patient, and no cases of tumor recurrence were observed during follow-up. The present case series indicates that the combined chest and transoral approach is feasible and effective for performing LND. Our review of different approaches for "scarless" (at the neck) LND identified advantages and disadvantages for all techniques. Our novel approach has unique advantages, and thus, it can provide an ideal surgical procedure for specific papillary thyroid carcinoma patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chen, Chen, Pang, Lin, Zhang, Cai, Zheng, Cao and Qin.)

Background: Recent years there have been witnessed considerable advances in endoscopic selective lateral neck dissection (LND). However, dissection of lymph nodes at level IV and level VI via the chest approach is inherently challenging. In this study, we used combined trans-oral and chest approach for endoscopic thyroidectomy in patients with cT1-2N1bM0 papillary thyroid carcinoma (PTC)., Methods: Clinical characteristics and surgical outcomes of ten patients with cT1-2N1bM0 PTC who underwent endoscopic thyroidectomy via combination of trans-oral and chest approach between September 2020 and September 2021 were retrospectively reviewed., Results: All 10 patients successfully underwent total thyroidectomy and selective LND via chest approach, while central neck dissection (CND) and supplementary dissection of lymph nodes at level IV were performed via the trans-oral approach. The mean number of positive/retrieved level II, III-IV, and VI lymph nodes were 0.6 ± 1.0/9.8 ± 5.0, 4.6 ± 2.8/23.1 ± 4.7, and 4.9 ± 3.4/10.3 ± 4.6, respectively. Four patients developed transient hypoparathyroidism which spontaneously resolved within 1 month. Five patients developed numbness of lateral neck and ear and one patient experienced limb lift restriction. No other complications or tumor recurrence occurred during follow-up., Conclusion: It is feasible to perform total thyroidectomy, CND, and selective LND via combined trans-oral and chest approach, and satisfactory short-term outcomes were observed in this cohort. This approach may offer one more option for cT1-2N1bM0 PTC patients, especially those in whom metastatic lymph nodes at level IV or level VI are detected by preoperative examination., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: To investigate the effects of the combination of berbamine (BBM) and ibrutinib on the proliferation and apoptosis of acute myeloid leukemia (AML) cells and the mechanism of combined action., Methods: The AML cell lines were treated with BBM, ibrutinib and the combination of the two drugs respectively, CCK-8 method was used to detect the cell proliferation inhibition rate of each group and calculate the combination index (CI). The cell apoptosis in each group was detected by flow cytometry. Western blot was used to determine the expression of related proteins in each group., Results: The cell viability in the combination group was significantly reduced, and the CI value of ED 50 /ED 75 /ED 90 <1. The expression of apoptotic related protein in the combination group was significantly up-regulated, while the expression of p-BTK, p-AKT, CREB, GSK3β and BCL-XL were significantly down-regulated., Conclusion: BBM and ibrutinib can synergistically inhibit the proliferation of AML cells and promote the apoptosis of AML cells. BBM and ibrutinib may play a synergistic effect through the p-BTK/p-AKT/CREB and GSK3β/BCL-XL signaling pathways.

With the in-depth study of circRNA, more and more biological studies have shown that circRNAs play an important role in mammals, such as cell proliferation, apoptosis, invasion, development and disease state. However, the regulatory mechanism of circRNA in lower vertebrates remains unclear. Here, we found a new circular RNA and named it circRara. We carried out the experimental study on its antiviral and antibacterial response, cell proliferation and activity. The results showed that circRara had a positive regulatory effect on the antiviral and antibacterial response, cell proliferation and activity in miiuy croaker. First, we found that the expression of circRara could be up-regulated under the stimulation of LPS and poly (I: C), but not the expression of linear Rara. In addition, the increase of circRara can increase the production of inflammatory factors and antiviral genes, which was confirmed by double luciferase reporter gene experiment and qPCR. These results will help to further understand the immunomodulatory mechanism of circRNA in teleost fish., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Digestive tract cancers are the common cause of cancer deaths in both China and worldwide. This study aimed to describe the burden, recent trends and lifetime risks in the incidence and mortality of digestive tract cancers in an urban district of Shanghai, China. Our study extracted data on stomach, colon, rectum and liver cancers diagnosed in Changning District between 2010 and 2019 from the Shanghai Cancer Registry. We calculated age-standardized incidence and mortality rates, the risks of developing and dying from cancer, and the estimated annual percent changes. Between 2010 and 2019, 8619 new cases and 5775 deaths were registered with digestive tract cancers in the district. The age-standardized incidence rates (ASIRs) of liver cancer decreased steadily, whereas the ASIRs of stomach, colon and rectum cancers remained stable from 2010 to 2019. The age-standardized mortality rates (ASMRs) of stomach and liver cancers showed significant declining changes from 2010 to 2019 in both sexes, but that of colon and rectum cancers remained stable during the entire period. The risks of developing and dying from digestive tract cancers were substantially higher in men than women. The burden of digestive tract cancer and its disparities between sex and age group remain major public health challenges in urban Shanghai. To reduce the burden of digestive tract cancers, the government and researchers should develop and promote a healthy diet, organize a screening, and reduce the prevalence of smoking, alcohol drinking, and hepatitis B virus and hepatitis C virus infections., (© 2022. The Author(s).)

