Upf2-Mediated Nonsense-Mediated Degradation Pathway Involved in Genetic Compensation of TrpA1 Knockout Mutant Silkworm (Bombyx mori).

Genetic mutations leading to premature termination codons are known to have detrimental effects. Using the Lepidoptera model insect, the silkworm (Bombyx mori), we explored the genetic compensatory response triggered by mutations with premature termination codons. Additionally, we delved into the molecular mechanisms associated with the nonsense-mediated mRNA degradation pathway. CRISPR/Cas9 technology was utilized to generate a homozygous bivoltine silkworm line BmTrpA1-/- with a premature termination. Transcript levels were assessed for the BmTrpA paralogs, BmPyrexia and BmPainless as well as for the essential factors Upf1, Upf2, and Upf3a involved in the nonsense-mediated mRNA degradation (NMD) pathway. Upf2 was specifically knocked down via RNA interference at the embryonic stage. The results comfirmed that the BmTrpA1 transcripts with a 2-base deletion generating a premature termination codon in the BmTrpA1-/- line. From day 6 of embryonic development, the mRNA levels of BmPyrexia, BmPainless, Upf1, and Upf2 were significantly elevated in the gene-edited line. Embryonic knockdown of Upf2 resulted in the suppression of the genetic compensation response in the mutant. As a result, the offspring silkworm eggs were able to hatch normally after 10 days of incubation, displaying a non-diapause phenotype. It was observed that a genetic compensation response does exist in BmTrpA1-/-B. mori. This study presents a novel discovery of the NMD-mediated genetic compensation response in B. mori. The findings offer new insights into understanding the genetic compensation response and exploring the gene functions in lepidopteran insects, such as silkworms.

Risk factors associated with false negative rate of sentinel lymph node biopsy in endometrial cancer: a systematic review and meta-analysis.

Objective: Currently, sentinel lymph node biopsy (SLNB) is increasingly used in endometrial cancer, but the rate of missed metastatic lymph nodes compared to systemic lymph node dissection has been a concern. We conducted a systematic review and meta-analysis to evaluate the false negative rate (FNR) of SLNB in patients with endometrial cancer and to explore the risk factors associated with this FNR. Data sources: Three databases (PubMed, Embase, Web of Science) were searched from initial database build to January 2023 by two independent reviewers. Research eligibility criteria: Studies were included if they included 10 or more women diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage I or higher endometrial cancer, the study technique used sentinel lymph node localization biopsy, and the reported outcome metrics included false negative and/or FNR. Study appraisal and synthesis methods: Two authors independently reviewed the abstracts and full articles. The FNR and factors associated with FNR were synthesized through random-effects meta-analyses and meta-regression. The results: We identified 62 eligible studies. The overall FNR for the 62 articles was 4% (95% CL 3-5).There was no significant difference in the FNR in patients with high-risk endometrial cancer compared to patients with low-risk endometrial cancer. There was no difference in the FNR for whether frozen sections were used intraoperatively. The type of dye used intraoperatively (indocyanine green/blue dye) were not significantly associated with the false negative rate. Cervical injection reduced the FNR compared with alternative injection techniques. Indocyanine green reduced the FNR compared with alternative Tc-99m. Postoperative pathologic ultrastaging reduced the FNR. Conclusions: Alternative injection techniques (other than the cervix), Tc-99m dye tracer, and the absence of postoperative pathologic ultrastaging are risk factors for a high FNR in endometrial cancer patients who undergo SLNB; therefore, we should be vigilant for missed diagnosis of metastatic lymph nodes after SLNB in such populations. Systematic review registration: http://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023433637.

Effect of different interventions on the treatment of high-risk human papillomavirus infection: a systematic review and network meta-analysis.

Background: Persistent infection with high-risk human papillomavirus (HR-HPV) can lead to cervical intraepithelial neoplasia and cancer. At present, there is no medication that specifically targets HR-HPV infection. Objective: This study aimed to evaluate the effectiveness of different interventions in promoting HR-HPV regression using a MeSH meta-analysis method. Methods: A search for randomized controlled trials (RCTs) reporting different interventions for the treatment of HR-HPV infection included PubMed, Web of Science, Embase and Cochrane Library from the inception of the databases to March 8, 2023. Two researchers independently screened the articles, extracted data, and evaluated the quality. The literature that met the inclusion criteria was selected, the quality and risk of bias of the included studies were assessed according to the Cochrane 5.1 manual, and NMA was performed using Stata 16.0. The area under the cumulative ranking probability graph (SUCRA) represented the probability that each treatment would be the best intervention. Results: Nine studies involving 961 patients and 7 treatment options were included in the analysis. The results of the network meta-analysis indicated the following rank order in terms of promoting HR-HPV conversion: Anti-HPV biological dressing > vaginal gel > imiquimod > REBACIN® > interferon > probiotics > observation/placebo > Polyphenon E. Conclusion: Anti-HPV biological dressing treatment was found to be significantly effective in promoting HR-HPV conversion. However, further validation of the findings is necessary due to the limited number and quality of studies included in the analysis. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42023413917.