Background: Diabetes is associated with endothelial cell dysfunction. E-selectin is an endothelial cell adhesion molecule, which is bound for endothelial cell activation. E-selectin gene+A561C polymorphism is associated with many different disorders: essential hypertension, stroke, angina pectoris, coronary heart disease, etc. But the association with type 2 diabetes remains unclear. Therefore, we aimed to investigate the role of E-selectin gene+A561C polymorphism and soluble E-selectin in type 2 diabetes in a Chinese population., Methods: This study involved 317 patients with type 2 diabetes and 285 normal healthy controls. Genotyping of E-selectin gene+A561C polymorphism was examined by polymerase chain reaction-restricted fragments length polymorphism (PCR-RFLP). Soluble E-selectin was examined by enzyme linked immunosorbent assay (ELISA). Biochemical markers were measured by Roche 7600 Automated Biochemical Analyzer., Results: We found that C allele frequency in E-selectin A561 C polymorphism of Chinese T2DM group was higher than control group. The level of soluble E-selectin in T2DM group was higher than control group. TC, TG, LDL-C, ApoB, and sE-selectin (soluble E-selectin) in AC and CC genotypes were higher than AA genotype., Conclusions: Our findings showed that E-selectin +A561C polymorphism was correlated in the Chinese population with type 2 diabetes. C allele and soluble E-selectin may be predisposing factors of Chinese population with type 2 diabetes.

Aims: To investigate the positional relationship between the ovary and Fallopian tube and the relationship between the ovarian position and tubal morphology., Material and Methods: A total of 195 patients with 338 fallopian tubes were enrolled in this retrospective study. The ovarian and tubal positions were defined relative to the uterus in all directions. Tubal morphology was classified as smooth or tortuous., Results: The distribution of the Fallopian tubes corresponded to the positions of the ipsilateral ovaries in the superoinferior direction (χ2 =197.653, p<0.001), mediolateral direction (χ2 =237.447, p <0.001) and anteroposterior direction (χ2 =109.746, p<0.001). Tubal morphology differed according to ovarian position in the superoinferior (χ2 =21.804, p<0.001), mediolateral directions (χ2 =4.679, p=0.031) but not in the anteroposterior direction (χ2 =0.793, p=0.373)., Conclusions: Evaluating the ovarian position can provide preliminary information on the distribution and shapeof the Fallopian tube, helping the operator choose the appropriate initial plane and the necessary approaches for inspection.

Acute myeloid leukaemia (AML) is a frequently fatal malignant disease of haematopoietic stem and progenitor cells. The molecular and phenotypic characteristics of AML are highly heterogeneous. Our previous study concluded that CaMKIIγ was the trigger of chronic myeloid leukaemia progression from the chronic phase to blast crisis, but how CaMKIIγ influences AML stem-like cells remains elusive. In this study, we found that CaMKIIγ was overexpressed in AML patients and AML cell lines, as measured by qRT-PCR and Western blot assays. Moreover, CaMKIIγ decreased when the disease was in remission. Using an shRNA lentivirus expression system, we established CaMKIIγ stable-knockdown AML cell lines and found that knockdown of CaMKIIγ inhibited the viability and self-renewal of AML stem-like cell lines. Additionally, the ratio of CD 34 + AML cell lines decreased, and CaMKIIγ knockdown induced the downregulation of Alox5 levels. We further detected downstream molecules of the Alox5/NF-κB pathway and found that c-myc and p-IκBα decreased while total IκBα remained normal. In conclusion, our study describes a new role for CaMKIIγ as a stem-like cell marker that is highly regulated by the Alox5/NF-κB pathway in AML stem-like cells. CaMKIIγ can participate in the viability and self-renewal of AML stem-like cells by regulating the Alox5/NF-κB pathway., (© 2020 John Wiley & Sons Ltd.)

B-cell acute lymphocytic leukemia (B-ALL) is a malignant blood cancer that develops in children and adults and leads to high mortality. THZ1, a covalent cyclin-dependent kinase 7 (CDK7) inhibitor, shows anti-tumor effects in various cancers by inhibiting cell proliferation and inducing apoptosis. However, whether THZ1 has an inhibitory effect on B-ALL cells and the underlying mechanism remains obscure. In this study, we showed that THZ1 arrested the cell cycle of B-ALL cells in vitro in a low concentration, while inducing the apoptosis of B-ALL cells in vitro in a high concentration by activating the apoptotic pathways. In addition, RNA-SEQ results revealed that THZ1 disrupted the cellular metabolic pathways of B-ALL cells. Moreover, THZ1 suppressed the cellular metabolism and blocked the production of cellular metabolic intermediates in B-ALL cells. Mechanistically, THZ1 inhibited the cellular metabolism of B-ALL by downregulating the expression of c-MYC-mediated metabolic enzymes. However, THZ1 treatment enhanced cell apoptosis in over-expressed c-MYC B-ALL cells, which was involved in the upregulation of p53 expression. Collectively, our data demonstrated that CDK7 inhibitor THZ1 induced the apoptosis of B-ALL cells by perturbing c-MYC-mediated cellular metabolism, thereby providing a novel treatment option for B-ALL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Abudureheman, Xia, Li, Zhou, Zheng, Zhou, Shi, Zhu, Yang, Chen, Zheng, Xue, Qing and Duan.)

Haloacetaldehydes (HALs), as emerging disinfection by-products in drinking water, are the third largest group by weight of identified disinfection by-products (DBPs) in drinking water. The formation of HALs is associated with the level of natural organic matter and halide in the source water, the treatment process of drinking water and the type of disinfectant. Recent studies have shown that HALs are more cytotoxic and genotoxic than regulated trihalomethanes and halo-acetic acids in drinking water. Currently, only a few countries and regions have set limit values for trichloroacetaldehyde with high detection rate in drinking water. However, there is growing evidence that unregulated HALs have a higher potential risk to human health compared to regulated HALs. This paper reviews the current research progress on the formation and transformation, cytotoxicity and genotoxicity of HALs in drinking water, and looks forward to the problems that should be paid attention in the future toxicological research of HALs in order to support the development of scientific drinking water standards.

B-cell acute lymphocytic leukemia (B-ALL), a common blood cancer in children, leads to high mortality. Cyclin-dependent kinase 9 inhibitor (CDK9i) effectively attenuates acute myeloid leukemia and chronic lymphoblastic leukemia by inducing apoptosis and inhibiting cell proliferation. However, the effect of CDK9i on B-ALL cells and the underlying mechanisms remain unclear. In this study, we showed that CDK9i induced the apoptosis of B-ALL cells in vitro by activating the apoptotic pathways. In addition, CDK9i restrained the glycolytic metabolism of B-ALL cells, and CDK9i-induced apoptosis was enhanced by co-treatment with glycolysis inhibitors. Furthermore, CDK9i restained the glycolysis of B-ALL cell lines by markedly downregulating the expression of glucose transporter type 1 (GLUT1) and the key rate-limiting enzymes of glycolysis, such as hexokinase 2 (HK2) and lactate dehydrogenase A (LDHA). Moreover, cell apoptosis was rescued in B-ALL cells with over-expressed c-Myc after treatment with CDK9i, which is involved in the enhancement of glycolytic metabolism. In summary, our findings suggest that CDK9 inhibitors induce the apoptosis of B-ALL cells by inhibiting c-Myc-mediated glycolytic metabolism, thus providing a new strategy for the treatment of B-ALL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Huang, Abudureheman, Xia, Chu, Zhou, Zheng, Zhou, Shi, Li, Zhu, Qing, Ji, Liang, Guo, Yin and Duan.)