The efficacy and safety of ocriplasmin for patients with vitreous macular traction.

PURPOSE: To estimate the efficacy and safety of ocriplasmin for patients with vitreous macular traction (VMT). METHODS: The PubMed, EMBASE and Ovid were searched up to May 2020 to identify related studies. Statistical analysis was conducted by R software version 3.6.3. Results in proportion with 95% confidence interval (CI) were calculated by means of Freeman-Tukey variant of arcsine square transformation. RESULTS: The pooling results indicated the overall complete release rate was 50% (95% CI [45%-54%]). For VMT patients younger than 65 years old, with smaller adhesion size of VMT (<1500 µm), phakic eyes, with macular hole (MH) and subretinal fluid (SRF), while without epiretinal membrane (ERM), ocriplasmin could achieve much higher complete release rates than those under opposite conditions. The general nonsurgical closure rate of MH was 34% (95% CI [30%-37%]), and it was positively correlated with the MH size. The visual improvement rate was 45% (95% CI [32%-59%]), and it was higher for patients with VMT resolution (59%, 95% CI [41%-75%]). The secondary pars plana vitrectomy (PPV) rate for patients without MH closure or VMT resolution was about 31% (95% CI [23%-39%]). The incidence of MH progression was 10% (95% CI [4%-18%]), and other severe adverse events such as endophthalmitis, retinal detachment and retinal tear were relatively rare. CONCLUSION: Ocriplasmin is an effective, reliable and relatively safe intervention for the treatment of VMT. The most suitable candidates were patients younger than 65 years old, with smaller adhesion size (<1500 µm), phakic eyes, with MH and SRF, while without ERM.

A Carboxyl-Functionalized Covalent Organic Framework Synthesized in a Deep Eutectic Solvent for Dye Adsorption.

Instead of using organic solvents, a deep eutectic solvent (DES) composed of tetrabutylammonium bromide and imidazole (Bu4 NBr/Im) was employed as a solvent for the first time to synthesize covalent organic frameworks (COFs). Due to the low vapor pressure of the Bu4 NBr/Im-based DES, a new carboxyl-functionalized COF (TpPa-COOH) was synthesized under environmental pressure. The as-synthesized TpPa-COOH has open channels, and the DES can be removed completely from the pores. The dye adsorption performance of TpPa-COOH was examined for three organic dyes with similar molecular sizes: one anionic dye (eosin B, EB) and two cationic dyes (methylene blue, MB and safranine T, ST). TpPa-COOH showed an excellent selective adsorption effect on MB and ST. The electronegative keto form in TpPa-COOH might help to form electrostatic and π-π interactions between the π-stacking frameworks of TpPa-COOH and the positive plane MB and ST molecules. The adsorption isotherms of MB and ST on TpPa-COOH were further investigated in detail, and the equilibrium adsorption was well modeled by using a Langmuir isotherm model. Together with hydrogen bonding, TpPa-COOH showed higher adsorption capacity for ST than for MB (1135 vs. 410 mg g-1 ). These results could provide a guidance for the green synthesis of adsorbents in removing organic dyes from wastewater.

RETINAL DETACHMENT AFTER ACUTE RETINAL NECROSIS AND THE EFFICACIES OF DIFFERENT INTERVENTIONS: A Systematic Review and Metaanalysis.

PURPOSE: To estimate the rate of retinal detachment (RD) after acute retinal necrosis (ARN) and evaluate the efficacies of different interventions. METHODS: The databases Medline and EMBASE from inception to March 2020 were searched to identify the relevant studies. R software version 3.6.3 was used to perform the statistical analyses. Results in proportion with 95% confidence interval were calculated using generalized linear mixed models. RESULTS: Sixty-seven studies involving 1,811 patients were finally included. The pooling results suggested the general RD rate of ARN was 47%. The RD rate increased with the extent of retinitis and was slightly lower when involved Zone III. The RD rate was 37% for herpes simplex virus ARN and 46% for varicella-zoster virus ARN; 52% for immunocompetent patients and 39% for immunocompromised patients. Retinal detachment presented in 2% of eyes at the first visit. Systemic antiviral therapy could lower the RD rate significantly from 67% to 43%, and prophylactic vitrectomy could lower the RD rate significantly from 45% to 22%. Systemic antiviral therapy plus vitrectomy achieved the lowest RD rate to 18%. Although the efficacy of prophylactic laser or intravitreal antiviral therapy was still limited. Prophylactic vitrectomy might significantly increase the incidence of proliferative vitreoretinopathy from 7% to 32%. CONCLUSION: About half of the eyes might develop RD during the entire course of ARN. Systemic antiviral therapy and prophylactic vitrectomy are effective interventions to prevent RD, whereas the roles of prophylactic laser or adjunctive intravitreal antiviral therapy are still unclear. Varicella-zoster virus ARN and cases with extensive retinitis might need intensified interventions.