Background: The performance of 17 routine chemical detection methods was evaluated by the Sigma (σ) index, and separate quality control standards were established according to the sigma values of different detection methods., Methods: The internal quality control (IQC) and external quality assessment (EQA) data of 17 assays in the biochemical laboratory of our hospital were collected from January to June 2019. Referring to the total allowed error (TEa) standards established in the Health Industry Standards of the People's Republic of China (WS/T 403-2012), the sigma metric of each assay was calculated, the performance level for inspection was evaluated, the quality goal index (QGI) was calculated for items with analysis performance < 5 sigma, and the main causes of poor performance were determined to guide quality improvement., Results: For level 1 internal quality control (IQC), five assays (AMY, Crea, UA, TP, and Na) showed a performance of ≥ 6 sigma levels. Five assays (GGT, LDH, ALP, K, and Ca) had a performance lower than 3 sigma. For level 2 IQC, nine assays (ALT, AST, CK, AMY, Crea, UA, TP, Na, and Mg) achieved 6 sigma, and four assays (GGT, LDH, ALP, and K) achieved less than 3 sigma. Among the 12 assays with a sigma value < 5, the precision of 1 assay should be improved first, the accuracy of 6 assays should be improved next, and both the precision and the accuracy of 5 assays should be improved., Conclusions: The sigma metric is the best tool for evaluating the performance of different test methods. Assays with high sigma values can be evaluated with single-rule quality control, while assays with low values should be evaluated with strict quality control rules.

The objective of this study was to analyze the infection rate and drug resistance of Ureaplasma urealyticum (UU) and Mycoplasma hominis (MH) in the genitourinary tract of Chinese patients. From December 2018 to June 2019, vaginal secretion or urinary secretion of outpatients in our hospital were selected for culture and drug sensitivity analysis of Ureaplasma urealyticum and Mycoplasma hominis. In 4082 Chinese samples, 1567 Mycoplasma were detected, a detection rate of 38.39%, among which 1366 cases were UU single positive, accounting for 33.47%, 15 cases were MH single positive, accounting for 0.36%, 186 cases were UU and MH mixed positive, accounting for 4.56%. The most affected age groups were 21-30 years and 31-40 years, accounting for 19.09 and 15.05%, respectively. The results of drug sensitivity showed that doxycycline, minocycline, josamycin, clarithromycin, and roxithromycin were more sensitive to mycoplasma infection. The distribution of Ureaplasma urealyticum and Mycoplasma hominis in the human genitourinary system and their sensitivity to antibiotics is different for sex and age groups.

Previous studies have shown that high salt induces artery stiffness by causing endothelial dysfunction via increased sodium influx. We used our unique split-open artery technique combined with protein biochemistry and in vitro measurement of vascular tone to test a hypothesis that bone morphogenetic protein 4 (BMP4) mediates high salt-induced loss of vascular relaxation by stimulating the epithelial sodium channel (ENaC) in endothelial cells. The data show that high salt intake increased BMP4 both in endothelial cells and in the serum and that exogenous BMP4 stimulated ENaC in endothelial cells. The data also show that the stimulation is mediated by p38 mitogen-activated protein kinases (p38 MAPK) and serum and glucocorticoid-regulated kinase 1 (Sgk1)/neural precursor cell expressed developmentally downregulated gene 4-2 (Nedd4-2) (Sgk1/Nedd4-2). Furthermore, BMP4 decreased mesenteric artery relaxation in a benzamil-sensitive manner. These results suggest that high salt intake stimulates endothelial cells to express and release BMP4 and that the released BMP4 reduces artery relaxation by stimulating ENaC in endothelial cells. Therefore, stimulation of ENaC in endothelial cells by BMP4 may serve as another pathway to participate in the complex mechanism of salt-sensitive (SS) hypertension., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2020 Xu Yang et al.)

Objective: To analyze the characteristics of lumbar spine-pelvic structure in degenerative lumbar spondylolisthesis and its significance in degenerative lumbar spondylolisthesis(DLS)., Methods: The clinical data of 45 patients with simple degenerative L 4, 5 -segment lumbar spondylolisthesis (spondylolisthesis group) admitted from April 2015 to January 2017 were retrospectively analyzed, which were compared with 50 healthy people with complete physical examination data in the same period(control group). Statistical analysis of the lumbar spine-pelvic structure parameters of the subjects through imaging data was performed to analyze the characteristics of the spine-pelvis of DLS patients. The degenerative characteristicsof intervertebral disc and articular process joint were observed in degenerative lumbar spondylolisthesis. Use Spearson to analyze the correlation between observation items., Results: The facet joint angle, lumbar lordosis angle (LL), pelvic incidence angle(PI), pelvic tilt angle (PT), sacral slope angle (SS) in spondylolisthesis group of L 4, 5 -segment were (36.5±11.2)°, (44.2±7.3)°, (66.5±11.6)°, ( 22.2±10.0)°, (33.4±11.3)°, respectively, while in control group were (44.4±8.2)°, (36.7±8.5)°, (55.4± 13.2)°, (14.4±7.0)°, (42.3±13.1)°. PI, LL, PT of spondylolisthesis group were obviously larger than that of control group ( P < 0.05), the facet joint angle and SS of spondylolisthesis group were smaller than that of control group( P <0.05). The correlation analysis showed that PI value was related to the PT and SS in two group. The degree of degeneration of intervertebral disc was related to the degree of spondylolisthesis. The degree of degeneration of L 3 -S 1 intervertebral disc and L 4, 5 facet jointin spondylolisthesis group was more serious (P <0.05)., Conclusion: Lumbar spinal pelvic structure of degenerative lumbar spondylolisthesis has undergone significant changes. Lumbar lordosis and pelvic dumping phenomenon in the mechanism of lumbar degeneration plays an important role. Lumbar facet joint degeneration and lumbar intervertebral disc degeneration are mutually promoted, and lumbar spondylolisthesis aggravates intervertebral disc and facet joint degeneration.

Since this article has been suspected of research misconduct and the corresponding authors did not respond to our request to prove originality of data and figures, "MiR-150 alleviates EMT and cell invasion of colorectal cancer through targeting Gli1, by H. Fan, X. Liu, W.-W. Zheng, Z.-H. Zhuang, C.-D. Wang, published in Eur Rev Med Pharmacol Sci 2017; 21 (21): 4853-4859-PMID: 29164577" has been withdrawn. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/13726.

During human erythroid maturation, Hsp70 translocates into the nucleus and protects GATA-1 from caspase-3 cleavage. Failure of Hsp70 to localize to the nucleus was found in Myelodysplastic syndrome (MDS) erythroblasts and can induce dyserythropoiesis, with arrest of maturation and death of erythroblasts. However, the mechanism of the nuclear trafficking of Hsp70 in erythroblasts remains unknown. Here, we found the hematopoietic transcriptional regulator, EDAG, to be a novel binding partner of Hsp70 that forms a protein complex with Hsp70 and GATA-1 during human normal erythroid differentiation. EDAG overexpression blocked the cytoplasmic translocation of Hsp70 induced by EPO deprivation, inhibited GATA-1 degradation, thereby promoting erythroid maturation in an Hsp70-dependent manner. Furthermore, in myelodysplastic syndrome (MDS) patients with dyserythropoiesis, EDAG is dramatically down-regulated, and forced expression of EDAG has been found to restore the localization of Hsp70 in the nucleus and elevate the protein level of GATA-1 to a significant extent. In addition, EDAG rescued the dyserythropoiesis of MDS patients by increasing erythroid differentiation and decreasing cell apoptosis. This study demonstrates the molecular mechanism of Hsp70 nuclear sustaining during erythroid maturation and establishes that EDAG might be a suitable therapeutic target for dyserythropoiesis in MDS patients., (© 2020 Federation of American Societies for Experimental Biology.)

BACKGROUND Acute lymphocytic leukemia (ALL) is a common blood cancer which induces high mortality in children. Bromodomains and extra-terminal (BET) protein inhibitors, such as JQ1 and ARV-825, are promising cancer therapeutic agents that can be used by targeting c-Myc. A recent work reported that JQ1 effectively attenuates ALL in vitro by suppressing cell proliferation and accelerating apoptosis. The purpose of this research was to probe into the potential mechanism of how JQ1 inhibits ALL cell proliferation in vitro. MATERIAL AND METHODS Cell viability of ALL cells were measured by CTG after treatment by JQ1. Cell cycle analysis was done by EdU and PI staining. Cell apoptosis was assessed by Annexin V/PI staining. Glycolysis was detected using Seahorse and LC-MS kits. The expression of glycolytic rate-limiting enzymes was assessed by RNA-seq, qRT-PCR, and Western blot. RESULTS JQ1 suppressed cell proliferation by arresting the cell cycle and inducing the apoptosis of acute lymphocytic leukemia cells. JQ1 inhibited cell proliferation of B-ALL cells by restraining glycolysis. Conversely, the cell cycle block of B-ALL cells induced by JQ1 was partially abolished after pretreatment with 2-Deoxy-D-glucose (2-DG), an inhibitor of glycolysis. Furthermore, JQ1 restrained the glycolysis of B-ALL cell lines by remarkably downregulating the rate-limiting enzymes of glycolysis, such as hexokinase 2, phosphofructokinase, and lactate dehydrogenase A. Moreover, the cell cycle arrest was reversed in B-ALL cells with overexpressed c-Myc treated by JQ1, which is involved in the enhancement of glycolysis. CONCLUSIONS The BET inhibitor JQ1 suppresses the proliferation of ALL by inhibiting c-Myc-mediated glycolysis, thus providing a new strategy for the treatment of ALL.