The polyp regression rate and treatment prognosis of different interventions for polypoidal choroidal vasculopathy: a systematic review and meta-analysis.

PURPOSE: To estimate the polyp regression rate and treatment prognosis of different interventions for polypoidal choroidal vasculopathy (PCV) and clarify its baseline characteristics. METHODS: The PubMed, EMBASE, and Ovid were searched up to January 2020 to identify related studies. R software version 3.6.3 was used to perform the statistical analyses. Results in proportion with 95% confidence interval (CI) were calculated by means of the Freeman-Tukey variant of arcsine square transformation. Chi-squared test and I2 statistics were used to evaluate the statistical heterogeneity. Sensitivity analysis and subgroup analyses were performed to identify the source of heterogeneity. RESULTS: This meta-analysis included 104 studies with 5816 patients. The pooling results indicated the general rate of complete polyp regression at post-treatment 12 months was 64% (95% CI [57~71%]), 89% (95% CI [81~95%]) for photodynamic therapy (PDT) monotherapy, 78% (95% CI [68~86%]) for PDT plus anti-vascular endothelial growth factor (anti-VEGF), and 42% (95% CI [35~49%]) for anti-VEGF monotherapy; PDT plus anti-VEGF showed the best efficacy in visual improvement and achieved the highest rate of dry macula (91%, 95% CI [78~99%]), while anti-VEGF monotherapy achieved the lowest polyp recurrence rate (14%, 95% CI [8~20%]); PDT monotherapy showed the best efficacy in pigment epithelial detachment regression (66%, 95% CI [58~83%]). Additionally, the baseline characteristics of PCV were also well described. CONCLUSION: PDT plus anti-VEGF is still valuable for the management of PCV; it could achieve not only satisfactory anatomical outcomes like dry macula rate and polyp regression rate but also ideal visual prognosis like BCVA improvement.

Perioperative anti-vascular endothelial growth factor agents treatment in patients undergoing vitrectomy for complicated proliferative diabetic retinopathy: a network meta-analysis.

Currently, controversies regarding the optimal time-point of anti-vascular endothelial growth factor (VEGF) pretreatment before pars plana vitrectomy (PPV) for proliferative diabetic retinopathy (PDR) still exist. To clarify this, we conducted a network meta-analysis, 26 randomized controlled trials including 1806 PDR patients were included. Compared with the sham group, performing anti-VEGF injection at preoperative (Pre-Op) 6 to 14 days could significantly improve post-operative best-corrected visual acuity (BCVA) and decrease the incidence of recurrent vitreous hemorrhage (VH). Meanwhile, it could significantly reduce the duration of surgery. Performing anti-VEGF injection at Pre-Op more than 14 days, 6 to 14 days or 1 to 5 days could significantly reduce the incidence of intra-operative bleeding, while no significant benefit existed at the end of PPV (P > 0.05). No significant difference existed between all those strategies and sham group in reducing the rate of silicone oil tamponade. Based on currently available evidence, performing the anti-VEGF pretreatment at pre-operative 6 to 14 days showed best efficacy in improving post-operative BCVA, reducing the duration of surgery and incidence of recurrent VH, it also achieves satisfactory effect in reducing the incidence of intra-operative bleeding.

[Feasibility of 3BER-S Process for the Deep Denitrification in Synch with the Removal of PAEs from Reclaimed Water].

In order to investigate the feasibility of deep denitrification and simultaneous removing phthalate esters (PAEs) in the process of reclaimed water treatment uses three-dimensional biofilm-electrode reactor coupled with sulfur autotrophic deep denitrification technology (3BER-S), the technological characteristics and mechanisms were analyzed based on determining the static adsorption capacity of biofilm cultured active carbon fillers in 3BER-S reactor together with the operation results of dynamic denitrification and simultaneous PAEs removing. The results showed that the average adsorption rates of DBP, DEHP were 85.84% and 97.12% in the biofilm cultured active carbon fillers, the equilibrium adsorption capacities were 0.1426 mg x g(-1) and 0.162 mg(-1) and the time spans of reaching adsorption saturation were 120 min and 60 min, respectively; The existence of PAEs had no obvious effect on denitrification, the reactor effluent concentration of TN was in range of 1-2 mg x L(-1) before and after the addition of PAEs, and the average removal rate of TN reached above 94%; 3BER-S denitrification system showed significant ability in removing PAEs, leading to effluent concentrations of DBP and DEHP of no more than 6 microg x L(-1) with removal rates of above 96%; this was due to the synergistic effect of absorption, biodegradation and electrochemistry. After treatment with 3BER-S technology, DBP and DEHP in simulative municipal secondary effluent met the regulated limitation of The Reuse of Urban Recycling Water Quality Standard for Groundwater Recharge (GB/T 19772-2005).