Objective: This study aimed to explore the expression and clinical significance of LINC01197 in serum of patients with pancreatic cancer (PC)., Patients and Methods: Fifty PC patients (patient group) treated in our hospital from March 2012 to April 2014 were collected, and another 50 normal people (normal group) were collected for physical examination. The LINC01197 expression in serum of the two groups was detected by qRT-PCR method, and the CA 19.9 expression in serum was detected by Roche automatic biochemistry. The expression and diagnostic value of CA 19.9 and LINC01197 in PC were analyzed, and the relationship between LINC01197 and prognosis of PC patients was observed., Results: The CA 19.9 expression in the patient group was significantly higher than that in the normal group (p<0.001). Their area under the curve was 0.791 and 0.944 respectively. The incidence of phases III+IV, lymphatic invasion, and distant metastasis in patients with low expression of LINC01197 is significantly higher than that in those with high expression, and has higher diagnostic value. With the progress of clinical staging, the TNM expression decreased gradually and there were differences between groups (p<0.001). Spearman's test analysis found that the decreased TNM staging of LINC01197 increased gradually (r=-0.816, p<0.001), and the area under the curve of LINC01197 distinguishing phase I and phase II+phase+III+phase IV was 0.930. The 1-year survival rate and 5-year survival rate of patients in low expression group were lower than those in high expression group (p1 year =0.037, p5 year =0.014). Distant metastasis is an independent prognostic factor for PC patients to survive for 1 to 5 years. Differentiation, TNM staging, and LINC01197 are independent prognostic factors for PC patients to survive for 5 years., Conclusions: The low expression of LINC01197 in PC patients indicates poor prognosis of patients and is expected to be a potential diagnostic and prognostic indicator of PC.

Leucine-rich repeat containing G-protein-coupled receptor 6 (LGR6) is a member of the rhodopsin-like 7-transmembrane domain receptor superfamily and has high homology to LGR4 and LGR5. LGR6 is highly expressed in osteoblastic progenitors, and LGR6-deficient mice show nail and bone regeneration defect. However, the effect of LGR6 on the osteogenic differentiation of osteoblastic progenitors and its underlying mechanisms are largely unknown. In this study, we overexpressed and knockdown LGR6 with lentivirus in the preosteoblastic cell MC3T3-E1 to observe the effect of LGR6 on osteogenic differentiation and explore its possible molecular mechanism. LGR6 overexpression promoted osteogenic differentiation and mineralization by stabilizing β-catenin to potentiate the Wnt/β-catenin signaling pathway in MC3T3-E1 cells. Conversely, LGR6 knockdown inhibited osteogenic differentiation and mineralization by enhancing β-catenin degradation to inactivate the Wnt/β-catenin signaling pathway. These results reveal that LGR6 is highly expressed in osteoblastic progenitors, and promotes osteogenesis by enhancing β-catenin stability to strengthen the Wnt signaling pathway. This study provides an important reference into the exact mechanisms of osteogenic differentiation., (Copyright © 2019. Published by Elsevier Inc.)

Aplastic anemia (AA) is a serious blood system disease that threatens human health. At present, the main cause of this disease is believed to be immune hyperfunction. However, the specific metabolic mode involved in the occurrence of lymphocytes in AA is still unknown. In addition, whether rapamycin, a specific blocker of the mTOR signaling pathway, plays a therapeutic role by inhibiting lymphocyte metabolism remains unclear. We induced an AA mouse model through the classical immune-mediated pathway and simultaneously administered rapamycin intervention therapy. First, the AA-associated phenotypic changes and the efficacy of rapamycin in the treatment of AA were discussed. Second, the proliferation and metabolic pathway of bone marrow (BM) lymphocytes in AA and the effect of rapamycin on this process were determined. Finally, the expression levels of mTOR pathway-related proteins were analyzed. By inhibiting the mTOR signaling pathway, rapamycin could ameliorate the phenotype of the immune-mediated AA model and inhibit the proliferation of T cells by preventing cell cycle transition from G0 to G1 phase. Moreover, we found that mitochondrial oxidative phosphorylation is involved in the metabolic reprogramming of T cells in AA and that rapamycin can inhibit this process. We confirmed that mitochondrial oxidative phosphorylation is involved in the metabolic reprogramming of T cells in AA and further extended the mechanism of rapamycin in treating AA by inhibiting the mTOR signaling pathway. This viewpoint may provide a new therapeutic idea for clinical applications., (Copyright © 2019. Published by Elsevier Inc.)

Bone marrow (BM) niche responds to chemotherapy-induced cytokines secreted from acute lymphoblastic leukemia (ALL) cells and protects the residual cells from chemotherapeutics in vivo. However, the underlying molecular mechanisms for the induction of cytokines by chemotherapy remain unknown. Here, we found that chemotherapeutic drugs (e.g., Ara-C, DNR, 6-MP) induced the expression of niche-protecting cytokines (GDF15, CCL3 and CCL4) in both ALL cell lines and primary cells in vitro. The ATM and NF-κB pathways were activated after chemotherapy treatment, and the pharmacological or genetic inhibition of these pathways significantly reversed the cytokine upregulation. Besides, chemotherapy-induced NF-κB activation was dependent on ATM-TRAF6 signaling, and NF-κB transcription factor p65 directly regulated the cytokines expression. Furthermore, we found that both pharmacological and genetic perturbation of ATM and p65 significantly decreased the residual ALL cells after Ara-C treatment in ALL xenograft mouse models. Together, these results demonstrated that ATM-dependent NF-κB activation mediated the cytokines induction by chemotherapy and ALL resistance to chemotherapeutics. Inhibition of ATM-dependent NF-κB pathway can sensitize ALL to chemotherapeutics, providing a new strategy to eradicate residual chemo-resistant ALL cells.

Background/aims: The aim of the present study was to investigate the effects of the combination treatment of pentasa and probiotics on the microflora composition and prognosis in patients with inflammatory bowel disease (IBD)., Materials and Methods: A total of 40 patients with IBD (19 control group and 21 observation group) were randomized. Patients in the control group were given pentasa, and patients in the observation group were given probiotics along with pentasa. The microflora composition, biochemical indices, inflammatory markers, and activity scores of the two groups were analyzed., Results: After treatment, the number of enterobacteria, enterococci, saccharomyces, and bacteroides; the levels of fecal lactoferrin, 1-antitrypsin, β2-microglobulin, high-sensitivity C-reactive protein, and interleukin (IL)-6; activity scores; and recurrence rate in the observation group were significantly lower than those in the control group. Bifidobacterium and lactobacillus counts and IL-4 levels were significantly higher in the observation group than in the control group., Conclusion: The combination of probiotics and pentasa can improve microflora composition in patients with IBD and reduce the level of inflammatory cytokines; therefore, it is worthy of further clinical validation.

Dioxins, polybrominated diphenyl ethers, and benzo(a)pyrene are common organic pollutants in food. They have been of concern to academics and government administrations due to high residue and persistence, easy accumulation and strong harmful effects. The National Research Council of the United States of America published Toxicity Testing in the 21st Century: A Vision and Strategy in 2007, which proposed a new concept of toxicity testing that toxicity testing should take full consideration of population exposure data and base on in vitro tests, human cell lines, toxicity pathways and high-throughput screening. Meanwhile, systems biology, bioinformatics and rapid assay technologies will be used to better understand toxicity pathways-the cellular response pathways that can lead to adverse health effects when sufficient perturbing induced by chemicals exposure. The new toxicity testing strategy has changed the traditional testing pattern and has brought a wide impact on the international relevant fields. The European Union, the World Health Organization, and the United States Environmental Protection Agency, the Food and Drug Administration, and the National Center for Toxicological Research have organized relevant discussions and exploratory studies to address the new toxicity testing concept and how to evaluate and utilize the results of traditional toxicity test researches. Compared to the discussion, 'whether to do it', ten years ago, the question, 'how to do it', has become the concern of the current discussion. Therefore, how to respond to the concept of toxicity testing and how to effectively utilize and excavate traditional toxicity test data have been the focus of multi-disciplines and interdisciplinary academia such as toxicology, food hygiene and environmental science. Therefore, this article provides an overview of the exposure levels of dioxin, polybrominated diphenyl ethers and benzo[a]pyrene, which are typical persistent organic pollutants in food in China and the current research status of toxic pathways based on whole animal experiments. The exposure level, toxic effect and toxicity mechanism of three contaminants are analyzed and summarized in order to provide basis for future results based on the 21st century toxicity test compared with traditional tests and data mining analysis of these two kinds of data. Meanwhile, it also lays the foundation for the establishment of a toxicity testing framework based on exposure characteristics, toxic pathways, and biomarkers.