[Optimization and application of method to determine plasma concentration of brucine].

The HPLC method for determining plasma concentration of brucine was optimized during the study on the effect of the extraction reagent, the extraction frequency and the volume of extraction solvent on the extraction recovery of brucine. The optimum sample treatment method was obtained in the study. Specifically, ammonia water was added, 4 mL extraction solvent (N-hexane-methylene chloride-isopropyl alcohol 65:30:5) were adopted to extract brucine for twice. The method to determine plasma concentration of brucine was applied in pharmacokinetic study to compare pharmacokinetic properties of intravenous injection (5 mg x kg(-1)) and transdermal administration (40 mg x kg(-1)) of brucine aqueous alkali. The results showed that both pharmacokinetic parameters of brucine after intravenous injection and transdermal administration were in conformity with the two-compartment model. After transdermal administration, the absolute bioavailability was calculated to be 18.72%. The optimized HPLC method can satisfy the demands of the pharmacokinetic study on brucine.

2-[(5-Chloro-2-oxidobenzyl-idene)aza-nium-yl]-2-methyl-propane-1,3-diol.

The title compound, C(11)H(14)ClNO(3), was prepared by the condensation of equimolar quanti-ties of 5-chloro-salicyl-aldehyde and 2-amino-2-methyl-propane-1,3-diol in methanol. In the crystal, it exists in the zwitterionic form, with nominal proton transfer from the phenol group to the imine N atom. This results in the formation of an intra-molecular N-H⋯O hydrogen bond, which generates an S(6) ring. Inter-molecular O-H⋯O hydrogen bonds arise from the hy-droxy groups, forming (001) sheets.

(E)-N'-(4-Hy-droxy-benzyl-idene)-3-nitro-benzohydrazide.

The mol-ecule of the title compound, C(14)H(11)N(3)O(4), assumes an E conformation about the C=N double bond. The benzene rings form a dihedral angle of 3.9 (2)°. The crystal structure is stabilized by N-H⋯O, O-H⋯N, O-H⋯O and C-H⋯O hydrogen bonds, forming layers parallel to (101). In addition, intra-layer π-π stacking inter-actions [centroid-centroid distance = 3.635 (2) Å] are observed.

2-Fluoro-N'-[(2-hydroxynaphthalen-1-yl)methylidene]benzohydrazide.

In the title mol-ecule, C(18)H(13)FN(2)O(2), the hy-droxy group is involved in an intra-molecular O-H⋯N hydrogen bond. The naphthyl ring system and the benzene ring form a dihedral angle of 31.0 (2)°. In the crystal, N-H⋯O hydrogen bonds link the mol-ecules into chains propagating in [101].

2-Bromo-4-chloro-6-(cyclo-hexyl-imino-meth-yl)phenol.

The title compound, C(13)H(15)BrClNO, was prepared by the condensation of equimolar quanti-ties of 3-bromo-5-chloro-salicyl-aldehyde with cyclo-hexyl-amine in methanol. There is an intra-molecular O-H⋯N hydrogen bond in the mol-ecule. The cyclo-hexyl ring adopts a chair conformation.

N'-[(2-Methoxynaphthalen-1-yl)methyl-idene]-4-methyl-benzohydrazide.

In the title compound, C(20)H(18)N(2)O(2), the mean planes of the naphthyl system and the benzene ring form a dihedral angle of 88.48 (10)°. In the crystal, N-H⋯O hydrogen bonds link the mol-ecules into C(4) chains, which propagate along the b-axis direction.

[Study on the interaction between daidzein and human serum albumin].

The binding reaction between daidzein and human serum albumin (HAS) was studied by fluorescence quenching spectra, synchronous fluorescence spectra and ultraviolet spectra. The results indicated that daidzein led to the quenching of the intrinsic fluorescence of HSA. The fluorescence quenching mechanism between daidzein and HSA was mainly static quenching, with non-radiation energy transfer occurring within single molecule. The binding constants (KA) between daidzein and HSA were 0.34 x 10(4) (23 degrees C), 1.10 X 10(4) (30 degrees C) and 4.36 x 10(4) (40 degrees C), respectively. According to the Forster theory of non- radiation energy transfer, the binding distances (r) were 1.50 nm (23 degrees C), 1.46 nm (30 degrees C) and 1.42 nm (40 degrees C), respectively. The thermodynamic parameters were calculated, which indicated that the hydrophobic force played major roles between daidzein and human serum albumin. The effect of daidzein on the conformation of HAS was investigated using synchronous spectrum.