MicroRNAs (miRNAs) regulate various biological processes during insect development; however, their role in larval-pupal development in oriental fruit fly, Bactrocera dorsalis (Hendel) remains unknown. In the current study, we address the biological function of a conserved miRNA, Bdo-Let-7 in the regulation of BdE75 gene, which belongs to the ecdysone signaling pathway and participates in the larval-pupal development in B. dorsalis. Using dual luciferase reporter assay in HEK293T cells we show that Bdo-Let-7 miRNA interacts with the 3' untranslated region of BdE75 gene and suppresses its expression. The Bdo-Let-7 and BdE75 are also co-expressed in the larval-pupal stages and in different tissues of B. dorsalis. In in vivo experiments, the injection of Bdo-Let-7 agomir and antagomir in third instar larvae down- and up-regulated the expression of BdE75, respectively. The 20-hydroxyecdysone (20E) injection assay shows that 20E up-regulated the expression of Bdo-Let-7 on the 5th day of the larvae. Moreover, abnormal pupation and eclosion were observed after larval Bdo-Let-7 antagomir injection. Based on these results, we show that Bdo-Let-7 regulates the ecdysone signaling pathway through the exact dose of BdE75 gene, and is indispensable for normal larval-pupal development in B. dorsalis., (© 2017 Institute of Zoology, Chinese Academy of Sciences.)

Objective: To investigate the impact of hypoxia-reoxygenation environment on the level of autophagy in osteoblasts. Methods: Osteoblasts were purified from the skulls of newborn SD rats within 24-48 hours by tissue block adherence culture and differential centrifugation. The osteoblasts were identified by alizarin red staining and alkaline phosphatase staining. The third generation osteoblasts were cultured in normal state and randomly divided into four groups: group A was cultured under normal condition for 36 hours; group B was cultured under normal condition for 18 hours, then under hypoxia for 18 hours; group C was cultured under hypoxia for 36 hours; group D was cultured under hypoxia for 18 hours, and then under normal condition for 18 hours. The ability to form calcium nodules of osteoblasts in the four groups was observed after culture. The proliferation activity of osteoblasts was detected by CCK-8 assay. The expressions of autophagy specified gene Beclin 1, microtubule-associated protein light chain 3(LC3) and collagen Ⅰ(COL-Ⅰ), bone morphogenetic protein 2 (BMP-2) genes were detected by real time polymerase chain reaction (RT-PCR), and the protein expressions of Beclin 1, LC3-Ⅰ,LC3-Ⅱ and P62 were detected by immunoblotting. Results: Alizarin red staining showed that osteoblasts in group A had the strongest calcification ability, and calcification ability of osteoblasts in group B,C and D lowered gradually, and it was lowest in group D. The proliferative activity under the CCK-8 detection in group A, B, C and D was 98%±8%, 90%±8%,82%±9%,76%±8%, respectively ( F= 35.764, P= 0.000). The mRNA expression of Beclin 1, LC3-Ⅱthe 4 groups increased gradurally (group D> group C> group B> group A)( F= 38.327, 16.583, both P< 0.05); and the mRNA expression of COL-Ⅰ, BMP-2 decreased gradually in the 4 groups (group A> group B> group C> group D) ( F= 20.387, 12.426, both P< 0.05). The protein expression of Beclin 1,LC3-Ⅱ/LC3-Ⅰ increased gradually in the groups (group D>group C>group B>group A) ( F= 26.843, 28.576, both P< 0.05), and the expression of P62 protein decreased gradually ( F= 18.946, P= 0.011). Conclusions: Hypoxia-reoxygenation environment can reduce the proliferation activity of osteoblasts and up-regulate the expression of autophagy-related genes in osteoblasts. Anoxic reoxygenation environment promotes the increasing of autophagy levels in osteoblasts.